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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.

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.

Recent retrospective studies have shown that increased intraoperative blood loss (IBL) during curative gastrectomy for patients with advanced gastric cancer is a negative prognostic indicator for recurrence. However, there are no reliable reports assessing this with a large-scale prospective cohort. This study aimed to evaluate the impact of IBL on long-term outcomes using data from the JCOG1001 phase III trial, which was designed to determine if bursectomy led to improved survival vs. nonbursectomy in patients with cT3/4a gastric cancer. This study included 1203 of the 1204 patients enrolled in the JCOG1001. From the tertiles of IBL (196 ml, 400 ml), we divided the patients into three groups: IBL

Introduction: There are little data concerning the long-term outcome of single-incision laparoscopic surgery (SILS) for colon cancer. Therefore, we investigated not only the short-term outcomes but also the long-term outcomes of SILS for right-side colon cancer. Methods: We retrospectively compared short- and long-term outcomes of SILS and conventional laparoscopic surgery (CLS) for right-sided colon cancer in our institution. Intergroup differences of short-term outcomes were evaluated using χ2 or Fisher exact tests and 2-sample Student t tests. The disease-free survival rates (long-term outcome) of stage II and III patients were estimated using the Kaplan-Meier method and compared using log-rank tests. Results: There were 290 operations conducted for right-side (cecum and ascending) colorectal cancers from April 2011 to July 2018. Open surgery was performed in 12 cases from start to the operation. SILS was performed in 196 cases and CLS in 55 cases. One patient underwent intraoperative conversion from SILS to laparotomy for bleeding control. In addition, 1 port was added to SILS in 3 cases. These 4 cases were included in the analysis as the SILS group according to the principle of intent to treat. Background: Factors including age, gender, body mass index, performance status, and tumor stage were not statistically different between the SILS and CLS groups. In short-term outcomes, the number of harvested lymph nodes was not statistically different. SILS required less operating time (p < 0.001) and resulted in a reduced bleeding volume (p < 0.001). There was no statistical difference in the frequency of overall complications (p = 0.06). The disease-free survival of stage II and III patients was not statistically different between the 2 groups. Conclusions: With the proper adaptation of SILS by an experienced surgeon, the short- and long-term outcomes of SILS were not inferior to those of CLS. Therefore, SILS could be a treatment option for right-sided colon cancer.

Aim Osteoporosis in patients after gastrectomy is increasing with the aging of gastric cancer patients. Bisphosphonates are effective treatments for osteoporosis; however, their safety or efficacy in postgastrectomy patients has not been established. The purpose of this multicenter prospective intervention study was to investigate the impact of monthly minodronate on osteoporosis after gastrectomy. Methods Of the 261 enrolled gastric cancer patients, 164 patients were diagnosed with osteoporosis based on criteria of the Japan Society of Osteoporosis. They were randomly assigned 1:1 to groups treated with active vitamin D (VD group) or monthly minodronate (MIN group). The primary endpoint was changes in lumbar bone mineral density (L‐BMD) 12 mo after the start of administration. The secondary endpoints were changes in bone metabolism markers, adverse events (AEs), or treatment completion rates. Results There was no significant difference in patient background between the VD (n = 82) and MIN (n = 82) groups. In the MIN group, the increase in L‐BMD was significantly higher than that in the VD group (4.52% vs 1.72%, P = .001), with a significant reduction in bone metabolism markers; blood NTX (−25.6% vs −1.6%, P, Monthly minodronate is safe and effective for osteoporosis after gastrectomy.

Background The robotic system has been applied in the treatment of gastric cancer (GC), and the procedure has been found to be safe and feasible. Situs inversus totalis (SIT) is a relatively rare autosomal recessive congenital anomaly. We successfully performed robot-assisted proximal gastrectomy (RAPG) and handsewn double-flap esophagogastrostomy for GC in a patient with SIT. Case presentation A 71-year-old woman was referred to us with an asymptomatic ulcerative lesion in the upper body of the stomach. Computed tomography revealed that she had SIT. She was diagnosed with cT1bN0M0, cStageIA gastric cancer. RAPG with lymph node dissection and handsewn double-flap esophagogastrostomy was performed. Robotic surgery enabled the surgeon to perform the surgery without changing his position and experiencing any confusion resulting from the patient’s reversed anatomy. It took 448 min, and no intraoperative complications occurred. Her postoperative course was uneventful; she was discharged on postoperative day 10. The final pathologic report showed pT1b1N0M0, pStage IA. Conclusions This is the first case describing RAPG with handsewn double-flap esophagogastrostomy for a SIT patient with early GC.

