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Postoperative acute kidney injury after digestive surgery can be a critical problem that causes morbidity or mortality. Although serum creatinine reflects the renal function, it takes time to measure, and only severe renal failure induces an increase in creatinine. We tried to calculate the renal artery pulsatility index as a parameter to enable the real-time monitoring of acute kidney injury, which can be measured by routine bedside ultrasonography. This study aimed to evaluate the accuracy of the renal artery pulsatility index for the early detection of acute kidney injury after digestive surgery.One hundred consecutive patients who underwent digestive surgery in a single institution from March to July 2018 were included. The renal artery pulsatility index was measured at 4 time points (preoperative day, postoperative day 1, postoperative day 4, and postoperative day 7). Perioperative acute kidney injury I was defined as a0.3 mg/dL increase in serum creatinine and a serum creatinine level of1.0 mg/dL at any postoperative time point. The association of the renal artery pulsatility index with perioperative acute kidney injury was analyzed.The preoperative renal artery pulsatility index (average 1.4) was significantly high in aged patients and those with diabetes mellitus, hypertension, or chronic kidney disease. Furthermore, a high preoperative renal artery pulsatility index (cut-off: 1.6) was a predictor of perioperative acute kidney injury (n = 13). Moreover, the postoperative renal artery pulsatility index significantly increased in acute kidney injury cases.The renal artery pulsatility index was strongly correlated with acute kidney injury in the perioperative period. It appears to be an effective and less invasive procedure for the real-time monitoring that enables the early detection of acute kidney injury after digestive surgery.

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.

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.

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

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.

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

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.

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.

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: 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.

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.

91 Background: Nab-paclitaxel (nab-PTX) is a candidate as second-line chemotherapy for gastric cancer, with the response rate (RR) of 28% and overall survival (OS) of 9.2 months in that setting in Japan (J-0200). Adverse events (AE) of grade 3 or more were frequent and included neutropenia in 49%, leucopenia in 20% and peripheral nerve disorder (PND) in 24%. Modified dose reduction criteria to manipulate the doses earlier might be more practical, given the relative dose intensity (RDI) of paclitaxel (PTX) in the conventional weekly regimen. Phase II prospective trial was conducted to explore the efficacy and safety of nab-PTX with modified dose reduction criteria. Methods: Patients with histologically confirmed metastatic or recurrent gastric adenocarcinoma that progressed during the fluoropyrimidine-containing first-line chemotherapy were eligible. Patients pretreated with PTX were excluded. Nab-PTX (260 mg/m2) was administered triweekly. Dose reduction was regulated according to predefined toxicity criteria which included neutropenia < 1000/mm3 and/or PND with grade 2 or more. Treatment was to be continued until PD, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression free survival (PFS). Secondary endpoints were OS, RR and toxicity. Results: A total of 50 patients were enrolled from 14 institutions, 47 of whom were eligible for efficacy analyses. The median number of treatment given was 4 cycles (range, 1-25). Of total administration throughout the trial of 280 cycles, dose reduction was needed in 52 cycles (22%). The RDI was 80%. The median PFS was 3.5 months (range, 0.4-20.2) that was equivalent to the expected value designed in the study. The median OS was 9.0 months (range, 1.4-22.1) and RR was 16% (95%CI 2-30). AE of grade 3 or more included neutropenia in 49%, leucopenia in 21% and PND in 11%. Febrile neutropenia occurred in 1 patient (2%). The median time to treatment failure was 3.5 months (range, 0.4-18.0). Conclusions: The modified dose reduction criteria for triweekly administration of nab-PTX resulted in decreased incidence of severe PND without fall in efficacy. Clinical trial information: UMIN000012247.

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.

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.

