Effects of neoadjuvant chemotherapy for patients with obstructive colon cancer: A multicenter propensity score-matched analysis (YCOG2101).

Aim: Obstructive colon cancer is locally advanced colon cancer with poor prognosis. However, the effect of neoadjuvant chemotherapy (NAC) on obstructive colon cancer remains unclear. Therefore, this study aimed to investigate the safety and efficacy of NAC in patients with obstructive colon cancer. Methods: From January 2012 to December 2017, we collected patient data for clinical stage II/III obstructive colon cancer at seven Yokohama Clinical Oncology Group (YCOG) institutions. The long-term outcomes of the NAC and non-NAC groups were analyzed retrospectively after adjusting for patients' background characteristics using propensity score matching. Results: Among the 202 eligible patients, propensity score matching extracted 51 patients each for the NAC and non-NAC groups. After matching, the groups showed no marked differences in the background factors. All the patients in the NAC group underwent diverting stoma construction. Nineteen patients (37.3%) experienced grade 3-4 adverse events during NAC. The incidence of postoperative complications was similar between groups. The 5-year progression-free survival rates were 75.8% in the NAC group and 63.0% in the non-NAC group (p = 0.22, log-rank test). The 5-year overall survival rates were 88.5% in the NAC group and 78.8% in the non-NAC group (p = 0.09, log-rank test). Conclusion: Although NAC was feasible for obstructive colon cancer after diverting stoma construction, its effects on long-term outcomes could not be proven.

Impact of the endoscopic surgical skill qualification system on conversion to laparotomy after low anterior resection for rectal cancer in Japan (a secondary analysis of the EnSSURE study).

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.

Multicenter randomized phase II study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases (YCOG1001).

PURPOSE: The high recurrence rate of colorectal cancer liver metastasis (CRCLM) after surgery remains a crucial problem. However, adjuvant chemotherapy after hepatectomy for CRCLM has not yet been established. This study evaluated the efficacy of adjuvant therapy with S-1 and oxaliplatin (SOX). METHODS: In a multicenter, randomized, phase II study, patients undergoing curative resection of CRCLM were randomly enrolled in a 1:1 ratio to either the low- or high-dose group. S-1 and oxaliplatin were administered from days 1 to 14 of a 3-week cycle as a 2-h infusion every 3 weeks. The dose of S-1 was fixed at 80 mg/m2. The doses in the low- and high-dose oxaliplatin groups were 100 mg/m2 (low-dose group) and 130 mg/m2 (high-dose group), respectively. This treatment was repeated eight times. The primary endpoint was the rate of discontinuation owing to toxicity. The secondary endpoints were the relapse-free survival (RFS) and frequency of adverse events (AEs). RESULTS: Between August 2010 and March 2015, 44 patients (low-dose group: 31 patients and high-dose group: 13 patients) were enrolled in the study. Of these, one patient was excluded from the efficacy analysis. In the high-dose group, five of nine patients were unable to continue the study due to toxicity in February 2013. At that time, recruitment to the high-dose group was stopped from the protocol. The relative dose intensity (RDI) for S-1 in the low- and high-dose groups were 49.8 and 48.7% (p = 0.712), and that for oxaliplatin was 75.9 and 73.0% (p = 0.528), respectively. The rates of discontinuation due to toxicity were 60 and 53.8% in the low- and high-dose groups, respectively, with no marked difference noted between the groups (p = 0.747). The frequency of grade ≥ 3 common adverse events was neutropenia (23.3%/23.1%), diarrhea (13.3%/15.4%), and peripheral sensory neuropathy (6.7%/7.7%). The disease-free survival (DFS) at 3 years was 52.9% in the low-dose group, which was not significantly different from that in the high-dose group (46.2%; p = 0.705). CONCLUSIONS: SOX regimens as adjuvant therapy after hepatectomy for CRCLM had high rates of discontinuation due to toxicity in both groups. In particular, the RDI of S-1 was < 50%. Therefore, the SOX regimen is not recommended as adjuvant chemotherapy after hepatectomy for CRCLM.

Curable leakage in stapled IPAA has little effect on the long-term pouch function.

