Genomic characterization of co-existing neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer.

Gallbladder carcinoma is the most common cancer of the biliary tract with dismal survival largely due to delayed diagnosis. Biliary tract intraepithelial neoplasia (BilIN) is the common benign tumor that is suspected to be precancerous lesions. However, the genetic and evolutionary relationships between BilIN and carcinoma remain unclear. Here we perform whole-exome sequencing of coexisting low-grade BilIN (adenoma), high-grade BilIN, and carcinoma lesions, and normal tissues from the same patients. We identify aging as a major factor contributing to accumulated mutations and a critical role of CTNNB1 mutations in these tumors. We reveal two distinct carcinoma evolutionary paths: carcinoma can either diverge earlier and evolve more independently or form through the classic adenoma/dysplasia-carcinoma sequence model. Our analysis suggests that extensive loss-of-heterozygosity and mutation events in the initial stage tend to result in a cancerous niche, leading to the subsequent BilIN-independent path. These results reframes our understanding of tumor transformation and the evolutionary trajectory of carcinogenesis in the gallbladder, laying a foundation for the early diagnosis and effective treatment of gallbladder cancer.

Intracholecystic tubular non-mucinous neoplasm (ICTN) of the gallbladder: a clinicopathologically distinct, invasion-resistant entity.

Preinvasive tumor-forming gallbladder neoplasms that are composed of small, non-mucinous tubules with complex architecture remain a poorly characterized group. Here, we evaluated the clinicopathological characteristics of this entity. Twenty-eight examples were analyzed. Tumors were invariably pedunculated polyps with thin stalks, often presented as loosely attached intraluminal nodules, with cauliflower architecture (akin to cholesterol polyps) comprised of compact, back-to-back acinar-like, small tubular units with minimal/no cytoplasm showing variable complexity, creating a picture distinct from the other tubular type dysplasia in the gallbladder. Their limited stroma showed distinctive amorphous amyloid-like hyalinization (39%). While some had round nuclei with single prominent nucleoli, others exhibited slightly more elongated nuclei with washed out chromatin reminiscent of papillary thyroid carcinoma. Squamoid/meningothelial-like morules (71%) and subtle neuroendocrine cell clusters (39%) were frequent. The level of cytoarchitectural atypia qualified as high-grade dysplasia (HGD) in all cases, but none were invasive. The background mucosa showed no dysplasia, but cholesterolosis. The majority (n = 8/12) showed diffuse MUC6 expression and lacked MUC5AC expression. Based on these observations, 635 gallbladder carcinomas were re-analyzed for residual/adjacent lesions with entity-defining characteristics disclosed here, and none could be identified. Preinvasive tubular non-mucinous neoplasm of the gallbladder, which we propose to classify as intracholecystic tubular non-mucinous neoplasm, is a clinicopathologically discrete entity, which tends to occur in uninjured gallbladders and in association with cholesterol polyps. By being tubular, non-mucinous and MUC6-positive, it is akin to intraductal tubulopapillary neoplasms of pancreatobiliary tract, but it is also different in many other aspects. Although their cytoarchitectural complexity warrants an HGD/carcinoma classification, they do not show invasion and their distinct characteristics warrant their separate classification.

Trends of gallbladder cancer incidence, mortality, and diagnostic approach in urban Shanghai between 1973 and 2009.

