Billroth II with Braun Enteroenterostomy Is a Good Alternative Reconstruction to Roux-en-Y Gastrojejunostomy in Laparoscopic Distal Gastrectomy.

Background. Although Billroth II (BII) reconstruction is simpler and faster than Billroth I or Roux-en-Y (RY) reconstruction in patients undergoing totally laparoscopic distal gastrectomy (TLDG), BII reconstruction is associated with several complications, including more severe bile reflux. BII Braun anastomosis may be a better alternative to RY reconstruction. Methods. This retrospective study included 56 consecutive patients who underwent TLDG for gastric cancer, followed by BII Braun or RY reconstruction, between January 2013 and December 2015. Surgical outcomes, including length of operation, quantity of blood lost, and postoperative complications, were compared in the two groups. Results. Clinicopathological characteristics did not differ between the BII Braun and RY groups. Mean length of operation was significantly longer in the RY than the BII Braun group (157.3 min versus 134.6 min, p < 0.010), but length of hospital stay, blood loss, and complication rate did not differ between the two groups. Ileus occurred in three patients (10.0%) in the RY group. Endoscopic findings 6 months after surgery showed bile reflux in seven (28%) patients in the BII Braun group and five (17.2%) in the RY group (p = 0.343), but no significant differences in rate of gastric residue or degree of gastritis in the remnant stomach in the two groups. Conclusions. B-II Braun anastomosis is a good alternative to RY reconstruction, reducing length of operation and ileus after TLDG.

Laparoscopy-assisted endoscopic full-thickness resection for gastric subepithelial tumors originated from the muscularis propria layer: a pilot study with literature review.

OBJECTIVE: Laparoscopy-assisted endoscopic full-thickness resection (LAEFTR) has been suggested as an alternative to laparoscopic wedge resection in the treatment of gastric subepithelial tumors (SETs). It is expected to minimize the resection of the tissue surrounding the tumors and maintain the function of the remnant stomach. Here, we performed a prospective pilot study to evaluate the efficacy of laparoscopy-assisted endoscopic full-thickness resection (LAEFTR) for patients with gastric SETs. MATERIAL AND METHODS: We enrolled twelve patients who were diagnosed with gastric SETs with an intraluminal growth pattern or which is located in the gastric antrum between October 2011 and September 2013. LAEFTR was performed endoscopically using an endoscopic knife to make an incision half way around the tumor circumference and a laparoscopic resection around the remaining tumor circumference, followed by its laparoscopic removal. The feasibility, safety, and effectiveness of LAEFTR for gastric SETs were evaluated. RESULTS: The median size of the tumors in twelve patients was 22 mm (21-33). Of the 12 patients, 8 received LAEFTR, while the others underwent conventional laparoscopic wedge resection, since their tumor outlines were clearly visible in laparoscopic view. In 8 patients who underwent LAEFTR, the mean total operation time (endoscopic procedure time/laparoscopic procedure time) were 117 (37/41) min. The tumors were completely resected with clear margin, and there was no perioperative and postoperative complications. CONCLUSIONS: LAEFTR currently seems to be the ideal treatment modality of intraluminal gastric SETs where their resection margins are difficult to define under laparoscopic guidance alone.

Modified overlap method using knotless barbed sutures (MOBS) for intracorporeal esophagojejunostomy after totally laparoscopic gastrectomy.

