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Neoadjuvant therapy followed by surgery is the standard treatment for locally advanced esophageal cancers. During neoadjuvant therapy, tumor-induced esophageal stenosis or adverse events often cause weight loss. However, little is known about the effects of weight loss during neoadjuvant therapy on postoperative complications or prognosis. We investigated the association between weight loss during neoadjuvant chemotherapy, postoperative infectious complications, and prognosis.Data from OGSG1003, a randomized phase-II trial comparing two regimens of neoadjuvant chemotherapy, cisplatin and fluorouracil plus Adriamycin and cisplatin and fluorouracil plus docetaxel, for locally advanced esophageal squamous cell carcinoma were used. Body weight was measured before neoadjuvant chemotherapy and esophagectomy. Multivariate analysis for infectious complications and prognosis was performed.The study included 134 patients. The median weight loss during neoadjuvant chemotherapy was 2.83% (-2.07% to 6.29%). Postoperative infectious complications were observed in 37 patients who had a significantly higher weight loss during neoadjuvant chemotherapy (5.18% vs. 1.90%, P = 0.002). Multivariate analysis revealed that 5% of weight loss during neoadjuvant chemotherapy was the only independent factor associated with postoperative infectious complications (odds ratio 2.69, 95% confidence interval 1.12-6.46, P = 0.027). Weight loss during neoadjuvant chemotherapy was significantly associated with worse recurrence-free survival in the univariate analysis (log-rank test, P = 0.002), but this association was marginal in the multivariate analysis (hazard ratio 1.73, 95% confidence interval 0.98-3.08, P = 0.058).Severe weight loss during neoadjuvant chemotherapy was an independent risk factor for postoperative infectious complications. Weight maintenance during neoadjuvant chemotherapy may reduce the incidence of postoperative infectious complications.

We herein investigated the association between early tumor shrinkage (ETS) and depth of response (DpR) and clinical outcomes in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil (bDCF) using data from the JCOG0807, a phase I/II trial of bDCF as first-line chemotherapy for metastatic esophageal cancer.ETS was defined as a percent decrease in the sum of the target lesions' longest diameter after 8 weeks, whereas DpR was defined as a percentage of the maximal tumor shrinkage during the treatment course. Multivariable analyses were conducted to identify significant prognostic variables in progression-free survival (PFS) and overall survival (OS): one for ETS and covariates, and another for DpR and covariates.Among 53 patients, 35 patients with ETS ≥ 20% (66.0%) had longer PFS (7.5 vs. 3.4 months, hazard ratio [HR]: 0.26, 95% confidence interval [95% CI] 0.14-0.49), OS (13.8 vs. 6.1 months, HR 0.20, 95% CI 0.11-0.39), and PPS (6.4 vs. 2.8 months, HR 0.38, 95% CI 0.20-0.72) than those with ETS 20%. In addition, 37 patients with DpR ≥ 30% (69.8%) had longer PFS (7.5 vs. 2.9 months, HR 0.17, 95% CI 0.08-0.34), OS (13.8 vs. 6.0 months, HR 0.14, 95% CI 0.07-0.27), and PPS (6.8 vs. 2.8 months, HR 0.30, 95% CI 0.15-0.58) than those with DpR 30%. Multivariable analyses revealed that each ETS and DpR was an independent factor of longer PFS and OS.ETS and DpR might be associated with clinical outcomes in patients with metastatic esophageal cancer treated with bDCF.

Purpose Fibroblast growth factor receptor 2 (FGFR2) and human epidermal growth factor receptor 2 (HER2) proteins are both molecular targets for cancer therapy. The objective of this study was to evaluate the expression status of FGFR2 and HER2 in patients with gastric cancer (GC) or colorectal cancer (CRC). Methods Archived tumor tissue samples from patients with histologically-confirmed GC or CRC suitable for chemotherapy were analyzed for FGFR2 and HER2 expression using immunohistochemistry and fluorescence in situ hybridization (HER2 in CRC only). Results A total of 176 GC patients and 389 CRC patients were enrolled. Among patients with GC, 25.6% were FGFR2-positive and 26.1% were HER2-positive. Among patients with CRC, 2.9% were FGFR2-positive and 16.2% were HER2-positive. No clear relationship was found between FGFR2 and HER2 status in either GC or CRC. In GC, FGFR2 and HER2 statuses did not differ between different primary cancer locations, whereas there were some differences between histological types. Based on FGFR2- and/or HER2-positive status, 117 patients were identified as potentially suitable for inclusion in clinical trials of therapeutic agents targeting the relevant protein (GC = 45, CRC = 72; FGFR = 56, HER2 = 62), of whom 7 were eventually enrolled into such clinical trials. Conclusions This study indicated the prevalence of FGFR2 and HER2 in GC and CRC in the Japanese population. The screening performed in this study could be useful for identifying eligible patients for future clinical trials of agents targeting these proteins. Trial registration Clinical trial registration Japic CTI No.: JapicCTI-163380. https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?directLink=RNlzx1PPCuT.PrVNPxPRwA.