PURPOSE: To describe and interpret secular time trends in gallbladder cancer (GBC) incidence, mortality, and diagnostic approach using 37 years of cancer registry data in urban Shanghai. METHODS: Data on registration of GBC in urban Shanghai during 1973 and 2009 were collected by the Shanghai Cancer Registry. To describe time trends and to identify specific time points when significant changes occurred, we used joinpoint regression analysis. RESULTS: The age-standardized rates (ASRs) of incidence increased from 1.1/100,000 (1973-1975) to 2.9/100,000 (2006-2009) in men and from 1.7/100,000 (1973-1975) to 3.9/100,000 (2006-2009) in women. ASRs of incidence increased significantly with estimated annual percent changes (EAPCs) of 2.8% in men and 2.5% in women. The mortality trends increased significantly, with EAPCs of 2.8% in men and 2.5% in women. The increasing incidence and mortality rates were primarily observed in men ⩾60 years of age and in women ⩾70 years of age. Notable downward trends in incidence and mortality were identified among women age 60-69 years over the last decade. The percentage of GBC diagnosed by pathology increased steadily over the years while the percentage of GBC diagnosed by imaging, surgery, and biochemistry sharply increased from 1987 onwards. CONCLUSIONS: Thirty-seven years of cancer registry data document a tremendous increase in incidence/mortality and a slight decline in incidence/mortality over the last decades for GBC, especially among women, in Shanghai. The development of diagnostic approaches and aging population may play important roles.

Intracholecystic Papillary-Tubular Neoplasms (ICPN) of the Gallbladder: A Short Review of Literature.

Increasing use of radiographic studies of the hepatobiliary system has led to a growing diagnostic rate of many asymptomatic polyps of the gallbladder which would have gone undiagnosed otherwise. Neoplastic polyps of the gallbladder are 5% of the total number of polyps of this organ. However, due to their malignant potential, the correct diagnosis and classification become of crucial importance. Lack of unified terminology and reporting criteria have led to a limited body of scientific evidence regarding their classification and management. Therefore in 2012 the novel and unified terminology, Intracholecystic papillary-tubular neoplasm was proposed for these lesions when they measure >1 cm. Smaller lesions are usually of no adverse outcome. Intracholecystic papillary-tubular neoplasms show 5 histologic subcategories: (1) pyloric gland subtype which is the most commonly encountered neoplastic polyp in the gallbladder and has the lowest rate of harboring high-grade dysplasia and invasive carcinoma and it shows diffuse cytoplasmic positivity with MUC6, a specific pyloric marker; (2) biliary subtype which is diffusely positive for MUC1 and has the highest risk of concurrent adenocarcinoma; (3) gastric foveolar subtype which is MUC5AC positive in all the cases. Most of the cases in this category are associated with some extent of high-grade dysplasia; (4) intestinal subtype which is the easiest one to recognize as it mimics tubular adenomas of the gastrointestinal tract and show MUC2 and CDX2 positivity; and (5) oncocytic subtype which is the least common.

Cystic duct cancer: Should it be deemed as a type of gallbladder cancer?

BACKGROUND: According to the latest American Joint Committee on Cancer and Union for International Cancer Control manuals, cystic duct cancer (CC) is categorized as a type of gallbladder cancer (GC), which has the worst prognosis among all types of biliary cancers. We hypothesized that this categorization could be verified by using taxonomic methods. AIM: To investigate the categorization of CC based on population-level data. METHODS: Cases of biliary cancers were identified from the Surveillance, Epidemiology, and End Results 18 registries database. Together with routinely used statistical methods, three taxonomic methods, including Fisher's discriminant, binary logistics and artificial neuron network (ANN) models, were used to clarify the categorizing problem of CC. RESULTS: The T staging system of perihilar cholangiocarcinoma [a type of extrahepatic cholangiocarcinoma (EC)] better discriminated CC prognosis than that of GC. After adjusting other covariates, the hazard ratio of CC tended to be closer to that of EC, although not reaching statistical significance. To differentiate EC from GC, three taxonomic models were built and all showed good accuracies. The ANN model had an area under the receiver operating characteristic curve of 0.902. Using the three models, the majority (75.0%-77.8%) of CC cases were categorized as EC. CONCLUSION: Our study suggested that CC should be categorized as a type of EC, not GC. Aggressive surgical attitude might be considered in CC cases, to see whether long-term prognosis could be immensely improved like the situation in EC.

[Tumor grading of the hepatobiliary system]. / Grading der Tumoren des hepatobiliären Systems.

