Choledochoduodenostomy continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

Debate continues as to whether choledochoduodenostomy (CDD) can be used instead of Roux-en-Y choledochojejunostomy (CDJ) when duct-to-duct (DTD) is not an option. We hypothesized that CDD and CDJ had similar rates of complications. All deceased-donor liver transplantations from September 2011 to March 2020 were categorized by biliary reconstruction. Primary outcomes were bleeding, bile leak, anastomotic stricture, and cholangitis. Of the 1,086 patients, 812 (74.8%) received a DTD; 225 (20.7%) received a CDD; and 49 (4.5%) received a CDJ. Cholangitis was significantly higher in CDJ compared to DTD and CDD (26.5% vs 6% vs 13.8%, p < 0.0001). When controlling for significant confounders, CDJ had 10.2 higher odds of cholangitis (95% CI 4.4-23.2) compared to DTD, and 3.3 higher odds compared to CDD (95% CI 1.4-7.8). When compared to DTD, CDJ and CDD had significantly lower odds of stricture. CDD continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

Membrane Emulsification-A Novel Solution for Treatment and Reuse of Produced Water from Oil Field.

Produced water (PW) is, by volume, the largest waste product of the oil- and gas-exploration industry and contains pollutants such as hydrocarbons and heavy metals. To meet the stringent environmental regulations, PW must be treated before discharging into the environment. The current study proposes a novel treatment method where PW is used to prepare oil-in-water emulsion with potential applications within the oil-exploration industry. The emulsions are prepared by applying hollow fiber membrane emulsification (ME) on PW, which inherently contains oil, as to-be-dispersed phase. The results demonstrate that the average droplet size of the emulsions is a function of pressure applied on to-be-dispersed phase and could be customized from 0.24 to 0.65 µm by varying the pressure from 0.25 to 1 bar, respectively. Stability of the emulsions was verified under high pressure and a temperature and storage period of more than 24 h. The calculations showed that an ME unit with <100 kg weight and <1 m3 volume is appropriate to transform the daily average volume of PW from the Danish part of the North Sea into the emulsions. The study provides a novel route, which also complies well with the requirements (low-weight and small spatial footprints) of the offshore oil rigs, to treat and reuse PW within the oil production process and, therefore, eliminates its environmental footprint.

Detection of early allograft dysfunction at 30 min of reperfusion in liver transplantation: An intraoperative diagnostic tool with real time assessment of graft function.

INTRODUCTION: During the anhepatic phase of liver transplantation (LT), fibrinolytic activity increases, since the liver clears tissue plasminogen activator (tPA). We hypothesize that patients who fail to reduce fibrinolytic activity following graft reperfusion will have an increased rate of early allograft dysfunction (EAD). METHODS: Assessment of fibrinolysis in liver transplant recipients was quantified with thrombelastography (TEG) LY30. Changes in LY30 were assessed after graft reperfusion. The 30-min post-reperfusion LY30 was subtracted from the anhepatic LY30 quantifying fibrinolytic changes (delta-LY30). RESULTS: Seventy-three primary LT patients were included in the analysis. Receiver operating characteristic curve (ROC) analysis identified an inflection point of delta-LY30-5.3% as a risk factor for EAD. EAD occurred in 44% of these patients compared to 5% in high delta-LY30 (p = 0.002). CONCLUSION: LT recipients that develop hyperfibrinolysis who fail to reduce fibrinolytic activity 30 min after graft reperfusion had an EAD rate 8-fold higher than patients who had a large reduction in LY30 following reperfusion.

A clinical coagulopathy score concurrent with viscoelastic testing defines opportunities to improve hemostatic resuscitation and enhance blood product utilization during liver transplantation.

BACKGROUND: An NIH clinical coagulopathy score has been devised for trauma patients, but no such clinical score exists in transplantation surgery. We hypothesize that that this coagulopathy score can effectively identify laboratory defined coagulopathy during liver transplantation and correlates to blood product utilization. METHODS: TEGs were performed and coagulopathy scores (1, normal bleeding - 5, diffuse coagulopathic bleeding) were assigned by the surgeons at 5 intra-operative time points. Blood products used during the case were recorded between time points. Statistical analyses were performed to identify correlations between coagulopathy scores, TEG-detected abnormalities, and blood product utilization. RESULT: Transfusions rarely correlated with the appropriate TEG measurements of coagulation dysfunction. Coagulopathy score had significant correlation to various transfusions and TEG-detected coagulopathies at multiple points during the case. High aggregate coagulopathy scores identified patients receiving more transfusions, re-operations, and longer hospital stays CONCLUSION: The combination of viscoelastic testing and a standardized clinical coagulopathy score has the potential to optimize transfusions if used in tandem as well as standardize communication between surgery and anesthesia teams about clinically evident coagulopathy.

