Comparison of the two histological subtypes of ampullary adenocarcinoma: a retrospective study.

OBJECTIVES: This study aimed to compare the intestinal and pancreatobiliary subtypes of ampullary adenocarcinoma in a large patient group due to limited data on survival and risk factors. METHODS: A retrospective analysis of the clinical and pathological findings and the survival of 184 patients with ampullary adenocarcinoma who underwent curative operation between 2007 and 2018 was performed. RESULTS: Pancreatobiliary subtype had a higher prevalence of jaundice before operation than the intestinal subtype (p < 0.05). Pancreatobiliary subtype had a larger tumor size (> 2 mm) (p < 0.01) and poorer differentiation (p < 0.05) than the intestinal subtype. Perineural invasion more frequently occurred in pancreatobiliary subtype than the intestinal subtype (p < 0.01) and pancreatobiliary subtype had a higher prevalence of positive dissected lymph nodes (p < 0.05) with an advanced disease stage (p < 0.01) than the intestinal subtype. Patients of the pancreatobiliary subtype had poorer disease-free and overall survival than patients of the intestinal subtype. No survival benefit of adjuvant chemotherapy was found in either patients of the intestinal subtype or pancreatobiliary subtype. No significant difference was found in any subtypes regarding the recurrent regions. CONCLUSIONS: Pancreatobiliary subtype exhibited a higher recurrence rate and a poorer overall survival rate with more unfavorable pathological characteristics than the intestinal subtype.

OBJETIVOS: Los datos sobre la supervivencia y los factores de riesgo del adenocarcinoma ampular son limitados debido a su rareza. Este estudio buscó comparar el subtipo intestinal y el subtipo pancreático-biliar en pacientes con adenocarcinoma ampular. MÉTODOS: Análisis retrospectivo de hallazgos clínicos y patológicos y la supervivencia de 184 pacientes con adenocarcinoma ampular tratados entre 2007 y 2018. RESULTADOS: El subtipo pancreático-biliar tuvo una mayor prevalencia de ictericia antes de la operación y un tamaño de tumor mayor, y una peor diferenciación, que el subtipo intestinal. La invasión perineural fue más frecuente en el subtipo pancreático-biliar, con una mayor prevalencia de linfonodos disecados positivos y un estadio avanzado de la enfermedad. Los pacientes del subtipo pancreático-biliar tuvieron una supervivencia libre de enfermedad y una supervivencia general peores que los pacientes del subtipo intestinal. No se encontró ningún beneficio de la quimioterapia adyuvante en pacientes del subtipo intestinal o pancreático-biliar. No hubo diferencia significativa en las regiones recurrentes. CONCLUSIÓN: El subtipo pancreático-biliar mostró una tasa de recurrencia y una tasa de supervivencia general peores, con características patológicas más desfavorables que el subtipo intestinal.

Genome-Derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care.

PURPOSE: The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management. EXPERIMENTAL DESIGN: The hidden-genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile-duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA-sequencing data from ampullary adenocarcinomas. Genomic classification (i.e., colorectal vs. pancreatic) was correlated with standard histologic classification [i.e., intestinal (INT) vs. pancreatobiliary (PB)] and clinical outcome. RESULTS: Colorectal genomic subtype prediction was primarily influenced by mutations in APC and PIK3CA, tumor mutational burden, and DNA mismatch repair (MMR)-deficiency signature. Pancreatic genomic-subtype prediction was dictated by KRAS gene alterations, particularly KRAS G12D, KRAS G12R, and KRAS G12V. Distal bile-duct adenocarcinoma genomic subtype was most influenced by copy-number gains in the MDM2 gene. Despite high (73%) concordance between immunomorphologic subtype and genomic category, there was significant genomic heterogeneity within both histologic subtypes. Genomic scores with higher colorectal probability were associated with greater survival compared with those with a higher pancreatic probability. CONCLUSIONS: The genomic classifier provides insight into the heterogeneity of ampullary adenocarcinoma and improves stratification, which is dictated by the proportion of colorectal and pancreatic genomic alterations. This approach is reproducible with available molecular testing and obviates subjective histologic interpretation.

