A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation.

OBJECTIVE: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). BACKGROUND: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. METHODS: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. RESULTS: HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%-24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%-94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. CONCLUSIONS: HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.

The Impact of Neoadjuvant Treatment on Survival in Patients Undergoing Pancreatoduodenectomy With Concomitant Portomesenteric Venous Resection: An International Multicenter Analysis.

OBJECTIVE: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers. SUMMARY OF BACKGROUND DATA: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients. METHODS: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018. RESULTS: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS. CONCLUSION: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT.

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry.

BACKGROUND: The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. METHODS: Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. RESULTS: Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). CONCLUSION: In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

Defining Benchmark Outcomes for Pancreatoduodenectomy With Portomesenteric Venous Resection.

OBJECTIVE: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers. SUMMARY BACKGROUND DATA: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection. METHODS: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998). RESULTS: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%. CONCLUSION: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

A 5-Year Follow-Up of The Benefits of an Exercise Training Program in Liver Recipients Transplanted Due to Familial Amyloidotic Polyneuropathy.

BACKGROUND: Supervised (SE) and home-based exercise (HBE) training regimes are effective on reconditioning patients with familial amyloidotic polyneuropathy (FAP) after liver transplantation, but research of the long-term retention of the benefits attained in patients with FAP has not yet been conducted. PURPOSE: In this 5-year follow-up study, we aimed to determine whether the exercise training gains in body composition, physical activity, and function promoted by a 24-week SE or HBE training regimes are retained in patients with FAP who resume normal activity. METHODOLOGY: Sixteen liver-transplanted patients with FAP were reassessed for body composition (dual X-ray absorptiometry), physical activity (questionnaire), and function (handgrip strength and 6-minute walk test). RESULTS: Total body fat increased with both exercise regimes during follow-up ( P < .05; η2 = 0.432-0.625) as well as femoral neck bone density ( P = .048; η2 = 0.119). However, gains in upper limbs muscle quality during follow-up ( P < .001; η2 = 0.597) were only found in the SE group ( P = .042; η2 = 0.245). Both exercise regimes showed retaining aptitudes in walking capacity ( P < .05; η2 = 0.329-0.460) and muscle mass ( P = .05; η2 = 0.245). Still, none could retain the physical activity levels. CONCLUSION: Long-term resumption of normal activity following a 24-week SE or HBE regime in patients with FAP resulted in loss of exercise induced increases in physical activity but counterweighted postoperative losses in bone mineral density and substantially retained the benefits in walking capacity, muscle mass, and quality, in particular, in the SE group.

A Fair Chance for Everyone: Total Tumor Volume as a Selection Tool in Liver Transplantation for Hepatocellular Carcinoma.

Total tumor volume (TTV) has been proposed as a more accurate means of selecting patients for liver transplantation (LT) due to hepatocellular carcinoma (HCC). We aim to analyze the role of TTV in a population with a short waiting time on list. METHODS: Analysis of a prospective database of patients submitted to LT for HCC between September 1992 and February 2014. TTV, Milan criteria (MC), UCSF (University of California San Francisco), and "Up to Seven" criteria were calculated both with preoperative imaging exams and histological data. RESULTS: The study population consisted of 231 out of patients. Median waiting time on list was 62.5 days. MC included 187 patients, while TTV ≤115 cm3 included 214. Microvascular invasion (HR 2.601, 95% CI 1.529-4.426), MC (HR 1.666, 95% CI 0.990-2.804), UCSF criteria (HR 2.995, 95% CI 1.875-4.875), TTV ≤115 cm3 (HR 2.898, 95% CI 1.398-6.007), and "Up to Seven" criteria (HR 2.139, 95% CI 1.353-3.383) proved to be independent factors for prognosis for disease-free survival. CONCLUSIONS: TTV ≤115 cm3 may be a useful tool to properly identify the best HCC candidates for LT in a population with a short waiting time on list. TTV gives more patients the opportunity of undergoing LT while maintaining similar rates of tumor recurrence and patient survival.

Outcomes of parenchyma-preserving hepatectomy and right hepatectomy for solitary small colorectal liver metastasis: A LiverMetSurvey study.

