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Purposes: The benefit of neo-adjuvant chemotherapy for liver-limited metastatic colorectal cancer is still controversial. This study defined the resectability regardless of the size and number of liver metastases, and attempted curative hepatic resection in all cases. Methods: Sixty-four patients that tolerated chemotherapy were diagnosed with CLM (colorectal liver metastases) without extrahepatic metastase from January 2007 to November 2010, and received an oxaliplatin-based regimen. This study assessed the resectability after chemotherapy, and the patients were divided in two groups; the resected and unresected group. Sixteen patients underwent hepatic resection without chemotherapy. Results: Thirty-five patients underwent surgical resection (resected group) and twenty-nine patients were considered unresectable (unresected group). All 35 patients in the resected group safely received oxaliplatin-based chemotherapy safely without serious adverse effects. No serious postoperative complications were observed. The median overall survival (MST) was significantly higher in the resected than in the unresected group (56.93 [95 % CI 38.13-75.73] and 25.07 months [95 % CI 17.87-32.26], respectively; P < 0.001). The median disease-free survival was 20.2 [95 % CI 8.82-31.65] months in the resected group. Conclusion: Preoperative chemotherapy for CLM is well tolerated and does not increase postoperative complications. Curative surgery with preoperative chemotherapy has the potential to improve the overall survival in patients with CLM. [ABSTRACT FROM AUTHOR]

Ectopic pancreas within the mesentery is rare. In this case report, a 61-year-old man with an ectopic pancreas within the jejunal mesentery for over 20 years developed chronic pancreatitis that progressed to acute exacerbation. Our computed tomography (CT) performed for acute abdomen assessment suggested acute appendicitis or Meckel's diverticulitis. However, a CT scan taken 20 years ago revealed a structure indicative of an ectopic pancreas in the mesentery, and further imaging findings taken 10 and 4 years ago confirmed progression to chronic pancreatitis. Furthermore, we found a pancreatic stone confined in the luminal structure that corresponded to the main pancreatic duct; this stone eventually caused acute exacerbation. In summary, we report a case of mesenteric ectopic pancreas that showed typical findings of progression and acute exacerbation of chronic pancreatitis on CT. [ABSTRACT FROM AUTHOR]

Background and aims: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. Methods: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. Results: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01–1.05, p = 0.0002), combined resection of adjacent organs [+/−] (OR 7.92, 95% CI 3.14–19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [−/+] (OR 4.46, 95% CI 2.01–9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99–1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54–8.04, p = 0.0028), combined resection of adjacent organs [+/−] (OR 5.96, 95% CI 2.15–16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [−/+] (OR 6.26, 95% CI 3.01–13.05, p < 0.0001). Conclusions: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. Trial Registration: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645. [ABSTRACT FROM AUTHOR]

Background: A bridge to surgery (BTS) using self-expandable metallic stents (SEMSs) is becoming the primary treatment for obstructive colorectal cancer (OCRC). In Japan, intestinal decompression was usually performed using decompression tubes (DTs). However, few reports have compared the outcomes of SEMS and DTs as BTS. Therefore, we compared the treatment outcomes of SEMS and DTs for OCRC. Methods: Data of 80 patients who underwent radical resection after endoscopic decompression for stage II or III OCRC between 2007 and 2021 were retrospectively analyzed. Patients were divided into two groups based on whether they received SEMS (n = 53) or DTs (n = 27). Results: The clinical success rate of decompression was 96.2% and 88.9% in the SEMS and DT groups, respectively. Additionally, 96.2% of patients who received SEMS were able to resume their routine diet without stricture symptoms. The rate of stoma construction and incidence of postoperative complications were lower in the SEMS group (p < 0.005 and p < 0.01, respectively). The 3-year relapse-free survival rates were 71.9% and 51.2% in the SEMS and DT groups, respectively, which were not significantly different (p = 0.10). Conclusion: BTS using SEMS might be an adequate treatment for stage II or III OCRC regardless of tumor location owing to the comparable oncological outcomes with DT and low perioperative complication rate. [ABSTRACT FROM AUTHOR]

