Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

Long-term recurrence after endoscopic versus surgical ampullectomy of sporadic ampullary adenomas: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Ampullary adenomas are treated both surgically and endoscopically, however, data comparing both techniques are lacking. We aimed to compare long-term recurrence of benign sporadic adenomas after endoscopic (EA) and surgical ampullectomy (SA). METHODS: A comprehensive literature search of multiple databases (until December 29, 2020) was performed to identify studies reporting outcomes of EA or SA of benign sporadic ampullary adenomas. The outcome was recurrence rate at 1 year, 2-year, 3 year and 5 years after EA and SA. RESULTS: A total of 39 studies with 1753 patients (1468 EA [age 61.1 ± 4.0 years, size 16.1 ± 4.0 mm], 285 SA [mean age 61.6 ± 4.48 years, size 22.7 ± 5.4 mm]) were included in the analysis. At year 1, pooled recurrence rate of EA was 13.0% (95% confidence interval [CI] 10.5-15.9], I2 = 31%) as compared to SA 14.1% (95% CI 9.5-20.3 I2 = 15.8%) (p = 0.82). Two (12.5%, [95% CI, 8.9-17.2] vs. 14.3 [95% CI, 9.1-21.6], p = 0.63), three (13.3%, [95% CI, 7.3-21.6] vs. 12.9 [95% CI, 7.3-21.6], p = 0.94) and 5 years (15.7%, [95% CI, 7.8-29.1] vs. 17.6% [95% CI, 6.2-40.8], p = 0.85) recurrence rate were comparable after EA and SA. On meta-regression, age, size of lesion or enbloc and complete resection were not significant predictors of recurrence. CONCLUSION: EA and SA of sporadic adenomas have similar recurrence rates at 1, 2, 3 and 5 years of follow up.

Surgical ampullectomy: A comprehensive review.

Tumours of the ampulla of Vater are relatively uncommon lesions of the digestive system. They are typically diagnosed at an earlier stage than other types of tumours in this region, due to their tendency to invoke symptoms by obstructing the bile duct or pancreatic duct. Consequently, many are potentially curable by excision. Surgical ampullectomy (SA) (or transduodenal ampullectomy) for an ampullary tumour was first described in 1899, but was soon surpassed by pancreatoduodenectomy (PD), which offered a more extensive resection resulting in a lower risk of recurrence. Ongoing innovation in endoscopic techniques over recent decades has led to the popularization of endoscopic papillectomy (EP), particularly for adenomas and even early cancers. The vast majority of resectable ampullary tumours are now treated using either PD or EP. However, SA continues to play a role in specific circumstances. Many authors have suggested specific indications for SA based on their own data, practices, or interpretations of the literature. However, certain issues have attracted controversy, such as its use for early ampullary cancers. Consequently, there has been a lack of clarity regarding indications for SA, and no evidence-based consensus guidelines have been produced. All studies reporting SA have employed observational designs, and have been heterogeneous in their methodologies. Accordingly, characteristics of patients and their tumours have differed substantially across treatment groups. Therefore, meaningful comparisons of clinical outcomes between SA, PD and EP have been elusive. Nevertheless, it appears that suitably selected cases of ampullary tumours subjected to SA may benefit from favourable peri-operative and long-term outcomes with very low mortality and significantly long survival, hence its role in this setting warrants further clarification, while it can also be useful in the management of specific benign entities. Whilst the commissioning of a randomised controlled trial seems unlikely, well-designed observational studies incorporating adjustments for confounding variables may become the best available comparative evidence for SA, potentially informing the eventual development of consensus guidelines. In this comprehensive review, we explore the role of SA in the modern management of ampullary lesions.

Transduodenal surgical ampullectomy: a procedure that requires a multidisciplinary approach.

Trans-duodenal surgical ampullectomy (TSA) was first described in 1899. Nowadays its role in ampullary tumor surgery is still a matter of debate and requires a multidisciplinary approach. The aim of this study is to evaluate the results of TSA as a curative treatment for benign and selected malignant tumors arising from the ampulla in a single-institution experience. Sixteen patients with periampullary tumors that underwent TSA in our surgical units between January 2012 and January 2017 were included in the study. Patient demographic characteristics, pre or postoperative endoscopic interventions, operative procedures, postoperative morbidity and mortality, hospitalization, follow-up time, and quality of life questionnaire were analyzed. Mean operative time was 238.5 min (range 180-390), mean tumor size was 2.3 cm (range 1.5-3.9). The microscopic surgical outcome was R0 for 14 patients. The most frequent findings in terms of histological type were high-grade dysplasia/pTis (43.7%), low-grade dysplasia in 37.5% patients, invasive adenocarcinoma in 2 cases (12.5%), chronic inflammation in 1 case (6.3%). The readmission rate was 18.8% (3/16) and in 2 cases (12.5%) relaparotomy was required. The cumulative median duration of follow-up was 50 months (range 1-96). 90-days mortality was 6.2%. Mean hospital stay was 12 days (range 8-60). Our results confirm that TSA offers good results in terms of morbidity and mortality; still, it remains a challenging procedure that requires particular surgical experience and operative skills. A pre-operative planning in a multidisciplinary board should be carried out prior to the procedure.

