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The 35th and 36th cases of adenocarcinoma arising in small bowel affected with regional enteritis are presented. The pathology of all reported cases is reviewed. An association between regional enteritis and carcinoma of the small bowel is suggested.
In two large controlled cooperative trials, 1118 patients undergoing surgical resection for large bowel cancer were randomized to be treated by surgery alone or to receive 5-fluorouracil during postoperative followup. The two studies differed slightly in the selection of patients for entry and in the dose regimens of 5-fluorouracil. Following examination of the removed specimen, "curative" and palliative stratifications based on evidence of residual disease were made, so that the two trials actually consisted of five separate patient groups, two groups of patients who had "curative" resections and the other three smaller groups of patients who had palliative resections with residual disease or tumor at a margin of the resected specimen. In all five groups, survival was slightly better in patients receiving chemotherapy although no single difference is statistically significant. Any suggestion that these slight advantages represent a true therapeutic 5-FU effect must be tempered by previous negative adjuvant studies by this group as well as others. Currently the group is conducting a trial using a combination of methyl-CCNU and 5-fluorouracil and has recently added a nonspecific immunostimulant, methanol extraction residue of BCG (MER), to one subgroup.
The pathology of six cases of alpha-chain disease (alpha-CD), four of which were followed until complete remission or death, was studied by histologic, immunofluorescence and ultrastructural techniques. The lesions could be classified in three histopographical stages. The late stage C is an immunoblastic sarcoma probably deriving from the same clone as the initial plasmacytic stage A, stage B being a transitional one between A and C. The asynchronism of the lesions in different organs in the same patient requires a laparotomy for an accurate staging which determines the prognosis and the treatment. Complete and prolonged remissions have been observed at stage A only, sometimes with oral antibiotic treatment alone. At all stages, alpha-CD and the "Mediterranean lymphoma" share identical aetiological, clinical and pathological features. Accurate immunological studies will determine the precise-frequency of alpha-CD protein synthesis in the latter syndrome.
Malabsorption studies were performed on five Iranian patients with primary small intestinal lymphoma. The effect of oral tetracycline (1.0 g daily) was also studied in three of the above subjects. The results of breath tests (utilizing glycine-1-14C-cholic acid) were abnormal in all five subjects before the antibiotic treatment. Oral tetracycline had a striking effect towards normalizing the results of breath tests. Schilling tests (with intrinsic factor) improve in two patients and steatorrhea improved in all and there was significant weight gain. The antibiotic had no apparent effect on D-xylose or folate absorption tests. It is concluded that bacterial overgrowth in the small intestinal lumen is an important contributory factor to the malabsorption syndrome of this disease.
The pathology of 25 cases of Mediterranean abdominal lymphoma, better designated as immunoproliferative small intestinal disease (IPSID), are reported from the American University of Beirut Hospital. The series includes nine cases with documented alpha heavy chain disease (alpha-HCD). The disease is characterized by the presence of a diffuse and compact bandlike lymphoplasmacytic infiltration of the proximal small intestinal mucosa. The presence of a concomitant malignant lymphoma in the intestine and/or mesenteric lymph nodes, and of alpha-heavy protein in the serum is commonly encountered. Two histopathologic variants of IPSID are present. The first is characterized by the diffuse infiltration of the mucosa, at sites away from tumoral masses, by either pure plasmacytic infiltration, or mixed lymphoplasmacytic infiltration. This variety is associated with the immunoblastic sarcoma type of malignant lymphoma, and with alpha chain disease (alpha-HCD). The second variant is characterized by a diffuse follicular lymphoid hyperplasia pattern in the small intestinal mucosa. The associated malignant lymphoma is diffuse and undifferentiated often having a starry-sky pattern. This variety is not associated with alpha-HCD. Both histologic variants share the same clinical antecedents. In five patients, mesenteric lymph nodes harbored immunoblastic sarcoma while the intestinal mucosae of the same patients were involved with a benign appearing lymphoplasmacytic infiltration. This finding stresses the need for staging laparatomy. Three patients, with alpha-HCD, had peripheral lymph node involvement with immunoblastic sarcoma. The disease apparently evolves in two stages: an immunoproliferative phase, probably reversible, and a later development of malignant lymphoma. The term immunoproliferative small intestinal disease accurately describes the nature of the entity.