Tumors of the liver, intrahepatic and extrahepatic bile ducts as well as the gallbladder are very heterogeneous and show different biological behavior. The 4­stage (i.e. well, moderately, poorly and undifferentiated) grading system for hepatocellular carcinoma proposed by the WHO takes tumor size and architecture as well as the extent of cell and nuclear pleomorphism into account. In addition, the WHO defines some special forms of hepatocellular carcinoma. For carcinomas of intrahepatic bile ducts the WHO provides a 3­stage (well, moderately and poorly differentiated) grading system, which is based on architectural and cytological changes. At this localization there are also additional special histological forms that have to be dealt with outside the grading system described. The WHO proposes a 3­stage (well, moderately and poorly differentiated) grading system for carcinomas of the extrahepatic bile ducts and the gallbladder, which considers the proportion of glands contained within the adenocarcinoma. Similar to cancers of the liver and intrahepatic bile ducts there are also numerous special histological forms, which are explained in this article.

Cytomorphology of neuroendocrine tumours of the gallbladder.

OBJECTIVE: Gallbladder neuroendocrine tumours (GB-NETs) are rare and account for 0.5% of all NETs. GB-NETs have an aggressive behaviour, which depends on the tumour grade. The cytomorphological spectrum of these tumours has never been described in detail. The present study evaluates the cytological features of GB-NETs and grades them according to the World Health Organization (WHO) classification. Furthermore, the expression of thyroid transcription factor-1 (TTF-1) has not been investigated previously in GB-NETs, although found in a subset of extrapulmonary NETs. METHODS: Twenty cases of GB-NET among 875 gallbladder carcinomas diagnosed by ultrasound-guided fine needle aspiration cytology (FNAC) over a period of nearly 4 years were studied. The following parameters were evaluated: architectural pattern, nuclear chromatin, nucleoli, mitoses, necrosis, moulding, apoptosis and smudge cells. Cases were categorized into well-differentiated (grades 1 and 2), small cell carcinoma (SCC) (grade 3) and mixed adenoneuroendocrine carcinoma. Nuclear positivity for TTF-1 was considered as positive. RESULTS: Morphologically, tumour cells were mainly arranged in rosettes in the well-differentiated category; sudden anisonucleosis and rare nuclear moulding with or without mitotic figures were other features. Eleven cases of SCC showed prominent nuclear moulding with frequent smudge cells, mitoses, apoptosis and necrosis. Three mixed adenoneuroendocrine carcinomas showed papillary fragments and an acinar arrangement of tumour cells. Four of the nine SCCs in which TTF-1 was evaluated on de-stained smears showed nuclear positivity. Histopathology was available in two SCCs and showed morphology similar to FNAC. CONCLUSION: Cytology plays an important role in the diagnosis of GB-NETs for appropriate subtype characterization, which is necessary for the prognostication of these tumours. TTF-1 may not be used for the differentiation of gallbladder SCCs from pulmonary SCCs.

Do histopathologic findings improve by increasing the sample size in cholecystectomies?

BACKGROUND: Gallbladder diseases present with cholelithiasis in a wide spectrum of adenomas and cancers. Two or three specimens are sampled in cholecystectomies in routine pathology practice. The aim of this study was to investigate the increase in frequency of histologic alterations in cholecystectomies, particularly precancerous lesions, by increasing the sample size to understand the carcinoma pathway. METHODS: Cholecystectomies of 432 patients with pathology records and materials from two medical centers were collected, and two groups were created. Initial data with two or three samples were allocated to Group 1 and the new six samples with the initial ones were allocated to Group 2. Hematoxylin and eosin (HandE) sections were examined for histopathologic alterations, and periodic acid-Schiff (PAS) Alcian blue (pH 2.5) and high iron diamine (pH 2.5) stains were used to signify the mucin profile in case of metaplasias. For the comparison of findings, non-parametric tests, McNemar's tests, chi-squared tests and Fisher's exact test were performed. RESULTS: Of the 432 patients, 308 (71.3%) patients were female and 124 (28.7%) patients were male. The mean age of patients was 47.9±14.6 years. Cholesterolosis was observed in 95 (22%) patients in Group 1 and 108 (25%) patients in Group 2. Gallstones were detected in 255 (59%) of the cholecystectomies. There was a significant difference between Group 1 and Group 2 by increasing the sample size when we compared cholesterolosis, metaplasia and polyps (P<0.05). Cholecystitis and dysplasia rates were the same in both of the groups. There was no cancer determined. CONCLUSION: Increasing the sample size in cholecystectomies increased the diagnosis of some histologic alterations, but further studies with a larger number of samples over a longer period time might increase the ability to determine precancerous lesions and concomitants.

