Especially noteworthy was the comparison of operative morbidity for surgical ampullectomy (42%) to pancreaticoduodenectomy for

benign disease (47%). Surgical ampullectomy remains a major surgical endeavor and for most surgeons, an operation they will have much less experience with than pancreaticoduodenectomy. The operative risk of surgical ampullectomy in a patient with severe comorbidities or poor performance status should not be taken lightly. With greater experience and availability of interventional endoscopy we may see a shift away from surgical ampullectomy towards increased use of Inhibitors,research,lifescience,medical endoscopic resections. In patients with significant operative risk this may provide the most favorable balance of risk and benefit. The authors address another important and very practical question of whether chemoradiation is beneficial after local resection. The authors demonstrate a 76% local failure rate at 5 years Inhibitors,research,lifescience,medical despite a 5 year metastasis free survival of 54%. Clearly, patients are succumbing to local disease, a situation where aggressive loco-regional adjuvant therapy would intuitively

appear beneficial. Two recent studies have Inhibitors,research,lifescience,medical demonstrated a benefit to ampullary cancer patients who received adjuvant therapy following pancreaticoduodenectomy (5,6). Preliminary data from the large PIK-75 datasheet randomized ESPAC-3 trial suggests survival benefit for chemotherapy alone while the Johns Hopkins-Mayo Clinic retrospective study demonstrated a survival benefit to adjuvant chemoradiation. While the present study was not able to show outcome benefit with chemoradiation, the authors do acknowledge the very small sample size and the disproportionate Inhibitors,research,lifescience,medical number of patients with positive margins and Inhibitors,research,lifescience,medical poorly differentiated tumors in the chemoradiation group. Also, adjuvant therapy did not include a chemotherapy alone component, which is common

in current adjuvant strategies for periampullary cancers. For patients who are clearly not candidates for pancreaticoduodenectomy and have ampullary tumors amenable to local resection, endoscopic or surgical ampullectomy and adjuvant chemoradiation still appears a rational option. Zhong et al. note the high (47%) margin positivity Rolziracetam rate associated with surgical ampullectomy for cancer and the inability to appropriately stage patients with lymphadenectomy. The technique used in this study is described as a mucosal resection incorporating the ampulla of Vater with reconstruction of the bile and pancreatic ducts and duodenal mucosal advancement. Surgical ampullectomy can be extended deeper, even full thickness into the pancreas. This may have averted some of the cases of margin positivity, although we are not given information on the specifics of margin assessment.