Consecutive Liver and Bone Marrow Transplantation for Erythropoietic Protoporphyria: Case Report and Literature Review.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disease of heme biosynthesis resulting in the accumulation of protoporphyrin, characterized by liver failure in a minority of cases. Although liver transplant (LT) is the therapeutic strategy for advanced hepatic disease, it does not correct the primary defect, which leads to recurrence in liver graft. Thus, hematopoietic stem cell transplantation (HSCT) is an approach for treating EPP. METHODS: We aim to describe the first sequential LT and HSCT for EPP performed in Latin America, besides reviewing the present-day literature. RESULTS: The patient, a 13-year-old female with a history of photosensitivity, presented with symptoms of cholestatic and hepatopulmonary syndrome and was diagnosed with EPP. Liver biopsy demonstrated cirrhosis. She was submitted to a successful LT and showed improvement of respiratory symptoms. However, she had disease recurrence on the liver graft. She underwent a myeloablative HSCT using a matched unrelated donor, conditioning with BuCy (busulfan and cyclophosphamide), and GvHD (graft vs. host disease) prophylaxis with ATG (thymoglobulin), tacrolimus and methotrexate. Neutrophil engraftment occurred on D+18. She has presented mixed chimerism, but normalization of PP levels, being 300 days after HSCT, in good state of health and normal liver function. CONCLUSIONS: Consecutive LT and HSCT for EPP is a procedure that has been described in 10 cases in the literature and, even though these patients are a highly diversified population, studies have shown favorable results. This concept of treatment should be considered in patients with established liver disease.

Immunosuppression in Visceral Transplantation: Current Trends and Future Perspectives.

Visceral transplant represents an immunologic challenge due to high intestinal graft immunogenicity. Over the last 20 years, significant advances in immunosuppression regimens have resulted in excellent short-term outcomes. Currently, visceral transplant is the standard of care for patients with gut failure having life-threatening complications and complex abdominal pathology. In this review, we describe immunosuppressive strategies in the visceral transplant field.

Pre-transplant ALBI Grade 3 Is Associated with Increased Mortality After Liver Transplantation.

BACKGROUND: Although MELD score is a reliable tool for estimating mortality in the waiting list, criteria for preoperative prediction of survival after liver transplantation (LT) are lacking. ALBI score was validated as a prognostic marker for hepatocellular carcinoma patients undergoing transarterial chemoembolization, hepatic resection, and sorafenib treatment but not for LT outcomes yet. This study aimed to evaluate ALBI score as a prognostic factor in LT. METHODS: This is a single-center analysis of patients undergoing LT between October 2001 and June 2017. Primary endpoint was overall post-LT mortality. Secondary endpoint was 90-day mortality. RESULTS: Of all 301 patients included in this study, 185 (61.5%) were males. The median age was 54.1 ± 11.3 years. Univariate and multivariate analysis revealed that ALBI grade 3 (HR 1.836, 95% CI 1.154-2.921, p = 0.010), low serum albumin (HR 0.628, 95% CI 0.441-0.893, p = 0.010), black race (HR 2.431, 95% CI 1.160-5.092, p = 0.019), and elevated body mass index (HR 1.061, 95% CI 1.022-1.102, p = 0.002) all were associated with decreased overall survival following LT. Patients with both ALBI grade 3 (n = 25) and calculated MELD score ≥ 25 had the lowest overall survival (p < 0.001). DISCUSSION: ALBI grade 3 was related to lower post-LT survival and can be utilized as a tool for risk stratification in LT.

Serum Factor V Is a Continuous Biomarker of Graft Dysfunction and a Predictor of Graft Loss After Liver Transplantation.

BACKGROUND: Factor V has never been compared to a validated early allograft dysfunction (EAD) definition. We aimed to assess factor V as a biomarker of EAD and a predictor of graft loss after liver transplantation (LT). METHODS: We retrospectively assessed the serum factor V levels on postoperative day 1 after LT. Patients were divided according to their factor V levels into the ≤36.1 U/mL and > 36.1 U/mL groups. The primary outcome was graft loss within 1, 3, and 6 months. The secondary outcome was EAD, as defined by Olthoff et al. Predictors of outcomes were identified by multivariable logistic regression. RESULTS: Two hundred twenty-seven patients were included in the study: 74 with factor V of 36.1 U/mL or less and 153 with factor V >36.1 U/mL. EAD was diagnosed in 41 (55.4%) of 74 patients with factor V of 36.1 U/mL or less and in 20/153 (13.1%) patients with factor V >36.1 U/mL (P < 0.001). According to the multivariable regression model, factor V was a continuous marker of EAD (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.94-0.98 per U/mL). Among the study groups, the 1-, 3-, and 6-month graft survival rates were 82%, 74%, and 74%, respectively, for patients with factor V of 36.1 U/mL or less and 98%, 95%, and 95%, respectively, for patients with factor V >36.1 U/mL (P = 0.001). Factor V was a continuous predictor for 3- and 6-month graft losses (OR, 0.96; 95% CI, 0.94-0.99 and OR, 0.97; 95% CI, 0.94-0.99 per U/mL), whereas EAD was not significant when adjusted for factor V. CONCLUSION: Factor V is an early marker for EAD and is a continuous predictor of short-term graft loss after LT.

