A Dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the Degree of Masters of Medicine in the branch of General Surgery, Johannesburg 2018 / Gallbladder cancer (GBCa) has a dismal prognosis, with poor short-term and long-term outcomes, even following surgery and all current adjuvant therapies. Routine submission of all postcholecystectomy gallbladder specimens (GBS) for histopathology to detect cancer is standard practice at all University of the Witwatersrand (Wits) hospitals, as at many institutions globally. The cost-ineffectiveness associated with the results adding no value to overall patient care is debated. The low reported rate of GBCa – between 0.27% and 3.6% of all GBS –prompted advocacy for selective GBS submission based on demographic, clinical, and macroscopic features as indications for evaluation, considered logical from a practical and cost-effective perspective, especially in resource-constrained healthcare systems. Retrospective analysis of histopathology reports of 1194 adult GBS was performed. The histopathology findings of GBS submitted to the National Health Laboratory Service (NHLS) between January 1, 2010 and December 31, 2012 from three Wits hospitals were entered into spreadsheets, categorised into malignant, premalignant, and benign, and analysed, allowing determination of the profile of gallbladder disease. The frequency of GBCa determined, multivariate analysis of demographic and diagnostic subtypes was used to identify associations or risk factors for GBCa. The mean age of adult patients was 46.62 years (standard deviation, 17.81; range, 34-87); 925 (77.5%) female and 269 (22.5%) male. Benign diseases were documented in 1159 (97.1%) adult GBS with acute and chronic cholecystitis, in 705 (59.04%) and 401 (33.58%) specimens, respectively, representing 92.6% of total GBS. Forty-five (4.43%) and 33 (2.7%) specimens were ‘normal’ and benign tumours, respectively. GBCa and premalignant diseases composed 20 (1.67%) and 8 (0.7%) specimens, respectively with incidental GBCa found in 7 (0.59%) of 20 GBCa cases. Surgeon’s macroscopic appearance assessments were inadequately documented, so the value of this practice could not be determined. A small number (48) of GBS were obtained from paediatric patients <18 years of age where-in acute cholecystitis was most commonly diagnosed, no malignancies but one case of cytological atypia detected. The GBS disease profile and incidence of GBCa in this study were consistent with reports from international literature. No single demographic or clinical factor was identified to guide the surgeon in being more selective in submitting GBS. However, with only 7 cases of incidental GBCa in 1194 adult specimens, the routine submission of all GBS specimens to rule out malignancy cannot be justified and is not cost-effective. / XL2018

名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成7年3月27日 金子健一朗氏の博士論文として提出された

INTRODUÇÃO: O câncer da vesícula biliar é a lesão maligna mais comum da árvore biliar e pouco se sabe sobre a sua carcinogênese. O possível caráter pré-neoplásico das alterações histológicas da vesícula biliar vem sendo estudado recentemente. O objetivo deste estudo foi identificar e quantificar as alterações histológicas da vesícula biliar no nosso meio e correlacioná-las com dados clínicos, e correlacionar as alterações metaplásicas, em separado, com as demais alterações encontradas. MÉTODOS: Neste estudo retrospectivo realizado entre novembro de 1999 a dezembro de 2006, foram avaliados 1.689 prontuários de doentes submetidos a colecistectomia laparoscópica por colecistolitíase. Os doentes foram divididos em relação à idade em doentes com até 60 anos e com mais de 60 anos. Em relação ao tempo de sintomas antes da cirurgia foram agrupados em doentes sem sintomas, doentes com sintomas até 1 ano, e doentes com sintomas por mais de 1 ano antes da cirurgia. Em relação ao tamanho e número dos cálculos foram agrupados em doentes com cálculos de até 10 mm, e aqueles com cálculos maiores que 10 mm, e em doentes com cálculos únicos ou múltiplos. RESULTADOS: Eram mulheres 1.238 doentes (73,3%) e 451 eram homens (26,7%). Apresentaram idade de até 60 anos 1.192 doentes (70,6%) e 497 (29,4%) apresentaram mais de 60 anos. Apresentaram cálculos menores que 10 mm 1.319 doentes (78,1%) e 370 