Citations

Screening for hepatopulmonary syndrome (HPS) using pulse oximetry is recommended in liver transplant (LT) candidates because mortality is increased, independently of the severity of the oxygenation defect. LT exception points may be afforded to those with HPS and severe hypoxemia. We assessed the screening characteristics of pulse oximetry for HPS. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study of adults undergoing their first LT evaluation. Patients underwent protocolized assessment of oxygen saturation by pulse oximetry (SpO2), arterial blood gas, spirometry, and contrast‐enhanced echocardiography (CE). HPS was defined as an alveolar‐arterial gradient ≥15 mm Hg (≥20 mm Hg if age >64 years), intrapulmonary vascular dilatation on CE, and absence of lung disease. The study sample included 363 patients. Of these, 75 (20.7%; 95% confidence interval [CI], 16.6%‐25.2%) met the criteria for HPS. The area under the receiver operating characteristic curve (or c‐statistic) for SpO2 in discriminating HPS was 0.59 (95% CI, 0.51‐0.66). An SpO2 <96%, recommended by practice guidelines as a threshold to require further testing, had low sensitivity (28%; 95% CI, 18%‐28%). The c‐statistic of SpO2 in discriminating HPS with a partial pressure of oxygen (PaO2) <60 mm Hg (eligible for LT exception points) was 0.76 (95% CI, 0.46‐1.00). An SpO2 cutoff of <96% had higher sensitivity for detecting HPS with PaO2 <60 mm Hg (71%; 95% CI, 38%‐100%) but was still inadequate. Conclusion: Pulse oximetry is not sufficiently sensitive to screen for HPS in LT candidates. Arterial blood gas and CE are required in LT candidates for diagnosis of HPS.

Even after 2 decades of experience in laparoscopic hepatectomy, data on purely laparoscopic approach for donor hepatectomy in adult living donor liver transplantation (LDLT) are limited. We report our initial experience of a purely laparoscopic approach for donor hepatectomy for adult recipients to explore its potential application in the management of donors. We did a retrospective data analysis of 54 consecutive patients operated on between May 2013 and February 2015. There were 41 right, 10 extended right, and 3 left hepatectomies. The median operative time was 436 minutes (range 294‐684 minutes), and warm ischemia time was 6 minutes (2‐12 minutes). Estimated blood loss was 300 mL (10‐850 mL), and none of the patients required intraoperative transfusion. Four cases were converted to open laparotomy. The major complication rate was 16.7%, and biliary complication was the most frequent cause. Patients with normal anatomy had a major complication rate of 9.3% as compared with 45.5% in patients with anatomic variations. All patients recovered, and there was no mortality. In conclusion, a purely laparoscopic donor hepatectomy for adult LDLT recipients seems to be a feasible option; with careful patient selection and when performed by experienced surgeons, it may afford results comparable to the open method.

Context.— Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts, hemosiderotic fibrolipomatous tumor (HFLT), and myxoinflammatory fibroblastic sarcoma (MIFS) are 3 distinct entities of low-grade spindle cell mesenchymal neoplasm. These tumors have similar clinical presentations and partially overlapping but distinctive pathologic features. A recurrent translocation, t(1;10)(p22;q24), has been detected in a subset of PHAT, HFLT, MIFS, and HFLT/MIFS hybrid cases. Translocation t(1;10)(p22;q24) involves transforming growth factor β-receptor 3 (TGFBR3) and meningioma-expressed antigen 5 (MGEA5) genes on chromosomes 1p22 and 10q24, respectively. However, the percentage of translocation in PHAT, HFLT, and MIFS varies significantly among different studies. The relationship among these tumors has been a controversial topic among experts. Objective.— To discuss the diagnostic and functional significance of translocation t(1;10)(p22;q24) TGFBR3/MGEA5 rearrangement in HFLT, PHAT, and MIFS. Data Sources.— PubMed was used for this study. Conclusions.— Diagnosis of HFLT, PHAT, and MIFS is challenging because of a lack of unique morphologic, immunophenotypic, molecular, and cytogenetic markers. The recurrent t(1;10)(p22;q24) translocation and/or TGFBR3/MGEA5 rearrangement was reported in 55 patients, with a relatively even distribution among HFLT, PHAT, and MIFS (17 HFLT, 15 MIFS, 13 MIFS/HFLT, and 10 PHAT). This indicates that current morphology-based diagnostic criteria do not identify reliably the subset of soft tissue tumor with t(1;10) translocation. Genetic heterogeneity of these tumors is supported by the recent detection of a mutually exclusive, second recurrent genetic change, t(7;17) TOM1L2-BRAF translocation or BRAF amplification, in a subset of MIFS.

