A Case Report of Neoadjuvant Gemcitabine Plus Cisplatin for Locally Advanced Unresectable Ampulla of Vater Carcinoma.

INTRODUCTION: Ampulla of Vater carcinoma (AVC) with para-aortic node (PAN) metastasis is considered unresectable and is equivalent to distant metastasis, contributing to poor outcomes. CASE PRESENTATION: A 60-year-old man was referred to our hospital and was diagnosed with an unresectable ampulla of Vater carcinoma that had metastasized to the para-aortic nodes. The patient received a systemic chemotherapy regimen comprising a combination of gemcitabine and cisplatin. Following five cycles of treatment, imaging studies revealed a significant reduction in the primary tumor and para-aortic node metastasis, rendering detection difficult. Pancreatoduodenectomy with para-aortic node dissection was performed as a radical surgery. Upon pathological examination, no residual tumors were identified in the resected specimen, indicating that the systemic chemotherapy achieved a complete pathological response. The postoperative course of the patient was uneventful, and he was discharged on the 25th postoperative day. The patient was followed up as an outpatient and remained stable without any recurrence for two months after surgery. CONCLUSION: Neoadjuvant chemotherapy with gemcitabine and cisplatin was useful for downstaging the ampulla in patients with Vater carcinoma. This finding may help physicians manage patients with similar presentations.

Clinical predictors of significant findings on EUS for the evaluation of incidental common bile duct dilation.

BACKGROUND AND AIMS: Although EUS is highly accurate for the evaluation of common bile duct (CBD) dilation, the yield of EUS in patients with incidental CBD dilation is unclear. METHODS: Serial patients undergoing EUS for incidental, dilated CBD (per radiologist, minimum of >6 mm objectively) from 2 academic medical centers without active pancreaticobiliary disease or significantly elevated liver function test results were evaluated. Multivariable logistic regression identified predictors of EUS with significant findings and a novel prediction model was derived from one center, internally validated with bootstrapping, and externally validated at the second center. RESULTS: Of 375 patients evaluated, 31 (8.3%) had significant findings, including 26 choledocholithiasis, 1 ampullary adenoma, and 1 pancreatic mass. Predictors of significant findings with EUS included age of ≥70 years (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5-10.0), non-biliary-type abdominal pain without chronic pain (OR, 6.1; 95% CI, 2.3-17.3), CBD diameter of ≥15 mm or ≥17 mm with cholecystectomy (OR, 6.9; 95% CI, 2.7-18.7), and prior ERCP (OR, 6.8; 95% CI, 2.1-22.5). A point-based novel clinical prediction model was created: age of ≥70 years = 1, non-biliary-type abdominal pain without chronic pain = 2, prior ERCP = 2, and CBD dilation = 2. A score of <1 had 93% (development) and 100% (validation) sensitivity and predicted a <2% chance of having a significant finding in both cohorts while excluding the need for EUS in ∼30% of both cohorts. Conversely, a score of ≥4 was >90% specific for the presence of significant pathology. CONCLUSIONS: Less than 10% of patients undergoing EUS for incidental CBD dilation had pathologic findings. This novel, externally validated, clinical prediction model may reduce low-yield, invasive evaluation in nearly one-third of patients.

Prediction of tumor recurrence after surgical resection of ampullary adenocarcinoma using magnetic resonance imaging.

OBJECTIVES: To predict tumor recurrence in patients who underwent surgical resection of ampullary adenocarcinoma using preoperative magnetic resonance (MR) imaging findings combined with clinical findings. METHODS: In this multicenter study, a total of 113 patients (mean age, 62.9 ± 9.8 years; 58 men and 55 women) with ampullary adenocarcinoma who underwent preoperative MR imaging and surgery with margin-negative resection between 2006 and 2017 were retrospectively included. The MR imaging findings were evaluated by two radiologists. Preoperative clinical findings were obtained. Cox proportional regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS). A nomogram was created based on the multivariable analysis and was internally validated. RESULTS: Multivariable analysis revealed that presence of infiltrative tumor margin (hazard ratio [HR]: 2.18, p = 0.019), adjacent organ invasion (HR: 3.31, p = 0.006), adjacent vessel invasion (HR: 5.42, p = 0.041), peripancreatic lymph node enlargement (HR: 2.1, p = 0.019), and jaundice (HR: 1.93, p = 0.043) were significantly associated with worse RFS of ampullary adenocarcinoma after surgical resection. These MR imaging and clinical findings were used to construct a nomogram. On internal validation, the calibration plots showed excellent agreement between the predicted probabilities and the actual rates of tumor recurrence, with Harrell's c-index of 0.746. CONCLUSIONS: Combination of preoperative MR imaging and clinical findings can be useful for predicting tumor recurrence after surgical resection of ampullary adenocarcinoma. Identifying these features before surgery may aid in better treatment planning and management of these patients. CLINICAL RELEVANCE STATEMENT: A predictive nomogram using preoperative MR imaging and clinical findings can be useful in estimating the recurrence-free survival after surgical resection of ampullary adenocarcinoma. KEY POINTS: • Presently, tumor size on imaging is the only non-invasive factor that correlates with recurrence-free survival from ampullary adenocarcinoma; other factors are obtained postoperatively. • Infiltrative tumor margin, adjacent organ invasion, adjacent vessel invasion, peripancreatic lymph node enlargement on MRI, and jaundice are significant predictors for recurrence. • A nomogram incorporating significant MR imaging and clinical findings showed good performance in predicting recurrence-free survival, which can help in treatment planning.

