oncolex logo
Utskriftsdato (23.5.2017)

Testicular cancer

The prognosis for testicular cancer is very good with modern treatment.

The majority of malignant tumors in the testes are germ cell tumors. Approximately 90% of all of these germ cell tumors originate in the testes (3).

Testicular germ cell tumors are separated into two main types:

  • Seminoma
  • Nonseminoma (often a mix of two or more cell types)
    • Embryonal carcinoma
    • Yolk sac tumor
    • Choriocarcinoma
    • Teratoma

The occurrence of the two types are about the same, however, they differ in aggressiveness and response to treatment. Seminomas peak later in life with a median age of 35 years while nonseminomas have a median age of 25 years.  

Mixed tumors with a seminal component are classified as nonseminomas. 

Ten to fifteen percent of all testicular germ cell tumors occur extragonadal, particularly retroperitoneally and in the mediastinum. Primary retroperitoneal germ cell tumors are most often associated with an occult testicular cancer, especially if the tumor is in the midline. Mediastinal extragonadal tumors are most often mature teratomas.

About 5% of all testicular tumors develop from other cell types in the testicle, primarily from hormone-producing cells (Leydig cells) or sex cord-gonadal stromal tumors (for example Sertoli cells).

Pediatric testicular tumors develop very differently than in post-pubescent men. Pediatric testicular tumors are therefore not discussed here in detail. (See childhood cancer)

Incidence

Compared to other cancers, testicular cancer is rare. Approximately 0.4% of men will be diagnosed with testicular cancer at some point during their lifetime.Testicular cancer is most frequently diagnosed among men aged 20-34. The incidence of testicular cancer is increasing and varies with geographic area and race.

In 2017, it is estimated to be 8,850 new cases of testicular cancer (1).


 

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

Source: Cancer Registry of Norway

 

 

Incidence of testicular cancer, 1954–2013.

Source: Cancer Registry of Norway

Etiology of testicular cancer

There are no known causes of testicular cancer, however, some risk factors are known.
  • Congenital deformities 
    • Cryptorchism. Two to four percent of all boys with cryptorchism will develop testicular cancer later in life. The risk increases significantly if the condition is not surgically corrected by puberty. In 5-20% of cases, the tumor develops in a normal descended testicle (3).
    • Gonadal dysgenesis. Different mutations in the division of sex chromosomes, with and without intersex conditions, increases the risk for developing tumors from germ cells from the sex cord-stromal cells.
  • Hereditary disposition
    • Familial accumulation occurs. The risk for testicular cancer increases 2-4 fold when the father has been diagnosed and 8-10 fold if the brother has the disease (5).
  • Infertility
  • HIV infection
    • It has recently been reported that testicular cancer occurs more often in men infected with HIV (3).
  • Environment 
    • In the last two decades, the incidence has increased significantly with respect to geographical differences, which has led to the presumption of environmental conditions as a contributing factor for testicular cancer. This environmental influence occurs early in utero. Hormonal factors have also been suspected, but the etiologic association is most likely complex and not fully understood.

Histology of testicular cancer

Germinal cell tumors

Due to the frequent appearance of several tumor type components in germinal tumors of the testis, the pathologist must study several microscopic sections. The correct tumor classification types and appearance in the actual tumor should be described. This is necessary in order to determine the optimal therapy.

Pure seminomas account for about 50% of all germinal cell tumors of the testis and are usually easily recognizeable by a pathologist. The other tumor types are more difficult to diagnose and more experience is necessary. These tumors are embryonal carcinoma, yolk sac tumor (endodermal sinus tumor), choriocarcinoma, or teratoma. Immunohistochemistry is often helpful in diagnosing the different types of germinal cell tumors.

The non-seminomatous tumor is are of a mixed tumor type where one part is seminoma. If non-seminomatous and seminomatous tumors coexist, the patient is treated according to the most malignant tumor type.

Since spread to abdominal lymph nodes is frequent, ultrasonography and/or radiographic examination is mandatory. When suspicious retroperitoneal  lymph nodes are detected, core biopsy or fine needle biopsy should be performed. An experienced cytopathologist can easily diagnose seminoma metastasis in fine needle aspiration smears. Primary germinal tumors of testis are diagnosed through fine needle aspiration of lymph node metastasis especially from retroperitoneum.

Testicle with seminoma. Click to enlarge. Photomicrograph of seminoma. Click to enlarge.

Intratubular germinal cell neoplasia of unclassified type (IGCNU)

IGCNU are atypical germinal cells with abundant vacuolated cytoplasm and large irregular nuclei with distinct nucleoli situated in the seminal tubules. These lesions are considered precursors to germinal cell tumors

Seminoma

Seminoma is a germinal cell tumor composed of uniform cells with glycogen-rich cytoplasm and large irregular nucleus with one or several distinct nucleoli and marked cell boundaries. Seminoma accounts for 50% of all testicular germinal cell tumors. They seldom occur in childhood, young adults, or in patients over 70 years of age. Seminoma metastasis can be diagnosed by fine needle biopsy because of its typical appearance in smears.

Non-seminomatous tumors

Non-seminomatous tumors account for 50% of all testicular germinal cell tumors. Endodermal sinus tumors and teratomas are seen in childhood and have a different clinical progress than in adults.

Embryonal carcinoma 

Embryonal carcinoma is the next most common testicular germinal cell tumor. These tumor cells are large with atypical nuclei and can grow in solid sheets,  as glands, or in a papillary fashion.

Yolk sack tumor (Endodermal sinus tumor)   

Yolk sac tumors usually present with a loose stroma and a component similar to embryonal carcinoma.  This tumor type can demonstrate different growth patterns, sometimes with differentiation towards liver and intestinal tissue. In children, this tumor appears as a single tumor type, while in adults it is part of a mixed tumor. Yolk sac tumors produce alpha fetoprotein AFP that can be detected and measured in serum, often in very high concentrations. AFP can also be detected in tumor sections by immunohistochemistry.

Teratoma

Teratoma is the next most common testicular tumor in childhood where it is considered benign. In adults, teratomatous tumors are always malignant.

Teratomas consist of different types of tissue and imitate fetal or more mature tissues. Immature components are often neuroectodermal or mesenchymal tissue, while more mature tissue is often cystic with epithelial differentiation or consists of smooth muscle, connective tissue, or cartilage. Since most teratoma consists of a mixture of tissues, the old separation into mature and immature types has been abandoned.
The different tissue components in teratoma can develop into secondary malignancies of the so-called somatic type (earlier “malignant transformation”). An example is development of squamous cell carcinoma from the skin-differentiated part of a teratoma.

Choriocarcinoma

Choriocarinoma is part of a testicular germinal cell tumor in 25% of tumors in adults. It very seldom appears as the single tumor component. Choriocarcinoma is almost never seen in childhood. This tumor produces HCG that can be detected in blood and also in histological sections by means of immunhistochemistry.

Microscopically, there are two types of cells: cyto- and syncytiotrophoblasts. The presence of syncytiotrophoblasts alone is not enough to confirm the diagnosis of choriocarcinoma. These tumors often show necrosis and vascular invasion.

Spermatocytic seminoma

This tumor was earlier believed to be a variant of seminoma, but is now considered to be a separate tumor type. Spermatocytic seminomas account for 1–2% of all germinal cells tumors of the testis and are only seen in adult men, usually older then 50 years.  Microscopically, the tumor cells are polymorphous and surrounded by a myxoid stroma. Spermatocytic seminomas very seldom metastasize, therefore, an orchiectomy is the only necessary treatment, even when the tumor is large. Development of sarcomas have been reported when spermatocytic seminomas have been left untreated for long time.

Sex cord-stromal tumors

There are several different tumor types in this group, but all of them are rare. Only a few of the most common are presented. The tumor often consists of immature tissue without tubulus, groups of leydig cells, or other gonadal stroma cells.

Leydig cell tumor    

These tumors originate from Leydig cells. They account for 1–3% of all testicular tumors and can sometimes produce hormones. Most of these tumors are benign and can be treated by local resection. Malignant transformation occurs in 10% and is related to increased size (> 5cm), increased cellular atypia, increased cell proliferation, necrosis, vessel invasion, and DNA aneuploidy

Sertoli cell tumor

< 1% of testicular tumors. Malignant variants are very rare.

Granulosa cell tumor

Granulosa cell tumors of the testis are microscopically identical to granulosa cell tumors of the ovary. This tumor is extremely rare in adult men, but a juvenile type accounts for 6% of testis tumor in childhood.

Gonadoblastoma

This tumor consists of two cell types: large germinal cell-like seminoma cells and small granulosa-like or sertoli cells. Cells looking like leydig cells or luteinized cells can also occur.

