GLP-1 receptor agonists are a transformative prehabilitation tool for weight loss in obese patients undergoing elective hernia repair.

BACKGROUND: Obesity is an independent risk factor for complications after abdominal hernia repair. Glucagon-like-peptide-1 (GLP-1) receptor agonists are gaining popularity as pharmacologic weight loss adjuncts and may help patients reach weight loss goals for surgery. We examine our early experience utilizing GLP-1 agonists versus lifestyle modifications alone to achieve weight loss in patients before elective hernia repair. METHODS: This single-center, retrospective review identified obese patients who underwent elective hernia repair from 2014 to 2023. Patients were asked to achieve a BMI ≤ 33 kg/m2 before surgery. Patients who lost weight with GLP-1 therapy in addition to lifestyle changes were compared to a control cohort that achieved similar preoperative weight loss without GLP-1 therapy. Primary outcome was mean time from GLP-1 agonist initiation and initial surgery clinic visit to surgery. Secondary outcomes were 30-day morbidity, mortality, and reoperation rates, and hernia recurrence. RESULTS: Forty-six patients with ventral/incisional, flank, umbilical, parastomal, inguinal, and hiatal hernias were identified (GLP-1 N = 24, control N = 22). 81.8% (N = 18) of controls had a ventral/incisional hernia, compared to 45.8% (N = 11) of GLP-1 patients (p = 0.03). Mean BMI at GLP-1 agonist initiation was similar to mean BMI at initial clinic visit for controls (38.1 ± 4.9 vs 38.2 ± 2.7 kg/m2, p = 0.66). Preoperative mean percentage total weight loss (14.9 ± 7.5 vs 12.4 ± 6.9 kg, p = 0.39) and mean BMI reduction (6.0 ± 3.8 vs 4.9 ± 2.3 kg/m2, p = 0.43) were similar between groups. The mean time from GLP-1 agonist initiation to surgery was significantly shorter than initial clinic visit to surgery for controls (6.3 ± 4.0 vs 14.7 ± 17.6 months, p = 0.03). There was no statistically significant difference in time from initial clinic visit to surgery between groups (7.6 ± 4.4 vs 14.7 ± 17.6 months, p = 0.06). There was no significant difference in 30-day morbidity between groups (8.3 vs 27.3%, p = 0.13). CONCLUSION: GLP-1 agonists accelerate preoperative weight loss for obese hernia patients without negatively impacting postoperative outcomes.

Robotic bariatric surgery reduces morbidity for revisional gastric bypass when compared to laparoscopic: outcome of 8-year MBSAQIP analysis of over 40,000 cases.

INTRODUCTION: Robotic-assisted metabolic and bariatric surgery (MBS) is gaining popularity. Revisional MBS is associated with higher perioperative morbidity compared to primary MBS. The optimal surgical approach to minimize complications in these complex cases is unclear. The goal of this study was to assess robot utilization in revisional MBS and compare laparoscopic and robotic revisional MBS outcomes in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. METHODS: A retrospective review of the MBSAQIP database was performed identifying revisional sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) cases from 2015 to 2022. Primary MBS, open/emergent cases, cases converted to another approach, and combined cases other than esophagogastroduodenoscopy were excluded. 30-Day outcomes for laparoscopic and robotic cases were compared using multivariate logistic regression adjusting for patient demographics, comorbidities, and operative variables. RESULTS: 41,404 Cases (14,474 SG; 26,930 RYGB) were identified. From 2015 to 2022, the percentage of revisional SG and RYGB cases performed robotically increased from 6.1% and 7.3% to 24.2% and 32.0% respectively. Laparoscopic SG had similar rates of overall morbidity, leak, bleeding, readmission, reoperation, and length of stay compared to robotic. Laparoscopic RYGB had significantly higher rates of overall morbidity (6.2% vs. 4.8%, p < 0.001, AOR 0.80 [0.70-0.93]), blood transfusion (1.5% vs. 1.0%, p < 0.05, AOR 0.74 [0.55-0.99]), superficial incisional SSI (1.2% vs. 0.4%, p < 0.001, AOR 0.30 [0.19-0.47]), and longer length of stay (1.87 vs. 1.76 days, p < 0.001) compared to robotic. Laparoscopic operative times were significantly shorter than robotic (SG: 86.4 ± 45.8 vs. 113.5 ± 51.7 min; RYGB: 130.7 ± 64.7 vs. 165.5 ± 66.8 min, p < 0.001). CONCLUSION: Robot utilization in revisional bariatric surgery is increasing. Robotic surgery has lower postoperative morbidity and shorter length of stay in revisional RYGB when compared to laparoscopic. Robotic platforms may have the capacity to improve the delivery of care for patients undergoing revisional bariatric surgery.

