Modern insights into the pathophysiology and treatment of pseudoachalasia.

BACKGROUND: Secondary achalasia or pseudoachalasia is a clinical presentation undistinguishable from achalasia in terms of symptoms, manometric, and radiographic findings, but associated with different and identifiable underlying causes. METHODS: A literature review was conducted on the PubMed database restricting results to the English language. Key terms used were "achalasia-like" with 63 results, "secondary achalasia" with 69 results, and "pseudoachalasia" with 141 results. References of the retrieved papers were also manually reviewed. RESULTS: Etiology, diagnosis, and treatment were reviewed. CONCLUSIONS: Pseudoachalasia is a rare disease. Most available evidence regarding this condition is based on case reports or small retrospective series. There are different causes but all culminating in outflow obstruction. Clinical presentation and image and functional tests overlap with primary achalasia or are inaccurate, thus the identification of secondary achalasia can be delayed. Inadequate diagnosis leads to futile therapies and could worsen prognosis, especially in neoplastic disease. Routine screening is not justifiable; good clinical judgment still remains the best tool. Therapy should be aimed at etiology. Even though Heller's myotomy brings the best results in non-malignant cases, good clinical judgment still remains the best tool as well.

Follow-up of participants with subjective cognitive decline from Tremembé epidemiologic study, Brazil.

Subjective cognitive decline is defined as a self-perceived cognitive decline but with normal performance in neuropsychological assessments. Objective: To verify the evolution of patients diagnosed with subjective cognitive decline compared to the cognitively normal group without any concern. Methods: This is a follow-up study based on data analysis from the Tremembé epidemiologic study, in Brazil. The 211 individuals classified as cognitively normal and 174 diagnosed as having subjective cognitive decline at baseline were invited to participate. Results: After a median follow-up time of five years, 108 subjective cognitive decline participants (62.0%) were reassessed. Of these, 58 (53.7%) kept this diagnosis, whereas 14 individuals (12.9%) progressed to mild cognitive impairment and 5 (4.6%) to dementia. In the cognitively normal group, 107 (50.7%) were reassessed, of which 51 (47.7%) were still classified likewise, 6 (5.6%) evolved to mild cognitive impairment and 9 (8.4%) to dementia. The presence of cognitive decline had a significant association with increasing age and depression symptoms. Considering the total number of baseline participants in each group: the subjective cognitive decline group showed higher percentage of mild cognitive impairment (p=0.022) and no difference was found in progression to dementia (p=0.468) between the groups after follow-up assessment. Conclusion: Most subjective cognitive decline participants at baseline kept their cognitive complaint at follow-up and this group progressed more to mild cognitive impairment than the other group. No difference in the progression to dementia was found, despite the higher incidence of dementia in the cognitively normal group.

O declínio cognitivo subjetivo (DCS) é definido como autopercepção de declínio cognitivo, mas com desempenho normal nas avaliações neuropsicológicas. Objetivo: O objetivo foi verificar a evolução dos pacientes diagnosticados com DCS em relação ao grupo cognitiva mente normal (CN), sem qualquer queixa. Métodos: Trata-se de um estudo de seguimento baseado na análise de dados do estudo epidemiológico de Tremembé, Brasil. Os 211 indivíduos classificados como CN e os 174 diagnosticados como DCS na fase inicial do estudo foram convidados a participar. Resultados: Após o tempo médio de seguimento de cinco anos, 108 participantes da DCS (62,0%) foram reavaliados. Deles, 58 (53,7%) mantiveram o diagnóstico de DCS, enquanto 14 (12,9%) evoluíram para comprometimento cognitivo leve (CCL) e cinco (4,6%) para demência. No grupo CN, 107 (50,7%) foram reavaliados, dos quais 51 (47,7%) ainda foram classificados como CN, seis (5,6%) evoluíram para CCL e nove (8,4%) para demência. A presença de declínio cognitivo teve associação significativa com o aumento da idade e com sintomas de depressão. Considerando-se o número total de participantes da fase inicial do estudo de cada grupo: o grupo DCS apresentou maior percentual de CCL (p=0,022) e não houve diferença na progressão para demência (p=0,468) entre ambos os grupos após a avaliação de seguimento. Conclusão: A maioria dos participantes DCS da fase inicial do estudo manteve sua queixa cognitiva no seguimento, e esse grupo progrediu mais para CCL. Não foi encontrada diferença na progressão para demência, apesar da maior incidência de demência no grupo CN.