Gonadoblastoma (GB) is seen in individuals with mixed gonad dysgenesis associated with cryporchism, hypospadia, gynecomastia, or female internal genitalia. The risk of developing GB in gonad dysgenesis is about 15-25%. Gonadoblastoma has high a risk of developing germinal cell tumors. GB seldom occurs in phenotypical and genotypical males.

Metastatic patterns of testicular cancer

For both seminoma and nonseminoma testicular cancer, metastasis occurs primarily to the retroperitoneal lymph nodes and subsequently further along the thoracic duct. Spreading can also occur hematogenically, especially for nonseminomas.

About 20% of patients having seminoma tumors have metastases at the time of diagnosis, most often lymph node metastases to the retroperitoneum and/or the supraclavicular region (4).

Nonseminomas often display rapid spreading and about 50% of patients have metastases at the time of diagnosis (4).

Staging of testicular cancer

The clinical staging of testicular cancer in Norway is based on the Royal Marsden Hospital staging system.

Classification of testicular cancer in clinical stages (Royal Marsden)

Stage Disease extensiveness
I No detected metastases, either clinically, radiologically, or biochemically
IMk+ Pathological values of the serum markers AFP and/or hCG beta, without other signs of metastases
II

Lymph node metastases under the diaphragm. The size is measured in horizontal diameter (A < 2cm, B 2-5 cm, C ³ 5 cm)

III Lymph node metastases above the diaphragm
IV

Extralymphatic metastases (most often to the lungs)

L1 3 metastases to the lungs, none > 2 cm
L2 > 3 - ≤ 20 metastases to the lungs, none > 2 cm
L3 < 20 metastases to the lungs, one or more > 2 cm
L4 > 20 metastases to the lungs

 

For the classification of testicular cancer, in addition to the staging, it should also be taken into account which risk profile or prognostic group the patient belongs to. Stage I has histological profiles while the other stages have prognostic groups. This applies to both seminal and nonseminal cancers. Risk profiles describe spreading while prognostic groups describe prognosis when the disease has metastasized.

Seminoma

Risk profiles for no metastatic disease, Stage I

  • Low risk profile - no invasion of rete testis and tumor size < 4 cm 
  • High risk profile - invasion of rete testis and/or tumor size ³ 4 cm
  • Locally advanced - infiltration of capsule

 

Prognosis groups for metastatic disease, Stage II, III, IV. International Germ Cell Cancer Collaborative Group’s classification (10).

Good prognosis (90% of patients) ® 86% 5 year survival 

  • Any primary site, and
  • No nonpulmonary visceral metastases, and
  • Any elevation of hCG and LD and normal AFP

Intermediary prognosis (10% of the patients) ® 72% 5 year survival

  • Any primary site, and 
  • Nonpulmonary visceral metastases, and
  • Any elevation of hCG and LD and normal AFP

For seminoma, there is not a poor prognostic group.

Non-seminoma

Risk profiles for no metastatic disease, Stage I

  • Low risk profile - no blood vessel infiltration
  • High risk profile - blood vessel infiltration  
  • Locally advanced - infiltration of capsule

Prognosis groups for metastatic disease, Stage II, III, IV. International Germ Cell Cancer Collaborative Group’s classification (10 ).

Good prognosis (56% of the patients) ® 92 % 5 year survival

  • Primary tumor in the testicles/retroperitoneum, and
  • No nonpulmonary visceral metastases, and
  • AFP < 1000 ng/ml, and
  • hCG < 5000 IE/l, and
  • LD < 1.5 x upper reference area

Intermediary prognosis (28% of the patients) ® 80% 5 year survival

  • Primary tumor in the testicles/retroperitoneum, and 
  • No nonpulmonary visceral metastases, and 
  • AFP > 1000 and < 10 000 ng/ml, or
  • hCG > 5000 and < 50 000 IE/l, or
  • LD > 1,5 and < 10 x upper reference area 

Poor prognosis (16% of the patients) ® 48% 5 year survival

  • Extragonadal primary tumor in the mediastinum, or
  • Nonpulmonary visceral metastases, or 
  • AFP > 10,000 ng/ml, or
  • hCG > 50 000 IE/l, or
  • LD > 10 x upper reference area  

Spreading occurs more often for nonseminomal tumors. About 50% of the patients have metastases at the time of diagnosis (4).

Different units are used internationally. The conversion factor from biological units (IE) to the SI-system for AFP is: 1kIE/l = 1.4 ng/ml.

Symptoms of testicular cancer

Testicular cancer gives rise to few symptoms. Often, a feeling of heaviness or a change in size is the only symptom. A primary tumor in the testis can be very small, but still metastasize, for example, to the retroperitoneal space.

Common symptoms

  • Mild pain or heaviness in the testicle
  • Sudden back pain may be due to a retroperitoneal lymph node tumor
  • Coughing or dyspnea due to metastases in the lungs or mediastinum

Clinical findings

  • A defined lump in an otherwise normal testicle
  • Change in consistency of the testicle. The cancerous testicle may be harder or softer than the contralateral testicle. 
  • Gynecomastia, due to production of estrogen-producing elements of the tumor
  • Edema or thrombosis in the lower extremity due to compression of the vena cava

Differential diagnoses of testicular cancer

  • Epidydimitis
  • Orchitis
  • Testicular torsion
  • Hydrocele
  • Varicocele
  • Spermatocele
  • Benign tumor
  • Other malignant tumor
    • Lymphoma
    • Sarcoma

Prognosis of testicular cancer

In 2014, there were an estimated 251,194 men living with testis cancer in the United States. The earlier testis cancer is caught, the better chance a person has of surviving five years after being diagnosed. 67.8% are diagnosed at the local stage and the 5-year survival for localized testis cancer is 99.3%. The number of testis cancer deaths is highest among men aged 20-34. Death rates have been stable over 2005-2014 (1).

The prognosis depends on the histology, extent of the disease, localization of metastases, tumor size and level of tumor markers. Patients with extragonadal nonseminoma with mediastinal localization fall into a poor prognostic group. Relapse after previous chemotherapy generally has a poor prognosis. About 25% of the patients live for 5 years. (2)

Five percent of patients with testicular cancer will develop new cancer in the contralateral testicle in their lifetime. (4)

Seminoma

All patients with metastasizing seminoma have either a good or intermediate prognosis. Seminoma in the good prognosis group has a 5-year survival of 86%, while the intermediary prognosis group has a 72% survival. (7)

Nonseminoma

Nonseminoma in the good prognostic group has a 5-year survival of 92%. In the intermediary prognostic group, 5-year survival is 80%. The poor prognostic group has a 48% of 5-year survival. (8)

 

 

Five-year relative survival of patients with testicular cancer, in percent, according to stage during the diagnosis period 1974–2013.

Source: Cancer Registry of Norway

 

References on testicular cancer

  1. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD
  2. Dahl, Olav, Lehne, Gustav. Cancer testis. In Dahl O, Lehne G, Baksaas I, Kvaløy S, Christoffersen T (eds) Cytostatika. Medikamentell kreftbehandling. 7. utgave. Helsebilioteket, Oslo, 2009; 401-408 ISBN 978-829923312-5
  3. DeVita VT Jr, Hellman S, Rosenberg SA. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, p 1269-90 
  4. Kåresen R, Wist E. Kreftsykdommer - en basisbok for helsepersonell. 2. utgave. Oslo: Gyldendal Norske Forlag; 2005. s. 237-42
  5. Heimdal K, Olsson H, Tretli S, Flodgren P, Børresen AL, Fosså SD: Familial testicular cencer in Norway and Southern Sweden. Br J Cancer 1996, 73, 964-69
  6. Shmoll HJ, Souchon R, Krege S, Albers P, Beyer J, Kollmannsberger C et al. European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG)  Ann Oncol 2004 sept; 15 (9) :1377-99
  7. Huddart RA, Birtle AJ. Recent advances in treatment of testicular cancer. Expert Rev Anticancer Ther 2005 feb; 5(1): 123-38
  8. Dearnaly DP, Huddart RA, Hawich A. Managing testicular cancer. Br. Med. J. 2001; 322: 1583-8
  9. Brydøy M, Fosså SD, Klepp O, Bremnes RM, Wist EA, Wentzel-Larsen T et al: Paternity following treatment for testicular cancer. J Natl Cancer Inst 2005 nov 2; 97(21): 1580-8
  10. Lehne G, Angelsen A, Langberg CW et al. Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av testikkelkreft. IS-1907 Helsedirektoratet 2011
  11. Einhorn LH, Wiliams SD, Chamness A, Brames MJ, Perkins SM, Abonour R: High-Dose Chemotherapy and Stem-Cell Rescue for Metastatic Germ-Cell Tumors. N Engl J Med 2007; 357: 340-8
  12. Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av testikkelkreft (2013) Helsedirektorate (National guidelines for diagnostic, treatment and follow-up care of testicular cancer, Norwegian Directorate of Health)
 

Diagnostics of testicular cancer

The work-up for testicular cancer includes:

  • anamnesis
  • clinical examinations
  • blood tests
  • radiology examinations
  • biopsy
  • sperm tests 

Ananamnesis

  • Are there others in the family with germ cell tumors?
  • Has the patient had descendency problems?
  • Has the patient had fertility problems?
  • Has the patient had orchitis previously?
  • Has the patient used anabolic steroids?
  • Has the patient previously undergone groin or scrotal surgery (change of lymphatic drainage)?