BACKGROUND: Compared to end-to-side anastomosis with a circular stapler, the overlap method is favored for intracorporeal esophagojejunostomy because it facilitates handling of the stapler, even in narrow spaces, and wider anastomosis. However, it associates with technical difficulties during anastomosis, including difficult traction on the esophageal stump that necessitates stay sutures. Here, we introduce a new modified overlap method that employs knotless barbed sutures (MOBS) and report the outcomes of our case series. METHOD: All consecutive patients who underwent intracorporeal esophagojejunostomy in 2015-2016 were included. All patients underwent surgery as follows: After esophageal transection with a linear stapler, two V-loc 90 sutures (Covidien, Mansfield, MA, USA) were sutured in the center of the stapled line. The opening was made between the two threads, and the intraluminal space was identified. The jejunum was ascended toward the esophageal stump by inserting a 45-mm-long linear staple. The anastomosis was made at the space between the right and left crura. After firing the linear stapler, the entry hole was closed bidirectionally using the pre-sutured threads. RESULTS: Forty patients underwent MOBS (27 by laparoscopy; 13 by robot). Mean total operative and MOBS procedural times were 180.6 and 22.4 min, respectively. Mean hospital stay was 6.9 days. Two patients had major complications (5.0 %). There were no anastomosis-related complications. Laparoscopy and robot subgroups did not differ in mean MOBS procedural times (22.2 vs. 22.7 min, p = 0.787). CONCLUSION: MOBS is a safe and feasible method that is a good option for intracorporeal esophagojejunostomy after laparoscopic gastrectomy.

Intraoperative Gastroscopy for Tumor Localization in Laparoscopic Surgery for Gastric Adenocarcinoma.

Determining resection margins for gastric cancer, which are not exposed to the serosal surface of the stomach, is the most important procedure during totally laparoscopic gastrectomy (TLG). The aim of this protocol is to introduce a procedure for intraoperative gastroscopy, in order to directly mark tumors during TLG for gastric cancer in the middle third of the stomach. Patients who were diagnosed with adenocarcinoma in the middle third of the stomach were enrolled in this case series. Before surgery, additional gastroscopy for tumor localization is not performed. Under general anesthesia, laparoscopic mobilization of the stomach is performed first. After the first portion of the duodenum is mobilized from the pancreas and clamped, the surgeon moves to the other side for the gastroscopic procedure. On the insertion of a gastroscope through the oral cavity into the stomach, 2 - 3 cc of indigo carmine is administered via an endoscopic injector into the gastric muscle layer at the proximal margin of the stomach. The location of stained serosa in the laparoscopic view is used to guide distal subtotal gastrectomy, however, total gastrectomy is performed if the tumor is too close to the esophagogastric junction. A specimen is sampled after distal gastrectomy to confirm sufficient length from resection margin to tumor before reconstruction. In our case series, all patients had tumor-free margins and required no additional resection. There was no morbidity related to the gastroscopic procedure, and the time required for the procedure has gradually decreased to about five minutes. Intraoperative gastroscopy for tumor localization is an accurate and tolerated method for gastric cancer patients undergoing totally laparoscopic distal gastrectomy.

Universal Verification Methodology Based Register Test Automation Flow.

In today's SoC design, the number of registers has been increased along with complexity of hardware blocks. Register validation is a time-consuming and error-pron task. Therefore, we need an efficient way to perform verification with less effort in shorter time. In this work, we suggest register test automation flow based UVM (Universal Verification Methodology). UVM provides a standard methodology, called a register model, to facilitate stimulus generation and functional checking of registers. However, it is not easy for designers to create register models for their functional blocks or integrate models in test-bench environment because it requires knowledge of SystemVerilog and UVM libraries. For the creation of register models, many commercial tools support a register model generation from register specification described in IP-XACT, but it is time-consuming to describe register specification in IP-XACT format. For easy creation of register model, we propose spreadsheet-based register template which is translated to IP-XACT description, from which register models can be easily generated using commercial tools. On the other hand, we also automate all the steps involved integrating test-bench and generating test-cases, so that designers may use register model without detailed knowledge of UVM or SystemVerilog. This automation flow involves generating and connecting test-bench components (e.g., driver, checker, bus adaptor, etc.) and writing test sequence for each type of register test-case. With the proposed flow, designers can save considerable amount of time to verify functionality of registers.

Is There any Role of Visceral Fat Area for Predicting Difficulty of Laparoscopic Gastrectomy for Gastric Cancer?

