Prenatal diagnosis of posterior mediastinal lymphangioma by two- and three-dimensional ultrasonography

Lymphangioma is a rare benign tumor characterized by proliferating lymph vessels and composed of large cyst spaces with endothelium-lined channels of varying dimensions. The incidence of lymphangioma is approximately one in 6000 pregnancies. Less than 1 % of lymphangiomas are purely mediastinal. The great majority of cases are of cystic lymphangioma, but very rarely there is a mixed lesion consisting of multiple cysts of dilated capillary and lymph vessels. We report a case of posterior mediastinal lymphangioma diagnosed at 28 weeks` gestation, in which three-dimensional ultrasonography was helpful in determining the precise location of the tumor. A Cesarean section was performed at 39 weeks and the tumor was resected on the 5(th) day postdelivery; histological examination revealed a mixed cystic lymphangioma. Copyright (C) 2008 ISUOG. Published by John Wiley & Sons, Ltd.

Nodules Less Than 20 mm and Vascular Invasion are Predictors of Survival in Small Hepatocellular Carcinoma

Background: The aims of this study were to analyze the overall survival of patients with cirrhosis and small hepatocellular carcinoma (HCC) and identify independent pretreatment predictors of survival in Brazil. Methods: Between 1998 and 2003, 74 patients with cirrhosis and small HCC were evaluated. Predictors of survival were identified using the Kaplan-Meier survival curves and the Cox model. Results: The overall survival rates were 80%, 41%, and 17% at 12, 36, and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 mo, range: I to 86 mo) for the entire group. Univariate analysis showed that model for endstage liver disease (MELD) score (P = 0.016), Child-Pugh classification (P = 0.007), alpha-fetoprotein level (P = 0.006), number of nodules (P = 0.041), tumor diameter (P = 0.009), and vascular invasion (P < 0.0001) were significant predictors Of Survival. Cox regression analysis identified vascular invasion (relative risk = 14.60, confidence interval 95% = 3.3-64.56, P < 0.001) and tumor size > 20 mm (relative risk = 2.14, confidence interval 95% = 1.07-4.2, P = 0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival. Conclusions: Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors Of LIP to 20 mm diameter is related to increased survival.

Prevention and reversion of nonalcoholic steatohepatitis in ob/ob mice by S-nitroso-N-acetylcysteine treatment

Objective: To evaluate the role oral administration of S-nitroso-N-acetylcysteine (SNAC), a NO donor drug, in the prevention and reversion of NASH in two different animal models. Methods: NASH was induced in male ob/ob mice by methionine-choline deficient (MCD) and high-fat (H) diets. Two animal groups received or not SNAC orally for four weeks since the beginning of the treatment. Two other groups were submitted to MCD and H diets for 60 days receiving SNAC only from the 31(st) to the 60(th) day. Results: SNAC administration inhibited the development of NASH in all groups, leading to a marked decrease in macro and microvacuolar steatosis and in hepatic lipid peroxidation in the MCD group. SNAC treatment reversed the development of NASH in animals treated for 60 days with MCD or H diets, which received SNAC only from the 31(st) to the 60(th) day. Conclusions: Oral administration of SNAC markedly inhibited and reversed NASH induced by MCD and H diets in ob/ob mice.

Peritumoural, but not intratumoural, lymphatic vessel density and invasion correlate with colorectal carcinoma poor-outcome markers

To evaluate whether lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) are useful markers of worse outcome in colorectal carcinoma and if LVD and LVI correlate to the classical clinical-pathological parameters, we analysed 120 cases of colorectal carcinomas selected from the files of Division of Pathology, Hospital das Clinicas, Sao Paulo University, Brazil. Assessment of LVD and LVI was performed by immunohistochemical detection of lymphatic vessels, using the monoclonal antibody D2-40. Higher LVD was found in the intratumoural area, when comparing with normal and peritumoural areas (p < 0.001). However, peritumoural LVD, but not intratumoural, correlated with both colonic-wall-invasion depth (p=0.037) and liver metastasis (p=0.012). Remarkably, LVI was found associated with local invasion (p=0.016), nodal metastasis (p=0.022) and hepatic metastasis (p < 0.001). Peritumoural LVD and LVI are directly related to histopathological variables indicative of poor outcome such as lymph-node status and liver metastasis.

