Faculty Bibliography

Transcriptional intermediary factor 1 gamma (Tif1gamma) (Ectodermin/PTC7/RFG7/TRIM33) is a transcriptional cofactor with an important role in the regulation of the TGFbeta pathway. It has been suggested that it competes with Smad2/Smad3 for binding to Smad4, or alternatively that it may target Smad4 for degradation, although its role in carcinogenesis is unclear. In this study, we showed that Tif1gamma interacts with Smad1/Smad4 complex in vivo, using both yeast two-hybrid and coimmunoprecipitation assays. We demonstrated that Tif1gamma inhibits transcriptional activity of the Smad1/Smad4 complex through its PHD domain or bromo-domainin pancreatic cells by luciferase assay. Additionally, there is a dynamic inverse relationship between the levels of Tif1gamma and Smad4 in benign and malignant pancreatic cell lines. Overexpression of Tif1gamma resulted in decreased level of Smad4. Both overexpression and knockdown of Tif1gamma resulted in growth inhibition in both benign and cancerous pancreatic cell lines, attributable to a G2-phase cell cycle arrest, but only knockdown of Tif1gamma reduces tumor cell invasiveness in vitro. Our study demonstrated that imbalanced expression of Tif1gamma results in inhibition of pancreatic ductal epithelial cell growth. In addition, knockdown of Tif1gamma may inhibit tumor invasion. These data suggest that Tif1gamma might serve as a potential therapeutic target for pancreatic cancer.

BACKGROUND: Base of tongue (BOT) is a difficult subsite to examine clinically and radiographically. Yet, anatomic delineation of the primary tumor site, its extension to adjacent sites or across midline, and endophytic vs. exophytic extent are important characteristics for staging and treatment planning. We hypothesized that ultrasound could be used to visualize and describe BOT tumors. METHODS: Transcervical ultrasound was performed using a standardized protocol in cases and controls. Cases had suspected or confirmed BOT malignancy. Controls were healthy individuals without known malignancy. RESULTS: 100% of BOT tumors were visualized. On ultrasound BOT tumors were hypoechoic (90.9%) with irregular margins (95.5%). Ultrasound could be used to characterize adjacent site involvement, midline extent, and endophytic extent, and visualize the lingual artery. No tumors were suspected for controls. CONCLUSIONS: Ultrasonography can be used to transcervically visualize BOT tumors and provides clinically relevant characteristics that may not otherwise be appreciable.

OBJECTIVE:: To conduct a systematic review to identify surgical strategies that may decrease leak after laparoscopic sleeve gastrectomy (LSG). BACKGROUND:: LSG is growing in popularity as a primary bariatric procedure. Technical aspects of LSG including bougie size remain controversial. METHODS:: Our systematic review yielded 112 studies encompassing 9991 LSG patients. A general estimating equation (GEE) model was used to calculate the odds ratio (OR) for leak based on bougie size, distance from the pylorus, and use of buttressing on the staple line. Baseline characteristics, including age and body mass index (BMI), were included. A linear repeated measures regression model compared excess weight loss (%EWL) between bougie sizes. RESULTS:: A total of 198 leaks in 8922 patients (2.2%) were identified. The GEE model revealed that the risk of leak decreased with bougie >/=40 Fr (OR = 0.53, 95% CI = [0.37-0.77]; P = 0.0009). Buttressing did not impact leak. There was no difference in %EWL between bougie <40 Fr and bougie >/=40 Fr up to 36 months (mean: 70.1% EWL; P = 0.273). Distance from the pylorus did not affect leak or %EWL. CONCLUSIONS:: Utilizing bougie >/=40 Fr may decrease leak without impacting %EWL up to 3 years. Distance from the pylorus does not impact leak or weight loss. Buttressing does not seem to impact leak; however, if surgeons desire to buttress, bioabsorbable material is the most common type used. Longer-term studies are needed to definitively determine the effect of bougie size on weight loss after LSG.

Introduction: The Surgical Apgar Score (SAS) has been shown to correlate with postoperative morbidity and mortality in patients undergoing general surgery, but has never been validated in a Veteran patient population. Methods: We has never been validated in a Veteran patient population. Methods: We prospectively collected data on demographics, medical history, type of surgery, and post-operative outcomes for any veteran undergoing general surgery during the period Oct 2006-Jul 2009 at the NY Harbor VAMC. We categorized patients in 4 groups according to their SAS, a 10-point scoring system calculated using limited intra-operative data (blood losses, lowest mean arterial pressure, lowest heart rate). Differences between SAS groups were evaluated with Pearson's chi² and ANOVA as appropriate. The study end-points were overall morbidity and 30-day mortality. Results: During the study period 1104 patients underwent general surgery. After exclusion of patients with pace-makers and/or missing variables, 1047 were available for analysis (SAS <=4: n=15; SAS 5-6: n=134; SAS 7-8: n=414; SAS 9-10: n=484). Demographics and baseline characteristics, intra-operative and post-operative outcomes are summarized in Table 1. Patients in the lower SAS groups had worse functional status, higher ASA score and higher number of existing comorbidities. SAS scores were lower after major or extensive surgery. Low SAS scores were associated with significant post-operative morbidity and 30-day mortality. Conclusions: The SAS is easily calculated from three routinely available intra-operative measurements. The SAS correlates with fixed pre-operative risk (acute conditions, pre-existing comorbidities, operative complexity) and effectively identifies veterans at high risk for post-operative complications. (Table Presented)

