Anastomotic Leak is Increased With Clostridium difficile Infection After Colectomy: Machine Learning-Augmented Propensity Score Modified Analysis of 46 735 Patients.

BACKGROUND: Clostridium difficile infection (CDI) is now the most common cause of healthcare-associated infections, with increasing prevalence, severity, and mortality of nosocomial and community-acquired CDI which makes up approximately one third of all CDI. There are also increased rates of asymptomatic colonization particularly in high-risk patients. C difficile is a known collagenase-producing bacteria which may contribute to anastomotic leak (AL). METHODS: Machine learning-augmented multivariable regression and propensity score (PS)-modified analysis was performed in this nationally representative case-control study of CDI and anastomotic leak, mortality, and length of stay for colectomy patients using the ACS-NSQIP database. RESULTS: Among 46 735 colectomy patients meeting study criteria, mean age was 61.7 years (SD 14.38), 52.2% were woman, 72.5% were Caucasian, 1.5% developed CDI, 3.1% developed anastomotic leak, and 1.6% died. In machine learning (backward propagation neural network)-augmented multivariable regression, CDI significantly increases anastomotic leak (OR 2.39, 95% CI 1.70-3.36; P < .001), which is similar to the neural network results. Having CDI increased the independent likelihood of anastomotic leak by 3.8% to 6.8% overall, and in dose-dependent fashion with increasing ASA class to 4.3%, 5.7%, 7.6%, and 10.0%, respectively, for ASA class I to IV. In doubly robust augmented inverse probability weighted PS analysis, CDI significantly increases the likelihood of AL by 4.58% (95% CI 2.10-7.06; P < .001). CONCLUSIONS: This is the first known nationally representative study on CDI and AL, mortality, and length of stay among colectomy patients. Using advanced machine learning and PS analysis, we provide evidence that suggests CDI increases AL in a dose-dependent manner with increasing ASA Class.

Modified Frailty Index Predicts Postoperative Outcomes in Patients Undergoing Radical Pelvic Surgery.

Patients undergoing radical pelvic surgery such as proctectomy or radical cystectomy are at risk of experiencing a variety of complications. Frailty renders patients vulnerable to adverse events. We hypothesize that frailty measured preoperatively using a validated scoring system correlates with increased likelihood of experiencing Clavien-Dindo grade IV complications and 30-day mortality and may be used as a predictive model for patients preoperatively. The NSQIP database was queried for patients who underwent proctectomy or radical cystectomy from 2008 to 2012. Preoperative frailty was calculated using the 11-point modified frailty index (MFI). Patients were scored based on the presence of indicators and categorized into two groups (<3 or ≥3). Major postoperative morbidities and mortality were identified and analyzed in each group. 10,048 proctectomy and cystectomy patients were identified. The MFI was found to be predictive of both 30-day mortality (P < 0.0001) and Clavien-Dindo grade IV complications (P < 0.0001). Receiver operating characteristic analysis demonstrated improved discriminative power of the MFI with the addition of American Society of Anesthesiologists class for both prediction of complications and 30-day mortality. An MFI score of ≥3 is predictive of postoperative morbidity and mortality. Providers should be encouraged to calculate frailty preoperatively to predict adverse outcomes.

Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis.