Decreased immunoexpression of survivin could be a potential marker in human non-alcoholic fatty liver disease progression?

Background/aim Regulation of apoptosis in non-alcoholic fatty liver disease (NAFLD) has been a theme of growing debate. Although no other study assessed the role of survivin in NAFLD, its expression has been reported in hepatic carcinogenesis because of other aetiological factors with relevant discrepancies. The aim of this study was to assess the pattern of survivin immunoexpression by tissue microarray along the whole spectrum of NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocelular carcinoma (HCC). Methods Liver biopsies from 56 patients with NAFLD were evaluated: 18 with steatosis, 21 non-cirrhotic NASH, 10 NASH-related cirrhosis, seven NASH-related HCC, as compared with 71 HCC related to other causes and with 12 normal livers. Results Survivin immunoexpression in NAFLD was restricted to cytoplasm and was found to be progressively lower in advanced stages, including cirrhosis and HCC: steatosis vs NASH-related cirrhosis (P=0.0243); steatosis vs NASH-related HCC (P=0.0010); NASH vs NASH-related cirrhosis (P=0.0318); and NASH vs NASH-related HCC (P=0.0007), thus suggesting a deregulation of apoptosis from NAFLD towards HCC. Interestingly, survivin immunoreactivity in NASH-related HCC was also found to be significantly lower than in HCC related to other causes (P < 0.05). Remarkably, nuclear staining for survivin was not detected in any case of NAFLD, contrasting to its presence in all other cases of HCC. Conclusions Survivin immunoexpression in NASH-related HCC is herein originally found substantially different than in HCC related to other causes, thus requiring further studies to elucidate the role of survivin in human NAFLD progression.

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals

Background: Many chronic liver diseases lead to progressive hepatic fibrosis, a condition that can ultimately result in loss of organ function and severe portal hypertension necessitating hepatic transplantation. Within the last few decades, studies have been conducted to demonstrate the possibility of drug modulation of hepatic fibrogenesis. Regarding biliary obstruction, it has been suggested that administration of corticosteroids could promote better late outcomes for children with biliary atresia submitted to Kasai`s portoenterostomy. Models used to test potential antifibrogenic drugs such as pentoxifylline (PTX) have not included growing animals. Methods: In this experimental study, 119 young rats (21st or 22nd days) were submitted to laparotomy and common bile duct ligation (CBDL) or to sham surgery (SHAM). Animals were allocated into 5 groups, according to surgical procedure, and administered the following solutions: (1) CBDL + distilled water, (2) SHAM + distilled water, (3) CBDL + PTX, (4) CBDL + prednisolone (PRED), and (5) CBDL + PTX + PRED (PTX + PRED). Each group was further divided into 2 subgroups according to the length of the experiment (15 or 30 days). At the end of the defined period, animals were weighed, and a hepatic fragment was collected from each one for analyses. Results: The PTX animals exhibited increased weight gain compared to animals in the PRED or PTX + PRED groups. Animals from the 3 therapeutic groups (PTX, PRED, and PTX + PRED) showed diminished collagen-filled area in portal spaces. Total portal space area was increased in the PTX group. Conclusions: Hepatic fibrosis induced by bile duct ligation in young rats could be modulated by pharmacologic interventions. Administration of PTX or PRED, or the combination of both, resulted in diminished collagen-filled areas in portal spaces. (C) 2009 Elsevier Inc. All rights reserved.

Clinical usefulness of B-type natriuretic peptide in the diagnosis of pleural effusions due to heart failure

Background and objective: Light`s criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light`s criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B-type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions. Methods: Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF. Results: The areas under the ROC curves were 0.987 (95% CI 0.93-0.998) for plasma BNP and 0.949 (95% CI 0.874-0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut-off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%). Conclusions: In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause.

