To compare operative morbidity, mortality, quality of life, and survival after pancreatoduodenectomy (PD) versus pancreatoduodenectomy with extended lymphadenectomy (PD/ELND) in patients with ...resectable pancreatic cancer.
From May 1997 to July 2003 there were 132 patients with biopsy examination–proven or suspected adenocarcinoma of the pancreatic head who agreed to participate in a single-institution, prospective, randomized trial. If resectable at operation, patients then were randomized to standard PD (40 patients) or PD/ELND (39 patients). Quality of life was assessed by using the Functional Assessment of Response to Cancer Therapy specific to the pancreas. Morbidity, mortality, and survival were analyzed.
Demographics and pathologic characteristics for both groups were similar. When comparing PD/ELND with standard PD, the median operating time was greater for the PD/ELND group (7.6 h vs 6.2 h,
P < .01), blood transfusion more likely (44% vs 22%,
P < .05), and the median number of lymph nodes resected was greater (36 vs 15 nodes,
P < .01). Morbidity and mortality rates were comparable. Median durations of stay were 11 and 10.5 days (
P = NS), respectively. There were no significant differences in 1-year (71% vs 82%), 3-year (25% vs 41%), 5-year (16.5% vs 16.4%), and median (19 vs 26 mo) survival (
P = .32). At 4 months postoperatively, diarrhea, body appearance, and bowel control scored lower on the Functional Assessment of Response to Cancer Therapy specific to the pancreas after PD/ELND (
P < .05).
Although a much larger study would have more power to compare statistically the survival between groups, both the decrement in quality of life and similar studies showing no survival difference make PD/ELND unattractive for further prospective investigation.
Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most ...programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without extrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n = 6), subsequent development of malignant ascites (n = 1), or death from intrahepatic biliary sepsis (n = 1). Eleven patients completed the protocol with successful OLT Except for 1 patient, all had early-stage disease (stages I and 11) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients > 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemother apy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma.
To date, at least four genes involved in DNA mismatch repair (MMR) have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colon cancer: hMSH2, hMLH1, hPMS1, and ...hPMS2. Additionally, loss of MMR function has been demonstrated to lead to the phenomenon of microsatellite instability (MIN) in tumors from these patients. In this study, we have examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in paraffin-embedded tumors from 7 patients with MIN+ sporadic cancer, 13 patients with familial colorectal cancer, and 12 patients meeting the strict Amsterdam criteria for hereditary nonpolyposis colon cancer. The relationship between the expression of these two gene products, the presence of germline or somatic mutations, and the presence of tumor MIN was examined. Nineteen of the 28 tumors studied demonstrated MIN, whereas mutations in hMLH1 and hMSH2 were detected in 6 and 2 patients, respectively. Of the eight MIN+/mutation+ cases, the absence of protein expression was observed for the corresponding gene product in all but one case (missense mutation in hMLH1). However, seven MIN+/mutation- cases also showed no expression of either hMLH1 (n = 5), hMSH2 (n = 1), or both (n = 1), whereas four MIN+/mutation- cases demonstrated normal expression for both. None of the MIN-/mutation- cases (n = 9) demonstrated an altered expression pattern for either protein. These data suggest that examination of protein expression by immunohistochemistry may be a rapid method for prescreening tumors for mutations in the MMR genes.
The CDH1 gene encodes E-cadherin, an epithelial cell adhesion molecule. Germline CDH1 mutations recently were identified in families with hereditary diffuse gastric carcinoma in a pattern suggestive ...of autosomal dominant inheritance with incomplete penetrance.
The proband was a woman age 47 years with a strong family history of diffuse gastric carcinoma. A germline E-cadherin gene mutation was identified in this patient, her brother, and three first cousins. All five family members underwent endoscopic evaluations, which were negative for malignancy, and elected to undergo a prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy.
Pathologic examination of the proband's stomach revealed several microscopic foci of intramucosal signet ring cell adenocarcinoma in the cardia and proximal gastric body. Postgastrectomy specimens from the proband's brother and three first cousins all showed intramucosal signet ring cell adenocarcinoma in various regions of the stomach. Immunoperoxidase studies performed on gastric tissue from these five patients demonstrated diminished or absent E-cadherin reactivity in the cancerous mucosa.