Clinical examinations

  • Examination of the testes, abdomen, lymph nodes in the groin and neck
  • Examination of the breasts for gynecomastia

Blood tests

  • Tumor markers (APF, hCG, LD) AFP and hCG should be taken at least twice, preferably in 2 consecutive days to assess changes in marker values. AFP has a half-life of 5-7 days and hCG has a half-life of 1-2 days. 
  • Hormone tests (FSH, LH, testosterone, estradiol, SHBG, prolactin)
  • Virus serology (HIV, Hepatitis B/C)

Radiology examinations

  • X-ray of thorax
  • CT of thorax, abdomen and pelvis to determine if there are metastases
  • Ultrasound of the testes

Biopsy

  • A biopsy is usually unnecessary for an orchiectomy because the ultrasound is usually sufficient to determine if there is a malignant tumor. If there is uncertainty, an open exploration of the testes is performed with frozen section diagnostics.
  • A biopsy of the contralateral testicle should be taken if there are germ cell tumors in the family, descent problems, infertility, or an atrophic testicle (volume < 12 ml).  
  • Biopsy from both testicles for extragonadal germ cell tumors, even if the ultrasound is normal.

Sperm tests 

  • Cryopreservation of sperm should be performed before chemotherapy, a retroperitoneal node dissection, or radiation. It is becoming more common to cryopreserve sperm before an orchiectomy. 

Alfa-fetoprotein (AFP) is elevated in 50–60% of patients with nonseminomas while seminomas do not produce AFP. Positive AFP tests therefore exclude seminoma.  hCG (human chorionic gonadotropin) is elevated in 30–35% of nonseminomas and 10–25% of seminomas.

Treatment of testicular cancer

Treating testicular cancer includes surgery, chemotherapy, and some radiation therapy. Treatment requires a close collaboration between the oncologist, urologist, pathologist, and radiologist. Choice of treatment depends on whether the cancer is seminoma or nonseminoma, the stage of the disease, and the extensiveness. Additionally, the level of tumor markers AFP and HCG are critical for the choice of treatment.

All patients with testicular cancer will undergo an orchiectomy before another treatment is initiated.

After an orchiectomy, supplementary treatment may be necessary in the form of chemotherapy or radiation. For localized relapse or few regional metastases, supplementary surgery or radiation may be an alternative. Patients with nonseminoma or retroperitoneal node metastases will undergo a routine retroperitoneal node dissection 4-6 weeks after chemotherapy. 

For stage I seminoma and nonseminoma with a low-risk profile, there is no treatment after an orchiectomy except for follow-up.  

Surgery of testicular cancer

Orchiectomy

An orchiectomy is carried out when the ultrasound and clinical examinations indicated malignancy. In cases where the preoperative diagnosis is ambiguous, an open exploration of the testicle should be performed where a wedge-shaped biopsy is removed for frozen section diagnostics. If the frozen section confirms malignancy, a radical orchiectomy should be performed.

It may also be necessary to take a biopsy from the contralateral testicle to assess if there are carcinoma in situ changes. APF, HCG and LD should be measured before the orchiectomy.

Sperm banking will be offered to the patient if possible. This is done in cases where the patient needs supplementary treatment which will affect fertility or if the other testicle is atrophic or absent.

See procedure

Retroperitoneal node dissection

A retroperitoneal node dissection is necessary for some patients after chemotherapy treatment is completed. This surgery is performed only for nonseminoma stage II, III, and IV.

This procedure is extensive. A low midline incision is made right below the sternum and down to the navel. The lymph nodes which are associated with the involved testicle is removed. If there is suspicion of metastasis, the contralateral lymph nodes are also checked.

Retroperitoneal node dissections have historically be associated with significant postoperative complications. A large portion of patients undergoing this type of surgery experienced retrograde ejaculation. This has since been reduced due to better surgical techniques applying surgery sparing nerves and lymph drainage.

See procedure

PROSEDYRER

Orchiectomy

General

In cases where the diagnosis cannot be determined clinically, an open exploration of the testicle must be performed. If malignant cells are verified by frozen section, a radical orchiectomy should be performed under the same anesthesia.

The procedure may be performed under general or epidural anesthesia. It is very important that frozen sectioning service is available in the surgical theater.

Indication

  • To determine whether clinical changes in the testicle are malignant and if so, remove the testicle.

Goal

  • To diagnose and cure the patient

Equipment

  • Universal tray

Preparation

  • The patient should understand the purpose of the procedure and the possibility that an orchiectomy may be performed under the same anesthesia. 
  • The patient must be questioned in advance about prosthetics.
  • If there is a solitary testicle, the patient must be informed about infertility and homone replacement possibilities.
  • Thrombosis prophylaxis
  • Plan for biopsy of the contralateral testicle, if necessary

Implementation

  • Make a diagonal incision in the groin up to the fascia.
  • Split the fascia from the outer inguinal canal opening, up and past the inner inguinal canal opening. 
  • The spermatic cord is dissected free in the upper third.
  • The permatic cord is clamped with a vessel forceps.
  • Release the rest of the spermatic cord and the testicle can be pulled up and out of the incision.
  • Cover the incision with a compress.
  • Remove a wedge-shaped piece of the tumor for frozen sectioning. If the tumor is so small that in cannot be clinically identified, peroperative ultrasound may ensure the biopsy. 

If a malignant tumor is confirmed by frozen section, a radical orchiectomy will be performed.

  • Divide all fibers of the cremaster muscle until the testicular vein is free.
  • Push the peritoneum away from the veins.
  • Clamp and ligate the retroperitoneal vein.
  • Clamp the duct the same way.
  • Close the anterior wall of the inguinal canal and perform thorough hemostasis.  
  • Place the testicle prosthesis in the scrotum if necessary.
  • Close the incision. 

Follow-up Care

  • Postoperative bleeding and hematoma
  • Further work-up and treatment depending on the extent of the cancer

Retroperitoneal node dissection for metastasizing testicular cancer

General

Testicular cancer metastasizes lymphatically. Metastases are localized in the drainage area from the inner inguinal opening along the common iliac vein to lateral to the caval vein for right-sided cancer and along the aorta for left-sided cancer. Spreading stays for a long time distally to the renal vein on both sides before it metastasizes further up under the diaphragmatic curae and further to the mediastinum. The metastasis area on the right side extends along and around the caval vein and aorto-cavale area and can "jump" over to the left side in the area distal to the renal vein. On the left side, the metastasis area is located along and around the aorta and can "jump" over to the right side, also msot often distal to the renal vein.

Indication

  • Testicular cancer with spreading to the retroperitoneal space

Goal

  • The main goal is to cure the disease. However, the surgery is also of diagnostic importance for identifying tumors in the lymph nodes and deciding whether this is benign or malignant. This will be of importance for possible supplementary treatment and also for the follow-up procedure.  

Equipment

  • Abdominal tray
  • Bookwalters retractor
  • Intestinal bag
  • Stapling instrument

Instruments for vascular surgery must be available.

Preparation

The case should be discussed by a team consisting of a urologist, oncologist, and radiologist. Localization of metastases should be documented by a radiologist. The oncologist should provide the disease history, extent of the primary diagnosis and preoperative treatment. The team should agree on the indication for the operation and how comprehensive the surgery should be. This is determined by the extent of the spreading and is assessed by CT images before and after chemotherapy. The operation may be assessed for total bilateral removal of all fat tissue with lymph nodes along and behind the caval vein and aorta, as well as the aorta/caval space, possibly up and behind the diaphragmatic crurae. If the spreading is so extensive that vascular and/or thoracic surgery may be necessary, then the images must be discussed with a vascular/thoracic surgeon.

  • Inform the patient
  • Thrombosis prophylaxis 
  • Bowel emptying
  • Premedication

Implementation

The patient lies in a supine position. The incision is made from the sternum and past the navel. A Bookwalters retractor is mounted. The small intestine with the mesentery is dissected free from the ligament of Treitz to the coecum. The small intestine is packed in an intestinal bag and held out of the abdominal cavity.

