Management strategy after diagnosis of Abernethy malformation: a case report

<p>Abstract</p> <p>Introduction</p> <p>The Abernethy malformation is a rare anomaly with a widely variable clinical presentation. Many diagnostic dilemmas have been reported. Nowadays, with the evolution of medical imaging, diagnosis can be made more easily, but management of patients with an Abernethy malformation is still open for discussion.</p> <p>Case presentation</p> <p>In this case study, we describe a 34-year-old Caucasian man who presented with a large hepatocellular carcinoma in the presence of an Abernethy malformation, which was complicated by the development of pulmonary arterial hypertension.</p> <p>Conclusion</p> <p>This case underlines the importance of regular examination of patients with an Abernethy malformation, even in older patients, to prevent complications and to detect liver lesions at an early stage.</p

Intraoperative Autologous Platelet-Rich Stroma Injection as Add-On to Fistula Curettage and Closure of the Internal Orifice Demonstrates a Favorable Outcome in Long-Term in Patients Suffering from Therapy-Refractory Perianal Fistulizing Crohn's Disease

Background:An injection with autologous platelet-rich stroma (PRS), a combination of stromal vascular fraction and platelet-rich plasma, as an add-on to fistula curretage and closure of the internal orifice proved to be safe and feasible for the treatment of patients with treatment-refractory perianal fistulizing Crohn's disease (pCD). This study aimed to assess the long-term outcomes in patients with pCD treated with autologous PRS injection. Methods:Adult patients with therapy-refractory pCD (failure to anti-tumor necrosis factor [TNF] therapy and/or fistula surgery), who underwent fistula curettage, closure of the internal fistula orifice, and autologous PRS injection in a Dutch tertiary referral center were included in an earlier conducted pilot study (n = 25). The primary outcome was complete clinical closure at long-term follow-up (closure of all treated external opening[s]). Secondary outcomes were partial clinical closure (closure of ≥1 treated external opening[s]), radiologic healing (fibrotic fistula tract on magnetic resonance imaging), and recurrence. Results:The majority of the patients were female (56%) (mean age 34.4 years [standard deviation - SD: 0.9], and mean follow-up 3.7 years [SD: 0.6]). The treatment-refractory character of the study cohort was displayed by the high rate of patients with ≥1 external opening (60%), prior exposure to an anti-TNF agent (92%), TOpClass classification system ≥ class 2b (36%), and the low rate of patients who underwent prior surgical interventions aimed at fistula closure (12%). During long-term follow-up, complete clinical closure was achieved in 88%. Partial clinical closure was achieved in all patients. Radiologic healing was achieved in 75% of the patients. Recurrence was reported in 8% of the patients who achieved prior clinical closure. No recurrences were observed in patients with radiologic healing. Seventeen unplanned re-interventions were reported in nine patients (36%), predominantly for residual fistulizing disease and in patients with severe therapy-refractory pCD (TOpClass classification system ≥ class 2b) at the time of inclusion. Conclusion:Additional PRS injection, fistula curettage, and closure of the internal orifice is a promising therapy for patients with (treatment-refractory) pCD and could improve clinical and radiologic healing rates. In addition, low recurrence rates were observed. Future randomized research is warranted in order to assess the effectiveness and positioning of PRS in the field of pCD.</p

Additional Intraoperative Autologous-Derived Platelet-Rich Stroma to Transanal Flap Repair for the Treatment of Cryptoglandular Transsphincteric Fistulas in a Tertiary Referral Center:Long-Term Outcomes of a Prospective Pilot Study

Transanal advancement flap repair (TAFR) fails in approximately 30–40% of patients with a cryptoglandular transsphincteric fistula. An additional intraoperative injection of autologous platelet-rich stroma (PRS) with TAFR proved to be safe, feasible, and effective in the short term for the treatment of cryptoglandular transsphincteric fistula in a tertiary referral center. In this study, we assessed the long-term outcomes in patients with a cryptoglandular transsphincteric fistula who were treated with an additional intraoperative autologous PRS injection with TAFR (n = 43). The majority of the patients (88%) had a complex transsphincteric fistula (high transsphincteric and/or multiple side tracts) and underwent (one or more) fistula procedure(s) aimed at fistula repair (56%) before study inclusion. At a median follow-up time of 4.2 years [IQR 3.5–5.1], long-term primary clinical closure (i.e., clinical closure of the treated external fistula opening(s) after TAFR with additional PRS injection without the need for any re-interventions during long-term follow-up) was observed in 77% of the patients. Subsequently, 94% of these patients also reached radiological healing (i.e., fibrotic fistula tract on MRI). Recurrence after clinical closure or radiological healing was observed in 9% and 5%. Unplanned re-interventions were performed in 12% of the patients for recurrent or residual fistulizing disease. In this uncontrolled pilot study, additional autologous PRS injection with TAFR showed promising outcomes, as long-term primary clinical closure and, subsequently, radiological healing was reached in the vast majority of tertiary referral patients with a (complex) cryptoglandular transsphincteric fistula at long-term follow-up. In addition, recurrence rates were low. Future randomized research is warranted to study the effects of PRS.</p

Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis

PURPOSE: Early detection of hepatocellular carcinoma (HCC) is essential for improved prognosis and long-term survival. To date, screening for HCC depends on serological testing (alpha-fetoprotein, AFP) and imaging (ultrasonography), both of which are not highly sensitive. A meta-analysis was performed to discuss recent developments in biomarkers that may be effective in screening for HCC. METHODS: A systematic search of PubMed, Embase, and Web of Science was performed for articles published between January 2005 and October 2010, and focusing on biomarkers for HCC in urine, serum, or saliva. Data on sensitivity and specificity of tests were extracted from each included article and displayed with a summary ROC. A meta-analysis was carried out in which the area under the curve for each biomarker was used to compare the accuracy of different tests. RESULTS: In seven well-defined studies, three biomarkers were identified for potential use, namely, Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA). Comparison with AFP showed that GP73 was superior (p = 0.006; 95 % CL −0.23, −0.12), IL-6 was similar (p = 0.66; 95 % CL −0.31, 0.25), and SCCA was inferior to AFP (p = 0.001; 95 % CL 0.12, 0.23). CONCLUSION: GP73 is a valuable serum marker that seems to be superior to AFP and can be useful in the diagnosis and screening of HCC. Although GP73 may improve the detection and treatment of one of the most common malignancies worldwide, additional research is required

Additional Intraoperative Autologous-Derived Platelet-Rich Stroma to Transanal Flap Repair for the Treatment of Cryptoglandular Transsphincteric Fistulas in a Tertiary Referral Center: Long-Term Outcomes of a Prospective Pilot Study

Transanal advancement flap repair (TAFR) fails in approximately 30–40% of patients with a cryptoglandular transsphincteric fistula. An additional intraoperative injection of autologous platelet-rich stroma (PRS) with TAFR proved to be safe, feasible, and effective in the short term for the treatment of cryptoglandular transsphincteric fistula in a tertiary referral center. In this study, we assessed the long-term outcomes in patients with a cryptoglandular transsphincteric fistula who were treated with an additional intraoperative autologous PRS injection with TAFR (n = 43). The majority of the patients (88%) had a complex transsphincteric fistula (high transsphincteric and/or multiple side tracts) and underwent (one or more) fistula procedure(s) aimed at fistula repair (56%) before study inclusion. At a median follow-up time of 4.2 years [IQR 3.5–5.1], long-term primary clinical closure (i.e., clinical closure of the treated external fistula opening(s) after TAFR with additional PRS injection without the need for any re-interventions during long-term follow-up) was observed in 77% of the patients. Subsequently, 94% of these patients also reached radiological healing (i.e., fibrotic fistula tract on MRI). Recurrence after clinical closure or radiological healing was observed in 9% and 5%. Unplanned re-interventions were performed in 12% of the patients for recurrent or residual fistulizing disease. In this uncontrolled pilot study, additional autologous PRS injection with TAFR showed promising outcomes, as long-term primary clinical closure and, subsequently, radiological healing was reached in the vast majority of tertiary referral patients with a (complex) cryptoglandular transsphincteric fistula at long-term follow-up. In addition, recurrence rates were low. Future randomized research is warranted to study the effects of PRS

Magnetization transfer imaging in ‘premanifest’ Huntington’s disease

To investigate whether magnetization transfer imaging (MTI) is a useful detector of diffuse brain abnormalities in ‘premanifest’ carriers of the Huntington’s disease (HD) gene mutation. Furthermore we examined the relations between MTI, clinical measures and CAG repeat length. Sixteen premanifest carriers of the HD gene without motor manifestation and 14 non-carriers underwent a clinical evaluation and a MRI scan. MTI analysis of whole brain, grey matter and white matter was performed producing magnetization transfer ratio (MTR) histograms. A lower peak height of the grey matter MTR histogram in carriers was significantly associated with more UHDRS motor abnormalities. Furthermore, a lower peak height of the whole brain, grey and white matter was strongly associated with a longer CAG repeat length. MTI measures themselves did not differ significantly between carriers and non-carriers. In premanifest HD mutation carriers, a lower MTR peak height, reflecting worse histological brain composition, was related to subtle motor abnormalities and higher CAG repeat length. Although we could not detect altered MTI characteristics in carriers of the HD gene mutation without clinical manifestations, we did provide evidence that the MTR peak height might reflect genetic and subclinical disease burden and may be of value in monitoring further disease progression and provide insight in clinical heterogeneity

Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease

An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington’s disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington’s disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington’s disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington’s disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington’s disease and their effect on brain structure

Seven-year clinical follow-up of premanifest carriers of Huntington's disease

Detecting subtle clinical abnormalities in the ‘premanifest’ phase of Huntington’s disease (HD) is of importance in the development of instruments to monitor early therapeutic intervention trials. The current study examined changes in motor function, cognition and behaviour over a period of seven years in premanifest carriers of the HD gene mutation. Twenty-nine carriers without unequivocal motor signs of HD and 43 non-carrier controls were prospectively examined four times. The assessments consisted of the Unified Huntington’s Disease Rating Scale (UHDRS) and an extensive neuropsychological test battery addressing global cognitive function, memory, language and executive function. Rate of Change (RoC) analysis was performed to measure longitudinal differences between carriers and non-carriers. Carriers performed consistently worse on executive function (Symbol Digit Modalities Test (SDMT), Stroop, Trail Making Test (TMT) and WAIS-R arithmetic). Over the years, carriers showed a decline in memory and concentration function (Wechsler Memory Scale (WMS)) and in motor function (UHDRS motor scale). Changes over time could be particularly ascribed to carriers converting to manifest HD. These results demonstrate that standardized motor assessments and objective memory and concentration tasks are sensitive to change over a period of 7 years, specifically in carriers converting to manifest HD. Executive tasks also showed subtle cognitive abnormalities in premanifest HD, but a decline over time could not be demonstrated