Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In Asia, adjuvant chemotherapy after gastrectomy with D2 or more extensive lymph-node dissection is standard treatment for people with pathological stage III gastric or gastro-oesophageal junction (GEJ) cancer. We aimed to assess the efficacy and safety of adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy administered in this setting. METHODS: ATTRACTION-5 was a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial conducted at 96 hospitals in Japan, South Korea, Taiwan, and China. Eligible patients were aged between 20 years and 80 years with histologically confirmed pathological stage IIIA-C gastric or GEJ adenocarcinoma after gastrectomy with D2 or more extensive lymph-node dissection, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and available tumour tissue for PD-L1 expression analysis. Patients were randomly assigned (1:1) to receive either nivolumab plus chemotherapy or placebo plus chemotherapy via an interactive web-response system with block sizes of four. Investigational treatment, either nivolumab 360 mg or placebo, was administered intravenously for 30 min once every 3 weeks. Adjuvant chemotherapy was administered as either tegafur-gimeracil-oteracil (S-1) at an initial dose of 40 mg/m2 per dose orally twice per day for 28 consecutive days, followed by 14 days off per cycle, or capecitabine plus oxaliplatin consisting of an initial dose of intravenous oxaliplatin 130 mg/m2 for 2 h every 21 days and capecitabine 1000 mg/m2 per dose orally twice per day for 14 consecutive days, followed by 7 days off treatment. The primary endpoint was relapse-free survival by central assessment. The intention-to-treat population, consisting of all randomly assigned patients, was used for analysis of efficacy endpoints. The safety population, defined as patients who received at least one dose of trial drug, was used for analysis of safety endpoints. This trial is registered with ClinicalTrials.gov (NCT03006705) and is closed. FINDINGS: Between Feb 1, 2017, and Aug 15, 2019, 755 patients were randomly assigned to receive either adjuvant nivolumab plus chemotherapy (n=377) or adjuvant placebo plus chemotherapy (n=378). 267 (71%) of 377 patients in the nivolumab group and 263 (70%) of 378 patients in the placebo group were male; 110 (29%) of 377 patients in the nivolumab group and 115 (31%) of 378 patients in the placebo group were female. 745 patients received assigned treatment (371 in the nivolumab plus chemotherapy group; 374 in the placebo plus chemotherapy group), which was the safety population. Median time from first dose to data cutoff was 49·1 months (IQR 43·1-56·7). 3-year relapse-free survival was 68·4% (95% CI 63·0-73·2) in the nivolumab plus chemotherapy group and 65·3% (59·9-70·2) in the placebo plus chemotherapy group; the hazard ratio for relapse-free survival was 0·90 (95·72% CI 0·69-1·18; p=0·44). Treatment-related adverse events occurred in 366 (99%) of 371 patients in the nivolumab plus chemotherapy group and 364 (98%) of 374 patients in the placebo plus chemotherapy group. Discontinuation due to adverse events was more frequent in the nivolumab plus chemotherapy group (34 [9%] of 371 patients) than the placebo plus chemotherapy group (13 [4%] of 374 patients). The most common treatment-related adverse events were decreased appetite, nausea, diarrhoea, neutrophil count decreased, and peripheral sensory neuropathy. INTERPRETATION: The results of this trial do not support the addition of nivolumab to postoperative adjuvant therapy for patients with untreated, locally advanced, resectable gastric or GEJ cancer. FUNDING: Ono Pharmaceutical and Bristol Myers Squibb.

Evaluation of the blood flow in reconstructed gastric tube and its relation to anastomosis leakage.

OBJECTIVES: Anastomotic leakage in esophageal cancer surgery may be reduced by evaluating the blood flow to the reconstructed organ, but quantitative evaluation of arterial and venous blood flow is difficult. This study aimed to quantitatively assess blood flow using a new technique, as well as determine the relationship between the blood flow in the gastric tube and anastomotic leakage using near-infrared spectroscopy. METHODS: This single-center, observational study included 50 patients aged 51-82 years who underwent radical esophagectomy with gastric tube reconstruction for esophageal cancer between June 2022 and January 2023. Regional tissue oxygen saturation was measured at the antrum (point X), the anastomotic point (point Z), and the midpoint between points X and Z (point Y) before and after gastric tube formation. These three points of oxygen saturation were investigated in relation to anastomotic leakage. RESULTS: When comparing the presence of leakage to its absence, regional tissue oxygen saturation at points X and Z after gastric tube formation was significantly lower (X: p = 0.03, Z: p = 0.02), with the decreasing rate significantly higher at point Z (p = 0.01). There was no significant difference in the decreasing rate of regional tissue oxygen saturation between points X and Y (X: p = 0.052, Y: p = 0.83). CONCLUSION: Regional tissue oxygen saturation levels may be useful for measuring blood flow and could be a predictor of anastomotic leakage.

