Effect of duodenal components of the refluxate on development of esophageal neoplasia in rats

When duodenal content is allowed to reflux into the esophagus of nitrosamine-treated rats, esophageal cancer is induced more rapidly and at higher frequency than after carcinogen treatment alone. The purpose of the present study was to identify the components of the duodenal content that are responsible for enhancing esophageal carcinogenesis. Eight-week-old Sprague-Dawley rats underwent one of four operations as follows: diversion of bile alone, pancreatic juice alone, both bile and pancreatic juice into the esophagus, or a control operation with no induced reflux. Two weeks after surgery, rats were treated with the esophageal carcinogen 2,6-dimethylnitrosomorpholine (48 mg/kg [0.1 of LDs0] intraperitoneally weekly for 20 weeks). The rats were killed at age 30 weeks. The esophagus was removed and full-length strips were examined under a microscope; separate segments were taken for flow cytometric evaluation. The prevalence of DNA aneuploidy and histologic esophageal papillomas or squamous cancer was increased in carcinogen-treated rats with pancreatic juice reflux (P <0.05 vs. control) and the combination of pancreatic and bile reflux (P <0.05 vs. control) but not in rats with bile reflux alone. We conclude that pancreatic juice is the most potent component of the duodenal refluxate in the promotion of esophageal carcinogenesis in rats.     

Effects of reflux of bile and/or pancreaticoduodenal juice on gastric carcinogenesis in rats

The present study was designed to investigate which fraction of duodenal contents was responsible for gastric carcinogenesis, bile or pancreaticoduodenal juice. A series of 61 male Wistar rats were subjected to one of following four operative procedures: total reflux (TR, n = 17), bile reflux (BR, n = 8), or pancreaticoduodenal reflux (PDR, n = 16), and simple laparotomy (control, n = 20). Fifty weeks after operations the animals were sacrificed. The incidence of gastric adenocarcinoma was 7/17 (41%) in TR group, 2/8 (25%) in BR group, 0/16 (0%) in PDR group, and 0/20 (0%) in control group. The incidence of cancer in the both TR and BR groups were significantly higher than PDR and control groups, respectively. Histologically, lesions of gastric cancers showed tubular adenocarcinoma or mucinous adenocarcinoma. There was a significant difference in the intragastric pH between the first three reflux groups and control group. The concentrations of the total bile acids of the both TR and BR groups were significantly higher than PDR and control groups, respectively. These results suggested that duodenogastric reflux induces adenocarcinoma in the rat gastric mucosa and bile rather than pancreatico-duodenal juice is related to increased risk for gastric cancer.     

胰十二指肠切除术改进胰肠及胃肠吻合方式52例观察

目的探讨胰十二指肠切除术改进胰肠及胃肠吻合方式对患者近期和远期并发症的影响。方法对52例行胰十二指肠切除术的患者进行消化道重建,方式为胰肠、胆肠和胃肠顺序。胰肠吻合在完成胰十二指肠切除后,游离胰腺残端2．5～3．0cm,将准备与胰腺吻合的空肠袢断端浆肌层剥除,制成黏膜瓣,长度与胰腺断面前后径相当,施行黏膜瓣覆盖胰腺断面的套叠式胰空肠端端吻合术;胃肠吻合是在胃或十二指肠球部与胰胆侧肠袢之间问置30cm空肠施行胃肠道重建。结果术后发生胰漏2例（3．8％）,经充分引流并给予生长抑素、肠内营养等保守治疗愈合,无腹腔感染及大出血等严重并发症。术后随访3年,随访率为88．5％（46／52）,术后半年95．0％（38／40）的患者消化吸收功能基本正常,营养状况良好,未发生逆行性胆管炎、胆汁反流性胃炎、胃肠吻合口溃疡。结论施行胰十二指肠切除消化道重建过程中,采用黏膜瓣覆盖胰腺断面的套叠式胰空肠端端吻合术有助于减少胰漏等近期并发症在胃或十二指肠球部与胰胆侧肠袢之间间置空肠,可减少胃肠道反流等远期并发症。     

