Trends and Outcomes in Simultaneous Liver and Kidney Transplantation in Australia and New Zealand

AimRates of simultaneous liver and kidney transplantation (SLKT) have increased, but indications for SLKT remain poorly defined. Additional data are needed to determine which patients benefit from SLKT to best direct use of scarce donor kidneys.MethodsData were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) database for all SLKT performed until the end of 2017. Patients were divided by pretransplant dialysis status into no dialysis before SLKT (preemptive kidney transplant) and any dialysis before SLKT (nonpreemptive). Baseline characteristics and outcomes were compared.ResultsBetween 1989 and 2017, inclusive, 84 SLKT procedures were performed in Australia, of which 24% were preemptive. Preemptive and nonpreemptive SLKT recipients did not significantly differ in age (P = .267), sex (P = .526), or ethnicity (P = .870). Over a median follow-up time of 4.5 years, preemptively transplanted patients had a statistically equivalent risk of kidney graft failure (hazard ratio (HR) 1.83, 95% confidence interval [CI]: 0.36-12.86, P = .474) and all-cause mortality (HR 1.69, 95% CI: 0.51-5.6, P = .226) compared to nonpreemptive patients. Overall, 1- and 5-year survival rates for all SLKTs were 92% (95% CI: 86-96) and 60% (95% CI: 45-75), respectively.ConclusionKidney graft and overall patient survival were similar between patients with preemptive kidney transplant and those who were dialysis dependent.     

Primary leiomyosarcoma of the skin: a comprehensive review on diagnosis and treatment

Sarcomas are a heterogeneous group of mesenchymal tumors which can affect bone and soft tissue. Leiomyosarcoma (LMS) is a rare subtype localized to the skin or subcutaneous tissue. Due to the heterogeneity of sarcomas, reviews and guidelines with an in-depth focus specifically on primary LMS of the skin are sparse. This article is intended to provide an up to date and systematic overview on diagnosis, treatment, and surveillance of this rare entity to provide a framework for decision making and management for dermato-oncologists. We discuss novel treatment options for advanced disease such as targeted therapy with kinase inhibitors and immune checkpoint blockade which may improve the prognosis even in advanced stages of LMS.     

The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications

Introduction: Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. Patients and methods: FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute‐on‐chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post‐treatment data were performed using paired t‐test. Results: The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 ± 9.46 mg/dL vs. 9.76 ± 7.05 mg/dL; P < 0.0001), ammonia (167.6 ± 75 mg/dL vs. 120 ± 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 ± 13.03 mg/dL vs. 8.18 ± 8.15 mg/dL; P < 0.0001), creatinine (0.54 ± 0.47 mg/dL vs. 0.46 ± 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 ± 0.05 vs. 7.44 ± 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. Conclusions: FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment. J. Clin. Apheresis 25:195–201, 2010. © 2010 Wiley‐Liss, Inc.     

Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature

Introduction

Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making.

Respiratory muscle metabolic activity on PET/CT correlates with obstructive ventilatory defect severity and prognosis in patients undergoing lung cancer surgery

Background and Objective

Respiratory muscle activity is increased in patients with chronic respiratory disease. ¹⁸F-FDG-PET/CT can assess respiratory muscle activity. We hypothesized that respiratory muscles metabolism was correlated to lung function impairment and was associated to prognosis in patients undergoing lung cancer surgery based on the research question whether respiratory muscle metabolism quantitatively correlates with the severity of lung function impairment in patients? Does respiratory muscle hypermetabolism have prognostic value?

Methods

Patients undergoing ¹⁸F-FDG-PET/CT and pulmonary function tests prior to lung cancer surgery were identified. Maximum Standardized Uptake Value (SUVm) were measured in each respiratory muscle group (sternocleidomastoid, scalene, intercostal, diaphragm), normalized against deltoid SUVm. Respiratory muscle hypermetabolism was defined as SUVm >90th centile in any respiratory muscle group. Clinical outcomes were collected from a prospective cohort.

Results

One hundred fifty-six patients were included, mostly male [110 (71%)], 53 (34%) with previous diagnosis of COPD. Respiratory muscle SUVm were: scalene: 1.84 [1.51–2.25], sternocleidomastoid 1.64 [1.34–1.95], intercostal 1.01 [0.84–1.16], diaphragm 1.79 [1.41–2.27]. Tracer uptake was inversely correlated to FEV1 for the scalene (r = −0.29, p < 0.001) and SCM (r = −0.17, p = 0.03) respiratory muscle groups and positively correlated to TLC for the scalene (r = 0.17, p = 0.04). Respiratory muscle hypermetabolism was found in 45 patients (28.8%), who had a lower VO₂ max (15.4 [14.2–17.5] vs. 17.2 mL/kg/min [15.2–21.1], p = 0.07) and poorer overall survival when adjusting to FEV1% (p < 0.01).

