Malignant Biliary Obstruction: Evidence for Best Practice

What should be done next? Is the stricture benign? Is it resectable? Should I place a stent? Which one? These are some of the questions one ponders when dealing with biliary strictures. In resectable cases, ongoing questions remain as to whether the biliary tree should be drained prior to surgery. In palliative cases, the relief of obstruction remains the main goal. Options for palliative therapy include surgical bypass, percutaneous drainage, and stenting or endoscopic stenting (transpapillary or via an endoscopic ultrasound approach). This review gathers scientific foundations behind these interventions. For operable cases, preoperative biliary drainage should not be performed unless there is evidence of cholangitis, there is delay in surgical intervention, or intense jaundice is present. For inoperable cases, transpapillary stenting after sphincterotomy is preferable over percutaneous drainage. The use of plastic stents (PS) has no benefit over Self-Expandable Metallic Stents (SEMS). In case transpapillary drainage is not possible, Endoscopic Ultrasonography- (EUS-) guided drainage is still an option over percutaneous means. There is no significant difference between the types of SEMS and its indication should be individualized

Endoscopic versus surgical treatment of ampullary adenomas: a systematic review and meta-analysis

The aim of this study is to address the outcomes of endoscopic resection compared with surgery in the treatment of ampullary adenomas. A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. For this purpose, the Medline, Embase, Cochrane, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scopus and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were scanned. Studies included patients with ampullary adenomas and data considering endoscopic treatment compared with surgery. The entire analysis was based on a fixed-effects model. Five retrospective cohort studies were selected (466 patients). All five studies (466 patients) had complete primary resection data available and showed a difference that favored surgical treatment (risk difference [RD] = -0.24, 95% confidence interval [CI] = -0.44 to -0.04). Primary success data were identified in all five studies as well. Analysis showed that the surgical approach outperformed endoscopic treatment for this outcome (RD = -0.37, 95% CI = -0.50 to -0.24). Recurrence data were found in all studies (466 patients), with a benefit indicated for surgical treatment (RD = 0.10, 95% CI = -0.01 to 0.19). Three studies (252 patients) presented complication data, but analysis showed no difference between the approaches for this parameter (RD = -0.15, 95% CI = -0.53 to 0.23). Considering complete primary resection, primary success and recurrence outcomes, the surgical approach achieves significantly better results. Regarding complication data, this systematic review concludes that rates are not significantly different

Endoscopic stenting for inoperable malignant biliary obstruction: a systematic review and meta-analysis

