Nadav Dujovny

Fluid management for laparoscopic colectomy: a prospective, randomized assessment of goal-directed administration of balanced salt solution or hetastarch coupled with an enhanced recovery program.

INTRODUCTION: No consensus exists regarding the optimal fluid (crystalloid or colloid) or strategy (liberal, restricted, or goal directed) for fluid management after colectomy. Prior assessments have used normal saline. This is the first assessment of standard, goal-directed perioperative fluid management with either lactated Ringer’s or hetastarch/lactated Ringer’s, with use of esophageal Doppler for guidance, in laparoscopic colectomy with an enhanced recovery protocol. METHODS: A double-blinded, prospective, randomized, three-armed study with Institutional Review Board approval was used for patients undergoing laparoscopic segmental colectomy assigned to the standard, goal-directed/lactated Ringer’s and goal-directed/hetastarch groups. A standard anesthesia and basal fluid administration protocol was used in addition to the goal-directed strategies guided by esophageal Doppler. RESULTS: Sixty-four patients undergoing laparoscopic colectomy (22 standard, 21 goal-directed/lactated Ringer’s, 21 goal-directed/hetastarch) had similar operative times (standard, 2.3 hours; goal-directed/lactated Ringer’s, 2.5 hours; goal-directed/hetastarch, 2.3 hours). The lactated Ringer’s group received the greatest amount of total and milliliters per kilogram per hour of operative fluid (standard, 2,850/18; goal-directed/lactated Ringer’s, 3,800/23; and goal-directed/hetastarch, 3,300/17; P < 0.05). The hetastarch group had the longest stay (standard, 64.9 hours; goal-directed/lactated Ringer’s, 71.8 hours; goal-directed/hetastarch, 75.5 hours; P < 0.05). The standard group received the greatest amount of fluid during hospitalization (standard, 2.5 ml/kg/h; goal-directed/lactated Ringer’s, 1.9 ml/kg/h; goal-directed/hetastarch, 2.1 ml/kg/h; P < 0.05). There was one instance of operative mortality in the goal-directed/hetastarch group. CONCLUSIONS: Goal-directed fluid management with a colloid/balanced salt solution offers no advantage and is more costly. However, goal-directed, individualized intraoperative fluid management with crystalloid should be evaluated further as a component of enhanced recovery protocols following colectomy because of reduced overall fluid administration.

Colorectal Cancer: Surveillance

The majority of patients with colon and rectal cancer undergo curative resection and become candidates for continuing surveillance. It is well understood that the risk of colorectal cancer recurrence is largely dependent on the stage of disease at initial presentation and the appropriate level of postoperative surveillance should reflect this degree of risk stratification. Therefore, considerable effort has been devoted to the follow-up and surveillance of patients who have undergone curative-intent surgery. Continued surveillance is imperative to detect both metachronous neoplasms and prevent the development of subsequent cancers. In theory, proper surveillance allows subsequent polyps to be removed before malignant transformation occurs and improve survival by early identification of treatable recurrent cancer. Furthermore, surveillance directs family members of patients with hereditary cancers to receive proper screening and genetic counseling.

Colorectal resection is associated with persistent proangiogenic plasma protein changes: Postoperative plasma stimulates in vitro endothelial cell growth, migration, and invasion

Introduction:Plasma vascular endothelial growth factor (VEGF) levels are elevated for weeks after minimally invasive colorectal resection (MICR). Decreased plasma angiopoietin-(Ang) 1 and increased Ang-2 levels have been noted on postoperative days (POD) 1 and 3. These proangiogenic changes may stimulate tumor growth postoperatively (postop). This studys purpose was to track plasma VEGF, Ang-1, and Ang-2 levels for 4 to 8 weeks after MICR for cancer and to assess the impact of preoperative (preop) and postop plasma on in vitro endothelial cell (EC) behavior. Methods:Blood samples from 105 MICR patients were taken preop, on POD 5 and at varying time points for 2 months. Samples from 7 day time blocks after POD 5 were bundled to permit statistical analysis. Plasma protein levels were measured via enzyme-linked immunosorbent assay. In vitro EC branch point formation, EC invasion, and EC migration assays were carried out with preop, POD 7 to 13 and 14 to 20 plasma. The t test and Bonferonni correction was used. Results:VEGF levels were significantly elevated on POD 5 and 7 to 13; lesser increases were noted on POD 14 to 20 and 21 to 27. Ang-2 levels were significantly increased at all time points postop. No significant Ang-1 changes were noted. When compared to preop EC culture results, there was significantly more EC branch point formation, EC invasion, and EC migration assays noted with POD 7 to 13 and POD 14 to 20 plasma. Conclusions:MICR is associated with proangiogenic plasma changes for 2 to 4 weeks and plasma from POD 7 to 13 and 14 to 20 stimulated EC growth, invasion, and migration. Postop plasma may stimulate the growth of residual tumor.