Remnant gastritis in gastric cancer patients causes loss of muscle mass 6 months after gastrectomy: a retrospective cohort study of Helicobacter pylori infection.

PURPOSE: In this study, we assessed the relationship between remnant gastritis and muscle mass loss and then investigated the potential relationship between Helicobacter pylori (HP) infection and remnant gastritis and muscle loss. METHODS: We reviewed the medical records of 463 patients who underwent distal gastrectomy between January 2017 and March 2020. Of these patients, 100 with pStage I after laparoscopic surgery were included in this analysis. RESULTS: A multivariate analysis showed that the total Residue, Gastritis, Bile (RGB) classification score, which indicates the degree of gastritis, was significantly associated with the rate of change (rate of decrease) in the psoas muscle area (PMA) during the first 6 months after surgery (p = 0.014). Propensity score matching was performed according to HP infection, and the rate of change in the PMA and the degree of remnant gastritis in 56 patients were compared. Neither was significantly associated with HP infection. CONCLUSIONS: Remnant gastritis did contribute to psoas muscle mass loss during the initial 6 months after gastrectomy, and HP infection was not significantly associated with either remnant gastritis or psoas muscle mass loss. Nevertheless, the potential for HP eradication to prevent muscle loss and improve the survival prognosis for gastrectomy patients merits further research.

A nonrandomized controlled trial: long-term outcomes of LATG/LAPG for cStage I gastric cancer: Japan Clinical Oncology Group Study JCOG1401.

BACKGROUND: A previous report confirmed the safety of laparoscopy-assisted total and proximal gastrectomies (LATG and LAPG) (JCOG1401). This report demonstrates the 5-year relapse-free survival (RFS) and overall survival (OS) after long-term follow-up to confirm the efficacy of these surgical methods as key secondary endpoints for cStage I gastric cancer. METHODS: This study enrolled patients who had histologically proven gastric adenocarcinoma and were diagnosed with clinical T1N0, T1N(+), or T2N0 tumors according to the 14th edition of the Japanese Classification of Gastric Carcinoma (3rd English edition). RESULTS: Between April 2015 and February 2017, 246 patients were enrolled, although one patient was excluded because of misregistration. Meticulous follow-up was continued for > 5 years for each patient, and the data were analyzed in March 2022. The 5-year RFS was 90.0% (95% confidence interval [CI] 85.5-93.2%), and the 5-year OS was 91.2% (95% CI 86.9-94.2%) in all enrolled patients. Grade 3 or 4 late postoperative complications were detected in 12.7% of patients. CONCLUSIONS: This single-arm study showed that the long-term outcomes of LATG/LAPG for cStage I gastric cancer were acceptable, which is considered one of the standard treatments when performed by experienced surgeons. Trail registration UMIN000017155 ( http://www.umin.ac.jp/ctr/ ).

Efficacy and safety of patient-controlled thoracic epidural analgesia alone versus patient-controlled intravenous analgesia with acetaminophen after laparoscopic distal gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND: Laparoscopic gastrectomy is a common procedure for early gastric cancer treatment. Improving postoperative pain control enhances patient recovery after surgery. The use of multimodal analgesia can potentially enhance the analgesic effect, minimize side effects, and change the postoperative management. The purpose of this study was to evaluate and compare the efficacies of the use of patient-controlled intravenous analgesia with regular acetaminophen (PCIA + Ace) and patient-controlled thoracic epidural analgesia (PCEA) for postoperative pain control. METHODS: We retrospectively collected the data of 226 patients who underwent laparoscopic distal gastrectomy (LDG) with delta-shaped anastomosis between 2016 and 2019. After 1:1 propensity-score matching, we compared 83 patients who used PCEA alone (PCEA group) with 83 patients who used PCIA + Ace (PCIA + Ace group). Postoperative pain was assessed using a numeric rating scale (NRS) with scores ranging from 0 to 10. An NRS score ≥ 4 was considered the threshold for additional intravenous rescue medication administration. RESULTS: Although NRS scores at rest were comparable between the PCEA and PCIA + Ace groups, NRS scores of patients in the PCIA + Ace group during coughing or movement were significantly better than those of patients in the PCEA group on postoperative days 2 and 3. The frequency of additional rescue analgesic use was significantly lower in the PCIA + Ace group than in the PCEA group (1.1 vs. 2.7, respectively, p < 0.001). The rate of reduction or interruption of the patient-controlled analgesic dose was higher in the PCEA group than in the PCIA + Ace group (74.6% vs. 95.1%, respectively, p = 0.0002), mainly due to hypotension occurrence in the PCEA group. Physical recovery time, postoperative complication occurrence, and liver enzyme elevation incidence were not significantly different between groups. CONCLUSIONS: PCIA + Ace can be safely applied without an increase in complications or deterioration in gastrointestinal function; moreover, PCIA + Ace use may provide better pain control than PCEA use in patients following LDG.

