Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

Background: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver.

Methods: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival.

A Predictive Noninvasive Single-Nucleotide Variation-Based Biomarker Signature for Resectable Pancreatic Cancer: Protocol for a Prospective Validation Study.

Background: Single-nucleotide variations (SNVs; formerly SNPs) are inherited genetic variants that can be easily determined in routine clinical practice using a simple blood or saliva test. SNVs have potential to serve as noninvasive biomarkers for predicting cancer-specific patient outcomes after resection of pancreatic ductal adenocarcinoma (PDAC). Two recent analyses led to the identification and validation of three SNVs in the CD44 and CHI3L2 genes (rs187115, rs353630, and rs684559), which can be used as predictive biomarkers to help select patients most likely to benefit from pancreatic resection.

Vascular injury during cholecystectomy: A multicenter critical analysis behind the drama.

Background: The management of a vascular injury during cholecystectomy is still very complicated, especially in centers not specialized in complex hepatobiliary surgery.

Methods: This was a multi-institutional retrospective study in patients with vascular injuries during cholecystectomy from 18 centers in 4 countries. The aim of the study was to analyze the management of vascular injuries focusing on referral, time to perform the repair, and different treatments options outcomes.

[Gallbladder carcinoma and extrahepatic cholangiocarcinoma].

Gallbladder carcinoma and extrahepatic cholangiocarcinoma In this article, we focus on three entities of malignant biliary tumors: gallbladder carcinoma, distal and perihilar cholangiocarcinoma. Those are rare malignant tumors which require an extensive interdisciplinary expertise in the treatment of hepato-pancreato-biliary conditions in order to provide an appropriate diagnostic work-up, correctly assess resectability and come up with a clear-cut multimodal treatment plan. Perihilar cholangiocarcinoma (Klatskin-tumour) usually requires the most complex evaluation of resectability, which involves not only the assessment of vascular in- and outflow and an adequate biliary drainage, but also aims to ensure that enough functional liver tissue is left after resection.

Germline and Somatic Genetic Variants in the p53 Pathway Interact to Affect Cancer Risk, Progression, and Drug Response.

Insights into oncogenesis derived from cancer susceptibility loci (SNP) hold the potential to facilitate better cancer management and treatment through precision oncology. However, therapeutic insights have thus far been limited by our current lack of understanding regarding both interactions of these loci with somatic cancer driver mutations and their influence on tumorigenesis. For example, although both germline and somatic genetic variation to the p53 tumor suppressor pathway are known to promote tumorigenesis, little is known about the extent to which such variants cooperate to alter pathway activity.

A common polymorphism in the retinoic acid pathway modifies adrenocortical carcinoma age-dependent incidence.

Background: Genome-wide association studies (GWASs) have enriched the fields of genomics and drug development. Adrenocortical carcinoma (ACC) is a rare cancer with a bimodal age distribution and inadequate treatment options. Paediatric ACC is frequently associated with TP53 mutations, with particularly high incidence in Southern Brazil due to the TP53 p.

Identification and Validation of a Biomarker Signature in Patients With Resectable Pancreatic Cancer via Genome-Wide Screening for Functional Genetic Variants.

Importance: Surgery currently offers the only chance for a cure in pancreatic ductal adenocarcinoma (PDAC), but it carries a significant morbidity and mortality risk and results in varying oncologic outcomes. At present, to our knowledge, there are no tests available before surgical resection to identify tumors with an aggressive biological phenotype that could guide personalized treatment strategies.

Objective: Identification of noninvasive genetic biomarkers that could direct therapy in patients whose cases are amenable to pancreatic cancer resection.

Robot-assisted versus laparoscopic single-incision cholecystectomy: results of a randomized controlled trial.

Background: Although single-port laparoscopic cholecystectomy (SILC) is safe and effective, inherent surgeons' discomfort has prevented a large-scale adaptation of this technique. Recent advances in robotic technology suggest that da Vinci Single-Site™ cholecystectomy (dVSSC) may overcome this issue by reducing the stress load of the surgeon compared to SILC. However, evidence to objectively assess differences between the two approaches is lacking.

