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To evaluate the efficacy and safety of the enhanced recovery after surgery (ERAS) protocol and quantify the impact of each ERAS item on postoperative outcomes.We used a generalized linear model to compare 289 colorectal cancer patients treated with the ERAS protocol between June, 2015 and April, 2021, with 99 colorectal cancer patients treated with the conventional colorectal surgery pathway between April, 2014 and June, 2015.The median length of hospital stay (LOHS) was significantly shorter in the ERAS group, at 9 days (range 3-104 days) vs. 14 days (range 4-44 days) (p 0.001), but the complication rates (Clavien-Dindo grade 2 or more) were similar (16.6% vs. 22.2%; p = 0.227). However, in the ERAS group, the higher the compliance with ERAS items, the lower the complication rate and LOHS (both p 0.001). Multiple regression analysis demonstrated that "Discontinuation of continuous intravenous infusion on POD1" and "Avoidance of fluid overload" were significantly associated with the LOHS (p 0.001 and p = 0.008).The ERAS protocol is safe and effective for elective colorectal cancer surgery, and compliance with the ERAS protocol contributes to shorter LOHS and fewer complications. Items related to perioperative fluid management had a crucial impact on these outcomes.

Purpose: The purpose of this study was to evaluate the safety and efficacy of an enhanced recovery after surgery (ERAS) protocol in elderly patients undergoing colorectal cancer surgery. Methods: The study included 273 patients undergoing laparoscopic colorectal surgery conducted following the ERAS protocol from June 2015 to April 2021 and 63 patients undergoing laparoscopic colorectal surgery according to conventional care (April 2014 to June 2015). Results: We compared elderly patients (age ≥75 years) in the ERAS and conventional care groups. The median (range) length of hospital stay (LOHS) was significantly shorter in the ERAS group (9 [4–95] days with ERAS vs. 13 [4–37] days with conventional care, p < 0.001), but the complication rate (Clavien–Dindo grade 2 or more) was similar (16.8% ERAS vs. 18.5% conventional care, p = 0.784). We found no significant differences between groups in postoperative mortality rates, reoperation rates, and readmission rates within 30 days. In a comparison of elderly and non-elderly patients receiving ERAS, the elderly group had significantly longer median (range) LOHS (8 [3–104] days for non-elderly vs. 9 [4–95] days for elderly patients, p = 0.028). Furthermore, overall compliance with the ERAS protocol was lower and median LOHS significantly longer for patients undergoing proctectomy compared with those undergoing colectomy. Conclusion: The ERAS protocol shows efficacy and safety for elderly patients undergoing laparoscopic colorectal cancer surgery, but proctectomy remains a challenge for adult patients of any age.

Objectives The efficacy of negative pressure wound therapy (NPWT) and its application to severely contaminated wounds sustained during surgery remain to be established. Here, we evaluated the efficacy of utilizing NPWT until delayed primary closure (DPC) by assessing the infection rates in patients with lower gastrointestinal perforations. Methods This prospective multicenter cohort study included 56 patients that underwent abdominal surgery for lower gastrointestinal perforations in eight institutions, from February 2016 to May 2017. All patients received NPWT after surgery before attempting DPC. The extent of peritonitis was categorized according to Hinchey's classification. Patients in stages II-IV were included. Results Five patients had surgical site infections (SSIs) during NPWT and did not receive a DPC (9%). Of the 51 patients that received DPCs, 44 had no infection (91%) and 7 developed SSIs after the DPC (13.7%). For stages II, III, and IV, the SSI rates were 0%, 22.6%, and 35.7%, respectively; the median (range) times to wound healing were 15 (10-36), 19 (11-99), and 19 (10-53) days, respectively. There were no significant differences between the stages. Conclusions NPWT followed by DPC resulted in low infection rates in each peritonitis stage. This approach appears promising as an alternative to traditional DPC alone for treating lower gastrointestinal perforations.