Surgical outcomes of reconstruction using the gastric tube and free jejunum for cervical esophageal cancer: analysis using the National Clinical Database of Japan.

BACKGROUND: Cervical esophageal cancer accounts for a small proportion of all esophageal cancers. Therefore, studies examining this cancer include a small patient cohort. Most patients with cervical esophageal cancer undergo reconstruction using a gastric tube or free jejunum after esophagectomy. We examined the current status of postoperative morbidity and mortality of cervical esophageal cancer based on big data. METHODS: Based on the Japan National Clinical Database, 807 surgically treated patients with cervical esophageal cancer were enrolled between January 1, 2016, and December 31, 2019. Surgical outcomes were retrospectively reviewed for each reconstructed organ using gastric tubes and free jejunum. RESULTS: The incidence of postoperative complications related to reconstructed organs was higher in the gastric tube reconstruction (17.9%) than in the free jejunum (6.7%) for anastomotic leakage (p < 0.01), but not significantly different for reconstructed organ necrosis (0.4% and 0.3%, respectively). The incidence rates of overall morbidity, pneumonia, 30-day reoperation, tracheal necrosis, and 30-day mortality using these reconstruction methods were 64.7% and 59.7%, 16.7% and 11.1%, 9.3% and 11.4%, 2.2% and 1.6%, and 1.2% and 0.0%, respectively. Only pneumonia was more common in the gastric tube reconstruction group (p = 0.03), but was not significantly different for any other complication. CONCLUSIONS: The incidence of overall morbidities and reoperation, especially anastomotic leakage after gastric tube reconstruction, suggested a necessity for further improvement. However, the incidence of fatal complications, such as tracheal necrosis or reconstructed organ necrosis, was low for both reconstruction methods, and the mortality rate was acceptable as a means of radical treatment.

Five-Year Survival Outcomes of Laparoscopy-Assisted vs Open Distal Gastrectomy for Advanced Gastric Cancer: The JLSSG0901 Randomized Clinical Trial.

Importance: Evidence of implementation of laparoscopic gastrectomy for locally advanced gastric cancer is currently insufficient, as the primary end point in previous prospective studies was evaluated at a median follow-up time of 3 years. More robust evidence is necessary to verify noninferiority of laparoscopic gastrectomy. Objective: To compare 5-year survival outcomes between laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) with D2 lymph node dissection for locally advanced gastric cancer. Design, Setting, and Participants: This was a multicenter, open-label, noninferiority, prospective randomized clinical trial. Between November 26, 2009, and July 29, 2016, eligible patients with histologically proven gastric carcinoma from 37 institutes in Japan were enrolled. Two interim analyses and final analysis were performed in October 2014, May 2018, and November 2021, respectively. Interventions: Patients were randomly assigned (1:1) to either the ODG or LADG group. The procedures were performed exclusively by qualified surgeons. Main Outcomes and Measures: The primary end point was 5-year relapse-free survival, and the noninferiority margin for the hazard ratio (HR) was set at 1.31. The secondary end points were 5-year overall survival and safety. Results: A total of 502 patients were included in the full-analysis set: 254 (50.6%) in the ODG group and 248 (49.4%) in the LADG group. Patients in the ODG group had a median (IQR) age of 67 (33-80) years and included 168 males (66.1%). Patients in the LADG group had a median (IQR) age of 64 (34-80) years and included 169 males (68.1%). No significant differences were observed in severe postoperative complications between the 2 groups in the safety analysis (ODG, 4.7% [11 of 233] vs LADG, 3.5% [8 of 227]; P = .64). The median (IQR) follow-up for all patients after randomization was 67.9 (60.3-92.0) months. The 5-year relapse-free survival was 73.9% (95% CI, 68.7%-79.5%) and 75.7% (95% CI, 70.5%-81.2%) for the ODG and LADG groups, respectively, and the HR was 0.96 (90% CI, 0.72-1.26; noninferiority 1-sided P = .03). Further, no significant difference was observed in overall survival time between the 2 groups, and the HR was 0.83 (95% CI, 0.57-1.21; P = .34). The pattern of recurrence was similar between the 2 groups. Conclusions and Relevance: Results of this study show that on the basis of 5-year follow-up data, LADG with D2 lymph node dissection for locally advanced gastric cancer, when performed by qualified surgeons, was proved noninferior to ODG. This laparoscopic approach could become a standard treatment for locally advanced gastric cancer. Trial Registration: UMIN Clinical Trial Registry: UMIN000003420.

