Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception.

Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR-122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.

Liver Transplantation: Analysis of Preservation Solutions in the Andalusian Registry.

BACKGROUND: The initial objective of this study is to analyze the impact on survival of the preservation solution used. Secondarily, the influence of donor age, underlying pathology, and graft ischemia time is investigated. METHODS: A multicenter retrospective analytical observational study has been carried out. A population of 1822 liver transplant recipients is studied in 4 Andalusian hospitals between 1995 and 2014. Survival of the patient and graft is analyzed by groups based on the conservation solution used, the age of the donor, the pathology indicated for transplant and the ischemia time, and the relationship between the variables through a bivariate study. A descriptive and predictive multivariate analysis of the variables was performed. RESULTS: Comparison of the graft and patient survival functions for each preservation solution did not differ significantly. The bivariate analysis shows a significantly higher utilization of Celsior and histidine-tryptophan-ketoglutarate solution in graft loss. The comparison between donor age groups showed significant differences in favor of donor grafts younger than 50 years. In the multivariate analysis of patient and graft survival, the donor age obtained a hazard ratio of 1.008 (P < .005) with donors older than 47.6 and 47.5 years, respectively. CONCLUSIONS: Survival analysis between pathology groups found significant differences, not obtaining predictive power for patient or graft survival in the multivariate study. No significant differences were found in survival according to ischemia time, but there was a relationship between early graft loss and longer mean cold ischemia times up to 18 hours.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

BACKGROUND: Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). METHODS: In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. RESULTS: CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. CONCLUSIONS: CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

Cardiac troponin and COVID-19 severity: Results from BIOCOVID study.

BACKGROUND: Myocardial injury is a common finding in COVID-19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated cardiac troponin, in a large population of COVID-19 patients, and further evaluated separately the role of troponin T and I. METHODS: This is a multicentre, retrospective observational study enrolling patients with laboratory-confirmed COVID-19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex-specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty-day mortality was defined as endpoint. RESULTS: A total of 1280 COVID-19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut-off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex-specific cut-off was used. This prevalence was significantly higher (42.9% vs 21.9%; P < .001) in patients in whom troponin T was measured in comparison with troponin I. Sex-specific elevated troponin levels were significantly associated with 30-day mortality, with adjusted odds ratios (ORs) of 3.00 for total population, 3.20 for cardiac troponin T and 3.69 for cardiac troponin I. CONCLUSION: In this multicentre study, myocardial injury was a common finding in COVID-19 patients. Its prevalence increased when a sex-specific cut-off and cardiac troponin T were used. Elevated troponin was an independent predictor of 30-day mortality, irrespective of cardiac troponin assay and cut-offs to detect myocardial injury. Hence, the early measurement of cardiac troponin may be useful for risk stratification in COVID-19.

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients.

BACKGROUND & AIMS: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. METHODS: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. RESULTS: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. CONCLUSIONS: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. LAY SUMMARY: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.

Minimally invasive distal pancreatectomy A retrospective review of 30 cases.

OBJECTIVES: Pancreatic surgery has been greatly influenced by the advent of laparoscopic surgery and increasing experience in its performance and by advances in techniques and surgical devices. This study aimed to represent two centers' initial experiences in laparoscopic distal pancreatic surgery. METHODS: This study was a bi-centric study including 30 patients undergoing distal pancreatectomy for pancreatic disorders. All the patients were operated on from November 2006 to November 2013 in Turkey and Spain. RESULTS: Laparoscopic spleen-preserving distal pancreatectomy was performed in 9 patients, laparoscopic distal pancreatectomy was performed in 14 patients, laparoscopic enucleation was performed in 4 patients, and single-incision laparoscopic distal pancreatosplenectomy with splenectomy was performed in 3 patients. CONCLUSIONS: Laparoscopic distal pancreatectomies for pancreatic disorders are feasible and safe procedures if performed by experienced laparoscopic surgeons. KEY WORDS: Laparoscopy, Pancreas, Multi-port, Tumor, SILS.

