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Delta‐like 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) group of Notch receptor ligands. Five DSL ligands are known in mammals, among which DLL3 has a unique structure. In the last few years, DLL3 has attracted attention as a novel molecular targeting gene in neuroendocrine carcinoma of the lung due to its high expression. However, the expression pattern and functions of DLL3 in the gastrointestinal tract and gastrointestinal neuroendocrine carcinoma remain unclear. In this study, we examined the expression and role of DLL3 in the gastrointestinal tract, as well as in gastrointestinal neuroendocrine carcinoma. Immunohistochemical staining of the human normal gastrointestinal tract revealed that DLL3 localized in neuroendocrine cells. DLL3 showed intense staining in chromogranin A‐positive gastric cancer specimens. Real‐time quantitative RT‐PCR and western blotting analyses showed considerable upregulation of DLL3 in gastrointestinal neuroendocrine carcinoma cell lines. Immuno‐electron microscopy demonstrated abundant expression of DLL3 in neurosecretory granules in these cells. Furthermore, gene silencing of DLL3 caused significant growth inhibition through the induction of intrinsic apoptosis. Our findings suggest that DLL3 is expressed in neuroendocrine cells of the gastrointestinal tract and that it has a pivotal role in gastrointestinal neuroendocrine carcinoma cells. Based on these findings, further investigations are required to achieve a breakthrough in developing therapeutic strategies for gastrointestinal neuroendocrine carcinoma. Delta‐like 3 is localized in neuroendocrine cells of the gastrointestinal tract. DLL3 is upregulated in gastrointestinal tract neuroendocrine cancer cells. SiR‐DLL3 inhibits cell growth through intrinsic apoptosis in ECC cells.

BackgroundTotal mesorectal excision (TME) has decreased the local recurrence rate and improved the overall survival of rectal cancer patients. However, urinary dysfunction remains a clinical problem after rectal cancer surgery. The aim was to assess the risk factors for postoperative urinary dysfunction.MethodsThis study was a single-center, retrospective analysis of 104 patients who underwent laparoscopic rectal surgery between November 2016 and October 2017. Postoperative urinary dysfunction was defined as the need for urinary catheter re-insertion or the presence of residual urine (≥ 150 mL) postoperatively.ResultsPostoperative urinary dysfunction was seen in 18 patients (17%). Multivariate analysis showed that male sex (odds ratio 3.89, p = 0.034) and anterior wall tumor location (odds ratio = 4.07, p = 0.037) were the predictors of postoperative urinary dysfunction. Compared with patients without risk factors, those with the two risk factors needed longer hospital stays (16 days vs. 30 days, p = 0.0022).ConclusionMale sex and anterior wall tumor location were the risk factors for urinary dysfunction after laparoscopic rectal surgery.

Background Laparoscopic low anterior resection for rectal cancer is considered to be more technically demanding than laparoscopic colectomy. This study aimed to analyze the learning curve for laparoscopic low anterior resection and to identify the factors that influence this learning curve. Methods Data from 250 consecutive patients undergoing laparoscopic low anterior resection for rectal cancer, excluding patients with a combined resection such as cholecystectomy, hepatectomy, hysterectomy, or gastrectomy, between December 1996 and April 2010 were analyzed. For operative time, the learning curve was analyzed using the moving average method. The conversion rate and the postoperative complication rate were evaluated in five groups of up to 50 patients each based on the number of cases required for analysis of operative time. In addition, risk factors that influenced conversion to open surgery and postoperative complications were analyzed. Results The learning curve analysis for operative time using the moving average method showed stabilization at 50 cases. The conversion rate decreased significantly by group 4 (151–200 cases). The postoperative complication rate decreased significantly by group 5 (201–250 cases). The significant factors for conversion to open surgery were male sex (odds ratio [OR], 2.6094; 95% confidence interval [CI], 1.1–6.4) and T stage (OR, 2.4793; 95% CI, 1.1–5.8). For postoperative complications, male sex (OR, 3.8590; 95% CI, 1.9–3.8) was significant. In addition, the risk factors for anastomotic leakage were male sex (OR, 15.7659, 95% CI, 3.2–284.8) and multiple firing (2 or more cartridges for rectal transection) (OR, 3.0589; 95% CI, 1.1–9.5). Conclusions The risk factors affecting the learning curve for laparoscopic low anterior resection were T stage and male sex. In laparoscopic low anterior resection, rectal transection in particular can be technically difficult, and standardization for accurate performance of the same technique for expanded indications is very important.

Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

BackgroundPatients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn’s disease.MethodsIntestinal cancers in ulcerative colitis and Crohn’s disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed..ResultsA total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn’s disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn’s disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P < 0.0001) and at earlier stages (stages 0–1, 71% vs. 27%, P < 0.0001) compared with Crohn’s disease-associated cancers. Colorectal cancers associated with Crohn’s disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn’s disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn’s disease patients.ConclusionsThe clinical and oncological features of ulcerative colitis- and Crohn’s disease-associated cancers were very different. Crohn’s disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis.

Recently, the feasibility of real‐time indocyanine green (ICG) fluorescence imaging–guided complete mesocolic excision in colon cancer surgery has been demonstrated; however, its application to the evaluation of lymphatic flow in widespread lymph node metastasis is uncertain. This study aimed to evaluate lymphatic flow using the real‐time ICG fluorescence imaging. A mouse model of subcutaneous inoculation of BJMC3879Luc2 cells, which have been demonstrated to highly metastasize to the lymph nodes, was used as an evaluation model. Tumor growth and lymphatic flow were monitored weekly by bioluminescent imaging and near‐infrared (NIR) fluorescence imaging, respectively. After sacrificing the mice, lymph node metastases were evaluated by bioluminescent imaging and histopathology. Lymphatic flows in a model of high lymph node metastasis were evaluated using NIR fluorescence imaging. Pathological metastases of bilateral axillary, femoral, and para‐aortic lymph nodes were detected in all inoculated mice (100%: 5/5). Real‐time NIR fluorescence imaging showed the primary lymphatic vessels staining through the metastatic lymph nodes as before the inoculation of the cancer cells. Hitherto, it has been considered that lymphatic flow was changed using the bypass pathway due to occlusion of the primary lymphatic vessels. In this presented study, real‐time ICG fluorescence imaging showed no changes in lymphatic flow after lymph node metastasis. Our results suggest that real‐time ICG fluorescence imaging may have potential for the guidance of colon cancer surgery in cases of widespread lymph node metastasis. This study aimed to evaluate lymphatic flow using real‐time indocyanine green fluorescence imaging in a highly metastatic mouse model.

BackgroundPreoperative carbohydrate loading (CHO) is one element of the enhanced recovery after surgery protocol. No clinical trial has investigated the impact of preoperative CHO on intraoperative body temperature.MethodsThis study was a single-center, prospective, randomized controlled clinical trial involving patients undergoing laparoscopic colon cancer surgery. The primary end point was the intraoperative core temperature during surgery, which was measured at 30-min intervals for 150 min after starting surgery. The secondary end points were short-term outcomes and body composition changes.ResultsFrom July 2013 to May 2014, we randomized 70 patients into the control group (n = 33) or CHO group (n = 31); six patients were excluded. The core temperature of the CHO group 90, 120, and 150 min after starting surgery was significantly lower than that of the control group (control vs. CHO, respectively: 90 min; 36.26 ± 0.41 vs. 36.05 ± 0.43 °C, p = 0.0233, 120 min; 36.30 ± 0.44 vs. 36.06 ± 0.50 °C, p = 0.0283, 150 min; 36.33 ± 0.50 vs. 36.01 ± 0.56 °C, p = 0.0186). We also found a significant difference in body weight loss (control vs. CHO, respectively: − 1.6 ± 0.8 vs. − 0.9 ± 1.4 kg, p = 0.0304) and loss of lower limb muscle mass (− 0.7 ± 0.7 vs. − 0.3 ± 0.6 kg, p = 0.0110) between the control and CHO groups, respectively.ConclusionCHO had no effect on raising the intraoperative core temperature, and no negative impact on the perioperative outcome. CHO prevented the loss of lower limb muscle mass, which may lead to better postoperative recovery.