Living Related Donor Liver Transplantation in Children

Objective. The objective of this study was to report our experience with pediatric orthotopic liver transplantation (OLT) with living related donors. Methods. We performed a retrospective chart analysis of 121 living related donor liver transplantations (LRDLT) from June 1998 to June 2010. Results. Indications were biliary atresia (BA; n = 81), primary sclerosing cholangitis (n = 5), alpha-1 antitrypsin deficiency (n = 4); cholestasis (n = 9), fulminant hepatic failure (n = 8), autoimmune hepatitis (n = 2), Alagille syndrome (n = 4), hepatoblastoma (n = 3), tyrosinemia (n = 2), and congenital hepatic fibrosis (n = 3). The age of the recipients ranged from 7-174 months (median, 22) and the weights ranged from 6-58 kg (median, 10). Forty-nine children (40.5%) weighed <= 10 kg. The grafts included the left lateral segment (n = 108), the left lobe (n = 12), and the right lobe (n = 1). The donors included 71 mothers, 45 fathers, 2 uncles, 1 grandmother, 1 grandfather, and 1 sister with a median age of 29 years (range, 16-53 ys) and a median weight of 68 kg (range, 47-106). Sixteen patients (12.9%) required retransplantation, most commonly due to hepatic artery thrombosis (HAT; n = 13; 10.7%). The other complications were biliary stenosis (n = 25; 20.6%), portal vein thrombosis (PVT; n = 11; 9.1%), portal vein stenosis (n = 5; 4.1%), hepatic vein stenosis (n = 6; 4.9%), and lymphoproliferative disorders (n = 8; 6.6%). The ultimate survival rate of recipients was 90.3% after 1 year and 75.8% after 3 years. Causes of early death within 1 month were HAT (n = 6), PVT (n = 2), severe graft dysfunction (n = 1), sepsis (n = 1), and intraoperative death in children with acute liver failure (n = 2). Causes of late deaths included lymphoproliferative disease (n = 3), chronic rejection (n = 2), biliary complications (n = 3), and recurrent disease (n = 3; hepatoblastoma and primary sclerosing cholangitis). Conclusions. Despite the heightened possibility of complications (mainly vascular), LRDLT represented a good alternative to transplantation from cadaveric donors in pediatric populations. It was associated with a high survival ratio.

Orthotopic Liver Transplantation in Biliary Atresia: A Single-Center Experience

Introduction. Biliary atresia (BA) is the leading indication for orthotopic liver transplantation (OLT) among children. However, there are technical difficulties, including the limited dimensions of anatomical structures, hypoplasia and/or thrombosis of the portal vein and previous portoenterostomy procedures. Objective. The objective of this study was to present our experience of 239 children with BA who underwent OLT between September 1989 and June 2010 compared with OLT performed for other causes. Methods. We performed a retrospective analysis of patient charts and analysis of complications and survival. Results. BA was the most common indication for OLT (207/409; 50.6%). The median age of subjects was 26 months (range, 7-192). Their median weight was 11 kg (range, 5-63) with 110 children (53.1%) weighing <= 10 kg. We performed 126 transplantations from cadaveric donors (60.8%) and 81 from living-related donors (LRD) (39.2%). Retransplantation was required for 31 recipients (14.9%), primarily due to hepatic artery thrombosis (HAT; 64.5%). Other complications included the following: portal vein thrombosis (PVT; 13.0%), biliary stenosis and/or fistula (22.2%), bowel perforation (7.0%), and posttransplantation lymphoproliferative disorder (PTLD; 5.3%). Among the cases of OLT for other causes, the median age of recipients was 81 months (range, 11-17 years), which was higher than that for children with BA. Retransplantation was required in 3.5% of these patients (P < .05), mostly due to HAT. The incidences of PVT, bowel perforation, and PTLD were significantly lower (P < .05). There was no significant difference between biliary complications in the 2 groups. The overall survival rates at 1 versus 5 years were 79.7% versus 68.1% for BA, and 81.2% versus 75.7% for other causes, respectively. Conclusions. Children who undergo OLT for BA are younger than those engrafted for other causes, displaying a higher risk of complications and retransplantations.

