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Utskriftsdato (28.3.2017)

Prostate cancer

Prostate cancer is the most common cancer form in men in most contries of the western world. The disease development varies, and it can take up to twenty years from when cell changes start via prostatic intraepithelial neoplasia (PIN) and indolent (latent) cancer and develop into clinical cancer.

The tumor types of prostate cancer differ in levels of malignancy. Therefore, the treatment schemes differ from no treatment to comprehensive multimodal treatment. To achieve optimal treatment results, it is important that these patients are evaluated by multidisciplinary teams including an urologist, oncologist, radiologist, and pathologist.

During the last 10–20 years, PSA, or prostate specific antigen, has been used for early detection of prostate diseases, including cancer. This has often led to detection of cancer at earlier stages during the course of the disease. The PSA level, measured by a blood test, is often high in the presence of prostate cancer. However, a high PSA reading is not specific for cancer.

There are many controversial aspects in the treatment of prostate cancer.  One of the questions is whether to detect the disease early by PSA-screening or whether the disease’s natural, untreated course is benign enough that curative treatment of early cancer with it’s subsequent serious side effects is unethical.

Incidence 

Compared to other cancers, prostate cancer is fairly common and represents 10.7% of all new cancer cases in the U.S.The number of new cases of prostate cancer was 129.4 per 100,000 men per year based on 2009-2013 cases. Prostate cancer is more common in older men than younger men and is most frequently diagnosed among men aged 65-74.

In 2016, it was estimated to be 180,890 new cases of prostate cancer in the United States. (6)

 

Age-specific incidence of prostate cancer, 2009–2013.

Source: Cancer Registry of Norway

 

 

Incidence of prostate cancer, 1954–2013.

Source: Cancer Registry of Norway

Etiology of prostate cancer

The cause of prostatic cancer is still unclear. Age, heredity, hormones, nutrition, environment, and lifestyle appear to have an influence on the development of the disease. Long-term androgen stimulation is considered to be a premise for developing prostate cancer.

Risk factors

  • 10% of prostate cancer cases are of a hereditary disposition. Familial accumulation is a strong risk factor. If one or more in a family have prostate cancer in a relatively young age, this is a strong indicator that the disease is hereditary.
  • Mutation of the breast cancer gene BRCA 2 increases the risk significantly. It is known that men with this gene mutation have twenty times the risk of developing prostate cancer before reaching 60 years. These patients are offered special monitoring and follow-up. Men having female relatives with early breast or ovarian cancer should be offered an evaluation for hereditary risk of prostate cancer.

Histology of prostate cancer

Photomicrograph of prostate carcinoma. Click to enlarge.

Prostate cancer is a heterogeneous group of malignant tumors that are classified according to the World Health Organization (2004). Ninety-five percent of these tumors are adenocarcinoma originating from the glands and ducts in the prostate. These tumors grow multifocally in the prostate and rarely produce macroscopic tumor nodules. More than 75% of the tumors appear in the peripheral zone. This produces a change in consistency, which can be felt during rectal exploration/palpation.

Most adenocarcinomas are of the acinar type, which are usually referred to as prostate carcinomas . More than 1% of prostate carcinomas are made up of other variants that often have a poor prognosis such as ductal carcinoma , mucinous carcinoma, signet ring cell carcinoma, and small cell carcinoma . Five percent of prostate cancer cases are made up of other types originating from transitional epithelial cells in the urethra or pars prostatic urethra (urothelial carcinoma), support tissue (sarcomas) or lymphoid tissue (lymphomas). Metastases also occur in the prostate, but it is more common that tumors in neighboring organs such as the bladder, rectum, or testis, infiltrate the prostate gland. 

Histological diagnosis

When an elevated PSA value in the serum is detected and prostate cancer is suspected, the diagnosis must be verified before treatment can be started. The pathologist plays a key role in the diagnosis of prostate cancer, as important differential diagnoses such as overgrowth or metastasis from other tumors, benign lesions such as adenosis, atrophy, or prostatitis must be ruled out.

Carcinoma typing, grading, and determination of tumor extension are important information to gather before the treatment and prognosis can be evaluated. The diagnosis is often made on ultrasound-guided biopsies, but sometimes also coincidental in transurethral resections (TUR-P) performed to treat urinary problems. 

The primary cancer diagnosis is always confirmed by two pathologists. The criteria used by the pathologist are architecture atypia (invasive growth, perineural infiltration , micro and cribriform glands) and cellular atypia (enlarge nuclei with prominent nulceoli ). Small foci with carcinoma are usually confirmed by immunohistochemical techniques. With invasive adenocarcinoma, there is usually a loss of basal cells present in benign glands and, in addition, the basal cell markers 34BE12 and p63  are also lost. The marker, alpha-methylacyl-CoA racemace (AMACR/p504s), is upregulated in prostate carcinoma , and can be detected with immunohistochemical techniques.

Needle biopsies

Needle biopsies are usually performed by the urologist via the rectum using ultrasound. Using this procedure, the posterior part of the prostate is reached where most prostate cancer originates. As a rule, 4 biopsies are taken from each lobe . When an MRI or clinical examination gives suspicion of a tumor in the anterior part of the prostate, but transrectal biopsies are negative, biopsies with access through the perineum should be performed. This procedure is performed under general anesthesia.

The needle biopsies are processed separately in order for the pathologist to determine the location of the cancer growth. Additionally, the pathologist must determine how many millimeters of the total length of the biopsy shows carcinoma growth. In addition to the Gleason score, the pathologist determines if there is perineural infiltration or tumor invasion into fat tissue or the seminal vesicles.

Transurethral prostate resection (TUR-P)

During a transurethral prostate resection, the tissue from the central part of the gland is resected to decrease the chance urinary problems. This is done through a scope via the urethra where tissue is removed using a laser knife. The pathologist will receive these tissue pieces fixed in formalin. After fixation, the material is weighed, and about five to eight paraffin blocks are processed from random tissue material .

The pathologist studies the sections from this tissue to determine if benign hyperplasia is the only abnormality. Incidental carcinoma is sometimes found and, if so, the percentage of tissue pieces with carcinoma involvement is determined. Grading is then done along with typing of the tumor. It may be difficult to determine the presence of carcinoma due to heat damage of the tissue .

If the pathologist suspects carcinoma, but the diagnosis cannot be confirmed, it is recommended to take needle biopsies from the peripheral zone.

Radical prostatectomy

When the investigation demonstrates a localized tumor and the tumor grading does not indicate aggresive carcinoma, the patient is a candidate for curative treatment such as a radical prostatecomy .

Examination of prostatectomy specimens is an involved procedure for the laboratory and the pathologist. The entire gland and seminal vesicles are embedded, sectioned, and examined microscopically. This often means 40-50 microscopic sections including several whole-organ sections from the central part of the gland are examined  .

The pathologist studies all sections in detail and describes tumor extension, grade and findings such as perineural carcinoma growth, and infiltration of the seminal vesicles and vessels. It is also reported whether the capsule around the gland is intact as well as if the resection borders are free of tumor.  If the margin is infiltrated by carcinoma, its location and extension should be stated. All of this information must be taken into account when planning the follow-up and deciding on additional therapy.

A positive correlation between MRI findings and macroscopic and microscopic findings is present usually only with large tumors .

Grading

For prostate carcinoma na special grading system described by Donald Gleason is used (1966). This grading system correlates very well with prognosis and has been replacing the WHO grading system. Contrary to the WHO system, Gleason grading is only based on glandular architecture, not cellular atypia. There are 5 Gleason grades, but Gleason grade 1 is hardly ever reported/used.

Example of biopsies with Gleason grade
(click to enlarge)

Grade 2

Tumor consists of well-delineated foci of small, regular nodes almost without any obvious infiltration in the stroma.

Grade 3

Tumor consists of infiltrating nodes of varying size and with varying distance between them. They usually infiltrate between normal nodes.

Grade 4

Tumor consists of complex, cribriform and confluent glands almost without any intervening stroma. There is also often only a tendency for glandular lumina.

Grade 5

Tumor consists of diffuse growing tumor cells with either large confluents sheets, single infiltrating cells, or large groups with central coagulation necrosis.

Score 7 (3+4)

Dominating pattern is grade 3.
Secondary pattern corresponds to grade 4.

 
Dr. Gleason's simplified diagram of the five histological grades of prostate carcinoma.
 

The most aggressive tumors have a Gleason score 5. A Gleason score is given for each needle biopsy as a sum of the dominating and secondary grade. The secondary grade is provided only if it makes up > 5%. A tertiary Gleason grade 4 or 5 is reported even if it makes up < 5%. If the Gleason score is 7b (4+3), the dominating Gleason grade is 4. This grade has a significantly poorer prognosis than a Gleason score of 7a. Tumors with Gleason score 4–5 are low-grade, while Gleason score 6–7a are intermediary, and Gleason score 7b-10 are high-grade. In radical prostatectomy specimens where tumor tissue usually has multifocal extensiveness , focus is provided only on the highest Gleason score and on tertiary Gleason grade 4–5, if applicable. Aggressive tumors such as ductal carcinoma, signet ring cell carcinoma, and small cell carcinoma are not graded. With very small carcinoma foci (< 0.5 mm) the Gleason score is not given, usually only a Gleason grade, if applicable. The Gleason score is also not reported after the patient has been treated with hormone or radiation therapy.

Prostatic intraepithelial neoplasia (PIN)

It is assumed that PIN is a pre-stage for prostatic carcinoma. The changes associated with PIN were first described in 1960 and the term has been used since 1986. PIN is more common in prostate glands with carcinoma than those without. Diagnostic testing for PIN has poor reproducibility between pathologists and also for the same pathologist.  Low-grade PIN (PIN 1) is therefore not reported. The pathologist specifies only the presence of isolated high-grade PIN (PIN 2–3), and in this case, it is recommended to take new biopsies to rule out malignancy. There are different variations of high-grade PIN. If there is ambiguity in an atypical gland with cribiform growth, immunohistochemical techniques can be used. For high-grade PIN, basal cell strata are preserved .

Metastatic patterns of prostate cancer

Initially, prostate cancer grows locally in the gland followed by infiltration through the gland capsule, out into the fat tissue, and into surrounding structures (seminal vesicles, urethra and bladder neck). Metastasis can occur in all T-stages. This happens lymphatically to regional lymph nodes and further to distant organs. Distant metastasis can also occur hematogenously.

At what time the disease is infiltrating or metastasize depends on the aggressiveness of the tumor (predicted by Gleason grade and score and other prognostic factors such as DNA Ploidy).

Distant metastases are often localized to the skeleton. These are osteosclerotic and primarily localized to red hematopoetic bone marrow (spine), flat bones (pelvis, ribs, sternum, skull), humerus, and femur. Metastases distal to elbows and knees are very rare.

Staging of prostate cancer

The tumor classification applies only to adenocarcinomas. Urethral cancer (transitional cell carcinoma) is classified as a tumor in the urethra (1).

The TNM-system describes how the disease has spread and at what time it is evident. “T” describes the spread of the local tumor in and around the prostate. “N” (node) expresses if it has spread to the lymph nodes. “M” expresses distant metastases.

The TNM-classification system differentiates between clinical classification (TNM) and pathology classification (pTNM).  TNM is based on the clinical examination of the primary report. This includes manual palpation of the prostate via the rectum (preferably under local anesthesia), transrectal ultrasound (TRUS) and possibly other image diagnostic investigations (CT, MRI), demarcation biopsies, and gland staging. According to the international TNM standard, TRUS and MRI contribute to the classification, but TRUS is a good supplement for stage determination. MRI will likley develop over time, but at present time it is not documented to be of great value.  

T1 and T2 correspond to localized disease. T3 and T4 correspond to locally advanced disease.

 

TX: Primary tumor not assessed.

T0: Primary tumor not evident.  

T1: No evidence of tumor by palpation, ultrasound, or other radiological method but cancer is evident by prostate biopsy.

  • T1a: Tumor in ≤ 5% of investigated tissue by TUR-P  (Transurethral Resection of the Prostate)
  • T1b: Tumor in > 5% of investigated tissue by TUR-P
  • T1c: Tumor evidence by needle biopsy (for example by raised PSA)

T2: Palpable or visible tumor limited to prostate the gland

  • T2a: Tumor  includes ½ of one lobe
  • T2b: Tumor  includes > ½ of one lobe
  • T 2c: Tumor bilateral

 

 

T3: Extracapsular tumor growth

NB: Growth in apex of prostate or in (but not through) the prostate capsule classifies as T2.

  • T3a: Extracapsular tumor growth (unilateral or bilateral), including microscopic bladder neck invasion.
  • T3b: Tumor infiltration into seminal vesicles

 

T4: The tumor is fixed to or is growing into surrounding structures (bladder, anal sphincter, rectum, levator musculature, and/or is fixed to the pelvic wall).

 

N0: No known spread to the lymph nodes.

N1: Regional lymph node spreading

M0: No known distant metastases 

M1: Distant metastases

Symptoms of prostate cancer

Prostate cancer at an early stage does not give any cancer specific symptoms. Only when tumors are involving the urinary tract, local symptoms corresponding to benign prostate hyperplasia (BHP) will develop.

Locally advanced or metastatic disease can be painful, cause bleeding, urine retention, hematospermia, and/or any symptoms of distant metastases.

Organ localized disease ≤ T2

  • Obstruction symptoms such as hesitant urination, decreased force in the stream of urination, difficulties in emptying the bladder completely.

Locally advanced disease

  • Hematuria (due to infiltration in the neck of the bladder and/or urethra)
  • Pain
  • Hematospermia (rare)
  • Hydro ureter, hydronephrosis, uremia may follow in cases of infiltration of the base of the bladder.

Metastatic disease

  • Pain in the back and bone
  • Neurological symptoms due to metastasis pressing on nerves and spinal nerve roots (vertebral column)
  • Fatigue and weight loss

Distant metastases occur most frequently in the axis skeleton. Sclerotic bone metastases are typical in prostate cancer, but osteolytic metastases which can cause fractures do occur. The greatest danger is pressure on the spinal nerve roots or spinal cord, and and the risk of spinal cord paralysis.

Differential diagnoses of prostate cancer

  • Benign prostate hyperplasia
  • Granulomatous prostate
  • Urinary tract infections
  • Degenerative skeletal/joint diseases mimicking metastases to the skeleton

Prognosis of prostate cancer

In 2013, there were an estimated 2,850,139 men living with prostate cancer in the United States. The earlier prostate cancer is caught, the better chance a person has of surviving five years after being diagnosed. 80.0% are diagnosed at the local stage and the 5-year survival for localized prostate cancer is 100.0%. Because there is screening for prostate cancer, most of the time it is caught before it spreads to other parts of the body. Men who have prostate cancer that is characterized as localized or regional are not as likely to die as men whose cancer is distant. In general prostate cancer has excellent survival rates, but death rates are higher in African American men, men who have advanced stage cancer, and men who are between the ages of 75 and 84. Prostate cancer is the sixth leading cause of cancer death in the United States. Death rates have been falling on average 3.5% each year over 2004-2013. (6)

The natural course of untreated prostate cancer is local growth without symptoms. After time, often multiple years, the disease causes local side effects, either due to the size or infiltration of the area around the gland, surrounding areas, or through the urethra. In principle, all types of prostate cancer can metastasize to the lymph nodes and possibly further to bone or organs. The time frame for such development is dependent on the type of tumor.  With a Gleason score of ≤ 6, development may take 10-20 years or longer. With a Gleason score of ≥ 8, the disease metastasizes before it is evident in the prostate.

Multiple factors are known to be significant in assessment of disease prognosis such as PSA, Gleason score, and T stage. The risk for recurrence can be calculated with nomograms based on serum PSA, Gleason score, and T stage.

Risk stratification (EAU guidelines 2008)
Risk group PSA Gleason score Clinical stage
Low risk ≤10 mg/dL ≤ 6   ≤T2a
Intermediate risk >10 < 20mg/dL = 7 =T2b
High risk PSA ≥ 20 8-10  ≥T2c

After curative treatment, regardless of treatment type, 80% of patients with organ localized disease survive for the first 5 years. The corresponding figure is about 75% for patients with locally advanced disease. Average survival for patients with distant metastases at the time of diagnosis is 3 years, but tumor type (Gleason grade and score) is also of importance.

Up until 30 years ago, 70-75% of all known prostate cancer was locally advanced (T>2) or metastatic. The introduction of the PSA test (see diagnostics) has led to a 75% localized disease at the time of detection (T≤2).

 

 

Five-year relative survival for patients with prostate cancer, in percent, according to stage and diagnosis period 1974-2013.

Source: Cancer Registry of Norway

 

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References on prostate cancer

  1. TNM atlas: illustrated guide to the TNM/pTNM classification of malignant tumours. 7th 2009, Sobin LH, Gospodarowicz, Wittekind Ch.  
  2. Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av prostatakreft, 2015
  3. Klepp O. Svulster i mannlige genitalia. I: Kåresen R, Wist E, red. Kreftsykdommer: en basisbok for helsepersonell. 2. utg. Oslo: Gyldendal Norsk Forlag; 2005. s. 229–243.
  4. Graff BA, Norderhaug IN. Robotassistert kirurgi ved prostatakreft. Oslo: Nasjonalt kunnskapssenter for helsetjenesten; 2006.  
  5. Screening and prostate-cancer mortality in a randomized European study. Schroder F H,et al.. N Engl J Med 2009b; (360): 1320-1328
  6. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, USA.gov.
  7. EAU Guidelines on Prostata Cancer 2015, N. Mottet (Chair) et. al

Diagnostics of prostate cancer

Examinations for prostate cancer includes:

  • Measurement of prostate specific antigen (PSA) in the serum
  • Digital rectal exploration (DRE)
  • Transrectal ultrasound (TRUS)
  • MRI of prostate and pelvis. MRI may be performed before taking biopsies to achieve more targeted  biopsies. The MRI images are then transferred to ultrasound before performing the biopsies. Prostate biopsies may also be performed as an ultrasound-guided transperineal /transrectal biopsy 
  • Skeletal scintigraphy
  • X-ray thorax
  • Additional image diagnostics
  • Pelvic node staging

Prostate specific antigen (PSA)

The most frequent way of diagnosing prostate cancer is by an increase in PSA level in the serum. PSA is a glycoprotein secreted by the glandular cells in the prostate and mixes with semen to prevent coagulation. PSA is normally evident in small concentrations in the serum of men at a mature age. The PSA-level in the serum increases with diseases of the prostate such as benign prostate hyperplasia (BPH), prostatitis, and prostate cancer. PSA is not a cancer marker, however most malignant prostate cells also produce PSA which causes an increased “leakage” of PSA to the serum. This permits diagnosing cancer at an early stage.  

Upper limit of normal for PSA in Norway (3)
< 50 years 3.0 ng/ml
50–59 years 3.5 ng/ml
60–69 years 4.5 ng/ml
> 69 years 6.5 ng/ml
  • In slight increases of PSA levels in the serum (< 10 ng/ml), BPH is more common than prostate cancer.
  • In the area of 10-30 ng/ml, prostate cancer is the most likely.
  • In a serum PSA > 100 ng/ml, there is almost always spreading from prostate cancer.

Digital rectal exploration (DRE)

DRE must be completed by the primary doctor if the symptoms or other findings cause suspicions of cancer. In this investigation, the size and consistency are evaluated and may provide valuable information.

Biopsy

The prostate is available for both transperineal and transrectal biopsy. Most common today is ultrasound guided transrectal biopsy. There is probably no qualitative impact whether the biopsy is taken transrectally or transperineally.

Before referral to a specialist for biopsy, the patient should be informed of the consequences of a malignant biopsy. In symptom-free patients over 70-75 years, it can be discussed whether curative treatment is appropriate. 

Metastasic work-up

Bone scintigraphy is a simple examination that require few resources. It has the status of a basic examination in intermediate and high risk prostate cancer cases. It is often supplemented with MRI of the bone, which is more sensitive for detecting spread to bone. MRI has also increased accuracy to detect possible spread to lymph nodes. PET-scans are currently not in general use, but are under development for prostate cancer work-up.

Pelvic lymph node staging of intermediary and high risk patients

Lymph node dissection in fossa obturatorius for diagnostic purposes has lost much of its relevance in recent years. New methods of diagnostic imaging such as MRI often provide enough information to determine whether the patient is a candidate for curative treatment.

At present, surgical removal of lymph nodes surrounding the prostate is done in the same session as radical prostatectomy with extended lymph node dissection. This may in some cases have a therapeutic effect.

PROSEDYRER

Ultrasound-guided histological biopsy from the prostate

General

Biopsy of the prostate is performed to diagnose prostate cancer and to assess the extent and localization of the tumor.

To determine the T-stage, a histological biopsy is included in addition to digital rectal exploration (DRE), transrectal ultrasound (TRUS). The tumor type (Gleason score) is assessed by the pathologist based on the biopsy material.

The biopsy is usually taken transrectally with local anesthesia. In special cases, perineal biopsies are done under short general anesthesia.

Indications

  • Palpable finding by DRE  
  • Normal DRE and TRUS, but raised serum-PSA (<3-4 ng/ml)

Goal

Diagnostic:

  • to confirm prostate cancer.
  • to determine T-stage.

Equipment

  • Leg holders

Preparation

Transrectal biopsy

  • Antibiotic prophylaxis 

Transperineal biopsy

  • Tape scrotum
  • Wash the perineum with colored chlorhexidine

Implementation

Transrectal biopsy

  • Place local anesthesia with a thin needle in the area around the prostate capsule.
  • Fill the condom with gel and cover the ultrasound probe. 
  • Insert ultrasound probe into the rectum.
  • Inspect the prostate and target volume.
  • Localize the suspect area in the prostate using ultrasound.
  • Insert the biopsy needle with the help of ultrasound into the desired area of the prostate.
  • Retract the biopsy pistol to take the biopsy.
  • Take 4-6 biopsies from each prostate lobe in a systematic pattern.
  • Place the biopsies into separate specimen containers with formalin.