Established supportive care to reduce the toxicity of neoadjuvant chemotherapy (NAC) is lacking. This multicenter randomized study compared the administration of synbiotics combined with enteral nutrition (EN) versus that of prophylactic antibiotics as supportive care treatment for patients with esophageal cancer undergoing NAC.Patients with advanced esophageal cancer scheduled to receive NAC were randomly administered either prophylactic antibiotics (antibiotic group) or synbiotics combined with EN (Syn + EN group). The primary endpoint was the febrile neutropenia (FN) incidence during the first course, and the secondary endpoints were other adverse events, changes in intestinal environment, including fecal microbiota, organic acid concentrations, pH, and chemotherapy tolerability.Eighty-one patients were enrolled. The FN incidence was nonsignificantly lower (P = 0.088) in the Syn + EN group. The incidences of grade 4 neutropenia and grades 2-4 diarrhea were significantly lower in the Syn + EN group (P = 0.014 and 0.033, respectively). Relative dose intensity was significantly higher in the Syn + EN group (92.0 ± 10.9%) than in the antibiotic group (83.2 ± 18.2%) (P = 0.01). Alpfa diversity was significantly higher in the Syn + EN group than in the antibiotic after chemotherapy (P = 0.002). The numbers of Bifidobacterium (P 0.05), Lacticaseibacillus (P 0.001), and Enterobacteriaceae (P 0.001) and the concentration of acetic acid (P 0.001) were significantly higher in the Syn + EN group than in the antibiotic group after chemotherapy. The severity of diarrhea and occurrence of FN were significantly correlated with Clostridioides difficile abundance and were significantly inversely correlated with acetic acid concentration after chemotherapy.Synbiotics combined with EN may be an alternative supportive care treatment to prophylactic antibiotics in patients with cancer undergoing toxic chemotherapy (https://jrct.niph.go.jp; jRCTs051180153).

Purpose: Outcomes of patients with rectal cancer who underwent preoperative chemoradiotherapy after complete smoking cessation are unknown. We evaluated the outcomes of patients with locally advanced low rectal cancer who underwent combined preoperative chemoradiotherapy after complete smoking cessation and total mesorectal excision with selective lateral lymph node dissection. Predictive factors associated with response to preoperative chemoradiotherapy were investigated. Methods: In this retrospective study at a tertiary medical center, 160 patients with locally advanced low rectal cancer who underwent surgical resection during January 2014–December 2019 were enrolled; data of 28 with stage II or III rectal cancer who underwent preoperative chemoradiotherapy and surgery were analyzed. Before chemoradiotherapy, a Smokerlyzer was used to measure expiratory carbon monoxide and monitor smoking cessation. Pathologic response rate and oncological outcomes were analyzed. Results: No major post-surgical complications occurred. Pathologic complete response was achieved in 8/28 patients (28.6%). Three-year recurrence-free and overall survival rates were 81.4% and 92.4%, respectively. No patient developed local recurrence in lateral pelvic lymph nodes. Survival did not differ significantly between patients with and without pathologic complete response. In univariate and multivariate analyses, pretreatment hemoglobin (>13.0) [hazard ratio: 7.00 (95% confidence interval, 1.090–45.20); p=0.0408] and clinically negative N stage before treatment [hazard ratio: 18.9 (95% confidence interval, 1.63–218.0); p=0.0187] were significantly associated with pathologic complete response. Conclusion: Preoperative chemoradiotherapy with complete smoking cessation followed by total mesorectal excision with selective lateral lymph node dissection was safely performed and resulted in high pathologic complete response rates and favorable survival outcomes.

Esophagogastric junction (EGJ) cancers are resected thorough esophagectomy or gastrectomy, with the incidence of postoperative complications influenced by the chosen procedure. In this prospective nationwide multicenter study, patients with cT2–T4 EGJ cancers were enrolled before surgery. Based on the protocol, surgeons performed a transthoracic esophagectomy (TTE) or a transhiatal gastrectomy (THG) and dissected all lymph nodes prespecified as the standardized procedure. Postoperative complications were correlated with the clinical factors in each procedure. A total of 345 patients were eligible for this study. TTE and THG were performed in 120 and 225 patients, respectively. Complications of Clavien-Dindo ≥ Grade II were found in 115/345 (33.3%) patients. Recurrent laryngeal nerve palsy was found only in the TTE group (p

Successful resection of intra-abdominal tumors using indocyanine green (ICG) fluorescence imaging has not been reported. Here, we report a rare case of an intra-abdominal desmoid-type fibromatosis successfully resected using this technique after intersphincteric resection (ISR) for rectal cancer. One year after ISR for rectal cancer in a 47-year-old man, computed tomography showed a 50-mm intra-abdominal tumor near the left common iliac vein. Surgical resection was performed. The tumor was located in the mesentery of the remnant rectum after ISR. ICG fluorescence imaging confirmed the blood supply to the mesentery of the distal remnant rectum after tumor excision. The anal canal was successfully preserved without creating a permanent colostomy. The tumor was safely resected with resection margins, diagnosed as desmoid-type fibromatosis. No tumor recurrence was observed 6 months post-resection. This was the first case report to demonstrate the utility of this technique for an intra-abdominal tumor resection.

Approximately 12–15% of gastric cancers (GCs) are human epidermal growth factor receptor-2 (HER2)-positive (HER2 immunohistochemistry 3 + or 2 + /in situ hybridization + [ERBB2/CEP17 ≥ 2.0]). While the anti-HER2 monoclonal antibody trastuzumab, in combination with chemotherapy, is the standard treatment for HER2-positive GC, other HER2-targeted therapies have not demonstrated survival benefits in patients with GC, despite showing efficacy in patients with HER2-positive breast cancer. This indicates that there are unique challenges to the use of currently available HER2-targeted therapies for the treatment of HER2-positive GC. Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate consisting of an anti-HER2 human monoclonal IgG1 antibody with the same amino acid sequence as trastuzumab, an enzymatically cleavable peptide-based linker, and DXd, a novel topoisomerase I inhibitor, as its released payload. T-DXd has a high drug–antibody ratio (approximately 8) and a demonstrated bystander antitumor effect. It has demonstrated significant efficacy when compared with standard therapies and is approved as third- or later-line treatment for HER2-positive GC in Japan and second- or later-line treatment in the US. T-DXd treatment is associated with gastrointestinal and hematological adverse events, and a risk of interstitial lung disease (ILD), with the ILD risk being higher in Japan than in countries other than Japan. However, most adverse events, including ILD, can be managed with proactive monitoring and T-DXd dose modification, and initiation of adequate treatment. In this review, we summarize the discovery and development of T-DXd and provide guidance for T-DXd safety management, including ILD monitoring, for patients with HER2-positive GC.