PURPOSE: Obesity is associated with morbidity following gastric cancer surgery, but whether obesity influences morbidity after laparoscopic gastrectomy (LG) remains controversial. The present study evaluated whether body mass index (BMI) and visceral fat area (VFA) predict postoperative complications. MATERIALS AND METHODS: A total of 217 consecutive patients who had undergone LG for gastric cancer between May 2003 and December 2005 were included in the present study. We divided the patients into two groups ('before learning curve' and 'after learning curve') based on the learning curve effect of the surgeon. Each of these groups was sub-classified according to BMI (<25 kg/m(2) and ≥25 kg/m(2)) and VFA (<100 cm(2) and ≥100 cm(2)). Surgical outcomes, including operative time, quantity of blood loss, and postoperative complications, were compared between BMI and VFA subgroups. RESULTS: The mean operative time, length of hospital stay, and complication rate were significantly higher in the before learning curve group than in the after learning curve group. In the subgroup analysis, complication rate and length of hospital stay did not differ according to BMI or VFA; however, for the before learning curve group, mean operative time and blood loss were significantly higher in the high VFA subgroup than in the low VFA subgroup (P=0.047 and P=0.028, respectively). CONCLUSIONS: VFA may be a better predictive marker than BMI for selecting candidates for LG, which may help to get a better surgical outcome for inexperienced surgeons.

Effects of Continuing Adjuvant S-1 for 1 Year on the Prognosis of Gastric Cancer Patients: Results from a Prospective Single Center Study.

PURPOSE: Although several clinical trials have proven the efficacy of adjuvant S-1 treatment in gastric cancers, it is still unclear which patients receive the most benefit. In this study, we prospectively recruited patients with locally advanced gastric cancer who had undergone curative resection followed by adjuvant S-1 administration to investigate which factors affect the outcomes. MATERIALS AND METHODS: Between July 2010 and October 2011, we enrolled 49 patients who underwent curative resection for stage II or III gastric cancer and who subsequently received adjuvant S-1 treatment for 1 year. RESULTS: Twenty-nine patients (59.2%) continued S-1 treatment for 1 year, and 12 patients (24.5%) experienced recurrent disease during the follow-up period. Patients with continuation of S-1 for 1 year had significantly increased rates of disease-free survival (P<0.001) and overall survival (P=0.001) relative to the patients who discontinued S-1 during year 1. Multivariate analysis indicated poor outcomes for patients with stage III disease and those who discontinued S-1 treatment. Excluding patients who discontinued S-1 due to cancer progression (n=7), adjuvant treatment with S-1 still demonstrated a significant difference in the disease-free survival rate between the patients who continued treatment and those who discontinued it (P=0.020). CONCLUSIONS: S-1 is tolerated as adjuvant treatment in gastric cancer patients. However, discontinuing S-1 treatment may be an unfavorable factor in the prevention of recurrence. S-1 adjuvant treatment should be continued for 1 year if possible through the proper management of toxicities.

Quantitative measurement of organic acids in tissues from gastric cancer patients indicates increased glucose metabolism in gastric cancer.

The levels of organic acids representing metabolic pathway end products are important indicators of physiological status, and may be associated with metabolic changes in cancer. The aim of this study is to investigate the levels of organic acids in cancerous and normal tissues from gastric cancer patients and to confirm the role of metabolic alterations in gastric carcinogenesis. Organic acids in normal and cancerous tissues from forty-five patients with gastric adenocarcinoma were investigated by gas chromatography-mass spectrometry in selected ion monitoring mode as methoxime/tert-butyldimethylsilyl derivatives. We analysed the significant differences in the levels of organic acids in normal and cancer tissues and investigated the correlation of these levels in cancer tissues with clinicopathological features. The levels of Krebs cycle components, including α-ketoglutaric acid, succinic acid, fumaric acid, malic acid and oxaloacetic acid, were significantly increased in cancer tissues compared to normal tissues. In addition, the levels of glycolytic products, including pyruvic acid and lactic acid, as well as the levels of ketone bodies, including 3-hydroxybutyric acid, were also significantly increased in cancer tissues compared to normal tissues. The levels of ketone bodies in cancer tissues with differentiated histology and in intestinal-type cancer tissues were significantly increased. The organic acid profiling analysis described here may be a generally useful clinical tool for understanding the complexity of metabolic events in gastric adenocarcinoma, and organic acids may have potential as metabolic markers for the future discovery of diagnostic and therapeutic modalities.

