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Modification of pancreatic carcinogenesis in the hamster model. 5. Effect of partial pancreatico-colostomy.

Studies were conducted to evaluate the possibility of a bile reflux mechanism in the etiology of induced pancreatic cancer. N-Nitrosobis(2-oxopropyl)amine (BOP) was administered to Syrian hamsters after partial pancreatico-colostomy. Either the gastric or the splenic lobe of the pancreas was anastomosed to the transverse colon in groups 1 and 2, respectively. Group 3 were sham-operated controls and group 4 were controls without surgery. Shortly after surgery all 4 groups received a single subcutaneous BOP injection (20 mg/kg body weight) and survivors were sacrificed 46 weeks after BOP treatment. BOP-induced pancreatic tumor patterns were not altered by pancreatico-colostomy when compared with those in sham-operated controls. In all BOP-treated hamsters the number and distribution of benign and malignant lesions were similar in each individual pancreatic segment, including the anastomosed lobe (A-lobe); some hamsters developed tumors only in the A-lobe. As in other pancreatic regions, the initial hyperplasia in the A-lobe primarily affected peri- and intra-insular ductules and less frequently involved the ducts. These findings support the theory that the carcinogen is bloodborne and indicate that BOP-responsive pancreatic cells are distributed on a volume basis in distinct proportions within the pancreatic segments. As in previous experiments a higher incidence of pancreatic neoplasms was found in BOP-treated controls (those not operated upon) than in partially pancreatico-colostomized hamsters, including those with sham operations. Hyperplastic and dyplastic development of colonic mucosa around the anastomosis could be related to a local effect of carcinogen or of its metabolites, which are known to be excreted via pancreatic secretions.

Animals↗

Localization of hepatitis A antigen in marmoset organs during acute infection with hepatitis A virus.

Twelve marmosets (Saguinus mystax) were inoculated intravenously (iv) with hepatitis A virus (HAV). One died early (day 12); seven were sacrificed at the time of elevation in level of alanine aminotransferase (serum glutamic-pyruvic transaminase), and four without elevation were not sacrificed but seroconverted. In the seven marmosets sacrificed during the acute stage of illness, hepatitis A antigen (HA Ag) was detected in the liver by immunofluorescence in all cases, by immune electron microscopy in four, and by enzyme-linked immunosorbent assay (ELISA) in three. The HA Ag appeared by immunofluorescence as very fine granules in the cytoplasm of hepatocytes and Kupffer cells. The HA Ag could not be detected by immunofluorescence in biopsy specimens taken from the duodenum, jejunum, ileum, or transverse colon in any of eight marmosets in which necropsy was performed during the acute or preacute stage of illness. These findings suggest that the gut is not involved during the acute phase of HAV infection following iv inoculation into marmosets. The ELISA results showed that only three of 12 marmoset livers obtained during the acute phase of HAV infection could be used as an antigen source in serologic testing for antibody to HA Ag. Thus, marmoset livers were no better as a source of HA Ag than acute-phase stools from patients with type A hepatitis.

Acute Disease↗

Successful radical surgery for an undifferentiated gallbladder carcinoma with lymph node metastases to the mesocolon.

We report successful radical systematic surgery for an undifferentiated gallbladder carcinoma with metastasis to the mesocolonic lymph nodes. The patient, a 70-year-old woman, was admitted with abdominal fullness and appetite loss. Imaging modalities revealed a 10-cm tumor originating from the gallbladder and infiltrating both the liver and transverse colon. As multiple mesocolonic lymph node metastasis was confirmed on laparotomy, right hemicolectomy with systematic lymph node dissection (D3 resection) was performed, in addition to extended cholecystectomy with partial resection of segments 4, 5 and 6 of the liver and distal gastrectomy. Histologically, the tumor was diagnosed as an undifferentiated carcinoma, and metastases were indentified in the mesocolonic lymph nodes (17/50 nodes) but not in the peri-gallbladder lymph nodes (0/16 nodes). The patient has been recurrence-free for 4 years after the operation. This case illustrates that even if gallbladder cancer infiltrates into adjacent organs with regional lymph node metastasis, it is of value to perform radical surgery with systematic lymph node dissection for the involved organs.

