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The number of patients who die from causes other than gastric cancer after R0 resection is increasing in Japan, due in part to the aging population. However, few studies have comprehensively investigated the clinicopathological risks associated with deaths from other causes after gastrectomy. This study aimed to build a risk score for predicting such deaths.We retrospectively reviewed clinical data for 3575 patients who underwent gastrectomy for gastric cancer at nine institutions in Japan between January 2010 and December 2014.The final study population of 1758 patients were assigned to Group A (n = 187): patients who died from other causes within 5 years of surgery, and Group B (n = 1571): patients who survived ≥ 5 years after surgery. Multivariate analysis identified nine characteristics as risk factors for poor survival: age ≥ 75 years, male sex, body mass index 22 kg/mThe risk score defined here may be useful for predicting deaths from other causes after curative gastrectomy.

Preoperative chemotherapy for gastric cancer may be effective from the standpoint of compliance, although there is insufficient evidence of its efficacy. We analyzed a multicenter database to clarify whether preoperative chemotherapy influenced the short-term outcomes of gastrectomy. We analyzed, retrospectively, 3571 patients who underwent gastrectomy between January, 2010 and December, 2014. Patients with clinical stage-III gastric adenocarcinoma were divided into a neoadjuvant chemotherapy (NAC) group and a non-NAC group. We performed propensity-matched comparative analysis to stratify the groups according to age, sex, tumor region, tumor type, preoperative stage, procedure, lymph node dissection, and tumor differentiation. Preoperative blood data, surgical findings, and postoperative complications were analyzed. Analysis of the matched NAC (n = 64) and non-NAC (n = 128) groups revealed that the preoperative values of neutrophils, platelets, and Hb were significantly lower in the NAC group. Blood loss during surgery was significantly higher, surgical times were longer, and the rate of repeat surgery was significantly lower in the NAC group; however, the rates of rehospitalization did not differ between the groups and mortality was 0% in both groups. Postoperative complications were not significantly different between the groups. NAC did not increase the complication rate of gastrectomy for gastric cancer.

In a randomized pivotal global phase III study, S-1 and oxaliplatin 100 mg/m2 (SOX100) combination chemotherapy was as effective as S-1 and cisplatin for advanced gastric cancer (AGC) and showed a favorable safety profile. In this phase II study, we analyzed survival outcomes to assess the efficacy and safety of the SOX regimen with oxaliplatin 130 mg/m2 (SOX130) in AGC. Patients with HER2-negative AGC received 80 mg/m2/day S-1 orally on days 1–14 and 130 mg/m2 oxaliplatin intravenously on day 1 of each 21-day cycle until the criteria for treatment withdrawal were fulfilled. The primary endpoint was the response rate (RR), and the null hypothesis of RR in the current trial was 45%. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were recorded according to CTCAE version 4.0. Seventy-one patients were enrolled from June 2015 to November 2016, but eight were excluded for ineligibility. Therefore, all final analyses were conducted with 63 patients. The confirmed RR was 46.0% (90% confidence interval [CI]: 36.1–56.3), and the disease control rate was 77.8% (90% CI: 68.1–85.1). The median PFS and OS were 4.9 (95% CI: 4.2–7.1) and 14.8 (95% CI: 11.1–18.9) months, respectively. Incidences of grade 3–4 AEs > 10% were anorexia (19.0%), peripheral neuropathy (12.7%), nausea (11.1%), and thrombocytopenia (11.1%). This study represents the first evaluation of SOX130 in patients with HER2-negative AGC. SOX130 showed an acceptable safety profile, but the prespecified statistical efficacy targets were not achieved.

We aimed to clarify the utility of lymph node ratio (LNR) for assessing the prognosis of patients with node-positive gastric cancer after curative gastrectomy. We retrospectively analyzed data of 973 patients with node-positive gastric cancer who had undergone curative gastrectomy at nine institutions from 2010 to 2014. Survival analysis was performed by comparing LNR low and high groups according to the optimal cutoff value of LNR, which was determined using receiver operating characteristic curve analysis. LNR high was significantly associated with shorter disease-free survival and was an independent predictor of recurrence in all patients. Moreover, we obtained the similar results from analysis of each N stage. The prevalence of lymph node and peritoneal recurrence appeared to be higher in the LNR high group. Correlation analysis showed that LNR was negatively correlated with the number of retrieved nodes within every N stage; however, disease-free survival did not differ significantly between LNR low and high groups of each N stage with 16–30, 31–40, or >40 retrieved nodes. LNR is a strong prognostic factor and predictor of recurrence in patients with node-positive gastric cancer who have undergone curative gastrectomy. The combination of LNR and N staging permits more accurate prognostic stratification of patients with gastric cancer and may contribute to developing novel prognostic models.