Patients with peritoneal dissemination of gastric cancer have poor oral intake caused by malignant bowel obstruction (MBO). Palliative surgery has often been undertaken to improve quality of life (QOL), but few prospective studies on palliative surgery in this patient population have been published. We prospectively investigated the significance of palliative surgery using patient-reported QOL measures. Patients underwent palliative surgery by small intestine/colon resection or small intestine/colon bypass or ileostomy/colostomy for MBO. The primary endpoint was change in QOL assessed at baseline, 14 days, 1 month, and 3 months following palliative surgery using the Euro QoL Five Dimensions (EQ-5D™) questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications. Between April 2013 and March 2018, 63 patients were enrolled from 14 institutions. The mean EQ-5D™ utility index baseline score of 0.6 remained consistent. Gastric-specific symptoms mostly showed statistically significant improvement from baseline. Forty-two patients (67%) were able to eat solid food 2 weeks after palliative surgery and 36 patients (57%) tolerated it for 3 months. The rate of overall morbidity of ≥ grade III according to the Clavien–Dindo classification was 16% (10 patients) and the 30-day postoperative mortality rate was 3.2% (2 patients). In patients with MBO caused by peritoneal dissemination of gastric cancer, palliative surgery did not improve QOL while improving solid food intake, with an acceptable postoperative morbidity and mortality rate.

To compare short-term outcomes between two- vs. three courses of neoadjuvant chemotherapy (NAC) to clarify the optimal treatment for esophageal squamous cell cancer (ESCC) in a multicenter, randomized, phase II trial. An optimal number of NAC cycles remains to be established for locally advanced ESCC. Patients with locally advanced ESCC were randomly assigned to either two (N = 91) or three (N = 89) courses of DCF (70 mg/m2 intravenous docetaxel and 70 mg/m2 intravenous cisplatin on day 1, and a continuous 700 mg/m2 fluorouracil infusion for 5 days) every 3 weeks followed by surgery. We compared the two groups for perioperative parameters, adverse events, and the response to NAC. The two- and three-course groups showed similar completion rates and overall NAC dose reductions. Although the two-course group showed significantly lower overall grades 3–4 leukopenia and anemia compared to the three-course group, the two groups had similar overall toxicity rates. Postoperative complications were not significantly different between the two groups, except arrhythmia (13 vs. 0%, P = 0.0007). Only two postoperative in-hospital deaths occurred in the three-course group, due to sepsis following severe pneumonia. Compared to the two-course group, the three-course group was associated with a significantly better clinical response (42.9 vs. 65.2%, P = 0.0027) and a relatively higher rate of pathological complete response (9.1 vs. 15.3%, P = 0.212). Both two- and three-course DCF regimens in the NAC setting seemed to be equally feasible in locally advanced ESCC patients. Additional DCF courses led to a better NAC response without increasing the incidence of adverse events or postoperative morbidity. University Hospital Medical Information Network Clinical Trials Registry of Japan (Identification Number UMIN 000015788).

Summary Background Findings of preclinical and clinical trials in colorectal cancer have shown promising antitumour effects of the co-formulation trifluridine/tipiracil and VEGF inhibition. We aimed to investigate the safety and activity of trifluridine/tipiracil and ramucirumab for previously treated advanced gastric cancer. Methods We did an open-label, single-arm, two-cohort, phase 2 study at eight centres in Japan. We enrolled patients with unresectable advanced gastric cancer or gastro-oesophageal junction adenocarcinoma. Cohort A included patients previously treated with one line of chemotherapy without ramucirumab and cohort B included patients previously treated with two to four lines of chemotherapy, including ramucirumab. Patients received trifluridine/tipiracil (35 mg/m2) orally twice daily on days 1–5 and days 8–12 of each 28-day treatment cycle, plus intravenous ramucirumab (8 mg/kg) on days 1 and 15. The primary endpoint was the disease control rate, assessed by investigators and defined as the proportion of patients with a confirmed best overall response, according to Response Evaluation Criteria in Solid Tumors version 1.1. This trial is registered on JapicCTI (JapicCTI-194596) and is ongoing but not recruiting. Findings Between April 8 and Oct 11, 2019, 64 patients were enrolled and included in the safety and activity analyses, 33 in cohort A and 31 in cohort B. In cohort A, the disease control rate was 85% (95% CI 68–95; 28 of 33 patients) and in cohort B it was 77% (59–90; 24 of 31 patients). Common treatment-related adverse events of grade 3 or worse were neutrophil count decreased (27 [82%] in cohort A and 23 [74%] in cohort B), white blood cell count decreased (eight [24%] and seven [23%]), and platelet count decreased (eight [24%] and four [13%]). Serious treatment-related adverse events were recorded in three patients in cohort A (fatigue and neutrophil count decreased; large intestine perforation; and febrile neutropenia, platelet count decreased, and anaemia). No patients in cohort B had a serious treatment-related adverse event, and no treatment-related deaths were reported in either cohort. Interpretation Trifluridine/tipiracil and ramucirumab showed an acceptable safety profile and clinical activity in patients with previously treated advanced gastric cancer regardless of previous ramucirumab exposure. Funding Taiho Pharmaceutical and Eli Lilly.

