Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

Background Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. Methods Observational retrospective multicenter study. Inclusion criteria: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. Results Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. Conclusion It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here (AU)

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. METHODS: Observational retrospective multicenter study. INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.

Ictericia congestiva desenmascarada con la ecografía clínica / Unmasking congestive jaundice with point-of-care ultrasound

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Reaffirmation of the importance of follow-up ultrasound studies in patients with high D-dimers and clinical suspicion of vein thrombosis.

BACKGROUND: Venous thromboembolism is a common disease seen in the emergency department and a cause of high morbidity and mortality, constituting a major health problem. OBJECTIVES: To assess the potential benefit of follow-up ultrasound of patients who attended the emergency department with suspected superficial venous thrombosis or deep venous thrombosis and were found to have an initial negative whole-leg (or arm) ultrasound study. METHODS: This retrospective study included patients aged 18 years or older who were consecutively referred to a thrombosis clinic from the emergency department, with abnormal D-dimer test and moderate to high pre-test probability of deep venous thrombosis (Well's score ≥ 1), but a negative whole-leg (or arm) ultrasound. Demographic characteristics, symptom duration, laboratory and ultrasound data were recorded. At one-week follow-up, an experienced physician repeated ultrasound, and recorded the findings. RESULTS: From January 2017 to April 2018, 54 patients were evaluated. The mean age was 66.8 years (SD 15.0) and 63% were women. The average D-dimer was 2159.9 (SD 3772.0) ng/mL. Ultrasound abnormalities were found in 12 patients (22.2%; 95% confidence interval of 12.5 to 36.0%), with 4 patients having proximal deep venous thrombosis, distal deep venous thrombosis in 2 patients and superficial venous thrombosis in 6 patients. We did not find any significant differences in demographic characteristics, venous thromboembolism risk factors or laboratory parameters between patients with negative and positive follow-up ultrasound. CONCLUSIONS: These preliminary findings suggest that a negative whole-leg (or arm) ultrasound in addition to an abnormal D-dimer in moderate to high deep venous thrombosis pretest probability patients, might be an insufficient diagnostic approach to exclude suspected deep venous thrombosis or superficial venous thrombosis. Confirmation of this higher than expected prevalence would support the need to repeat one-week ultrasound control in this population.

Spruce xylan/HEMA-SBA15 hybrid hydrogels as a potential scaffold for fibroblast growth and attachment.

A hybrid hydrogel (GHC-SBA15) based on spruce xylan (HC), 2-hydroxyethyl methacrylate (HEMA), and mesoporous silica (SBA15) was prepared with the intended use of fibroblast attachment and growth. Xylan was functionalized with acryloyl chloride to introduce vinyl groups and was crosslinked by radical polymerization with HEMA in presence of SBA15. Infrared spectroscopy and nuclear magnetic resonance confirmed the copolymerization of HEMA with xylan. Up to 20 wt.% addition, SBA15 was homogenously incorporated in the structured hydrogel network as observed by SEM. Moreover, nitrogen adsorption-desorption, small angle X-ray scattering and transmission electron microscopy indicated that the mesoporous SBA15 framework was maintained and that the hybrid hydrogel was a physical mixture of SBA15 with the copolymer HC/HEMA. Rheological analysis revealed that addition of 20% w/w SBA15 into hydrogel enhanced significantly the mechanical properties. In addition, we demonstrate that fibroblast L929 cells grew and spread on GHC-SBA15. Cell viability was within the expected range.

Vaccine effectiveness and use of collar impregnated with insecticide for reducing incidence of Leishmania infection in dogs in an endemic region for visceral leishmaniasis, in Brazil.

Although a national programme for control of visceral leishmaniosis (VL) is being run in Brazil, the disease continues to spread. This programme is essentially based on culling infected dogs from endemic regions. Thus, there is an urgent need to develop other control measures against VL to deter its advance. Here, a subunit vaccine, a recombinant vaccine, an insecticide-impregnated collar and the associations between these measures were evaluated for reducing the incidence of Leishmania infection in dogs. This was through a cohort study conducted in an endemic region of Brazil, considering the incidence and time of total exposure over a period of 1 year. The incidence of VL was estimated by means of serological and molecular diagnostic tests, 180 and 360 days after the application of the control measures. The estimates of the effectiveness (EF) were not significant in any cohort. The EF of the subunit vaccine, the recombinant vaccine and the collar were 26.4%, 32.8% and 57.7% and the upper limit of the 95% confidence interval for EF were 63.7%, 67.9% and 82.5%, respectively. In conclusion, under the conditions of this study, none of the immunogens for VL control was sufficiently effective to protect dogs against infection. On the other hand, use of collars impregnated with insecticide seems to constitute a method with better prognosis, corroborating other studies in this field.