The use of thromboelastography to assess post-operative changes in coagulation and predict graft function in renal transplantation.

BACKGROUND: End stage renal disease (ESRD) is associated with elevated fibrinogen levels and fibrinolysis inhibition. However, there is a paucity of data on how renal transplantation impacts coagulation. we hypothesize that renal transplantation recipients with good functioning grafts will have improved fibrinolytic activity following surgery. METHODS: Kidney recipients were analyzed pre-operatively and on post-operative day 1(POD1) using three different TEG assays with and without two concentration of tissue-plasminogen activator (t-PA). TEG indices and percent reduction in creatinine from pre-op to POD1 were measured, with >50% defining "good" graft function. Follow up was done at 6, 12, and 24 months. RESULTS: Percent lysis(LY30) on POD1 the t-PA TEG was significantly correlated to change creatinine from pre-op to POD-1(p = 0.006). A LY30 ≥ 23% was associated with good early graft function, and lower creatinine at 24-months(p = 0.028) compared to recipients with low POD1 LY30. CONCLUSIONS: Post-operative tPA-TEG LY30 is associated with favorable early and late outcomes in kidney transplant.

Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy.

AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions. METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O2 content was computed as [hemoglobin (gm/dL) × 1.37 (mL O2/gm) × SpO2%) + (0.003 × PaO2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin. RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O2/100 mL blood vs 16.8 ± 3.3 mL O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r(2) = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006). CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.

The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen: a cross-sectional comparison of established screening tools in a German-Swiss population.

The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) has recently been developed as a fast and easy cognitive screening tool specifically designed for patients with motor impairments in routine clinical use. The German/Swiss-German version of the ECAS was validated in a German-Swiss consortium. One hundred and thirty-six non-demented ALS patients and 160 healthy controls were included in the study. In addition, the Frontal Assessment Battery (FAB), Montreal Cognitive Assessment (MoCA) and Consortium to Establish a Registry for Alzheimer's Disease plus Scale (CERAD plus) were administered to subgroups of patients. Results showed that administration of ECAS was fast (mean 24 min). Similar to the population in the UK version, ALS patients performed significantly worse in the ALS-specific functions (p < 0.001), specifically in the domain of language (p < 0.001), verbal fluency (p = 0.005) and executive functions (p = 0.02), but not for the non-ALS-specific functions. Carers reported behavioural abnormalities in about 30% and psychotic symptoms in 6% of the patients. Compared to ECAS, FAB, MoCA and CERAD were more generic and performance was not adjusted to motor speed. We conclude that the German/Swiss-German version of the ECAS is a fast and easy to administer cognitive screening instrument sensitive for ALS-specific dysfunctions and behaviour change.

Clinical and methodological confounders in assessing the cerebellar cognitive affective syndrome in adult patients with posterior fossa tumours.

The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman as a constellation of symptoms including dysexecutive syndrome, spatial cognitive deficit, linguistic deficits and behavioural abnormalities in patients with a lesion in the cerebellum with otherwise normal brain. Neurosurgical patients with cerebellar tumours constitute one of the cohorts in which the CCAS has been described. In this paper, we present a critical review of the literature of this syndrome in neurosurgical patients. Thereafter, we present a prospective clinical study of 10 patients who underwent posterior fossa tumour resection and had a detailed post-operative neuropsychological, neuropsychiatric and neuroradiological assessment. Because our findings revealed a large number of perioperative neuroradiological confounding variables, we reviewed the neuroimaging of a further 20 patients to determine their prevalence. Our literature review revealed that study design, methodological quality and sometimes both diagnostic criteria and findings were inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n = 10) showed very frequent neuroradiological confounding complications (e.g. hydrocephalus; brainstem compression; supratentorial lesions and post-operative subdural hygroma); the impact of such features had largely been ignored in the literature. Findings from our clinical study showed various degree of deficits in neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3, attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes), but no patient had full-blown features of CCAS. Our study, although limited, finds no robust evidence of the CCAS following surgery. This and our literature review highlight a need for guidelines regarding study design and methodology when attempting to evaluate neurosurgical cases with regard to the potential CCAS.