PURPOSE: This study aimed to evaluate the frequency and grade of anastomotic leakage (AL) in stapled ileal pouch-anal anastomosis (IPAA) and its long-term impact on the pouch functions. METHODS: A longitudinal cohort study was conducted on UC patients who underwent stapled IPAA at Yokohama City University Medical Center between 2007 and 2018. The diagnosis and grading of AL were performed in accordance with the recommendations of the International Study Group of Rectal Cancer. We assessed the functional pouch rate, late complication, pouch survival rate, bowel function (bowel movements per day, soiling, spotting, difficulty in distinguishing feces from flatus) and pouch inflammation (pouchitis disease activity index; PDAI) in the long-term period. RESULTS: Two hundred seventy-six patients were analyzed. Twenty-three (8.3%; grade B/C; 13/10) patients were diagnosed with AL, but a functional pouch was achieved in all the twenty-three patients. Anastomotic stricture was significantly more common in patients with AL (AL group) than in patients without AL (non-AL group; AL/non-AL: 13.0/3.2%, p = 0.020). There were no differences in other late complications. Furthermore, the pouch survival rate did not differ between the AL and non-AL groups (100.0/97.9%/10 years, p = 0.494). There were no differences between the groups in bowel movements per day, spotting, soling, difficulty in distinguishing feces from flatus, or PDAI postoperatively. CONCLUSIONS: Curable AL may not affect late complications (except anastomotic stricture), pouch survival, the bowel function, or pouch inflammation over the long term. Perioperative management to prevent the severity of AL is as important as preventing its occurrence.

Identification of Patients with Locally Advanced Rectal Cancer in Whom Preoperative Radiotherapy Can Be Omitted: A Multicenter Retrospective Study at Yokohama Clinical Oncology Group (YCOG1307).

OBJECTIVES: The present study aimed to identify patients with locally advanced rectal cancer in whom preoperative radiotherapy (RT) can be omitted. METHODS: This study was a retrospective multi-institutional study for patients with pathological stage II and III rectal cancer who underwent surgery without preoperative therapy between January 2008 and December 2012. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors of local recurrence (LR). RESULTS: The 5-year cumulative local recurrence rate (LRR) of 815 patients was 11.2%. Independent predictive factors of LR were determined by a multivariate analysis to be a tumor location of <10 cm from the anal verge, a tumor diameter of ≥50 mm, undifferentiated histological type, and advanced T-N substage (T3N+ or T4Nany). In lower rectal cancer located <10 cm from the anal verge (n = 510), the 5-year cumulative LRR of patients without any remaining three factors was 4.4%, with one factor was 13.0%, with two factors was 22.2%, and with all three factors was 41.6%. CONCLUSIONS: Preoperative RT may be omitted in patients with lower rectal cancer with no risk factors. However, in addition to the present risk factors, we need to further examine the extramural vascular invasion (EMVI) status and circumferential resection margin (CRM) using magnetic resonance imaging (MRI) findings. The trial was registered with UMIN Clinical Trails Registry, number 000006039.

Five-millimeter Trocar Site Hernia with a Parastomal Hernia Sac: A Case Report.

Here, we report our experience with a 5-mm trocar site hernia (TSH) near a stoma. This is the first report describing the relationship between TSH and extraperitoneal colostomy. A 72-year-old man underwent laparoscopic abdominoperineal resection with extraperitoneal sigmoid colostomy and partial hepatectomy for rectal cancer accompanied by synchronous liver metastasis (pT3N1aM1a Stage IVA Union for International Cancer Control [UICC] 8th edition). The surgical procedures were completely performed without morbidity. After 1 year, he presented to our hospital with sudden nausea. Computed tomography (CT) revealed small bowel obstruction due to a 5-mm TSH, 1 cm from the stoma. The patient underwent laparoscopic hernia repair. The incidence of a 5-mm TSH is low. However, an abdominal wall vulnerability caused by the extensive exfoliation of the retroperitoneum due to the construction of the colostomy was observed, and the extraperitoneal colostomy influenced the onset of the 5-mm TSH. When the port and hernia sites are located in close proximity to each other, even a 5-mm trocar site may increase the incidence of TSH.

A multicenter, propensity score-matched cohort study about short-term and long-term outcomes after laparoscopic versus open surgery for locally advanced rectal cancer.

