Reversibility of adenomatous hyperplasia in the gastric stump after diversion of bile reflux in rats

Morphological and phenotypical patterns of proliferative epithelial lesions induced in the gastric stump mucosa by duodenal content reflux after Billroth II partial gastrectomy (BII) were evaluated in rats. Control animals were either sham-operated or submitted at different times after BII to Roux-en-Y (RY) surgical procedure which prevents duodenal reflux. The lesions were analysed using routine haematoxylin and eosin staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical Concanavalin A, galactose oxidase Schiff and sialidase galactose oxidase Schiff reactions). Mucosal hyperplasia (H) was observed in the group submitted to BII procedure 6 weeks after surgery. Adenomatous hyperplasia (AH) also appeared 6 weeks after induction of the reflux and its incidence and size increased until the 54th week of the experiment. RY procedure performed in the normal animals at the beginning of the experiment or at the 24th week after BII gastrectomy led to a significantly lower incidence of AH which was related to the moment of surgery. Most of H was due to pyloric mucosal hyperplasia. AH consisted mainly of gastric type glands but in some animals glands of the intestinal type were present probably originating from the intestinal mucosa. Six mucinous adenocarcinomas were observed, all of them of intestinal type. This study demonstrates that AH induced by BII procedure is a reversible lesion and that the anomalous epithelial proliferation in the stoma may lead to adenocarcinomas.     

Changes in rectal epithelial cell proliferation and intestinal bile acids after subtotal colectomy in familial adenomatous polyposis.

Subtotal colectomy and ileorectal anastomosis in familial adenomatous polyposis patients can induce temporary regression of adenomas in the rectum. The mechanism for this phenomenon is unclear. We evaluated the effect of colectomy on rectal mucosal proliferation, in relation to changes in bile acid metabolism. Four familial adenomatous polyposis patients were studied before and 3-6 months after surgery, and eight others 7-22 years postoperatively. Within 6 months after surgery, the size of the proliferative zone of the colonic crypts was found to be reduced (P less than 0.05). The proliferative activity of total colonic crypts was not affected within this period. More than 7 years postoperatively, increased cell proliferation of total crypts (P less than 0.02), as well as mid (P less than 0.05) and basal (P less than 0.05) crypt compartments, were observed compared to shortly after colectomy. In duodenal bile, deoxycholic acid was absent shortly after operation, whereas several years after operation only a small fraction (2%) was present. Fecal secondary bile acid excretion diminished after colectomy and did not change several years postoperatively. In postoperative stools only, small proportions of ursocholic and ursodeoxycholic acids (about 5% each) were consistently found. As subtotal colectomy causes a temporary decrease in the length of the proliferative zone of rectal crypts toward a normal pattern, this may explain regression of rectal polyps. This temporary effect may be mediated, at least in part, by decreased amounts of cytotoxic secondary bile acids in the rectal lumen.     

Lanzoprazole promotes gastric carcinogenesis in rats with duodenogastric reflux

Background Duodenogastric reflux is known to cause an increased frequency of cancer in the glandular portion of the stomach in rats. Furthermore, it is debated whether inhibition of gastric acid secretion may promote gastric carcinogenesis. In the present study we examined the combined effect of gastroduodenal reflux and acid inhibition with respect to the development of gastric carcinoma in the rat.Methods Following the construction of a gastrojejunostomy in male Wistar rats, half of them were given the proton pump inhibitor lanzoprazole for 1 year. The rats were then killed and the pH in the stomach and gastrin in blood were measured. The stomach was examined macroscopically as well as histologically.Results Gastrin levels at autopsy were significantly increased in treated rats compared to the control group, confirming an effect of lanzoprazole on gastric acid secretion. Body weight was significantly reduced in the treated rats. Thirty of 79 rats developed gastric cancer, and they were all adenocarcinomas of the Lauren intestinal type. Gastric cancers occurred significantly more often in lanzoprazole-treated rats (50%) compared with controls (27%).Conclusion Lanzoprazole given orally enhances the carcinogenic effect of duodenogastric reflux in rats.     