Novel method for evaluating the indication for endoscopic papillectomy in patients with ampullary adenocarcinoma.

This study aimed to determine the clinicopathological features of the subtypes of ampullary carcinoma (AC) to explore the indications for endoscopic papillectomy (EP) in early AC. Fifty-seven patients with AC who underwent curative resection were retrospectively reviewed. The 0/IA stages were significantly more common in the intestinal type (I-type) than in the mixed and pancreatobiliary type (M&PB-type) (90.7% vs 35.7%, P < 0.001). Tis/T1a tumors limited to the ampulla [Tis/T1a(ampulla)] were significantly more likely to be I-type than M&PB-type (74.4% vs 14.3%, P = 0.002). The tub1 rate was significantly higher in the I-type than in the M&PB-type (81.4% vs 35.7%, P = 0.001). In the I-type, the tub1 rate was significantly higher for Tis/T1a(ampulla) than for T1a tumors limited to the sphincter of Oddi (100% vs 42.9%, P = 0.004). These observations suggest that I-type AC with tub1 is an indication for EP. The concordance rate of pathological subtypes between endoscopic biopsy and resected specimens was high (κ = 0.8053, P < 0.001). Tis/T1a(ampulla) showed no lymphovascular or perineural invasion. An endoscopic imaging finding of early AC with I-type and tub1 on biopsy could be an indication for EP. Identifying the pathological subtype of AC by endoscopic biopsy could be a novel preoperative approach for evaluating the indications for EP.

Clinicopathological characteristics of non-ampullary duodenal tumors and their phenotypic classification.

The tumorigenesis of non-ampullary duodenal epithelial tumors (NADETs) might be different between the oral and anal sides of Vater's papilla. We conducted an immunohistological review to elucidate the clinicopathological features according to the tumor location and phenotypic classification. A review of an institutional database identified 121 patients with 125 superficial NADETs. NADETs were histologically evaluated and classified into the intestinal or gastric type based on immunohistochemical analysis. Clinicopathological factors were compared based on the tumor location and phenotype. Logistic regression analysis was performed to identify independent predictors for gastric-type NADETs. According to location analysis, the mucin phenotype was significantly different (oral side, intestinal-type 64.8%, gastric-type 35.3%; anal side, intestinal-type 87.3%, gastric-type 12.7%; P < 0.01). Although the incidence of adenoma was significantly predominant in the intestinal type (75.3%), most gastric-type NADETs were cancerous (64.3%). Notably, most gastric-type NADETs were adenocarcinomas even when the tumor size was ≤0 mm. In multivariate analysis, tumor location on the oral side (odds ratio [OR], 4.42), villous structure (OR, 6.44), and low tumor gland density (OR, 9.49) were independent predictors of gastric-type tumors. Gastric-type NADETs significantly differ from intestinal-type NADETs in terms of tumor location, morphology, and biology.

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study.

BACKGROUND: Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies. METHODS: In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score. RESULTS: Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival. CONCLUSIONS: Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence.

The Prognostic Relevance of the New 8th Edition of the Union for International Cancer Control Classification of TNM Staging for Ampulla of Vater Carcinoma.