Relative dose intensity and 1-year psoas muscle index reduction rate as prognostic factors in gastric cancer patients with postoperative adjuvant chemotherapy.

BACKGROUND: Higher relative dose intensity (RDI) of chemotherapy improves the clinical outcomes of various cancers. The psoas muscle index (PMI) is related to sarcopenia, and patients with low PMI have worse prognoses. However, few studies have demonstrated its clinical relevance in gastric cancer. METHODS: This retrospective study included 188 stage II/III gastric cancer patients who had undergone curative gastrectomy between January 2013 and March 2017, 124 of whom had received postoperative S-1 adjuvant chemotherapy. RESULTS: Per receiver operating characteristic analysis, patients were divided into high and low RDI groups, between which relapse-free survival differed marginally significantly and disease-specific survival differed significantly. In patients who received adjuvant chemotherapy, multivariate analysis found that high RDI and low PMI reduction rate 1 year after surgery were significantly associated with better relapse-free survival. Low RDI can be predicted by a combination of low preoperative PMI and non-distal gastrectomy, whereas high PMI reduction rate at 1 year can be affected by non-distal gastrectomy. CONCLUSION: High RDI with preserved psoas muscle up to 1 year after gastrectomy may be associated with prognoses in gastric cancer requiring postoperative adjuvant chemotherapy. Since RDI and PMI reduction rate can be predicted preoperatively, respectively, interventional consideration is possible for optimal adjuvant therapy in gastric cancer.

Dismal prognosis of elderly gastric cancer patients who underwent gastrectomy with American Society of Anesthesiologists (ASA) 3.

BACKGROUND: Although the American Society of Anesthesiologists (ASA) score of 3 is relatively common in elderly patients, there have been few debates on the indications for gastrectomy in elderly gastric cancer (GC) patients with ASA3. Therefore, this study aimed to investigate gastrectomy's clinical relevance in elderly patients with GC and ASA3. METHODS: We retrospectively analyzed 228 consecutive elderly GC patients (aged ≥ 75 years) without prior treatments who underwent curative gastrectomy between 2013 and 2017. RESULTS: Thirty-three patients with ASA3 showed significantly poorer prognosis than those with ASA1 and 2 (p = 0.004). The multivariate Cox proportional hazards model showed that ASA3 (p = 0.021) and pStage (p = 0.007) were independent prognostic factors, respectively. Elderly GC patients with pStage III and ASA3 exhibited uniquely dismal prognosis (p < 0.001); however, several survivors were still confirmed. Postoperative complications (PCs) were only the final remnant independent prognostic factor (p = 0.020) among the 33 elderly GC patients with ASA3, where dead patients included cancer-specific and other deaths, especially pneumonia. PCs were independently associated with prognostic nutritional index (PNI) (< 42.7) in elderly GC patients, and the most frequent complication was pneumonia, which was significantly associated with ASA3 and marginally associated with PNI in a multivariate analysis. CONCLUSIONS: ASA3 has a dismal prognosis after curative gastrectomy in the elderly GC patients, but the number of survivors was confirmed. Curative gastrectomy is not considered contraindicated even in elderly GC with ASA3. Preoperative malnutrition is associated with PCs, which proposing preoperative nutritional intervention in the context of treatment strategy for the elderly GC patients with ASA3.