Case 1, the patient was a 51-year-old man. Upper gastrointestinal endoscopy revealed a submucosal tumor with delle at the posterior wall of the gastric body, and the biopsy demonstrated a diagnosis of GIST. Abdominal CT scan showed a tumor at the size of 130×110×90 mm. Six months after administration of 400 mg/day of imatinib, the maximum diameter was reduced to 55 mm, then partial gastrectomy was performed by laparoscopic surgery. He continued to take imatinib after the surgery for 3 years, and he is alive without recurrence 4 years postoperatively. Case 2, the patient was a 68-year-old man. An abdominal CT scan showed a tumor at the size of 160×120×85 mm on the posterior outside of the stomach, but no submucosal tumor could be identified by upper gastrointestinal endoscopy. Gastric GIST was suspected and he started taking imatinib 400 mg/day. Because the Grade 3 generalized eruption was appeared, imatinib was discontinued, and then the dose was reduced. Nine months after the initiation of the treatment, the maximum diameter was reduced to 90 mm, and laparoscopic partial gastrectomy was performed. The patient is followed up without administration of imatinib after the surgery, and is alive without recurrence for 1 year and 6 months postoperatively. We report 2 cases that the large gastric GIST was able to be resected safely and completely due to tumor shrinkage by neoadjuvant imatinib therapy.

The patient was a 72-year-old man with a history of pancreatic cancer and IPMA treated with distal pancreatectomy. He had recurrence-free period after adjuvant chemotherapy with S-1. But 6 years after the surgery, a diameter of 1 cm mass was noted in the remnant pancreas on MRI examination after hepatocellular carcinoma treatment. The mass was diagnosed as remnant pancreatic cancer, and he had undergone partial pancreatectomy of remnant pancreas. The pathological diagnosis was pancreatic ductal carcinoma with negative margin. However, 6 months after the reoperation, epigastric pain appeared, and CT scan showed a pseudocyst of 10 cm in size. The diagnosis was local recurrence with positive cytology, and then puncture drainage was performed. After repeated drainages, adhesion of the cystic lesion, and chemotherapy, the cytology became negative and the cystic lesion disappeared, but peritoneal dissemination metastasis also appeared. The patient died of the primary disease 7 years and 8 months after the first surgery and 1 year and 11 months after the second surgery. There has been no report of local recurrence in the form of pancreatic pseudocyst after pancreatic cancer surgery, and we report this case with literature discussion.

Case 1: A 67-year-old male had a type 1 tumor in the stomach with a lymph node metastasis 50 mm in size. He was diagnosed with cT4aN(+)M0, cStage Ⅲ and received preoperative docetaxel plus oxaliplatin plus S-1(DOS)therapy. After 3 courses of the regimen, the patient underwent laparoscopic total gastrectomy. The final stage was ypT3N1(1/38) M0, ypStage ⅡB, R0, and the pathological response was Grade 2b. Case 2: A 64-year-old male had a type 3 tumor in the abdominal esophagus and a lymph node metastasis 15 mm in size. He was diagnosed with cT3N(+)M0, cStage Ⅲ and received preoperative DOS therapy. After 3 courses, he underwent laparoscopic esophagectomy. The final stage was ypT0N0M0, ypStage 0, R0, and the pathological response was Grade 3. DOS therapy may be effective as a neoadjuvant chemotherapy.

A 65-year-old man with 1 month of general malaise was admitted to our hospital. Thoracoabdominal CT showed that the supra-clavicular, sub-carina, and para-aortic lymph nodes were swelling. Upper gastrointestinal endoscopy revealed 2 type 1 tumors at the esophagogastric junction, and the biopsy showed Group 5, well to moderately differentiated adenocarcinoma. The clinical diagnosis was cardiac gastric cancer and cStage Ⅳ(cT3N3M1[LYM]). We started capecitabine plus oxaliplatin as the first-line chemotherapy, and weekly paclitaxel plus ramucirumab was administered as the second-line treatment. The second-line treatment was successful, and the effect of PR was obtained. However, considering the period of TTF, while the therapeutic effect continued, we switched to third-line treatment with nivolumab after 7 courses of the second treatment. With the third-line treatment, PR was maintained for 1 year and 3 months, and good quality of life and performance status were obtained for a long period without irAE. However, after 32 courses, because the tumor marker was elevated and lymph nodes were enlarged, we judged PD and switched to the fourth-line treatment with nab-paclitaxel plus ramucirumab. The tumor marker levels decreased, the lymph nodes shrank, and PR was achieved again with the fourth-line treatment. The treatment is still ongoing 2 year and 8 months after the diagnosis.