Liver Transplantation Utilizing Mixed Biologic and Synthetic Arterial Conduits.

Arterial conduits are necessary in nearly 5% of all liver transplants and are usually constructed utilizing segments of donor iliac artery. However, available segments of donor iliac artery may not be lengthy enough or may not possess enough quality to enable its inclusion in the conduit. Although there are few reports of arterial conduits constructed solely utilizing prosthetic material, no previous reports of conduits composed of a segment of donor iliac artery and prosthetic material (mixed biologic and synthetic arterial conduits) were found in the medial literature to date. Two cases reporting successful outcomes after creation of mixed biologic and prosthetic arterial conduits are outlined in this report. Reason for creation of conduits was complete intimal dissection of the recipient's hepatic artery in both cases. In both cases, available segments of donor iliac artery were not lengthy enough to bridge infrarenal aorta to porta hepatis. Both patients have patent conduits and normally functioning liver allografts, respectively, at 4 and 31 months after transplant. Mixed biologic and synthetic arterial conduits constitute a viable technical option and may offer potential advantages over fully prosthetic arterial conduits.

Hirschsprung disease and hepatoblastoma: case report of a rare association / Doença de Hirschsprung e hepatoblastoma: relato de caso de uma associação rara

ABSTRACT CONTEXT: Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. CASE REPORT: A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). CONCLUSION: It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.

RESUMO CONTEXTO: A doença de Hirschsprung é uma desordem do desenvolvimento do sistema nervoso entérico, que é caracterizada pela ausência de células ganglionares no intestino distal, ocorrendo em cerca de 1 a cada 500.000 nascimentos. O hepatoblastoma é uma neoplasia maligna do fígado que geralmente ocorre em crianças de 6 meses a 3 anos, com prevalência de 0,54 casos por 100.000. RELATO DE CASO: Um menino com diagnóstico de atresia intestinal na primeira semana de vida evoluiu com diagnóstico concomitante de doença de Hirschsprung. Catarata congênita e surdez neurossensorial foram diagnosticadas. Surgiu lesão hepática com posterior confirmação de hepatoblastoma, tratado com ressecção cirúrgica de 70% do volume hepático e quimioterapia neoadjuvante (ifosfamida, cisplatina e doxorubicina). CONCLUSÃO: Sabe-se que a doença de Hirschsprung pode estar associada a síndromes de predisposição ao câncer, da mesma forma que o hepatoblastoma já foi correlacionado a certas síndromes congênitas malformativas. No entanto, até o momento, a associação de hepatoblastoma com a doença de Hirschsprung não foi descrita. Relatamos o caso de um menino que nasceu com atresia ileal, doença de Hirschsprung, catarata congênita bilateral e com posterior diagnóstico de hepatoblastoma.

Hirschsprung disease and hepatoblastoma: case report of a rare association.

CONTEXT: Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. CASE REPORT: A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). CONCLUSION: It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.

Regeneração hepática em animais jovens com estenose da veia porta ou ligadura da artéria hepática: estudos histológicos, moleculares e avaliação dos efeitos da insulina e do tacrolimus como agentes regenerativos / Liver regeneration in growing animals with portal vein stenosis or hepatic artery ligation: histological and molecular studies, and evaluation of the effects of insulin and tacrolimus as regenerative agents