The prognosis of patients with gastric cancer and positive peritoneal lavage cytology is poor, even after gastrectomy. Though the standard therapy for this population is radical gastrectomy followed by S-1 chemotherapy, treatments vary among institutions and eras. We conducted a multicenter retrospective study to investigate the prognostic factors for cytology-positive gastric cancer. We reviewed the medical records obtained from 6 institutions, covering 2000–2019. There were 128 patients with positive cytology and no other distant metastases that underwent R1 gastrectomy. Univariate and multivariate analyses to identify prognostic factors for overall survival were conducted using Cox’s proportional hazards models. The median overall survival time was 18.6 months. In univariate analyses, age (≥ 80 years vs.

After D2 gastrectomy for advanced gastric cancer, patients with a high drainage fluid amylase level (d-AMY) on the first postoperative day (1POD) have an especially high risk of severe abdominal infectious complications (AICs), which could be fatal. On the hypothesis that prolonged antibiotic administration could reduce the incidence of severe AICs, we conducted a randomized phase II study to evaluate the optimal treatment duration of prophylactic antibiotics for patients who underwent D2 gastrectomy and had elevated d-AMY on 1POD. Patients whose d-AMY was >3000 IU/L on 1POD after D2 gastrectomy for gastric cancer were randomly assigned to normal prophylactic antibiotic treatment given only on the day of surgery (Group A) or to prolonged antibiotic treatment given for 1 week after surgery (Group B). The primary endpoint was the incidence of severe AICs (Clavien–Dindo grade IIIa or higher). This trial was registered as UMIN000012152. This study was started in December 2013 and stopped in February 2019 because of poor patient accrual. Finally, 35 and 37 patients were assigned to groups A and B, respectively. The incidences of AICs were 22.9% (eight of 35) in group A and 13.5% (five of 37) in group B. One-sided P value of the Fisher exact test was 0.234. No adverse reactions to antibiotic prophylaxis were observed in any of the patients. Prolonged prophylactic antibiotic administration had a marginal benefit in preventing grade III or higher AICs and caused no treatment-related morbidities.

A male in his twentieth was referred to our hospital for jaundice. Computed tomography(CT)showed dilation of the intrahepatic and extrahepatic bile ducts and showed a lesion at the ampulla of Vater, which caused obstructive jaundice. Upper gastrointestinal endoscopy revealed a tumor of protruded-predominant type with raised margins at the ampulla of Vater, and biopsy from the lesion indicated malignancy. With no apparent distant metastasis, radical resection was assumed to be possible, thus we performed subtotal stomach preserved pancreatoduodenectomy. Before the operation, endoscopic retrograde biliary drainage(ERBD)was unsuccessful because of the existence of the tumor, so percutaneous transhepatic cholangio drainage(PTCD)was conducted. After the operation, although pancreatic fistula(ISGPF Grade B)occurred, it improved with conservative treatment, and he discharged at 30 postoperative days. Histopathological examination revealed signet-ring cell carcinoma among the tumor at the ampulla of Vater, which was infiltrating into the pancreas. Final diagnosis was pT3, pN0, M0, pStage ⅡA. Now he is alive without recurrence for 3 and a half years.

A woman in her 50s underwent sigmoid colectomy and D3 lymph node dissection for sigmoid cancer(pT3, N0, M0, Stage Ⅱ: Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma 9th). She received adjuvant chemotherapy with capecitabine. Seven months after surgery, contrast-enhanced computed tomography( CECT) scan revealed a small mass in the segment 2 (S2) of the liver with dilation of peripheral intrahepatic bile duct, and the size of this mass and the bile duct dilatation were gradually increased. FDG positron emission tomography(FDG-PET)/CT showed abnormal FDG uptakes in the lesion of S2, and EOB-MRI detected other small lesions in the S6 and S7. Considering the results of image examinations, multiple lesions intrahepatic cholangiocarcinoma was firstly assumed. However, immunohistochemistry of the tumor obtained by endoscopic retrograde cholangiopancreatography (ERCP) showed cytokeratin 7-negative. Based on preoperative diagnosis of liver metastasis from colon cancer rather than intrahepatic cholangiocarcinoma, we performed left lobectomy, partial hepatectomy of S6 and S7 and cholecystectomy. In the resected specimen, the tumor was macroscopically located in the intrahepatic bile ducts. Microscopically, there existed atypical epithelial cells with glandular duct-like structure, and the lesions was histopathologically diagnosed as metastasis from colon cancer. She was discharged on the 10th postoperative day, and she is alive without recurrence one year after surgery.

Background This study evaluated the association between early tumor response at 8 weeks, previously reported as a positive outcome prognosticator, and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients enrolled in the ABSOLUTE trial. Methods HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D) utility index score in patients with complete response (CR) + partial response (PR) and progressive disease (PD) at 8 weeks, and time-to-deterioration (TtD) of the EQ-5D score, with the preset minimally important difference (MID) of 0.05, was compared between these populations. Among the enrolled patients, 143 and 160 patients were assessable in weekly solvent-based paclitaxel (Sb-PTX) arm and weekly nanoparticle albumin-bound paclitaxel (nab-PTX) arm, respectively. Results Changes of the EQ-5D score from baseline to 8 weeks in the nab-PTX arm were 0.0009 and − 0.1229 in CR + PR and PD patients, respectively; the corresponding values for the Sb-PTX arm were − 0.0019 and − 0.1549. For both treatments, changes of the EQ-5D score from baseline at 8 weeks were significantly larger in patients with PD than in those with CR + PR. The median TtD was 3.9 and 2.2 months in patients with CR + PR and PD, respectively, for nab-PTX [hazard ratio (HR) = 0.595, 95% confidence interval (CI) 0.358–0.989]. For Sb-PTX, the corresponding values were 4.7 and 2.0 months (HR = 0.494, 95% CI 0.291–0.841). Conclusions Early tumor shrinkage was associated with maintained HRQOL in AGC patients on the second-line chemotherapy with taxanes.