Background: We previously reported the feasibility and efficacy of neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer. Here, we report the results of a long-term follow-up study. Methods: This was a multi-institutional, prospective phase 2 study of patients with locally advanced rectal cancer. Patients received neoadjuvant chemotherapy with molecularly targeted agents before undergoing total mesorectal excision. Six cycles of modified FOLFOX (mFOLFOX6) with bevacizumab were administered to KRAS-mutant patients, and mFOLFOX6 with cetuximab was administered to KRAS-wild-type patients. Here, we report the secondary end points of overall survival, relapse-free survival, and local recurrence rate. Results: Sixty patients were enrolled in this study. R0 resection was achieved in 98.3% (59/60) patients, and pathological complete response was achieved in 16.7% (10/60) patients. After a median follow-up of 5.4 years, the 5 year overall survival was 81.6%, the 5 year relapse-free survival was 71.7%, and the 5 year local recurrence rate was 12.6%. None of the patients who achieved pathological complete response developed recurrence within 5 years. Conclusions: The use of molecularly targeted agents in the neoadjuvant setting for locally advanced rectal cancer has an acceptable prognosis. [ABSTRACT FROM AUTHOR]

Hatano E, Tanaka A, Kanazawa A, Tsuyuki S, Tsunekawa S, Iwata S, Takahashi R, Chance B, Yamaoka Y. Inhibition of tumor necrosis factor-induced apoptosis in transgenic mouse liver expressing creatine kinase. Liver International 2004: 24: 384–393. © Blackwell Munksgaard 2004 The mitochondrion acts as a pivotal decision center in many types of apoptotic responses. To clarify the effects of the enhanced mitochondrial function on tumor necrosis factorα (TNFα)-induced apoptosis, we studied hepatic injuries in transgenic mice whose livers express creatine kinase (CK). Mice fed a diet containing 10% creatine, came to accumulate phosphocreatine and to enhance hepatic ATP levels and mitochondrial oxidative phosphorylation activities. TNFα-mediated hepatic apoptosis in normally fed and Cr-feeding CK transgenic mice were assessed. TNFα and actinomycin D cause severe liver failure in normally fed transgenic mice, and in the wild-type mice. In contrast, no significant elevations in transaminase levels after injection were observed in Cr feeding transgenic mice. The disruption of the mitochondrial transmembrane potential at 2 h after TNFα injection, prior to ATP depletion, activation of caspase 3 like protease, and DNA fragmentation at 4–6 h after injection, were observed in normally fed transgenic mice. These were fully suppressed in Cr feeding transgenic mice. However, anti-Fas antibody-induced apoptosis was not inhibited in both groups. The results indicate that TNFα-induced apoptosis was inhibited in CK transgenic mice livers by maintaining mitochondrial function. [ABSTRACT FROM AUTHOR]

