Gallbladder polyps: correlation and agreement between ultrasonographic and histopathological findings in a population with high incidence of gallbladder cancer / Pólipos da vesícula biliar: correlação e concordância entre achados ultrassonográficos e histopatológicos em uma população com alta incidência de câncer de vesícula biliar

ABSTRACT BACKGROUND: Gallbladder polyps are becoming a common finding in ultrasound. The management has to consider the potential risk of malignant lesions. AIMS: The aim of this study was to analyze the ultrasound findings in patients undergoing cholecystectomy due to gallbladder polyps and compare them for histopathological findings (HPs). METHODS: Patients with an ultrasonographic diagnosis of gallbladder polyp and who underwent cholecystectomy from 2007 to 2020 were included in the study. RESULTS: A total of 447 patients were included, of whom 58% were women. The mean age was 45±12 years. The mean size of polyps in US was 7.9±3.6 mm. Notably, 9% of polyps were greater than 10 mm, and single polyps were significantly larger than the multiple ones (p=0.003). Histopathological findings confirmed the presence of polyps in 88.4%, with a mean size of 4.8±3.4 mm. In all, 16 cases were neoplastic polyps (4.1%), 4 of them being malignancies, and all were single and larger than 10 mm. We found a significant correlation between ultrasound and histopathological findings polyp size determination (r=0.44; p<0.001). The Bland-Altman analysis obtained an overestimation of the US size of 3.26 mm. The receiver operating characteristic (ROC) curve analysis between both measures obtained an area under the receiver operating characteristic curve (AUC) of 0.77 (95%CI 0.74-0.81). Ultrasound polyps size larger than 10 mm had an odds ratio (OR) of 8.147 (95%CI 2.56-23.40) for the presence of adenoma and malignancy, with a likelihood ratio of 2.78. CONCLUSIONS: There is a positive correlation and appropriate diagnostic accuracy between ultrasound size of gallbladder polyps compared to histopathological records, with a trend to overestimate the size by about 3 mm. Neoplastic polyps are uncommon, and it correlates with size. Polyps larger than 10 mm were associated with adenoma and malignancy.

RESUMO RACIONAL: Os pólipos da vesícula biliar estão se tornando um achado comum na ultrassonografia (US). O manejo deve levar em consideração o risco de lesões malignas. OBJETIVOS: Analisar os achados da ultrassonografia em pacientes submetidos à colecistectomia por pólipos vesicais e compará-los com os achados histopatológicos. MÉTODOS: Foram revisados os prontuários médicos dos pacientes com diagnóstico ultrassonográfico de pólipo vesicular e submetidos à colecistectomia no período de 2007 a 2020. RESULTADOS: Foram incluídos no estudo 447 pacientes. A média de idade foi 45±12anos, sendo 58% mulheres. O tamanho médio dos pólipos na US foide 7,9±3,6mm. Nove por cento foram maiores que 10 mm, e os pólipos únicos encontrados foram maiores do que os múltiplos (p=0,003). A HP confirmou a presença de pólipos em 88,4%, tamanho médio 4,8±3,4mm. Dezesseis eram pólipos neoplásicos (4,1%) e quatro deles malignos, únicos e maiores que 10 mm. Foi encontrado correlação significativa entre a determinação do tamanho do pólipo ao ultrassonografia e histopatológicos (r=0,44; p<0,001). A análise de Bland-Altman obteve uma superestimação do tamanho do pólipo ao US em 3,26 mm. A análise da curva da característica de operação do receptor entre as duas medidas obteve uma área sob a curva curva da característica de operação do receptor (AUC) de 0,77 (IC95% 0,74-0,81). Pólipos ao ultrassonografia maiores que 10 mm apresentaram razão de chance (OR) de 8,147 (IC95% 2,56-23,40) para presença de adenoma e malignidade, com razão de verossimilhança de 2,78. CONCLUSÕES: Há uma correlação positiva e acurácia diagnóstica apropriada entre o tamanho dos pólipos da vesícula biliar por ultrassonografia em comparação com os achados histopatológicos, com uma tendência de superestimar o tamanho em cerca de 3 mm. Pólipos maiores que 10 mm foram associados a adenoma e malignidade.