Choledochopancreatic elongated common channel disorders

A choledochopancreatic end-to-side ductal anastomosis was successfully performed in 40 puppies as an experimental animal model of choledochopancreatic elongated common channel disorders. Follow-up periods were up to 1 year after surgery. Fusiform dilatation was developed in all puppies. The dilatation was completed within 1 week after surgery and did not increase its size after that. Also, all puppies developed pancreatic juice reflux into the bile duct. As for the etiology of the dilatation of the bile duct, temporary stricture of anastomosis was a more important factor than the pancreatic juice reflux in our models. In the biliopancreatic juice, we found no significant change of bile acid analysis between the control and our operated puppies, but almost all pancreatic enzyme activities were elevated. Bile acid was considered to play an important role in the activation of pancreatic enzymes. Epithelial hyperplasia was the only significant pathological change in the bile duct wall. Definite chronic pancreatitis developed in one puppy 16 months after surgery and was considered to be caused by the reflux of bile into the pancreatic duct. The action of biliopancreatic juice to both the bile duct and to the pancreas was mild and chronic.     

Contributions of bile and pancreatic juice to cell proliferation in ileal mucosa

To determine the relative contributions of bile and pancreatic juice to adaptive intestinal hyperplasia, cell proliferation in rat ileal mucosa was studied after supplying bile alone or the combined pancreaticobiliary effluent direct to mid-small bowel. Bile was routed through the choledochus cannulated above the pancreas. Pancreaticobiliary secretions were diverted through a transposed duodenal segment containing the papilla. Diversion of bile into the mid-bowel with and without pancreatic juice caused similar increases in ileal ribonucleic acid (RNA) (16% to 50%) and deoxyribonucleic acid (DNA) (22% to 41%) contents at both 48 hours and 1 week after operation. Specific activity of DNA after injection of tritiated thymidine was greatest after diversion of the combined effluent. After 1 month nucleic acid contents in the upper ileum after pancreaticobiliary diversion were 37% to 59% higher than after transection or biliary diversion (P less than 0.005). Likewise, after biliary diversion villous height and crypt depth were increased only at 1 week, but after diversion of both secretions increases were found at 1 week and 1 month. High luminal concentrations of bile cause transient cell proliferation in ileal mucosa, but the additional presence of pancreatic juice prolongs this adaptive response.     

Endoscopic evaluation of various methods of anastomosis after gastrectomy

Resection of the stomach is still the principal method for surgical management of gastric and duodenal ulcer. The functional condition of the anastomosis depends on the method used. The authors conducted comparative endoscopic evaluation of anastomoses formed after Hofmeister-Finsterer, Billroth I, Andreo and Vitebsky according to the following criteria: shape and diameter; contractile and obturator function; gastrointestinal reflux; morphological changes in the zone of the anastomosis and the gastric stump. The authors analyse their own material concerning fibrogastroscopy in 168 patients after gastric resection, the anastomosis was established after Hofmeister-Finsterer in 93 of them after Vitebsky in 46, after Billroth I in 21, and after Andreo in 8. Vitebsky's modification of Billroth II anastomosis and Andreo's modification of Billroth I anastomosis possess the best functional capacities. Billroth I and Billroth II gastroenterostomy in Hofmeister-Finsterer's modification do not possess contractile and obturator property, which promotes reflux of bile into the gastric stump and the development of reflux gastritis and other complicating factors.     

The extent of bile reflux and development of gastric cancer after resections in rat

Authors performed gastric resections (Billroth II, Billroth I, Billroth II+, Braun anastomosis and Roux Y reconstruction) and laparotomies in five groups, of 110 Wistar male rats. Thirty-eight weeks postoperatively the surviving 91 animals were sacrificed, and histological study was made of the frequency of gastric stump cancer in the individual groups and the extent of bile reflux characteristic of the individual GEA types was measured. Based on their results, the risk of stump cancer was higher in operation types associated with considerable bile reflux (a cancer incidence rate of 50% after Billroth II, 28.5% after Billroth I). Following gastric resections accompanied by insignificant bile reflux (Billroth II + Braun, Roux Y) the risk of gastric stump cancer was significantly lower.     