Introduction: Oxaliplatin‐induced peripheral neuropathy (OIPN) is a common adverse events that can limit a patient's quality of life during/after chemotherapy. However, no appropriate methods have been established yet for monitoring the risk of progression of OIPN. Methods: A simple assessment tool using gem clips, the CLIP test, was established and its performance in predicting the risk of progression to ≥grade 2 peripheral sensory neuropathy (CTCAE ver. 4.0) was investigated in patients receiving chemotherapy with oxaliplatin. Results: Among 101 patients included in this study, 71 patients developed CTCAE ≥grade 1 peripheral neuropathy (grade 1, n = 67; grade 2, n = 4) at a median of 63 (range, 14–259) days after the start of treatment. Of the 67 patients with grade 1 peripheral neuropathy, 17 showed progression to ≥grade 2 neuropathy after a median interval of 84 (range, 21–246) days. Of these patients, 27 showed a positive result of the CLIP test at a median of 91 (range, 14–224) days, excluding one patient who already showed a positive result of the test at the baseline. Therefore, the risk ratio for the development of CTCAE ≥grade 2 peripheral neuropathy was 8.3 in the patients who showed a positive result on the CLIP test. Multivariate analysis confirmed that a positive results on the CLIP test was significantly correlated with the risk of future development of CTCAE ≥grade 2 peripheral neuropathy (odds ratio, 9.37; P = 0.002). Conclusion: A positive result on the CLIP test predict is predictive of the risk of progression of OIPN during chemotherapy with oxaliplatin. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of reintroducing modified FOLFOX6 (mFOLFOX6) or CAPOX with or without bevacizumab in recurrent colorectal cancer patients after oxaliplatin adjuvant chemotherapy. Methods: Patients that participated in this trial had a medical history of adjuvant chemotherapy, including oxaliplatin with a cumulative dose greater than 400 mg/m2, and recurrence that was diagnosed more six months post adjuvant chemotherapy. Primary endpoints were response rate (RR) and disease control rate (DCR), while key secondary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 31 patients were enrolled between October 2012 and October 2016. Of the 29 eligible patients, 7 received mFOLFOX6 and 22 received CAPOX. The RR was 62.1% (95% confidence interval 42.3–79.3) and the DCR was 82.8% (95% confidence interval 64.2–94.2). The RR for oxaliplatin-free interval was 100.0% in months 6–12 and 56.0% after 12 months. Median TTF, PFS, and OS were 6.3, 10.8, and 28.7 months, respectively. Grade 3 or worse peripheral sensory neuropathy developed in 6.5%. Allergic reactions occurred in 12.9% of the patients, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. Conclusion: Reintroduction of oxaliplatin was feasible and achieved high RR or DCR in patients after more than 6 months post oxaliplatin adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to examine the technical and oncological feasibility of laparoscopic surgery (LAP) in elderly patients with a history of abdominal surgery.Methods: We conducted a propensity score-matched case-control study of colorectal cancer (CRC) patients aged ≥80 years that were treated at 41 hospitals between 2003 and 2007. We included 601 patients who had a history of abdominal surgery and underwent curative and elective surgery for stage 0 to III CRC. After the matching procedure, 153 patients were included in each cohort. The surgical outcomes of LAP and open surgery (OS) were compared. P-values of <0.05 were considered statistically significant.Results: LAP resulted in a significantly longer surgical time (220 vs. 170 min, p < 0.001), but significantly less intraoperative blood loss (39 vs. 100 ml, p < 0.001). A number of postoperative recovery-related parameters, including the length of the hospitalization period (12 vs. 14 days, p = 0.002), and the days to the resumption of fluid (2 vs. 3 days, p < 0.001) and solid food intake (4 vs. 5 days, p < 0.001), were significantly better in the LAP group. Moreover, the overall morbidity rate (43 vs. 66 %, p = 0.009) and the frequency of postoperative ileus (7 vs. 19 %, p = 0.023) were significantly lower in the LAP group, while the frequencies of other morbidities did not differ significantly between the groups. In the survival analyses, overall survival and disease-free survival did not differ between the two groups.Conclusions: In this population, LAP can be performed safely in elderly CRC patients with a history of abdominal surgery, and LAP resulted in a lower postoperative morbidity rate than OS. [ABSTRACT FROM AUTHOR]