Cancer patients have poor prognoses when lymph node (LN) involvement is present in both high-grade urothelial cell carcinoma (HG-UCC) of the bladder and colorectal cancer (CRC). More than 50% of patients with muscle-invasive UCC, despite curative therapy for clinically-localized disease, will develop metastases and die within 5 years, and metastatic CRC is a leading cause of cancer-related deaths in the US. Xenograft models that consistently mimic UCC and CRC metastasis seen in patients are needed. This study aims to generate patient-derived orthotopic xenograft (PDOX) models of UCC and CRC for primary tumor growth and spontaneous metastases under the influence of LN stromal cells mimicking the progression of human metastatic diseases for drug screening. Fresh UCC and CRC tumors were obtained from consented patients undergoing resection for HG-UCC and colorectal adenocarcinoma, respectively. Co-inoculated with LN stromal cell (LNSC) analog HK cells, luciferase-tagged UCC cells were intra-vesically (IB) instilled into female non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and CRC cells were intra-rectally (IR) injected into male NOD/SCID mice. Tumor growth and metastasis were monitored weekly using bioluminescence imaging (BLI). Upon sacrifice, primary tumors and mouse organs were harvested, weighed, and formalin-fixed for Hematoxylin and Eosin and immunohistochemistry staining. In our unique PDOX models, xenograft tumors resemble patient pre-implantation tumors. In the presence of HK cells, both models have high tumor implantation rates measured by BLI and tumor weights, 83.3% for UCC and 96.9% for CRC, and high distant organ metastasis rates (33.3% detected liver or lung metastasis for UCC and 53.1% for CRC). In addition, both models have zero mortality from the procedure. We have established unique, reproducible PDOX models for human HG-UCC and CRC, which allow for tumor formation, growth, and metastasis studies. With these models, testing of novel therapeutic drugs can be performed efficiently and in a clinically-mimetic manner.

Disease-free Survival and Local Recurrence for Laparoscopic Resection Compared With Open Resection of Stage II to III Rectal Cancer: Follow-up Results of the ACOSOG Z6051 Randomized Controlled Trial.

OBJECTIVE: To determine the disease-free survival (DFS) and recurrence after the treatment of patients with rectal cancer with open (OPEN) or laparoscopic (LAP) resection. BACKGROUND: This randomized clinical trial (ACOSOG [Alliance] Z6051), performed between 2008 and 2013, compared LAP and OPEN resection of stage II/III rectal cancer, within 12 cm of the anal verge (T1-3, N0-2, M0) in patients who received neoadjuvant chemoradiotherapy. The rectum and mesorectum were resected using open instruments for rectal dissection (included hybrid hand-assisted laparoscopic) or with laparoscopic instruments under pneumoperitoneum. The 2-year DFS and recurrence were secondary endpoints of Z6051. METHODS: The DFS and recurrence were not powered, and are being assessed for superiority. Recurrence was determined at 3, 6, 9, 12, and every 6 months thereafter, using carcinoembryonic antigen, physical examination, computed tomography, and colonoscopy. In all, 486 patients were randomized to LAP (243) or OPEN (243), with 462 eligible for analysis (LAP = 240 and OPEN = 222). Median follow-up is 47.9 months. RESULTS: The 2-year DFS was LAP 79.5% (95% confidence interval [CI] 74.4-84.9) and OPEN 83.2% (95% CI 78.3-88.3). Local and regional recurrence was 4.6% LAP and 4.5% OPEN. Distant recurrence was 14.6% LAP and 16.7% OPEN.Disease-free survival was impacted by unsuccessful resection (hazard ratio [HR] 1.87, 95% CI 1.21-2.91): composite of incomplete specimen (HR 1.65, 95% CI 0.85-3.18); positive circumferential resection margins (HR 2.31, 95% CI 1.40-3.79); positive distal margin (HR 2.53, 95% CI 1.30-3.77). CONCLUSION: Laparoscopic assisted resection of rectal cancer was not found to be significantly different to OPEN resection of rectal cancer based on the outcomes of DFS and recurrence.

Impact of a Novel Surgical Wound Protection Device on Observed versus Expected Surgical Site Infection Rates after Colectomy Using the National Surgical Quality Improvement Program Risk Calculator.