Bite by byte: can fitness wearables help bariatric patients lose more weight after surgery?

BACKGROUND: Multidisciplinary approaches to weight loss have been shown to improve outcomes in bariatric patients. Few studies have been performed assessing the utility and compliance of fitness tracking devices after bariatric surgery. We aim to determine whether use of an activity tracking device assists bariatric patients in improving postoperative weight loss behaviors. METHODS: A fitness wearable was offered to patients undergoing bariatric surgery from 2019 to 2022. A telephone survey was conducted to elucidate the impact of the device on the patient's postoperative weight loss efforts 6 to 12 months after surgery. Weight loss outcomes of sleeve gastrectomy (SG) patients receiving the fitness wearable (FW) were compared to those of a group of SG patients who did not receive one (non-FW). RESULTS: Thirty-seven patients were given a fitness wearable, 20 of whom responded to our telephone survey. Five patients reported not using the device and were excluded. 88.2% reported that using the device had a positive impact on their overall lifestyle. Patients felt that using the fitness wearable to keeping track of their progress helped them both to achieve short-term fitness goals and sustain them in the long run. From the patients that utilized the device, 44.4% of those that discontinued felt like it helped them build a routine that they maintained even after they were no longer using it. Demographic data between FW and non-FW groups (age, sex, CCI, initial BMI, and surgery BMI) did not differ significantly. The FW group trended towards greater %EWL at 1 year post-operation (65.2% versus 52.4%, p = 0.066) and had significantly greater %TWL at 1 year post-operation (30.3% versus 22.3%, p = 0.02). CONCLUSION: The use of an activity tracking device enhances a patient's post-bariatric surgery experience, serving to keep patients informed and motivated, and leading to improved activity that may translate to better weight loss outcomes.

Robotic left-stapled total intracorporeal bowel anastomosis versus stapled partial extracorporeal anastomosis: operative technical description and outcomes.

BACKGROUND: Although there is extensive literature on robotic total intracorporeal anastomosis (TICA) for right colon resection, left total ICA using the da Vinci Xi robotic platform has only been described in short case series previously. In this study, we report on the largest cohort of robotic left total ICA, provide a description of our institution's techniques, and compare outcomes to robotic left partial extracorporeal anastomosis (PECA). METHODS: Patients who underwent robotic left colectomy for any underlying pathology from July 1, 2016 through April 30, 2020 were identified by procedure code. A technical description is provided for two unique techniques performed at our institution. Outcomes included operative time, length of stay, supply cost, post-operative ileus, post-operative morbidity and mortality and need for complete mobilization of the splenic flexure. RESULTS: From a review of our institution's data, 83 robotic TICA cases were identified and 76 robotic PECA cases were identified. Common procedures included low anterior resection, sigmoidectomy, left hemicolectomy, and rectopexy with resection. TICA was associated with significantly shorter intraoperative time compared to PECA. CONCLUSIONS: Our series shows that TICA is a safe and feasible technique that does not increase the risk of adverse outcomes. Using either the anvil-forward or anvil-backward technique, we were able to reliably reproduce this method in a total of 83 patients undergoing left colon resection for either benign or malignant diseases.

A Novel Color-Coded Liver Metastasis Mouse Model to Distinguish Tumor and Adjacent Liver Segment.

