Search

Introduction: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. Method: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. Results: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7–2.0) and 8.9 months (95% CI: 6.5–11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3–1.5) and 6.8 months (95% CI: 5.0–8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8–1.9) and 7.0 months (95% CI: 5.3–8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1–2.3) and 8.9 months (95% CI: 6.7–11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. Conclusion: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

Background Some studies have reported that adhesion prevention barriers (APBs) reduce adhesion after abdominal surgery; however, evidence showing that APBs reduce the incidence of postoperative small bowel obstruction (SBO), one of the most serious complications after abdominal surgery, is little. One concern is that APBs are usually applied only under the midline incision, although adhesion can occur at any place in the peritoneum where an incision is made during surgery. INTERCEEDⓇ is an APB that reportedly prevents postoperative SBO after surgery. This study aims to assess the clinical utility of INTERCEEDⓇ for the prevention of SBO after laparoscopic colorectal cancer surgery and determine whether the application site of INTERCEEDⓇ affects the incidence of SBO. Methods/Design This study is a prospective, multicenter, observational study conducted in Japan. The primary end point is the incidence of postoperative SBO 2 years after laparoscopic colorectal cancer surgery. The secondary end points include whether the site of the application of INTERCEEDⓇ affects the incidence of SBO. Each surgeon selects one of the following three procedures: 1) INTERCEEDⓇ is placed only under the midline incision; 2) INTERCEEDⓇ is placed at the site of bowel mobilization and/or lymph node dissection, but not under the midline incision; and 3) INTERCEEDⓇ is placed at both sites. Discussion This is the first study to assess whether the placement of APBs affects the incidence of SBO. The study results may lead to a subsequent randomized study.

Several studies have demonstrated that diverse systemic inflammatory-based prognostic parameters predict a poor prognosis in patients with gastric cancer. However, few studies have focused on the relationships between postoperative complications and systemic inflammatory-based prognostic parameters after curative gastrectomy. We investigated the relationships between postoperative complications and these parameters and assessed the clinical utility of the parameters as predictors of postoperative complications in patients with stage I–III gastric cancer. We retrospectively reviewed 300 patients who underwent curative gastrectomy for stage I–III gastric cancer. All postoperative complications were classified as infectious or noninfectious. We evaluated the relationships between postoperative complications and clinical factors, including systemic inflammatory-based prognostic parameters. In total, 101 patients (33.7%) had postoperative Clavien–Dindo grade II–IV complications, and 54 (18.0%) patients developed infectious complications including pancreatic fistula, pneumonia, anastomotic leak, intra-abdominal abscess, and cholecystitis. The relationships between postoperative complications and systemic inflammatory-based prognostic parameters were evaluated by the areas under the receiver operating characteristic curves. Postoperative pneumonia was identified as the most sensitive complication to the systemic inflammatory-based prognostic parameters. Multivariate analysis revealed that preoperative neutrophil-to-lymphocyte ratio (odds ratio, 14.621; 95% confidence interval, 1.160–184.348; p = 0.038) was an independent predictor of pneumonia. Preoperative neutrophil-to-lymphocyte ratio may be a useful predictor of postoperative pneumonia in patients with stage I–III gastric cancer after curative gastrectomy.

Aim Appendicitis is divided into two categories: complicated appendicitis (CA) and uncomplicated appendicitis (UA). In pediatric patients with CA, the use of interval appendectomy (IA), which is non‐operative management followed by elective surgery, has decreased the number of postoperative complications. Before discussing the merit of IA for adult patients, we need to clarify whether the frequency and seriousness of the complication rate after emergency surgery is higher for CA than for UA. Methods This retrospective cohort study included adult patients who underwent appendectomy and who were registered in the National Clinical Database (NCD) from 2014 to 2016. Patients with CA who underwent emergency appendectomy comprised the CA group. Patients with UA comprised the UA group. Patients with chronic or recurrent appendicitis who underwent elective appendectomy comprised the elective appendectomy (EA) group. Primary outcomes were all morbidity, serious morbidity, and mortality within 30 days after appendectomy. Results We included 109 256 patients in the study: 14 798 CA, 86 876 UA, and 7582 EA patients. Compared with the UA group, the rates of all morbidity, serious morbidity, and mortality were significantly higher in the CA group. All morbidity, serious morbidity, and mortality rates were significantly lower in the EA group than in the other two groups. Conclusions We confirmed that emergency surgery for CA places the patient at relatively higher risk. We also showed that the risk associated with EA is significantly lower than that for the other methods., This retrospective cohort study included adult patients who underwent appendectomy and who were registered in the National Clinical Database from 2014 to 2016. Compared with the uncomplicated appendicitis group, the rates of all morbidity, serious morbidity, and mortality were significantly higher in the complicated appendicitis group. All morbidity, serious morbidity, and mortality rates were significantly lower in the elective appendectomy group than in the other two groups.

TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1–5 and 8–12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.

To systematically review the effects of surgeon fatigue on postoperative mortality and postoperative complications after elective and non-elective surgeries. A database search was conducted for original articles published in PubMed between 2000 and 2020 with the keywords: “surgeon,” “sleep deprivation,” “sleep deprived,” “fatigued,” “mortality,” “morbidity,” and “outcomes.” We selected articles that disclosed actual numbers of patients who underwent surgery by fatigued or rested surgeons, rates of postoperative mortality, or total postoperative complications. Of the 1427 articles identified, 16 met the selection criteria and were included. Eight of the 16 also included total postoperative complications. Analysis revealed no significant differences in the rates of postoperative mortality after elective and non-elective surgeries or total postoperative complications of elective surgeries or non-elective surgeries performed by fatigued vs. rested surgeons. The relative risks were 1.03 [95% confidence interval (CI), 0.86–1.24], 1.08 (95% CI, 0.85–1.38), 0.99 (95% CI, 0.95–1.04), and 0.93 (95% CI, 0.67–1.28), respectively. Surgeon fatigue does not affect the rates of postoperative mortality or total postoperative complications after elective surgeries and may have little to no effect on the rates of postoperative mortality or total postoperative complications after non-elective surgeries.

Anastomotic leak is one of the most serious postoperative complications, and intraoperative adequate perfusion plays a key role in preventing its development in gastric cancer surgery. This study aimed to investigate the relationships between anastomotic leak and the parameters defined by an assessment of intraoperative anastomotic perfusion using a near-infrared indocyanine green (ICG) fluorescence system and to evaluate the usefulness of this ICG fluorescence assessment in gastric cancer surgery. We retrospectively reviewed data of 100 patients who underwent gastric cancer surgery. In a visual assessment based on fluorescence intensity, we classified ICG fluorescence image patterns as homogeneous, heterogeneous, or faint. In a chronological assessment, the first or second time point of ICG fluorescence appearance on one or the other side of the anastomosis was defined as FT or ST, respectively. The time difference in ICG fluorescence appearance between FT and ST was defined as TD. The relationships between anastomotic leak and the evaluated clinical factors, including the parameters identified by the ICG fluorescence assessment, were evaluated using univariate or multivariate analysis. Although no signs of leak were found by surgeons’ subjective judgments, four patients developed postoperative anastomotic leak of Clavien–Dindo grade III or IV. Multivariate analysis revealed that TD was an independent predictor of anastomotic leak (odds ratio 35.361, 95% confidence interval 1.489–839.923, p = 0.027). A novel parameter identified using near-infrared ICG fluorescence assessment may be useful to predict anastomotic leak in gastric cancer surgery. UMIN Clinical Trials Registry: #UMIN000030747 ( https://www.umin.ac.jp/ctr/index.htm ).

The present study was performed to compare postoperative pain following transinguinal preperitoneal repair (TIPP) and transabdominal preperitoneal repair (TAPP) performed by a single surgeon with adequate experience in each procedure.Adult patients who underwent herniorrhaphy for elective unilateral primary inguinal hernia repair from April 2013 to October 2019 were identified. After propensity score matching, a numeric rating scale was used to compare postoperative pain scores at 1 day, 1 week, and 1 month between patients who underwent TAPP and TIPP.Among 784 patients who underwent herniorrhaphy during the study period, 354 were analyzed by propensity score matching (TAPP, TAPP is preferable to TIPP in patients undergoing elective unilateral primary inguinal hernia repair in terms of reducing short-term pain.