BACKGROUND: Surgical site infection (SSI) remains a persistent and morbid problem in colorectal surgery. A novel surgical device that combines barrier surgical wound protection and continuous surgical wound irrigation was evaluated in a cohort of elective colorectal surgery patients. A retrospective analysis was performed comparing rates of SSI observed in a prospective cohort study with the predicted rate of SSI using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Risk Calculator. PATIENTS AND METHODS: A prospective multi-center study of colectomy patients was conducted using a study device for surgical site retraction and protection, as well as irrigation of the incision. Patients were followed for 30 days after the surgical procedure to assess for SSI. After completion of the study, patients' characteristics were inserted into the ACS-NSQIP Risk Calculator to determine the predicted rate of SSI for the given patient population and compared with the observed rate in the study. RESULTS: A total of 108 subjects were enrolled in the study. The observed rate of SSI in the prospective study using the novel device was 3.7% (4/108). The predicted rate of SSI in the same patient population utilizing the ACS-NSQIP Risk Calculator was estimated to be 9.5%. This demonstrated a 61% difference (3.7% vs. 9.5%, p = 0.04) in SSI from the NSQIP predicted rate with the use of the irrigating surgical wound protection and retraction device. CONCLUSIONS: These data suggest the use of a novel surgical wound protection device seems to reduce the rate of SSIs in colorectal surgery.

Clopidogrel bisulfate (Plavix) does not increase bleeding complications in patients undergoing rubber band ligation for symptomatic hemorrhoids.

BACKGROUND: The incidence of postprocedural bleeding in patients undergoing rubber band ligation (RBL) for symptomatic internal hemorrhoids while taking clopidogrel bisulfate is unknown. To determine the postprocedural bleeding risk of RBL for patients taking clopidogrel compared with age- and sex-matched controls. MATERIALS AND METHODS: This is a retrospective case-controlled cohort study analyzing data from 2005 to 2013 conducted at a single tertiary care academic center. The study included a total of 80 rubber bands placed on 41 patients taking clopidogrel bisulfate and 72 bands placed on 41 control patients not taking clopidogrel matched for age and sex. The 30-d rates of significant and insignificant bleeding events after RBL were recorded. A bleeding event was considered significant if the patient required admission to the hospital, transfusion of blood products, or additional procedures to stop the bleeding. Insignificant bleeding was defined as passage of blood or clots per rectum with spontaneous cessation and no need for additional intervention. RESULTS: There was no significant difference in the number of bleeding events per band placed in the clopidogrel group when compared with the control group (3.75% versus 2.78%, P = 0.7387). The rate of significant (2.5% versus 1.39%, P = 0.6244) and insignificant bleeding events (1.25% versus 1.39%, P = 0.9399) was also similar between the two groups. Two significant bleeding events occurred in the clopidogrel group requiring intervention: cauterization in one patient and colonoscopy and transfusion in the other. CONCLUSIONS: The risk of a bleeding complication after RBL for hemorrhoids does not appear to be increased in patients taking clopidogrel. Our results support the practice of continuing clopidogrel bisulfate in the periprocedural period as the associated risk of thrombosis is greater than the risk of bleeding.

