Simultaneous colorectal and hepatic procedures for colorectal cancer result in increased morbidity but equivalent mortality compared with colorectal or hepatic procedures alone: outcomes from the National Surgical Quality Improvement Program

AbstractBackgroundSimultaneous colorectal and hepatic surgery for colorectal cancer (CRC) is increasing as surgery becomes safer and less invasive. There is controversy regarding the morbidity associated with simultaneous, compared with separate or staged, resections.MethodsData for 2005–2008 from the National Surgical Quality Improvement Program (NSQIP) were used to compare morbidity after 19 925 colorectal procedures for CRC (CR group), 2295 hepatic resections for metastatic CRC (HEP group), and 314 simultaneous colorectal and hepatic resections (SIM group).ResultsAn increasing number of simultaneous resections were performed per year. Fewer major colorectal and liver resections were performed in the SIM than in the CR and HEP groups. Patients in the SIM group had a longer operative time and postoperative length of stay compared with those in either the CR or HEP groups. Simultaneous procedures resulted in higher rates of postoperative morbidity and major morbidity than CR procedures, but not HEP procedures. This difference was driven by higher rates of wound and organ space infections, and a greater incidence of septic shock. Mortality rates did not differ among the groups.ConclusionsHospitals in the NSQIP are performing more simultaneous colonic and hepatic resections for CRC. These procedures are associated with increases in operative time, length of stay and rate of perioperative complications. Simultaneous procedures do not, however, increase perioperative mortality

Gastrointestinal stromal tumor (GIST) recurrence following surgery: review of the clinical utility of imatinib treatment

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Surgery with complete removal of the tumor is the primary treatment for resectable GIST and the only chance of cure. However, recurrence after surgery is common. The 2 main prognostic factors are the mitotic activity and the size of the tumor. Tumor rupture is also a risk factor for postoperative recurrence, and extra care should be taken while manipulating this soft and friable tumor. Imatinib mesylate (IM, Gleevec®, Novartis, Basel, Switzerland) is a tyrosine kinase inhibitor and was first studied in the palliative setting for metastatic GIST patients in the year 2000. It is now the cornerstone of metastatic GIST treatment. IM also plays an important role as an adjuvant treatment for resectable GIST and has been shown to increase the recurrence-free survival in phase III studies. However, some points remain to be clarified. Notably, the ideal duration of adjuvant IM after surgery is still unclear. It is also difficult to determine the exact place of surgery in metastatic or recurrent GIST patients in the IM era. A multidisciplinary approach is, therefore, mandatory to offer GIST patients the best treatment available

Genetic Association Study Identifies HSPB7 as a Risk Gene for Idiopathic Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06×10−6, OR = 0.67 [95% CI 0.57–0.79] for the minor allele T). Three more SNPs showed p < 2.21×10−5. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n = 564, n = 981 controls, p = 2.07×10−3, OR = 0.79 [95% CI 0.67–0.92]), France 1 (n = 433 cases, n = 395 controls, p = 3.73×10−3, OR = 0.74 [95% CI 0.60–0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26×10−4, OR = 0.63 [95% CI 0.50–0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28×10−13, OR = 0.72 [95% CI 0.65–0.78]). None of the other three SNPs showed significant results in the replication stage

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Combined pancreaticoduodenectomy and extended right hemicolectomy: outcomes and indications

AbstractBackgroundPancreaticoduodenectomy (PD) combined with an en bloc extended right hemicolectomy is required to achieve complete oncological resection of various malignancies. Information regarding the indications and outcomes of this procedure is limited.Study designPatients requiring PD combined with extended right hemicolectomy for primary tumours from 2002 to 2008 were identified.ResultsPD combined with an en bloc extended right hemicolectomy was required in 14 patients, constituting 8% of pancreaticoduodenal resections. Pancreatic adenocarcinoma (8), retroperitoneal sarcoma (2) and colon cancer (2) were the main primary tumours resected. The indication for an extended right hemicolectomy was extensive tumour involvement of the transverse mesentery in seven patients. Clear tumour margins were achieved in 11 individuals. The median operating time was 10h with intra-operative transfusions required in three patients. One or more complications were noted in eight, with delayed gastric emptying and pancreatic fistula the most common. The median length of hospital stay was 8 days. The overall 2-year survival in this series was 37%, with a median survival of 20 months in pancreatic cancer patients.ConclusionsThis series suggests that PD combined with an en bloc extended right hemicolectomy is feasible and can achieve complete tumour clearance with acceptable morbidity