Current status in remnant gastric cancer after distal gastrectomy

Remnant gastric cancer(RGC) and gastric stump cancer after distal gastrectomy(DG) are recognized as the same clinical entity. In this review, the current knowledges as well as the non-settled issues of RGC are presented. Duodenogastric reflux and denervation of the gastric mucosa are considered as the two main factors responsible for the development of RGC after benign disease. On the other hand, some precancerous circumstances which already have existed at the time of initial surgery, such as atrophic gastritis and intestinal metaplasia, are the main factors associated with RGC after gastric cancer. Although eradication of Helicobacter pylori(H. pylori) in remnant stomach is promising, it is still uncertain whether it can reduce the risk of carcinogenesis. Periodic endoscopic surveillance after DG was reported useful in detecting RGC at an early stage, which offers a chance to undergo minimally invasive endoscopic treatment or laparoscopic surgery and leads to an improved prognosis in RGC patients. Future challenges may be expected to elucidate the benefit of eradication of H. pylori in the remnant stomach if it could reduce the risk for RGC, to build an optimal endoscopic surveillance strategy after DG by stratifying the risk for development of RGC, and to develop a specific staging system for RGC for the standardization of the treatment by prospecting the prognosis.     

Clinicopathologic features of remnant gastric cancer over time following distal gastrectomy

AIM: To investigate remnant gastric cancer(RGC) at various times after gastrectomy, and lay a foundation for the management of RGC.METHODS: Sixty-five patients with RGC 2 years and 10 years after gastrectomy(RGC Ⅰ) and forty-nine with RGC 10 years after gastrectomy(RGC Ⅱ) who underwent curative surgery were enrolled in the study.The clinicopathologic factors, surgical outcomes, and prognosis were compared between RGC Ⅰ and RGC Ⅱ.RESULTS: There was no significant difference in surgical outcomes between RGC Ⅰ and RGC Ⅱ. For patients reconstructed with Billroth Ⅱ, significantly more patients were RGC Ⅱ compared with RGC(71.9%vs 21.2%, P 0.001), and more RGC Ⅱ patients had anastomotic site locations compared to RGC Ⅰ(31.0%vs 56.3%, P = 0.038). The five-year survival rates for the patients with RGC Ⅰ and RGC Ⅱ were 37.6%and 47.9%, respectively, but no significant difference was observed. Borrmann type and tumor stage were confirmed to be independent prognostic factors in both groups.CONCLUSION: RGC Ⅱ is located on the anastomotic site in higher frequency and more cases develop after Billroth Ⅱ reconstruction than RGC Ⅰ.     

Expression of 8-hydroxydeoxyguanosine in the gastric remnant after distal gastrectomy

BACKGROUND/AIMS: The correlation between remnant gastritis after distal gastrectomy for gastric cancer and expression of 8-hydroxydeoxyguanosine (8-OHdG) and inducible oxide synthase (iNOS) as a marker of oxidative DNA damage was investigated. METHODOLOGY: Ninety-seven patients who had undergone curative distal gastrectomy for gastric cancer were studied. Reconstructive procedures included Billroth I, Billroth II, and Roux-Y reconstruction in 42, 27, and 28 patients, respectively. Histologic and immunohistochemical analyses were performed on biopsy specimens of the gastric mucosa obtained endoscopically within 2 weeks before and 12 weeks after surgery. The grades of remnant gastritis were evaluated according to the updated Sydney System. 8-OHdG and iNOS expression levels, detected immunohistochemically, were graded. RESULTS: Neutrophil infiltration correlated with expression of 8-OHdG (p = 0.02). Expression of iNOS also correlated with 8-OHdG (p = 0.02). The ratio of postoperative to preoperative infiltration of neutrophils was less in patients who underwent Roux-Y reconstruction than in others (p = 0.04). CONCLUSIONS: These results suggest that remnant gastritis possibly causes DNA damage. Excess production of reactive oxygen species correlates with carcinogenic DNA changes. Roux-Y reconstruction may reduce carcinogenesis in the gastric remnant.     