We investigated the safety and efficacy of circadian chronotherapy via the hepatic artery(chrono-HAI)as a prehepatectomy chemotherapy for initially unresectable colorectal liver metastases. Five-day course of chrono-HAI using 5-FU, l-LV, and L-OHP plus systemic panitumumab with 9-day interval were administered to 24 patients with failure for previous chemotherapy. Response rate and Grade 3 adverse effect(AE) were 63% and 54%, respectively. Among 22 patients( excluding 2 CR patients), conversion surgery could be performed in 10(45%). Two-year overall survival of patients with surgery (58%)was longer in those without(20%, p=0.057). Although incidence of AE was a bit high, chrono-HAI plus systemic panitumumab is an effective prehepatectomy chemotherapy for patients with aggressive colorectal liver metastases.

TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects.This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%).Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.

219 Background: Epidermal growth factor receptor (EGFR) blockade can effectively shrink tumors in metastatic colorectal cancer (CRC) patients without RAS nor BRAF mutations. However, some patients without RAS nor BRAF mutations in their primary tumors have them in metastatic tumors (heterogeneity). Circulating tumor DNA (ctDNA) can reflect these mutations in metastatic tumors. Here, we evaluated the efficacy of EGFR blockade in patients who had no RAS nor BRAF mutations in their primary tumors, but who had them in ctDNA. Methods: We prospectively enrolled 100 patients with confirmed metastatic CRC without RAS nor BRAF mutations in their primary tumors. Patients were treated with first-line systemic chemotherapy that included EGFR blockade. We obtained ctDNA from each patient before they started chemotherapy, and at the time they acquired resistance. We detected RAS, BRAF (V600E), and PIK3CA mutations using digital polymerase chain reaction. Results: In the ctDNA obtained before starting chemotherapy, RAS, BRAF, and PIK3CA mutations were detected in 10, 4, and 2 of the 100 patients, respectively. No patients had both RAS and BRAF mutations in their ctDNA; however, one patient had both BRAF and PIK3CA mutations. Eighty-nine patients had measurable tumor lesions. Of those, 3 experienced a complete response (CR), 72 had a partial response (PR), 12 had stable disease (SD), and 2 had progressive disease (PD). Of 14 patients who had measurable tumors and RAS or BRAF mutations in the ctDNA, 11 (79%) had a PR and 3 (21%) had SD. Of 75 patients who had measurable tumors and no RAS or BRAF mutations in the ctDNA, 3 (4%) experienced a CR, 61 (81%) had PR, 9 (12%) had SD, and 2 (3%) had PD. Patients with RAS or BRAF mutations and patients with neither mutation had response rates of 79% and 85%, respectively. There was no significant difference. Conclusions: As we previously reported, incidence of RAS and BRAF heterogeneity were 10% and 4%, respectively. Heterogeneity of RAS and BRAF mutations had no effect on the response rate of EGFR blockade as first line chemotherapy. Other possible causes of resistance could be MET or HER-2 amplification, PIK3CA mutation, or ALK fusion. The effect of heterogeneity on the duration of response is of great interest; however, one-third of patients are still undergoing treatment with EGFR blockade. Clinical trial information: 000031177 .

Regorafenib significantly improves overall survival in previously treated metastatic colorectal cancer patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of regorafenib. These toxicities appear soon after treatment initiation. The ReDOS study demonstrated the effectiveness of a weekly dose-escalation therapy of regorafenib starting with a lower daily dose; however, its usefulness in Asian subjects is unknown. We conducted a phase II study to evaluate the safety and survival benefit of regorafenib dose-escalation therapy for Japanese patients.Patients with sufficient organ function, who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3, if no severe drug-related toxicities were observed. The primary endpoint was cancer progression-free survival (PFS). Tumor response and progression were assessed radiologically every 8 weeks. This study was registered in the University Hospital Medical Information Network (UMIN#UMIN000028933).57 patients were enrolled and all started regorafenib at 80 mg/day. 32 patients (56.1%) were subsequently escalated to 120 mg/day and 19 (33.3%) to 160 mg/day. Only 8 patients (14.0%) discontinued treatment because of adverse events. Median PFS was 1.9 months. Median overall survival was 8.9 months, the response rate was 0%, and the disease control rate was 31.6%. The most frequent adverse event greater than grade 3 was hypertension (19.3%), followed by HFSR (14.0%).Regorafenib dose-escalation therapy is well tolerated with PFS-like regorafenib standard therapy.