Colágenas Recombinantes para Andamios de Ingeniería de Tejidos / Recombinant Collagens for Tissue Engineering Scaffolds

Resumen: Las colágenas son cada día más atractivas en la fabricación de andamios para Ingeniería de Tejidos, por su biocompatibilidad, manejo y capacidad de producirlas industrialmente. El objetivo del presente artículo fue presentar un análisis sobre el avance en la investigación, el desarrollo y producción de colágenas recombinantes de humano, los sistemas de producción y sus usos en Ingeniería de Tejidos. Se realizó una revisión de la literatura científica internacional arbitrada en bases de datos como Scopus, PubMed y Google Académico y se empleó aquella relevante a nuestro objetivo. Se encontró que el desarrollo de colágenas recombinantes de humano muestra un avance significativo y en la actualidad los sistemas de expresión, como bacterias y plantas, presentan ventajas sobre la calidad de la estructura y la biocompatibilidad, aunque con rendimientos todavía bajos. Mientras que existe escasa información sobre sus aplicaciones en Ingeniería de Tejidos, principalmente cartílago y hueso, en modelos animales y estudios clínicos. En las fuentes de información no se incluyeron patentes, por lo que nuestros hallazgos están limitados a publicaciones científicas. El presente trabajo, presenta los avances más recientes sobre la ingeniería de colágenas recombinantes y sus aplicaciones biomédicas en fabricación de tejidos con potencial uso clínico. Por lo que su factibilidad en la medicina regenerativa es prometedor y se requiere mayor investigación que permita su aplicación en un futuro cercano.

Abstract: Due to its biocompatibility, handling and industrial production capacity, collagens have been increasingly attractive in the manufacture of scaffolds for Tissue Engineering. The aim of the present work was to present an analysis on the progress in research, development and production of human recombinant collagens, expression systems and their uses in Tissue Engineering. A review of the international scientific peer-reviewed literature in databases such as Scopus, PubMed and Google Scholar was done and that relevant to our objective was employed. The development of human recombinant collagens was found to be significant, and currently the expression systems, like bacteria and plants, show advantages over structure quality and biocompatibility, albeit with still restricted yields. However, there is narrow information about its applications in Tissue Engineering, mostly studied for cartilage and bone, in animal models and clinical studies. We did not include patents in the study, thus our findings are limited to scholar data. The present work presents the most recent advances in the engineering of recombinant collagens and their biomedical applications in the manufacture of tissues with potential clinical applications. The potential of recombinant collagens in regenerative medicine is promising and more research is needed that might allow a broad application in the near future.

Role of Transarterial Chemoembolization to Downstage Hepatocellular Carcinoma Within the Milan Criteria.

The practice of treating candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC), with locoregional therapies, is common in most transplantation centers. We present our results using transarterial chemoembolization (TACE) as a neo-adjuvant treatment in our center between 2002 and 2013 to determine its effectiveness in downstaging (DS) HCC within the Milan criteria (MC). Clinical variables were recorded of both donors and recipients, such as diagnosis and treatment, variables related to its etiology, the use of TACE as a neo-adjuvant treatment, immunosuppressive therapy, toxicity, recurrence of disease, exitus, and others. Sixty-four patients were analyzed. Median age was 57 (range, 51-64) years. In this study, 84% (54) were male and 16% (10) were women. Etiology of HCC was viral in 47% (30), alcoholic in 25% (16), and other in 28% (18). TACE was conducted in 45 patients (70%). Every patient included in our study presented a T2 stage (of tumor-nodes-metastasis [TNM]) before surgery, thus within the MC. However, DS protocol was performed in 5 patients (7.8%). We performed a bivariate analysis, having assessed that the use of TACE decreases T2 stage into T1-T0 stage (P < .05). We have also calculated the recurrence-free survival, which reaches up to 80% to 125 months. Furthermore, even though the statistical differences are not consistent due to the simple size presented, we conclude that TACE is a safe and effective therapy to control HCC progression during the waiting list time.