O transplante hepático é o único tratamento efetivo para uma variedade de doenças hepáticas irreversíveis. No entanto, o número limitado de doadores pediátricos leva ao uso de enxertos hepáticos de doadores adultos, com necessidade de anastomoses vasculares mais complexas. Essas anastomoses tornam-se complicadas pela diferença no calibre dos vasos entre o doador e o receptor, resultando em alterações do fluxo sanguíneo, estenose da anastomose venosa ou arterial e trombose. Os efeitos para regeneração hepática decorrentes da privação do fluxo sanguíneo pela veia porta ou pela artéria hepática não estão completamente elucidados. Experimentalmente, quando um lobo do fígado não recebe o fluxo venoso portal, é observada atrofia deste segmento e hipertrofia do restante do órgão perfundido. Embora existam vários modelos experimentais para estudo da regeneração hepática, poucos são focados em animais em crescimento. Além disso, os efeitos regenerativos de drogas como o tacrolimus e a insulina precisam ser pesquisados, com o objetivo de encontrar um tratamento ideal para a insuficiência hepática ou um método de estimular a regeneração do fígado após ressecções ou transplantes parciais. O objetivo do presente estudo é descrever modelos de regeneração hepática em ratos em crescimento com: 1) ausência de fluxo hepático arterial e 2) redução do fluxo portal. Adicionalmente, o estudo avalia o efeito pró-regenerativo do tacrolimus e da insulina nesses modelos descritos. MÉTODOS: cento e vinte ratos (entre 50 e 100g de peso) foram divididos em 6 grupos, de acordo com o tipo de intervenção cirúrgica: Grupo 1, incisão abdominal sem intervenção hepática; Grupo 2, hepatectomia a 70%; Grupo 3, hepatectomia a 70% + estenose de veia porta; Grupo 4, hepatectomia a 70% + ligadura da artéria hepática; Grupo 5, hepatectomia a 70% + estenose de veia porta + insulina; Grupo 6, hepatectomia a 70% + estenose de veia porta + tacrolimus. Os animais dos grupos 1 ao 4 foram...

Liver transplantation is an effective treatment for a variety of irreversible liver diseases. However, the limited number of pediatric donor livers leads to the use of adult livers, which usually require more complex vascular anastomoses. These anastomoses are complicated by differences in vessel caliber between donors and recipients, resulting in vascular flow anomalies, stenosis of the venous or arterial anastomosis and thrombosis . The effects of portal vein or hepatic arterial flow privation in hepatic regeneration have not been completely elucidated. Experimentally, when a liver lobe is deprived of portal vein flow, atrophy is observed with hypertrophy of the other perfused parts of the organ, and interleukin-6 (IL-6) is required for normal liver regeneration. Although several experimental models are currently used to study the liver regeneration mechanisms, few studies have focused on the growing animal. In addition, the regenerative effects of drugs (e.g., tacrolimus and insulin) have been experimentally studied, aiming to find an ideal treatment for hepatic failure or a method of stimulating liver regeneration after extensive resection or partial transplants. The aim of the present investigation was to describe the new models of liver regeneration in growing rats with: 1) absence of arterial blood hepatic inflow and 2) reduced portal flow. Additionally, it was studied whether tacrolimus or insulin could have any pro-regenerative effect under such conditions. METHODS/MATERIALS: one hundred and twenty rats (50-100 g body weight) were divided into 6 groups based on the intervention type: Group 1 (sham), abdominal incision without intervention; Group 2, 70% hepatectomy; Group 3, 70% hepatectomy + portal vein stenosis; Group 4, 70% hepatectomy + ligation of the hepatic artery; Group 5, 70% hepatectomy + portal vein stenosis + insulin; and Group 6, 70% hepatectomy + portal vein stenosis + tacrolimus. Animals in groups 1 to 4 were...

Effects of tacrolimus and insulin in a liver regeneration model in growing animals with portal vein stenosis: immunohistochemical and molecular studies.

The aim of the present investigation was to describe a new model of liver regeneration in growing rats with reduced portal flow. In addition, it was studied whether tacrolimus and insulin could have any pro-regenerative effect under such conditions. Ninety-five rats were divided into five groups: Group 1 (sham), abdominal incision without intervention; Group 2, 70% hepatectomy; Group 3, 70% hepatectomy + PV stenosis; Group 4, 70% hepatectomy + portal vein stenosis + insulin; and Group 5, 70% hepatectomy + portal vein stenosis + tacrolimus. The remnant liver lobes were harvested for analyses. The liver weight decreased in the PV stenosis group and it increased with the use of insulin and tacrolimus. The mitotic activity was higher in the hepatectomy, insulin and tacrolimus groups and this parameter was reduced by portal stenosis. Levels of interleukin 6 (IL-6) were higher in the hepatectomy group compared to the sham and PV stenosis groups. The expression of IL-6 and Ki67 was significantly increased in the insulin and tacrolimus groups compared to the portal stenosis group. A highly reproducible model was standardized to study liver regeneration with portal blood inflow reduction in weaning rats. It was demonstrated that insulin or tacrolimus administration may partially reverse the harmful effects of PV stenosis.