A survey of the clinical outcomes of cervical esophageal carcinoma surgery focusing on the presence or absence of laryngectomy using the National Clinical Database in Japan.

BACKGROUND: One upside of cervical esophageal carcinoma is that radical surgery can be performed by laryngectomy, even for tumors with tracheal invasion. However, this approach drastically reduces the quality of life, such as by losing the vocal function. Cervical esophageal carcinoma is rare, and no comprehensive reports have described the current state of surgery. Using a Japanese nationwide web-based database, we analyzed the surgical outcomes of cervical esophageal carcinoma to evaluate the impact of larynx-preserving surgery. METHODS: Based on the Japan National Clinical Database, 215 surgically treated cases of cervical esophageal carcinoma between January 1, 2018, and December 31, 2019, were enrolled. Clinical outcomes were compared between the larynx-preserved group and the laryngectomy group. RESULTS: Ninety-four (43.7%) patients underwent larynx-preserving surgery. A total of 177 (82.3%) patients underwent free jejunum reconstruction. More T4b patients and more patients who underwent preoperative radiotherapy were in the laryngectomy group. There were no significant differences in the frequency and the severity of morbidities between the two groups. However, in the laryngectomy group, in-hospital death within 30 days after surgery was observed in 1 patient, and the postoperative hospital stay was significantly longer (P = 0.030). In the larynx-preserved group, recurrent nerve paralysis was observed in 24.5%. Re-operation (35.3%, P = 0.016), re-intubation (17.6%, P = 0.019) and tracheal necrosis (17.6%, P = 0.028) were significantly more frequent in patients who underwent pharyngolaryngectomy with total esophagectomy and gastric tube reconstruction than in others. CONCLUSION: Larynx-preserving surgery was therefore considered to be feasible because it was equivalent to laryngectomy regarding the short-term surgical outcomes.

Short-term results of robot-assisted colorectal cancer surgery using Senhance Digital Laparoscopy System.

BACKGROUND: The Senhance Digital Laparoscopy System (Asensus Surgical Inc, Morrisville, NC, United States), which was introduced for the first time in Japan by our hospital, is a new surgical assistive robot following the da Vinci Surgical System. We herein report the short-term outcomes of 55 colorectal cancer surgery cases using this system at our hospital to assess the feasibility and safety of our procedures. MATERIALS AND METHODS: We retrospectively reviewed the patient backgrounds and surgical outcomes of 55 patients who underwent Senhance-assisted laparoscopic colorectal cancer surgery. RESULTS: The median age was 71 years. There were 31 males and 24 females, and the median body mass index was 23.1 kg/m2 . Fifteen patients had a history of abdominal surgery. The most common surgical technique was ileocecal resection (18 cases, 32.7%), followed by high anterior resection (11 cases, 20.0%). D2 or D3 dissection was performed in each operation, and D3 dissection was performed in 41 cases (74.5%). The median operative time was 240 minutes, the median blood loss was 5 mL, there were no intraoperative complications, and there were no cases of intraoperative blood transfusion. The median postoperative hospital stay was 7 days, which was comparable to conventional laparoscopic surgery. Postoperative complications of grade 2 or higher in the Clavien-Dindo classification were observed in two cases. CONCLUSION: The short-term results of 55 colorectal cancer surgery cases using the Senhance Digital Laparoscopy System were excellent and the system was introduced and surgery was safely performed.

Impact of loss of skeletal muscle mass within 6-12 months after gastrectomy and S1 adjuvant chemotherapy on the survival prognosis of elderly patients with gastric cancer.

BACKGROUND AND PURPOSE: We investigated the impact of postoperative changes in the psoas muscle mass index (PMI) after gastrectomy and S1 adjuvant chemotherapy (AC) on the long-term outcomes of elderly patients with gastric cancer. METHODS: We reviewed the medical records of 228 patients aged over 75 years, who underwent distal, proximal, or total gastrectomy between January, 2013 and March 2017. Among these patients, 78 with pStage IIA-IIIC who survived for at least 1 year without recurrence after gastrectomy were the subjects of this analysis. RESULTS: The log-rank test using the cut-off value from the rate of change in PMI from 6 to 12 months after gastrectomy (late rate of decrease) showed significantly poorer prognosis for the group above the cut-off value for both overall survival (OS) and recurrence-free survival (RFS) (RFS: PMI decrease ≥ 1.55%, p < 0.001; OS: PMI decrease ≥ 1.55%, p < 0.001). Patients with a relative dose intensity of S1 below 68.7% and a late rate of decrease in PMI above 1.55% were found to have a poor prognosis. CONCLUSION: It is necessary to prevent decline in the PMI of elderly patients from 6 months after gastrectomy and to administer adjuvant chemotherapy with about two-thirds or more RDI of S1 to improve their survival prognosis.

