Stratifying Mortality in a Model for End-Stage Liver Disease Waiting List: A Brazilian Single-Center Study.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) system reliably predicts mortality in cirrhotic patients. However, the etiology of liver disease and presence of portal vein thrombosis are not directly taken into account in MELD score. Its impact on the outcomes of patients on the waiting list is still unclear. The aim of this study was to investigate mortality and access to transplantation regarding etiology of liver disease and portal vein thrombosis (PVT). METHODS: A total of 465 adult patients on the liver waiting list from August 2015 to August 2016 were followed up until August 2017. Patients were divided into groups according to the etiology of liver disease and presence of PVT. RESULTS: The most frequent etiologies were hepatitis C (26.88%), alcoholic cirrhosis (26.02%) and cryptogenic cirrhosis (10.75%). Death while on the waiting list occurred in 168 patients (36.1%) and was more frequent in nonalcoholic steatohepatitis (NASH, 65.4%) and alcoholic cirrhosis (41.3%). A total of 142 (30.5%) patients underwent transplantation and viral, autoimmune, and biliary diseases showed higher proportion of transplantation (36.3%, 53.8%, and 34%, respectively; P < .01). Mean delta-MELD at the study endpoint was higher in patients with autoimmune hepatitis, biliary diseases, and NASH (8.3 ± 7.2, 8.3 ± 9.1, and 7.5 ± 9.1, respectively; P < .01). A total 77 patients (16.7%) presented PVT. There was no significant difference in outcomes between patients with and without PVT. CONCLUSIONS: Patients with NASH and alcoholic liver disease had higher mortality while on the waiting list, whereas patients with viral and autoimmune hepatitis had higher transplantation rate. Outcomes were not influenced by PVT.

Shortage of Donors for Intestinal Transplantation in São Paulo, Brazil.

BACKGROUND: The number of deceased organ donors has decreased slightly over the past 4 years. Although the pool of intestinal transplantation candidates is relatively small, donor allocation is challenging because of the inability to maintain the donor in a good condition and the complexities involved in making a suitable weight match between donors and recipients. Our goal was to analyze the epidemiologic profile of potential donors based on the organs offered by the regional Organ Procurement Organization from Hospital das Clinicas-USP (OPO/HC-USP) and attempt to estimate possible matches and program viability. METHODS: We retrospectively analyzed information from the OPO/HC-USP database regarding organs offered over the past 7 years as well as patients listed in our program. Data were collected regarding donor characteristics (eg, sex, age, race, body mass index, blood type, cause of death) and medical care details (eg, intensive care unit stay, use of vasopressor agents and antibiotics). RESULTS: In this time period, there were 18,103 brain death notifications in the state of São Paulo; 5,202 (35%) became viable donors, resulting in 5,201 (99%) effectively used livers and kidneys. Most potential donors were male, in their 40s, white, and had blood type O. Only 3 potential donors from OPO/HC-USP would have reached the established minimum criteria for intestinal donation over these 7 years.

Evidence That Anorectal Transplantation Is the Logical Treatment for Serious Anorectal Dysfunction and Permanent Colostomy.

Anorectal dysfunction resulting in fecal incontinence or permanent colostomy is a current public health concern that strongly impairs patient quality of life. Present treatment options for this complex disease are expensive and usually ineffective. Anorectal transplantation is the logical treatment for fecal incontinence and permanent colostomy. This procedure has been clinically effective in a few cases reported in the medical literature. Furthermore, experiments in rats, pigs, and dogs have shown promising results, with functional recovery of the graft. In this article we describe the scientific evidence that anorectal transplantation may be an important option for treating anorectal dysfunction.

Functional outcome of autologous anorectal transplantation in an experimental model.

