Pancreaticobiliary Type Research Articles

Mucins in the diagnosis and differential diagnosis of pancreatic cystic neoplasms

胰的膀胱的瘤说明 10% ～ 15% 所有膀胱的胰腺的损害。胰的膀胱的损害的多数(85% ～ 90%) 是胰的膀胱的瘤是的 pseudocysts.Although 稀罕，他们从对恶意的瘤良性。临床的挑战是膀胱的瘤的微分诊断和管理，它代表 10% ～ 25% 主要的胰腺的瘤。象有膀胱的特征的损害一样的胰腺的瘤和瘤最近被考察了。报导的胰腺的膀胱的瘤的发生是可变的。因为从把胰的膀胱的瘤的发生和生物学比作西方的系列的中国的 tne 案例上没有大、系统的学习，我们在 6 年从中山医院考察了膀胱的瘤的所有案例。大多数在我们的系列的瘤根据最近的世界健康组织被分类() 分类。粘蛋白是广泛地在上皮的房间被表示的一组高相对的分子的集体 glycoproteins。上皮的房间的恶意的转变通常与粘蛋白的反常 glycosylation 被联系。在现在的学习，我们在胰的膀胱的瘤检验了很好描绘的粘蛋白(MUC1， MUC2， MUC4， MUC5AC，和 MUC6 ) 的表示。目标是识别粘蛋白侧面，它是在胰腺的膀胱的瘤的微分诊断的一个特定的标记。

Can endoscopic resection be applied for early stage ampulla of Vater cancer?

Although endoscopic resection can provide a wide tumor resection with a negative resection margin, it is not yet recommended as a curative therapy for ampulla of Vater cancer. To investigate the microinvasion rate and the diagnostic accuracy of endoscopic biopsy to properly judge the safety of endoscopic resection for ampulla of Vater cancer. Single-center, retrospective study. Academic medical center. One hundred fifty-nine patients who were finally diagnosed with ampulla of Vater cancer after curative surgical resection. We surveyed the pathologic concordance rate of endoscopic biopsy and the surgical pathology. For the 36 early stage (Tis or T1) cancers, we surveyed the presence of microlymphovascular invasion, gross appearance (intra-ampullary type, periampullary type, or mixed type), and pathologic subtype (intestinal type or pancreaticobiliary type). Presence of microinvasion in early staged ampulla of Vater cancer. Endoscopic biopsy failed to reveal malignancy in 15.9% of the 126 cases. Microlymphovascular invasion was present in 17 cases (56.7%) of the 30 T1 cancers but was absent in all cases of the 6 Tis cancers (P = .02). Neither the gross appearance (P = .51) nor the pathologic subtype (P = .28) could predict the microinvasion rate. Single-center, retrospective study with small number of patients. Although endoscopic resection improves the low predictability of endoscopic biopsy, surgical resection should be performed for the T1 stage ampulla of Vater cancer because of the high lymphovascular invasion rate. On the other hand, the safety of endoscopic resection should be evaluated by a large-scale study on Tis cancers to consider the absence of microinvasion.

High Expression of Intestinal-Type Mucin (MUC2) in Intraductal Papillary Mucinous Neoplasms Coexisting With Extrapancreatic Gastrointestinal Cancers

It is known that intraductal papillary mucinous neoplasm (IPMN) is associated with a high incidence of extrapancreatic neoplasms. We tried to uncover the characteristics and gene expressions of IPMNs that coexist with other extrapancreatic gastrointestinal cancers. We retrieved the surgical specimens from 54 IPMN patients, including 7 cases of IPMNs that coexisted with extrapancreatic gastrointestinal cancers. The immunohistochemical staining (p21, Bcl-2, p53, intestinal-type secretory mucin [MUC2], and MUC5AC) and the pathological subtypes of the tumor papillae (the intestinal type, pancreaticobiliary type, null type, or unclassified type) were analyzed. MUC2 expression was noticed more frequently in the IPMN coexisting with extrapancreatic cancers (6/7) than in the IPMN without extrapancreatic cancers (18/47; P = 0.04). There were no differences in p21 (P = 0.12), p53 (P = 0.25), and MUC5AC (P = 1.0) expressions between the 2 groups. IPMN with extrapancreatic cancers was noticed in all subtypes of papillae. Regardless of the subtypes of papillae, transcription of the MUC2 might be related with the synchronous extrapancreatic gastrointestinal cancer development that is seen with IPMN. Therefore, careful systemic surveillance is needed to detect coexisting gastrointestinal cancer for all the subtypes of IPMN with MUC2 expression.