Impact of the first era of the coronavirus disease 2019 pandemic on gastric cancer patients: a single-institutional analysis in Japan.

BACKGROUND: Little is known about the disadvantages of the coronavirus disease 2019 (COVID-19) pandemic in patients with gastric cancer. This study aimed to examine the negative impact of the COVID-19 pandemic on patients with gastric cancer in the first era in Japan. METHODS: This retrospective study included 725 patients diagnosed with gastric cancer who visited our hospital between April 2019 and March 2021. The number of patients and their characteristics before and during the COVID-19 pandemic were compared. RESULTS: The number of patients diagnosed with gastric cancer during the COVID-19 pandemic decreased by 26.2% (from 417 to 308; p = 0.013) compared to that before the COVID-19 pandemic. There was a significant decrease in cStage I cancer and an increase in cStage III cancer (p = 0.004). Patients were often symptomatic (p = 0.029), especially those with stenosis-related symptoms (p < 0.001) and longer symptom duration (p < 0.001). The number of endoscopic resections was decreased by 34.8% (p = 0.005). The number of total gastrectomy was higher than that of partial gastrectomy (p = 0.021). The median time to treatment was significantly shorter (p < 0.001). CONCLUSIONS: In Japan, delays diagnosing patients with gastric cancer, probably due to refraining from consultation, may have resulted in an increase in the diagnosis of advanced-stage cancer. Moreover, an increasing proportion of patients required more invasive gastrectomy. Therefore, it may be necessary to educate patients not to refrain from consultation, even during the COVID-19 pandemic, as it can have a negative impact on treatment, policy decision, and prognosis of gastric cancer.

Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: The additive or synergistic sustained antitumour effect of immune checkpoint inhibitors in combination with oxaliplatin-based chemotherapy has previously been reported. We investigated the efficacy of nivolumab plus oxaliplatin-based chemotherapy versus placebo plus oxaliplatin-based chemotherapy as first-line therapy for patients with HER2-negative, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer. METHODS: We did a randomised, multicentre, double-blind, placebo-controlled, phase 2-3 trial (ATTRACTION-4) at 130 centres (hospitals, cancer centres, and medical centres) across Japan, South Korea, and Taiwan. We enrolled patients aged 20 years and older with previously untreated (except for neoadjuvant or adjuvant chemotherapy completed ≥180 days before recurrence), HER2-negative, unresectable, advanced or recurrent gastric or gastro-oesophageal junction cancer (regardless of PD-L1 expression), at least one measurable lesion per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1), and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned (1:1) to chemotherapy every 3 weeks (intravenous oxaliplatin 130 mg/m2 on day 1 plus either oral S-1 40 mg/m2 [SOX] or oral capecitabine 1000 mg/m2 [CAPOX], twice daily on days 1-14), in addition to either 360 mg nivolumab intravenously every 3 weeks (nivolumab plus chemotherapy group) or placebo (placebo plus chemotherapy group). Randomisation was done using an interactive web response system with block sizes of four and stratified by intensity of PD-L1 expression, ECOG performance status score, disease status, and geographical region. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoints were centrally assessed progression-free survival and overall survival in the intention-to-treat population, which included all randomly assigned patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT02746796. Trial recruitment is complete and follow-up is ongoing. FINDINGS: Between March 23, 2017, and May 10, 2018, 724 patients were randomly assigned to treatment: 362 patients to the nivolumab plus chemotherapy group and 362 to the placebo plus chemotherapy group. At the time of data cutoff on Oct 31, 2018, with a median follow-up of 11·6 months (IQR 8·7-14·1), median progression-free survival at a prespecified interim analysis was 10·45 months (95% CI 8·44-14·75) in the nivolumab plus chemotherapy group and 8·34 months (6·97-9·40) in the placebo plus chemotherapy group (hazard ratio [HR] 0·68; 98·51% CI 0·51-0·90; p=0·0007). At the time of data cutoff on Jan 31, 2020, with a median follow-up of 26·6 months (IQR 24·1-29·0), median overall survival at the final analysis was 17·45 months (95% CI 15·67-20·83) in the nivolumab plus chemotherapy group and 17·15 months (15·18-19·65) in the placebo plus chemotherapy group (HR 0·90; 95% CI 0·75-1·08; p=0·26). The most common treatment-related grade 3-4 adverse events were neutrophil count decreased (71 [20%] of 359 patients in the nivolumab plus chemotherapy group vs 57 [16%] of 358 patients in the placebo plus chemotherapy group) and platelet count decreased (34 [9%] vs 33 [9%]). Treatment-related serious adverse events of any grade were observed in 88 (25%) patients in the nivolumab plus chemotherapy group and in 51 (14%) in the placebo plus chemotherapy group, of which the most common was decreased appetite (18 [5%] vs ten [3%]). Six treatment-related deaths occurred: three in the nivolumab plus chemotherapy group (one each of febrile neutropenia, hepatic failure, and sudden death) and three in the placebo plus chemotherapy group (one each of sepsis, haemolytic anaemia, and interstitial lung disease). INTERPRETATION: Nivolumab combined with oxaliplatin-based chemotherapy significantly improved progression-free survival, but not overall survival, in Asian patients with untreated, HER2-negative, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer, and could potentially be a new first-line treatment option for these patients. FUNDING: Ono Pharmaceutical and Bristol-Myers Squibb.

