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Aim: 5‐Fluorouracil/folinic acid and oxaliplatin plus bevacizumab (FOLFOX + BV) is a standard chemotherapy regimen for metastatic colorectal cancer (mCRC). This study was aimed at evaluating the preventive effects of shakuyakukanzoto against oxaliplatin‐induced neurotoxicity associated with FOLFOX + BV administration. Methods: In this single‐arm, open‐label, phase II clinical trial, we enrolled patients with previously untreated, histologically confirmed mCRC from six hospitals in Japan who were aged 20 years and older and had an Eastern Cooperative Oncology Group performance status of 0–1. The patients received shakuyakukanzoto 2.5 g thrice daily, orally, until disease progression and/or unacceptable toxicity was noted. The primary endpoint was the incidence of neurotoxicity following oxaliplatin administration at a dose of 500 mg/m2. Neurotoxicity was evaluated according to the Neurotoxicity Criteria of Debiopharm (DEB‐NTC). The trial was registered in the UMIN Clinical Trials Registry of Japan (UMIN000001853). Results: Forty‐one non‐pretreated mCRC patients were included between April 2009 and September 2013. At an oxaliplatin dose of 500 mg/m2, neurotoxicity of DEB‐NTC grade 1–2 developed in 25.0% of patients; no patient had DEB‐NTC grade 3 neurotoxicity. The most common grade 3/4 adverse events were neutropenia (34.1%), hypertension (24.4%), and fatigue (9.8%). The response rate of the 38 patients with measurable lesions was 55.2%. The median progression‐free and overall survival was 14.9 and 35.2 months respectively. Conclusion: Shakuyakukanzoto substantially reduced oxaliplatin‐induced neurotoxicity without negatively affecting tumor response or survival in FOLFOX + BV‐treated patients with CRC. [ABSTRACT FROM AUTHOR]

Aim: Due to the overwhelming spread of SARS‐CoV‐2 and its disruption of the healthcare system, delays and reduced numbers were reported for colorectal cancer screening, colonoscopies, and surgery during the COVID‐19 pandemic. This multicenter retrospective study investigated the still poorly understood impact of the COVID‐19 pandemic on colorectal cancer treatment in Japan. Methods: This study was organized by the Clinical Study Group of Osaka University, which comprised 32 major institutions in Osaka. We retrospectively analyzed the number of surgeries and colonoscopies performed and the characteristics of patients who underwent surgery for colorectal cancer between March 2019 and February 2021. We compared data collected before and during the COVID‐19 pandemic. We also assessed the methods used for detecting colorectal cancer, including fecal occult blood test, abdominal symptoms, and anemia. Results: The COVID‐19 pandemic caused reductions in the annual numbers of surgeries (3569 vs 3198) and colonoscopies (67 622 vs 58 183) performed in the 2020 fiscal year, compared to the 2019 fiscal year. During the COVID‐19 pandemic, a significantly lower proportion of patients were treated for clinical stages ≤I (24.2% vs 26.9%; P =.011), compared to the proportion treated before the pandemic. Fecal occult blood tests for detecting colorectal cancer were used significantly less frequently during the COVID‐19 pandemic (26.2% vs 29.6%; P =.002). These trends were more significant in larger institutions. Conclusion: The COVID‐19 pandemic reduced the number of colonoscopies and surgeries performed for colorectal cancer and hindered the detection of asymptomatic early‐stage cancers, and its impact varied by hospital size. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant oxaliplatin plus oral capecitabine (XELOX) is recommended for patients with curatively resected colon cancer. However, its safety and tolerability in Asian patients is unclear; therefore, we evaluated the safety and efficacy of adjuvant XELOX in Japanese patients with curatively resected stage III colon cancer (MCSCO-1024) and present the interim safety data.Methods: This prospective, multi-center, open-label, single-arm phase II study recruited patients with curatively resected stage III colon cancer. The protocol was a 120-min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and oral capecitabine (2000 mg/m2/day) in two divided doses for 14 days of a 3-week cycle, for a total of eight cycles (24 weeks). The primary endpoint was the 3-year disease-free survival, and secondary endpoints were the treatment completion rate, safety profile (rate and severity of adverse events), and correlation of adverse events, such as peripheral sensory neuropathy (PSN), with the administration period of oxaliplatin, etc.Results: From November 2011 to August 2014 (34 months), 196 patients were enrolled. Safety was analyzed in 190 patients. The median total doses of capecitabine and oxaliplatin were 215,586.9 and 777.2 mg/m2, respectively, while the median relative dose intensities were 82.5 and 76.0%, respectively. The overall treatment completion rate was 73.7%. The most frequent treatment-related adverse event was PSN (88.4%), while the most frequent grade ≥3 treatment-related adverse events were neutropenia (12.6%), PSN (6.3%), diarrhea (4.2%), and thrombocytopenia (4.2%). There were no treatment-related deaths.Conclusions: Adjuvant XELOX is tolerable for Japanese patients with Stage III colon cancer. [ABSTRACT FROM AUTHOR]

