Hepatocellular Carcinoma in Ceará: Epidemiology and Treatment in a Reference Liver Transplant Center in Northeast Brazil.

Hepatocellular carcinoma remains a significant worldwide malignancy and an important cause of cancer-related death. The incidence is increasing globally. In Latin America, there is no consistent data on the epidemiology of hepatocellular carcinoma. However, Brazil is considered a country with an intermediate incidence of this liver neoplasm. In the state of Ceará, situated in the northeast region of Brazil, there are no consistent clinical and epidemiologic data on the actual incidence and the treatment of hepatocellular carcinoma. The purpose of this article is to describe epidemiologic characteristics and treatment forms of patients with hepatocellular carcinoma who were treated in a Liver Transplant Center. A retrospective observational study was conducted using the database from the register of 299 patients with hepatocellular carcinoma between June 2004 and February 2022. Only patients born in Ceará were included. Therefore, most patients were eligible, based on the Milan Criteria, to undergo liver transplantation with a Model End Stage Liver Disease score of 12.48 ± 4.66 points, and the waiting list time was approximately 7 months with 8.7% hepatocellular carcinoma recurrence after liver transplant. A total of 38.5 % of cases were outside the Milan criteria at the time of cancer diagnosis, and transarterial chemoembolization was the main treatment choice. In conclusion, the diagnosis of hepatocellular carcinoma in Ceará mainly occurs in male patients with hepatitis C or alcoholism, with a mean age of 61.55 years and a previous diagnosis of liver disease. Liver transplantation was the best curative therapeutic form in patients with cirrhosis and hepatocellular carcinoma in Ceará, where a significant number of patients were diagnosed with intermediate and advanced-stage hepatocellular carcinoma, so public health policies are important for the screening and monitoring of liver disease.

Outcomes of Liver Transplant Recipients With Model for End-Stage Liver Disease Exception: Single-Center Experience in the Northeast of Brazil.

The Model for End-Stage Liver Disease (MELD) exception policy in liver transplantation is based on symptoms and clinical conditions not included in the calculated MELD score. Therefore, patients with chronic liver disease, like refractory ascites, chronic encephalopathy, recurrent cholangitis, and refractory pruritus, may benefit with extra points. The objective of this study was to establish the profile of the patients submitted to liver transplantation with MELD exceptions based on symptoms in the University Hospital Walter Cantídio, Ceara, Brazil, between the years of 2012 and 2015, analyzing donor and recipient data, with special attention to patients with refractory ascites and recurrent encephalopathy, including survival rates. The results demonstrated acceptable survival rates for MELD exception patients (78.4% in 3 years), showing that maybe this allocation criterion should be maintained, or even expanded.

Genetic diversity of high performance cultivars of upland and irrigated Brazilian rice.

The objective of this study was to analyze the diversity and discrimination of high-performance Brazilian rice cultivars using microsatellite markers. Twenty-nine rice cultivars belonging to EMBRAPA Arroz e Feijão germplasm bank in Brazil were genotyped by 24 SSR markers to establish their structure and genetic discrimination. It was demonstrated that the analyzed germplasm of rice presents an expressive and significant genetic diversity with low heterogeneity among the cultivars. All 29 cultivars were differentiated genetically, and were organized into two groups related to their upland and irrigated cultivation systems. These groups showed a high genetic differentiation, with greater diversity within the group that includes the cultivars for irrigated system. The genotyping data of these cultivars, with the morphological e phenotypical data, are valuable information to be used by rice breeding programs to develop new improved cultivars.

L-Alanyl-Glutamine Attenuates Oxidative Stress in Liver Transplantation Patients.

BACKGROUND: Ischemia/reperfusion injury during liver transplantation can cause severe damage to the graft. The objective of this randomized, double-blind study was to evaluate the possible protective effects of L-alanyl-glutamine on the liver graft. METHODS: The sample included 33 patients from a liver transplantation service in Northeastern Brazil. Before cold ischemia, the patients received 50 g of L-alanyl-glutamine (treatment group) or saline (control group) through the portal vein. The graft was biopsied at the time of recovery, at the beginning of warm ischemia, and at the end of transplantation to determine malondialdehyde (MDA), heat-shock protein (Hsp)70, nuclear factor kappa-beta (NFkB), superoxide dismutase (SOD), and reduced glutathione (GSH) levels. RESULTS: The blood parameters were similar in the two groups. In the treatment group, MDA did not increase at the beginning of cold ischemia and decreased at the end of transplantation. This phenomenon was not observed in the control group. GSH, SOD, Hsp70, and NFkB levels were similar in the two groups. CONCLUSIONS: Our findings suggest that preconditioning with L-alanyl-glutamine attenuates the effects of ischemia/reperfusion-related oxidative stress and reduces lipid peroxidation in the grafts of liver transplantation patients.