Delayed gastric emptying after distal gastrectomy for gastric cancer

BACKGROUND/AIMS: Gastric surgery may potentiate delayed gastric emptying. The aims of the study were to determine the frequency and causes of delayed gastric emptying in patients who had undergone distal gastrectomy for gastric carcinoma and to assess which factors predispose to its development. METHODOLOGY: 209 patients, who had undergone gastrectomy, were evaluated. RESULTS: Delayed gastric emptying occurred in 4.3% of patients receiving a Billroth-I, and 15.5% of patients receiving a Roux-Y reconstruction (p = 0.01). The patients who had these consecutive symptoms following Roux-Y operation were all clinically diagnosed as having Roux stasis syndrome. The delayed gastric emptying after Roux-Y operation was more frequent in patients receiving extensive lymph node dissection than those receiving conventional dissection (p<0.05). The symptoms spontaneously subsided, and postoperative body weight loss was not significant. CONCLUSIONS: In spite of the strong association between delayed gastric emptying and the Roux-Y procedure, it enables a relatively early return to oral intake.     

Progression of remnant gastric cancer is associated with duration of follow-up following distal gastrectomy

AIM: To re-evaluate the recent clinicopathological features of remnant gastric cancer (RGC) and to develop desirable surveillance programs.METHODS: Between 1997 and 2008, 1149 patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Japan. Of these, 33 patients underwent gastrectomy with lymphadenectomy for RGC. Regarding the initial gastric disease, there were 19 patients with benign disease and 14 patients with gastric cancer. The hospital records of these patients were reviewed retrospectively.RESULTS: Concerning the initial gastric disease, the RGC group following gastric cancer had a shorter interval [P < 0.05; gastric cancer vs benign disease: 12 (2-22) vs 30 (4-51) years] and were more frequently reconstructed by Billroth-I procedure than those following benign lesions (P < 0.001). Regarding reconstruction, RGC following Billroth-II reconstruction showed a longer interval between surgical procedures [P < 0.001; Billroth-II vs Billroth-I: 32 (5-51) vs 12 (2-36) years] and tumors were more frequently associated with benign disease (P < 0.001) than those following Billroth-I reconstruction. In tumor location of RGC, after Billroth-I reconstruction, RGC occurred more frequently near the suture line and remnant gastric wall. After Billroth-II reconstruction, RGC occurred more frequently at the anastomotic site. The duration of follow-up was significantly associated with the stage of RGC (P < 0.05). Patients diagnosed with early stage RGC such as stage I-II tended to have been followed up almost every second year.CONCLUSION: Meticulous follow-up examination and early detection of RGC might lead to a better prognosis. Based on the initial gastric disease and the procedure of reconstruction, an appropriate follow-up interval and programs might enable early detection of RGC.     

Uncut Roux-en-Y reconstruction after distal gastrectomy for gastric cancer

Introduction: Uncut Roux-en-Y gastrojejunostomy is a modification of the Billroth II procedure with Braun anastomosis, in which a jejunal occlusion is fashioned to avoid the Roux Stasis Syndrome. This review aimed to summarize the current knowledge about the uncut Roux-en-Y anastomosis operation, so that surgeons may be able to make informed decisions about its clinical application. Additionally, we hope that our findings will guide future research on this topic.

Areas covered: The original uncut technique was associated with dehiscence or recanalization of the jejunal occlusion, and was therefore not widely applied. However, with recent improvements in the method of jejunal occlusion, the uncut Roux-en-Y reconstruction may be an appropriate alternative for digestive tract reconstruction after distal gastrectomy. This review summarizes the basic research on and clinical applications of uncut Roux-en-Y gastrojejunostomy from the following several aspects: origin of the uncut reconstruction technique, rationale for uncut reconstruction based on data from animal experiments, clinical results of the uncut reconstruction, recanalization and its countermeasures, and so on.

Expert commentary: The uncut Roux-en-Y gastrojejunostomy is a controversial yet promising method of gastrointestinal reconstruction after distal gastrectomy. Prospective randomized controlled trials and long-term follow-up outcomes are required to support the modified technique in the future.     

