The survival impact of preoperative FOLFOX for resectable locally advanced rectal cancer: the R-NAC-01 study.

PURPOSE: In this follow-up of the R-NAC-01 study, we assessed the long-term oncological benefit of four courses of modified leucovorin, 5-fluorouracil (FU), and oxaliplatin (mFOLFOX6) chemotherapy before rectal surgery. METHODS: In this prospective, multicenter study (UMIN 000012559) involving 11 hospitals in Japan, patients with lower rectal cancer underwent four cycles of mFOLFOX6 chemotherapy and subsequent surgery within four to six weeks. The 3-year recurrence-free survival and local recurrence rates were then reported. RESULTS: Of 41 patients (36 males, 5 females; mean age: 60.8 years old) who received 4 courses of chemotherapy, 40 underwent total mesorectal excision, and 1 underwent total pelvic exenteration. R0 resection was achieved in 40 patients, but none showed a pathological complete response. Twenty-nine patients received adjuvant chemotherapy for an average of 4 months. The 3 year recurrence-free survival and local recurrence rates in patients undergoing curable resection were 72.8% and 8.5%, respectively. cStage III patients with adjuvant chemotherapy had a significantly higher 3 year recurrence-free survival than those without adjuvant chemotherapy (76.6 vs. 40.0%, log-rank p = 0.03). CONCLUSION: Four courses of mFOLFOX6 chemotherapy before surgery may be a promising treatment strategy for locally advanced rectal cancer. Adjuvant chemotherapy might be needed for cStage III patients, even after four courses of neoadjuvant mFOLFOX6.

Preoperative FOLFOX in resectable locally advanced rectal cancer can be a safe and promising strategy: the R-NAC-01 study.

PURPOSE: The aim of this study was to assess the safety of rectal surgery after 5-fluorouracil-leucovorin-oxaliplatin chemotherapy (FOLFOX6). METHODS: This was a prospective, multicenter study in 11 Japanese hospitals. We included patients with rectal cancer who received 4 courses of modified FOLFOX6 (mFOLFOX6) before rectal surgery and examined the postoperative complication rate, the clinicopathological response, and the rate of chemotherapy-related adverse events (UMIN 000012559). RESULTS: The study population included 36 men and 5 women. The average age of the patients was 60.8 years and the average body mass index was 23.1 kg/m2. After 4 courses of chemotherapy, grade 2 peripheral nerve disorder and other grade 3 adverse events were seen in 3 patients each (7.3%). Twenty-eight (73.7%) and 8 (21.1%) patients underwent low anterior resection and abdominoperineal resection, respectively. The pelvic nerves were preserved in 35 patients. Surgical morbidity (grade ≥ 3) occurred in 4 patients (10.5%). Anastomotic leakage occurred after surgery in 2 patients (7.1%). No patients achieved pathologically complete remission. However, downstaging of the clinical stage and N stage was seen in 17 (41.5%) and 22 (53.7%) patients, respectively. CONCLUSIONS: Surgery after four courses of mFOLFOX6 chemotherapy can be a safe and promising strategy for patients with locally advanced rectal cancer.

Novel anti-inflammatory agent 3-[(dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease.

OBJECTIVE AND DESIGN: To examine the effect of 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G), a novel anti-inflammatory agent that inhibits lipopolysaccharide (LPS) activation of RAW264.7 macrophages, on murine models of colitis and RAW264.7 cells. MATERIALS AND METHODS: Colitis was induced by rectally infusing trinitrobenzenesulfonic acid (TNBS) (1.5 mg in 50% ethanol) in BALB/c mice or orally administering 3% dextran sulfate sodium (DSS) for 5 days in C57BL/6 mice. The severity of colitis was assessed after intraperitoneally injecting DTCM-G (40 mg/kg). The anti-inflammatory properties of DTCM-G and its mechanisms were investigated in LPS-stimulated RAW264.7 cells. RESULTS: DTCM-G significantly ameliorated TNBS-induced colitis, according to the body weight loss, disease activity index, colonic obstruction, macroscopic colonic inflammation score, mucosal myeloperoxidase activity, and histopathology. Immunohistochemistry and isolated lamina propria mononuclear cells showed significantly reduced colonic F4/80(+) and CD11b(+) macrophage infiltration. DTCM-G significantly suppressed tumor necrosis factor (TNF)-α and interleukin (IL)-6 messenger RNA expression in the colon and attenuated DSS-induced colitis, according to the disease activity index and histopathology. In RAW264.7 cells, DTCM-G suppressed LPS-induced TNF-α/IL-6 production and enhanced glycogen synthase kinase-3ß phosphorylation. CONCLUSIONS: DTCM-G attenuated murine experimental colitis by inhibiting macrophage infiltration and inflammatory cytokine expression. Thus, DTCM-G may be a promising treatment for inflammatory bowel disease.