Antiviral action of hydromethanolic extract of geopropolis from scaptotrigona postica against antiherpes simplex virus (HSV-1)

The studies on chemical composition and biological activity of propolis had focused mainly on species Apis mellifera L. (Hymenoptera: Apidae). There are few studies about the uncommon propolis collected by stingless bees of the Meliponini tribe known as geopropolis. The geopropolis from Scaptotrigona postica was collected in the region of Barra do Corda, Maranhão state, Brazil. The chemical analysis of hydromethanolic extract of this geopropolis (HMG) was carried out through HPLC-DAD-ESI-MS/MS and the main constituents found were pyrrolizidine alkaloids and C-glycosyl flavones. The presence of alkaloids in extracts of propolis is detected for the first time in this sample. The antiviral activity of HMG was evaluated through viral DNA quantification experiments and electron microscopy experiments. Quantification of viral DNA from herpes virus showed reduction of about 98% in all conditions and concentration tested of the HMG extract. The results obtained were corroborated by transmission electron microscopy, in which the images did not show particle or viral replication complex. The antiviral activity of C-glycosyl flavones was reported for a variety of viruses, being observed at different points in the viral replication. This work is the first report about the antiviral activity of geopropolis from Scaptotrigona postica, in vitro, against antiherpes simplex virus (HSV).

Ten-year experience with liver transplantation for hepatocellular carcinoma in a Federal University Hospital in the Northeast of Brazil.

Hepatocellular carcinoma (HCC) is the most frequent and important primary liver tumor, with annual worldwide incidence of over 1 million cases, accounting for at least 500,000 deaths per year. The majority of cases of HCC occur in the setting of liver cirrhosis. In this retrospective, descriptive, and analytical study, between May 2002 and April 2012, 664 liver transplantations (LT) were conducted at a Federal University Hospital in the Northeast of Brazil, among which 140 LT were performed in patients with HCC. The tumor was more frequent in men with an average age of 56 years and infected with hepatitis C virus, many with a history of alcohol abuse. Alpha-fetoprotein was not useful in the diagnosis, and imaging methods have failed to diagnose the nodules in 19 patients (13.6%). Transarterial chemoembolization was the most-used bridging therapy to inhibit tumor growth for patients with HCC eligible for transplantation. The implementation of the Model for End Stage Liver Disease score in 2006 brought benefits to these patients. The rate of HCC recurrence after LT was 8.57% and occurred more often in the first 2 years after transplantation, with the liver graft being the most common site. Significant risk factors for recurrence were a long time on the LT waiting list, number of liver nodules over 3.5, and the presence of vascular invasion. In conclusion, LT for HCC leads to excellent long-term survival, with relatively few patients dying from tumor recurrence.

Results from a liver transplant center in northeastern Brazil that performed more than 100 transplants in 2011.

BACKGROUND: Orthotopic liver transplantation is an essential approach performed in several centers around the world. Our center lies in northeastern Brazil and has performed this procedure since 2002. In 2011, 126 liver transplants were performed at our institution. METHODS: This study is a retrospective and descriptive analysis of the data collected from the medical records of those transplants. Epidemiological and clinical aspects were considered in this evaluation. The outcome analysis considered overall survival rates within 30 days and 1 year after transplantation. RESULTS: The sample of 124 patients showed 60% of all patients came from other regions, particularly the North and Midwest regions of Brazil, which had a combined population of >30 million in 2011. The most frequent etiologies for end-stage liver disease were hepatitis C and alcoholism. The average calculated MELD (Model for end-stage liver disease) was 21.0. Patient survival curves were 88.4% after 30 days and 81.5% after 1 year. CONCLUSION: The development of effective perioperative management for this procedure resulted in improved outcomes. Our center's performance is based on a multidisciplinary approach performed by qualified personnel, careful pre- and postoperative follow-up and continuous improvement of services.