Transperineal biopsy

  • Short general anesthesia is given. 
  • Fill the condom with gel and cover the ultrasound probe.  
  • Insert the ultrasound probe into the rectum.
  • Inspect the prostate and target volume.
  • Localize suspect area in the prostate with the help of ultrasound.  
  • Insert the biopsy needle in the perineum.
  • Insert the needle into the prostate with the help of ultrasound.
  • Retract the biopsy pistol to take the biopsy.
  • Take 5-10 biopsies from each lobe of the prostate in a systematic pattern.
  • Place the biopsies into separate specimen containers with formalin.

Follow-up

The result of the test is usually available after 14 days. When prostate cancer is confirmed, the patient is referred for further investigation and treatment.

Observations

  • Fever and/or chills (bacteremia)
  • Blood in the urine, stool, or sperm is normal
Ultrasound-guided histological biopsy from the prostateUltrasound guided histological biopsy from the prostateUltrasound guided histological biopsy from the prostateUltrasound-guided histological biopsy from the prostate
Ultrasound-guided histological biopsy from the prostate

Prostate processing and embedding

General

Typing, grading, and specification of a tumor is a tedious process that is crucial for the choice of treatment method and the prognosis of the patient. The diagnosis is most often made on biopsies from the prostate, but can also be made by coincidence during a transurethral resection of the prostate (TUR-P) performed for therapeutic purposes on patients with incontinence problems.

Pathologists play a key role in diagnosing prostate cancer, since they classify and grade the tumor, determine the extent, and whether there is infiltration of pericapsular tissue, vessels or seminal vesicals. It must also be investigated whether the capsule is intact and if there is tumor present in the resection margins. This is of significant value for the follow-up schedule with PSA testing, and for assessing if the patient will need additional treatment. A positive correlation between MRI findings and macroscopic and microscopic findings is usually present only with large tumors .

The primary cancer diagnosis must always be verified by at least two pathologists.

Definitions

The criteria used by pathologists to determine malignancy are:

  • architectual atypia (invasive growth, perineural infiltration  micro and cribriform glands)
  • cellular atypia (enlarged nuclei with prominent nucleoli) .

Small foci with carcinoma must be confirmed with with immunohistochemical techniques. When there the tumor grows invasively, there is loss of basal cells and the basal cell markers, 34BE12 and p63 , are lost. The marker, alpha-methylacyl-CoA racemace (AMACR/p504s), is upregulated in prostate carcinoma , and can be detected with immunohistochemical techniques.

Preparation

The entire prostate gland with seminal vesicles is embedded and examined under a microscope.

Around 40-50 sections are assessed by a pathologist , including large sections from main parts of the prostate .

 

Implementation

  • The pathologist weighs, measures, describes the external appearance.  
  • A probe is placed through the urethra to better orient the prostate.
  • The surface of the prostate is then dyed. The dorsal surface is dyed black, the left lobe blue, and right lobe green. 
  • The probe is then removed and the prostate is dried. The seminal vesicals are then cut from the prostate. 
  • A small end from the apax and base are then cut, and the apex and base are separated through the urethra. 
  • A sagittal section is made from each half in the apex and base. A cross section is then made of the middle part as a large section.
  • A cross section from the seminal vesicals is then made.
  • Calcificationsare removed if necessary before the sections are placed in blocks with the referral number and block number.
  • All of the sections are fixed for an additional 48 hours in formalin before further processing.
  • The blocks are then placed in a processing machine where the tissue is dehydrated, rinsed, and infiltrated with paraffin using alcohol, xylenes, and paraffin.
  • The tissue is then embedded in liquid paraffin that solidifies into a block allowing to make very thin slices of tissue. 
  • The paraffin blocks are stored in a freezer until the sections are made.
  • The technician slices 1-2 μmm sections which are transferred to a slide glass in a water bath.
  • The sections are then transferred to a staining maching where the paraffin is removed and they are stained with haematoxylin and eosin, dehydrated, and mounted.

Follow-up

It may be necessary to do immunohistochemical testing before the final diagnosis is made.

The result is usually available after one week unless additional analyses are necessary. Complicated cases may require more time. Occasionally, the pathologist will consult an expert out of the country.
Prostate cancerProstate cancerProstate cancerProstate cancer
Prostate cancerProstate cancerProstate cancer

Bone scintigraphy

General

Bone scintigraphy is one of the most common nuclear medicine investigations. The investigation is particularly useful because images of the skeleton can be taken from head to toe, or back to front, by a relatively simple procedure.

The investigation is highly sensitive for showing unhealthy processes in the skeleton but the specificity is proportionately low. It is especially sensitive for active, sclerotic tumors.

Limitations

  • Small, osteolytic tumors, metastases, especially in plasmacytoma, but also in malignant melanomas, kidney cancer, and thyroid cancer, can be overlooked
  • For bone pain and “negative” bone scan, an MRI should be performed
  • In patients with treatment response from bone metastases, one will usually see an increase in uptake of metastases after 3 months after start of effective treatment. This is a sign of healing.
  • Radiation induced insufficiency breaks should not be interpreted as metastases
  • MRI is more sensitive and specific for finding bone metastases in the spine and pelvis. But MRI is much more resource-demanding, therefore a bone scan will often be the first choice.

Sources of error

  • False negative bone scan occurs with myelomatose and in osteolytic metastases
  • Apparent outbreak of bone metastases can occur in conjunction with treatment despite clinical improvement (flare phenomenon)

Indications

  • Stage grouping of cancer with a tendency for bone marrow and bone metastases
  • Primary bone tumor
  • Unclear bone pain in patients without known cancer disease
  • Sclerotic tumors for example bone metastases from prostate cancer, breast, or lung

Goal

  • To diagnose primary tumors or relapse

Preparation

  • The patient should be well hydrated.
  • Loose metal objects such as jewelry and coins should be removed.
  • Radiopharmaceutical 99mTc bisphosphonate complex is given. In Norway, the most widely used complex for this procedure is methylene bisphosphonate, MDP.

Implementation

  • The 99mTc bisphosphonate complex is injected intravenously. 99mTc-labelled bisphosphonate binds to the osteoblasts, especially in the areas with high perfusion and high osteoblast activity.  
  • In dynamic image taking for assessment of blood supply and vascularization, images are taken during injection of the radiopharmaceutical drug.
  • Static images of the whole body or parts of the body are taken around 2.5 hours after the injection.
  • Between injection and image taken, the patient should drink copious amounts of water (about 1 liter) and eliminate as often as possible to reduce radiation exposure in the bladder.
  • The bladder should be empty before image capture. (Around 50% of injected activity is eliminated via the kidney in the urine during the first hours.
  • With a one-head camera, the whole body test takes around 30 minutes.
  • With a two-head camera, the whole body test takes around 50 minutes.
  • It is important that the patient remains completely still during the test. If the patient is unable to lie still for at least 20 minutes, multiple images can be taken instead of one whole body scan.
  • It can be necessary to supplement image taking with individual images using special angles (3-10 minutes per image).

Follow-up

  • The patient should continue to drink lots of water for the rest of the day after the test, as the radioactivity is eliminated via the kidneys.
  • The radiation exposure to persons in contact with the patient is insignificant, but the patient should still avoid extended contact with children and pregnant mothers the day of the test.
  • The result of the test is often available the following day.
Bone ScintigraphyBone ScanBone ScanBone Scan

Positron Emission Tomography (PET)

General

Positron Emission Tomography (PET) is a nuclear medical examination method. PET is a well-documented, well-established and very useful tool in oncological imaging.

Indications

Oncological imaging for:

  • Staging the primary diagnosis and recurrence
  • Evaluating the effect of aggressive chemotherapy treatment
  • Evaluating the effect of completed treatment, including differentiating scar tissue from viable residue tissue
  • Suspicion of recurrence (for example, increased level of tumor marker in the blood)

Goal

  • To provide concrete diagnostic information that will provide a basis for the choice of the best possible treatment.

Definitions

PET has a very high sensitivity and can register absorption of radiopharmaceutical agents in extremely low concentrations. Since the central atoms in biochemical compounds (carbon, oxygen, nitrogen) all have positron-emitting isotopes that can be produced in small hospital cyclotrons, it is possible to mark a number of central molecules such as oxygen, water, amino acids, various metabolites, hormones, and neurotransmitters.

For clinical PET, dextrose is usually used where a hydroxide group is replaced by 18F (18-flourine), a compound that is called 18F-FDG (flourine-18 labeled deoxyglucose). 18F-FDG has a high affinity for cells with increased metabolism, for example cancer cells. The substance is transported into the cells and phosphorylates glucose to 18F-FDG-phosphate, but no further break-down occurs. Because cell membranes are impermeable to phosphorylated deoxyglucose, an intracellular accumulation of the substance occurs.

Limitations

  • Small tumors ( < 0,5 cm) and tumors with low to moderate absorption can escape detection.
  • Inflammatory conditions will produce increased absorption.
  • For patients with diabetes (especially those requiring insulin) and non-fasting patients, high muscular absorption will reduce the sensitivity for tumor detection.
  • Some tumor types have low FDG absorption (for example, prostate and bronchoalveolar carcinoma).

Sources of error

  • Infections and inflammatory conditions (including post-operative changes) will result in increased absorption.
  • Normally, the intestine can have a high absorption.
  • Myocardium often displays high absorption, also in fasting patients.
  • 18 F-FDG is excreted through the kidneys and FDG in the urinary tract can be misinterpreted.
  •  Absorption in brown fat tissue can be misinterpreted as a tumor if PET is not compared with CT. PET/CT combined in the same apparatus gives better specificity than PET alone.

Equipment

  • PET/CT-scanner  
  • Radio-pharmaceutical agent: 18F-FDG is formed by radiating a heavier natural variant of oxygen with protons. This occurs in a cyclotron. Fluorine-18 (18F) is produced at the hospital cyclotron located at Rikshospitalet .

Preparation

Patient preparation depends on the clinical diagnosis.

  • Fast for at least 6 hours before the examination in order to increase the absorption of 18F-FDG. But the patient should drink plenty (2-4 glasses per hour. Water, tea, or coffee without sugar or cream/milk added can be substituted for water.
  • Measurement of s-glucose is performed before injection of 18F-FDG.
  • After intravenous injection of 18F-FDG, it is very important that the patient lies relaxed in a quiet room without talking and avoiding all forms of stimuli, in order to avoid non-specific absorption of 18F-FDG in the muscles.
  • Tranquilizers and painkillers are often administered prior to the injection.
  • The patient should be warm and comfortable prior to the injection in order to prevent absorption in the brown fat, which may affect the interpretation.

There will be other precautions for neurological and cardiological diagnoses.

Implementation

  • The patient must lie completely still while the images are being taken.
  • A whole-body examination takes approximately 25 minutes.
  • For PET, tissue absorption is displayed by positron-emitting, radiopharmaceutical preparations.

Registration of emission

  • The positron is considered a positively charged electron.
  • When the positron leaves the radioactive core, it will travel up to a few millimeters before it collides and fuses with an electron and is transformed into energy; this is called annihilation.
  • The mass of the positron and the electron is transformed into energy in the form of two photons, each of 511 keV, which are emitted in diametrically opposing directions (180°).
  • A ring detector around the patient will catch the photons.
  • The two photons will encounter the ring detector at the same time (coincident detection), and because they have moved in exactly opposite directions, the detection will precisely localize the radiation focus (for example, a lymph node with tumor tissue).
  • A modern PET-camera with ring detector can map the entire body in 20 minutes.
  • The PET-scanners have integrated CT, so that the information from PET is accurately localized anatomically.

Examples of findings

  • Anal cancer: Anal tumor and metastasis in lymph node
  • Hodgkin's lymphoma (HL): HL with involvement of: soft tissue in the larynx , vertebra L4 ,  os pubis L  and femur
  • Cancer of the rectum: Adenocarsinom in rektosigmoideum liver metastases
  • Intracranial tumors: Astrocytoma grade II/III, left parietal lobe  high-grade glioblastoma, right frontal lobe 
  • Lung cancer: Lung tumor  lung cancer with lymph node spread
  • Sarcoma: Soft tissue sarcoma in the left thorax
  • Cancer in the esophagus: Tumor in the distal esophagus
  • Colon cancer: Metastasis-suspect lesion in adrenal gland

Follow-Up

  • At the end of the examination, the radioactivity is small, but the patient should keep a distance (about 3 meters) from children and pregnant ladies the day of the scan.
  • The result will normally be available the following day.
Postitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDG
Postitron emission (PET) with <sup>18</sup>F-FDGPositron emissions tomografi (PET) with <sup>18</sup>F-FDGPositron emission tomography (PET) with <sup>18</sup>F-FDGPositron emission tomography (PET) <sup>18</sup>F-FDG
Positron emission tomography (PET) with <sup>18</sup>F-FDGPositron emission tomography (PET) <sup>18</sup>F-FDGPositron emission tomography (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDG
Postitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDG
Positron emmissions tomography (PET) with<sup>18</sup>F-FDGPositron emission tomography (PET) with <sup>18</sup>F-FDGPositron emission tomografi (PET) with <sup>18</sup>F-FDG

Treatment of prostate cancer

Treating prostate cancer is in close correlation with the stage of the disease and extent. It is very important to differentiate between prostate cancer that is treated to cure the disease or in a palliative situation. Unfortunately, the boundaries between these groups are not clear. Many circumstances are taken into consideration when choosing treatment such as the age of the patient, comorbidity, and side effects of different treatment types. It is very important to explain the treatment alternatives. The patient's partner should be included in the discussion of treatment alternatives, and it may also be beneficial to have both the oncologist and surgeon present information together. 

The treatment forms chosen may vary between country, hospital, and specialist, which is not a favorable situation for the patient.

Curative treatment

Due to PSA screening, many patients today have organ localized disease at the time of diagnosis (T ≤ 2), and it is therefore possible to offer more patients treatment intended to cure the disease. 

Possible treatments may be:

  • radical prostatectomy
  • external conform radiation therapy
  • brachytherapy
  • combined brachytherapy and external radiation therapy
  • combined hormone treatment and radiation therapy

The frequency of recurrence and survival is considered equal for surgery and radiation therapy. The side effect profile for these treatment methods differes, but quality of life studies show equal quality of life for patients having undergone different treatment types. For T3 disease (capsule rupture), both surgery and radiation is considered in some cases.

Focal therapy

With focal therapy the tumor is removed without removing the entire prostate.

  • Cryoablation therapy
  • High-Intensity Focused Ultrasound - HIFU ( heat therapy)
  • Photodynamic therapy (PTD)

None of these treatments are available in Norway today.

Observation/waiting

Curative treatment (surgery or radiation) may have severe side effects and reduce the patient's quality of life. In many cases, prostate cancer has a low growth potential and metastasize late. If the patient is high in age, the disease may not cause serious problems within their lifetime. If the disease is not very agressive, it is usually best for the patient to forgo treatment.

"Active monitoring" means the disease is monitored (3–6–12 months) to obtain an impression of the malignancy potential of the tumor and possibly initiate curative treatment at a later time if the disease shows signs of progression. It is then possible to postpone treatment and bothersome side effects for multiple years, or possibly avoid treatment completely.  

Palliative treatment

Some patients who already have signs of the disease either have locally advanced disease or metastasis. There are many treatment options for these patients, even if they are not intended to cure the disease. 

Patients who cannot be given curative treatment because of advanced disease at diagnosis or other causes, can be offered different palliative alternatives. The purpose of palliative treatment is to help the patient live as long and good life as possible with the disease.

Treatment alternatives often combined are:

  • Hormone manipulation
  • Surgery
  • Radiation treatment
  • Chemotherapy

Hormone manipulation

The prostate cells are dependent on testosterone stimulation to grow and develop. This applies also to most malignant prostate cells. If the production of testosterone is stopped, most of the malignant cells will die (apoptosis) and both the local tumor and metastases will go into remission. This remission can last many years, but the disease is not cured. The tumors can start to grow again, despite lack of stimulation by testosterone. The disease is then testosterone independent (hormone refractory).

Hormone manipulation can dramatically alter the clinical course of the disease, even if it is unknown whether the treatment prolongs the patient’s life.  It is unclear whether such hormone treatment should be started early or wait until the patient has clinical symptoms or metastases. In recent years, there have been reports that hormonal manipulation provides a somewhat longer survival. To start treatment at an early point in time requires assessment of the side effects from treatment versus the relatively marginal improvement in survival. In recent years, new hormon drugs have become available. Treatment with enzalutamide or abiraterone have shown prolonged survival.

Surgery

For local symptoms (obstruction/bleeding), transurethral resection of the prostate/tumor (TUR-P) is good palliation. This can also be combined with radiation therapy. For bone metastases in weight bearing bones, and for neurological symptoms from the spinal cord, orthopedic surgery should be assessed, in combination with postoperative radiation therapy. 

For infiltration of the base of the bladder with obstruction of the urethra, the urinary tract from the kidney must be secured. The alternatives are re-implantation of the urethra if bladder outflow is good, or stenting of the ureteres if the prognosis is not good. Urinary diversion (Bricker diversion, cutaneous ureterostomy, pyelostomy) may be appropriate depending on the prognosis and general medical condition. 

Radiation therapy

  • To prevent metastases
  • Pain treatment
  • Spinal column for threatening neurological symptoms
  • Palliative radiation of the prostate tumor

Palliative radiation therapy is given as external radiation therapy. The goal is to reduce pain or to reduce the tumor size and thereby remove or reduce locoregional problems. Adjuvant radiation therapy is also given after metastasis surgery (vertebral column, bones). Targeted radiation therapy (radium 223) may be used as pain treatment and may in some cases cause prolonged survival.

Chemotherapy

For locally advanced cancer or metastases from hormone refractory cancer, there is sufficient documentation to consider the use of chemotherapy with docetaxel (Taxotere®).

Surgery of prostate cancer

Radical prostatectomy

Radical prostatectomy (RP) is an established treatment with curative aims. RP includes removal of the entire prostate as well as the prostatic urethra and both seminal vesicles with subsequent anastomosis between the neck of the bladder and the urethra.

The surgery may be performed with open access, but is increasingly performed with robot-assisted laparoscopy.

There is no difference in side effects or postoperative complications of the different methods of radical prostatectomy, and oncological results are considered to be equal.

Local relapse will be more frequent in patients who had unfavorable histology of the operation specimen (pT3 and possibly invasion into margins). A large percentage of these patients will have PSA-relapse within 5-7 years. They should be assessed for adjuvant radiation therapy to the prostate region given about 3 months after surgery. If there is evidence of metastasis to the lymph nodes and/or other metastases, the disease is disseminated and curative treatment is unlikely.

Surgery and lymph node dissection

Staging procedure for intermediary and high risk patients

Since only 38 % of prostate-draining lymph nodes are localized to fossa obturatoria, is isolated removal of lymphatic tissue in this area of limited value. However, in cases where there are indications for surgical N-staging, it is recommended to perform an extended lymph node dissection, in which 63-75% of the draining lymph nodes are localized.

In some hospitals, an extensive lymph node dissection in context with radical prostatectomy is performed in cases where there is a high risk of lymph nodes metastasis. There is also evidence that extensive lymph node dissection may have therapeutic effect.

Palliative treatment

  • Transurethral resection of prostate (TUR-P)
  • Maintain drainage of upper urinary tract (hydroureter, hydronephrosis)
  • Metastasis surgery (for neurological symptoms)
  • Orthopedic surgery (for threatening fractures of metastastatic bones)

PROSEDYRER

Radical prostatectomy

General

A radical prostatectomy is, in addition to high-dose radiation therapy, the only internationally recognized curative treatment option for localized prostate cancer.

During the procedure, the prostate and seminal vesicles (or parts) are removed. The neck of the bladder is anastomosized directly to the urethra. A nerve sparing technique is attempted to conserve erectile function.  

Radical surgery is preferred for patients having at least 10 years expected survival time and organ-localized cancer. Patients with locally advanced cancer are increasingly considered. In such cases, supplementary treatment is often likely.

The surgery can be performed as open surgery or as robot-assisted laparoscopic surgery. There is no difference in side-effects or postoperative complications between these methods. 

At Oslo University Hospital, all radical prostatectomies are performed by robot-assistance. This tendency is also consistent with the rest of Norway, western Europe, and the US. 

Advantages of robot-assisted laparoscopic surgery compared to surgery:

  • Shorter reconvalescence
  • Less blood loss
  • Less scars
  • Less postoperative pain
  • Shorter sick-leave period 

Indications

  • Localized prostate cancer

  • Locally advanced prostate cancer

Goal

 

  • Cure the disease

Equipment

  • Laparoscopy
  • Robot instruments
  • Urological robot forceps
  • 0° optic
  • Suction/rinse

Preparation

  • Thrombosis prophylaxis
  • Foley catheter
  • Trendelenburgs position

Implementation

  • During the operation, the patient lies in the supine position and extreme Trendelenburg position.
  • Five trocar ports are made. The abdominal cavity is inflated.
  • The robot is docked.
  • The peritoneum is opened around the bladder.
  • Lymph nodes are removed if necessary as described under lymph node dissection.
  • Open the endopelvic fascia and divide the puroprostatic ligaments.
  • Incise the neck of the bladder down to the deferens ducts which are divided.
  • Dissect both seminal vesicles which are pulled up.
  • Denonvilliers' fascia is incised and a layer between the rectum and prostate is reached.  
  • Divide side ligaments to the prostate using a nerve-sparing technique if possible.
  • Split the urethra close to the prostate and place in a plastic bag.
  • Anastomosize between the bladder and the urethral stump.
  • Test anastomosis by instilling saltwater into the bladder.
  • The prostate is removed via the umbilical opening.