Aging societies comprise an increasing number of elderly gastric cancer (GC) patients. We herein attempted to determine whether D2 lymphadenectomy is beneficial for older GC patients. We retrospectively analyzed a multi-institutional dataset including 3484 patients who received surgical resection for GC. For the analysis, we selected patients aged ≥ 80 years who were clinically diagnosed with T1N + or T2-4 GC. To balance the essential variables including the type of gastrectomy and the stage of progression, propensity score matching was conducted, and we compared the background clinical factors and postoperative outcomes of the patients allocated to the D2 (n = 87) and non-D2 (n = 87) dissection groups. The D2 group had significantly longer operative times, more blood loss, and more retrieved lymph nodes (median 32 vs 24, P

Peritoneal dissemination is the key to the prognosis of gastric cancer (GC) and can be detected early with peritoneal lavage cytology. No studies have examined preoperative prognostic factors in GC patients who have positive cytology but no other non-curative factors.We conducted a retrospective analysis using a multicenter database of 3575 patients who underwent gastrectomy between 2010 and 2014. Patients with positive peritoneal lavage cytology as a sole non-curative factor were retrieved, and correlations between parameters and the prognosis were compared.A total of 66 patients were identified as eligible. In the receiver operating characteristic (ROC) curve analysis, the neutrophil-to-platelet ratio (NPR) had the greatest area under the curve value and was selected. We divided the NPR into two groups based on the optimal cutoff value of the NPR (2.000), as determined by the ROC curve analysis. A high preoperative NPR was the only prognostic factor. The NPR-high group had shorter overall survival than the NPR-low group (hazard ratio 1.85, 95% confidence interval 1.05-3.28, P = 0.032).Our analysis indicated that the preoperative NPR serves as a prognostic factor in GC patients with positive peritoneal lavage cytology in the absence of other non-curative factors.

Little is known about the changes in prognostic factors after adjuvant S-1 monotherapy has become widespread as a standard of care for patients with gastric cancer (GC) in East Asia. The present study compared prognostic factors of patients with stage II/III GC treated with or without S-1 adjuvant to formulate appropriate risk stratification strategies. We designed a large multicenter dataset and retrospectively analyzed 847 patients with GC stage II or III, who underwent curative gastrectomy between 2010 and 2014. Clinicopathological features and prognostic factors were compared between the two patient groups: surgery-alone (n = 266) and S-1 adjuvant (n = 581). There were no significant differences in pathological tumor depths, nodal status, and disease stages between groups. Recurrence-free survival was significantly longer in the S-1 adjuvant group. For the surgery-alone group, independent prognostic factors were (in order of hazard ratio): (1) invasive growth, (2) high preoperative carcinoembryonic antigen levels, (3) total gastrectomy. For the S-1 adjuvant group, macroscopic tumor size (≥50 mm) was identified as another independent prognostic factor next only to pN2/3. There was overlap between the survival curves of patients with tumor size ≥50 mm in both groups. After receiving adjuvant S-1 monotherapy, ≥50 mm patients had significantly higher prevalence of peritoneal and lymph node metastasis as initial recurrences compared with

Background Insufficient data are available on the prognostic significance of complications after resection of gastric cancer. Therefore, we aimed to assess this gap in our knowledge by studying patients with resectable gastric cancer. Methods A multi‐institutional retrospective database comprising clinical information of 3575 patients who received resection of gastric cancer from 2010 to 2014 at nine institutions. Grades 2 or greater complications of the Clavien‐Dindo classification were judged as clinically relevant postoperative complications, and their associations with postoperative survival were assessed. We assessed the effect of complications on times of initiation and continuation of postoperative adjuvant chemotherapy by S‐1. Results A total of 2954 patients were included in the analysis. Clinically relevant postoperative complications occurred in 664 (23%) patients. Patients’ recurrence‐free survival rate incrementally decreased as the grade of complications became greater. Patients with abdominal complications (eg, leakage of pancreatic fluids, intra‐abdominal abscess, and anastomotic leakage) and those with nonabdominal complications (eg, pneumonia) experienced worse recurrence‐free survival compared to those without complications. Patients who had complications were generally at greater risk of disease recurrence, except for those who underwent laparoscopic surgery and those with pathological stage I. Delayed initiation and shorter continuation of adjuvant S‐1 chemotherapy was experienced by patients with postoperative complications. Conclusions Postoperative complications adversely affected the prognosis in patients with resectable gastric cancer.

This study aimed to evaluate the estimation of the physiological ability and surgical stress (E-PASS) scoring system for predicting the short- and long-term outcomes in gastric cancer (GC) surgery. We analyzed a multi-institutional dataset to study patients who underwent gastrectomy with a curative intent between 2010 and 2014. This study evaluated the associations between the optimal E-PASS score cutoff value and the following outcomes: (1) the incidence of postoperative complications in stage I–III GC patients and (2) the prognosis in stage II–III GC patients. A total of 2495 GC patients were included. A cutoff value of 0.419 was determined using the ROC curve analysis. Postoperative complications were observed more frequently in the E-PASS-high group than that in the E-PASS-low group (30% vs. 17%, p

Splenectomy for proximal gastric cancer was found to have no survival benefit in a randomized trial clarifying the role of splenectomy (JCOG0110 study). However, since tumor with invasion to the greater curvature and Type 4 tumor were excluded in JCOG0110, the benefit of splenectomy for these tumors is not known. A multicenter dataset of patients with gastric cancer who underwent gastrectomy between 2010 and 2014 was created. From the dataset, 114 eligible patients with proximal advanced gastric cancer with invasion to the greater curvature or Type 4 tumor were enrolled. There were 60 patients in the gastrectomy with splenectomy (Spx) group and 54 patients in the spleen-preserving (Prs) group. To balance the essential variables, propensity score analysis was performed, estimating the propensity score with a logistic regression model. Adjusted overall survival (OS) and adjusted disease-free survival (DFS) were estimated using the inverse probability of treatment weighting (IPTW) method. There were significant differences in age, performance status, comorbidity, macroscopic type, and clinical T stage between the Spx and Prs groups. The model for estimating the propensity score was well adapted (c-statistic: 0.830, 95%CI: 0.754–0.906). Adjusted OS was identical between the two groups (HR = 1.089, 95%CI: 0.759–1.563; p = 0.644). The DFS curve of Prs group was consistently tended to be lower than Spx, but the difference was not significant (HR = 0.813, 95%CI: 0.572–1.156; p = 0.249). The efficacy of splenectomy was minimal for proximal advanced gastric cancer even with invasion to the greater curvature or Type 4 tumor.

