Tratamento cirúrgico do adenoma hepático roto: experiência de 17 anos / Surgical treatment of ruptured hepatocellular adenoma: 17 years of experience

Introdução: o adenoma hepático roto é uma complicação incomum, exigindo alta suspeita clínica devido ao risco que representa. Exige pronta investigação diagnóstica com exames radiológicos. Após reposição volêmica, seu tratamento pode envolver desde a embolização transarterial hepática até a cirurgia de urgência. Objetivo: analisar fatores de risco e o tratamento cirúrgico dos adenomas hepáticos com rotura detectados em nosso serviço. Método: foram avaliados retrospectivamente os prontuários de 28 pacientes com adenoma hepático operados no período de 1995 a 2012. Foram analisadas variáveis epidemiológicas e clínicas, os sinais de rotura foram categorizados como intraperitoneal ou subcapsular, o tumor classificado como único ou múltiplo. Foram avaliados o tempo cirúrgico e a perda sanguínea intraoperatória. Resultado: dos 28 casos, 3 (11%) estavam rotos. Os três eram do sexo feminino, apresentaram rotura espontânea e duas faziam uso de anticoncepcional oral. Não se observou sinal de malignização em nenhum. A idade média foi de 32 anos. Foi realizado tratamento cirúrgico por hepatectomia direita em todos. Dois apresentaram rotura intraperitoneal e subcapsular e uma subcapsular apenas. O tamanho médio das lesões foi de 10 cm, sendo que, em dois casos, era única, e em uma múltipla. Médias de sangramento foram de 1000 ml, transfusão de 4 concentrados de hemácias e tempo cirúrgico de 6 horas. Nenhuma das pacientes apresentava cirrose, consumia bebidas alcoólicas ou alteração significativa dos níveis das enzimas hepáticas. No pós-operatório, um paciente evolui com pneumonia e uma paciente apresentou insuficiência hepática, evoluindo a óbito. Conclusão: o adenoma hepatocelular roto é uma condição potencialmente ameaçadora à vida, associada em nossa amostra ao tamanho da lesão e ao uso de anticoncepcional oral. O tratamento cirúrgico está associado a ressecções hepáticas maiores, com necessidade de transfusão sanguínea. A experiência vivida em nosso centro demonstra que o uso da radiologia intervencionista possa ser um procedimento para reduzir esta mortalidade.

Background: spontaneous hepatic rupture is a rare clinical event that needs to be carefully evaluated due to the high risks involved. The diagnosis is often made after abdominal imaging. Volemic resuscitation, selective transarterial embolization or surgical resections have been used. Aim: the aim of this study was to describe the epidemiology, risk factors and treatment performed in our service. Methods: we reviewed the medical records of 28 patients from 1995 to 2012 with a diagnosis of hepatocellular adenoma. We analyzed epidemiology, clinics variables, the ruptured adenomas were divided into either intrahepatic hemorrhage or intraperitoneal bleeding categories. Results: three (11%) of the 28 patients had ruptured hepatocellular adenoma. These three patients were women, had spontaneous ruptures and a background of oral contraceptive use. The mean age was 32 years old. They were submitted to right hepatectomy; two were associated with intrahepatic and intraperitoneal hemorrhage while one had only intrahepatic bleeding and none had malignant transformation. The mean diameter of the lesion was 10cm, two was unique and one was multiple. The means of bleeding loss was 1000ml, surgical time of six hours and transfusion of four red blood cells bag. No one of the patients has cirrhosis, alcoholism or significant variation of liver enzymes profile. In the postoperative period one patient had pneumonia while another had hepatic insufficiency and died. Conclusion: spontaneous hepatic rupture is a potential hazard to patients associated with the size of the tumor and the potency of the oral contraceptive used. In this condition emergency surgery can be required leading to a major resection with accompanying blood transfusion. Our experience concluded that interventional radiology procedures can decrease mortality.

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression in hepatocellular carcinoma. A clinicopathological analysis with emphasis on diagnostic value.