BACKGROUND: Occasionally, right hepatectomy, rather than parenchyma-preserving hepatectomy, has been performed for solitary small colorectal liver metastasis. The relative oncologic benefits of parenchyma-preserving hepatectomy and right hepatectomy are unclear. This study compared the outcomes of patients with solitary small colorectal liver metastasis in the right liver who underwent parenchyma-preserving hepatectomy and those who underwent right hepatectomy. METHODS: The study population consisted of a multicentric cohort of 21,072 patients operated for colorectal liver metastasis between 2000 and 2015 whose data were collected in the LiverMetSurvey registry. Patients with a pathologically confirmed solitary tumor of less than 30 mm in size in the right liver were included. The short- and long-term outcomes of patients who underwent parenchyma-preserving hepatectomy were compared to those of patients who underwent right hepatectomy. RESULTS: Of the 1,720 patients who were eligible for the study, 1,478 (86%) underwent parenchyma-preserving hepatectomy and 242 (14%) underwent right hepatectomy. The parenchyma-preserving hepatectomy group was associated with lower rates of major complications (3% vs 10%; P < .001) and 90-day mortality (1% vs 3%; P = .008). Liver recurrence occurred similarly in both groups (20% vs 22%; P = .39). The 5-year recurrence-free survival and overall survival rates were similar in both groups. However, in patients with liver-only recurrence, repeat hepatectomy was more frequently performed in the parenchyma-preserving hepatectomy group than in the right hepatectomy group (67% vs 31%; P < .001), and the overall 5-year survival rate was significantly higher in the parenchyma-preserving hepatectomy group than in the right hepatectomy group (55% vs 23%; P < .001). CONCLUSION: Parenchyma-preserving hepatectomy should be considered the standard procedure for solitary small colorectal liver metastasis in the right liver when technically feasible.

Resection of colorectal liver metastases after second-line chemotherapy: is it worthwhile? A LiverMetSurvey analysis of 6415 patients.

PURPOSE: Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line. PATIENTS AND METHODS: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed. RESULTS: After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2. CONCLUSION: CLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy.

The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis.

BACKGROUND: Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM). METHODS: Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed. RESULTS: Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS. DISCUSSION: In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection.

The role of fibrinogen glycation in ATTR: evidence for chaperone activity loss in disease.

Transthyretin amyloidosis (ATTR) belongs to a class of disorders caused by protein misfolding and aggregation. ATTR is a disabling disorder of autosomal dominant trait, where transthyretin (TTR) forms amyloid deposits in different organs, causing dysfunction of the peripheral nervous system. We previously discovered that amyloid fibrils from ATTR patients are glycated by methylglyoxal. Even though no consensus has been reached about the actual role of methylglyoxal-derived advanced glycation end-products in amyloid diseases, evidence collected so far points to a role for protein glycation in conformational abnormalities, being ubiquitously found in amyloid deposits in Alzheimer's disease, dialysis-related amyloidosis and Parkinson's diseases. Human fibrinogen, an extracellular chaperone, was reported to specifically interact with a wide spectrum of stressed proteins and suppress their aggregation, being an interacting protein with TTR. Fibrinogen is differentially glycated in ATTR, leading to its chaperone activity loss. Here we show the existence of a proteostasis imbalance in ATTR linked to fibrinogen glycation by methylglyoxal.

[Thyroid Metastasis as the Initial Presentation of an Asymptomatic Clear Cell Renal Carcinoma]. / Metástase Tiroideia como Manifestação Inicial de um Carcinoma Renal de Células Claras Assintomático.

INTRODUCTION: Clear cell renal carcinoma metastases to the thyroid gland are rare and only diagnosable after an immunohistochemistry analysis of the histological sample. The purpose of this article is to report a case of thyroid metastasis as the initial presentation of a clear cell renal carcinoma. CASE REPORT: Male patient with a solid nodule in the left lobe of the thyroid, 5.3 cm in diameter, suspicious of malignancy, for which a total thyroidectomy with central compartment lymphadenectomy was performed. Histology revealed two clear cell renal carcinoma metastases. After evaluation of the kidney, the patient underwent radical nephrectomy four months later. DISCUSSION: What makes this case interesting is that thyroid metastases as the initial presentation of renal cell carcinoma are rare, but if treated early, a 'double surgical resection' is possible, leading to a 5 year survival rate of 80%.

Introdução: A metastização para a glândula tiroideia de um carcinoma renal de células claras é rara e só diagnosticável após análise imunohistoquímica de uma amostra histológica. O objetivo deste artigo é reportar um caso de metastização tiroideia como primeira manifestação de um carcinoma renal de células claras.Caso Clínico: Doente do sexo masculino com um nódulo sólido no lobo esquerdo da tiróide, com 5,3 cm, suspeito de malignidade, submetido a tiroidectomia total com linfadenectomia do compartimento central. A análise histológica concluiu serem duas metástases de carcinoma renal de células claras. Após estudo dirigido ao rim, o doente foi submetido a nefrectomia radical quatro meses depois. Discussão: O interesse deste caso reside no facto de a metastização para a tiroide como primeira manifestação de carcinoma renal de células claras ser rara mas, se tratada precocemente, permite uma 'dupla resseção cirúrgica' que pode levar a sobrevidas aos cinco anos de 80%.

