Resected Ampullary Adenocarcinoma Research Articles

Elevated CA 19-9 is associated with worse survival in patients with resected ampullary adenocarcinoma

BackgroundThe prognostic utility of Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) in ampullary adenocarcinoma is unclear. We sought to evaluate the association between initial tumor marker levels and survival in patients with resected ampullary adenocarcinoma. MethodsThis was a single-institution, retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma from 1999 to 2021. CA 19-9 was assessed after biliary decompression. Contal and O'Quigley method determined optimal biomarker cutoff levels which were correlated with overall survival (OS) using the Kaplan-Meier method and Cox Proportional Hazards Regression. ResultsA total of 180 patients underwent pancreatoduodenectomy. Patients with CA 19-9 >100 U/mL had a shorter median OS (28 vs. 132 months, p < 0.001) compared to patients with CA 19-9 ≤ 100 U/mL at diagnosis. Survival was similar between pancreaticobiliary and intestinal tumor subtypes when CA 19-9 was >100 U/mL (OS:25 vs. 33 months, p = 0.415). By Cox regression analysis, CA 19-9 >100 U/mL was independently associated with worse OS (HR 2.8, p = 0.001). ConclusionsPreoperative CA 19-9 >100 U/mL was associated with shorter OS in patients with resected ampullary adenocarcinoma. CA 19–9 may be useful when counseling patients about prognosis or when considering the role of perioperative systemic therapy.

Prognostic significance of extranodal extension of nodal metastasis in adenocarcinoma of the ampulla of Vater

Although nodal metastasis (NM) is an important prognostic factor of ampullary adenocarcinoma, the prognostic implication of extranodal extension (ENE) is not well characterized. NM with ENE status was investigated in 279 surgically resected ampullary adenocarcinoma patients and compared with other clinicopathologic factors, including overall survival (OS) and recurrence-free survival (RFS). Expression of epithelial-mesenchymal transition (EMT) markers, including E-cadherin, Twist, and Snail, was assessed in a subset of the cohort. NM was observed in 94 cases (33.7%), of which ENE was observed in 32 cases (34%). NM with ENE was more frequently associated with tumors with poor differentiation than NM without ENE (P=.017). The 5-year OS and RFS rates of patients with NM and ENE was significantly worse (13.0% and 6.3%) than those with NM without ENE (37.7% and 21.4%) and those without NM (57.6% and 50.2%, respectively; P<.001). When pN category was matched, the OS and RFS was worse in patients with ENE than in those without ENE (P<.05). Moreover, the expression of E-cadherin and Twist was significantly different between NM areas with and without ENE (all, P<.001). Since ENE was associated with poorly differentiated ampullary adenocarcinomas and showed different expression of EMT markers, EMT could be a possible mechanism of ENE. Ampullary adenocarcinoma patients with ENE had worse OS and RFS than those without ENE. Therefore, evaluation of ENE can provide additional survival information for patients with surgically resected ampullary carcinoma.

The prognostic role of epidermal growth factor receptor mutation in completely resected ampullary adenocarcinoma.

Theaim ofthis study is to make adifferential diagnosis and prognosis oftheampullary adenocarcinoma subtypes. We also investigated therole ofprognostic markers PD-1 and PD-L1, and epidermal growth factor receptor (EGFR). Local or locally advanced stage ampullary adenocarcinoma patients who had undergone pancreaticoduodenectomy at thetime ofdiagnosis were included. MUC1, MUC2, MUC5AC, CDX2, CK7, CK20, PD-1, and PDL-1 were analysed immunohistochemically, and EGFR was analysed by real-time polymerase chain reaction. According to histopathological and immunohistochemical evaluation, we found 27 patients as pancreatobiliary type and 56 patients as intestinal type adenocarcinoma. Themedian survival ofpatients with intestinal and pancreatobiliary type adenocarcinoma was 23 months and 76 months ( p = 0.201), respectively. When thesurvival ofPD1-positive ( n = 23) and PD-L1-positive ( n = 18) patients were compared with thepatients with negative staining ( n = 60, n = 65), no significant difference was found. Epidermal growth factor receptor mutation was detected in atotal of6 patients, and 5 ofthese 6 mutations were shown in intestinal type tumours and one in apancreatobiliary type tumour. Asignificant difference was determined in terms ofoverall survival for thepatients with EGFR mutations compared to those without ( p = 0.008). In conclusion, we could reveal theprognostic significance ofEGFR mutation, which is also atarget molecule.

