C-reactive protein-to-albumin ratio as a risk factor for anastomotic leakage after anterior resection for rectal cancer with intraoperative use of indocyanine green fluorescence imaging.

INTRODUCTION: Indocyanine green fluorescence imaging (ICG-FI) reduces anastomotic leakage (AL) in rectal cancer surgery. However, no studies investigating risk factors for anastomotic leakage specific to the group using ICG-FI have ever previously been conducted. The purpose of this retrospective multicenter study was to ascertain the risk factors for AL in the group using ICG-FI. METHODS: A total of 638 patients who underwent laparoscopic or robotic anterior resection for rectal cancer between April 2018 and March 2023 were included in this study. Patients were divided into two groups: the ICG-FI group (n = 269) and the non-ICG-FI group (n = 369) for comparative analysis. The effects of clinicopathological and treatment-related factors on AL in the ICG-FI group were evaluated using both univariate and multivariate analyses. RESULTS: The incidence of AL in the ICG-FI group was 4.8%. Although there was no significant difference in the incidence of AL between the two groups, it was observed to be lower in the ICG-FI group. A multivariate analysis revealed a preoperative C-reactive protein-to-albumin ratio (CAR) ≥ 0.049 (odds ratio, 3.73; 95% confidence interval, 1.01-13.70; p = 0.048) as an independent risk factor for AL in the ICG-FI group. CONCLUSIONS: In this study, CAR was the only identified risk factor for AL in the ICG-FI group. It was suggested that CAR could be a criterion for early surgical intervention, prior to the escalation of risks, or for considering interventions such as diverting stoma creation.

Prospective observational study comparing the perioperative outcomes of laparoscopic colectomy with or without epidural anesthesia: the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC) 1806.

PURPOSE: There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA). METHODS: This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery. RESULTS: We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O. CONCLUSION: These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia.

Short- and long-term outcomes of transanal decompression tube and self-expandable metallic stent for obstructive colorectal cancer based on a multicenter database (KYCC2110).

AIM: There are well-known methods for decompressing the colorectal tract before surgery, including transanal decompression tubes (TDT) and self-expanding metallic stents (SEMS). This study aimed to compare the short and long-term results in patients with malignant large bowel obstruction in whom TDT or SEMS were placed before surgery. METHODS: This retrospective observational study enrolled 225 patients with malignant large bowel obstruction in whom TDT or SEMS were placed preoperatively and underwent R0 resection between 2008 and 2020. One-to-two propensity score matching was performed according to patient characteristics. Short- and long-term outcomes were compared. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were the overall survival (OS) and postoperative complication rate. RESULTS: Fifty-seven patients in the TDT group and 114 in the SEMS group were matched. The 3-year RFS rates were 66.7% in the TDT group and 69.9% in the SEMS group (p = 0.54), and the 3-year OS rates were 90.5% in the TDT group and 87.1% in the SEMS group (p = 0.52). No significant differences in the long-term results were observed between the two groups. Regarding short-term results, the SEMS group had significantly fewer stoma construction (p = 0.007) and shorter postoperative hospitalization (p < 0.001). The incidence of postoperative complications (grade ≥ 2) was significantly lower in the SEMS group (p = 0.04). CONCLUSION: No significant differences in the long-term results were observed between the TDT and SEMS group. The SEMS showed significant usefulness in terms of improving short-term outcomes.

Analysis of surgical outcomes of laparoscopic versus open surgery for locally advanced mid-transverse colon cancer.

PURPOSE: This study compared the surgical outcomes between laparoscopic colectomy (LC) and open colectomy (OC) for mid-transverse colon cancer (MTC). METHODS: This multicenter retrospective study compared the short- and long-term surgical outcomes for patients with advanced MTC (T3 and T4 with or without nodal involvement) who underwent LC or OC between January 2008 and December 2019 using a propensity score-matched analysis. RESULTS: A total of 177 patients with advanced MTC were enrolled. After matching, 58 cases for the OC and LC groups were selected. No significant differences in age, sex, tumor progression, or procedure type (extended resection or segmental resection) existed between groups. The LC group had significantly less blood loss (20 mL vs. 50 mL, p=0.048) and a shorter postoperative hospital stay (8 days vs. 12 days, p<0.001) than the OC group. Postoperative complications (Clavien-Dindo grade ≥ 2) occurred in 27.6% and 25.9% of the OC and LC groups respectively (p=1). Three patients (5.2%) and one patient (1.7%) of the OC and LC groups respectively developed anastomotic leakage (p=0.62). Re-operation was required in five patients (8.6%) in the OC group and one patient (1.7%) in the LC group (p=0.21). No surgery-related deaths occurred in either group. The 3-year overall survival rates (stage II: LC 100% vs. OC 92.8%, p=0.15; stage III: 88.9% vs. 84.3%, p=0.88, respectively) were similar between the two groups. CONCLUSION: LC is a minimally invasive technique with lesser blood loss, shorter postoperative hospital stays, and oncologic equivalence to OC. Hence, LC is useful for MTC treatment. TRIAL REGISTRATION: UMIN000042676.