Feasibility of new-generation endocytoscopy for the real-time diagnosis of ampullary lesions: A pilot study (with video).

BACKGROUND AND AIM: An early and accurate diagnosis of ampullary neoplasia is crucial; however, sampling bias is still a major concern. New-generation endocytoscopy enables real-time visualization of cellular structures and enables an accurate pathological prediction; however, its feasibility for small ampullary lesions has never been investigated. METHODS: We developed a novel endocytoscopic (EC) classification system for ampullary lesions after an expert review and agreement from five experienced endoscopists and one pathologist. We then consecutively enrolled a total of 43 patients with an enlarged ampulla (< 3 cm), all of whom received an endocytoscopic examination. The feasibility of endocytoscopy was evaluated, and the performance of the EC classification system was then correlated with the final histopathology. RESULTS: In five cases (11.6%), the endocytoscope could not approach the ampulla, and these cases were defined as technical failure. Among the remaining 38 patients, 8 had histopathology-confirmed adenocarcinoma, 15 had adenoma, and 15 had non-neoplastic lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification system to diagnose ampullary neoplasias were 95.7%, 86.7%, 91.7%, 92.9%, and 92.1%, respectively. Moreover, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification to diagnose ampullary cancer were 62.5%, 100%, 100%, 90.9%, and 92.1%, respectively. One case with intra-ampullary papillary-tubular carcinoma was classified as having a non-neoplastic lesion by endocytoscopy. CONCLUSIONS: Endocytoscopy and the novel EC classification system demonstrated good feasibility to discriminate ampullary neoplasias from non-neoplastic lesions and may be useful for optical biopsies of clinically suspicious ampullary lesions.

Evaluation of Malignancy Risk of Ampullary Tumors Detected by Endoscopy Using 2-[18F]FDG PET/CT.

OBJECTIVE: We aimed to investigate whether 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. MATERIALS AND METHODS: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[18F]FDG PET/CT for endoscopy-detected ampullary tumors 5-87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. RESULTS: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in early-phase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13-36.18; P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80-13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41-19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00-14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16-21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874-0.956] vs. 0.815 [0.732-0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816-0.967) in candidates for endoscopic papillectomy. CONCLUSION: Adding 2-[18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Underwater endoscopic papillectomy for a small neuroendocrine tumor of the ampulla of Vater.

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare. Therefore, there is a lack of comprehensive information regarding their pathogenesis. We herein present the case of a patient with a 5-mm ampullary NET who demonstrated the presence of lymphatic invasion after undergoing endoscopic papillectomy. A 44-year-old woman was referred to our hospital for treatment of a grade 1 NET in the ampulla of Vater. Endoscopic ultrasonography revealed a hypoechoic mass within the submucosal layer without obvious infiltration into the common bile duct or the main pancreatic duct. We performed underwater endoscopic papillectomy (UEP) to remove the tumor with a negative margin. Pathological evaluation of the resected specimen showed a grade 1 NET with a negative margin. However, pancreaticoduodenectomy was subsequently performed because of the risk of lymph node metastasis, which was expected due to the significant number of NET cells infiltrating the endothelium of the lymphatic vessels. No lymph node metastasis or recurrence was observed during the 26-month follow-up period. UEP is a useful method to achieve complete resection for diagnostic and therapeutic purposes. UEP may be a novel option for endoscopic treatment of ampullary NET.

Endoscopic papillectomy could be rewarding to patients with early stage duodenal ampullary carcinoma?