Adjuvant therapy (AT) in patients (pts) with radically resected ampullary adenocarcinoma (AA): A monocentric retrospective analysis.

e16142 Background: Ampullary adenocarcinoma (AA) is a rare tumor. Radical surgery is the only curative treatment for localized AA. The role of AT is not clearly defined and previous evidence in literature is poor and controversial. Hence, we retrospectively analyzed radically resected AA pts at our Institution, investigating the impact of AT on survival and the role of possible prognostic and/or predictive factors. Methods: Radically resected AA pts were retrospectively included in the analysis, divided into two groups: pts receiving AT and pts undergoing only postoperative observation (PO). The following variables were collected: gender; age (≤ 65 vs &gt; 65 years); baseline ECOG PS (0 vs ³ 1); histologic subtype (pancreatobiliary vs intestinal); tumor stage (T1-2 vs T3-4); nodal status (N0 vs N+), margin status (R0 vs R+); radiotherapy (yes vs no), AT regimen [Gemcitabine (GMZ)-based vs fluoropyrimidine (FP)-based treatment)]. The objective of the analysis was to evaluate the impact of AT on overall survival (OS). Univariate and multivariate analyses were performed. Results: From 2007 to 2021, a total of 69 pts with radically resected AA were identified: 41 (59%) pts received AT, 28 (41%) PO. The median age was 65 years (41-81), 42 (61%) were males, ECOG PS was ³ 1 in 45 (65%) pts. Tumor characteristics were: 31 (45%) pancreatobiliary, 26 (38%) intestinal, 9 (13%) mixed subtype and 3 (4%) not available; 41 (59%) pts had T3-T4 stage tumor; 34 (49%) were N+. Out of 41 pts receiving AT, 27 (66%) pts were treated with FP-based AT, 14 (34%) with GMZ-based AT; 16 (23%) pts received also RT. In the overall population, median OS was 59.8 months. At the univariate analysis, there was a statistically significant association of T status with OS (p 0.03), confirmed at multivariate analysis (p 0.03). Further variables (ECOG PS, AT, nodal status and histologic subtype) were not associated with survival. Among the 41 pts receiving AT, median OS was 58.7 months. At the univariate analysis, AT regimen was significantly associated with OS (p 0.02), and it was confirmed at the multivariate analysis. In particular, median OS was 59.8 and 28.3 months in pts receiving FP- and GMZ-based AT, respectively [HR 0.26, (95% CI: 0.09-0.78), p = 0.001]. Conclusions: Among pts with radically resected AA, AT, compared with PO, was not associated with a significant survival benefit. However, among pts receiving AT, FP-based regimen seems to significantly improve OS in comparison to GMZ-based regimen, independently of histologic subtype. Our findings, from a retrospective and limited case series, add to controversial literature data and miss to clarify the real impact of AT in radically resected AA pts. A randomized trial of AT vs PO would provide further information in this setting.

P-155 Adjuvant therapy (AT) in patients (pts) with radically resected ampullary adenocarcinoma (AA): A monocentric retrospective analysis