OBJECTIVE: The aim of this study was to investigate the clinical relevance of the 8th edition of the Union for International Cancer Control classification of TNM staging for ampulla of Vater carcinoma (AC). METHODS: A total of 104 consecutive patients who underwent macroscopic curative resection for AC between January 2002 and September 2017 were investigated. RESULTS: Significant differences in recurrence-free survival (RFS) were found between T1a and T1b (p = 0.0030), but not between T1b and T2 (p = 0.9319), T2 and T3a (p = 0.0732), or T3a and T3b (p = 0.2118). The prognostic impact of the depth of duodenal invasion and pancreatic invasion, which define the T category, were evaluated. With regard to duodenal invasion, significant differences in RFS were found between the negative and submucosa classifications (p = 0.0012) and the muscularis propria and serosa classifications (p = 0.0131), but not between the submucosa and muscularis propria classifications (p = 0.6390). With regard to pancreatic invasion, significant differences in RFS were found between the negative and ≤ 0.5 cm classifications (p = 0.0001), and ≤ 0.5 cm and > 0.5 cm classifications (p = 0.0062). A Cox proportional hazard analysis for RFS revealed that duodenal invasion (submucosa or muscularis propria/negative, hazard ratio [HR] 5.08; serosa/negative, HR 7.42), and pancreatic invasion (≤ 0.5 cm/negative, HR 8.23; > 0.5 cm/negative, HR 9.81) were independent prognostic factors. An alternative new T category was proposed, based on the HRs, as follows: T1, tumor limited to the ampulla of Vater or sphincter of Oddi; T2, duodenal invasion (submucosa or muscularis propria); T3, pancreatic invasion (≤ 0.5 cm) or duodenal invasion (serosa); and T4, pancreatic invasion (> 0.5 cm). This alternative T category can well classify each subgroup with prognostic differences. CONCLUSIONS: Reconsideration of the T category based on the prognostic impact of TNM factors, including the depth of duodenal and pancreatic invasion, are required in the 8th edition T category.

Identification of ampullary carcinoma mixed subtype using a panel of six antibodies and its clinical significance.

OBJECTIVES: To investigate the function of immunomarkers CK7, CK20, CK17, CDX2, MUC1, and MUC2 in the identification of primary ampullary carcinoma mixed subtype. METHODS: Forty-two cases of primary ampullary carcinoma were performed by immunohistochemical studies. The correlation between the mixed subtype and the other two subtypes and patient survival data was analyzed using the SPSS 16.0 statistical software. RESULTS: Among 42 cases, 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns: 91.7% (11/12) for CK7, 83.3% (10/12) for CK20; 66.7% (8/12) for CK17, CDX2, and MUC1; and 50% (6/12) for MUC2. Ten (83.3%) mixed types coexpressed four or more immunomarkers. Eight (19%) intestinal subtypes mainly showed a positive expression of CK20, CDX2, and MUC2. Twenty-two (52.4%) pancreaticobiliary subtypes showed a positive expression of CK7, MUC1, and CK17. Stages III and IV diseases in mixed subtype (25%) and intestinal subtype (25%) were less than pancreaticobiliary subtype(63.6%) (p = 0.039). Follow-up data appeared to show a better survival rate for patients with mixed subtype than those with pancreaticobiliary subtypes. CONCLUSION: Immunohistochemical staining provided a more reliable means of diagnosing mixed ampulla carcinoma. Accurate subtyping of ampullary carcinoma is clinically important to select effective chemotherapy regimens and to assess disease prognosis.

Proposed new staging system for ampulla of Vater cancer with greater discriminatory ability: multinational study from eastern and western centers.

BACKGROUND: We built a multinational retrospective database of patients with ampulla of Vater cancer to develop a reliable new staging system. METHOD: This study included 841 patients with ampulla of Vater cancer after curative surgery at Seoul National University Hospital (n = 440) and Johns Hopkins University medical institutions (n = 401) between 1985 and 2013. RESULTS: The 5-year overall survival (OS) rates of patients staged according to the 7th American Joint Committee on Cancer staging system were 80.3%, 60.9%, 58.1%, 36.6%, 17.9%, and 25.0% for Stages IA (n = 140), IB (n = 194), IIA (n = 115), IIB (n = 348), III (n = 33), and IV (n = 4), respectively. Five-year OS rates were similar in patients with Stage IB (T2N0M0) and IIA (T3N0M0) tumors (P = 0.556), but differed significantly between other pairs of groups. The number of positive lymph nodes (PLN) enhanced prognosis when stratified as 0, 1-2 and ≥3 (P < 0.001). The revised staging system consisted of Stages I (T1, PLN 0), IIA (T2-T3, PLN 0), IIB (T1-T3, PLN 1-2), III (PLN ≥3 or any T4), and IV (any M1), with 5-year OS rates differing significantly in each pair of groups, including Stages I and IIA (P < 0.001). CONCLUSION: This new staging system has better discriminatory ability in stratifying 5-year OS rates based on a large multinational database.