INTRODUÇÃO: A prótese biliar endoscópica é aceita em todo o mundo como a primeira escolha de tratamento paliativo na obstrução biliar maligna. Atualmente ainda persistem dois tipos de materiais utilizados em sua confecção: plástico e metal. Consequentemente, muitas dúvidas surgem quanto a qual deles é o mais benéfico para o paciente. Esta revisão reúne as informações disponíveis da mais alta qualidade sobre estes dois tipos de prótese, fornecendo informações em relação à disfunção, complicação, taxas de reintervenção, custos, sobrevida e tempo de permeabilidade; e pretende ajudar a lidar com a prática clínica nos dias de hoje. OBJETIVO: Analisar, através de metanálise, os benefícios de dois tipos de próteses na obstrução biliar maligna inoperável. MÉTODOS: Uma revisão sistemática de ensaios clínicos randomizados (RCT) foi conduzida, com a última atualização em março de 2015, utilizando EMBASE, CINAHL (EBSCO), Medline, Lilacs / Centro (BVS), Scopus, o CAPES (Brasil), e literatura cinzenta. As informações dos estudos selecionados foram extraídas tendo em vista seis desfechos: primariamente disfunção, taxas de reintervenção e complicações; e, secundariamente, custos, sobrevivência e tempo de permeabilidade. Os dados sobre as características dos participantes do RCT, critérios de inclusão e exclusão e tipos de próteses também foram extraídos. Os vieses foram avaliados principalmente através da escala de Jadad. Esta metanálise foi registrada no banco de dados PROSPERO pelo número CRD42014015078. A análise do risco absoluto dos resultados foi realizada utilizando o software RevMan 5, calculando as diferenças de risco (RD) de variáveis dicotômicas e média das diferenças (MD) de variáveis contínuas. Os dados sobre a RD e MD para cada desfecho primário foram calculados utilizando o teste de Mantel-Haenszel e a inconsistência foi avaliada com o teste Qui-quadrado (Chi2) e o método de Higgins (I2). A análise de sensibilidade foi realizada com a retirada de estudos discrepantes e a utilização do efeito aleatório. O teste t de Student foi utilizado para a comparação das médias aritméticas ponderadas, em relação aos desfechos secundários. RESULTADOS: Inicialmente foram identificados 3660 estudos; 3539 foram excluídos por título ou resumo, enquanto 121 estudos foram totalmente avaliados e foram excluídos, principalmente por não comparar próteses metálicas (SEMS) e próteses plásticas (PS), levando a treze RCT selecionados e 1133 indivíduos metanálise. A média de idade foi de 69,5 anos, e o câncer mais comum foi de via biliar (proximal) e pancreático (distal). O diâmetro de SEMS mais utilizado foi de 10 mm (30 Fr) e o diâmetro de PS mais utilizado foi de 10 Fr. Na metanálise, SEMS tiveram menor disfunção global em comparação com PS (21,6% versus 46,8% p < 0,00001) e menos reintervenções (21,6% versus 56,6% p < 0,00001), sem diferença nas complicações (13,7% versus 15,9% p = 0,16). Na análise secundária, a taxa média de sobrevida foi maior no grupo SEMS (182 contra 150 dias - p < 0,0001), com um período maior de permeabilidade (250 contra 124 dias - p < 0,0001) e um custo semelhante por paciente, embora menor no grupo SEMS (4.193,98 contra 4.728,65 Euros - p < 0,0985). CONCLUSÃO: SEMS estão associados com menor disfunção, menores taxas de reintervenção, melhor sobrevida e maior tempo de permeabilidade. Complicações e custos não apresentaram diferençaINTRODUCTION: Endoscopic stenting is accepted worldwide as the first choice palliative treatment for malignant biliary obstruction. There are still two types of materials currently being used, which are plastic and metal. Therefore, many doubts are raised as to which one is the most beneficial to the patient. This review gathers the highest quality information available about these two types of stent, giving information in regards to dysfunction, complication, reintervention rates, costs, survival, and patency time; and intends to help handle clinical practice nowadays. OBJECTIVE: To analyze through meta-analyses the benefits of two types of stents in the inoperable malignant biliary obstruction. METHODS: A systematic review of randomized clinical trials (RCT) was conducted, with the last update on March 2015, using EMBASE, CINAHL (EBSCO), MEDLINE, LILACS/CENTRAL (BVS), SCOPUS, CAPES (Brazil), and gray literature. Information of the selected studies was extracted in sight of six outcomes: primarily regarding dysfunction, reintervention and complication rates; and secondarily costs, survival, and patency time. The data about characteristics of trial participants, inclusion and exclusion criteria and types of stents were also extracted. The biases were mainly assessed through the Jadad scale. This meta-analysis was registered in the PROSPERO database by the number CRD42014015078. The analysis of the absolute risk of the outcomes was performed using the software RevMan 5, by computing risk differences (RD) of dichotomous variables and mean differences (MD) of continuous variables. Data on RD and MD for each primary outcome were calculated using the Mantel-Haenszel test and inconsistency was qualified and reported in Chisquared (Chi2) and the Higgins method (I2). Sensitivity analysis was performed withdrawing discrepant studies and using random effect. Student\'s t-test was used for the comparison of weighted arithmetic means regarding secondary outcomes. RESULTS: Initial searching identified 3660 studies; 3539 were excluded through title or abstract, while 121 studies were fully assessed and were excluded mainly because they did not compare Self Expanding Metal Stents (SEMS) and Plastic Stents (PS), leading to thirteen RCT selected and 1133 subjects meta-analyzed. The mean age was 69.5 years old, that were affected mostly by bile duct (proximal) and pancreatic tumors (distal). The preferred SEMS diameter used was the 10 mm (30 Fr) and the preferred PS diameter used was 10 Fr. In the meta-analysis, SEMS had lower overall stent dysfunction compared to PS (21.6% versus 46.8% p < 0.00001) and fewer reintervention (21.6% versus 56.6% p < 0.00001), with no difference in complications (13.7% versus 15.9% p=0.16). In the secondary analysis, the mean survival rate was higher in the SEMS group (182 versus 150 days - p < 0.0001), with a higher patency period (250 versus 124 days - p < 0.0001) and a similar cost per patient, although lower in the SEMS group (4193.98 versus 4728.65 Euros - p < 0.0985). CONCLUSION: SEMS are associated with lower stent dysfunction, lower reintervention rates, better survival, and higher patency time. Complications and costs do not show differenc

Endoscopy-focused primary, secondary and tertiary prevention of colorectal cancer

