Charles R. Scoggins

336 Background: The prognosis of patients with gallbladder cancer (GBC) who present with jaundice has historically been considered dismal, however recent Eastern literature has demonstrated that surgical resection can be associated with long-term survival. The objective of this study was to utilize a contemporary, Western, multi-institutional dataset to examine the prognostic significance of preoperative jaundice on short- and long-term outcomes after GBC resection. Methods: Patients with GBC managed surgically from 2000 to 2015 in 10 academic institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium were stratified based on the presence of preoperative jaundice (bilirubin > 3 mg/ml or requiring preoperative biliary drainage). Postoperative morbidity, mortality, and overall survival were compared. Results: Of 449 patients with GBC evaluated for resection, 301 (67%) eventually underwent curative-intent resection. Resectability for cure was much lower in patients with preoperative jaundice (48% vs. 79%, p < 0.001). Of 273 patients who underwent curative-intent resection and had available preoperative bilirubin levels, 53 (19%) had preoperative jaundice and were noted to have tumors of T3/4 stage (63% vs 42%, P = 0.008), with lymph node metastasis (63% vs. 41%; p = 0.014), lymphovascular invasion (68% vs 39%; p = 0.003), and R1 margins (37 vs. 9%; p < 0.001). Patients with jaundice more commonly required CBD (55% vs 32%, P = 0.004), major liver (25% vs. 7%; p < 0.001) and portal vein resection (8% vs. 0.5%; p = 0.006), as well as intraoperative blood transfusion (29 % vs. 11%; p = 0.002). Overall morbidity (57% vs. 38%; p = 0.031) and in-hospital mortality (7.5% vs. 1.4%; p = 0.029) rates were higher in patients with jaundice. Overall survival after curative-intent resection was worse in patients with jaundice (median 12 vs 33 months; p < 0.001). Conclusions: Half of GBC patients presenting with jaundice are not resectable for cure and when they are, their 5-year survival is 12%. These patients should not be excluded from multidisciplinary treatment strategies that include surgery, however expectations should be clearly set and selection should be cautious.

Background Esophageal anastomotic leak is associated with high morbidity and mortality and potentially lethal if not recognized promptly and treated aggressively. While many studies have attempted to delineate the surgical techniques associated with lower rates of anastomotic leak, few have attempted to determine its long term effects on adjuvant therapy and patient quality of life. Methods We reviewed our prospective 350 patient esophageal‐gastric database and found 194 esophageal anastomoses performed from 1994 to 2013. Leaks were classified based on timing, severity, and location. We then compared their postoperative courses of adjuvant treatment, morbidity/mortality, and quality of life measured by Karnofsky performance status and EORTC score. Statistical correlations were calculated with χ², T‐test, Kaplain–Meier, ANOVA, and Cox Regression analyses as appropriate. Results Of 194 patients receiving esophageal anastomoses for cancer, 35 (18%) developed clinically diagnosed anastomotic leak 27 from esophagogastric and 8 from esophagojejunal. These groups were similar in preoperative history, preoperative staging, and type of tumor. Type of operation and variations in operative technique did not significantly affect leak rate. Patients with a leak were more likely to require intraoperative transfusion (47.1% vs. 24.1%, P = 0.013). As expected, they had a greater prevalence of perioperative complications to include pneumonia (38.6% vs. 16.3%, P = 0.001), pulmonary embolus (11.3% vs. 4.3%, P = 0.043), ileus (11.4% vs. 1.6%, P = 0.006%), empyema (11.4% vs. 0%, P > 0.001), and catheter related blood stream infections (8.6% vs. 0%, P = 0.001). Despite this increase in perioperative morbidity, there was no statistically significant difference in 90 day peri‐operative mortality (2.8% vs. 2.3%) with similar ability to receive adjuvant therapy (38.6% vs. 48.0%, P = 0.303), quality of life scores (93.2 vs. 93.1, P = 0.9), and survival at 12 months (93% vs. 94%, P = 0.3). Conclusion Anastomotic leak after oncologic resection does not preclude adjuvant therapy and, when managed appropriately, does not affect long term performance status or survival. J. Surg. Oncol. 2015 111:855–861.