Background: Although liver resection combined with preoperative chemotherapy is expected to improve outcomes of patients with resectable colorectal liver metastasis (CRLM), there is as yet insufficient clinical evidence supporting the efficacy of preoperative systemic chemotherapy. The aim of this phase II study was to assess the feasibility and efficacy of preoperative FOLFOX systemic chemotherapy for patients with initially resectable CRLM. Methods: A prospective multi-institutional phase II study was conducted to evaluate the feasibility and efficacy of preoperative chemotherapy for resectable CRLM (ClinicalTrials.gov identifier number NCT00594529). Patients were scheduled to receive 6 cycles of mFOLFOX6 therapy before liver surgery. The primary endpoint was the macroscopic curative resection rate. Results: A total of 30 patients were included in this study. Two patients who were diagnosed with hepatocellular and intrahepatic cholangiocellular carcinoma based on pathology were excluded from the analysis. More than half of the patients (57 %) had solitary liver metastasis. The completion rate of preoperative chemotherapy was 64.3 % and the response rate was 53.6 %. Two patients were unable to proceed to liver resections due to disease progression and severe postoperative complications following primary tumor resection. Macroscopic curative resection was obtained in 89.3 % of eligible patients. Postoperative mortality and severe complication (≥Gr. 3) rates were 0 and 11 %, respectively. The 3-year overall and progression-free survival rates were 81.9 and 47.4 %, respectively. Conclusion: Our phase II study demonstrated the feasibility of liver resection combined with preoperative mFOLFOX6 therapy in patients with initially resectable CRLM. Further study is warranted to address the oncological effects of preoperative chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied. Methods/design: The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients' clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative. Discussion: A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the "personalized therapy" in adjuvant chemotherapy for colon cancer. [ABSTRACT FROM AUTHOR]

Background: This Japanese multicenter retrospective study evaluated short- and long-term outcomes of palliative laparoscopic procedures for symptomatic stage IV colorectal cancer compared with conventional open procedures. Methods: Of 968 eligible patients with stage IV colorectal cancer enrolled during January 2006-December 2007 from 41 participating surgical units (Japan Society of Laparoscopic Colorectal Surgery Group), we studied 409 patients who underwent palliative resection of symptomatic primary colorectal tumor. Results: Data from patients with laparoscopic resection ( n = 98) and open colorectal resection ( n = 311) were analyzed. Eleven (11.2 %) laparoscopic operations were converted to an open procedure. Fewer complications were reported for laparoscopic resections than for open procedures (13.3 vs. 26.7 %; p = 0.0042). Postoperative hospital stay was significantly shorter in the laparoscopic vs. open resection group (median, 14 vs. 17 days; p = 0.0242). Postoperative chemotherapy treatment was administered to 245 (78.9 %) patients in the open and 78 (79.6 %) patients in the laparoscopic resection group. Time from surgery to start of postoperative chemotherapy was significantly shorter in the laparoscopic vs. open resection group (median, 32 vs. 27 days; p = 0.0487). Median survival time between the two groups was not significantly different (22.0 vs. 22.2 months; p = 0.948). Conclusions: Laparoscopic palliative resection results in reduced postoperative complications and earlier recovery with acceptable long-term outcomes comparable with open surgery. When performed by experienced surgeons in selected patients, it may be a safe and feasible option. Because of the potential of significant bias arising from the included studies, further randomized controlled trials should be undertaken to confirm this bias. [ABSTRACT FROM AUTHOR]