Outcomes of ileocolic resection and right hemicolectomies for Crohn's patients in comparison with non-Crohn's patients and the impact of perioperative immunosuppressive therapy with biologics and steroids on inpatient complications

BACKGROUND The purpose of this study was to compare medication use and complication rates between Crohns disease (CD) and non-CD patients undergoing ileocolic resections and right hemicolectomies. METHODS A review of patients who underwent ileocolic resections and right hemicolectomies from January 1, 2003, through December 31, 2010, was performed. Data collected included demographics and clinical information, biologics use (eg, infliximab, adalimumab), other medication use (eg, steroids), complications, and mortality. RESULTS There were 791 records reviewed, with 93 CD patients. There was no significant difference in major or minor complications, anastomotic leaks, operating room time, or postoperative ileus occurrence between the CD and non-CD groups (P > .05). Use of biologics and steroids were significantly higher among the CD patients. Mortality, age, and American Society of Anesthesiologists score were significantly higher in the non-CD group. CONCLUSIONS Ileocolic resections and right hemicolectomies in CD patients are not associated with an increase in complication rates even when the patients use steroids and biologics in the preoperative period.

Bioabsorbable staple line reinforcement in restorative proctectomy and anterior resection: a randomized study.

BACKGROUND: Anastomotic complications, including leaks, strictures/stenoses, and bleeding, cause considerable mortality and morbidity after colorectal surgery. OBJECTIVE: The aim of this study was to assess whether the use of a synthetic, bioabsorbable staple line reinforcement material with circular staplers would reduce postoperative anastomotic leakage in patients with a colorectal, coloanal, or ileoanal anastomosis. DESIGN: This was a randomized study that compared outcomes in patients in whom the reinforcement material was used with those in patients who were not given the material. SETTINGS: This study was conducted at several centers in the United States. PATIENTS: The 258 patients (123 in the reinforcement group and 135 control subjects) underwent surgery for a variety of conditions, but most (n = 200) were treated for rectal cancer. MAIN OUTCOME MEASURES: The main outcome measures were occurrence of anastomotic leaks and other complications according to the study protocol. RESULTS: There were no significant differences in the 2 study groups with respect to age, BMI, ASA physical status, operating time, diagnosis, previous chemoradiotherapy, surgical technique, or 30-day complications, except for a higher rate of small-bowel obstruction (p = 0.03) and anastomotic stricture (p = 0.006) in the control group. The overall anastomotic leak rate was 12% (bioabsorbable staple line reinforcement, 11.4%; no bioabsorbable staple line reinforcement, 12.6%). LIMITATIONS: The study was nonblinded and was terminated at the first planned interim analysis because of insufficient power to detect an intergroup difference in anastomotic leak rate in the time allotted for the investigation. CONCLUSIONS: Reinforcing the circular staple line in colorectal anastomoses with bioabsorbable material did not significantly affect the anastomotic leak rate but may have reduced anastomotic strictures. Most strictures did not require an anastomotic revision or delay in stoma closure. The bioabsorbable material may positively affect some aspects of the healing of circular stapled colorectal anastomoses; however, additional research on factors associated with anastomotic leakage is needed.

Anastomotic leaks: technique and timing of detection

BACKGROUND Despite the proven benefits of laparoscopic colorectal surgery, the rate of anastomotic leaks has not changed. This study looks at the time of presentation of anastomotic leaks between laparoscopic and open colectomies. METHODS Retrospective chart review was performed between July 2008 and 2012. Two groups were created, laparoscopic and open. The time of presentation of significant leaks requiring reoperation were compared between the groups by index colectomies. Statistical analysis is presented as paired t test and chi-square test (P < .05). RESULTS From 1,424 segmental colectomies, the anastomotic leak rate between the two groups was not statically significant (P = .69). No difference in the time of leak detection was evident (P = .67). Mortality rate was equal between the groups. The overall complication rate of the entire cohort was statically significant (P ≤ .001). CONCLUSION The timing of anastomotic leak detection does not differ between laparoscopy and open colorectal resections.

Serum Adiponectin, Resistin, and Circulating Soluble Receptor for Advanced Glycation End Products in Colectomy Patients

Aim. Surgical trauma and associated complications are frequently related to physiological stress during colectomy. This study evaluated the response of adiponectin, resistin, and circulating soluble receptor for advanced glycation end products (sRAGE) in colectomy patients with or without an enhanced recovery protocol. Method. Serum samples were collected from 44 colectomy patients at 3 timframes. The surgical procedures were laparoscopic (LAP), hand-assisted laparoscopic (HALS), or open colectomy (OPEN). Adiponectin, resistin, and sRAGE levels were determined by ELISA. Repeated measures ANOVA was applied and P values < 0.05 were considered significant. Results. A total of 132 (44 × 3) sera were used for analysis. Levels of adiponectin was significantly decreased between PREOP and POD3 (P < 0.001). Conversely, concentrations of resistin significantly increased from PREOP to POD1 and returned to baseline value by POD3 (P < 0.001). Serum sRAGE levels were significantly higher in LAP in comparison with HALS (P = 0.004) and OPEN (P < 0.001). sRAGE levels were significantly higher in sera of patients that underwent ERP (P < 0.001). Conclusions. Serum adiponectin, resistin, and sRAGE have the potential to develop into a panel of stress markers. Higher sRAGE levels in sera of LAP and ERP patients may be indicative of a protective and syngeristic role for colectomy recovery.