Long-term Results of Domino Liver Transplantation for Hepatocellular Carcinoma Using the "Double Piggy-back" Technique: A 13-Year Experience.

OBJECTIVES: The aim of this study was to evaluate the long-term outcome of liver transplantation (LT) for hepatocellular carcinoma (HCC) with Domino LT (DLT) using the "Double Piggy-back" technique. BACKGROUND DATA: DLT using livers from familial amyloidotic polyneuropathy (FAP) patients is a well-described technique and useful for expanding the donor pool. However, data on long-term results for HCC are limited, particularly regarding the use of the "Double Piggy-back" technique. METHODS: Between 2001 and 2014, a total of 260 patients undergoing LT for HCC were analyzed from a prospective database. Of those, 114 were submitted to DLT. Comparisons between groups were performed using propensity score matching. RESULTS: Median follow-up was 34 months (1-152). Overall and disease-free 5-year survival rates for the whole population were 58% and 56%, respectively. There were 177 (68%) patients within Milan Criteria and an additional 26 (10%) within University of California San Francisco (UCSF) criteria. Patients older than 50 years were more likely to receive an FAP liver [odds ratio (OR) 1.94, confidence interval (CI) 1.02-3.69]. DLT patients had more major complications (23.7% vs 13.0%, P = 0.025). Only patients undergoing DLT presented with piggy-back syndrome (7% vs 0%, P = 0.001). After adjusting for potential confounders, DLT and cadaveric LT had a similar 5-year survival rate (59% vs 44%, respectively, P = 0.117). Thirteen patients (11.4%) evidenced FAP disease but not before 6 years after DLT. CONCLUSIONS: DLT for HCC is feasible and achieves equivalent results to cadaveric LT. The benefit of expanding the donor pool must be balanced against higher morbidity and a real risk of disease transmission.

Liver Transplantation for Hereditary Transthyretin Amyloidosis: After 20 Years Still the Best Therapeutic Alternative?

BACKGROUND: Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein, we present survival data from the largest available database on transplanted hereditary TTR patients to serve as a base for comparison. METHODS: Liver transplantation was evaluated in a 20-year retrospective analysis of the Familial Amyloidosis Polyneuropathy World Transplant Registry. RESULTS: From April 1990 until December 2010, data were accumulated from 77 liver transplant centers. The Registry contains 1940 patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was 55.3%. Multivariate analysis revealed modified body mass index, early onset of disease (<50 years of age), disease duration before Ltx, and TTR Val30Met versus non-TTR Val30Met mutations as independent significant survival factors. Early-onset patients had an expected mortality rate of 38% that of the late-onset group (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61% that of non-TTR Val30Met patients (P < 0.001). With each year of duration of disease before Ltx, expected mortality increased by 11% (P < 0.001). With each 100-unit increase in modified body mass index at Ltx, the expected mortality decreased to 89% of the expected mortality (P < 0.001). Cardiovascular death was markedly more common than that observed in patients undergoing Ltx for end-stage liver disease. CONCLUSIONS: Long-term survival after Ltx, especially for early-onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing alternative treatments, especially in early-onset TTR Val30Met patients, requires consideration.

Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease.

Transthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progression. Since non-mutated transthyretin also forms amyloid in systemic senile amyloidosis and some mutation bearers are asymptomatic throughout their lives, non-genetic factors must also be involved in transthyretin amyloidosis. We discovered, using a differential proteomics approach, that extracellular chaperones such as fibrinogen, clusterin, haptoglobin, alpha-1-anti-trypsin and 2-macroglobulin are overrepresented in transthyretin amyloidosis. Our data shows that a complex network of extracellular chaperones are over represented in human plasma and we speculate that they act synergistically to cope with amyloid prone proteins. Proteostasis may thus be as important as point mutations in transthyretin amyloidosis.

Role of neoadjuvant chemotherapy in resectable synchronous colorectal liver metastasis; An international multi-center data analysis using LiverMetSurvey.

