A Novel Fluorescence-Based Leak Test Method for Rectal Anastomoses Using Aerosolized Indocyanine Green.

BACKGROUND: The intraoperative air leak test is commonly performed during rectal surgery to evaluate anastomotic integrity. However, its drawbacks include occasional difficulties in visualizing the exact point of the leak while maintaining the pelvis under saline, the need for repeat testing to identify the leak point, and a lack of continuous visualization of the leak point. OBJECTIVE: To evaluate the feasibility and clinical applicability of using aerosolized indocyanine green, a fluorescent tracer, for detecting rectal anastomotic leakage. DESIGN: Animal preclinical study. SETTING: Animal laboratory at Kagawa University. PATIENTS: Six healthy adult female beagles were included. INTERVENTIONS: An anastomotic leakage model with a single air leak point was created in each dog. Indocyanine green was aerosolized using a nebulizer kit with a stream of carbon dioxide flowing at 1.5 to 2.0 L/min. The aerosol was administered into the rectum transanally, and laparoscopic observations were performed. MAIN OUTCOME MEASURES: Air leak points were observed using a near-infrared fluorescence laparoscope, after which the presence of corresponding indocyanine green fluorescence was verified. RESULTS: Aerosolized indocyanine green was visualized laparoscopically at all anastomosis sites but not elsewhere. The median time from the administration of the aerosol to its visualization was 4.5 seconds. Pathological examinations were performed 4 weeks postsurgery in all dogs, and no histological abnormalities related to aerosolized indocyanine green administration were observed at the anastomosis sites. LIMITATIONS: The leak points were surgically created and did not occur naturally. CONCLUSIONS: Visualization of air leaks at the sites of rectal anastomosis was laparoscopically achievable by administering aerosolized indocyanine green transanally into the rectum in our canine model. This novel fluorescent leak test could be a valid alternative to established methods.

Transperineal minimally invasive surgery during laparoscopic abdominoperineal resection for low rectal cancer could improve short-term outcomes: A single-institution retrospective cohort study.

PURPOSE: Transperineal minimally invasive surgery (TpMIS) during laparoscopic abdominoperineal resection (APR) is an emerging approach that allows for the precise treatment of lower rectal cancer. However, evidence regarding the efficacy of TpMIS is insufficient. This study evaluated the efficacy of TpMIS during laparoscopic APR for patients with lower rectal cancer. METHODS: Patients who underwent laparoscopic APR with TpMIS (TpMIS group; n = 12) and those who underwent conventional laparoscopic APR for low rectal cancer (conventional group; n = 13) were enrolled consecutively in this retrospective study. Standardized TpMIS was performed at our institution. Patient and tumor characteristics and intraoperative, postoperative, and pathological outcomes were compared between groups. The primary outcome was postoperative perineal wound infection. RESULTS: No patients in the TpMIS group experienced postoperative perineal wound infection; however, five (38.5%) patients in the conventional group experienced postoperative perineal wound infection (significant difference; p = 0.016). The estimated blood loss (median, 81 mL vs. 463 mL) and incidence of postoperative urinary dysfunction (8.3% vs. 46.1%) were significantly lower in the TpMIS group than in the conventional group. The postoperative hospital stay (median, 13 vs. 20 days) of the TpMIS group was significantly shorter than that of the conventional group. Pathological outcomes did not differ between groups. The positive circumferential resection margin rates of the TpMIS and conventional groups were 8.3% and 15.4%, respectively. CONCLUSION: TpMIS during laparoscopic APR was associated with significant improvements in the postoperative outcomes of patients with low rectal cancer.

[A Case of Intrahepatic Cholangiocarcinoma and Early Postoperative Recurrences Using Comprehensive Genome Profiling to Implement Effective Treatment].