A 75-year-old man was admitted to our hospital for breathing difficulty. CT showed a 20 cm mass with clear boundaries and internal non-uniformity, which we suspected to be a gastrointestinal stromal tumor(GIST). Surgical resection was been considered to be risky because the mass was close to surrounding organs, such as the stomach, liver and diaphragm. Thus, we chose imatinib therapy. After 2 months, he was admitted to our hospital for anemia. CT showed the size of mass to be smaller, but the area of low density with internal non-uniformity had increased. We diagnosed intratumoral bleeding, and chose surgical resection. The mass was under the omentum, and had infiltrated the extrahepatic area and lesser curvature of the stomach. We diagnosed the mass derived from the stomach, and performed partial gastrectomy with partial liver resection. Pathological diagnosis was extrahepatically growing hepatocellular carcinoma(HCC, pT3N0M0, pStage Ⅲ).

120 Background: Triplet regimen, FOLFOXIRI, plus bevacizumab is considered as one of standard first-line treatments in metastatic colorectal cancer (mCRC). On the contrary, FOLFOXIRI plus anti-EGFR antibody has been shown to be a promising regimen with greater depth of response (DpR) in patients with RAS wild-type mCRC from the VOLFI and MACBETH trials (J Clin Oncol 2019, JAMA Oncol 2018). We therefore performed a randomized phase II study, DEEPER trial (JACCRO CC-13) [NCT02515734], to investigate the efficacy and safety of cetuximab (cet) vs. bevacizumab (bev) in combination with modified (m)-FOLFOXIRI in previously untreated mCRC patients with RAS wild-type tumors. We have reported a significantly better DpR of m-FOLFOXIRI plus cet compared to bev as the primary endpoint (Tsuji A, et al. ASCO 2021). Methods: This trial was a randomized phase II trial to evaluate modified (m)-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, 5-FU 2400 mg/m2) plus cet vs. bev as initial treatment in terms of DpR during the entire course as the primary endpoint in 360 patients with RAS wild-type mCRC. The aim of the trial was to show that median DpR of cet arm was more than 12.5% higher than bev arm, with a power of 85% at a significance level of 0.05, in per protocol set (PPS) consisted of patients evaluable for the DpR. Secondary endpoints included progression-free survival, overall survival, overall response rate, early tumor shrinkage rate, secondary resection rate, and toxicity. A total of 359 patients were enrolled between July 2015 and June 2019. For the PPS (median age 65y, 64% male, PS0/1: 91%/9%, left/right primary: 84%/16%), 159 and 162 patients were randomly assigned to the cet and bev arms, respectively. Clinical outcomes will be analyzed according to primary tumor sidedness which is included in the stratification factor. Additionally, we will collect data of BRAF status, and analyze the clinical outcomes in mCRC patients with RAS/ BRAF wild-type tumors and/or left-sided tumors. Pre-planned survival analysis will be performed to compare the two treatment arms at the time of 3 years after last patients’ enrollment using a log-rank test. All statistical tests are two-sided, and P values ≤ 0.05 are deemed significant. Statistical analyses will be performed using SAS version 9.4. Clinical trial information: NCT02515734 .

Chemotherapy with panitumumab is expected to be well tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). However, skin toxicities are its most common adverse events. The aim of this trial was to evaluate the efficacy and safety of pre-emptive antibiotic treatment with clarithromycin (CAM) to prevent panitumumab skin toxicities.We conducted a phase lll, multicenter, open-label, randomized clinical trial on mCRC patients treated with panitumumab. Eligible patients were randomly assigned 1:1 to pre-emptive antibiotic and control groups. In the pre-emptive group, CAM administration (200 mg twice per day) continued daily through the panitumumab treatment period. The control regimen consisted of skin care only. The primary end point was the incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period.Of 156 enrolled patients, 78 received pre-emptive antibiotic treatment, and 78 received reactive treatment. The number and incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period were 16 (21.3%) and 41 (54.7%) for the pre-emptive and control groups, respectively (HR, 0.32; 95% CI, 0.17-0.56). There was almost no difference in the rate of other adverse events between the two groups, but the incidence of grade ≥ 3 diarrhea in the pre-emptive group was high, at 8% vs. 1.3% in the control group. There were no treatment-related deaths.Prophylactic oral CAM together with relatively simple skin care was found to be effective in suppressing the development of grade ≥ 2 skin toxicities induced by panitumumab.UMIN000011485 DATE OF REGISTRATION: Sep 1st, 2013.

