Tumor budding and dedifferentiation in gallbladder carcinoma: potential for the prognostic factors in T2 lesions.
ABSTRACT Dedifferentiation (DD) is often encountered in gallbladder carcinoma (GBC) and poor prognosis with budding (BD) has been reported for other malignancies. However, the features of DD and BD in GBC remain unclear. The purpose of this study was to clarify the features and prognostic potential of DD and BD in GBC. A total of 80 patients with GBC (excluding intramucosal cancer) were enrolled. DD was histopathologically evaluated as tumors in which the grade of the invasive front is higher than the grade at the surface. BD was defined as an isolated single cancer cell or a cluster of fewer than five cancer cells at the invasive front. Of the 80 patients, 47 (58.8%) were positive for BD and 33 (41.2%) were positive for DD. Both BD and DD correlated significantly with disease-specific survival in univariate analysis (P < 0.0001 and P = 0.0013, respectively), but they were not identified as independent prognostic factors by multivariate analysis. In univariate analysis according to T stage, both BD and DD correlated significantly with survival in patients with T2 (n = 32) tumor (P = 0.0011 and P = 0.0018, respectively), whereas no prognostic impact in patients with T1b (n = 8), T3 (n = 34), or T4 (n = 6) tumor. Both DD and BD are frequently observed in GBC and reflect prognosis, particularly for T2 lesions. Therefore, the status of BD and DD should be taken into consideration in pathological reports on GBC.
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ABSTRACT: The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade, 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade and 0.52 for Grade. Grade has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC.The American journal of surgical pathology 02/2014; 38(2):197-204. · 4.59 Impact Factor
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ABSTRACT: Gallbladder cancer (GBC) shows a marked geographical variation in its incidence. Middle-aged and elderly women are more commonly affected. Risk factors for its development include the presence of gallstones, chronic infection and pancreaticobiliary maljunction. Controversy remains in regard to the theory of carcinogenesis from adenomyomatosis, porcelain gallbladder and adenoma of the gallbladder. The surgical strategy and prognosis after surgery for GBC differ strikingly according to T-stage. Discrimination of favorable cases, particularly T2 or T3 lesions, is useful for the selection of surgical strategies for individual patients. Although many candidate factors predicting disease progression, such as depth of subserosal invasion, horizontal tumor spread, tumor budding, dedifferentiation, Ki-67 labeling index, p53 nuclear expression, CD8+ tumor-infiltrating lymphocytes, mitotic counts, Laminin-5-gamma-2 chain, hypoxia-inducible factor-1a, cyclooxygenase-2 and the Hedgehog signaling pathway have been investigated, useful prognostic makers or factors have not been established. As GBC is often discovered incidentally after routine cholecystectomy and accurate preoperative diagnosis is difficult, close mutual cooperation between surgeons and pathologists is essential for developing a rational surgical strategy for GBC.World journal of clinical cases. 10/2014; 2(10):515-21.
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ABSTRACT: INTRODUCTION: The 5-year survival of patients with gallbladder cancer remains low. However, patients can be stratified into prognostic categories based on established factors such as T, N, and R status. New concepts regarding prognostic significance of lymph node disease, the importance of residual gallbladder fossa disease, and the gravity of presentation with jaundice are reviewed. In addition, a number of new prognostic factors proposed in recent years are considered. METHODS: PubMed was searched for "gallbladder cancer" with builder "date-completion" 2008 to present. A total of 1,490 articles were screened from which 168 were retrieved. From this, 40 articles specifically related to prognosis form the basis for this review. DISCUSSION: Key factors of prognostic significance remain T and N stage and R0 resection. Residual disease either in the gallbladder fossa, lymph nodes, or cystic duct margin dictates hepatectomy, lymphadenectomy and bile duct resection, respectively. Adequate lymphadenectomy requires removal of six nodes, and hepatectomy must be sufficient to achieve R0. Subtleties regarding lymph node ratio, significance of pathological features such as dedifferentiation, and budding may hold value for stratifying patients with early stage disease, but require further investigation.Digestive Diseases and Sciences 05/2013; · 2.26 Impact Factor