Risk analysis of carcinogenesis in the remnant stomach with measurement of ornithine decarboxylase activity

Gastric ornithine decarboxylase (ODC) activity was measured as a biomarker of tumor-promoting activity in the remnant stomach of rats and humans. Gastrectomy of Wistar rats utilizing the Billroth I method caused a significantly high induction of ODC, and use of the Billroth II method caused a significantly higher induction of ODC than the Billroth I method. In humans, ODC activity of remnant gastric cancer tissue, normal-appearing mucosa of remnant gastric cancer patient, and remnant gastric mucosa without cancer after the Billroth II method were significantly higher than that of normal gastric mucosa without gastrectomy. ODC activity of remnant gastric mucosa without cancer after the Billroth II method was significantly higher than that after the Billroth I method. Risk of carcinogenesis was high in the remnant stomach, especially after the Billroth II method. © 1994 Wiley-Liss, Inc.     

Duodenogastric reflux and gastric stump carcinoma

Gastric stump carcinoma after gastric surgery for benign disease is now widely recognized as a distinct clinical entity. The stump carcinoma was often found to be localized to the anastomosis, known to be the site with severe duodenogastric reflux. For this reason, duodenogastric reflux, including the reflux of bile and pancreatic juice, after a Billroth II procedure for benign disease is frequently discussed as an important factor related to the development of stump carcinoma. Many experiments have implicated bile acids, the main component of the duodenal juice, in gastric carcinogenesis. In particular, rat models without the use of the carcinogen, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), showed adenocarcinoma in the remnant stomach that was related to the severity of duodenogastric reflux. However, human data are, inevitably, much less consistent. Whether the incidence of stump carcinoma is higher than that of gastric carcinoma in general is still controversial. Concerning the histogenesis of stump carcinoma after benign disease, a relationship between gastritis cystica polyposa (GCP) and gastric type adenocarcinoma has been suggested. Recently, the population at risk of gastric stump carcinoma for benign disease has been diminishing significantly, and the incidence of gastric stump carcinoma after surgery for malignant disease has been increasing. The influence of duodenogastric reflux in the gastric remnant after malignant disease may differ from its influence in the gastric remnant after benign disease. Further clinical study is needed to elucidate the pathogenetic factors involved in gastric stump carcinoma. Received: July 30, 2001 / Accepted: October 16, 2001     

残胃癌的临床病理特征及预后分析

目的探讨残胃癌的临床病理特征及预后相关因素。方法回顾性分析45例残胃癌患者的临床病理资料,并进行随访。结果45例残胃癌患者的男女比例为44：1。初次手术距残胃癌的诊断时间为5～42年,平均23年。残胃病变位于吻合口28例,位于贲门9例,其余部位8例。未分化癌1例,低分化腺癌36例,中分化腺癌7例,高分化腺癌1例。根治性切除患者的1、3、5年生存率分别为100．0％、78．8％和47．2％,非根治性切除患者的1、3、5年生存率分别为62．5％、25．0％和0,两组患者生存率差异有统计学意义（P〈0．05）。10例病变未切除患者均于2年内死亡,平均生存时间为12个月。各病理分期患者间生存率差异有统计学意义（P〈0．05）。结论残胃癌多于Billroth Ⅱ式胃大部切除术后10年以上发生,男性多于女性,病变主要位于吻合口附近。进展期残胃癌病理类型以低分化腺癌常见。残胃癌的预后与病理分期、能否行根治性切除密切相关。     

Does remnant gastric cancer really differ from primary gastric cancer? A systematic review of the literature by the Task Force of Japanese Gastric Cancer Association