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.     

Reconstructive procedure after distal gastrectomy to prevent remnant gastritis

BACKGROUND/AIMS: Gastroduodenostomy (Billroth I) or gastrojejunostomy (Billroth II) after distal gastrectomy is associated with duodenogastric reflux and remnant gastritis. This study sought to determine which reconstructive procedure is least likely to cause remnant gastritis and to determine the correlation between duodenogastric reflux and remnant gastritis. METHODOLOGY: Sixty patients who underwent curative distal gastrectomy for gastric cancer were classified into three groups by reconstructive procedure: group A, Roux-Y (n=18); group B, Billroth I (n=25); group C, Billroth II (n=17). Intragastric bile reflux was monitored using the Bilitec 2000 14 days after surgery, and endoscopy was performed and a patient questionnaire was completed 12 weeks after surgery. RESULTS: Bile reflux occurred in 23.9%, 40.4%, and 73.4% of the time (p<0.001), and remnant gastritis developed in 33%, 76%, and 100% of patients (p<0.001), in groups A, B, and C, respectively. Helicobacter pylori infection did not correlate with remnant gastritis (p=0.57). Symptoms following Roux-Y reconstruction were comparable to those following Billroth I and II reconstructions. CONCLUSIONS: Roux-Y reconstruction following distal gastrectomy is superior to Billroth I and II reconstruction in preventing remnant gastritis because it reduces duodenogastric reflux.     

Clinical outcomes of endoscopic treatment for gastric epithelial neoplasm in remnant stomach after distal gastrectomy

Backgrounds/aimWe aimed to evaluate the feasibility of endoscopic treatment for gastric epithelial neoplasm in the remnant stomach after distal gastrectomy and compared the clinical outcomes by tumor location and endoscopic treatment modality.MethodsWe reviewed the data of patients who underwent endoscopic treatment for gastric epithelial neoplasms in the remnant stomach after distal gastrectomy between January 1996 and August 2013. The treatments included endoscopic resection or argon plasma coagulation.ResultsHerein, 107 patients (median age, 65.1 years; 92 men) encompassing 117 cases of gastric neoplasms in the remnant stomach after distal gastrectomy were endoscopically treated. Forty of these lesions were located at anastomotic sites; they were treated with endoscopic resection in 29 cases (72.5%) and argon plasma coagulation in 11 cases (27.5%). For 77 lesions located on the non-anastomotic site, endoscopic resection was performed in 68 cases (88.4%) and argon plasma coagulation was performed in nine cases (11.7%; p = 0.031). The mean endoscopic resection duration was significantly longer in the anastomotic site group than in the non-anastomotic site group (43.6 vs. 26.3 min, p = 0.018). Recurrence was observed in five (12.8%) patients in the former and in one (1.3%) in the latter (p = 0.015); all the patients were successfully retreated with endoscopic resection or APC.ConclusionsEndoscopic treatment for gastric epithelial neoplasm in a remnant stomach after distal gastrectomy is effective and safe. However, closely monitoring for recurrence should be conducted, particularly when the tumor is located at the anastomotic site.     

Gastric cancer arising from the remnant stomach after distal gastrectomy: A review

Gastric stump carcinoma was initially reported by Balfore in 1922, and many reports of this disease have since been published. We herein review previous reports of gastric stump carcinoma with respect to epidemiology, carcinogenesis, Helicobacter pylori (H. pylori) infection, Epstein-Barr virus infection, clinicopathologic characteristics and endoscopic treatment. In particular, it is noteworthy that no prognostic differences are observed between gastric stump carcinoma and primary upper third gastric cancer. In addition, endoscopic submucosal dissection has recently been used to treat gastric stump carcinoma in the early stage. In contrast, many issues concerning gastric stump carcinoma remain to be clarified, including molecular biological characteristics and the carcinogenesis of H. pylori infection. We herein review the previous pertinent literature and summarize the characteristics of gastric stump carcinoma reported to date.     