Cirrhotic cardiomyopathy in end‐stage liver disease is currently characterized by blunted contractile systolic response to stress with or without diastolic dysfunction in the absence of known heart disease. Since the establishment of the diagnostic criteria of cirrhotic cardiomyopathy in 2005, there have been multiple studies regarding its pathophysiology and pretransplant clinical course. The data regarding the post‐transplant course of this entity are sparse. This review addresses the course and prognosis of the elements of cirrhotic cardiomyopathy after liver transplantation (LT). To this end, there is limited compelling evidence demonstrating the reversibility of this entity post‐LT. Cirrhotic cardiomyopathy may, in fact, increase the risk of post‐transplant complications. This review reveals a need to refine the diagnostic criteria of cirrhotic cardiomyopathy in view of the remarkable progress in the sphere of echocardiographic evaluation of systolic and diastolic dysfunction. The post‐transplant course and outcomes related to cirrhotic cardiomyopathy may be better evaluated in the setting of updated diagnostic criteria.

AbstractThis study used resting state functional magnetic resonance imaging (rsfMRI) to investigate whole brain networks in patients with persistent postural perceptual dizziness (PPPD). We compared rsfMRI data from 38 patients with PPPD and 38 healthy controls using whole brain and region of interest analyses. We examined correlations among connectivity and clinical variables and tested the ability of a machine learning algorithm to classify subjects using rsfMRI results. Patients with PPPD showed: (a) increased connectivity of subcallosal cortex with left superior lateral occipital cortex and left middle frontal gyrus, (b) decreased connectivity of left hippocampus with bilateral central opercular cortices, left posterior opercular cortex, right insular cortex and cerebellum, and (c) decreased connectivity between right nucleus accumbens and anterior left temporal fusiform cortex. After controlling for anxiety and depression as covariates, patients with PPPD still showed decreased connectivity between left hippocampus and right inferior frontal gyrus, bilateral temporal lobes, bilateral insular cortices, bilateral central opercular cortex, left parietal opercular cortex, bilateral occipital lobes and cerebellum (bilateral lobules VI and V, and left I–IV). Dizziness handicap, anxiety, and depression correlated with connectivity in clinically meaningful brain regions. The machine learning algorithm correctly classified patients and controls with a sensitivity of 78.4%, specificity of 76.9%, and area under the curve = 0.88 using 11 connectivity parameters. Patients with PPPD showed reduced connectivity among the areas involved in multisensory vestibular processing and spatial cognition, but increased connectivity in networks linking visual and emotional processing. Connectivity patterns may become an imaging biomarker of PPPD.

Abstract The trend toward precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration-resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer–related genes. CTCs were isolated from the whole blood of mCRPC patients (n = 41) and multiplex qPCR was performed to evaluate expression of prostate cancer–related target genes (n = 78). A large fraction of patients (27/41, 66%) had detectable CTCs. Increased androgen receptor (AR) expression (70% of samples) and evidence of Wnt signaling (67% of samples) were observed. The TMPRSS2:ERG fusion was expressed in 41% of samples, and the aggressive prostate cancer–associated long noncoding RNA SChLAP1 was upregulated in 70%. WNT5a [HR 3.62, 95% confidence interval (CI), 1.63–8.05, P = 0.002], AURKA (HR 5.56, 95% CI, 1.79–17.20, P = 0.003), and BMP7 (HR 3.86, 95% CI, 1.60–9.32, P = 0.003) were independently predictive of overall survival (FDR &lt; 10%) after adjusting for a panel of previously established prognostic variables in mCRPC (Halabi nomogram). A model including Halabi, WNT5a, and AURKA expression, termed the miCTC score, outperformed the Halabi nomogram alone (AUC = 0.89 vs. AUC = 0.70). Understanding the molecular landscape of CTCs has utility in predicting clinical outcomes in patients with aggressive prostate cancer and provides an additional tool in the arsenal of precision-based therapeutic approaches in oncology. Implications: Analysis of CTC gene expression reveals a clinically prognostic “liquid biopsy” signature in patients with metastatic castrate-resistance prostate cancer. Mol Cancer Res; 16(4); 643–54. ©2018 AACR.