The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (− 12.8% versus − 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p

Aim Neoadjuvant chemotherapy (NAC) is promising to improve the survival of resectable gastric cancer. However, suitable regimen and treatment duration for NAC have not yet been established. Methods We conducted a randomized phase II trial to compare two and four courses of neoadjuvant S‐1/cisplatin (SC) and S‐1/cisplatin/docetaxel(DCS) using a two‐by‐two factorial design for locally resectable advanced gastric cancer. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous‐type cancer received two or four courses of SC or DCS. Then, patients underwent D2 gastrectomy and adjuvant S‐1 chemotherapy for 1 year. The primary endpoint was 3‐year overall survival. The planned sample size was 120 eligible patients. Results Between October 2011 and September 2014, 132 patients were assigned to CS (n = 66; 33 in 2‐courses and 33 in 4‐courses) and DCS (n = 66; 33 in 2‐courses and 33 in 4‐courses). The 3‐year OS was 58.1% in CS and 60.0% in DCS with hazard ratio of 0.80 (95% CI, 0.48‐1.34), while it was 53.1% in the two courses and 65.0% in the four courses with hazard ratio of 0.72 (95% CI, 0.43‐1.22). In the survival analysis by duration in each regimen, the 3‐year OS was 58.1% for both two and four courses in CS, while it was 48.5% for two courses of DCS and 71.9% for four courses of DCS. Conclusions Considering high 3‐year OS, four courses DCS has a value to be tested in a future phase III study to confirm superiority of neoadjuvant chemotherapy for locally advanced gastric cancer., Overall survival curves stratified by regimens, number of courses.

Cisplatin plus S-1 (CS) is the standard first-line chemotherapy for advanced gastric cancer (AGC) in Japan. A previous phase III trial showed that docetaxel plus S-1 (DS) was effective for AGC without measurable lesions, but no studies have compared these two regimens. Eligible patients had unresectable or recurrent HER2-negative AGC without measurable lesions. Patients were randomized to DS (docetaxel 40 mg/m2 on day 1, S-1 80–120 mg on days 1–14, every 3 weeks) or CS (cisplatin 60 mg/m2 on day 8, S-1 80–120 mg on days 1–21, every 5 weeks). The primary endpoint was overall survival (OS). All patients had unresectable primary disease. Sixty-one patients were randomly assigned to DS (n = 30) or CS (n = 31). One CS patient was ineligible due to HER2 positivity. The median number of cycles was 9.5 (range 2–49) with DS and 5.5 (range 1–10) with CS. There were no treatment-related deaths. The most common grade 3–4 non-hematological toxicity was fatigue (7% with DS, 13% with CS), followed by anorexia (3% with DS, 10% with CS) and diarrhea (3% with DS, 10% with CS). The 2-year OS rates were 43.3% with DS and 30.0% with CS (log-rank P = 0.113), with a hazard ratio of 0.617 (95% confidence interval 0.337–1.128), indicating non-inferiority of DS to CS with respect to OS (P

Background Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. Methods In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent GC and prior or scheduled treatment with nivolumab as third-line or higher therapy between September 2017 and February 2019 were collected from 23 institutions. The tumour-positive score (TPS) and combined positive score (CPS) of PD-L1 expression and mismatch repair (MMR) were analysed by immunohistochemistry. Associations between clinicopathological factors and tumour-response rate, hyperprogressive disease (HPD) rate and survival were assessed. Results Of 200 eligible patients, 143 had measurable lesions. The response and HPD rates were 17.5% and 22.1%, respectively. The response rate was significantly higher in patients with performance status (PS) 0–1 (P = 0.026), non-peritoneal metastasis (P = 0.021), PD-L1 TPS ≥ 1 (P = 0.012), CPS ≥ 5 (P = 0.007) or ≥ 10 (P P P = 0.026), liver metastasis (P P = 0.048). Multivariate analysis revealed that CPS (P = 0.001) and MMR (P = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis (P P = 0.004) and CRP (P Conclusions PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC. Clinical trial registration UMIN000032164.

Perioperative treatment is an accepted standard approach for treating locally advanced gastric cancer (LAGC). Histopathological tumor regression with

We previously reported the HERBIS-4A phase II trial comparing S-1 plus cisplatin (SP) with capecitabine plus cisplatin (XP) in chemotherapy-naive patients with HER2-negative advanced gastric cancer (GC). We performed a pooled analysis of HERBIS-4A and HERBIS-2, the phase II trial comparing SP with XP in HER2-negative recurrent GC patients with a recurrence-free interval after S-1 adjuvant therapy of ≥ 6 months. Patients were randomly assigned to receive either SP [S-1 (40–60 mg twice daily for 21 days) plus cisplatin (60 mg/m2 on day 8), every 5 weeks] or XP [capecitabine (1000 mg/m2 twice daily for 14 days) plus cisplatin (80 mg/m2 on day 1), every 3 weeks]. In the pooled analysis, SP (n = 44–50) showed a longer progression-free survival [6.4 versus 5.1 months; hazard ratio (HR), 0.666; P = 0.062], overall survival (14.8 versus 10.6 months; HR, 0.695; P = 0.099), and time to treatment failure (4.6 versus 3.6 months; HR, 0.668; P = 0.045) as well as a higher disease control rate (86.4% versus 68.1%, P = 0.149) compared with XP (n = 47–51). A significant survival advantage for SP over XP was apparent in patients with a performance status of 0, a differentiated-type tumor histology, or a primary tumor localization to the upper portion of the stomach. Our pooled analysis supports the use of SP in the first-line setting for patients with HER2-negative advanced or recurrent GC with a recurrence-free interval of ≥ 6 months. The HERBIS-2 trial was registered with UMIN-CTR as UMIN000006105.