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目的探讨胃大部切除术后残胃返流液的致癌活性，为残胃癌的临床监测及胃术后治疗提供科学的依据。方法通过Ames实验室及MTT增殖实验，分别检测48例长期胃术后十二指肠返流液的肿瘤启动性(即致突变性)及促癌(增殖)活性。结果B-Ⅱ式术后返流液的促癌活性明显高于B-Ⅰ式(P=0.751)，但返流液的肿瘤启动性与手术术式无关(P＞0.05)；返流液pH值与促癌活性高度相关(rs=0.73,P＜0.001)，而与肿瘤启动性无关。结论通过胃术后病人的十二指肠返流液证实了残胃癌的返流学说；返流液促癌活性是残胃癌高发的主要决定因素。并提示有必要对残胃中、重度不典型增生的病人实施内镜监控。     

Correction of chronic disorders of duodenal patency in the prevention of postoperative complications of peptic ulcer

Experiments on dogs demonstrated the role of chronic disorders of duodenal patency (ChDDP) in the development of immediate and late-term postoperative complications of gastric and duodenal ulcer, like incompetence of the duodenal stump, reflux gastritis, progression of duodenostasis existing before the operation, the afferent loop syndrome, postresection cholecystitis and pancreatitis, the dumping syndrome. The formation of valvar anastomoses and early recognition and correction fo ChDDP in resection of the stomach (554 patients) made it possible to reduce significantly both the mortality rates (0.18%) and the percentage of other complications.     

Short common bile duct or high implantation. Apropos of 2 cases]

The authors report a case of so-called short common bile duct or highly implanted common bile duct, associated with double duodenal ulcer, with an unfavourable course in a very young girl. The pathological characteristics and the course suggested it was a congenital case of short bile duct, which is a rare disease, as 37 cases have been reported over a period of 25 years. 32 were associated with duodenal ulcer, which is often resistant to medical treatment, and becomes complicated in 33% of cases. The relationship between the two conditions remains hypothetical. Biliodigestive reflux was the first sign in 66% of cases. Retrograde opacification of the bile ducts under duodenoscopy should permit a diagnosis and precise pre-operative assessment. The abnormality has no special treatment, but the treatment of the associated disease, of the ulcer in particular, should be adapted to the ectopic bile duct to avoid serious injury. At operation, careful examination before dissection will determine the [site] of the papilla and of the opening of the biliary and pancreatic ducts. Vagotomy should be associated with a drainage operation, if possible, or gastrectomy may be performed with gastro-jejunal anastomosis leaving behind the posterior ulcer. Many precautions are necessary including the duodenal stump and details of these are given here.     

Gastric juice protects against the development of esophageal adenocarcinoma in the rat.

OBJECTIVE: The authors investigate the effects of gastric juice on tumorigenesis in a rat model of esophageal adenocarcinoma. SUMMARY BACKGROUND DATA: In rats treated with the carcinogen methyl-n-amyl nitrosamine, squamous cancer of the esophagus develops in a time- and dose-dependent manner. When methyl-n-amyl nitrosamine treatment is preceded by an operation to induce reflux of duodenal and gastric juice into the esophagus, there is an increased yield of esophageal tumors, many of which are adenocarcinomas. When only gastric juice refluxes into the esophagus, the tumor yield is less and adenocarcinomas are not found. METHODS: Two hundred seventy 8-week old Sprague-Dawley rats were studied. Twenty unoperated rats served as controls. The remaining rats underwent the following operations: esophagoduodenostomy with gastric and vagal preservation to induce duodenogastroesophageal reflux (n = 48); esophagoduodenostomy with antrectomy and Billroth 1 reconstruction to produce reflux of duodenogastric juice with the exclusion of the antrum (n = 53); esophagoduodenostomy with proximal gastrectomy to induce hypergastrinemia and reflux of duodenogastric juice with exclusion of the body and forestomach (n = 51); esophagoduodenostomy plus total gastrectomy to produce reflux of duodenal juice alone (n = 50); and esophagoduodenostomy with vagal and gastric preservation but with division of the duodenum just beyond the pylorus and reimplantation into the jejunum, 13 cm distal to the esophagoduodenostomy. This produced reflux of duodenal juice with gastric juice diverted downstream, (n = 48). At 10 weeks of age, all rats were given 4 weekly doses of carcinogen (methyl-n-amyl nitrosamine, 25 mg/kg intraperitoneally), and survivors were killed at 36 weeks of age. RESULTS: The prevalence rate of esophageal adenocarcinoma was 30% in rats with duodenogastroesophageal reflux and 87% in rats with reflux of duodenal juice alone. Fifty-six percent of rats with reflux of duodenogastric juice with exclusion of the antrum and 72% of rats with reflux of duodenogastric juice with the exclusion of the body and forestomach developed adenocarcinoma, showing a progression increase in the prevalence of adenocarcinoma as less gastric juice was permitted to reflux with duodenal juice into the esophagus. CONCLUSION: In this rat model, the presence of gastric juice in refluxed duodenal juice against the development of esophageal adenocarcinoma. The protective effect appears to be due to acid secretion from the stomach. Continuous profound acid suppression therapy may be detrimental by encouraging esophageal metaplasia and tumorigenesis in patients with duodenogastroesophageal reflux.     