BACKGROUND: It is difficult to distinguish between a tumor and its liver segment with traditional use of indocyanine green (ICG) alone. In the present study, a method was used to limit ICG to the liver segment adjacent to a tumor. A spectrally-distinct fluorescently-labeled tumor-specific antibody against human carcinoembryonic antigen-related cell-adhesion molecules was used to label the metastatic tumor in a patient-derived orthotopic xenograft mouse model to enable color-coded visualization and distinction of a colon-cancer liver metastases and its adjacent liver segment. MATERIALS AND METHODS: Nude mice received surgical orthotopic implantation in the liver of colon-cancer liver metastases derived from two patients. An anti- carcinoembryonic antigen-related cell-adhesion molecules monoclonal antibody (mAb 6G5j) was conjugated to a near-infrared dye IR700DX (6G5j-IR700DX). After three weeks, mice received 6G5j-IR700DX via tail-vein injection 48 hours before surgery. ICG was intravenously injected after ligation of the left or left lateral Glissonean pedicle resulting in labeling of the segment with preserved blood-flow in the liver. Imaging was performed with the Pearl Trilogy and FLARE Imaging Systems. RESULTS: The metastatic liver tumor had a clear fluorescence signal due to selective tumor targeting by 6G5j-IR700DX, which was imaged on the 700 nm channel. The adjacent liver segment, with preserved blood-flow in the liver, had a clear fluorescence ICG 800 nm signal, while the left or left lateral segment had no fluorescence signal. Overlay of the images showed clear color-coded differentiation between the tumor fluorescing at 700 nm and the adjacent liver segment fluorescing at 800 nm. CONCLUSIONS: Color-coding of a liver tumor and uninvolved liver segment has the potential for improved liver resection.

Humanized Anti-Tumor-Associated Glycoprotein-72 for Submillimeter Near-Infrared Detection of Colon Cancer in Metastatic Mouse Models.

BACKGROUND: Tumor-associated glycoprotein (TAG)-72 is a pancarcinoma antigen that is overexpressed in greater than 80% of colorectal adenocarcinomas. CC49 is a TAG-72-specific antibody. The aim of the present study was to demonstrate selective imaging of colon tumors and metastases with the humanized TAG-72 antibody (anti-huCC49) conjugated to a near-infrared fluorophore in orthotopic mouse models. METHODS: Anti-huCC49 was conjugated to near-infrared dye IR800CW. Mouse imaging was performed with the Pearl Trilogy Small Animal and FLARE Imaging Systems. Subcutaneous mouse models of colon cancer cell line LS174T were used to determine the optimal dose of administration and timing of imaging. Orthotopic mouse models of LS174T were established by surgical orthotopic implantation of LS174T tumors onto the serosa of the cecum. Peritoneal carcinomatosis models were established by injection of LS174T cells into the peritoneum of nude mice. Mice were administered anti-huCC49-IR800 via tail vein injection. Mice were euthanized 72 h later and imaged after laparotomy. RESULTS: Subcutaneous LS174T xenografts demonstrated optimal tumor detection 72 h after administration with 50 µg anti-huCC49-IR800CW. Tumors were visualized with fluorescence imaging with a mean tumor-to-liver ratio of 7.39 (standard deviation: 2.76). In the orthotopic model, metastases smaller than 1 mm were fluorescently visualized that were invisible with bright light. CONCLUSIONS: Anti-huCC49-IR800CW provides sensitive and specific imaging of colon cancer and metastases at a submillimeter resolution in metastatic nude mice models. This provides a promising near-infrared probe for the imaging of colon cancer and metastases for preoperative diagnosis and fluorescence-guided surgery.

Multiquadrant surgery in the robotic era: a technical description and outcomes for da Vinci Xi robotic subtotal colectomy and total proctocolectomy.

