Challenges to innovation arising from current companion diagnostics regulations and suggestions for improvements.

A companion diagnostic is a diagnostic test that provides information essential for the safe and effective use of a corresponding therapeutic product. To obtain marketing approval, the companion diagnostic must demonstrate acceptable analytical and clinical performance. Companion diagnostic regulations are intended to protect patients by ensuring quality and consistency of treatment-guiding biomarker testing in clinical trials and clinical practice.

Clinical perspectives on the value of testing for and mutations in advanced NSCLC.

Standard first-line therapy for patients with metastatic non-small cell lung cancer (mNSCLC) without identified actionable mutations consists of regimens comprising immune checkpoint inhibitors (ICIs), alone or in combination with platinum-based chemotherapy (CTx). However, approximately 20-30% of patients with mNSCLC (including some patients with high tumor programmed cell death ligand-1 expression) display primary resistance to ICIs, either alone or in combination with CTx. Mutations in tumor suppressor genes (), and () often detected in patients with mutations, are associated with an aggressive disease phenotype and resistance to standard ICI regimens.

The Role of Hepatobiliary Scintigraphy as the Initial Investigative Modality for Significant Bile Leak following Laparoscopic Cholecystectomy.

Introduction: Currently, the rate of bile duct injury and leak following laparoscopic cholecystectomy (LC) is still higher than for open surgery. Diverse investigative algorithms were suggested for bile leak, shifting from hepatobiliary scintigraphy (HBS) toward invasive and more sophisticated means. We aimed to analyze the use of biliary scan as the initial modality to investigate significant bile leak in the drain following LC, attempting to avoid potential unnecessary invasive means when the scan demonstrate fair passage of nuclear substance to the intestine, without leak.

Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer.

Analysis of the genomic landscape of prostate cancer has identified different molecular subgroups with relevance for novel or existing targeted therapies. The recent approvals of the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and rucaparib in the metastatic castration-resistant prostate cancer (mCRPC) setting signal the need to embed molecular diagnostics in the clinical pathway of patients with mCRPC to identify those who can benefit from targeted therapies. Best practice guidelines in overall biospecimen collection and processing for molecular analysis are widely available for several tumour types.

Factors contributing to unintentional parathyroidectomy during thyroid surgery.

Unintentional parathyroidectomy during thyroid surgery has an incidence ranging between 1% and 31% across institutions. Many studies have identified malignancy and central neck dissection as risk factors for losing parathyroid glands, but few studies have evaluated the impact of other factors such as lymphocytic thyroiditis, hyperthyroidism, or concomitant primary hyperparathyroidism. The purpose of this study was to investigate which factors contribute to parathyroid loss during thyroid surgery.

[Not Available].

Background: The relationships between physicians and patients are very complex. One of their principles is to receive informed consent from the patient. This principle facilitates patient autonomy.

2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection.

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations.

Cognitive Function of Patients with Crohn's Disease is Associated with Intestinal Disease Activity.

Background: Systemic inflammation and nutritional deficiencies are characteristics of Crohn's disease (CD) and have been suggested to influence cognitive performance. This study assessed cognitive function in patients with CD.

Methods: Participants were adult patients with CD arriving at routine follow-up.

The molecular basis of rectal cancer.

The majority of rectal carcinomas are sporadic in nature, and relevant testing for driver mutations to guide therapy is important. A thorough family history is necessary and helpful in elucidating a potential hereditary predilection for a patient's carcinoma. The adequate diagnosis of a heritable tendency toward colorectal carcinoma alters the management of a patient disease and permits the implementation of various surveillance algorithms as preventive measures.

Bortezomib for acute antibody-mediated rejection in liver transplantation.

Antibody-mediated rejection (AMR) is an uncommon, but challenging type of rejection after solid organ transplantation. We review three cases of AMR in ABO-compatible liver transplant recipients. These cases were characterized by severe acute rejection resistant to steroids and antithymocyte globulin, histologic evidence of plasma cell infiltrates, C4d positivity and high serum anti-HLA donor-specific antibodies.

EUS clarifies the natural history and ideal management of GISTs.