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7-, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20-, MUC2-). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.

Neoplastic diseases of the papilla of Vater.

Although it is quite small, the papilla of Vater is an important part of the body. Carcinoma of the papilla may be one of the smallest cancers that can cause death. The 5-year survival rate after resection was 51%, which is not satisfactory. In this article, the topics discussed are (1) pathogenesis, (2) histological characteristics, and (3) the molecular biological characteristics of carcinoma of the papilla of Vater. From results obtained by the investigation of 576 autopsied and 51 resected cases, atypical epithelium was found most frequently in the common channel, where pancreatic juice and bile mix physiologically. Atypical epithelia may be a precursor of carcinoma of the papilla of Vater. Carcinoma of the papilla of Vater could be classified into two types histologically, an intestinal type and a pancreaticobiliary type. The prognosis of patients with the intestinal type was much better than that of patients with the pancreaticobiliary type. These two types of carcinoma should be treated by different operative procedures or adjuvant therapies. Regarding the molecular biological characteristics of carcinoma of the papilla of Vater; (1) K- ras mutation is mainly associated with the intestinal type, and carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms; (2) p53 overexpression may play a role in tumor ulceration; and (3) p21/Waf1 overexpression was significantly correlated with a poor prognosis.

Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up.

A broad histomorphologic spectrum of ampullary carcinomas of Vater make a reproducible histologic classification difficult. Using cytokeratin immunohistochemistry, we present a new classification of ampullary carcinomas and analyze their clinical significance. Fifty-five invasive carcinomas of Vater's ampulla were histologically classified into pancreaticobiliary, intestinal, and other types. Serial sections of all carcinoma specimens were additionally stained with antibodies to cytokeratins (CK7, CK20), apomucins (MUC1, MUC2, MUC5AC), CEA, CA19-9, Ki67, and p53. Follow-up of patients from 4 months to 22 years after surgery (mean interval, 51.6 months) was evaluated. Most carcinomas of the ampulla of Vater were of immunohistochemically pancreaticobiliary type (iPT, CK7+, CK20-; 54.5%) or intestinal type (immunohistochemically intestinal type [iIT], CK7-, CK20+; 23.6%). Some carcinomas of immunohistochemically "other" type (iOT both CK7+ and CK20+ or CK7- and CK20-; 21.8%) had precursor lesions of iIT or iPT. Carcinomas positive for MUC2 or CEA were associated with iIT (MUC2, P < 0.001; CEA, P = 0.003), whereas MUC5AC-positive carcinomas were related to iPT (P = 0.005). Our classification based on cytokeratin-immunohistochemistry correlated well with the histologic classification according to published criteria (kappa-coefficient = 0.398; P < 0.001). Furthermore, histologically unusual types could be histogenetically related to pancreaticobiliary duct mucosa or intestinal mucosa. Therefore, all 4 signet-ring cell carcinomas were iIT carcinomas. Thus, cytokeratin immunohistochemistry allows a reproducible, histogenetically based categorization of ampullary carcinomas. However, neither histopathologic nor immunohistochemical subgroups significantly correlated with clinical outcome in our German collective. The overall survival was significantly shorter in males (P = 0.032) and patients with positive nodal stage (N1 < N0; P = 0.0025).

Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms.