The effects of anesthetic regimen in 90% hepatectomy in rats.

PURPOSE: To evaluate the influence of the anesthetic regimen on anesthetic recovery, survival, and blood glucose levels following a 90% partial hepatectomy in rats. METHODS: Thirty adult male Wistar rats were divided into two groups according to their anesthetic regimens: intraperitoneal ketamine and xylazine or inhaled isoflurane. In order to prevent hypoglycemia, glucose was administered intraperitoneally and glucose (20%) was added to the drinking water. RESULTS: Anesthetic recovery time was longer in the ketamine and xylazine group. The survival rate after 72 hours was lower (log rank=0.0001) in the ketamine and xylazine group (0.0%) than in the isoflurane group (26.7%). The blood glucose after six hours was lower (p=0.017) in the ketamine and xylazine group (63 ± 31.7 mg/dL) than in the isoflurane group (98 ± 21.2 mg/dL). The prolonged anesthesia recovery time associated with ketamine and xylazine decreased the survival rate and blood glucose levels after 90% hepatectomy. CONCLUSION: Isoflurane anesthesia reduced the recovery time and incidence of hypoglycemia and increased the survival rate in the early hours, providing a therapeutic window that is suitable for experimental studies.

The effects of anesthetic regimen in 90% hepatectomy in rats / Os efeitos do regime anestésico na hepatectomia de 90% em ratos

PURPOSE: To evaluate the influence of the anesthetic regimen on anesthetic recovery, survival, and blood glucose levels following a 90% partial hepatectomy in rats. METHODS: Thirty adult male Wistar rats were divided into two groups according to their anesthetic regimens: intraperitoneal ketamine and xylazine or inhaled isoflurane. In order to prevent hypoglycemia, glucose was administered intraperitoneally and glucose (20%) was added to the drinking water. RESULTS: Anesthetic recovery time was longer in the ketamine and xylazine group. The survival rate after 72 hours was lower (log rank=0.0001) in the ketamine and xylazine group (0.0%) than in the isoflurane group (26.7%). The blood glucose after six hours was lower (p=0.017) in the ketamine and xylazine group (63±31.7 mg/dL) than in the isoflurane group (98±21.2 mg/dL). The prolonged anesthesia recovery time associated with ketamine and xylazine decreased the survival rate and blood glucose levels after 90% hepatectomy. CONCLUSION: Isoflurane anesthesia reduced the recovery time and incidence of hypoglycemia and increased the survival rate in the early hours, providing a therapeutic window that is suitable for experimental studies.

OBJETIVO: Avaliar a influência do regime anestésico sobre a recuperação anestésica, a sobrevida em 72 horas e a glicemia após hepatectomia parcial de 90% em ratos. MÉTODOS: Trinta ratos Wistar machos adultos foram distribuídos em dois grupos conforme o regime anestésico: combinação de ketamina e xilazina intraperitoneal ou isoflurano inalatório. Para prevenção de hipoglicemia foi administrada glicose intraperitoneal e adicionado glicose (20%) na água de beber. RESULTADOS: A recuperação anestésica no grupo ketamina e xilazina foi mais prolongada. Durante primeira hora após hepatectomia, nenhum rato anestesiado com ketamina e xilazina despertou. Todos do grupo isoflurano estavam ativos minutos após final da cirurgia. A sobrevida em 72 horas foi menor (Log rank=0,0001) no grupo ketamina e xilazina (0,0%) que no grupo isoflurano (26,7%). Glicemia em 6 horas do grupo ketamina e xilazina (63±31,7 mg/dL) foi menor (p=0,017) que no grupo isoflurano (98 ±21,2 mg/dL). Prolongado tempo de recuperação anestésica com ketamina e xilazina diminuiu sobrevida e glicemia após hepatectomia 90%. CONCLUSÃO: Anestesia com isoflurano reduziu tempo de recuperação e hipoglicemia, além de aumentar a sobrevida nas primeiras horas, possibilitando uma janela terapêutica adequada para estudos experimentais.

Transmission of clear cell tumor in a graft liver from cadaveric donor: case report.