Prediction of lateral lymph node metastasis using OSNA method for mesorectal lymph nodes in low rectal cancer: A prospective study by the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC1801).

BACKGROUND AND OBJECTIVES: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. METHODS: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. RESULTS: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. CONCLUSIONS: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.

Does the Endoscopic Surgical Skill Qualification System improve patients' outcome following laparoscopic surgery for colon cancer? A multicentre, retrospective analysis with propensity score matching.

BACKGROUND: This study aimed to investigate the short-term and oncological impact of the Endoscopic Surgical Skill Qualification System (ESSQS) by the Japan Society for Endoscopic Surgery on the operator performing laparoscopic surgery for colon cancer. METHODS: This retrospective cohort study was based on medical records from a multicentre database. A total of 417 patients diagnosed with stage II/III colon and rectosigmoid cancer treated with curative resection were divided into two groups according to whether they were operated on by qualified surgeons (Q group, n=352) or not (NQ group, n=65). Through strict propensity score matching, 98 cases (49 in each group) were assessed. RESULTS: Operative time was significantly longer in the NQ group than in the Q group (199 vs. 168 min, p=0.029). The amount of blood loss, post-operative complications, and duration of hospitalisation were similar between both groups. No mortality was observed. One conversion case was seen in the NQ group. The 3-year recurrence-free survival rate was 86.6% in the NQ group and 88.2% in the Q group, which was not statistically significant (log-rank p=0.966). CONCLUSION: Direct operation by ESSQS-qualified surgeons contributed to a shortened operation time. Under an organised educational environment, almost equivalent safety and oncological outcomes are expected regardless of the surgeon's qualifications.

Lateral lymph node dissection for mid-to-low rectal cancer: is it safe and effective in a practice-based cohort?

BACKGROUND: Most evidence regarding lateral lymph node dissection for rectal cancer is from expert settings. This study aimed to evaluate the safety and efficacy of this procedure in a practice-based cohort. METHODS: A total of 383 patients who were diagnosed with stage II-III mid-to-low rectal cancer between 2010 and 2019 and underwent primary resection with curative intent at a general surgery unit were retrospectively reviewed. After propensity matching, 144 patients were divided into the following groups for short- and long-term outcome evaluation: mesorectal excision with lateral lymph node dissection (n = 72) and mesorectal excision (n = 72). RESULTS: This practice-based cohort was characterized by a high pT4 (41.6%) and R1 resection (10.4%) rate. Although the operative time was longer in the lateral dissection group (349 min vs. 237 min, p < 0.001), postoperative complications (19.4% vs. 16.7%, p = 0.829), and hospital stay (18 days vs. 22 days, p = 0.059) did not significantly differ; 5-year relapse-free survival (62.5% vs. 66.4%, p = 0.378), and cumulative local recurrence (9.7% vs. 15.3%, p = 0.451) were also in the same range in both groups. In the seven locally recurrent cases in the lateral dissection group, four had undergone R1 resection. CONCLUSIONS: Lateral lymph node dissection was found to be safe in this practice-based cohort; however, the local control effect was not obvious. To maximize the potential merits of lateral lymph node dissection, strategies need to be urgently established to avoid R1 resection in clinical practice.

Laparoscopic surgery in patients diagnosed with clinical N2 colon cancer.