There is no standard chemotherapy for esophageal squamous cell carcinoma (ESCC) refractory to first-line fluoropyrimidine- and platinum-based chemotherapy. We therefore performed a randomized, selection-design phase II trial to compare docetaxel (DTX) and paclitaxel (PTX) in this setting. Eligible patients were randomly assigned to receive either DTX (70 mg/m2 on day 1 of each 21-day cycle) or PTX (100 mg/m2 on days 1, 8, 15, 22, 29, and 36 of each 49-day cycle). The primary end point was overall survival (OS), and secondary end points included progression-free survival (PFS), time to treatment failure (TTF), response rate (RR), and safety. Seventy-eight eligible patients (N = 39 in each group) were included for efficacy analysis. The median OS was significantly longer in the PTX group (8.8 vs. 7.3 months; hazard ratio [HR], 0.62; P = 0.047). A significant benefit of PTX over DTX was also apparent in the median PFS (4.4 vs. 2.1 months; HR, 0.49; P = 0.002) and median TTF (3.8 vs. 2.1 months; HR, 0.45; P PTX showed a significantly better efficacy as well as a more manageable toxicity compared with DTX.

The impact of thoracic duct (TD) resection on prognosis is controversial. This study aimed to examine the impact of TD resection. In this six-institution, matched-cohort study, 2269 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy between 2000 and 2017 were enrolled for analysis of long-term outcomes, including overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and recurrence patterns. Based on a propensity score, 642 TD-resected and 642 TD-preserved patients with all stages of disease were selected. At 5 years, the TD-resected group had an OS of 57.7%, a DFS of 50.9%, and a CSS of 62.2%. These rates were significantly higher than the corresponding rates of 48.7% (p = 0.0078), 41.0% (p = 0.0297), and 55.3% (p = 0.0473) in the TD-preserved group. The OS in the TD-preserved and TD-resected groups was similar for the patients with cStage 1 or 2 (p = 0.6265), but it was significantly higher in the TD-resected group for the patients with cStage 3 or 4 (p = 0.0052). The incidence of total recurrence did not differ between the two groups. However, the incidence of hematogenous recurrence in the TD-resected group (19.0%) was significantly lower than in the TD-preserved group (26.2%) (p = 0.0021). For cT4a tumors, the incidence of local recurrence in the TD-resected group (2.4%) was significantly lower than in the TD-preserved group (18.4%) (p = 0.0183). Performance of TD resection may help to improve prognosis, especially for patients with advanced esophageal squamous cell carcinoma, by reducing hematogenous and local recurrence. Prospective trials are needed to determine whether prophylactic TD resection has a positive impact on the prognosis of patients with esophageal cancer.

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).

Background Application of laparoscopic gastrectomy (LG) to advanced gastric cancer is still controversial due to lack of sufficient surgical and oncological outcomes. The purpose of this study was to elucidate the feasibility of LG for advanced gastric cancer by multicenter prospective cohort study. Methods A total of 98 patients with clinical stage II or III gastric cancer from 8 institutes were analyzed in this study. The primary endpoint was incidence of severe postoperative complications of Clavien-Dindo classification grade Ⅲa or higher. Results Sixty-six patients underwent laparoscopic distal gastrectomy (LDG), 10 patients laparoscopic proximal gastrectomy (LPG), 21 patients laparoscopic total gastrectomy (LTG), and 1 patient received gastro-jejunostomy. Seven patients had positive lavage cytology (CY1) and R0 rate was 90.8%. Three patients (3.1%) required conversion to open surgery. The incidence of overall postoperative complications and severe postoperative complications were 17.3% and 9.2%, respectively, those were comparable to the data of open surgery for advanced gastric cancer previously published. By surgical procedure, the incidence of severe postoperative complications of LDG, LPG, and LTG were 4.6, 0, and 28.6% and the rate of severe anastomotic leakage of LDG, LPG, and LTG were 0, 0, and 9.5%, respectively. Total gastrectomy was an only independent risk factor of severe postoperative complications in LG for advanced gastric cancer (odds ratio 8.75; 95% confidence interval 1.70-56.69, P = .0092). Discussion The incidence of severe postoperative complications after LG performed by qualified surgeons was acceptable even in cases of advanced gastric cancer; however, careful attention is required to adopt LTG. (UMIN000025733).