BACKGROUND: Common colorectal procedures that require access to all quadrants of the abdomen are subtotal colectomy (STC) and total proctocolectomy (TPC). These are frequently performed with a surgical robot, but multiquadrant operations have unique challenges during robot-assisted surgery. METHODS: Patients who underwent robotic STC or TPC with the da Vinci Xi surgical robot at our institution from July 1, 2016 through June 30, 2019 were identified by diagnosis and procedure codes. A technical description is provided for the techniques utilized at our institution. Outcomes included operative times (OT), supply cost and length of stay. Associated morbidity and mortality was also analyzed. RESULTS: From a review of our institution's robotic surgery data, 37 cases were identified that utilized the described technique. Of these cases, 21 were robotic STC and 16 were TPC. Total mean OT was 276.86 min (SD ± 119.49). Mean OT was further analyzed by year, which demonstrated an overall decrease in OT from 350.91 min (SD ± 46.38) in 2016 to 221.43 min (SD ± 16.46) in 2018 (p = 0.008). A total of 21 cases were performed prior to 2018. Overall OT for STC was 222.81 min (SD ± 14.54) compared to overall TPC OT 347.81 min (SD ± 34.35). Median length of stay was 5 days [25th and 75th percentiles 4, 6, respectively]. There was no 30-day mortality and only one return to operating room for mesenteric bleeding. There was a low risk of mortality associated with this technique. CONCLUSIONS: The current study provides the largest cohort of patients assessed who have undergone multiquadrant robotic STC or TPC. The study provides a detailed description of the technique utilized at our institution. There was no associated 30-day mortality and a low risk of morbidity. The data suggest that the learning curve for improved operative time is between 15 and 20 cases.

General surgery training in the era of robotic surgery: a qualitative analysis of perceptions from resident and attending surgeons.

BACKGROUND: The use of the surgical robot has increased annually since its introduction, especially in general surgery. Despite the tremendous increase in utilization, there are currently no validated curricula to train residents in robotic surgery, and the effects of robotic surgery on general surgery residency training are not well defined. In this study, we aim to explore the perceptions of resident and attending surgeons toward robotic surgery education in general surgery residency training. METHODS: We performed a qualitative thematic analysis of in-person, one-on-one, semi-structured interviews with general surgery residents and attending surgeons at a large academic health system. Convenient and purposeful sampling was performed in order to ensure diverse demographics, experiences, and opinions were represented. Data were analyzed continuously, and interviews were conducted until thematic saturation was reached, which occurred after 20 residents and seven attendings. RESULTS: All interviewees agreed that dual consoles are necessary to maximize the teaching potential of the robotic platform, and the importance of simulation and simulators in robotic surgery education is paramount. However, further work to ensure proper access to simulation resources for residents is necessary. While most recognize that bedside-assist skills are essential, most think its educational value plateaus quickly. Lastly, residents believe that earlier exposure to robotic surgery is necessary and that almost every case has a portion that is level-appropriate for residents to perform on the robot. CONCLUSIONS: As robotic surgery transitions from novelty to ubiquity, the importance of effective general surgery robotic surgery training during residency is paramount. Through in-depth interviews, this study provides examples of effective educational tools and techniques, highlights the importance of simulation, and explores opinions regarding the role of the resident in robotic surgery education. We hope the insights gained from this study can be used to develop and/or refine robotic surgery curricula.

Anti-Claudin-1 Conjugated to a Near-Infrared Fluorophore Targets Colon Cancer in PDOX Mouse Models.

