446 Background: The START-2 trial demonstrated that docetaxel plus S-1 (DS) was superior to S-1 alone (S-1) in terms of recurrence-free survival (RFS) and overall survival (OS) as the adjuvant chemotherapy for stage III gastric cancer (GC) patients (pts) (J Clin Oncol 2019, Gastric Cancer 2022). We conducted the START-2 AR study as a retrospective analysis using data from the START-2 trial to develop a prognostic model for stage III GC pts treated with postoperative chemotherapy. Methods: Among 912 pts in the START-2 trial, 599 pts signed the consent form to participate in the START-2 AR study. There were 542 pts (265 pts in DS group and 277 pts in S-1 group) without missing values of prognostic candidates. Pts were randomly divided into a training set and a validation set with a ratio of 7:3. Prognostic model for RFS was developed using random survival forest (RSF) with the training set. The RSF model was applied to the validation set to assess its performance, evaluated using Harrell's C-index. We calculated tertiles of risk scores from the RSF model to divide the training set into low-, middle-, and high-risk subgroups. These cut-off values were used to classify the validation set. A Cox proportional hazard model was applied to compare the prognosis among the risk groups. Results: There were no statistically significant differences in patient characteristicsbetween the 599 pts in the START-2 AR study and the 912 pts in the STRAT-2 trial. RFS was comparable between the two groups. The RSF model for the training set (n = 380) yielded a C-index of 0.873, identifying the number of metastatic lymph nodes, serum albumin, CEA, tumor diameter, the primary tumor location, platelet count, age as prognostic factors in order of importance. In the validation set (n = 162), the C-index was 0.648. Both the low-risk group (n = 35) (hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.17 – 0.68, p < 0.01) and the middle-risk group (n = 74) (HR: 0.55, 95% CI: 0.33 – 0.89, p = 0.02) in the validation set had significantly better RFS compared to the high-risk group (n = 53). Among the 76 pts in the low-risk group treated with DS, 44 were categorized into the low-risk group when assuming they had been treated with S-1 alone. The analysis of 599 pts after multiple imputation yielded results consistent with those from the complete data. Conclusions: We developed the RSF-based predictive model for stage III GC pts, which demonstrated good performance. The number of metastatic lymph modes was identified as the most important prognostic factor. Risk stratification based on this model effectively differentiated prognostic outcomes. Future external validation of the model is required. Clinical trial information: UMIN000011438.

Daiobotanpito (DBT) is a Kampo formula traditionally used to treat abscesses in intestinal disorders. This double-blind, multicenter, randomized controlled trial was conducted at participating hospitals in Japan. Patients with CT-proven moderate acute diverticulitis received conventional therapy along with an oral DBT (treatment group) or placebo (control group) administered thrice a day for 10 days (Registration: jRCTs041180063). The primary outcome was the treatment success rate: fever reduction to < 37.5 °C within 3 days or/and elimination of abdominal pain within 4 days. Secondary endpoints included hospitalization days, changes in the inflammatory response, number of days before food intake, recurrence rate within 1-year, and adverse event rate. 171 participants were included in this study. No significant difference was observed in the treatment success rates between the DBT and placebo groups (P = .348). However, the DBT group showed a significant reduction in CRP levels on day 5 (P = .023), and patients with abscesses started oral intake significantly earlier than those in the placebo group (P = .046). In conclusion, the results of this study do not suggest that an add-on treatment with DBT in patients with moderate acute diverticulitis provides additional benefit., However, DBT may offer clinical benefits in cases involving abscesses or severe inflammation. Further prospective studies focusing on complicated diverticulitis are necessary.

In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m2) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.

PURPOSE:While regarded as function-preserving gastrectomy, few prospective longitudinal clinical trials have addressed the postoperative quality of life (QOL) after pylorus-preserving gastrectomy (PPG). We prospectively compared chronological changes in postoperative body weight and the QOL between PPG and distal gastrectomy (DG) for pathological Stage I gastric cancer (GC). METHODS:We conducted a multi-institutional prospective study (CCOG1601) to evaluate patients who underwent DG and PPG. The QOL was examined using the European Organization for Research and Treatment of Cancer Quality of life questionnaire-C30 (EORTC QLQ-C30) and the Post-Gastrectomy Syndrome Assessment Scale-37 (PGSAS-37). A total of 295 patients were enrolled from 15 institutions, and propensity score matching was performed to adjust for the essential variables for comparison analyses. RESULTS:After propensity score matching, 25 pairs of patients were identified. In the first postoperative month, DG achieved a superior nausea and vomiting score (EORTC QLQ-C30) and meal-related distress, indigestion, and dumping scores (PGSAS-37). No significant differences were noted between DG and PPG in the long-term QOL. Postoperative body weight loss was similar in both groups. CONCLUSIONS:This prospective observational study failed to demonstrate the superiority of PPG over DG in terms of postoperative body weight changes and the QOL.

Large type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue. In this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences. Of patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95

296 Background: Proximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach when oncological safety is ensured, with expectation for improvement of nutritional status and quality of life (QOL) attributable to the remnant stomach. Although few studies compare postoperative outcomes of patients who undergo total gastrectomy (TG) and PG based on questionnaires, their significant limitations include the retrospective design, use of a questionnaire not specific to a postgastrectomy setting, and observation at a fixed time or after a short postoperative period. Methods: A multi-institutional prospective study (CCOG1602) of patients who undergo PG or TG for cStage I gastric cancer was conducted. We used the Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-37 and The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30) to evaluate the changes in body weight and QOL over a 3-year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery. Results: We enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. There were no differences in age, sex, or preoperative body mass index between the TG and PG groups. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (Cohen's D 0.656) during postoperative year 1 and 15.0% and 10.8% for TG and PG (Cohen's D 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS-37, the PG group experienced a better trend in the indigestion subscale (Cohen's D –1.085) and total symptom score (Cohen's D –0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC-QLQ-C30 identified no difference between the groups at any time point during the 3-year postoperative period. Conclusions: The CCOG1602 demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion. Clinical trial information: UMIN000020070 .