A survival benefit of extensive intraoperative peritoneal lavage (EIPL) has been reported in patients with gastric cancer with positive peritoneal cytology. The hypothesis of this study was that EIPL may reduce peritoneal recurrence in patients with advanced gastric cancer who undergo surgery with curative intent.This was an open-label, multi-institutional, randomized, phase 3 trial to assess the effects of EIPL versus standard treatment after curative gastrectomy for resectable gastric cancer of T3 status or above. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival, peritoneal recurrence-free survival and incidence of adverse events.Between July 2011 and January 2014, 314 patients were enrolled from 15 institutions and 295 patients were analysed (145 and 150 in the EIPL and no-EIPL groups respectively). The 3-year DFS rate was 63·9 (95 per cent c.i. 55·5 to 71·2) per cent in the EIPL group and 59·7 (51·3 to 67·1) per cent in the control group (hazard ratio (HR) 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). The 3-year overall survival rate was 75·0 (67·1 to 81·3) per cent in the EIPL group and 73·7 (65·9 to 80·1) per cent in the control group (HR 0·91, 0·60 to 1·37; P = 0·634). Peritoneal recurrence-free survival was not significantly different between the two groups (HR 0·92, 0·62 to 1·36; P = 0·676). No intraoperative complications related to EIPL were observed.EIPL did not improve survival or peritoneal recurrence in patients who underwent gastrectomy for advanced gastric cancer. Registration number: 000005907 (http://www.umin.ac.jp/ctr/index.htm).Se ha descrito que un lavado peritoneal extenso intraoperatorio (extensive intraoperative peritoneal lavage, EIPL) proporciona un beneficio en la supervivencia en pacientes con cáncer gástrico con citología peritoneal positiva. La hipótesis de este estudio era que el EIPL podría disminuir la recidiva peritoneal en pacientes con cáncer gástrico avanzado sometidos a cirugía con intención curativa. MÉTODOS: Ensayo clínico fase 3, abierto, multicéntrico y aleatorizado para evaluar los efectos de un lavado peritoneal extenso intraoperatorio (EIPL) frente a tratamiento estándar tras gastrectomía curativa por cáncer gástrico ≥T3 resecable. La variable de resultado primaria fue la supervivencia libre de enfermedad (disease-free survival, DFS), y las variables de resultado secundarias fueron la supervivencia global (overall survival, OS), la supervivencia libre de recidiva peritoneal y la incidencia de efectos adversos.Entre julio de 2011 y enero de 2014, se reclutaron 314 pacientes de 15 instituciones y se analizaron los datos de 295 pacientes (145 en el grupo con EIPL y 150 en el grupo sin EIPL). La DFS a los 3 años fue 63,9% (i.c. del 95% 55,5-71,2) en el grupo con EIPL y 59,7% (i.c. del 95% 51,3-67,1) en el grupo control (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,57-1,16), P = 0,249). La OS a los 3 años fue 75,0% (i.c. del 95% 67,1-81,3) en el grupo con EIPL y 73,7% (i.c. del 95% 65,9-80,1) en el grupo control (HR 0,91 i.c. del 95% 0,60-1,37), P = 0,634). No se observaron diferencias estadísticamente significativas entre los dos grupos en la supervivencia libre de recidiva peritoneal (P = 0,676, HR 0,92 (i.c. del 95% 0,62-1,36). No se observaron complicaciones intraoperatorias relacionadas con EIPL. CONCLUSIÓN: El EIPL no mejoró la supervivencia o la recidiva peritoneal en pacientes sometidos a gastrectomía por cáncer gástrico avanzado.

Postoperative malnutrition after gastrectomy is deemed inevitable, which could have prejudicial influence on survival for gastric cancer patients. A prospective feasibility study was conducted to evaluate the efficacy of postoperative oral nutritional supplements. Stage I–III gastric cancer patients who underwent distal or total gastrectomy received oral administration of Racol® NF (Otsuka Pharmaceutical Factory, Japan), a liquid enteral nutritional formula, as a supplement to regular meals. Racol® NF administration at a recommended dosage of 400 kcal/400 ml per day was started within 7 days postoperatively and was continued for 3 months postoperatively. The primary end point was ratio of the weight loss at 3 months postoperatively to the preoperative body weight (body weight loss ratio). Secondary end points were the adherence to Racol® NF therapy and changes in body composition. One hundred eighteen patients were registered before surgery, 82 of whom were eligible for efficacy analyses. The average rate of body weight loss after 3 months postoperatively was 8.3%. The mean daily intake of Racol® NF was 211 ml. There was a significant correlation between adherence to Racol® NF therapy and body weight loss ratio (P

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.

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.

Despite recent clinical trials, the sensitivity and resistance of metastatic gastric cancer to anti-HER2 and anti-EGFR therapy are still unclear. To clarify the HER2 and EGFR expression status in the metastatic sites, we immunohistochemically compared HER2 and EGFR expression between primary and metastatic tumors from 52 gastric cancer patients with liver metastases and 85 patients with peritoneal metastases. The HER2 positivity rate of primary and metastatic tumors in patients with liver metastases, especially with intestinal-type histology (70.6 and 80.0 %, respectively), was significantly higher than in primary and metastatic tumors (22.4 and 16.4 %, respectively) in patients with peritoneal metastases. HER2 positivity of the primary tumor and liver metastases showed good concordance (87.5 %) in patients with liver metastases. In contrast, the EGFR positivity rate of metastatic tumors (70.1 %) in patients with peritoneal metastases was significantly higher than that of metastatic tumors (37.5 %) in patients with liver metastases. HER2 and EGFR expression tended to be mutually exclusive, and HER2/EGFR double-positive cases were rare in patients with liver or peritoneal metastases. In four such patients with HER2/EGFR double-positive primary tumors, the HER2- and EGFR-positive areas were separate, and corresponding liver metastasis was only positive for HER2 and peritoneal metastasis only positive for EGFR. These results indicate that HER2 and EGFR are preferentially expressed in the liver and peritoneal metastases, respectively, which would be potential targets for anti-HER2 and anti-EGFR molecular therapy in metastatic gastric cancer patients.