Follow-up

Observations

  • Bleeding
  • Anastomotic dehiscence
  • Urinary tract infection  
  • Deep venous thrombosis/lung embolism

The patient will have the Foley catheter in place for 14 days. He will be trained to clean the catheter and use a leg before returning home. The patient should also be informed about erection and continence training. After a robot-assisted radical prostatectomy, the patient is usually discharged on the second postoperative day.

The Foley catheter is removed after 10 days and a urine sample is collected for bacterial testing

The pathology report may take 2-3 weeks. This histological examination is very resource-demanding for a pathology laboratory.

The patient have a follow-up examination with an urologist 6 weeks postoperatively.

 

Radical ProstatectomyRadical ProstatectomyRadical prostatectomy

Lymph node dissection for intermediate and high risk prostate cancer

General

Studies show that an extended lymph node dissection including the area around the internal and external iliac arteries, as well as the traditional obturator area, may be therapeutic in certain patients having few lymph node metastases. A correlation exists between the number of removed lymph nodes and the time to progression, and certain patients do not have PSA recurrence after 10 years without adjuvant therapy. However, an extensive lymph node dissection causes increased morbidity with lymphocele and lymphedema. Therefore, the benefit of the procedure must outweigh the risk.

At Oslo University Hospital, routine robot-assisted laparoscopic lymph node dissections are performed during the same surgery as the prostatectomy. This procedure is rarely performed alone.  

Indications

  • Staging of intermediary and high risk cancer

Goal

  • To diagnose microscopic tumor spreading
  • Possible curative effect if performed with radical prostatectomy

Preparation

  • Enema
  • Thrombosis prophylaxis
  • Antibiotic prophylaxis
  • Foley catheter

Implementation

During open surgery, a low midline incision is made from the symphysis to the umbilicus. The entire procedure is extraperitoneal.

  • During laparoscopy, the procedure is performed transperitoneally.
  • Remove fatty tissue and lymph nodes in one area limited to the urethral crossing over the common iliac artery, laterally to the external iliac artery and medially to the internal iliac artery. 
  • Identify the obturatorial nerve and obturatorial artery
  • Dissect the fatty tissue off the nerve and vein.
  • Ligate distal lymph vessels.
  • Check the hemostasis.

If staging is completed to assess curative radiation treatment, the nodes are put in formalin.

Follow-up

Observations

  • Bleeding
  • Anastomotic dehiscence
  • Urinary tract infection
  • Blood clot/lung embolism

The patient will have a Foley catheter. He will be trained to clean the catheter and use a leg bag before returning home. The patient should also be informed about erection and continence exercises. After a lymph node dissection with robot-assisted radical prostatectomy, the patient is normally discharged after the second postoperative day.

The Foley catheter is removed at the outpatient clinic 10 days postoperatively. A urine sample is taken for bacterial testing.

The patient will then have an outpatient follow-up check with an urologist 6 weeks after the operation.

The pathology report may take 2 to 3 weeks. This diagnostic test is very resource-demanding for a pathology laboratory.

Delayed effects

  • Incontinence
  • Impotence

Bilateral orchiectomy

General

Prostate cells, both normal and malignant, are dependent on testosterone stimulation to grow and divide. This is exploited in palliative treatment of prostate cancer. For metastatic disease, treatment aims at halting production of testosterone. Ninety-five percent of testosterone is produced in the testicles.

Production of testosterone in the testicles is most often done chemically with an injection every three months for life. Alternatively, surgical castration of both testicles can be done operatively.

An orchiectomy can be performed through the inguinal or scrotal area.

Indications

  • Locally advanced prostate cancer (T3/T4)
  • Metastatic prostate cancer (N1/M1)

Goals

  • Palliation

  • To reduce symptoms from the disease and prevent serious complications such as spinal cord complications

 

 

Equipment

  • Surgery tray

Preparation

  • Shave the pubis and scrotum

Implementation

The procedure is performed under local anesthesia, spinal anesthesia, or general anesthesia.

Scrotal bilateral orchiectomy

  • Incise the scrotum along the medial raphe
  • Lift one testicle out of the scrotum.
  • Ligate and divide the spermatic cord.
  • Ligate and divide the testicular vessels separately.
  • Repeat on other testicle.
  • Check hemostasis.
  • Insert testicle prosthesis in scrotum if appropriate.
  • Close the incision.

Inguinal bilateral orchiectomy

  • Make a cross incision over the outer inguinal opening.
  • Lift the testicle out of the scrotum
  • Isolate the spermatic cord.
  • Ligate and divide the spermatic cord.
  • Ligate and divide the testicular vessels separately. 
  • Repeat on the other side.
  • Check hemostasis.
  • Insert testicle prosthesis in the scrotum if applicable.
  • Close the incision.

Follow-up

Complications

  • Postoperative bleeding and hematoma with subsequent infection.

Following orchiectomy

  • Loss of libido with erectile dysfunction 
  • Hot flashes
  • Fatigue
  • Osteoporosis
  • Muscular atrophy

Transurethral resection of the prostate (TUR-P) for prostate cancer

General

Transurethral resection of the prostate (TUR-P) is performed as palliative treatment for prostate cancer:

  • when the tumor obstructs emptying of the bladder
  • for bleeding due to tumor breakthrough of the urethra/neck of the bladder 

Indications

  • Obstruction symptoms
  • Urine retention 
  • Bleeding

Goal

  • Palliation

Equipment

  • Resectoscope
  • Xylocain gel®
  • Ellik® evacuator
  • 3-way catheter
  • NaCl for irrigation

Preparation

  • A urine sample must be provided for a bacterial test.

If a urinary infection is present, the patient should be treated with antibiotics pre-, per-, and postoperatively.   

Implementation

The procedure is done under spinal or general anesthesia. The patient should have leg supports.

  • Wash the perineum and external genitalia with chlorhexidine.
  • Drape the area allowing for peroperative rectal exploration.
  • Place Xylocain gel® in the urethra.
  • Insert resectoscope, guided by vision, into the bladder.
  • Inspect bladder for pathological findings.
  • Inspect the size of the prostate and possible breakthrough of tumor.
  • Inspect the urethral part of prostate all the way to the colliculus.
  • Resect  tissue of the urethral part of the prostate. Resect tissue to obtain an adequate channel down to the funicle. When the tumor infiltrates towards the sphincter, extended resection may cause incontinence.
  • The tissue specimens remains in the bladder during the resection. The resected surface will always bleed. It is therefore necessary to flush the area during resection to maintain a good view. All rinse fluid is collected in the bladder. When the bladder is full, the resection instrument is retrieved from the resectoscope to release the rinse fluid containing blood. Alternatively, a suprapubic catheter can be installed to drain the rinse fluid during the entire operation.
  • Continually maintain hemostasis during the procedure.
  • Empty the bladder of the resected tissue using an evacuator. Remaining pieces of tissue can cause complications.
  • Check hemostasis.
  • Place a 3-way catheter for continuous flushing.

Follow-up

There should be continuous flushing through a 3-way catheter for approximately 24 hours is done, depending on bleeding. If there is no ongoing bleeding, the catheter can be removed after 24 hours. When there is spontaneous voiding and residual urine < 50 ml, the patient can be discharged. If the patient had a urinary tract infection during the procedure, antibiotics should be given for one week based on a bacterial resistance test.

Complications

  • Per- and postoperative bleeding (frequent due to abundance of vessels in the tumor). Coagulated blood in the bladder must be evacuated.
  • Infections
  • Incontinence (rare, but can occur if tumor infiltrates down to the sphincter area)
Transurethral resection of the prostate (TUR-P)Transurethral resection of the prostate (TUR-P)Transurethral resection of the prostate (TUR-P)Transurethral resection of the prostate (TUR-P)

Drug therapy of prostate cancer

Multiple types of drug therapies are used to treat prostate cancer at different disease stages.  

  • Endocrine therapy
  • Chemotherapy
  • Bisphosphonates and RANK ligand inhibitors
  • Androgen synthesis inhibitors
  • Other drugs

Hormone manipulation

Hormone manipulation is used when tumor spreading has been confirmed, or the tumor has advanced locally and is not a candidate for curative treatment. This type of treatment may extend life, retard tumor growth rate, and reduce the amount of cancer cells in many patients.

Hormone manipulation can also be given along with comprehensive curative radiation therapy to the prostate gland (radical radiation therapy). This is done when there is no detected spreading, and will improve the prognosis for patients receiving radical radiation therapy in high or intermediary risk groups.

Hormone manipulation for advanced disease can increase quality of life and relieve symptoms, however the treatment may also cause side effects and reduce quality of life. In these situations, balance is the goal in terms of choice of treatment regimen and when treatment is initiated. 

The two main hormone manipulation alternatives used are:  

  • Antiandrogens
  • Testosterone deprivation (chemical or surgical castration) 

Antiandrogen therapy 

Antiandrogen therapy is primarily for patients with locally advanced disease without confirmed spreading and who are not candidates for radical surgery or radiation therapy, with spreading to lymph nodes.  In the event of bone or other metastasis, testosterone blocking treatment is standard. Use of antiandrogen therapy for limited spreading to bone is considered for certain patients without ordinary indication.

Treatment with antiandrogens is not castration. Antiandrogens block testosterone chemically to avoid stimulation of prostate cancer cells. Testosterone production is still maintained and the patient avoids to a great extent the side effects of castration.

There are two main relevant side effects requiring action: 

  • Soreness in the breasts and/or enlargement of breasts. This is prevented in most patients by short-term radiation therapy to the breasts at the start of treatment. If the breasts are not irradiated at the start of treatment, it is not possible to reverse enlargement with radiation therapy later. Surgery will then be necessary.  
  • Liver function values must be checked at treatment start and at regular intervals, since liver function is influenced by treatment with these drugs. 

There are essentially two types of antiandrogens used in the treatment of prostate cancer today, either steroid antiandrogens or non-steroidal antiandrogens. The most important non-steroidal antiandrogens are bicalutamid and flutamid.

Bicalutamid is taken once daily. Flutamid is taken 3 times daily, however this drug is rarely used. 

 

Testosterone deprivation treatment

Stop of testosterone production (castration) is done by: 

  • surgical removal of both testicles (immediate stop of testosterone production) 
  • chemical castration by addition of LHRH analogues or LHRH antagonists

The side effects of this treatment are hot flashes, reduced/elevated libido with subsequent erectile dysfunction, fatigue, muscle weakness, joint pain, depression and mood swings. These side effects are due to lack of testosterone. Surgical and chemical castration usually have an equivalent effect on the disease, and largely have the same side effect profiles. The side effects of castration treatment may be different, partially depending on the age of the patient. For younger men, the influence on sexual function may be the most frightening. The majority of patients lose interest for sexual activity over time. After many years of testoterone deprivation, the patient may develop osteoporosis and have an increased risk for diabetes and heart disease.

LHRH therapy

Chemical castration with “Lutinizing Hormone Releasing Hormone” analogues (LHRH) leads to a temporary increase of serum testosterone with a risk of a transient worsening of the disease for 2-3 weeks. The LHRH-treatment should therefore always be combined with antiandrogens the first months. The advantage of LHRH is first and foremost that if discontinued within 1-2 years, the testicles will resume testosterone production (castration treatment is reversible).  So-called “intermittent androgen suppression” may be appropriate for some patients.

LHRH antagonists (degarelix) provide the same reduction in testosterone, but without the transient initial increase. These patients do not need antiandrogens if the disease is extensive at the start of treatment. 

Combination of LHRH-analogues and antiandrogens (total androgen blockade) 

In some cases, antiandrogen and LHRH treatments are combined. However, it is not confirmed whether this treatment improves survival.

Estrogen therapy 

With production of female sex hormones, testosterone production is reduced with a similar effect on the development of prostate cancer as for LHRH analogues or LHRH-antagonists. The relevant drug is polyestradiolphosphate. In addition to the possible beneficial effect, estrogen treatment may to some extent increase the risk thrombo-embolic events and heart disease. Estrogen therapy is currently not widely used for these patients. An advantage of this drug is that it causes few hot flashes.

Chemotherapy

In the event of progression after castration treatment (surgical or chemical), chemotherapy is the standard treatment today for suitable patients. Treatment can often be given to patients in their upper eighties with a function level of 0-2.

In randomized studies, docetaxel has been shown to increase survival in hormone refractory, metastasizing disease. The effect appears to be optimal in a regimen where docetaxel is given once every third week. Risk of osteoporosis with increased risk of infection may however be less with weekly administration in 5 or 6 subsequent weeks. This should be considered if the patient is 75-80 years.

Data became available in 2010 for second line chemotherapy with cabazitaxel giving extended survival after treatment with docetaxel. Cabazitaxel is approved and used in Norway. The risk for osteoporosis with neutropenia with threat of serious infections is greater with this treatment than with docetaxel. The number of suitable patients for this treatment is drastically less than for docetaxel. The general tolerance for this drug is relatively good, and it seems the risk for bothersome paresthesia is less. 

Bisphosphonates and RANK ligand inhibitors

Zoledronic acid and denosumab have documented effects on pain and bone-related symptoms on castration-resistant disease with bone metastases. This treatment is given intravenously or subcutaneously every 4 weeks and is combined with calcium and vitamin D supplements. Survival is not prolonged with this treatment, and there are no data to confirm optimal treatment duration.

Among the side effects are transient reduction of general health (especially after first treatment), fever, skin rash, and osteonecrosis of the jawbone. It is critical that patients are examined by a dentist before starting this treatment, and that extractions or other dental work that may influence the jawbone is avoided after treatment is initiated, unless absolutely necessary. The dentist should then consult with the maxillofacial surgeon. Treatment with zoledronic acid requires regular monitoring of liver function. 

Androgen synthesis inhibitors

Abiraterone is an androgen synthesis inhibitor, which affects the production of cancer cells in the adrenal glands and cancer cells of hormones that resemble testosterone stimulating growth of prostate cancer cells. It has been shown in a randomized study that treatment with this drug extends survival after previous treatment with docetaxel. There are also positive results with treatment of abiraterone given before chemotherapy, but due to crossover it is less certain what the survival gain is in these patients. Side effects are very mild (less side effects were reported in the treated arm than the placebo arm). 

Abiraterone is given with steroids, normally prednisolone 5 mg x 2 due to the risk for suppression of adrenal steroid production. This drug is now approved for use both before and after chemotherapy and for castration-resistant patients with metastases.

Other drugs

There are multiple other drugs showing promising results which are either under approval by drug authorities in the EU and Norway, or are in final research phases. They are not routinely available. Among these are enzalutamide and alpharadin. These drugs have been shown to extend survival in phase III studies. These are available for certain programs/protocols, but they are often time-limited and availability changes erratically.  

Drugs under investigation

There will always be drugs under investigation around the world, also in Norway in periods. It is important to keep in mind that a drug under investigation may have no documented effect and cannot/should not be used without a protocol. There are examples where use of drugs under investigation have produced the opposite effect - shortening survival or quality of life for patients.

PROSEDYRER

Sun Exposure under Drug Therapy

General

Correct information about the possibility of sunbathing may affect patients health and quality of life.

Precautions in connection with sunbathing should be followed under medical cancer treatment and for 2-3 weeks after end of treatment.

Drug cancer treatment includes chemotherapy, antibodies and other drugs used in cancer treatment.

Indication

Sun exposure in connection with drug cancer treatment.

Goal

Prevent sun damage of the skin during and after cancer drug treatment.

Definitions

Photosensitivity

Increased sensitivity to ultraviolet light have been associated with certain drugs used in cancer treatment. Photosensitivity reactions can be expressed in various ways. They can be phototoxic, which is by far the most common, or photoallergic (8,14). Druginduced photosensitivity is mainly caused by wavelengths in the UVA range, but UVB rays may also be involved (8).

Phototoxicity

A phototoxic reaction is reminiscent of a reinforced sunburn, with redness, edema, pain and increased sensitivity in sun-exposed areas of the skin. This is caused by a photochemical reaction of a photosensitive drug and irradiation of sunlight on the skin, which leads to skin cell death. In severe cases, blistering can occur (14). Symptoms may appear immediately or as a delayed inflammatory reaction (3). Higher doses of medication will give an increased risk of skin reaction (14). Healing of skin area will often lead to a hyperpigmentation that can last from weeks to months before they might disappear (8). Although the incidence of drug-induced photosensitivity is unknown, phototoxic reactions is possibly more common than is diagnosed or reported.

Photoallergy

An immunological reaction usually occurring 24-72 hours after sun exposure. The reaction degenerates as an itchy, eczema-like eruptions. In acute cases, one can see rash liquids. The prevalence of eczema is usually limited to sun-exposed skin, but can in severe cases spread to larger areas of the body. Unlike a phototoxic reaction, photoallergy is less dependent on the dose of the causative drug (8).

Photoinstability

Some drugs can be degraded when exposed to light. This can happen both before administration and when the drug is circulating in the body. This degradation can cause redness/rash and edema of the skin. This applies especially for dacarbazine (9). It is unknown whether the effect of the drug is affected and it is therefore recommended that one avoids direct sunlight as long as the drug is active in the body.

PPE ( palmoplantar erythrodysesthesia = Acral erythema )

PPE is also called hand-foot syndrom. The condition starts with altered skin sensation that develops into burning pain, swelling and redness of palm of the hands and soles of the feet. The symptoms can also occur in other parts of the body that is subjected to pressure, for example under tight clothing. In severe cases large blisters and ulceration can develop. The pain can be so severe that daily activities is limited.

PPE is often seen with liposomal doxorubicin (Caelyx®) and high dose cytarabine, but may in principle occur with any anthracyclines, taxanes and fluorouracil (5- FU® ) (9,14) .

Acne-like rash

Pimple-like eruptions in skin areas with a lot of sebaceous glands such as the face, scalp, chest and neck. In contrast to common acne, the liquid-filled blisters does not contain any bacteria (9,10,15).

Hyperpigmentation

Hyperpigmentation is a common side effect in patients receiving chemotherapy, especially alkylating drugs and antibiotics with cytostatic effect. The area that has increased pigmentation may be localized or diffusely distributed. It can occur in the skin, mucous membranes, hair and nails. Pigment changes can be normalized upon discontinuation of the drug, but it may also persist.

Fluorouracil is one of the most common drugs which can provide hyperpigmentation. Others are; metotrexate, busulfan, doxorubicin liposomal, Hydroksyurea®, procarbazine, bleomycin, cyclophosphamide, doxorubicin , ifosfamide, tegafur, mitoxantrone, daunorubicin, fluorouracil, cisplatin, carmustine, thiotepa, docetaxel, vinorelbine, vincristine, imatinib and combination regimens (14).

An increased pigmentation in sun-exposed areas with the use of methotrexate, fluorouracil and capecitabine is described (16,17,18). Beyond that there is little evidence in the literature  that hyperpigmentation aggravates by sun exposure.

Radiation Recall Dermatitis (RRD)/Photo Toxic recall reaction

Flares of an inflammatory skin reaction in an area of ​​previous radiation damaged skin resulting from sunburn or external radiation. RRD can occur from months to years after the initial radiation damage.

Drugs that can provide RRD are; bleomycin, capecitabine, cyclophosphamide, dactinomycin, cytarabine, daunorubicin, docetaxel, doxorubicin liposomal, doxorubicin, etoposide, fluorouracil, gemcitabine, Hydroksyurea® , idarubicin, lomustine, melphalan, methotrexate, paclitaxel, tamoxifen and vinblastine (14). EGFR inhibitors (cetuximab , gefitinib and erlotinib) may also cause other skin reactions that may be exacerbated by sun exposure (9,10,19).

Preparation

The patient is given written and verbal information by the medical responsible doctor and nurse at the start of the drug cancer treatment, and it is repeated as necessary.

Implementation

General Precautions

Prevention and protection:
  • Limit sun exposure during the first days after the cure.
  • Observe skin daily to detect any skin reactions early.
  • Avoid getting sunburned.
  • View extra care between 12.00-15.00 (2).
  • Wear protective clothing and headgear (2,3,4,5,6).
  • Wide-brimmed hats protect better than caps (2.4).
  • Please note that the window glass does not protect against UVA rays (7).
  • Use sunscreen; to protect against UVA and UVB rays, a minimum SPF 15 (3,4,6,8) is applied several times daily.
  • Use mild skin care products without perfumes.

In case of an eruption, sun exposure (including solarium) should be avoided until the skin is healed. Adverse skin reactions can be alleviated with moist and cooling compresses. Mild cortisone salves can also be highly effective. For very severe cases, systemic cortisone might be necessary (3,6,7,9).

When a photosensitive reaction occurs, it is important to consider what other medications the patient is receiving which can also trigger such reactions. For example, steroids, some antibiotics, diuretics and NSAIDs.

Medicaments that most commonly cause skin reactions

Medicament Common reactions Remedial action
Dakarbazin (DTIC)


Phototoxic/photoinstability
See general precautions
Redness in skin, tingling of the scalp and general unwellness
Avoid sunlight completely the day of the treatment (9)
Methotrexate
Phototoxic

See general precautions
Acne-like rash
Avoid direct sun exposure, heat and humidity (9,10). Avoid soap, alcohol based skin products (9). Use moisturizing products and oil bath (4,9,10).
Palmoplantar erythrodysesthesia = Acral erythema (PPE)

Preventive: Pyridoxin (vitamine B6) (2,6,9)

Avoid sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths

(2, 9)

Fluorouracil (5-FU®)

 

Phototoxic See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2,6,9)

Avoid sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths   (2, 9)

Radiation recall
Treatment as with phototoxic

Kapecitabin (Xeloda®)

 

Phototoxic See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE)

Preventive: Pyridoxin (vitamin B6) (2, 6, 9). Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths (2, 9)

Vinblastin

 

Phototoxic
See general precautions
Radiation recall Treatment as with phototoxic
Doxorubicin liposomal (Caelyx®)
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths (2, 9)

Tegafur

 

Phototoxic
See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths    (2, 9)

EGFR-hemmere

(Cetuximab, panitumab, erlotinib, gefitinib, lapatinib, vandetanib)

Phototoxic
See general precautions
Acne-like rash
Avoid direct sun exposure, heat and humidity (9,10). Avoid soap, alcohol based skin products (9). Use moisturizing products and oil bath(4, 9, 10).