Introduction Sarcomatoid carcinoma (SC) is a rare subtype of malignant neoplasm with a poor prognosis that involves both carcinomatous and sarcomatous components. Although it may develop in various organs, SC in the large intestine has rarely been reported. It is not rare for patients with SC to have distant metastasis, reflecting its highly aggressive oncologic features, but cases with brain metastasis on initial visit are rare. In this report, we described a case of SC in the transverse colon with brain metastases whose initial symptom was neurological disorder, and reviewed 31 reported cases of SC. Case presentation A 70-year-old man was admitted to our hospital with the chief complaints of gait disorder and severe dizziness. Head magnetic resonance imaging revealed tumor masses in the anterior lobe and cerebellum. A large tumor in the transverse colon was detected by colonoscopy and abdominal enhanced computed tomography (CT), and was diagnosed as undifferentiated adenocarcinoma by histology. Laparoscopic extended right hemicolectomy was performed to remove the obstruction, and the resected specimens revealed an invasive tumor consisting of a mixture of carcinomatous and sarcomatous components. According to the immunopathological study, the patient was diagnosed with SC. The clinical course was extremely aggressive, and the patient died on the 28th postoperative day because of disease progression. Conclusion To the best of our knowledge, this is the first case of SC in the transverse colon with a neurological disorder derived from brain metastases. This experience may contribute to the guidance regarding proper therapeutic options for SC.

Aim We previously reported in a randomized controlled trial that Billroth I and Roux‐en‐Y reconstructions were generally equivalent regarding body weight change and nutritional status 1 year after distal gastrectomy for gastric cancer. We describe the long‐term follow‐up data 5 years after distal gastrectomy. Methods We analyzed consecutive gastric cancer patients who were randomly assigned to undergo Billroth I or Roux‐en‐Y reconstruction after distal gastrectomy. We evaluated body weight change, nutritional status, late complications, quality of life (QOL) using the European Organization for Research and Treatment of Cancer Core QOL Questionnaire, and dysfunction using the Dysfunction After Upper Gastrointestinal Surgery for Cancer, 5 years after surgery. Results A total of 228 patients (Billroth I = 105; Roux‐en‐Y = 123) were eligible for efficacy analyses in this study. Body weight loss 5 years after surgery did not differ significantly between the Billroth I and Roux‐en‐Y groups (10.0% ± 7.9% and 9.6% ± 8.4%, respectively; P = .70). There were no significant differences in other aspects of nutritional status between the two groups. Reflux esophagitis occurred in 19.0% of the patients in the Billroth I group vs 4.9% in the Roux‐en‐Y group (P = .002). Regarding QOL, Billroth I was significantly inferior to Roux‐en‐Y on the diarrhea scale (Billroth I: 28.6, Roux‐en‐Y: 16.0; P = .047). Regarding dysfunction, no score differed significantly between the two groups. Conclusions Billroth I and Roux‐en‐Y reconstructions were generally equivalent regarding body weight change, nutritional status, and QOL 5 years after distal gastrectomy, although Roux‐en‐Y more effectively prevented reflux esophagitis and diarrhea., Billroth I and Roux‐en‐Y reconstructions were generally equivalent regarding body weight change, nutritional status, and quality of life 5 years after distal gastrectomy, excluding reflux esophagitis and diarrhea.

Advanced gastric cancer with liver metastasis is classified as stage IV disease and is generally treated with systemic chemotherapy. Despite recent advances in chemotherapy regimens, the prognosis for gastric cancer with liver metastasis is poor. Recent studies reported the effectiveness of upfront chemotherapy followed by conversion surgery for gastric cancer with liver metastasis. Here, we report a case of an advanced stage IV gastric cancer with liver metastasis treated with upfront systemic chemotherapy followed by conversion surgery, which resulted in pathological complete response and good prognosis.A 79-year-old man diagnosed with human epidermal growth factor receptor type 2 (HER2)-positive gastric cancer with multiple liver metastases. He underwent systemic chemotherapy with capecitabine, cisplatin, and trastuzumab. After 14 courses of chemotherapy, the primary tumor and liver metastases shrank, suggesting a partial response. We performed distal gastrectomy with D2 dissection plus lateral hepatic segment resection. Pathological examination revealed no residual tumor cells in the primary or metastatic sites, which indicated a pathological complete response. The postoperative course was uneventful. The patient was discharged on postoperative day 8. Adjuvant S-1 chemotherapy was started on postoperative day 46 and given for 1 year. The patient has been alive and recurrence-free for approximately 5 years after surgery.This case shows the possibility of conversion surgery after systemic chemotherapy for stage IV advanced gastric cancer with liver metastasis.