Neoplasms in children after organ transplantation are related to the type and intensity of immunosuppression and the donor-recipient serostatus, especially in relation to the Epstein-Barr virus. The patient was a two-yr-old female child with biliary atresia who underwent a liver transplantation from a female cadaver donor. Two adults received kidney transplants from the same donor. Nine months after transplantation, one of the adult recipients developed an urothelial tumor in the kidney graft. Imaging tests were repeated monthly in the liver-transplanted child and revealed no abnormalities. However, one yr and two months after the transplantation, the patient developed episodes of fever. At that time, imaging and liver biopsy showed a clear cell tumor of urothelial origin in the graft and the disease was limited to the liver. The patient underwent liver retransplantation, and she is currently free of tumor recurrence. Although rare, the occurrence of tumors in the post-transplant period from cadaver donors, without previously diagnosed tumors, is one of the many problems encountered in the complex world of organ transplantation.

Traqueostomia pediátrica: relato de uma série de casos / Pediatric tracheostomy: Cases report series

Objetivo: Determinar a faixa etária, indicações e complicações de traqueostomia realizada em crianças até 12 anos de idade. Métodos: Revisão retrospectiva de 26 crianças submetidas à traqueostomia no período de novembro de 1999 a julho de 2003, em hospital geral terciário. Resultados: Aidade média das crianças foi de 32 meses; 17 (65,4%) eram menores de 1 ano. O procedimento foi eletivo em 20 (76,9%) e de emergência 6 (22,1%). As principais indicações foram ventilação mecânica prolongada em 13 (50%), estenose subglótica em 5 (19,3%) e malformações congênitas em 4 (15,4%). As complicações foram tecido de granulação no traqueostoma em 7 (26,9%), hemorragia em 3 (11,5%), obstrução da cânula em 3 (11,5%), enfisema subcutâneo em 2 (7,7%), pneumotórax em 2 (7,7%), decanulaçao acidental em 2 (7,7%), estenose laríngea em 1 (3,8%) e infecção da ferida operatória em 1 (3,8%). Não foram observadas diferenças significativas entre as complicações observadas nos procedimentos eletivos e de urgência. Treze pacientes morreram por complicações não relacionadas à traqueostomia; onze (42,2%) permaneceram com traqueostomia, e 2 (7,7%) foram decanulados. Conclusões: Nos últimos anos ocorreram mudanças nas indicações e faixa etária das crianças submetidas à traqueostomia: ela é mais comumente realizada em crianças menores de um ano, e mais freqüentemente devido à intubação prolongada. A traqueostomia é um procedimento seguro quando é realizada por cirurgião treinado com a técnica cirúrgica e com cuidados pós-operatórios de hospital terciário de referência (AU)

Objective: To determine age of surgery, indications and complications of tracheostomy in children until 12 years old. Method: Retrospective review of 26 children submitted to tracheostomy from November 1999 to July 2003 at a tertiary general hospital. Results: The mean age was 32 months; 17 (65.4%) were under 1 year old. In 20 (76.9%) the procedure was elective, whereas in 6 (22.1%) it was performed as emergency. The main indications of tracheostomy were prolonged mechanical ventilation in 13 patients (50%), subglottic stenosis in 5 (19.3%) and congenital malformations in 4 (15.4%). The most common complications were granulation at the site of the stoma in 7 (26.9%), bleeding in 3 (11.5%) , blockage of the cannula in 3 (11.5%), subcutaneous emphysema in 2 (7.7%) , pneumothorax in 2 (7.7%), accidental decannulation in 2 (7.7%), larynx stenosis in 1 (3.8%), surgical wound infection in 1 (3.8%). Regarding complications , it was not observed any significant difference between elective and emergency procedures. Thirteen patients (50%) died due to complications not related to the tracheostomy; eleven (42.2%) kept the tracheostomy, and 2 (7.7%) were decannulated. Conclusions: In the last few years there were changes in pediatric tracheostomy. It is being indicated more often in children under one year old, and more recently due to prolonged intubation. Tracheostomy is a safe procedure when performed by trained surgeon with appropriate technique and postoperative care at tertiary hospital (AU)

Tumor size as a surrogate end point for the detection of early breast cancer: a 30-year (1972-2002), single-center experience in southern Brazil.