Background Second-line chemotherapy (SLC) improves survival in advanced gastric cancer (AGC). Patients receiving SLC are categorized into two disease status groups: tumour progression after first-line chemotherapy and early recurrence after adjuvant chemotherapy. Differences between these groups have not yet been clarified. Patients and methods A total of 163 eligible patients registered in the randomized phase III TRICS trial evaluating SLC for patients with AGC was classified into the progressive disease (PD) group (n = 55) or the early relapse (ER) group (n = 108). We compared overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. Adjusted OS and adjusted PFS were estimated using inverse probability of treatment weighting (IPTW). Results The ER group had a lower median age than the PD group (66 vs. 72 years; P = 0.016), performance status (PS) 0 was more frequently seen in the ER group (87% vs. 71%; P = 0.012). The adjusted median OS was 13.7 months in the ER group and 13.6 months in the PD group (IPTW hazard ratio [HR]: 1.023; P = 0.854). The adjusted median PFS was 4.9 months in the ER group and 4.4 months in the PD group (IPTW HR: 0.707; P = 0.004). ORR was significantly better in the ER group than the PD group (21.3% vs. 4.9%; P = 0.020). No significant differences were observed in the incidence of adverse events. Conclusions ER was associated with improved PFS and better ORR than PD, although no difference in survival was demonstrated. From the viewpoint of treatment outcome, it seems appropriate to treat patients with ER in the same way as patients with PD. Clinical trial registration UMIN 000002571.

Basic and clinical reports have suggested that eicosapentaenoic acid (EPA) exhibits anti-tumor activity. The present study evaluated whether perioperative EPA could improve the survival of patients with localized gastric cancer as a key secondary endpoint of a randomized clinical study. The present study was designed as multicenter, open-label, superiority, randomized trial to confirm the preventive effect of EPA on body weight loss after total gastrectomy for gastric cancer. Eligible patients were randomized to either the standard-diet group (EPA-off group) or EPA-on group by a centralized dynamic method. An EPA-enriched supplement (ProSure

A woman in her 30s visited our hospital complaining primarily of melena. Colonoscopy revealed the presence of a type 1 tumor in 2 cm from anal verge. Contrast-enhanced CT showed an unresectable massive liver metastasis in the left lobe of the liver and another metastasis in the right lobe. The patient received front-line chemotherapy with Leucovorin, fluorouracil, oxaliplatin, and irinotecan(FOLFOXIRI)plus bevacizumab(BEV). A year later, a marked reduction of liver metastases and primary lesions was confirmed by CT scan imaging. A multidisciplinary team recommended resection of the liver metastases followed by laparoscopic intersphincteric resection for primary lesions. However, after 1 year, a recurrence was diagnosed in the liver; hence, FOLFOXIRI plus BEV was reintroduced for volume reduction. The patient underwent a repeat hepatectomy since enough volume reduction was confirmed. One year later, she experienced a re-relapse of the metastasis in the liver. Currently, she is still undergoing chemotherapy following 7 years since the first visit. Long-term survival can be expected following surgical treatment during chemotherapy.

A man in his 50s underwent laparoscopic sigmoid colectomy for sigmoid colon cancer with liver metastasis(cT4aN1M1a, cStage Ⅳa), followed by partial liver resection(S4, S6). One and a half years after the initial surgery, CEA and CA19-9 increased, and contrast-enhanced CT and MRI showed a hypovascular lesion with dilation of the distal pancreatic duct in the pancreatic body. Adenocarcinoma was detected by brushing cytology of the lesion and pancreatic juice cytology by ERCP. From the results of various examinations, the lesion was diagnosed as pancreatic ductal adenocarcinoma. We performed distal pancreatectomy, and initially the histopathological diagnosis was pancreatic body cancer(pT3N1aM0, pStage ⅡB). In a follow-up CT after surgery, a suspected metastatic lymph node was pointed out in the mediastinum, but it was difficult to distinguish between metastasis from colorectal cancer and one from pancreatic cancer. Immunostaining of the tumor tissue and comparative study of the excised specimens of colon and pancreas was performed in order to assume the primary lesion of the lymph node. As a result, both tissues were CK7(-)/CK20(+), and the lesion at first considered to be primary pancreatic cancer was originally the pancreatic metastasis from colon cancer. Bone metastases were also found on FDG-PET/CT around the same time, and then systemic chemotherapy for colorectal cancer was introduced. Four and a half years have passed since the first surgery, and he is still alive and undergoing treatment.

A man in his 60s underwent pancreaticoduodenectomy(PD)for ampullary cancer(pT3, N1, M0, pStage ⅡB). One year after the operation, lymph node recurrence was observed, and gemcitabine/cisplatin regimen was introduced. Once the disease was controlled, but the tolerability of chemotherapy deteriorated due to severe anorexia and general fatigue around the 6th course of the regimen, thus we stopped the chemotherapy. The performance status was remarkably dropped and the oral intake was notably decreased, and subsequently he got hospitalized. Blood examination on admission showed signs of liver failure(Alb 1.9 g/dL, T-Bil 2.0 mg/dL, PT 36.2%, NH3 159μg/dL). CT scan revealed marked deterioration of fatty liver and newly recognized retention of ascites. We diagnosed this clinical state as liver dysfunction caused by aggravation of nonalcoholic fatty liver disease(NAFLD)due to pancreatic exocrine insufficiency after PD. Immediately pancreatic enzyme replacement therapy(pancrelipase)was performed, and liver function gradually improved. He was discharged 17 days after admission. One month after discharge, CT scan showed that the fatty liver was markedly improved and the ascites disappeared. Around the same time, the chemotherapy was able to be resumed with the improvement of general condition.