Ampullary adenocarcinoma (AA) is a rare tumor. Radical surgery is the only curative treatment for localized AA. The role of AT is not clearly defined and previous evidence in literature is poor and controversial. Hence, we retrospectively analyzed radically resected AA pts at our Institution, investigating the impact of AT on survival and the role of possible prognostic and/or predictive factors. Radically resected AA pts were retrospectively included in the analysis, divided into two groups: pts receiving AT and pts undergoing only postoperative observation (PO). The following variables were collected: gender; age (≤ 65 vs > 65 years); baseline ECOG PS (0 vs 3 1); histologic subtype (pancreatobiliary vs intestinal); tumor stage (T1-2 vs T3-4); nodal status (N0 vs N+), margin status (R0 vs R+); radiotherapy (yes vs no), AT regimen [Gemcitabine (GMZ)-based vs fluoropyrimidine (FP)-based treatment)]. The objective of the analysis was to evaluate the impact of AT on overall survival (OS). Univariate and multivariate analyses were performed. From 2007 to 2021, a total of 69 pts with radically resected AA were identified: 41 (59%) pts received AT, 28 (41%) PO. The median age was 65 years (41-81), 42 (61%) were males, ECOG PS was 3 1 in 45 (65%) pts. Tumor characteristics were: 31 (45%) pancreatobiliary, 26 (38%) intestinal, 9 (13%) mixed subtype and 3 (4%) not available; 41 (59%) pts had T3-T4 stage tumor; 34 (49%) were N+. Out of 41 pts receiving AT, 27 (66%) pts were treated with FP- based AT, 14 (34%) with GMZ-based AT; 16 (23%) pts received also RT. In the overall population, median OS was 59.8 months. At the univariate analysis, there was a statistically significant association of T status with OS (p 0.03), confirmed at multivariate analysis (p 0.03). Further variables (ECOG PS, AT, nodal status and histologic subtype) were not associated with survival. Among the 41 pts receiving AT, median OS was 58.7 months. At the univariate analysis, AT regimen was significantly associated with OS (p 0.02), and it was confirmed at the multivariate analysis. In particular, median OS was 59.8 and 28.3 months in pts receiving FP- and GMZ-based AT, respectively [HR 0.26, (95% CI: 0.09-0.78), p = 0.001]. Among pts with radically resected AA, AT, compared with PO, was not associated with a significant survival benefit. However, among pts receiving AT, FP-based regimen seems to significantly improve OS in comparison to GMZ- based regimen, independently of histologic subtype. Our findings, from a retrospective and limited case series, add to controversial literature data and miss to clarify the real impact of AT in radically resected AA pts. A randomized trial of AT vs PO would provide further information in this setting.

Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients with Resected Ampullary Adenocarcinoma

Introduction: The purpose of this study is to assess the prognostic accuracy of the 7th and 8th AJCC staging system for ampullary cancer(AAC) and externally validate the 8th edition for resected AAC in an international cohort.

Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients with Resected Ampullary Adenocarcinoma

Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients with Resected Ampullary Adenocarcinoma

Survival Benefit of Adjuvant Chemotherapy After Pancreatoduodenectomy for Ampullary Adenocarcinoma: a Propensity-Matched National Cancer Database (NCDB) Analysis

BackgroundThe benefit of adjuvant chemotherapy (AC) after pancreatoduodenectomy (PD) for ampullary adenocarcinoma is uncertain. We aimed to evaluate the association of AC with survival in patients with resected ampullary adenocarcinoma. MethodsUsing the National Cancer Database (NCDB) data from 2004 to 2016, patients with non-metastatic ampullary adenocarcinoma who underwent PD were identified. Patients with neoadjuvant radiotherapy and chemotherapy and survival < 6 months were excluded. Propensity score matching was used to account for treatment selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of AC with survival. ResultsOf 3186 (43%) AC and 4172 (57%) no AC (noAC) patients, 1720 AC and 1720 noAC patients remained in the cohort after matching. Clinicopathologic variables were well balanced after matching. After matching, AC was associated with improved survival (median 47.5 vs 39.6 months, p = 0.003), which remained after multivariable adjustment (HR: 0.83, CI95%: 0.76–0.91, p < 0.001). Multivariable interaction analyses showed that this benefit was seen irrespective of nodal status: N0 (HR: 0.81, CI95%: 0.68–0.97, p < 0.001), N1 (HR: 0.65, CI95%: 0.61–0.70, p < 0.001), N2 (HR: 0.73, CI95%: 0.59–0.90, p = 0.003), N3 (HR: 0.59, CI95%: 0.44–0.78, p < 0.001); and margin status: R0 (HR: 0.85, CI95%: 0.77–0.94, p < 0.001), R1 (HR: 0.69, CI95%: 0.48–1.00, p < 0.001). Stratified analyses by nodal and margin status demonstrated consistent results. ConclusionIn this large retrospective cohort study, AC after resected ampullary adenocarcinoma was associated with a survival benefit in patients, including patients with node-negative and margin-negative disease.

Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma

IntroductionAmpullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. Materials and methodsAn international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006–2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. ResultsOverall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73–0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73–0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. ConclusionA prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.

Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study.

Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P=0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P =0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.

Development of a prediction model for survival in patients with resected ampullary adenocarcinoma: international multicenter study

Development of a prediction model for survival in patients with resected ampullary adenocarcinoma: international multicenter study

Clinico-pathological correlates and survival outcomes in 214 resected ampullary adenocarcinomas – are outcomes different in intestinal and pancreatobiliary subtypes with adjuvant gemcitabine?

BackgroundEvidence suggests that intestinal type (IT) and pancreatobiliary (PB) subtypes of ampullary adenocarcinoma (AC) may have different outcomes. The current study evaluated differences in outcomes between these subtypes and the benefit of adjuvant chemotherapy (AT). MethodsA prospectively maintained database of patients who underwent upfront resection for AC from January 2012 to March 2016 was conducted. A dedicated pathologist reported differentiation between IT and PB subtypes. Results214 patients were included for analysis: 105 PB subtype and 109 IT subtype. With a median follow up of 46.3 months, estimated 4 year overall survival (OS) was 65.8%. In patients with stage II–III disease, lymph-node ratio (LNR) < 0.2 [Not reached (NR) vs. 30.72 months; p = 0.002], absence of perineural invasion (PNI) (NR vs. 31.61 months; p = 0.032) and AT (gemcitabine – 96.1%) (NR vs. 22.28 months) were prognostic for superior OS. There was no difference in OS between IT and PB subtypes, but both subtypes with stage II–III disease benefitted from AT statistically as compared to observation (IT: NR vs. 28.62 months; PB: 18.46 months vs. 58.09 months; p < 0.001). ConclusionsAC-IT and AC-PB did not have a different OS when treated with resection and adjuvant gemcitabine, though adjuvant therapy benefitted both subtypes individually.

Histopathologic predictors of survival and recurrence in resected ampullary adenocarcinoma: International multicenter cohort study

Background: A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums AAC can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma (AAC) with curative intent. Methods: A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in nine European tertiary referral centers between February 2006 and December 2017, was performed. Collected data included demographics, histopathologic details, survival and recurrence. OS and DFS analyses were performed using Kaplan-Meier curves and Cox proportional hazard models. Results: Overall, 887 patients were included, with a mean age of 66 ± 10 years. The median OS was 64 months with 1-, 3-, 5- and 10-year OS rates of 89%, 63%, 52% and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09 – 5.21]), perineural invasion (HR = 1.50 [1.01 – 2.23]) and adjuvant chemotherapy (HR = 0.69 [0.48 – 0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65 – 4.27]). Sensitivity analysis performed in this study, revealed adjuvant chemotherapy was only an independent predictor of increased OS in the 293 patients with pancreaticobiliary subtype (HR = 0.61 [0.40 – 0.93, p = 0.023) but not for the 211 patients with intestinal subtype (HR = 1.06 [0.57 – 1.95], p=0.861). Conclusion: Unfavorable predictors of OS were LN involvement and perineural invasion. Whereas, adjuvant chemotherapy independently predicted improved OS. DFS was independently predicted by LN involvement. Sub-analysis of the histopathologic subtypes revealed that patients with the pancreaticobiliary subtype benefit from adjuvant chemotherapy in terms of survival, whereas patients with intestinal histopathologic subtype did not.

Histopathologic Predictors of Survival and Recurrence in Resected Ampullary Adenocarcinoma: International Multicenter Cohort Study.

The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma with curative intent. A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums ampullary adenocarcinoma can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in 9 European tertiary referral centers between February 2006 and December 2017 was performed. Collected data included demographics, histopathologic details, survival, and recurrence. OS and DFS analyses were performed using Kaplan-Meier curves and Cox proportional hazard models. Overall, 887 patients were included, with a mean age of 66 ± 10 years. The median OS was 64 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 63%, 52%, and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin, and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09-5.21]), perineural invasion (HR = 1.50 [1.01-2.23]), and adjuvant chemotherapy (HR = 0.69 [0.48-0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65-4.27]). Independent predictors of OS in resected ampullary cancer were N-stage, perineural invasion, and adjuvant chemotherapy. N-stage was the only predictor of DFS. These findings improve predicting survival and recurrence after resection of ampullary adenocarcinoma.