BACKGROUND: Although anorectal transplantation is a challenging procedure, it is a promising option for patients who have completely lost anorectal function or in whom it failed to develop, as in congenital malformations. The paucity of animal models with which to test functional outcomes was addressed in this study of anorectal manometry in rats. METHODS: Wistar rats were assigned randomly to four groups: orthotopic anorectal transplantation, heterotopic transplantation, sham operation, or normal control. Bodyweight and anal pressure were measured immediately before and after operation, and on postoperative days 7 and 14. ANOVA and Tukey's test were used to compare results for bodyweight, anal manometry and length of procedure. RESULTS: Immediately after the procedure, mean(s.d.) anal pressure in the orthotopic group (n = 13) dropped from 31·4(13·1) to 1·6(13·1) cmH2 O (P < 0·001 versus both sham operation (n = 13) and normal control (n = 15)), with partial recovery on postoperative day 7 (14·9(13·9) cmH2 O) (P = 0·009 versus normal control) and complete recovery on day 14 (23·7(12·2) cmH2 O). Heterotopic rats (n = 14) demonstrated partial functional recovery: mean(s.d.) anal pressure was 26·9(10·9) cmH2 O before operation and 8·6(6·8) cmH2 O on postoperative day 14 (P < 0·001 versus both sham and normal control). CONCLUSION: Orthotopic anorectal transplantation may result in better functional outcomes than heterotopic procedures. Surgical relevance Patients with a permanent colostomy have limited continence. Treatment options are available, but anorectal transplantation may offer hope. Some experimental studies have been conducted, but available data are currently insufficient to translate into a clinical option. This paper details functional outcomes in a rat model of anorectal autotransplantation. It represents a step in the translational research that may lead to restoration of anorectal function in patients who have lost or have failed to develop it.

Home parenteral nutrition program and referral of potential candidates for intestinal and multivisceral transplantation in a single Brazilian center.

Intestinal failure is a multifaceted condition that may require high-complexity treatment and a multidisciplinary program, including home parenteral nutrition therapy (HPNT) and intestinal transplantation. In this article, we profile a Brazilian single-center experience with 128 cases of HTPN followed for the last 30 years and appraise the referral for potential intestinal and multivisceral transplantation.

Does anti-hepatitis B virus vaccine make any difference in long-term number of liver transplantation?

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B infection is associated with an increased risk of cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Our aim is to analyze, through a mathematical model, the potential impact of anti-HBV vaccine in the long-term (that is, decades after vaccination) number of LT. METHODS: The model simulated that the prevalence of HBV infection was 0.5% and that approximately 20% of all the liver transplantation carried out in the state of São Paulo are due to HBV infection. RESULTS: The theoretical model suggests that a vaccination program that would cover 80% of the target population would reach a maximum of about 14% reduction in the LT program. CONCLUSION: Increasing the vaccination coverage against HBV in the state of São Paulo would have a relatively low impact on the number of liver transplantation. In addition, this impact would take several decades to materialize due to the long incubation period of liver failure due to HBV.

Total pancreatectomy: porcine model for inducing diabetes - anatomical assessment and surgical aspects.

BACKGROUND: The swine is an essential model for carrying out preclinical research and for teaching complex surgical procedures. There is a lack of experimental models describing anatomical and surgical aspects of total pancreatectomy in the pig. MATERIALS AND METHODS: The experiments were performed on 10 white male swine weighing 27-33 kg. The animals were premedicated with midazolam (0.4 mg/kg, i.m.) and ketamine (4 mg/kg, i.m.). Anesthesia was induced with propofol (1-2 mg/kg, i.v.) and was maintained with propofol and fentanyl (0.3 mg and 0.1 µg/kg/min, respectively, i.v.). The surgical period ranged from 44 to 77 min. The pancreas anatomy, and the main arterial, venous and pancreatic duct anatomy were assessed. RESULTS: The pancreas anatomy was composed of 3 lobes, the 'splenic', 'duodenal' and 'connecting' lobe which is attached to the anterior portion of the portal vein. The splenic artery and the junction of the splenic vein and portal vein were divided. The left gastric artery was dissected and separated from its origin at the splenic artery. The head of the pancreas is disposed in a C shape. The pancreas was dissected and liberated from the right portion of the portal vein and the infrahepatic vena cava. The pancreas was separated from the duodenum preserving the pancreaticoduodenal artery, then we performed the total pancreatectomy preserving the duodenum, common bile duct and spleen. CONCLUSION: Total pancreatectomy with duodenum, bile duct and spleen preservation in the pig is feasible and an important instrument for research purposes and teaching surgical technique.

Anorectal transplantation.