Subsequent to a medical examination, a 61-year-old male was referred to our hospital with jaundice. He was diagnosed with intrahepatic cholangiocarcinoma involving the hepatic hilum and was referred to our department to undergo a left trisectionectomy of the liver, extrahepatic bile duct resection, and regional lymphadenectomy. He was discharged on postoperative day 39 without liver failure. Two months postoperatively, positron-emission tomography/computed tomography(PET/ CT)indicated recurrences in the bone, and paraaortic lymph node. Gemcitabine and cisplatin combination first-line therapy was administered. Disease progression occurred after 4 courses of therapy. Gene panel testing was performed and the patient was switched to pembrolizumab owing to high microsatellite instability. After 2 courses of pembrolizumab, notable shrinkage of the paraaortic lymph node recurrence was confirmed on computed tomography as well as a partial response. PET-CT revealed disappearance of abnormal accumulation in all lesions at 20 months postoperatively. This has been sustained for 24 months following surgery without remarkable immune-related side-effects.

Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer.

OBJECTIVE: We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy. METHODS: Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry. RESULTS: Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group. CONCLUSION: The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.

Indocyanine green fluorescence imaging during laparoscopic rectal cancer surgery could reduce the incidence of anastomotic leakage: a single institutional retrospective cohort study.

BACKGROUND: There is insufficient evidence on whether indocyanine green (ICG) fluorescence angiography can reduce the incidence of anastomotic leakage (AL). This retrospective cohort study aimed to evaluate the effect of ICG fluorescence angiography on AL rates in laparoscopic rectal cancer surgery at a single institution. METHODS: Patients who underwent laparoscopic low anterior resection or intersphincteric resection with ICG fluorescence angiography (ICG group; n = 73) and patients who underwent a similar surgical procedure for rectal cancer without ICG fluorescence (non-ICG group; n = 114) were enrolled consecutively in this study. ICG fluorescence angiography was performed prior to transection of the proximal colon, and anastomosis was performed with sufficient perfusion using ICG fluorescence imaging. AL incidence was compared between both groups, and the risk factors for AL were analyzed. RESULTS: AL occurred in 3 (4.1%) and 14 (12.3%) patients in the ICG and non-ICG groups, respectively. In the ICG group, the median perfusion time from ICG injection was 34 s, and 5 patients (6.8%) required revision of the proximal transection line. None of the patients requiring revision of the proximal transection line developed AL. In univariate analysis, longer operating time (odds ratio: 2.758; 95% confidence interval: 1.023-7.624) and no implementation of ICG fluorescence angiography (odds ratio: 3.266; 95% confidence interval: 1.038-11.793) were significant factors associated with AL incidence, although the creation of a diverting stoma or insertion of a transanal tube was insignificant. CONCLUSION: ICG fluorescence angiography was associated with a significant reduction in AL during laparoscopic rectal cancer surgery. Changes in the surgical plan due to ICG fluorescence visibility may help improve the short-term outcomes of patients with rectal cancer.

Ampullary carcinoma of the duodenum: current clinical issues and genomic overview.

Ampullary carcinomas of the duodenum are uncommon. Moreover, the diversity in the clinical outcomes of these patients makes it difficult to interpret previous studies and clinical trial results. The difficulty in proper staging of ampullary carcinomas, especially with regard to the T category of the tumor in the TNM system, reflects the anatomic complexity and non-uniform histopathologic subtypes. One major reason for this difficulty in interpretation is that the tumors may arise from any of the three epithelia (duodenal, biliary, or pancreatic) that converge at this location. Generally, ampullary carcinomas are classified into intestinal and pancreaticobiliary types based on morphology and immunohistochemical features. While many studies have described their specific characteristics and clinical impact, the prognostic value of these subtypes is controversial. In recent years, whole-exome sequencing analyses have advanced our understanding of the genomic overview of ampullary carcinoma. Gene mutations serve as prognostic and predictive biomarkers for this disease. Therefore, basic knowledge of the genomic profile of ampullary carcinomas is required for surgeons to understand how best to apply precision medicine as well as surgery and adjuvant therapies. This review provides an overview of the current basic and clinical issues of ampullary carcinoma.

Laparoscopic hand-sewn esophagojejunal anastomosis in laparoscopic proximal gastrectomy for early gastric cancer.