Development of a prediction model for survival in patients with resected ampullary adenocarcinoma: an international multicenter study

Development of a prediction model for survival in patients with resected ampullary adenocarcinoma: an international multicenter study

Incidence and comparative outcomes of periampullary cancer: A population-based analysis demonstrating improved outcomes and increased use of adjuvant therapy from 2004 to 2012.

Periampullary adenocarcinoma (PAC) is stratified anatomically: ampullary adenocarcinoma (AA), distal cholangiocarcinoma (DCC), duodenal adenocarcinoma (DA), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine differences in incidence, prognosis, and treatment in stage-matched PAC patients in a longitudinal study. PAC patients were identified in The National Cancer Database from 2004 to 2012. Clinicopathological variables were compared between subtypes. Covariate-adjusted treatment use and OS were compared. The 116 705 patients with PAC were identified: 1320 (9%) AA, 3732 (3%) DCC, 7142 (6%) DA, and 95 511 (82%) PDAC. DA, DCC, and PDAC were associated with worse survival compared with AA (hazard ratio [HR], 1.10; 95% CI, 1.1-1.1; HR, 1.50; 95% CI, 1.4-1.6, and HR, 1.90; 95% CI, 1.8-1.9). Among resected patients, DA was associated with improved survival compared with AA (HR, 0.70; 95% CI, 0.67-0.75); DCC and PDAC were associated with worse survival (HR, 1.41; 95% CI, 1.31-1.53 and HR, 2.041; 95% CI, 1.07-2.12). Resected AA, PDAC, and DA, but not DCC, demonstrated significantly improved survival over the studied period. While all patients had increased adjuvant therapy (AT) receipt over time (P < 0.001), only patients with PDAC had increased neoadjuvant therapy (NAT) receipt ( P < 0.001). Resected PDAC, AA, and DA were associated with clinically significant improved survival over time, mirroring a concurrent associated increased receipt of AT.

Preoperative CA19-9 is an independent factor for poor prognosis in resected ampullary adenocarcinoma

Preoperative CA19-9 is an independent factor for poor prognosis in resected ampullary adenocarcinoma

Determining the Adequate Examined Lymph Node Count in Resected Ampullary Adenocarcinoma—A National Cohort Study

BackgroundThe evaluation of lymph node involvement is an essential component of cancer staging. Examining an inadequate number of lymph nodes potentially results in understaging. Current guidelines for lymph node retrieval for ampullary adenocarcinoma are based on data extrapolated from other periampullary malignancies and may not be applicable. The aim of this study was to determine the number of lymph nodes that should be examined in resection specimens to optimize staging in ampullary adenocarcinoma. MethodsPatients with ampullary adenocarcinoma from 2004 to 2014 were identified in the National Cancer Database. We determined the minimum examined lymph node (ELN) count by modeling each potential ELN count from 2 to 30 in a multivariable regression analysis and confirmed the results with a sensitivity analysis. ResultsWe identified 7451 patients of whom 52.2% had T3 or T4 disease and 51.4% had lymph node metastases. The median ELN count was 13 (interquartile range, 8–19). Increasing ELNs were independently associated with an increased likelihood of having positive nodal disease (odds ratio, 1.03; 95% confidence interval [CI], 1.03–1.04) and improved overall survival in both node-negative (hazard ratio [HR], 0.98; 95% CI, 0.97–0.99) and node-positive patients (HR, 0.99; 95% CI, 0.986–0.998). We determined that at least 17 lymph nodes should be examined. Overall survival for patients with 17 or more ELNs was superior than for those with fewer than 17 ELNs. ConclusionIncreasing ELNs were independently associated with improved overall survival in patients with resected ampullary adenocarcinoma. At least 17 lymph nodes should be examined for optimal nodal staging.

Pathologic Subtypes of Ampullary Adenocarcinoma: Value of Ampullary MDCT for Noninvasive Preoperative Differentiation.

