Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures.

OBJECTIVE: Despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). DESIGN: A prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. RESULTS: An initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. CONCLUSION: Implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.

Circulating Tumor Cells in Patients Undergoing Resection of Colorectal Cancer Liver Metastases. Clinical Utility for Long-Term Outcome: A Prospective Trial.

BACKGROUND: Patients with resected colorectal cancer liver metastases display heterogeneous clinical behavior. The identification of new prognostic factors would help in making more accurate decisions. OBJECTIVE: The aim of this study was to evaluate the survival impact of circulating tumor cells (CTCs) in this setting. METHODS: We conducted a prospective study of patients with resected liver metastases of colorectal cancer. Patients were included in the study from February 2009 to January 2013. The CellSearch System™ was employed for the detection of pre- and postsurgery CTCs. A positive test was defined as two or more CTCs/7.5 mL of blood. Recurrence rate, disease-free survival, and overall survival were calculated, and univariate and multivariate analyses were performed. RESULTS: Forty-four patients were included in our study. After a median follow-up of 60 months (range 28-74), 32 patients experienced recurrence (72.7%). The CTCs number was determined and the test was positive in 8 patients (18.6%) before surgery and 13 patients (29.5%) after surgery. The postoperative detection of CTCs was not related to any clinical outcome; however, the preoperative detection of CTCs was significantly related to behavior. All patients in the preoperative CTC-positive group relapsed, versus 65% in the CTC-negative group (p = 0.051). Disease-free survival was 19 months in the preoperative CTC-negative group versus 7 months in the CTC-positive group (p = 0.01). Additionally, overall survival was 69 months in the preoperative CTC-negative group versus 17 months in the CTC-positive group (p = 0.004). Preoperative CTC count remained significant in multivariate analysis. CONCLUSIONS: In this cohort of colorectal cancer liver metastases patients, the presence of two or more preoperative CTCs was associated with disease progression and poor survival despite complete resection.

Acute recurrent pancreatitis secondary to hepatocellular carcinoma invading the biliary tree.

Hepatocellular carcinoma rarely invades the biliary tree. Clots or tumor embolus passing though the bile duct can cause pancreatitis by a mechanism similar to gallstone pancreatitis. We present the case of a patient with recurrent acute pancreatitis, initially suspicious of biliary origin. Despite cholecystectomy he had new episodes of acute pancreatitis. Hepatocellular carcinoma was diagnosed after the third episode. ERCP findings suggested the presence of a fistula connecting the tumor and the biliary tree. The patient was operated and the hepatocellular carcinoma was resected. Its pathological analysis confirmed the communication between the tumor and the biliary duct.

[Acute postoperative confusional syndrome in the elderly patient]. / Síndrome confusional agudo postoperatorio en el paciente anciano.

With the progressive aging of the population surgical candidates have more comorbidities resulting in a higher risk to develop postoperative complications. One of the most frequent postoperative complications in the elderly is acute confusional state or delirium, which may have devastating consequences: higher mortality, and risk of medical complications during admission and, a higher risk of functional decline, institutionalization, and cognitive impairment at discharge. For all these reasons and with the aim of optimising surgical procedures, it is essential to identify patients at risk of delirium in order to take appropriate preventive action and provide early treatment. In the present article we review the current evidence on the management of postoperative delirium in the elderly.

Feasibility and morbidity and mortality in two hundred consecutive cases of pancreaticogastrostomy after pancreaticoduodenectomy. / Factibilidad y morbimortalidad en doscientos casos consecutivos de pancreaticogastrostomía después de duodenopancreatectomía.

BACKGROUND: Postoperative mortality associated with pancreaticoduodenectomy (PD) in high-volume hospitals is below 5%, yet morbidity rates range between 45% and 60%. Recent studies show a lower incidence of complications and postoperative pancreatic fistula (POPF) in pancreaticogastrostomy (PG). The primary objective was to assess the incidence and predictive factors for complications: POPF, post-pancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) following the criteria of the ISGPS and Clavien-Dindo classifications. METHODS: A prospective observational study that included all patients who underwent PD between 2008 and 2016. PG was the surgical procedure of choice for PD reconstruction. RESULTS: Two hundred forty-nine patients underwent surgery with intention of performing a PD. The feasibility of PG was 90.5%. One hundred and six (53%) patients had complications, 36 (18%) were severe (Clavien-Dindo grade ≥III). Death within 90 postoperative days was 4%. DGE was the most frequent complication (22.5%), followed by PPH (21%). The clinical POPF rate was 15% (6% Clavien-Dindo grade ≥III). The primary risk factors associated with complications were age >70 years (1.9 [1-3.55]), being male (1.89 [1; 3.6]) and soft pancreatic texture (3.38 [1.5; 7.37]). CONCLUSIONS: In this paper, we report a feasibility study for PG (90.5%). The primary risk factors associated with complications were age >70 years, being male and soft pancreatic texture. Soft pancreatic texture is also associated with the development and severity of POPF.