Conclusion

Our findings show respiratory muscle hypermetabolism is associated with lung function impairment and has prognostic significance. ¹⁸F-FDG/PET-CT should be considered as a tool for assessing respiratory muscle activity and to identify high-risk patients.     

Fine needle sclerotherapy as a new effective therapeutic approach for nonparasitic splenic cysts: A case series

BackgroundNonparasitic splenic cysts are rare. Until now, surgical intervention has been the standard therapy of symptomatic splenic cysts.AimsWe herein present a retrospective analysis of an approach using percutaneous ultrasound-guided fine needle aspiration and sclerotherapy.MethodsOut of 88,151 ultrasound reports, we identified 138 patients who presented with splenic cysts. A single splenic cyst was found in 88% (mean size 28.9 mm). Twelve patients underwent percutaneous therapy of symptomatic splenic cysts. They were younger, had larger splenic cysts and more often cyst internal echoes than the 126 untreated patients (all p < 0.0001).ResultsInitial sclerotherapy was performed with polidocanol 1% in 9 patients and with NaCl 10% in 2 patients. One hemorrhagic cyst was only purged. Serious adverse events were not noted. Eight patients had to undergo 1–11 further percutaneous cyst therapies. 15 of these 30 reinterventions were cyst aspiration therapies, only, and 11 of them were sclerotherapies with NaCl 10%. Four patients were readmitted to hospital for cyst retreatment. After 57 ± 43 months of follow-up, cyst size significantly decreased (p < 0.0001). Only two patients had a complicated course of cyst therapy.ConclusionsPercutaneous ultrasound-guided sclerotherapy is a new approach for symptomatic splenic cysts. In most patients, cyst size and symptoms can be significantly reduced during one hospital stay.     

Chronic nicotine exposure stimulates biliary growth and fibrosis in normal rats

BackgroundEpidemiological studies have indicated smoking to be a risk factor for the progression of liver diseases. Nicotine is the chief addictive substance in cigarette smoke and has powerful biological properties throughout the body. Nicotine has been implicated in a number of disease processes, including increased cell proliferation and fibrosis in several organ systems.AimsThe aim of this study was to evaluate the effects of chronic administration of nicotine on biliary proliferation and fibrosis in normal rats.MethodsIn vivo, rats were treated with nicotine by osmotic minipumps for two weeks. Proliferation, α7-nicotinic receptor and profibrotic expression were evaluated in liver tissue, cholangiocytes and a polarized cholangiocyte cell line (normal rat intrahepatic cholangiocyte). Nicotine-dependent activation of the Ca²⁺/IP₃/ERK 1/2 intracellular signalling pathway was also evaluated in normal rat intrahepatic cholangiocyte.ResultsCholangiocytes express α7-nicotinic receptor. Chronic administration of nicotine to normal rats stimulated biliary proliferation and profibrotic gene and protein expression such as alpha-smooth muscle actin and fibronectin 1. Activation of α7-nicotinic receptor stimulated Ca²⁺/ERK1/2-dependent cholangiocyte proliferation.ConclusionChronic exposure to nicotine contributes to biliary fibrosis by activation of cholangiocyte proliferation and expression of profibrotic genes. Modulation of α7-nicotinic receptor signalling axis may be useful for the management of biliary proliferation and fibrosis during cholangiopathies.     

A new side effect of immunosuppression: high incidence of hearing impairment after liver transplantation.

Little is known about hearing impairment in patients after organ transplantation. We conducted a single-center study to evaluate hearing impairment in patients after orthotopic liver transplantation (OLT). A questionnaire was sent to 695 adult patients after OLT to assess characteristics and course of auditory impairment. Risk factors such as ototoxic drugs were taken into consideration. Clinical follow-up, including immunosuppressive therapy, was analyzed in detail. The questionnaire was completed by 521 patients (75%). Hearing impairment was reported by 184 patients (35%). A total of 43 patients (8%) suffered from hearing abnormalities prior to OLT. The remaining 141 patients (27%) developed hearing impairment after transplantation. Main problems were hearing loss (52%), tinnitus (38%), and otalgia (30%). There was no association of post-OLT hearing disorders with age or known risk factors. In 43% of patients, onset of hearing impairment was within 2 yr post-OLT. Hearing loss was positively associated with tacrolimus immunosuppression in univariate (P < 0.05) and multivariate analysis (P < 0.02). Patients using a hearing aid received tacrolimus more frequently than cyclosporine (P < 0.05). In conclusion, subjective hearing impairment is frequent in patients after OLT and contributes to post-OLT morbidity. Calcineurin inhibitor-related neurotoxicity appears as a possible mechanism. Further prospective investigations with objective hearing tests are necessary to confirm these results and to evaluate the role of immunosuppression.