Background/Objective: Oral tegafur/uracil and leucovorin (UFT/LV) therapy is effective and safe for elderly patients with advanced or metastatic colorectal cancer (CRC). However, there are few studies on the combination of bevacizumab with UFT/LV. This clinical study evaluated the efficacy and safety of UFT/LV plus bevacizumab as a first-line therapy for elderly patients with advanced or metastatic CRC. Methods: Forty patients with advanced or metastatic CRC aged ≥75 years were enrolled in this multicenter, open-label, single-arm phase II study. All patients received oral UFT (300-600 mg) and LV (50 mg) twice daily on days 1-21 and intravenous bevacizumab (5 mg/kg) on days 1 and 15 of a 4-week cycle (University Hospital Medical Information Network No. UMIN000003447). Results: The median follow-up period was 14.7 months. The response rate was 20.0% [95% confidence interval (CI): 9.1-35.6], median progression-free survival was 8.9 months (95% CI: 5.3-11), and median overall survival was 21.7 months (95% CI: 13.7-23.4). The only grade 3 hematological toxicity was neutropenia (3.0%), and the incidence rates of grade 3 nonhematological toxicity were low at ≤10%. Conclusion: UFT/LV plus bevacizumab is a promising first-line regimen for elderly patients with advanced or metastatic CRC. The combination is well tolerated and efficacious. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To investigate the safety and efficacy of fondaparinux (FPX) for venous thromboembolism (VTE) prophylaxis in Japanese patients undergoing colorectal cancer surgery. Methods: The subjects of this multicenter, open-label, prospective observational study were patients undergoing resection of the colon/rectum for colorectal cancer. All patients were given FPX 2.5 or 1.5 mg by subcutaneous injection, once daily for 4-8 days, starting 24 h after surgery. The primary endpoint was any major bleeding event and the secondary endpoint was any symptomatic VTE event. Results: Between February 2009 and December 2010, 619 patients from 23 institutions were enrolled in this study. The median duration of FPX prophylaxis was 4 days. The incidence of major bleeding was 0.81 % [5/619, 95 % confidence interval (CI) 0.3-1.9] and the incidence of minor bleeding was 9.5 % (59/619, 95 % CI 7.3-12.1). There was no fatal bleeding or symptomatic VTE. Multivariable analysis revealed the following to be risk factors for bleeding events: preoperative platelet count <15 × 10/µl [odds ratio (OR) 4.521], male sex (OR 2.078), and blood loss during surgery <50 ml (OR 2.019). Conclusion: The administration of 2.5/1.5 mg FPX 24 h after colorectal cancer surgery is safe and effective. [ABSTRACT FROM AUTHOR]