PURPOSE: This study evaluated the results of laparoscopic surgery (LAP) compared to open surgery (OP) for locally advanced mid-to-lower rectal cancer. METHODS: From February 2008 to December 2014, we collected patient data with clinical stage II/III mid-to-lower rectal cancer who underwent resection with LAP or OP at 13 institutions associated with the Yokohama Clinical Oncology Group (YCOG). The short-term outcomes and long-term prognoses associated with LAP and OP were analyzed after adjusting for the patients' backgrounds using propensity score matching. RESULTS: Among 1091 eligible cases, a propensity score matching with six covariates-age, sex, body mass index, American Society of Anesthesiologists physical status category, tumor location, and clinical stage-extracted 237 cases each for the LAP and OP groups, respectively. After matching, there were no differences in background factors between the two groups except for the presence or absence of preoperative treatment. Operative time was significantly longer in the LAP group than that in the OP group (p < 0.001), while the amount of bleeding and the length of postoperative hospital stay were significantly lower in the LAP group than that in the OP group (p < 0.001 and p = 0.001, respectively). There were no significant differences between groups in the incidence of postoperative complications. The 3-year overall survival and relapse-free survival rates were 90.5% and 88.6% and 78.3% and 71.6% in the LAP and OP groups, respectively, which did not differ significantly. CONCLUSIONS: The short-term outcomes and long-term prognoses of LAP in this cohort study indicated that LAP could be a therapeutic option for locally advanced rectal cancer. TRIAL REGISTRATION: UMIN000040406.

Optimal extent of central lymphadenectomy for right-sided colon cancers: is lymphadenectomy beyond the superior mesenteric vein meaningful?

PURPOSE: The objective of the current study was to assess the therapeutic benefit of lymphadenectomy according to the extent of lymphadenectomy. METHODS: Patients undergoing colectomy for right-sided colon cancer were identified. Distribution of lymph node metastases (DLNM) of 1, 2 and 3 were defined as lymph node metastasis (LNM) in the pericolic nodes, the intermediate nodes and the front of the SMV near the origin of the major artery, respectively. The therapeutic index (TI) was calculated based on the frequency of LNM and the 5 year overall survival (OS) rate of patients with LNM. RESULTS: Among 344 patients who met the inclusion criteria, roughly half had LNM (n = 150, 43.7%). While 107 (31.1%) and 30 (8.7%) patients had DLNM1 and DLNM2, respectively, only 13 patients (3.8%) were defined as DLNM3. However, there was no significant difference in 5 year OS by DLNM (DLNM1 71.1%, DLNM2 78.7%, DLNM3 50.4%, p = 0.61). Overall, the TI of lymphadenectomy for D3 area was approximately 1/10 of the TI for D1 (1.9 vs.22.1), given the low frequency of LNM (3.8%) and poor 5 year OS of patients with LNM (50.4%). This trend was consistent irrespective of primary tumor locations. CONCLUSION: The survival benefit from central lymphadenectomy namely D3 was low among patients with right-sided colon cancers.

Predictive Ability of Preoperative PT-INR and Postoperative MCP1 for Post-hepatectomy Liver Failure.

BACKGROUND: We sought a diagnostic tool using perioperative variables that might predict post-hepatectomy liver failure (PHLF). PATIENTS AND METHODS: In 68 patients undergoing major hepatectomy, data on inflammatory markers and coagulation factors were prospectively collected and were compared between patients with International Study Group of Liver Surgery definition grade B/C PHLF (LF group) and those without LF (non-LF group). RESULTS: Preoperatively, the LF group (n=9; 13.2%) had a lower platelet count and a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity and a higher prothrombin time-International Normalized Ratio (PT-INR) than the non-LF group. On postoperative day 1, the LF group had significantly higher serum interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2), and IL10 levels than the non-LF group. The logistic regression model that included preoperative PT-INR and CCL2 on postoperative day 1 predicted grade B/C PHLF with 100% sensitivity and 89.8% specificity. CONCLUSION: Our findings suggest that the combination of preoperative PT-INR and CCL2 on postoperative day 1 can predict PHLF earlier and precisely after major hepatectomy.

Efficacy of prolonged elemental diet therapy after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: A pilot prospective randomized trial (UMIN000004108).