Aged↗

Oral administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) yields PhIP-DNA adducts but not tumors in male Syrian hamsters congenic at the N-acetyltransferase 2 (NAT2) locus.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine carcinogen present in well-done meat. PhIP must undergo host-mediated bioactivation to exert its mutagenic and carcinogenic effects. Following N-hydroxylation, N-acetyltransferases catalyze the O-acetylation (activation) of N-hydroxy-PhIP to an electrophile causing DNA damage. A well-defined genetic polymorphism in N-acetyltransferase 2 (NAT2) activity exists in humans and the Syrian hamster. Since some human epidemiological studies suggest an association between acetylator genotype and cancer susceptibility in individuals who consume well done meats, this study was designed to investigate the specific role of acetylator genotype in PhIP-induced tumors using a Syrian hamster model congenic at the NAT2 locus. Following oral administration of PhIP to male rapid and slow acetylator Syrian hamsters, DNA adducts were identified in each tissue examined with levels in the relative order: pancreas > heart and urinary bladder > prostate, small intestine and transverse colon > ascending colon, liver, cecum, descending colon, and rectum. However, no tumors were observed in male rapid and slow acetylator congenic hamsters administered 11 oral doses of PhIP (75 mg/kg) and maintained on a high fat diet for one year.

Acetylation↗

Metastatic epithelioid sarcoma with an N-ras oncogene mutation.

At age 25 a Japanese woman noticed an elastic-hard nodule 2 cm in diameter on the anterior side of her right leg. The nodule had developed an ulcer in its center. Simple resection was performed several times. However, the lesion recurred repeatedly. The patient underwent amputation of the right leg at the age of 34, because the diagnosis of epithelioid sarcoma was established histologically. No recurrence was observed for 9 years. Recently, the patient noticed multiple painful, ulcerative nodules about 1 cm in diameter on her scalp, trunk, and extremities. She refused extensive resection for a religious reason and died of massive hematemesis. Autopsy revealed metastatic epithelioid sarcoma in the skin, lungs, kidneys, pancreas, transverse colon, thyroid, and sternum. Chromosomal analysis of the tumor revealed various aberrations and an N-ras oncogene mutation.

Adult↗

Unexpected childhood death due to a rare complication of ventriculoperitoneal shunting.

A 10-year-old boy with Arnold-Chiari malformation, spina bifida, and a ventriculoperitoneal shunt for hydrocephalus died unexpectedly, having appeared to be only mildly unwell with fever on the night before death. At autopsy, the shunt was partially obstructed with an associated enterococcal meningitis. The tip of the shunt was located within the transverse colon, which was embedded in a mass of fibrous adhesions resulting from previous abdominal surgery. Blood cultures were sterile. Intestinal perforation is a rare complication of ventriculoperitoneal shunting that may be associated with the development of meningitis and unexpected death. The autopsy assessment of children with such indwelling devices requires examination of the functional state of the shunt, full septic workup, and determination of the precise location of the tip of the catheter within the peritoneal cavity.

Arnold-Chiari Malformation↗

Reversible ischemic colitis in young women. Association with oral contraceptive use.