Dementia in developing countries: does education play the same role in India as in the West? / Demência nos países em desenvolvimento: a edução desempenha o mesmo papel na Índia como no ocidente

Evidence suggests that education protects from dementia by enhancing cognitive reserve. However, this may be influenced by several socio-demographic factors. Rising numbers of dementia in India, high levels of illiteracy and heterogeneity in socio-demographic factors provide an opportunity to explore this relationship. OBJECTIVE: To study the association between education and age at dementia onset, in relation to socio-demographic factors. METHODS: Association between age at dementia onset and literacy was studied in relationship to potential confounding factors such as gender, bilingualism, place of dwelling, occupation, vascular risk factors, stroke, family history of dementia and dementia subtypes. RESULTS: Case records of 648 dementia patients diagnosed in a specialist clinic in a University hospital in Hyderabad, India were examined. All patients were prospectively enrolled as part of an ongoing longitudinal project that aims to evaluate dementia subjects with detailed clinical, etiological, imaging, and follow-up studies. Of the 648 patients, 98 (15.1%) were illiterate. More than half of illiterate skilled workers were engaged in crafts and skilled agriculture unlike literates who were in trade or clerical jobs. Mean age at onset in illiterates was 60.1 years and in literates 64.5 years (p=0.0002). Factors independently associated with age at dementia onset were bilingualism, rural dwelling and stroke, but not education. CONCLUSION: Our study demonstrates that in India, rural dwelling, bilingualism, stroke and occupation modify the relationship between education and dementia.

Evidências sugerem que a educação protége de demência pelo fortalecimento da reserva cognitiva. Todavia, pode ser influenciado por vários fatores socioeconômicos. O aumento no número de demência na Índia, altos índices de analfabetismo e heterogeneidade de fatores sociodemográficos fornecem uma oportunidade para explorar estas relações. OBJETIVO: Estudar a associação entre educação e idade no início da demência em relação aos fatores sociodemográficos. MÉTODOS: A associação entre idade de início da demência e alfabetismo foi estudado em relação aos potenciais fatores confundidores, como gênero, bilinguismo, local de moradia, ocupação, fatores de risco vasculares, acidente vascular cerebral (AVC), história familiar de demência e subtipos de demência. RESULTADOS: Arquivos de 648 pacientes com demência, diagnosticados numa clínica especializada no Hospital Universitário em Hyderabad, foram avaliados. Todos os pacientes foram prospectivamente incluídos num projeto de acompanhamento longitudinal cujo objetivo é avaliar indivíduos com demência através de estudo de detalhado de acompanhamento clínico, etiológico e de imagem. Dos 648 pacientes, 98 (15%) eram analfabetos. Mais da metade dos analfabetos estavam envolvidos em trabalhos manuais ao contrário dos alfabetizados, envolvidos em comércio ou escritórios. A idade média de início em analfabetos foi de 60,1 anos e entre alfabetizados 64,5 anos de idade (p=0,0002). Os fatores independentemente associados à idade de início da demência foram bilinguismo, AVC, moradia rural, mas não educação. CONCLUSÃO: Nosso estudo demonstra que na Índia, moradia rural, bilinguismo, AVC e ocupação modificam a relação entre educação e demência.

Screening for cognition and behaviour changes in ALS.

This study presents the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), developed for ALS patients with physical disability for use by health care professionals. The screen is designed to detect the specific profile of cognition and behaviour changes in ALS and to differentiate it from other disorders. Forty-eight ALS patients (none with evident dementia), 40 healthy controls and 20 carers were recruited. The ECAS, a 15-20-min screen, includes an ALS-Specific score (executive functions and social cognition; fluency; language); an ALS Non-specific score (memory; visuospatial functions); and a carer behaviour screen of five domains characteristic of frontotemporal dementia (FTD). Data from healthy controls produced abnormality cut-offs of 77/100 ALS-Specific score; 24/36 ALS Non-specific score; 105/136 ECAS Total. Twenty-nine percent of patients showed abnormal ALS-Specific scores, and 6% also showed abnormal ALS Non-specific scores. The most prevalent deficit occurred in language functions (35%) followed by executive functions and fluency (23% each). Forty percent of carers reported behaviour change in at least one domain, while 15% met criteria for possible FTD. In conclusion, the ECAS is an effective within-clinic assessment for ALS that determines the presence, severity and type of cognitive and/or behavioural changes, an essential first step to managing these symptoms.