Beyond the medications listed in the table the literature gives som evidence that these substances may cause phototoxic skin reactions :

  • paclitaxel (Taxol®)
  • docetaxel (Taxotere®)
  • hydroxycarbamide ( Hydroksyurea® )
  • imatinib ( Glivec® ) and Dapson® and that paclitaxel can provide radiation recall .

References


  1. LOV-1999-07-02-63 Pasientrettighetsloven - pasrl. Lov om pasientrettigheter.
  2. Polovich M, White JM, Kelleher LO. Chemotherapy and biotherapy guidelines: recommendations for practice. Pittsburgh, PA: Oncology Nursing Society; 2005.
  3. González E, González S. Drug photosensitivity, idiopathic photodermatoses,and sunscreens. J Am Acad Dermatol 1996;35:871-85;quiz 886-7.
  4. Liffrig, JR. Phototrauma prevention. Wilderness Environ Med 2001;12:195-200.
  5. Tan E. Skin toxicity of chemotherapy drugs [created 2007, last updated  2010 Mar 5]. Hentet 1. desember 2010 fra: http://dermnetnz.org/reactions/chemotherapy-toxicity.html
  6. Gould JW, Mercurio MG, Elmets CA. Cutaneous photosensitivity diseases induced by exogenous agents. J Am Acad Dermatol 1995;33:551-73.
  7. Payne, AS & Bernandin, RM. Sunburn [topic last updated 2010 Oct 06]. I: BMJ Best Practice. Hentet 23. november 2010 fra http://bestpractice.bmj.com
  8. Zhang AY, Elmets CA. Drug-induced photosensitivity [updated 2010 Jan 15]. Hentet 1. desember 2010 fra: http://emedicine.medscape.com/article/1049648-overview
  9. Ulrich J, Hartmann JT, Dörr W, Ugurel S. Skin toxicity of anti-cancer therapy. J Dtsch Dermatol Ges 2008;6:959-77.
  10. Agero AL, Dusza SW, Benvenuto-Andrade C, Busam KJ, Myskowski P, Halpern AC.Dermatologic side effects associated with the epidermal growth factor receptor inhibitors. J Am Acad Dermatol 2006;55:657-70
  11. Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr Opin Oncol 2002;14:212-6.
  12. Mangili G, Petrone M, Gentile C, De Marzi P, Viganò R, Rabaiotti E. Prevention strategies in palmar-plantar erythrodysesthesia onset: the role of regional cooling. Gynecol Oncol 2008;108:332-5.
  13. Tanyi JL, Smith JA, Ramos L, Parker CL, Munsell MF, Wolf JK. Predisposingrisk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer. Gynecol Oncol 2009;114:219-24.
  14. Payne AS, Savarese DMF. Cutaneous complications of conventional chemotherapy agents. I: UpToDate [version 18.2 2010]. Hentet 1. desember 2010 fra: http://www.uptodate.com
  15. Heidary N, Naik H, Burgin S. Chemotherapeutic agents and the skin: an update. J Am Acad Dermatol 2008;58:545-70.
  16. RELIS Sør. Hyperpigmentering av cytostatika og forverring av sollys. I: RELIS database 2010, Spm.nr 4736. Hentet 1. desember fra: http://relis.arnett.no/Utredning_Ekstern.aspx?Relis=2&S=4736
  17. Hendrix JD Jr, Greer KE. Cutaneous hyperpigmentation caused by systemic drugs. Int J Dermatol 1992;31:458-66.
  18. Schmid-Wendtner MH, Wendtner CM, Volkenandt M, Heinemann V. Clinical picture: leopard-like vitiligo with capecitabine. Lancet 2001;358(9293):1575.
  19. Segaert S, Tabernero J, Chosidow O, Dirschka T, Elsner J, Mancini L, et al. The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. J Dtsch Dermatol Ges 2005;3:599-606.

Preparation of Chemotherapy, Spills, and Cleaning a LAF Bench

General

Preparation of chemotherapy outside of a pharmacy

At Oslo University Hospital, the pharmacy primarily prepares chemotherapy for each patient. If it is necessary to dilute/mix the medicine at the department, then this should occur in a designated room with a LAF bench (laminar airflow bench). Many chemotherapy drugs are carcinogenic and teratogenic, and it is extremely important for health personnel to follow directions for preparation of of these medications. At Oslo University Hospital, all chemotherapy should be prepared and administered by a nurse who has completed a cytostatic treatment course at Oslo University Hospital, or by nurses who are certified cancer nurses from Oslo University College.

Pregnant women and employees under physician orders not to temporarily or permanently work with chemotherapy drugs, should not handle or be exposed to these chemicals. Nursing mothers may handle chemotherapy drugs as long as they follow the general guidelines for chemotherapy handling. For each work place, there should be written guidelines for handling of chemotherapy drugs and for first aid for spills and maintenance of fume hoods etc..

Designated room with LAF-bench to dilute/mix chemotherapy

  • The ventilation should be separate from the main ventilation and fumes should be vented to the outside and if necessary, filtered.
  • The room should be well illuminated for visual control of the fluid.
  • The LAF bench should be a workbench having sterile, filtered air from the ceiling with defined speed and an approved fume hood. The bench should be routinely tested and approved.

Goal

  • To protect nurses and surroundings from exposure to cytotoxic chemicals and to preserve the sterility of the drug.

Handling of chemotherapy spills

Chemotherapy drugs are a heterogeneous group of drugs in which many are known mutagens, teratogens and/or carcinogens. Allergic reactions have also been reported. Studies show that there is a health risk during exposure of chemotherapy drugs and there are guidelines for minimizing exposure of health personnel to these chemicals. Workers in daily contact with these drugs will be more at risk due to the increasing use of chemotherapy. Chemotherapy spills refers to spills during preparation and leakage from infusion bags.

Goal

  • To ensure that spills of chemotherapy drugs or waste materials that contain these chemicals are handled in a safe way to protect health and safety.

Cleaning of LAF-bench

The Norwegian Work Authority recommends that each workplace should have written guidelines for handling chemotherapy drugs, first aid for spills, and maintenance of fume hoods etc. A LAF-bench (laminar airflow bench) is a bench protecting workers from the drug being prepared and also protects from microbiological organisms. Those who carry out cleaning should have training and knowledge of the risk for exposure to chemotherapy drugs.

Goal

  • Maintain a clean LAF bench
  • Avoid contamination and preserve the sterility of the drug 
  • Protect people and surroundings from exposure

Source

Applicable directives and guidelines (www.lovdata.no)

  • Warn against exposure to chemicals at the workplace (Kjemikalieforskriften §24), mandated by The Norwegian Labour Inspection Agency from 5 May 2001, last edition from 26 April 2005.
  • Guidance for chemical directives attachment VII Cytostatica from September 2003 (www.arbeidstilsynet.no).

Equipment

  Preparation of chemotherapy in a hospital

  • 2 pairs of gloves: vinyl gloves inside and sterile, powder-free latex gloves outside
  • Protective coat with long arms/plastic apron
  • Arm protectors
  • LAF bench
  • Dilution fluid
  • Syringes and cannulas
  • Sterile compresses
  • Disposable cloths
  • 70% ethanol
  • Absorbent benchcoat with plastic underside for the work bench
  • If a LAF bench is not used, use a protective mask with aerosol filter and protective goggles.

Handling of chemotherapy spills

Spill kit includes:

  • 2 pairs of nitrile gloves, long
  • 2 pairs of latex gloves, long
  • 2 pairs of shoe covers
  • Plastic coat\apron
  • 1 mask
  • 2 diapers
  • 1 bed absorbent bed sheet
  • 2 plastic bags with zippers (30 x 40 cm)
  • 4 thin, white plastic bags (60 x 90 cm)
  • Absorbant material   
  • 8 disposable wash cloths

Washing of LAF-bench

  • Plastic apron
  • Arm protectors
  • Gloves: either double vinyl gloves or special gloves
  • Disposable cloths
  • 70% ethanol
  • Bucket and soapy water
  • Waste container with plastic bag for chemotherapy waste (biohazardous waste)

 

 

Preparation

Preparation of chemotherapy outside of the pharmacy

For preparation of chemotherapy drugs, use gloves and a protective lab coat with long arms or tight-fitting cuffs.   Use two pairs of gloves where the inner pair is vinyl or other latex-free material. The outer glove should be sterile and of latex or other material which is impenetrable.  The gloves are recommended to be changed every half hour for preparation of chemotherapy drugs, and right away with spills.

  • Start the LAF-bench a minimum of 30 minutes before use.
  • Wash hands
  • Put on the inner gloves
  • Disinfect the work surface with 70% ethanol
  • Cover the work surface with a benchcoat. This should not cover the vent; otherwise, the bench will not function properly.
  • Read the dilution directions and find the necessary equipment and medications as described.
  • Choice of dilution system/fluids
    • A transfer cannula should be used in preference to a syringe where possible to maintain a closed system as much as possible.
    • If a syringe is used: use a syringe with Luer lock connection. These have a better connection between the syringe and the cannula.
  • Check the expiration on the drug packaging and infusion fluid.
  • Check that the drug in liquid form does not contain particles or visible solids.
  • Check that the packaging does not have any cracks or leakages.
  • Perform necessary calculations, date, and sign the work form.
  • Obtain another nurse to double check: right patient, work form, drug, dosage, fluid type and volume, as well as calculations.  All checks should be against the original ordination. The person doing the check should sign and date it.
  • Set out necessary equipment on the LAF-bench or where the work will take place. The equipment should be placed in the corner within the ventilation of the LAF-bench.  Remove the outer packaging of the sterile gloves and lay the gloves on the bench.
  • Put on the protective clothing (coat/apron and arm protectors)
  • Put on the sterile gloves in the bench
  • Disinfect the rubber membrane on the infusion bag and hood windows as well as the ampules.
  • Make sure the protective glass on the LAF-bench is pulled down to the correct work level as recommended by the manufacturer of the bench.

Handling of chemotherapy spills

All, except the workers who clean the spill, should leave the room.  Preferably, two people should help each other to remove the spill.  This way, one can ensure that proper precautions are taken.

At Oslo University Hospital, a packet is available from the pharmacy for chemotherapy spills.

Washing of LAF-bench

  • The LAF-bench should be operating under cleaning.
  • The sash should be down, as under normal working conditions.
  • Use a plastic apron, arm protectors, and gloves.

 

 

Implementation

Preparation of chemotherapy drugs outside of a pharmacy

Aseptic procedure

  •   To avoid turbulence of the sterile, laminar air stream:
    • Work at least 15 cm inside the perforation with steady movements
    • Avoid hands or other objects from coming between the airflow and the medicine.
  • Make only one medicine at a time.
  • A full syringe or finished bag should be labeled for the next preparation.  The label should be labeled with the patients name, birthdate, drug and dosage, preparation date, expiration, and the name of the person who prepared and checked the medicine.
  • Avoid spills and aerosol formation
    • Use a dry, sterile compress around neck of the ampule when it is broken.
    • When the cannula is removed from the syringe, hold a sterile compress around the barrel neck to catch any spills.
    • Hold the syringe/ampule such that the opening is directed away from the face.
    • For solid substances, solvent should be added along the glass wall to avoid whirling of particles.
    • With positive/negative pressure in the hood glass: apply a filter cannula first to reduce pressure.
    • With use of adapter: place adapter first in the infusion bag and connect to the hood glass with medicine.
    • When the air is removed from the syringe, place the cannula cap on the cannula again while the syringe is held vertically with the cannula upright. A sterile compress should be held around the opening between the cannula and the syringe to collect spillage.
    • Clean up spills at once
  • After each addition, the contents of the infusion container should be mixed well by inverting and repeating 5-6 times.
  • Infusion fluid which has been added to should be marked satisfactorily.
  • The finished solution should be scrutinized for solid or foreign particles. All solid should be dissolved.
  • If visible changes occur under the mixing procedure, the physician should be contacted and the fluid should not be used. Store the infusion fluid and packaging of the added drug and contact the pharmacy (chemist) for further clarification.
  • All used equipment should be rolled up in the benchcoat (alternatively, all used equipment can be placed in a plastic bag which can be tied or closed with zipper) and disposed of in box with plastic bag for chemotherapy waste/biohazardous waste.
  • LAF-bench should be stopped at least 30 minutes after use.

Multiple additions

  • Addition of multiple drugs for chemotherapy solutions should be avoided. If it is still appropriate, there should be clear documentation of the mixture.
  • Different chemotherapies can mix if their mixing properties are documented (and checked with pharmacist).

Handling of chemotherapy spills

  • Use two pairs of disposable latex\nitrile gloves, plastic coat, mask, shoe covers (used with floor spills) and protective goggles.
  • Lay the smallest diaper in the middle of the spilled fluid. Then, place the absorbent bed sheet over the diaper and the rest of the fluid. Use more diapers and absorbent material if necessary.
  • Dispose of used diapers, absorbent material, bed sheets, and gloves is appropriate waste container, which can be closed.
  • Use new gloves and wash thereafter with soapy water and disposable wash cloths a minimum of three times. Use a new cloth before each wash. Used cloths should not be put back in the wash solution.  Used cloths and gloves should be disposed in the appropriate waste containers (in plastic bags which can be closed).
  • The plastic bags with used equipment should be disposed of in the appropriate containers which are properly labeled.

Washing of LAF-bench

  • Other than a cannula bucket, nothing should be stored in the bench after the last preparation.
  • Washing with 70% ethanol is sufficient if there are no visible spills.
  • For visible spills, wash the bench with soapy water and spray afterwards with 70% ethanol (see procedure under). Soapy water is the most effective for removing chemotherapy spills.

Routine washing

  • Washing should be done every 1-4 weeks depending on frequency of use.
  • Spills and dust pose risks for washing.
  • It is important that any remaining solution of chemotherapy is not spread under washing.
  • Use disposable cloths.
  • To avoid contamination of washing water, the washing hand should not be dipped in the water.
  • Wash with slow movements and use a new cloth as needed.
  • Cloths that have been in contact with the bench should not be put back in the washing water and should be discarded in proper waste container.
  • Wash first the walls from top to bottom with soapy water (the cleanest to the most contaminated) – place the cloth on a squeegee for hard-to-reach areas.
  • The filter in the ceiling of the bench should not be washed.
  • Wash the work surface in the bench – wash from back to forward (from the cleanest to the most contaminated).
  • Raise the work surface.
  • Wash the work surface on the underside, especially the closest, perforated part.
  • Then wash the underside bottom of the work surface.
  • Wash thereafter all surfaces (not the ceiling) with 70% ethanol.
  • Remove protective clothing.
  • Discard all protective clothing for one-time use and washcloths in the appropriate waste container.
  • Wash hands.
  • Replace the cannula bucket.
  • There should be a record for bench washing; the employee who washes should sign and date the record.

Follow-up

Aerosol formation with spraying or squirting can occur:
  • when a syringe is used and cannula is retracted for transfer
  • when an ampule is broken
  • when air is removed to measure volume
  • with a leak in a syringe or IV catheter
  • with waste handling

First aid if contact with chemotherapy drugs

  • Skin: Rinse well with water for 15 minutes. Wash contacted area with regular soap.
  • Eyes: Rinse well with water, or use spray bottle with NaCl 9 mg/ml (at least 20-30 minutes of continual rinsing).
  • Contact a doctor.

Radiation therapy of prostate cancer

Prostate cancer is not especially sensitive to radiation. It is therefore problematic to obtain an optimal radiation dose due to side effects. Modern radiation therapy has, however, made it possible to drastically increase the radiation dose toward the prostate itself.

Radiation therapy with a curative goal can be given as:

  • Radical conformal external radiation therapy
  • Brachytherapy
  • Brachytherapy combined with conformal external radiation therapy

Radiation therapy can be an appropriate alternative to surgery in localised disease (T ≤ 2). Radiation therapy with a curative aim can also be appropriate, possibly combined with hormone treatment, in T3-disease.

External radiation therapy

External radiation therapy with a curative goal is given over 5-9 weeks, with 5 treatments a week. The treatment can  be given in a true out-patient setting, or with hotel accommodations, depending on travel time and the patients general condition/wishes.

It can also be appropriate to give external radiation therapy after a radical prostatectomy (adjuvant), for local relapse after radical prostatectomy or cryotherapy (salvage), and to reduce pain and tumor size (palliative).

Procedures

  • Primary external radiation therapy
  • Adjuvant external radiation therapy
  • Palliative external radiation therapy

Brachytherapy

For brachytherapy the radiation source is implanted within the target organ/tumor and delivers radiation of  a high dose, but short penetration. This permits a high radiation dose to the tumor and limits radiation damage to neighboring organs.

Brachytherapy in prostate cancer can be given in two ways. Both ways the radiation source is inserted into the gland transperineally, guided by transrectal ultrasound (TRUS).

In the first method, radioactive “seeds” are implanted permanently into the prostate. These radioactive sources provide a low radiation dose over a prolonged period of time (“low dose-rate”). The other method, the so-called “after loading-technique” is used in which the radiation dose is inserted in the prostate by means of hollow needles. The radiation is completed after a few minutes and the radiation source is removed (“high dose-rate”). 

Twenty years ago, at RR HF, a study was completed with “seed” implantation. The hospital now has a treatment option with “after loading” brachytherapy combined with external radiation therapy. This is performed with a curative aim on patients with high risk disease.

Radiation therapy combined with hormone treatment

Hormone treatment is often completed 3-6 months before radiation therapy to reduce the tumor size. A smaller target volume provides less toxicity and a possibility for dose-escalation. Studies also show that hormone treatment before and after radiation therapy increases the cancer cells’ radiation sensitivity and shows improved survival for some groups of patients.

Possible treatment of relapse after radical prostatectomy

For PSA-increase after radical prostatectomy (PSA measured in serum), local relapse or metastasis should be assessed. If no metastases are proven and with unfavorable histology (pT3 or non-free surgical margins) external salvage radiation treatment toward the “prostate bed” may be considered. The treatment is not more mutilating to the patient than primary radiation therapy. It can be discussed whether histological verification of recurrence is necessary, but the effect seems to be stronger when radiation treatment is given at a low PSA-level. It appears also to be a connection between dose and response, but it has not been shown that a total dose above 70 Gy provides additional response. When there is clinical suspicion of local recurrence (palpable at ultrasound or MRI) this should be verified by biopsy.

Local relapse after primary radiation treatment

In patients who have undergone curative radiation therapy, PSA-serum will fall to nadir value during the course of 6 to 12 months. Nadir value should fall < 1 ng/ml. If there is a rise in serum PSA of over 2ng/ml above the lowest PSA level, the disease is perceived as active (PSA-relapse). When cancer can still be proven by biopsy of the local tumor, surgery with curative intent may be concidered. With current techniques one can not repeat radiation therapy with curative intent.

The treatment methods under discussion are:

  • Salvage radical prostatectomy. This can be completed but the side effect rate is clearly higher than after primary radical prostatectomy. The curation rate is unknown.
  • Salvage cryoablation. Can be completed but the side effect rate is clearly higher than for primary cryoablation. The curation rate is unknown.

Curative treatment options in patients with local recurrance after primary radiation therapy are so uncertain, and the side effects are so serious, that treatment should only be performed in a protocol setting.

PROSEDYRER

Brachytherapy for prostate cancer

General

In brachytherapy, the radioactive source is implanted directly into the prostate. This involves a number of advantages compared to external radiation treatment.

Benefits compared to external radiation treatment

  • Problem with positioning of patient and organ movement is eliminated.
  • Allows increased dosing to the target volume and thereby possible increase in curative potential. 
  • Shorter treatment time
  • Saves normal tissue structures (especially rectum and bladder)

Disadvantages of brachytherapy

  • Invasive procedure with the need for anesthesia
  • Over dosing of urethra (the apex-region)
  • Obesity can cause technical problems
  • Increase in risk for complications in diabetes and symptom-causing arteriosclerosis in the pelvis
  • Risk of underdosage outside the prostate gland

To ensure the irradiation of possible microscopic cancer outside the prostate capsule, brachytherapy is always given combined with conformal (organ configured) external radiation therapy.
We destinguish between high-dose (HDR) and low-dose (LDR) brachytherapy.  In HDR, a boost dose is given with iridium 192 before external radiation therapy. The radiation sources are implanted transperineally. In LDR, the seeds are implanted with iridium 131 permanently in the prostate. Theoretically, there is a great difference between these two methods for administration of brachytherapy.  The practical implication of this is uncertain.

It can be appropriate to give hormone treatment in addition to the radiation therapy in patients where:

  • The volume of the prostate is large (< 60 cc)
  • The tumor has grown through the capsule (T3 and/or serum-PSA > 20 ng/ml and/pr Gleason score ≥ 8

Indications

  • T1/T2 pN0, PSA  ≥ 20
  • T1/T2 pN0, Gleason score ≥ 8
  • T2 pN0, 20 < PSA < 70
  • T3 pN0, PSA < 70

Contraindications

  • Obstructive symptoms from the urinary tract
  • IPSS > 12 (significant urine retention)
  • Pathology in urethra (tumor breakthrough, stenosis/strictures)
  • Infiltration to tthe rectum and/or seminal vesicles
  • TUR-P < 6 months or large cavity
  • Large adenoma  in the prostate (lobus tertius)
  • Large volume > 60 cc (many needles, os pubis)
  • A lot of prostate calcification
  • Serum PSA > 50
  • Previous rectal amputation

Goal

  • Curative treatment

 

Preparation

In addition to biopsy, measurement of PSA and possibly lymph node staging, the following is normally done:

  • Skeletal scintigraphy: To map possible metastases to the bone, a bone scan  is performed ahead of  radiation therapy. If the bone scan shows an increase in radioactive uptake, it may be necessary with supplementary x-ray examination, most often of the spine, pelvis, and hips.
  • Pulmonary x-ray

In some instances, MRI investigations and supplementary biopsies may also be necessary.