Ampullary carcinoma is often of mixed or hybrid histologic type: an analysis of reproducibility and clinical relevance of classification as pancreatobiliary versus intestinal in 232 cases.

Histologic classification of ampullary carcinomas as intestinal versus pancreatobiliary is rapidly becoming a part of management algorithms, with immunohistochemical classification schemes also being devised using this classification scheme as their basis. However, data on the reproducibility and prognostic relevance of this classification system are limited. In this study, five observers independently evaluated 232 resected ampullary carcinomas with invasive component >3 mm. Overall interobserver agreement was 'fair' (κ 0.39; P<0.001) with complete agreement in 23%. Using agreement by 3/5 observers as 'consensus' 40% of cases were classified as 'mixed' pancreatobiliary and intestinal. When observers were asked to provide a final diagnosis based on the predominant pattern in cases initially classified as mixed, there was 'moderate' agreement (κ 0.44; P<0.0001) with 5/5 agreeing in 35%. Cases classified as pancreatobiliary by consensus (including those with pure-pancreatobiliary or mixed-predominantly pancreatobiliary features) had shorter overall (median 41 months) and 5-year survival (38%) than those classified as pure-intestinal/mixed-predominantly intestinal (80 months and 57%, respectively; P=0.026); however, on multivariate analysis this was not independent of established prognostic parameters. Interestingly, when compared with 476 cases of pancreatic ductal adenocarcinomas, the pancreatobiliary-type ampullary carcinomas had better survival (16 versus 41 months, P<0.001), even when matched by size and node status. In conclusion, presumably because of the various cell types comprising the region, ampullary carcinomas frequently show mixed phenotypes and intratumoral heterogeneity, which should be considered when devising management protocols. Caution is especially warranted when applying this histologic classification to biopsies and tissue microarrays. While ampullary carcinomas with more pancreatobiliary morphology have a worse prognosis than intestinal ones this does not appear to be an independent prognostic factor. However, pancreatobiliary-type ampullary carcinomas have a much better prognosis than their pancreatic counterparts.

Histological and Molecular Subclassification of Pancreatic and Nonpancreatic Periampullary Cancers: Implications for (Neo) Adjuvant Systemic Treatment.

The benefit of adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC) has been confirmed in randomized controlled trials. For nonpancreatic periampullary cancers (NPPC) originating from the distal bile duct, duodenum, ampulla, or papilla of Vater, the role of adjuvant therapy remains largely unclear. This review describes methods for distinguishing PDAC from NPPC by means of readily available and recently developed molecular diagnostic methods. The difficulties of reliably determining the exact origin of these cancers pathologically also is discussed. The review also considers the possibility of unintentional inclusion of NPPC in the most important adjuvant trials on PDAC and the subsequent implications for interpretation of the results. The authors conclude that correct determination of the origin of periampullary cancers is essential for clinical management and should therefore be systematically incorporated into clinical practice and future studies.

Comparison between the location and the histomorphological/immunohistochemical characteristics of noninvasive neoplasms of the ampulla of Vater.