Comparison of the sixth and seventh editions of the AJCC TNM classification for gallbladder cancer.

BACKGROUND: This study aimed to compare the seventh edition of the tumor node metastasis (TNM) staging system to the sixth edition to validate its usefulness in predicting prognosis for gallbladder cancer. METHODS: Gallbladder cancer patients were staged according to both the sixth and seventh editions of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: A total of 142 patients underwent cholecystectomy for gallbladder cancer. According to the seventh edition, the survival time of N1 and N2 was different (P = 0.006), and the survival difference between N0 and N1 became significant after excluding cases with no lymph node dissection (P = 0.035). The -2 log likelihoods of the sixth and seventh edition TNM stages were 216.282 and 217.460, respectively, suggesting non-superiority of the seventh edition. Excluding cases with no lymph node dissection resulted in a lower -2 log likelihood score for both editions (sixth, 157.002; seventh, 158.758). CONCLUSIONS: Sufficient lymph node dissection allows better prognostic stratification by application of the AJCC staging system. Even though the new N stage of the seventh edition showed some improvement in predicting prognosis, the overall performance of the seventh edition was not much better than the sixth. Further improvement is needed in the gallbladder cancer staging system.

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.

Cáncer de vesícula biliar según tipo histológico y clasificación TNM en Arequipa, Perú / Gallbladder cancer according to its histological type and TNM staging, Arequipa, Perú

Introducción: El cáncer de vesícula biliar está aumentando su incidencia, especialmente en grupos étnicos específicos, como el indígena americano. La utilización del tipo histológico y estadiaje TNM son criterios útiles para diseñar un tratamiento apropiado y pronosticar la sobrevida en los pacientes. Objetivos: Determinar el tipo histológico de cáncer de vesícula biliar y el estadiaje de presentación según la clasificación TNM. Material y Métodos: Es un estudio de tipo transversal y analítico. Se evaluaron 73 pacientes con diagnóstico anatomopatológico de cáncer de vesícula biliar, en los cuales se determina el tipo histológico más frecuente y la pertenencia a un estadío de la clasificación TNM. El estudio se llevó a cabo en el Hospital Honorio Delgado de Arequipa, durante el periodo temporal de enero 2005 hasta junio 2010. Resultados: El tipo histológico más frecuente fue el adenocarcinoma con 71,2%. Asimismo el subtipo histológico más común fue el adenocarcinoma tubular con 42,3% de casos. El estadío TNM más frecuente fue el IIB con 35,5% de casos, seguido por el IVcon 24,6%. Conclusión: En el Hospital Honorio Delgado de Arequipa el tipo histológico de cáncer de vesícula biliar más frecuente entre los años 2005-2010 es el adenocarcinoma tubular. Asimismo los pacientes se mostraban al momento del diagnóstico en el estadío IIB con mayor frecuencia.

Introduction: Gallbladder cancer is increasing in specific ethnic groups such as the native American. The use of the TNM staging is a useful approach to design appropriate treatment and predict a reliable survival in patients. Objectives: To determine the histológico type of gallbladder cancer and the staging of presentation according to the classification TNM. Material and Methods: This was across-sectional and analytical study. Assessed 73 patients with diagnosis of gallbladder cancer histopathological, which determines the histological type more frequent and belonging to a stage of the TNM classification. The study was realized in the Hospital Honorio Delgado of Arequipa, Perú, the temporary period January 2005 to June 2010. Results: The most frequent histological type was adenocarcinoma 71.2%. The most common histological subtype was tubularadenocarcinoma with 42.3% of cases. The TNM stage more frequent was the IIB with 35.5% of cases, followed by the IV with 24.6%. Conclusion: In Hospital Honorio Delgado of Arequipa histological type of gallbladder cancer more frequent among the years 2005 - 2010 is tubular adenocarcinoma. Also the patients showed at the time of thediagnosis in stage IIB with greater frequency.

Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas.

The information in the literature on squamous cell and adenosquamous carcinomas of the gallbladder is highly limited. In this study, 606 resected invasive gallbladder carcinoma cases were analyzed. Squamous differentiation was identified in 41 cases (7%). Those without any identifiable glandular-type invasive component were classified as pure squamous cell carcinomas (8 cases) and those with the squamous component constituting 25-99% of the tumors were classified as adenosquamous carcinomas (26 cases) and included into the analysis. The remaining 7 that had <25% squamous component were classified as adenocarcinoma with focal squamous change and excluded. The clinicopathological characteristics of adenosquamous carcinoma/squamous cell carcinomas were documented and contrasted with that of ordinary gallbladder adenocarcinomas. The average patient age was 65 years (range 26-81); female/male ratio, 3.8. In only 13%, there was a preoperative clinical suspicion of malignancy. Grossly, 58% presented as thickening and hardening of the wall and 6% were polypoid. In 12%, mucosa adjacent to the tumor revealed squamous metaplasia. All pure squamous cell carcinomas had prominent keratinization. Giant cells and tumor-infiltrating eosinophils were observed in 29 and 51% of the squamous cell carcinomas/adenosquamous carcinomas versus 10% (P=0.02) and 6% (P=0.001) in gallbladder adenocarcinomas, respectively. All but three cases had 'advanced' (pT2 and above) carcinomas. Follow-up was available in 31 patients: 25 died of disease (median=5 months, range 0-20), and 6 were alive (median=64 months, range 5-112.5). The survival of patients with squamous cell carcinomas/adenosquamous carcinomas was significantly worse than that of gallbladder adenocarcinomas (P=0.003), and this adverse prognosis persisted when compared with stage-matched advanced gallbladder adenocarcinoma cases (median=11.4 months, P=0.01). In conclusion, squamous differentiation was noted in 7% of gallbladder carcinomas. The incidence of adenosquamous carcinoma (defined as 25-99% of the tumor being squamous) was 4%, and that of pure squamous cell carcinoma (without any documented invasive glandular component) was 1%. Pure squamous cell carcinomas often showed prominent keratinization. The overall prognosis of adenosquamous carcinoma/squamous cell carcinoma appears to be even worse than that of ordinary adenocarcinomas. Most patients died within a few months; however, those few who were alive beyond 2 years in this cohort experienced long-term survival.

[The current TNM system for gastrointestinal tumors part II]. / Aktuelles TNM-System der gastrointestinalen Tumoren Teil II.

Entirely new classifications are those for gastrointestinal stromal tumours, gastrointestinal neuroendocrine tumours, intrahepatic cholangiocarcinoma and perihilar extrahepatic bile duct carcinomas. Major and praxis-relevant alterations concern colorectal tumours and include new classifications of carcinomas and carcinoids of the appendix. Minor alterations are seen in the classification of hepatocellular carcinomas. No changes were made for tumours of the anal canal, the gallbladder (excluding the inclusion of tumours of the cystic duct) and tumours of the pancreas and the ampulla of Vater.

Neoplasias benignas de vesicula biliar, un paradigma nacional / Benign neoplasms of gallbladder, a national paradigm