Tumors with clinically recognizable mucin production arising from bile duct, "mucin-producing bile duct tumors (MPBTs)," have not been studied yet for their pathologic features and classification in details. The clinical findings of MPBT have a lot of similarities to those of pancreatic intraductal papillary-mucinous neoplasm. In the present study, we examined 30 MPBTs and classified them into two distinct morphologic categories: 22 cases of "columnar type" composed of pseudostratified columnar cells with basophilic cytoplasm and columnar nuclei and 8 cases of "cuboidal type" composed of pancreaticobiliary and/or oncocytic pattern. Pancreaticobiliary pattern showed abundantly branched papillae lined by acidophilic cuboidal cells with round nuclei, whereas oncocytic pattern was characterized by intraepithelial lumina and cribriform pattern composed of abundant oxyphilic cells with round nuclei, and these patterns overlapped frequently. There were significant differences in the clinicopathologic findings including macroscopic findings, morphometric data, mucin expression profiles (MUC2 expression in columnar type and MUC6 expression in cuboidal type), and cell proliferative activities between columnar type and cuboidal type. Patients with columnar type showed significantly poorer survival than those with cuboidal type. We concluded that columnar type and cuboidal type of MBPTs belong to different lineage of neoplasm and that they are counterparts of "intestinal type" and "pancreaticobiliary type" of pancreatic intraductal papillary-mucinous neoplasm, respectively.

Differences in mucus and K-ras mutation in relation to phenotypes of tumors of the papilla of Vater

To investigate their hypothesis that K-ras mutation is correlated with epithelial metaplastic change, the authors classified tumors of the papilla of Vater histologically and according to mucin histochemistry as either intestinal type (complete or incomplete) or pancreaticobiliary type (ordinary or metaplastic) and analyzed the tumors for K-ras mutation during tumorigenesis. Fifty-two tumors of the papilla of Vater (5 adenomas, 24 carcinomas with adenoma component, and 23 carcinomas) obtained from surgical specimens were evaluated. The mucus phenotype was analyzed with MUC1, MUC2, MUC5AC, sialyl Lewis(a) (CA 19-9), HID-AB, and ConA III stainings. K-ras codon 12 mutation was detected by nested polymerase chain reaction (PCR)-restriction fragment length polymorphism and enriched PCR-enzyme-linked minisequence assay. The presence of adenoma component and intramucosal tumor spreading in the ampulloduodenum was significantly higher in intestinal-type tumors (90%, 27 of 30 tumors, and 100%, 30 of 30 tumors, respectively) than in pancreaticobiliary-type tumors (9%, 2 of 22 tumors, and 23%, 5 of 22 tumors, respectively) (P < 0.0001). MUC2 expression was positive in intestinal-type tumors but not in pancreaticobiliary-type tumors. K-ras mutation rates for incomplete intestinal-type tumors (78%, 7 of 9) and metaplastic pancreaticobiliary-type tumors (64%, 7 of 11), which showed MUC5AC (gastric-type apomucin) expression in cytoplasm, were significantly higher than in complete intestinal-type tumors (33%, 6 of 21) and ordinary pancreaticobiliary-type tumors (18%, 2 of 11) (P = 0.01 and P = 0.03, respectively). In pancreaticobiliary-type tumors, K-ras mutation was more frequently recognized in tumors with ampullopancreatic duct tumor extension (75%, 3 of 4) than in those with ampullobiliary duct extension (0%, 0 of 6) (P = 0.01). Furthermore, sequences of K-ras codon 12 were common in 17 carcinomas with adenoma component that were analyzed for both adenoma and carcinoma. Tumors of the papilla of Vater can be classified histologically as either intestinal type or pancreaticobiliary type, and they have different features according to tumor location, association with adenoma, and MUC2 expression. Furthermore, K-ras mutation is supposed to be associated with tumors arising in the area from the ampulloduodenum to the ampullopancreatic duct, with metaplastic mucus occurring in both intestinal and pancreaticobiliary types.

