Giant hepatic hemangioma in a patient with cirrhosis: challenging to manage.

Giant hepatic hemangiomas are occasional in patients with cirrhosis. It remains a challenge to decide on the need for treatment and choose the most appropriate intervention. A 62-year-old woman was recently diagnosed with cirrhosis and complained of upper abdominal fullness, reduction in oral food intake, and weight loss of 6 kg over the last three years. Upper digestive endoscopy evidenced thin-caliber esophageal varices and significant extrinsic compression of the lesser gastric curvature. Abdominal computed tomography revealed an exophytic tumor in the left hepatic lobe, measuring 11.5 cm, which had progressive centripetal contrast enhancement from the arterial phase, compatible with hepatic hemangioma. Serum tumor markers were negative, and her liver function was unimpaired. The patient underwent surgical resection (non-anatomical hepatectomy of segments II and III) which had no immediate complications, and the histopathological evaluation confirmed cavernous hepatic hemangioma. Two weeks later, she was admitted to the emergency room with jaundice, signs of hepatic encephalopathy, and moderate ascites, and was further diagnosed with secondary bacterial peritonitis. As no perforations, abscesses, or fistulas were observed on subsequent imaging tests, clinical management was successfully carried out. This case highlights that giant hepatic hemangiomas may be symptomatic and warrant treatment. In the setting of cirrhosis and portal hypertension, physicians should be aware of the risk of hepatic decompensation following surgical resection, even in patients with Child-Pugh class A.

15-Year progression to liver cancer in the lack of treatment for lysosomal acid lipase deficiency: A case report.

RATIONALE: Lysosomal acid lipase deficiency (LAL-D) is a poorly diagnosed genetic disorder characterized by the accumulation of cholesteryl esters and triglycerides in many tissues, leading to dyslipidemia and cardiovascular complications. In the liver, deposits are found within hepatocytes and Kupffer cells, generating microvesicular steatosis, progressive fibrosis, and cirrhosis. Sebelipase alfa is the target therapy which can improve laboratory changes and reduce the progression of liver damage, but this is not yet widely available. PATIENT CONCERNS: We are reporting a 15-year follow-up of a Brazilian man who was diagnosed with cirrhosis at age 43 and with LAL-D at age 53, but he has never been treated with sebelipase alfa for economic reasons. During the coronavirus disease 2019 (COVID-19) pandemic, he lost follow-up and missed three 6-month ultrasound exams for liver cancer screening. DIAGNOSIS: At age 58, a remarkable deterioration in liver function was observed and he was diagnosed with hepatocellular carcinoma (HCC) outside the Milan Criteria (two nodules measuring 48mm and 25mm). Three other individuals with LAL-D and progression to liver cancer have been reported so far and none of them underwent enzyme replacement therapy: an 11-year-old girl with HCC, a 51-year-old male with cholangiocarcinoma, and a 21-year-old male with hepatocellular-cholangiocarcinoma. The latter had the same mutation in the gene LIPA as our patient, but a relationship between this variant and malignancies has not yet been established. LESSONS: We emphasize how important is to treat LAL-D patients after diagnosis in order to avoid worsening liver function and progression to neoplasms. Untreated individuals should be considered at a higher risk but the most appropriate liver cancer screening program for this subgroup is still unknown.

Hepatobiliary phases in magnetic resonance imaging using liver-specific contrast for focal lesions in clinical practice.

BACKGROUND: Challenging lesions, difficult to diagnose through non-invasive methods, constitute an important emotional burden for each patient regarding a still uncertain diagnosis (malignant x benign). In addition, from a therapeutic and prognostic point of view, delay in a definitive diagnosis can lead to worse outcomes. One of the main innovative trends currently is the use of molecular and functional methods to diagnosis. Numerous liver-specific contrast agents have been developed and studied in recent years to improve the performance of liver magnetic resonance imaging (MRI). More recently, one of the contrast agents introduced in clinical practice is gadoxetic acid (gadoxetate disodium). AIM: To demonstrate the value of the hepatobiliary phases using gadoxetic acid in MRI for the characterization of focal liver lesions (FLL) in clinical practice. METHODS: Overall, 302 Lesions were studied in 136 patients who underwent MRI exams using gadoxetic acid for the assessment of FLL. Two radiologists independently reviewed the MRI exams using four stages, and categorized them on a 6-point scale, from 0 (lesion not detected) to 5 (definitely malignant). The stages were: stage 1- images without contrast, stage 2- addition of dynamic phases after contrast (analogous to usual extracellular contrasts), stage 3- addition of hepatobiliary phase after 10 min (HBP 10'), stage 4- hepatobiliary phase after 20 min (HBP 20') in addition to stage 2. RESULTS: The interobserver agreement was high (weighted Kappa coefficient: 0.81- 1) at all stages in the characterization of benign and malignant FLL. The diagnostic weighted accuracy (Az) was 0.80 in stage 1 and was increased to 0.90 in stage 2. Addition of the hepatobiliary phase increased Az to 0.98 in stage 3, which was also 0.98 in stage 4. CONCLUSION: The hepatobiliary sequences improve diagnostic accuracy. With growing potential in the era of precision medicine, the improvement and dissemination of the method among medical specialties can bring benefits in the management of patients with FLL that are difficult to diagnose.