[A Case of Advanced Colon Cancer with Long-Term and Re-Administration of Regorafenib].

A 54-year-old woman diagnosed with sigmoid colon cancer and multiple liver metastases underwent sigmoidectomy, partial hepatectomy, and RFA in September 2009. Because of postoperative liver and lung recurrence, 5 regimens with combinations of L-OHP/CPT-11 plus anti-VEGF antibody/anti-EGFR antibody was performed. Following these treatments, she underwent hepatic arterial infusion therapy with UFT/Krestin for progressive liver metastases. Starting in November 2014, regorafenib was administered, with an immediate decrease in tumor marker levels; tumor reduction demonstrated enhanced effect against liver metastases. After 8 months of administration, we stopped regorafenib and changed to TAS-102 due to diarrhea and eating disorders. However, TAS-102 was not effective; there were significant increases in tumor markers, liver function tests, and tumor size on computed tomography, and worsening of abdominal pain. After re-administration of regorafenib, a rapid decrease in tumor marker levels and improvement of liver dysfunction and abdominal pain were observed. Re-administration continued for 8 months until best supportive care was instituted. In cases with observed therapeutic effect of regorafenib, long-term or re-administration is possible, with extension of the prognosis depending on the adjustment, and without size reduction of metastatic tumors.

Chondroma of the diaphragm mimicking a giant liver tumor with calcification: report of a case.

Extraskeletal chondroma is an unusual benign tumor, which rarely arises in the diaphragm. We report a case of chondroma of the diaphragm in a 31-year-old woman. Initially, a benign liver tumor with calcification was suspected, based on pre and intraoperative examination findings. Although parts of the tumor were contiguous with the diaphragm, its connections with the diaphragm were much narrower than its connection with the liver, which suggested a liver tumor. Pathological examination subsequently revealed that the chondroma was contiguous with the diaphragm and that there was a distinct border between the tumor and the liver; thus, the tumor was diagnosed as a chondroma of the diaphragm.

Preoperative mechanical bowel preparation using conventional versus hyperosmolar polyethylene glycol-electrolyte lavage solution before laparoscopic resection for colorectal cancer (TLUMP test): a phase III, multicenter randomized controlled non-inferiority trial.

BACKGROUND: A hyperosmolar ascorbic acid-enriched polyethylene glycol-electrolyte (ASC-PEG) lavage solution ensures excellent bowel preparation before colonoscopy; however, no study has demonstrated the efficacy of this lavage solution before surgery. This study aimed to establish the non-inferiority of ASC-PEG to the standard polyethylene glycol-electrolyte solution (PEG-ELS) in patients undergoing laparoscopic resection for colorectal cancer. METHODS: This was a prospective, single-blind, multicenter, randomized, controlled, non-inferiority clinical trial. Overall, 188 patients scheduled for laparoscopic colorectal resection for single colorectal adenocarcinomas were randomly assigned to undergo preparation with different PEG solutions between August 2017 and April 2020 at four hospitals in Japan. Participants received ASC-PEG (Group A) or PEG-ELS (Group B) preoperatively. The primary endpoint was the ratio of successful bowel preparations using the modified Aronchick scale, defined as "excellent" or "good." RESULTS: After exclusion, 86 and 87 patients in Groups A and B, respectively, completed the study, and their data were analyzed. ASC-PEG was not inferior to PEG-ELS in terms of effective bowel preparation prior to laparoscopic colorectal resection (0.93 vs. 0.92; 95% confidence interval, - 0.078 to 0.099, p = 0.007). The total volume of cleansing solution intake was lower in Group A than in Group B (1757.0 vs. 1970.1 mL). Two and three severe postoperative adverse events occurred in Groups A and B, respectively. Patient tolerance of the two solutions was almost equal. CONCLUSIONS: ASC-PEG is effective for preoperative bowel preparation in patients undergoing laparoscopic resection for colorectal cancer and is non-inferior to PEG-ELS.