Aim Appendiceal mucinous neoplasms are rare, and thus the literature is sparse with regard to histological types, staging, and prognosis. In particular, it is unclear how long‐term outcome may differ between mucinous adenocarcinomas and other adenocarcinomas. In the present study, we aimed to investigate the histological types and stages of appendiceal neoplasms, and to evaluate the prognostic impacts of these factors in patients with mucinous adenocarcinomas and non‐mucinous adenocarcinomas. Methods Patients with appendiceal tumors diagnosed between 2007 and 2016 were retrospectively identified from the databases of 19 institutions in the Clinical Study Group of Osaka University, Colorectal Group. Results A total of 266 patients with appendiceal tumors were identified, of whom 130 had pathologically diagnosed adenocarcinomas, including 57 with mucinous adenocarcinomas and 73 with non‐mucinous adenocarcinomas. Five‐year overall survival (OS) rates were 64.5% for mucinous adenocarcinomas, and 49.0% for non‐mucinous adenocarcinomas. OS was significantly shorter among patients with non‐mucinous adenocarcinomas compared to mucinous adenocarcinomas. Among patients with mucinous adenocarcinomas, 5‐year OS rates were 53.6% for stage 0/I, 82.6% for II/III, and 48.4% for IV. Among patients with non‐mucinous adenocarcinomas, 5‐year OS rates were 90.9% for stage 0/I, 68.8% for II/III, and 7.1% for IV. Analysis of patients with stage IV disease revealed significantly shorter OS among patients with non‐mucinous adenocarcinomas compared to mucinous adenocarcinomas. Conclusion Our present findings showed a better prognosis in patients with mucinous adenocarcinomas compared to non‐mucinous adenocarcinomas. In this setting, Union for International Cancer Control staging was associated with prognosis for non‐mucinous adenocarcinomas, but not for mucinous adenocarcinomas.

During the follow‒up of Vater papillary adenoma, a 74‒year‒old man was admitted to our hospital with a chief complaint of upper abdominal pain and diagnosed as cholangitis with obstructive jaundice. Cholestasis had been considered to be caused by papillary adenoma, however, EUS exam showed continuous bile duct wall irregularity from papilla of Vater. So we diagnosed as papillary carcinoma with extension to the distal bile duct. Preoperative CT showed the stenosis at the root of celiac artery, and hepatic blood flow was considered to be supplied via the pancreatic head arcade from superior mesenteric artery, so an anastomosis of gastroduodenal artery and inferior pancreaticoduodenal artery was performed during pancreaticoduodenectomy( PD). Like this case, when performing PD with celiac artery stricture, it is important to evaluate hepatic blood flow before and during surgery and prepare for the arterial reconstruction.

Primary duodenal carcinoma is a rare disease among gastrointestinal malignancies and has little evidence. We evaluated retrospectively the treatment status of 16 cases of primary duodenal carcinoma in our hospital between 2010 and 2019. The median age was 72(58-88)years and 63% of patients were male, and Each stage were Stage 0 in 4 cases, Stage Ⅰ in 1 case, Stage ⅢA in 2 cases, Stage ⅢB in 3 cases, and Stage Ⅳ in 6 cases(UICC 8th edition). Initial treatment was endoscopic therapy in 3 cases, surgery in 10 cases, chemotherapy in 1 case, and best supportive care in 2 case. The 2-year survival rate was 51.3% and the MST was 25.4 months in all cases. The Stage 0, Stage Ⅰ cases had all recurrence-free survival, while the Stage ⅢA or higher cases, 2-year survival rate was 33.8% and the MST was 20.0 months. Also, XELOX was often selected as the first-line treatment for chemotherapy regimens including recurrence treatment.