Role of bile reflux and Helicobacter pylori infection on inflammation of gastric remnant after distal gastrectomy

OBJECTIVE: The influence of the main pathogenic factors on remnant gastritis is still to be evaluated. The aim of this study was to investigate the role of bile reflux and Helicobacter pylori infection on endoscopic inflammation and histological changes of gastric remnant after distal gastrectomy. METHODS: A total of 281 patients with a more than 1‐year history of distal gastrectomy were retrospectively involved after excluding those with tumors and ulcers on endoscopy. The severity of endoscopic remnant gastritis and bile reflux were recorded during the endoscopy. The histological changes including chronic inflammation, activity, atrophy, intestinal metaplasia and H. pylori were evaluated independently. RESULTS: An endoscopic inflammation of remnant gastric mucosae was found in 81.1% (228/281) of the patients. The prevalence of H. pylori infection and bile reflux in patients with endoscopic remnant gastritis was more common than in those without gastritis (21.5%vs 0%, 88.6%vs 24.5%, P < 0.0001). The score of histological chronic inflammation was significantly higher in patients with bile reflux than in those without obvious bile reflux (1.65 vs 1.45, P = 0.02). Chronic inflammation (1.82 vs 1.57), activity (0.78 vs 0.34), atrophy (0.67 vs 0.41) and intestinal metaplasia (0.67 vs 0.27) in H. pylori‐positive patients were all significantly more severe than in H. pylori‐negative patients. CONCLUSION: Bile reflux and H. pylori infection exacerbates the severity of endoscopic remnant gastritis and chronic histological inflammation.     

Esophageal cancer after distal gastrectomy

The effect of gastrectomy on the subsequent development of esophageal cancer was investigated. Duodenogastroesophageal reflux is thought to be common in patients after distal gastrectomy, but whether this contributes to the development of esophageal cancer in such patients is controversial. We retrospectively evaluated 153 patients who underwent subtotal esophagectomy for thoracic esophageal cancer between January 2002 and July 2005. They were divided into two groups, according to whether or not they had previously undergone a gastrectomy: group 1, comprising 14 patients who had undergone gastrectomy and group 2, comprising 139 patients who had not. Clinical profiles of the patients were obtained from the medical records and the whole resected esophagus was histopathologically examined. The interval between gastrectomy and esophagectomy in group 1 was significantly shorter in the patients who had undergone gastrectomy for gastric cancer (10.5 +/- 4.2 years) than in those who had undergone gastrectomy for a peptic ulcer (28.9 +/- 3.0 years). The interval was also somehow shorter in the patients for whom anastomosis had been performed by Billroth I (21.3 +/- 5.6 years) compared with Billroth II (29.7 +/- 3.2 years), although the difference did not reach its statistical significance (P = 0.11). Moreover, the proportion of lower third tumors in patients after gastrectomy was significantly higher compared with that of the patients with intact stomach. These findings suggest that a history of gastrectomy is associated with more lower-third squamous cell esophageal carcinoma.     

Correlation between duodenogastric reflux and remnant gastritis after distal gastrectomy

BACKGROUND/AIMS: Many patients who undergo distal gastrectomy develop remnant gastritis. This report describes the correlation between remnant gastritis and the amount of duodenogastric reflux and looks at the relationship between Helicobacter pylori infection and duodenogastric reflux in remnant gastritis. METHODOLOGY: Sixty-two patients who underwent curative distal gastrectomy for gastric cancer with radical lymphadenectomy were studied. The period of bile reflux (percent time) into the gastric remnant was measured with the Bilitec 2000 under standardized conditions. Remnant gastritis was semi-quantified using the neutrophil infiltration score based on the updated Sydney System, and the presence of H. pylori infection was determined 12 weeks after the surgery. RESULTS: Overall, the correlation was not significant between the neutrophil infiltration score and the percent time (p=0.08). Similarly, the correlation was not significant in patients with H. pylori infection (p=0.30), but it was significant in patients without H. pylori infection (p=0.03). CONCLUSIONS: Duodenogastric reflux after distal gastrectomy can cause remnant gastritis in patients without H. pylori infection. Reconstruction with biliary diversion is protective against the development of remnant gastritis.     