An Optimal Orthotopic Mouse Model for Human Colorectal Cancer Primary Tumor Growth and Spontaneous Metastasis.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Small animal models allow for the study of different metastatic patterns, but an optimal model for metastatic colorectal cancer has not been established. OBJECTIVE: The purpose of this study was to determine which orthotopic model most accurately emulates the patterns of primary tumor growth and spontaneous liver and lung metastases seen in patients with colorectal cancer. DESIGN: Using luciferase-tagged HT-29 cells coinoculated with lymph node stromal analog HK cells, 3 tumor cell delivery models were compared: intrarectal injection, intracecal injection, and acid enema followed by cancer cell instillation. Tumor growth was monitored weekly by bioluminescent imaging, and mice were sacrificed based on primary tumor size or signs of systemic decline. Liver and lungs were evaluated for metastases via bioluminescent imaging and histology. SETTINGS: The study was conducted at a single university center. MAIN OUTCOME MEASURES: Primary tumor and metastasis bioluminescent imaging were measured. RESULTS: Intrarectal injection had the lowest mortality at 4.0% (1/25) compared with the intracecal group at 17.4% (4/23) and the acid enema followed by cancer cell instillation group at 15.0% (3/20).The primary tumors in intrarectal mice had the highest average bioluminescence (3.78 × 10 ± 4.94 × 10 photons) compared with the mice in the intracecal (9.52 × 10 ± 1.92 × 10 photons; p = 0.012) and acid enema followed by cancer cell instillation groups (6.23 × 10 ± 1.23 × 10 photons; p = 0.0016). A total of 100% of intrarectal and intracecal mice but only 35% of mice in the acid enema followed by cancer cell instillation group had positive bioluminescent imaging before necropsy. Sixty percent of intrarectal mice had liver metastases, and 56% had lung metastases. In the intracecal group, 39% of mice had liver metastases, and 35% had lung metastases. Only 2 acid enema followed by cancer cell instillation mice developed metastases. LIMITATIONS: Tumor injections were performed by multiple investigators. Distant metastases were confirmed, but local lymph node status was not evaluated. CONCLUSIONS: Intrarectal injection is the safest, most reproducible, and successful orthotopic mouse model for human colorectal cancer primary tumor growth and spontaneous metastasis.

A Novel Wound Retractor Combining Continuous Irrigation and Barrier Protection Reduces Incisional Contamination in Colorectal Surgery.

BACKGROUND: Surgical site infection (SSI) remains a persistent and morbid problem in colorectal surgery. Key to its pathogenesis is the degree of intraoperative bacterial contamination at the surgical site. The purpose of this study was to evaluate a novel wound retractor at reducing bacterial contamination. METHODS: A prospective multicenter pilot study utilizing a novel wound retractor combining continuous irrigation and barrier protection was conducted in patients undergoing elective colorectal resections. Culture swabs were collected from the incision edge prior to device placement and from the exposed and protected incision edge prior to device removal. The primary and secondary endpoints were the rate of enteric and overall bacterial contamination on the exposed incision edge as compared to the protected incision edge, respectively. The safety endpoint was the absence of serious device-related adverse events. RESULTS: A total of 86 patients were eligible for analysis. The novel wound retractor was associated with a 66% reduction in overall bacterial contamination at the protected incision edge compared to the exposed incision edge (11.9 vs. 34.5%, P < 0.001), and 71% reduction in enteric bacterial contamination (9.5% vs. 33.3%, P < 0.001). The incisional SSI rate was 2.3% in the primary analysis and 1.2% in those that completed the protocol. There were no adverse events attributed to device use. CONCLUSIONS: A novel wound retractor combining continuous irrigation and barrier protection was associated with a significant reduction in bacterial contamination. Improved methods to counteract wound contamination represent a promising strategy for SSI prevention (NCT 02413879).

Morbidity Following Coloanal Anastomosis: A Comparison of Colonic J-Pouch vs Straight Anastomosis.