Background: Several studies have demonstrated that diverse systemic inflammatory-based prognostic parameters predict poor prognosis in patients with gastric cancer. However, few studies focused on the relationships between postoperative complications and systemic inflammatory-based prognostic parameters after curative gastrectomy. We investigated the relationships between postoperative complications and these parameters to identify parameter-specific postoperative complications, and assessed the clinical utility of the parameters as predictors of postoperative complications in stage I–III gastric cancer patients.Methods: We retrospectively reviewed 300 patients who underwent curative gastrectomy for stage I–III gastric cancer. A postoperative complication sensitive to the systemic inflammatory-based prognostic parameters was identified using a receiver operating characteristic curve, and we evaluated the relationships between the identified postoperative complication and other clinical factors.Results: In total, 101 patients (33.7%) had postoperative Clavien–Dindo grade II–IV complications, namely anastomotic complications, such as leak, stenosis, or hemorrhage (35 patients, 11.7%); pancreatic fistula (16 patients, 5.3%); and pneumonia (14 patients, 4.7%). Postoperative pneumonia had the most sensitive relationship to five systemic inflammatory-based prognostic parameters, and was associated with poor prognosis in stage I–III gastric cancer patients after curative gastrectomy. Multivariate analysis revealed that preoperative neutrophil-to-lymphocyte ratio (odds ratio: 5.228, 95% confidence interval: 1.269–21.541; P=0.022) was an independent predictor of postoperative pneumonia.Conclusions: Preoperative neutrophil-to-lymphocyte ratio may be a useful predictor of postoperative pneumonia in stage I–III gastric cancer patients after curative gastrectomy.

The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned intermittent oxaliplatin strategy in metastatic colorectal cancer (mCRC). Patients with untreated mCRC were administered CAPOX (130 mg/m2 oxaliplatin on day 1, 2000 mg/m2/day capecitabine on days 1–14, every 21 days) + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety. Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. Median PFS was 14.1 months (95% confidence interval [CI], 8.6–19.5), and median TTF was 12.3 months (95% CI, 10.3–14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, peripheral sensory neuropathy, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%. CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients. UMIN ID: 000,005,732, date of registration: June 7, 2011. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695

Background Although diffusion-weighted magnetic resonance imaging (DWI) for detecting lymph node (LN) metastasis is reported to be a successful modality for primary malignant tumors, there are few studies relating to esophageal cancer. This study aimed to clarify the diagnostic performance of DWI for assessing LN metastasis compared with positron emission tomography (PET) in patients with esophageal squamous cell cancer (eSCC). Methods Seventy-six patients with histologically proven eSCC who underwent curative esophagectomy without neoadjuvant treatment were reviewed retrospectively. Harvested LNs were divided into 1229 node stations with 94 metastases. Diagnostic abilities and prognostic significance were compared. Results In a station-by-station evaluation, the sensitivity was higher in DWI than PET (67% vs. 32%, P P P = 0.048), as was PET-N status (HR 2.481; P = 0.033). Conclusions DWI, which depends on cancer cell volume followed by elevated intranodal density, is a non-invasive modality and showed higher sensitivity than PET. It has clinical impact in predicting postoperative survival for patients with eSCC alongside its diagnostic ability and has significant performance in clinical practice.

We herein describe a case of laparoscopic surgery for an esophageal duplication cyst using a near‐infrared indocyanine green fluorescence system. A 64‐year‐old woman with a cystic tumor adjacent to the esophagogastric junction was referred to our hospital for treatment. Esophagogastroduodenoscopy and abdominal CT revealed a 70‐mm submucosal tumor derived from the abdominal esophagus. We performed laparoscopic resection and then evaluated the tissue perfusion of the abdominal esophagus by using a near‐infrared indocyanine green fluorescence system. A Dor fundoplication was performed to prevent postoperative gastroesophageal reflux disease and reinforce the mucosal layer defect. The postoperative course was uneventful, and pathological evaluation confirmed that the tumor was an esophageal duplication cyst. The patient did not develop recurrence in the 24 months after surgery. We have demonstrated that laparoscopic resection of an esophageal duplication cyst may be performed effectively with intraoperative assessment of tissue perfusion using a near‐infrared indocyanine green fluorescence system.