The presence of chronic inflammation and nutritional status in cancer patients affects its prognosis. There is a clinical need for a prognostic predictor that is objective and accurate, and that can be easily evaluated by preoperative screening. We evaluated the importance and usefulness of the preoperative modified systemic inflammation score (mSIS) to predict the long-term outcome of patients undergoing curative resection for gastric cancer (GC). Of the 3571 patients who underwent curative resection for GC in nine institutions between January 2010 and December 2014, 1764 patients who met the inclusion criteria were included. The mSIS was formulated according to the serum albumin level (ALB) and lymphocyte-to-monocyte ratio (LMR) as follows: mSIS 0 (ALB ≥ 4.0 g/dL and LMR ≥ 3.4), mSIS 1 (ALB

We analyzed the effect of a microscopic positive margin on survival outcomes after gastrectomy for gastric cancer METHODS: We analyzed a multi-institutional dataset to study patients who underwent gastrectomy with curative intent between 2010 and 2014. We used propensity score matching to strictly balance the patients' oncological features, backgrounds, and postoperative treatment to compare the survival outcomes of those with microscopic positive margins and those with negative margins.Among 3029 patients, 32 (1.1%) had positive margins. After matching, we enrolled 128 patients in this retrospective analysis: 32 with a positive margin and 96 with a negative margin. The recurrence-free survival of the positive-margin group was significantly shorter than that of the negative-margin group (hazard ratio [HR], 1.62, 95% confidence interval, 1.00-2.63, p = 0.0485). Consistent results were observed for patients with pStages I-III disease (HR, 1.65, p = 0.0835), whereas the survival curves overlapped in those with pStage IV disease (HR, 1.29, p = 0.5934). The prevalence of overall recurrence in the positive-margin group was higher than that in the negative-margin group (75% vs 58%, p = 0.0917). This trend was consistent with locoregional recurrence (9% vs 3%) and distant recurrence (69% vs 55%).The survival of patients after curative gastrectomy for gastric cancer was worse in those with microscopic positive margins than in those with negative margins.

In a randomized pivotal global phase III study, S-1 and oxaliplatin 100 mg/mPatients with HER2-negative AGC received 80 mg/mSeventy-one patients were enrolled from June 2015 to November 2016, but eight were excluded for ineligibility. Therefore, all final analyses were conducted with 63 patients. The confirmed RR was 46.0% (90% confidence interval [CI]: 36.1-56.3), and the disease control rate was 77.8% (90% CI: 68.1-85.1). The median PFS and OS were 4.9 (95% CI: 4.2-7.1) and 14.8 (95% CI: 11.1-18.9) months, respectively. Incidences of grade 3-4 AEs 10% were anorexia (19.0%), peripheral neuropathy (12.7%), nausea (11.1%), and thrombocytopenia (11.1%).This study represents the first evaluation of SOX130 in patients with HER2-negative AGC. SOX130 showed an acceptable safety profile, but the prespecified statistical efficacy targets were not achieved.

Discontinuation of postoperative S-1 adjuvant monotherapy is a frequent problem in the management of patients with gastric cancer. A total of 355 stage II/III gastric cancer patients who underwent gastrectomy and adjuvant S-1 were retrospectively analyzed using a multicenter dataset. We randomly assigned patients into either discovery or validation cohort in a 2:1 ratio. In the discovery cohort, 29 parameters were assessed as candidate factors to predict discontinuation of S-1 adjuvant within 6 months. A scoring system was designed using independent risk factors identified by the multivariate analysis. Reproducibility was tested in the validation cohort. Overall, 92 patients (25.9%) discontinued the treatment within 6 months because of adverse effects. Age, preoperative urea nitrogen (UN) and the preoperative albumin-to-bilirubin index (ALBI) showed the highest area under the curve (AUC) for the discontinuation of S-1 adjuvant within 6 months in each category: body status, blood tests and indices. In the multivariate analysis, age ≥ 64 years, preoperative UN ≥ 15.2 mg/dl and preoperative ALBI ≥ −0.265 were identified as independent risk factors. A scoring scale consisting of these three factors was developed for the prediction of drug discontinuation and demonstrated a greater AUC (0.728) than that of each of the three constituents. The time to treatment discontinuation decreased incrementally as the risk score increased. The reproducible findings were confirmed in the validation cohort. We identified risk factors and developed a scoring scale to predict S-1 adjuvant monotherapy discontinuation in patients with stage II/III gastric cancer.

AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in stage II/III gastric cancer. METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage II/III gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy. RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival. Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences. CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy.