Impact of the coronavirus disease 2019 pandemic on first-visit patients with oesophageal cancer in the first infection wave in Saitama prefecture near Tokyo: a single-centre retrospective study.

BACKGROUND: Although the novel coronavirus disease 2019 did not lead to a serious medical collapse in Japan, its impact on treatment of oesophageal cancer has rarely been investigated. This study aimed to investigate the influence of the pandemic on consultation status and initial treatment in patients with primary oesophageal cancer. METHODS: A retrospective study was conducted among 546 patients with oesophageal cancer who visited our hospital from April 2018 to March 2021. Pre-pandemic and pandemic data were compared with the clinical features, oncological factors and initial treatment as outcome measures. RESULTS: Diagnoses of oesophageal cancer decreased during the early phase of the pandemic from April to June (P = 0.048); however, there was no significant difference between the pre-pandemic and pandemic periods throughout the year. The proportion of patients diagnosed with distant metastases significantly increased during the pandemic (P = 0.026), while the proportion of those who underwent initial radical treatment decreased (P = 0.044). The rate of definitive chemoradiotherapy decreased by 58.6% relative to pre-pandemic levels (P = 0.001). CONCLUSIONS: Patients may have refrained from consultation during the early phase of the coronavirus disease 2019 pandemic. The resultant delay in diagnosis may have led to an increase in the number of patients who were not indicated for radical treatment, as well as a decrease in the number of those who underwent definitive chemoradiotherapy. Our findings highlight the need to maintain the health care system and raise awareness on the importance of consultation.

Short- and long-term outcomes of laparoscopic distal gastrectomy versus open distal gastrectomy for gastric cancer in overweight patients.

PURPOSE AND BACKGROUND: Gastrectomy for gastric cancer in overweight patients is associated with a high incidence of postoperative complications and difficulties in achieving adequate lymph node dissection. We conducted this study to compare the outcomes of laparoscopic and open distal gastrectomy (ODG) for gastric cancer in overweight Japanese patients. METHODS: This retrospective study analyzed data from 180 patients with a body mass index ≥ 25 who underwent distal gastrectomy for pStage I-III gastric cancer. Postoperative complications, the number of harvested lymph nodes, and long-term survival were compared between ODG and laparoscopic distal gastrectomy (LDG). RESULTS: Postoperative complications of Clavien-Dindo (CD) grade ≥ 2 and ≥ 3 were significantly higher after ODG than after LDG (p < 0.001 and p = 0.004). Multivariate analysis identified age and ODG as factors related to complications of CD ≥ 2 (p = 0.014 and 0.002). The number of harvested lymph nodes at region 4sb was significantly higher in LDG for patients with pStage III disease. The 5-year lymph node recurrence-free survival tended to be better in LDG; however, no difference was found between ODG and LDG at any pathological stage. There were no significant differences in the 5-year overall and recurrence-free survival rates after ODG vs. LDG. CONCLUSIONS: LDG for gastric cancer appears to be associated with a lower incidence of postoperative complications than ODG, without compromising long-term survival, even for overweight patients.