BACKGROUND: Anorectal transplantation is a valid procedure for the treatment of anorectal dysfunction; however, the lack of a suitable animal model has hampered the development of this method. We describe a simple technique for anorectal transplantation in the rat and compare this procedure with colostomy. METHODS: The anorectal segment including the skin surrounding the anus were freed by abdominal and perineal dissection. In a heterotopically transplanted group the segment was exteriorized by the formation of an anus through an abdominal incision. In an orthotopically transplanted group the segment was replaced in its original position and reimplanted by suturing. In another group a distal colostomy was performed. A sham-treated control group (simulated surgical procedure) was also included. Changes in behavior, characteristics of the stool, body weight and survival rate were assessed by daily clinical examination. Moribund animals, those with a weight loss of more than 30%, and those surviving at 1 month were killed by an overdose of anesthetic. The results were analyzed using the Mann Whitney, Student's t and chi-squared tests, and p<0.05 was considered significant. RESULTS: Within 4 days after the operation, animals submitted to orthotopic or heterotopic transplantation had achieved normal defecation, body weight gain and clinical evolution similar to the sham-treated group. The overall mortality in these groups was 4.16%. In contrast, colostomized animals showed a high incidence of diarrhea, intestinal obstruction, stress posture and violent behavior (p

Small bowel and colon transplantation in rats using porto-portal cuff anastomosis.

Portal versus systemic venous drainage and colon grafting are major controversies in the techniques of intestinal transplantation. The rat is the best animal for research in this field. Nevertheless, this model requires complex microvascular anastomoses that are responsible for the high incidence of technical failures. A cuff technique is an easier anastomosis method than a hand-suture. We describe a simplified rat model of small bowel and colon transplantation using a porto-portal cuff anastomosis. DONOR: The entire small bowel, cecum, and ascending colon are harvested on a vascular pedicle, consisting of a long aortomesenteric conduit and portal vein. The right colonic vessels are preserved. The graft is flushed and a cuff device is placed on the end of the portal vein. RECIPIENT: The graft is implanted through an end-to-side aorto-aorta hand-sewn anastomosis. A segment between the first and second jejunal branch is isolated between clamps to insert into the portal cuff. After reperfusion, the recipient's mesentery is divided just below the cuff anastomosis. The recipient jejunum, ileum, and ascending colon are removed en bloc, and the graft is anastomosed in continuity with the remaining naive intestine concluding the operation. This simplified technique surmounts the technical obstacles in rats because it is easily and quickly performed, maintaining the physiological portal drainage, preserving graft ileocecal valve and ascending colon, and reaching acceptable success after a short period of training.

Interferon alpha-2B and liver resection to treat multifocal hepatic epithelioid hemangioendothelioma: a relevant approach to avoid liver transplantation.

BACKGROUND: Hepatic epithelioid hemangioendothelioma is a rare malignant tumor of vascular origin with frequent multifocal appearance. Liver resection may cause tumor spread. Liver transplantation has been indicated for unresectable nodules. We hypothesized that adjuvant interferon treatment is effective to prevent metastasis after liver resection. We report a case of multifocal hepatic epithelioid hemangioendothelioma successfully treated with interferon pulse therapy and bilobar hepatic resection. METHODOLOGY: CT scan and magnetic resonance imaging diagnosed three nodules in the liver (segments IV, VI and VII). Histopathology and specific immunostaining of a percutaneous nodule biopsy confirmed the diagnosis of hepatic epithelioid hemangioendothelioma. The treatment protocol included daily interferon alpha 2b 9 weeks before and 1 week after resection of liver segments IV, VI and VII. RESULTS: The postoperative outcome was complicated by a self-limited biliary fistula. The patient remains tumor free at 3 years after liver resection and currently enjoys excellent health. CONCLUSION: Interferon pulse therapy and hepatic resection was a good option to treat multifocal bilobar hepatic epithelioid hemangioendothelioma; it may prevent metastasis dissemination.

Analysis of chronic rejection and obliterative arteriopathy. Possible contributions of donor antigen-presenting cells and lymphatic disruption.