Semantic memory: nouns and action verbs in cognitively unimpaired individuals and frontotemporal lobar degeneration / Memória semântica: substantivos e verbos de ação em indivíduos sem distúrbios cognitivos e pacientes com degeneração lobar frontotemporal

ABSTRACT. Among the instruments to evaluate semantic memory, the Pyramids and Palm Trees (PPT) and the Kissing andDancing (KDT) tests are widely used but none have a performance referential for cognitively normal and impaired Brazilianpopulations. Objective: [A] To study these two tests in a sample of young healthy Brazilian individuals living in São Paulo;[B] To apply the results to the evaluation of two cases diagnosed with frontotemporal lobar degeneration. Methods: Weevaluated 50 normal participants (41 females and 9 males) aged between 20-63 years, with schooling level of 14-20 years.In addition, two individuals diagnosed with frontotemporal lobar degeneration were examined, one with behavioral-variantfrontotemporal dementia and the other with semantic dementia. Results: On the two tests, no effects of age, gender andschooling on the performance of normal individuals were observed. According to the performance of the sample of controls,scores below 46 points on the PPT and below 47 on the KDT are suggestive of deficits in semantic memory. The analysesof both cases indicated double dissociation in establishing associations between nouns and action verbs. Although the twopatients had low scores on both tests, the patient with behavioral-variant frontotemporal dementia performed better on thePPT compared to the KDT, while the patient with semantic dementia showed the reverse, performing better on the KDT.Conclusion: The PPT and KDT are suitable tests for use in the Brazilian population, with minimal need for adjustments.They are applicable tools both for cognitive assessment and research in semantic memory. In the present study, we obtainedrepresentative values of performance for cognitively unimpaired individuals and demonstrated the utility of these instrumentsfor cognitive assessment of patients with FTLD.

RESUMO. Entre os instrumentos dirigidos à avaliação da memória semântica, temos os testes Pirâmides e Palmeiras(Pyramids and Palm Trees - PPT) e o Beijando e Dançando (Kissing and Dancing - KDT), para os quais não existemreferências de desempenho de população brasileira normal e patológica. Objetivo: [A] Estudar esses dois testes emamostra de indivíduos jovens, sadios brasileiros, residentes na cidade de São Paulo; [B] Aplicar os resultados na avaliaçãode dois casos diagnosticados no espectro da degeneração lobar frontotemporal. Métodos: Avaliamos 50 participantesnormais (41 mulheres e 9 homens) com idade entre 20-63 anos e escolaridade entre 14-20 anos. Adicionalmente foramexaminados dois sujeitos com diagnóstico de degeneração lobar frontotemporal: um com demência frontotemporal-variantecomportamental e outro com demência semântica. Resultados: Não observamos efeitos de idade, gênero e escolaridadena performance dos indivíduos normais nos dois testes. Obtivemos os valores de 46 pontos no PPT e 47 no KDT comoindicativos de risco de déficit em memória semântica. A análise dos dois casos mostrou dupla dissociação na determinação de associações entre substantivos e verbos. Embora os pacientes apresentassem escores rebaixados nos dois testes, opaciente com demência frontotemporal-variante comportamental obteve melhor desempenho no PPT quando comparadoao KDT e o paciente com demência semântica mostrou padrão inverso, com melhor desempenho no KDT. Conclusão: Ostestes PPT e KDT são aplicáveis à população brasileira, com necessidade de mínimos ajustes. Foi possível obter valoresrepresentativos de desempenho de população sadia, assim como vislumbrar o emprego em avaliações cognitivas dememória semântica nas DLFT.

Screening for cognitive dysfunction in corticobasal syndrome: utility of Addenbrooke's cognitive examination.