Implication of the presence of a variant hepatic artery during the Whipple procedure.

INTRODUCTION: The anatomical variants of the hepatic artery may have important implications for pancreatic cancer surgery. The aim of our study is to compare the outcome following a pancreatoduodenectomy (PD) in patients with or without a variant hepatic artery arising from superior mesenteric artery. MATERIAL AND METHODS: We reviewed 151 patients with periampullary tumoral pathology. All patients underwent oncological PD between January 2005 and February 2012. Our series was divided into two groups: Group A: Patients with a hepatic artery arising from superior mesenteric artery; and Group B: Patients without a hepatic artery arising from superior mesenteric artery. We expressed the results as mean +/- standard deviation for continuous variables and percentages for qualitative variables. Statistical tests were considered significant if p < 0.05. RESULTS: We identified 11 patients with a hepatic artery arising from superior mesenteric artery (7.3%). The most frequent variant was an aberrant right hepatic artery (n = 7), following by the accessory right hepatic artery (n = 2) and the common hepatic artery trunk arising from the superior mesenteric artery (n = 2). In 73% of cases the diagnosis of the variant was intraoperative. R0 resection was performed in all patients with a hepatic artery arising from superior mesenteric artery. There were no significant differences in the tumor resection margins and the incidence of postoperative complications. CONCLUSION: Oncological PD is feasible by the presence of a hepatic artery arising from superior mesenteric artery. The complexity of having it does not seem to influence in tumor resection margins, complications and survival.

Implicaciones de las variantes arteriales hepáticas durante la duodenopancreatectomía cefálica oncológica / Implication of the presence of a variant hepatic artery during the Whipple procedure

INTRODUCCIÓN: las variantes anatómicas de la arteria hepática pueden tener importantes implicaciones en la cirugía oncológica del páncreas. Nuestro objetivo es comparar los resultados tras un procedimiento de Whipple en pacientes con y sin presencia de una arteria hepática variante procedente de la arteria mesentérica superior. MATERIAL Y MÉTODOS: estudio analítico observacional retrospectivo en el que hemos analizado 151 pacientes con patología tumoral periampular sometidos a una duodenopancreatectomía desde enero de 2005 hasta febrero de 2012. Diferenciamos entre 2 grupos: grupo A (variante de la arteria hepática) y grupo B (no evidencia de variante de la arteria hepática). Hemos expresado los resultados como la media ± desviación estándar para las variables continuas y porcentajes para las cualitativas. Los test estadísticos fueron considerados significativos si la p < 0,05. RESULTADOS: hemos detectado 11 pacientes con anomalías de la arteria hepática (7,3%). La variante más frecuentemente fue la arteria hepática derecha aberrante (n = 7), seguida de la arteria hepática derecha accesoria (n = 2) y tronco de la arteria hepática común procedente de la arteria mesentérica superior (n = 2). En el 73% de los casos la detección de la variante arterial fue intraoperatoria. En todos los pacientes se realizó una resección R0. No se han apreciado diferencias significativas en los márgenes de resección tumoral, complicaciones, ni en la supervivencia. CONCLUSIÓN: la cirugía oncológica de la región céfalopancreática en presencia de una variante de la artería hepática es factible. La complejidad que supone tener una variante anatómica de la arteria hepática no parece influir en los márgenes de resección tumoral, complicaciones o supervivencia