Left-sided dissection

  • All fatty tissue with lymph nodes is dissected from the common iliac vein to around the crossing of the ureter. Along with the rest of the testicular vessels, the fatty tissue is freed from the posterior abdominal wall and common iliac artery up to the bifurcation by retrograde dissection.  
  • Spare the inferior mesenterial artery. If there are metastases in this area, this may be removed.
  • Dissect the ureter and secure it. 
  • All fatty tissue and nodes in front of the aorta are dissected from the aorta. It is important to secure the lumbar vessels while releasing up toward the renal vein.
  • Remove all fatty tissue along the renal vein. 
  • Ligate the testicular vessels. During the dissection, ganglion and nerves are identified. These should be spared to avoid retrograde ejaculation. 

Right-sided dissection

In principle, the procedure is the same, however, the surgeon works more toward the caval vein and in the aorto/caval space.

Total retroperitoneal node dissection

This includes both sides. The surgeon must often dissect both the caval and aorta from the posterior abdominal wall to include all of the nodes.  

The operation is concluded by securing full hemostasis and lymphostasis. A drain is installed when the surgeon decides. The small intestine is reinserted in the abdominal cavity and the peritoneum is adapted.

Follow-up

Observations

  • Postoperative intestinal paresis
  • Chyle leakage from the lymphatic duct
  • Retrograde ejaculation  

Upon discharge, the patient should confer with the oncologist for further follow-up.

The patient should have follow-up with their primary doctor.

Drug therapy of testicular cancer

Before starting chemotherapy, kidney function should be evaluated (GFR) as well as an EKG. Cisplatin, etoposide, bleomycin and ifosfamide are considered the most effective for treatment of malignant germ cell tumors.

If metastases are found, the primary treatment is almost always chemotherapy with combinations of cisplatin, etoposide, and bleomycin. Depending on the extent of the disease, 3-4 courses are usually administered. The accumulative bleomycin dose should not surpass 360,000 IE due to the increase in risk of lung damage. 

Recently, one course of carboplatin has been introduced as adjuvant treatment for stage I seminoma with a high risk profile. For seminoma, bleomycin can be excluded for stage III, and instead give 4 EP courses, which corresponds to 3 BEP courses. For recurrence, TIP treatments are used as any internationally established standard second line treatments do not exist. Alternatively, paclitaxel-gemcitabin can be used and possibly combined with cisplatin or oxaliplatin. Other variations are EMA-CO (especially for choriocarcinoma), VIP, VeIP, and OI. 

High-dose chemotherapy with stem cell support (HMAS) is used for recurrence during the first two years.

Click for flow-chart:

  • Seminoma
  • Nonseminoma  

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 testicular cancer

Adjuvant radiation therapy for stage I seminoma is no longer recommended as standard treatment. Today, chemotherapy for testicular cancer is given as a single course of carboplatin. The treatment is simpler to carry-out, causes less acute side effects and is not associated with the same delayed side effects such as secondary cancer and benign abdominal illnesses, as radiation therapy.

If radiation therapy is chosen it is administered for seminoma stage I and stage II A,

Patients with nonseminoma should usually not have radiation therapy.

In cases where there is a new primary tumor in the other testicle in a patient previously treated with an orchiectomy, a tumor resection should be considered instead of a new orchiectomy. This is possible for small tumors, however, the surgical treatment must then be followed by radiation treatment to the remaining testis with 2 Gy x 10, for a total 20 Gy. By sparing testicular tissue, testosterone production is preserved, and hormone substitution is not necessary. 

PROSEDYRER

Radiation therapy for testicular cancer

General

Adjuvant radiation therapy for testicular cancer is no longer recommended as standard treatment. It can be considered for seminoma stage I og II A.
Patients with nonseminoma should usually not have radiation therapy.

Indications

Seminoma stage I and II A

Goal

To cure 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 malignancy.

ITV (Internal Target Volume)

Target volum

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 set-up margin taking into account internal movements, variation in patient positioning, and field modeling.

 

Target volume

GTV (=Gross Tumor Volume)

Is defined as any enlarged metastatic lymph node, that is clinical stage IIA

CTV (=Clinical Target Volume)

CTV of the para-aortic region comprises the combined volume of the inferior vena cava and aorta including visible lymph nodes, the ipsilateral kidney vein without lateral margin, and any GTV with 1,4 cm margins in all directions from the upper border of the T11 vertebral body to the aortic bifurcation. If the ipsilateral iliacal lymh nodes are to be included (for example clinical stage  IIA), CTV must be expanded with the combined volume of the common and the external iliacal vessels down to the upper limit of the foramen obturatorium including all visible lymph nodes and any GTV with 1,4 cm margins in all directions.
In the case of prior inguinal or scrotal surgery or in locally advanced disease (T4 tumor) inguinal lymph nodes with 1,4 cm margins in all directions should be added to the CTV.

ITV (=Internal Target Volume)

ITV (internal target volume) is equal to CTV since the movement of this body part is ignorable

PTV (Planning Target Volume)

PTV (planning target volume) is equal to ITV plus planning margins (penumbra).

 

Preparation

Position/Fixation

  • The patient lies in the supine position
  • Fixation in accordance with local practice to ensure reproducible position throughout the treatment
  • The orchiectomy scar is marked with a lead wire
  • The contralateral  testis is shielded with lead
  • Special gonadal shielding is usually not necessary, but gonadal dosage calculation should be done for patients under 50 years

Technique

Dose planning with CT. Volumtarget is based on the blood vessels, this because spread via lymph vessels follow blood vessels like aorta, vena cava inferior, ipsilateral renal vein and ipsilateral pelvic veins (iliaca communis and externa).

Radiation quality

Minimum 6 MV photons

Organs at risk

Both kidneys are marked as organs at risk. Not more than 25% of each kidney tolerates more than 20 Gy radiation dose.

Implementation

Seminoma stage I

Radiation dose

  • 2 Gy x 10 (total 20 Gy), 5 fractions a week  to the paraaortal lymph nodes.

The radiation field should include ipsilateral iliacal and inguinal lymph nodes, if the tumor is stage T4 or the patient underwent scrotal or inguinal surgery.

Seminoma stage II A

Radiation dose

  • 2 Gy x 15 (total 30 Gy), possibly 1.8 Gy x 15 (total 27 Gy), 5 fractions a week to paraaortal and ipsilateral iliacal lymph nodes.

If  the patient underwent  scrotal or inguinal surgery or if the tumor is stage 4, inguinal lymph nodes is included  in the target volume.

Follow-up

Organs at risk

Kidneys

  • Patients treated with cisplatin-based chemotherapy should not have aminoglycosides the first 3 months after treatment.

Skin

  • Acute dermatitis in the scrotal skin may occur since there are many skin folds and the skin is exposed to moisture during fractions.

Mucosa

  • In the urethra and rectum, mucositis  may occur with dysuria  and  rectal symptoms.

The gastrointestinal tract

  • Nausea, diarrhea, abdominal pain (stomach ache) and fatigue (tiredness).

Long-term risks

  • Irradiation of the testicles in the mentioned doses will cause permanent sterility. Reliable birth control is still recommended during treatment and the first year after. Testosterone production may decline many years after treatment and should be evaluated regularly. 
  • Secondary malignancy caused by radiation therapy.

Complication treatment of testicular cancer

Both drug and radiation therapy cause side effects to a varying degree. It is usually necessary to provide supportive care to reduce the side effects.

Drug therapy can cause

  • Nausea to varying degrees. Good prophylaxis and treatment is critical. See procedure.
  • Febrile neutropenia due to a reduced immune system. Fever is often the only symptom. See procedure.
  • Need for transfusions of SAG thrombocytes.

Radiation therapy can cause

  • Nausea

Sperm Banking

If possible, all patients should be offered sperm baking if they will undergo treatment that will compromise their fertility. Chemotherapy reduces the quality of sperm, but this usually normalizes after 1-2 years. About 71% of all testicular cancer patients are able to have children after their first treatment (9). See procedure.

PROSEDYRER

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.

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.

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.

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.

Sperm Banking

General

Sperm banking services may apply to patients having a disease or undergoing treatment which reduces or eradicates the patient's fertility. The decision for storage is made by the doctor in charge of the patient in cooperation with the chief physician at the andrology laboratory.

Stored sperm can only be used for assisted fertilization by the patient's spouse or partner in a stable relationship (duration more than 2 years).

The offer for freezing and storing sperm does not guarantee treatment with assisted fertilization. The decision for this is made by the treating doctor according to guidelines and laws for assisted fertilization.

The patient may store up to three samples. The samples should be taken with a few days in between and the patient should not have ejaculated for two days prior to sample collection.

Indications

  • Cancer treatment rendering a man infertile.

Goal

  • The possibility of having children after treatment is concluded.

Equipment

  • A urine sample container.
  • A room for the patient to be undisturbed.

Preparation

  • Inform the patient verbally and in writing.
  • Conform to rules and guidelines.
  • A blood test for HIV and hepatitis to rule out infectious sperm.

Imlementation

  • The sperm sample is collected via masturbation and is collected directly into a urine sample container. A condom should not be used as this contains spermicide.
  • The sample should be allowed to cool and should be delivered to the andrology laboratory in less than one hour after ejaculation.