The 30-year experience in improving detection of breast cancer in the Breast Unit of the Hospital de Clínicas, Federal University of Rio Grande do Sul, Brazil (1972-2002) is reported. We retrospectively analyzed the behavior of surrogate parameters of early breast cancer detection, such as the mean tumor diameter at diagnosis, clinical staging, as well as the percentage of breast conservative surgery along this period of three decades. From 2,103 identified women, 1,607 women met our criteria for study entry and had follow-up information, constituting our study cohort. Statistical tests were two-sided and considered significant at p < 0.05. There was a decrease of about 0.8 cm in the median tumor diameter over this 30-year period. The incidence of early-stage tumors increased progressively over time, and the percentage of patients presenting with stage I breast cancer doubled in 30 years. The Halsted procedure that represented 11.5% of surgeries in the 1970s is a very rare procedure nowadays (<1% of cases). Modified radical mastectomy was the procedure applied in about 50% of women with invasive breast cancer during these 30 years of observation. Notably, breast conservative surgery increased from 17.3% in the 1970s to 43.2% in the 2000s, while the decrease in tumor size and clinical staging was accompanied by an increased number of breast conservative surgical procedures. In geographic areas where coordinated preventive efforts are not thoroughly available, analysis of subsets of the patient population using tumor size as a surrogate represents an indirect way to observe long-term effects of prevention. The present study shows that tumor size is a surrogate for populations from developing countries too and gives scientific support for the design of continuous comprehensive programs of breast cancer prevention in this setting.

Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice.

BACKGROUND: Pancreatic ductal adenocarcinoma has a poor long-term prognosis. Experimental models are necessary to understand not only its biologic behavior, but also the early pancreatic lesions known as pancreatic intraepithelial neoplasia (PanIN) and to develop new treatments. The aim of this study was to evaluate pancreatic carcinogenesis induced by 7,12-dimethyl-1,2-benzanthracene (DMBA) implantation in mice according to the PanIN classification system. METHODS: Ninety male, Mus musculus, CF-1 mice underwent a median laparotomy and 1 mg of DMBA was implanted into the proximal pancreas held in place by a purse-string suture. Mice were killed after 30 and 60 days after which the excised pancreata were fixed in formalin, embedded in paraffin, and stained with hematoxylin-eosin for histologic analysis. The specimens were evaluated blind by 2 pathologists for the presence of the following histology: normal ducts, reactive hyperplasia, PanIN-1A, PanIN-1B, PanIN-2, and PanIN-3, and adenocarcinoma. RESULTS: In the 30-day group, pathologic evaluation showed 4 (17%) reactive hyperplasia, 16 (67%) PanIN lesions, and 4 (17%) adenocarcinomas. In the 60-day group, there were 10 (27%) specimens with reactive hyperplasia, 13 (35%) with PanIN lesions, and 14 (38%) with adenocarcinomas. The difference between groups was statistically significant (P<.05). All pancreata with adenocarcinoma had concomitant PanIN lesions. CONCLUSIONS: The DMBA experimental model in mice induces PanIN lesions and ductal adenocarcinoma that have similar histology to that of human pancreatic cancer. This model may be useful for study of pancreatic carcinogenesis, particularly the molecular progression of early pancreatic ductal lesions.

Ressecções pancreáticas: experiência do grupo de vias biliares e pâncreas do Hospital de Clínicas de Porto Alegre entre 2000 e 2003 / Pancreatic resections: experience of the pancreato-biliary group at Hospital de Clínicas de Porto Alegre, Brazil, between 2000 and 2003

Este trabalho apresenta a experiência de 20 ressecções pancreáticas e tem como objetivo principal ressaltar a importância dos centros de referência para doenças de tratamento cirúrgico complexo, como é o caso dos portadores de neoplasia da confluência biliopancreática. De 60 doentes com neoplasia biliopancreática tratados no período de janeiro de 2000 a janeiro de 2003, 20 foram submetidos a ressecção: 16 a duodenopancreatectomia, três a ressecção corpo-caudal e um a ressecção da Papila de Vater. As complicações mais freqüentes foram: cinco fístulas pancreáticas, sete abscessos intra-abdominais e oito infecções do aparelho respiratório. A mortalidade foi de 0 por cento. Nos Estados Unidos, em hospitais com pequena experiência, nos anos de 1984 a 1991, a mortalidade foi de 21,8 por cento; já em centros de referência, foi de 4 por cento. Em série anterior do Hospital de Clínicas de Porto Alegre, referente ao período de 1988 a 1999, a mortalidade foi de 20 por cento. A presente série confirma a experiência internacional: o resultado das ressecções pancreáticas é melhor em centros de referência. A indicação da cirurgia, os cuidados pré e pós-operatórios e a experiência de uma equipe que realiza o procedimento no mínimo de 10 a 15 vezes por ano são fundamentais para a obtenção de bons resultados, com a gradativa diminuição do tempo de internação e dos custos hospitalares