To determine useful factors when selecting an appropriate procedure for noninvasive ampullary neoplasia, we investigated the relationship between the location and the histomorphological/immunohistochemical characteristics of 56 noninvasive ampullary neoplasms obtained by endoscopic papillectomy (EP). All subjects were classified according to histomorphology and location of neoplasms, and we evaluated the characteristics of each classified group using complementary immunohistochemical procedures. The CK20-positive rates of each location type were also evaluated. Subjects presented with 52 intestinal-type adenomas (low/high grade, 32:20) and 4 noninvasive pancreatobiliary papillary neoplasms (low/high grade, 1:3). Twenty-seven periampullary (peri-AMP)-type tumors and 23 extended-type tumors comprised the intestinal type, and the intra-ampullary (intra-AMP) type was composed of 4 pancreatobiliary and 2 intestinal histomorphological types. The CK20-positive rates of these 3 location types differed significantly (peri-AMP type, 50.6% ± 21.0%; extended type, 35.4% ± 18.6%; intra-AMP type, 6.9% ± 6.3%). The CK20-positive rate for intestinal-type tumors of the intra-AMP location type was lower than that of the peri-AMP location type. Intestinal-type tumors without CDX2 expression included extended and intra-AMP types, which are tumors that may show positive vertical margins when EP is performed. In this study, we found that an understanding of pancreatobiliary-type histology is an important aspect for the investigation of tumors involving the common channel of the ampulla. Furthermore, immunostaining of CDX2 and CK20 provides beneficial information if considering whether to perform an EP.

The utility of immunohistochemistry in subtyping adenocarcinoma of the ampulla of vater.

Histologic classification of ampullary carcinomas into intestinal, pancreatobiliary, or other subtypes is easily achievable in some cases but difficult in others. Immunohistochemical (IHC) stains may allow distinction between the subtypes; however, their added value to routine hematoxylin and eosin (H&E) evaluation has not been systematically evaluated. Inconsistent histologic subtyping has hampered current clinical research and therapeutic trials. In this study, a consecutive series of 105 ampullary carcinomas was subtyped first by H&E evaluation and then by the evaluation of an IHC panel composed of CK7, CK20, CDX2, MUC1, and MUC2, and the added value of IHC was analyzed. By H&E, a consensus diagnosis, defined as concordant subtyping among at least 3 of the 4 independent study pathologists, was achieved in 81 of the 105 (77%) cases. There was excellent agreement for poorly differentiated and mucinous subtypes (κ=0.72 and 0.89, respectively) but only good agreement for intestinal and pancreatobiliary subtypes (κ=0.57 and 0.48, respectively) and poor agreement for mixed subtype (κ=0.09). By IHC, CK7 showed no informative value (being positive in ≥70% of the cases in both intestinal and pancreatobiliary subtypes), whereas a subtyping schema incorporating the combination staining patterns of CK20, CDX2, MUC1, and MUC2 did. By this schema, "intestinal subtype" was defined as having (1) positive staining for CK20 or CDX2 or MUC2 and negative staining for MUC1, or (2) positive staining for CK20, CDX2, and MUC2, irrespective of the MUC1 result; and "pancreatobiliary subtype" was defined as having positive staining for MUC1 and negative staining for CDX2 and MUC2, irrespective of CK20 results. Cases not fitting one of these 3 categories were regarded as "ambiguous" immunohistochemically. By combining this schema with H&E evaluation, 97 of the 105 cases (92%) could be classified into either intestinal or pancreatobiliary subtype. In particular, immunophenotyping allowed categorization of 75% of poorly differentiated adenocarcinomas and 69% of cases with mixed histologic features as either intestinal or pancreatobiliary subtype. Most mucinous adenocarcinomas (88%) were clearly intestinal subtype by IHC. Thus, our IHC schema enhanced the subtyping of ampullary carcinoma and, in combination with H&E evaluation, allowed a dichotomous classification in 92% of the cases. Should further independent studies reaffirm our findings, this schema may serve as a valuable tool in both diagnostic and research settings.

Differential expression of E-cadherin, ß-catenin, and S100A4 in intestinal type and nonintestinal type ampulla of Vater cancers.

BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, ß-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. METHODS: A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, ß-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. RESULTS: Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and ß-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous ß-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. CONCLUSIONS: Dysregulation of E-cadherin, ß-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.