BACKGROUND/PURPOSE: There is currently no consensus on the use of endoscopic papillectomy (EP) for early stage duodenal ampullary adenocarcinoma. This study aimed to evaluate the feasibility of EP for patients with early stage duodenal ampullary adenocarcinoma. METHODS: Patients who underwent EP for ampullary adenocarcinomas were investigated. Complete and clinical complete resection rates were evaluated. Clinical complete resection was defined as either complete resection or resection with positive or unknown margins but no cancer in the surgically resected specimen, or no recurrence on endoscopy after at least a 1-year follow-up. RESULTS: Adenocarcinoma developed in 30 patients (carcinoma in situ [Tis]: 21, mucosal tumors [T1a(M)]: 4, tumors in the sphincter of Oddi [T1a(OD)]: 5). The complete resection rate was 60.0% (18/30) (Tis: 66.7% [14/21], T1a[M]: 50.0% [2/4], and T1a[OD]: 40.0% [2/5]). The mean follow-up period was 46.8 months. The recurrence rate for all patients was 6.7% (2/30). The clinical complete resection rates of adenocarcinoma were 89.2% (25/28); rates for Tis, T1a(M), and T1a(OD) were 89.4% (17/19), 100% (4/4), and 80% (4/5), respectively. CONCLUSIONS: EP may potentially achieve clinical complete resection of early stage (Tis and T1a) duodenal ampullary adenocarcinomas.

Tip-in endoscopic papillectomy for ampullary adenoma near diverticulum to minimize complications.

Toyonaga and colleagues present a novel "tip-in endoscopic papillectomy" approach for resecting ampullary tumors, aiming to minimize complications like perforation and residual tumor by adapting the colonic polyp endoscopic mucosal resection tip-in method. The technique is described with accompanying video in a case of ampullary tumor near a diverticulum.

[Carcinoma in situ arising in adenomyomatous hyperplasia of the ampulla of Vater: the first case report].

A man in his 70s was admitted to our hospital due to jaundice and upper abdominal pain. Laboratory findings indicated elevated serum hepatobiliary enzyme and amylase levels. Contrast-enhanced computed tomography revealed smooth wall thickening of the terminal bile duct (tBD) with a faintly enhanced inner line. ERCP revealed stenosis from the tBD to the ampulla of Vater (AV) with upstream dilatation. Intraductal ultrasound (IDUS) circumferentially revealed a thickened wall preserving a three-layered structure throughout the same region. Furthermore, a thick innermost hyperechoic layer was identified in the bile duct portion of the AV (Ab). Findings suggestive of adenocarcinoma were obtained from the tissue samples from the biliary stricture using biopsy forceps. Thus, pancreatoduodenectomy was performed. A pathological examination revealed a thickened AV wall spreading over the tBD with hyperplasia of the glands and smooth muscle fibers. In addition, low-grade biliary intraepithelial neoplasia (BilIN) was scattered throughout the lesion, and high-grade BilIN was partly observed in the peribiliary glands of the Ab. Based on these results, a diagnosis of carcinoma in situ arising in adenomyomatous hyperplasia (ADMH) of the AV was made. To date, there are no reports on ADMH-associated carcinoma of the BD or AV. We here report this original case with the IDUS findings, which are presumed to reflect the histologic features of ADMH showing ductal proliferation surrounded by smooth muscle fibers. Also, we discuss the process through which carcinoma arises from ADMH in AV.

Endoscopic ampullectomy of a giant pedunculated ampullary adenoma.

The authors present a case of a 72-year-old woman with a personal history of arterial hypertension, dyslipidemia and gallstones. For suspected choledocholithiasis, a MR-Cholangiopancreatography was performed, which revealed the presence of an endoluminal polypoid structure in the third duodenal portion.

Gel immersion endoscopic ultrasonography for ampullary tumors.

Toyonaga and colleagues present gel immersion endoscopic ultrasonography for ampullary tumors. They propose that gel immersion endoscopic ultrasonography is usefulness in evaluating of ampurally tumors because it allows clear and stable observation for an extended period with a low filling gel volume without papilla compression of the duodenal papilla.

Estimation of the organ of origin of peri-ampullary malignancy by preoperative CT scan.

BACKGROUND: Tumors occurring within the pancreatic head commonly arise from the pancreas, duodenal ampulla, distal bile duct, or duodenum. However, they are difficult to distinguish on standard preoperative imaging. PURPOSE: To assess the ability of specialist reporting of preoperative computed tomography (CT) scans to determine the organ of origin of pancreatic cancer (PC). MATERIAL AND METHODS: Blinded re-reporting of preoperative imaging from five hospitals was undertaken of a consecutive cohort of 411 patients undergoing surgery for PC between January 2006 and May 2014. Radiological identification of tumor site was determined by the presence of the main tumor bulk within the pancreatic head parenchyma and estimation of the pathological organ of origin of the PC was based on all the reported features. RESULTS: Each pathological tumor type was noted to have distinct radiological features. Localization of a visible tumor within the pancreatic parenchyma was seen most commonly in PC (92%) than other tumor types (P < 0.0001). Local invasion into the duodenum was a characteristic feature seen in 79% of patients with ampullary tumors and isolated dilation of the bile duct without dilation of the pancreatic duct was seen most commonly in patients with ampullary or bile duct cancer. In the assessment of tumor origin, good agreement (kappa = 0.6, 0.51-0.68) was noted between the consensus radiology opinion and the final histology result. Overall accuracy was greatest for ampullary cancer (88.1%) and lowest for PC (83.2%). CONCLUSION: Radiological assessment of preoperative imaging provides a high degree of accuracy in predicting the organ of origin of peri-ampullary cancer.