Duodenal stump after duodenal switch procedure confused with subhepatic abscess

BACKGROUND: Duodenal switch operation is an effective procedure in patients with pathologic transpyloric duodenogastric bile reflux and subsequent alkaline reflux gastritis. Despite its effectiveness duodenal switch remains an infrequently performed procedure for a selected subgroup of patients and therefore few physicians are familiar with the postoperative anatomic situs. METHODS: We report on a 37-old-female who received duodenal switch procedure. Shortly afterward she attended an external emergency department because of upper abdominal pain. There the duodenal stump was misdiagnosed as subhepatic abscess and she received interventional drainage which was located within the duodenal stump. RESULTS: Eventually we removed the ill-placed drainage and the patient recovered under conservative therapy. CONCLUSIONS: The aim of this short communication is to raise awareness of the changed anatomic situs in patients with suprapapillary bile diversion to prevent such dangerous misdiagnosis.     

Contribution to the methods of formation of pancreatojejunal anastomosis during pancreatoduodenal resection

A method preventing a contact of the intestinal content and bile with the wound surface of the stump and pancreatic juice in the pancreatic ducts was proposed in order to prevent reflux of the infected intestinal content in the ducts of the pancreas. The work was fulfilled in experiment and in clinic. The article is well illustrated and recommended for publication as having a scientific and practical value.     

胰胆返流与胆道癌关系的实验研究

选用杂种犬１５条，随机分为３组。Ａ组胰腺与胆囊吻合，Ｂ组胰管开口段上十二指肠与胆囊吻合；Ｃ组空肠与胆囊吻合。三组动物分别于术后４个月～９个月处死病检。结果Ａ、Ｂ组术后胆汁淀粉酶明显比术前高（Ｐ＞０．０１）；Ｃ组术前后胆汁淀粉酶变化不大（Ｐ＞０．０５）。说明Ａ、Ｂ组有胰液流入胆囊内。Ａ、Ｂ组５条犬胆囊内有胆泥，Ｃ组无胆泥。Ａ、Ｂ组胆囊粘膜上皮增生明显，３只形成腺肌瘤，２只呈腺瘤样增生，大部分有粘液变     

Active trypsin and reflux oesophagitis: an experimental study in rats

In order to clarify the role of active trypsin, bile acids and pepsin in reflux oesophagitis, a comparable series of experiments was performed in rats before and after reflux-inducing operations. Three control procedures were used--laparotomy (n = 10), oesophageal transection and reanastamosis (n = 7) and a Roux-en-Y reconstruction (n = 9)--and seven experimental procedures in order to produce gastric, bile and pancreatic reflux (G + B + P) (n = 9), gastric and pancreatic reflux (B + B) (n = 8), bile and pancreatic reflux (B + P) (n = 10), pancreatic reflux alone (P) (n = 9), gastric reflux alone (G) (n = 8), bile reflux alone (B) (n = 9) and gastric with bile reflux (G + B) (n = 9). Macroscopic and histologically confirmed oesophagitis was produced in groups G + B + P, G + P, B + P and P. The trypsin levels were significantly elevated in these groups, compared to both the control and other experimental groups (P less than 0.01). Bile acid levels were insignificantly different between the groups. Because these experiments involved vagal transection, no oesophagitis was found in the gastric juice reflux group. This study has shown for the first time a correlation between the presence of active trypsin in the oesophagus and the occurrence of oesophagitis. It is possible that active components of duodenal juice may contribute to the development of reflux oesophagitis in man.     

Role of pyloric reflux in experimental stress ulceration during haemorrhagic shock.

The significance of pyloric reflux of bile and duodenal juice in experimental gastric stress ulceration was studied using a swine shock ulcer model. Following a haemorrhagic shock of 3 h duration, nine of the ten control piglets (90%) with normal bile flow have gastric mucosal lesions. None of the five piglets with permanent bile diversion (ligation of common bile duct; cholecystojejunostomy) has gastric lesions. Intragastric instillation of pure bile prior to the shock in piglets with permanent bile diversion induced gastric lesions in only one of the five test animals (20%). If duodenal juice was used instead, four of the six test animals (67%) have lesions. The results indicate that, in the pig, an uninterrupted flow of bile into the duodenum is a prerequisite for the development of gastric mucosal lesions following haemorrhagic shock. They also suggest that duodenal juice containing both bile and pancreatic juice has a stronger ulcerogenic influence on shocked porcine gastric mucosa than bile alone.     