The patient was a 75-year-old woman who was referred to our department because she had type 3 advanced gastric cancer on the posterior wall of the gastric body. Following a thorough examination, she was diagnosed as cT4aN3M1 (#16a1 int, #16b2 lat), cStage Ⅳ, an unresectable advanced gastric cancer with multiple extranodal lymph node metastases. As radical resection was not possible, chemotherapy(SOX therapy)was started. After the start of chemotherapy, the main lesion and metastatic lymph nodes shrank markedly. At the time of 7 courses, it was judged that R0 resection by conversion surgery was possible, and surgical treatment was performed. The patient underwent sub-total gastrectomy with D2 dissection and para-aortic lymph node dissection. The specimen was submitted for pathological examination and showed no residual tumor component including the main lesion and dissected lymph nodes, indicating a complete pathological response. She was started on S-1 as adjuvant chemotherapy on postoperative day 51 and has been recurrence-free for approximately 5 months after surgery.

Osteoporosis leads to fragility fractures and is a major public health problem. We conducted this study to analyze the prevalence of and risk factors for osteoporosis after gastrectomy in older patients.This multicenter prospective trial comprised older patients without recurrence of gastric cancer for 3 years after curative surgery. The prevalence of osteoporosis was identified using the World Health Organization bone mineral density (BMD)-based definition. Univariate and multivariate analyses were performed to identify the risk factors for osteoporosis.BMD values were measured in 267 of the 271 enrolled patients. The prevalence of osteoporosis was 38.2% (men 24.0%; women 60%). Analysis using FRAXThe prevalence of osteoporosis in older patients after gastrectomy was 38.2%. Moreover, female sex, age, low body mass index after gastrectomy, and a history of fracture were risk factors significantly associated with osteoporosis. Thus, older patients undergoing gastrectomy should have proactive surveillance and receive treatment for osteoporosis.

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

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

Atezolizumab plus bevacizumab combination therapy is the first cancer immunotherapy that has shown efficacy in the treatment of hepatocellular carcinoma(HCC). We report a case of HCC with recurrent peritoneal dissemination for which atezolizumab plus bevacizumab combination therapy was effective. The patient, a 63-year-old man, underwent transarterial embolization(TAE)for ruptured HCC, and a mass with dissemination on the caudal side of liver S3 was observed. Laparoscopic lateral hepatic resection plus resection of the dissemination plus cholecystectomy was thus performed in September 2019. However, in November 2019, multiple peritoneal dissemination recurrence was observed, and lenvatinib therapy was initiated. In May 2020, PD was observed, and we had switched to sorafenib therapy. However, in October 2020, further tumor growth and rapid increase in tumor markers(AFP 25,668 ng/mL, PIVKA-Ⅱ 64,960 mAU/mL)were observed, and the patient was judged to have PD. Atezolizumab plus bevacizumab combination therapy was initiated in the same month. Subsequently, a CT scan in January 2021 showed a marked decrease in tumor size, indicating PR. The tumor markers have since normalized(AFP 5 ng/mL, PIVKA-Ⅱ 28 mAU/mL). The patient has been treated with atezolizumab plus bevacizumab combination therapy again and is maintaining PR as an outpatient.

The patient was a 78-year-old man who underwent upper gastrointestinal endoscopy, revealing a sub-circumferential type 2 tumor in the lower body of the stomach. Histopathology revealed poorly differentiated adenocarcinoma. Computed tomography(CT)showed lymph node and liver metastasis(S6, S8), which corresponded to clinical Stage Ⅳ(cT4bcN2cM1 [HEP]). Five courses of XP therapy were administered for Stage Ⅳ disease. The sizes of the primary lesion and metastatic liver tumors were reduced, and a partial response was achieved. Distal gastrectomy and partial hepatectomy were performed. The resected specimen was diagnosed as ypT4b(transverse colon mesenteric), ypN0, ypM1(HEP). Thus, the final Stage was Ⅳ. During adjuvant chemotherapy with S-1, the para-aortic, left common iliac, and external peri-iliac lymph node metastases were detected by CT imaging 6 months after the operation. This prompted XP therapy resumption. The lymph node metastases worsened despite 2 additional XP courses. Progressive disease prompted the change in regimen to PTX plus RAM. After 7 courses, swollen lymph nodes were observed and CPT-11 was initiated. Since the disease continued to progress, nivolumab therapy was administered. The para-aortic, left common iliac, and external peri-iliac lymph nodes shrank after nivolumab initiation. The patient has responded well to nivolumab for more than 3 years without immunological adverse events.