Endoscopic Papillectomy.

Most ampullary lesions (ALs) are sporadic, involve the major papilla, and are premalignant (adenomas). They are often diagnosed as an incidental finding during endoscopy or imaging procedures. Diagnosis and staging of ALs include endoscopic, histologic, and radiological evaluations. Currently, endoscopic papillectomy is the preferred treatment for ALs in most situations. In this article, we will describe the diagnostic work-up and focus on the endoscopic treatment, including indications, technique, outcomes, complications, and follow-up.

Diagnostic accuracy of endoscopic ultrasound and intraductal ultrasonography for assessment of ampullary tumors: a meta-analysis.

BACKGROUND: Accurate preoperative assessment of ampullary tumors (ATs) is critical for determining the appropriate treatment. The reported diagnostic accuracy of endoscopic ultrasound (EUS) and intraductal ultrasonography (IDUS) for detecting tumor depth (T-staging) and regional lymph node status (N-staging) varies across studies. METHOD: An electronic search of the MEDLINE and Embase databases was conducted to identify studies that assessed the diagnostic accuracy of EUS and IDUS for ATs. Sensitivities and specificities of eligible studies were summarized using either fixed effects or random-effects model. RESULTS: Twenty-one studies were included in the final analysis. The pooled sensitivity and specificity of EUS were 0.89 and 0.87 for T1, 0.76 and 0.91 for T2, 0.81 and 0.94 for T3 and 0.72 and 0.98 for T4, respectively. For IDUS, estimates from five studies were 0.90 and 0.88 for T1, 0.73 and 0.91 for T2 and 0.79 and 0.97 for T3, respectively. For N-staging, 16 studies using EUS were included with sensitivity and specificity of 0.61 and 0.77, respectively. Moreover, estimates of IDUS for N-staging were 0.61 and 0.92, respectively. CONCLUSION: Our results imply that EUS and IDUS have good diagnostic accuracy for T-staging of ATs. However, the accuracy of EUS or IDUS is less satisfactory for N-staging. More well-designed prospective studies are warranted to confirm our findings.

Ampullary GIST tumor as an incidental finding after a cephalic duodenopancreatectomy due to a suspicion of a nonfunctional neuroendocrine tumor.

The case of a patient who had a cephalic duodenopancreatectomy performed because of a nonfunctional neuroendocrine tumour located in the pancreatic head is reported. Such tumour was diagnosed by a CT scan, an echoendoscopy and some punctures of the tumour to take some samples for cytology. The final anatomopathological study informed about the presence of an ampullary GIST tumour, which is a very infrequent entity, so a bibliographical search and a revision of the cases published up to this day was done.

Neuroendocrine tumor of the ampulla of Vater showing chronological endoscopic changes.

We report a rare case of neuroendocrine tumor of the ampulla of Vater in a 53-year-old Japanese male. The patient was admitted to our institution for workup of presyncope secondary to anemia. Medical history was pertinent for coronary artery disease, for which he had drug eluting stents (DES) placed and was on aspirin and clopidogrel therapy. Upper endoscopic evaluation revealed bleeding from an erosion at the ampulla of Vater. Endoscopic therapy with epinephrine and thrombin injection allowed for successful hemostasis and repeat endoscopy 6 months later did not show any changes in lesion character. Repeat endoscopy at 1 year, however, revealed erythema and further erosion on the ampulla of Vater as the lesion had progressed. The patient was diagnosed with carcinoma of the ampulla of Vater. Abdominal computed tomography showed a 9-mm hypervascular tumor at the ampulla of Vater and the patient underwent open pancreatoduodenectomy and lymphadenectomy. Histologically, the tumor consisted of small-sized round cell proliferations with a solid nest pattern. Immunostaining results indicated that the tumor cells were positive for synaptophysin and 2.5% were positive for Ki-67. The final diagnosis was sporadic non-functional neuroendocrine tumor (NET) G1 of the ampulla of Vater. This case demonstrates that NET of the ampulla of Vater, while rare, can have significant changes and growth over time and highlights the importance of follow-up endoscopic evaluations.