BACKGROUND: Low rectal tumors are often treated with sphincter-preserving resection followed by coloanal anastomosis. OBJECTIVE: The purpose of this study was to compare the short-term complications following straight coloanal anastomosis vs colonic J-pouch anal anastomosis. DESIGN: Patients were identified who underwent proctectomy for rectal neoplasia followed by coloanal anastomosis in the 2008 to 2013 American College of Surgeons National Surgical Quality Improvement Program database. Demographic characteristics and 30-day postoperative complications were compared between groups. SETTINGS: A national sample was extracted from the American College of Surgeons National Surgical Quality Improvement Project database. PATIENTS: Inpatients following proctectomy and coloanal anastomosis for rectal cancer were selected. MAIN OUTCOME MEASURES: Demographic characteristics and 30-day postoperative complications were compared between the 2 groups. RESULTS: One thousand three hundred seventy patients were included, 624 in the straight anastomosis group and 746 in the colonic J-pouch group. Preoperative characteristics were similar between groups, with the exception of preoperative radiation therapy (straight anastomosis 35% vs colonic J-pouch 48%, p = 0.0004). Univariate analysis demonstrated that deep surgical site infection (3.7% vs 1.4%, p = 0.01), septic shock (2.25% vs 0.8%, p = 0.04), and return to the operating room (8.8% vs 5.0%, p = 0.0006) were more frequent in the straight anastomosis group vs the colonic J-pouch group. Major complications were also higher (23% vs 14%, p = 0.0001) and length of stay was longer in the straight anastomosis group vs the colonic J-pouch group (8.9 days vs 8.1 days, p = 0.02). After adjusting for covariates, major complications were less following colonic J-pouch vs straight anastomosis (OR, 0.57; CI, 0.38-0.84; p = 0.005). Subgroup analysis of patients who received preoperative radiation therapy demonstrated no difference in major complications between groups. LIMITATIONS: This study had those limitations inherent to a retrospective study using an inpatient database. CONCLUSION: Postoperative complications were less following colonic J-pouch anastomosis vs straight anastomosis. Patients who received preoperative radiation had similar rates of complications, regardless of the reconstructive technique used following low anterior resection. See Video Abstract at http://links.lww.com/DCR/A468.

Use of Sodium Hyaluronate/Carboxymethylcellulose Bioresorbable Membrane in Loop Ileostomy Construction Facilitates Stoma Closure.

BACKGROUND: Loop ileostomy is a common adjunct to surgical procedures for low rectal cancers and inflammatory bowel disease. Ileostomy closure through a limited incision can be technically challenging. We hypothesized that placing a sodium hyaluronate/carboxymethylcellulose (SH/CMC) bioresorbable membrane at loop ileostomy creation would decrease stoma closure time without increasing morbidity. METHODS: In a retrospective review at a single institution with 6 board-certified colorectal surgeons, patients with loop ileostomy creation and closure between September 1999 and December 2011 were grouped based on SH/CMC placement at ileostomy creation. Data were abstracted for age, sex, body mass index (BMI), primary diagnosis, length of surgery, staff surgeon, interval between surgeries, and postoperative morbidity. The primary endpoint was the length of the surgery for ileostomy closure. Secondary outcome measures were length of stay, wound infection rate, and other complications. RESULTS: A total of 293 patients were identified. Group 1 (with SH/CMC) included 146 patients, and Group 2 (without SH/CMC) included 147 patients. The groups were matched according to age, sex, BMI, interval between creation and closure, and indication for surgery. The average surgical time for closure was significantly shorter in Group 1 (46.4 minutes ± 2.7) compared to Group 2 (60 minutes ± 2.3) (P=0.0001). We found no difference between the groups in length of stay, wound infection rate, or complication rate. CONCLUSION: The use of SH/CMC in loop ileostomy creation significantly decreases the operative time required for stoma closure with no increase in the complication rate.

Emerging Trends in the Etiology, Prevention, and Treatment of Gastrointestinal Anastomotic Leakage.

Anastomotic leaks represent one of the most alarming complications following any gastrointestinal anastomosis due to the substantial effects on post-operative morbidity and mortality of the patient with long-lasting effects on the functional and oncologic outcomes. There is a lack of consensus related to the definition of an anastomotic leak, with a variety of options for prevention and management. A number of patient-related and technical risk factors have been found to be associated with the development of an anastomotic leak and have inspired the development of various preventative measures and technologies. The International Multispecialty Anastomotic Leak Global Improvement Exchange group was convened to establish a consensus on the definition of an anastomotic leak as well as to discuss the various diagnostic, preventative, and management measures currently available.

Management of Colorectal Anastomotic Leak.