This study aimed to evaluate the predictive value of the preoperative Controlling Nutritional Status (CONUT) score, which comprehensively reflects protein and lipid metabolism as well as the immunocompetence among patients with stage 2 or 3 gastric cancer. From a retrospective database of 3484 patients who underwent gastrectomy for gastric cancer at nine Japanese institutions between 2010 and 2014, data for 626 patients with stage 2 or 3 cancer were retrieved. The study evaluated the significance of the associations between the optimal CONUT score cutoff values with the prognosis and the incidence of postoperative complications. The study determined that 2 was the optimal CONUT score cutoff value for predicting mortality 2 years after surgery. The patients with a CONUT score of 2 or higher (CONUT-high group) were significantly older and had a worse Eastern Cooperative Oncology Group performance status, lower body mass index, and more advanced tumor-node-metastasis stage than the patients with a CONUT score lower than 2 (CONUT-low group). Overall, the survival time was significantly shorter in the CONUT-high group than in the CONUT-low group [hazard ratio (HR) 1.97; P

The prognostic significance of the number of retrieved lymph nodes (RLNs) in gastric cancer remains controversial. Therefore, we designed a multicenter collaborative database to investigate the correlation between the number of RLNs and prognosis of patients with advanced gastric cancer after curative resection. We retrospectively analyzed 1103 patients who underwent gastrectomy for stage II/III gastric cancer between 2010 and 2014. Lymph nodes, which were retrieved by surgeons from surgically resected specimens, were validated by pathologists. A target population and the optimal cutoff were determined using receiver operating characteristic (ROC) curve analysis. After propensity score matching of eight variables, including splenectomy and adjuvant chemotherapy, the prognostic significance of RLNs was evaluated. According to ROC curve analysis, the optimum cutoff score for predicting postoperative survival was 40. After matching, the backgrounds of patients in the RLN

The influence of intraoperative blood loss (IBL) on postoperative long-term outcomes of patients with gastric cancer is controversial. Here, we used a large multicenter dataset from nine institutes to evaluate the prognostic impact of IBL on patients with stage II/III gastric cancer. The study analyzed 1013 patients with stage II/III gastric cancer who underwent gastrectomy without preoperative treatment and intraoperative transfusion. Patients were equally divided into learning and validation cohorts using a table of random numbers. The optimal cutoff value of IBL to predict recurrence was determined using the learning cohort, and the prognostic significance of the proposed cutoff was validated using the second cohort. The optimal cutoff value of IBL determined with the learning cohort using the receiver operating characteristic curve analysis was 330 ml. In the validation cohort, IBL > 330 ml was significantly associated with high body mass index, total gastrectomy, and postoperative complications, but not disease stage and the frequency of adjuvant chemotherapy. The disease-free and disease-specific survival rates of patients in the IBL > 330 ml (IBL-high) group were significantly shorter compared with those in the IBL ≤ 330 ml group. IBL-high was identified as an independent prognostic factor of disease recurrence (hazard ratio 1.45, 95% confidence interval 1.01–2.09, P = 0.0420). The hazard ratio of the IBL-high group was greater in the surgery-alone subgroup compared with that of the postoperative adjuvant-chemotherapy subgroup. Our analysis of a multicenter dataset indicates that IBL adversely influenced long-term outcomes of patients with stage II/III gastric cancer.

Background The three dominant recurrence patterns of gastric cancer are peritoneal, hematogenous, and nodal recurrence. Correlation between initial recurrence site and prognosis is poorly understood, particularly after standardization of postoperative S‐1 adjuvant chemotherapy. Methods We analyzed a multi‐institutional database of 3484 patients who underwent gastrectomy for gastric cancer between 2010 and 2014. Patients who experienced recurrences after curative gastrectomy classified into peritoneal, hematogenous, or nodal recurrence groups, according to their initial recurrence sites, and their prognoses were compared. Results We included 313 patients in the analysis, of whom 190 patients (63%) were treated with postoperative adjuvant chemotherapy. Pathological disease states were stage I: n = 20 (6%), stage II: n = 62 (20%), and stage III: n = 231 (74%). Patients were categorized into groups by peritoneal (n = 127), hematogenous (n = 123), and nodal (n = 63) recurrence. The peritoneal recurrence group tended to have longer recurrence‐free survival, but shorter post‐recurrence survival, than the other two groups. Median disease‐specific survival after curative resection by group were peritoneal: 25.8 months, hematogenous: 29.0 months, and nodal: 27.8 months (peritoneal vs hematogenous, P = .152; hematogenous vs nodal, P = .955; peritoneal vs nodal, P = .213). Conclusions Prognoses after curative resection for gastric cancer were similar among patients with peritoneal, hematogenous, or nodal recurrences., We used a multi‐institutional dataset to see whether prognosis and site of initial recurrence after curative resection for gastric cancer were correlated. We found that prognoses were similar among patients with peritoneal, hematogenous, or nodal recurrences.

Background: Curative treatment for gastric cancer (GC) comprising gastrectomy with systematic lymph node dissection can result in postoperative complications. Postoperative pneumonia is sometimes fatal, like surgery-related complications such as anastomotic leakage. In this retrospective study, we analyzed a multi-institutional collaborative dataset with the aim of identifying predictors of postgastrectomy pneumonia. Methods: From a retrospective database of 3,484 patients who had undergone gastrectomy for GC at nine Japanese institutions between 2010 and 2014, 1,415 patients who met all eligibility criteria were identified as eligible for analysis. Predictive values of 31 candidate variables for postoperative pneumonia were assessed. Results: Forty-two patients (3.0%) had grade II or higher postoperative pneumonia. Preoperative systemic inflammation score (SIS) had the greatest area under the curve (0.655) for predicting postoperative pneumonia (optimal cutoff value = 2). The odds ratio (OR) of high SISs associated with postoperative pneumonia was 3.10 (95% confidence interval [CI], 1.54–6.07; p < 0.001). Multivariate binomial logistic analysis identified high SIS as an independent risk factor for postoperative pneumonia (OR, 2.31; 95% CI, 1.19–4.48; p = 0.013). A forest plot revealed that ORs of high SISs were highest in female patients. Conclusions: Our findings indicate that the preoperative SIS may serve as a simple predictor of postgastrectomy pneumonia, assisting physicians’ efforts to take preventive measures against this complication.