Alterações histológicas da vesícula biliar de doentes submetidos à colecistectomia por colelitíase / Gallbladder histological alterations in patients undergoing cholecystectomy for cholelithiasis

RESUMO Objetivo: descrever os achados histológicos das vesículas biliares de pacientes submetidos à colecistectomia e avaliar a presença de fatores associados ao câncer incidental da vesícula. Métodos: estudo descritivo, transversal e observacional de 1.278 exames anatomopatológicos de vesículas biliares oriundas de colecistectomias por colelitíase e de seus respectivos laudos, realizadas no período de janeiro de 2008 a dezembro de 2017. Resultados: o achado anatomopatológico mais frequente foi a colecistite crônica, presente em 1.251 pacientes (97,8%), seguido pela colesterolose em 131 (10,2%). O câncer de vesícula foi identificado em seis pacientes, com prevalência de 0,5% nesta amostra. Houve associação significativa entre a presença de câncer e idade ≥60 anos e com a espessura da parede ≥0,3cm. Conclusão: houve baixa prevalência de câncer de vesícula na população avaliada, maior ocorrência na população idosa e associação de tumor com espessamento da parede vesicular.

ABSTRACT Objective: to describe the histological findings of the gallbladders of patients undergoing cholecystectomy and to evaluate the presence of factors associated with gallbladder incidental cancer. Methods: we conducted a descriptive, cross-sectional, observational study with 1,278 histopathological exams of gallbladders coming from cholecystectomy for cholelithiasis and of their reports, held from January 2008 to December 2017. Results: the most common pathological finding was chronic cholecystitis, present in 1,251 patients (97.8%), followed by gallbladder cholesterolosis, in 131 (10.2%). Gallbladder cancer was identified in six patients, with a prevalence of 0.5% in this sample. There was a significant association between the presence of cancer and age ≥60 years and wall thickness ≥0.3cm. Conclusion: there was low prevalence of gallbladder cancer in this population, higher occurrence in the elderly and association of the tumor with gallbladder wall thickness.

Gene expression profiling reveals upregulated FUT1 and MYBPC1 in children with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.

Obesidad y cáncer en Chile: estimación de las fracciones atribuibles poblacionales / Obesity and cancer in Chile: Estimation of population attributable fractions

Background: Obesity is a risk factor for the development of certain types of cancer. Aim: To estimate the proportion of cancers potentially attributable to obesity in men and women in Chile based on the calculation of population attributable fractions (PAF %). Material and Methods: Cancer sites studied were those where obesity is a known risk factor based on the updated World Cancer Research Fund (WCRF) analysis. Namely, colorectal, endometrium, esophagus, breast, pancreas, kidney and gallbladder cancers were analyzed. Overall and specific PAFs% were calculated for cancer sites and sex from known estimates of relative risk and national prevalence of overweight and obesity. Results: The overall estimates of cancer PAF% for obesity were approximately 20%, without differences between men and women. Highest cancer PAFs% were for endometrial (47%) in women, and esophageal (35%) and pancreatic (31%) in men. The largest sex differences in PAFs% were for gallbladder (higher in women) and colorectal (higher in men). Results are closer to those reported from developed countries (USA and United Kingdom) than those from developing countries (Brasil, China). Conclusions: In Chile about 20% of all cancers could be prevented by obesity prevention and control strategies.

Cholecystectomy for asymptomatic gallstones can reduce gall bladder cancer mortality in northern Indian women.

Gall bladder cancer (GBC) is a leading cause of cancer-related mortality in the northern parts of the Indian subcontinent. A majority of patients with GBC are middle-aged women, who normally would have substantial family responsibilities. Most patients are diagnosed with advanced cancer and are suitable for palliative care only. There is a strong association between long-standing gallstone disease and the development of GBC. Although randomized trials are lacking, prospective population-based data from low-risk and high-risk regions reveal that cholecystectomy reduces the mortality from GBC. Prophylactic cholecystectomy is recommended in populations with high incidence of GBC. The morbidity and mortality of laparoscopic cholecystectomy in uncomplicated gallstone disease is very low in India. Because of these reasons we argue that prophylactic cholecystectomy should be offered to young healthy women from high-risk regions of India whenever they are diagnosed to have asymptomatic gallstones. Simultaneously, population-based observational studies could be undertaken to generate more evidence.

Cholecystectomy in patients with asymptomatic gallstones to prevent gall bladder cancer--the case against.

Gallstones (GS) are common in northern India. GS are the most important risk factor for gall bladder cancer (GBC). Data from the West, however, indicate that the risk of GBC in persons with asymptomatic GS is very small and does not warrant prophylactic cholecystectomy. Can these recommendations be applied to northern India where incidence rates of GBC are one of the highest in the world? Not all persons with asymptomatic GS require cholecystectomy. There may, however, be a case for offering cholecystectomy to a young woman in northern India with a large GS or a gall bladder packed with GS, though there is no evidence to support this recommendation. Type of stone, tumor markers and genetic markers need to be investigated to identify those with asymptomatic GS who are at the highest risk of developing GBC so that they can selectively be offered pre-emptive cholecystectomy to prevent GBC.

Inflammatory pseudotumor of gall bladder fossa of liver.