Validation of New York/California Score in the Preoperative Period of Liver Transplant for Hepatocellular Carcinoma at University of Campinas's Hospital.

Liver transplant is the main treatment for hepatocellular carcinoma and there is currently an important demand from patients waiting in transplant queues. Thus, it is extremely important to improve the criteria for selecting patients who will undergo transplant to mitigate graft loss and reduce cases of recurrence. Thus, it becomes necessary to use models, such as the New York/California (NYCA), that include alpha fetoprotein as a marker of recurrence and prognosis. The aim of this study was to assess whether the NYCA score correlated with the presence of tumor recurrence after transplant in patients undergoing orthotopic liver transplant at the Clinics Hospital of the University of Campinas. We had 214 patients undergoing liver transplant who met the inclusion Milan criteria. The age of the patients ranged from 34 to 77 years, with a median age of 61 years. The mean waiting time on the transplant list was 6.12 months. After calculating the NYCA score, it was possible to stratify 13 patients (6.1%) as high risk, 64 patients (29.9%) as medium risk, and 137 patients (64%) as low risk. Patients with recurrence had higher scores with a mean of 4 points in relapse and 2 points in the absence of relapse (P = .0011). Patients with recurrence had statistically higher high- and medium-risk scores (P = .0010). Therefore, the NYCA score was higher in patients with recurrence. Therefore, in this study, our findings suggest the possibility of using the NYCA score as an aid to detect patients with a higher risk of tumor recurrence.

Validation of Metroticket Score in the Preoperative Period of Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer in the world, and liver transplant (LT) is a good therapeutic option in selected cases because it treats the neoplasm and the underlying disease. Recurrence after LT is usually aggressive and has low survival; thus, an adequate selection of recipients is ideal. The new models aim to assess the individual risk of HCC recurrence in patients undergoing LT and to improve post-LT survival. In this study, our aim was to assess the applicability of the "Metroticket" score, correlating it with our rates of recurrence and survival after LT. Overall survival at 5 years in our study differed from that in Metroticket 2.0 because that study did not consider only recurrence as the cause of death; our study evaluated only patients with recurrence, so we were able to validate the score as a predictor of greater tumor aggressiveness after LT.

Association of acidosis with coagulopathy and transfusion requirements in liver transplantation.

The relationship between acidosis and coagulopathy has long been described in vitro and in trauma patients, but not yet in orthotopic liver transplantation (OLT). The association of metabolic acidosis with coagulopathy and with transfusion requirements was evaluated in patients submitted to OLT. Changes in acid-base and coagulation parameters were analyzed by repeated measures. Regression analyses [adjusted for sex, age, model for end stage liver disease (MELD) score, and baseline values of hemoglobin, fibrinogen, international normalized ratio, platelets] determined the association of acid-base parameters with coagulation markers and transfusion requirement. We included 95 patients, 66% were male, 49.5% of the patients had hepatocellular carcinoma and the mean MELD score was 20.4 (SD 8.9). The values of all the coagulation and acid-base parameters significantly changed during OLT, particularly in the reperfusion phase. After adjustments for baseline parameters, the decrease in pH and base excess (BE) values were associated with a decrease in fibrinogen levels (mean decrease of fibrinogen level = 14.88 mg/dL per 0.1 unit reduction of pH values and 3.6 mg/dL per 1 mmol/L reduction of BE levels) and an increase in red blood cells transfusion (2.16 units of RBC per 0.1 unit reduction of pH and 0.38 units of RBC per 1 mmol/L reduction of BE levels). Among multiple factors potentially associated with adverse outcomes, decreasing pH levels were independently associated with the length of hospitalization but not with in-hospital mortality. Metabolic acidosis is independently associated with decreased fibrinogen levels and increased intraoperative transfusion requirement during OLT. Awareness of that association may improve treatment strategies to reduce intraoperative bleeding risk in OLT.

Liver transplantation for hepatocellular carcinoma: impact of expansion criteria in a multicenter cohort study from a high waitlist mortality region.

This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).

Diarrhea: a missed D in the 4D glucagonoma syndrome.