INTRODUCTION: The anatomical variants of the hepatic artery may have important implications for pancreatic cancer surgery. The aim of our study is to compare the outcome following a pancreatoduodenectomy (PD) in patients with or without a variant hepatic artery arising from superior mesenteric artery. MATERIAL AND METHODS: We reviewed 151 patients with periampullary tumoral pathology. All patients underwent oncological PD between January 2005 and February 2012. Our series was divided into two groups: Group A: Patients with a hepatic artery arising from superior mesenteric artery; and Group B: Patients without a hepatic artery arising from superior mesenteric artery. We expressed the results as mean +/- standard deviation for continuous variables and percentages for qualitative variables. Statistical tests were considered significant if p < 0.05. RESULTS: We identified 11 patients with a hepatic artery arising from superior mesenteric artery (7.3%). The most frequent variant was an aberrant right hepatic artery (n = 7), following by the accessory right hepatic artery (n = 2) and the common hepatic artery trunk arising from the superior mesenteric artery (n = 2). In 73% of cases the diagnosis of the variant was intraoperative. R0 resection was performed in all patients with a hepatic artery arising from superior mesenteric artery. There were no significant differences in the tumor resection margins and the incidence of postoperative complications. CONCLUSION: Oncological PD is feasible by the presence of a hepatic artery arising from superior mesenteric artery. The complexity of having it does not seem to influence in tumor resection margins, complications and survival

Impact of donor and recipient CYP3A5 and ABCB1 genetic polymorphisms on tacrolimus dosage requirements and rejection in Caucasian Spanish liver transplant patients.

Studies of liver transplant (LT) patients, mainly in Asians, have evaluated the influence of the CYP3A5*1 allele and P-glycoprotein gene ABCB1 on tacrolimus pharmacokinetics or biopsy-proven acute rejection (BPAR) incidence, with no conclusive results. To investigate these issues, 98 Caucasian Spanish LT patients with tacrolimus, mycophenolate mofetil and steroids and 88 cadaveric donors were genotyped for the SNPs CYP3A5 6986G>A, ABCB1 1236C>T, ABCB1 2677G>A/T and ABCB1 3435C>T;. On day 7 post-LT, patients with a native CYP3A5*1 allele had significantly lower tacrolimus trough concentrations C0 (P = .03) and dose-adjusted concentrations C0 /D (P = .02) than CYP3A5 *3/*3 homozygotes. Three months post-LT, patients carrying a liver with CYP3A5*1 had significantly lower C0 /D (P = .03) and took significantly higher tacrolimus doses (P = .03) than the corresponding *3/*3 homozygotes. ABCB1 SNPs showed no significant association with tacrolimus variables. The 3-month incidence of BPAR was 10.2%, with no statistically significant differences related to CYP3A5 (14.3% in expresser vs. 9.5% in non-expresser) or ABCB1 genotype of either patient or donor. We conclude that in Caucasian Spanish LT patients, a native or graft-borne CYP3A5*1 allele tends to lower tacrolimus concentrations and increase dosage needs, but has no significant impact on the incidence of BPAR.

[Descriptive study of infectious complications in 109 consecutive liver transplant recipients]. / Estudio descriptivo de las complicaciones infecciosas en 109 receptores de trasplantes hepáticos consecutivos.

INTRODUCTION: Infectious disease is a common, serious complication in liver transplant recipients. The etiology of these infections undergoes changes related with technical advances, prophylaxis, and local epidemiology. METHODS: Prospective study in patients who underwent liver transplantation from July 2003 to December 2005 at the Hospital Universitario Virgen del Rocío. An observational description of infections occurring during the first 2 years following transplantation was carried out. RESULTS: The incidence of infection was 1.32 episodes per patient over follow-up (443 +/- 248 days). The most frequent infections were surgical site (16%), cytomegalovirus (CMV) (14%), and urinary tract (11%). Etiologies included bacterial (64%), viral (31%), and fungal (5%) causes. The most common pathogens were CMV (21%), Escherichia coli (20%), among which, 40% were extended-spectrum beta-lactamase ESBL-producers, and Enterococcus spp. (11%). More than half the infectious episodes (58%) occurred in the first 4 months after transplantation. The 30-day mortality rate was 18%. In the group with infection, patient and graft survivals were 75% and 73% at the end of follow-up, and in the group without infection, survival was 80% in both cases (P=NS). CONCLUSIONS: The most common infectious syndromes following liver transplantation were surgical site infection, CMV infection, and urinary tract infection. Bacteria were the most commonly isolated microorganisms, and there was a high rate of ESBL-producing E. coli.