Follow-up of participants with subjective cognitive decline from Tremembé epidemiologic study, Brazil / Seguimento dos participantes com declínio cognitivo subjetivo do estudo epidemiológico de Tremembé, Brasil

ABSTRACT. Subjective cognitive decline is defined as a self-perceived cognitive decline but with normal performance in neuropsychological assessments. Objective: To verify the evolution of patients diagnosed with subjective cognitive decline compared to the cognitively normal group without any concern. Methods: This is a follow-up study based on data analysis from the Tremembé epidemiologic study, in Brazil. The 211 individuals classified as cognitively normal and 174 diagnosed as having subjective cognitive decline at baseline were invited to participate. Results: After a median follow-up time of five years, 108 subjective cognitive decline participants (62.0%) were reassessed. Of these, 58 (53.7%) kept this diagnosis, whereas 14 individuals (12.9%) progressed to mild cognitive impairment and 5 (4.6%) to dementia. In the cognitively normal group, 107 (50.7%) were reassessed, of which 51 (47.7%) were still classified likewise, 6 (5.6%) evolved to mild cognitive impairment and 9 (8.4%) to dementia. The presence of cognitive decline had a significant association with increasing age and depression symptoms. Considering the total number of baseline participants in each group: the subjective cognitive decline group showed higher percentage of mild cognitive impairment (p=0.022) and no difference was found in progression to dementia (p=0.468) between the groups after follow-up assessment. Conclusion: Most subjective cognitive decline participants at baseline kept their cognitive complaint at follow-up and this group progressed more to mild cognitive impairment than the other group. No difference in the progression to dementia was found, despite the higher incidence of dementia in the cognitively normal group.

RESUMO. O declínio cognitivo subjetivo (DCS) é definido como autopercepção de declínio cognitivo, mas com desempenho normal nas avaliações neuropsicológicas. Objetivo: O objetivo foi verificar a evolução dos pacientes diagnosticados com DCS em relação ao grupo cognitiva mente normal (CN), sem qualquer queixa. Métodos: Trata-se de um estudo de seguimento baseado na análise de dados do estudo epidemiológico de Tremembé, Brasil. Os 211 indivíduos classificados como CN e os 174 diagnosticados como DCS na fase inicial do estudo foram convidados a participar. Resultados: Após o tempo médio de seguimento de cinco anos, 108 participantes da DCS (62,0%) foram reavaliados. Deles, 58 (53,7%) mantiveram o diagnóstico de DCS, enquanto 14 (12,9%) evoluíram para comprometimento cognitivo leve (CCL) e cinco (4,6%) para demência. No grupo CN, 107 (50,7%) foram reavaliados, dos quais 51 (47,7%) ainda foram classificados como CN, seis (5,6%) evoluíram para CCL e nove (8,4%) para demência. A presença de declínio cognitivo teve associação significativa com o aumento da idade e com sintomas de depressão. Considerando-se o número total de participantes da fase inicial do estudo de cada grupo: o grupo DCS apresentou maior percentual de CCL (p=0,022) e não houve diferença na progressão para demência (p=0,468) entre ambos os grupos após a avaliação de seguimento. Conclusão: A maioria dos participantes DCS da fase inicial do estudo manteve sua queixa cognitiva no seguimento, e esse grupo progrediu mais para CCL. Não foi encontrada diferença na progressão para demência, apesar da maior incidência de demência no grupo CN.

Clinical Validation of a Novel Scoring System Based on Donor and Recipient Risk Factors for Predicting Outcomes in Liver Transplantation.