Abstract B50: Targeting KRASG12D colorectal cancer with combined inhibition of PI3K/mTOR and MAPK signaling

Compounds validated in preclinical models frequently exhibit limited efficacy when transitioned into human trials. As a result, many patients are stratified into treatment regimens that have little impact on their disease. With the goal of establishing preclinical models that can more accurately predict tumor responses, there has been a recent emphasis to develop patient-derived xenograft (PDX) models. We strove to develop new PDX models of colorectal cancer (CRC) to test the feasibility of targeted therapy using small molecule inhibitors. Following transplantation of patient tumor specimens into athymic nude mice, sixteen PDX models were successfully established. Common somatic mutations were determined using custom gene panels and targeted with appropriate inhibitors against PI3K/AKT, mTOR and/or MAPK signaling. In four independent models, single agent therapies against PI3K and mTOR had little impact on tumor growth. Conversely, robust declines in tumor burden were universally observed in all models with MEK inhibition with the exception of one, a KRAS G12D mutant model. Within this model, tumor response was achieved only with dual inhibition of mTOR and MAPK signaling. Given the unmet clinical need to treat tumors with aberrant KRAS signaling, these results encourage further investigation into combination treatment strategies with these small molecule inhibitors. Citation Format: Danielle Burgenske, David Monsma, Dawna Dylewski, Stephanie Scott, Aaron Sayfie, Donald Kim, Martin Luchtefeld, Katie Martin, Paul Stephenson, Galen Hostetter, Nadav Dujovny, Jeffrey MacKeigan. Targeting KRASG12D colorectal cancer with combined inhibition of PI3K/mTOR and MAPK signaling. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr B50.

Tu1519 High Definition Colonoscopy Increases Adenoma Detection Rate

Objective: To test the hypothesis that ever smokers would suffer more recurrences and worse overall and disease-free survival than never smokers following colon cancer resection. Summary Background Data: Smoking is associated with an increased risk of developing colon polyps, specifically aggressive polyps, as well as an increased risk of colon cancer. Large database studies have shown an increased risk of colon cancer mortality among smokers, but it is not clear whether this risk is related to differences in the biology/ aggressiveness of the disease or differences in clinical response to treatment. Methods: The medical records of 2540 patients with resected stage I-III colon cancers treated at a single institution were reviewed. Demographics, tumor and surgical variables, and follow-up information were recorded. Univariate and multivariate analyses were performed to examine predictors of overall and disease-free survival as well as time to recurrence of colon cancer. Results: Tumor variables and chemotherapy administration were similar among smokers and nonsmokers. Overall survival was significantly higher for never smokers compared to ever smokers (5 year OS 79.8% nonsmokers versus 72.3% ever smokers, p ,0.0001; HR 1.51, 95% CI 1.30 -1.74). Disease free survival was significantly higher for nonsmokers compared to smokers. Time to cancer recurrence was also significantly influenced by smoking status. Smoking status remained a poor prognostic factor in multivariate models for overall and disease-free survival as well as time to recurrence. Conclusions: This study confirms that ever smokers have worse colon cancer outcomes than never smokers. Surgeons should refer all smokers with colon polyps or cancers for smoking cessation programs. Multivariate Predictors of Disease-Free and Overall Survival

728 First Time Colonoscopy in the Elderly Yields a High Rate of Curable Colorectal Cancer

included patient demographics, operative details, post-operative weight loss, and time interval between surgery and second imaging. Indications for post-operative imaging included abdominal symptoms. For purposes of this study, all imaging was re-reviewed by a radiologist whereby the common hepatic duct was measured at the level of the porta hepatis to determine interval changes. Results: A total of 551 patients underwent Roux-en Y gastric bypass during the study period. Of these, 82 had biliary imaging both before and after surgery. Thirtythree patients had post-operative imaging at least 3 months following gastric bypass. Mean age was 44 years (21-65) and 79% were female. There were 8 patients who had remote cholecystectomy prior to gastric bypass and 25 patients with gallbladders. In all 33 patients, mean hepatic duct diameter was 5.2 +/2 mm and 7.1 +/2.6 mm pre-operatively and post-operatively respectively (p <0.01). Patients with prior cholecystectomy had hepatic duct diameters of 7.9 +/1.3 mm and 9.5 +/3.5 mm pre-operatively and post-operatively respectively (p=0.3). Patients who had not previously undergone cholecystectomy had hepatic duct diameters of 4.3 +/1.1 mm and 6.4 +/1.8 mm pre-operatively and post-operatively respectively (p<0.01). Overall excess weight loss was 26.8% at a mean follow-up of 8 months (3-14). Conclusions: Hepatic duct diameter increases after Roux-en Y gastric bypass. Patients with prior cholecystectomy have a trend toward increased hepatic duct diameter, though this change was not statistically significant. A better understanding of this phenomenon may limit the need for further work-up in patients with incidentally detected biliary dilation and help to redefine what is considered normal and abnormal in this population.