Follow-Up

  • The sperm sample is held in under quarantine until HIV and hepatitis results are available.
  • The sperm can be stored for 10 years and possibly longer if the patient desires.
  • After filling 55 years or death the sperm is destroyed.

Intravenous Extravasation of Cytotoxic Drugs

General

Intravenous extravasation occurs when there is an accidental leak of intravenous cytotoxic fluid (chemotherapy drug) from the vein to surrounding tissue.  

If chemotherapy is given in a peripheral vein, a large vein should be used, which is preferably in the underarm. Before the infusion begins, the vein should be checked for leaks by injecting NaCl 9 mg/ml or glucose 50 mg/ml. Backflow should also be checked. The patient must be informed that pain or burning in the area is not normal and they must inform the doctor.

Cytotoxic chemotherapy drugs should always be given through a central vein catheter to reduce the risk of intravenous extravasation.

Risk factors for intravenous extravasation:

  • Small veins (infants and children)
  • Brittle veins (elderly patients)
  • Reduced physical health (cancer patients)
  • Sclerosizing veins
  • Rolling veins
  • Poor circulation (if the needle is placed in an arm with edema)
  • Obstructed vena cava (raised venous pressure may cause leakage)
  • Conditions such as diabetes and radiation damage
  • Obesity

Chemotherapeutic drugs are separated into three groups according to the degree of toxicity:

  • Non-cytotoxic/irritating
  • Tissue irritant
  • Cytotoxic

Cytotoxic drugs can cause blisters or ulcerations leading to skin necrosis if extravasation occurs. If intravenous extravasation is left untreated, it can lead to permanent tissue damage, necrosis, scar formation around ligaments, nerves and joints, infections, abscesses, contractures, and in the worst case, amputation.

Indication

  • Intravenous extravasation of cytotoxic drugs. 

Goal

  • Limit damage of tissue from intravenous extravasation.

Definitions

Non-cytotoxic drugs or non-irritants

Non-cytotoxic/non-irritant drugs normally do not cause skin necrosis.

Irritants

Drugs that are tissue irritants can cause pain in and around the injection site and along the vein. They can also cause inflammation. Some tissue irritating drugs cause ulceration if a large amount leak extravasally.

Cytotoxic drugs

Cytotoxic drugs are categorized into subgroups according to the mode of damage. This categorization is important for the choice of treatment.

DNA-binding

DNA binders absorb locally into the cells, bind to DNA, and cause cell death. After cell death, the drug molecule can be liberated from the dead cell and start killing healthy cells. This group is divided into these subgroups:  

  • Anthracycline
  • Alkylating drugs
  • Other

For doxorubicin and mitomycin, progrediating tissue damage has been reported over weeks, and in some cases, months after intravenous extravasal injection.

Non DNA-binding

This group of medications can lead to cell death through other mechanisms than DNA binding drugs. This group is divided into:

  • Vinca alkaloids
  • Taxanes

 

Chemotherapy cytotoxicity (1)
Cytotoxic, necrosis

Irritant, can cause flaking or inflammation

Non-cytotoxic or non-irritant
Amsacrine Cisplatin Aldesleukin
Decarbazine Doxorubicin liposomal Alemtuzumab
Dactinomycin Estramustine** Asparaginase
Docetaxel**** Etoposide Bleomycin
Doxorubicin* Floxuridine Bevacizumab
Epirubicin* Florouracil Bortezomib
Daunorubicin* Irinotecan Cetuximab
Idarubicin* Carboplatin Cyclophosphamide**
Irinotecan Carmustin** Cytarabine
Kloremtin** Oxaliplatin Fludarabine
Mitoguazon Pemetrexed Gemcitabine
Mitomycin-C Ralitrexed Ibritumomab tiuxetan
Mitoxanthrone Temoporfin Ifosfamide**
Paclitaxel**** Teniposide Interferon
Plicamycin Topotecan Cladribine
Streptozocin Methylene blue***** Clofarabine
Verteporphin   Melfalan**
Vinblastine***   Methotrexate
Vindesine***   Rituximab 
Vincristine***   Tiotepa**
Vinorelbine***   Trastuzumab

 * = Anthracycline

** = Alkylating agents

*** = Vinca alkaloids

**** = Taxanes

*****= Methylene blue is not a chemotherapy drug, but is used for ifosfamide-induced encephalopathy, and is therefore included on the list.  

All chemotherapy drugs can damage tissue in high concentrations.

References

 

  1. Allwood M, Stanley A WP. The Cytotoxics Handbook. Ed. 4th ed. 2002. 2001
  2. Ekstravasation Guidelines Implementeringsværktøj [Online] 2007 [hentet 10. mars 2009]; Tilgjengelig fra URL: http://www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=2726

Preparation

Identification of an extravasal injection

  • A burning, stinging pain or other acute change of the puncture site.
  • Local redness or inflammation of the skin around the puncture site.
  • The infusion rate slows/stops.
  • Swelling of the puncture site.

Extravasation has probably also occurred if blood cannot be aspirated, resistance is felt on the plunger when a syringe is used, and/or there is no current if the drug is infused. 

 

Implementation

Flow chart for treatment of intravenous extravasation of cytotoxic drugs:

Emergency response:

  • Stop the infusion immediately.
  • Allow the needle to remain and aspirate with as much water as possible. Avoid applying direct pressure on the area of extravasation.  
  • The volume, type, and time of extravasation should be recorded.
  • A doctor/plastic surgeon should be called for to examine the patient.
  • The damaged area and skin manifestations should be marked/photographed.
  • The affected area should be kept elevated.
  • The remaining chemotherapy should not be discarded.
  • The patient should be informed about what is happening and what must be done. 
  • The needle is removed while aspirating.
  • Pain medication is administered if necessary.

Based on which medication has leaked extravasally, the doctor or plastic surgeon will decide whether conservative treatment or primary surgery is necessary.

Conservative treatment

Conservative treatment consists of two different treatment strategies to limit the damage by extravasation: localize/neutralize and spread/dilute (2).

Localize and neutralize:

  • Place an ice pack on the area for 15-20 minutes, at least 4 times daily for multiple days. A coldpack is used to limit spreading of the drug. Studies have indicated that there is reduced cellular uptake of drugs at lower temperatures (2).
  • The drug that has leaked extravasally is neutralized by a specific drug if the instructions are followed.
  • The affected area of the body should be kept elevated.

Spread and dilute (applies to vincristine, vinorelbine, vindesine, and vinblastine):

  • Warm compresses are placed on the area for 15–20 minutes, at least 4 times daily, for multiple days.
  • To dilute the drug that has leaked extravasally, many subcutaneous injections are given with hyaluronidase diluted with sterile water.

If the patient has lasting pain or blisters, surgical treatment should be considered by excising the area with direct sutures, skin transplant, or flap reconstruction.

Another type of reconstruction may be necessary at a later time. 

Treatment 

Dexrazoxan (Savene®)

Dexrazoxan is an EDTA analong used to treat extravasation of anthracycline (doxorubicin, daunorubicin, epirubicin, idarubicin). The mechanism of action is not fully understood, but it is believed that it may work through two mechanisms. By chelating iron, the formation of the iron-doxorubicin complex and  iron-mediated hydroxy radicals are hindered, which cause oxidative damage to cell membranes and proteins. Another possible mechanism is inhibition of topoisomerase II (3).

Treatment lasts for 3 days. In all cases of extravasation of anthracycline, this treatment should be assessed by an oncologist and surgeon/plastic surgeon.

  • The first infusion should start as soon as possible and within 6 hours after extravasation. 
  • On the following two days, the infusions should occur at the same time as the previous infusion (+/- 3 hours).
  • If possible, the infusion should be placed in a vein where there is no extravasation.
  • An ice pack or cooling element used on the area must be removed at least 15 minutes before the infusion starts to ensure sufficient blood circulation.

Cost

A package costs about NOK 100,000.-. If the expiration date runs out, the drug is replaced by the pharmaceutical company free of cost.

Dimethylsulfoxide (DMSO)

DMSO (70–90% solution) quenches free radicals and prevents formation of sores. The solution can be used after extravasation of cytotoxic drugs (anthracycline, mitomycin C, doxorubicin, idarubicin, epirubicin andactinomycin D) together with cooling of the area when other treatment methods cannot be used (5, 6). DMSO cannot be used in combination with dexrazoxan (3, 4).

  • An area twice as big as the affixed area is treated with the solution every 8 hours for one week.(6)

Hyaluronidase

Hyaluronidase is an enzyme that breaks down hyaluronic acid found in connective tissue. This leads to permeability and increased diffusion of the drug that is leaking extravasally, and is used only to spread the drug out into the tissue (spread and dilute).  