BACKGROUND AND OBJECTIVES: The use of neo-adjuvant chemotherapy in resectable synchronous liver metastasis is ill defined. The aim of this study was to evaluate neo-adjuvant chemotherapy on outcomes following liver resection for synchronous CLM. METHODS: An analysis of a multi-centric cohort from the LiverMetSurvey International Registry, who had undergone curative resections for synchronous CLM was undertaken. Patients who received neo-adjuvant chemotherapy prior to liver surgery (group NAS; n = 693) were compared with those treated by surgery alone (group SG; n = 608). Baseline clinicopathological variables were compared. Predictors of overall (OS) and disease free survival (DFS) were subsequently identified. RESULTS: Clinicopathological comparison of the groups revealed a greater proportion of solitary metastasis in the SG compared to the NAS group (58.8% versus 38.4%; P < 0.001) therefore a separate analysis of solitary versus multi-centric analysis was performed. N-stage (> N1), number of metastasis (> 3), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer OS, while N-stage (> N1), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer DFS. Neo-adjuvant chemotherapy did not independently affect outcome. CONCLUSION: We present an analysis of a large multi-center series of the role of neo-adjuvant chemotherapy in resectable CLM and demonstrate no survival advantage in this setting.

Hepatic Actinomycosis.

Actinomycosis is a rare disorder caused by an anaerobic gram-positive bacillus (Actinomyces), predominantly by the Actinomyces israelii species. Only 20% of cases show an abdominal manifestation, the appendix and ileocecal valve being the most frequent locations. Definitive diagnosis is based on microbiological cultures, microscopy or macroscopy examination. Nevertheless, histological examination of the percutaneous biopsy and blood microbiological cultures are rarely positives. Preoperative diagnosis is hampered by the lack of specific clinical and imaging manifestations, which often mimic malignancy. The rate of preoperative diagnosis is less than 10%, however, the outcome is excellent, with a low mortality rate. The authors describe the case of a patient who was diagnosed with primary hepatic actinomycosis only by a histological examination of the surgical specimen of left hepatectomy extended to segments V and VIII, for suspected malignant lesion. This case demonstrates the difficulties in diagnosing hepatic actinomycosis.

A actinomicose é uma entidade clínica rara, causada por uma bactéria anaeróbia gram-positiva (Actinomyces), predominantemente da espécie Actinomyces israelii. Apenas em 20% dos casos apresenta manifestação abdominal, sendo o apêndice e a válvula ileocecal as localizações mais frequentes. Os autores descrevem o caso de um doente em que foi feito o diagnóstico de actinomicose hepática primária apenas pelo exame histológico da peça cirúrgica de hepatectomia esquerda alargada aos segmentos V e VIII, por suspeita de lesão maligna. Este caso demonstra a dificuldade diagnóstica da actinomicose hepática. O diagnóstico pré-operatório é dificultado pela falta de manifestações clínicas e imagiológicas específicas, muitas vezes simulando doença maligna. Para além disso, as culturas e o exame histológico de biópsia percutânea raramente são positivos. A taxa de diagnóstico pré-operatório é inferior a 10%, contudo o prognóstico é bom, apresentando uma taxa de mortalidade de cerca de 7,6%.

Management of biliary cystic tumors: a multi-institutional analysis of a rare liver tumor.

OBJECTIVE: To characterize clinical and radiological features associated with biliary cystic tumors (BCTs) of the liver, and to define recurrence-free and overall survival. BACKGROUND: Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are rare tumors that arise in the liver. METHODS: Between 1984 and 2013, 248 patients who underwent surgical resection of BCA or BCAC were identified. Clinical and outcome data were analyzed. RESULTS: Median total bilirubin, CA19-9, and carcinoembryonic antigen (CEA) levels were 0.6 mg/dL, 15.0 U/mL, and 2.7 ng/mL, respectively. Preoperative imaging included computed tomography only (62.5%), magnetic resonance imaging only (6.9%), or CT + MRI (18.5%). Features on cross-sectional imaging included multiloculation (56.9%), mural nodularity (16.5%), and biliary ductal dilatation (17.7%). The presence of these factors did not reliably predict BCAC versus BCA (sensitivity, 81%; specificity, 21%). Median biliary cyst size was 10.0 cm (interquartile range, 7-13 cm). Operative interventions included unroofing/partial excision of the lesion (14.1%), less than hemihepatectomy (48.8%), or hemi-/extended hepatectomy (36.3%). On pathology most lesions were BCA (89.1%), whereas 27 (10.9%) were BCAC. At last follow-up, there were 46 (18.3%) recurrences; 2 patients who initially had BCA recurred with BCAC. Median overall survival was 18.1 years; 1-year, 3-year, and 5-year survival was 95.0%, 86.8%, and 84.2%, respectively. Long-term outcomes were associated with BCAC versus BCA, as well as the presence of spindle cell/ovarian stroma (both P < 0.05). CONCLUSIONS: Among patients undergoing surgery for BCT, associated malignancy was uncommon (10%) and no preoperative findings reliably predicted underlying BCAC. After excision of BCA, long-term outcomes were good; however, patients with BCAC had a worse long-term prognosis.