This is the case of a 77-year-old man with hepatitis C. AFP was increased by 95.9 ng/mL, and abdominal computed tomography(CT)revealed a 20 mm mass in the S6 segment of the liver. Therefore, the patient was referred to our hospital for further examination. Abdominal echo at our hospital showed a 10 mm, low echoic lesion in S6, which tended to shrink. Similarly, CT showed a low-concentration nodule of 10 mm in S6, but the contrast effect in the arterial phase was not clear. EOB-MRI showed a 10 mm nodule of DWI hyperintensity and hepatocyte phase hypointensity in S6. Based on these, a diagnosis of hepatocellular carcinoma(T1N0M0, StageⅠ)was made, and we decided to perform surgery. Intraoperative findings showed no tumor on the liver surface, and echo did not reveal a reproducible nodule. The tumor site was estimated using a 3-dimensional image analysis system created preoperatively. Laparoscopic partial resection of the liver S6 segment was performed at a position distant from the estimated tumor site. Rapid pathological examination showed no malignant findings, but no significant lesion was found in the residual liver, and the surgery was completed. The postoperative pathological diagnosis revealed no clear tumor. EOB-MRI was performed again postoperatively, but no tumor was found in the residual liver. The tumor site that had been indicated preoperatively was resected, and we hypothesized that the hepatocellular carcinoma had spontaneously regressed. Although several mechanisms have been reported for the spontaneous regression of hepatocellular carcinoma, few cases of spontaneous regression during surgery have been reported. We do not have a definite opinion on the treatment protocol for hepatocellular carcinoma that regresses spontaneously; therefore, we will report on past cases.

A 70-year-old man visited our hospital because of a body weight loss. Upper gastrointestinal fiberscope revealed a type 3 tumor and an enhanced MRI showed 30 or more liver metastases. He received docetaxel plus cisplatin plus S-1(DCS)therapy. Although main tumor had shrinked only partially, multiple liver metastases could not be detected. Thus, he was performed distal gastrectomy. After gastrectomy, he received S-1 plus oxaliplatin(SOX)therapy followed by S-1 therapy. Two years and 2 months after surgery, chemotherapy was finished because of no signs of tumor progression. He is alive without recurrence for 2 years and 11 months after gastrectomy.

A 78-year-old man diagnosed with advanced gastric cancer and para-aortic lymph node metastases at clinical stage cT3 (SS)N1M1(LYN), Stage Ⅳwas treated with S-1/docetaxel(S-1/DTX)therapy. Eight months later, lymph node metastases resolved on abdominal CT, and the primary lesion appeared scarred when viewed by upper gastrointestinal endoscopy; this was considered to be a complete response(CR). S-1/DTX therapy was administered for a total of 16 courses, followed by 13 courses ofS -1 therapy. During the treatment, CR was maintained. Though chemotherapy was completed 2 years and 2 months after its initiation, the patient's serum CEA level was found to be elevated. As the serum CEA level gradually increased, S-1/DTX therapy was resumed. Three months after chemotherapy was restarted, PET-CT revealed multiple bone metastases. The chemotherapy protocol was changed to paclitaxel/ramucirumab therapy followed by nivolumab therapy. Disease control was difficult, and the patient died 9 months after reinstituting chemotherapy(3 years and 8 months after the first chemo- therapy). This case report summarizes our treatment ofa patient with advanced gastric cancer using S-1/DTX therapy for an extended period of time.

A 69-year-old woman was admitted to our hospital because of abdominal pain. Abdominal CT revealed free air, so we performed an emergency operation. Although the perforation site could not be confirmed, pancreatic cancer invading the stomach, spleen, and transverse colon was found. As a splenic abscess and peritoneal dissemination were also found, we created a colostomy and placed drains. Although the postoperative course was good, the splenic abscess continuous with the tumor remained. We thought that early removal of the drain would be difficult, so chemotherapy was introduced while continuing drainage. Fortunately, the pancreatic cancer was controlled, and the abscess tended to shrink, so we removed the tube 137 days after the surgery. After that, we continued chemotherapy, but in the second year after the surgery, the liver metastasis acutely exacerbated and DIC also developed, resulting in cancer death. If surgical intervention is difficult, as in this case, chemotherapy may be considered as an option, keeping in mind the possibility of exacerbation of infection.