Ischemic colitis, a condition of middle-aged to elderly patients, occurs uncommonly in younger persons. In this study, we describe the clinical and pathological features of 18 young adults (mean age, 29 years; age range, 17-39 years) with spontaneous ischemic colitis, 17 of whom were women. All presented with abrupt onset of severe, cramping abdominal pain followed by hematochezia. Colonoscopic visualization of the mucosa showed segmental hyperemia, friability, and erosion affecting the distal transverse colon (three cases), splenic flexure (three cases), descending colon (five cases), and sigmoid (seven cases). Mucosal biopsy documented superficial ischemic necrosis in seven patients; 11 patients had full-thickness mucosal necrosis with regeneration. Colonic mucosa proximal and distal to the ischemic segment was endoscopically normal in all patients and histologically normal in the eight patients in whom biopsies were obtained. All patients recovered with supportive care. Median duration of illness was 2.1 days (range, 1-4 days). Ten women (59%) were using low-dose estrogenic oral contraceptive agents, compared with the 1988 national average of 18.5% oral contraceptive users among females aged 15 to 44 years. The calculated odds ratio yielded a greater than sixfold relative risk for the occurrence of ischemic colitis among oral contraceptive users. In addition, four women not currently on hormonal contraceptive therapy had a past history of oral contraceptive use; the three remaining women were taking estrogen as replacement therapy after oophorectomy. In one patient, documented reversible ischemic colitis recurred on resumption of oral contraceptive use; four women reported symptoms and signs of recurrent ischemia but did not seek further medical evaluation. Our data indicate that transient colonic ischemia represents a form of acute segmental colitis in young adults; before the 5th decade of life, spontaneous ischemic colitis is a disorder found almost exclusively in women and is associated with the clinical use of exogenous estrogenic agents.

Adolescent↗

Histopathology and mismatch repair status of 458 consecutive colorectal carcinomas.

Defects in the mismatch repair (MMR) genes hMLH1 and hMSH2 have been found in 10% to 20% of sporadic colorectal carcinomas and also many cases of hereditary nonpolyposis colorectal cancer syndrome. Patients with these tumors have an improved prognosis and may show greater sensitivity to chemotherapy. We examined 458 resected colorectal carcinomas from 430 consecutive patients and used immunohistochemistry to determine which tumors lacked expression of these genes (MMR-d). We correlated the status of MMR-d or "intact" expression with stage, site, and histology. Eighty-nine of 458 tumors (19.4%) were MMR-d, including 80 hMLH1 and 9 hMSH2 tumors. A total of 6% of patients had synchronous tumors, and 37.7% of these were MMR-d (P=0.0008). A high proportion of patients with previous breast cancer (4 of 6 patients) had hMLH1-defective colorectal carcinomas. MMR-d tumors presented at an earlier stage than intact tumors, and the node-positive MMR-d tumors were less likely than intact tumors to have pericolonic extranodal tumor deposits (18.2% vs. 44%). The proportion of tumors at each site that were MMR-d increased progressively from cecum (32%) to ascending (35%) to transverse colon, where 41% of all tumors were defective. The proportions then rapidly decreased, reaching the lowest rate (4.7%) in the rectum. Both types of MMR-d tumors more often had expansive borders, intraepithelial lymphocytosis, peritumoral lymphoid, and Crohn's-like lymphoid responses than the intact tumors; the frequencies of these features diminished with advancing stage. Tumor budding was less common in stage II and III MMR-d tumors than in intact tumors. Keloid and myxoid type stromas correlated with stage and vascular invasion and were not related to mismatch repair status. Significant differences existed between the hMLH1 and hMSH2 tumors. The reported right-sided preponderance of MMR-d tumors is due to most hMLH1, but not hMSH2, tumors being found there (87.5% vs. 44.4%). hMSH2 tumors were most common in the rectum (55.6%). Mucinous tumors were common in hMLH1 tumors (36.3%) but not in hMSH2 tumors (11.1%). hMLH1 tumors were most likely to be poorly differentiated (70%), which was uncommon with hMSH2 tumors (22.2%). hMSH2 tumors were more likely to be confined to the wall (66.7%) than hMLH1 (20%) or intact tumors (23%). We conclude that hMLH1 and hMSH2-defective tumors have distinctly differing histologic features from each other.

Adaptor Proteins, Signal Transducing↗

Comparison of Payne and Scott operations for morbid obesity.