INTRODUCCION: En Chile, la indicación quirúrgica más frecuente corresponde a patología vesicular biliar, donde es posible encontrar tumores benignos y malignos, de morfología similar, lo que dificulta el diagnóstico diferencial. OBJETIVO: Caracterizar los hallazgos anatomopatológicos referentes a lesiones tumorales benignas de vesícula encontradas por colecistectomía. MATERIAL Y METODOS: Estudio observacional analítico, se analizaron retrospectivamente 5.699 biopsias correspondientes a todas las vesículas recibidas en Laboratorio de Anatomía Patológica de Concepción (LAP) durante los años 1998 y 2007. Estudio extrapolable al total de población chilena colecistectomizada anualmente con un 95 por ciento de confiabilidad y 80 por ciento de poder (p=0.05). RESULTADOS: 4.730 (83 por ciento) correspondieron a mujeres, conrelación hombre/mujer de 1: 4.9 (p<0.001). 279 vesículas presentaron lesiones tumorales benignas (4.9 por ciento). Las lesiones predominantes fueron las pseudotumorales (92.8 por ciento). La alteración más frecuente correspondió a pólipo (45.8 por ciento), en su mayoría de colesterol (53.1 por ciento) y múltiples (86.7 por ciento); seguido por la hiperplasia adenomiomatosa (41.2 por ciento). Dentro de los tumores epiteliales solo se encontraron adenomas (6 por ciento), manifestándose en su totalidad como pólipo acompañado en un 47 por ciento de displasia y en solo un caso de carcinoma in situ. De las lesiones de aspecto polipoídeo, la mayoría fueron lesiones pseudotumorales (87.1 por ciento), seguidas por adenomas (10.4 por ciento) y un 2.5 por ciento de cáncer. CONCLUSIONES: Destacan la baja frecuencia de lesiones tumorales benignas en el grupo estudiado, con incidencias menores a las internacionales para pólipos e hiperplasia adenomiomatosa, pero más altas que las reportadas para adenomas. La aparición de cáncer manifestado como pólipo de pequeño tamaño suma importancia al diagnóstico diferencial de estas lesiones en dicha localización.

BACKGROUND: In Chile, the most common surgical indication is the pathology of the gallbladder, where is likely to find benign and malignant lesions of similar morphology, making it difficult the differential diagnosis. OBJETIVE: To characterize the anatomo pathological findings of benign lesions of the gallbladder encountered by cholecystectomy. MATERIAL AND METHODS: Observational analytic study, 5.699 biopsies were hindsightanalyzed for all the gallbladders received at the Pathology Laboratory of Concepción (LAP) from 1998 to 2007. The study can be extrapolated to all the chilean cholecystectomized population with a reliability of 95 percent and 80 percent of power (p=0.05). RESULTS: 4,730 (83 percent) were women with a male/female ratio of 1: 4.9 (p<0.001). 279 gallbladders showed benign tumoral lesions (4.9 percent). The pseudotumoral lesions were predominant (92.8 percent). The most frequent alteration was polyp (45.8 percent), mostly of cholesterol (53.1 percent) and multiple (86.7 percent), followed by adenomatous hyperplasia (41.2 percent). Within the epithelial tumors, only adenomas were found (6 percent), expressed entirety as polyps, 47 percent with accompanying dysplasia and in just a case of carcinoma in situ. Of the polypoid lesions, most were pseudotumoral (87.1 percent), followed by adenomas (10.4 percent) and 2.5 percent of cancer. CONCLUTIONS: It is highlighting the low frequency of benign tumoral lesions in the studied group, with lower incidences than internationaly reported for polyps and adenomatous hyperplasia, but higher for adenomas. The emergence of cancer manifested as polyp greats the importance to the differential diagnosis of these injuries in that location.

Prediction of prognosis in gallbladder carcinoma by CD147 and MMP-2 immunohistochemistry.