INTRODUCTION: Claudins are tight-junction proteins, which maintain an epithelial barrier in normal colon cells. Overexpression of Claudin-1 has been implicated for development of colon cancer. We postulated that Claudin-1 may be a useful target in near-infrared imaging and fluorescence-guided surgery. METHODS: We conjugated Claudin-1 antibody to LI-COR IR800DyeCW (Claudin-1-IRDye800CW). Western blotting of 9 human colon cancer cell lysates was performed. Animal imaging was performed with the LI-COR Pearl Trilogy Fluorescence Imaging System. A dose-response study was carried out with subcutaneous LS174T colon cancer cell line models. Increasing doses of Claudin-1-IRDye800CW via tail vein injection were administered to three groups of mice. Two groups of mice were used as controls (antibody alone, and dye alone). In vivo imaging was performed at 24, 48, and 72 h after administration of the conjugated dye. Orthotopic implantation of patient-derived tumors and cell lines was performed and peritoneal carcinomatosis models were created. After tumor growth, mice were administered Claudin-1-IRDye800CW and imaged in vivo 48 h later. The mice were euthanized and laparotomy was performed to assess internal organs and toxicity. RESULTS: Western blotting revealed that all colon cancer cell lysates expressed varying amounts of Claudin-1. All tumors demonstrated strong and specific fluorescence labeling at 800 nm, even with the lowest dose of 12.5 µg of Claudin-1-IRDye800CW. CONCLUSIONS: Claudin-1 is a useful target for near-infrared antibody-based imaging for visualization of colorectal tumors for future use in fluorescence-guided surgery.

Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft.

BACKGROUND: Overexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model. MATERIALS AND METHODS: MUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 µg) intravenously. RESULTS: In the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465). CONCLUSION: MUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.

Proof of concept of improved fluorescence-guided surgery of colon cancer liver metastasis using color-coded imaging of a tumor-labeling fluorescent antibody and indocyanine green restricted to the adjacent liver segment.

BACKGROUND: Indocyanine green has been used for fluorescence-guided surgery of liver metastasis and labeling of liver segments. However, indocyanine green is nonspecific, and indocyanine green labeling does not always clearly outline tumor margins. In addition, it is difficult to distinguish between a tumor and its adjacent liver segment colored with indocyanine green alone. In the present study, we performed fluorescence-guided surgery in an orthotopic colon-cancer liver metastasis mouse model by labeling the metastatic liver tumor with an anti-carcinoembryonic antigen fluorescent antibody and with indocyanine green restricted to the adjacent liver segment. METHODS: A liver metastasis model was established with human LS174T colon cancer tumor fragments. To label the tumor, mice received SGM-101, an anti-carcinoembryonic antigen antibody conjugated to a near-infrared fluorophore (700 nm), currently in clinical trials, 3 days before surgery. Indocyanine green (800 nm) was injected after ligation of the tumor-bearing Glissonean pedicle with fluorescence labeling restricted to the liver segment adjacent to the tumor. Bright-light surgery and fluorescence-guided surgery were performed to resect the liver metastasis. To assess recurrence, mice underwent necropsy 3 weeks after surgery and the tumor was weighed. RESULTS: Fluorescence-guided anatomic left lateral lobectomy and fluorescence-guided partial liver resection were both performed with color-coded double labeled imaging. Tumor weight 3 weeks after surgery was significantly lower with fluorescence-guided surgery compared to bright-light surgery (38 ± 57 mg vs 836 ± 668 mg, P = .011) for partial liver resection. CONCLUSION: The present study provides a proof-of-concept that color-coded and double labeling of the tumor and adjacent liver segment has the potential to improve liver metastasectomy.

Anti-mucin 4 fluorescent antibody brightly targets colon cancer in patient-derived orthotopic xenograft mouse models: A proof-of-concept study for future clinical applications.

BACKGROUND: There is a high rate of positive surgical margins with resection of liver metastases in colorectal cancer (CRC). The present study reports using a fluorescent anti-mucin 4 (MUC4) antibodies to label primary CRC and liver metastases to better visualize tumor margins in mouse models. METHODS: Western blotting for MUC4 protein expression of normal colon and CRC tumor lysates was performed. Orthotopic primary and liver metastatic CRC mouse models received anti-MUC4 antibody conjugated to IR800 (MUC4-IR800). Mice were sacrificed and imaged after 48 hours. RESULTS: Western blotting demonstrated increased MUC4 expression in a human CRC cell line and patient-derived primary and liver-metastatic CRCs. The LS174T orthotopic primary CRC model tumor to background ratio (TBR) was 2.04 (±0.35). The patient-derived orthotopic xenograft (PDOX) primary CRC model TBR was 2.17 (±0.35). The PDOX liver metastasis model TBR was 1.56 (±0.53). CONCLUSION: MUC4-IR800 provided bright labeling of primary and liver tumors in CRC orthotopic mouse models, demonstrating their future clinical potential for margin visualization in fluorescence guided surgery.