Differential Expression of E-Cadherin, beta-Catenin, and S100A4 in Intestinal Type and Nonintestinal Type Ampulla of Vater Cancers

BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, beta-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. METHODS: A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, beta-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. RESULTS: Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and beta-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous beta-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. CONCLUSIONS: Dysregulation of E-cadherin, beta-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.

Ampullary region carcinomas: definition and site specific classification with delineation of four clinicopathologically and prognostically distinct subsets in an analysis of 249 cases.

Ampullary (AMP) carcinomas comprise a heterogeneous group of cancers lacking adequate subcategorization. In the present study, 249 strictly defined primary AMP carcinomas (ACs) identified in 1469 malignant pancreatoduodenectomy specimens were analyzed for defining features. Gross and microscopic findings were used to determine tumor epicenter and extent of preinvasive component. ACs were classified into 4 distinct subtypes based on location: (1) Intra-AMP (25%): Invasive carcinomas arising in intra-ampullary papillary-tubular neoplasms with zero to minimal, duodenal surface involvement (<25% of the tumor). These tumors were more commonly found in men, they had a relatively large overall size (mean, 2.9 cm) but had smaller invasive component (mean, 1.5 cm), and were predominantly of a lower TNM stage (85%, T1/2; and 72% N0). They carried the best prognosis among the 4 groups (3-y survival, 73%). (2) AMP-ductal (15%): These were tumors forming constrictive, sclerotic, plaque-like thickening of the walls of the common bile duct and/or pancreatic duct resulting in mucosa-covered, button-like elevations of the papilla into the duodenal lumen. There was no significant exophytic (preinvasive) growth. These were the smallest tumors (mean overall size, 1.9 cm; mean invasion size 1.7 cm), but carried the worst prognosis (3-y survival, 41%), presumably due to the pancreatobiliary histology/origin (in 86%); however, even this group had significantly better prognosis when compared with 113 ordinary pancreatic ductal adenocarcinomas (3 y, 11%; P<0.0001). (3) Peri-AMP-duodenal (5%): Massive exophytic, ulcero-fungating tumors growing into the duodenal lumen and eccentrically encasing the ampullary orifice with only minimal intra-ampullary luminal involvement. These were mostly of intestinal phenotype (75%) and some had mucinous features. Although these tumors were the largest (mean overall size 4.7 cm; and mean invasion size 3.4 cm), and had the highest incidence of lymph node metastasis (50%), they carried an intermediate prognosis (3-y survival, 69%) to that seen among a group of 55 nonampullary duodenal carcinoma controls. (4) AC-not otherwise specified ("papilla of Vater"; 55%): Ulcero-nodular tumors located at the papilla of Vater, which do not show the specific characteristics identified among the other 3 subtypes. In conclusion, ACs comprise 4 clinicopathologic subtypes that are prognostically distinct.

Pathologic staging of pancreatic, ampullary, biliary, and gallbladder cancers: pitfalls and practical limitations of the current AJCC/UICC TNM staging system and opportunities for improvement.