We report the case of a patient who underwent additional surgical resection of a rectal neuroendocrine tumor(NET)G1 with a tumor diameter of 5 mm after endoscopic resection, and lymph node metastasis was observed. The patient was a 33- year-old woman. A lower gastrointestinal endoscopy was performed to examine the blood in the stool. A submucosal tumor of 5 mm in size was found in the rectum Ra, and endoscopic mucosal resection was performed. Pathological examination of the resected tissue revealed NET G1; HE staining revealed negative margins and no vascular invasion, but additional immunostaining revealed lymphatic invasion(Ly1a). Additional surgical resection was decided, and a laparoscopy-assisted low anterior resection D3 were performed. The surgical resection specimen showed no residual NET component in the rectum, but metastasis was found in one lymph node. The postoperative course of the patient has been uneventful, and the patient is currently undergoing without recurrence 6 months after the surgery. In the case of NET G1, it is important to search for detailed vascular invasion by immunostaining even in small lesions, and if vascular invasion is found, additional surgical resection should be considered.

We present a case of jejunal perforation just below the Treitz ligament treated with primary suture after administration of ramucirumab(RAM). The patient was a 74-year-old male. He was diagnosed with Stage Ⅳ sigmoid colon cancer with liver and lung metastasis. Laparoscopic sigmoid colon cancer resection was performed previously. As adjuvant chemotherapy, the patient received 3 courses of CapeOX plus bevacizumab(BEV)and 20 courses of FOLFOX plus BEV and was in PR. After operation for liver and lung metastases, the patient was observed without any treatment, but pelvic recurrence and lung metastasis were noted, and FOLFIRI plus RAM was started. On the 7th day after the second course, the patient experienced abdominal pain. Since an intestinal perforation was suspected, emergency surgery was performed on the same day. There was a 5-mm-diameter perforation in the jejunum just below the Treitz ligament, and were small ischemic changes near the perforation. The rest of the intestine was clear, the perforation was suspected due to RAM. Since anastomosis was difficult, we performed primary suture and decompression of the location. The postoperative course was uneventful, and the patient was discharged on POD 18. Currently, RAM has been discontinued and chemotherapy is being continued with FOLFIRI.

A 50s year old woman was referred to former hospital for abdominal pain and melena. Colonoscopy revealed an ascending colon cancer(cT4aN1bM0, cStage Ⅲb, UICC)and gastrointestinal endoscopy revealed an esophagogastric junction cancer(cT1bN0M0, cStage ⅠA, UICC). Preoperative CT showed mild bilateral hydronephrosis. Laparoscopic right hemicolectomy( Lap-RHC, D3)was performed for ascending colon cancer then, and abdominal CT was taken 2 days before the robot-assisted proximal gastrectomy(RAPG, D1+). Right hydronephrosis was observed. No evidence of obvious ureteral damage was found during Lap-RHC. When retrograde pelvic ureterography was performed and a stenosis was found at the right renal pelvis and ureteral junction. It is considered that the ureter stenosis became prominent due to the postoperative inflammatory change of Lap-RHC. RAPG was performed as scheduled. Two months after discharge, a renal fistula was constructed. Pyeloplasty is scheduled to be performed in the future.

Laparoscopic surgery is a safe, minimally invasive, and effective approach in managing abdominal malignancies. Laparoscopic anatomical resection has been covered by insurance in Japan since 2016. Here, we have reported the short-term outcomes of gallbladder cancer in laparoscopic cholecystectomy, gallbladder bed resection, or S4a/S5 liver resection with lymph node dissection.Between May 2012 and December 2020, 28 patients underwent laparoscopic cholecystectomy for gallbladder cancer at Kansai Rosai Hospital. Two patients underwent laparoscopic choledochotomy with lymph node dissection, 6 patients underwent gallbladder bed resection, and 7 patients underwent S4a/S5 liver resection. The control group included 13 patients who received open surgery between July 2010 and November 2019. The patient age was 74.2 and 74.4 years, while the male to female ratio was 19/24 and 8/5 in the laparoscopic and open surgery groups, respectively. According to the Japanese Society of Hepato-Biliary-Pancreatic Surgery, the pathological stage was 0/Ⅰ/Ⅱ/Ⅲ A/ⅢB/ⅣA/ⅣB in 4/17/13/4/2/1/2 and 0/1/2/3/1/1/5 patients(p=0.0100)in the laparoscopic and open surgery groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2101001).The laparoscopic surgery group had an average operation time of 223.3 minutes, an estimated blood loss of 18.7 g, and a hospital stay of 8.5 days. The open surgery group had an average operation time of 514.5 minutes, an estimated blood loss of 1,274.3 g, and a hospital stay of 33.9 days. There was no postoperative bleeding or bile leakage in both groups. After laparoscopic cholecystectomy, the 5-year disease-free survival rate was 100% among Stage 0 or Ⅰ patients, 64.8% among Stage Ⅱ patients, and 0% in Stage Ⅲ or Ⅳ patients. The 5-year overall survival rate was 100% among Stage 0 or Ⅰ patient and 66.7% among Stage Ⅱ patients. The 1-year overall survival rate was 50% among Stage Ⅲ or Ⅳ patients. After laparoscopic liver resection with lymph node dissection, the 5-year disease-free survival rate was 100% among Stage Ⅰ or Ⅱ patients and 66.7% among Stage Ⅲ or Ⅳ patients. The 5-year overall survival rate was 100% among Stage Ⅰ or Ⅱ patients and 62.5% among Stage Ⅲ or Ⅳ patients.Laparoscopic cholecystectomy in Stage 0 or Ⅰ patients and laparoscopic gallbladder bed resection or S4a/S5 liver resection with lymph node dissection were safe and effective approaches to gallbladder cancer management.