A review of tumor-specific fluorescence-guided surgery for colorectal cancer.

The present study reviews the use of tumor-specific antibodies conjugated to fluorescent dyes in preclinical and clinical studies to enhance visualization of primary tumors and metastases for fluorescence-guided surgery (FGS) in colorectal cancer (CRC). A search strategy was developed using the peer-reviewed National Center for Biotechnology Information (NCBI) database on PubMed. Studies using tumor-specific fluorescence imaging and FGS techniques on murine models of colorectal cell lines or patient-derived orthotopic xenograft (PDOX) colorectal cancer are reviewed. A total of 24 articles were identified that met the inclusion criteria, 21 preclinical and 3 clinical trials. The most widely used target antigen in preclinical and clinical trials was carcinoembryonic antigen (CEA). Mouse studies and clinical studies have demonstrated that the use of FGS in CRC can aid in decreased residual tumor and decreased rates of recurrence. As the mainstay of colorectal cancer treatment is surgery, the addition of intraoperative fluorescence imaging can help locate tumor margins, visualize occult micro-metastases, drive surgical decision making and improve patient outcomes.

Outcomes for a Large Cohort of Patients with Rectal Neuroendocrine Tumors: an Analysis of the National Cancer Database.

BACKGROUND: Rectal neuroendocrine tumors comprise 20% of neuroendocrine tumors in the alimentary tract, but there is controversy surrounding the optimal management of this disease. The purpose of this study is to better define treatment for patients with rectal neuroendocrine tumors. METHODS: Using the National Cancer Database, we analyzed patients with rectal neuroendocrine tumors between 2004 and 2015. Patients with metastatic disease and missing treatment data were excluded. We examined overall survival stratified by tumor size, treatment type, and presence of positive lymph nodes using Kaplan-Meier analysis with log-rank test. Cox proportional hazard regression model was performed to identify factors associated with overall survival. RESULTS: In total, 17,448 patients with rectal neuroendocrine tumors were identified; 16,531 of these patients met inclusion criteria. The majority of patients had tumors ≤ 10 mm (9216 patients, 79.8%), and approximately 90% underwent local excision. The probability of 5-year overall survival was significantly higher for patients with smaller tumors (≤ 10 mm: 94.1% 11-20 mm: 85.7%, > 20 mm: 71.8%; p < 0.001) and those with no positive lymph nodes (91.4% versus 53.3%, p < 0.001). The probability of 5-year overall survival differed based on treatment modality (local excision: 93.6%, radical resection: 79.1%, observation alone: 77.1%; p < 0.001). On multivariable Cox regression, when compared to local excision, radical resection was not associated with a difference in overall survival but observation alone was associated with significantly worse OS (HR = 2.750, p < 0.001). CONCLUSIONS: There is a significant difference in overall survival between patients who underwent local excision versus observation alone. Excision of the tumor should be offered to all patients with rectal neuroendocrine tumors who are appropriate surgical candidates, regardless of the tumor size.

Humanized Fluorescent Tumor-associated Glycoprotein-72 Antibody Selectively Labels Colon-cancer Liver Metastases in Orthotopic Mouse Models.

BACKGROUND/AIM: Fluorescence imaging has been shown to improve intra-operative detection of liver metastasis. The present study aimed to determine whether humanized anti-TAG-72 antibody (huCC49) conjugated to a near-infrared dye provides selective labeling of colorectal-cancer liver metastasis in orthotopic mouse models. MATERIALS AND METHODS: Humanized anti-TAG-72 (huCC49) was conjugated to IRDye800CW (huCC49-IR800). Orthotopic liver-metastasis nude-mouse models (n=5) were established with the human colon-cancer LS174T cell-line. Three weeks later, mice were administered huCC49-IR800 and intra-vital imaging was performed 48 h later. The mean tumor-to-liver ratio (TLR) was calculated. RESULTS: Intra-vital imaging demonstrated clear tumor margins with minimal liver fluorescence 48 h after administration of 50 µg huCC49-IR800 with mean TLR=7.53 (SD±2.76). CONCLUSION: Anti-TAG-72 monoclonal antibody conjugated to IRDye800 provides distinct and bright labeling of colorectal tumors in orthotopic nude-mouse models of liver metastasis. TAG-72 may be a useful target for intra-operative imaging of colorectal cancer liver metastasis in the clinic.