Gastric remnant cancer compared with primary proximal gastric cancer

BACKGROUND/AIMS: Recently, detections of early-stage gastric remnant cancer and small proximal gastric cancer are increasing. The aim of this study was to compare pathologic and prognostic data of gastric remnant cancer with those of primary proximal gastric cancer including upper gastric cancer based on a recent 15-year experience at a single institute in Japan. METHODOLOGY: Among 698 patients who underwent gastrectomy for cancer between 1984 and 1998, 15 (2.1%) were patients with gastric remnant cancer. During the same period, 139 patients underwent primary gastrectomy for proximal gastric cancer which included 71 with upper gastric cancer confined to the upper one-third of the stomach. Clinicopathologic findings of gastric remnant cancer were compared with those of proximal gastric cancer. RESULTS: Of 15 gastric remnant cancers, 8 (53%) were stage I tumors. Although gastric remnant cancer and proximal gastric cancer was not different in several clinicopathologic factors, gastric remnant cancer and upper gastric cancer confined to the upper one-third of the stomach was different with regard to the frequency of tumor size > or = 4 cm (60% vs. 32%, p < 0.05), poorly differentiated type (67% vs. 38%, p < 0.05), serosal invasion (40% vs. 11%, p < 0.01), lymph node metastasis (47% vs. 20%, p < 0.05), stage III or IV disease (47% vs. 10%, p < 0.01), and noncurative gastrectomy (20% vs. 1%, p < 0.01). The 5-year survival rate of gastric remnant cancer (69%) was higher than that of proximal gastric cancer (57%) and lower than that of upper gastric cancer (81%), although the differences were not statistically significant. CONCLUSIONS: In our recent series, a half of gastric remnant cancers are stage I tumors. Although gastric remnant cancers are similar to proximal gastric cancers, they are more advanced and their surgical results are less satisfactory when compared with upper gastric cancers confined to the upper one-third of the stomach.     

Early gastric stump cancer following distal gastrectomy

Background—Gastric stump cancer(GSC) is usually diagnosed at an advanced stage, and consequently theprognosis is poor.
Aims—To investigate theclinicopathological characteristics of GSC at an early stage to assistin its identification, and thereby improve its prognosis.
Methods—Forty three patients withresected early GSC were compared with 156 patients with resectedprimary early cancer in the upper third of the stomach.
Results—Sixty five per cent (28/43)of the early GSC patients showed the elevated type endoscopically,although the frequency of the depressed type in GSC has tended toincrease in the past five years. This occurred in less than 26%(40/156) of the primary early cancers. Half of the early GSCs werelocated on the lesser curvature (47%), and revealed differentiatedadenocarcinoma (81%) histologically. The male:female ratio of earlyGSC cases was about 6:1, which was much higher than that in patientswith primary early cancer. The five year survival rates of patientswith early GSCs and early primary cancers were 84% and 95%,respectively. GSC had a favourable prognosis, if it was detected at anearly stage.
Conclusion—To detect early GSC, ourresults suggest that special attention should be given to elevated aswell as depressed lesions on the lesser curvature of the stomach,particularly in men, during endoscopic examinations.

Keywords:gastric stump cancer; early gastric cancer; prognosis; endoscopy

     

Treatment of gastric remnant cancer post distal gastrectomy by endoscopic submucosal dissection using an insulation-tipped diathermic knife