PURPOSE: The benefits of laparoscopic surgery for colorectal cancer have been well established. Several randomized controlled trials have demonstrated similar oncological outcomes between laparoscopic and open surgery for colon cancer. However, whether or not laparoscopic surgery is acceptable in patients with clinical N2 colon cancer is unclear. Therefore, the present study aimed to evaluate the safety and oncological outcomes of laparoscopic surgery for clinical N2 colon cancer. METHODS: This retrospective study assessed a prospective database and identified 262 consecutive patients with clinical N2 colon cancer who underwent either laparoscopic or open primary resection between 2000 and 2016. After propensity-score matching, 162 patients were analyzed. The primary outcome of interest was the 3-year recurrence-free survival rate, and the secondary outcome of interest was the postoperative complication rate. RESULTS: The 3-year recurrence-free survival rate did not differ markedly between the laparoscopic and open surgery groups (77.4% vs. 76.5%, p = 0.620). In addition, the incidence of postoperative complications did not differ markedly between the laparoscopic and open surgery groups (16.6% vs. 24.0%, p = 0.317). CONCLUSIONS: Our findings suggest that laparoscopic surgery is safe and effective for clinical N2 colon cancer. Laparoscopic resection can be considered in patients diagnosed with clinical N2 colon cancer.

[A Case of Malignant Peritoneal Mesothelioma Resected Four Times in Five Years].

We report a long-surviving case of malignant peritoneal mesothelioma requiring 4 operations in 5 years. A 63-year-old man was diagnosed with gastrointestinal stromal tumor(GIST)that was excised for the first time in June 2011. The pathological diagnosis was malignant peritoneal mesothelioma. Thereafter, we excised recurrences of the tumor in the hepatic hilum in December 2011. Similar operations were performed in March 2012 and August 2015 because of tumors in the small bowel mesentery and the segment 8 of the liver. The pathological diagnosis was malignant peritoneal mesothelioma. It is an extremely rare variant of malignant peritoneal mesothelioma. There is no record of multiple excision of malignant peritoneal mesothelioma for recurrences. In this case, the cause of long survival was considered to be the excision of recurrent tumors.

[Eight Cases of Primary Carcinoma of the Vermiform Appendix].

Primary carcinoma of the vermiform appendix is a rare neoplasm, and its treatment strategy has not yet been established. We retrospectively analyzed 8 cases of primary carcinoma of the vermiform appendix from 2007 to 2017. Six cases were male and two were female, with a median age of 60.5 years. Ileocecal resection and right hemicolectomy were performed in 7 cases and 1 case, respectively. Regarding pathological staging, 5 cases were of pStage Ⅱ, 2 were of pStage Ⅲa, and 1 was of pStage Ⅳ. Three cases had recurrences after curative resection. The postoperative median overall survival time was 45 months. Three cases with a tumor diameter of 20mm were alive without any recurrence; however, 3 of 5 cases with a tumor diameter of B21mm had recurrences. Although only 1 of 3 cases with adjuvant chemotherapy(pStage Ⅲa case)had recurrence, 2 of 4 cases without adjuvant chemotherapy, including a pStage Ⅱ case, had recurrences. Early diagnosis, surgery, and adjuvant chemotherapy could improve the long-term outcomes of patients with primary carcinoma of the vermiform appendix.

A prospective randomized controlled trial of subcutaneous passive drainage for the prevention of superficial surgical site infections in open and laparoscopic colorectal surgery.

INTRODUCTION: A number of studies have evaluated the effects of subcutaneous drainage during digestive surgery. All of the previous studies assessed the usefulness of active-suctioning drain, including two randomized controlled studies which found no benefit for the placement of active-suctioning drains in digestive surgery. The utility of passive drainage has not been evaluated previously. The purpose of this study was to evaluate the efficacy of subcutaneous passive drainage system for preventing surgical site infections during major colorectal surgery. PATIENTS AND METHODS: A total of 263 patients who underwent major colorectal surgery were enrolled in this study. Patients were randomly assigned to receive subcutaneous passive drainage or no drainage. The primary outcome measured was the incidence of superficial surgical site infections. The secondary outcomes measured were the development of hematomas, seromas, and wound dehiscence. RESULTS: Finally, a total of 246 patients (124 underwent passive drainage, and 122 underwent no drainage) were included in the analysis after randomization. There was a significant difference in the incidence of superficial surgical site infections between patients assigned to the passive drainage and no drainage groups (3.2 % vs 9.8 %, respectively, P = 0.041). There were no cases that developed a hematoma, seroma, or wound dehiscence in either group. A subgroup analysis revealed that male gender, age ≥75 years, diabetes mellitus, American Society of Anesthesiologists (ASA) status ≥2, blood loss ≥100 ml, and open access were factors that were associated with a beneficial effect of subcutaneous passive drainage. CONCLUSIONS: Subcutaneous passive drainage provides benefits over no drainage in patients undergoing major colorectal surgery.