PURPOSE: In Asian countries, proximal gastrectomy is a standard treatment option for early primary gastric cancer located in the upper third of the stomach. However, laparoscopic proximal gastrectomy (LPG) is not widely employed due to the technical difficulty of laparoscopic esophagojejunal anastomosis. Therefore, we began performing laparoscopic hand-sewn esophagojejunal anastomosis. In this report, we describe the technique of this method and the short-term surgical outcomes. METHODS: Between February 2016 and June 2020, 18 patients underwent LPG with double-tract reconstruction at our institution. Laparoscopic hand-sewn esophagojejunal anastomosis was attempted for all patients. RESULTS: The median operative time for the 18 patients was 431 min (range: 301-549 min), and the estimated blood loss was 100 mL (range: 0-1524 mL). The median time for the hand-sewn esophagojejunostomy was 42 min (range: 26-81 min). Only one case was converted to open surgery after the reconstruction due to bleeding from an artery of the lesser curvature. No anastomotic leakage was observed in any patients (0/18, 0 %); however, two patients developed anastomotic stenosis (2/18, 11%). The mean length of postoperative hospital stay was 10 days (range: 8-28 days). CONCLUSION: The laparoscopic hand-sewn esophagojejunal anastomosis in LPG is a simple, cost-effective, and safe procedure. We believe that our method is a feasible choice. However, careful and longer follow-up of more patients is necessary to determine the advantages of our method.

Early gastric cancer with an Adachi type VI (group 26) vascular anomaly diagnosed preoperatively and treated by laparoscopic surgery: a case report.

BACKGROUND: It is important to understand the branching pattern of the celiac artery for a safe surgery. Various branching anomalies of the celiac artery were classified by Adachi in 1928. In Adachi's classification, type VI (group 26) is a rare anatomical anomaly (0.4%) that requires care when carrying out a surgery in gastric cancer patients with this anomaly. Herein, we reported a case treated successfully with laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer. CASE PRESENTATION: An 84-year-old female was referred to our division for an additional surgical treatment for early gastric cancer that was resected by endoscopic submucosal dissection. A three-dimensional computed tomography angiography revealed an angioplany of the common hepatic artery branching from the left gastric artery. According to Adachi's classification, the anomaly of this patient corresponded to type VI (group 26). Preoperative anatomical information of this rare anomaly helped us to safely perform a laparoscopic distal gastrectomy and lymph node dissection with common hepatic artery preservation. The patient had an uneventful postoperative course and was discharged on postoperative day 11. CONCLUSIONS: We consider that Group 26 anomalies require the most precise anatomical understanding among Adachi classification type VIs, since it affects hepatic blood flow and can cause serious complications. In this time, we reported a successful case to perform laparoscopic distal gastrectomy with safety and accuracy by preoperative understanding of the precise vascular anatomy.

New Concept Air Conditioning System for the Operating Room to Minimize Patient Cooling and Surgeon Heating: A Historical Control Cohort Study.

BACKGROUND: Intraoperative hypothermia is a common adverse event. For avoiding the complication due to hypothermia, many warming devices and methods have been used in perioperative period. It has been reported that more patients undergoing laparoscopic surgery tend to have hypothermia than with open surgery. To avoid intraoperative hypothermia, many kinds of warming tools have been used. But, it was also reported that some warming methods increased perceptions of distraction and physical demand. METHODS: To achieve both patients' normothermia and surgeons' comfort, new air conditioning (AC) system was designed with considering the characteristics of laparoscopic surgery. The temperature of the airflows to the patient and to the surgeons can be adjusted independently in this new system. The new system has two parts. One controls the temperature of the central area over the operation table. The air from this part falls on the patients. The other part is the lateral area beside the operating table; the air from this part falls on the surgeons. The subjects of this study were 160 gastric cancer patients and 316 colorectal cancer patients undergoing laparoscopic surgery. The temperature of the central flow was set 23.5 °C, and the temperature of the lateral flow was set 22 °C just after the anesthesia. The number of timepoints the patient spent in hypothermic state, defined as a temperature cooler by 0.5 °C or more than that at the starting point of surgery, was determined in each patient. RESULTS: In the results, the rate of hypothermic state in old operation rooms was 23.8% and that in new operation rooms was 2.7% in male gastric cancer patients (p < 0.01). And those were 37.1% in old operation rooms and 0.9% in new operation rooms in female gastric cancer patients (p < 0.01). The rate of hypothermic state in old operation rooms was 30.0% and that in new operation rooms was 9.5% in male colorectal cancer patients (p < 0.01). And those were 41.6% in old operation rooms and 8.9% in new operation rooms in female colorectal cancer patients (p < 0.01). The similar results were showed in the study, which subjects were limited the patients undergoing surgery in 2015 and 2016; which were the last year the old operation rooms were used and the first year the new operation rooms were used. CONCLUSIONS: Thus, the usefulness of the new air conditioning system for achieving both patients' normothermia and comfort of surgeons could be verified in this study.

(Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations.

BACKGROUND: Although constitutive activating mutations in the Wnt/ß-catenin signalling pathway are important for colorectal cancer development, canonical signalling through Wnt ligands is essential for ß-catenin activation. Here, we investigated the role of (pro)renin receptor ((P)RR), a component of the Wnt receptor complex, in the pathogenesis of colorectal cancer. METHODS: (P)RR silencing was performed in human colorectal cancer cells containing constitutive activating mutations in the Wnt/ß-catenin pathway. (P)RR overexpression was induced in normal colon epithelial cells. Protein and mRNA levels of pathway components were detected, and Wnt signalling activity was measured using a ß-catenin reporter. Cell proliferative activity and apoptosis were evaluated using WST-1 assay and flow cytometry. Xenografts were induced in nude mice. RESULTS: (P)RR expression was greater in colorectal cancer tissues and cells than in normal colorectal samples. Patients with strong (P)RR expression took more proportion in groups with poorly-differentiated, advanced and rapidly-progressing cancers. (P)RR silencing attenuated the pathway in colorectal cancer cells, impaired their proliferation in vitro and vivo. (P)RR overexpression enhanced the pathway and proliferation of normal colon epithelial cells. CONCLUSIONS: Aberrant (P)RR expression promotes colorectal cancer through the Wnt/ß-catenin signalling pathway despite constitutive pathway-activating mutations. (P)RR is a potential diagnostic and therapeutic target for colorectal cancer.

Pure laparoscopic pancreas parenchymal dissection using CUSA for distal pancreatectomy.

Although stapler dissection and closure is commonly used for laparoscopic distal pancreatectomy (LDP), it is risky in patients with thick pancreatic parenchyma or titanium allergy. We performed laparoscopic pancreatic parenchymal dissection with cavitron ultrasonic surgical aspirator (CUSA) successfully in a patient with titanium allergy. Slinging the pancreas with nylon tape delineates the surgical plane. Pancreatic parenchyma was transected by CUSA in an almost bloodless field. Pancreatic duct branches and vessels were adequately exposed and dissected with a vessel sealing system. The main pancreatic duct was closed with Hem-O-lock. CUSA is an alternative to stapler dissection during LDP in select patients.

Phenotypic characterization and clinical outcome in ampullary adenocarcinoma.

BACKGROUND: Although various features of ampullary adenocarcinoma have been reported, the impact of genetic alterations and rare subtypes on clinical outcome remains unclear. METHODS: We determined the expression of proteins, including MUC1, MUC2, p53, p16, Smad/Dpc4, and ß-catenin, and genetic mutations such as KRAS, BRAF, and GNAS mutations in 69 patients with ampullary adenocarcinoma to clarify their relationships with clinicopathological findings and subtypes. RESULTS: Kaplan-Meier survival analysis indicated that abnormal p53 labeling was significantly associated with a shorter overall survival. MUC1-positive and MUC2-negative expressions were significantly associated with lymphatic invasion, pancreatic invasion, lymph node metastasis, and advanced UICC stage. The KRAS mutation was significantly associated with large tumor size and pancreatic invasion. There were 35 intestinal (50%), 15 pancreatobiliary (22%), and 11 mixed subtype (16%) tumors. Patients with the mixed subtype showed significantly poor outcome. The invasiveness of the mixed subtype was similar to that of the pancreatobiliary subtype; moreover, the mixed subtype showed a high incidence of abnormal ß-catenin immunolabeling (73%). CONCLUSIONS: Protein expression and genetic mutation are clinically associated with the characteristics of ampullary adenocarcinoma. The mixed subtype may have a distinct tumor nature as compared to other two major subtypes. J. Surg. Oncol. 2016;114:119-127. © 2016 Wiley Periodicals, Inc.