doentes (21,9%) apresentaram cálculos maiores que 10 mm. Foi observado inflamação aguda em 174 doentes (10,3%), gangrena em 23 (1,4%), abscesso em 8 (0,4%), colesterolose em 305 (18,1%), adenomiomatose em 40 (2,4%), colecistite xantogranulomatosa em 29 (1,7%), fibrose em 12 (0,7%), escleroatrofia em 20 (1,2%), pólipo hiperplásico em 3 (0,2%), pólipo de colesterol em 17 (1,0%), metaplasia pilórica em 72 (4,3%), metaplasia intestinal em 18 (1,1%), displasia em 4 (0,2%), câncer em 2 (0,1%). Não foram observados pólipos adenomatosos. CONCLUSÕES: O sexo masculino apresenta maior freqüência de complicações inflamatórias que o feminino. Não há relação entre o tempo de sintomas e uma maior ocorrência das alterações histológicas estudadas, excetuando-se a colecistite xantogranulomatosa. Nos doentes idosos há maior ocorrência de adenomiomatose, gangrena e abscesso. Há aumento progressivo de idade para a ocorrência de metaplasia pilórica, metaplasia intestinal, displasia e câncer. O tamanho dos cálculos não guarda relação com a ocorrência das alterações estudadas, exceto para colecistite aguda que se associou com cálculos pequenos e múltiplos. Há associação entre a ocorrência de metaplasia pilórica e adenomiomatose, metaplasia pilórica e displasia, metaplasia pilórica e câncer. Há também associação entre a ocorrência de metaplasia intestinal e metaplasia pilórica, metaplasia intestinal e adenomiomatose, metaplasia intestinal e displasia, metaplasia intestinal e câncer. / INTRODUCTION: Gallbladder cancer is the most common malignant lesion of the biliary tree; yet, little is known about its carcinogenesis. The possible preneoplastic character of histological gallbladder alterations has been studied in recent medical literature. The purpose of this study was to identify and quantify histological gallbladder alterations in our population, to correlate them with clinical data, and to correlate the metaplastic alterations, separately, with the other histological alterations found. METHODS: In this retrospective study conducted between November,1999 and December, 2006, the medical records of 1.689 patients who were submitted to laparoscopic cholecystectomy by cholecystolithiasis were analyzed. The patients were classified according to age: 60 years or younger, and older than 60. In relation to the duration of symptoms before the surgery, they were grouped according to: patients without symptoms, patients with symptoms for 1 year or less, and patients with symptoms for over 1 year before the surgery. In relation to the size and number of the gallstones, they were grouped according to: patients with gallstones of 10 mm or less, and those with gallstones over 10 mm, and those with single or multiple gallstones. RESULTS: There were 1,238 (73.3%) female and 451 (26.7%) male patients. In relation to age, 1,192 patients were 60 or younger (70.6%) and 497 (29.4%) were older than 60. There were 1.319 (78.1%) patients with gallstones smaller than 10 mm and 370 patients (21.9%) with gallstones larger than 10mm. Acute choelcystitis was observed in 174 patients (10.3%), gangrene in 23 (1.4%), abscess in 8 (0.4%), cholesterolosis in 305 (18.1%), adenomyomatosis in 40 (2.4%), xanthogranulomatous cholecystitis in 29 (1.7%), fibrosis in 12 (0.7%), sclero-atrophic gallbladder in 20 (1.2%), hyperplasic polyp in 3 (0.2%), cholesterol polyp in 17 (1.0%), pyloric metaplasia in 72 (4.3%), intestinal metaplasia in 18 (1.1%), dysplasia in 4 (0.2%), and cancer in 2 (0.1%). No adenomatous polyp was found. CONCLUSIONS: Male patients have more inflammatory complications than females. With the exception of xanthogranulomatous cholecystitis, there is no correlation between symptom duration and an increased occurrence of the histological alterations studied. In the elderly patients, the occurrence of adenomyomatosis, gangrene and abscess is more frequent. The size of gallstones has no relationship with the occurrence of the histological alterations studied, except for acute cholecystitis, which is associated with small and multiple gallstones. There is an association between pyloric metaplasia and the following: adenomyomatosis, dysplasia, and cancer. There is also an association between intestinal metaplasia and the following: pyloric metaplasia, adenomyomatosis, dysplasia, and cancer.

