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. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.
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. All three patients were treated with bortezomib, a proteasome inhibitor effective in depleting plasma cells. After treatment, all patients had improved or normal liver function tests, resolution of C4d deposition and significant decline in their HLA donor-specific antibodies.
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. However, there is no standard protocol for molecular diagnostic testing in prostate cancer. Here, we provide a series of recommendations on specimen handling, sample pre-analytics, laboratory workflow, and testing pathways to maximise the success rates for clinical genomic analysis in prostate cancer. Early involvement of a multidisciplinary team of pathologists, urologists, oncologists, radiologists, nurses, molecular scientists, and laboratory staff is key to enable optimal workflow for specimen selection and preservation at the time of diagnosis so that samples are available for molecular analysis when required. Given the improved outcome of patients with mCRPC and homologous recombination repair gene alterations who have been treated with PARP inhibitors, there is an urgent need to incorporate high-quality genomic testing in the routine clinical pathway of these patients.
uvenile polyposis (JP or JPS for juvenile polyposis syndrome) is an autosomal dominant disorder that often presents in childhood. It is characterized by the presence of hamartomatous (juvenile) polyps that vary in number from fi ve to several hundred (1, 2). Th e polyps are found primarily in the colorectum, but they can be present throughout the gastrointestinal tract, from the stomach to the rectum (2). Even though these polyps are normally benign, patients have an increased risk of gastrointestinal cancer (1-3). Th is disease occurs in approximately 1 in 100,000 people (4), and in 50% to 60% of the patients a germline mutation in SMAD4 (5) or bone morphogenic protein receptor 1A (BMPR1A) (6) genes can be found. Hereditary hemorrhagic telangiectasia (HHT; Osler-Weber-Rendu syndrome) is another autosomal dominant disorder distinguished by vascular dysplasia in multiple organs that can result in excessive bleeding. Th is syndrome was initially described by Osler in 1901 in a report of a familial form of recurrent mucous membrane bleeding from telangiectasias (3). Characteristic features include telangiectasias of the skin and oral and nasal mucosa, epistaxis, and arteriovenous malformations (AVMs) of the lungs, liver, brain, and gastrointestinal tract that can lead to hemorrhage and stroke (7-9). Th e frequency of this syndrome diff ers between populations, but it ranges from 1 in every 1300 Afro-Caribbeans in the Netherlands Antilles (10) to 1 in every 40,000 people in northern England (4). Approximately 80% of the families have a mutation in the endoglin (ENG) (5) or activin receptor-like kinase 1 (ALK1) (6) genes, while the remaining 20% of patients have a mutation in the SMAD4 gene (7) or in new loci mapped to chromosome 5 and chromosome 7 (8). A syndrome that combines JP and HHT was fi rst described in 1980 (9, 10). Th ese patients exhibit symptoms of both
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. Charts of 269 patients undergoing thyroid surgery at a tertiary care medical center from 2010 to 2013 were retrospectively reviewed. Sixty-six patients (24.5%) experienced unintentional parathyroidectomy. Bivariate analysis showed no significant differences in patient characteristics. Patients with unintentional parathyroid removal had a significantly smaller largest thyroid nodule size (P ¼ 0.002), higher rate of central neck dissection (30.3% vs 7.9%, P < 0.0001), and higher rate of malignancy (50% vs 36.0%, P ¼ 0.04). Multivariable analysis showed that the strongest risk factor for unintentional parathyroidectomy was central neck dissection (P ¼ 0.0008; odds ratio 4.72, confidence interval 1.91-11.71). In conclusion, central neck dissection for thyroid malignancy is the strongest risk factor for unintentional thyroidectomy. The presence of concomitant primary hyperparathyroidism, lymphocytic thyroiditis, or hyperthyroidism did not appear to increase the risk of unintentional parathyroidectomy.
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