Conventional cytology is not beneficial for predicting peritoneal recurrence after curative surgery for gastric cancer: results of a prospective clinical study.

PURPOSE: The role of peritoneal washing cytology in determining further treatment strategies after surgery for gastric cancer remains unclear. One reason for this is the fact that optimal procedures to increase the accuracy of predicting peritoneal metastasis have not been established. The aim of this study was to evaluate the efficacy of cytology using samples harvested from two different abdominal cavity sites during gastric cancer surgery. MATERIALS AND METHODS: We prospectively recruited 108 patients who were clinically diagnosed with locally advanced gastric cancer (higher than cT1 stage disease). Peritoneal washing fluids were collected from the pouch of Douglas and the subphrenic area. Patients were prospectively followed up for 2 years to determine the recurrence and survival rates. RESULTS: Thirty-three patients dropped out of the study for various reasons, so 75 patients were included in the final analysis. Seven patients (9.3%) showed positive cytology findings, of whom, three showed peritoneal recurrence. Tumor size was the only factor associated with positive cytology findings (P=0.037). The accuracy and specificity of cytology for predicting peritoneal recurrence were 90.1% and 94.2%, respectively, whereas the sensitivity was 50.0%. The survival rate did not differ between patients with positive cytology findings and those with negative cytology findings (P=0.081). CONCLUSIONS: Peritoneal washing cytology using samples harvested from two different sites in the abdominal cavity was not able to predict peritoneal recurrence or survival in gastric cancer patients. Further studies will be required to determine whether peritoneal washing cytology during gastric cancer surgery is a meaningful procedure.

Dichloroacetate attenuates hypoxia-induced resistance to 5-fluorouracil in gastric cancer through the regulation of glucose metabolism.

In this study, we investigated whether gastric cancer with hypoxia-induced resistance to 5-fluorouracil (5-FU) could be re-sensitized following treatment with low-dose dichloroacetate (DCA), an inhibitor of the glycolytic pathway. The expression profiles of hypoxia-inducible factor-1α (HIF-1α) and pyruvate dehydrogenase kinase-1 (PDK-1) were analyzed in tissues from 10 patients with gastric cancer who had different responses to adjuvant 5-FU treatment. For the in vitro assays, cell viability and apoptosis were evaluated with and without treatment with 20mM DCA in the AGS and MKN45 cell lines, as well as in PDK1 knockdown cell lines. The expression levels of HIF-1α and PDK-1 were both elevated in the tumor tissues relative to the normal gastric tissues of most patients who showed recurrence after adjuvant 5-FU treatment. Cellular viability tests showed that these cell lines had a lower sensitivity to 5-FU under hypoxic conditions compared to normoxic conditions. Moreover, the addition of 20mM DCA only increased the sensitivity of these cells to 5-FU under hypoxic conditions, and the resistance to 5-FU under hypoxia was also attenuated in PDK1 knockdown cell lines. In conclusion, DCA treatment was able to re-sensitize gastric cancer cells with hypoxia-induced resistance to 5-FU through the alteration of glucose metabolism.

5-Fluorouracil, mitomycin-c, and polysaccharide-k versus uracil-ftorafur and polysaccharide-K as adjuvant chemoimmunotherapy for patients with locally advanced gastric cancer with curative resection.