Objective: Combined chemotherapy with S-1 and irinotecan (IRIS) for metastatic colorectal cancer has been reported to be effective and safe. However, there are only a few studies on the effects of adding bevacizumab to IRIS. We conducted a clinical study to evaluate the efficacy and safety of IRIS plus bevacizumab as first-line therapy for metastatic colorectal cancer. Methods: Forty metastatic colorectal cancer patients were enrolled in this phase II study. All patients received irinotecan (80 mg/m2) and bevacizumab (7 mg/kg) on days 1 and 15 and S-1 (40-60 mg twice daily) on days 1-21 of a 5-week repeated cycle. Results: The response rate was 47.4% [95% confidence interval (CI) 31.5-63.2], progression-free survival was 11.9 months (95% CI 9.4-16.8), and overall survival was 23.4 months (95% CI 19.0-inf). The only grade 3 hematological toxicity was neutropenia (16%) and the incidences of grade 3 nonhematological toxicity were low at <10%, other than diarrhea (10.9%). Conclusion: In this clinical study, we revealed IRIS plus bevacizumab to be a promising first-line regimen for metastatic colorectal cancer with a low incidence of serious toxicities, in which favorable response rates and extension of survival time can be expected. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: A number of clinical trials, including the FIRIS study, have shown that S-1 plus irinotecan (IRIS) is safe and effective in patients with colorectal cancer. Several different treatment protocols for IRIS are commonly used in Japan, besides the one used in the FIRIS study. This study was designed to evaluate the feasibility of a 5-week cycle of IRIS. Methods: Between January 2005 and February 2008, a total of 55 patients with metastatic colorectal cancer were enrolled at nine centers in Japan. All patients received irinotecan intravenously (80 mg/m) on days 1 and 15 and S-1 orally (40-60 mg twice daily, according to body surface area) on days 1-21 of a 5-week repeated cycle. Results: The overall response rate was 29.1 %. The response rate was 43.8 % in patients who received IRIS as first-line therapy and 23.1 % in those who received IRIS as second-line or subsequent therapy. The median survival time was 678 days (22.6 months). Adverse events of Grade 3 or higher that occurred at an incidence of ≥10 % were neutropenia (12.7 %) and diarrhea (10.9 %). Conclusion: Our efficacy and safety data suggest that a 5-week cycle of IRIS is an effective alternative to used currently regimens. [ABSTRACT FROM AUTHOR]

Adjuvant oxaliplatin plus capecitabine (XELOX) therapy is recommended for patients with curatively resected colon cancer. However, prospective data on its practical application in Japanese patients are limited. Therefore, we aimed to conduct a long-term clinical evaluation of the efficacy and safety of adjuvant XELOX in patients with curatively resected stage III colon cancer (MCSCO-1024). This prospective, multi-center, open-label, single-arm, phase II study enrolled patients with curatively resected stage III colon cancer. The treatment protocol consisted of a 120-minute intravenous infusion of oxaliplatin (130 mg/m 2 ) on day 1 and two divided doses oral capecitabine (2000 mg/m 2 /day) for 14 days in a 3-week cycle, totaling eight cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 5-year overall survival and long-term prognosis of peripheral sensory neuropathy. A total of 196 patients were enrolled between November 2011 and August 2014 (34 months). The 3-year DFS rate was 73%, and the 5-year overall survival rate was 87%. The overall incidence of peripheral sensory neuropathy was 17%, with a 1% rate of grade 3 neuropathy after 5 years. Adjuvant XELOX demonstrated utility and safety in the clinical management of Japanese patients with stage III colon cancer., (© 2024. The Author(s).)

Laparoscopic pancreaticoduodenectomy(LPD)is less invasive and provides better cosmetic outcomes than open pancreaticoduodenectomy( OPD). LPD without vascular excision and lymph node dissection has been covered by insurance since 2016 in Japan. On the other hand, secondary small bowel volvulus is a rare condition caused after abdominal operation. A 77-year-old woman underwent a laparoscopic pancreaticoduodenectomy with pancreatic cancer of pT2N0M0, pStageⅠB. She suffered from epigastric pain after meal. The abdominal CT revealed counterclockwise rotation of the SMV on SMA about 540 degree. Gastrointestinal endoscopy showed no abnormal findings in May 2017. Her abdominal pain was disappeared in July 2017. But the pain was recurred in May 2019. The abdominal CT revealed mesenteric edema and counterclockwise rotation about 810 degree. Her abdominal pain was disappeared again in February 2020. The counterclockwise rotation was decreased about 540 degree. Between May 2012 and February 2020, 50 patients underwent LPD at Kansai Rosai Hospital. 111 patients who received OPD between 2010 and February 2015 were included for comparison. No significant differences were noted between the LPD and OPD groups with respect to patient age(67.9 vs 70.3), gender(M/F: 31/19 vs 70/41). The intraoperative blood loss was lower(106 g vs 1,064 g, p<0.0001)and the operation time was longer (624 vs 535 min, p<0.0001)in the LPD group than the OPD group. Small bowel volvulus over 270 degree was 7/43 vs 5/106(p=0.0338), and over 360 degree was 6/44 vs 1/110(p=0.0014), respectively. Small bowel volvulus after pancreaticoduodenectomy was frequently observed in the laparoscopic group.