AIMS: Patients with hepatocellular carcinoma (HCC) usually present with advanced disease and rarely qualify for curative therapy. Immunohistochemical markers that help to discriminate benign from malignant processes early, and that have prognostic significance, would be useful. Expression of the oncofetal protein insulin-like growth factor II mRNA-binding protein 3 (IMP3) in malignant cells of different tumour types correlates with reduced overall survival. METHODS AND RESULTS: Tissue microarrays (TMAs) containing 55 normal liver samples, 365 HCCs (122 with corresponding non-tumorous liver), 10 hepatocellular adenomas, 13 focal nodular hyperplasias and nine dysplastic nodules from western European patients were stained for IMP3. IMP3 was analysed in 61 core needle biopsies and findings were compared to glypican-3 and CD34. HCCs in TMAs were strongly positive for IMP3 in 18.4% of cases compared to absent expression in normal and non-tumorous liver tissue and benign liver tumours. Patients with IMP3 expression in HCCs showed significantly poorer overall survival in multivariate analysis (P = 0.044). Of the 61 core needle biopsies analysed, 32 (52.5%) of the HCCs were IMP3-positive. CONCLUSIONS: In core needle biopsies, IMP3 expression seems to be of limited use as a single marker for the diagnosis of HCC, given a sensitivity of 52%, but it may be helpful in combination with other markers.

Enhanced hepatocarcinogenicity by combined inhalation and oral exposures to N,N-dimethylformamide in male rats.

N,N-Dimethylformamide (DMF), a ubiquitous contaminant in living and working environments, enters the human body by inhalation, as well as by oral and dermal routes of exposure. In order to provide bioassay data for carcinogenic risk assessment of humans exposed to DMF by multiple routes of exposure, hepatocarcinogenic effect of combined inhalation and oral exposures of rats to DMF was examined. A group of 50 male F344 rats, 6-week-old, was exposed by inhalation to 0 (clean air), 200, or 400 ppm (v/v) of DMF vapor-containing air for 6 hr/day and 5 days/week during a 104-week period, and each inhalation group was given ad libitum DMF-formulated drinking water at 0, 800 or 1,600 ppm (w/w) for 104 weeks. Incidences of hepatocellular adenomas and carcinomas and their combined incidences were significantly increased in the combined-exposure groups compared with the untreated control group or each of the inhalation-alone and oral-alone groups with matching concentrations. Incidences of hepatocellular adenomas and carcinomas induced by the combined exposures were greater than the sum of the two incidences of the hepatocellular adenomas and carcinomas induced by the single-route exposures through inhalation and ingestion. The combined exposures enhanced tumor malignancy. It was concluded that the combined inhalation and oral exposures markedly enhance the incidences and malignancy of hepatocellular tumors, suggesting that the hepatocarcinogenic effect of the combined exposures is greater than the effect that would be expected under the assumption that the two effects of single-route exposures through inhalation and drinking are additive.

Isolated resection of the caudate lobe: indications, technique and results.

BACKGROUND/AIMS: This paper reports a series of 24 isolated caudate lobe resections (ICLR), performed for 13 benign tumors (10 hemangiomas, 2 focal nodular hyperplasias, 1 adenoma) and 11 malignant tumors (3 hepatocarcinomas, 1 peripheral cholangiocarcinoma and 7 metastatic - 5 colorectal carcinomas, 1 breast carcinoma, 1 adrenal carcinoma). Klatskin tumors were excluded. METHODOLOGY: There were 10 hemangioma enucleations, 7 Spiegel lobe resections and 7 high dorsal resections. Total vascular exclusion was performed in 7 cases. Vascular resection with reconstruction was necessary in 5 cases. RESULTS: Complications occurred in 7 cases (3 bile leaks, 3 abdominal fluid collections and one liver failure leading to death). From the 10 patients with malignant tumors who survived the operation, 7 developed recurrences: 2 intrahepatic, 1 retroperitoneal, 4 systemic. Five patients are alive (3 without recurrence). One patient died of multiple complications after a repeat hepatectomy and colectomy. Three patients died from generalized disease. Another patient, with generalized disease, was lost from follow-up. CONCLUSIONS: ICLR is a difficult operation, especially with malignant tumors. Total vascular exclusion of the liver is routinely recommended in high dorsal resection. Malignant tumors located in the caudate lobe have a poor prognosis; local and, especially, distant metastases are frequent. Aggressive chemotherapy and follow-up are recommended.

[Liver resection and liver transplantation in liver cell adenoma, hepatocellular carcinoma and fibrolamellar liver carcinoma]. / Leberresektion und Lebertransplantation bei Leberzelladenom, hepatozellulärem Karzinom und fibrolamellärem Leberkarzinom.