One hundred five patients were operated upon for morbid obesity using accepted criteria for operation. Forty-five patients with the Payne operation (35 cm of jejunum anastomosed end-to-side to 10 cm of ileum) were compared with 45 patients having the Scott operation (30 cm of jejunum anatomosed end-to-end to 15 cm of ileum with the proximal cut end of ileum vented into the transverse colon). The weight loss in the first two years was similar, although the Scott procedure patients lost slightly more weight. Comparison of the two groups by a new grading system also showed little difference in the two procedures. The Scott procedure takes longer and subjects the patient to an additional anastomosis. Study of a smaller group of patients having the Scott operation with varying lengths of jejunum and ileum indicates that there should not be less than 30 cm of jejunum nor more than 15 cm of ileum left in continuity. The length of jejunum is particularly important in the production of weight loss, and accurate intraoperative measurement of intestinal length is crucial. In the postoperative period the length of functional jejunum and ileum can be determined by upper gastrointestinal barium roentgenograms.

Adult↗

Malignant tumors in choledochal cysts.

Between 1960 and 1975, 17 patients with congenital cystic dilatation of the common bile duct (choledochal cyst) were treated and three were associated with malignant tumors in the cysts and one was with carcinoma of the gallbladder. Preoperative diagnosis of adenocarcinoma in the choledochal cyst was established in one patient by cytologic examination of the bile which was obtained during the procedure of endoscopic pancreaticocholangraphy (EPCG) and percutaneous transhepatic cholangiography (PTC). Definitive treatment of the choledochal cysts associated with malignant tumors in the biliary tract was accomplished by excision of the cysts with tumor and choledochojejunostomy in two patients, by cystoduodenostomy following external drainage in one and by cholecystectomy with resection of invaded transverse colon in one with cancer of the gallbladder. Successful excision of choledochal cysts in 11 patients including three cases associated with malignant tumors in the biliary tract during the last 15 year period is the basis of this report.

Adenocarcinoma↗

Abdominal organ cluster transplantation for the treatment of upper abdominal malignancies.

Ten patients with primary malignant tumors of the biliary tract, duodenum, or stomach and with secondary involvement of the liver underwent removal of most or all of the stomach, liver, pancreas, spleen, duodenum, proximal jejunum, terminal ileum, and ascending and transverse colon. The void in the upper abdomen was filled with an organ cluster graft consisting of the liver, pancreas, duodenum, and variable segments of proximal jejunum. Eight of the ten patients are alive after 3 to 9 months, all with good liver and pancreas function, and most with satisfactory function of the gastrointestinal tract. One of the surviving patients was in the hospital for 4 months because of multiple enteric fistulas and infections; the other seven survivors were discharged after an average of 43 +/- 17.61 (SD) days. Recurrent tumor has not been proved in any of the surviving recipients and is suspected in only one. The study of such cases should provide insight and guidelines applicable to other visceral transplantation procedures that may be attempted in the future.

Abdominal Neoplasms↗

Gastrointestinal myoelectric and clinical patterns of recovery after laparotomy.

The objective of this study was to define the patterns of myoelectric activity that occur throughout the gastrointestinal tract during normal recovery from laparotomy. Electrodes were placed on the stomach, jejunum, and transverse colon of 44 patients undergoing laparotomy. Basal electric rhythms in all areas showed no changes in frequency after operation (up to 1 month). Gastric spike wave activity showed a gradient of increasing activity from fundus to antrum. Antral spike activity was unchanged during the study. Jejunal spike activity was present in the earliest recordings and occurred in 45.9% +/- 3.5% to 59.9% +/- 5.5% of slow waves. Recovery of normal colon discrete and continuous electric response activity occurred on postoperative day 5.9 +/- 1.5. Bowel sounds returned on day 2.4 +/- 0.5 and passage of flatus and stool occurred on day 5.1 +/- 0.2. The myoelectric parameters measured are not absolutely predictive of uneventful recovery from postoperative ileus but they are, as a group, more informative than any currently available clinical criteria.

