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Serum C-Reactive Protein As Predictor of Recurrence in Patients UndergoingIleo-Colonic Resection for Crohn's Disease. Results of a LongitudinalProspective StudyEdoardo Iaculli, Cristina Fiorani, Sara Onali, Giorgia Tema, Roberto Pezzuto, LiviaBiancone, Rosa Scaramuzzo, Khrystyna Porokhnavets, Achille Gaspari, Giuseppe S. Sica

BACKGROUND Previous studies have evaluated the ability of biological markers to detectdisease relapse in Crohn's disease (CD). Yet no studies have targeted a method to anticipaterecurrence after surgical resection. C-Reactive Protein (CRP) is a valuable marker for predict-ing the outcome of several diseases including CD. The exact role of CRP as a prognosticfactor for future recurrence in CD is not yet determined. Moreover no data are availableinvestigating specific CRP modifications in these patients following surgery. Objective ofpresent study was to determine the perioperative behaviour of the CRP in CD patientsundergoing elective ileo-cecal resection. Our hypothesis is that perioperative CRP changesare disease-specific and therefore could detect subset of patient with more aggressive disease.Secondary objective was to investigate the role of CRP as a potential early prognosticmarker for future recurrence. METHODS 52 patients undergoing IC resection for CD wereprospectively enrolled. Serial CRP levels were assessed perioperatively: time 0, postoperativeday (POD) 1 and POD 6. CD patients' perioperative CRP findings were compared against sameinterval assessments of two control groups undergoing right colectomy and appendicectomy.Crohn's Disease Activity Index (CDAI) and Rutgeerts' score (RS) were evaluated for recurrenceduring 3 year follow-up protocol. RESULTS As expected, in all 3 groups CRP significantlyincreased 24 hours after surgery vs baseline but the increase was significantly higher in CDpatients than in controls (p, 0.001). Comparing to control groups CRP remained remarkablyhigh in CD (mean 32.2mg/L) at POD 6. Difference between groups was statistical significant(p 0.03). All CD patients evaluated at 3 year follow up were in clinical remission. Endoscopicrecurrence (RS .2) was found in 51% at 1 year and in 42% at 3 years. Possible relationbetween endoscopic recurrence rate or severity and perioperative CRP levels was investigated:multivariate ordinal regression showed that postoperative increment of CRP is a prognosticfactor of recurrence at 3 years. CONCLUSION Present preliminary data show disease-specificperioperative CRP levels for CD patients that reflect immunomodulation impairment involvedin disease etiology. The degree of such immunitary change and consequent severity of diseasemight be explored early after surgery by determining CRP alterations. Data from larger seriescan confirm that perioperative CRP levels might be considered a novel prognostic factorsof surgical recurrence.

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Predictors of Recurrence and Post Recurrence Survival in Patients WithResected Ampullary AdenocarcinomaIrene Epelboym, Susan Hsiao, James A. Lee, Beth Schrope, John A. Chabot, HelenRemotti, John D. Allendorf

Background: Ampullary neoplasms are a rare subset of intestinal cancers, the only treatmentfor which is complete surgical resection. Controversy exists, however, with regard to needfor and type of adjuvant therapy. The management approach is even less clear for thosepatients in whom the disease recurs. In this report, we aim to determine patient andhistological factors predictive of recurrence, and to describe the survival experience of thosewith recurrent disease. Methods: Patients who underwent surgical resection for ampullaryadenocarcinoma at our institution were identified, and histological diagnosis was confirmedby independent pathologist review. Presenting features, operative characteristics, postopera-tive outcomes, and overall and disease free survival were evaluated. Selected resectionspecimens were stained for presence of CK7, CK20, and CDX2 using standard methods.Continuous variables were compared using Student's t-test. Categorical variables were com-pared using chi-square or Fisher's exact test. Predictors of recurrence were analyzed usinglogistic regression. Survival was evaluated using Kaplan-Meier method, and differencesamong groups were assessed by log-rank test. Results: Between 1990 and 2011, 79 patientsunderwent pancreaticoduodenectomy for ampullary adenocarcinoma. Thirty patientsreceived adjuvant chemotherapy, which was gemcitabine based for 29 (96.6%). Among 74R0 resections, there were 24 cases of recurrence over 273 person-years (median follow-up28.7 months, median time to recurrence 8.7 months). Four (16.7%) were in the surgicalbed and 20 (83.3%) distantly, predominantly in the liver. In univariable analysis, no singledemographic or clinical characteristic, nor histologic staining pattern, was a statisticallysignificant predictor of recurrence. Lymph node positivity was significant in univariable butnot in multivariable analysis, and pathologic T stage was unassociated with recurrence.Recurrent disease was managed by surgical resection in 2 cases, one local and one metastatic,after which the patients survived 15.8 and 3.4 months, respectively. Fifteen patients receivedchemotherapy (either 5FU or gemcitabine based) only. Systemic therapy was not offered to2 patients. Post-recurrence survival was not significantly different among those who hadsurgery, chemotherapy, or no treatment (8.8 vs 8.0 vs 3.9 months, p=0.39). Additionally,among those who received chemotherapy, difference in median post-recurrence survivalwas not statistically significant in 5FU compared with gemcitabine groups (16 vs 3.5 months,p=0.107). Conclusions: Optimal treatment approach for recurrent ampullary adenocarcinomaremains unclear. Survival is equivalent whether surgical resection or systemic chemotherapyis employed, and no single cytotoxic protocol is associated with improved outcome.