Ligation Method to Specifically Label a Liver Segment With Indocyanine Green in an Orthotopic Nude-Mouse Liver-Metastasis Model.

BACKGROUND/AIM: The visualization of hepatic segments with indocyanine green (ICG) fluorescence can aid in anatomic liver resection. The present study aimed to develop a method to specifically label an hepatic segment in a nude mouse model with liver metastasis. MATERIALS AND METHODS: An orthotopic mouse model was established by surgical orthotopic implantation (SOI) of a patient-derived colon-cancer liver metastasis in the left lobe of the liver. Three weeks after SOI, the left Glissonean pedicle was ligated and 10 µg ICG was administrated intravenously. Images were obtained with the Pearl Trilogy Imaging System. RESULTS: All mice expressed an 800 nm signal from ICG on the right lobe of the liver. The left lobe of the liver, in which the tumor was located, showed no fluorescence and had ischemia due to successful ligation of the Glissonean pedicle. CONCLUSION: The ligation of the Glissonean pedicle enables specific liver-segment labeling with ICG, which has potential clinical application for liver metastasectomy.

Near-infrared photoimmunotherapy is effective treatment for colorectal cancer in orthotopic nude-mouse models.

BACKGROUND: Photoimmunotherapy (PIT) employs the use of a near-infrared (NIR) laser to activate an antibody conjugated to a NIR-activatable dye to induce cancer cell death. PIT has shown to be effective in a number of studies, however, there are no data on its use in colorectal cancer in an orthotopic model. METHODS: Humanized anti-CEA antibody (M5A) was conjugated to NIR-activatable IRDye700DX (M5A-700). PIT was validated in vitro with a colon cancer cell-line, using a laser intensity of either 4 J/cm2, 8 J/cm2, or 16 J/cm2. Orthotopic colon cancer mouse models were established by surgical implantation of LS174T tumor fragments onto the cecum. M5A-700 was administered and PIT was performed 24 hours later using a 690 nm laser. Repeat PIT was performed after 7 days in one group. Control mice received laser treatment only. RESULTS: In vitro PIT demonstrated tumor cell death in a laser intensity dose-dependent fashion. In orthotopic models, control mice demonstrated persistent tumor growth. Mice that underwent PIT one time had tumor growth arrested for one week, after which re-growth occurred. The group that received repeated PIT exposure had persistent inhibition of tumor growth. CONCLUSION: PIT arrests tumor growth in colon cancer orthotopic nude-mouse models. Repeated PIT arrests colon cancer growth for a longer period of time. PIT may be a useful therapy in the future as an adjunct to surgical resection or as primary therapy to suppress tumor progression.

Local excision versus radical resection in patients with rectal neuroendocrine tumours: a propensity score match analysis.