Estudio descriptivo de las complicaciones infecciosas en 109 receptores de trasplantes hepaticos consecutivos / Descriptive study of infectious complications in 109 consecutive liver transplant recipients

Introducción Las infecciones en los receptores de trasplante hepático (TH) son frecuentes y graves; sin embargo, son cambiantes en relación con los avances técnicos, la profilaxis y la epidemiología local. Métodos Estudio prospectivo de pacientes con TH realizado entre julio de 2003 y diciembre de 2005. Observación descriptiva de las infecciones durante los 2 primeros años postrasplante. Resultados La incidencia de infección fue de 1,32 episodios por sujeto durante (..) (AU)

Introduction: Infectious disease is a common, serious complication in liver transplant recipients. The etiology of these infections undergoes changes related with technical advances, prophylaxis, and local epidemiology. Methods: Prospective study in patients who underwent liver transplantation from July 2003 to December 2005 at the Hospital Universitario Virgen del Rocio. An observational description of infections occurring during the first 2 years following transplantation was carried out. Results: The incidence of infection was 1.32 episodes per patient over (..) (AU)

Papel de la desnutrición en la síntesis de colágeno en anastomosis cólicas primarias: análisis de procolágeno y telopéptido carboxiterminal mediante radioinmunoanálisis / Role of malnutrition in collagen synthesis in primary colonic anastomosis. Analysis of procollagen and carboxyterminal telopeptide through radioimmunoassay

Introducción: Diversos factores clínicos, anatomopatológicos y técnicos influyen en la cicatrización correcta de las suturas intestinales tras la práctica de una resección intestinal. Uno de los factores más implicados es el estado nutricional del paciente. Objetivos: Evaluar la influencia de la desnutrición inducida en la viabilidad de una anastomosis intestinal primaria mediante el análisis del procolágeno (PINP) y del telopétido carboxiterminal del colágeno I (ICTP) depositados en ella. Material y método: Usamos 40 ratas Wistar y material de radioinmunoanálisis (kits comerciales de RIA ICTP-RIA® e Intact PINP®). Se formaron 2 grupos de ratas, 20 animales para cada grupo: grupo control (A) y grupo "desnutrición" (B). Se analizó PINP e ICTP mediante RIA sobre tejido colónico homogeneizado, preanastomótico y anastomótico. Resultados: Hay menores valores de PINP en el colon de las ratas del grupo B que en el del grupo A (0,3620 y 0,4340 µg/g, respectivamente) (p = 0,032). Hay un mayor valor de ICTP analizado en el colon del grupo B (0,9545 en contraposición a 0,8460 µg/g, en el grupo A) (p = 0,875). En las anastomosis del grupo B hay menos síntesis de PINP que en el grupo A (0,376 y 0,468 µg/g, respectivamente; p = 0,002). Conclusiones: La anastomosis colónica incrementa las concentraciones de PINP e ICTP en el tejido cicatrizal (p < 0,001); la desnutrición reduce la colagenización de las anastomosis (p < 0,001)

Introduction: Various clinical, pathological and technical factors influence the viability of intestinal suturing after intestinal resection. One of the most important factors is the patient's nutritional status. Objectives: To evaluate the influence of induced nutrition on the viability of primary intestinal anastomosis by means of analysis of collagen I procollagen (PINP) and telopeptide (ICTP) deposited in the anastomosis. Material and method: 40 Wistar rats and material for the radioimmunoassay (ICTP-RIA® and Intact PINP® commercial radioimmunoassay kits) were used. We used two groups of 20 rats each: control group (A) and a "malnourished" group (B). PINP and ICTP were analyzed through radioimmunoassay of homogenized, preanastomotic and anastomotic colonic tissue. Results: PINP levels were lower in the colons of group B rats than in the control group (0.3620 and 0.4340 µg/g respectively) (p = 0.032). ICTP levels were higher in the colons of group B rats than in those of group A rats (0.9545 versus 0.8460 µg/g respectively) (p = 0.875). PINP synthesis was lower in the anastomoses of group B than in group A (0.376 and 0.468 µg/g respectively; p = 0.002). Conclusions: Colonic anastomosis increases PINP and ICTP levels in scar tissue (p < 0.001). Malnutrition reduces collagenization of colonic anastomoses (p < 0.001)