Positive association between dietary fat intake and risk of gastric stump carcinoma in rats

Effect of high- and low-fat diets on gastric stump carcino-genesiswas experimentally investigated. A total of 130 Wistar malerats weighing 250–300 g received either sham operationor Billroth II partial gastrectomy, the resection of the distaltwo-thirds glandular stomach and reconstruction of gastro-jejunostomy.After surgery, each group of rats was switched from a standarddiet (CRF-1) to a special diet containing either 15% soybeanoil (high-fat) or 0.5% soybean (low-fat), fed ad libitum andtap water, and were killed 50 weeks after surgery. Gastric tumourswere observed only in the animals that underwent gastrectomy,while no tumours were detected in the animals following thesham operation. Tumours located invariably at the gastrojejunostoma,were carcinomas or adenomas in histology. Carcinomas developedin 12 of 29 gastrectomy animals (41%) fed the high-fat dietand 4 of 27 gastrectomy animals (15%) fed the low-fat diet.The difference was significant (P < 0.05). The incidenceof adenoma was also significantly higher in the gastrectomyanimals fed the high-fat diet (38%) than that in those fed thelow-fat diet (15%) (P < 0.05). A daily faecal output of bileacids was significantly greater in the gastrectomy animals fedthe high-fat diet (19.0 ± 16.4 µmol/day) than thatin those fed the low-fat diet (11.2 ± 6.2 µmol/day;P < 0.05). This study suggests that increased fat intakeis associated with a high risk of gastric stump carcinoma.     

Gastric stump cancer after distal gastrectomy for benign gastric ulcer in a population-based study

The risk of cancer in the gastric remnant after distal gastrectomy for benign ulcer disease has been assessed mainly in studies of small sample size, selected series and limited follow-up time. This was a population-based cohort study of patients who had undergone distal gastrectomy for benign ulcer disease in 1964-2008 in Sweden. Data for follow-up for cancer and censoring for death were obtained from nationwide registries of Cancer and Population, respectively. The number of observed cancer cases in the gastrectomy cohort was divided by the expected number, calculated from the cancer incidence of the Swedish population of corresponding age, sex and calendar year. Relative risks were presented as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). The distal gastrectomy cohort included 18,912 patients and 323,676 person-years at risk. The observed total number of gastric stump cancers (n = 140) was not higher than expected (SIR 0.84, 95% CI 0.71-0.99). There was no increased SIR with latency periods shorter than 30 years; increase was seen only among patients who had undergone gastric resection over 30 years earlier (SIR 2.29, 95% CI 1.38-3.57). Sex, age, ulcer location and type of surgical reconstruction were not associated with any considerable differences in SIR. In conclusion, this large population-based study revealed an increased risk of cancer in the gastric remnant only 30 years or longer after gastric resection for benign disease, whereas other factors did not influence this risk.     

残胃癌与初发胃癌外科治疗及预后的比较研究

目的:回顾分析残胃癌与初发胃癌手术治疗及预后的差异.方法:对我院2000-01-2007-12收治的残胃癌根治手术切除患者69例,并取同期手术治疗的初发胃癌69例做对照研究.结果:残胃癌组和胃癌组相比,手术时间[(225.4±34.9) min vs(184.0±30.9)min]、术中出血[(416.8±338.6)mL vs(227.8±185.3)mL]、联合脏器切除率(30.43％ vs 4.35％)、术后并发症(27.54％ vs 7.25％)、术后住院时间[(15.4±5.6) d vs(12.5±3.8)d]的差异有统计学意义,P＜0.05;而清除淋巴结数目[(17.3±5.6)枚vs(17.9±6.4)枚]、3年生存率(40.6％ vs 53.6％)相比差异无统计学意义,P＞0.05.结论:残胃癌手术难度较大、并发症高,术后住院时间长,但其预后与初发胃癌无差异.     

胃癌组织中微血管、微淋巴管生成和增殖细胞分布与胃癌预后的关系

Objective  

We investigated the relationship between lymphangiogenesis, angiogenesis and cell proliferation in gastric cancer.     