In Japan, CPT-11 is often used to treat unresectable gastric cancer in the second-line setting. However, evidence regarding benefit of second-line chemotherapy remains sparse, especially after failing S-1.A phase II study to evaluate the efficacy and safety of weekly administration of CPT-11 at a dose of 100 mg/m(2) after failing a S-1-containing first-line treatment was planned with response rate as a primary end point. UGT1A1*6, *27, and *28 genotyping were performed in all cases, and those found to have either homozygous for *28, homozygous for *6, heterozygous for both *6 and *28, and heterozygous for *27 were rendered ineligible for the phase II trial.Two patients of homozygous for *28, two patients of homozygous for *6, and one patient of heterozygous for *27 were found among 39 recruited patients. The median number of courses delivered was 3 courses. The overall response rate was 15.4 % and disease control rate was 65.4 %. The median time to treatment failure was 87.5 days and median overall survival was 268 days. Twenty-two (73 %) of 30 valuable patients experienced protocol-specified skip of treatment and 8 (30 %) of patients could continue treatment with dose reduction. ≥G3 neutropenia was found in 30 % and ≥G3 anorexia and diarrhea were found in 23 and 17 %, respectively.Weekly CPT-11 at 100 mg/m(2) showed moderate response among gastric cancer patients who were refractory to S-1, but the disease control rate seemed meaningful. Even after selection of patients by UGT1A1 polymorphism of *6, *27, and *28, severe toxic events could not be prevented completely.

症例は53歳，男性．便秘と下腹部不快感を主訴に受診，画像上骨盤内に92mmの腫瘍を認めた．精査の結果，前立腺に浸潤する直腸gastrointestinal stromal tumor（以下GIST）と診断された．当初，根治的切除として骨盤内臓全摘術を考慮したが，機能温存を図るためneoadjuvant therapyとしてメシル酸イマチニブを400mg/日で8カ月間投与し，腫瘍の縮小が得られた後に手術を施行した．腹会陰式直腸切断術に前立腺合併切除を付加し，尿道は再建することが可能であった．GISTに対するneoadjuvant therapyは，現在臨床試験中でその有用性は確立されていないものの，局所進行GISTに対する治療において，臓器機能を温存し，安全に根治的な外科的切除を可能にする有効な戦略であると考えられる．

We have previously reported the molecular detection of peritoneal micrometastases in patients with gastric cancer by quantifying carcinoembryonic antigen (CEA) mRNA in the peritoneal washes. Patients with CEA mRNA exceeding a cutoff value have a significant risk for developing peritoneal carcinomatosis, but optimal treatment for this population remains unknown. CEA mRNA (+) patients with gastric cancer were treated postoperatively with S-1 monotherapy. Overall survival, the primary endpoint of this phase II trial, was compared with the historical control, which is comprised of CEA mRNA (+) patients who were not given postoperative chemotherapy. A total of 32 patients with CEA mRNA (+) gastric cancer were enrolled. Twelve patients (37.5%) relapsed; ten showed peritoneal relapse. Three-year survival was similar between the study population and the historical control (67.3% vs. 67.1%, respectively). S-1 monotherapy, which significantly reduced risk for recurrence in stage II/III gastric carcinoma in another phase III trial, seems not to be as effective in eradicating free cancer cells in the abdominal cavity.

1 Background: Extensive intraoperative peritoneal lavage (EIPL) for gastric cancer reportedly improved survival by physically removing and reducing intraperitoneal-free cancer cells in a small-scale randomized trial (Ann Surg 2009). To confirm this, we conducted a multicenter randomized Phase III trial. Methods: Eligibility criteria: (i) histologically confirmed primary gastric adenocarcinoma, (ii) clinically T3(SS), T4a(SE) or T4b(SI), (iii) clinically M0, and (iv) scheduled for total or distal gastrectomy. Patients were intraoperatively randomized to either the EIPL group or the non-EIPL group after confirming the ≥T3 status and resectability. In the EIPL group, peritoneal lavage was conducted at least 10 times using 1L of saline before the closure of the abdomen. In the non-EIPL group, the lavage was conducted with ≤3L of saline. The primary end-point was disease-free survival (DFS). To detect the difference of 15% in 3-year DFS with a both-sided alpha of 5% and 80% power, the planned sample size was 300 cases. This study was registered as UMIN000005907. Results: Between July 2011 and January 2014, 314 patients were registered from 15 institutions. After excluding the R1/R2 resection cases, 295 patients (145 in the EIPL group and 150 in the non-EIPL group) were analyzed. There were no significant differences between the groups in clinicopathologic characteristics. The median volume of saline for the peritoneal lavage was 10.0 L (10 - 12) for the EIPL group and 3.0 L (1 - 4) for the non-EIPL group. No difference was observed in the incidence of postoperative complications. The 3-year DFS was 63.9% in the EIPL group and 59.7% in the non-EIPL group (p = 0.25, Hazard ratio 0.81 [95% CI 0.57-1.16]). The overall survival rate of the EIPL group and non-EIPL group were 75.0%, 73.7% (3 years), and 62.5%, 57.1% (5 years), respectively (p = 0.65). In the subset analysis, no subgroup with significant difference in survival was identified. Conclusions: Although EIPL for advanced gastric cancer was safe and suggested some efficacy, the primary endpoint designed based on the previous small-scale trial was not met. Clinical trial information: 000005907.