A 82-year-old man presented with diarrhea and fatigue. He had no past medical or surgical history except chronic renal failure. Locally advanced rectal cancer with invasion to left ureter was detected in computed tomography. Colonoscopy revealed a circular lesion 12 cm from the anal verge. Biopsy showed moderately differentiated adenocarcinoma. There was no sign of distal metastasis and we decided to conduct radical surgery. Robot-assisted laparoscopic lower anterior resection with partial resection of left ureter, and diverting ileostomy were carried out. Besides, urinary tract reconstruction of ureterocystoneostomy using Lich-Gregoir technique was conducted by urologists also with robot assistance. The pathological stage of the disease was pT4b(left ureter)N1bM0, pStage Ⅲc. The resection margin was secured and radical surgery was achieved. The patient was discharged on postoperative day 22nd without postoperative complication. He is alive without recurrence at 6 months after the operation.

Patient undergoing R0 resection have the good survival advantage following surgery for recurrent rectal cancer. Robotic surgery for anastomotic local recurrence of rectal cancer has never been reported before. An 80-year-old woman who had undergone high anterior resection for rectal cancer 1 years previously got colonoscopy. It revealed a 10 mm sized, elevated lesion on the anastomotic site, and a biopsy revealed an adenocarcinoma(tub1). Computed tomography and positron emission tomography-computed tomography showed no signs of distant metastasis, and we decided to conduct radical surgery with robot-assisted laparoscope. Robot-assisted laparoscopic lower anterior resection with resection of left hypogastric nerve was carried out. Histological assessment showed that R0 resection was performed. The patient was discharged on postoperative day 8th without postoperative complication. She is alive without recurrence at 1 year after the last operation.

The case was a 61-year-old woman. She was diagnosed with autosomal dominant polycystic kidney disease(ADPKD)at the age of 38 and started hemodialysis at the age of 42. She was diagnosed with rectal cancer(RS)at the age of 61. Laparoscopic high anterior resection and D3 lymphadenectomy were carried out. Although the intra-abdominal space was limited by the huge renal cysts, laparoscopic surgery can be safely performed by arranging the port closer to the midline, taking the patient's position sufficiently, and using some useful tips. Laparoscopic surgery for the patient with ADPKD was considered a useful approach.

We reported a case of rectal cancer with unresectable liver metastases treated with resection of the primary lesion followed by systemic chemotherapy with curative resection. A woman in her 40s was diagnosed with rectal RS carcinoma and unresectable liver metastasis, mFOLFOX6 plus panitumumab therapy was initiated after laparoscopic high anterior resection of the rectal lesion. After 5 courses of chemotherapy, significant shrinkage of the liver metastatic lesion and increase of the remnant liver volume were observed. Percutaneous transhepatic portal vein embolization( PTPE) was performed with the aim of further preserving remnant liver volume. Since the hepatic reserve was sufficient, the treatment strategy was to perform radical hepatectomy. Extended right hepatic lobectomy, S4 partial resection, and cholecystectomy were performed. The patient didn't relapse at 11 months after hepatectomy.

In Japan, the standard treatment for squamous cell anal cancer(SCAC)has not been established. Herein, we report a case of SCAC that completely responded to chemoradiotherapy(CRT).A woman in her 80s presented with anal pain and bleeding. Computed tomography revealed bilateral inguinal adenopathy and a tumor in the anal canal. Histopathological examination of endoscopic biopsies showed adenocarcinoma. Thus, she was diagnosed with anal canal adenocarcinoma and lymph node metastases:cT3, cN1a(No. 292), cM0, cStage Ⅲc(Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, 9th edition). Owing to her advanced age and refusal of a stoma, CRT(S-1, mitomycin C, and radiotherapy)was administered with the expectation that salvage surgery in the form of rectal amputation would eventually be necessary. The tumor noticeably shrank after CRT. The patient is alive to this date,14 months after the final round of CRT.

A woman in her 60s realized heart palpitations and was pointed out anemia. CT revealed a tumor measuring 7 cm, with internal necrosis, originating from the gallbladder and invading the liver, and diagnosed as gallbladder cancer. There existed no distant metastasis and we performed cholecystectomy with partial resection of segment 4a+5 of the liver and lymph node resection. Histopathological examination revealed highly atypical cells with large nuclei and polynuclear cells and poor cell junctions in the specimen, and the tumor was histologically diagnosed as an undifferentiated carcinoma. Metastases were not detected in dissected lymph nodes, and this case was diagnosed as undifferentiated carcinoma of gallbladder, T3a, N0, M0, Stage ⅢA(JSHBPS 6th). She was discharged at 13 days after the operation with no apparent postoperative complications. Postoperative adjuvant chemotherapy with administration of TS-1 was conducted for half a year. Now over 5 years have passed since the operation, and she is alive without recurrence.

The risk factors for recurrence in patients with pStage Ⅱ colorectal cancer still remains controversial. The aim of this study was to investigate the risk factors for recurrence after surgery in patients with pStage Ⅱ colorectal cancer.We retrospectively reviewed 311 patients with primary pStage Ⅱ colorectal cancer who underwent radical resection without neoadjuvant therapy at our institute between January 2014 and December 2019.Of 311 patients, 32 patients(10.3%)developed recurrences after surgery at a median follow-up of 32.9(0.23-74.2)months. The 3-year and 5-year recurrence-free survival(RFS)rate was 88.4% and 87.6%, respectively. A multivariate analysis for RFS showed that only pT4 (HR: 4.06, 95%CI: 1.60-10.29, p=0.003) was an independent risk factor.This study revealed that pT4 was an independent risk factor for recurrence after surgery in patients with pStage Ⅱ colorectal cancer.