Neoadjuvant androgen block

For large prostates (>60 cc), hormone treatment before radiation therapy may be  appropriate. The prostate can shrink 40-50% after 3-6 months with LH-RH agonist treatment. Cytoreduction of target volume causes less toxicity and better oportunity for dose escalation.

At Oslo University Hospital, 6 month neoadjuvant therapy is given for:

  • T1/T2 with Gleason ≥ 8
  • T2 with PSA > 20
  • T3

Preparation of patient for HDR-brachytherapy

  • Fast previous night
  • Foley catheter is inserted in the morning of the treatment
  • Pre-medication one hour before scheduled treatment
  • Patients who are taking  long-term pain medication should take it as usual. An additional dose can be given with the rest of the premedication.
  • Enema is only given to patients with constipation to avoid unnecessary bowel  irritation after external radiating of the pelvis.

Implementation

HDR-Brachytherapy

Brachytherapy is performed under general or spinal anesthesia.

Brachytherapy is given as 10 Gy x 2 with two week intervals. Thereafter, conformal external radiation therapy 50 Gy over five weeks 1-2 weeks after brachytherapy. 

  • Patient in supine position with leg supports.
  • The ultrasound probe is placed in the rectum and contrast is introduced.
  • Based on the US examination, a preliminary assessment of the number of needles and their position in the prostate is done.
  • Multiple needles are introduced  parallel to each other transperineally into the prostate.
  • An ultrasound investigation is repeated to calculate radiation dose for each individual needle.
  • The radiation plan is assessed by an oncologist, who makes adjustments with regards to tumor and organs at risk such as bladder and rectum, and finally decides if one obtains an adequate irradiation.
  • The plan is then transferred to the treatment machine. This has in the mean time been connected to the inserted applicators.
  • Treatment is given (5-10 minutes). Pole-formed iridium 192 sources are fed into the applicators with after-loading technique. 
  • The equipment is removed and the patient can return to the bed.
  • Total time for the entire process is  on average 1 hour and 30 minutes.

Follow-up

Acute complications

  • Postoperative fever
  • Urethra/bladder
    • Cystitis symptoms
    • Pollakisuria
    • Incontinence
    • Hematuria
    • Dysuria can be treated with alfa-blocker and anti-inflammatory drugs
  • Rectum:
    • Tenesmus
    • Local soreness
    • Sphincter disturbances

Chronic complications

Related to total dose, radiated volume, fractioning, and patient related factors (diabetes, inflammatory bowel disease, previous pelvic operation)

  • Impotence
    • Up to 50% (30-60%), depending on age
    • It is important to resume sex life early after external radiation therapy before fibrosis worsens the condition
  • Chronic cystitis (4-8%), possibly with hematuria and bladder shrinkage
  • Urethra strictures (3-6%, increased risk by indwelling catheter
  • Chronic proctitis (1-4%)
  • Incontinence (0.5%-1.5%)
  • Osteoradionecrosis

Follow-up

Follow-up after 3, 6, 12, 18, 24, and 26 months. Thereafter, yearly for 5 years.

Additionally the patient should be seen by the referring physician at local hospital when appropriate.

Brachytherapy for prostate cancerBrachytherapy for prostate cancerBrachytherapy for prostate cancerBrachytherapy for prostate cancer
Brachytherapy for prostate cancerBrachytherapy for prostate cancerBrachytherapy for prostate cancer. Brachytherapy for prostate cancer

Primary external radiation therapy for prostate cancer

General

External radiation therapy to the prostate is completed as 4-field conformal (organ configured) radiation therapy.

Conformal radiation therapy distinguishes itself from conventional radiation therapy by delivering a higher dose toward a reduced target volume. This provides a reduced toxicity to the neighboring structures (rectum, bladder, nerves).

It can be appropriate to give hormone treatment in addition to radiation treatment in patients where:

  • Volume of the prostate is great (> 60 cc)
  • The tumor has grown through the capsule (T3) and/or PSA > 20 and/or Gleason score ≥ 8

Goal

  • Curative treatment

Indications

  • T1/T2 pN0, PSA ≤ 20
  • T1/T2 pN0, Gleasonscore ≥ 8
  • T2 pN0, 20 < PSA < 70
  • T3 pN0, PSA < 70

Definitions

Target Volume

 

Target volume definitions from ICRU
(International Commission on Radiation Units and Measurements)

GTV (= Gross Tumor Volume)

Tumor volume

Palpable or visible/demonstrative area of malignant growth.

CTV (= Clinical Target Volume)

Clinical target volume

Tissue volume which contains GTV and/or subclinical microscopic malignant disease.

ITV (= Internal Target Volume)

Target volume

Volume containing CTV and one inner margin taking into account inner movements and revisions of CTV. 

PTV (= Planning Target Volume)

Planning volume

Geometric volume containing ITV and one Setup margin taking into account patient movement, variation in patient positioning, and field modeling.

Preparation

In addition to clarification with biopsy, measurement of PSA and possible gland staging, the following is normally performed:
  • Bone scan: A bone scan is usually done before radiation therapy to map possible metastases to the bone.  If the bone scan shows an increase in radioactive uptake, it can be necessary to supplement with x-ray, most often of the spine, pelvis, and hips.
  • X-ray thorax

In some instances, it be also be necessary with MR investigations and supplementary biopsies.

Neoadjuvant androgen blockade

For large prostates (>60 cc), hormone treatment before radiation therapy can be appropriate. The prostate can shrink 40-50% after 3-6 months with LH-RH agonist. Cytoreduction of target volume provides less toxicity and better possibility for dose escalating.

At Rikshospitalet HF, 6 month neoadjuvant therapy is administered for:

  • T1/T2 with Gleason ≥ 8
  • T2 with PSA > 20
  • T3

Preparation for patients before external radiation therapy

  • Empty rectum one week before CT dosage plan and during entire treatment period.
  • Empty bladder before CT dosage plan and before each treatment.

The CT for dosage planning is taken on the simulator apparatus at the radiation department. It is very important the patient is well medicated for pain and is able to lie still on their back for the required period of time. If appropriate, pre-medication of 1-2 g paracetamol can be administered. For patients already taking opiates, an extra dose may be necessary. The patient lies on a flat examination table with only a thin mattress. The patient obtains a standardized pillow under their knees and a large pillow under their head. This set-up is identical to that used on the treatment apparatus.

Intravenous contrast is used routinely. Patients using anti-diabetics of the metformin-type (“Metformin”, “Glucophage”) should not take these in the last 48 hours before CT dosage planning. 

The planning of the radiation field with marking, estimation of radiation field, necessary adjustments and checks, as well as preparation of documentation from the simulator, usually takes one week under normal routine.

The simulator setting is completed one week after the CT. Again, it is just as important to have the patient well medicated for pain and able to lie still. The simulator setting often takes one hour (canbe two hours in difficult cases). The simulator is an X-ray apparatus with a radiation apparatus set-up and dimension. This provides the possibility of obtaining good control images of the field set up.  This will be used to compare with the shade images of the radiated fields which can be obtained on the treatment apparatus.

After, the simulator transfers the final treatment plan to the radiation machines. This takes two working days under a normal routine.

Start of radiation treatment can then take around 10 days after the dosage plan CT.

Implementation

Currently, 37 radiation doses  are usually  given as one treatment daily, 5 days per week.

The first series includes 25 treatments with a daily dose of 2 Gy toward the prostate and seminal vesicles. If the tumor does not include the seminal vesicles, the remaining 12 treatments are administered toward a smaller radiation field. It should also be considered  whether larger parts of the rectum and bladder should be protected.

  • T1-T3a: 2 Gy x 25 to the prostate and seminal vesicles. Thereafter, boost to the prostate 2 Gy x 12. Total dose is 74 Gy.
  • T3b: 2 Gy x 37 to prostate and seminal vesicles

Target Volume

The adjustment of target volume must take into consideration multiple factors including:

  • Demonstrated macro tumor
  • Assumed microscopic disease
  • Variations in positioning of the patient (systematic and coincidental)
  • Inner movements (systematic and coincidental) of target volume and organs at risk.

Details relating to the practical use of different target volumes and the margins between them are being revised.

Field Limits

Currently, 4 radiation fields are used with 2 cm margins around the prostate and seminal vesicles, except the side field toward the bowel, where the margin is 1-1.5 cm.  The lower limit is 2 cm caudal to the opening of the symphysis.

Weighting

  • 100% to the front
  • 40% to the back
  • 60% from the sides
  • If there is no weighting: 0.5 Gy toward each of the fields

Follow-up

Acute complications

  • Postoperative fever
  • Urethra/bladder
    • Cystitis symptoms
    • Pollakisuria
    • Incontinence
    • Hematuria
    • Dysuria can be treated with alfa-blocker and anti-inflammatory drugs
  • Rectum:
    • Tenesmus
    • Local soreness
    • Sphincter disturbances

Chronic complications

Related to total dose, radiated volume, fractioning, and patient related factors (diabetes, inflammatory bowel disease, previous pelvic operation)

  • Impotence
    • Up to 50% (30-60%), depending on age
    • It is important to resume sex life early after external radiation therapy before fibrosis worsens the condition
  • Chronic cystitis (4-8%), possibly with hematuria and bladder shrinkage
  • Urethra strictures (3-6%, increased risk by indwelling catheter
  • Chronic proctitis (1-4%)
  • Incontinence (0.5%-1.5%)
  • Osteoradionecrosis

Follow-up

Follow-up after 3, 6, 12, 18, 24, and 26 months. Thereafter, yearly for 5 years.

Additionally the patient should be seen by the referring physician at local hospital when appropriate.

External radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy for prostate cancer
External radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy for prostate cancer

Adjuvant external radiation therapy for prostate cancer

General

For patients with infiltration through the capsule (pT3) and microscopic involved margins after prostatectomy, it is additional radiation therapy is given. This is performed as external radiation.

This type of treatment is given to reduce the local relapse frequency, but has no definite effect on survival. Multiple studies are in progress to identify alternative methods of treatment for this patient group. It may also be an alternative for these patients to await the rise of the PSA-level in the serum postoperatively before radiation therapy is started. Preferably, this should be done before the level has increased above 1 ng/ml.

Indications

  • Previous prostatectomy
  • pT3 or involved resection margins
  • Rising serum PSA (< 1 ng/ml) after prostatectomy

Goal

  • Curative the disease

Definitions

Target Volume

 

Target volume definitions from ICRU
(International Commission on Radiation Units and Measurements)

GTV (= Gross Tumor Volume)

Tumor volume

Palpable or visible/demonstrative area of malignant growth.

CTV (= Clinical Target Volume)

Clinical target volume

Tissue volume which contains GTV and/or subclinical microscopic malignant disease.

ITV (= Internal Target Volume)

Target volume

Volume containing CTV and one inner margin taking into account inner movements and revisions of CTV. 

PTV (= Planning Target Volume)

Planning volume

Geometric volume containing ITV and one Setup margin taking into account patient movement, variation in patient positioning, and field modeling.

 

 

Preparation

In addition to clarifying with biopsy, measurement of PSA and possibly node staging, the following is normally performed:
  • Skeletal scintigraphy (bone scan): To map possible metastases to the bone, a bone scan is usually performed before radiation therapy. If the bone scan shows an increase in radioactive uptake, it may be necessary to supplement with x-ray, most often of the spine, pelvis, and hips.
  • X-ray of thorax

In some cases, it may also be necessary to do an MRI examination and supplementary biopsies.

Preparation for the patient

  • Empty the rectum from 1 week before the CT dosage plan and during the entire treatment period.
  • Empty the bladder before the CT dosage plan and before each treatment.

The CT for dosage planning is taken on the simulator apparatus at the radiation department. It is very important the patient is well medicated for pain and is able to lie still on their back for the required period of time. If appropriate, pre-medication of 1-2 g paracetamol can be administered. For patients already taking opiates, an extra dose may be necessary. The patient lies on a flat examination table with only a thin mattress. The patient obtains a standardized pillow under their knees and a large pillow under their head. This set-up is identical to that used on the treatment apparatus.

Intravenous contrast is used routinely. Patients using anti-diabetics of the metformin-type (“Metformin”, “Glucophage”) should not take these in the last 48 hours before CT dosage planning. 

The planning of the radiation field and marking, estimation of radiation field, necessary adjustments and checks, as well as preparation of documentation from the simulator, usually takes one week under normal routine.

The simulator setting is completed one week after the CT. Again, it is just as important to have the patient well medicated for pain and able to lie still. The simulator setting often takes one hour (can be two hours in difficult cases). The simulator is an X-ray apparatus with a set-up and dimension like a radiation apparatus. This provides the possibility of obtaining good control images of the field set up. This will be used to compare with the shade images of the radiated fields which can be obtained on the treatment apparatus.

After, the simulator transfers the final treatment plan to the radiation machines. This takes two working days under a normal routine.

Start of radiation treatment can then take around 10 days after the dosage plan CT.

Implementation

2 Gy x 35 is given, total 70 Gy

Target Volume

The setting of target volume must take into consideration multiple factors including:

  • Visible macro tumor
  • Assumed microscopic disease
  • Variations in positioning of the patient (systematic and coincidental)
  • Inner movements (systematic and coincidental) of target volume and risk organ

The details associated with the practical use of different target volumes and the margins between these are under revision.

Field Limits

Currently, 4 radiation fields are used with 2 cm margins around the prostate and seminal vesicles, except the side field toward the bowel, where the margin is 1-1.5 cm. The lower limit is 2 cm caudal to opening of symphysis.

Weighting

  • 100% to the front
  • 40% to the back
  • 60% from the sides
  • If there is no weighting: 0.5 Gy toward each of the fields

Follow-up

The same as in primary external radiation therapy.

Acute Complications

  • Urethra/bladder
    • Cystitis symptoms
    • Pollakisuria
    • Incontinence
    • Hematuria
    • Dysuria can be treated with alfa-blocker and anti-inflammatory drugs
  • Rectum:
    • Tenesmus
    • Local soreness
    • Sphincter disturbances

Chronic complications

These are related to total dose, radiated volume, fractioning, and patient related factors (diabetes, inflammatory bowel disease, previous pelvic operation).

  • Impotence
    • Up to 50% (30-60%), depending on age
    • I t is important to resume sexual relations early after external radiation therapy before fibrosis worsens status)
  • Chronic cystitis (4-8%), possibly with hematuria and bladder shrinkage
  • Urethra strictures (3-6%, increased risk for internal catheter
  • Chronic proctitis (1-4%)
  • Incontinence (0.5%-1.5%)
  • Osteoradionecrosis
External radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy for prostate cancer
External radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy of prostate cancer

Palliative external radiation therapy for prostate cancer

General

In palliative radiation therapy toward locally advanced hormone resistant prostate cancer or metastases from prostate cancer, external radiation is used. Radiation therapy is performed to reduce pain and decrease the tumor size thereby reducing or removing locoregional problems.

Goal

  • Palliative treatment

Indications

  • Locally advanced hormone resistant tumor (with possible invasion into the bladder and/or bowel)
  • Symptom from skeletal metastases
  • Compression of the spinal cord
  • Other local symptom caused by metastasis 

Definitions

 

Target Volume

 

Target volume definitions from ICRU
(International Commission on Radiation Units and Measurements)

GTV (= Gross Tumor Volume)

Tumor volume

Palpable or visible/demonstrative area of malignant growth.

CTV (= Clinical Target Volume)

Clinical target volume

Tissue volume which contains GTV and/or subclinical microscopic malignant disease.

ITV (= Internal Target Volume)

Target volume

Volume containing CTV and one inner margin taking into account inner movements and revisions of CTV. 

PTV (= Planning Target Volume)

Planning volume

Geometric volume containing ITV and one Setup margin taking into account patient movement, variation in patient positioning, and field modeling.

Preparation

Primary spreading has, in most cases, already occurred in this patient group. Further examinations will therefore depend on the symptoms, and can include the need for X-ray, bone scan, and MRI investigations.

Preparation for the patient

For palliative radiation treatment of the prostate area see: preparation of primary curative radiation therapy.

For other palliative radiation treatment, the preparation will depend on the situation.

Implementation

Locally advanced hormone resistant tumor

Usually, 2 Gy x 25 is given, with one treatment per day for 5 days a week.

Target Volume

Adjustment of target volume in the pelvis must take into consideration multiple factors:

  • Identified macroscopic tumor
  • Assumed microscopic disease
  • Variations in positioning of the patient (systematic and coincidental)
  • Inner movements (systematic and coincidental) of target volume and risk organ

Field Limitations

Currently, 2 radiation fields (from the front and back) with 2 cm margins around the prostate.

Bone metastases

  • For pure pain reducing treatment, standard fractioning 8Gy x 1. This treatment can be repeated once
  • For spinal cord  lesion, danger of fracture, postoperatively, neurological symptoms and base of  the scull: 3 Gy x 10
  • Half-body radiation: In elderly and frail patients with advanced hormone resistant disease and complications from more surrounding and diffuse metastases to half of the body radiation with a high single fraction (upper 6Gy x 1, lower 8Gy x 1) may achieve good pain reduction.

Follow-up

Acute complications

  • Cystitis
  • Ureterititis
  • Diarrhea
  • Dermatitis
  • Nausea

Chronic complications

  • Proctitis
  • Ureteritis
  • Urethra strictures (especially if the patient has inlaid Foley catheter during the treatment period)

Check

Examination by doctor every 14 days during the treatment period, thereafter to see the GP or local hospital.

External radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy for prostate cancer
External radiation therapy for prostate cancerExternal radiation therapy for prostate cancerExternal radiation therapy for prostate cancer

Complication treatment of prostate cancer

Surgery, chemotherapy, and radiation therapy cause side effects to varying degrees.

It may be necessary to provide supportive care in order for the patient to complete and obtain the full effect of planned treatment.

Supportive care can also be provided to reduce side effects and improve the patient's quality of life during and after treatment.

PROSEDYRER

Treatment of Nausea Induced by Chemotherapy

General

The majorities of chemotherapy drugs are emetic to varying degrees and may cause nausea and vomiting. Today, there are efficient antiemetic drugs that can significantly reduce the side effects.

Other factors that can aggravate or prolong the presence of nausea and vomiting are: pain, anxiety, electrolyte disturbances, constipation, dyspepsia, and ulcers.

There is a distinction between acute nausea, which occurs within the first 24 hours, and late nausea, which occurs later than 24 hours after the treatment.

Acute nausea can be effectively treated with 5HT3-antagonists (ondansetron, tropisetron, palonosetron), and possibly combined with steroids. Dopamine antagonists (metoklopramid, metopimazine) also have some effect on acute nausea. If this treatment is not effective, it may be improved with aprepitant.

If standard prophylaxis and treatment of nausea is not satisfactory, other nausea regimens should be tried.

Indication

  • Nausea induced by chemotherapy drugs.

Goal

  • Prevention and treatment of nausea and vomiting.

Definitions

Chemotherapies according to emetic potential

High emetogenicity   

Group 1

Moderate emetogenicity   

 Group 2

Low/minimal emetogenicity

Group 3

All cisplatin-containing regimens (CiFu, GemCis, BEP, TIP, VIP, PV, AP, EDP, DHAP, ECX, weekly dose cisplatin, and others) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosfamide, vincristine, prokarbazine, prednisolone)
Doxorubicin/epirubicine weekly dose
Doxorubicin/ifosfamide Bendamustine
Docetaxel
FEC-60 og FEC-100
(fluorouracil, epirubicin, cyklophosfamide)
Carboplatin
ENAP (etoposide, mitoxsantrone, cytarabine, prednisolone)
ABVD (doxorubicin, bleomycin, vinblastine, dakarbazine Carboplatin/pemetrexed
FLv (fluorouracil)
FOLFIRINOX
Carboplatin/vinorelbine
FuMi (fluorouracil, mitomycin)

CHOP (cyclophosfamide, doxorubicin, vincristine, prednisolone)
Gemcitabine

CHOEP (cyclophosfamide, doxorubicin, vincristine, etoposide, prednisolone)
Methotrexate weekly dose
   Dakarbazine
Navelbine
      ECO/ACO (epirubicin/doxorubicin, cyclophosfamide, vincristine)
Paclitaxel
       EOX (epirubicin, oxaliplatin, capecitabine)
Pemetrexed
      EPOCH-F (etoposide, prednisolone, vincristine, cyclofosfamide, doxorubicin, fludarabine)

    EPOCH-F (etoposide, prednisolone, vincristine, cyclophosfamide, doxorubicin, fludarabine)
 
    FLIRI (fluorouracil, irinotecan)
 
    FLOX (fluorouracil, oxaliplatin)    
   Gemcitabine/carboplatin      
   HD-Cytarabine
   
    HD-Methotrexate    
  IGEV (ifosfamide, gemcitabine, vinorelbine)
  
   IME (ifosfamide, methotreksate, etoposide)  
   Irinotecan  
   Streptozocin  
   Vorphase (cyclophosfamide)
 

References

  1. Lehne G, Melien Ø, Bjordal K, Aas N, Mella O. Kvalme og oppkast ved cytostatikabehandling i: Dahl O, Christoffersen T, Kvaløy S, Baksaas. Cytostatic Medication cancer treatment. 7. edition. Oslo. Department of Pharmacotherapeutics and The Norwegian Cancer Society, 2009, p 119-130.

Preparation

Nausea regimens are selected according to the emetogenicity of the relevant drugs.

  • Inform about the risk for and treatment of nausea. 
  • In the event of anxiety or conditional nausea, give tranquilizers if necessary.

Implementation

  • Start with an optimal antiemetic regimen starting with the first cycle of chemotherapy in order to counteract the amplification of the nausea that often occurs with a new treatment.
  • Start the oral antiemetic regimen 1-2 hours before chemotherapy and approx. 15-30 minutes before an intravenous injection.
  • If the patient is already nauseous, the medication should be administered parenterally or rectally.

