Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception.

Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR-122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

BACKGROUND: Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). METHODS: In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. RESULTS: CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. CONCLUSIONS: CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

Minimally invasive distal pancreatectomy A retrospective review of 30 cases.

OBJECTIVES: Pancreatic surgery has been greatly influenced by the advent of laparoscopic surgery and increasing experience in its performance and by advances in techniques and surgical devices. This study aimed to represent two centers' initial experiences in laparoscopic distal pancreatic surgery. METHODS: This study was a bi-centric study including 30 patients undergoing distal pancreatectomy for pancreatic disorders. All the patients were operated on from November 2006 to November 2013 in Turkey and Spain. RESULTS: Laparoscopic spleen-preserving distal pancreatectomy was performed in 9 patients, laparoscopic distal pancreatectomy was performed in 14 patients, laparoscopic enucleation was performed in 4 patients, and single-incision laparoscopic distal pancreatosplenectomy with splenectomy was performed in 3 patients. CONCLUSIONS: Laparoscopic distal pancreatectomies for pancreatic disorders are feasible and safe procedures if performed by experienced laparoscopic surgeons. KEY WORDS: Laparoscopy, Pancreas, Multi-port, Tumor, SILS.

Implication of the presence of a variant hepatic artery during the Whipple procedure.

INTRODUCTION: The anatomical variants of the hepatic artery may have important implications for pancreatic cancer surgery. The aim of our study is to compare the outcome following a pancreatoduodenectomy (PD) in patients with or without a variant hepatic artery arising from superior mesenteric artery. MATERIAL AND METHODS: We reviewed 151 patients with periampullary tumoral pathology. All patients underwent oncological PD between January 2005 and February 2012. Our series was divided into two groups: Group A: Patients with a hepatic artery arising from superior mesenteric artery; and Group B: Patients without a hepatic artery arising from superior mesenteric artery. We expressed the results as mean +/- standard deviation for continuous variables and percentages for qualitative variables. Statistical tests were considered significant if p < 0.05. RESULTS: We identified 11 patients with a hepatic artery arising from superior mesenteric artery (7.3%). The most frequent variant was an aberrant right hepatic artery (n = 7), following by the accessory right hepatic artery (n = 2) and the common hepatic artery trunk arising from the superior mesenteric artery (n = 2). In 73% of cases the diagnosis of the variant was intraoperative. R0 resection was performed in all patients with a hepatic artery arising from superior mesenteric artery. There were no significant differences in the tumor resection margins and the incidence of postoperative complications. CONCLUSION: Oncological PD is feasible by the presence of a hepatic artery arising from superior mesenteric artery. The complexity of having it does not seem to influence in tumor resection margins, complications and survival.

Impact of donor and recipient CYP3A5 and ABCB1 genetic polymorphisms on tacrolimus dosage requirements and rejection in Caucasian Spanish liver transplant patients.

Studies of liver transplant (LT) patients, mainly in Asians, have evaluated the influence of the CYP3A5*1 allele and P-glycoprotein gene ABCB1 on tacrolimus pharmacokinetics or biopsy-proven acute rejection (BPAR) incidence, with no conclusive results. To investigate these issues, 98 Caucasian Spanish LT patients with tacrolimus, mycophenolate mofetil and steroids and 88 cadaveric donors were genotyped for the SNPs CYP3A5 6986G>A, ABCB1 1236C>T, ABCB1 2677G>A/T and ABCB1 3435C>T;. On day 7 post-LT, patients with a native CYP3A5*1 allele had significantly lower tacrolimus trough concentrations C0 (P = .03) and dose-adjusted concentrations C0 /D (P = .02) than CYP3A5 *3/*3 homozygotes. Three months post-LT, patients carrying a liver with CYP3A5*1 had significantly lower C0 /D (P = .03) and took significantly higher tacrolimus doses (P = .03) than the corresponding *3/*3 homozygotes. ABCB1 SNPs showed no significant association with tacrolimus variables. The 3-month incidence of BPAR was 10.2%, with no statistically significant differences related to CYP3A5 (14.3% in expresser vs. 9.5% in non-expresser) or ABCB1 genotype of either patient or donor. We conclude that in Caucasian Spanish LT patients, a native or graft-borne CYP3A5*1 allele tends to lower tacrolimus concentrations and increase dosage needs, but has no significant impact on the incidence of BPAR.

[Etiology and diagnosis of severe retroperitoneal hematoma: therapeutic options and surgical indication]. / Etiología y diagnóstico del hematoma retroperitoneal complicado, actitud e indicación quirúrgica.

Retroperitoneal hematoma is a rare entity with clinical consequences that vary according to the speed and amount of bleeding. Thus, it may be asymptomatic, in which case it is usually diagnosed incidentally through imaging tests, or severe, in which case the most common symptoms are pain and hypovolemic shock. We report three cases of severe retroperitoneal hematoma. Although the literature on the subject describes a wide variety of causes, in all three patients the etiology was tumoral, consisting of one suprarenal myelolipoma, one renal adenocarcinoma and one suprarenal metastasis from bronchogenic adenocarcinoma. Computed tomography was the imaging test employed not only to determine the nature of the process (hematoma, abscess, tumor) but also to assess compression of adjacent structures and the occurrence of active bleeding. Conservative treatment consisting of volemic replacement and correction of coagulation was initially attempted. However, all three patients required emergency surgery due to hemodynamic instability in two patients and compression of the vena cava in the other.