Background: Intestinal failure is the most critical complication of Crohn's disease. Intestinal failure requires home parenteral nutrition, which worsens the quality of life of the patients and sometimes causes life-threatening complications., Aims: The purpose of this study was to investigate the incidence and risk factors for intestinal failure in Crohn's disease., Methods: We performed a retrospective analysis of Crohn's disease patients (162 cases) at Osaka University Hospital between January 2000 and December 2017. Kaplan-Meier analysis was used to investigate the cumulative incidence of intestinal failure. To identify the risk factors of intestinal failure, patient characteristics were analyzed by multivariate analysis, including disease classification, surgical history, medical treatment other than surgery, and cumulative inflammation was calculated using the average C-reactive protein value and disease duration., Results: The cumulative incidence of intestinal failure 5, 10, and 15 years after Crohn's disease diagnosis was 2.6%, 3.4%, and 8.6%, respectively. Multivariate analysis identified the following as independent risk factors for intestinal failure in Crohn's disease: residual small intestinal length < 200 cm (odds ratio 7.51, 95% confidence interval 2.14-29.96), non-use of anti-tumor necrosis factor-alpha therapy (3.34, 1.22-10.74), and cumulative inflammation (1.01, 1.001-1.038). We created a new predictive nomogram consisting of these risk factors., Conclusions: Intestinal failure occasionally occurred during long-term treatment of Crohn's disease. Cumulative inflammation for the first time, in addition to short residual small intestinal length and non-use of anti-tumor necrosis factor-alpha therapy, was shown to be potential risk factors for intestinal failure in Crohn's disease.

Background: The number of elderly patients with colon cancer is increasing in Japan. Postoperative delirium (POD) is a major complication for elderly patients who undergo surgery, and postoperative pain is a common inducer of POD. We reported previously that single-incision laparoscopic surgery (SLS) significantly reduces postoperative pain compared to conventional laparoscopic surgery (CLS). Data are lacking about the effect of SLS on POD. This retrospective study evaluated the clinical benefits of SLS for POD in elderly patients with colon cancer., Methods: This retrospective case-control study included colon cancer patients (n = 134) over 75 years old who underwent elective surgery from 2009 to 2015 at Osaka University Hospital. Of these patients, 110 were evaluated using the comprehensive geriatric assessment (CGA) before surgery and were classified into lower or higher risk groups based on their scores., Results: The rate of POD was significantly lower in the SLS group than the CLS group (13.8% vs. 30.0%; p = 0.0161). In the CGA-based higher risk group, the rate of POD was significantly higher in the CLS group than the SLS group (p = 0.0153)., Conclusions: SLS for elderly colon cancer patients may lower the incidence of POD compared with CLS.

Background/aims: Crohn's disease (CD) is an inflammatory bowel disease. The risk of colorectal cancer (CRC) is increased in patients with CD. In Japan, anorectal cancer accounted for >60% of CRCs associated with CD. These anorectal cancers are typically diagnosed in advanced stages, because a surveillance protocol remains to be established. This study aimed to assess various biopsy methods for detecting CRC., Methods: This study included 72 patients (113 examinations) with CD who underwent cancer surveillance between August 2008 and October 2015. Surveillances were performed with a core needle biopsy in perianal regions (54 cases), endoscopic biopsy (90 cases), and excisional biopsy (34 cases). When it was difficult to perform colonoscopy in an outpatient setting, due to perianal pain or stricture, we employed examinations under anesthesia for surveillance., Results: The total CRC detection rate was 6.19% (7 examinations). CRC detection rates were 1.85% (1 case) with core needle biopsy, 5.56% (5 cases) with endoscopic biopsy, and 5.88% (2 cases) with excisional biopsy., Conclusions: We showed that it was important to employ various biopsy methods in cancer surveillance to detect CRC among patients with CD., (© 2016 S. Karger AG, Basel.)