Single-center transfusion rate for 555 consecutive liver transplantations: impact of two eras.

Orthotopic liver transplantation (OLT) is the treatment of choice for patients with acute or chronic end-stage liver disease, irresectable primary liver tumor, and metabolic disorders. Historically, OLT has been associated with considerable blood loss and the need for transfusions. However, over the years there has been reduction is need for blood products. The aim of this article was to compare two distinct eras for perioperative blood transfusion rate among patients undergoing OLT; Era I, 200 transplantations in 188 patients, and Era II, 355 transplantations in 339 patients. The donor mean age was 33.70 (Era I) versus 35.34 (Era II). Cause of death in both eras was traumatic brain injury followed by cerebral vascular accident. Organ recipient data showed a mean age of 48.87 (Era I) versus 46.49 (Era II). During Era I patients with Child B (56.8%) prevailed, followed by Child C (35.4%) and Child A (7.8%). In Era II also patients with Child B (53.1%) prevailed, followed by Child C (39.6%) and Child A (7.3%). The prevalence of hepatocellular carcinoma (HCC) during Era I was 9% (18) and in Era II 20% (71). The use of blood products in the perioperative period: was as follows packed red blood cells 1.76 (Era I) versus 0.57 (Era II) units; fresh frozen plasma 1.89 (Era I) versus 0.49 (Era II) units; platelets 2.16 (Era I) versus 0.28 (Era II) units; and cryoprecipitate 0.08 (Era I) versus 0.03 (Era II) units. OLT using the piggyback technique was performed with a transfusion rate below <30%, and it reduced blood loss and prevented severe hemodynamic instability.

Obese and nonobese recipients had similar need for ventilatory support after liver transplantation.

BACKGROUND: Obesity is a risk factor for patients undergoing major surgery. In liver transplantation, the morbidity and mortality in these patients may be higher owing to concomitant diseases that may prolong hospital stay. Moreover, the restrictive respiratory pattern in these patients, associated with pulmonary complications related to liver disease can impact the postoperative recovery. We sought to analyze the impact of high body mass index (BMI) on hospital and intensive care unit (ICU) stay, necessity and length of use either invasive and noninvasive ventilatory support in the early postoperative period after liver transplantation. PATIENTS AND METHODS: Between January 2007 and March 2009, we performed 85 liver transplantations in adult patients. BMI was calculated on the day of the transplantation. Data from 136 recipients undergoing OLT were reviewed by age, gender, etiology of liver disease, Model for End-Stage Liver Disease score, Child-Pugh class, cold and warm ischemic times, ICU stay, duration of invasive mechanical, and use of noninvasive ventilation (NIV). We divided the patients into 3 groups: Group 1, (normal weight BMI 18.5-24.99), versus group 2 overweight--BMI 25-29.99; versus group 3, obese--BMI ≥30. RESULTS: Groups 1, 2, and 3 had similar lengths of stay in the ICU, necessity of NIV as well as 6 month, 1- and 2-year survivals (P > .05). CONCLUSION: High BMI patients showed similar results to normal or overweight patients. Obesity should not be contraindication to liver transplantation.

Successful organ transplantation from donors poisoned with a carbamate insecticide.

Currently, liver transplantation is the only option for patients with end-stage liver disease. In Brazil, the mortality rate on the waiting list is about 25%. Multiple strategies to expand the donor pool are being pursed, however, grafts from poisoned donors are rarely used. This report documents successful liver, kidney and heart transplantations from four female donors who suffered brain death by hypoxia despite cardiopulmonary resuscitation following Aldicarb exposure ([2-methyl-2-(methylthio)propionaldehyde O-(methylcarbamoyl)-oxime]). The success rate of 12 grafts from four donors poisoned by Aldicarb was 91% 6 months after transplantation. Poisoned patients are another pool of organ donors who at present are probably underused by transplantation services. More studies are necessary to confirm the safety for the recipients.