Etiología y diagnóstico del hematoma retroperitoneal complicado, actitud e indicación quirúrgica / Etiology and diagnosis of severe retroperitoneal hematoma: therapeutic options and surgical indication

El hematoma retroperitoneal es una entidad poco frecuente cuya repercusión clínica varía en función de la velocidad y la cuantía de la hemorragia: desde asintomático, que suele diagnosticarse casualmente en pruebas de imágenes, hasta complicado, cuyo síntomas característicos son el dolor y el shock hipovolémico. Presentamos 3 casos clínicos de hematoma retroperitoneal complicado. Si bien la bibliografía describe múltiples causas, en nuestros pacientes el origen fue siempre tumoral: 1 mielolipoma suprarrenal, 1 adenocarcinoma renal y 1 metástasis suprarrenal de adenocarcinoma broncogénico. La tomografía computarizada fue la prueba de imagen utilizada, no sólo para definir la naturaleza del proceso (hematoma, absceso, tumor), sino también para valorar la compresión de estructuras adyacentes y la existencia de hemorragia activa. Aunque se intentó el tratamiento conservador mediante reposición de la volemia y corrección de la coagulación, en todos los casos fue necesaria intervención quirúrgica urgente, 2 por inestabilidad hemodinámica y 1 por compresión de la vena cava (AU)

Retroperitoneal hematoma is a rare entity with clinical consequences that vary according to the speed and amount of bleeding. Thus, it may be asymptomatic, in which case it is usually diagnosed incidentally through imaging tests, or severe, in which case the most common symptoms are pain and hypovolemic shock. We report three cases of severe retroperitoneal hematoma. Although the literature on the subject describes a wide variety of causes, in all three patients the etiology was tumoral, consisting of one suprarenal myelolipoma, one renal adenocarcinoma and one suprarenal metastasis from bronchogenic adenocarcinoma. Computed tomography was the imaging test employed not only to determine the nature of the process (hematoma, abscess, tumor) but also to assess compression of adjacent structures and the occurrence of active bleeding. Conservative treatment consisting of volemic replacement and correction of coagulation was initially attempted. However, all three patients required emergency surgery due to hemodynamic instability in two patients and compression of the vena cava in the other (AU)

[Etiology and diagnosis of severe retroperitoneal hematoma: therapeutic options and surgical indication]. / Etiología y diagnóstico del hematoma retroperitoneal complicado, actitud e indicación quirúrgica.

Retroperitoneal hematoma is a rare entity with clinical consequences that vary according to the speed and amount of bleeding. Thus, it may be asymptomatic, in which case it is usually diagnosed incidentally through imaging tests, or severe, in which case the most common symptoms are pain and hypovolemic shock. We report three cases of severe retroperitoneal hematoma. Although the literature on the subject describes a wide variety of causes, in all three patients the etiology was tumoral, consisting of one suprarenal myelolipoma, one renal adenocarcinoma and one suprarenal metastasis from bronchogenic adenocarcinoma. Computed tomography was the imaging test employed not only to determine the nature of the process (hematoma, abscess, tumor) but also to assess compression of adjacent structures and the occurrence of active bleeding. Conservative treatment consisting of volemic replacement and correction of coagulation was initially attempted. However, all three patients required emergency surgery due to hemodynamic instability in two patients and compression of the vena cava in the other.