[Colorectal metastases - Current treatment strategies].

Colorectal metastases - Current treatment strategies In the course of their disease, more than 50 % of patients with colorectal cancer develop metastases. They are most frequently localized in the liver, followed by the peritoneum and the lungs. The therapeutic options and prognosis of colorectal metastases have improved markedly in recent years.

Robot-assisted single-site compared with laparoscopic single-incision cholecystectomy for benign gallbladder disease: protocol for a randomized controlled trial.

Background: Recent advances in robotic technology suggest that the utilization of the da Vinci Single-Site™ platform for cholecystectomy is safe, feasible and results in a shorter learning curve compared to conventional single-incision laparoscopic cholecystectomy. Moreover, the robot-assisted technology has been shown to reduce the surgeon's stress load compared to standard single-incision laparoscopy in an experimental setup, suggesting an important advantage of the da Vinci platform. However, the above-mentioned observations are based solely on case series, case reports and experimental data, as high-quality clinical trials to demonstrate the benefits of the da Vinci Single-Site™ cholecystectomy have not been performed to date.

CD44 SNPrs187115: A Novel Biomarker Signature that Predicts Survival in Resectable Pancreatic Ductal Adenocarcinoma.

Purpose: Although pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor, like other common cancers, it displays a wide range of biology. However, at present, there are no reliable tests to predict patients' cancer-specific outcomes and guide personalized treatment decisions. In this study, we aim to identify such biomarkers in resectable PDAC by studying SNPs in the CD44 gene, which drives the progression of pancreatic cancer.

Prediction of outcome in multiorgan resections for cancer using a bayes-network.

Background/aims: The long-term success of multivisceral resections for cancer is difficult to forecast due to the complexity of factors influencing the prognosis. The aim of our study was to assess the predictivity of a Bayes network for the postoperative outcome and survival.

Methodology: We included each oncologic patient undergoing resection of 4 or more organs from 2002 till 2005 at the Ulm university hospital.

Alternate splicing of the p53 inhibitor HDMX offers a superior prognostic biomarker than p53 mutation in human cancer.

Conventional high-grade osteosarcoma is the most common primary bone malignancy. Although altered expression of the p53 inhibitor HDMX (Mdmx/Mdm4) is associated with cancer risk, progression, and outcome in other tumor types, little is known about its role in osteosarcoma. High expression of the Hdmx splice variant HDMX-S relative to the full-length transcript (the HDMX-S/HDMX-FL ratio) correlates with reduced HDMX protein expression, faster progression, and poorer survival in several cancers.

A RASSF1A polymorphism restricts p53/p73 activation and associates with poor survival and accelerated age of onset of soft tissue sarcoma.

RASSF1A (Ras association domain containing family 1A), a tumor suppressor gene that is frequently inactivated in human cancers, is phosphorylated by ataxia telangiectasia mutated (ATM) on Ser131 upon DNA damage, leading to activation of a p73-dependent apoptotic response. A single-nucleotide polymorphism located in the region of the key ATM activation site of RASSF1A predicts the conversion of alanine (encoded by the major G allele) to serine (encoded by the minor T allele) at residue 133 of RASSF1A (p.Ala133Ser).

Elevated transcript levels from the MDM2 P1 promoter and low p53 transcript levels are associated with poor prognosis in human pancreatic ductal adenocarcinoma.

Unlabelled: OBJECTDIVES: Mouse double minute 2 is a key negative regulator of the p53 protein, a central node in the mediation of tumor suppression. The MDM2 gene contains 2 differently regulated promoters, MDM2-P1 and MDM2-P2, which differ strongly in their biological and clinical importance.

Methods: We assess the clinical significance of the expression of messenger RNA (mRNA) transcripts originating from both MDM2 promoters, measured with quantitative reverse transcription polymerase chain reaction in microdissected tissues from 57 patients with pancreatic ductal adenocarcinoma (PDAC).