Controversy exists regarding the value and indications for inguinal dissection alone or in combination with an iliac/obturator lymph node dissection for melanoma. We reviewed patients from a multicenter prospective clinical trial and a single center who underwent inguinal dissection alone or combined with an iliac/obturator dissection for cutaneous melanoma. Analyses were stratified and compared by microscopic or macroscopic (palpable or detected by imaging) disease. The study was composed of 134 patients with a median follow-up of 39 months. Indications for inguinal dissection were microscopic disease in 94 (70%) patients and macroscopic nodal disease in 40 (30%) patients. An iliac/obturator dissection yielded tumor-positive pelvic nodes in 25% vs 55% in the microscopic vs macroscopic groups, respectively (p = 0.10). No risk factors for positive pelvic nodes were identified. For both microscopic and macroscopic disease, addition of an iliac/obturator dissection to an inguinal dissection did not significantly reduce the risk of pelvic nodal recurrence. Five-year overall survival rates for 4 groups were compared: microscopic disease, inguinal dissection alone (72%); microscopic disease, iliac/obturator dissection (68%); macroscopic disease, inguinal dissection alone (51%); and macroscopic disease, iliac/obturator dissection (44%) (p = 0.0163). On survival analysis, addition of an iliac/obturator dissection in either microscopic or macroscopic disease did not affect disease-free survival or regional lymph node recurrence-free survival. The addition of an iliac/obturator dissection to an inguinal dissection for both microscopic and macroscopic nodal disease did not significantly affect lymph node recurrence rates, disease-free survival, or overall survival.

174 Background: Reports have demonstrated the activity of combining both Irinotecan and Oxaliplatin into a FOLFOXIRI therapy. An option to gain similar benefits and less toxicity to FOLFOXIRI would be to administer the irinotecan through an hepatic arterial apporach. The aim of this study was to assess the maximal response and adverse event rates of Irinotecan Drug Eluting Beads (DEBIRI) with FOLFOX and Bevacizumab (Bev) as a first line treatment for unresectable colorectal liver metastasis (CLMs). Methods: Metachronous and Synchronous CLMs were randomly assigned to mFOLFOX6/Bev or mFOLFOX6, Bev and DEBIRI (FOLFOXDEBIRI). Primary end point was optimal response rates and adverse events. Secondary endpoints were patients (pts) converted to resection and survival. Results: The intention-to-treat population comprised 70 pts, 40 pts randomly assigned to the FOLFOXDEBIRI arm and 30 pts to FOLFOX/Bev arm. Both were similar with synchronous disease (50% vs. 36%), extent liver involvement (35% vs. 31%), but greater percentage in the FOLFOXDEBIRI arm of ECOG 1/2 (57% vs. 31%), p=0.04) and extra-hepatic disease (51% vs. 36%, p=0.02). Median number of chemotherapy cycles was similar in both arms of 8, with a similar Grade 3/4 adverse event rate of 54% FOLFOXDEBIRI and 46% FOLFOX/Bev arm. The overall response rate was significantly greater in the FOLFOXDEBIRI arm vs. FOLFOX/BEV at 2 mons (78% vs. 54%), 4 mons (95% vs. 70%) and 6 mons (76% vs. 60%, p=0.03). Significantly greater downsizing to resection in the FOLFOXDEBIRI arm vs. FOLFOX/Bev (35% vs. 16%, p=0.05), with an improved median progression free survival (15.3 mons vs. 7.6 mons). Overall improvement in hepatic specific progression free survival was seen in the treatment arm (12.8 mons vs. 10.5 mons). Conclusions: Simultaneous mFOLFOX6 with bevacizumab and hepatic arterial irinotecan drug eluting beads is safe, without causing chemotherapy delivery delays and without increasing chemotherapy toxicity. Simultaneous FOLFOXDEBIRI leads to improved overall response rates, improved hepatic progression free survival, and more durable overall progression free survival in patients downsized to resection. Clinical trial information: NCT00932438.

Background This study sought to determine clinical and molecular factors related to recurrence and survival in patients with ICC following hepatectomy. Methods Database review identified 34 patients. Molecular markers (Ki67, p53, beta‐catenin) and standard pathological evaluations were performed. Results The most common resections were right (n = 11), extended right (n = 8), and left hepatectomy (n = 7). The 30‐ and 90 ‐day mortality rates were 5.9% and 11.8%. The median tumor size was 7.8 cm. Nine patients (26.5%) had positive lymph nodes and ten patients (29.4%) received adjuvant therapy. Median follow up was 33.5 months. The median disease‐free interval was 6 months. The median overall survival was 37.9 months. Univariate predictors of recurrence were tumor size (P = 0.02) and differentiation (P = 0.05). On multivariate analysis, differentiation (P = 0.03; OR = 0.38; 95% CI: 0.17–0.89) remained significant. Univariate predictors of survival were tumor size (P = 0.02), lymphovascular invasion (P = 0.02), satellite nodules (P = 0.006), beta‐catenin expression (P = 0.008), and recurrence (P = 0.026). On multivariate analyses, satellite lesions (P = 0.05, OR = 3.15, 95% CI: 0.96–10.4) and beta‐catenin (P = 0.04, OR = 3.23; 95% CI: 1.1–9.7) remained significant and differentiation (P = 0.045; OR = 0.42; 95% CI: 0.18–0.98) was an additional predictor. Conclusion Future clinical trials could include certain molecular and pathologic factors to assist in determining the necessity and type of adjuvant therapy. J. Surg. Oncol. 2014 109:98–103.