Perivascular epithelioid cell tumor of the rectum: report of a case and review of the literature.

We report a case of perivascular epithelioid cell tumor arising in the rectum of a 55-year-old woman. The tumor was treated by transanal endoscopic microsurgery. After 1 year follow-up, the patient is alive with no radiologic or endoscopic evidence of recurrence. Perivascular epithelioid cell tumor is a rare mesenchymal tumor characterized by co-expression of melanocytic and smooth muscle markers. This rare tumor can arise in various organs, including the falciform ligament, uterus, uterine cervix, liver, kidney, lung, breast, cardiac septum, pancreas, prostate, thigh, and gastrointestinal tract. Perivascular epithelioid cell tumor of the gastrointestinal tract is very rare, with only 23 previously reported cases. We review the literature on perivascular epithelioid cell tumors arising in the gastrointestinal tract.

Multicenter prospective study on anastomotic leakage after right-sided colon cancer surgery with laparoscopic intracorporeal overlap anastomosis (KYCC 2101).

Aim: Intracorporeal anastomosis (IA) is becoming increasingly popular and replacing extracorporeal anastomosis (EA) for reconstruction in laparoscopic and robotic surgery for right-sided colon cancer (LSRCC). Intracorporeal overlap anastomosis (IOA) is the most widely used IA technique. This study aimed to examine the safety of IOA by investigating its short-term results during the implementation phase. Methods: This multicenter prospective cohort study was conducted by the Kanagawa Yokohama Colorectal Cancer (KYCC) Study Group. Patients with stage 1-3 colon cancer who planned to undergo LSRCC with IOA reconstruction were eligible. The incidence of anastomotic leakage (AL) of Clavien-Dindo (C-D) grade ≥3 was evaluated as the primary endpoint, and other surgical outcomes and postoperative complications of C-D grades ≥2 were the secondary endpoints. Results: A total of 127 patients were enrolled, of whom 120 were finally analyzed. The incidence of C-D grade ≥2 complications was 8.3%. The incidence of C-D grade ≥3 AL was 0.8%. This trend was lower than that reported in previous randomized controlled trials (RCTs) and acceptable. Additionally, 1.7% of the patients developed abdominal abscesses, and no cases of anastomotic stenosis were observed. The median operative time was 257 min, and the reconstruction procedure required 32 min. Stapler closure of the enterotomy and facility experience of more than 30 cases were associated with a shorter reconstruction time during IOA. Conclusion: IOA is feasible and can be safely performed during the implementation phase in patients undergoing LSRCC.

The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease.

BACKGROUND: The guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies. METHODS: 144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed. RESULTS: Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as stageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In stageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology. CONCLUSIONS: Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with stageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis.

Impact of Infectious Complications on Survival and Recurrence of Patients With Stage II/III Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIM: Postoperative complications are associated with increased recurrence in colorectal cancer (CRC). We investigated the impact of infectious complications on the recurrence of CRC and overall survival after curative surgery in a single study group. PATIENTS AND METHODS: In total, 1,668 patients who underwent radical resection for CRC in Yokohama City University, Yokohama Minami Kyosai Hospital, and Kanagawa Cancer Center between 2011 and 2019 were reviewed. Patients were classified into those with infectious complications (IC group) and those without infectious complications (Non-IC group). The risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: Postoperative complications were found in 560 of the 1,668 patients (33.5%), and IC, which occurred in 312 patients (18.7%), included pneumonia, anastomotic leakage, and intraperitoneal abscess. The 5-year OS rates in the Non-IC and IC groups were 95.5% and 90.4%, respectively, while the 5-year RFS rates were 74.4% and 68.1%, respectively. The multivariate analysis demonstrated that postoperative IC were significant independent risk factors for OS and RFS. CONCLUSION: The presence of postoperative IC after CRC resection is associated with decreased long-term survival. The surgical procedure, surgical strategy, and perioperative care should be carefully planned in order to avoid causing IC.

Laparoscopic-assisted surgery versus open surgery for transverse colon cancer: A multicenter retrospective study.