Approximately 30% patients with stage III colon cancer (CC) develop local recurrence and/or distant metastasis, even if postoperative adjuvant chemotherapy with oxaliplatin plus 5-fluorouracil and leucovorin (5-FU/LV) has been completed. In the present study, molecular analysis was performed to identify molecular markers of tumor recurrence in patients with stage III CC receiving oxaliplatin-based adjuvant chemotherapy. The FACOS study was conducted as a phase II study to evaluate the safety and efficacy of oxaliplatin-based treatment for stage III CC patients. Of the 132 CC patients enrolled in the present study, gene expression analysis using a microarray was conducted in 51 patients. Of these 51 patients, 6 developed recurrence within 5 years. The topmost 5% genes that showed differential expressions between cases that developed/did not develop recurrence were selected, and a set of predictive molecular markers for recurrence was identified. Of the 34,694 genes in the microarray, 1,734 genes were extracted as topmost 5% genes showing differential expressions between cases with and without recurrence. Among these, 10 genes, includingADH1A, ADH1C, CA12, CHP2, HMGCS2, SNAR-A1, TPI1, MS4A12, PLA2G10 and PTPRO, were identified as markers that could clearly divide patients with and without recurrence. Although several prediction models of tumor recurrence have been reported for CC, the set of 10 genes that the present study identified may be useful to predict the risk of recurrence in stage III CC patients receiving oxaliplatin-based adjuvant chemotherapy. Based on these results, high-risk patients with CC should be carefully observed to detect tumor recurrence during the follow-up period.

A phase II trial was conducted to investigate the benefit of oxaliplatin-based adjuvant chemotherapy in Japanese stage III colon cancer patients. Eligible patients were scheduled to receive 12 cycles of mFOLFOX6 or 8 cycles of CAPOX in adjuvant settings. The primary endpoint was the 3-year disease-free survival (DFS). Cox proportional hazards regression was performed to identify risk factors for a worse DFS. A total of 130 patients, including 73 patients receiving mFOLFOX6 and 57 patients receiving CAPOX, were enrolled from 16 institutions between April 2010 and April 2014. The 3-year DFS was 82.2%, exceeding the expected primary endpoint of 81.7%. The 3-year DFS tended to be higher in patients receiving mFOLOFOX6 than in those receiving CAPOX (mFOLFOX6, 86.3%; CAPOX, 76.9%; P = 0.06). The 3-year DFS rates did not differ markedly based on the risk stratification (T1/T2/T3 N1 vs. T4 or N2) indicated by the IDEA COLLABORATION study (P = 0.22). In the multivariate analysis, stage IIIC (P = 0.046) and early discontinuation (P

Low anterior resection syndrome (LARS) commonly develops after an anal sphincter-preserving operation (SPO). The etiology of LARS is not well understood, as the anatomical components and physiological function of normal defecation, which may be damaged during the SPO, are not well established. SPOs may damage components of the anal canal (such as the internal anal sphincter, longitudinal conjoint muscle, or hiatal ligament), either mechanically or via injury to the nerves that supply these organs. The function of the rectum is substantially impaired by resection of the rectum, division of the rectococcygeus muscle, and/or injury of the nervous supply. When the remnant rectum is small and does not function properly, an important functional role may be played by the neorectum, which is usually constructed from the left side of the colon. Hypermotility of the remnant colon may affect the manifestation of urge fecal incontinence. To develop an SPO that minimizes the risk of LARS, the anatomy and physiology of the structures involved in normal defecation need to be understood better. LARS is managed similarly to fecal incontinence. In particular, management should focus on reducing colonic motility when urge fecal incontinence is the dominant symptom.

Background: In the first-line treatment of metastatic colorectal cancer (mCRC) patients with CAPOX plus bevacizumab, the optimal duration of maintenance treatment without oxaliplatin to avoid discontinuation of therapy due to peripheral sensory neuropathy (PSN) remains unknown. The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned oxaliplatin intermittent strategy in mCRC.Methods: Patients with untreated mCRC were administered CAPOX [oxaliplatin 130 mg/m2 and capecitabine (2000 mg/m2 daily) as intermittent treatment for 14 days, followed by a 7-day treatment-free interval, every 3 weeks] + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety.Results: Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. The relative dose intensity and the cumulative dose of oxaliplatin during the overall treatment period were 649.1 mg/m2 and 1132.5 mg, respectively. Median PFS was 14.1 months (95% confidence interval [CI], 8.6–19.5), and median TTF was 12.3 months (95% CI, 10.3–14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, PSN, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%.Conclusion: CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients.Trial registration: This trial was registered with the University Hospital Medical Information Network on 7 June 2011 (UMIN ID: 000005732).