重建贲门、胃底预防食管癌术后反流性食管炎的临床价值分析

目的 通过在管胃的基础上重建贲门(人工贲门)、胃底(人工胃底)探讨手术方式对预防食管癌术后胃食管反流的临床效果.方法 将73例食管癌患者按手术方式不同分成单纯管胃组(37例)和管胃+抗反流组(36例),分别在术后的1、6、12个月对患者术后的反流症状、上消化道造影、24 h pH值监测及胃镜结果 进行比较.结果 全组无手术死亡患者.术后反流症状、上消化道造影、胃镜等结果 提示管胃+抗反流组与管胃组组间比较差异无统计学意义(P>0.05).两组患者在24 h pH值测定术后1个月、6个月的总反流数,术后1个月、6个月的反流>5 min数,术后6个月、1年的pH值<4时间比较,差异有统计学意义(P<0.05),提示管胃+抗反流组抗反流效果总体优于单纯管胃组.其中管胃+抗反流组无吻合口瘘出现,但吻合口狭窄发生率要高于管胃组(19.4%vs 10.8%).结论 管胃+重建贲门、胃底术式较单纯管胃术式能更好地控制食管癌术后胃食管反流,且降低了术后出现吻合口瘘的风险.     

Cell proliferative activity in adenomatous hyperplasia of the liver and small hepatocellular carcinoma. An immunohistochemical study demonstrating proliferating cell nuclear antigen.

BACKGROUND. Recently, adenomatous hyperplasia (AH) of the liver, a sizable parenchymal nodule in the cirrhotic liver, has been considered a preneoplastic lesion in human hepatocarcinogenesis. METHODS. The authors evaluated cell proliferative activity by immunostaining for proliferating cell nuclear antigen (PCNA) in AH (n = 30), small hepatocellular carcinoma (HCC) (n = 14), and their surrounding regenerative nodules (SRN). RESULTS. AH was categorized histologically as ordinary or atypical. Ordinary AH (n = 8) had no hepatocellular atypia, whereas atypical AH (n = 22) was composed of atypical hepatocytes that were equivocal as to benignity and malignancy. Three atypical AH contained overt malignant foci. The PCNA labeling index of ordinary AH was lower than that of SRN and the index of atypical AH was higher than that of SRN except in two cases. The PCNA labeling index of malignant foci within atypical AH was higher than that of nonmalignant areas of atypical AH and was similar to that of small HCC. For small HCC, the PCNA labeling index was much higher than that of SRN and correlated with small HCC grades. CONCLUSIONS. These data suggest that ordinary AH is a largely developed regenerative nodule with little proliferative activity and that it is not a preneoplastic lesion; the data also indicate that atypical AH has much proliferative activity, from which malignant foci with greater proliferative activity emerge. Atypical AH with or without malignant foci may represent an early stage of multi-step hepatocarcinogenesis in humans.     

N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps

This investigation is part of an effort to develop chemoprevention for carcinogenesis of the large bowel. The agent investigated is N-acetylcysteine (NAC). We used as a predictive biomarker, the proliferative index (PI), in a short-term human study. Patients with previous adenomatous colonic polyps are a cohort with increased risk for colon cancer and an increased PI of colonic crypts. They were randomly assigned to an experimental group given 800 mg/day of NAC for 12 weeks or a placebo group. Using proliferative cell nuclear antigen immunostaining, the PI of colonic crypts was measured prior to and after the treatments. The PI of the NAC group was decreased significantly (P < 0.02) while the placebo group showed no difference (P > 0.45). Since this decrease in PI may be an indicator of decreased risk of colon cancer, more extensive studies of the potential of NAC as a chemopreventive agent for colon cancer appear warranted.     

Complete regression of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the gastric stump after eradication of Helicobacter pylori

Recent studies have suggested that Helicobacter pylori (H. pylori)-associated gastritis may play an important role in the pathogenesis of primary gastric lymphoma. Recently, triple therapy using proton pump inhibitor, amoxicillin, and clarithromycin, has been established for the eradication therapy of H. pylori infection, and is also recommended for the treatment of the superficial type of low-grade gastric MALT (mucosa-associated lymphoid tissue ) lymphoma. MALT lymphoma of the gastric stump is rare, and total resection or chemotherapy for MALT lymphoma of the gastric stump has been previously reported. Therefore, there is no evidence that eradication therapy is effective for low-grade MALT lymphoma of the gastric stump. Our case illustrates the remarkable efficacy of eradication of H. pylori for low-grade MALT lymphoma of the gastric stump without other modalities such as surgery and systemic chemotherapy.     