Factors influencing lymph node metastasis in patients with ampullary adenocarcinoma.

AIM: In cases of ampullary carcinoma, lymph node involvement affects the selection of treatment strategies. This study aimed to identify clinicopathologic features of ampullary carcinoma with lymph node metastases. METHODS: The records of 74 consecutive patients with ampullary adenocarcinoma who underwent pancreaticoduodenectomy (PD) with regional lymph node dissection were retrospectively analyzed. RESULTS: Twenty-two patients (30%) with lymph node metastasis had significantly worse survival after resection than those without lymph node metastasis (p = 0.017). Univariate analyses revealed that preoperative biliary drainage; elevated serum carbohydrate antigen 19-9 (≥36 U/ml); moderate-to-poor pathologic grade (G2/3); perineural, vascular, lymphatic, pancreas, and duodenal invasion; and T category were significantly associated with lymph node metastasis. In multivariate analysis, only pathologic grade (G2/3) remained significantly associated with lymph node metastasis (hazard ratio, 6.51; p = 0.035). In sub-classified analysis for T category, lymph node metastasis was found in 5 of 22 cases (22.7%) of T1 tumors. Four of five cases with lymph node metastases had a dominant G2/3 component, whereas only 2 of 17 cases without lymph node metastases had a G2/3 component in T1 tumors (p = 0.0036). CONCLUSIONS: Pathologic grade (G2/3) was significantly and independently associated with lymph node metastasis and was also a significant predictor in T1 tumor cases.

Neoadjuvant chemoradiotherapy is associated with prolonged relapse free survival in patient with MRI-detected extramural vascular invasion (mrEMVI) positive rectal cancer: A multicenter retrospective cohort study in Japan.

PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) is employed for the local control of locally advanced rectal cancer; however, its prognostic impact is limited and often impairs pelvic organ function. Therefore, careful patient selection is essential. This study aimed to investigate the impact of nCRT on relapse-free survival (RFS) by stratifying patients according to MRI detected circumferential resection margin (mrCRM) or extramural vascular invasion (mrEMVI), as the ability of MRI findings to identify patients who will have beneficial outcomes from nCRT is uncertain. METHODS: We retrospectively analyzed patients with clinical stage II-III lower rectal cancer who underwent surgical resection with or without nCRT between 2010 and 2011 at 69 hospitals in Japan. The impact of nCRT on RFS was evaluated using multivariable Cox regression models in the entire cohort and in subgroups stratified by mrCRM or mrEMVI status. RESULTS: In the entire cohort (nCRT, n = 172; surgery alone, n = 503), nCRT showed a trend toward improved RFS, although the difference was not statistically significant (HR, 0.74; 95 % CI, 0.54-1.03; P = 0.074). Among mrCRM-negative and mrEMVI-negative patients, there were no significant differences in RFS between the nCRT and surgery-alone groups. Among mrCRM-positive patients, nCRT tended to improve the RFS (HR, 0.70; 95 % CI, 0.46-1.06; P = 0.089). Among mrEMVI-positive patients, nCRT significantly prolonged the RFS (HR, 0.62; 95 % CI, 0.38-1.00; P = 0.048). CONCLUSIONS: Compared to surgery alone, nCRT did not significantly improve RFS in the overall population but significantly improved RFS in mrEMVI-positive patients.

A case of chronic expanding hematoma mimicking a cystic pancreatic tumor.