Antiemetic regimens

Mildly emetic chemotherapy

  • Metoclopramide 10 mg is given intravenously before treatment with cytostatic agents.
  • Metoclopramide 10 mg is given orally uptil 3 times.

Moderately emetic chemotherapy

Ondansetron 8 mg orally 2 x daily. In the event of nausea before treatment, give ondansetron intravenously. If this has little effect, try ondansetron 8 mg x 3 or change to a 5HT3-antagonist, for example, tropisetron 5 mg orally/intravenously or palonosetron 250 µg intravenously.

Highly emetic chemotherapy, or if other treatment does not help

For highly emetic chemotherapy drugs, or if other treatment is not adequate, a 5HT3-antagonist can be given orally or intravenously. It should be combined with dexamethasone 8-16 mg intravenously ½-1 hour before treatment, and further, 8 mg x 2 intravenously or orally on the first day.

In addition, dopamine antagonists may be given, for example, metoclopramide 10 mg x 3.

In some cases, traditional nausea treatment is not sufficient. In this case, the patient can be treated with aprepitant. Aprepitant is used for highly emetic regimens and for patients where the usual antiemetic treatment has failed during moderate emetogenic treatment. Aprepitant is given orally 1 hour before chemotherapy and is combined with dexamethasone and 5HT3-antagonists:  125 mg capsules orally on day 1, then 80 mg orally on days 2-5, depending on the duration of the treatment. Aprepitant can enhance the effect of taxane and etoposide, as well as vinorelbine, and can reduce the effect of warfarin.

The regimen is repeated daily if highly emetic treatment is given over a number of days.

Delayed nausea

Aprepitant in combination with dexamethasone and 5HT3-antagonists is preferable if there is a high risk of delayed nausea and vomiting. This is offered especially to patients who have previously experienced delayed nausea.

Conditional nausea

In the event of conditional nausea, diazepam or other tranquilizers may be considered. Diversion or desensitization can be tried in more serious cases.

Follow-up

Ondansetron can have a constipating effect. Use of a laxative for several days should be considered.

Febrile Neutropenia

General

Febrile neutropenia occurs in compromised immune systems due to a low number of leukocytes, especially granulocytes. Patients with a declining number of granulocytes after chemotherapy, can during bacterial sepsis, quickly develop extensive neutropenia and become critically ill. Febrile neutropenia can be a life-threatening condition.

A patient with neutropenia and simultaneous fever or clinical suspicion of systemic infection should be treated as quickly as possible with broad spectrum antibiotics including gram-negative and gram-positive coverage as soon as the required microbiological samples are taken.

The clinical situation is most critical in patients who have not yet started antibiotic treatment. When broad-spectrum antibiotic treatment is started, monitoring the fever may be permitted.

Fever is often the only symptom. Some have septicemia without fever. One should therefore also be aware of other symptoms such as lethargia, diarrhea, or visible sign of infection. The local clinical symptoms and signs (redness, pain, temperature increase, swelling (boil), and reduced organ function) are most often very much reduced or completely absent during neutropenia.

Indications

  • A patient with neutropenia and simultaneously fever or clinical suspicion of systemic infection

Goals

  • Avoid septicemia.
  • The patient is able follow the planned scheme of treatment.

Definitions

Fever is defined as:

  • a single (rectal) temperature ≥ 38.5 °C or
  • temperature ≥ 38 °C for more than 2 hours or
  • temperature ≥ 38 °C measured three times during 24 hours

There is a known increase of infections when neutrophil < 1.0 x 109/l.  The infection risk increases with degree and duration of neutropenia. The neutropenia is considered severe when granulocytes are ≤ 0.5 x 109/l.

Preparation

The following diagnostic tests should be performed:

  • Adequate microbiologic tests: blood culture x 2-3, throat/nasopharynx, urine, catheter opening any surgical incisions. All blood cultures should be taken simultaneously to avoid losing valuable time.
  • Blood culture and other microbiological samples should be taken before antibiotic treatment is started
  • Blood tests with differential count of leukocytes, thrombocytes, Hb, CRP, SR, creatinine
  • X-ray of chest

Information

Before initiation of chemotherapy, the patient should be extensively informed, both verbally and in writing, of febrile neutropenia and  its consequences.

A patient who can develop febrile neutropenia should obtain a written statement of the condition to present to other treatment providers.

Use of an isolated or private room

Patients with neutrophil granulocytes ≤ 0.3 x 109/l should have a private room if possible. Guidelines for protective isolation should be followed. Thorough washing of hands is especially important.

 

Implementation

  • Treatment is started as soon as possible.  Treatment may be postponed a maximum of 30 minutes to complete microbiological testing.
  • Start septicemia treatment for fever if neutropenia is expected, regardless of granulocyte value.

Antibiotic regimen

  • Benzylpenicillin sodium 5 mg IE x 4 tobramycin or gentamicin 5-10 mg/kg x1
  • Tazocin® 4 g x 3
  • Cefotaxime® 1 g x 4 if aminoglycoside should be avoided
  • Ceftazidim® 1 g x 4  with suspicion of pseudomonas infection
  • Meronem ® 0.5 g x 4 usually 2nd or 3rd choice

When using aminoglycoside, the first dose should be high. Keep in mind the following:

  • age
  • sex
  • kidney function
  • fat index   

Otherwise, the dose should be decided from concentration of aminoglycoside determined after the second day and thereafter monitored 2x per week. 

Serum concentration of tobramycin and gentamycin

For single dose in 24 hours

  • Trough concentration (0-test = 24 hour test) < 0.5 mg/l
  • Top concentration (30 minute after infusion is completed) > 12 mg/l

For multiple doses in 24 hours

  • Trough concentration < 2 mg/l, top concentration (30 minutes after the infusion is completed) preferably > 8-10 mg/l 
  • Avoid aminoglycoside :
    • If kidney function is reduced. Avoid aminoglycoside if cisplatin is used. If cisplatin has been previously used, many patients will have subclinically reduced kidney function. If necessary, use aminoglycoside for a short period and monitor kidney function closely.
    • If carboplatin is used, determine glomerulus filtration rate (GFR) for each new treatment. Penicillin/aminoglycoside can be used if GFR is stable (has not declined more than 15% if initial value is in the normal range)
    • With sarcoma: Protocols with very high doses methotrexate and ifosfamid (> 5 g/m2) should be used in sarcoma treatment. It is not abnormal for these patients to have an increase in creatinine.
    • with massive ascites
    • with suspicion of or documented myeloma kidney (myelomatosis)
    • If aminoglycoside has been used in the past two weeks
  • Suspicion of staphylococcus aureus as a cause of infection (relatively rare)
    • Give penicillinase-stable penicillin, cloxacillin, or dicloxacillin, possibly clindamycin instead of ordinary penicillin. Yellow staphylococci are also killed by cefotaxime and by merop
  • Gram-positive cocci in multiple blood cultures and if the patient has clinical signs of infection
    • Use vancomycin 500 mg x 4 until resistance determination is available
  • Poor patient condition and suspicion of gram-negative septicaemia
    • Use “double gram-negative” with for example ceftazidim or tobramycin
    • Other preparations with good effects against most gram-negative bacteria are meropenem and ciprofloxacin
  • Suspicion of anaerobic infection
    • Use an anaerobic drug: Metronidazol 500 mg x 3, clindamycin 600 mg x 4, piperacillin/tazobactam 2g x 4 or meronem 500 mg x 4.  This especially applies if there is suspicion of anaerobic infection under the diaphragm such as gallbladder, intestines, perforation, abscess.
    • penicillin is often adequate for anaerobic infections above the diaphragm.

With continuing clinical signs of infection, adjust the antibiotic treatment according to resistance determination in blood culture. Maintain gram-negative coverage.

Systemic fungal treatment

By persistent fever after multiple days with broad spectrum antibiotic treatment, one should consider empirical treatment of possible candida-sepsis, for example with fluconazole 600 mg the first 24 hours, and thereafter 400 mg x 1.

If candida is documented without adequate response to fluconazole, a fungicide drug should be used, for example amphotericin B.

If suspected infection with Aspergillus apply voriconazole, amphotericin B or caspofungin.

Follow-up

Observe for symptoms of a new infection.

Bone Marrow Stimulation with G-CSF

General

Bone marrow stimulation with G-CSF (Neupogen®, Granocyte®) is only recommended for febrile neutropenia which does not respond to antibiotic treatment, severe neutropenia (granulocytes < 0.5 x 109 /L for more than 1 week), and in cases where it is necessary to administer curative treatment with sufficient dosage intensity.

Indications 

  • To maintain dosage intensity for curative treatment; when a reduction in dosage will significantly reduce the chance of cure.
  • As prophylaxis for treatments associated with a high risk for febrile neutropenia (> 40 %)
  • Febrile neutropenia that does not respond quickly to antibiotic treatment
  • Long-lasting neutropenia

Goal

  • Maintain treatment intensity

Preparation

The patient should be adequately informed about the treatment.

Implementation

  • The dosage of Neupogen® is 5 µg/kg daily. The treatment is initiated, at the earliest, 48 hours after the treatment is completed. The treatment continues for 10 days.
  • The dosage of Neulasta® is 6 mg subcutaneously administered 24 hours after chemotherapy is completed. The neutrophil cells are counted on day 15.
  • The subsequent course is started on day 21, if the neutrophil count is 0.5 or higher, and the patient has not had febrile neutropenia.
  • It is important not to postpone the treatment if the neutrophil count is 0.5 or higher. The neutrophil count will compulsory decline after ending Neupogen® stimulation. Low values at the start of treatment should not be alarming if the values during hospitalization have been high enough to avoid febrile neutropenia.
  • Stimulation late in the cycle should only be performed for long-lasting, severe neutropenia. At least 48 hours should pass after completed stimulation treatment before the next chemotherapy course  is started. In these cases, it is always important to check that the doses are correct and to recalculate GFR etc. Continuation of chemotherapy will either require a drastic dosage reduction or secondary prophylaxis with G-CSF.

 

Follow-up Care

It is of utmost importance that the patient is informed of the risk of infections associated with a low neutrophil count.

Patients at risk for developing  very low values, must be  informed to take their temperature if they feel unwell or  febrile. In case of  a temperature above 38 °C they should contact their doctor immediately.

Smoking cessation in connection with cancer treatment

General

In patients treated with surgery, radiation and/or chemotherapy, the treatment efficacy may be affected by smoking. Smoking has an impact on both metabolism and pharmacokinetics.

Smoking may inhibit wound healing after surgery and increase the probability of surgical site infections. Because smokers generally have more mucus in the airways and are less able to remove it, they also may have a increased risk of serious lung complications during anesthesia. However, it is disputed whether or not it is beneficial to quit smoking directly prior to surgery and this should be considered in each case individually. (28,30-33). Smokers are more prone to stagnation of bronchial secretion than non-smokers and rapid postoperative extubation is important. 

Patients who continue smoking during radiation therapy have a lower risk of complete respons, development of secondary cancer, increased toxicity and several other side effects compared to non-smokers and smokers that quit before treatment. Continued smoking during radiation therapy is also associated with oral mucositis, impaired ability to taste, dry mouth, reduced voice quality, weight loss, cachexia, fatigue, pneumonia, bone-and soft tissue necrosis.

Tobacco may have an effect the metabolism and the mechanisms of chemotherapy and in this way may make the treatment less effective. Smokers undergoing chemotherapy may also experience a weakened immune system, increased rates of infection, exacerbation of common side effects, weight loss, cachexia, fatigue and cardiac or pulmonary toxicity. Some findings suggest that it may also apply to monoclonal antibodies.

Cancer patients who quit smoking before chemo- and radiation therapy get a total symptom burden equal to that of non-smokers, but those who continue to smoke state a higher symptom burden. Targeted measures in smoking cessation may increase quality of life and lead to less treatment interruptions.

A lot of patients wonder if there is any point to quit smoking after receiving a cancer diagnosis. tudies show that continued smoking is associated with increased treatment-related toxicity, increased risk of second primary cancers, reduced quality of life, reduced treatment effect and reduced survival in patients with cancer. This applies to both cancer diagnoses where smoking is a known causal factor, as with lung- and head and neck cancers and in cases where smoking has no known correlation with the diagnosis. Studies conducted on smoking and cancer diagnoses such as breast cancer, prostate cancer, colorectal cancer, esophageal cancer, cervical and ovarian cancer as well as leukemia and lymphoma cancers show that to continuation of smoking after a proven cancer diagnosis is associated with increased risk of mortality.

Studies support that quitting smoking improves cancer, and emphasizing the potential importance of targeted smoking cessation in cancerpatients during and after treatment. The link between tobacco and impact on cancer and cancer treatment is a complex matter.

Regarding the significance of the various components much is still unkown. When it comes to tobacco use in cancer treatment research is primarily done on the link between cigarette smoking and efficacy of cancer treatment. Nevertheless, it cannot be excluded that using other smokeless tobacco products such as snuff and chewing tobacco, may also impact the cancer treatment. According to international guidelines all tobacco use should be stopped during cancer treatment.


Benefits of smoking cessation and risks of continued smoking in patients with cancer
Quitting smoking results in the following benefits: Continued smoking results in a risk of :
  • improved treatment results.
  • less side effects
  • fewer infections
  • improved respiration and circulation
  • increased survival
  • reduced efficacy of treatment.
  • postoperative complications and longer recovery.
  • cardiovascular and respiratory complications.
  • recurrence of cancer, and secondary cancer.
  • shortened life expectancy.

 

Indication

Weaning of nicotine in connection to cancer treatment. 

Goal

Healthcare providers should convey evidence-based information to patients about how smoking affects cancer treatment, the risk of side effects and prognosis and also provide guidance and relevant treatment for smoking cessation.

Preparation

Patients require clear, formalized and fact-based guidance and continuous follow-up. Many patients want encouragement for smoking cessation early in the disease. Being hospitalized is a good opportunity because patients have access to support and help to reduce nicotine withdrawal symptoms and discomfort.

A patient recently diagnosed with cancer is often motivated to quit smoking and also receptive to conversations about how to do this. Motivation or willingness to quit often changes during the treatment, and use of tobacco and motivation should therefore be discussed at every consultation.

Clarifying the patient´s smoking habit is important. The time of day the patient lights their first cigarette says something about the degree of addiction. Making the patient aware of the situations in which he or she smokes most; at work, at home or in social settings, can help break unwanted patterns of behavior.

Implementation

The best and most direct approach to motivate the patient is telling that tobacco use will decrease the effectiveness of treatment and the most important thing the patient can do himself is to stop using tobacco.

  • Speak directly to the patient about how tobacco use may decrease the effectiveness of treatment.
  • Discuss smoking cessation with the patient at each visit.
  • Clarify any misunderstandings about the risks of tobacco use. Point out the importance of quitting.

Sometimes there may be misunderstandings about what kind of health risk smoking during and after cancer treatment may entail.

Advice to those who are not ready for smoking cessation
The smokers statement The response of health care professionals
Justifications
The damage from smoking is already done.
Some damage is done, but continued smoking will still damage your health and reduce the effects of treatment. Quitting smoking is more important now than ever.
This response tells the patient that it is not too late to quit smoking, and the effect of treatment will be positive.

I have reduced smoking.
That is great, and now you need to focus on quitting completely. What do you think keeps you from quitting altogether?
This response tells the patient the importance of quitting completely, as the benefits of quitting at baseline are documented.
This is not a good time to quit smoking.
The benefits of quitting are greatest now, before treatment begins. What is needed to make you feel ready to quit smoking?
 
This response make the patient aware of the fact that quitting smoking optimizes the cancer treatment.

Health professionals must assist the patient identifying realistic expectations and goals for smoking cessation. For some, it may feel easier to scale down the number of cigarettes than to quit completely. The patient should know that every puff affects their health, and that the total health benefits can only be achieved through smoking cessation. For patients unable to stop completely, a gradual reduction may be a step in the right direction.

The probability of success for smoking cessation significantly increases for those who receive professional help in combination with nicotine replacement therapy (NRT) or non-nicotine based products. For the best possible effect of NRT the patient needs professional guidance to find the right product and dosage. For some patients combining two products or receiving a higher dosage than recommended will give the best effect. Sometimes the product must be replaced during the treatment.

Treatment with nicotine replacement therapy

Topical products are patches (Nicorette®, Nicotinell®), chewing gum (Nicorette®, Nicotinell®), lozenges (Nicorette®, Nicotinell®), inhalator (Nicorette®) or a combination of these. These products contain nicotine and therefore reduce the withdrawal symptoms experienced after smoking cessation.

  • Patch: Nicorette® 5 mg,10 mg and 15 mg/16 hours up to 6 months or Nicotinell® 7 mg,14 mg og 21 mg/24 hours up to 3 months.
  • Chewing gum: Nicorette®/Nicotinell® 2 mg and 4 mg, 8-12 pcs/day up to 12 months.
  • Lozenges: Nicorette® 2 mg and 4 mg, typically 8-12 pcs/day, maximum respectively 15 pcs/day up to 9 months or Nicotinell® 1 mg and 2 mg, typically 8-12 pcs/day, maximum is respectively
    25 and 15 pcs/day up to 12 months.
  • Inhalator: Nicorette® 10 mg/dosage container, 4-12 pcs/day up to 6 months.

Combination therapy means combining patches with chewing gum, lozenges or an inhalator.

  • Nicorette® patch15 mg/16h and Nicorette chewing gum 2 mg. 5-6 chewing gums daily. Maximum 24 pcs/day
  • Nicorette® patch 15 mg/16h and Nicorette® inhalator 10 mg: 4-5 dosage-container daily. Maximum 8 pcs/day

Nicotine replacement therapy increases the chance of smoking cessation by 50 to 70% after six months. Two products used in combination increase the chance of smoking cessation compared to the use of only one product.

Side effects

  • Headache, dizziness, nausea, flatulence and hiccup.
  • Irritation in the mouth and esophagus using chewing gum/ lozenges/inhalator
  • Skin irritations while using patches.

Precautions

  • Precaution in acute cardiovascular disease, peripheral arterial disease, cerebrovascular disease, hyperthyroidism, diabetes mellitus, kidney- and liver failure and peptic ulcers.
  • Should not be used during pregnancy, unless the potential benefit outweighs the potential risk.
  • The products should not be used during breastfeeding.

Treatment with non-nicotine medications

Bupropion (Zyban®) is a selective reuptake inhibitor of dopamine and norepinephrine. The mechanism behind why the ability to refrain from smoking increases by using bupropin is unknown. A should be set for smoking cessation for the second week of treatment.

Bupropion increases the chance of smoking cessation after 6 months by nearly 70%.

Side effects

  • Dry mouth, nausea, insomnia, hypersensitivity reactions and seizures (convulsions)

Precautions

  • Contraindicated in people with disease that can cause convulsions,  people with substance abuse or other circumstances lowering the seizure threshold.
  • Depression, which in rare cases includes suicidal thoughts and – behavior including  suicide attempt.
  • Safety and efficacy have not been established for people under 18 years.
  • Should not be used during pregnancy.

Varenicline (Champix®) is a partial agonist by a subtype of nicotinic receptors. It has both agonistic activity with lower intrinsic efficacy than nicotine and antagonistic activity in the presence of nicotine.

A date for smoking cessation should be set. Treatment should start 1-2 weeks, or up to 35 days, before that date. The starting dose is 0,5 mg one time daily on days 1-3, then 0,5 mg two times daily on days 4-7, then 1 mg two times daily on day 8 and until the end of treatment. The treatment should last for 12 weeks.

Side effects

  • Nausea, sleep disturbances, headache, constipation, flatulence and vomiting

Precations

  • Links have been reported between the use of varenicline and an increased risk of cardiovascular events, suicidal thoughts, depression and aggressive and erratic behavior
  • Safety and efficacy have not been established for people under 18 years of age
  • Should not be used during pregnancy

Follow-up

If the patient experiences a relapse, it is important to inform them that this is completely normal, and encourage them to continue. If the most common measures do not work,
consideration should be given both to increase the NRP and to provide closer follow-up by health care providers.

Guidance in smoking cessation is described in the literature as brief and clear advice and then further follow-up with a telephone helpline offering treatment for addiction and behavior change/issues. It is not necessary for the patient to have decided to quit smoking in order to be referred to a quitline. If the patient agrees to receive a call from quitline, he or she will be followed up by a supervisor. Supervisors are bound by confidentiality, are up-to-date professionally and offer free follow-up counseling calls for up to a year.

References

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Tversnitt_forflytning

Nutrition during Cancer Treatment

General

Monitoring the patient's nutritional status is an important part of cancer treatment. The goal is to identify malnutrition as early as possible in order to initiate treatment as quickly as possible.

Measures include diet according to symptoms and the nutritional condition. The patient should be offered nutrition-rich food, snacks, nutritional drinks, tube feeding and intravenous nutrition.

Because cancer treatment breaks down both cancer cells and normal cells, the body requires an adequate supply of nourishment to increase growth of new cells. 

In cancer patients, the sensation of hunger is not always present to the necessary degree. In these cases, it is important to take actions to improve the nutritional status of the patient. The nutritional condition is easiest followed by monitoring body weight over time.

Indication

  • Cancer treatment (chemotherapy, radiation, surgery).

Goal

  • Maintain nutritional status in order for the patient to have the best possible conditions for implementing treatment.

Definitions

Subjective Global Assessment (SGA)

Subjective Global Assessment (SGA) is a scheme for classifying the patient's nutritional status.

Other tables that are frequently used are Malnutrition Universal Screening Tool (MUST), Mini Nutritional Assessment (MNA) and Nutrition Risk Score (NRS). In principle, these schemes are prepared in the same way as SGA, but they are not validated for patients with cancer.