The purpose of this study was to evaluate the utility of ampullary MDCT in the noninvasive, preoperative differentiation of pancreatobiliary and intestinal subtypes of ampullary adenocarcinoma. This retrospective study included 32 patients (20 men, 12 women; age range, 41-81 years) with resected ampullary adenocarcinoma who underwent preoperative contrast-enhanced ampullary MDCT. Two radiologists, blinded to pathologic diagnosis of adenocarcinoma subtype, evaluated the presence of seven MDCT features independently. MDCT findings and ampullary adenocarcinoma subtypes were correlated using chi-square and Fisher exact tests. Interobserver agreement was evaluated using the Cohen kappa statistic. When evaluated with ampullary MDCT, the intestinal and pancreatobiliary subtypes were significantly different in terms of lesion morphology (p < 0.0001), papillary shape (p < 0.0001), common bile duct (CBD) infiltration and dilatation (p = 0.003 and p = 0.0004, respectively), duodenopancreatic groove infiltration (p = 0.0009), and pancreaticoduodenal artery involvement (p = 0.004). Pancreatobiliary subtype tumors were more often infiltrative in morphology (18/18) and showed retracted papilla (14/18), CBD (18/18) and main pancreatic duct (MPD) infiltration (12/18), dilated CBD (18/18) and MPD (13/18), fixed duodenopancreatic groove appearance (15/18), and pancreaticoduodenal artery involvement (12/18). Intestinal subtype carcinomas were more frequently nodular (14/14) and had a bulging papilla (13/14), a free duodenopancreatic groove appearance (11/14), and no pancreaticoduodenal artery involvement (2/14). When all features were taken into account, MDCT showed sensitivity of 85.7% and specificity of 83.3% in differentiating intestinal and pancreatobiliary subtype tumors. Accuracy, positive predictive value, and negative predictive value of MDCT were 84.4%, 80%, and 88.2%, respectively. Interobserver agreement was almost perfect for the presence of each imaging feature (κ > 0.8). Ampullary MDCT can be useful to differentiate pancreatobiliary and intestinal subtypes of ampullary adenocarcinoma preoperatively, provided the duodenum is optimally distended at imaging.

Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2, CDX2, mucins and cytokeratins

IntroductionSubclassification of ampullary adenocarcinomas into intestinal and pancreatobiliary type has prognostic and therapeutic implications. Immunohistochemical staining against specific biomarkers has been proven to be a useful adjunct in determining the exact histotype. Furthermore the immunohistochemical profile is suggestive of the molecular pathogenic mechanisms through which the tumor evolved. The aim of this study was to correlate p53, MDM2, CK7, CK20, MUC1, MUC2 and CDX2 expression in ampullary adenocarcinomas with the type of differentiation and patients’ survival. Material and methodsForty-seven radically resected ampullary adenocarcinomas were included in this study. Thirty-eight of them were eligible for survival analysis. Patients’ data were retrospectively collected. All tumors were classified as intestinal or pancreatobiliary type, according to histologic criteria, and immunohistochemically stained against the aforementioned markers. ResultsThere were 18 intestinal and 29 pancreatobiliary type ampullary adenocarcinomas. A trend was found between intestinal type tumors and large tumor size. CK20, MUC2 and CDX2 expression was more prevalent in intestinal type tumors, while MUC1 was more frequently expressed in pancreatobiliary type tumors. Neither p53 nor MDM2 differential expression between the two histotypes reached statistical significance. Multivariate analysis indicated CK20 and MUC1 as independent predictors of the histotype. Mean and median survival was 90.3 and 55 months respectively. Overall 5-year survival rate was 48%. Survival analysis indicated TNM stage as the only independent prognostic factor. Although significant difference in survival rates among the two histotypes was implied based on survival plots, this difference could not gain statistical significance. ConclusionImmunoreactivity against CK20 and MUC1 in ampullary carcinomas is a useful adjunct to histologic examination in determining histotype. None of the immunohistochemical markers studied has prognostic significance. Future studies focused on other signaling pathways should seek further evidence of distinct tumorigenic mechanisms between histotypes of ampullary adenocarcinoma.