Hepatocellular adenomas are rare benign conditions but represent an indication for resection due to their risk of rupture and malignant mutation. Surgical resection should include a safety margin according to oncologic principles. Surgical resection does represent the optimal treatment modality for hepatocellular carcinoma without accompanied cirrhosis of the liver. The rare fibrolamellar carcinoma has the best prognosis. Liver transplantation is usually not performed in HCC without cirrhosis. In case of HCC with cirrhosis in stage I and II the relapse free 5-year-survival rate is more than 50% after liver transplantation. In the UICC-stages III and IV the results of liver transplantation are worse, which points to the impact of exact preoperative staging. Liver resection in HCC and cirrhosis is indicated in stage I and II in case of good liver function. In case of liver resection the survival rates are worse with significantly higher relapses compared to liver transplantation. For small, functionally irresectable hepatocellular carcinoma in cirrhosis liver transplantation is the treatment of choice today.

[Spiral CT portography in preoperative diagnosis of liver metastases]. / Die Spiral-CT-Portographie in der präoperativen Diagnostik von Lebermetastasen.

Within a period of 12 months we preoperatively performed spiral CT portography (CT-AP) including individual determination of contrast injection kinetics, in 18 consecutive patients. The findings were compared with the microscopic findings in 15 resected specimens. A total of 51 perfusion defects were identified with CT-AP, 40 of which were finally diagnosed as metastases. A total of 36 hepatic lesions were identified at microscopy. 28 of which were metastases, all seen at CT-AP. 12 perfusion defects were misdiagnosed false positive as being of metastatic origin. Thus the sensitivity of CT-AP was 100%, the specificity 65% and the overall accuracy 78%. Therefore, CT-AP using the spiral CT technique is currently the most accurate method for preoperative staging of metastatic disease of the liver. Improvements of the scanning and contrast injection techniques will further improve the clinical value of this examination.

Experimental studies on the long-term effects of methylphenidate hydrochloride.

Toxicology and carcinogenesis studies of methylphenidate hydrochloride, a drug used in the treatment of attention-deficient disorders, were performed in F344 rats and B6C3F1 mice. In these studies, methylphenidate hydrochloride was administered for 2 years at doses of 0, 100, 500 or 1000 ppm in the feed to rats and at doses of 0, 50, 250, 500 ppm to mice in groups that consisted of 50 animals/dose/sex/species. The average amount of methylphenidate consumed per day was estimated to be 4-47 mg/kg/day for rats and 5-67 mg/kg/day for mice. Survival was similar in dosed and control groups. An increase in benign tumors of the liver and increased liver weights were observed in male and female mice at the high dose. An increase in hepatoblastomas was also seen in high dose male mice. Methylphenidate was not mutagenic in the Salmonella assay system, and it is hypothesized that this tumorigenic effect might be due to nongenotoxic effects of the chemical such as an increase in cell proliferation. Increased incidences of neoplasms were not seen in rats. However, there was a notable decrease in mammary gland fibroadenomas in female rats and a marginal decrease in benign pheochromocytomas in male rats. Epidemiology studies of methylphenidate have found no evidence of a carcinogenic effect in humans and like our findings in rats, report a less than expected rate of cancers in patients taking methylphenidate.

[The therapeutic strategy in benign liver tumors: a 20-year experience]. / La strategia terapeutica dei tumori epatici benigni: esperienza di 20 anni.

Therapeutic choices for benign liver tumours have changed over the last 20 years. From 1975 to December 1993, we observed 145 hemangiomas (HMG) (57.2% females-mean age 47.3 years, 42.8% males-mean age 50.4 years): we resected 42 symptomatic hemangiomas: mortality rate was 2.3%. 93 HMG without symptoms were only followed-up: 5 of these increased in size and were resected. 27 symptomatic cases over 50 focal nodular hyperplasia (FNH) were resected, 7 cases were resected and 3 biopsied during laparotomy performed for other pathology. Postoperative mortality was nil. 13 cases were only followed-up after diagnosis by imaging techniques and fine needle biopsy: over a mean period of 23 months. No variations have been recorded. Increases in GGT and ALP were present respectively in 34% and 22% of FNH-cases. Scintigraphic techniques were the most diagnostically accurate (96.2%). All 16 hepatocellular adenomas (HCA) were removed (11 females, 5 males), postoperative mortality was nil: oestrogen administration was present in 36.4% of female cases, histological diagnosis v/s well differentiated hepatocellular carcinoma was difficult in 2 cases, whilst 3 cases had spontaneous rupture. We resected also 8 cases of biliary adenomas in order to determine a precise diagnosis v/s liver metastases, and 4 biliary cystadenomas for their malignant potential. Asymptomatic HMG and FNH for their low tendency to increase, can be only observed, whilst HCA must be fully resected for risk of bleeding and misdiagnosis v/s well differentiated hepatocellular carcinoma.