Inflammatory pseudotumor has been described in the lung, liver and other sites, but pseudotumors of the gall bladder fossa have not been reported earlier. We report a 39-year-old woman with inflammatory pseudotumor of the liver in the gall bladder fossa that resembled carcinoma gall bladder.

Silent gallstones: a therapeutic dilemma.

Asymptomatic gall stones are defined as stones that have not caused biliary colic or other biliary symptoms. Nearly two-third of patients with gall stones are asymptomatic. Studies of the natural history of asymptomatic gall stones suggest that the cumulative probability of developing biliary colic after 10 years ranges from 15% to 25%. The incidence of other complications is much less. The operative mortality of elective cholecystectomy is <0.5% but increased mortality is seen in elderly persons (>60 year of age), particularly in those with complications such as acute cholecystitis. Most decision analysis studies do not favour prophylactic cholecystectomy for asymptomatic cholelithiasis. Nonetheless, many studies have listed certain criteria for carrying out elective cholecystectomy in asymptomatic patients. The authors, from their own experience and after reviewing the literature, propose the following criteria for cholecystectomy: life expectancy >20 years, calculi >3 cm in diameter, particularly in individuals in geographical regions with a high prevalence of gall bladder cancer or calculi <3 mm, chronically obliterated cystic duct, non-functioning gallbladder and calcified (porcelain) gallbladder. The widespread use of diagnostic abdominal ultrasonography has led to the increasing detection of clinically unsuspected gall stones. This, in turn, has given rise to a great deal of controversy regarding the optimal management of asymptomatic or 'silent' gall stones. While cholecystectomy is the undisputed gold standard treatment for symptomatic gall stones, the natural history of silent gall stones is not known well enough to recommend a definitive therapeutic strategy for such patients. The treatment options for asymptomatic or silent gall stones range from no treatment to selective cholecystectomy in at-risk group to elective cholecystectomy in all patients. There are a large number of proponents for each of these options so that each merits careful consideration. In this article, the authors examine the evidence for and against treating silent gall stones with the aim of providing more specific guidelines for the management of patients found to have asymptomatic gall stones.

Pancreatico-biliary ductal union.

A long common channel distal to the pancreaticobiliary junction is the commonest anomalous arrangement of the pancreaticobiliary ductal system and is mostly observed in patients with congenital choledochal cysts. APBDU without choledochal cyst is a high-risk condition for the development of gallbladder carcinomas. Prophylactic excision of the extrahepatic biliary system and reconstruction of the biliary tract with hepatico-jejunostomy are recommended. APBDU should always be kept in mind when a patient with a long history of abdominal pain is found to have gall bladder wall thickness even without gallstones on imaging by a CT Scan or Ultra Sound. ERCP should be performed in these patients in order to detect APBDU. This may allow early detection of carcinoma of the biliary tract. Presence of common channel may be associated with a lower incidence of gallstones. However it requires corroboration by other studies. On the other hand carcinoma of the gall bladder appears to have a close association with abnormally long common channel.

Metástasis de carcinoma mamario lobulillar a vesícula biliar: estudio con inmunohistoquímica de receptores hormonales / Mammary lobular carcinoma metastatic to the gallbladder: immunohitochemistry and estrogen/progesterone receptors study

Se presenta un caso de carcinoma mamario lobulillar que cinco años después presenta metástasis a vesícula biliar. La metástasis fue sospechada por el estudio histológico y confirmada por medio de inmunohistoquímica para receptores de estrógenos y progesterona.

Câncer da vesícula biliar / Carcinoma of the gallbladder

A incidência de câncer da vesícula biliar näo é bem conhecida, porém aumenta com a idade em ambos os sexos. A presença de cálculos é considerada um fator de risco importante para o cancer da vesícula. O diagnóstico prediz mau prognóstico com sobrevida em cinco anos, variando de 3 a 5 porcento na maioria das séries. A sobrevida média para pacientes que näo säo submetidos a ressecçäo varia entre dois e seis meses. Está claro, portanto, que o câncer da vesícula biliar é uma doença altamente letal e persistem controvérsias sobre o manuseio ideal. O presente estudo tem por objetivo revisar aspectos relacionados ao diagnóstico e tratamento do câncer da vesícula.(au)