Influence of Waiting List in Recurrence Disease of Hepatocellular Carcinoma.

BACKGROUND: We describe the results of our liver transplantation (LT) patients for hepatocellular carcinoma (HCC) in 2004 to 2012 to determine the differences on the basis of time on the waiting list to establish the risk of recurrence of liver disease. METHODS: Clinical variables were recorded for both donors and recipients as well as variables of diagnosis, the use of transarterial chemoembolization during the waiting list time (WLT), complications, re-transplantation, and exitus. Fifty-eight patients were analyzed. Mean age was 57 ± 8 years (men, 83%; 48 patients). Viral etiology of HCC was 50% (n = 29); alcoholic, 26% (n = 15); and others, 24% (n = 14). RESULTS: Exitus was established in 24 patients (41%); only 5 patients (7%) were attributable to HCC. In the cohort of patients with less than 6 months of WLT, we registered both higher rates of downstaging protocols (10.7% vs 7.5%) and tumor size (3 cm vs 2 cm) compared with the other group. Bivariate studies were conducted according to the WLT (WLT <6 months, WLT ≥6 months), finding differences in recurrence of liver disease (P < .05). This fact was confirmed after a binary logistic regression. CONCLUSIONS: Our results in a subgroup of less than 6 months of WLT included patients with increased tumor size or presentation of multiple nodes, with a worse prognosis and therefore to be prioritized in the treatment of LT. Therefore, in our population there is a significant risk of tumor recurrence in patients with less WLT for LT, but it cannot be overestimated to all type of patients with HCC.

Complications Associated With Liver Transplantation in Recipients With Body Mass Index >35 kg/m(2): Would It Be a Poor Prognosis Predictive Factor?

BACKGROUND: Obesity is a global epidemic that continues to increase in a great number of countries, and it has become a major public health problem in Spain. Unfortunately, the impact of obesity on survival in liver transplantation (LT) recipients is underestimated and controversial. The aim of this study was to determine if obesity is a risk factor for morbidity and mortality after LT. METHODS: In a retrospective cohort study of the records of 180 consecutive patients who had undergone to LT from 2007 to 2013, 11 obese patients with body mass index (BMI) >35 kg/m(2) were identified. Their data have been compared with recipients with BMI 20-25 kg/m(2). RESULTS: There were no differences in demographic data, Child-Pugh score, Model for End-Stage Liver Disease score, or cause of liver failure. BMI >35 kg/m(2) recipients had a significantly higher rate of portal vein thrombosis before LT, compared with the BMI 20-25 kg/m(2) group (36.5% vs 13.9%; P = .041). There were also no differences in development of post-reperfusion syndrome. The groups were also comparable concerning morbidity rate after LT, stay in the intensive care unit, and global hospital stay. However, the mortality rate was significantly higher in the obese group compared with the nonobese group (72.7% vs 38.9%; P = .032). CONCLUSIONS: The results of the study clearly demonstrate higher mortality rates in obese patients undergoing LT; thus, it is fair to consider obesity as a poor prognosis predictive factor concerning mortality rate.

Immunosuppression Strategies in the Treatment of Hepatocellular Carcinoma in Virgen de las Nieves University Hospital.

BACKGROUND: We describe an observational, retrospective study that included patients who underwent a liver transplantation (LT) for hepatocellular carcinoma (HCC) in our center between 2004 and 2012. METHODS: Clinical variables were recorded for donors and recipients as diagnosis and treatment, immunosuppressive therapy, toxicity, graft dysfunction, recurrence, and exitus. Fifty-eight patients were analyzed. The mean age was 57 ± 8 years. The viral etiology of HCC was 50% (n = 29), alcoholic 26% (n = 15), and others, 24% (n = 14). Regarding initial immunosuppressive strategy (IS), 51 patients (87.9%) were treated with standard regimen with corticosteroids (CS) and tacrolimus (TA), compared with 7 patients with impaired renal function (12.1%) who underwent a delayed therapy with calcineurin inhibitors (CNI) + mycophenolate mophetil (MMF) + CS. Concomitant use of anti-CD25 monoclonal antibodies was less than 10%. Regarding maintenance, 43 patients (74.1%) were treated with MMF + CNI versus 15 treated only with TA (25.9%). RESULTS: Recurrence of HCC was approximately 12%: 7 patients (2 hepatic only, 5 also extra-hepatic). Exitus was established in 19 patients (32.75%); only 3 patients (5.17%) were attributable to HCC. Bivariate studies were conducted according to the initial IS (standard regimen versus delayed therapy) and maintenance therapy (MMF + TA versus TA alone), with no differences in any of them in recurrence, treatment toxicity, graft rejection, and dysfunction. CONCLUSIONS: In our experience with the IS, we found no differences in the development of recurrent disease, treatment toxicity, development of graft dysfunction, or rejection. We believe that individualized immunosuppressive therapy in these patients is safe and effective.