INTRODUCTION: The motor features of corticobasal syndrome (CBS) are well recognized but the fact that many, if not all, affected patients develop cognitive impairment is still underrecognized. The dementia of CBS overlaps most with a language variant of frontotemporal dementia: progressive nonfluent aphasia (PNFA). The aim of this study was to determine the usefulness of Addenbrooke's Cognitive Examination-Revised (ACE-R) in the evaluation of CBS and to document similarities and differences between CBS and PNFA. MATERIALS AND METHODS: Patients with well-defined CBS or PNFA from two tertiary referral centers were selected along with matched controls. RESULTS: Twenty-one patients with CBS, 23 patients with PNFA and 47 age- and education- matched controls were included. Both CBS and PNFA groups showed substantial impairment on the ACE-R (f = 17.3-80.2, p < 0.001) and were significantly impaired in all domains (p < 0.001). The only significant difference between CBS and PNFA was in the visuospatial domain (p < 0.009), being worse in CBS. Using a cutoff of 88/89 out of 100, 90% of CBS and 82.6% of PNFA patients were impaired. At this cutoff of 88/89, ACE-R in CBS had sensitivity and specificity values of 91 and 98%, respectively.

Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal.

Our center has attempted to minimize corticosteroid (CS) use in all of our orthotopic liver transplantation (OLT) recipients. Because patients with autoimmune hepatitis (AIH) typically require CSs after transplantation, we reviewed our experience in this cohort of patients to determine (1) patient outcomes including recurrent disease and (2) long-term requirements for CS use in AIH patients. From 1988 to 2006, 1102 OLTs were performed in 1032 adult patients at the University of Colorado, of whom 66 (6%) with AIH received 68 allografts. Recurrence was defined by a clinically worsening examination and histological evidence from biopsy. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Twelve potential predictors of CS discontinuation were considered: age, gender, presence of inflammatory bowel disease (IBD), type of graft (cadaver or living donor), recurrence of AIH, warm ischemia time, follow-up time (time since transplant), and immunosuppressants (cyclosporine, tacrolimus, sirolimus, azathioprine, and mycophenolate mofetil). Overall survival at 5 years was 91%. The 1- and 5-year recurrence-free survival was 88% and 59%, respectively. Risk (incidence) of recurrent AIH at 1, 3, and 5 years was 12%, 26%, and 36%, respectively. Disease recurred in 23 of 66 patients or 34.8%. Of the 23 patients who developed recurrent disease, none received a second transplant because of recurrent disease. CSs were withdrawn in 50% of patients at the time of review. Only 2 factors on multivariate analysis were strongly associated negatively with CS withdrawal: (1) an increasing dose of the immunosuppressant and (2) the presence of IBD. Controlling for these other factors, we found that recurrent disease did not strongly influence CS withdrawal. In conclusion, outcomes in AIH patients were quite favorable, and none of the patients required retransplantation for recurrent AIH. With a CS minimization approach, one-half of the patients were able to remain CS-free.

Adjustable gastric banding in a morbidly obese patient during liver transplantation.

The increase in morbidly obese (MO; BMI >35) patients requiring liver transplant has mirrored the growing prevalence of obesity in the USA. However, there is considerable debate among physicians whether these patients should undergo transplantation. This is because outcome analysis shows that long-term survival following transplant is adversely affected by complications caused by MO. To date, there is little experience treating MO in transplant patients. Sustained weight reduction in MO liver transplant recipients would likely improve long-term survival and resolve the debate over whether these patients should receive a transplant. Three investigators have described good outcomes from bariatric surgical interventions following liver transplantation. But this requires a second operation with all the attendant risks of additional surgery and anesthesia. This report details an innovative step in the care of the MO transplant recipient: the placement of a gastric band at the time of transplantation. We describe the success of the combined procedure at 6 months following transplantation.

Clinically recurrent primary sclerosing cholangitis following liver transplantation: a time course.