BACKGROUND: A chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach. CASE PRESENTATION: We report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space. CONCLUSION: Chronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence.

Omental flap wrapping with fixation to the cut surface of the liver for reducing delayed gastric emptying after left-sided hepatectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication following left-sided hepatectomy. The goal of this study was to clarify the clinical implications of an omental flap wrapping procedure that includes fixation to the cut surface of the liver to reduce the incidence of DGE after left-sided hepatectomy. METHODS: The study included 50 consecutive patients who underwent left-sided hepatectomy between January 2000 and July 2011. Clinicopathologic risk factors for DGE after left-sided hepatectomy were identified using univariate and multivariate models. The incidence of DGE, digestive symptoms, and postoperative complications were compared between two groups: 25 patients treated with the omental flap wrapping and fixation procedure and 25 patients who did not receive such a flap. RESULTS: A univariate analysis revealed that a lack of the omental flap, the lymph node clearance, and use of left hemihepatectomy were associated with postoperative DGE. The multivariate analysis indicated that the lack of the omental flap was the only independent significant factor associated with the DGE (odds ratio, 21.23; p = 0.0002). There was a significant difference in the incidence of DGE between the patients with (4 %) and without an omental flap (36 %). The incidence of gastric distension and the use of prokinetic drugs were also significantly lower in patients with an omental flap than in patients without the flap, and patients with an omental flap resumed a solid diet significantly earlier. CONCLUSIONS: This retrospective single-center study revealed that it was possible to reduce the incidence of DGE using a procedure involving omental flap wrapping with fixation to the cut surface of the liver after left-sided hepatectomy.

Vasoactive intestinal peptide blockade suppresses tumor growth by regulating macrophage polarization and function in CT26 tumor-bearing mice.

Macrophages are a major population of immune cells in solid cancers, especially colorectal cancers. Tumor-associated macrophages (TAMs) are commonly divided into M1-like (tumor suppression) and M2-like (tumor promotion) phenotypes. Vasoactive intestinal peptide (VIP) is an immunoregulatory neuropeptide with a potent anti-inflammatory function. Inhibition of VIP signaling has been shown to increase CD8+ T cell proliferation and function in viral infection and lymphoma. However, the role of VIP in macrophage polarization and function in solid tumors remains unknown. Here, we demonstrated that conditioned medium from CT26 (CT26-CM) cells enhanced M2-related marker and VIP receptor (VPAC) gene expression in RAW264.7 macrophages. VIP hybrid, a VIP antagonist, enhanced M1-related genes but reduced Mrc1 gene expression and increased phagocytic ability in CT26-CM-treated RAW264.7 cells. In immunodeficient SCID mice, VIP antagonist alone or in combination with anti-PD-1 antibody attenuated CT26 tumor growth compared with the control. Analysis of tumor-infiltrating leukocytes found that VIP antagonist increased M1/M2 ratios and macrophage phagocytosis of CT26-GFP cells. Furthermore, Vipr2 gene silencing or VPAC2 activation affected the polarization of CT26-CM-treated RAW264.7 cells. In conclusion, the inhibition of VIP signaling enhanced M1 macrophage polarization and macrophage phagocytic function, resulting in tumor regression in a CT26 colon cancer model.

Internal hernia after laparoscopic sigmoidectomy with splenic flexural mobilization and high ligation of the inferior mesenteric vein: A case report.

Several studies have recently reported the rare occurrence of internal herniation of the small bowel after laparoscopic colorectal surgery. Most cases of internal herniation after laparoscopic colorectal surgery occur due to a mesenteric defect. However, there have been no reports on the indications for closing mesenteric defects to prevent the development of an internal hernia. This study reports a case of an internal hernia of the proximal jejunum near the ligament of Treitz in a patient who underwent laparoscopic sigmoidectomy with splenic flexural mobilization and high ligation of the inferior mesenteric vein. Assessing the risk for internal herniation before completing the initial surgery is crucial. Additionally, mesenteric defect closure should be performed to prevent the development of internal hernias among patients with a potential risk.