"A thesis submitted to the University of Adelaide and Nagoya University in fulfilment of the requirements for the joint degree of Doctor of Philosophy"Colorectal cancer (CRC) is among the commonest and deadliest types of cancer. It is the second highest in economic burden among all cancers and the thirteenth of all diseases in Australia. In Japan, it has been gaining importance and in 2018 CRC was identified as second in incidence among all cancers for both women and men, and the leading cause of death amongst all cancers in women and the third leading cause of death in men. Research that can improve the prevention and treatment of this cancer is of the utmost importance. In primary prevention, I studied the factors that contribute to the development of colorectal lesions (e.g. colorectal adenomas and sessile serrated adenomas/polyps). This was a prospective study carried out at the Lyell McEwin Hospital (South Australia) examining whether and by how much factors such as alcohol consumption and smoking are associated with colorectal lesions. A cohort of 291 procedures and 260 patients was recruited. In this cohort, we found that different factors are associated with different histologic subtypes of lesions. Furthermore, in terms of primary prevention of CRC, I sought to discover how to optimally conduct colonoscopy (e.g. in the morning or afternoon). This, added to research on the simplification of methods for assessing quality measures (e.g. adenoma detection rate – ADR – through adenoma detection quotient - ADQ), was aimed at optimising CRC screening programs. In the retrospective cohort of 2,657 procedures performed at the Lyell McEwin Hospital (South Australia), morning endoscopy lists were associated with better detection and ADQ was a reliable predictor of ADR. With respect to secondary prevention, I undertook several studies. The main aim of these studies was to assess advanced endoscopic imaging (e.g. narrow band imaging - NBI) nationally and internationally, comparing different endoscopic classification methods for colorectal lesions to evaluate how well each performed. Two of our studies showed that the modified Sano's (MS) classification was the most accurate tool for predicting the histology of colorectal lesions during colonoscopy. The first of these two studies involved a single centre randomised trial on 348 patients comparing the MS with the NBI international colorectal endoscopic (NICE) classification, but did not include the differentiation of sessile serrated adenomas/polyps (SSA/Ps) in the comparison. The second, a prospective study between Australia (exploratory phase with 483 colorectal lesions included) and Japan (validation phase with 30 colorectal lesions evaluated by four endoscopists), involved the comparison of the MS, NICE and Japan NBI expert team (JNET) classifications. The last two classifications were combined with the workgroup serrated polyps and polyposis (WASP) add-on to allow the comparison including SSA/Ps' differentiation. The results from both studies were then used as a template for the development of a computer-aided diagnosis (CAD) system that could enable expert-level accuracy for any endoscopist. A CAD system was created, learning from 1,235 colorectal images, and tested with data from two different centres (Australia and Japan) and imaging technologies (i.e. NBI and blue laser imaging - BLI), showing results comparable to expert endoscopists. The mean AUC from the exploratory phase reached 94.3% (internal NBI dataset) while the mean AUCs for the validation phase scored 84.5% with the external NBI dataset and 90.3% with the external BLI dataset. In addition to imaging, two other studies also focused on secondary prevention by specifically looking at (i) the different microbiota profile of early and invasive CRCs; and (ii) the learning curve of colorectal endoscopic submucosal dissection (ESD). The former study, conducted at Nagoya University (Aichi prefecture) was based on DNA extraction of colonic mucosa brush and faecal samples from 25 patients and found to be statistically different relative to the abundance of several bacteria related with each type; this included the Fusobacterium nucleatum (a known bacterium species related to invasive CRC) as well as nine other genera of bacteria. The latter study evaluated how the learning curve of the complex ESD procedure progressed in an expert Japanese endoscopy centre. This retrospective study comprised a large colorectal ESD database of 590 procedures (514 patients) performed by 26 endoscopists at Nagoya University Hospital (Aichi prefecture). Although the speed of dissection continuously improved throughout the years, ESD could be performed safely by non-experts. Lastly, considering tertiary prevention, I evaluated the necessity of routine biopsies for the follow up of previous endoscopic resection of colorectal lesions, and proposed an innovative classification which provides a highly sensitive diagnosis of recurrence on a scar. This classification was conceived and prospectively explored at the Lyell McEwin Hospital (South Australia) with 100 scars (82 patients) and validated in five other countries in addition to Australia (i.e. Malaysia, Brazil, Japan, Singapore and United States of America) by 49 endoscopists where it achieved similar results. The evidence produced during the research for this thesis has the potential to immediately influence not only research but also clinical practice related to primary, secondary and tertiary prevention of CRC. I strongly believe that this influence will contribute to improved clinical outcomes related to this burdensome diseaseThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 202