Weight loss is one of the most important signs of change in nutritional status. A weight loss of more than 15% over the past 6 months or more than 5% over the last month is a significant and serious weight loss. If the weight loss occurs in combination with low BMI (body mass index) (< 20 kg/m2 for adults) and/or a food intake of less than 60% of the calculated requirement over the past 10 days, the patient will be malnourished or be at nutritional risk.

Calculation of nutrition and fluid requirements

  • Ambulatory patients:  30-35 kcal/kg/day
  • Bed-ridden patients:  25-30 kcal/kg/day
  • Elderly above 70 years:  Recommended amount is reduced by 10%
  • Fluid requirement:  30-35 ml/kg/day

Nutritionally enriched diet / enrichment of food and beverages

Nutritional beverages may be used as a meal in itself or between meals. Nutritional drinks can be a more valuable snack than "normal" food, because it is often easier for the patient to drink than to eat. It has been shown that if nutritional drinks are introduced as snacks, it does not affect the energy intake during the main meals.

There are a number of ready-made nutritional drinks on the market. Some of the products are of nutritionally complete. They contain carbohydrates, protein and fat and are supplemented with all the necessary vitamins, minerals and trace minerals and possibly fiber. Some of these products can be used as the sole source of nutrition. The energy content varies from 85-200 kcal/100 ml and some products have a high protein content. Other nutritional drinks are supplement drinks adjusted to individual needs such as allergies, intolerance and special conditions associated with illnesses.

The products are also adapted to age, and the dose is determined individually by a clinical dietician/doctor.

Many patients prefer homemade nutritional drinks based on full fat milk, cream, ice cream, fruit and possibly flavor supplements. These are free of additives and have a fresher taste. The energy and protein content is close to the commercial products and at the same time they are more sensibly priced.

Tube feeding

Tube feeding is preferable to total parenteral nutrition (TPN) when the digestive system is working. Nutrition supply to the intestine is more physiological. It protects against bacterial growth, maintains the intestine's mucous membrane structure and function, and promotes motility. Tube feeding involves less risk of metabolic complications.

Tube feeding is used in the event of

  • insufficient food intake (less than 60% of energy requirements) over the past 5-7 days despite oral intake
  • weight loss >2 % over the past week, >5 % over the past month or >10% over the past 6 months
  • danger of weight loss due to planned treatment
  • low albumin values (under 35 g/l, lower limit for normal area)
  • stenosis with feeding obstacles in pharynx/gullet

Tube feeding must not be used for the following conditions.

  • Paralysis or ileus of the alimentary tract
  • Short bowel syndrome
  • Serious diarrhea
  • Serious acute pancreatitis
  • Obstruction of the intestine
  • Serious fluid problems

Tube feeding solutions

The tube feeding solution must be nutritionally complete because they shall be used as the sole source of nourishment. The most frequently used are standard (1 kcal/ml), fiber-containing (1 kcal/ml) or energy-rich (1.5 kcal/ml). There are also tube feeding solutions which are adapted to patients with digestion and absorption problems, patients with diabetes or lactose allergy, and intensive care patients.

Tube feeding solutions, which are adapted to cancer patients are energy-rich (1.5 kcal/ml). They contain extra omega-3 fatty acids, rich in MCT acid and enriched with extra vitamins and minerals. Recommended dosage is 500 ml/day.

Parenteral nutrition

Parenteral nutrition should only be used if food by mouth or tube feeding cannot be maintained. Parenteral nutrition can also be used as a supplement to tube feeding or ordinary food. 

Precautions must be taken for kidney failure, heart failure, lung failure, large fluid and electrolyte loss, diabetes mellitus and liver failure.

Preparation

The patient is classified as well-nourished, somewhat malnourished or seriously malnourished on the basis of information about weight development, food intake, symptoms and physical functioning. This classification has been shown to correlate well with more objective measurements of nutritional status and morbidity, mortality and quality of life.

Actions include individual adjustment of diet according to symptoms and nutritional status.

Tube feeding

The end of the tube is often inserted into the stomach. In the event of poor gastric function, total gastrectomy or pancreatic resection, the feeding tube should be inserted in the duodenum or jejunum. The position of the feeding tube is vital for the choice of feeding-tube solution and mode of administration.

The most common solution is to insert the tube nasogastrically, but it can also be done through the abdominal wall (PEG).

Parenteral nutrition

It is preferable to use intravenous or parenteral nutrition as a supplement to oral/tube feeding instead of only TPN (total parenteral nutrition).

  • Central veins must be used for TPN with high osmolality.
  • Peripheral veins can be used for short-term parenteral nutrition. In this case, a large vein on the forearm is used and a small needle. Nutrition is then given as more diluted solutions.

Implementation

All patients are weighed regularly (1–2 times each week). This is a prerequisite to being able to register changes in the nutritional status.

Varied and healthy food contributes to the growth of new cells and enhances the immune system.

  • Fruit, berries and vegetables are rich in vitamins, minerals, antioxidants and fiber, which contribute to enhances the immune system and contributes to keeping the digestive system working.
  • Fish, shellfish, poultry, meat, eggs, cheese, milk, beans and nuts are rich in proteins, which are the building blocks of new cells.
  • Bread, rice, pasta, porridge and breakfast cereals supplement the diet with proteins, carbohydrates, fiber, vitamins and minerals.
  • Oil, margarine, butter, mayonnaise products, nuts, cream, heavy cream, desserts etc. are fat and energy rich products, which are important to maintain the energy intake at a satisfactory level.
  • Cancer patients also have a requirement for plenty of fluid, especially during treatment, to discharge waste.

Often, the patients must have an individually adjusted diet. In the event of lack of appetite, it is generally more important that you eat (enough food) than what you eat (the right food). It is beneficial to have small portions and for the food to be as abundant in energy as possible. These patients will often have a need for 6–8 small meals everyday to obtain their energy requirements.

Enrichment of food and drink is done in order to increase the energy content of the food product without increasing the volume. Full-fat products such as full-fat milk, cream, butter, heavy cream, mayonnaise, sugar, honey, eggs and cheese etc. are primarily used. Enrichment powders from pharmacies may also be used. Some powders are nutritionally complete, i.e. they contain everything the body requires in terms of energy and nutrients, while others only contain pure energy (carbohydrates, fat and/or protein). 

Tube feeding

Tube feeding is given continuously with a low drop rate or by interval/bolus administration (individually adapted meals with high drop rate).

When the patient's energy and fluid requirements are fulfilled, it will be decided whether the patient will be given bolus or continuous supply at night, in order to increase mobilization during the day. However, this requires that the patient does not have diarrhea, nausea or other complaints associated with the supply of nutrition.

For a running feeding tube:

  • Every 4-8 hours, it should be aspirated in order to monitor the gastric emptying. This applies especially to immobile and weak patients.
  • Weekly or more often, the nutrition program/fluid balance, evaluation, edema control, blood tests (albumin, K, Mg, P, blood glucose) should be monitored weekly or more often.
  • Every 4-6 weeks, the tube should be changed. Alternate the uses of nostrils avoid irritation in the nose through prolonged feeding.

Experience shows that the use of infusion pumps causes fewer side effects and ensures correct volume and rate.

Bolus supply

Initiation of tube feeding with bolus supply is only recommended

  • if the patient been taking any food until the last 24 hours
  • if the patient is taking some food and requires tube feeding for additional nourishment

It is recommended to use pumps for bolus supply for the first 1–2 days.

Continuous supply

If the patient cannot tolerate bolus supply (vomiting, abdominal discomfort, nausea, diarrhea), reverting to continuous supply should be considered.

Tube feeding should always be administered continuously to very malnourished patients or if the tube end is located distally to the pylorus.

Parenteral nutrition

If the patient has a satisfactory nourishment status, begin with 100% of the requirement. If the patient is seriously malnourished, start with 80 % of the requirement and increase slowly to 100% over the course of three days.

The patient must be monitored closely in relation to

  • electrolytes (potassium, phosphate and magnesium).
  • infusion rate.
  • twenty-four hour urine sample and fluid balance should be calculated daily.
  • glucose in the blood and urine, and electrolyte in the blood should be examined daily at the start.
  • liver tests, kidney function tests and triglycerides should be taken examined at least once every week.

For TPN treatment longer than 1 month, vitamins and trace elements should be examined.

Follow-up

The patient's nutrition status should be monitored at follow-up visits after the end of treatment.

Transfusions

General

Transfusions of blood components are often necessary for the patient to complete the planned cancer treatment.

Blood transfusions are appropriate for low hemoglobin (Hb) and thrombocyte transfusions for low thrombocytes (trc) which also poses a risk for serious bleeding.

Normal values

  • Hemoglobin 13.4–17 g/dl
  • Platelets 145–348 109/l

Indications

Blood transfusion

Assessment for a blood transfusion based on:

  • Hb/hct
  • symptoms/sign/function level
  • underlying disease (heart/lung, serious infection)
  • expected development of anemia (marrow function, current bleeding)
  • acute blood loss > 15% of total blood volume
  • Hb < 8.0 g/dl and symptom causing chronic anemia
  • Hb < 8.0 g/dl and reduced bone marrow production without sign of regeneration
  • Hb < 8.0 g/dl in perioperative period
  • Hb < 7.0 g/dl in patients without symptoms of other disease
  • Hb < 10.0 and receiving radiation therapy

Platelet transfusion

The patient is assessed for thrombocyte transfusion based on:

  • clinical status (bleeding, bleeding tendency, or fever/infection)
  • ongoing bleeding and thrombocytopenia < 50x19/l
  • degree of thrombocytopenia and cause of thrombocytopenia (reduced production or increased consumption)

Prophylactic platelet transfusion

  • For values < 10x109/l secondary to previous chemotherapy
  • Before invasive procedures
  • For spinal puncture and installation of central vein catheter, thrombocytes should be 30x109/l and 
  • Puncture biopsies (liver/kidney/tumor) > 40x109/l
  • For major surgeries, thrombocytes should be > 50x109/l. After surgery, thrombocytes should be monitored and transfusion repeated, if necessary.

Remember clinical evaluations: possible bleeding, other risk factors for bleeding, diagnosis, treatment, prognosis.

Goal

  • Complete the planned treatment
  • Ensure hemostasis 
  • Ensure adequate oxygen transport to peripheral tissue.
  • Maintain intravascular fluid volume for adequate circulations of vital organs

Definitions

Blood

For a blood transfusion for anemia, SAGMAN erythrocytes are used. One unit is obtained from 450 ml blood. Most of the plasma is removed and replaced with 100 ml SAGMAN solution (Saltwater-Adenine-Glucose-Mannitol). Hematocrit is about 0.60%.

Platelets

One unit contains 240-300 x 109 platelets and is prepared from blood donors with type O and A. In acute situations, the receiver's blood group is of minor importance.
Two kinds of platelet products are available:
  • Apheresis platelets produced from thrombophereses from one donor
  • Buffcoat platelets produced from buffy coat from 4 donors

All cellular blood products should be leukocyte filtered. Leukocyte filtration is done to remove antigen-presenting and virus-bearing cells. 99.99% of leukocytes in the unit are removed.

Radiation

Blood and thrombocytes are irradiated to a minimum of 25 Gy in the blood bank to eliminate T-lymphocytes.

This is done for:

  • Bone marrow transplant or stem cell transplant (1 month before or 3 months after HMAS until 1 year after allogeneic stem cell transplant)
  • For use of HLA-compatible platelet concentrations
  • For all transfusions from relatives
  • For use of fresh blood
  • For use of fludarabine

Preparation

Blood tests

Before the first blood transfusion, the following blood tests are performed:
  • Virus antigens
    • HCV
    • HBV
    • HIV
Every three days, and as needed, pre-transfusion tests are taken.

Compatibility

Erythrocyte concentration—Rh(D) negative products can usually be given to everyone while Rh(D) positive can only be given to Rh(D) positive receivers.

Thrombocyte concentration—Rh(D) negative girls and women in fertile ages who obtain Rh(D) positive thrombocyte products should be given a prophylaxis for Rh immunization. Boys/men and women who are over the fertile age may obtain thrombocytes regardless of Rh(D) type.

Implementation

Blood components should never be given together with other medications.
  • Premedication if the patient has reacted to previous transfusions.
  • Secure venous access
  • The blood product is checked to ensure the correct unit is given to the correct patient.
  • Use blood set with filter
  • Give SAGMAN over 1 hour and thrombocytes 20-30 minutes per unit.
  • Rinse the set with NaCl 9 mg/ml at the end of the infusion
  • Store the blood product bag for one day before discarding

Observations

The patient should be observed during the transfusion with emphasis on reactions. Most serious transfusion reactions occur within the first 20 minutes.

Symptoms of transfusion reaction:
  • chills
  • fever
  • feeling of heat in the face
  • breathing difficulty
  • itching
  • nervousness
  • fall in blood pressure
  • shock
Suspect/manifest blood transfusion reaction:
  • Stop transfusion immediately
  • Start treatment if necessary (intravenous fluid, adrenalin, steroids, oxygen, respirator)
  • Check blood bag and compatibility form. The residue should be sent to the blood bank.

Follow-up

Hemoglobin and thrombocytes are checked.

If poor effect of platelet transfusion, platelet value should be checked after approximately one hour. The value should have increased by approximately 30x109/l or more after a standard dose.

If the increase is drastically less, the cause may be:
  • Abnormally high consumption. This is an indication for more frequent transfusions.
  • Antigens against HLA or platelet-specific antigens. The patient must be examined in cooperation with the blood bank to find compatible donors.

Cold Gloves and Socks

General

Clinical studies (Journal of Clinical Oncology – July 1, 2005 from Southwest Technologies) have shown that use of cold gloves and socks reduces nail loss and skin damage in patients receiving docetaxel and pegylated liposomal doxorubicin.

Indications

  • Docetaxel treatment for prostate and breast cancer
  • Pegylated liposomal doxorubicin treatment for ovarian cancer

Contraindications

  • Should not be used in patients with curative treatment (adjuvant/neoadjuvant treatment of breast cancer)
  • Raynaud's disease
  • Distal metastases
  • Distal arterial insufficiency
  • Cold intolerance

Goal

  • To avoid loosening/loss of nails or skin damage
  • Preventing neuropathy

Equipment

The gloves and socks are made of a glycerine gel which maintains its elasticity also when frozen. The outer fabric is water-proof and elastic. The Velcro holds the products securely in place.

  • Elasto-Gel cold gloves and/or socks
  • Disposable gloves/socks for use inside

Preparation

  • The products should be stored in the plastic bag in a freezer which maintains a temperature of -25 to -35°C for at least 12 hours before use. The elasticity is maintained in temperatures down to -30 °C.
  • Gloves/socks should be used at each treatment to maintain the effect.

Implementation

  • Wear disposable gloves/socks inside for hygienic reasons.
  • Put on gloves/socks 15 minutes before treatment and remove at the earliest 15 minutes after the end of treatment.
  • If the treatment lasts 1-1 ½ hours, the gloves/socks should be changed. This should take place after 45 minutes (or more often) if the patient feels they become too warm.
  • Change the gloves/socks as quickly as possible to avoid reflexes caused by dilatation of blood vessels.

Follow-up

  • Allow the gloves/socks to dry after use before they are put in the freezer again.
  • As needed, clean the surfaces in contact with skin with soapy water and dry thereafter. Never immerse the gloves/socks in water.
Hypothermia gloves and socksHypothermia gloves and socksHypothermia gloves and socksHypothermia gloves and socks
Hypothermia gloves and socks

Smoking cessation in connection with cancer treatment

General

In patients treated with surgery, radiation and/or chemotherapy, the treatment efficacy may be affected by smoking. Smoking has an impact on both metabolism and pharmacokinetics.

Smoking may inhibit wound healing after surgery and increase the probability of surgical site infections. Because smokers generally have more mucus in the airways and are less able to remove it, they also may have a increased risk of serious lung complications during anesthesia. However, it is disputed whether or not it is beneficial to quit smoking directly prior to surgery and this should be considered in each case individually. (28,30-33). Smokers are more prone to stagnation of bronchial secretion than non-smokers and rapid postoperative extubation is important. 

Patients who continue smoking during radiation therapy have a lower risk of complete respons, development of secondary cancer, increased toxicity and several other side effects compared to non-smokers and smokers that quit before treatment. Continued smoking during radiation therapy is also associated with oral mucositis, impaired ability to taste, dry mouth, reduced voice quality, weight loss, cachexia, fatigue, pneumonia, bone-and soft tissue necrosis.

Tobacco may have an effect the metabolism and the mechanisms of chemotherapy and in this way may make the treatment less effective. Smokers undergoing chemotherapy may also experience a weakened immune system, increased rates of infection, exacerbation of common side effects, weight loss, cachexia, fatigue and cardiac or pulmonary toxicity. Some findings suggest that it may also apply to monoclonal antibodies.

Cancer patients who quit smoking before chemo- and radiation therapy get a total symptom burden equal to that of non-smokers, but those who continue to smoke state a higher symptom burden. Targeted measures in smoking cessation may increase quality of life and lead to less treatment interruptions.

A lot of patients wonder if there is any point to quit smoking after receiving a cancer diagnosis. tudies show that continued smoking is associated with increased treatment-related toxicity, increased risk of second primary cancers, reduced quality of life, reduced treatment effect and reduced survival in patients with cancer. This applies to both cancer diagnoses where smoking is a known causal factor, as with lung- and head and neck cancers and in cases where smoking has no known correlation with the diagnosis. Studies conducted on smoking and cancer diagnoses such as breast cancer, prostate cancer, colorectal cancer, esophageal cancer, cervical and ovarian cancer as well as leukemia and lymphoma cancers show that to continuation of smoking after a proven cancer diagnosis is associated with increased risk of mortality.

Studies support that quitting smoking improves cancer, and emphasizing the potential importance of targeted smoking cessation in cancerpatients during and after treatment. The link between tobacco and impact on cancer and cancer treatment is a complex matter.

Regarding the significance of the various components much is still unkown. When it comes to tobacco use in cancer treatment research is primarily done on the link between cigarette smoking and efficacy of cancer treatment. Nevertheless, it cannot be excluded that using other smokeless tobacco products such as snuff and chewing tobacco, may also impact the cancer treatment. According to international guidelines all tobacco use should be stopped during cancer treatment.


Benefits of smoking cessation and risks of continued smoking in patients with cancer
Quitting smoking results in the following benefits: Continued smoking results in a risk of :
  • improved treatment results.
  • less side effects
  • fewer infections
  • improved respiration and circulation
  • increased survival
  • reduced efficacy of treatment.
  • postoperative complications and longer recovery.
  • cardiovascular and respiratory complications.
  • recurrence of cancer, and secondary cancer.
  • shortened life expectancy.

 

Indication

Weaning of nicotine in connection to cancer treatment. 

Goal

Healthcare providers should convey evidence-based information to patients about how smoking affects cancer treatment, the risk of side effects and prognosis and also provide guidance and relevant treatment for smoking cessation.

Preparation

Patients require clear, formalized and fact-based guidance and continuous follow-up. Many patients want encouragement for smoking cessation early in the disease. Being hospitalized is a good opportunity because patients have access to support and help to reduce nicotine withdrawal symptoms and discomfort.

A patient recently diagnosed with cancer is often motivated to quit smoking and also receptive to conversations about how to do this. Motivation or willingness to quit often changes during the treatment, and use of tobacco and motivation should therefore be discussed at every consultation.

Clarifying the patient´s smoking habit is important. The time of day the patient lights their first cigarette says something about the degree of addiction. Making the patient aware of the situations in which he or she smokes most; at work, at home or in social settings, can help break unwanted patterns of behavior.

Implementation

The best and most direct approach to motivate the patient is telling that tobacco use will decrease the effectiveness of treatment and the most important thing the patient can do himself is to stop using tobacco.

  • Speak directly to the patient about how tobacco use may decrease the effectiveness of treatment.
  • Discuss smoking cessation with the patient at each visit.
  • Clarify any misunderstandings about the risks of tobacco use. Point out the importance of quitting.

Sometimes there may be misunderstandings about what kind of health risk smoking during and after cancer treatment may entail.

Advice to those who are not ready for smoking cessation
The smokers statement The response of health care professionals
Justifications
The damage from smoking is already done.
Some damage is done, but continued smoking will still damage your health and reduce the effects of treatment. Quitting smoking is more important now than ever.
This response tells the patient that it is not too late to quit smoking, and the effect of treatment will be positive.

I have reduced smoking.
That is great, and now you need to focus on quitting completely. What do you think keeps you from quitting altogether?
This response tells the patient the importance of quitting completely, as the benefits of quitting at baseline are documented.
This is not a good time to quit smoking.
The benefits of quitting are greatest now, before treatment begins. What is needed to make you feel ready to quit smoking?
 
This response make the patient aware of the fact that quitting smoking optimizes the cancer treatment.

Health professionals must assist the patient identifying realistic expectations and goals for smoking cessation. For some, it may feel easier to scale down the number of cigarettes than to quit completely. The patient should know that every puff affects their health, and that the total health benefits can only be achieved through smoking cessation. For patients unable to stop completely, a gradual reduction may be a step in the right direction.

The probability of success for smoking cessation significantly increases for those who receive professional help in combination with nicotine replacement therapy (NRT) or non-nicotine based products. For the best possible effect of NRT the patient needs professional guidance to find the right product and dosage. For some patients combining two products or receiving a higher dosage than recommended will give the best effect. Sometimes the product must be replaced during the treatment.

Treatment with nicotine replacement therapy

Topical products are patches (Nicorette®, Nicotinell®), chewing gum (Nicorette®, Nicotinell®), lozenges (Nicorette®, Nicotinell®), inhalator (Nicorette®) or a combination of these. These products contain nicotine and therefore reduce the withdrawal symptoms experienced after smoking cessation.