AIM： To evaluate the effectiveness of endoscopic submucosal dissection using an insulation-tipped diathermic knife （IT-ESD） for the treatment of patients with gastric remnant cancer. METHODS： Thirty-two patients with early gastric cancer in the remnant stomach, who underwent distal gastrectomy due to gastric carcinoma, were treated with endoscopic mucosal resection （EMR） or ESD at Sumitomo Besshi Hospital and Shikoku Cancer Center in the 10-year period from January 1998 to December 2007, including 17 patients treated with IT-ESD. Retrospectively, patient backgrounds, the one-piece resection rate, complete resection （CR） rate, operation time, bleeding rate, and perforation rate were compared between patients treated with conventional EMR and those treated with IT-ESD. RESULTS： The CR rate （40% in the EMR group vs 82% in the IT-ESD group） was significantly higher in the IT-ESD group than in the EMR group; however, the operation time was significantly longer for the IT- ESD group （57.6 ± 31.9 min vs 21.1 ± 12.2 min）. No significant differences were found in the rate of underlying cardiopulmonary disease （IT-ESD group, 12% vs EMR group, 13%）, one-piece resection rate （100% vs 73%）, bleeding rate （18% vs 6.7%）, and perforation rate （0% vs 0%） between the two groups. CONCLUSION： IT-ESD appears to be an effective treatment for gastric remnant cancer post distal gastrectomy because of its high CR rate. It is useful for histological confirmation of successful treatment. Thelong-term outcome needs to be evaluated in the future.     

Endoscopic submucosal dissection for cancers of the remnant stomach after distal gastrectomy

BACKGROUND: Endoscopic submucosal dissection (ESD) of early gastric cancer is less invasive than surgical resection, and if technically feasible, it may result in less long-term morbidity than does incisional surgery. However, ESD is technically difficult in patients who have had a previous distal gastrectomy. OBJECTIVE: Our purpose was to retrospectively assess the results of ESD of early gastric cancer in the remnant stomach. DESIGN: Case series. SETTING AND PATIENTS: A total of 31 lesions in 30 patients with early remnant gastric cancer were treated with ESD at Okayama University Hospital, Tsuyama Central Hospital, Hiroshima City Hospital, Kagawa Prefectural Central Hospital, and Mitoyo General Hospital from March 2001 to January 2007. INTERVENTION: ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection rate, complete resection rate, operation time, and complications. RESULTS: En bloc resection and complete resection were achieved in 30 (97%) and in 23 (74%) lesions, respectively. The median operation time required for ESD in the remnant stomach was 113 minutes (range 45-450 minutes). Perforation occurred in 4 (13%). The incidence of delayed bleeding requiring blood transfusion was 0%. LIMITATION: Short duration of follow-up. CONCLUSIONS: ESD is feasible in the remnant stomach but has a relatively high complication rate and should only be performed by experienced endoscopists.     

Influence of bile reflux and Helicobacter pylori infection on gastritis in the remnant gastric mucosa after distal gastrectomy

Background Two main pathogenic factors, bile reflux and Helicobacter pylori infection, have been identified in the remnant stomach, but it is still unclear which factor is important in the pathogenesis of gastritis in the remnant stomach after distal gastrectomy.Methods In 184 patients who had had distal gastrectomy performed using the Billroth-I procedure (B-I; n-106), Billroth-II procedure (B-II; n-36), and jejunal interposition (J-I; n-42) we examined the severity of remnant gastritis endoscopically and carried out examinations for H. pylori infection and histological examination.Results The endoscopic severity of remnant gastritis was grade 1 or more in 101 of the 106 B-I patients (95.3%) and in all 36 B-II patients (100%). But, of the 42 J-I patients, the grade was 0 in 33 (78.6%). The endoscopic severity of remnant gastritis was significantly milder for J-I than for B-I (P < 0.001) and B-II (P < 0.001). H. pylori infection was confirmed in 59 of the 106 B-I patients (55.6%), 21 of the 36 B-II patients (58.3%), and 32 of the 42 J-I patients (76.1%). The rate of H. pylori infection was higher for J-I patients than for B-I (P < 0.05), but not for B-II patients (P = 0.1495). The severity of chronic and active inflammatory cellular infiltration tended to be inverse proportional relation with the endoscopic severity of the remnant gastritis. Furthermore, the histological inflammation and activity scores of H. pylori-positive patients were higher than those of H. pylori-negative patients, without regard to the endoscopic grade of gastritis.Conclusions Reconstruction techniques play an important role in the prevention of bile reflux, and we found that endoscopically more severe remnant gastritis was associated with a lower rate of H. pylori infection and with a lower degree of inflammatory cellular infiltration.