BACKGROUNDS AND AIMS: This randomized clinical trial examined efficacy of prolonged elemental diet (ED) therapy after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC), which often causes postoperative malnutrition leading to worsened short- and long-term outcomes. METHODS: Thirty-nine patients with PDAC receiving PD was randomly assigned to prolonged ED group (PEDG) and control group (CG). Fat-free ED (Elental®, EA Pharma CO., Ltd., Tokyo, Japan) via tube jejunostomy was initiated on postoperative day 1 and increased to maintain with 600 kcal/day in addition to oral intake. ED was discontinued if sufficient oral intake was achieved in CG but continued during 3 postoperative months in PEDG. Primary outcome was complication necessitating readmission. Secondary outcomes were nutritional parameters, relative dose intensity (RDI) in cases of adjuvant chemotherapy, and survival outcomes. RESULTS: Twenty patients were assigned to CG and 19 to PEDG. Cumulative post-discharge readmission rate was significantly lower in PEDG than in CG (PEDG vs CG; 12.6% vs 43.7% at 12-post-discharge-month; p = 0.018). Total calorie and ED-derived protein intakes were significantly larger in PEDG than in CG up to 3-postoperative-month but thereafter similar among groups. Lymphocyte counts were significantly increased and neutrophil-to-lymphocyte-ratio (NLR) was significantly reduced in PEDG than in CG at 2-, 3-, and 6-postoperative-month. However, other outcome measures did not differ among groups. CONCLUSION: This trial failed to show survival benefit of prolonged ED therapy but demonstrated its favorable effect on increased lymphocyte counts, reduced NLR, and prevention of complications necessitating readmission, those which may lead to survival benefit with some modifications.

The maximum chemiluminescence intensity predicts severe neutropenia in gemcitabine-treated patients with pancreatic or biliary tract cancer.

PURPOSE: To assess the predictive ability of the maximum chemiluminescence intensity (CImax) for severe neutropenia (SN) during neoadjuvant chemo(radio)therapy [NAC(RT)] in patients with advanced pancreatic or biliary tract cancer. METHODS: Clinicopathological variables and blood test data before NAC(RT) were evaluated in 64 patients with advanced pancreatic or biliary tract cancer who received gemcitabine plus tegafur/gimeracil/oteracil as NAC(RT). RESULTS: Thirty-nine patients (60.9%) developed Grade 3-4 SN. The median time between commencing NAC(RT) and the onset of SN was 15 (range 10-36) days. SN occurred during the NAC period, not the RT period. The CImax, neutrophil count, serum interleukin-6 level, C-reactive protein level, complement C3 titer, serum complement titer, and 50.0% hemolytic unit of complement before NAC(RT) were significantly lower in patients with SN than in those without SN (P < 0.05). Multivariate analysis confirmed the CImax to be the sole independent predictor of SN (P < 0.05). The optimal threshold for the CImax was 46,000 RLU/s. The sensitivity and specificity were 46.2% and 80.0%, respectively. Majority of the patients (81.8%) with a low CImax before NAC(RT) experienced SN during NAC(RT). CONCLUSIONS: CImax before NAC(RT) predicts SN during NAC(RT) in patients with advanced pancreatic or biliary tract cancer.

IL-7 and procalcitonin are useful biomarkers in the comprehensive evaluation of the severity of acute cholangitis.

BACKGROUND: The incidence of biliary tract infection (BTI), especially healthcare-associated cholangitis, is increasing. However, there are few reports concerning biomarkers of acute cholangitis. We therefore performed an exhaustive investigation of several biomarkers. METHODS: We retrospectively measured 11 cytokines, six chemokines and procalcitonin (PCT), and endotoxin activity assay (EAA) values (IRB: 110512019) of 61 samples with acute cholangitis. RESULT: The 28-day mortality rate was 9.8%. The levels of most cytokines and chemokines were significantly correlated with each other. A low IL-7 level was found to predict blood culture positivity. Low IL-7 level was also found to predict disseminated intravascular coagulation. Low IL-7 levels and a high PCT level were found to be predictors of severe cholangitis. The 28-day mortality in the group of patients with an IL-7 level of ≤6.0 and a PCT level of >0.5 was 18.2%. It was significantly higher than in the other group. CONCLUSION: The combined use of IL-7 and PCT may be useful for evaluating severe acute cholangitis; these results may suggest that severe acute cholangitis is affected by immunosuppressive changes.