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.

The influence of electrolytes in the adsorption kinetics of reactive BF-5G blue dye on bone char: a mass transfer model.

The discharge of harmful dyes in water bodies is a serious pollution problem, dangerous for the ecosystem's equilibrium and human health. In this sense, the aim of this work was to determine the influence of electrolytes (NaCl, KCl, CaCl2 and MgCl2) in the adsorption of Reactive Blue BF-5G dye, the most common dye used in industrial process for fabric colouring, using bovine bone char as the adsorbent. The bovine bone char was characterized by pH of point of zero charge (pHPZC), N2 adsorption-desorption isotherms, Fourier transform-infrared spectroscopy (FT-IR) and X-ray diffractometry (XDR). The characterization revealed a mesoporous structure (pore mean diameter of 94 Šand SBET ∼107 m2 g-1) with negative charge distribution at the surface (pHPZC = 3.8). The adsorption experiments revealed that the presence of KCl enhanced the material adsorption capacity (qmax = 195 mg g-1), that the Sips isotherm best fitted the experimental data (R2 > 0.9 except for KCl solution) and the adsorption process was mono- and multilayered. The kinetic adsorption experiments indicated that the inorganic electrolytes increased the initial adsorption velocity and the data was best modelled by the surface diffusional model (SDM), implying a resistance (aqueous > CaCl2 > NaCl > MgCl2 > KCl) to mass transfer at the surface of the pores which, in turn, prevented the dye diffusion to the interior of the adsorbent (qe = 71 mg g-1). Therefore, small quantities of KCl can be used to lower the mass transfer resistance and provide higher adsorption capacity with reduced time of operation, thus increasing the overall process efficiency.

Low-protein diet does not alter reproductive, biochemical, and hematological parameters in pregnant Wistar rats.

The aim of this study was to investigate the reproductive, biochemical, and hematological outcomes of pregnant rats exposed to protein restriction. Wistar rat dams were fed a control normal-protein (NP, 17% protein, n=8) or a low-protein (LP, 8% protein, n=14) diet from the 1st to the 20th day of pregnancy. On the 20th day, the clinical signs of toxicity were evaluated. The pregnant rats were then anesthetized and blood samples were collected for biochemical-hematological analyses, and laparotomy was performed to evaluate reproductive parameters. No sign of toxicity, or differences (P>0.05) in body weight gain and biochemical parameters (urea, creatinine, albumin, globulin, and total protein) between NP and LP pregnant dams were observed. Similarly, hematological data, including red blood cell count, white blood cell count, hemoglobin, hematocrit, red blood cell distribution width (coefficient of variation), mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, % lymphocytes, absolute lymphocyte count, platelet count, and mean platelet volume were similar (P>0.05) at the end of pregnancy. Reproductive parameters (the dam-offspring relationship, ovary mass, placenta mass, number of corpora lutea, implantation index, resorption index, and the pre- and post-implantation loss rates) were also not different (P>0.05) between NP and LP pregnant dams. The present data showed that a protein-restricted diet during pregnancy did not alter reproductive, biochemical, and hematological parameters and seems not to have any toxic effect on pregnant Wistar rats.

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.

Maternal low-protein diet induces changes in the cardiovascular autonomic modulation in male rat offspring.

BACKGROUND AND AIMS: Maternal undernutrition induces development of the arterial hypertension. We investigated the effects of a maternal low-protein diet on cardiovascular autonomic control in the offspring. METHODS AND RESULTS: Male Wistar rats were divided into two groups according to the diets of their mothers during gestation and lactation: the control (normal protein, NP, 17% casein; n = 14) and low-protein (LP, 8% casein; n = 14) groups. Direct measurements of arterial pressure (AP) were recorded from wakeful 90-day-old male offspring. The LP offspring presented higher mean AP than did the NP rats (NP: 93 ± 4 vs. LP: 113 ± 2 mmHg; p < 0.05), whereas the heart rate (HR) was similar in the two groups. In the spectral analysis, the LP group showed higher power at low (NP: 1.98 ± 0.25 vs. LP: 3.7 ± 0.3 mmHg²; p < 0.05) and high (NP: 1.28 ± 0.18 vs. LP: 2.13 ± 0.42 mmHg²; p < 0.05) frequencies of systolic arterial pressure (SAP). In the pulse interval, the LP group presented an increase in the LF/HF ratio (NP: 0.32 vs. LP: 0.56; p < 0.05). After propranolol (4 mg/kg, intravenous (iv)), the bradycardia was higher in the LP group (NP: -36 ± 8 vs. LP: -94 ± 12 bpm; p < 0.05), after methylatropine (2 mg/kg, iv), the tachycardia was similar to NP group. After administration of the ganglionic blocker (hexamethonium; 25 mg/kg, iv), the LP animals showed larger delta variation in the AP (NP: -33.7 ± 5 vs. LP: -53.6 ± 4 mmHg; p < 0.05). CONCLUSION: The rats subjected to protein malnutrition presented an increase in the cardiovascular sympathetic tone, which contributed to the elevated AP observed in these animals.

Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil.

Approximately 200 million people suffer from type 2 diabetes (T2D) worldwide, and the rapid increase in the prevalence of this disease is likely a result of multiple environmental factors, such as increased food intake and decreased physical activity in genetically predisposed individuals. Different population studies have demonstrated a strong association of two polymorphic variations in the TCF7L2 gene, the noncoding single nucleotide polymorphisms (SNPs) rs7903146 (C/T) and rs12255372 (G/T), with T2D. Herein, we analyzed the association of these SNPs with T2D in a population from northeastern Brazil. Our results showed that the genotype and allele frequencies in TCF7L2 rs7903146 and rs12255372 were similar in the patient and control groups (P > 0.05). In addition, the allele frequencies were not significantly associated with T2D risk [rs7903146: odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.52-1.76, P = 1.00, and rs12255372: OR = 1.38, 95%CI = 0.72-2.62, P = 0.41]. These data suggest that the TCF7L2 SNPs rs7903146 and rs12255372 may not significantly contribute to T2D susceptibility in this population. However, our results may reflect the small number of subjects. Alternatively, these results may be attributable to specific ethnic effects, as most of the previously reported associations were demonstrated with predominantly European populations. To reach a definitive conclusion on the role of such gene variants for T2D in mixed populations, additional efforts are necessary to replicate this study with larger populations from areas with more ethnic heterogeneity.

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.

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.

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.

Enhancement of carotid chemoreceptor reflex and cardiac chemosensitive reflex in the acute phase of myocardial infarction of the anesthetized rabbit.

In the acute phase of cardiac ischemia there is an imbalance of the autonomic outflow with a depression of the baroreceptor reflex. Carotid chemoreceptor stimulation evokes an increase on arterial blood pressure and bradycardia in the anesthetized and paralyzed animal. The activation of cardiac chemosensitive fibers elicit the Bezold-Jarisch reflex comprising a decrease of arterial blood pressure and bradycardia. In the present study, we studied the modifications of the carotid chemoreceptor reflex and the Bezold-Jarisch reflex elicited during the acute phase of myocardial infarction (MI) in the anesthetized and paralyzed rabbit. Rabbits were anesthetized with pentobarbitone, paralyzed and artificially ventilated. The carotid sinus region was exposed and a cannula was inserted retrogradely through the external carotid artery into the carotid bifurcation; the carotid body was stimulated by a lobeline injection. A catheter was advanced, via the right carotid artery, to the origin of the aorta and the Bezold-Jarisch reflex was evoked by an injection of ATP. The baroreflex was provoked by an increase in after-load or by clamping the common carotid artery. Heart ischemia was provoked by ligation of the descending coronary artery. Arterial blood pressure, carotid artery pressure, heart rate and electrocardiogram were monitored. Stimulation of cardiovascular and cardiac receptors was performed before and after coronary ligation. Results show an overall increase in the cardiovascular reflex responses elicited by stimulation of chemically activated receptors and an overall decrease of the baroreceptor responses after MI. In conclusion, these data show the existence of an enhancement of the reflex cardiovascular responses to carotid chemoreceptor and cardiac chemosensitive receptors stimulation and confirmed the depression of baroreceptor reflexes following heart ischemia that could account for the imbalance of the autonomic output observed in the acute phase of myocardial infarction.

Autoimmune progesterone urticaria.

Autoimmune progesterone dermatitis is a rare cutaneous disorder characterized by recurrent and cyclic skin eruption with variable morphology, occurring during the luteal phase. A case of autoimmune progesterone urticaria in a 47-year-old woman is reported. An intradermal progestin test revealed a strong reactivity against this hormone. Treatment with tamoxifen and leuprolide acetate induced only a partial remission of urticaria. Bilateral oophorectomy was performed with absolute clearing of cutaneous lesions.

Efficacy of prophylactic droperidol, ondansetron or both in the prevention of postoperative nausea and vomiting in major gynaecological surgery. A prospective, randomized, double-blind clinical trial.

We conducted a prospective, randomized, double-blind clinical trial comparing droperidol 1.25 mg intravenously (i.v.) (group 1, n = 30), ondansetron 4 mg i.v. (group 2, n = 30), or both (group 3, n = 30) in the prevention of postoperative nausea and vomiting (PONV) in the first 24 h following major gynaecological procedures under combined general and epidural anaesthesia. PONV was analysed by a linear nausea/vomiting score, incidence of nausea and vomiting, and the need for antiemetic rescue. Our results showed a similar incidence of nausea and vomiting in all groups (G1 33%, G2 40%, G3 43%). However, when comparisons were made according to the time of assessment, combination therapy resulted in significantly lower PONV than droperidol in the first hour (0% vs. 13%, P < 0.05) and second hour (0% vs. 13%, P < 0.05), and than ondansetron on the first hour (0% vs. 13%, P < 0.05). A trend persisted up to the fourth hour but was not statistically significant in either group. In conclusion, droperidol and ondansetron are effective agents in the prevention of PONV, and their combination seems to provide slightly better results than either drug alone.