This randomized phase II trial compared tegafur–uracil/leucovorin (UFT/LV) plus oxaliplatin (TEGAFOX) to UFT/LV as adjuvant chemotherapy for patients with high-risk stage II/III colorectal cancer. From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/m2 oxaliplatin on days 1 and 15, 300 mg/m2/day UFT and 75 mg/day LV on days 1–28, every 35 days for five cycles) or UFT/LV. The primary study endpoint was disease-free survival. The 3-year disease-free survival rate was 84.2% in the TEGAFOX arm, versus 62.1% for UFT/LV. The stratified hazard ratio for disease-free survival for TEGAFOX compared to UFT/LV was 0.338 (P < 0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P < 0.01). The rates of any-grade neutropenia, thrombocytopenia, aspartate aminotransferase/alanine aminotransferase elevation, and peripheral sensory neuropathy were higher in the TEGAFOX group, whereas the incidence of grade ≥ 3 adverse events did not differ between the groups. TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer. UMIN ID: 000007696, date of registration: April 10, 2012

This randomized phase II trial compared tegafur-uracil/leucovorin (UFT/LV) plus oxaliplatin (TEGAFOX) to UFT/LV as adjuvant chemotherapy for patients with high-risk stage II/III colorectal cancer.From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/mThe 3-year disease-free survival rate was 84.2% in the TEGAFOX arm, versus 62.1% for UFT/LV. The stratified hazard ratio for disease-free survival for TEGAFOX compared to UFT/LV was 0.338 (P0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P0.01). The rates of any-grade neutropenia, thrombocytopenia, aspartate aminotransferase/alanine aminotransferase elevation, and peripheral sensory neuropathy were higher in the TEGAFOX group, whereas the incidence of grade ≥ 3 adverse events did not differ between the groups.TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer.UMIN ID: 000007696, date of registration: April 10, 2012.

Background: There are no standardised criteria for the determination of the ‘regional’ pericolic node in colon cancer surgery, which represents a major cause of the international uncertainty regarding the optimal bowel resection margin. This prospective cohort study aimed to determine ‘regional’ pericolic nodes based on detailed mapping for feeding arteries and lymph nodes. Methods: In all, 2,996 patients with stages I–III colon cancer who underwent curative surgery between June 2013 and December 2017 at 25 institutions in Japan were included. The anatomical distributions of the feeding artery and lymph nodes were determined in resected fresh surgical specimens based on in vivo measurements of the bowel. Findings: The mean number of retrieved pericolic nodes was 20·9 per patient. In all patients except seven (0·2%), the primary feeding artery was distributed within 10 cm of the primary tumour. The metastatic pericolic node location most distant from the primary tumour was within 3 cm in 837 patients, 3–5 cm in 130 patients, 5–7 cm in 39 patients and 7–10 cm in 34 patients. Only four patients (0·1%) had pericolic lymphatic spread beyond 10 cm; all of whom had T3/4 tumours accompanying extensive mesenteric lymphatic spread, and three developed systemic recurrence. The positive pericolic node distance from the primary tumour did not differ depending on the primary tumour location or the distribution of the feeding arteries. Postoperatively, none of the 2996 patients developed recurrence in the remaining pericolic nodes. Interpretation: Based on the distribution of metastatic lymph nodes and prognostic outcomes, the pericolic nodes designated as ‘regional’ were those located within 10 cm of the primary tumours. Despite the fact that surgeons tend to prefer complete mesocolic excision, these findings should be fully considered when determining the bowel resection margin. Funding: Japanese Society for Cancer of the Colon and Rectum Declaration of Interest: All authors declare no competing interests. Ethical Approval: This study was conducted according to the Declaration of Helsinki and comparable Japanese ethical standards. The study was approved by the Institutional Review Boards of the JSCCR and each participating institution. Written informed consent was obtained from all study participants

We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial. Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated. A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%). Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.