Introduction: Previous randomized controlled trials demonstrated similar oncological outcomes between laparoscopic-assisted (LA) and open (OP) colectomy; however, patients with transverse colon cancer were not analyzed. The aim of this study was to confirm the oncological safety and the advantages of the short- and long-term results of LA surgery for transverse colon cancer in comparison to OP surgery. Materials and Methods: The study data were retrospectively collected from the databases of four hospitals. Patients with transverse colon cancer who underwent LA or OP R0 or R1 resection were registered. Results: Among the 204 patients, 149 underwent OP colectomy and 55 underwent LA colectomy. The median follow-up period was 43 months. The rate of conversion to OP resection was 7.3%. The 5-year overall survival rate of the LA group was higher than that of the OP surgery group for all-stage patients (97.5% vs. 91.1%, P = 0.108), and it was similar in Stage II and Stage III patients (94.1% vs. 94.2%, P = 0.510). The LA group had significantly lower blood loss and a significantly longer operative time in comparison to the OP surgery group. Furthermore, the postoperative hospital stay was significantly shorter (9 vs. 13 days, P = 0.001) and the incidence of Grade ≥III complications was lower in the LA group (3.7% vs. 14.8%, P = 0.031). Conclusion: We concluded that LA surgery for transverse colon cancer is oncologically safe and yields better short-term results in comparison to OP surgery.

A Case of Robotic Posterior Rectopexy for Full-thickness Rectal Prolapse.

We describe our experience with robotic posterior rectopexy for a patient with full-thickness rectal prolapse. To our knowledge, this is the first report of such a case in the literature. A 94-year-old woman presented with a history of gradually worsening rectal prolapse. On examination, we found that the rectum was completely prolapsed, and we observed a prolapsed intestinal tract. Surgery was indicated and robotic rectopexy was performed without intraoperative complications. The postoperative course was uneventful, and she was discharged 10 days after the operation. One year later, there were no signs of recurrence. Robotic surgery has become common in recent years. We used robotic surgery for rectopexy, including the suturing procedure. Suturing in robotic surgery is easier than that in laparoscopic surgery, and we demonstrated that robotic rectopexy could be safely and easily performed. The trial was registered in the UMIN clinical trial registry (number 000040378).

MDM2 gene amplification in colorectal cancer is associated with disease progression at the primary site, but inversely correlated with distant metastasis.

MDM2 is a crucial negative regulator of the TP53 tumor suppressor and almost 10% of human tumors exhibit MDM2 amplification. Although TP53 pathway perturbation has been extensively examined in colorectal cancer (CRC), only one previous report has evaluated MDM2 amplification in relation to clinicopathological factors. In that report, MDM2 amplification was shown to be associated with disease progression from Dukes' Stages A to D. In this study, we investigated MDM2 amplification by quantitative PCR and fluorescence in situ hybridization (FISH) together with the SNP309 genotypes, and analyzed the correlations with TP53 and KRAS mutations and clinicopathological features in 211 Japanese CRC patients. MDM2 amplification was detected in 8% of the specimens and its incidence was significantly higher in Dukes' stage C than in the combined earlier Stages A and B (P = 0.025). Unexpectedly, the incidence was significantly decreased in Stage D metastatic disease (P = 0.043). The copy number gain ranged from four to eight copies and was generally concordant with gain of centromere 12 using FISH analysis. Together with the results of centromere 1 FISH and TP53 copy number assessment, the MDM2 increment most likely resulted from chromosome 12 gain. The mechanism of the copy number gain and incidence in Dukes' Stage D differed considerably from the previous report. Ethnic or geographic factors could be responsible for these differences. Several promising therapeutic strategies targeting the TP53-MDM2 system are being developed. Further understanding of the significance of MDM2 and MDM2 amplification in CRC is required to facilitate personalized treatment for CRC patients.

[Three cases of advanced gastric cancer successfully treated by combination therapy of biweekly S-1 and docetaxel].

We report three cases of advanced gastric cancer successfully treated by combination therapy of S-1 and docetaxel (DOC). We administered S-1 orally at 80 mg/m² on days 1 to 7 and days 15 to 21, and DOC intravenously at 40 mg/m² on day 1 and 15, and evaluation was conducted every two courses. Case 1: A 73-year-old man with gastric cancer of cT4a, accompanied with bulky N2 lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by total gastrectomy, which revealed his histological grade to be 1b. Case 2: A 65-year-old man with gastric cancer of cT4a, accompanied with bulky lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by distal gastrectomy, which revealed his histological grade to be 1b. Case 3: A 76-year-old woman with gastric cancer of cT4b (panc), was treated with four courses of S-1 and DOC. After that, the main tumor was judged to be cT4a, followed by total gastrectomy, which revealed her histological grade to be 1b. Combined S-1 and DOC chemotherapy is an effective regimen for the treatment of unresectable gastric cancer.