Experimental study of the effect of bile juice on the remnant gastric cancer development

Experimental studies were performed to investigate the role, if any, of bile reflux in cancer development in the stomach. A 20% solution of human bile juice and 50 micrograms/ml of the known carcinogenic MNNG were given perorally and heterochronically to male Wistar rat, and the incidence of carcinoma in the gastric gland of the rat was studied. The animals were divided into 4 groups: Group I, to which only MNNG was given. Group II, to which human bile juice and then MNNG were administered. Group III, to which MNNG and then human bile juice were administered. And Group IV, to which only human bile juice was given. The incidence of cancer was 37.5% (3/8) in Group II, 25% (2/8) in Group III, and 0% in Group I (0/12) and IV (0/12). The gastric gland mucosa was histologically examined at various times and also by microautoradiography using 3H-TdR. The results suggested that a reverse flow of bile juice to the human remnant stomach may induce an increase in proliferative cells in the lacunar epithelia of the stomach mucosa and that a predisposed site would then be available for cancer development.     

Sphincter-valve gastroduodenal anastomosis in surgery of stomach ulcer

A method of gastroduodenoanastomosis has been developed which allows exclusion or considerable reduction of the pathological effect of the duodenogastric reflux upon the gastric stump mucosa after distal resection of the stomach in patients with gastric ulcer. Complex examinations of the patients after operations have shown that the developed by the authors sphincter-valvular gastroduodenoanastomosis facilitates the rhythmic-portion evacuation of the gastric contents and prevents the reflux of the duodenal contents into the gastric stump.     

Experimental studies on reflux of pancreatic juice into the biliary tract, with special reference to the effects in the hepato-biliary system

The purpose of this study was to evaluate an effect of reflux of the pancreatic juice into the bile duct on the hepato-biliary system. Forty mongrel dogs including 35 adults and 5 puppies were used and divided into two groups according to the procedures to induce the reflux Group I (15 adults and 2 puppies): the main pancreatic duct was anastomosed to the fundus of the gallbladder. Group II (20 adults and 3 puppies): the duodenal pouch including the opening of the main pancreatic duct was anastomosed to the fundus of the gallbladder. In this model the pancreatic juice flowed into the bile duct after activation within the duodenum. Amylase and phospholipase A2 activities in the bile increased in both groups. Activation of phospholipase A2 was more dominant in Group II than in Group I. Pure pancreatic phospholipase A2 was activated only if the pancreatic juice was mixed with bile and its activation became more dominant when it entered into the duodenum. In both groups, the bile duct was dilated, and histology showed destruction of the mucosa and elastic fibers with inflammatory cell infiltration. These changes were especially severer in Group II with reflux of the pancreatic enzymes activated within the duodenum. In the liver, mild fibrosis and inflammatory cell infiltration in the portal area were observed. On the pathogenesis of hepato-biliary changes due to reflux of the pancreatic juice into the bile duct, phospholipase A2 is one of the most important factors among pancreatic enzymes.     

The "divided stomach"--a model for separate acid and alkali collection in the pig

Bile duct ligation (BDL) in the pig results uniformly in fatal oesophago-gastric ulceration which appears to be related to hypersecretion of acid. The presence of bile in normal porcine gastric juice may interfere with studies of acid secretion. The present studies were conducted in pigs with the stomach divided into two separate pouches (proximal and antral) which allowed individual collection of acid or alkali secretion. In normal pigs, division of the stomach resulted in a 30-50% decrease in secretion, rather than any increase in measureable acid. In BDL pigs, there was an 8- to 15-fold increase in alkali collection by antral pouches which may have been in response to acid hypersecretion, or merely duodenal or pancreatic juice reflux. No normal pigs with divided stomachs developed significant ulceration suggesting that such ulcers were not related to exclusion of bile from the stomach. It is proposed that a total gastric fistula may be used in the pig for studies of acid secretion, and that the model with divided stomach may be used for assessment of the effects of secretagogues or hormones upon individual acid or alkali secretion.