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Adenomas of the Ampulla of Vater: A Comparison of Outcomes of Operativeand Endoscopic ResectionsEdwin O. Onkendi, Jordan Rosedahl, William S. Harmsen, Florencia G. Que

Background: Data comparing operative and endoscopic resection of adenomas of the ampullaof Vater is limited. We reviewed our experience in the treatment of adenomas of the ampullaof Vater and compared the operative and endoscopic approaches. Methods: Retrospectivereview of all patients in the gastrointestinal endoscopy and surgical databases treated foradenomas of ampulla of Vater at our institution from 1992 to 2009. Clinicopathologic

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factors, morbidity, mortality, recurrence and survival of patients treated by endoscopic andsurgical resection were comparatively analyzed. Results: A total of 137 patients (mean age59.3 yrs), were treated for adenomas of the ampulla of Vater; 75 (55%) males, follow up91% (mean 4.6 years). The adenomas were tubular in 55 (40%) patients, tubulovillous in62 (45%) and villous in 20 (15%). Obstructive jaundice was more common in the operativeresection group (p ,0.01)). Endoscopic resection was performed in 100 (73%) patients;operative resection was performed in 37 (27%). Sixty seven percent of patients requiredonly 1 endoscopic resection [piecemeal resection in 24 (36%)], while 33 (24%) required 2or more resections (range 2-5). Patients who underwent operative resection often had largertumors .3.6 cm (p,0.001) or intraductal extension (p=0.04). Intraductal extension andulceration had no effect on recurrence (p values=0.62, 1.0) in both groups. Postoperativecomplications occurred in 48% of patients; post-endoscopic complications in 30% of patients(p=.09). Post endoscopic resection complications included bleeding in 18 (7 required transfu-sion or endoscopic or angiographic intervention); pancreatitis (mild in 11; severe necrotizingin 1); ampullary obstruction from edema or blood clot in 2 and duodenal perforation in 1.Postoperative complications included pancreatic leak (9), surgical site infection (4), anasto-motic leak (3), delayed gastric emptying (2), myocardial ischemia or dysrhythmia (2), andrenal failure (1). One patient died of pancreatic leak with MOSF following operative resectionof a 6 cm sessile adenoma (mortality of 2%). Endoscopic resection was associated with a3-fold higher risk of recurrences than operative resection, 5% of which were invasive cancersin both groups. Performing 2 or more endoscopic resections for complete tumor removalrelative to 1 complete initial resection was associated with 5 times higher risk of recurrence(p,0.001). Conclusion: Endoscopic resection of adenomas of ampulla of Vater is associatedwith a 3-fold higher recurrence rate than operative resection; recurrences may be invasive.There is a 5-fold higher risk of recurrence if 2 or more endoscopic resections are neededfor complete tumor removal as compared to one complete initial resection. Operative resectionis associated with lower recurrence rates for larger tumors and tumors with intraductal exten-sion.

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Clinical Outcomes for Neuroendocrine Tumors of the Duodenum and Ampullaof Vater: A Population-Based StudyReese W. Randle, Shuja Ahmed, Naeem A. Newman, Clancy J. Clark

BACKGROUND: Neuroendocrine tumors (NETs) of the duodenum are quite rare represent-ing only 4% of all carcinoid tumors. Limited single-institution case series indicated thatampullary NETs have worse survival than NETs located in the duodenum. The aim of thecurrent study was to evaluate the overall survival (OS) of patients with ampullary NETscompared to patients with duodenal NETs using a population based registry. METHODS:We conducted a retrospective comparative cohort study using the Surveillance, Epidemiology,and End Results (SEER) registry from 1988 to 2009. Patients with pathology confirmedNETs of the duodenum and ampulla of Vater were identified, and overall survival wasevaluated using Kaplan-Meier estimates and Cox proportional hazard regression. Multi-variable survival analyses included covariates with p , 0.1 and less than 10% of datamissing. RESULTS: The study cohort included 1360 (92%) patients with duodenal NETsand 120 (8%) with ampullary NETs. Ampullary NETs were larger (median tumor size 18vs. 10 mm, p,0.001), higher grade (poorly and undifferentiated tumor 42% vs. 12%,p,0.001), and higher SEER historic stage (distant metastasis 18% vs. 9%, p ,0.001) thanduodenal NETs. Ampullary NETs were also more likely to be resected (78% vs. 60%,p,0.001). OS was significantly worse for patients with ampullary NETs than for patientswith duodenal NETs (median OS 98 vs. 143 months; HR 1.38, 95% CI 1.02-1.86, p=0.037). For resected patients (n=878), OS was similar between ampullary and duodenalNETs (median OS 182 vs. 164 months; HR 1.42, 95% CI 0.96-2.09, p=0.078). Usingunivariate survival analyses, significant predictors for worse OS in resected patients includedolder age (p,0.001), larger tumor size (p=0.035), higher grade (p,0.001), higher SEERhistoric stage (p,0.001), and radiation treatment (p=0.003). After adjusting for significantpredictors of OS, ampullary NETs had significantly worse OS than duodenal NETs (HR1.63, 95% CI 1.05-2.53, p=0.031). CONCLUSIONS: NETs of the ampulla of Vater are moreadvanced at presentation and have worse OS than duodenal NETs. After controlling forsignificant predictors of OS, tumor location remained an independent predictor of OS inresected patients.

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