Few well-controlled studies have compared postoperative complications between Billroth I (B-I) and Roux-en-Y (R-Y). The aim of the present study was to compare the incidence of overall and severe postoperative complications by reconstruction method after distal gastrectomy. We performed a multi-institutional dataset study of patients who underwent distal gastrectomy with B-I or R-Y reconstruction from 2010 to 2014. Using propensity scores to strictly balance the significant variables, we compared postoperative complications between the techniques. After matching, we enrolled 1014 patients (n = 507 in each group). The incidence of postoperative complications in the R-Y group was significantly higher vs the B-I group (29% vs 17%, P

Laparoscopic gastrectomy (LG) is a standard approach for patients with clinical stage I gastric cancer in East Asia; however, following surgery, these patients may be pathologically diagnosed with stage II or III cancer. The prognosis of patients with gastric cancer migration from clinical stage I to pathological stage II or III after LG has not been completely clarified. To compare the prognosis following LG and open gastrectomy (OG) in patients with pathological stage II or III gastric cancer who were preoperatively diagnosed with stage I cancer, we conducted a retrospective analysis using a multicenter dataset comprising details of 3480 patients who underwent gastrectomy between 2010 and 2014 at nine participating institutions. We used propensity score matching to reduce selection bias. After propensity score matching, 146 patients were finally selected. There were no significant differences in the number of dissected lymph nodes. Morbidity rates, length of postoperative hospital stay, and time between surgery and initiation of adjuvant chemotherapy were comparable between the two groups. Moreover, there were no significant differences in the overall, disease-specific, and relapse-free survival rates between the LG and OG groups. The LG group tended to have more patients with hematogenous recurrence, whereas the OG group tended to have more patients with peritoneal recurrence. Our multicenter dataset analysis indicated that the prognosis of patients with gastric cancer migration from clinical stage I to pathological stage II or III was independent of the surgical approach.

Background: Little information from prospective clinical trials is available on the influences of surgical approaches on postoperative body compositions and nutritional status. We designed a prospective non-randomized trial to compare postoperative chronological changes in body composition and nutritional status between laparoscopic and open distal gastrectomy for stage I gastric cancer (GC). Methods: Body compositions and nutritional indicators in blood tests were measured at the baseline and at the 1st, 3rd, 6th, and 12th postoperative months (POM). The primary end point was the decrease relative to the baseline in the body muscle mass at POM 6. Results: Ninety-six patients for the laparoscopic group and 52 for the open group were eligible for data analysis. No significant differences were found in any baseline demographics, body compositions, and nutritional indicators between the groups. The changes of body muscle mass at POM 6 were similar in both groups. Overall, no significant differences between the groups were observed in any of the body composition and nutritional indicators during the first year after surgery. Conclusions: Postoperative body compositions and nutritional status were not affected by surgical approaches during the first 12 months after surgery in patients who underwent distal gastrectomy for stage I GC.

This study aimed to evaluate whether the timing of initiating postoperative chemotherapy with S-1 monotherapy affects gastric cancer patients’ prognosis. A multi-institution dataset identified patients with pStage II or III gastric cancer who received S-1 monotherapy for over 6 months after curative resection between 2010 and 2014. Patients were divided into three groups based on the timing of S-1 monotherapy initiation. Prognostic factors for relapse-free survival (RFS) were investigated. We classified 401 patients into groups as follows: S-1 administered within 6 weeks (n = 247), between 6 and 8 weeks (n = 95), and after 8 weeks (n = 59). The RFS times were not significantly different in the within 6 weeks group and the between 6 and 8 weeks group, but the after 8 weeks group had a shorter RFS time compared with the other two groups (within 6 weeks group vs. after 8 weeks group; P = 0.0044). By disease stage, this trend was the same. The multivariable analysis showed that a larger tumor size (≥ 50 mm), pStage III, and the after 8 weeks group were independent prognostic factors for RFS (after 8 weeks group: hazard ratio, 2.05; P = 0.0069). The prevalence of hematogenous metastasis as the initial recurrence site increased by delayed initiation of S-1. A forest plot revealed that delayed administration after 8 weeks was associated with a greater risk of recurrence in most subgroups. Postoperative chemotherapy with S-1 monotherapy for gastric cancer is recommended to begin within 8 weeks after surgery.