Glucagonoma is a rare and slow-growing pancreatic tumor that usually manifests as glucagonoma syndrome. It is mainly characterized by a typical Dermatosis named necrolytic migratory erythema (NME), Diabetes and glucagon oversecretion. Deep vein thrombosis and Depression complete this set. We report the case of an advanced glucagonoma with liver spread, where all these 4D symptoms occurred but a chronic secretory Diarrhea was the most relevant feature. A 65-year-old man was referred to our center to investigate multiple hepatic nodules evidenced by abdominal tomography. He had a recent diagnosis of diabetes and complained of significant weight loss (25 kg), crusted skin lesions and episodes of a large amount of liquid diarrhea during the past 6 months. On admission, there were erythematous plaques and crusted erosions on his face, back and limbs, plus angular cheilitis and atrophic glossitis. The typical skin manifestation promptly led dermatologists to suspect glucagonoma as the source of our patient's symptoms. A contrast-enhanced abdominal computed tomography showed a hypervascularized pancreatic lesion and multiple hepatic nodules also hypervascularized in the arterial phase. Despite initial improvement of diarrhea after subcutaneous octreotide, the patient's impaired nutritional status limited other therapeutic approaches and he died of respiratory failure due to sepsis. His high levels of serum glucagon were not yet available so we performed an autopsy, confirming the diagnosis of metastatic glucagonoma with NME on histology. Chronic diarrhea is not a common feature in glucagonoma syndrome; however, its severity can lead to serious nutritional impairment and set a poor outcome.

Microvascular invasion in hepatocellular carcinoma: is it predictable with quantitative computed tomography parameters?

OBJECTIVE: To investigate whether quantitative computed tomography (CT) measurements can predict microvascular invasion (MVI) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a retrospective analysis of 200 cases of surgically proven HCCs in 125 consecutive patients evaluated between March 2010 and November 2017. We quantitatively measured regions of interest in lesions and adjacent areas of the liver on unenhanced CT scans, as well as in the arterial, portal venous, and equilibrium phases on contrast-enhanced CT scans. Enhancement profiles were analyzed and compared with histopathological references of MVI. Univariate and multivariate logistic regression analyses were used in order to evaluate CT parameters as potential predictors of MVI. RESULTS: Of the 200 HCCs, 77 (38.5%) showed evidence of MVI on histopathological analysis. There was no statistical difference between HCCs with MVI and those without, in terms of the percentage attenuation ratio in the portal venous phase (114.7 vs. 115.8) and equilibrium phase (126.7 vs. 128.2), as well as in terms of the relative washout ratio, also in the portal venous and equilibrium phases (15.0 vs. 8.2 and 31.4 vs. 26.3, respectively). CONCLUSION: Quantitative dynamic CT parameters measured in the preoperative period do not appear to correlate with MVI in HCC.

OBJETIVO: O objetivo deste estudo foi investigar se parâmetros quantitativos da tomografia computadorizada (TC) podem predizer invasão microvascular (IMV) no carcinoma hepatocelular (CHC). MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, 200 CHCs comprovados de 125 pacientes submetidos consecutivamente a transplante ou ressecção hepática entre março/2010 e novembro/2017. Foram realizadas medidas quantitativas da densidade das lesões e do parênquima hepático adjacente pré-contraste e nas fases arterial, portal e de equilíbrio das TCs. Parâmetros de impregnação foram comparados com a presença de IMV nos laudos anatomopatológicos. Regressões logísticas univariadas e multivariadas foram utilizadas para avaliar os parâmetros da TC como potenciais preditores de IMV. RESULTADOS: Dos 200 CHCs, 77 (38,5%) tinham IMV no anatomopatológico. Não houve diferença estatística na razão de atenuação entre CHCs com IMV e os sem IMV na fase portal (114,7 para IMV positiva e 115,8 para IMV negativa) ou de equilíbrio (126,7 para IMV positiva e 128,2 para IMV negativa), nem na razão de washout relativa nas fases portal e de equilíbrio (15,0 para IMV positiva e 8,2 para IMV negativa na fase portal, e 31,4 para IMV positiva e 26,3 para IMV negativa na fase de equilíbrio). CONCLUSÃO: Não houve relação entre os parâmetros quantitativos da TC pré-operatória e IMV dos CHCs.

Liver transplantation for hepatocellular carcinoma: evaluation of the alpha-fetoprotein model in a multicenter cohort from Latin America.

BACKGROUND & AIMS: The French alpha-fetoprotein (AFP) model has recently shown superior results compared to Milan criteria (MC) for prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin-American cohort. METHODS: Three hundred twenty-seven patients with HCC were included from a total of 2018 patients transplanted at 15 centres. Serum AFP and imaging data were both recorded at listing. Predictability was assessed by the Net Reclassification Improvement (NRI) method. RESULTS: Overall, 82 and 79% of the patients were within MC and the AFP model respectively. NRI showed a superior predictability of the AFP model against MC. Patients with an AFP score >2 points had higher risk of recurrence at 5 years Hazard Ratio (HR) of 3.15 (P = 0.0001) and lower patient survival (HR = 1.51; P = 0.03). Among patients exceeding MC, a score ≤2 points identified a subgroup of patients with lower recurrence (5% vs 42%; P = 0.013) and higher survival rates (84% vs 45%; P = 0.038). In cases treated with bridging procedures, following restaging, a score >2 points identified a higher recurrence (HR 2.2, P = 0.12) and lower survival rate (HR 2.25, P = 0.03). A comparative analysis between HBV and non-HBV patients showed that the AFP model performed better in non-HBV patients. CONCLUSIONS: The AFP model could be useful in Latin-American countries to better select patients for LT in subgroups presenting with extended criteria. However, particular attention should be focused on patients with HBV.