BACKGROUND: Despite the small but significant survival benefit of adjuvant chemotherapy in locally advanced gastric cancer (LAGC), the optimal regimen remains to be determined. We conducted a randomized trial comparing oral (PO) chemoimmunotherapy (CITX) with intravenous (IV) CITX in LAGC patients (stages IB-IIIB) with curative resection (≥ D2 dissection). METHODS: The patients were randomized to the IV (5-fluorouracil 500 mg/m(2) weekly for 24 weeks, mitomycin-C 8 mg/m(2) every 6 weeks × 4) or the PO (uracil-ftorafur (UFT) 400-600 mg/day for 12 months) group. Patients in both groups received PO polysaccharide-K (3 g/day for 4 months). The planned number of patients was 368 for proving the non-inferiority of PO CITX compared to IV CITX for overall survival. RESULTS: The trial was closed prematurely after enrolling 82 patients (44 in the IV group, 38 in the PO group). With a median follow-up of 82 months, there were no significant differences in the 5-year disease-free survival (73% vs. 55%, p = 0.358) and overall survival (77% vs. 66%, p = 0.159) between the 2 groups. The IV group demonstrated a higher incidence of grade 2 or 3 neutropenia, thrombocytopenia, and vomiting. CONCLUSIONS: PO CITX with UFT appeared to be at least non-inferior to 5-fluorouracil and mitomycin-C CITX, with lower toxicity in the adjuvant treatment for LAGC.

Outcomes of Critical Pathway in Laparoscopic and Open Surgical Treatments for Gastric Cancer Patients: Patients Selection for Fast-Track Program through Retrospective Analysis.

PURPOSE: The aim of this study is to investigate the clinical factors affecting on the cure rate by invasive and open surgery for gastric cancer and to establish a subgroup of patients who can be applied by the early recovery after surgery program through this retrospective analysis. MATERIALS AND METHODS: In this retrospective study, we analyzed 425 patients who underwent gastric cancer surgery between January 2011 and December 2011 and were managed with conventional clinical therapies. This clinical algorithm was made when the patient was in minimally invasive surgery group and discharged from hospital one day faster than them in open surgery group. RESULTS: The completion rate of the clinical pathway was 62.4%. Despite the different applications of clinical pathway, completion rate in minimally invasive surgery group was significantly higher than that of open group (P<0.001). In multivariate analysis, the surgical procedure of minimally invasive surgery (odds ratio=4.281) was the most predictable factor to complete clinical pathway. Additionally, younger patients (odds ratio=1.933) who underwent distal gastrectomy (odds ratio=1.999) without combined resection (odds ratio=3.069) were predicted to accomplish the clinical pathway without any modifications. CONCLUSIONS: We concluded that high efficacy of the clinical pathway for gastric cancer surgery was expected to selected patients through retrospective analysis (expected completion rate=85.4%). In addition, these patients would become enrolled criteria for early recovery program in gastric cancer surgery.

Efficacy of intraoperative gastroscopy for tumor localization in totally laparoscopic distal gastrectomy for cancer in the middle third of the stomach.

BACKGROUND: Determining resection margins for gastric cancer, which generally is not exposed to the serosal surface of the stomach, is the most important priority during totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the usefulness of intraoperative gastroscopy for direct marking of tumors during TLG for gastric cancer in the middle third of the stomach. METHODS: From May 2011 through July 2012, 20 patients with a diagnosis of adenocarcinoma in the middle third of the stomach were enrolled in this case series. Preoperative gastroscopy for tumor localization was not performed for these patients. After the first portion of the duodenum was mobilized from the pancreas and clamped with a laparoscopic intestinal clamp, 2-3 ml of indigo carmine was administered through an endoscopic injector into the gastric muscle layer at the proximal margin of the tumor. RESULTS: Based on intraoperative gastroscopic findings, distal subtotal gastrectomy was performed for 18 patients, with the authors deciding to perform total gastrectomy for two patients. A specimen was extracted after distal gastrectomy to confirm sufficient distance from the resection margin to the tumor before reconstruction. All the patients had tumor-free margins and required no additional resection. No morbidity related to gastroscopic procedure occurred, and the time required has been gradually decreased to about 5 min. CONCLUSIONS: Intraoperative gastroscopy for tumor localization is an accurate and comfortable method for gastric cancer patients undergoing totally laparoscopic distal gastrectomy.