Tumors of the ampulla-pancreatobiliary tract are encountered increasingly; however, their staging can be highly challenging due to lack of familiarity. In this review article, the various issues encountered in staging of these tumors at the pathologic level are evaluated and possible solutions for daily practice as well as potential improvements for future staging protocols are discussed. While N-stage parameters have now been well established (the number of lymph nodes required in pancreatoduodenectomies is 12), the T-staging has several issues: for the pancreas, the discovery of small cancers arising in intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) necessitates the creation of substages of T1 (as T1a, b, and c); lack of proper definition of "peripancreatic soft tissue" and "common bile duct involvement" (as to which part is meant) makes T3 highly subjective. Increasing resectability of main vessels (portal vein) brings the need to redefine a "T" for such cases. For the ampulla, due to factors like anatomic complexity of the region and the under-appreciation of three-dimensional spread of the tumors in this area (in particular, the frequent extension into periduodenal soft tissues and duodenal serosa, which are not addressed in the current system and which require specific grossing approaches to document), the current T-staging lacks reproducibility and clinical relevance, and therefore, major revisions are needed. Recently proposed refined definition and site-specific subclassification of ampullary tumors highlight the areas for improvement. For the extrahepatic bile ducts, the staging schemes that use the depth of invasion may be more practical to circumvent the inconsistencies in the histologic layering of the ducts; better definition of terms like "periductal spread" is needed. For the gallbladder, since many gallbladder cancers are "unapparent" (found in clinically and grossly unsuspected cholecystectomies), establishing proper grossing protocols and adequate sampling are crucial. Since the gallbladder does not have the distinct layering of the other gastrointestinal organs, the definitions of Tis/T1a/T1b lack practicality, and therefore, "early gallbladder carcinoma" category proposed in high-risk regions may have to be recognized instead. Involvement of the Rokitansky-Aschoff sinuses should be a part of the evaluation and management of these early gallbladder cancers; for advanced cancers, documentation of hepatic versus serosal involvement is necessary. In summary, T-staging of ampulla-pancreatobiliary tract tumors has many challenges. Proper grossing and appreciation of histo-anatomic subtleties of this region are crucial in addressing these issues and achieving more applicable and clinically relevant staging systems in the future.

A new approach for evaluating the resectability of pancreatic and periampullary neoplasms.

OBJECTIVE: To establish a new standard for assessing the resectability of pancreatic and periampullary tumors by the Medical Image Three-Dimensional Visualization System (MI-3DVS). METHODS: Eighty cases of pancreatic and periampullary tumors were examined. The 64-slice multidetector CT (64-MDCT) images and patient data were processed by MI-3DVS. The main elements examined by MI-3DVS included tumor shape, size, and location; distribution of related vessels; luminal morphology of large vessels; distribution and morphology of the small peripancreatic veins; morphology, degree of dilation, and obstructive sites of bile and pancreatic ducts. Based on vascular characteristics of MI-3DVS findings, the cases were classified into five types. Type I and II were resectable, type III were potentially resectable or resectable with combined vascular resection and reconstruction, and type IV and V were unresectable. The outcome was then compared with corresponding CT angiography (CTA) analysis and actual surgical observations. RESULTS: Among the 80 cases, MI-3DVS indicated that 60 were resectable and the remaining 20 were not. In contrast, CTA indicated 50 resectable cases and 30 unresectable cases. For 57 cases of pancreatic ductal carcinomas and all 80 cases periampullary tumors, MI-3DVS assessment yielded a positive predictive value of 100%, negative predictive value of 100%, a sensitivity of 100%, a specificity of 100%, and an accuracy of 100%. While CTA generated corresponding values of 96%, 60%, 80%, 90%, 82.5%. The overall differences between the two methods were significant (P < 0.05). CONCLUSION: The new classification system is able to reliably assess the resectability of pancreatic and periampullary tumors.

[Tumors of Vater's ampulla]. / Tumoren der Papilla Vateri.

Tumors of Vater's ampulla are generally uncommon. In this location intestinal type adenomas are frequently found, followed by noninvasive papillary neoplasms of the pancreaticobiliary type and neuroendocrine tumors (carcinoids). Carcinomas of Vater's ampulla represent about 0.5% of all gastrointestinal malignancies. Intestinal type adenocarcinoma is the most common malignant epithelial tumor followed by the pancreaticobiliary type adenocarcinoma. Highly malignant neuroendocrine carcinomas of Vater's ampulla are very uncommon. Carcinomas of the ampullary region can be sporadic or a component of several disease syndromes. Designation of large carcinomas as tumors with an ampullary or extra-ampullary origin can be difficult but is of relevance for a TNM conform classification. Helpful in the decision are the relationship between the tumor centre and Vater's ampulla, the existence of premalignant lesions in the ampullary epithelium as well as histology and immunostaining of the tumor.