Aim Although the oncological impact of lateral lymph node dissection on enlarged lateral lymph nodes has been gradually accepted over the last decade, that on lateral lymph nodes without swelling remains doubtful. This study aimed to develop a prediction model for the future risk of lateral local recurrence and to clarify the value of adding lateral lymph node dissection in locally advanced rectal cancer without enlarged lateral lymph nodes. Methods This retrospective, multi‐institutional study recruited 812 patients with cStage II/III low rectal cancer without enlarged lateral lymph nodes <7 mm. Total lateral local recurrence was a hypothetical value of future risk of lateral local recurrence when lateral lymph node dissection was never performed. Results Overall, total lateral local recurrences were observed in 67 patients (8.3%). In the multivariate analyses, the strongest risk factor for total local recurrences was no preoperative chemoradiotherapy (odds ratio [OR][95%Cl]: 33.2 [4.56–241.7], P < 0.001), followed by tumor distance ≤40 mm (OR [95%Cl]: 2.71 [1.51–4.86], P < 0.001) and lateral lymph node 5–7 mm (OR[95%Cl]: 2.38 [1.26–4.48], P = 0.007). In patients with lateral lymph nodes of 5–7 mm, the total lateral recurrence rate was 4.8% after preoperative chemoradiotherapy. Lateral lymph node dissection could reduce from a total lateral local recurrence of 21.6% to an actual lateral local recurrence of 8.0% in patients without preoperative treatment. Conclusion We introduce a novel prediction model of future risk of lateral local recurrences, which has the potential to enable us to indicate lateral lymph node dissection selectively according to the patients' risks. A novel prediction model could provide future risk of lateral local recurrence according to the status of preoperative treatment, size of lateral lymph node, and tumor distance from the anal verge. Lateral lymph node dissection that might improve only lateral control could be added based on the individual risks.

Good short-term outcomes of intracorporeal ileocolic anastomosis (IIA) in totally laparoscopic colectomy for right-sided colon cancer (TLRC) have been shown in many reports, but no standardized technique for enterotomy closure after stapled side-to-side ileocolic anastomosis has so far been established. We retrospectively compared the short-term outcomes between 13 consecutive patients receiving either TLRC with IIA by conventional enterotomy closure (n = 6) or closure of the enterotomy using two barbed sutures (CEBAS) (n = 7) from July 2019 to April 2020. No anastomotic bleeding or leakage was observed in either group. Time to enterotomy closure was significantly shorter with the CEBAS method (16.5 ± 3.7 min) than with the conventional method (24.5 ± 4.7 min, p = 0.0059). The CEBAS method in TLRC with IIA was thus found to be technically feasible and it might reduce the stress associated with intracorporeal enterotomy closure.

Stoma closure has been associated with a high rate of surgical site infection (SSI) and the optimal skin closure method is still controversial. The aim of this study was to compare the short-term and long-term outcomes between the conventional linear closure (CC) and the persestring closure (PC) using propensity score matching analysis. We analysed the data of 360 patients who underwent stoma closure with CC or PC between January 2000 and December 2014. The propensity score was calculated from age, gender, body mass index, primary disease, type of stoma, diabetes mellitus, history of smoking, steroid use, the American Society of Anesthesiologists score, Prognostic Nutritional Index and modified Glasgow Prognostic Score. There was no difference in operative variables between the two groups. The CC group and the PC group were comparable with regards to overall SSI (25.0 vs. 7.8%; P = 0.007), superficial SSI (21.9 vs. 4.7%; P = 0.003). Significant risk factor for SSI was conventional linear closure (OR, 4.14; 95% CI, 1.448–13.91). Our study suggests that a pursestring stoma closure leads to less SSI.