Anastomotic leakage is a major cause of prolonged hospitalization after gastrectomy and sometimes leads to fatal complications, such as abdominal abscess and sepsis. Arginine, glutamine, and β-hydroxy-β-methylbutyrate (HMB) are indispensable for biosynthesis of collagen, which plays an important role in the process of wound healing. However, treatment effects of amino acid supplements containing HMB on the healing process of anastomotic leakage after gastrectomy remain unclear. We designed an open-label, multicenter, phase II clinical trial to evaluate the therapeutic efficacy of an enteral amino acid supplement consisting of arginine, glutamine, and HMB (Abound, Abbott Japan Co., Ltd., Tokyo, Japan) in patients with anastomotic leakage after gastrectomy. Patients who are diagnosed with anastomotic leakage within 14 days after gastrectomy are eligible for this trial and the target sample size is 20. A pack of Abound is administered twice a day for 2 weeks. The primary objective of this clinical trial is to determine the length of time between diagnosis and cure of anastomotic leakage. The secondary endpoints include the safety of Abound, duration of drainage placement and fasting, postoperative hospital stay, surgical procedure, and blood test data. Variables are compared between enrolled patients and a historical control consisting of 20 patients who underwent gastrectomy between 2004 and 2016 at Nagoya University Hospital. We herein describe the study design and the concept in this protocol paper.

Background Advanced gastric cancer frequently recurs even after radical resection followed by adjuvant chemotherapy. The aim of this study was to evaluate the relationship between pathological infiltrative pattern (INF) and initial recurrence patterns in patients with stage II/III gastric cancer using a large multicenter database. Methods We retrospectively analyzed 1098 eligible patients who underwent curative gastrectomy for stage II/III gastric cancer at nine institutions between 2010 and 2014. Patients were categorized into the INF‐a/b and INF‐c groups and adjusted using propensity score matching. Results After propensity score matching, 686 patients (343 for each) were classified in the INF‐a/b and INF‐c groups. There were no significant differences in overall and disease‐free survival between the two groups. In the INF‐a/b group, frequencies of recurrence at the peritoneum, lymph node, and liver were equivalent. In contrast, the peritoneum was the most frequent site and accounted for 60% of the total recurrences in the INF‐c group. The cumulative peritoneal recurrence rate was significantly higher in the INF‐c group than in the INF‐a/b group (hazard ratio 2.47). INF‐c was a significant risk factor for peritoneal recurrences in most subgroups including age, sex, macroscopic type, tumor differentiation, and disease stage, and whether the postoperative treatment was given. Multivariate analysis identified INF‐c as an independent risk factor for peritoneal recurrences. The cumulative liver recurrence rate was significantly higher in the INF‐a/b group than in the INF‐c group (hazard ratio 3.44). Conclusions INF may represent an important predictor of recurrence patterns after curative resection of stage II/III gastric cancer.

Background/Aims: Identification of nutritional indicators to predict short-term and long-term outcomes is necessary to provide appropriate treatment to patients with gastric cancer. Methods: We designed an analysis of a multicenter dataset of patients with gastric cancer who underwent gastrectomy between 2010 and 2014. We enrolled 842 eligible patients who had stage II/III gastric cancer. The area under the curve (AUC) values were compared among prognostic nutritional index (PNI), calculated as 10 × albumin g/dL + 0.005 × total lymphocyte count/mm3, and its constituents, and the predictive value of preoperative PNI for postoperative short-term and long-term outcomes was evaluated. Results: Preoperative PNI exhibited higher AUC values (0.719) for 1-year survival than its constituents, and the optimal cutoff value was 47. The disease-free and overall survival of patients in the PNI-low group were significantly shorter compared with those in the PNI-high group. The prognostic difference between the PNI-high and PNI-low groups was significantly greater in the subgroup of patients who underwent total gastrectomy. Clinically relevant postoperative complications were more frequently observed in the PNI-low group. Conclusions: The preoperative PNI is a useful predictor reflecting the incidence of complications after gastrectomy and the prognosis of patients with stage II/III gastric cancer.

Aneurysm formation is a potential complication of granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis. It is a very rare complication, but immediate diagnosis and therapy should be performed because an aneurysm can be life-threatening if it ruptures. An accessory left gastric artery (ALGA) is also a rare variant gastric artery that may obtain its blood supply from the left hepatic artery and left gastric artery. We herein describe a 57-year-old Japanese man who was diagnosed with GPA complicated by aneurysm rupture in an ALGA. Emergency surgery was performed after failure of arterial coil embolization to interrupt blood flow in the ALGA. The patient underwent partial resection of the lesser omentum, which contained all aneurysms. During partial resection of the lesser omentum, both the left gastric artery and ALGA were ligated because they were thought to be feeders of the aneurysms. Postoperative recovery was uneventful; no bleeding or recurrence of the aneurysms occurred. Immediate diagnosis and therapy should be performed for patients with GPA with symptoms of vascular ischemia or aortitis. Endovascular intervention is the first-choice therapy especially for hemodynamically stable patients with ruptured aneurysms or aneurysms located on variant arteries, which may have multiple blood supplies. In the present case, although endovascular treatment failed, the approach described herein was helpful during open surgery.

