Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants

Video-assisted thoracoscopic lung biopsy in children

Minimal invasive surgical techniques have gained high acceptance in thoracic surgery during the last 10 years. Video-assisted thoracoscopy (VATS) is less invasive than open thoracotomy and its development is associated with expansion of indication for lung biopsies. Lung biopsy remains an important investigation in the diagnosis of few of the lung disorders despite improved diagnostic yield of high resolution computed tomography scanning. Thoracoscopic lung biopsy is becoming the procedure of first choice for the diagnosis of many localized and diffuse lung diseases. We report a small series of eight patients who underwent VATS lung biopsy to demonstrate the safety and efficacy of this procedure

Successful separation of Xipho-Omphalopagus twins

Xipho-omphalopagus twins are conjoined twins sharing some part of gastrointestinal system and lower sternum. These types of twins have best chances of survival if successfully separated. We report a case of successfully separated Xipho-omphalopagus twins, highlighting the importance of proper planning and team effort in such separations

Role of laparoscopic cholecystectomy in children

The present study is undertaken to establish the usefulness of laparoscopic cholecystectomy and to know its merits and demerits as compared to open cholecystectomy in children. In all, 28 patients who underwent cholecystectomy (8 open and 20 laparoscopic cholecystectomy) in B.Y.L. Nair hospital between July 1999 and March 2004 were analyzed. Calculous cholecystitis was found to be the most common indication for surgery. Operative time for laparoscopic cholecystectomy was more than that in open cholecystectomy in the early phase of laparoscopy, which got reduced as we gained experience. The requirement of parenteral antibiotics and analgesics and the duration of stay were significantly shorter with laparoscopy. The advantages for a child in laparoscopic cholecystectomy as compared to open cholecystectomy are minimal pain, avoidance of an upper abdominal incision, cosmesis and shorter duration of hospitalization with quick return to home and school. Thus, laparoscopic cholecystectomy is safe and efficacious in children

Pharmacokinetics of rectal compared to intramuscular paracetamol in children undergoing minor surgery

Objectives : Although paracetamol is a widely accepted and safe analgesic, guidelines regarding its definite analgesic dose are lacking. This study was, therefore, undertaken to compare the pharmacokinetics of paracetamol when administered by two routes, viz, intramuscular and rectal, in children undergoing minor surgery. Design : Randomized, controlled, assessor-blind, comparative clinical trial. Materials and Methods: Following Institutional Ethics Committee approval and valid consent, children undergoing minor surgery were randomized to receive paracetamol either intramuscularly or rectally. Blood samples were collected at fixed intervals for estimation of drug levels. Results : Fifty children (43 boys, 7 girls; ages 3 to 12 years; weight 10 to 40 kg) were enrolled in the study. 26 patients were randomized to receive paracetamol intramuscularly (mean dose 14.8 ± 0.9 mg/kg) and 24 to receive the paracetamol as a rectal suppository (mean dose 29.5 ± 1.4 mg/kg). Complete pharmacokinetic analysis was possible in only 29 patients, as the blood samples of the others were either not received or were inadequate for analysis. The mean maximum plasma concentration (C max ) with rectal paracetamol (n = 13) was 6.04 ± 2.21 mg/ml with a T max of 2.5 ± 0.89 h, while with intramuscular paracetamol (n = 16), the C max was 10.34 ± 7.09 mg/ml and the T max 1.47 ± 0.64 h. The area under the concentration-time curve (AUC 0-12 ) was 42.26 ± 22.29 µg.h/ml and 43.60 ± 26.45 µg.hr/ml for rectal and intramuscular paracetamol, respectively. Patients in the intramuscular group needed rescue medication earlier as compared to those in the rectal group (P < 0.05). Conclusion : Although the drug levels achieved with rectal paracetamol were less than that achieved with intramuscular administration, it was higher than the lower limit for analgesic effect (3-5 µg/ml). Patients who received paracetamol intramuscularly needed rescue medication earlier compared to those receiving paracetamol rectally, indicating a more prolonged duration of action with rectally administered paracetamol. Hence, rectal paracetamol can be used as a safe, effective, and more acceptable analgesic alternative in children

Analysis of the new GCFR upper and lower plenum flow-through shields

Analysis of the proposed GCFR upper and lower plenum flow-through shields has been performed using both discrete ordinate (DOT) and Monte Carlo (MORSE) methods. Several shields having one change of direction in the coolant path (chevron) and two changes of direction (herringbone) were investigated. The shields were modeled as unit cells with periodic boundary conditions. From plenum fluence calculations and design constraints at the reactor vessel liner, it was determined that all the shield configurations analyzed should be adequate for the necessary radiation attenuation

Review of video-assisted thoracoscopy in children

Open thoracotomy is the standard procedure for various thoracic diseases against which other procedures are compared. Currently Video Assisted Thoracoscopic Surgery (VATS) has gained widespread acceptance in the management of a variety of thoracic disorders. It decreases the morbidity and duration of hospital stay. A total of 133 children with various thoracic diseases who presented at a University Teaching Hospital in the Department of Pediatric Surgery, from June 2000 to December 2007, were included. Of the 133 patients,116 patients had empyema, all of whom were subjected to VATS, and an attempt at debridement/decortication and drainage was made. Other thoracic disorders treated included lung abscesses, lung biopsies, hydatid cysts, and so on. Patients with empyema were treated according to their stage of disease. Of the 116 patients who underwent thoracoscopy, 16 had to be converted to open surgery due to various reasons. The mean duration for removal of drain was three days and the average total duration of hospital stay was six days. Similarly the application of VATS was advantageous in other thoracic diseases

Esophageal lung – A rare bronchopulmonary foregut malformation

Esophageal lung is a rare variety of communicating bronchopulmonary foregut malformation characterized by a fistula between an isolated portion of respiratory tissue and esophagus or stomach. It may involve the entire lung or one of the pulmonary lobes. Only 20 cases have been reviewed in 2011. Fifty percent of cases are associated with a tracheoesophageal fistula. We report a case of a 6 month old girl who was previously operated for TEF repair, with esophageal lobe which was successfully excised. The relevant literature is reviewed