Background: the novel severe acute respiratory syndrome coronavirus 2 virus that emerged in December 2019 causing coronavirus disease 2019 (COVID-19) has led to the sudden national reorganization of health care systems and changes in the delivery of health care globally. The purpose of our study was to use a survey to assess the global effects of COVID-19 on colorectal practice and surgery. Materials and methods: a panel of International Society of University Colon and Rectal Surgeons (ISUCRS) selected 22 questions, which were included in the questionnaire. The questionnaire was distributed electronically to ISUCRS fellows and other surgeons included in the ISUCRS database and was advertised on social media sites. The questionnaire remained open from April 16 to 28, 2020. Results: a total of 287 surgeons completed the survey. Of the 287 respondents, 90% were colorectal specialists or general surgeons with an interest in colorectal disease. COVID-19 had affected the practice of 96% of the surgeons, and 52% were now using telemedicine. Also, 66% reported that elective colorectal cancer surgery could proceed but with perioperative precautions. Of the 287 respondents, 19.5% reported that the use of personal protective equipment was the most important perioperative precaution. However, personal protective equipment was only provided by 9.1% of hospitals. In addition, 64% of surgeons were offering minimally invasive surgery. However, 44% reported that enough information was not available regarding the safety of the loss of intra-abdominal carbon dioxide gas during the COVID-19 pandemic. Finally, 61% of the surgeons were prepared to defer elective colorectal cancer surgery, with 29% willing to defer for ≤ 8 weeks. Conclusion: the results from our survey have demonstrated that, globally, COVID-19 has affected the ability of colorectal surgeons to offer care to their patients. We have also discussed suggestions for various practical adaptation strategies for use during the recovery period. We have presented the results of a survey used to assess the global impact of coronavirus disease 2019 (COVID-19) on the delivery of colorectal surgery. Despite accessible guidance information, our results have demonstrated that COVID-19 has significantly affected the ability of colorectal surgeons to offer care to patients. We have also discussed practical adaptation strategies for use during the recovery phase., NA

Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan.We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy.SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P 0.001). Oxaliplatin-induced SOS persisted for 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13).This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.

Laparoscopic transverse colectomy is technically difficult. In mini-laparotomy surgery, colectomy for midtransverse colon cancer can easily be performed, but exact D2 lymph node dissection is very difficult for a variety of vessels in the transverse colon. Using 3D-CT imaging, we present a case of D2 lymph node dissection where mini-laparotomy transverse colectomy was performedby a small incision similar to that usedin laparoscopic surgery.The patient was a 60-yearoldwoman with early transverse colon cancer, which was locatedin the mid-transverse colon. Surgical treatment was plannedfor pT1b(1.5mm)andpVM1 in pathological findings after EMR. Using CT colonography(CTC), the location of the primary tumor was identified. Using simulation CTC(sCTC), composedof CTC and 3D imaging of the arteries andveins, the dominant artery was identified and D2 lymph node dissection was simulated. In addition, body surface 3D imaging and permeable surface 3D imaging of the abdominal trunk were performed. Using body surface 3D-sCTC, composedof sCTC and body surface 3D imaging, the minimum incision to enable D2 lymph node dissection was simulated.Using sCTC, it was identified that the dominant artery was the right branch of the middle colic artery(MCA Rt)andthe accompanying vein was branchedfrom the gastrocolic trunk(GCT). D2 lymph node dissection to separate the branching root of MCA Rt and the accompanying vein was simulated. Next, surgical incision was simulated using body surface 3D-sCTC. Because the branching roots of MCA Rt andGCT were locatedabout 5 cm cranial from the upper rim of the navel, a 7 cm upper abdominal midline incision was designed in addition to a 2 cm umbilical incision. Mini-laparotomy transverse colectomy with a 7 cm incision was performedin accordance with the simulation. The operation time was 2 hours and5 1 minutes, andbloodloss was due to occult bleeding. The patient was discharged 7 days after surgery without complications, and the final diagnosis was pT1bN0M0, StageⅠwith no recurrence for 4 years and2 months after surgery. The cranial incision from the upper rim of the navel has shrank about 3 cm, and the umbilical incision is not noticeable.D2 lymph node dissection of minilaparotomy transverse colectomy can be a treatment option for early transverse colon cancer through using body surface 3DsCTC.