Sequential analysis of changes that lead to chronic rejection was undertaken in an animal model of chronic rejection and obliterative arteriopathy. Brown Norway rats are pretreated with a Lewis bone marrow infusion or a Lewis orthotopic liver allograft and a short course of immunosuppression. They are challenged 100 days later with a Lewis heterotopic heart graft without immunosuppression. The heart grafts in both groups undergo a transient acute rejection, but all rats are operationally tolerant; the heart grafts are accepted and remain beating for more than 100 days. Early arterial remodeling, marked by arterial bromodeoxyuridine incorporation, occurred in both groups between 5 and 30 days during the transient acute rejection. It coincided with the presence of interstitial (but not arterial intimal) inflammation and lymphatic disruption and resulted in mild intimal thickening. Significant arterial narrowing occurred only in the bone-marrow-pretreated rats between 60 and 100 days. It was associated with T lymphocyte and macrophage inflammation of the heart graft that accumulated in the endocardium and arterial intima and adventitia near draining lymphatics. There also was loss of passenger leukocytes from the heart graft, up-regulation of cytokine mRNA and major histocompatibility class II on the endothelium, and focal disruption of lymphatics. In contrast, long-surviving heart grafts from the Lewis orthotopic liver allograft pretreated group are near normal and freedom from chronic rejection in this group was associated with persistence of donor major histocompatibility class-II-positive hematolymphoid cells, including OX62+ donor dendritic cells. This study offers insights into two different aspects of chronic rejection: 1) possible mechanisms underlying the persistent immunological injury and 2) the association between immunological injury and the development of obliterative arteriopathy. Based on the findings, it is not unreasonable to raise the testable hypothesis that direct presentation of alloantigen by donor antigen-presenting cells is required for long-term, chronic-rejection-free allograft acceptance. In addition, chronic intermittent lymphatic disruption is implicated as a possible mechanism for the association between chronic interstitial allograft inflammation and the development of obliterative arteriopathy.

Alteraçöes histopatológicas do intestino delgado após preservaçäo hipotérmica com as soluçöes da Universidade de Wisconsin e Euro-Collins. Estudo experimental / Histopathological changes of the small bowel after hypothermic preservation with University of Wisconsin and Euro-Collins solutions. Experimental study

Existe interesse em prolongar o tempo de isquemia hipotérmica do intestino delgado (ID) com o uso de soluçöes de preservaçäo. OBJETIVO. Oobjetivo deste trabalho foi comparar as alteraçöes do ID isolado sob preservaçäohipotérmica com as soluçöes da Universidade de Wisconsin (UW) e Euro-Collins (EC) utilizando método de análise histopatológica. MÉTODO. Utilizaram-se 40 ratos Wistar (250-300g) cujo ID foi retirado por meio de técnica microcirúrgica e tratado com soluçäo UW ou soluçäo EC. Realizaram-se biópsias do jejuno proximal e íleo distal periodicamente, de 8 em 8 horas, a partir da retirada do ID (tempo 0) até 48 horas. Classificaram-se as alteraçöes histopatológicas encontradas no ID, quantitativamente, em 4 graus de gravidade de lesäo. De acordo com a progressäo de degeneraçäo hidrópica na vilosidade, os resultados obtidos foram analisados por estatística näo-paramétrica (p<0,05). RESULTADOS. Observou-se aumento significante da freqüência do acometimento do ID por lesöes isquêmicas ao longo dos períodos de tempo analisados para ambos os grupos. A freqüência e a gravidade das lesöes foram significantemente maiores no grupo EC do que no grupo UW, para os segmentos jejunais no tempo 8 horas, no jejuno e íleo no tempo 24 horas, e no jejuno e íleo no tempo 48 horas. CONCLUSÄO. concluiu-se que a soluçäo UW näo impediuo aparecimento de lesöes isquêmicas do ID, porém apresentou melhor açäo protetora, ao longo do tempo, nos segmentos jejunal e ileal, reduzindo a gravidade e a freqüência das lesöes histopatológicas, quando comparada com a soluçäo EC

[Histopathological changes in the small intestine after hypothermic preservation with University of Wisconsin and Euro-Collins solutions. Experimental study]. / Alterações histopatológicas do intestino delgado após preservação hipotérmica com as soluções da Universidade de Wisconsin e Euro-Collins. Estudo experimental.

PURPOSE: The objective of this study is to compare small bowel histopathologic alterations under hypothermic preservation with University of Wisconsin (UW) and Euro-Collins (EC) solutions. METHODS: In 40 Wistar rats (250-300g) the small bowel was microsurgically withdrawn and randomly treated with UW solution or EC solution. Periodic intestinal biopsies were taken from the proximal jejunum and distal ileum each 8 hours after small bowel withdrawing (time 0) until 48 hours. The histopathologic alterations were semiquantitatively classified in 4 degrees of severity and the obtained results were analysed statistically by appropriated tests (p < 0.05). RESULTS: There was a significant increase of the small bowel ischaemic lesions over the time for both experimental groups. The lesions frequency and severity were significantly more increased in the EC group than in the UW group, for jejunal segments at 8 hours, in jejunal and ileal segments at 24 and in jejunal and ileal segments at 48 hours. CONCLUSION: The UW solution did not avoid the development of small bowel ischaemic lesions but, with time, it protected better jejunal and ileal segments, decreasing frequency and severity of histopathological alterations, when compared to EC solution.