292 Background: Billroth I (B-I) or Roux-en-Y (R-Y) are common reconstruction technique after distal gastrectomy, each with advantages and disadvantages and which is the most successful remains unclear. The aim of the present study was to clarify the difference of postoperative complications between the two techniques. Methods: A multi‐institutional retrospective database comprising clinical information of 3484 patients who received resection of gastric cancer from 2010 to 2014 at nine institutions. Using propensity scores to strictly balance the significant variables, and we compared the overall and severity postoperative complications. We considered Clavien–Dindo grade ≥ II postoperative complications clinically relevant, and grade ≥ III severe postoperative complications. Results: After matching, we enrolled 1086 patients (n=543 in each group). The incidence of postoperative complications in the R-Y group was significantly higher vs the B-I group (28% vs 17%, respectively; P

Purpose Patients with pathological stage T1N+ or T2-3N0 gastric cancer may experience disease recurrence following curative gastrectomy. However, the current Japanese Gastric Cancer Treatment Guidelines do not recommend postoperative adjuvant chemotherapy for such patients. This study aimed to identify the prognostic factors for patients with pT1N+ or pT2-3N0 gastric cancer using a multi-institutional dataset. Materials and methods We retrospectively analyzed the data obtained from 401 patients with pT1N+ or pT2-3N0 gastric cancer who underwent curative gastrectomy at 9 institutions between 2010 and 2014. Results Of the 401 patients assessed, 24 (6.0%) experienced postoperative disease recurrence. Multivariate analysis revealed that age ≥70 years (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.09-7.23; P=0.030) and lymphatic and/or venous invasion (lymphovascular invasion (LVI): HR, 7.88; 95% CI, 1.66-140.9; P=0.005) were independent prognostic factors for poor recurrence-free survival. There was no significant association between LVI and the site of initial recurrence. Conclusions LVI is an indicator of poor prognosis in patients with pT1N+ or pT2-3N0 gastric cancer.

A73 -year-old man underwent a sigmoidectomy for sigmoid colon cancer with liver metastasis. After the operation, he received CapeOX combined with bevacizumab therapy. After 6 courses, the liver metastasis was undetectable on computed tomography scans. After 15 courses, computed tomography revealed ascites, and chemotherapy was discontinued. Two months later, computed tomography revealed portal vein thrombosis. Owing to the chronic nature of the thrombosis, thrombolytic therapy was not initiated. However, preservation therapy using antiplatelet drugs for 1 month resolved the ascites and the thrombosis. The risk of serious thrombosis must be considered when using bevacizumab.

症例は61歳の女性で，53歳時より原発性胆汁性肝硬変・シェーグレン症候群・膜性腎症にて加療中である．今回，右季肋部痛を主訴に受診し，腹部CTで肝左葉外側区域に径9 cmの腫瘍を指摘された．身体検査所見では掻痒感を認めるも黄疸はなく，血液生化学検査で胆道系酵素・IgMの上昇，抗ミトコンドリア抗体陽性を認めた．肝炎ウィルスマーカーおよび腫瘍マーカーは陰性であった．画像検査所見にて腫瘍は被膜様構造を伴う境界明瞭な腫瘤として描出された．内部は脂肪成分に富み造影による早期濃染を認めた．鑑別診断として大型の高分化型肝細胞癌と肝血管筋脂肪腫が考えられたが，確定診断はつかず肝左葉切除術を施行した．摘出標本の病理組織学的検査にて肝血管筋脂肪腫と診断された．術後1年経過した現在のところ明らかな再発所見を認めていない．今回，原発性胆汁性肝硬変の経過中に急速に増大した肝血管筋脂肪腫の1例を経験したので報告する．

症例は21歳，女性．約1年前に子宮外妊娠の疑いにて左付属器摘出術を施行され，病理結果で卵巣癌と診断された．術後に血中hCG高値を認め，化学療法が施行されていたが，CTにて右ドーム部に増大傾向にある約3cm大の腫瘤を認めたため，播種性転移を疑い手術を施行した．術中所見は，右横隔膜にヘルニア嚢を有する径3cm大の筋層欠損部を認め，同部より胸腔へ突出する肝を認めるのみであり，術中超音波検査でも肝内に腫瘤は認めず，ヘルニア門を縫合閉鎖し手術終了とした．成人の右側Bochdalek孔ヘルニアは非常に稀な疾患であり，今回われわれは，その経時的な変化を画像で捉えた症例を経験したため若干の文献的考察を加えて報告する．

はじめに：P0CY1症例の臨床病理組織学的因子，予後について検討し，P1症例と比較した．方法：当院で1996年から2005年までに手術を施行した656例の胃癌症例のうち，開腹時に腹腔洗浄細胞診（以下，CY）を施行した339例を対象とした．CYはPapanicolaou染色にて判定し，ClassVをCY1と診断した．結果：P0は281例でそのうちCY1は33例（11.7％）であった．P0CY1全例が深達度T3もしくはT4で，リンパ節転移陽性であり，P0CY0と比較してT因子，N因子の進展を認めた．生存期間を比較すると，P0CY0，P0CY1，P1の順に不良であった．腹膜播種陽性例を胃癌取扱い規約第12版に従い，P1，P2，P3に分類してP0CY1も含め比較したところ，P0CY1，P1はP3に比べ生存期間は長かった．また，P0CY1の腹腔洗浄細胞診における癌細胞数の多寡による比較を行うと，癌細胞数少数例のほうが多数例に比べ生存期間は長かった．胃切除，リンパ節郭清を行ったP0CY1のうち，有意差はないがMSTはD2群が497日，D0，D1群が264日という結果であった．考察：CY1は予後不良因子であるが，P1より生存期間は長い．腹腔洗浄細胞診における癌細胞数の多寡は予後予測因子になりうると考えられた．