Experience of the transplant unit from Virgen de las Nieves Hospital in using liver grafts from asystolic donors.

Given the shortage of donors, it has become increasingly necessary to use alternative sources to meet the growing demand for organs, and evolution in the use of asystolic donors is proving to be an important resource in helping to meet those needs. The goal of this study is to describe the initial results of our experience with Type II asystolic donation. An observational retrospective study was conducted to analyze the variables of four cases in this type of donation. After the analysis we conclude that, despite the limited number of cases in our series, the results are compatible with larger series and permit us to continue to value this method as a resource for broadening the donor pool.

Liver transplantation using low-weight recipients from a graft split program.

We present our experience with a split liver (SL) program shared with the children's liver transplantation (LT) program from 2 different hospitals in the use of partial grafts from cadaver donors in brain death. We describe an observational, retrospective study, which included patients who underwent a SL transplantation in our center between January 2006 and December 2012. Clinical variables were recorded of both donors and recipients and their data were analyzed using SPSS 19.0 software. Of a total of 204 LT, 4 (2%) patients were treated with a SL. The causes of LT were alcoholic cirrhosis in 2 cases, cryptogenic cirrhosis, and primary biliary cirrhosis (PBC). In all cases there was a temporary portocaval shunt. The confluence of the hepatic veins of the recipient was anastomosed to the donor vena cava and arterial anastomosis was performed. The reconstruction was hepato-choledochal in all cases. There were no cases of postreperfusion syndrome or vascular thrombosis and no retransplantation was necessary. Currently, 3 of the 4 cases are still alive. Death in the other patient was due to mesenteric ischemia. Our center has participated in the development of a protocol that considers the indication of this technique provided expert groups are involved in its development, regardless of hospital level. This will expand the pool of donors and partially solve the current problems with available grafting.

Perioperative values of glutathione peroxidase activity and malondialdehyde levels in enolic cirrhotic recipients of a liver transplant.

Reactive oxygen species play a central role in ischemia-reperfusion injury after organ transplantation. They are degraded by endogenous radical scavengers such as antioxidant enzymes. The purpose of this study was to evaluate the temporal variation in glutathione peroxidase (GPX) activity and malondialdehyde (MDA) levels among alcoholic cirrhotic recipients of liver transplantations. The study included 30 recipients: 26 males and 4 females in the provided blood samples before and after transplantation. The results showed significant enhancement of MDA levels at 1 and 6 hours after transplantation: 4.458 ± 2.273 µmol/L and 4.4628 ± 2.405 µmol/L respectively (P < .001). In contrast, GPX activity showed a maximum at 3 days there after 3.541 ± 2,315 nmol/mg protein. In conclusion, although MDA levels show an enormous increase at 1 hour after transplantation suggesting lipid peroxidation, they were compensated by GPX activity thereafter, indicating control of the oxidative stress generated by liver transplantation.

Echocardiographic study in cirrhotic patient candidates for liver transplantation.

We studied 81 cirrhotic patients who were candidates for liver transplantation to evaluate frequently detected cardiac alterations by echocardiographic study. Patients were distributed into three groups: group 1 comprised alcoholic cirrhotic patients (n = 40); group 2, viral cirrhotic patients (hepatitis C or B virus) (n = 35); and group 3, patients with primary biliary cirrhosis (n = 6). Cardiac chambers and diastolic functions were estimated by two-dimensional transthoracic echocardiography in M mode and Doppler. The most frequently detected cardiac structural alterations were left atrial diameter enlargement in 100% of the women and 40% of the men in group 1; 87.5% of the women and 15.4% of the men in group 2; and 33.3% of the women in group 3. Interventricular wall thickness enlargement in 50% of the women and 27.8% of the men in group 1, 25% of the women and 30.8% of the men in group 2, and 16.4% of the women in group 3. The prevalence of diastolic dysfunction was 45% in group 1, 32.3% in group 2, and 16.4% in group 3 (P > .05). There were no significant differences between the groups in cardiac chamber dimensions, left ventricular wall thickness, or prevalence of diastolic dysfunction.