Although total gastrectomy was performed as a prophylactic intervention, occult gastric carcinoma was discovered in all five patients. Thus, total gastrectomy should be curative for gastric carcinoma in these patients. Based on their successful outcomes and the lack of efficacious surveillance methods for diffuse gastric carcinoma, prophylactic total gastrectomy may be the management of choice for germline E-cadherin gene mutation carriers. However, prophylactic total gastrectomy should be undertaken cautiously because the procedure may be associated with considerable morbidity.
Background: Formation of a submucosal fluid cushion has become integral to endoscopic mucosal and polyp resection. Solutions available for injection into the submucosa of the GI tract create ...short-lasting submucosal fluid cushions or are costly. The feasibility, durability, and histologic response to submucosal fluid cushions created by injection of hydroxypropyl methylcellulose were studied in the esophagus of pigs.
Methods: Thirty-six esophageal submucosal fluid cushions created with hydroxypropyl methylcellulose were studied in 12 animals divided in 2 groups of 6 animals each. In Group I, 18 submucosal fluid cushions were created by submucosal injection of hydroxypropyl methylcellulose followed by tattooing. In Group II, 18 submucosal fluid cushions were created by submucosal injection of hydroxypropyl methylcellulose, with sites marked by an endoscopically placed suture. In all cases, the duration of the submucosal fluid cushion was measured. After 7 days, submucosal fluid cushion sites were assessed by EGD, necropsy, and histologic evaluation.
Results: The mean submucosal fluid cushion duration was 36 minutes (3-45 minutes) and 38 minutes (5-45 minutes) for, respectively, Groups I and II. EGD and necropsy after 1 week showed normal-appearing mucosa at the site of all submucosal fluid cushions in both groups. Some Group I animals additionally had nodules at the tattoo sites. Histologic assessment demonstrated minimal alterations in 33 of 36 (92%) submucosal fluid cushion sites and localized mild inflammatory reaction in 3 of 36 (8%). In Group I, 8 of 18 (44%) tattoo sites exhibited a significant inflammatory reaction, including 3 abscesses.
Conclusions: Hydroxypropyl methylcellulose creates a long-lasting submucosal fluid cushion with minimal tissue reaction and should be considered a low-cost option for creating submucosal fluid cushions. The use of tattooing with carbon black should be carefully considered when histologic study is required to assess potential inflammatory tissue responses to an invasive technique or instillation of foreign material in the GI tract. (Gastrointest Endosc 2003;57:41-7.)
Nonresponse or relapse of symptoms is common in patients with celiac disease treated with gluten free diet. Refractory sprue (RS) is defined as initial or subsequent failure of a strict gluten-free ...diet to restore normal intestinal architecture and function in patients who have celiac-like enteropathy. The aims of this study were: 1) to identify causes of persistent symptoms in patients referred with presumed diagnosis of nonresponsive celiac disease (NCD); and 2) to characterize patients with true RS.
Patients were identified who had been systematically evaluated for NCD between January 1997, and May 2001. Patient records and small bowel biopsy results were reviewed.
A total of 55 patients were referred with a presumed diagnosis of NCD. Six did not have celiac disease and had other diseases responsible for their symptoms. Diarrhea, abdominal pain, and weight loss were the most common reasons for evaluation in cases of NCD, whereas weight loss, steatorrhea, and diarrhea were the most common presenting features of RS (nine patients). Of the 49 patients with celiac disease, 25 were identified as having gluten contamination. Additional diagnoses accounting for persistent symptoms included: pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, T-cell lymphoma, pancreatic cancer, fructose intolerance, protein losing enteropathy, cavitating lymphadenopathy syndrome, and tropical sprue.
Based on this study, we conclude the following: 1) gluten contamination is the leading reason for NCD; 2) of NCD cases, 18% are due to RS; and 3) alternative diseases or those coexistent with celiac disease and gluten contamination should be ruled out before a diagnosis of RS is made.
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