Colon↗

The value of barium enema and colonoscopy in patients infected with HIV.

Double contrast barium enema (DCBE) and colonoscopy were prospectively compared with rigid sigmoidoscopy, rectal biopsy and microbiological examination in the analysis of stool specimens in 58 HIV-1-infected patients with diarrhoea (more than three liquid motions/day for greater than 1 month). In 26 patients no cause for the diarrhoea was found. In 17 patients the cause of diarrhoea was microbiological, and in 19 rectal histology provided a specific diagnosis. In all these patients sigmoidoscopic appearances were abnormal except in those with Cryptosporidium alone. Colonoscopy provided additional information in only one individual, with cytomegalovirus ulcers of the transverse colon. DCBE was abnormal in only seven cases (cytomegalovirus in three, Kaposi's sarcoma in two, Giardia lamblia in two) and in no case provided additional information. A combination of stool microbiology and rectal histology gave a sensitivity of 97% with a positive predictive value of 100%. The sensitivities of DCBE and colonoscopy with histology were low (16 and 62%, respectively) although the specificity for each test was high, with high positive predictive values. We conclude that neither barium enema nor colonoscopy add usefully to rigid sigmoidoscopic biopsy and stool microscopy in HIV-positive patients with diarrhoea.

Barium Sulfate↗

Use of intraoperative radionuclide study and colonoscopy in gastrointestinal hemorrhage.

Tc-99m labeled red cell imaging is used in the diagnosis and localization of gastrointestinal hemorrhage. A patient in whom a preoperative scan was positive in the right paraumbilical region is discussed. Intraoperative Tc-99m labeled red cell imaging was used in conjunction with colonoscopy, and the site of active bleeding was found in the proximal transverse colon, which had been displaced downward because of adhesions.

Colonoscopy↗

Extensive gastric varices demonstrated by technetium-99m red blood cell scintigraphy.

An alcohol abuse patient complicated by chronic pancreatitis had splenic vein thrombosis leading to gastric varices and underwent abdominal Tc-99m red blood cell scintigraphy. First pass study, sequential images up to 1 hour, and a 2.5 hour image showed abnormal radioactivity in the left side of the abdomen and midabdomen. In 24 hour images, the high level of activity in the left side persisted; in addition, there was accumulation of radioactivity in the cecum, ascending, transverse colon, the splenic flexure, and descending colon. A splenectomy was performed and during the surgical procedure, a large dilated vein in the greater omentum was noted. It is reemphasized that delayed imaging up to 24 hours is important when the results of earlier images are equivocal or negative.

Alcoholism↗

Efficacy of hepatobiliary scintigraphy in demonstrating cholangio-colic fistulae. Is formation of internal biliary fistula related to external leak closure?

The authors present four cases of internal biliary fistulae (IBF) identified on hepatobiliary scintigraphy. All of the cases share common history of external biliary leak closure. Scintigraphy in all four cases showed a similar pattern of direct visualization of transverse colon without any significant small bowel activity. This suggests an increased frequency of IBF formation in cases with external fistulous tract closure. Retrospectively, it appears that spontaneous closure of external leak may be pathological consequence of formation of IBF involving hepatic flexure.

Adult↗

CT appearance of diaphragmatic pseudotumors.

Invaginations of the muscular fibers of the diaphragm into the upper abdomen may appear as nodules of soft tissue density on computed tomographic (CT) sections in deep inspiration. If these nodules indent the adjacent stomach or distal transverse colon, they may mimic small mural tumors or metastatic implants. Similar nodules protruding from the diaphragmatic crura into the adjacent retroperitoneal fat may be mistaken for enlarged lymph nodes on CT. Differential diagnosis of these pseudotumors from pathologic lesions is based on their continuity peripherally with the diaphragm and their separation from the hollow viscera by subdiaphragmatic fat. Decubitus and expiratory CT sections are valuable diagnostic aids.

Adolescent↗