Background/aims: Gastrointestinal stromal tumors (GISTs) are mesenchymal gastrointestinal tumors expressing C-kit (CD117). Endoscopic ultrasonography (EUS) evaluations of GISTs can help determine optimal therapy and follow-up care. The current study assesses the natural history of 100 GISTs evaluated by EUS, and the impact of EUS on their management.

The impact of endoscopic ultrasonography on the management of suspected pancreatic cancer--a comprehensive longitudinal continuous evaluation.

Objectives: Between 1997 and 2001, a single-center chart review demonstrated significant impact of endoscopic ultrasonography (EUS) in evaluating suspected pancreatic cancer (PCA). Repeating and comparing this review with that from 2001 to 2004 was performed to determine whether increased use of EUS results in more patients being accurately chosen for curative versus palliative procedures, and for surgical versus nonsurgical oncotherapy.

Methods: The complete systematic review was made up of electronic files from the gastroenterology, oncology, and pathology departments of patients presenting with suspected PCA.

Screening for developmental delay in the setting of a community pediatric clinic: a prospective assessment of parent-report questionnaires.

Objectives: Our goal for this study was to prospectively test whether parent-completed questionnaires can be effectively used in the setting of a busy ambulatory pediatric clinic to accurately screen for developmental impairments. Specific objectives included (1) assessing the feasibility of using parent-report instruments in the setting of a community pediatric clinic, (2) evaluating the accuracy of 2 available screening tests (the Ages and Stages Questionnaire and Child Development Inventory), and (3) ascertaining if the pediatrician's clinical judgment could be used as a potential modifier.

Methods: Subjects were recruited from the patient population of a community clinic providing primary ambulatory pediatric care.

Obstructing gastric heterotopic pancreas: case report and literature review.

Heterotopic pancreas (HP) is generally an asymptomatic lesion and is a rare cause of gastric outlet obstruction. We report such a case in which both upper gastrointestinal series and abdominal computerized tomography (CT) demonstrated an antral mass; surgical and histological results are also reported.

Nimesulide-induced acute hepatitis.

Objective: To report the occurrence of nimesulide-induced acute hepatitis confirmed by biopsy and an in vitro lymphocyte toxicity assay.

Case Summary: A 54-year-old Arabic woman treated with nimesulide for chronic low back pain was admitted to the hospital with acute hepatitis confirmed by biopsy. Her liver function test results returned to normal within one month after nimesulide discontinuation.

Linear EUS for bile duct stones.

Background: Radial scanning endoscopic ultrasonography (EUS) has been shown, in experienced hands, to be a safe and accurate means of detecting bile duct stones. We compared linear array EUS with endoscopic retrograde cholangiopancreatography (ERCP), in our first 50 cases, to evaluate efficacy of this examination as well as the learning curve for this indication.

Methods: A retrospective study was conducted on 50 patients with suspected choledocholithiasis.

The role of endoscopic retrograde cholangiopancreatography in the laparoscopic era.

Background: The optimal approach to patients with suspected common bile duct (CBD) stones remains unsettled. Options include pre- and postoperative endoscopic retrograde cholangiopancreatography (ERCP) or laparoscopic exploration of the CBD. This retrospective study evaluates the role of ERCP in the management of suspected CBD stones, with an emphasis on indications, endoscopic findings, and outcome.

A prospective study evaluating the usefulness of continuous supplemental oxygen in various endoscopic procedures.

The influence of oxygen supplementation on the prevalence of hypoxemia during endoscopic procedures was studied in 289 patients in a prospective clinical trial. The frequency of oxygen desaturation was found to decrease significantly in patients receiving oxygen via nasal prongs, compared to patients not receiving oxygen supplementation. The effect was demonstrated especially in patients who underwent an additional procedure during their endoscopic examinations.

[Endoscopic retrograde cholangiopancreatography in diagnosis of biliary atresia].

The differential diagnosis between neonatal hepatitis and biliary atresia in the newborn is difficult and has therapeutic implications. Despite important advances in diagnostic tools, 10-20% of newborns with jaundice remain without definitive diagnosis. In recent years ERCP has played a decisive role in achieving definitive anatomic diagnosis, thus avoiding unnecessary exploratory laparotomy.