Validation studies demonstrated that the 12-RS assay, known as Oncotype DX Colon Cancer Assay, can identify a wide range of recurrence risk in stage II/III colon cancer (CC). The objective of this prospective study was to evaluate the decision impact of the 12-RS assay on adjuvant chemotherapy recommendation for stage II/III CC patients (UMIN000028784). Patients who had curatively resected stage II, IIIA or IIIB CC were eligible. Physicians formulated a treatment recommendation and completed a pre-assay questionnaire, and then the 12-RS assay was performed. Following receipt of the 12-RS result, the treatment recommendation was revised in a post-assay questionnaire. The primary endpoint was the proportion of changes in a treatment recommendation between pre- and post- assay. The threshold value for the proportion of changes was assumed 20%. The target enrollment was 300 patients (100 stage II and 200 stage III CC). Between November 2017 and January 2019, 305 patients were registered from 14 centers. Of 275 who were evaluable, stage II/III was 97/178 patients. The RS < 30 was observed in 82% (low-risk), between 30 and 40 in 15% (intermediate-risk) and ≥41 in 4% (high-risk) of patients. The primary analysis showed that a treatment recommendation change was observed in 109 (40%) out of 275 patients (95% CI, 34-45%; P < 0.001). In patients with stage III CC, a change was observed in 80 (45%) out of 178 patients (39-51%; P < 0.001). In patients with stage II CC, a change was observed in 29 (30%) out of 97 patients (24-35%; P < 0.001). Physicians reported that the 12-RS assay increased the confidence in a change between pre- and post-assays for 36% of overall (P < 0.001), 38% of stage III (P < 0.001), and 31& of stage II patients (P < 0.001), respectively. This is the first study to evaluate the impact of the 12-RS assay on adjuvant treatment recommendations for stage III CC. The 12-RS results significantly influenced treatment recommendations. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to develop a suitable method for the prolonged culture and maintenance of human hepatocytes with preservation of both proliferative capacity and differentiated functions.Materials and methods. Primary human hepatocytes were isolated from small pieces of liver tissue obtained from 15 patients who underwent hepatic resection. Hepatocytes were cultured in keratinocyte-stimulating factor medium supplemented with 10% human serum, 10 mM nicotinamide, 10 ng/ml epidermal growth factor, 0.5 μg/ml insulin, 10−7 M dexamethasone, and antibiotics. Hepatic differentiation and function were analyzed by immunocytochemistry, Western blot, ELISA, lidocaine metabolism, and urea synthesis. Ultrastructural analysis of cultured hepatocytes was performed by electron microscopy.Results. Many primary hepatocytes were maintained for more than 56 days. Hepatocytes proliferated during the initial 14 days, and bromodeoxyuridine labeling indices were 15.2, 12.2, and 6.2% at days 5, 10, and 15, respectively. Electron micrographs of the hepatocytes at day 28 demonstrated numerous mitochondria, rough endoplasmic reticulum, large peroxisomes, and glycogen granules. Albumin secretion increased for the first 14 days and then gradually decreased thereafter but was maintained at levels greater than 2 μg/ml/h until day 56. α1-Antitrypsin, α1-antichymotrypsin, and ceruloplasmin production was also observed at day 56, while lidocaine metabolism and urea synthesis were maintained for a long time.Conclusion. This hepatocyte culture method facilitates the prolonged culture of primary human hepatocytes with preservation of hepatocyte differentiation, function, and proliferative capacity. [Copyright &y& Elsevier]

Background Validation studies demonstrated that the 12-RS assay, known as Oncotype DX Colon Cancer Assay, can identify a wide range of recurrence risk in stage II/III colon cancer (CC). The objective of this prospective study was to evaluate the decision impact of the 12-RS assay on adjuvant chemotherapy recommendation for stage II/III CC patients (UMIN000028784). Method Patients who had curatively resected stage II, IIIA or IIIB CC were eligible. Physicians formulated a treatment recommendation and completed a pre-assay questionnaire, and then the 12-RS assay was performed. Following receipt of the 12-RS result, the treatment recommendation was revised in a post-assay questionnaire. The primary endpoint was the proportion of changes in a treatment recommendation between pre- and post- assay. The threshold value for the proportion of changes was assumed 20%. The target enrollment was 300 patients (100 stage II and 200 stage III CC). Results Between November 2017 and January 2019, 305 patients were registered from 14 centers. Of 275 who were evaluable, stage II/III was 97/178 patients. The RS < 30 was observed in 82% (low-risk), between 30 and 40 in 15% (intermediate-risk) and ≥41 in 4% (high-risk) of patients. The primary analysis showed that a treatment recommendation change was observed in 109 (40%) out of 275 patients (95% CI, 34-45%; P < 0.001). In patients with stage III CC, a change was observed in 80 (45%) out of 178 patients (39-51%; P < 0.001). In patients with stage II CC, a change was observed in 29 (30%) out of 97 patients (24-35%; P < 0.001). Physicians reported that the 12-RS assay increased the confidence in a change between pre- and post-assays for 36% of overall (P < 0.001), 38% of stage III (P < 0.001), and 31& of stage II patients (P < 0.001), respectively. Conclusions This is the first study to evaluate the impact of the 12-RS assay on adjuvant treatment recommendations for stage III CC. The 12-RS results significantly influenced treatment recommendations. [ABSTRACT FROM AUTHOR]