BACKGROUND: The rectum is a common site for neuroendocrine tumours of the gastrointestinal tract. Diagnosis of these tumours has been increasing in recent years, highlighting the need to better define treatment options for patients with rectal neuroendocrine tumours (rNETs). METHODS: We performed a retrospective analysis using the National Cancer Database (2004-2014) to compare overall survival (OS) between local excision (LE) and radical resection (RR). To minimize bias, we performed three propensity score-matched comparisons stratified by tumour size: <10 mm, 10-20 mm, >20 mm. We compared OS by Kaplan-Meier analysis. We also examined margin status and postoperative outcomes for each comparison. RESULTS: A total of 12 996 patients underwent surgical treatment for rNET. There was no significant difference in probability of 10-year OS between LE and RR for patients with tumours <10 mm (88.6% versus 83.8%, P = 0.631, respectively) and tumours 10-20 mm (69.5% versus 69.3%, P = 0.226, respectively). In patients with tumours >20 mm, probability of 10-year OS was significantly longer in the LE group (76.5% versus 37.0%, P < 0.001). For all tumour sizes <10 mm and >20 mm, RR had significantly higher rates of 30-day readmission and negative margins. In subset analysis, there was no difference in OS for patients with positive margins after LE versus negative margins after RR for all tumour size groups. CONCLUSIONS: Our findings suggest that LE is a reasonable treatment option in patients with rNETs, especially for patients with high perioperative risk. Limitations to this study include its retrospective nature and inability to analyse surgeon decision-making.

Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models.

BACKGROUND: Monoclonal antibody (mAb) 6G5j is a novel anti-CEACAM monoclonal antibody. Our aim was to investigate mAb 6G5j binding characteristics and to validate fluorescence targeting of colorectal tumors and metastases in patient derived orthotopic xenograft (PDOX) models with fluorescently labeled 6G5j. MATERIALS/METHODS: The MAb 6G5j binding profile was analyzed with ELISA, Western blot and immunohistochemistry. MAb 6G5j was conjugated to near-infrared dye IR800CW (LI-COR). Western blotting was performed with various colon cancer cell lysates to determine CEACAM expression. Nude mice received orthotopic implantation of patient-derived primary colon cancer and patient-derived colon cancer metastases. Mice were administered varying doses of 6G5j-IR800CW via tail vein injection and imaged 24 and 48 hours later. RESULTS: MAb 6G5j bound to human CEACAM1, 3, 5, 6 and 8. Western blotting demonstrated varied expression of CEACAMs in 15 of 16 colon cancer lysates. Dose and time-response imaging demonstrated optimal imaging 48 hours after administration of 50 µg 6G5j-IR800CW (Tumor-to-liver ratio (TLR) 3.17, SEM ± 0.45). Primary cancers and multiple metastases were fluorescently visualized. CONCLUSIONS: Anti-CEACAM antibody 6G5j binds multiple CEACAMs which may lead to improved detection of tumor margins for tumors and metastases that have variable expression of CEA and other CEACAMs. 6G5j mAb may be useful for colon cancer detection for pre-surgical diagnosis and fluorescence-guided surgery.

Fluorophore-conjugated Helicobacter pylori recombinant membrane protein (HopQ) labels primary colon cancer and metastases in orthotopic mouse models by binding CEA-related cell adhesion molecules.

HopQ is an outer-membrane protein of Helicobacter pylori that binds to human carcinoembryonic antigen-related cell-adhesion molecules (CEACAMs) with high specificity. We aimed to investigate fluorescence targeting of CEACAM-expressing colorectal tumors in patient-derived orthotopic xenograft (PDOX) models with fluorescently labeled recombinant HopQ (rHopQ). Western blotting, flow cytometry and ELISA were performed to determine the efficiency of rHopQ binding to CEACAMs. rHopQ was conjugated to IR800DyeCW (rHopQ-IR800). Nude mice received orthotopic implantation of colon cancer tumors. Three weeks later, mice were administered 25 µg or 50 µg HopQ-IR800 and imaged 24 or 48 h later. Intravital images were analyzed for tumor-to-background ratio (TBR). Flow cytometry and ELISA demonstrated binding of HopQ to CEACAM1, 3 and 5. Dose-response intravital imaging in PDOX models demonstrated optimal results 48 h after administration of 50 µg rHopQ-IR800 (TBR = 3.576) in our protocol. Orthotopic models demonstrated clear tumor margins of primary tumors and small regional metastases with a mean TBR = 3.678 (SD ±â€¯1.027). rHopQ showed specific binding to various CEACAMs in PDOX models. rHopQ may be useful for CEACAM-positive tumor and metastasis detection for pre-surgical diagnosis, intra-operative imaging and fluorescence-guided surgery.