A 62-year-old man was referred to our hospital with complaints of upper abdominal pain and weight loss while being treated for diabetes mellitus at his family doctor. He was diagnosed as locally advanced unresectable pancreatic adenocarcinoma that involved superior mesenteric artery(SMA). Gemcitabine(GEM)and S-1 combined chemoradiotherapy(CRT) was administered. After CRT, CT test showed improved involvement of SMA, and radical resection was possible. We performed the radical pancreaticoduodenectomy and adjuvant chemotherapy, and he has been followed up for more than 5 years after the operation without recurrence. For locally advanced unresectable pancreatic adenocarcinoma, CRT or chemotherapy is recommended in the Pancreatic Cancer Practice Guidelines(2019 edition). However, the prognosis is extremely poor. We report a case of locally advanced unresectable pancreatic adenocarcinoma that was successfully curatively resected due to the good response of CRT.

We report a case of cholangiocellular carcinoma(CCC)with high-frequency microsatellite instability(MSI-H)in Lynch syndrome that was managed using a multimodal treatment approach including an immune checkpoint inhibitor. The patient was a 74-year-old man who presented with fever as the chief complaint. He had a history of Vater's papilla cancer and colorectal cancer in Lynch syndrome. A diagnosis of CCC in the left lobe of the liver was made, and left hepatectomy and left caudate lobectomy were performed. From about 2 years and 5 months after the operation, the patient developed several episodes of cholangitis, and recurrence of CCC was diagnosed based on the results of biliary cytology. Gemcitabine and cisplatin therapy was started, but exacerbation of bile duct stenosis associated with cancer progression was observed, and pembrolizumab, an immune checkpoint inhibitor, was started as the solid cancer had an MSI-H status. The tumor markers then improved and the cholangitis subsided. We experienced a case of recurrence of CCC with MSI-H in Lynch syndrome managed by multimodal treatment including an immune checkpoint inhibitor.

Recent retrospective studies have shown that increased intraoperative blood loss (IBL) during curative gastrectomy for patients with advanced gastric cancer is a negative prognostic indicator for recurrence. However, there are no reliable reports assessing this with a large-scale prospective cohort. This study aimed to evaluate the impact of IBL on long-term outcomes using data from the JCOG1001 phase III trial, which was designed to determine if bursectomy led to improved survival vs. nonbursectomy in patients with cT3/4a gastric cancer.This study included 1203 of the 1204 patients enrolled in the JCOG1001. From the tertiles of IBL (196 ml, 400 ml), we divided the patients into three groups: IBL 200 ml representing small blood loss (SBL, n = 404), 200 ml ≤ IBL 400 ml representing medium blood loss (MBL, n = 393), and IBL ≥ 400 ml representing large blood loss (LBL, n = 406). The impact of IBL on relapse-free survival (RFS) was evaluated with univariable comparisons and multivariable Cox regression analyses.Three-year RFS after SBL, MBL, and LBL was 81.7%, 74.8%, and 70.6%, respectively. Multivariable analysis identified IBL, Eastern Cooperative Oncology Group performance status, pT, pN, and postoperative adjuvant chemotherapy as independent predictors of RFS. Compared with SBL as a reference, the hazard ratios of MBL and LBL were 1.461 (P = 0.012) and 1.520 (P = 0.009), respectively.Based on the analysis of data from a large-scale prospective study, an IBL of ≥ 200 ml after curative surgery for patients with cT3/4a gastric cancer was an independent predictor of reduced RFS.

