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Lymphoma in the gastrointestinal tract

This diagnosis is often made based on explorative laparotomy in patients with ileus symptoms. One reason that these patients have a poorer prognosis is that lymphomas in the small intestine, which commonly go hand-in-hand with chronic intestinal conditions such as Morbus Crohn and ulcerous colitis, are usually of the T-cell type, which are less sensitive to chemotherapy.  


Indolent stomach lymphomas

Extranodal marginal zone B-cell lymphomas (MALT) stage PeIA

If marginal zone B-cell lymphoma is confirmed by endoscopic biopsy, it is necessary to take new biopsies. A biopsy should be taken from the antrum and corpus for a urease quick test, 10 biopsies from the macroscopically involved areas, as well as quadrant biopsies from macroscopically uninvolved areas. Histological grading based on Witherspoon's method on a scale from 0-5 is done, where grades 4 and 5 are malignant. For making the diagnosis, it is necessary to do a molecular genetic examination for immunglobulin gene rearrangement and also histochemical or immunohistochemical examination for helicobacter pylori. Beyond these tests, standard lymphoma evaluation is performed including CT of chest/abdomen/pelvis, ultrasound of liver/spleen/paraaortal space, ENT examination, and bone marrow biopsy as mentioned earlier.

Eradication of Helicobacter pylori with triple treatment for 7 days with Klacid® 250 mg x 2, Elyzol® 500 mg x 2, and Lanzo® 30 mg x 1 has in multiple studies been shown to give complete remissions in about 2/3 of patients with marginal zone B-cell lymphoma (MALT) confined to stomach mucosa in stage PeIA. It may take over one year before remission is complete, and long-term results of treatment are now being published. Recurrence after eradication treatment may occur, but they are in most cases microscopic. This treatment strategy requires an exact follow-up program with repeated clinical examinations and endoscopy with biopsies (histology and PCR analysis) after 3 and 6 months, then biannually for 3 years, followed by annually for 5 years. Ultrasound in the upper abdomen is done yearly during the same period. Triple treatment is so promising that it is considered standard treatment in Norway as long as guidelines are followed for diagnostics, treatment, and follow-up. 

Adequate long-term follow-up is not available to indicate whether this treatment provides a lasting cure, contrary to local radiation therapy. Half of patients have a remaining monoclonal population after treatment is over. It is worth mentioning that subgroups with t(1;14)(p22;q32) og t(11;18)(q21;q21) are associated with resistance to Helicobacter pylori eradication.

A gastric resection or gastrectomy is not indicated other than for imminent threat of perforation or significant bleeding from tumor. 

Local microscopic recurrence is monitored only by gastroscopy with biopsy; no treatment is necessary. It is not uncommon for the recurrence to disappear over time. Local microscopic recurrence in the stomach and/or regional lymph nodes are treated with radiation therapy to the stomach and regional nodes along the curvatures, coeliac regions, splenic hilum, and subpyloric area fractionated in 2 Gy x 15 (curative). For details around planning radiation therapy, see the chapter or radiation therapy. Advanced recurrence is treated according to guidelines given for general indolent lymphomas without a curative intention. 

Other indolent lymphomas stages PeIA and PeIIA localized

Treatment is local radiation therapy, 2 Gy x 12 to the stomach, lymph nodes along the curvatures, coeliac regions, splenic hilum, and the subpyloric lymph nodes. For details, see the chapter on radiation therapy. For serious bleeding and/or massive invasion of serosa, a gastric resection is considered or gastrectomy after interdisciplinary discussion between oncologist and surgeon. If the surgery is radical, no additional treatment is given for stage PeI. Supplementary radiation therapy of 2 Gy x 12 is given to regional lymph nodes for stage PeII. Only local radiation therapy is given as described above if there is no indication for surgery. 

Other indolent lymphomas stage PeII (involvement of lymph node stations beyond the first station) and stage IV

These cases are are considered incurable and are treated as advanced indolent lymphomas. They are left untreated and observed unless treatment is required, which is then the same as for indolent lymphomas. 

Aggressive stomach lymphomas

Mantle cell lymphomas in the stomach

Consider whether the patient should be included in study protocols. With localized disease, treatment is the same as that given for diffuse large cell B-cell lymphomas. 

Diffuse large cell B-cell lymphomas in the stomach

Consider primary surgery based on guidelines given above for indolent lymphomas. For stages PeI and PeII (localized), the same principles are followed as those described for large cell B-cell lymphoma stage I/II. Three to six courses of CHOP-based therapy with rituximab are given followed by radiation therapy (2 Gy x 15-20) with field modeling as for indolent lymphomas PeI-PeII (localized). If radiation therapy is to be avoided, it is possible to treat with chemotherapy with only 6-8 courses based on guidelines for large cell B cell lymphoma. Advanced stages PeII and IV are treated as advanced diffuse large cell B cell lymphoma. Supplementary radiotherapy is considered on an individual basis such as for absence of CR locally after chemotherapy. HDT with SCS may be considered as an alternative.

Intestinal lymphomas (duodenum, small and large intestines including the rectum)

The need for surgery should always be considered before starting chemotherapy. Radiation therapy is rarely indicated since lesions are often multifocal and because the intestines are mobile, which makes the radiation field difficult to determine. Diffuse large cell B cell lymphomas are treated according to regular guidelines. In some cases, the lesions are unifocal, and may be possible to remove surgically. Chemotherapy is otherwise given in 3-6 courses without subsequent radiation therapy. For intestinal T-cell lymphomas and mantle cell lymphomas, the patient should be considered for inclusion in the respective Nordic phase II study. In patients with Burkitt's lymphoma, the disease is often localized to the ileocoecal transition and should be treated according to guidelines for this lymphoma group described in the section on Burkitt's lymphoma.

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