はじめに: 上部胃癌の手術術式の選択にあたり, 噴門側胃切除が至適術式として採用できるか否かをリンパ節郭清の程度も含め, 壁深達度とリンパ節転移の状況に基づき検討した. 方法: 1973年から2005年に行われたH0P0M0のU領域, 初発単発胃癌切除例401例を対象とし, No.4d, 5, 6, 10, 11のリンパ節の転移の特徴, 臨床病理組織学的因子につき検討した. 結果: 深達度SSまでのNo.10転移例は郭清例126例中5例 (4.0%) であり, 全例病変の占居部位は胃上部左半にあった. 4例は腫瘍径が40mm以上であり, 1群リンパ節転移を伴っていた. No.11転移例は郭清例126例中8例 (6.3%) で, そのうちNo.11dの転移例は3例のみであり, 全例病変の占居部位は胃上部左半にあり, 1群リンパ節転移を伴っていた. そのうち, 2例は腫瘍径が40mm以上であった. No.4d転移例は郭清例189例中3例 (1.6%) で, 全例腫瘍径は40mm以上, 病変の占居部位は胃上部左半にあった. No.5, 6リンパ節転移例は認めなかった. 深達度SE, SIではそれぞれのリンパ節転移率は高率となる傾向であった. 結語: 深達度SSまでで占居部位が小彎に限局, あるいは腫瘍径が40mm未満もしくは1群リンパ節転移を認めない場合, No.4d, 5, 6, 10, 11dのリンパ節転移例はごくまれであった. したがって, 上部胃癌では上記の条件を満たす場合, 噴門側胃切除術, D1+No.7, 8a, 9, 11pのリンパ節郭清は至適術式と考えてよいと思われた.

Underphosphorylated retinoblastoma (Rb) protein inhibits progression around the cell cycle by binding to transcription factors like E2F; subsequent hyperphosphorylation of Rb protein releases E2F from the complex so that it can then drive the cell into S phase. We immunolocalized Rb protein in human cells during the cell cycle. Rb protein translocated into nucleoli after DNA replication completed, and the nucleolar Rb was shown to be in the hyperphosphorylated form by immunoblotting. This form, but not its underphosphorylated counterpart, interacted with the nucleolar protein nucleophosmin/B23. The two formed a salt-resistant complex in vitro, and the two could be immunoprecipitated together from nucleolar extracts. These results suggest that hyperphosphorylated Rb protein is imported into nucleoli late in S or G2 phase with nucleophosmin/B23. Analysis of the nucleolar location of Rb protein using various deletion mutants tagged with the green fluorescent protein implicated pocket A of Rb protein as the region responsible for nucleolar targeting; this region also interacted with nucleophosmin/B23. Nucleolar translocation of Rb mutant was inhibited by introducing nucleophosmin/B23 antisense oligomer. These results suggest that nucleolar translocation of Rb protein is promoted by the binding with nucleophosmin/B23 via the pocket A region.

An 80-year-old female visited our hospital with the chief complaint of lower abdominal pain and diarrhea. She was diagnosed to have rectal cancer. Hartmann operation was performed and curative resection was successfully achieved. Postoperative stage was III according to the classification of the Japanese Society for Cancer of the Colon and Rectum(The 7th Edition). She was treated with oral tegafur(UFT 300mg/body/day)as adjuvant chemotherapy for 6 months. Paraaortic lymph node metastasis and local recurrence were diagnosed by abdominal CT 1 year after the surgery. Her performance status score was 0. She was treated with modified FOLFOX6 chemotherapy combined with bevacizumab. Abdominal CT revealed a partial response after 5 courses. She experienced grade 2 leukocyopenia, grade 3 neutropenia, grade 2 proteinuria and grade 2 hypertension.

Oxaliplatin is the third-generation platinum complex to be active in advanced colorectal cancer. In Japan, it was approved in April 2005. FOLFOX regimen(a combination of leucovorin and fluorouracil with oxaliplatin) has been one of the standard chemotherapy regimens for metastatic colorectal cancer.To evaluate the efficacy and feasibility of FOLFOX4 and mFOLFOX6 regimens as first-line chemotherapy in Japanese patients with metastatic colorectal cancer, 23 consecutive patients with histologically confirmed colorectal cancer who were treated between June 2005 and August 2007 were investigated in this retrospective study. FOLFOX4 was used for treatment in 13 patients(57%), and mFOLFOX6 was in 10 patients(43%).The objective response rate was 50.0%. The median survival time was 17.4 months. The median number of cycles was 8.0, with a median relative dose intensity of 74.5% for oxaliplatin. Grade 3 or 4 hematological toxicities were leukocytopenia in four patients, and neutropenia in 12 patients, while non-hematological toxicities such as nausea, anorexia and sensory neuropathy occurred in only one patient each adverse event. No treatment-related deaths occurred.FOLFOX regimen has good efficacy in Japanese patients with metastatic colorectal cancer as first-line chemotherapy, with an acceptable overall toxicity profile.

We report a patient with advanced gastric cancer responding remarkably to neoadjuvant combination chemotherapy consisting of paclitaxel and S-1. The patient was a 65-year-old female who had large type 2 advanced gastric cancer with severe lymph node metastasis(cT3, cN3, cH0, cP0, cM0, cStage IV), treated with paclitaxel/S-1 as neoadjuvant chemotherapy. After the second course, according to UGI, gastroscope and CT findings, a significant tumor reduction was obtained. Distal gastrectomy with D2 nodal dissection were performed. The histological diagnosis was pT1, pN1, pStage IB. The histological effect of main tumor was judged to be Grade 2. The patient has now been in good health without a recurrence for 10 months after surgery. This case suggests that neoadjuvant chemotherapy with paclitaxel/ S-1 is a potential regimen for advanced gastric cancer.