Rex Shunt for Acute Portal Vein Thrombosis After Pediatric Liver Transplantation in Children With Biliary Atresia

Background/Purpose. Posttransplantation portal vein thrombosis (PVT) can have severe health consequences, and portal hypertension and other consequences of the long-term privation of portal inflow to the graft may be hazardous, especially in young children. The Rex shunt has been used successfully to treat PVT patients since 1998. In 2007, we started to perform this surgery in patients with idiopathic PVT and late posttransplantation PVT. Herein we have reported our experience with this technique in acute posttransplantation PVT. Methods. Three patients of ages 12, 15, and 18 months underwent cadaveric (n = 1) or living donor (n = 2) orthotopic liver transplantation (OLT). All patients had biliary atresia with portal vein hypoplasia; they developed acute PVT on the first postoperative day. They underwent a mesenteric-portal surgical shunt (Rex shunt) using a left internal jugular vein autograft (n = 2) or cadaveric iliac vein graft (n = 1) on the first postoperative day. Results. The 8-month follow-up has confirmed shunt patency by postoperative Doppler ultrasound. There have been no biliary complications to date. Conclusions. The mesenteric-portal shunt (Rex shunt) using an autograft of the left internal jugular or a cadaveric vein graft should be considered for children with acute PVT after OLT. These children usually have small portal veins; reanastomosis is often unsuccessful. In addition, this technique has the advantage to avoid manipulation of the hepatic hilum and biliary anastomosis. Although this study was based on a limited experience, we concluded that this technique is feasible, with great benefits to and low risks for these patients.

Milia en plaque

Milia en plaque is a rare type of primary milia. Issues related to esthetics and differential diagnoses represent a concern to patients and a challenge for physicians. In this paper, a case of milia en plaque is reported and a review of the literature is described.

Multiple Clinical Presentations of Lymphoproliferative Disorders in Pediatric Liver Transplant Recipients: A Single-Center Experience

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation that has been linked to Epstein-Barr virus (EBV) infection. The aim of this article was to describe a single-center experience with the multiplicity of clinical presentations of PTLD. Among 350 liver transplantations performed in 303 children, 13 survivor children displayed a histological diagnosis of PTLD (13/242 survivors; 5.4%). The age at diagnosis ranged from 12 to 258 months (median, 47), and the time from transplantation ranged from 1 to 84 months (median, 13). Ten of these children (76.9%) were EBV-naive prior to transplantation. Fever was present in all cases. The clinical signs at presentation were anemia (92.3%), diarrhea and vomiting (69.2%), recurrent upper airway infections (38.4%), Waldeyer ring lymphoid tissue hypertrophy (23.0%), abdominal mass lesions (30.7%), massive cervical and mediastinal adenopathy (15.3%), or gastrointestinal and respiratory symptoms (30.7%). One child developed fulminant hepatic allograft failure secondary to graft involvement by PTLD. Polymorphic PTLD was diagnosed in 6 patients; 7 had the diagnosis of lymphoma. Treatment consisted of stopping immunosuppression as well as starting intravenous gancyclovir and anti-CD20 monoclonal antibody therapy. The mortality rate was 53.8%. The clinical presentation of PTLD varied from fever of unknown origin to fulminant hepatic failure. The other symptoms that may be linked to the diagnosis of PTLD are pancytopenia, tonsil and adenoid hypertrophy, cervical or mediastinal lymph node enlargement, as well as abdominal masses. Despite numerous advances, the optimal treatment approach for PTLD is not completely known and the mortality rate is still high.