Orthotopic liver transplantation for hepatocellular carcinoma: one center's experience in the Northeast of Brazil.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. In this study, we sought to assess the outcome of patients with HCC who underwent orthotopic liver transplantation (OLT) in a center in the northeast of Brazil. Between May 2002 and July 2008, 294 OLTs were performed at our center. In 45 patients, HCC was confirmed by histological examination of the explant. Patients were predominantly men of ages ranging from 14-67 years. Hepatitis C virus was involved in 55.4% of the cases. Alpha fetoprotein (AFP) levels were normal in 65.2% of the patients and surpassed 100 ng/mL in only 10.4%. The median waiting time on the list was 10 months. Seventeen patients (37.7%) presented a solitary nodule, 19 (42.2%) had 2 or 3 nodules, and 9 patients (20%) had more than 3 nodules. The maximal diameter of the largest tumor was <3 cm in 26 patients (57.7%) and exceeded 5 cm in 6 patients (13.3%). Ten tumors were well differentiated, 32 were moderately differentiated, and 3 were poorly differentiated. Eleven tumors showed microvascular invasion. There have been 4 tumor recurrences. There was an association between microvascular invasion and tumor recurrence with a statistically significant relative risk. In conclusion, OLT is an excellent option for patients with HCC. The recurrence rate was low (<10%). However, we believe that more prospective studies are needed about OLT beyond the Milan criteria because our study suggested that microvascular invasion may be more important than tumor size or number.

Continuous versus interrupted suture for hepatic artery anastomosis in liver transplantation: differences in the incidence of hepatic artery thrombosis.

BACKGROUND: Hepatic artery thrombosis (HAT) is a serious complication after orthotopic liver transplantation (OLT) and remains a significant cause of graft loss. HAT following OLT has been reported in 3% to 9% of patients. Among the surgical factors considered to be associated with HAT, arterial reconstruction might be the most important. The goal of this study was to compare the incidence of HAT between interrupted suture (IS) and continuous suture (CS) techniques during hepatic artery reconstruction in liver transplantation. METHODS: We performed a retrospective analysis of 200 consecutive liver transplantations occurring between May 2002 and December 2006, including medical records for: age, gender, cold ischemic time, warm ischemic time, type and number of arterial anastomosis. Hepatic artery anastomoses were performed using a 7-0 prolene with a running CS in the first 105 patients (CS group), and with an IS in the last 95 patients (IS group). RESULTS: Statistical analysis of age, gender, cold and warm ischemia time, and number of hepatic artery anastomoses was not different between the CS and IS groups. Eleven episodes of HAT were identified in the CS group (10%) and two episodes (2%) in the IS cohort, a significant difference (P = .0173). CONCLUSIONS: Our results suggested that IS might be a better choice for hepatic artery anastomosis with a lower incidence of HAT.

A new biliodigestive anastomosis technique after hepatic artery thrombosis as bridge to liver retransplantation: a case presentation.

Arterial complications after liver transplantation are frequent. Hepatic artery thrombosis (HAT) is usually associated with biliary complications. Herein we have reported a case of a patient who was admitted for jaundice, itch, and elevated aspartate aminotransferase and alanine aminotransferase levels at 6 weeks after liver transplantation. HAT associated with a biloma was diagnosed and an urgent operation performed requiring a new biliodigestive anastomosis technique. Fourteen months after the first transplant, the patient was retransplanted. The operation performed may be an alternative to treat biliary complications due to late HAT.

Malignant hyperthermia in a liver transplant patient: a case report.

Malignant hyperthermia is an autosomal dominant disorder with incomplete penetrance and variable expression. This syndrome is characterized by a hypermetabolic response to all commonly used inhalational anesthetics and depolarizing muscle relaxants. It can happen during or after the anesthesia. We describe a case of malignant hyperthermia during orthotopic liver transplantation. Our patient was a 48-year-old man, born in Brazil but with European ascendance, who developed malignant hyperthermia associated with the use of isoflurane. He was treated with dantrolene, which caused hepatic graft dysfunction. It is important that transplant teams be able to recognize and treat this complication.

Domino liver transplantation with double piggyback: is this the best technique? A case report.

Sequential or domino liver transplantation is a well-established procedure for patients with familial amyloidotic polyneuropathy (FAP). Donation for domino liver transplantation imposed the resection of the inferior vena cava along with the liver, requiring complete suprarenal vena cava clamping and usually the use of venovenous bypass. We describe a successful case in which it was possible to perform the FAP hepatectomy by the piggyback technique.