The aim of this article is to present strategies for preventing and managing the failure of the surgical restoration of intestinal continuity. Despite improvements in surgical technique and perioperative care, anastomotic leaks still occur, and with them occur increased morbidity, mortality, length of stay, and costs. Due to the devastating consequences for patients with failed anastomoses, there have been a myriad of materials and techniques used by surgeons to create better intestinal anastomoses. We will also discuss the management strategies for anastomotic leak when they do inevitably occur.

Current State of Colorectal Surgery Training: A Survey of Program Directors, Current and Recently Matched Colorectal Residents, and Recent Colorectal Graduates.

BACKGROUND: Colorectal residency has become one of the more competitive postgraduate training opportunities; however, little information is available to guide potential applicants in gauging their competitiveness. OBJECTIVE: The aim of this study was to identify the current trends colorectal residency training and to identify what factors are considered most important in ranking a candidate highly. We hypothesized that there was a difference in what program directors, current and recently matched colorectal residents, and recent graduates consider most important in making a candidate competitive for a colorectal residency position. DESIGN: Three 10-question anonymous surveys were sent to 59 program directors, 87 current and recently matched colorectal residents, and 119 recent graduates in March 2015. SETTINGS: The study was conducted as an anonymous internet survey. MAIN OUTCOME MEASURES: Current trends in applying for a colorectal residency, competitiveness of recent colorectal residents, factors considered most important in ranking a candidate highly, and what future colorectal surgeons can expect after finishing their training were measured. RESULTS: The study had an overall response rate of 43%, with 28 (47%) of 59 program directors, 46 (53%) of 87 current and recently matched colorectal residents, and 39 (33%) of 119 recent graduates responding. The majority of program directors felt that a candidate's performance during the interview process was the most important factor in making a candidate competitive, followed by contact from a colleague, letters of recommendation, American Board of Surgery In-Training Exam scores, and number of publications/presentations. The majority of current and recently matched colorectal residents felt that a recommendation/telephone call from a colleague was the most important factor, whereas the majority of recent graduates favored letters of recommendation as the most important factor in ranking a candidate highly. LIMITATIONS: Limitations to the study include its small sample size, selection bias, responder bias, and misclassification bias. CONCLUSIONS: There are differences in what program directors and current/recent residents consider most important in making an applicant competitive for colorectal residency.

The Role of Transanal Surgery in the Management of T1 Rectal Cancers.

The management of T1 rectal cancers is based on finding the balance between optimal oncologic outcomes and acceptable functional results for the patient. While radical resection involving a proctectomy is considered the most oncologically adequate option, its adverse effects on patient reported outcomes makes this a less than ideal choice in certain circumstances. While local excision can circumvent some of the adverse functional outcomes, its inadequacy in assessing metastatic lymph node disease and the subsequent negative impact of untreated positive lymph nodes on patient prognosis is a cause for concern. As a result, the therapeutic strategy has to be based on patient and disease-related factors in order to identify the best treatment choice that maximizes survival benefit and preserves health-related quality of life. After adequate preoperative staging work up, in selected patients with favorable pathological features, local excision can be considered. These cancers can be removed by transanal local excision or transanal endoscopic microsurgery, depending on the location of the cancer and expertise available. While perioperative morbidity is minimal, close postoperative follow-up is essential.

Non-physician endoscopists: A systematic review.