Endoscopic or surgical ampullectomy for intramucosal ampullary tumor: the patient populations are not the same.

PURPOSE: To evaluate and compare the results of endoscopic ampullectomy (EA) and surgical ampullectomy (SA) for benign tumors. MATERIAL AND METHOD: From 2005 to 2018, 66 patients were eligible for ampullectomy (adenoma, ultrasound grading≤T1, N0). The principal endpoint was the rate of complete resection: R0 resection without local recurrence and no recurrence after a single operative procedure and with final pathology confirming the operative indications. Secondary endpoints were: morbidity, mean length of stay (LOS), preoperative and final pathology results, complete (or incomplete) resection, mean duration of follow-up, local recurrence rate and late complications (biliary stricture). RESULTS: Among the 41 patients eligible for EA, 36 ampullectomies were performed, while five were referred for SA because of intracanalar invasion that had not been diagnosed initially. The rate of complete treatment was 48% (13/27), the morbidity was 10%; the LOS was 3.3days; no adenomatous lesion was found on the definitive pathology in 9 patients (25%). The resection was R1 in 30% but there were no R2 resections. The median duration of follow-up was 20months, the rate of local recurrence was 22% and the rate of late biliary stricture was 2%. Among the 30 patients who were eligible for SA, (25 plus the five referred by endoscopists after intracanalar invasion was found), SA was eventually performed in 24: five patients were converted to pancreatoduodenectomy, one patient was found to have metastatic disease and had no resection. An extemporaneous frozen-section pathology examination was performed in 22 of the 24 SA patients and confirmed healthy margins on the bile ducts and pancreatic ducts. The rate of complete treatment was 71% (17/24), morbidity was 35%; LOS was 10days; seven patients (29%) were found to have invasive adenocarcinoma, and six of these (86%) underwent subsequent pancreatoduodenectomy. None of the resections were R1 or R2; median follow-up was 21months; there was no local recurrence; biliary stricture rate was 8%. CONCLUSION: The short-term and long-term results of patients undergoing endoscopic or surgical ampullectomy are different. The lesions resected by EA were less advanced, with simpler postoperative course. The lesions for which SA was performed were more advanced, and had more morbid sequelae, but with a better rate of complete treatment and better long-term results.

Trans-duodenal ampullectomy for ampullary neoplasms: early and long-term outcomes in 36 consecutive patients.

BACKGROUND: Trans-duodenal ampullectomy (TDA) is a surgical option for the treatment of selected ampullary neoplasms. The aim of this study was to evaluate our experience with TDA for the treatment of ampullary neoplasms, focusing on indications, technical aspects, and short- and long-term outcomes. METHODS: All TDAs for ampullary neoplasms performed between January 2010 and December 2018 at our institution were retrospectively evaluated. Patients had ampullary neoplasms with low-grade dysplasia or in situ carcinoma (Tis) not suitable for an endoscopic approach, ampullary carcinoma unfit for pancreaticoduodenectomy (PD), or ampullary neuroendocrine G1-tumours. RESULTS: Thirty-six patients were included in the study: 9 (25.0%) with neoplasms with low-grade dysplasia, 4 (11.1%) with G1 neuroendocrine tumours and 23 (63.9%) with Tis or invasive carcinoma. Mean operative time was 252.5 min. Overall and severe (Clavien-Dindo > IIIa) morbidity rate was 44.4% and 13.9%, respectively. No 90-day mortality was observed. At follow-up, no deaths were observed and local recurrence rate was 11.1% for patients with ampullary adenomas with low-grade dysplasia. Among four patients with neuroendocrine neoplasms, only one developed recurrence (pulmonary). Tis, T1 and T2 lesions were found in 16 (69.6%), 2 (8.7%) and 5 (21.7%) patients, respectively: recurrence occurred in 3 patients with Tis lesions (one malignant), no patients with T1 neoplasms and 2 patients with T2 lesions (3 patients had a survival of > 3 years). CONCLUSIONS: TDA is a feasible and effective surgical procedure for the treatment of ampullary adenomas with low-grade dysplasia when endoscopic approach is contraindicated or has failed. For lesions with evidence of malignancy, TDA seems to be an oncological safe procedure for Tis ampullary cancer and a good palliative procedure for patients unfit for PD. Moreover, TDA may be appropriate for the treatment of G1 ampullary neuroendocrine neoplasms. A large multicentre study of TDA for early ampullary cancers is needed.

Surgical Ampullectomy with Complete Resection of the Common Bile Duct: a New Procedure for Radical Resection of Non-invasive Ampulloma with Biliary Extension.