  • Hyaluronidase is administered subcutaneously or intradermally in 5-10 locations on the border of the area where the drug has leaked extravasally (7).

Surgical treatment

"Wash-out"

The washing out technique can be used with chemotherapy drugs when tissue damage is likely. When used with anthracycline, it is important that this is performed before the chemotherapy drug goes intracellularly.

In most cases, this is a very successful method if it is performed within 6 hours after the extravasation.

  • The patient receives regional anesthesia.
  • Multiple small incisions must be made to ensure sifficient access to the damaged subcutaneous tissue.
  • With an infiltration needle, which is usually used for liposuction, isotonic NaCl is flushed through the tissue and drains through the incisions.
  • The infiltrated fluid is then carefully removed by suction through a small needle used for liposuction.
  • The procedure is repeated until 300-500 ml fluid is used.

References

  1. Ekstravasation Guidelines Implementeringsværktøj [Online] 2007 [hentet 10. mars 2009]; Tilgjengelig fra URL: http://www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=2726
  2. Hasinoff BB. Dexrazoxane use in the prevention of anthracycline extravasation injury. Future Oncol 2008; 2006: 1–15.
  3. Statens legemiddelverk. Preparatomtale. 2008
  4. Langstein HN, Duman H, Seeling D, Butler CF, Evens GR. Retrospective study of the management of chemotherapeutic extravasation injury. Ann Plastic Surg 2002; 49: 369–74. 
  5. Bertelli G, Gozza A, Forno GB, Vidili MG, Silvestro S, Venturini M et al. Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: A prospective clinical study. J Clin Oncol 1995; 13: 2851–5.
  6. Clinical Pharmacology© 2008 database. Hyaluronidase. 2008.

Follow-Up

For conservative treatment 

The damaged tissue should be observed for multiple weeks (with mitomycin at least 13 weeks) since necrosis can occur after months.

For emergency surgical treatment

Patients treated by a plastic surgeon should receive follow-up care by the surgeon until the wound has healed.

 

Intravenous extravasation of cytotoxic drugs.Intravenous extravasation of cytotoxic drugs.Extravasation of tissue toxic chemotherapy

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

  1. Gritz E, Fingeret M, Vidrine D. Tobacco control in the oncology setting. American Society of Clinical Oncology, eds Cancer Prevention An ASCO Curriculum Alexandria, VA: American Society of Clinical Oncology. 2007.
  2. ASCO ASoCO. Tobacco Cessation Guide for Oncology providers,. 2012 (02.12.2014).
  3. Zevallos JP, Mallen MJ, Lam CY, Karam-Hage M, Blalock J, Wetter DW, et al. Complications of radiotherapy in laryngopharyngeal cancer: Effects of a prospective smoking cessation program. Cancer. 2009;115(19):4636-44.
  4. Obedian E, Fischer DB, Haffty BG. Second malignancies after treatment of early-stage breast cancer: Lumpectomy and radiation therapy versus mastectomy. Journal of Clinical Oncology. 2000;18(12):2406-12.
  5. Park SM, Lim MK, Jung KW, Shin SA, Yoo K-Y, Yun YH, et al. Prediagnosis smoking, obesity, insulin resistance, and second primary cancer risk in male cancer survivors: National Health Insurance Corporation Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2007;25(30):4835.
  6. Van Den Belt-Dusebout AW, De Wit R, Gietema JA, Horenblas S, Louwman MWJ, Ribot JG, et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. Journal of Clinical Oncology. 2007;25(28):4370-8.
  7. Warren GW, Kasza KA, Reid ME, Cummings KM, Marshall JR. Smoking at diagnosis and survival in cancer patients. International Journal of Cancer. 2013;132(2):401-10.
  8. Hooning MJ, Botma A, Aleman BMP, Baaijens MHA, Bartelink H, Klijn JGM, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. Journal of the National Cancer Institute. 2007;99(5):365-75.
  9. Li CI, Daling JR, Porter PL, Tang M-TC, Malone KE. Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor–positive invasive breast cancer. Journal of Clinical Oncology. 2009;27(32):5312-8.
  10. Kenfield SA, Stampfer MJ, Chan JM, Giovannucci E. Smoking and prostate cancer survival and recurrence. JAMA - Journal of the American Medical Association. 2011;305(24):2548-55.
  11. Joshu CE, Mondul AM, Meinhold CL, Humphreys EB, Han M, Walsh PC, et al. Cigarette smoking and prostate cancer recurrence after prostatectomy. Journal of the National Cancer Institute. 2011;103(10):835-8.
  12. Phipps AI, Baron J, Newcomb PA. Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: The Seattle Colon Cancer Family Registry. Cancer. 2011;117(21):4948-57.
  13. Kountourakis P, Correa AM, Hofstetter WL, Lee JH, Bhutani MS, Rice DC, et al. Combined modality therapy of cT2N0M0 esophageal cancer. Cancer. 2011;117(5):925-30.
  14. Waggoner SE, Darcy KM, Fuhrman B, Parham G, Lucci J, Monk BJ, et al. Association between cigarette smoking and prognosis in locally advanced cervical carcinoma treated with chemoradiation: A Gynecologic Oncology Group study. Gynecol Oncol. 2006;103(3):853-8.
  15. Schlumbrecht MP, Sun CC, Wong KN, Broaddus RR, Gershenson DM, Bodurka DC. Clinicodemographic factors influencing outcomes in patients with low-grade serous ovarian carcinoma. 2011. p. 3741-9.
  16. Nagle CM, Bain CJ, Webb PM. Cigarette smoking and survival after ovarian cancer diagnosis. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2557-60.
  17. Ehlers SL, Gastineau DA, Patten CA, Decker PA, Rausch SM, Cerhan JR, et al. The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia. Bone Marrow Transplant. 2011;46(2):285-90.
  18. Talamini R, Polesel J, Spina M, Chimienti E, Serraino D, Zucchetto A, et al. The impact of tobacco smoking and alcohol drinking on survival of patients with non-Hodgkin lymphoma. International Journal of Cancer. 2008;122(7):1624-9.
  19. Toll B, Brandon T, Gritz E, Warren G, Herbst R. AACR Subcommittee on Tobacco and Cancer. Assessing tobacco use by cancer patients and facilitating cessation: an American Association for Cancer Research policy statement. Clin Cancer Res. 2013;19:1941-8.
  20. Arntzen A, Sandvold B. Hvordan veilede om røykeslutt? Sykepleien Forskning. 2010;5(3):182-90.
  21. Dresler CM. Is it more important to quit smoking than which chemotherapy is used? 2003. p. 119-24.
  22. Hsu CCT, Kwan GNC, Chawla A, Mitina N, Christie D. Smoking habits of radiotherapy patients: Did the diagnosis of cancer make an impact and is there an opportunity to intervene? J Med Imag Radiat Oncol. 2011;55(5):526-31.
  23. Richards J. Words as Therapy: Smoking Cessation. The journal of family practice. 1992;34(6):687-92.
  24. Cooley ME, Lundin R, Murray L. Smoking cessation interventions in cancer care: opportunities for oncology nurses and nurse scientists. Annual review of nursing research. 2009;27:243.
  25. Mazza R, Lina M, Boffi R, Invernizzi G, De Marco C, Pierotti M. Taking care of smoker cancer patients: a review and some recommendations. Annals of Oncology. 2010;21(7):1404-9.
  26. Waller LL, Weaver KE, Petty WJ, Miller AA. Effects of continued tobacco use during treatment of lung cancer. 2010. p. 1569-75.
  27. Peppone LJ, Mustian KM, Morrow GR, Dozier AM, Ossip DJ, Janelsins MC, et al. The Effect of Cigarette Smoking on Cancer Treatment-Related Side Effects. Oncologist. 2011;16(12):1784-92.
  28. Kuri M, Nakagawa M, Tanaka H, Hasuo S, Kishi Y. Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery. Anesthesiology. 2005;102(5):892.
  29. Krueger JK, Rohrich RJ, Mustoe TA. Clearing the smoke: The scientific rationale for tobacco abstention with plastic surgery. 2001. p. 1074-5.
  30. Nakagawa M, Tanaka H, Tsukuma H, Kishi Y. Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery. Chest. 2001;120(3):705-10.
  31. Barrera R, Shi W, Amar D, Thaler HT, Gabovich N, Bains MS, et al. Smoking and timing of cessation: Impact on pulmonary complications after thoracotomy. Chest. 2005;127(6):1977-83.
  32. Mason DP, Subramanian S, Nowicki ER, Grab JD, Murthy SC, Rice TW, et al. Impact of Smoking Cessation Before Resection of Lung Cancer: A Society of Thoracic Surgeons General Thoracic Surgery Database Study. Annals of Thoracic Surgery. 2009;88(2):362-71.
  33. Gajdos C, Hawn MT, Campagna EJ, Henderson WG, Singh JA, Houston T. Adverse Effects of Smoking on Postoperative Outcomes in Cancer Patients. Ann Surg Oncol. 2012;19(5):1430-8.
  34. Alsadius D, Hedelin M, Johansson KA, Pettersson N, Wilderang U, Lundstedt D, et al. Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer. Radiother Oncol. 2011;101(3):495-501.
  35. Chen AM, Chen LM, Vaughan A, Sreeraman R, Farwell DG, Luu Q, et al. Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcome. International Journal of Radiation Oncology Biology Physics. 2011;79(2):414-9.
  36. Eifel PJ, Jhingran A, Bodurka DC, Levenback C, Thames H. Correlation of smoking history and other patient characteristics with major complications of pelvic radiation therapy for cervical cancer. Journal of Clinical Oncology. 2002;20(17):3651-7.
  37. Bjarnason GA, MacKenzie RG, Nabid A, Hodson ID, El-Sayed S, Grimard L, et al. Comparison of Toxicity Associated With Early Morning Versus Late Afternoon Radiotherapy in Patients With Head-and-Neck Cancer: A Prospective Randomized Trial of the National Cancer Institute of Canada Clinical Trials Group (HN3). International Journal of Radiation Oncology Biology Physics. 2009;73(1):166-72.
  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 testicular cancer