Remnant gastric cancer, most frequently defined as cancer detected in the remnant stomach after distal gastrectomy for benign disease and those cases after surgery of gastric cancer at least 5 years after the primary surgery, is often reported as a tumor with poor prognosis. The Task Force of Japanese Gastric Cancer Association for Research Promotion evaluated the clinical impact of remnant gastric cancer by systematically reviewing publications focusing on molecular carcinogenesis, lymph node status, patient survival, and surgical complications. A systematic literature search was performed using PubMed/MEDLINE with the keywords “remnant,” “stomach,” and “cancer,” revealing 1154 relevant reports published up to the end of December 2014. The mean interval between the initial surgery and the diagnosis of remnant gastric cancer ranged from 10 to 30 years. The incidence of lymph node metastases at the splenic hilum for remnant gastric cancer is not significantly higher than that for primary proximal gastric cancer. Lymph node involvement in the jejunal mesentery is a phenomenon peculiar to remnant gastric cancer after Billroth II reconstruction. Prognosis and postoperative morbidity and mortality rates seem to be comparable to those for primary proximal gastric cancer. The crude 5-year mortality for remnant gastric cancer was 1.08 times higher than that for primary proximal gastric cancer, but this difference was not statistically significant. In conclusion, although no prospective cohort study has yet evaluated the clinical significance of remnant gastric cancer, our literature review suggests that remnant gastric cancer does not adversely affect patient prognosis and postoperative course.     

The ornithine decarboxylase activity of the gastric remnant mucosa: the effect of the duodenal juice with bile on the gastric mucosa

Using male Wister rats, the ornithine decarboxylase (ODC) activity in the fundic mucosa has been determined from the duodenal juice with bile of a reflux model. The activity at 24 hours postoperatively presented a value approximately 18 times higher than the preoperative level. Though this level declined subsequently, it still was approximately two times higher four weeks later. The ODC activity in the corporal mucosa of humans was compared in 25 normal persons, in 21 patients with a gastric adenoma in 29 patients with a gastric cancer, in 20 patients who had undergone a Billroth I operation and in 20 patients who had undergone a Billroth II operation. No differences in ODC activity were observed among those with a gastric adenoma, a gastric cancer, and normal cases but significantly higher values were seen in cases with a remnant stomach, particularly those who had undergone Billroth II reconstructive surgery. Further, this activity tended to be especially high from 5 to 15 years postoperatively in cases with a gastric remnant.     

A long-term survival case of metachronous liver metastasis from gastric cancer

A 62-year-old man was admitted for gastric cancer. He was performed a distal gastrectomy with Billroth I reconstruction in August 1999. Then he had remnant gastric cancer and metachronous liver cancer in November 2002. He was performed a total gastrectomy and partial hepatic resection. The histological findings of remnant stomach and liver cancer showed a same pattern of the primary gastric cancer. Another metachronous liver cancer appeared in March 2006. He was treated with chemotherapy using S-1 (day 1-21) and CDDP 20 mg/m2 (day 1, 8 and 15) q5w. The size of liver metastasis was kept the same for 16 months.     

Promoting effect of partial gastrectomy on carcinogenesis in the remnant stomach of rats after oral administration of N-methyl-N'-nitro-N-nitrosoguanidine

The promoting effect of partial gastrectomy in the development of cancer in the remnant stomach was examined in rats after oral administration of N-methyl-N'-nitro-N-nitrosoguanidine, using various surgical approaches. The incidence with which cancer developed in the remnant stomach following gastrectomy was lower than the incidence of gastric cancer in the entire glandular stomach. The incidence of cancer in the remnant stomach following Billroth II procedure according to Mayo's method, was higher than the incidence of cancer with other reconstructive methods as well as the corresponding area in the nonresected groups. There was a correlation between the incidence of cancer and the total bile acid concentration in the remnant stomach.     

Intraabdominal Roux-en-Y reconstruction with a novel stapling technique after laparoscopic distal gastrectomy

Laparoscopic gastrectomy is widely used as minimally invasive surgery for gastric carcinoma. Billroth I or Roux-en-Y reconstruction is commonly performed after laparoscopic distal gastrectomy (LDG). Roux-en-Y reconstruction after LDG is one of the best methods for reconstruction of the alimentary tract when Billroth I reconstruction is difficult. There are few reports of intracorporeal Roux-en-Y reconstruction after LDG because of the technical difficulties of such a procedure. In particular, in the case of a very small gastric remnant, gastrojejunostomy using endoscopic linear staplers becomes more complicated. We developed a new technique for intracorporeal Roux-en-Y reconstruction: a modified stapling technique to allow the gastrojejunostomy to be made on the stomach transecting line that is applicable even when the residual stomach is very small. Roux-en-Y reconstruction with our modified technique was performed in six patients. There was no intraoperative complication or conversion to minilaparotomy or conventional celiotomy in any patient. Oral intake was easy and adequate after surgery. The present Roux-en-Y reconstruction procedure is feasible. Herein we describe an intraabdominal Roux-en-Y reconstruction with a modified stapling technique after LDG.     