Expression of cyclin D1 and p53 and its correlation with proliferative activity in the spectrum of esophageal carcinomas induced after duodenal content reflux and 2,6-dimethylnitrosomorpholine administration in rats

Alterations in expression of the p53 and cyclin D1 genes have been implicated in the development of esophageal carcinomas in both humans and animal models. We hypothesize that altered expression of cyclin D1 and p53 may be involved in the sequential development of esophageal carcinomas with glandular differentiation induced by the carcinogen, 2,6-dimethylnitrosomorpholine (DMNM) in rats with duodenal content reflux esophagitis. In the present study Sprague-Dawley rats were given DMNM 15 days after performing an esophago-jejunostomy in order to induce chronic duodenal content reflux esophagitis. Expression and localization of p53, cyclin D1 and Ki-67 were examined by immunohistochemical analyses. Twenty of 24 animals developed different types of esophageal carcinomas, including pure squamous carcinoma, adenosquamous carcinoma and pure adenocarcinoma. Undifferentiated basaloid areas were frequently observed in these tumors. Cyclin D1 overexpression was observed in hyperplastic lesions and increased through dysplasia and in undifferentiated areas of infiltrating carcinoma. Cyclin D1 expression coincided with increased Ki-67 expression and decreased along with cell differentiation. The p53 immunohistochemical pattern was parallel to that of cyclin D1, although the percentage of positive cells was usually smaller in all lesions and increased p53 expression started at the dysplastic stage. These findings suggest that overexpression of cyclin D1 may be an early event in DMNM-induced rat esophageal tumorigenesis, causing increased proliferation of esophageal stem cells. Abnormal p53 expression may then be required to promote the development of neoplastic transformation from dysplastic epithelium through invasive phenotype, being more evident in cancer cells with squamous differentiation.     

Duodenal stump fistula after gastric surgery for malignancies: a retrospective analysis of risk factors in a single centre experience

Background

Duodenal stump fistula (DSF) is the most severe surgical complication after gastrectomy. This study was designed to assess the incidence, to observe the consequences, and to identify the risk factors associated with DSF after gastrectomy.

Methods

All procedures involving total or sub-total gastrectomy for cancer, performed between January 1987 and June 2012 in a single institution, were prospectively entered into a computerized database. Risk factors analysis was performed between DSF patients, patients with complete uneventful postoperative course and patients with other major surgical complications.

Results

Over this 25 years period, 1287 gastrectomies were performed. DSF was present in 32 cases (2.5 %). Mean post-operative onset was 6.6 days. 19 patients were treated conservatively and 13 surgically. Mean DSF healing time was 31.2 and 45.2 days in the two groups, respectively. Mortality was registered in 3 cases (9.37 %), due to septic shock (2 cases) and bleeding (1 case). In monovariate analysis, heart disease (p < 0.001), pre-operative lymphocytes number (p = 0.003) and absence of manual reinforcement over duodenal stump (p < 0.001) were found to be DSF-specific risk factors, whereas liver cirrhosis (p = 0.002), pre-operative albumin levels (p < 0.001) and blood losses (p = 0.002) were found to be non-DSF-specific risk factors. In multivariate analysis heart disease (OR 5.18; p < 0.001), liver cirrhosis (OR 13.2; p < 0.001), bio-humoral nutritional status impairment (OR 2.29; p = 0.05), blood losses >300 mL (OR 4.47; p = 0.001) and absence of manual reinforcement over duodenal stump (OR 30.47; p < 0.001) were found to be independent risk factors for DSF development.

Conclusions

Duodenal stump fistula still remains a life-threatening complication after gastric surgery. Co-morbidity factors, nutritional status impairment and surgical technical difficulties should be considered as important risk factors in developing this awful complication.