The albumin–bilirubin (ALBI) grade is calculated using albumin and bilirubin values. We determined the optimal cutoff value of the ALBI grade for predicting the postoperative prognosis of gastric cancer (GC). We retrospectively reviewed a multicenter database of 3571 patients who underwent gastrectomy for GC between January 2010 and December 2014. The modified ALBI (mALBI) grade was determined using cutoff values: grade 1 (mALBI ≤ − 2.70), 2 (mALBI − 2.70 to − 2.10), and 3 (mALBI > − 2.10). We used a validation cohort to evaluate reproducibility. The entire cohort (n = 956) was randomly assigned to the learning or validation cohorts (n = 478 each). The former was categorized into the following groups by the preoperative mALBI grade: grade 1 (n = 235), grade 2 (n = 162), and grade 3 (n = 81). The disease-specific survival (DSS) rates of the learning and validation cohorts were significantly shortened in association with higher mALBI grade (learning, p = 0.0068; validation, p = 0.0100). A multivariate analysis revealed that mALBI grade 3 served as an independent prognostic factor for DSS. Furthermore, mALBI grade 2 or 3 was associated with a greater risk of disease-specific death in most subgroups. The mALBI grade accurately predicted the long-term postoperative prognosis of locally advanced GC.

Introduction: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are widely used for various cancers, with the cut-off values of 5.0 ng/mL and 37.0 IU/mL, respectively. However, these cutoff values are not for specific diseases or purposes but are uniformly used for any disease and any purpose . It is also unclear as to whether patients are at equal risk of recurrence if they are below the cutoff values. This study aimed to investigate the optimal cutoff of serum tumor markers in the stratification of recurrence risk after curative resection of gastric cancer. Methods: We constructed a nine-center integrated database of patients recieved gastrectomy between January 2010 and December 2014 with a 5-year follow-up period. We determined the cutoff value of preoperative serum tumor marker levels correlated with postoperative recurrences and evaluated its performance in risk stratification for recurrences in 948 patients with pStage II/III gastric cancer who underwent radical resection. Results: The hazard ratio for postoperative recurrences increased at two points of preoperative CEA levels; 3.6 ng/mL and 5.0 ng/mL, which were set as cutoffs. These two cutoffs stratified relapse-free survival into three levels. Conclusions: By adding a second cutoff value for preoperative serum CEA, which was proposed specifically for the prediction of recurrences, patients can be stratified into low-, intermediate-, and high-risk recurrences after curative resection of gastric cancer.

To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM. Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS). There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69–2.01], P = 0.539: OS, 1.03 [0.46–2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS. There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).

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/m2, Eastern Cooperative Oncology Group Performance Status (≥ 1), diabetes mellitus, cardiovascular/cerebrovascular disease, other malignant diseases, preoperative albumin level < 3.5 g/dL, and total gastrectomy. Patients with risk scores of 0–2, 3–4, or 5–9 (based on 1 point per characteristics) were classified into Low-risk, Intermediate-risk, and High-risk groups, respectively. The 5-year survival rates were 96.5

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

A 75-year-old woman diagnosed with squamous cell carcinoma of the anal canal was treated using chemoradiotherapy and revealed a complete response to the tumor. After 6 months of treatment, swollen para-aortic lymph nodes were found to develop. The patient received the same regimen of chemoradiotherapy again, resulting in lymph node disappearance. However, 2 months later, PET-CT revealed accumulation of FDG in the axillary and cervical lymph nodes. Chemoradiotherapy was performed for the third time. Swollen lymph nodes were found to disappear. After 12 months, para-aortic, axillary, and cervical lymph nodes developed, following which she received BSC; subsequently, she died after 38 months of the carcinoma diagnosis.

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 < 0.0001). Among pStage II–III GC patients (n = 1009), the overall survival time of the E-PASS-high group was significantly shorter than that of the E-PASS-low group (hazard ratio 2.08; 95% confidence interval 1.64–2.65; p < 0.0001). A forest plot revealed that E-PASS-high was associated with a greater prognostic factor for overall survival in most subgroups. The E-PASS scoring system may therefore be a useful predictor of the short- and long-term outcomes in patients with GC who have undergone radical gastrectomy.

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 < 4.0 g/dL or LMR < 3.4), and mSIS 2 (ALB < 4.0 g/dL and LMR < 3.4). Patients were categorized into preoperative mSIS 0 (n = 955), mSIS 1 (n = 584), and mSIS 2 (n = 225) groups. The overall survival times and the disease-free survival times of patients in preoperative mSIS 0,1 and 2 sequentially shortened (P < 0.0001), and mSIS 1 and 2 were identified as an independent prognostic factor (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.06–1.272, P = 0.0125 and HR 1.63, 95% CI 1.21–2.19, P = 0.0012). A stepwise increase in the prevalence of hematogenous recurrences was directly proportional to the mSIS. A forest plot revealed that mSIS 0,1 was associated with a greater risk of overall survival in most subgroups. Preoperative mSIS can be easily calculated, and it is suggested that it is useful as a prognostic predictor of patients with different disease stages, for stratifying and evaluating clinical outcomes.

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.

We analyzed the effect of a microscopic positive margin on survival outcomes after gastrectomy for gastric cancer 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.

Purpose 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. Methods 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. Results 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. Conclusions NAC did not increase the complication rate of gastrectomy for gastric cancer.

Abstract 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.

Background. 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. Methods. 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. Results. 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. Conclusions. 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.