The Incapacity of the Surgeon to Identify NASH in Bariatric Surgery Makes Biopsy Mandatory

Nonalcoholic steatohepatitis (NASH) is a morbid condition highly related to obesity. It is unclear if the macroscopic liver appearance correlates with the histopathologic findings. The goal of this prospective study was to determine the relationship between the intraoperative liver appearance and the histopathologic diagnosis of NASH in morbidly obese subjects undergoing bariatric surgery. We also aimed to determine variables that could predict NASH preoperatively. Consecutive 51 subjects undergoing bariatric surgery without evidence of other liver disease underwent intraoperative liver biopsy. An intraoperative liver visual (macroscopic and tactile examination) was recorded. The liver aspect was compared with the liver histologic findings. Histological assessment was categorized into two groups: NASH and non-NASH (including normal histology and simple steatosis). Clinical and biochemical parameters were obtained from the patient databases and were compared between groups to identify preoperatively predictive factors of NASH. From 51 patients, only one presented totally normal histology. Forty-three (86.2%) presented simple steatosis, and seven (13.7%) were classified as NASH. Clinical parameters were not different between groups. At biochemical analysis, only VLDL cholesterol level was significantly higher in the NASH group (p = 0.037) but yet within the normal range. Association between macroscopic liver appearance and the presence of histological NASH is poor (sensitivity of 14%, specificity of 56%, positive predictive value of 5%, and negative predictive value of 80%). No predictor of NASH was found. Surgeons` evaluation could not identify NASH individuals. Routine liver biopsy during bariatric operations is mandatory to differentiate NASH and nonalcoholic fatty liver disease.

Lymphadenectomy in Colorectal Cancer Liver Metastases Resection: Incidence of Hilar Limph Nodes Micrometastasis

Background: Liver resection is considered the best treatment for metastatic colorectal cancer. Several prognostic factors have been investigated, and many studies have shown that hepatic hilum lymph nodes involvement has a negative impact on prognosis. The present study evaluated the frequency of microscopic involvement of hilar lymph nodes, through systematic lymphadenectomy and analysis of micrometastases in patients undergoing hepatectomy due to colorectal metastasis. Methods: A total of 28 patients underwent hepatic resection with hilar lymphadenectomy. Lymph nodes considered negative by conventional hematoxylin and eosin (H&E) staining were analyzed by serial sectioning with 100-mu m intervals and immunohistochemistry (IHC) with antihuman pancytokeratin antibody AE1/AE3. Results: In average, 6.18 lymph nodes were dissected per patient. No morbidity or mortality was associated to lymphadenectomy. In two patients, conventional H&E analysis showed presence of microscopic lymph node metastasis. H&E analysis allowed the identification of three other patients with lymph node micrometastases. The overall frequency of microscopic metastases, including micrometastasis, was 18%. Conclusions: Systematic lymphadenectomy allowed the detection of microscopic lymph node metastases, resulting in more accurate staging of extrahepatic disease. The inclusion of IHC increased the detection of lymph node micrometastasis. J. Surg. Oncol. 2009;100:534-537. (C) 2009 Wiley-Liss, Inc.

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Mutations in PKD1 cause the majority of cases of autosomal dominant polycystic kidney disease (ADPKD). Because polycystin 1 modulates cell proliferation, cell differentiation, and apoptosis, its lower biologic activity observed in ADPKD might influence the degree of injury after renal ischemia/reperfusion. We induced renal ischemia/reperfusion in 10- to 12-wk-old male noncystic Pkd1(+/-) and wild-type mice. Compared with wild-type mice, heterozygous mice had higher fractional excretions of sodium and potassium and higher serum creatinine after 48 h. In addition, in heterozygous mice, also cortical damage, rates of apoptosis, and inflammatory infiltration into the interstitium at time points out to 14 d after injury all increased, as well as cell proliferation at 48 h and 7 d. The mRNA and protein expression of p21 was lower in heterozygous mice than wild-type mice at 48 h. After 6 wk, we observed dilated tubules, microcysts, and increased renal fibrosis in heterozygotes. The early mortality of heterozygotes was significantly higher than that of wild-type mice when we extended the duration of ischemia from 32 to 35 min. In conclusion, ischemia/reperfusion induces a more severe injury in kidneys of Pkd1-haploin-sufficient mice, a process that apparently depends on a relative deficiency of p2l activity, tubular dilation, and microcyst formation. These data suggest the possibility that humans with ADPKD from PKD1 mutations may be at greater risk for damage from renal ischemia/reperfusion injury.