Follow-up is intended to discover early recurrence, monitor and treat toxicity caused by chemotherapy, and to offer support and help for topics such as fertility and hormone deficiency. The frequency of follow-up depends on the stage of the disease and the treatment the patient has received. In addition to imaging and blood tests, a thorough examination of the remaining testicle and superficial lymph node stations is important.

Most recurrences of testicular cancer occur in the first 1-2 years after primary treatment. Some recur after 3-4 years or later. Patients with nonseminoma who have had chemotherapy can develop slow-growing mature teratoid tumors (teratomas), especially retroperitoneally. Mature teratomas are not susceptible to chemotherapy or radiation therapy. Teratoma components of metastasizing cancer requires life-long follow-up for growing teratoma syndrome which can cause local compression problems and may transform into malignant tumors.

Patients with both testicles removed need testosterone treatment for life. This is usually done by injection of Nebido® 1000 mg s.c every 8–12 weeks.

A sperm analysis is performed on all patients one year after treatment is finished.

Follow-up schedule for Testicular Cancer

Seminoma (10)

Recommendation for seminoma stage I - IV and recurrence:

1. year 2. year 3-4. year 5. year 6-10. year

Clinical examination

Every 4. month

Every 4. month

Every 6. month

Every 12. month

Every 12. month

Tumor markers

Every 4. month

Every 4. month

Every 6. month

Every 12. month

Every 12. month

Chest X-ray

At 12 months

At 24 months

At 36 months

At 60 months

At 10 years

MRI abdomen/pelvis

Every 4. month

Every 4. month

Every 6. month

Every 12. month

Every 12. month

Testosterone, lipids, glucose

At 12 months

 

At 36 months

At 60 months

At 10 years

Blood pressure

At 12 months At 60months At 10 years

All patiens with seminoma are followed up for 10 years. At the final medical control, at 10 years, the patient receives final written information. If the MRI availability is limited, CT may be used. The number of CT examinations should not exceed 10 in the control period.

Non-seminoma (10)

The follow-up schedule varies depending on the chosen treatment strategy.

  • Observation
  • Adjuvant chemotherapy
  • Nerve sparing retroperitoneal lymph node dissection.

Follow-up observation strategy

Recommendation for nonseminoma stage I, low risk profile:

1. year 2. year 3. year 4-5. year 7. year 10. year

Clinical examination

Every 4.month

Every 6. month

Every 6. month

Every 6.month

Option

Option

Tumor markers

Every 2. month

Every 3. month

Every 3. month

Every 6. month

Option

Option

Chest X-ray

Every 4. month

Every 6. month

At 36 months

Every 12. month

Option

Option

MRI abdomen/pelvis

Every 4. month

Every 6. month

At 36 months

At 60 months

Option

Option

Testosterone, lipids, glucose

At 12 months

 

At 36 months

At 60 months

Option

Option

One can consider the follow-up at 7 and 10 years, to detect late recurrence of teratoma. At the final control (5 or 10 years) the patient receives final written information. If the MRI availability is limited, CT may be used. The number of CT examinations should not exceed 10 in the control period.

Follow-up adjuvant chemotherapy

Recommendation for nonseminoma stage I, high risk profile:

1. year 2. year 3. year 4-5. year 6-10. year

Clinical examination

Every 6. month

Every 6.month

Every 6. month

Every 6. month

Every 12. month

Tumor markers

Every 2. month

Every 3. month

Every 6. month

Every 6. month

Every 12. month

Chest X-ray

Every 6. month

Every 6. month

At 36 months

Every 12. month

At 10 years

MRI abdomen/pelvis

Every 6.month

Every 6.month

At 36 months

At 60 months

At 10 years

Testosterone, lipids, glucose

At 12 months

 

At 36 months

At 60 months

At 10 years

The patient receives written information at the final 10 year control . If the MRI availability is limited, CT may be used. The number of CT examinations should not exceed 10 in the control period.

Follow-up nerve sparing retroperitoneal node dissection (RPLND)

The recommended minimum follow-up is the same as the observation strategy.

Follow-up for nonseminoma stage Mk+, II – IV and after treatment for recurrence

Recommendation:

1. year 2. year 3. year 4-5. year 6-10. year

Clinical examination

Every 4. month

Every 6. month

Every 6. month

Every 6. month

Every 12. month

Tumor markers

Every 2. month

Every 3. month

Every 3. month

Every 6. month

Every 12. month

Chest X-ray

Every 4. month

Every 6. month

Every 6. month

Every 12. month

At 7 and 10 years

MRI abdomen/pelvis

Every 4. month

Every 6.month

Every 6. month

Every 12. month

At 7 and 10 years

Testosterone, lipids, glucose

At 12 months

 

At 36 months

At 60 months

At 10 years

Blood pressure

At 12 months

At 60 months

At 10 years

If the MRI availability is limited, CT may be used. The number of CT examinations should not exceed 10 in the control period. The patient receives written information at the final medical follow-up. Patients who have been proven teratoma in the primary tumor or in the resected tissue at retroperitoneal lymph node dissection (RPLND) should have annual follow-ups. These controls include clinical examinations and blood tests (tumor markers, hormones, blood lipids and blood glucose) supplemented with radiological examinations.

Long-term follow-up

Outpatient clinic controls

Patients are followed up to 10 years at an oncology outpatient clinic after treatment for testicular cancer, with diagnosis of recurrence as the main objective. Examination of the remaining testicle is mandatory. Tumor development in the remaining testicle can occur in 2-5% of the patients. At this medical control it is also important to diagnose and treat delayed side effects caused by the treatment.

At the last control in the oncology outpatient clinic, the patient is given a document that describes his treatment. For testicular cancer survivors emphasis is also placed on typical health risks , that is possible to reduce with preventive measures .

Medical controls and necessary measures are left to the patient's GP. The goal of this medical control is to prevent, diagnose and treat delayed side effects caused by testicular cancer treatment.

The most common delayed side effects are:

  • Cardiovascular disease. Cisplatin-based chemotherapy increases the risk of cardiovascular dicease.
  • Hypogonadism. Up to 20% experience endocrine hypogonadism/testosterone deficiency. Reduced libido, erectile dysfunction and fatigue are common symptoms. If the symptoms are severe testosterone treatment is considered. Lifelong testosterone substitution is necessary after bilateral orchiectomy and low testosterone levels after CIC (Carcinoma in citu) treatment.
  • Fertility. Abnormal sperm quality often occurs in patients with testicular cancer. In addition, chemotherapy and radiation treatment negatively affect fertility and sex hormones . Therefore, samples to evaluate sex hormones (testosterone, LH, FSH and SHBG) should be taken and sperm analysis performed before treatment. Cryopreservation of sperm should be offered. If the patient wants cryopreservation, this should preferably be done before orchiectomy, but in any case before chemotherapy. The results of a large national study of men, previously treated for testicular cancer, shows that fertility gradually diminish with increasing treatment intensity. But even among men who had accumulated high-dose cisplatin (> 850 mg), almost half of them became fathers without cryopreserved sperm.
  • Retrograde ejaculation. Retrograde ejaculation may occur in some men after RPLND, but the proportion is significantly reduced after nerve-sparing surgical technique was introduced. For men who want to become fathers, treatment with α-sympathomimetic drugs (Rinexin ®, Tofranil ® [imipramine, unregistered product]) may be an option as the drugs can reverse the retrograde ejaculation
  • Nephrotoxicity
  • Neurotoxicity
  • Ototoxicity
  • Pulmonary toxicity
  • Secondary malignancy (particularly in the gastrointestinal area)

Medical follow-up with the GP (family doctor)

Regular medical controls with the patient's GP are recommended 2-3 years after the follow-up with an oncologist. Thereafter, the recommendation is every 2-3 years, more frequently in patients with pathological findings.