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.

Laparoscopic liver resection (LLR) has been reported as a safe, minimally invasive, and effective surgery for the management of liver tumor. However, the efficacy and safety of laparoscopic repeat liver resection (LRLR) for recurrent liver tumor are unclear. Here, we analyzed the surgical results of LRLR. From June 2010 to May 2019, we performed 575 LLR surgeries in our department, and 454 of them underwent pure LLR for the single tumor. We classified the patients who received pure LLR for the single tumor into three groups: LRLR (n = 80), laparoscopic re-operation after previous abdominal surgery (LReOp; n = 136), and laparoscopic primary liver resection (LPLR; n = 238). We compared patient characteristics and surgical results between patients undergoing LRLR, LReOp and LPLR. We found no significant differences between LRLR and LPLR in the conversion rate to laparotomy (p = 0.8033), intraoperative bleeding (63.0 vs. 152.4 ml; p = 0.0911), or postoperative bile leakage rate (2.50 vs. 3.78%; p = 0.7367). We also found no significant difference in the surgical results between LReOp and LPLR. However, the number of patients undergoing the Pringle maneuver was lower in the LRLR group than the LPLR group (61.3 vs. 81.5%; p = 0.0004). This finding was more pronounced after open liver resection than laparoscopic liver resection (38.9 vs. 67.7%; p = 0.0270). The operative time was significantly longer in patients with proximity to previous cut surface than patients with no proximity to previous cut surface (307.4 vs. 235.7 min; p = 0.0201). LRLR can safely be performed with useful surgical results compared to LPLR.

Advances and improvements in cancer diagnosis and treatment have made it possible to find multiple primary cancers. We report here a rare case of metachronous quintuple cancer involving the stomach, rectum, colon, liver and prostate. An 80s‒ year‒old male was referred to our hospital with abnormality on upper GI series. He had undergone a distal gastrectomy in May 2005. Postoperative diagnosis was advanced gastric cancer (pT2N1M0, pStage ⅡA). In August 2006, anterior resection was performed with a diagnosis of advanced rectal cancer(pT3N0M0, pStage Ⅱa). For ascending colon polyps, endoscopic submucosal dissection was performed with a diagnosis of adenocarcinoma in adenoma(pTisN0M0, pStage 0)in September 2007. In June 2016, laparoscopic ileocecal resection was performed with a diagnosis of advanced cecum cancer(pT3N0M0, pStage Ⅱa). Follow up CT images showed a liver tumor in S4. Partial liver resection was performed in October 2010. Postoperative pathological diagnosis was hepatocellular carcinoma(pT2N0M0, pStage Ⅱ). Prostate cancer(cT2aN0M0)was treated by androgen deprivation therapy from February 2018. Although he had high‒frequency microsatellite instability, germline mutations in hMLH1 and hMSH2 genes were not detected. Histopathological examination showed that each tumor was an independent tumor and had not metastasized from any others. The patient had a good clinical course after these treatment until now.

Summary Background Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is standard care for stage II gastric cancer. Whether the duration of S-1 could be shortened to 6 months (corresponding to four courses) without worsening survival is unclear. The aim of this study was to investigate the non-inferiority of four courses of S-1 compared with eight courses of S-1 for patients with stage II gastric cancer. Methods We did a phase 3, open-label, randomised controlled, non-inferiority trial at 59 hospitals in Japan. Patients aged 20–80 years with stage II adenocarcinoma of the stomach were randomly assigned (1:1) to eight courses or four courses of S-1. Randomisation was done by the Japan Clinical Oncology Group Data Center website, using a minimisation method with a random component using institution, stage (IIA vs IIB), age ( vs ≥70 years), and mode of operation (open gastrectomy with bursectomy vs open gastrectomy without bursectomy vs laparoscopic gastrectomy) as adjustment factors. One course was 80 mg/day per m 2 of S-1 administered for 4 weeks followed by a rest for 2 weeks. The primary endpoint was relapse-free survival, analysed by intention to treat, with a non-inferiority margin for the hazard ratio (HR) set at 1·37. This study is registered at UMIN-Clinical Trial Registry, number UMIN000007306. Findings Between Feb 16, 2012, and March 19, 2017, 590 patients were enrolled (295 per group). 528 (89%) patients were analysed at the first planned interim analysis in March, 2017, at which time the point estimate of HR for the four-course group compared with the eight-course group was 2·52 (95% CI 1·11–5·77), which exceeded 1·37 and met the prespecified criteria for early termination. Predictive probability for showing non-inferiority at the final analysis was calculated to be 2·9%. The study was stopped for futility. Updated 3-year relapse-free survival analysed in May, 2017, was 93·1% (95% CI 87·8–96·1) for the eight-course group and 89·8% (84·2–93·5) for the four-course group (HR 1·84, 95% CI 0·93–3·63). The most common grade 3–4 adverse event was neutropenia, observed in 46 (16%) patients in the eight-course group and 51 (17%) patients in the four-course group. Interpretation S-1 for 1 year should remain as standard adjuvant chemotherapy for stage II gastric cancer. Funding Japan Agency for Medical Research and Development; the Ministry of Health, Labour and Welfare of Japan; the National Cancer Center Research and Development Fund, Japan.