BACKGROUND: Previous studies have shown accelerated gastric emptying after sleeve gastrectomy. This study aimed to determine whether a correlation exists between immediate postoperative gastroduodenal transit time and weight loss after laparoscopic sleeve gastrectomy (LSG). Specifically, correlation tests were conducted to determine whether more rapid transit after LSG correlated with increased weight loss. METHODS: Data were collected from an institutional review board-approved electronic registry. All LSGs were performed over a 40-Fr bougie, starting 5 to 7 cm proximal to the pylorus. Gastroduodenal transit time (antrum to duodenum) was calculated from a postoperative day 1 esophagram. Pearson's correlation coefficient was used for statistical analysis. RESULTS: The analysis included 62 consecutive LSG patients. The mean gastroduodenal transit time was 12.3 +/- 19.8 s. Almost all the patients (99 %) had a transit time less than 60 s. The mean percentage of excess weight loss (%EWL) was 23.8 +/- 9.8 % at 3 months, 37.9 +/- 11.8 % at 6 months, and 52.2 +/- 10.8 % at 12 months. No correlation was found between gastroduodenal transit time and %EWL at 3, 6, or 12 months. CONCLUSION: No correlation was found between gastroduodenal transit time and weight loss after LSG.

OBJECTIVE: To determine the effects of body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) on outcomes after liver resection performed at Veterans Affairs medical centers. Design, Setting, and PATIENTS: We queried the Veterans Affairs Surgical Quality Improvement Program database for liver resections (2005-2008) and grouped the patients into 5 BMI categories: normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese class 1 (BMI 30.0-34.9), obese class 2 (BMI 35.0-39.9), and obese class 3 (BMI >/=40.0). Differences in risk factors and perioperative complications across groups were analyzed in univariate and multivariate analyses. RESULTS: Of 403 patients who underwent hepatectomy, 106 (26%) were normal weight, 161 (40%) were overweight, 94 (23%) were obese class 1, 31 (8%) were obese class 2, and 11 (3%) were obese class 3. Among these groups, higher BMI was associated with increased rates of hypertension (52%, 61%, 77%, 77%, and 73%, respectively; P = .002) and diabetes (18%, 27%, 36%, 39%, and 45%, respectively; P = .04) and lower incidence of smokers (53%, 35%, 30%, 16%, and 9%, respectively; P < .001). The BMI groups were similar in demographic characteristics and metrics correlating with preexisting liver disease. There were no differences across BMI groups in overall and specific morbidity or in length of stay. Compared with the other groups, obese class 3 patients received more blood transfusions (mean [SD], 4.3 [2.7] in obese class 3 patients vs 1.1 [0.2] in normal-weight patients; P = .02) and had a higher 30-day mortality (27% in obese class 3 patients vs 6% in normal-weight patients; P = .05). Multivariate analyses confirmed obese class 3 as an independent predictor of postoperative mortality. CONCLUSIONS: Obesity did not increase postoperative complications after liver resection in veterans. After adjusting for other clinical factors, extreme obesity (BMI >/=40.0) was an independent risk factor for increased mortality.

BACKGROUND: Major thoracic or neck surgery or penetrating trauma can cause injury to the thoracic duct and development of a chylothorax. Chylothorax results in metabolic and immunologic disorders that can be life threatening, with a mortality rate reaching 50%. The management of chyle leaks is dependent on the etiology and daily output. Interventions are used to treat only leaks unresponsive to medical management or those with an output exceeding 1,000 ml/day. METHODS: This study reviewed the existing literature on the percutaneous management of chyle leaks. The authors evaluated five case series and three case reports inclusive of 90 patients in which percutaneous treatment for chylothorax was attempted between 1998 and 2004. RESULTS: For 71 patients, percutaneous treatment was technically successful, and chylothorax resolved in 49 of the patients (69%). Percutaneous treatment of chylothorax was associated with a 2% morbidity rate and no mortality. For 19 patients whose percutaneous approach failed, either surgical ligation or pleurodesis was performed. CONCLUSIONS: The percutaneous management of chyle leak is feasible, with low morbidity and mortality rates and a high rate of effectiveness. This approach should be considered before more invasive procedures