Comparison of intracorporeal reconstruction after laparoscopic distal gastrectomy with extracorporeal reconstruction in the view of learning curve.

PURPOSE: The intracorporeal reconstruction after laparoscopic gastrectomy can minimize postoperative pain, and give better cosmetic effect, while it may have technical difficulties and require the learning curve. This study aimed to analyze the surgical outcome of intracorporeal reconstruction according to the surgeon's experience comparing with extracorporeal procedure. MATERIALS AND METHODS: From January 2009 to September 2011, intracorporeal reconstruction in laparoscopic surgery for gastric cancer was performed for 71 patients (Intra group). During same period, 231 patients underwent laparoscopy-assisted gastrectomy (Extra group). These patients were classified into initial (1st to 20th case of intra group), intermediate (21th to 46th case), and experienced (after 47th case) phases. RESULTS: Intracorporeal procedures included 35 cases of Billroth-I, 30 Billroth-II and 6 Roux en Y reconstructions. In the initial phase, operation time (P=0.022) were significantly longer for the patients of intra group than them of extra group. Although the difference was not significant, the length of hospital stay was longer and complication rate was higher in the intra group. In intermediate and experienced phases, there was no difference between two groups in operation time and hospital stay. In these phases, complication rate was lower in the intra group than the extra group (3.9% versus 9.7%). The pain scale was significantly lower post operation day 5 in the intra group. CONCLUSIONS: Intracorporeal reconstruction after laparoscopic distal gastrectomy was feasible and safe, and the technique was stabilized after 20th case if the surgeon has sufficient experiences when we compared it with extracorporeal reconstruction.

Trends and outcomes of minimally invasive surgery for gastric cancer: 750 consecutive cases in seven years at a single center.

BACKGROUND: The aims of this study were to investigate trends in minimally invasive surgery (MIS) for gastric cancer through the experience of a single center and to predict the direction of the development of MIS. METHODS: During a 7-year period, 2,160 patients underwent curative gastric cancer surgery. Changes in the proportion and pathologic features of a total of 750 cases that involved MIS, as well as the surgical methods and outcomes of MIS, were analyzed. RESULTS: An analysis of the patient population treated by MIS revealed that the proportion of patients with T2 or greater tumors on the basis of pathologic findings was initially <5.0% but had recently increased to 24.3%. Although the proportions of intracorporeal anastomosis and robotic surgery had recently increased, the complication rate and operative time had stabilized 2 years after the 1st MIS. CONCLUSIONS: Given these results, the application of MIS for gastric cancer is expected to become more frequent. In addition, new modalities will be preferred by both surgeons and patients to reduce the invasiveness of gastric cancer surgery.

Comparison of Surgical Outcomes between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: The Learning Curve of Robotic Surgery.

PURPOSE: Laparoscopic gastrectomy is a widely accepted surgical technique. Recently, robotic gastrectomy has been developed, as an alternative minimally invasive surgical technique. This study aimed to evaluate the question of whether robotic gastrectomy is feasible and safe for the treatment of gastric cancer, due to its learning curve. MATERIALS AND METHODS: We retrospectively reviewed the prospectively collected data of 100 consecutive robotic gastrectomy patients, from November 2008 to March 2011, and compared them to 282 conventional laparoscopy patients during the same period. The robotic gastrectomy patients were divided into 20 initial cases; and all subsequent cases; and we compared the clinicopathological features, operating times, and surgical outcomes between the three groups. RESULTS: The initial 20 robotic gastrectomy cases were defined as the initial group, due to the learning curve. The initial group had a longer average operating time (242.25±74.54 minutes vs. 192.56±39.56 minutes, P>0.001), and hospital stay (14.40±24.93 days vs. 8.66±5.39 days, P=0.001) than the experienced group. The length of hospital stay was no different between the experienced group, and the laproscopic gastrectomy group (8.66±5.39 days vs. 8.11±4.10 days, P=0.001). The average blood loss was significantly less for the robotic gastrectomy groups, than for the laparoscopic gastrectomy group (93.25±84.59 ml vs. 173.45±145.19 ml, P<0.001), but the complication rates were no different. CONCLUSIONS: Our study shows that robotic gastrectomy is a safe and feasible procedure, especially after the 20 initial cases, and provides a satisfactory postoperative outcome.