INTRODUÇÃO: O câncer da vesícula biliar é a lesão maligna mais comum da árvore biliar e pouco se sabe sobre a sua carcinogênese. O possível caráter pré-neoplásico das alterações histológicas da vesícula biliar vem sendo estudado recentemente. O objetivo deste estudo foi identificar e quantificar as alterações histológicas da vesícula biliar no nosso meio e correlacioná-las com dados clínicos, e correlacionar as alterações metaplásicas, em separado, com as demais alterações encontradas. MÉTODOS: Neste estudo retrospectivo realizado entre novembro de 1999 a dezembro de 2006, foram avaliados 1.689 prontuários de doentes submetidos a colecistectomia laparoscópica por colecistolitíase. Os doentes foram divididos em relação à idade em doentes com até 60 anos e com mais de 60 anos. Em relação ao tempo de sintomas antes da cirurgia foram agrupados em doentes sem sintomas, doentes com sintomas até 1 ano, e doentes com sintomas por mais de 1 ano antes da cirurgia. Em relação ao tamanho e número dos cálculos foram agrupados em doentes com cálculos de até 10 mm, e aqueles com cálculos maiores que 10 mm, e em doentes com cálculos únicos ou múltiplos. RESULTADOS: Eram mulheres 1.238 doentes (73,3%) e 451 eram homens (26,7%). Apresentaram idade de até 60 anos 1.192 doentes (70,6%) e 497 (29,4%) apresentaram mais de 60 anos. Apresentaram cálculos menores que 10 mm 1.319 doentes (78,1%) e 370 doentes (21,9%) apresentaram cálculos maiores que 10 mm. Foi observado inflamação aguda em 174 doentes (10,3%), gangrena em 23 (1,4%), abscesso em 8 (0,4%), colesterolose em 305 (18,1%), adenomiomatose em 40 (2,4%), colecistite xantogranulomatosa em 29 (1,7%), fibrose em 12 (0,7%), escleroatrofia em 20 (1,2%), pólipo hiperplásico em 3 (0,2%), pólipo de colesterol em 17 (1,0%), metaplasia pilórica em 72 (4,3%), metaplasia intestinal em 18 (1,1%), displasia em 4 (0,2%), câncer em 2 (0,1%). Não foram observados pólipos adenomatosos. CONCLUSÕES: O sexo masculino apresenta maior freqüência de complicações inflamatórias que o feminino. Não há relação entre o tempo de sintomas e uma maior ocorrência das alterações histológicas estudadas, excetuando-se a colecistite xantogranulomatosa. Nos doentes idosos há maior ocorrência de adenomiomatose, gangrena e abscesso. Há aumento progressivo de idade para a ocorrência de metaplasia pilórica, metaplasia intestinal, displasia e câncer. O tamanho dos cálculos não guarda relação com a ocorrência das alterações estudadas, exceto para colecistite aguda que se associou com cálculos pequenos e múltiplos. Há associação entre a ocorrência de metaplasia pilórica e adenomiomatose, metaplasia pilórica e displasia, metaplasia pilórica e câncer. Há também associação entre a ocorrência de metaplasia intestinal e metaplasia pilórica, metaplasia intestinal e adenomiomatose, metaplasia intestinal e displasia, metaplasia intestinal e câncer. / INTRODUCTION: Gallbladder cancer is the most common malignant lesion of the biliary tree; yet, little is known about its carcinogenesis. The possible preneoplastic character of histological gallbladder alterations has been studied in recent medical literature. The purpose of this study was to identify and quantify histological gallbladder alterations in our population, to correlate them with clinical data, and to correlate the metaplastic alterations, separately, with the other histological alterations found. METHODS: In this retrospective study conducted between November,1999 and December, 2006, the medical records of 1.689 patients who were submitted to laparoscopic cholecystectomy by cholecystolithiasis were analyzed. The patients were classified according to age: 60 years or younger, and older than 60. In relation to the duration of symptoms before the surgery, they were grouped according to: patients without symptoms, patients with symptoms for 1 year or less, and patients with symptoms for over 1 year before the surgery. In relation to the size and number of the gallstones, they were grouped according to: patients with gallstones of 10 mm or less, and those with gallstones over 10 mm, and those with single or multiple gallstones. RESULTS: There were 1,238 (73.3%) female and 451 (26.7%) male patients. In relation to age, 1,192 patients were 60 or younger (70.6%) and 497 (29.4%) were older than 60. There were 1.319 (78.1%) patients with gallstones smaller than 10 mm and 370 patients (21.9%) with gallstones larger than 10mm. Acute choelcystitis was observed in 174 patients (10.3%), gangrene in 23 (1.4%), abscess in 8 (0.4%), cholesterolosis in 305 (18.1%), adenomyomatosis in 40 (2.4%), xanthogranulomatous cholecystitis in 29 (1.7%), fibrosis in 12 (0.7%), sclero-atrophic gallbladder in 20 (1.2%), hyperplasic polyp in 3 (0.2%), cholesterol polyp in 17 (1.0%), pyloric metaplasia in 72 (4.3%), intestinal metaplasia in 18 (1.1%), dysplasia in 4 (0.2%), and cancer in 2 (0.1%). No adenomatous polyp was found. CONCLUSIONS: Male patients have more inflammatory complications than females. With the exception of xanthogranulomatous cholecystitis, there is no correlation between symptom duration and an increased occurrence of the histological alterations studied. In the elderly patients, the occurrence of adenomyomatosis, gangrene and abscess is more frequent. The size of gallstones has no relationship with the occurrence of the histological alterations studied, except for acute cholecystitis, which is associated with small and multiple gallstones. There is an association between pyloric metaplasia and the following: adenomyomatosis, dysplasia, and cancer. There is also an association between intestinal metaplasia and the following: pyloric metaplasia, adenomyomatosis, dysplasia, and cancer.