Lymphoid hyperplasia with a polyp form of the gallbladder macroscopically mimicking carcinoma.

Lymphoid hyperplasia is a type of tumor-like hyperplasia of lymphoid tissue. There have been few reports on lymphoid hyperplasia of the gallbladder. Here, we report a case of lymphoid hyperplasia with a polyp form of the gallbladder macroscopically mimicking carcinoma. Liver dysfunction was diagnosed in a 75-year-old woman who presented with a gallbladder mass measuring 20 mm during an annual health checkup. Antibody tests for infectious diseases were positive for anti-HBs and anti-HBc antibodies. Accordingly, a laparoscopic cholecystectomy was performed. Macroscopically, the mass was a papillary/sessile tumor (29 × 25 mm) located in the fundus of the gallbladder. Histologically, the tumor was accompanied by an erosion on a portion of the surface layer, while the remaining epithelium showed regenerative changes and mild hyperplasia. No atypia was observed in the constituent epithelium. Hyperplasia of the polarized lymphoid follicles was observed in the interstitium, and tingible body macrophages were scattered in the germinal center. Immuno-histologically, the germinal center showed CD20 positivity, weak CD10 positivity, Bcl-2 negativity, and a high Ki-67 index (MIB-1). These findings suggested that the proliferating lymphoid follicles were reactive rather than neoplastic. Therefore, we diagnosed the patient with lymphoid hyperplasia of the gallbladder and chronic cholecystitis.

Verification of the Utility of Palliative Radiotherapy for Hemostasis of Gastric Cancer Bleeding: a Case Control Study.

PURPOSE: Bleeding from unresectable gastric cancer is a localized condition that adversely affects quality of life. Radiotherapy can be used to treat gastric cancer bleeding when surgery, endoscopic treatment, and intravascular embolization are ineffective. This study evaluated the utility of radiotherapy for unresectable hemorrhagic gastric cancer. METHODS: We retrospectively analyzed data from 33 patients with gastric cancer bleeding who underwent palliative radiotherapy in our hospital between April 2013 and May 2020. In this study, successful hemostasis was defined as > 1 month after starting radiotherapy with the patient alive and showing no need for blood transfusion, no drop in hemoglobin, and no evidence of melena or hematemesis. RESULTS: Patients comprised 26 men (79%) and 7 women (21%), with a median age of 71 years (range, 41-78 years). Hemostasis was achieved in 24 patients (73%). Thirty-two patients (94%) have been discharged home or transferred to the hospice. Patients with successful hemostasis from radiotherapy showed significantly longer overall survival than patients with unsuccessful hemostasis (p = 0.0026). No toxicities of grade 2 or more were encountered. CONCLUSIONS: This retrospective study found that palliative radiotherapy for gastric cancer bleeding was useful and safe and can improve remaining quality of life in patients with poor prognosis.

Effectiveness and safety of a newly introduced multidisciplinary perioperative enhanced recovery after surgery protocol for thoracic esophageal cancer surgery.

OBJECTIVE: Data are sparse regarding the multidisciplinary perioperative enhanced recovery after surgery protocol (E-P) for thoracic esophageal cancer surgery that was newly used at another institution. Therefore, this study aimed to retrospectively evaluate the effectiveness and safety of the protocol. METHODS: We enrolled 101 patients who underwent transthoracic esophagectomy for E-P at the Shizuoka Cancer Center Hospital (SCC). The outcomes obtained at the SCC were compared with the outcomes of 140 patients treated with E-P at the Saitama Medical University International Medical Center (SMU). At the SMU, we compared the results before and after the introduction of E-P. RESULTS: The rates of morbidity, pulmonary complications, and postoperative pneumonia were 44%, 31%, and 6.9% at the SCC and 44%, 27%, and 6.5% at the SMU (P = 0.91, 0.55, and 0.88, respectively). The mean time to walk was 1.1 and 1.5 days at the SCC and SMU, respectively (P < 0.001). The median length of hospital stay was longer at the SMU than at the SCC (24.0 versus 20.8 days; P = 0.004). In the comparative study before and after the introduction of E-P, the rate of postoperative pneumonia was 16% in the conventional management group and 6.5% in the E-P group (P = 0.02). CONCLUSION: Postoperative pneumonia was reduced before and after introduction of E-P. As similar short-term postoperative outcomes were promising (except for the time to walk and postoperative hospital stay), the same E-P that was safely performed at the SMU can be implemented as a standard practice.