AIM: To investigate whether the presence of CD147 and MMP-2 in cancerous gallbladder tissues might help us to predict the patients' prognosis. METHODS: Tissue samples from 168 patients with gallbladder carcinomas and 37 patients with chronic cholecystitis were stained with anti-CD147 and anti-MMP-2 antibodies for immunohistochemical analysis. Then, the association of their expression with clinicopathologic characteristics and 108 patients' prognosis was analyzed. RESULTS: CD147 and MMP-2 were detected mainly in cancerous tissues, but also expressed in some chronic cholecystitis patients. Out of 168 patients with gallbladder carcinoma 121 (72.02%) and 136 (80.95%) patients showed CD147 and MMP-2 positive expression, whereas the 37 patients with chronic cholecystitis only 5 (13.51%) and 3 (8.11%) patients expressed them, respectively. Pathologic findings demonstrated that the intensity of CD147 and MMP-2 staining in cancerous tissues was associated significantly with histological types (P = 0.03), distant metastasis (P < 0.01), and Nevin stages (P = 0.02) of gallbladder carcinomas. Using a proportional hazard model, the survival rate of the patients with CD147+/MMP-2+ expression was the lowest (P < 0.01), and including information on CD147 and MMP-2 staining patterns within cancerous tissues along with clinical cancer staging may improve the accuracy of predicting patients' prognosis. CONCLUSION: The results suggest that the expression of CD147 and MMP-2 may be an important feature of gallbladder carcinomas. The detection of these two markers combined with cancerous staging may increase the ability of investigators to predict the prognosis of patients with gallbladder carcinomas.

A new scoring system for gallbladder cancer (aiding treatment algorithm): an analysis of 335 patients.

BACKGROUND: There is currently no preoperative staging/scoring system available for gallbladder cancer. Unfortunately, in gallbladder cancer, patients manifest advanced stages of the disease. There is need for a methodology that can aid accurate preoperative staging and the subsequent treatment algorithm. We thus sought to validate a new scoring system, the Tata Memorial Hospital Staging System (TMHSS), for gallbladder cancer. METHODS: TMHSS is based on the cumulative impact of specific features of computed tomographic scan, presence or absence of jaundice, and serum cancer antigen 19-9 levels. This scoring system was first proposed in 2004. Patients with gallbladder cancer were enrolled onto the testing sample for TMHSS to ascertain its validity. A total of 335 consecutive patients with gallbladder cancer who sought care at the Tata Memorial Hospital between May 1, 2005, and December 31, 2006, were studied. Treatment was suggested on the basis of current existing protocols. Each patient was assigned a TMHSS score, and the treatment decision taken was compared with the algorithm generated for each individual score. Concurrence of the decision taken with the score generated algorithm was tested by the Kendall tau-b test. RESULTS: Ordinal-by-ordinal analysis of the value of the test was .75, which showed excellent concurrence and a statistically significant P value (P < .0001). CONCLUSION: TMHSS provides an excellent correlative treatment plan for patients with gallbladder cancer. It has the potential to reduce unnecessary surgical explorations and to direct patients to the ideal treatment strategy, thereby offering a degree of prognostication.

Surgical strategy for advanced gallbladder carcinoma according to invasive depth of the tumor.

BACKGROUND/AIMS: The postoperative survival rate is dependent on the invasive depth of the gallbladder carcinoma. When this carcinoma has invaded beyond the subserosal layer, lymph node and adjacent organ involvement is found in a large number of patients, and long-term survival cannot be achieved. The aim of this study is to establish a surgical strategy for advanced gallbladder carcinoma according to the invasive depth. METHODOLOGY: A retrospective analysis was conducted of 44 patients with the gallblader carcinoma. The invasive depth was histologically defined by the Japanese Society of Biliary Surgery system as follows. (hinf0: within muscle layer, hinf1a: subserosal layer, hinf1b: hepatic infiltration within 5 mm, hinf2.3: hepatic infiltration more than 5 mm) RESULTS: Wedge resection of the gallbladder bed was performed in 5 cases, and in four of the five patients (80%), intrahepatic recurrence occurred within 6 months. S4a+S5 subsegmentectomy of the liver is performed in 11 cases (hinf0,1a/b:n=5, hinf2,3:n=6) and the postoperative survival rate was significantly better in cases of hinf0,1a/b (p<0.05). In cases of hinf2,3 an extended hepatic lobectomy (n=5) tended to obtain a better survival rate, compared with S4a+S5 subsegmentectomy (n=6)(p=0.13). CONCLUSIONS: S4a+S5 subsegmentectomy of the liver is a standard operation for GB carcinoma with subserosal invasion.