Occurrence of a heterochronous cancer in the remnant stomach following partial gastrectomy in gastric cancer

Thirty-six cases of a heterochronous cancer in the remnant stomach following a partial gastrectomy for gastric cancer have been compared with 12 cases of gastric cancer following a gastrectomy for benign diseases. Lesions of a heterochronous cancer are characteristically similar to those of a synchronous multiple gastric cancer. Patients with a heterochronous cancer were found to have high rates of synchronous multiple cancers in the resected stomach as compared with none found in gastric cancer patients following surgical operation for a benign disease. Lesions of cancer after surgery for a benign disease when found were mostly in the anastomosis of the remnant stomach. These findings suggest that a heterochronous gastric cancer may develop into lesions of multiple cancers.     

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.     

N-nitroso compounds and Helicobacter pylori in the gastric remnant.

AIMS AND BACKGROUND: The aims of this study were to investigate the role of N-nitroso compounds (NOC) and Helicobacter pylori (H. pylori) in gastric stump carcinogenesis. METHODS AND STUDY DESIGN: Analyses of biochemical parameters such as pH and NOC concentration were carried out on 65 fasting gastric juice samples obtained at endoscopy from 45 patients previously submitted to partial gastrectomy for benign peptic ulcer disease (23 Billroth I, 22 Billroth II/Reichel-Polya) and 20 normal controls. Biopsy specimens were taken to determine histology and H. pylori status. RESULTS: Significantly higher mean pH values and NOC concentrations were found in partial gastrectomies compared to normal controls. In relation to surgical methods, higher mean pH values and NOC concentrations were observed in the gastric juice of patients with Billroth II compared to Billroth I gastrectomies. Independently of the type of surgical reconstruction, higher mean NOC levels were recorded in patients with more severe histological changes and H. pylori infection. CONCLUSIONS: All these data suggest that high levels of NOC in gastric juice and H. pylori infection could be cofactors in gastric stump carcinogenesis.     

不同吻合器应用于远端胃癌手术毕Ⅱ式吻合的疗效比较*

目的:比较远端胃癌根治术毕Ⅱ式吻合应用圆形吻合器与直线吻合器实施消化道重建的近期安全性、有效性及术后生存质量。方法:回顾性分析2013年1月至2017年7月北京大学肿瘤医院胃肠肿瘤中心四病区行根治性远端胃大部切除术的132例胃腺癌患者的临床资料。根据消化道重建采用吻合器形状的不同,分为圆形吻合器组64例（48.5%）和直线吻合器组68例（51.5%）。比较两组患者术中情况、术后恢复情况、并发症发生率以及术后1年残胃情况。结果:两组手术时间、手术方式、术中出血量、淋巴结清扫数目以及阳性淋巴结数目的差异均无统计学意义（均P > 0.05）。直线吻合器组患者较圆形吻合器组患者术后首次排气时间（中位数:3.0 d vs. 4.0 d）、首次进食时间（中位数:7.0 d vs. 8.0 d）、首次拔除腹腔引流管时间（中位数:7.0 d vs. 9.0 d）及术后住院时间（中位数:8.0 d vs. 10.0 d）均较短,差异具有统计学意义（均P < 0.05）;两组患者术后并发症发生率分别为10.9%和1.5%,差异无统计学意义（P=0.056）。术后1年胃镜检查结果显示,两组患者的食物潴留、残胃黏膜炎及胆汁反流发生率,差异均无统计学意义（P > 0.05）。结论:在远端胃癌根治术毕Ⅱ式吻合中,直线吻合器组患者术后胃肠道功能恢复更快,患者住院时间更短,更具优势。      