Gastroscopy ofa 79-year-old man complaining ofanemia showed a type 3 tumor at the lesser curvature ofthe gastric body. A biopsy revealed poorly differentiated HER2-negative adenocarcinoma. Abdominal CT showed the tumor at the lesser curvature ofthe gastric body, multiple lymph nodes with a maximum diameter of 25mm at the lesser curvature, and a mass measuring 50mm with ring enhancement on S6 ofthe liver. The clinical diagnosis was cT4aN2M1(Hep), cStage Ⅳ. He was treated with chemotherapy comprising 4 courses ofS -1 plus oxaliplatin. Although the tumor had shrunk remarkably, chemotherapy was discontinued because of anorexia. Therefore, we performed total gastrectomy and hepatic partial resection(S6). The final staging was ypT3N0M0, ypStage ⅡA. We achieved R0 resection, and he has shown no recurrence without adjuvant chemotherapy for 3 years.

We report 2 cases with long-term survival following stereotactic body radiotherapy(SBRT)for liver metastasis from gastric cancer. Case 1 was a 65-year-old man. We performed distal gastrectomy for gastric cancer with liver metastasis prior to chemotherapy due to pyloric stenosis. Postoperative S-1 chemotherapy was administered. Two liver metastases observed before the operation were temporarily reduced in size but subsequently enlarged; therefore, SBRT was performed 13 months postoperatively. The liver metastases showed a complete response(CR)and the patient is alive 4 years and 11 months after SBRT(6 years postoperatively). Case 2 was a 71-year-old woman. After performing distal gastrectomy, liver metastasis emerged during postoperative S-1 adjuvant chemotherapy; therefore, SBRT was performed 11 months postoperatively. She was then administered weekly paclitaxel. However, she underwent a right hepatic lobectomy 13 months after SBRT for suspected remnant or marginal recurrence by abdominal enhanced CT. Histopathological examination showed that the tumors contained fibrotic connective tissue with no viable cancer cell remnants; therefore, the therapeutic effect was determined to be of Grade 3. The patient is alive without recurrence in the remnant liver 4 years and 7 months after SBRT(5 years and 6 months after the operation of gastric cancer). Thus, SBRT for liver metastasis from gastric cancer may be considered an effective local treatment.

A 61-year-old man with advanced gastric cancer underwent distal gastrectomy after chemotherapy. Fifteen months later, peritoneal metastasis and colon stenosis were detected. Therefore, subtotal colectomy and ileosigmoidostomy were performed. Three weeks later, paclitaxel(PTX)treatment was initiated, followed by nab-PTX with ramucirumab(Ram)treatment at 7 weeks postoperatively. The patient experienced sudden abdominal pain diagnosed as gastrointestinal perforation 13 weeks postoperatively. Operative findings showed that the anastomosis of the ileosigmoidostomy was perforated, and this was treated using sutures. Angiogenesis inhibitors should be carefully administered even 4 weeks or more after surgery.

The prognosis of pancreatic cancer with superior mesenteric arterial invasion is very poor and judgment of surgical indication is very difficult. We report a case that received multimodal therapy for pancreatic cancer with superior mesenteric arterial invasion. A 43-year-old woman consulted a local doctor because of upper abdominal pain. Ultrasonography revealed a nodule in the pancreatic body and elevated CA19-9 values. She was referred to our hospital for evaluation and therapy. Computed tomography showed a low-density area in the pancreatic body and around the superior mesenteric artery. The clinical diagnosis was pancreatic cancer with superior mesenteric arterial invasion. She received chemoradiation therapy(RT, 50.4 Gy, gemcitabine[GEM]plus TS-1)followed by distal pancreatectomy. She received adjuvant chemotherapy(TS-1)for 6 months. However, follow-up CTperformed 10 months after surgery revealed local recurrence. The patient received chemotherapy( GEM)for 8 months and GEM plus nab-PTX for 22 months. She died from the cancer 50 months after the primary operation.

