Pancreatic steatosis on computed tomography is an early imaging feature of pre-diagnostic pancreatic cancer: A preliminary study in overweight patients

BackgroundThe prevalence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, driven by factors such as aging and an increasing prevalence of obesity and diabetes mellitus. To improve the poor survival rate of PDAC, early detection is vital. Recently, pancreatic steatosis has gained novel interest as a risk factor for PDAC. This study aimed to investigate if pancreatic steatosis on computed tomography (CT) is an early imaging feature in patients with pre-diagnostic PDAC.MethodsA retrospective case-control study was performed. Patients diagnosed with PDAC (2010–2016) were reviewed for abdominal non-contrast CT-imaging 1 month-3 years prior to their diagnosis. Cases were matched 1:4 with controls based on age, gender and imaging date. Unenhanced CT-images were evaluated for pancreatic steatosis (pancreas-to-spleen ratio in Hounsfield Units <0.70) by a blinded radiologist and results were compared between cases and controls.ResultsIn total, 32 cases and 117 controls were included in the study with a comparable BMI (29.6 and 29.2 respectively, p = 0.723). Pancreatic steatosis was present in 71.9% of cases compared to 45.3% of controls (Odds ratio (OR) 3.09(1.32–7.24), p = 0.009). Adjusted for BMI and diabetes mellitus, pancreatic steatosis on CT remained a significant independent risk factor for PDAC (Adjusted OR 2.70(1.14–6.58), p = 0.037).ConclusionPancreatic steatosis measured on CT is independently associated with PDAC up to three years before the clinical diagnosis in overweight patients. If these data are confirmed, this novel imaging feature may be used to identify high-risk individuals and to stratify the risk of PDAC in individuals that already undergo PDAC screening.     

Inappropriate shock and percutaneous cardiac intervention: A lesson to learn in the cath lab

Coronary disease is a common condition in patients affected by heart failure with severely reduced ejection fraction (HFrEF). This condition represents an indication for implantable cardioverter defibrillator (ICD) in order to reduce the risk of sudden death related to arrhythmias. Nevertheless, inappropriate shocks are associated with worse quality of life, hospitalization, and death. We present the case of an inappropriate shock related to percutaneous coronary intervention during the insertion and advancement of the guidewire into the left anterior descending artery (LAD) in a patient with an ICD. Physicians’ awareness about the clinical implication of noise arising during a coronary procedure is very important in patients with an ICD or pacemaker, to avoid inappropriate shock or pacing inhibition and to raise the possibility of lead implantation in or helix protrusion into the coronary lumen.     

Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma

The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHLs) is associated with chromosomal translocations that deregulate the expression of various oncogenes. Recently, a novel mechanism of genetic lesion, termed aberrant hypermutation, has been identified in diffuse large B-cell lymphoma (DLBCL) of immunocompetent hosts. In these tumors, the somatic hypermutation (SHM) process that normally targets immunoglobulin V (IgV) genes in B cells appears to misfire and causes mutations in the 5' sequences of multiple proto-oncogenes, including PIM-1, PAX-5, RhoH/TTF, and c-MYC. To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these 4 genes in various histologic subtypes. Mutations in 1 gene or more were detected in 19 of 39 (48.7%) AIDS-NHL cases (10 of 18 AIDS-diffuse large B-cell lymphoma; 4 of 11 AIDS-Burkitt lymphoma; 4 of 6 AIDS-primary effusion lymphoma; 1 of 4 AIDS-primary central nervous system lymphoma), with 9 of 39 (23.1%) cases carrying mutations in 2 or more genes. Overall, PIM-1 was mutated in 5 of 39 (12.8%), PAX-5 in 8 of 39 (20.5%), RhoH/TTF in 9 of 39 (23.1%), and c-MYC in 7 of 27 (25.9%) AIDS-NHL cases. Mutations were represented mainly by single base pair substitutions (n = 63) with rare deletions/insertions (n = 5) and displayed features typical of the IgV-associated SHM process. In addition, a number of mutations in PIM-1 and c-MYC were found to affect coding exons, leading to amino acid substitutions with likely functional consequences. Analysis of intraclonal heterogeneity documented that the aberrant hypermutation activity may be ongoing in at least some cases. These data indicate that aberrant hypermutation is associated with various subtypes of AIDS-NHL and may represent a major contributor to their pathogenesis.     

Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: a bridge to transplantation

BACKGROUND AND OBJECTIVES: Arsenic trioxide (ATO) has been reported to be a safe and effective treatment for relapsed acute promyelocytic leukemia (APL). The aim of this study was to evaluate the efficacy and toxicity as well as the eligibility to stem cell transplantation (SCT) in a series of 7 patients with relapsing APL, managed with ATO. DESIGN AND METHODS: Seven patients with relapsing APL while on maintenance treatment with all-trans-retinoic acid (ATRA) or who were ATRA refractory-received ATO at a dose of 10 mg daily by 2-hour intravenous infusion until complete remission (CR). After consolidation chemotherapy, patients were programmed to receive autologous or allogeneic stem cell transplantation (SCT) according to donor availability. The median age of the patients was 55 (21-71) years: 2 patients presented with concomitant extramedullary relapse. RESULTS: Six patients (86%) achieved CR after a median of 35 ATO doses (20-49) with negligible toxicity; one patient died from pneumonia. After consolidation with a four-day course of cytarabine at 1 g/m2 and mitoxantrone 6 mg/m2, two patients underwent allogeneic SCT, two received PML/RARa negative autologous peripheral blood stem cells collected after consolidation plus granulocyte colony-stimulating factor, one failed mobilization and received a second consolidation course. One elderly patient refused further treatment and relapsed 6 months later. After a median follow-up of 15 months from CR2 achievement, 5 patients are alive in continuous CR. INTERPRETATION AND CONCLUSIONS: The high CR rate and the mild toxicity confirm that ATO represents a valid alternative to salvage chemotherapy for patients relapsing while on ATRA treatment or who are ATRA-refractory. Allogeneic or autologous SCT after ATO-induced CR is feasible in the majority of patients.     

The P303T mutation in the human factor VII (FVII) gene alters the conformational state of the enzyme and causes a severe functional deficiency

We report the results of in vitro expression and biochemical characterization of the naturally occurring type II mutation Pro303Thr (P303T) in the factor VII (FVII) gene. Recombinant activated mutated FVII (FVIIa303T), compared with the activated wild-type FVII (FVIIaWT), showed reduced amidase activity toward synthetic substrates, especially when the observed reduced binding affinity for human soluble tissue factor (TF) (K(d) from 4.4 nmol/l for FVIIaWT to 17.3 nmol/l for FVIIa303T) was overcome by a fully saturating TF concentration. Likewise, factor X (FX) hydrolysis by FVIIa303T showed a reduced activity in the absence (and more severely in the presence) of TF (k(cat)/K(m) from 2.3 x 10(7)/mol/l s for FVIIaWT to 8.7 x 10(5)/mol/l s for FVIIa303T). These results showed that the mutant FVIIa is more shifted toward a zymogen-like form compared to FVIIaWT, suggesting that P303 facilitates the conformational transitions that stabilize the active form of FVIIa. The alteration of these allosteric equilibria is especially evident in the presence of TF, which was unable to shift the equilibrium toward a fully active FVIIa form. Additional experiments showed that both TF-catalysed FVII303T autoactivation and FVII303T activation by activated FX in the presence of TF were severely impaired, mainly because of an increase of the K(m) value. Altogether, these defects may explain the severe bleeding symptoms in a patient carrying the FVIIP303T mutation.     

Effects of aerobic or resistance exercise training on cardiovascular autonomic function of subjects with type 2 diabetes: A pilot study

Background and aims

Both aerobic (AER) and resistance (RES) training improve metabolic control in patients with type 2 diabetes (T2DM). However, information on the effects of these training modalities on cardiovascular autonomic control is limited. Our aim was to compare the effects of AER and RES training on cardiovascular autonomic function in these subjects.

Intravenous methylene blue venography during laparoscopic paediatric varicocelectomy

Introduction

One of the challenges of varicocele surgery is to prevent hydrocele formation while still ensuring success. Methylene blue has been used to identify and preserve lymphatic vessels, and venography has been a standard component of sclerotherapy and percutaneous retrograde techniques. The authors have combined both approaches during laparoscopic varicocelectomy and report their experience.

Methods

A prospective study was performed of adolescents with idiopathic varicocele and spontaneous venous reflux on Doppler ultrasound. A pampiniform plexus vein was cannulated via scrotal incision before creating the pneumoperitoneum. A mixture of methylene blue and Omnipaque™ was injected into the pampiniform plexus with fluoroscopic screening. Laparoscopic selective vein ligation was then performed using 5 mm endoscopic clips or a bipolar vessel sealing device such as Plasmakinetic™ or Ligasure™. Venography was repeated to confirm complete ligation of the internal testicular veins. Patients were followed-up at 3, 6, and 9 months post-surgery with clinical examination and Doppler ultrasound. Data are presented as median (interquartile range).

Results

Twenty-four patients underwent laparoscopic selective vein ligation with venography and methylene blue injection. The median age was 14.7 (14.6–15.7) years. The recurrence rate was 12%. No patients developed a hydrocele. The length of surgery was 120 (100–126) minutes.

Conclusion

Intra-operative intra-venous methylene blue injection and venography helps to identify venous duplications of the internal testicular veins and enhances the success rate of laparoscopic selective vein ligation. This approach prevents hydrocele formation but has a 12% recurrence rate, which appears to be higher than some techniques described in the literature.