Gene network profiling before and after transplantation in alcoholic cirrhosis liver transplant recipients.

The main objective of this study was to define a gene network profile network in liver transplant recipients with alcoholic cirrhosis before and after liver transplantation. Genes were selected from data obtained in a previous study of liver transplant recipients with alcoholic cirrhosis. Selected up-regulated genes were further validated by quantitative real-time polymerase chain reaction in different groups of liver transplant recipients with alcoholic cirrhosis (n=5). Selected genes up-regulated before transplantation were: TNFRSF9 (tumor necrosis factor [TNF] receptor superfamily, member 9); IL2RB (interleukin-2 receptor beta); BCL2L2 (BCL2-like 2); NOX5 (NADPH) oxidase, EF-hand calcium binding domain 5); PEX5 (peroxisomal biogenesis factor 5); PPARG (peroxisome proliferator-activated receptor gamma); NIBP (IKK2 binding protein); NKIRAS2 (NFKappaBeta inhibitor interacting Ras-like 2); IL4 (interleukin-4); IL-4R (interleukin 4 receptor); ADH1A (alcohol dehydrogenase 1A, class 1); ALDH1L1 (aldehyde dehydrogenase 1 family, member L1); MPO (myeloperoxidase); NPPA (natriuretic peptide precursor A); BCL2A1 (BCL2-related protein A1); GADD45A (growth arrest and DNA-damage-inducible alpha); TEGT (Bax inhibitor 1); PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide); IFNGR2 (interferon gamma receptor 2); JAK2 (Janus Kinase 2); FAS (Fas, TNF receptor superfamily, member 6); TANK (TRAF family member-associated NFKB activator); TTRAP (TRAF and TNF receptor-associated protein); and ANXA5 (annexin A5).

Hepatopulmonary syndrome among cirrhotic candidates for liver transplantation.

This study assess of hepatopulmonary syndrome (HPS) prevalence and the influence of etiology among cirrhotic patients due to an alcoholic or viral etiology. We examined the records of patients were distributed as Group 1, alcoholic (n = 40) and Group 2, hepatic cirrhosis of viral etiology (n = 35). Hepatic cirrhosis status was estimated by CHILD and MELD scores. Presence of clinical ascites spell out was noted as well as size and diastolic functions of the cardiac chambers using two-dimensional transthoracic echocardiography in M mode and by Doppler. HPS was studied with agitated saline serum and intravenous contrast administration. HPS was considered to be present when serum or contrast passed to the left chamber before the 5th cardiac cycle. There was no significant differences among related to sex, age, cirrhosis status or ascites. HPS frequency was 35% in Group 1 versus 64.7% among Group 2-Patients (P = .01). Taking into account the results, we concluded that HPS frequency was related to cirrhotic etiology. Upon multivariate analysis a patients with cirrhosis from viral etiology showed significantly increased HPS frequency compared with those displaying cirrhosis of an alcoholic etiology.

Perioperative levels of glutathione reductase in liver transplant recipients with hepatitis C virus cirrhosis.

Surgical intervention causes oxidative stress leading to an adaptive responses by the body. To evaluate changes in the defense capacity of antioxidant enzymes, we determined the activity of glutathione reductase (GR) levels among liver transplant recipients with due to hepatitis C virus cirrhosis. The study was performed in 22 patients (16 males and 6 females) of average ages 52.63 ± 5.49 years for males and 59.67 ± 5.65 years for females. Blood samples for glutathione reductase activity were drawn on admission before as well as at 1, 6, and 12 h and 1, 2, 3, 5 and 7 days after the liver transplantation. Perioperative glutathione reductase levels were significant (P = .014) over the period using Bonferroni tests. GR activity reached a maximum (15.6112 ± 6.56035 nmol/mg protein) at 3 days after liver transplantation (T3d) (P = .001). The increased GR activity values detected perioperatively indicated scavenging of reactive oxygen species generated after liver transplantation of hepatitis C virus cirrhosis patients.