112 Background: Ramucirumab (RAM) plus FOLFIRI has been considered as the standard care of second-line treatment in metastatic colorectal cancer (mCRC). However, there have been few data which prospectively evaluated the efficacy and safety of RAM or other anti-VEGF drugs plus FOLFIRI after anti-EGFR antibody therapy in RAS wild-type mCRC. We therefore investigated the efficacy and safety of RAM plus FOLFIRI as second-line treatment in patients with RAS wild-type mCRC previously treated with oxaliplatin-containing chemotherapy with anti-EGFR antibody. Methods: The JACCRO CC-16 was a multicenter, phase 2 trial to evaluate the efficacy and safety of RAM (8 mg/kg) plus FOLFIRI (irinotecan 150 mg/m2, bolus 5-FU 400 mg/m2, infusional 5-FU 2400 mg/m2) in mCRC patients with RAS wild-type tumors and ECOG PS 0 or 1, after first-line doublet or triplet plus anti-EGFR antibody therapy. The primary endpoint was 6-month progression-free survival (PFS) rate. The secondary endpoints included PFS, overall survival, objective response rate (ORR), early tumor shrinkage (ETS), and safety. We hypothesized a threshold 6-month PFS rate of 30% and an expected 6-month PFS rate of 45% for the protocol treatment. A sample size of 74 patients was required (one-sided α, 0.05; β, 0.2). Results: A total of 92 patients were enrolled between October 2018 and December 2020. Ninety-one patients, excluding one ineligible patient, were analyzed as the full analysis set: median age 66.0-y (range, 29–84), 46% female, 81% ECOG PS 0, 40% with primary tumor, 95% left-sided (rectum, sigmoid or descending colon) primary tumors, 70%/42% with liver/lung metastases. In prior first-line treatment, 19 (21%) patients were treated with triplet plus anti-EGFR antibody. The median number of treatment cycles was 10 (range, 1–56). Primary endpoint was met; at data cut-off, with 76 events, 6-month PFS rate was 58.2% (95% CI; 47.4-67.6). The median PFS was 7.0 months. The ORR, disease control rate, and ETS were 10.7%, 86.9%, and 16.9%, respectively. In the safety population of 92 patients, any grade adverse events (AEs) were neutropenia (75%), hypertension (59%), proteinuria (34%), and diarrhea (33%). Grade 3-4 AEs were neutropenia (48%), hypertension (27%), proteinuria (4%), diarrhea (3%), and febrile neutropenia (3%). No treatment-related death was observed. Conclusions: This is the first prospective study to demonstrate that RAM plus FOLFIRI as second-line treatment has favorable PFS rate and tolerability after anti-EGFR antibody containing chemotherapy in RAS wild-type mCRC patients. Clinical trial information: jRCTs061180002.

The efficacy of postoperative chemotherapy for patients with ypStageⅠgastric cancer has not been evaluated. We investigated the characteristics and prognosis of7 patients with ypStage Ⅰgastric cancer. cStages were ⅡA, ⅡB, ⅢB, and Ⅳin 1, 1, 1, and 4 patients, respectively. S-1 plus cisplatin and docetaxel plus cisplatin plus S-1 were administered in 5 and 2 patients, respectively, for 2-8 courses before gastrectomy. Microscopic curative resection was performed for all patients. ypStage was 0, ⅠA, and ⅠB in 1, 2, and 4 patients. All patients received postoperative chemotherapy with S-1 or docetaxel plus S-1(DS). The 5-year recurrence-free survival was 71% and the 5-year overall survival was 68%. Two patients developed recurrence. One patient developed recurrence 1 year and 1 month after gastrectomy in spite of S-1 treatment for 4 months. Another patient developed recurrence 11 months after gastrectomy after DS treatment for 4 months followed by S-1. The other 5 patients received S-1 for 1-5 years and have survived without recurrence. Although the prognosis ofypStage Ⅰgastric cancer was comparatively good, the regimen and courses ofpostoperative chemotherapy should be evaluated in a prospective study.