A genetic variant in a PP2A regulatory subunit encoded by the PPP2R2B gene associates with altered breast cancer risk and recurrence.

A recent candidate gene association study identified a single nucleotide polymorphism (SNP) in the PPP2R2B gene (rs319217, A/G) that manifests allelic differences in the cellular responses to treatment with chemotherapeutic agents (Vazquez et al., Nat Rev Drug Discov 2008;7:979-87). This gene encodes a regulatory subunit of protein phosphatase 2A (PP2A), one of the major Ser/Thr phosphatases implicated in the negative control of cell growth and division.

Single-nucleotide polymorphisms in the p53 signaling pathway.

The p53 tumor suppressor pathway is central both in reducing cancer frequency in vertebrates and in mediating the response of commonly used cancer therapies. This article aims to summarize and discuss a large body of evidence suggesting that the p53 pathway harbors functional inherited single-nucleotide polymorphisms (SNPs) that affect p53 signaling in cells, resulting in differences in cancer risk and clinical outcome in humans. The insights gained through these studies into how the functional p53 pathway SNPs could help in the tailoring of cancer therapies to the individual are discussed.

Chemosensitivity profiles identify polymorphisms in the p53 network genes 14-3-3tau and CD44 that affect sarcoma incidence and survival.

The p53 regulatory network responds to cellular stresses by initiating processes such as cell cycle arrest and apoptosis. These responses inhibit cellular transformation and mediate the response to many forms of cancer therapies. Functional variants in the genes comprising this network could help identify individuals at greater risk for cancer and patients with poorer responses to therapies, but few such variants have been identified as yet.

Recent natural selection identifies a genetic variant in a regulatory subunit of protein phosphatase 2A that associates with altered cancer risk and survival.

Purpose: A regulated p53-dependent stress response is crucial in suppressing tumor formation and mediating the response to commonly used cancer therapeutics. However, little is known about the human, inherited genetics of this important signaling pathway.

Experimental Design: Studies of human genetic variants in the p53 tumor suppressor gene and MDM2 oncogene have shown that single nucleotide polymorphisms (SNP) can affect p53 signaling, confer cancer risk, and alter outcome, and also suggest that the pathway is under evolutionary selective pressure.

MDM2 SNP309 associates with accelerated pancreatic adenocarcinoma formation.

Objectives: The G-allele of a single nucleotide polymorphism in the promoter of the MDM2 gene (MDM2 SNP309, T/G) associates with the acceleration of tumor formation and an increased risk for developing various malignancies. In this report, the possible role of the MDM2 SNP309 locus with regard to sex, age, and p53 mutational status in the development and progression of pancreatic ductal adenocarcinoma (PDAC) was examined.

Methods: One hundred three PDAC patients with comprehensive clinical, histopathologic, and follow-up data and 499 controls were included into the study and their MDM2 SNP309 genotypes obtained.

Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival.

Pancreatic cancer is the eighth most common cancer and has an overall 5-year survival rate lower than 10%. Because of their ability to regulate gene expression, microRNAs can act as oncogenes or tumor-suppressor genes and so have garnered interest as possible prognostic and therapeutic markers during the last decade. However, the prognostic value of microRNA expression in pancreatic cancer has not been thoroughly investigated.

Interleukin-13 exerts autocrine growth-promoting effects on human pancreatic cancer, and its expression correlates with a propensity for lymph node metastases.

Background And Aims: Interleukin-13 (IL-13) is an anti-inflammatory cytokine produced in cells of hematopoetic origin. It is not known whether pancreatic cancer cells produce IL-13 or whether IL-13 can modulate pancreatic cancer cell growth and influence the frequency of lymph node metastases.

Materials And Methods: Cell growth and signaling were analyzed by cell counting, colorimetric proliferation assays, fluorescent-activated cell sorting, and in vitro kinase activity assays.