AIM: To examine the available evidence on safety, competency and cost-effectiveness of nursing staff providing gastrointestinal (GI) endoscopy services. METHODS: The literature was searched for publications reporting nurse endoscopy using several databases and specific search terms. Studies were screened against eligibility criteria and for relevance. Initial searches yielded 74 eligible and relevant articles; 26 of these studies were primary research articles using original datasets relating to the ability of non-physician endoscopists. These publications included a total of 28883 procedures performed by non-physician endoscopists. RESULTS: The number of publications in the field of non-specialist gastrointestinal endoscopy reached a peak between 1999 and 2001 and has decreased thereafter. 17/26 studies related to flexible sigmoidoscopies, 5 to upper GI endoscopy and 6 to colonoscopy. All studies were from metropolitan centres with nurses working under strict supervision and guidance by specialist gastroenterologists. Geographic distribution of publications showed the majority of research was conducted in the United States (43%), the United Kingdom (39%) and the Netherlands (7%). Most studies conclude that after appropriate training nurse endoscopists safely perform procedures. However, in relation to endoscopic competency, safety or patient satisfaction, all studies had major methodological limitations. Patients were often not randomized (21/26 studies) and not appropriately controlled. In relation to cost-efficiency, nurse endoscopists were less cost-effective per procedure at year 1 when compared to services provided by physicians, due largely to the increased need for subsequent endoscopies, specialist follow-up and primary care consultations. CONCLUSION: Contrary to general beliefs, endoscopic services provided by nurse endoscopists are not more cost effective compared to standard service models and evidence suggests the opposite. Overall significant shortcomings and biases limit the validity and generalizability of studies that have explored safety and quality of services delivered by non-medical endoscopists.

The critical roles of tumor-initiating cells and the lymph node stromal microenvironment in human colorectal cancer extranodal metastasis using a unique humanized orthotopic mouse model.

Colorectal cancer (CRC) is the second-most common cause of cancer-related mortality. The most important prognostic factors are lymph node (LN) involvement and extranodal metastasis. Our objective is to investigate the interactions between CD133(+)CXCR4(+) (CXC receptor 4) colorectal cancer tumor-initiating cells (Co-TICs) and the LN stromal microenvironment in human CRC extranodal metastasis. We established a unique humanized orthotopic xenograft model. Luciferase-tagged CRC cell lines and human cancer cells were injected intrarectally into nonobese diabetic/SCID mice. Mesenteric LN stromal cells, stromal cell line HK, or CXCL12 knockdown HK (HK-KD-A3) cells were coinoculated with CRC cells. Tumor growth and metastasis were monitored by bioluminescent imaging and immunohistochemistry. We found that this model mimics the human CRC metastatic pattern with CRC cell lines or patient specimens. Adding LN stromal cells promotes CRC tumor growth and extranodal metastasis (P < 0.001). Knocking down CXCL12 impaired HK cell support of CRC tumor formation and extranodal metastasis. When HK cells were added, sorted CD133(+)CXCR4(+) Co-TICs showed increased tumor formation and extranodal metastasis capacities compared to unseparated and non-Co-TIC populations. In conclusion, both Co-TIC and LN stromal factors play crucial roles in CRC metastasis through the CXCL12/CXCR4 axis. Blocking Co-TIC/LN-stromal interactions may lead to effective therapy to prevent extranodal metastasis.

Perfusion assessment in laparoscopic left-sided/anterior resection (PILLAR II): a multi-institutional study.

BACKGROUND: Our primary objective was to demonstrate the utility and feasibility of the intraoperative assessment of colon and rectal perfusion using fluorescence angiography (FA) during left-sided colectomy and anterior resection. Anastomotic leak (AL) after colorectal resection increases morbidity, mortality, and, in cancer cases, recurrence rates. Inadequate perfusion may contribute to AL. The PINPOINT Endoscopic Fluorescence Imaging System allows for intraoperative assessment of anastomotic perfusion. STUDY DESIGN: This is a prospective, multicenter, open-label, clinical trial that assessed the feasibility and utility of FA for intraoperative perfusion assessment during left-sided colectomy and anterior resection at 11 centers in the United States. RESULTS: A total of 147 patients were enrolled, of whom 139 were eligible for analysis. Diverticulitis (44%), rectal cancer (25%), and colon cancer (21%) were the most prevalent indications for surgery. The mean level of anastomosis was 10 ± 4 cm from the anal verge. Splenic-flexure mobilization was performed in 81% and high ligation of the inferior mesenteric artery in 61.9% of patients. There was a 99% success rate for FA, and FA changed surgical plans in 11 (8%) patients, with the majority of changes occurring at the time of transection of the proximal margin (7%). Overall morbidity rates were 17%. The anastomotic leak rate was 1.4% (n = 2). There were no anastomotic leaks in the 11 patients who had a change in surgical plan based on intraoperative perfusion assessment with FA. CONCLUSIONS: PINPOINT is a safe and feasible tool for intraoperative assessment of tissue perfusion during colorectal resection. There were no anastomotic leaks in patients in whom the anastomosis was revised based on inadequate perfusion with FA.