BACKGROUND Adequate donor and recipient matching in liver transplantation is crucial to improve patient survival. Our objective was to propose and validate a new model for predicting outcomes using donor and recipient scoring criteria. MATERIAL AND METHODS We retrospectively analyzed data of all patients (n=932) who underwent liver transplantation (n=1106) from January 2006 to December 2018. For score standardization, 30% (n=280) of patients were randomly selected for analysis and divided into 3 categories: ≤4 points, 5 to 8 points, and >8 points. Scoring system validation was performed on a dataset with 70% (n=652) of the patients. RESULTS Survival of the stratified group (30%) was significant (P<0.001). Scores of 4 to 8 points presented lower risk of death (1.74 [CI 0.97-3.13; P=0.062]), while >8 points presented higher risk (2.74 [CI 1.36-5.57; P=0.005]). In the validation score (70%), global survival was significant (P<0.0016); patients with scores of 4 to 8 points had lower risk of death (1.16 [CI 1.16-2.38; P=0.005]); and scores >8 points (2.22 [CI 1.40-3.50; P<0.001]), retransplant, fulminant hepatitis, previous large abdominal/biliary tree surgery, MELD score, and serum creatinine before liver transplantation >1.5 mg/dL (P<0.05) presented higher risk. Individual recipient factors with 4 to 8 points had a lower risk of death (2.29 [CI 1.82-2.87; P<0.0001]) than those with scores >8 points (4.02 [CI 2.22-7.26; P<0.0001]). CONCLUSIONS A novel prognostic-based scoring system using donor and recipient characteristics was proposed and clinically validated. Two-factor scoring indicated the superiority of the predictability outcome and improved prediction of higher mortality.

Prognostic Factors Evaluation for Liver Transplant Mismatching: A New Way of Selecting and Allocating Organs.

BACKGROUND: Liver transplant (LT) is the standard therapy for end-stage liver disease. Advances in surgical techniques and immunosuppression protocols improved the results of LT by increasing long-term survival. Nevertheless, an adequate match between the donor and recipient is paramount for avoiding futile liver transplants. We aimed to identify the prognostic factors in donor-recipient LT matching. METHODS: Retrospective analysis of adult LT was conducted from January 2006 to December 2018, which included the following transplant modalities: deceased donor LT (DDLT), living donor LT (LDLT), combined liver-kidney transplant (CLKT), and domino LT (DLT). RESULTS: Among 1101 patients who underwent LT, 958 patients underwent DDLT, 92 patients underwent LDLT, 45 patients underwent CLKT, and 6 patients underwent DLT. The overall survival (OS) in 1, 5, and 10 years were 89%, 83%, and 82%, respectively. For DDLT, OS in 1, 5, and 10 years were 91%, 84%, and 82%, respectively. For LDLT, OS in 1, 5, and 10 years were 89%, 72%, and 69%, respectively. For CKLT, OS in 1, 5, and 10 years were 90%, 71%, and 71%, respectively. None of the DLT patients died. For DDLT, the factors that affected OS were the presence of fulminant liver failure (odds ratio [OR], 2.23; 95% CI, 1.18-4.18; P = .001), hemodialysis before LT (OR, 2.12; 95% CI, 1.27-3.5; P = .004), retransplant (OR, 4.74; 95% CI, 2.75-8.17; P = .000), and recipient age >60 years (OR, 1.86; 95% CI, 1.27-2.73; P = .001). For hospitalization before LT (due to an acute-on-chronic liver failure), the OR was 2.10 (95% CI, 1.29-3.42; P = .003). Donor intensive care unit time >7 days (OR, 1.46; 95% CI, 1.04-2.06; P = .02) was also associated with overall mortality. CONCLUSIONS: We identified prognostic factors in donor-recipient LT matching. Furthermore, we demonstrated that an adequate organ allocation with donor-recipient selection might increase graft survival and reduce waiting list mortality.

Feasibility of Large Liver Grafts in Adults.

INTRODUCTION: Size mismatch between donor and recipients may negatively influence postoperative results of liver transplantation (LT). In deceased donor LT for adults, large grafts are occasionally rejected due to the fear of primary nonfunction. The aim of this study is to assess the feasibility of using large liver grafts in adults undergoing deceased donor LT. METHODS: We performed a retrospective study including adult patients who underwent deceased donor LT at our center between January 2006 and September 2019. Recipients with donors aged less than 18 years and those receiving split-liver grafts were excluded. Graft weight of 1800 grams was the cutoff used to divide patients in 2 groups: group 1 (graft weighing < 1800 g) and group 2 (grafts weighing ≥ 1800 g). RESULTS: A total of 806 patients were included in the study. group 1 and 2 included 722 and 84 recipients, respectively. A larger proportion of male recipients was obseved in group 2: 64.8% vs 76.2% (P = .0037). Mean graft weight in group 1 and 2 was, respectively, 1348 ± 231.81 g and 1986.57 ± 165.51 g (P < .001), which resulted in significantly higher graft weight/recipient weight ratio and graft weight/standard liver volume ratio in group 2. In group 2, there were 9 (10.71%) patients with portal vein thrombosis as well as 24 patients (28.5%) with bulky ascites and 44 grafts (52.3%) with steatosis. Primary closure of the abdominal wall was not possible in 5 patients (5.9%) from this group. Primary nonfunction was diagnosed in 14 cases (16.6%), with liver retransplantation being performed in 6 of them. Male to female sex combination occurred in 19% of LT in group 2. CONCLUSION: The use of large grafts is feasible; however, proper matching between donor and recipient is paramount, especially taking into consideration graft steatosis, portal vein thrombosis and the presence of bulky ascites.