The medical control should include:

  • Medical history with regard to symptoms of cardiovascular disease
  • Measurement of blood pressure, height / weight (BMI), waist circumference
  • Blood samples:
    • Fasting blood lipids (total cholesterol, HDL and LDL cholesterol, triglycerides)
    • Glucose
    • Testosterone
    • LH
  • Lifestyle advice with focus on smoking, diet and physical activity
  • Prophylaxis of cardiovascular disease according to current guidelines
  • Testosterone substitution in proven hypogonadism, possibly in consultation with the endocrinologist

PROSEDYRER

Fatigue before, during, and after Cancer Treatment

General

There are many reasons why cancer patients feel fatigued. In many patients, the causes are synergistic. Cancer patients are often very sick during treatment periods and may experience extreme fatigue during intensive chemotherapy. It is also very important to be aware that fatigue is a symptom of many other medical conditions, both physical and psychological, which also affects cancer patients. Some known causes of fatigue associated with cancer and cancer treatment are: 

  • Cancer itself
  • An operation
  • Current or recently concluded chemotherapy
  • Current or recently finished radiation therapy
  • Severe anemia
  • Other symptoms such as pain and nausea 
  • Fever or infection
  • Too little fluid or food intake
  • Reduced lung function
  • Changes in sleep
  • Worries, anxiety, stress, or depression

For some of these conditions, such as infections, there is medical treatment available. Fatigue that occurs after an operation or during chemotherapy and radiation therapy will, for most, gradually disappear when strength is regained. If a patient was feeling healthy after treatment and all of the sudden experiences fatigue, they should contact their doctor. If a patient feels fatigue and at the same time feels stressed, worried, or down, they may be reluctant to speak to their doctor or health personnel about it. It is still recommended to talk about these problems. Talking about it may be therapeutic, and provides room for discussing measures with a qualified person with experience with patients that have the same problems. For cured patients experiencing chronic fatigue, it may be difficult to pinpoint a specific cause. Many of these patients experience improvement by changing their lifestyle to a lower tempo than before the diagnosis.

Definition

Everyone knows what it feels like to be tired, fatigued, or lethargic when sick. This feeling is the most common side effect of cancer and cancer treatment. A symptom is a condition or state that something is not right in the body. Other frequent symptoms associated with cancer and cancer treatment are reduced appetite and nausea. Most patients who experience fatigue associated with cancer say that the feeling does not improve with rest, and many describe a lack of energy or exhaustion.  

If fatigue arises during chemotherapy or radiation therapy, most patients experience that it will gradually go away when treatment is over and their strength is regained. This type of fatigue is considered acute. Improvement may take time depending on the intensity of treatment. Some patients experience that fatigue lasts for months, or even years. This is considered chronic fatigue. The ability to carry out daily activities, a lack of humor, health-related worries, a reduced capacity to carry out work functions, or less energy for family, can also accompany chronic fatigue. Most patients will find it difficult to be told by their doctor that they are considered healthy, while their friends and family expect them to be normal again, despite having a lack of energy and ability to perform activities they want to.  

For many, feeling fatigued is often accompanied by having difficulty concentrating, poor memory, and an increased need for sleep. Most patients will need more sleep than before they became sick. For many, sleep is not restful, and it may take time to "get going" in the morning. Many also experience that they quickly become drained of strength if they exert themselves, and that it takes a long time before regaining strength after exertion. Exertion in this context can mean both physically and mentally such as working on a task that requires concentration.

Preparation

Fatigue can occur in all phases of cancer illness. Some patients feel it before the diagnosis, and almost all patients experience fatigue during radiation therapy or chemotherapy. A minority of patients experience long term fatigue after cancer treatment is over and the disease is cured. Patients who cannot be cured will almost always feel tired, worn-out, and exhausted. The degree of fatigue in these patients varies depending on the cancer type, spreading, and other symptoms of the disease.

The patient should be given necessary information on both causes of fatigue and measures he/she can take.

Implementation

General measures that can reduce feeling tired and fatigued

Following suggestions are meant as general advice that may not necessarily apply to everyone in all situations. This advice is based on results from studies, experiences from cancer patients, and recommendations from experts. Each patient should assess what works for them. It is recommended to express concerns and seek advice for what measures you can take and what you should avoid.

General advice
  • Try to live as "normal" as possible.
  • Try to plan your day to include time to rest.
  • Take many small breaks during the day instead of a few long ones.
  • Rest after strenuous activity.
  • Plan your daily activities and do those that are most important for you.
  • Set realistic goals for yourself and try to be happy with those you accomplish.
  • Try to recognize activities that make you especially tired/fatigued and limit them, or spread them out over longer intervals. 
  • Try to accept that you do not have the energy to do the things you could previously.
  • Assess what is important for you to do yourself and what you can allow others to do.
  • Assume you will be tired after something strenuous even if you experience the activity as positive.

Physical activity and exercise

Exercise and physical activity that is appropriate for you will reduce the feeling of fatigue. Regular exercise is the most effective measure against chronic fatigue in cancer patients. Nevertheless, both too much and too little exercise can worsen fatigue, therefore, it is important to find a level (frequency and intensity) that suits you. You should never exercise so intensely that you must stop a session or exercise period because you are exhausted. Remember that daily form varies for everyone and adjust your exercise routine accordingly. Make long-term goals (months) and gradually increase activity, and carefully for a period. 

  • Activities such as walking, biking, swimming, dance, and aerobics are recommended.
  • Light exercise periods at regular intervals are better than intense, sporadic periods.
  • Always start with a slow tempo and increase gradually before finishing with a slow tempo again.
  • Always sit down and rest after exercise but try not to lay down and sleep.
  • Physical therapists and sport pedagogs can provide advice on exercises that are right for you. The principles are the same for all exercise, but it should be adjusted for your energy level.  

Sleep

Many cancer patients with chronic fatigue have sleep pattern disturbances. It is important to maintain a normal rhythm even if you feel like sleeping during the day.

  • Try to wake up at the same time every day and keep a regular bedtime.
  • Avoid too much activity right before bedtime.
  • Try not to sleep during the day because this will disturb your biological rhythm.
  • But, a short afternoon nap may be energizing!
  • Rest during the day by relaxing in a good chair, but try not to fall asleep.
  • Speak to your doctor about lasting sleep disturbances.

Nutrition

Having a reduced appetite or intake of food can also result in a lack of strength and energy. We recommend eating healthy food regularly, and to follow the national guidelines on nutrition. Special diets or supplements do not improve fatigue unless there is a deficiency.

Work situation

Some patients do not have the strength to continue working, or they must reduce their hours because of chronic fatigue. Consulting with a social worker may be beneficial for guidance regarding your work situation, your welfare rights, and financial situation. 

Some adjustments that you and your employer can make:

  • Discuss the possibility for more simple or easier tasks, especially if you have a physically demanding profession.
  • Assess the possibility of reducing your hours.
  • Remember to take regular breaks also at work, if possible.
  • Assess the possibility of flexi-time to work during the hours you have energy, as well as the possibility of working from home.

Care for children

Caring for children or adolescents may be very difficult when you are fatigued or lack energy and strength. There are, however, some measures you can take:

  • Explain to your children that you are tired and are not able to do as much as you used to.
  • Discuss what the children can help you with and allow them to take part in household chores.
  • Try to establish permanent household chores for all family members.
  • Try to do activities that suit you that do not require too much energy, and can be performed without too much exertion. 
  • Ask and accept help from others for driving to and from activities, school, etc. if this relieves you.

Drug therapy

In Norway, there is currently no specific drug therapy for chronic fatigue associated with cancer. If the fatigue is due to specific conditions, this is of course treated with medication, if possible. Sometimes, such treatments improve the fatigue, but other times they do not. Examples of treatment that often reduce fatigue are treatment for infections and depression. 

Treatment with medications that stimulate production of red blood cells is not recommended for cancer patients due the the danger of serious side effects.

Follow-up

Information about fatigue

Healthcare workers in cancer care will often have knowledge about fatigue and cancer. Most general care physicians have general experience with fatigue but meet relatively few cancer patients. There is a lot of information available on the internet of varying quality. Below is a list of web adresses and some literature. Be aware that you may find opposing advice because knowledge on treatment especially, is limited.

Some articles/books:

  • Armes J., m.fl. (2004). Fatigue in cancer. Oxford University Press.
  • Berger A.M., m.fl. (2009). NCCN Clinical Practice Guidelines in Oncology. Cancer-Related Fatigue. www.nccn.org
  • Patarca-Montero R. (2004). Handbook of cancer-related fatigue. Haworth Medical Press