The Effects of Helicobacter pylori on the prognosis of patients with curatively resected gastric cancers in a population with high infection rate.

PURPOSE: The goal of this study was to assess the correlation between the Helicobacter pylori status of patients who underwent curative resection for gastric adenocarcinoma and their prognosis in Eastern societies where H. pylori infection is prevalent. METHODS: Between 2006 and 2007, 192 patients who had a curative resection for the treatment of gastric adenocarcinoma were enrolled in the study. Of these patients, 18 were excluded due to an inexact evaluation of the H. pylori status, thereby leaving 174 patients in the final analysis. Serologic testing for H. pylori was assessed using an enzyme-linked immunosorbent assay kit for immunoglobulin G, and the histological presence of H. pylori was identified using the Giemsa stain. RESULTS: Of the 174 patients, 111 patients (63.8%) were confirmed for H. pylori infection. H. pylori status did not correlate with the overall or disease-free survival. For patients with stage III or IV gastric cancer, a positive H. pylori status was a significant predictive factor for recurrence over that of a negative H. pylori status (P = 0.019). Negative H. pylori status was a predictive factor for recurrence in multivariable analysis (relative risk, 2.724; 95 confidence interval, 1.192 to 6.228). CONCLUSION: Helicobacter pylori status did not correlate with the clinicopathologic factors of gastric adenocarcinoma. However, a negative Helicobacter pylori status may be a predictive factor for recurrence in patients diagnosed with advanced gastric adenocarcinoma.

Helicobacter pylori infection as an independent prognostic factor for locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection.

A few studies reported the association between negative Helicobacter pylori infection and poor clinical outcome in resected gastric cancer patients. We investigated the H. pylori infection status and its association with the clinical outcome in 274 locally advanced gastric cancer patients (American Joint Committee on Cancer stage IB: 25, II: 82, IIIA: 80, IIIB: 39 and IV: 48) who underwent adjuvant chemotherapy after curative resection (≥ D2 dissection). H. pylori infection status in hematoxylin and eosin stained corporal and antral mucosa of non-tumor tissue was graded according to the updated Sydney System and categorized as H. pylori negative (normal or mild infection) and H. pylori positive (moderate or marked infection). Eighty-one patients received 5-fluorouracil (5-FU) and doxorubicin-based chemotherapy, while 193 patients underwent 5-FU, mitomycin-C and polysaccharide-K chemotherapy. The median follow-up duration of survivors was 144 (120-184) months. In univariate analysis, patients with H. pylori negative status (108 patients) demonstrated significantly poor 10-year overall survival (OS) compared to those with H. pylori-positive status (166 patients; 21.3% vs. 71.1%, p < 0.0001). H. pylori negative status was associated with poor outcome in all stages except stage IIIB. In multivariate analysis, H. pylori-negative status was the most significant independent prognostic factor of poor OS (hazard ratio: 3.45, 95% confidence interval: 2.43-4.89, p < 0.0001) followed by old age (>54 years, p < 0.0001), advanced stage (stage III or IV, p = 0.001), and Borrmann type IV (p = 0.027). H. pylori infection status seems to have strong prognostic significance in locally advanced gastric cancer. H. pylori-negative patients may need careful follow-up after curative resection.