Histopathologic Evaluation of Acute on Chronic Liver Failure.

BACKGROUND: Currently, the diagnosis of acute on chronic liver failure (ACLF) is clinical, and its early identification and proper management are essential for a better prognosis. The aim of this study was to identify histopathologic parameters by analyzing cirrhotic liver explants that could aid in the early recognition of this entity and to determine prognostic factors that would influence ACLF management. METHOD: We performed a retrospective analysis of histopathologic material from liver explants from patients transplanted because of chronic hepatitis C virus infection from January 2007 to July 2017. Twenty-nine (n = 29) cases without hepatocellular carcinoma were selected. Histopathologic analysis included the Laennec classification, vascularization, and portal vein thrombosis. RESULTS: According to the diagnosis of ACLF, patients were divided in 2 groups: group ACLF (n = 10) and group no acute on chronic liver failure (NO-ACLF) (n = 19). Considering the whole series, mean age was 51 ± 11.48 years and prevalence of men was 58.62%. The mean Model of End-Stage Liver Disease (MELD) score at time of transplantation was significantly higher in the ACLF group than in the NO-ACLF group (35 ± 7 vs 22 ± 6, respectively, P < .05) as was the mean total bilirubin (14.38 ± 13.31 vs 8.84 ± 10.46 mg/dl, respectively, P < .05). Histopathologic analysis of explanted livers according to Laennec staging system of cirrhosis was as follows: 1. Group NO-ACLF: 1 case (5.25%) grade 3, 6 cases (31.58%) grade 4B, and 12 cases (63.16%) grade 4C; and 2. Group ACLF: 4 cases (40%) grade 4B and 6 cases (60%) grade 4C. Cholestasis was found in 1 patient in the NO-ACLF group (5%) and in 4 patients in the ACLF group (40%) (P = .03). We studied 30-day and 10-year survival respectively, which were 80% and 60% in the ACLF group and 83% and 70% in the NO-ACLF group (P = .794 and P = .657). CONCLUSION: In this preliminary approach, clinical and histologic findings contributed to the differential diagnosis of ACLF. The mean MELD score at time of liver transplantations, total bilirubin levels, and histologically evident cholestasis were significantly higher in patients with ACLF than in those without ACLF.

Adult-to-Adult Living Donor Liver Transplant: Hemodynamic Evaluation, Prognosis, and Recipient Selection.

BACKGROUND: Living donor liver transplant (LDLT) is a well-established treatment for end-stage liver disease. A better recipient selection and hemodynamic evaluation may improve transplant outcomes. The aim of this study was to establish recipient parameters that could enhance the results of adult-to-adult LDLT. METHODS: We performed a retrospective study of all adult-to-adult LDLTs from a single center between January 2006 and December 2018. Variables analyzed included demographic and clinical parameters, laboratory tests, performance of intraoperative temporary portocaval shunt (TPCS), graft weight/recipient weight ratio (GW/RW), preoperative portal vein thrombosis (PVT), previous major abdominal surgery, and patient survival. Patients were divided in 2 groups according to GW/RW (0.8% cutoff point). RESULTS: A total of 92 adult-to-adult LDLTs were analyzed, encompassing 53 male patients (57.6%). Mean Model for End-Stage Liver Disease score was 13.97 (SD, 4.74), and 57 patients (61.95%) had Child-Pugh-Turcotte score B. Mean GW/RW was 1.1% (SD, 0.37%). Group 1 with GW/RW > 0.8% (n = 74) and group 2 with it ≤ 0.8% (n = 13) presented mean GW/RW of 1.14% (SD, 0.24%) and 0.69% (SD, 0.09%) and P < .01, respectively. Eighteen patients (19.56%) presented PVT, with a worse survival than those without PVT (P = .006). Sixteen patients (17.39%) with previous major abdominal or biliary operations also presented higher mortality (P = .341). Forty-six (50%) intraoperative TPCSs were performed with a better 1- and 3-year patient survival. Receiver operating characteristic curve analysis showed PVT area under the curve of 0.701 (95% CI, 0.526-0.876; P = .018), positive predictive value of 0.69, and negative predictive value of 0.62. Multivariate analysis showed important risk regarding PVT (odds ratio, 6.160; 95% CI, 1.566-24.223; P = .004) and retransplant (odds ratio, 4.452; 95% CI, 0.843-23.503; P = .06). CONCLUSIONS: Better recipient selection without PVT or previous major abdominal surgery, an adequate GW/RW, and intraoperative TPCS with hemodynamic modulation significantly improve outcomes of adult-to-adult LDLT.