Extension of ampulloma into the lower common bile duct (CBD) is observed in up to 30% of cases. This biliary extension can prevent complete tumor resection thus is considered as a contraindication for endoscopic and even surgical ampullectomy. For ampullomas associated with a prolonged biliary extension, a pancreaticoduodenectomy is associated with a high morbidity and can be considered as an overtreatment for a benign neoplasm. The present study describes a new surgical approach including ampullectomy with complete resection of the intrapancreatic CBD and restoration of both biliary and pancreatic flow by two separate anastomoses. This procedure was performed in seven patients for a non-invasive ampulloma with a 25- to 70-mm CBD involvement. No patients died and three developed postoperative complications. Resection was R0 in all patients but one. With a 24-month median follow-up (range = 3-84), no patients developed pancreatic insufficiency or tumor recurrence.

Non-Whipple Operations in the Management of Benign, Premalignant and Early Cancerous Duodenal Lesions.

AIM: We reviewed our 20-year experience with non-Whipple operations (pancreas-preserving duodenectomy and transduodenal ampullectomy) for the treatment of benign, premalignant or early-stage malignant duodenal lesions. PATIENTS AND METHODS: Twenty-four patients who underwent non-Whipple operations between January 1996 and December 2015 were identified from an institutional database and retrospectively analyzed. RESULTS: Between 1996 and 2015, 10 patients underwent pancreas-preserving duodenectomy and 14 patients underwent transduodenal ampullectomy. The mean follow-up was 25.8 months (range=6-54 months) and no patient was lost to follow-up. Eighteen patients had preoperative diagnosis of duodenal adenomatosis, three patients had preoperative diagnosis of duodenal adenocarcinoma, one had a bleeding polyp and two had localized inflammation. Average operative time was 145 min (range=127-168 min) for transduodenal ampullectomy and 183 min (range=173-200 min) for pancreas-preserving duodenectomy (p<0.05). The estimated blood loss for transduodenal ampullectomy was 85 vs. 125 ml for pancreas-preserving duodenectomy (p<0.05). Early postoperative complications were noted in 13 cases (54.17%). There were no postoperative (90-day) deaths observed in this series and there were no recurrences during follow-up for the patients operated on with neoplastic lesions. CONCLUSION: For carefully selected patients, transduodenal ampullectomy and pancreas-preserving duodenectomy may be used in place of the Whipple operation for benign and occasionally early-stage malignant (Tis and T1) duodenal and ampullary disease.

Characteristic endoscopic ultrasound findings of ampullary lesions that predict the need for surgical excision or endoscopic ampullectomy.

BACKGROUND AND OBJECTIVES: The management of ampullary lesions has evolved to include endoscopic ampullectomy (EA) as a curative approach to cancers of the ampulla of Vater. With this change comes a need to risk-stratify patients at initial diagnosis. MATERIALS AND METHODS: Patients with verified ampullary lesions (N = 50) were analyzed in a case-control design. We evaluated endoscopic ultrasound (EUS) data to define characteristics that yield a high sensitivity in selecting candidates for EA. RESULTS: Using data from previously published studies yielded a sensitivity of 0.765 in appropriately identifying the 34 surgical cases. Expanding these characteristics increased the sensitivity of EUS to 0.971 in identifying surgical candidates. Additionally, of advanced disease cases, the expanded characteristics correctly identified these cases with a sensitivity of 1.0-improved over 0.708 using prior published data. CONCLUSION: EA should be strongly considered if ampullary lesions are found to fit the following characteristics after EUS evaluation: lesion size <2.5 cm, invasion ≤4 mm, pancreatic duct dilatation ≤3 mm, ≤T1 lesion, no lymph nodes present, and no ductal stent in place. Furthermore, EUS data can be used to identify all high-risk lesions. With these characteristics identified, clinicians are better able to risk-stratify patients using EUS as either appropriate for or too high-risk for endoscopic resection.

Endoscopic papillectomy: The limits of the indication, technique and results.

In the majority of cases, duodenal papillary tumors are adenomas or adenocarcinomas, but the endoscopy biopsy shows low accuracy to make the correct differentiation. Endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography are important tools for the diagnosis, staging and management of ampullary lesions. Although the endoscopic papillectomy (EP) represent higher risk endoscopic interventions, it has successfully replaced surgical treatment for benign or malignant papillary tumors. The authors review the epidemiology and discuss the current evidence for the use of endoscopic procedures for resection, the selection of the patient and the preventive maneuvers that can minimize the probability of persistent or recurrent lesions and to avoid complications after the procedure. The accurate staging of ampullary tumors is important for selecting patients to EP or surgical treatment. Compared to surgery, EP is associated with lower morbidity and mortality, and seems to be a preferable modality of treatment for small benign ampullary tumors with no intraductal extension. The EP procedure, when performed by an experienced endoscopist, leads to successful eradication in up to 85% of patients with ampullary adenomas. EP is a safe and effective therapy and should be established as the first-line therapy for ampullary adenomas.