Orthotopic liver transplantation (OLT) is the treatment of choice for patients with end-stage primary sclerosing cholangitis (PSC). This study sought to chronicle the natural history of PSC recurrence following OLT and identify clinical variables that may contribute to disease reemergence. From 1988 to 2006, 1102 OLTs were performed in 1032 adults at the University of Colorado Health Sciences Center. Of these, 130 patients (12.6%) with PSC received 146 allografts. Recurrence was defined by a clinically worsening examination and radiographic evidence. A total of 9 potential predictors were considered, using both bivariate log rank and multivariate Cox analysis, including: age > 55, gender, surgical technique (piggyback technique), presence of inflammatory bowel disease, intact colon before transplant, or cholangiocarcinoma (CCA), cold ischemia time, sirolimus-based immunosuppression, and graft type. The 1, 5, and 10-year recurrence-free survival was 91%, 76%, and 61%, respectively. The crude incidence of disease recurrence was 22 of 130 patients or 16.9%. Patients' risk of recurrent PSC at 1, 5, and 10 years was 2%, 12%, and 20%, respectively (mortality censored). Of the 22 patients that developed recurrent disease, 7 received a second transplant. Of the 9 factors considered, the presence of CCA prior to OLT is significantly predictive of disease recurrence [risk ratio (RR) = 3.77; P = 0.0038]. Once a patient was diagnosed with recurrent disease, the median survival without receiving a second transplant was 39.1 months (95% confidence interval: 27.6-50.6 months). In conclusion, recurrent PSC following OLT is a formidable but protracted problem following OLT. Patients may require a second transplant following reemergent disease with reasonable survival benefit.

Predictors of long-term outcome following liver transplantation for hepatocellular carcinoma: a single-center experience.

Orthotopic liver transplantation (OLT) is increasingly being applied for cure in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC). In recipients with limited tumor burden, OLT achieves reasonable long-term outcome. This study sought to identify clinical and pathologic variables predictive of long-term disease-free survival and the presence of vascular invasion. From 1992 to 2006, 130 patients underwent OLT for cirrhosis and HCC. Malignancy was diagnosed in 107 patients prior to OLT and in 23 patients on pathologic examination of the explant. Nine clinical and pathologic variables were considered including: TNM stage, nodularity, vascular invasion, Milan criteria, incidental lesion, differentiation, tumor size, preOLT transarterial chemoembolization (TACE), and administration of sirolimus-based immunosuppression. The overall incidence of HCC recurrence was 17% with the majority (82%) being stage III. Cumulatively, tumor recurrence-free survival (RFS) is 84, 74, and 67% at 1, 3, and 5 years respectively. Independent predictors of RFS included stage III and poorly differentiated lesions (P<0.05). Furthermore, stage III tumors and those >3.5 cm in size were predictive of vascular invasion. Importantly, preOLT, TACE and postOLT sirolimus had no influence on survival. Pathologic variables including tumor stage and grade have a significant impact on outcome. Importantly, it seems that TACE and sirolimus had no beneficial effect.

Sirolimus and liver transplantation: clinical implications for hepatocellular carcinoma.

Sirolimus (SRL) is a macrolide antibiotic that has potent antifungal and immunosuppressive properties; preclinical studies suggest that SRL may possess a significant antiproliferative influence in vitro. Recently, several studies have documented a negative effect by SRL on both primary tumor growth and the proliferation of metastatic foci in various rodent models of hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) is increasingly becoming a viable treatment option for patients with end stage liver disease and concomitant HCC. As such, an immunosuppressive agent with antineoplastic activity is inherently attractive in the setting of OLT for malignancy. Regrettably, the cumulative experience with SRL-based immunosuppression in this patient population is limited. Herein, the authors review the experience to date with SRL as a primary immunosuppressive agent following OLT, and discuss the clinical implications of SRL-based therapy in OLT recipients with cirrhosis and cancer.

Once-daily tacrolimus extended release formulation: experience at 2 years postconversion from a Prograf-based regimen in stable liver transplant recipients.

Compliance with complex immunosuppressant drug therapies in transplant recipients might be improved with regimens that require less frequent dosing. A once-daily extended release (XL) formulation of tacrolimus has been developed that allows a 1:1 conversion from the twice-a-day tacrolimus (TAC) formulation and has a good exposure to trough concentration correlation. In an open-label, multicenter study, stable liver transplant recipients (n=69) were converted from twice-a-day TAC to XL once-daily in the morning, and were maintained for at least 2 years postconversion using the same therapeutic monitoring and patient care techniques employed with TAC. Two years after conversion, the incidence of biopsy-confirmed acute rejection was 5.8% (4 of 69); patient and graft survival was 98.6% (68 of 69). The safety profile of XL was consistent with that previously reported for TAC. Liver transplant recipients can be converted from twice-a-day TAC to once-daily XL and maintained for at least 2 years postconversion with neither unique efficacy nor safety concerns.