Defining and predicting textbook outcomes for perihilar cholangiocarcinoma: analysis of factors improving achievement of desired postoperative outcomes

BACKGROUND: Definition of textbook outcome (TO), defined as a single indicator combining the most advantageous short-term outcomes, is still lacking for perihilar cholangiocarcinoma (PHC). The primary endpoint of the present study is to analyze the rate of achievement of a disease-specific TO for PHC within a high volume tertiary referral centre. Secondary endpoints are to identify predictive factors of TO-achievement and to analyze the impact of achieving TO on long-term results. METHODS: Between 2010 and 2022, a total of 237 patients undergoing combined liver and biliary resection for PHC at tertiary referral centre were included. Disease-specific TO were defined as: no 90-day mortality, no postoperative complications, no readmission, no intraoperative transfusions and resection margins. A logistic regression model was developed to identify predictors associated with TO-achievement. Kaplan-Meier curves were designed to determine TO's impact on survival. RESULTS: TO was achieved in 60 (25.3%) patients. At multivariate logistic regression, preoperative biliary drainage [odds ratio (OR) 2.90 (1.13-3.40), P =0.026], high prognostic nutritional index [OR 7.11 (6.71-9.43), P =0.007[ and minimally invasive approach [OR 3.57 (2.31-3.62), P =0.013] were identified as independent predictors of TO. High ASA score [OR 0.38 (0.17-0.82), P =0.013] decreased the odds of TO. A significant improvement in both overall survival and disease-free survival was associated to TO fulfilment. CONCLUSION: Since the achievement of TO correlates with better disease-free and overall survival, every effort should be made to ameliorate modifiable aspects prior to surery: management within referral centres with dedicated experience in biliary tract cancer and preoperative optimization protocol may positively contribute to improve postoperative outcomes, increasing the chance to obtain TO. Moreover, the implementation of advanced minimally invasive programs plays as well

INTRAHEPATIC CHOLANGIOCARCINOMA DEVELOPMENT IN A PATIENT WITH A NOVEL BAP1 GERMLINE MUTATION AND LOW EXPOSURE TO ASBESTOS

BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations

Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions

Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers

Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy

Where Are All the Mycobacterium avium Subspecies paratuberculosis in Patients with Crohn's Disease?

Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne's disease, in dairy cows and every other species of mammal in which it has been identified. MAP has been identified in the mucosal layer and deeper bowel wall in patients with Crohn's disease by methods other than light microscopy, and by direct visualization in small numbers by light microscopy. MAP has not been accepted as the cause of Crohn's disease in part because it has not been seen under the microscope in large numbers in the intestines of patients with Crohn's disease. An analysis of the literature on the pathology of Crohn's disease and on possible MAP infection in Crohn's patients suggests that MAP might directly infect endothelial cells and adipocytes and cause them to proliferate, causing focal obstruction within already existing vessels (including granuloma formation), the development of new vessels (neoangiogenesis and lymphangiogenesis), and the “creeping fat” of the mesentery that is unique in human pathology to Crohn's disease but also occurs in bovine Johne's disease. Large numbers of MAP might therefore be found in the mesentery attached to segments of intestine affected by Crohn's disease rather than in the bowel wall, the blood and lymphatic vessels running through the mesentery, or the mesenteric fat itself. The walls of fistulas might result from the neoangiogenesis or lymphangiogenesis that occurs in the bowel wall in Crohn's disease and therefore are also possible sites of large numbers of MAP. The direct visualization of large numbers of MAP organisms in the tissues of patients with Crohn's disease will help establish that MAP causes Crohn's disease

Endocrine neoplasms of the pancreas: pathologic and genetic features.

Pancreatic endocrine neoplasms (PENs) are diagnostically challenging tumors whose natural history is largely unknown. Histopathology allows the distinction of 2 categories: poorly differentiated high-grade carcinomas and well-differentiated neoplasms. The latter include more than 90\% of PENs whose clinical behavior varies from indolent to malignant and cannot be predicted by their morphology.To review the literature and report on additional primary material about the clinicopathologic features, classification, staging, grading, and genetic features of PENs.Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institution.The diagnosis of PEN is generally easy, but unusual features may induce misdiagnosis. Immunohistochemistry solves the issue, provided that the possibility of a PEN has been considered. Morphology allows the distinction of poorly differentiated aggressive carcinomas from well-differentiated neoplasms. The World Health Organization classification criteria allow for the discernment of the latter into neoplasms and carcinomas with either benign or uncertain behavior. The recently proposed staging and grading systems hold great promise for permitting a stratification of carcinomas into clinically significant risk categories. To date, inactivation of the MEN1 gene remains the only ascertained genetic event involved in PEN genesis. It is inactivated in roughly one-third of PENs. The degree of genomic instability correlates with the aggressiveness of the neoplasm. Gene silencing by promoter methylation has been advocated, but a formal demonstration of the involvement of specific genes is still lacking. Expression profiling studies are furnishing valuable lists of mRNAs and noncoding RNAs that may advance further the research to discover novel markers and/or therapeutic targets

A NEW BIOACTIVE PROSTHESIS FOR HARD TISSUE AUGMENTATION OF THE FACIAL SKELETON: HISTOLOGICAL RESULTS.

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