The incidence of cardiovascular thrombotic complications after laparoscopic resection in colorectal cancer in Japanese hospitals: A large-scale clinical study.

Aim: The aim of this retrospective study was to investigate the incidence of cardiovascular thrombotic complications after laparoscopic resection in colorectal cancer. Methods: This study involved 2017 patients with stages 0-III colorectal cancer who underwent laparoscopic surgery at 17 Japanese hospitals between January 2010 and December 2013. We assessed the incidence of postoperative cardiovascular thrombotic and haemorrhagic complications. Results: Laparoscopic surgeries were performed in 1152 men and 865 women with 1405 colon and 612 rectal cancers, respectively. Overall, 3%, 38%, 17%, 8%, and 9% of patients had comorbidities of heart failure, high blood pressure, diabetes, history of stroke, and vascular disease, respectively. Antithrombotic agents were being consumed by 17% of patients. The types (and perioperative rest periods) of the antithrombotic agents were aspirin in 58% (18.6 days), clopidogrel in 19% (21.1 days), cilostazol in 13% (13.3 days), and warfarin potassium in 21% (14.6 days) of cases with antithrombotic agents. Surgical time and blood loss in the total cohort were 234 minutes and 56 mL. Four cases (0.2%) had cardiovascular thrombotic complications, including one severe cardiac infarction and one stroke with major sequelae (CHADS2 scores were 2 points in both cases). Hemorrhagic complications occurred in 19 cases (0.9%). In particular, the incidence of the major gastroduodenal haemorrhagic ulcer was higher in cases with antithrombotic agents than without them (0.05% vs 0%, P = .02). Conclusion: The incidence of cardiovascular thrombotic complications was rare, although severe cardiac infarction and stroke could occur even after minimally invasive surgery in colorectal cancer.

Portal Annular Pancreas With Common Hepatic Artery Trajectory Abnormality: A Case Report and Review of the Literature.

ABSTRACT: Portal annular pancreas (PAP) is a rare congenital pancreatic anomaly, in which the uncinate process of the pancreas fuses to the body of pancreas behind the portal vein. Here, we report a case of PAP with common hepatic arterial anomaly, which was identified during surgery. A 57-year-old man who had branch type intraductal papillary mucinous neoplasm in the head of the pancreas developed a nodule in the cystic lesion. We planned pylorus preserving pancreaticoduodenectomy. The common hepatic artery from the celiac artery passing behind the portal vein was revealed in preoperative examinations. During surgery, we discovered that the uncinate process of the pancreas was fused with the body of the pancreas behind the portal vein. We divided the pancreas at the anterior and posterior of the portal vein. The main pancreatic duct was present in the anterior pancreatic stump. We performed pancreaticojejunostomy in the anterior stump and closed the posterior stump by interrupted suture. Forty-four surgical cases of PAP have been reported in the English medical literature. There are few previous reports of PAP which involved an arterial anomaly. Clinicians should consider PAP preoperatively to ensure that the surgeon can appropriately plan pancreatic resection to avoid postoperative complications.

Mentor Tutoring: An Efficient Method for Teaching Laparoscopic Colorectal Surgical Skills in a General Hospital.

OBJECTIVE: We retrospectively assessed the efficacy of our mentor tutoring system for teaching laparoscopic colorectal surgical skills in a general hospital. MATERIALS AND METHODS: A series of 55 laparoscopic colectomies performed by 1 trainee were evaluated. Next, the learning curves for high anterior resection performed by the trainee (n=20) were compared with those of a self-trained surgeon (n=19). RESULTS: Cumulative sum analysis and multivariate regression analyses showed that 38 completed cases were needed to reduce the operative time. In high anterior resection, the mean operative times were significantly shorter after the seventh average for the tutored surgeon compared with that for the self-trained surgeon. In cumulative sum charting, the curve reached a plateau by the seventh case for the tutored surgeon, but continued to increase for the self-trained surgeon. CONCLUSIONS: Mentor tutoring effectively teaches laparoscopic colorectal surgical skills in a general hospital setting.

A novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates inflammatory colonic injury in mice.

BACKGROUND: In inflammatory bowel disease (IBD), gut inflammation is associated with the activation of nuclear factor kappa B (NF-κB), a key pro-inflammatory transcription factor. AIM: To investigate the therapeutic potential of a novel, specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), we examined its effect on IBD using murine experimental colitis models. METHODS: The in vitro effect of DHMEQ was evaluated by inflammatory cytokine production and p65 immunostaining using HT-29 and RAW264.7 cells. The in vivo therapeutic effect of DHMEQ was studied in colitis induced by dextran sulphate sodium (DSS) and trinitrobenzenesulphonic acid (TNBS). In these, progression and severity of colitis was mainly assessed by the disease activity index (DAI), histopathology, cellular infiltration, and mRNA expression levels of pro-inflammatory cytokines in the colonic tissues. RESULTS: In RAW264.7 cells, DHMEQ significantly inhibited tumour necrosis factor (TNF)-α and interleukin (IL)-6 production induced by LPS in a dose-dependent manner by blocking the nuclear translocation of NF-κB. In addition, DHMEQ inhibited IL-8 production induced by LPS in HT-29 cells. DHMEQ significantly ameliorated DSS colitis as assessed by DAI scores, colonic oedema, and histological scores. Immunohistochemistry revealed that DHMEQ inhibited colonic infiltration of nuclear p65(+) cells, CD4(+) lymphocytes, and F4/80(+) macrophages. mRNA expression levels of the pro-inflammatory cytokines, such as IL-1ß, TNF-α, IL-6, IL-12p40, IL-17, and MCP-1 were also suppressed by DHMEQ administration. Furthermore, DHMEQ significantly ameliorated TNBS colitis as assessed by body-weight changes and histological scores. CONCLUSION: DHMEQ ameliorated experimental colitis in mice. These results indicate that DHMEQ appears to be an attractive therapeutic agent for IBD.

Dual-ports laparoscopy-assisted distal gastrectomy compared with conventional laparoscopy-assisted distal gastrectomy.

PURPOSE: We performed laparoscopic gastrectomy using an umbilical port in addition with one other port (dual-ports laparoscopy-assisted distal gastrectomy, DP-LADG) since December 2009. We describe a retrospective study to evaluate the possibility of DP-LADG compared with conventional LADG (C-LADG). METHODS: The indication for DP-LADG was preoperative clinical Stage IA gastric cancer. We compared 20 patients who underwent DP-LADG with 24 patients of clinical Stage IA patients who underwent C-LADG. RESULTS: The mean operation time was significantly longer for DP-LADG (250.5 min) than for C-LADG (197.5 min); however, the mean operation time for the last 5 patients undergoing DP-LADG (209 ± 31.1 min) was almost the same as that for C-LADG. There were no significant differences between DP-LADG and C-LADG in terms of blood loss, number of lymph nodes dissected, rates of conversion to open surgery, postoperative complications, and length of postoperative hospital stay. CONCLUSIONS: DP-LADG is technically feasible.

Surgical effects of obesity on laparoscopy-assisted distal gastrectomy.

PURPOSE: To compare the effects of obesity on laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG). METHODS: A retrospective study was conducted on 249 patients, who underwent LADG and 224 patients who underwent ODG. RESULTS: The regression coefficient of the primary regression equation between operative time and body mass index (BMI) for LADG was greater than ODG; and between blood loss and BMI for LADG was almost the same as ODG. In overweight patients (BMI ≥25), no significant difference was seen between LADG and ODG regarding postoperative complications, and the benefits of the less-invasive nature of LADG were also seen in some parameters. CONCLUSION: Obesity-associated difficulties are more while performing LADG than during ODG; however, the influence of obesity on LADG decreases with surgical experience. Moreover, even in overweight patients, the benefits of the less-invasive nature of LADG still remain, but the degree of the benefits is smaller than that in nonobese patients.