Background Large type 3 and type 4 gastric cancers have extremely poor prognoses. To address this, neoadjuvant chemotherapy may be a promising approach. The phase III JCOG0501 study, conducted to confirm the superiority of neoadjuvant S-1 plus cisplatin followed by D2 gastrectomy over upfront surgery, showed no survival benefit for neoadjuvant S-1 plus cisplatin. In Korea, the PRODIGY study, which was a phase III study of neoadjuvant docetaxel plus oxaliplatin plus S-1 (DOS) followed by surgery and adjuvant S-1 versus surgery and adjuvant S-1 for gastric cancer of T2-3N+ or T4Nany, showed that progression-free survival (PFS) was significantly superior in the neoadjuvant DOS arm. Therefore, DOS therapy may be a promising candidate for preoperative chemotherapy for large type 3 or type 4 gastric cancer. Methods Preoperative docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 will be intravenously administered on day1 every three weeks. S-1 will be orally administered 80 mg/m2 on days 1–14 of a 21-day cycle. Patients will receive three courses of treatment and gastrectomy with ≥D2 lymph node dissection. Postoperative S-1 plus docetaxel therapy (DS) will be administered according to the JACCRO GC-07 (START-2) study. The primary endpoint is the 3-year PFS rate. Secondary endpoints include PFS time, overall survival time, pathological response rate, response rate according to RECIST version1.1, proportion of completion of neoadjuvant chemotherapy, R0 resection rate, proportion of completion of surgery, proportion of completion of protocol treatment, proportion of negative conversion of CY, adverse event occurrence rate, and nutritional evaluation. The null hypothesis for the 3-year PFS rate is 45% and the expected value is 60%. The total sample size is 46 considering that the registration period and follow-up period are two and three years, respectively. Discussion This is a prospective, multicenter, single-arm, open-label, phase II trial assessing the efficacy and safety of preoperative DOS and postoperative DS for large type 3 or type 4 gastric cancer. The results will inform future phase III trials and are expected to lead to new treatment strategies for large type 3 or type 4 gastric cancer. Trial registration Registered with Japan Registry of Clinical Trials on October 11, 2019 (jRCTs051190060).

It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40–60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology.

The optimal treatment for liver metastasis from gastric cancer (LMGC) remains uncertain. The relevance of surgical resection is controversial. We conducted a prospective multicenter interventional study of surgical resection for LMGC. Patients with synchronous or metachronous LMGC who were surgically fit were registered. The primary endpoint was 3-year overall survival (OS) of patients who underwent R0 resection. Secondary endpoints were R0 resection rate, operative morbidity and mortality, 3-year recurrence-free survival (RFS) of R0 patients, and OS in all registered patients. Seventy patients were registered from 24 institutions between December 2011 and November 2019 and received preoperative chemotherapy. Three patients were ineligible, and 19 patients discontinued treatment, with disease progression in 12, adverse events in 4, and consent withdrawal in 3 before surgery. Of the 48 patients eventually undergoing surgery, R0 resection of the primary and/or metastatic GC was accomplished in 43 patients, while 1 patient discontinued treatment for positive peritoneal lavage cytology and 4 patients were considered ineligible based on postoperative pathological findings other than GC. The R0 resection rate of all eligible patients was 68.3% [95% confidence interval (CI) 55.3–79.4%, 43/63 patients], while that of all resected patients was 89.6% (95% CI 77.3–96.5%, 43/48 patients). Postoperative complications were identified in 12 out of 43 patients (27.9%), and Clavien–Dindo grade III or higher complications occurred in seven patients (16.3%). No hospital mortality was observed. R0 resection for LMGC could be performed in approximately two-thirds of all eligible patients, with acceptable surgical morbidity and mortality.

Background We previously reported the good feasibility and favorable efficacy of perioperative capecitabine plus oxaliplatin (CapeOx) in patients (pts) with clinical T3(SS)/T4a(SE) N1-3 M0 gastric cancer (GC) in a phase II study in which the pathological response rate, the primary endpoint, of 54.1% was demonstrated. Here, we report 3-year follow-up data. Methods The eligibility criteria included clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of Gastric Carcinoma-3rd English Edition (JCGC). Three cycles of neoadjuvant CapeOx (capecitabine, 2000mg/m2 for 14 days; oxaliplatin, 130mg/m2 on day 1, every 3 weeks) were administered, followed by 5 cycles of adjuvant CapeOx after D2 gastrectomy. Three-year overall survival and relapse-free survival are presented here, and analyzed by cohorts based on pathologic response rate (pRR). Results Thirty-seven pts were enrolled from July 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of neoadjuvant CapeOx and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29). The overall survival (OS) rate and relapse-free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Further, the 3-year OS rate in pts with pathological response of grade 1a (n = 13) and grade 1b or higher (n = 20) was 69.2% (95% CI: 48.2-99.5%) and 100.0%, respectively, based on JCGC. Pathological response rate was classified according to JCGC as follows: grade 0, the tumor was not affected; grade 1a, less than one-third of the tumor was affected; grade 1b, one to two thirds of the tumor was affected; grade 2, greater than or equal to two thirds was affected; and grade 3, no residual tumor. A pathological response was defined as grade 1b or greater. Conclusion Perioperative CapeOx showed good feasibility and favorable prognosis, especially in pts with pathological response of grade 1b or higher and was found to be useful in predicting prognosis. The data obtained using this novel approach warrant further investigation (Trial ID: UMIN000021641, jRCTs051180109).