Backgrounds In ATTRACTION-2 trial, nivolumab (NIVO) showed better outcome compared with best supportive care in advanced gastric cancer (AGC) patients (pts) at least two previous regimens. (NIVO has changed the treatment of AGC in Japan.) Methods: From Nov 2017 to Feb 2019, we retrospectively investigated 25 pts with AGC who received NIVO. Results: The patient demographics were as follows: median age, 67 (range, 39-82); male/female ratio, 18:7; performance status (PS) 0/1/2, 9/14/2; unresectable /recurrent, 20 /5; HER2 positive, 3; deep vein thrombosis, 3; intestinal type /diffuse type, 13 /12; primary site EGJ/UML/UM/ML/U/M/L, 2/2/1/3/5/4/8; site of metastases lymph node /liver /peritoneum /ovary, 13 /8 /9 /1; and previous treatment regimens 2 regimens /3 regimens /≥4 regimens, 9 /10 /6. Response rate (RR) was 12% and disease control rate (DCR) was 28%. The median progression free survival (PFS) was 4.1 months (95% confidence interval [CI], 2.8-NA) and the median overall survival (OS) was 11.8 months (95% CI, 8.2-12.8). In histologic subtypes and PS, there were no difference in PFS and OS between pts with intestinal type and diffuse type as well as between those with PS of 0 and 1-2. As for the number of previous treatment regimens, there was no difference in PFS between pts who received ≥3 regimens and pts who received 2 regimens. However, the former had significantly longer OS compared with the latter. Ten patients (40%) developed immune-related adverse event (ir-AE) and four (16%) did severe ir-AE (≥grade 3). Conclusions: The current study showed better results and longer OS for AGC pts who received NIVO with acceptable toxicities. The limitation is a small number of patients accompanied by a potential of selection with retrospective manner, thus warrants a further studies. [ABSTRACT FROM AUTHOR]

In ATTRACTION-2 trial, nivolumab (NIVO) showed better outcome compared with best supportive care in advanced gastric cancer (AGC) patients (pts) at least two previous regimens. (NIVO has changed the treatment of AGC in Japan.) Methods: From Nov 2017 to Feb 2019, we retrospectively investigated 25 pts with AGC who received NIVO. Results: The patient demographics were as follows: median age, 67 (range, 39-82); male/female ratio, 18:7; performance status (PS) 0/1/2, 9/14/2; unresectable /recurrent, 20 /5; HER2 positive, 3; deep vein thrombosis, 3; intestinal type /diffuse type, 13 /12; primary site EGJ/UML/UM/ML/U/M/L, 2/2/1/3/5/4/8; site of metastases lymph node /liver /peritoneum /ovary, 13 /8 /9 /1; and previous treatment regimens 2 regimens /3 regimens /≥4 regimens, 9 /10 /6. Response rate (RR) was 12% and disease control rate (DCR) was 28%. The median progression free survival (PFS) was 4.1 months (95% confidence interval [CI], 2.8-NA) and the median overall survival (OS) was 11.8 months (95% CI, 8.2-12.8). In histologic subtypes and PS, there were no difference in PFS and OS between pts with intestinal type and diffuse type as well as between those with PS of 0 and 1-2. As for the number of previous treatment regimens, there was no difference in PFS between pts who received ≥3 regimens and pts who received 2 regimens. However, the former had significantly longer OS compared with the latter. Ten patients (40%) developed immune-related adverse event (ir-AE) and four (16%) did severe ir-AE (≥grade 3). Conclusions: The current study showed better results and longer OS for AGC pts who received NIVO with acceptable toxicities. The limitation is a small number of patients accompanied by a potential of selection with retrospective manner, thus warrants a further studies. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied.Methods/design: The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients' clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative.Discussion: A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the "personalized therapy" in adjuvant chemotherapy for colon cancer.Trial Registration: ClinicalTrials.gov: NCT00918827, UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002013. [ABSTRACT FROM AUTHOR]