Metachronous triple malignant lymphoma of the stomach

A 72-year-old female who had undergone partial gastrectomy (Billroth I method) 8 years earlier because of a diagnosis of malignant carcinoma of the stomach (histopathological diagnosis: ML. Histiocytic, Diffuse--Rappaport--) visited our hospital because of dysphagia for the past three months. X-ray and fiberscopic examination revealed the same malignancy in the remnant stomach. Curative extirpation of the remnant stomach, resection of the lower esophagus and pancreatosplenectomy were performed. There were two lesions in the resected specimen. One was a large tumor of Borrmann 3 type (8 cm in diameter) at the EGJ; the other was a small IIc-like tumor (2 cm in diameter) at the surgical stump on the lessercurvature. These three metachronous malignant lymphomas returned the same pathological findings. Compared to carcinoma, malignant lymphoma of the stomach occurs more frequently in the fornix and the tendency for multiple occurrence is strong. When partial gastrectomy is performed for malignant lymphoma of the stomach, follow-up of the remnant stomach must be carried out carefully.     

The completely mobilized remnant stomach: A new choice to reconstruct the esophagus in lower thoracic esophageal carcinoma with a history of distal gastrectomy

Objective

It is a significant surgical challenge to reconstruct esophagus for the patients following distal gastrectomy (DGE). Remnant stomach seems to be a better choice compared with colon or jejunal. But many complicated surgical methods were performed because of limitation of feeding vessels. We found the remnant stomach remained viable when all the feeding vessels were dissected. We used the completely mobilized stomach to reconstruct esophagus successfully in 29 lower thoracic esophageal carcinoma patients with a history of DGE.

Relationship of p53 and Helicobacter pylori to clinicopathological features of human remnant stomach cancer after gastric surgery for primary gastric cancer.

The purpose of this study was to evaluate the biological features of gastric cancer of the remnant stomach (RSC). Twenty-one patients underwent resection of the remnant stomach for RSC and were divided into two groups: the RSCB group consisted of 11 patients who underwent distal gastrectomy for benign disease and the RSCM group consisted of 10 patients who underwent gastrectomy for primary gastric cancer. The interval between primary surgery and the appearance of gastric cancer in the remnant stomach was significantly shorter in the RSCM group than in the RSCB group. Invasion of adjacent organs was more frequent in the RSCM group than in the RSCB group and the Ki-67 labeling index of the tumors was significantly higher in the former group. Furthermore, p53 overexpression by tumors was almost twice as common in the RSCM group as in the RSCB group. Although there was no significant difference of the H. pylori positivity between the two groups, the rate for both groups was higher than reported in previous studies. Mutation of p53 may play an important role in the high proliferative activity of tumors in the RSCM group and H. pylori infection may be closely related to carcinogenesis in patients with RSC.     

Suture-line recurrence at a jejunojejunal anastomosis after gastrectomy for gastric cancer

Local recurrence at a gastrojejunal anastomosis is common in patients after gastrectomy for gastric carcinoma, but recurrence at a jejunojejunal anastomosis without recurrence at a gastrojejunal anastomosis is extremely rare. We report a case of suture-line recurrence at a jejunojejunal anastomosis without recurrence at the gastrojejunal anastomosis or in the remnant stomach in a patient 23 months after receiving a Billroth II gastrectomy for gastric cancer. We attributed the implantation of cancer cells at the jejunojejunal anastomosis to contamination of the stapler with cancer cells exfoliated in the gastric mucus during the construction of the gastrojejunal anastomosis. We therefore consider that different surgical instruments, such as automatic anastomotic devices and automatic suturing devices, must be used in each phase of the surgical procedure for gastric cancer.     

A clinicopathological study on carcinoma of the gastric stump, with special reference to mucosal change

Ten carcinomas of the gastric stump reconstructed by Billroth I (one case) and Billroth II (9 cases) methods were treated an average of 20 (range: 7-46) years after partial gastrectomy. Because of highly advanced carcinoma, total gastrectomy with resection of invaded organs was performed. The 5-year survival rate was 33%, and was not different from that in patients with carcinoma of the cardia. Thus, the prognosis of gastric stump carcinoma was not poor if extended radical operation was carried out. The mucosa showed severe atrophic gastritis with intestinal metaplasia or atrophic and hypertrophic gastritis in patients with carcinoma. However, the mucosa was hyperplasia of the glands in almost all patients with stomal ulcer. Thus, our findings suggest that atrophic change with intestinalization plays a role in gastric carcinogenesis.