From studies of nitrate balance in man and analyses of fecal and ileostomy samples, the possibility that nitrite and nitrate are formed de novo in the intestine, possibly by heterotrophic nitrification has emerged. This proposition significantly alters our previous conceptions of man's exposure to nitrite and suggests that nitrite may play a role in the cause of intestinal cancer. Heterotrophic nitrification has been demonstrated in various microorganisms. Our work has shown that intestinal heterotrophic microbial isolates from man are able to oxidize nitrogenous compounds to nitrite. These isolates include both procaryotes and eucaryotes.
Histologic material from 156 patients treated with surgery for cancer of the large bowel was studied with regard to tumor host interaction and with particular emphasis on the reactions of the regional lymph nodes. Prognostic evaluation of the tumor included the extent of the primary lesion according to Dukes' classification and the grade of differentiation of the carcinoma. Morphologic evidence of host resistance was judged by the presence and degree of lymphoplasmacytic infiltration of the tumor and the reactions of the regional lymph nodes, which were classified in four histologic patterns: lymphocyte predominance, germinal center predominance, lymphocyte depletion, and unstimulated. Of the factors evaluated, those that appeared to correlate best with five-year survival were the stage of the disease, the grade of differentiation of the carcinoma, the degree of lymphoplasmacytic infiltration of the tumor, the lymphocyte predominance pattern, and, to a lesser degree, the germinal center predominance pattern. None of the other morphologic features related to lymph nodes showed favorable prognostic significance. The relationship of morphology to host immune mechanisms is discussed.
A malignant lymphoma of the small bowel developed in a 75-year-old woman who had severe late-onset hypogammaglobulinemia with intestinal malabsorption and nodular lymphoid hyperplasia. The tumor arose in the midst of the abnormal lymphoid follicles and appeared to be of B-immunoblastic type. Immunoperoxidase staining, however, failed to reveal immunoglobulins in the tumor cells. In vitro immunologic studies showed that immunoglobulin production by the patient's peripheral lymphocytes had decreased and that this decrease was mediated by hydrocortisone-sensitive suppressor cells. These findings suggest that nodular lymphoid hyperplasia of the intestine in the context of severe immunodeficiency is a premalignant condition.
Two hundred and seven large bowel cancer patients (93% of all cases diagnosed in a defined community between 1965 and 1976) were matched at random with non-cancer subjects of same age, sex, and place of residence. Men with cancer, aged 75 years and younger than, had a more frequent history of work in a local factory handling synthetic fiber than controls (22 versus 10; P less than 0.025). In this factory 45% of cancers occurred before age 60, while this was true in only 24% of cancer cases outside the factory (P less than 0.05). There was a greater tendency for cancers in factory workers to occur in the colon than in the rectum. Heredity was not found to be a risk factor for large bowel cancer. The rate of prior appendectomy was higher in men with colon cancer (P less than 0.05) and the rate of prior cholecystectomy was lower in females with colonic cancer (P less than 0.05). A previous hemorroidectomy was also found more often in males with colonic cancer (P less than 0.05). Long-standing severe constipation was present more often in patients with cancer (P less than 0.01). There was some evidence for a compounding influence of different risk factors, as studied by relative risk ratio. This study confirms the existence of a high risk of large bowel cancer in a group of workers in a synthetic fiber factory and suggests other factors antecedent to large bowel cancer.
Primary lymphomas of the small intestine (PIL) show definite racial and geographic distribution. Clinical and laboratory data on 132 patients with PIL treated and followed up over a 14-year period in Baghdad, Iraq, are presented. Based on the pattern of involvement of the bowel and the histopathologic appearance of the tumor, the patients can be divided into three main groups. Ninety-seven patients had diffuse lymphoplasmacytic infiltration affecting large segments of the upper bowel. Abdominal pain, anorexia, weight loss, diarrhea, malabsorption, and clubbing of the fingers are the most common clinical findings. The barium appearance of the small intestine and peroral jejunal biopsy specimens are abnormal in nearly all cases. This clinicopathologic entity has been referred to in the literature as Mediterranean lymphoma (ML). Ten of 34 patients tested had free alpha-heavy chain in the serum. Twenty-three cases had other "Western" variants of lymphoma (18 lymphocytic and 5 plasmacytic). The lesions were localized, occurring most frequently in the lower ileum or ileocecal area. The most common presentation was intestinal obstruction. Twelve children had Burkitt's lymphoma (BL), presenting most commonly with abdominal masses and/or intestinal obstruction. These patients responded poorly to cyclophosphamide, and the disease disseminated early and extensively. None of the patients with the localized lymphomas or BL had free alpha chain in the serum.