P53 and p21/Waf1 protein expression and K- ras codon 12 mutation in carcinoma of the papilla of Vater

OBJECTIVE: There have been few studies on the molecular biological characteristics of carcinoma of the papilla of Vater. In this study, p53 and p21/Waf1 expression and K- ras codon 12 mutation in carcinoma of the papilla of Vater were investigated. METHODS: Thirty-seven cases of carcinoma of the papilla of Vater were studied. Macroscopically, the carcinoma was ulcerative in 15 cases and nonulcerative in 22 cases. Histologically, nine were intestinal type, 27 were pancreaticobiliary type, and one was undifferentiated. Formalin-fixed, paraffin-embedded sections were immunohistochemically stained for p53 and p21. K- ras codon 12 mutation was detected with the two-step polymerase chain reaction-restriction fragment length polymorphism method, followed by direct sequencing. RESULTS: p53 overexpression was found in 17 of 37 cases (46%) and was more frequent in the ulcerative type than in the nonulcerative type (67% vs 32%, p < 0.05). p21/Waf1 protein expression was found in 15 of 37 cases (41%), and was not correlated with that of p53. K- ras codon 12 mutation was found in 14 of 37 cases (38%), and was more frequently detected in the intestinal type than in the pancreaticobiliary type (66% vs 30%, p < 0.05). On direct sequencing, the mutations were mainly GGT to GAT (9/14) and GGT to GTT (4/14). The type of mutation did not correlate with the histological type. CONCLUSIONS: In carcinoma of the papilla of Vater, p53 overexpression may play a role in tumor ulceration. p21/Waf1 expression is induced via a p53-independent pathway. Carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms, and K- ras mutation is mainly associated with the intestinal type.

P53 and p21/Waf1 protein expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater.

There have been few studies on the molecular biological characteristics of carcinoma of the papilla of Vater. In this study, p53 and p21/Waf1 expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater were investigated. Thirty-seven cases of carcinoma of the papilla of Vater were studied. Macroscopically, the carcinoma was ulcerative in 15 cases and nonulcerative in 22 cases. Histologically, nine were intestinal type, 27 were pancreaticobiliary type, and one was undifferentiated. Formalin-fixed, paraffin-embedded sections were immunohistochemically stained for p53 and p21. K-ras codon 12 mutation was detected with the two-step polymerase chain reaction-restriction fragment length polymorphism method, followed by direct sequencing. p53 overexpression was found in 17 of 37 cases (46%) and was more frequent in the ulcerative type than in the nonulcerative type (67% vs 32%, p < 0.05). p21/Waf1 protein expression was found in 15 of 37 cases (41%), and was not correlated with that of p53. K-ras codon 12 mutation was found in 14 of 37 cases (38%), and was more frequently detected in the intestinal type than in the pancreaticobiliary type (66% vs 30%, p < 0.05). On direct sequencing, the mutations were mainly GGT to GAT (9/14) and GGT to GTT (4/14). The type of mutation did not correlate with the histological type. In carcinoma of the papilla of Vater, p53 overexpression may play a role in tumor ulceration. p21/Waf1 expression is induced via a p53-independent pathway. Carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms, and K-ras mutation is mainly associated with the intestinal type.

Different clinicopathologic findings in two histologic types of carcinoma of papilla of Vater.

The aim of this study was to investigate the differences between the clinicopathological findings in two histologic types of carcinoma of the papilla of Vater. We histologically classified carcinoma of the papilla into two types: 1) an intestinal type that resembles tubular adenocarcinoma of the stomach or colon, and 2) a pancreaticobiliary type that is characterized by papillary projections with scant fibrous cores. We examined 53 cases of resected carcinoma of the papilla. The intestinal‐type carcinomas were similar to the intestinal mucosa in that they had lysozyme‐containing, Paneth or argyrophil cells, as demonstrated by the immunohistochemically positive stainings for the anti‐lysozyme antibody. Although both the sizes of the two types of carcinomas and the age distributions of cases with the two types of carcinoma were almost the same, the prognosis of the cases with the intestinal type was much better than that of the cases with the pancreaticobiliary type. Histological lymph node metastasis was found significantly more often in the pancreaticobiliary type. This result was supported by the fact that small carcinomas of the intestinal type showed little or no invasion into the surrounding interstitium, as opposed to the pancreaticobiliary type, which had a strong infiltrative tendency. The pathogenesis of carcinoma of the papilla of Vater should be further evaluated, taking into consideration the existence of these two histologic types.