  • Patch: Nicorette® 5 mg,10 mg and 15 mg/16 hours up to 6 months or Nicotinell® 7 mg,14 mg og 21 mg/24 hours up to 3 months.
  • Chewing gum: Nicorette®/Nicotinell® 2 mg and 4 mg, 8-12 pcs/day up to 12 months.
  • Lozenges: Nicorette® 2 mg and 4 mg, typically 8-12 pcs/day, maximum respectively 15 pcs/day up to 9 months or Nicotinell® 1 mg and 2 mg, typically 8-12 pcs/day, maximum is respectively
    25 and 15 pcs/day up to 12 months.
  • Inhalator: Nicorette® 10 mg/dosage container, 4-12 pcs/day up to 6 months.

Combination therapy means combining patches with chewing gum, lozenges or an inhalator.

  • Nicorette® patch15 mg/16h and Nicorette chewing gum 2 mg. 5-6 chewing gums daily. Maximum 24 pcs/day
  • Nicorette® patch 15 mg/16h and Nicorette® inhalator 10 mg: 4-5 dosage-container daily. Maximum 8 pcs/day

Nicotine replacement therapy increases the chance of smoking cessation by 50 to 70% after six months. Two products used in combination increase the chance of smoking cessation compared to the use of only one product.

Side effects

  • Headache, dizziness, nausea, flatulence and hiccup.
  • Irritation in the mouth and esophagus using chewing gum/ lozenges/inhalator
  • Skin irritations while using patches.

Precautions

  • Precaution in acute cardiovascular disease, peripheral arterial disease, cerebrovascular disease, hyperthyroidism, diabetes mellitus, kidney- and liver failure and peptic ulcers.
  • Should not be used during pregnancy, unless the potential benefit outweighs the potential risk.
  • The products should not be used during breastfeeding.

Treatment with non-nicotine medications

Bupropion (Zyban®) is a selective reuptake inhibitor of dopamine and norepinephrine. The mechanism behind why the ability to refrain from smoking increases by using bupropin is unknown. A should be set for smoking cessation for the second week of treatment.

Bupropion increases the chance of smoking cessation after 6 months by nearly 70%.

Side effects

  • Dry mouth, nausea, insomnia, hypersensitivity reactions and seizures (convulsions)

Precautions

  • Contraindicated in people with disease that can cause convulsions,  people with substance abuse or other circumstances lowering the seizure threshold.
  • Depression, which in rare cases includes suicidal thoughts and – behavior including  suicide attempt.
  • Safety and efficacy have not been established for people under 18 years.
  • Should not be used during pregnancy.

Varenicline (Champix®) is a partial agonist by a subtype of nicotinic receptors. It has both agonistic activity with lower intrinsic efficacy than nicotine and antagonistic activity in the presence of nicotine.

A date for smoking cessation should be set. Treatment should start 1-2 weeks, or up to 35 days, before that date. The starting dose is 0,5 mg one time daily on days 1-3, then 0,5 mg two times daily on days 4-7, then 1 mg two times daily on day 8 and until the end of treatment. The treatment should last for 12 weeks.

Side effects

  • Nausea, sleep disturbances, headache, constipation, flatulence and vomiting

Precations

  • Links have been reported between the use of varenicline and an increased risk of cardiovascular events, suicidal thoughts, depression and aggressive and erratic behavior
  • Safety and efficacy have not been established for people under 18 years of age
  • Should not be used during pregnancy

Follow-up

If the patient experiences a relapse, it is important to inform them that this is completely normal, and encourage them to continue. If the most common measures do not work,
consideration should be given both to increase the NRP and to provide closer follow-up by health care providers.

Guidance in smoking cessation is described in the literature as brief and clear advice and then further follow-up with a telephone helpline offering treatment for addiction and behavior change/issues. It is not necessary for the patient to have decided to quit smoking in order to be referred to a quitline. If the patient agrees to receive a call from quitline, he or she will be followed up by a supervisor. Supervisors are bound by confidentiality, are up-to-date professionally and offer free follow-up counseling calls for up to a year.

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  38. Browman GP, Wong G, Hodson I, Sathya J, Russell R, McAlpine L, et al. Influence of Cigarette Smoking on the Efficacy of Radiation Therapy in Head and Neck Cancer. The New England Journal of Medicine. 1993;328(3):159-63.
  39. Browman GP, Mohide EA, Willan A, Hodson I, Wong G, Grimard L, et al. Association between smoking during radiotherapy and prognosis in head and neck cancer: A follow-up study. Head Neck-J Sci Spec Head Neck. 2002;24(12):1031-7.
  40. Travis LB, Gospodarowicz M, Curtis RE, Clarke EA, Andersson M, Glimelius B, et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. Journal of the National Cancer Institute. 2002;94(3):182-92.
  41. Ford MB, Sigurdson AJ, Petrulis ES, Ng CS, Kemp B, Cooksley C, et al. Effects of smoking and radiotherapy on lung carcinoma in breast carcinoma survivors. Cancer. 2003;98(7):1457-64.
  42. Dresler CM, Gritz ER. Smoking, smoking cessation and the oncologist. 2001. p. 315-23.
  43. Balduyck B, Nia PS, Cogen A, Dockx Y, Lauwers P, Hendriks J, et al. The effect of smoking cessation on quality of life after lung cancer surgery. Eur J Cardiothorac Surg. 2011;40(6):1432-8.
  44. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, et al. Effects of smoking on the pharmacokinetics of erlotinib. Clinical Cancer Research. 2006;12(7 I):2166-71.
  45. Helsedirektoratet. Forberedelse til røykeslutt 2011. Available from: http://helsedirektoratet.no/publikasjoner/forberedelser-til-roykeslutt/Publikasjoner/forberedelse-til-roeykeslutt.pdf   
  46. Brunnhuber K, Cummings KM, Feit S, Sherman S, Woodcock J. Putting evidence into practice: Smoking cessation: BMJ Publishing Group; 2007.
  47. Helsedirektoratet. Røyketelefonen 2013 [updated 12.12.201102.12.2014]. Available from: http://www.helsedirektoratet.no/folkehelse/tobakk/snus-og-roykeslutt/royketelefonen/Sider/default.aspx.
  48. Legemiddelverk S. Legemidler A-Å 2013 [02.12.2014]. Available from: http://www.legemiddelverket.no/Legemiddelsoek/Sider/Legemidler_A-AA.aspx.
  49. Hughes JR, Stead LF, Lancaster T, Rev CDS. Antidepressants for smoking cessation. Cochrane Database of Systematic Reviews: Reviews 2007. 2014 (1).
  50. Stead LF, Perera R, Bullen C, Mant D, Hartmann-Boyce J, Cahill K, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012;11(11).
  51. Cahill K, Stead LF, Lancaster T, Polonio IB. Nicotine receptor partial agonists for smoking cessation. Sao Paulo Med J. 2012;130(5):346-7

Follow-up care after treatment of prostate cancer

Surgery

Control after 6 weeks where the patient is informed about the histological results. Based on the histology, further follow-up of the disease is planned.

  • If a favourable histology and postoperative PSA decrease to unmeasurable levels, the patient will be observed by the patient`s regular doctor with semiannual PSA measurements. Patients are referred back to the urologist if PSA levels rise. 
  • If unfavourable histological result, the patient will be followed up by an urologist with a customized program depending on the stage of the disease. 

Radiation therapy

For brachytherapy

  • Follow up at Oslo University Hospital after 3 months and after 1 year
  • PSA testing every six months

For external radiation therapy

  • Follow up after 3 months at local hospital/local doctor 
  • Follow up at Oslo University Hospital after 1 year
  • PSA testing every 6 months

Complications

The most frequent complications after treatment of prostate cancer is urine leakage and erectile dysfunction.

Urine leakage

  • The patient is given a standardized training schedule with pelvic floor exercises.
  • Patients with significant incontinence problems is referred to an urodynamic work-up and assessment for incontinence treatment.
  • If urinary incontinence persists, the patient will be evaluated for possible surgery with sling or artificial urinary sphincter.

Erectile dysfunction

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Lymphedema

General

According to etiology, there are two general classifications of lymphedema primary and secondary lymphedema. Primary lymphedema is caused by deficient or faulty development of the lymph system. Secondary lymphedema occur as a complication from trauma or diseases which damage the lymphatic vessels or lymph nodes. The primary cause of lymphedema in the western world, is impaired or disrupted flow of lymph fluid caused by cancer or cancer treatment (secondary lymphedema).

Lymphedema occurs when the transport capacity of the lymph system is reduced significantly.
The swelling is caused by an accumulation of fluid (rich in protein) in the tissue, due to reduced drainage of lymph fluid (1,2). The swelling is often chronic. A lymphedema can lead to pain/discomfort and changes in the soft tissues in the affected area (fibrosis) (3,4). Lymphedema occurs most often during the first 2-3 years after cancer treatment (5 6). Without treatment, lymphedema can lead to progressive swelling.

In some cancer treatment the lymph nodes and fatty tissue are removed, most often in the axilla, pelvis and the groin. This treatment causes damage to the lymphatic wessels and reduces the number of lymph nodes. The subsequent reduced capacity for drainage of lymph fluid in the arm and leg may result in lymphedema.

Radiation therapy may cause tissue scarring and fibrosis. The combination of surgery and radiation therapy to the axilla additionally increases the risk of developing lymphedema.

Cancer related lymphedema can also occur due to metastasis in areas where blocking the central lymph vessels in advanced disease.

Factors which may increase the risk for developing lymphedema are:

  • obesity
  • infection in the area where lymphedema occurs
  • overheating/sunburn
  • trauma of the arm/leg on the operated side

Indications for treatment

Lymphedema in the arm/hand, breast, leg, groin, face and neck after treatment of:

  • breast cancer where axillary dissection is performed
  • gynecologic cancer where the lymph nodes in the pelvis or the groin are removed
  • melanoma where the lymph nodes in the axilla or the groin are removed
  • lymphoma and cancer of the head and neck region where lymph nodes in the neck region are removed
  • prostate cancer where the lymph nodes in the pelvis or the groin are removed
  • sarcoma where lymph nodes are removed

Without treatment the lymphedema can increase in size. This may cause skin changes (fibrosis), increased swelling and therefore more discomfort in the area (3).

Contraindications

Absolute
  • acute infections, local or general (erysipelas)
  • arterial insufficiency with risk of necrosis
  • thrombosis and embolism
Relative

Untreated cancer disease, heart failure, or kidney failure

Goal

  • reduce lymphedema
  • relieve tormenting side effects
  • improve function 
  • prevent complications such as skin changes and inflammation in the area (erysipelas)

References

1. Rockson SG. Diagnosis and management of lymphatic vascular disease. J Am Coll Cardiol 2008;52:799-806.
2. Lawenda BD, Mondry TE, Johnstone PAS. Lymphedema: (Review) A primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin 2009;59:8-24.
3. Mortimer PC. The patophysiology of lymphedema. Cancer 1998;83(12 Suppl American): 2798-802.
4. Erickson VS, Pearson ML, Ganz PA, Adams J, Kahn KL. Review: Arm edema in breast cancer patients. J Natl Cancer Inst 2001;93:96-111.
5. Nesvold IL, Dahl AA, Løkkevik E, Mengshoel AM, Fosså SD. Arm and shoulder morbidity in breast cancer patients after breast-conserving therapy versus mastectomy. Acta Oncol 2008;47:835-842.
6. Norman SA, Russel Locario A, Potashnik SL, et al (2009) Lymphedema in breast cancer survivors: incidence, degree, time course, treatment, and symptoms. J Clin Oncol 2009;27:390-397.
7. Johansen J, Overgaard J, Blichert Toft M, Overgaard M. Treatment morbidity associated with the management of the axilla in breast-conserving therapy. Acta Oncol 2000;39:349-54

Definitions

Complete psysical therapy treatment of lymphedema

Consists of manual lymph drainage, compression therapy, skin care and instruction in exercises and self-treatment (1). The treatment is performed by physical therapists with special expertise.
The treatment may be extensive at the start. In cases of severe swelling one usually start with manual lymph drainage followed by bandaging of the arm/leg (1).

Manual Lymph Drainage

This is a kind of massage which requires guided training to perform optimally. The goal is to encourage the drainage of lymph fluid and thereby reduce the swelling of the tissue (2). It is quite different from other kinds of massage applied within physiotherapy. The anatomical conditions of the lymph system is the basis for manual lymph drainage. These are: the course of the large lymph veins, the borders of different lymphatic functional regions (watershed), natural anastomoses crossing these lines, and the lack of valves in the lymphatic vessels .

Bandaging

Bandaging is used mostly at the start of a treatment to reduce swelling. When the swelling is reduced a compression stocking is adjusted.

Compression stocking

Clinical experience and research show that compression is the most important treatment. (3;4) Accordingly it is of great importance to adjust a compression stocking for the arm or leg. If there is swelling of the hand, a compression glove might help.
A compression stocking is used to increase tissue tension. The pressure from the stocking increases absorption of tissue fluid. The stocking provides a graded pressure highest distally and lowest proximally. To adjust the stocking, the circumference of the arm or leg is measured at several defined points. There are several compression classes, but the most commonly used are class 1 and 2. The stocking should provide a constant pressure without causing discomfort. It may take some time to get used to the compression stocking. Some choose to use the stocking occasionally, while others wear it daily.
A facemask at night is recommended to treat lymphedema in the neck and face region (5). Patiens with lymphedema in the groin can be helped by using a bike pant or a panty. Bandaging, tubigrip or bike pants may benefit if there is swelling of the penis and scrotum .

Intermittent pressure massage with pulsation

Treatment is carried out with an electronically powered apparatus which blows air in a double-walled cuff. The cuff, covering the whole arm or leg, has multiple channels and creates a peristaltic pressure wave in proximal direction. The treatment encourages the lymph drainage and thereby reduces the swelling (4).

References

1. The diagnosis and treatment of peripheral lymphedema. Consensus document of the International Society of Lymphology Executive Committee. Lymphology 2003;36:84-91.
2. McNeely ML, Peddle CJ, Yurick JL, Dayes IS, Mackey JR. Conservative and dietary interventions for cancer-related lymphedema: A systematic review and meta-analysis. Cancer 2010.
3. Badger C, Preston N, Seers K, Mortimer P. Physical therapies for reducing and controlling lymphedema of the limbs. Cochrane Database Syst Rev 2004;CD003141.
4. Johansson K, Albertsson M, Ingvar C, Ekdahl C. Effects of compression bandaging with or without manual lymph draining treatment in patients with postoperative arm lymphedema. Lymphology 1999;32:103-110.
5. Deng J, Ridner SH, Murphy BA. Lymphedema in patients with head and neck cancer. 2011;38:1-10.

                                                                          

Preparation

Main points of information

Information should be given to patients who have received surgery only or combined with radiotherapy with increased risk of getting lymphedema. The patient usually gets information about lymphedema after the surgery. Sufficient information and guidance is important and crucial for both avoiding getting lymphedema and being able to identify lymphedema at the very beginning.

  • The function and purpose of the lymphatic system
  • Causes of lymphedema
  • Symptoms of lymphedema
  • Different treatment options
  • Precaution
  • Complications/side effects caused by the disease and treatment
  • The importance of maintaining mobility in the arm or leg

Symptoms of lymphedema

  • A feeling of uncomfortable change
  • A feeling of heaviness
  • Bursting pain
  • Changes of consistency (visible or palpable) in the soft tissues
  • Suspicion of increased circumference
  • Swelling may disappear overnight, but usually returns during daytime
  • Some have swelling sporadically

The dominating symptom is lasting swelling in the involved area. Other symptoms will to a large extent depend on the amount, duration, and localization of the edema.

Moderate swelling after cancer surgery, can be a reaction which often spontaneously disappears.

Diagnostics

Lymphedema is usually measured using a clinical method. There are multiple methods to measure the extent of lymphedema. The gold standard is the water displacement method, which measures and compares the volumes of both arms/legs. But a method of comparing volume by using several circumferential measurements of the arms/legs is often used in research and sometimes in the clinical setting. The most widely used method is measurement of circumference at multiple anatomic points on the arm/leg with comparison with the contralateral arm/leg. A difference in circumference of ≥2cm is often defined as lymphedema. Stemmer sign is also used.

Implementation

With development of lymphedema, it is important to take precautionary measures as soon as possible. Treatment with compression is the component which seems to be most effective in reducing the swelling. Manual lymph drainage is often used in combination with bandaging in the first 1-2 weeks of the treatment. This complete decongestive therapy is a composite treatment including multiple techniques which are performed by a specially trained physical therapist.

The intensive phase

  • Compression treatment – possibly with bandaging and thereafter adjustment of an elastic stocking
  • Manual lymph drainage
  • Circulation and drainage inducing exercises
  • Skin care

During the intensive phase, the patient is usually treated 5 days a week with continuously bandaging until the desired volume reduction is achieved. This usually takes one to two weeks.

Bandaging

After stimulating the lymphatic flow by manual lymph drainage, a compression stocking is used or the whole arm is bandaged for one to two weeks. The bandages should be worn as long as they are not too uncomfortable. Correct bandaging with short, elastic bandages provide the tissue with high pressure under activity and low pressure while resting.

  • An ointment with a low pH (5.5) should be applied to the skin.
  • A light tube gauze should be worn.
  • The padding is then applied.
  • The bandaging starts distally to the lymphedema.
  • The bandages are laid evenly, circularly, and in multiple layers.
  • The pressure should decrease gradually from distal to proximal.
  • The pressure is regulated partially with the bandaging technique and mainly by the number of layers of bandages.

Compression stocking

  • The stocking may be removed at night.
  • At night an ointment is preferably applied to the skin.
  • With incipient  lymph edema, wear the stocking during activity.
  • In moderate and extensive lymph edema, the stocking is usually worn all day.
  • The stocking should be washed at least every third day.

A poorly customized stocking may create faulty compression. The most frequent error is that the compression stocking is used after it has lost its elasticity (worn out) and therefore has less effect.

Manual Lymph Drainage

The massage strokes should be performed in the direction of the lymphatic drainage with light pressure and with slow motions. The treatment should not be painful.

Manual lymph drainage has four main movements: standing circles, pumping grip, turning grip, and corkscrew grip.

Pressure massage with pulsator

Pulsation is never a first choice for treatment of lymphedema, but could be a measure over time when monitoring has shown that the treatment is effective. At the start, the patient should be informed about possibly complications. Sometimes, an increase in edema is seen proximal to the cuff. Further pulsation treatment should then be postponed until manual lymph drainage and exercises have improved the condition. If the pressure is too high, the lymphatic vessels may be damaged and the amount of interstitial fluid may increase.
The pressure should be moderate and the patient should experience the treatment as comfortable. It is not the amount of pressure that is important, but uniform rhythmic pressure wave. Tuning of rate and pressure are adjusted for each patient.
Usually, the treatment should last for twenty minutes at the start increasing gradually to thirty to forty minutes. Can be used daily or when needed. Pulsation treatment may also be performed by the patient at home.

Skin Care

Regardless of whether the patient has lymphedema or not, it is important to hinder the occurrence of scratches, sores, and unnecessary skin irritation. Use of gloves is appropriate in some situations. The patient should also be cautious of overheating and sunburn. The main goal of skin care is to prevent infections, because this can trigger an eruption of lymph edema.

Regular use of bandages and compression stockings dries out the skin. Use of skin care products and cleansers with a low pH (5.5) are recommended. Good skin care keeps the skin soft and supple and maintains the skins natural ability to fight infection.

Disinfecting ointment and adhesive tape should be used in the event of an ulcer or scratch or if there is danger of infection.

Maintenance phase

  • Use of elastic stocking and/or glove as needed
  • Skin care
  • Regular exercises to facilitate the muscle-joint pump
  • Possible intermittent pressure massage with pulsator

The patient obtains some treatment during the maintenance phase and may have treatment by a physical therapist if necessary. In the short term, the treatment is almost always satisfactory. In the long run, the result depends on the patient practicing the measures recommended. The pulsator may usually be borrowed from a health care center.

Exercises to improve mobility and lymph flow of the shoulder/arm

Dynamic exercises with a relaxation phase are optimal. "Throwing" movements may feel uncomfortable. Many experience that it is better to walk with poles, but it is important to maintain a loose grip of the pole.

Correctly adjusted movement exercises:

  • induce circulation without straining the reduced lymphatic system
  • provide adequate joint movements
  • stimulate dynamic change between tension and relaxation, preferably in conjunction with respiration

Movement therapy in a heated pool may be favorable for some lymphedema patients. Water pressure stimulates lymphatic drainage and simultaneously activates circulation and movement.

 

Follow-Up

If necessary, the patient may obtain a referral for physical therapy in their home area for further follow-up. Follow-up and guidance by a physical therapist with the necessary skills is important. Some with serious lymphedema will need frequent treatment for the rest of their life. But others will be able to manage the treatment themselves by adhering to the guidelines that they have learned. Compression with stockings and skincare are often sufficient treatment. So many patients do not need physical therapy as treatment, but rather information and functional guidance.

Moderate physical activity improves joint movement, circulation, and well-being, as well as stimulation of lymph drainage. Blood pressure should not be measured and vaccinations should not be given in the treated arm. Gloves are recommended for gardening.

Complications

Fibrosis of the dermis and epidermis with affects some persons with lymphedema. The skin loses its elasticity and is more easily traumatized than normal skin.

The immune system is weakened in the edematous area. This may be for multiple reasons, among others, weakened transport of dendritic cells, lymphocytes, and proteins. If the area’s regional lymph nodes are removed, this will also weaken the local immune system.

In some edema patients, especially secondary lymphedema, a distinctive reaction (erysipelas) may occur in the skin of the affected area. This will usually start acutely with a strong feeling of malaise with high fever, hyperemia with flushing, and increased swelling of the skin. The area of skin involvement is often limited. The symptoms are usually improved after four to six days but it is not uncommon for the edema to deteriorate. The condition should be treated with antibiotics (penicilin) as quickly as possible.

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Lymph edema in the arm.Lymph edema in the arm.