Natural history of Wolcott-Rallison syndrome: A systematic review and follow-up study.

BACKGROUND AND AIMS: To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes. METHODS: PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed. RESULTS: Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013). CONCLUSION: Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.

Management and outcomes after liver transplantation for progressive familial intrahepatic cholestasis: A systematic review and meta-analysis.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous rare congenital cholestatic liver disease. Disease progression might necessitate liver transplantation (LT). The aim of this study was to describe the outcome of PFIC1-4 patients after LT. METHODS: Electronic databases were searched to identify studies on PFIC and LT. Patients were categorized according to PFIC type, genotype, graft type, age at LT, time of follow-up, and complications and treatment during follow-up. RESULTS: Seventy-nine studies with 507 patients met inclusion criteria; most patients were classified as PFIC1-3. The median age at LT was 50 months. The overall 5-year patient survival was 98.5%. PFIC1 patients with diarrhea after LT were at significant risk of developing graft steatosis ( p < 0.0001). Meta-analysis showed an efficacy of 100% [95% CI: 73.9%-100%] for surgical biliary diversion to ameliorate steatosis and 94.9% [95% CI: 53.7%-100%] to improve diarrhea (n = 8). PFIC2 patients with bile salt export pump (BSEP)2 or BSEP3-genotype were at significant risk of developing antibody-induced BSEP deficiency (AIBD) ( p < 0.0001), which was reported in 16.2% of patients at a median of 36.5 months after LT. Meta-analysis showed an efficacy of 81.1% [95% CI: 47.5%-100%] for rituximab-based treatment regimens to improve AIBD (n = 18). HCC was detected in 3.6% of PFIC2 and 13.8% of PFIC4 patients at LT. CONCLUSIONS: Fifty percent of PFIC1 patients develop diarrhea and steatosis after LT. Biliary diversion can protect the graft from injury. PFIC2 patients with BSEP2 and BSEP3 genotypes are at significant risk of developing AIBD, and rituximab-based treatment regimens effectively improve AIBD. PFIC3 patients have no PFIC-specific complications following LT.

Magnetic Resonance Imaging/Ultrasound Fusion-guided Transperineal Versus Magnetic Resonance Imaging/Ultrasound Fusion-guided Transrectal Prostate Biopsy-A Systematic Review.

CONTEXT: Magnetic resonance imaging (MRI)-targeted biopsies have changed the dogma in prostate cancer diagnosis. Biopsies can be performed either transrectally (MRI-guided and transrectal ultrasound fusion transrectal biopsy [MRI-TRUSB]) or transperineally (MRI-guided and transrectal ultrasound fusion transperineal biopsy [MRI-TPB]). OBJECTIVE: To evaluate the detection and complication rates of MRI-TRUSB and MRI-TPB. EVIDENCE ACQUISITION: We performed a literature search in PubMed, Scopus, EMBASE, and CENTRAL, and selected randomized controlled trials (RCTs) and observational studies comparing MRI-TRUSB versus MRI-TPB. EVIDENCE SYNTHESIS: Our search identified 3608 studies; we included five in the qualitative and two in the quantitative synthesis. On per-patient pooled analysis for clinically significant prostate cancer (csPCa), MRI-TPB detection rates were significantly higher (relative risk 1.28 [95% confidence interval {CI} 1.03-1.60], p = 0.03). On a per-lesion analysis, MRI-TPB anterior csPCa detection rates were statistically significantly higher (relative risk 2.46 [95% CI 1.22-4.98], p = 0.01). On a per-lesion analysis, MRI-TPB and MRI-TRUSB overall cancer detection rates were 75% and 81.6% (p= 0.53), and csPCa detection rates were 65.7% and 75.5% (p = 0.40), respectively. MRI-TPB had lower complication rates (odds ratio 2.56 [95% CI 1.14-5.56, p < 0.05]). On Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evaluation, we rated all outcomes as "very low" certainty of the evidence for all outcome measures. CONCLUSIONS: This review highlights the paucity of good-quality evidence comparing MRI-TPB and MRI-TRUSB. MRI-TPB achieves better detection for csPCa, anterior tumors, and lower infective complications. While RCTs are the highest quality of evidence that can address existing evidence limitations, there are concerns regarding infective complications associated with the MRI-TRUSB. Therefore, the authors propose that researchers and clinicians adopt a pragmatic approach by maintaining prospective databases, internal auditing of the MRI-TPB approach, and comparing these data with historical MRI-TRUSB cohorts. PATIENT SUMMARY: We looked at the outcomes by comparing magnetic resonance imaging (MRI)-guided and transrectal ultrasound fusion transrectal biopsy with MRI-guided and transrectal ultrasound fusion transperineal biopsy (TPB). The analysis suggests, based on very low certainty evidence, that MRI-TPB has better detection for clinically significant prostate cancer, anterior tumors, and lower complications.