Benefits of a Multimodal Regimen for Postsurgical Pain Management in Colorectal Surgery.

BACKGROUND: Postoperative pain management is a major concern and a significant component of postoperative care pathways for surgery patients. METHODS: We performed a retrospective medical record review of 233 consecutive patients undergoing major colorectal surgery from October 2011 to January 2013 at an academic medical center. All patients were managed with similar enhanced recovery pathways; 66 patients received multimodal postsurgical pain management that included liposomal bupivacaine intraoperatively, and 167 patients received conventional pain management with intravenous opioids. Comparisons were made using t test and chi-square analysis with StatView (SAS Institute Inc.). RESULTS: Patients receiving multimodal pain management with liposomal bupivacaine injected in the surgical site at the end of major colorectal procedures had lower postoperative pain scores and used significantly less opioids at 12, 24, 36, 48, 60, and 72 hours (P=0.03). Patients in the multimodal group also had a significantly decreased risk of opioid-related adverse events, with decreased use of antipruritic medications and antiemetic medications postoperatively. A significant decrease in length of postoperative hospital stay was seen in the multimodal group (7.2 vs 9.0 days, P=0.04). CONCLUSION: The use of multimodal pain management including liposomal bupivacaine during major colorectal surgeries improved postoperative outcomes, decreased lengths of stay, and increased bed availability.

Activation of c-Myc and Cyclin D1 by JCV T-Antigen and ß-catenin in colon cancer.

During the last decade, mounting evidence has implicated the human neurotropic virus JC virus in the pathology of colon cancer. However, the mechanisms of JC virus-mediated oncogenesis are still not fully determined. One candidate to mediate these effects is the viral early transcriptional product T-Antigen, which has the ability to inactivate cell cycle regulatory proteins such as p53. In medulloblastomas, T-Antigen has been shown to bind the Wnt signaling pathway protein ß-catenin; however, the effects of this interaction on downstream cell cycle regulatory proteins remain unknown. In light of these observations, we investigated the association of T-Antigen and nuclear ß-catenin in colon cancer cases and the effects of this complex in the activation of the transcription and cell cycle regulators c-Myc and Cyclin D1 in vitro. Gene amplification demonstrated the presence of viral sequences in 82.4% of cases and we detected expression of T-Antigen in 64.6% of cases by immunohistochemistry. Further, we found that T-Antigen and ß-catenin co-localized in the nuclei of tumor cells and we confirmed the physical binding between these two proteins in vitro. The nuclear presence of T-Antigen and ß-catenin resulted in the significant enhancement of TCF-dependent promoter activity and activation of the ß-catenin downstream targets, c-Myc and Cyclin D1. These observations provide further evidence for a role of JCV T-Antigen in the dysregulation of the Wnt signaling pathway and in the pathogenesis of colon cancer.

Current status: new technologies for the treatment of patients with fecal incontinence.

Fecal incontinence is a frequent and debilitating condition that may result from a multitude of different causes. Treatment is often challenging and needs to be individualized. During the last several years, new technologies have been developed, and others are emerging from clinical trials to commercialization. Although their specific roles in the management of fecal incontinence have not yet been completely defined, surgeons have access to them and patients may request them. The purpose of this project is to put into perspective, for both the patient and the practitioner, the relative positions of new and emerging technologies in order to propose a treatment algorithm.