Adjuvant chemotherapy with oxaliplatin combined with a fluoropyrimidine derivative is widely accepted as standard therapy for patients with stage III colon cancer, since few clinical data are available for Japanese patients. The FACOS trial investigated the tolerability of modified FOLFOX6 (mFOLFOX6) and XELOX regimens in Japanese colon cancer patients. Twelve cycles of mFOLFOX6 or 8 cycles of XELOX were given to patients with eligibility: stage III curatively resected colon cancer, performance status of 0–1, age from 20 to 75 years, and adequate organ function. The primary endpoint was 3-year disease-free survival. Secondary endpoints were the incidence of adverse events (AEs) and the completion rate of study therapy. From April 2010 to April 2014, a total of 132 patients were enrolled. Safety was analyzed in 130 patients, with finalized data from 73 patients receiving mFOLFOX6 and 57 patients receiving XELOX. A total of 130 patients (100%) experienced AEs (any grade), and 52 patients (40.0%) experienced AEs of grade ≥ 3. No significant difference in the frequency of grade ≥ 3 AEs was observed between mFOLFOX6 and XELOX groups. Continuation of the planned cycle rate of protocol treatment was 69.9% in the mFOLFOX6 group and 68.4% in the XELOX group. Treatment was discontinued because of AEs in 14 patients (19.2%) in the mFOLFOX6 group and 8 (14.0%) in the XELOX group. Mean relative dose intensity for oxaliplatin was 78.0% in the mFOLFOX6 group and 82.8% in the XELOX group. As adjuvant chemotherapy for stage III colon cancer, mFOLFOX6/XELOX regimens are acceptable.

Diverticular disease of the colon occurs quite frequently in developed countries, and its prevalence has recently increased in Japan. The appearance of diverticulosis increases with age, although mostly remaining asymptomatic. Approximately 20% of cases require treatment. As the Western lifestyle and number of elderly people increase, the need for medical treatment also increases. Computed tomography (CT) is the gold standard for diagnosing diverticulitis. Complicated diverticulitis is classified by the size and range of abscess formation and the severity of the peritonitis. Each case should be classified based on clinical and computed tomography (CT) findings and then treated appropriately. Most patients with uncomplicated diverticulitis (stages 0–Ia) can be treated conservatively. Diverticulitis with a localized abscess (stages Ib–II) is generally resolved with conservative treatment. If the abscess is larger or conservative treatment fails, however, percutaneous drainage or surgery should be considered. Operative treatment is considered standard therapy for severe diverticulitis with perforation and generalized peritonitis (stages III–IV). Colonic diverticulitis treated conservatively frequently recurs. Elective surgery after recovery should be considered carefully and decisions made on a case‐by‐case basis. Because cases of colonic diverticulitis will undoubtedly increase in Japan, it is likely that we will be confronted with increasing numbers of treatment decisions. We therefore need to have a systematic strategy for treating the various stages of colonic diverticulitis appropriately. We herein review the management of complicated diverticulitis.

It is reported that simulation computed tomography colonography(S-CTC), which combines CTC and 3-dimensional(3D)vascular imaging, is useful in colorectal cancer surgery. However, it is difficult to create 3D vascular images using non-contrast CT. Laparoscopic transverse colectomy is said to be technically difficult. Mini-laparotomy surgery for mid-transverse colon cancer is quite easy to perform. However, exact D2 lymph node dissection is very difficult. We present a case of D2 lymph node dissection during mini-laparotomy transverse colectomy performed using S-CTC, which involves the creation of 3D vascular images using non-contrast CT.The patient was a 77-year-old man with transverse colon cancer located in the mid-transverse colon, cT2N0M0, Stage Ⅰ. He had coexisting chronic renal failure. Non-contrast CT was performed prior to surgery, and the images were processed using workstation Zaiostation2.Both the artery and the vein created from non-contrast CT could be visualized clearly until the marginal vessels. Using noncontrast S-CTC in combination with CTC and 3D artery imaging, it was identified that the dominant artery was the left branch of the middle colic artery(MCA Lt), while the right branch of the MCA(MCA Rt)and accessory MCA(AMCA)were 10 cm or more apart. The fusion of 3D artery and vein imaging made it evident that the vein accompanying MCA Lt branched from the superior mesenteric vein. Using non-contrast S-CTC, D2 lymph node dissection, dissection of the branching root of MCA Lt and the vein at the same level was simulated. Thus, mini-laparotomy transverse colectomy was performed through a 7 cm incision, in accordance with the simulation.Non-contrast S-CTC was useful for performing D2 lymph node dissection during mini-laparotomy transverse colectomy.