Eighty-eight cancer patients with the presence of one or more adverse factors for healing (carcinomatosis, adhesions, prior chemotherapy and radiation therapy, bowel obstruction, anemia, and low leukocyte count or albumin value) were prospectively randomized to undergo conventional two-layer hand suturing (45 patients) or mechanical stapling with a GIA/TA instrument (U.S. Surgical Corp., Norwalk, CT) (43 patients) of the large or small bowel anastomosis. Age, sex, complete blood count findings, and all biochemical plasma values were comparable in both groups. The anastomosis took an average of 19 minutes for the sutured and 9 minutes for the stapled technique (P = 0.0001), but the average length of operation, postoperative return of bowel function, and hospital stay were comparable in both groups. Bowel fistula was seen in one case of stapled anastomosis (P = not significant). The pulmonary and wound complication rates were the same in both groups. Of the four deaths (4.5%) due to causes unrelated to bowel anastomosis, three occurred in the stapled and one in the sutured group. It was concluded that a stapled anastomosis is as safe as a sutured one in patients with advanced-stage cancer. It saves time in anastomosis, but does not save time in postoperative return of the bowel function and hospital stay.
BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) is an autosomal dominant disease characterized by early-onset intestinal neoplasms, localization of tumors in the proximal colon, and frequent association with cancers at other sites, especially the endometrium, skin, and stomach. The identification of HNPCC is often difficult, owing to the lack of biomarkers and the extreme frequency of sporadic colorectal cancer in the Western World. METHODS: The authors reviewed the clinical data and the family trees of all patients (n = 817) with colorectal malignancies registered in the local health district between 1984-1989 with the following objectives: (1) to identify families with HNPCC and (2) to establish the frequency of the syndrome in northern Italy. Six clinical criteria were defined (vertical transmission, familial aggregation, early age at onset, right colon localization, multiple tumors, and mucinous carcinoma), all indicative of an increased possibility of HNPCC: RESULTS: The registered families were divided into various subgroups according to the presence (in the nuclear pedigree) of four or more criteria (41 families, 5.0% of total), three criteria (58 families, 7%), two criteria (73, 8.9%), or less than two criteria (203 families, 24.8%). The remaining 380 case families did not show criteria suggesting a genetic component. One hundred thirty-three genealogic trees were extended further to gather information on second-degree and third-degree relatives. The expanded pedigrees were further analyzed to ascertain if they met the recently proposed requisites for HNPCC: Nineteen of 37 (51%) families with four criteria met the minimum requisites and could therefore be considered HNPCC: Similarly, HNPCC was diagnosed in six extended pedigrees of the three-criteria (16.6%) and in three families (8.5%) of the two-criteria subgroups. The difference in the detection of HNPCC among various subgroups was statistically significant (P < 0.001). From the observed findings, the frequency of HNPCC in this population can be estimated to be between 3.4-4.5% of all cases of colorectal cancer. CONCLUSIONS: HNPCC can be identified in the general population through the data of a colorectal cancer registry if the nuclear pedigrees of all incident cases are traced and a proportion of them selectively expanded. The observed frequency of HNPCC was rather consistent with previous estimates in other populations.
BACKGROUND: Primary T-cell lymphoma of the small intestine is rare, and most cases have proved rapidly fatal. METHODS: We describe a case of lymphoma involving the small intestine uniformly and extensively in a 28-year-old man on initial examination seen with long-standing diarrhea, malabsorption, and recurrent episodes of intestinal obstruction. Clinical remission was obtained with pentostatin (2'-deoxycoformycin, supplied by Professor Catovsky, London UK) after the patient had failed to improve under conventional chemotherapy. Tumor specimens as well as mesenteric lymph node, liver, and bone marrow specimens were studied with conventional pathology and immunochemistry. Additionally, mesenteric lymph nodes and peripheral blood cells were studied for T-cell receptor (TCR) gene rearrangement and karyotype. RESULTS: Lymphoma cells were small T-lymphocytes with irregular pleomorphic nuclei, bearing the CD3, CD4 and TCR alpha-beta phenotype. Peripheral-blood cytology and bone marrow biopsy were normal. Southern blot analysis of the TCR beta-chain gene revealed the same monoclonal rearrangement in the mesenteric lymph nodes and peripheral blood lymphocytes. An as yet undescribed t(4;16)(q26;p13) translocation, involving the region where the interleukin-2 (IL-2) gene has been mapped, was present in the mesenteric lymph nodes and peripheral blood lymphocytes. CONCLUSION: We believe this is the first description of an extensive, small intestinal lymphoma of low-grade malignancy made up of monoclonal T-cells with a TCR alpha-beta and helper/inducer phenotype, associated with a novel chromosomal translocation.
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