A 69-year-old man was found to have a hepatocellular carcinoma of 2.3 cm in diameter, with extrahepatic growth in liver S4 during follow-up for chronic hepatitis C and liver cirrhosis. We performed a laparoscopic partial liver resection, but the tumor capsule was injured by the retractor used to keep the working space at the bleeding site. The pathological diagnosis was moderately differentiated hepatocellular carcinoma(pT2N0M0, pStage Ⅱ). 7 months after the surgery, intrahepatic reoccurrence appeared. Thus, transcatheter arterial chemoembolization(TACE)and radiofrequency ablation were performed. However, a single recurrence ofperitoneal dissemination appeared 8 months after the reoperation. We selected laparoscopic operation this time. Intraperitoneally, we found 4 peritoneal disseminated lesions and resected all the lesions macroscopically. However, even after the resection, peritoneal dissemination recurred and increased. Therefore, we continued treatment with sorafenib and S-1 as systemic therapy, TACE and transcatheter arterial infusion(TAI)for the multiple recurrences in the liver, and radiotherapy for the peritoneal dissemination focuses. However, his general condition worsened, and liver failure occurred. Thus, he was shifted to complete palliative treatment and died 2 years 6 months after the initial operation. The recurrent form ofhepatocellular carcinoma is mainly an intrahepatic recurrence, and recurrence ofperitoneal dissemination is rare. In this case, the intraoperative operation was considered to be the possible cause ofthe recurrence.

We experienced a case of multiple esophageal intramural metastasis from adenocarcinoma of the esophagogastric junction. A 58-year-old man was admitted complaining of dysphagia. Upper gastrointestinal endoscopy revealed a type 3 tumor at the esophagogastric junction. Biopsy showed Group 5, poorly differentiated adenocarcinoma. Abdominal CT indicated regional and para-aortic lymph node metastasis. Then the clinical diagnosis was established as Siewert type Ⅲ adenocarcinoma and cT4aN2M1(LYM), cStage Ⅳ. After conducting 4 courses of SP(S-1/cisplatin)therapy, endoscopy showed partial response of the primary tumor and the submucosal nodules in the lower esophagus. We performed lower esophagectomy and total gastrectomy by left thoracotomy and laparotomy. Six esophageal nodules were identified in the lower esophagus, and pathological examination proved the poorly differentiated adenocarcinoma. The esophageal tumors were diagnosed as intramural metastases. The patient showed hepatic and lymphatic recurrence 9 months after surgery, and died 15 months after surgery. Esophageal intramural metastasis from esophagogastric junction adenocarcinoma is relatively rare. We discuss this case along with a review of the literature.

In this paper, we consider estimation of the conditional mode of an outcome variable given regressors. To this end, we propose and analyze a computationally scalable estimator derived from a linear quantile regression model and develop asymptotic distributional theory for the estimator. Specifically, we find that the pointwise limiting distribution is a scale transformation of Chernoff's distribution despite the presence of regressors. In addition, we consider analytical and subsampling-based confidence intervals for the proposed estimator. We also conduct Monte Carlo simulations to assess the finite sample performance of the proposed estimator together with the analytical and subsampling confidence intervals. Finally, we apply the proposed estimator to predicting the net hourly electrical energy output using Combined Cycle Power Plant Data., This paper supersedes "On estimation of conditional modes using multiple quantile regressions" (Hirofumi Ohta and Satoshi Hara, arXiv:1712.08754)

We develop a general framework for statistical inference with the 1-Wasserstein distance. Recently, the Wasserstein distance has attracted considerable attention and has been widely applied to various machine learning tasks because of its excellent properties. However, hypothesis tests and a confidence analysis for the Wasserstein distance have not been established in a general multivariate setting. This is because the limit distribution of the empirical distribution with the Wasserstein distance is unavailable without strong restriction. To address this problem, in this study, we develop a novel non-asymptotic Gaussian approximation for the empirical 1-Wasserstein distance. Using the approximation method, we develop a hypothesis test and confidence analysis for the empirical 1-Wasserstein distance. Additionally, we provide a theoretical guarantee and an efficient algorithm for the proposed approximation. Our experiments validate its performance numerically., Comment: 36 pages