Presentation of cancer of the gallbladder at Mayo Hospital, Lahore

Carcinoma of the gallbladder is a progressive malignant disorder with a poor and painful prognosis and high mortality rate'. Our study highlights the enhanced presentation of the carcinoma of gallbladder in patients having cholecystectomies in general ward and its possible aetiological factors in the population of Pakistan in general and Punjab in particular. Analysis of case records and histopathology reports of 100 patients who underwent cholecystectomies was done, with the objective to determine the incidence of cancer of gall bladder and highlight the possible aetiological factors. Out of a total of 100 patients 89% were females and 11% were males. The total incidence of cancer of the gall bladder in these patients was 16% the highest yet reported in literature and if was seen that it was more common in females [13%] who are relatively quite young in age. The aetiological factors held responsible were the unmistakable association of gallstones, the delayed treatment, repeated attacks of cholecystitis, multiparty, congenital abnormalities of biliary tract and infections of the biliary system. Though various modalities of treatment have been described but bulk of the above can be controlled and prevented

Carcinoma vesicular incidental durante colecistectomía laparoscópica / Incidental gallbladder cancer during laparoscopic cholecystectomy

La ultrasonografía es el método diagnóstico más utilizado para detectar la patología vesicular y la colecistectomía laparoscópica es la técnica quirúrgica más usada para su tratamiento. Se ha detectado un posible mayor riesgo de diseminación de células neoplásicas durante cirugía laparoscópica. Se presentan 14 casos con diagnóstico de cáncer vesicular diagnosticados durante la cirugía o en el postoperatorio mediante el estudio histológico. Cuatro pacientes se convierten a cirugía abierta por sospecha de cáncer y dos por razones técnicas (colecistitis aguda y fístula colecistocolónica) y en los otros ocho casos se completó el procedimiento laparoscópico. En tres de estos pacientes se comprobó metástasis precoz en el postoperatorio y correspondió a pacientes en etapa T2-T3. En el resto de los pacientes con tumores T1 se comprobó metástasis después de los dos años de operado en un caso y los otros están libres de enfermedad. Se sugiere que ante sospecha de cáncer vesicular se debiera tratar de comprobar el diagnóstico en el preoperatorio e indicar en lo posible cirugía abierta para plantear cirugía más oncológica

Carcinoma de la vesícula biliar / Gallbladder carcinoma

El cáncer primitivo de la vesícula es poco frecuente y de difícil diagnóstico. Afecta con mayor frecuencia a mujeres (75 por ciento) mayores de 65 años. Los principales factores de riesgo como el sexo femenino y la edad avanzada se vinculan con la colelitiasis (la cual se asocia entre el 45 y el 100 por ciento). Su presentación clínica no es característica y la mayoría de los pacientes concurren a la consulta con la enfermedad avanzada. El 90 por ciento apróximadamente son adenocarcinomas.

Cáncer de la vesícula biliar: expresión inmunohistoquímica de la proteína relacionada con receptor estrogénico (p29) y de la proteína inducida por estrógeno (pS2) / Cáncer of gallbladder: immunohistochemical expression of estrogen receptor related protein (p29) and estrogen induced protein (pS2)

The high frequency of gallblader cancer in women suggest a role for estrogens in its development. The aim of this study was to study the immunohistochemical expression in of p29 estrogen receptor associated protein and pS2 estrogen induced protein in 111 pathological samples of gallbladder carcinoma, coming from 88 women and 23 men, 30 metastases of gallbladder cancer, coming from 25 women and 5 men and in 25 non-tumoral gallbladders. In the latter, p29 protein was positive in 12 samples (48 percent) and pS2 in 15 cases (60 percent). p29 was positive in 40 percent and pS2 in 32 percent of tumors. p29 expressed with higher frequency in metastases than in primary tumors (57 and 31 percent respectively, p<0.02). Early tumors had a significantly lower expression of p29 than advanced tumors or than metastases. Both proteins expressed in 18 percent of samples (synchronic expression) whereas one of both proteins did so in 60 percent of cases (asynchronic expression). We conclude that most gallbladder cancer samples express proteins associated to estrogen receptor or induced by estrogens

Colelitíase e câncer primário da vesícula biliar / Cholelithiasis and primary cancer of the gallbladder

Os autores fazem uma revisäo bibliográfica e analisam a relaçäo entre colelitíase e câncer primário da vesícula biliar, baseados na experiência em 50 casos do Departamento de Cirurgia (Serviço de Cirurgia Geral do Hospital Universitário Clementino Fraga Filho) da Faculdade de Medicina da Universidade Federal do Rio de Janeiro, no período de março/1978 a junho de 1992. A idade média dos pacientes foi de 60,5 anos, predominando nas mulheres (47 casos - 94 porcento). Relatam uma estreita relaçäo entre colelitíase e câncer da vesícula biliar. Ambas as afecçöes coexistiram em 34 casos (68 porcento) dos pacientes, levando à aprovaçäo da hipótese de que a colelitíase constitui o fator principal na etiopatogenia do câncer vesicular, portanto torna-se imperativo nÝo procrastinar o tratamento cirúrgico da litíase da vesícula biliar.