Evaluation of hepatic function after orthotopic liver transplantation: a comparative study using Belzer and Collins solutions.

Belzer and Collins are solutions used in liver transplantation. The purpose of this study was to compare liver function after utilization of two different schemes of graft preservation using both solutions. Between December 2004 and September 2005, 43 liver transplantations were performed. Twenty-three of these used 2 L of Collins solution and 2 L of Belzer solution as the preservation solution. The others used three L of Collins and 1 L of Belzer solution as the preservation solution. The cold ischemia time of both groups was similar. We analyzed liver function using the serum ALT, AST, bilirubin and international normalized ratio. On the first day after the transplantation, the level of international normalized ratio of the group of patients that used 1 L of Belzer was significantly higher than the other group (P<.05). The levels of ALT, AST, and bilirubin were not different on day 7 after transplantation. We concluded that using only 1 L of Belzer solution is as efficient with the advantage that it is less expensive.

Renal effects of serine-7 analog of lymphoguanylin in ex vivo rat kidney.

Guanylin and uroguanylin compose a family of natriuretic, diuretic, and kaliuretic peptides that bind to and activate apical membrane receptor guanylyl cyclase signaling molecules in renal and intestinal epithelia. Recently, a complementary DNA encoding an additional member of the guanylin family of cGMP-regulating peptides was isolated from lymphoid tissues of the opossum and was termed lymphoguanylin (LGN). A peptide analog of opossum LGN was synthesized containing a single disulfide bond with the internal cysteine-7 replaced by a serine residue (LGN(Cys7-->Ser7)). The biological activity of LGN(Ser) was tested by using a cGMP bioassay with cultured T84 (human intestinal) cells and opossum kidney (OK) cells. LGN(Ser) has potencies and efficacies for activation of cGMP production in the intestinal and kidney cell lines that are 100- and 1,000-fold higher than LGN, respectively. In the isolated perfused rat kidney, LGN(Ser) stimulated a maximal increase in fractional Na+ excretion from 24.8 +/- 3.0 to 36.3 +/- 3.3% 60 min after administration and enhanced urine flow from 0.15 +/- 0.01 to 0.24 +/- 0.01 ml. g(-1). min(-1). LGN(Ser) (0.69 microM) also increased fractional K+ excretion from 27.3 +/- 2.3 to 38.0 +/- 3.0% and fractional Cl- excretion from 26.1 +/- 0.8 to 43.5 +/- 1.9. A ninefold increase in the urinary excretion of cGMP from 1.00 +/- 0.04 to 9.28 +/- 1.14 pmol/ml was elicited by LGN(Ser), whereas cAMP levels were not changed on peptide administration. These findings demonstrate that LGN(Ser), which contains a single disulfide bond like native LGN, activates guanylyl cyclase-C (GC-C) receptors in T84 and OK cells and may be very helpful in studying the physiological importance of activation of GC-C in vivo. LGN(Ser) also exhibits full activity in the isolated perfused kidney equivalent to that observed previously with opossum uroguanylin, suggesting a physiological role for LGN in renal function. Thus the single amino acid substitution enhances the activity and potency of LGN.

The role of phospholipase A(2) and cyclooxygenase in renal toxicity induced by microcystin-LR.

We have shown previously that exposure to microcystin-LR (MCLR) causes renal toxic effects in isolated perfused rat kidney. That study was extended further to approach the perspective of pharmacological blockade of renal toxic effects by MCLR through the use of experimental therapeutic agents. An isolated kidney perfusion system was utilized and samples of urine and perfusate were collected at 10min intervals to determine the levels of inulin, sodium, potassium and osmolality. Dexamethasone (20microg ml(-1)) and indomethacin (10microg ml(-1)) were administered in the beginning of the perfusion and MCLR was employed in a dose of 1microg ml(-1) after an internal control of 30min to evaluate the perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR) and urinary flow (UF). Dexamethasone and indomethacin antagonized the toxic effects of MCLR on PP, RVR, GFR and UF. Histologic analysis of dexamethasone and indomethacin treated groups did not show any vascular or interstitial alterations. MCLR potentially impairs the renal function, probably causing vascular and glomerular lesions and, promoting renal alterations through direct or indirect actions. These data seem to indicate that the renal alterations promoted by MCLR involves also phospholipase A(2) and arachidonic acid-derived mediators.