Background Cholangiocarcinomas are a heterogeneous group of malignancies arising from a number of cells of origin along the biliary tree. Although most cases in Western countries are sporadic, large population-based studies have identified a number of risk factors. This review summarises the evidence behind reported risk factors and current understanding of the molecular pathogenesis of cholangiocarcinoma, with a focus on inflammation and cholestasis as the driving forces in cholangiocarcinoma development. Risk Factors for cholangiocarcinogenesis Cholestatic liver diseases (e.g. primary sclerosing cholangitis and fibropolycystic liver diseases), liver cirrhosis, and biliary stone disease all increase the risk of cholangiocarcinoma. Certain bacterial, viral or parasitic infections such as hepatitis B and C and liver flukes also increase cholangiocarcinoma risk. Other risk factors include inflammatory disorders (such as inflammatory bowel disease and chronic pancreatitis), toxins (e.g. alcohol and tobacco), metabolic conditions (diabetes, obesity and non-alcoholic fatty liver disease) and a number of genetic disorders. Molecular pathogenesis of cholangiocarcinoma Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-ɑ, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. Accumulating bile acids from cholestasis lead to reduced pH, increased apoptosis and activation of ERK1/2, Akt and NF-κB pathways that encourage cell proliferation, migration and survival. Other mediators upregulated in cholangiocarcinoma include Transforming Growth Factor-β, Vascular Endothelial Growth Factor, Hepatocyte Growth Factor and several microRNAs. Increased expression of the cell surface receptor c-Met, the glucose transporter GLUT-1 and the sodium iodide symporter lead to tumour growth, angiogenesis and cell migration. Stromal changes are also observed, resulting in alterations to the extracellular matrix composition and recruitment of fibroblasts and macrophages that create a microenvironment promoting cell survival, invasion and metastasis. Conclusion Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. An understanding of the molecular pathogenesis of cholangiocarcinoma is vital when developing new diagnostic biomarkers and targeted therapies for this disease.
Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low-or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI).Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression.
Background: Differentiating hepatic mucinous cystic neoplasms (MCNs) from simple hepatic cysts (SCs) preoperatively is a challenging task. Our aim was to determine whether radiological features on ultrasound scan (USS), CT or MRI, cyst fluid tumour markers, or multidisciplinary team (MDT) outcomes could differentiate MCN from SC. Methods: A retrospective review of radiological features, cyst fluid tumour marker levels and MDT outcomes in 52 patients was performed. Results: There were 13 patients with MCN, 38 with SC and one ciliated foregut cyst. MCNs were more often solitary (p = 0.006). Although no other individual radiological characteristic on USS, CT or MRI was predictive of MCN, MDT outcomes stating that a cyst was complex in nature were highly predictive (p = 0.0007). Cyst fluid carbohydrate antigen 19-9, carcino-embryonic antigen and cancer antigen 125 were unable to differentiate MCN from SC (p = 0.45, p = 0.49, and p = 0.73, respectively). Conclusions: MDT outcomes are of greatest value when trying to differentiate MCN from SC, as well as having a solitary cyst on imaging. Conventional cyst fluid tumour markers are unhelpful. All suspicious cystic liver lesions should be discussed pre-operatively by a hepatobiliary MDT to determine the most appropriate surgical approach.
Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract. Complete surgical resection can be curative, but the majority of patients are diagnosed with advanced disease and usually die within a year of diagnosis. Most deaths are attributable to local disease progression rather than distant metastases, supporting the use of locoregional therapies. There is evidence that locoregional therapies can provide local tumor control resulting in increased survival while avoiding some of the side effects of systemic treatments, increasing potential treatment options for patients who may be unsuitable for systemic palliative treatments. This review considers the evidence for locoregional therapies in cholangiocarcinoma, which can be classified into endoscopic, vascular, percutaneous and radiation oncological therapies. Current guidelines do not recommend the routine use of locoregional therapies due to a lack of prospective data, but the results of ongoing trials are likely to increase the evidence base and impact on clinical practice.
Aims and MethodA questionnaire was distributed to patients in a psychiatric hospital in Birmingham, UK, to identify the factors that affect their satisfaction with the ward round.ResultsThe questionnaire was completed by 42 patients (53% response rate). Waiting time was the only variable to be significantly correlated with total score of patient satisfaction. Regression analysis also identified diagnosis and patients meeting their consultant before the first ward round as significant predictors of patient satisfaction.Clinical ImplicationsReducing waiting time and ensuring that the consultant meets the patient before the first ward round would make a significant improvement to the in-patient experience, without causing much disruption to standard clinical practice.
ObjectiveCurrent surveillance strategies for duodenal adenomatosis in familial adenomatous polyposis (FAP) miss malignancies and underestimate cancer risk in ampullary disease. This study aimed to evaluate the utility of endoscopic ultrasound (EUS) in the assessment of FAP patients with duodenal and/or ampullary polyposis referred for surgical intervention.DesignA retrospective analysis of FAP patients undergoing index EUS between December 2006 and May 2015 was performed. Follow-up was completed in January 2018, including review of all EUS procedures and surgical interventions (median follow-up 6 years).ResultsFifty-five patients underwent 188 EUS procedures. Six patients (11%) developed malignancy (three duodenal, three ampullary). Ampullary cancer risk was underestimated by Spigelman stage and overestimated by Kashiwagi classification. Ultrasound findings were poor predictors of malignancy, with common bile duct dilatation being the only finding present in one EUS prior to a diagnosis of ampullary cancer. The best predictors of ampullary malignancy were an ampullary polyp size >3 cm and an increase >1 cm in ampullary polyp size. Ampullary polyp size >3 cm provided the best predictive value, correctly identifying two of the three cases of ampullary cancer and both patients with high-grade dysplasia. EUS biopsy failed to detect malignancy later confirmed by surgical histology in two patients.ConclusionEUS surveillance confers little additional benefit to standard endoscopic surveillance in FAP patients. The best predictor of ampullary malignancy is an ampullary polyp >3 cm; this could be regarded as a relative indication for surgery.
Sciatic hernias are one of the rarest types of hernia and often pose diagnostic difficulty to clinicians. We report a case of an 80-year-old lady with a sciatic hernia who had a falsely negative computed tomography (CT) but was found to have a colonic hernia on ultrasonography. The authors recommend that for patients in which there is a high degree of clinical suspicion for a sciatic hernia and a negative CT, ultrasonography may be considered as a useful imaging modality to confirm the diagnosis.
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