Intraoperative Temporary Portocaval Shunt in Liver Transplant.

BACKGROUND: Intraoperative temporary portocaval shunt (TPCS) has been performed during liver transplant to improve hemodynamics and renal function as well as to decrease bleeding during hepatectomy. The aim of this study was to evaluate the impact of TPCS on liver transplant in a long-term single-center study. METHODS: From January 2006 to December 2018, all deceased donor transplants were retrospectively evaluated. Patients were divided in 2 groups: group 1, including those in whom intraoperative TPCS was performed and group 2, including those without TPCS. We analyzed recipient characteristics, survival, mortality, and complication rates in the intraoperative and postoperative periods. RESULTS: A total of 999 deceased donor liver transplants were studied, with 509 patients in group 1 and 490 in group 2. There were 156 cases (15.61%) of preoperative portal vein thrombosis in the whole series. Postoperative renal function (P = .029) as well as length of hospital and intensive care unit stay (P = .0001) were better in group 1. Surgery time and warm ischemia time was also shorter in group 1 (P = .0001). Complications with Clavien-Dindo score ≥ 3 were higher in group 2 (P = .006). Multivariate analysis showed important risk with fulminant hepatitis (odds ratio, 2.127; 95% CI, 1.408-3.213; P < .0001) and Model for End-Stage Liver Disease > 29 (odds ratio, 2.492; 95% CI, 1.862-3.336; P < .0001). Overall survival in group 1 at 1, 5, and 10 years were 78%, 70%, and 68%, respectively. In group 2, they were 70%, 60%, and 58%, respectively (P = .027). CONCLUSIONS: Patients who underwent intraoperative TPCS presented better postoperative renal function, less intraoperative blending, shorter surgical and warm ischemia time, shorter length of hospital and intensive care unit stay, and better overall survival after transplant. Moreover, TPCS should be used patients with severe conditions, such as fulminant hepatitis and Model for End-Stage Liver Disease score > 29.

Intraoperative Surgical Portosystemic Shunt in Liver Transplantation: Systematic Review and Meta-Analysis.

BACKGROUND Expanded clinical and surgical techniques in liver transplantation can markedly improve patient and graft survival. The main purpose of this study was to evaluate the efficacy of intraoperative portocaval shunts in liver transplantation. MATERIAL AND METHODS Searches were conducted in Cochrane, MEDLINE, and EMBASE databases, and updated in January 2018. The following specific outcomes of interest were defined and evaluated separated using 2 different reviews and meta-analyses for 1) hemi-portocaval shunt (HPCS) and 2) temporary portocaval shunt (TPCS). Comparative studies were analyzed separately for both surgical portocaval shunt modalities. RESULTS Only 1 well-designed randomized controlled trial was found. Most studies were retrospective or prospective. Initially, we found 1479 articles. Of those selected, 853 were from PubMed/MEDLINE, 32 were from Cochrane and 594 were from EMBASE. Our meta-analysis included a total of 3232 patients for all the included studies. Results found that 41 patients with HPCS experienced increased 1-year patient survival (OR 16.33; P=0.02) and increased 1-year graft survival (OR 17.67; P=0.01). The TPCS analysis with 1633 patients found patients had significantly shorter intensive care unit length of stay (days) (P=0.006) and hospital length of stay (P=0.02) and had decreased primary nonfunction (PNF) (OR 0.30, P=0.02) and mortality rates (OR 0.52, P=0.01). CONCLUSIONS Intraoperative surgical portosystemic shunt in relation to liver transplantation with TPCS was able to prevent PNF, decrease hospital length of stay and unit care length of stay. Furthermore, in analyzing data for patients with HPCS, we observed increases in the 1-year graft and patient survival rates. More prospective randomized trials are needed to arrive at a more precise conclusion.