Background/aim Trastuzumab with S-1 plus cisplatin was proved to be effective for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer with measurable lesions. However, the efficacy and safety of this regimen in the absence of measurable lesions are unknown. Patients and methods Patients with HER2-positive gastric cancer without measurable lesions received cisplatin plus trastuzumab intravenously on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The primary end-point was overall survival, and 40 patients were planned to be enrolled. Results Fifteen patients were enrolled. The median overall survival was 14.4 months. The 1- and 3-year overall survival rates were 66.7 % and 26.7 %, respectively. Major grade 3-4 adverse events included neutropenia (47%), anemia (40%), diarrhea (20%), nausea (20%), and anorexia (20%). Conclusion Trastuzumab with S-1 plus cisplatin might be effective and tolerable for HER2-positive advanced gastric cancer without measurable lesions.

Background/Aim: If both distant metastases and the primary tumour of colorectal cancer (CRC) are resectable, resection of the distant metastases is considered. The aim of this retrospective study was to determine the efficacy of curative resection of both primary and metastatic lesions in organs other than liver or lung in CRC patients. Patients and Methods: The medical records of 23 CRC patients who received R0 resection for primary and metastatic regions between 2009 and 2018 were retrospectively analyzed. Results: The 3-year overall survival (OS) in all 23 cases was 80.0%. There was no clinicopathological factor associated with OS on univariate analysis. Conclusion: Curative surgical resection appears to be useful for distant CRC metastases to organs other than liver or lung.

Background There is no standard chemotherapy for esophageal squamous cell carcinoma (ESCC) refractory to first-line fluoropyrimidine- and platinum-based chemotherapy. We therefore performed a randomized, selection-design phase II trial to compare docetaxel (DTX) and paclitaxel (PTX) in this setting. Patients and methods Eligible patients were randomly assigned to receive either DTX (70 mg/m2 on day 1 of each 21-day cycle) or PTX (100 mg/m2 on days 1, 8, 15, 22, 29 and 36 of each 49-day cycle). The primary end-point was overall survival (OS), and secondary end-points included progression-free survival (PFS), time to treatment failure (TTF), response rate (RR) and safety. Results Seventy-eight eligible patients (N = 39 in each group) were included for efficacy analysis. OS was significantly longer in the PTX group than in the DTX group (median, 8.8 versus 7.3 months; hazard ratio [HR], 0.62; P = 0.047). A significant benefit of PTX over DTX was also apparent in PFS (median, 4.4 versus 2.1 months; HR, 0.49; P = 0.002) and TTF (median, 3.8 versus 2.1 months; HR, 0.45; P Conclusion PTX showed a significantly better efficacy as well as a more manageable toxicity compared with DTX. Clinical trial registration UMIN000007940.

Pancreatic neuroendocrine tumor(p-NET)is a relatively rare disease, and treatment is multidisciplinary with resection, local therapy, radiotherapy, and chemotherapy. We report on a case in which long-term survival was achieved by multidisciplinary treatment. The case is a 47-year-old male. He was referred to our hospital because of the diagnosis of pancreatic tail tumor and underwent distal pancreatectomy in May 2008. And he was diagnosed as p-NET G1 by the pathological results. After 3 TACE treatments and 1 partial liver resection for recurrent liver metastasis, multiple liver metastases and lymph node metastases were found in August 2014. As a result of the everolimus treatment, the determination of efficacy to lymph nodes was CR and liver lesions were CR with the addition of TACE treatment. In July 2017, he had multiple liver metastases and right humeral metastases, and has been treated with radiotherapy for bone metastases and has maintained CR. After TACE in November 2017, he received 9 rounds of lanreotide treatment. In December 2018, he again had liver metastases and lymph node recurrence. He has been treated with everolimus treatment again and is maintaining SD in outpatient treatment.