Serum levels of keratin-18 fragments [tissue polypeptide-specific antigen (TPS)] are correlated with hepatocyte apoptosis in alcoholic hepatitis.

Apoptosis is a major feature in alcoholic hepatitis. During apoptosis, the M30 neoepitope becomes exposed after keratin-18 cleavage. The tissue polypeptide-specific antigen (TPS) is a keratin-18 fragment that is routinely used as a tumor marker. Serum TPS levels are increased in patients with alcoholic hepatitis. The aim of this study was to investigate the possible relationship of TPS levels with hepatocyte apoptosis in alcoholic hepatitis. Thirty-one patients with alcoholic hepatitis and 22 with fatty liver were included. Hepatocyte apoptosis was evaluated by M30 immunostaining. Serum TPS levels were measured by a commercial immunoassay. The apoptotic score was higher in patients with alcoholic hepatitis than in patients with fatty liver. There was a significant correlation between the apoptotic score and TPS levels. The correlation of the apoptotic score with TPS levels was stronger than with standard liver tests. Serum TPS may be a marker of apoptosis in alcoholic hepatitis.

Pancreatic fusocellular sarcoma. The importance of endoscopic ultrasound-guided fine needle aspiration in the differential diagnosis of solid pancreatic tumors.

In the presence of a pancreatic tumor, the main diagnostic problem is to determine the benign o malignant nature of the lesion, and then to evaluate its resectability. A preoperative biopsy was usually rejected based on the fact that negative results do not exclude malignancy, that such biopsy may hamper the possibility of curative surgery because of potential seeding along the biopsy s trajectory, that surgical morbidity and mortality are low, and also because of the high diagnostic sensitivity of the various imaging techniques. Biopsy for solid pancreatic tumors was limited to irresectable tumors, and isolated cases with suspicion of tuberculosis, lymphoma or neuroendocrine tumors. Nowadays the performance of a pancreatic biopsy is becoming essential for the correct management of solid lesions, and is useful not only to establish malignancy, but also for a better knowledge of all kind of pathologies and, thus, for better therapeutic management. In this context, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has proven a safe technique with a low rate of complications and a diagnostic accuracy superior to other procedures, this being considered the method of choice for the study of solid pancreatic lesions. An illustrative example is the case we report in this article -a patient diagnosed of a solid, locally advanced-stage pancreatic tumor with imaging techniques (abdominal ultrasounds and EUS) under EUS-guided FNA; the procedure could establish a final diagnosis of pancreatic fusocellular sarcoma.

[The immunohistochemical expression of cyclin B1 is associated with higher SUV in 18F-FDG-PET in non-small cell lung cancer patients. Initial results]. / La expresión inmunohistoquímica de ciclina B1 conlleva mayores valores de SUV en la 18F-FDG-PET de pacientes con carcinomas no microcíticos de pulmón. Primeros resultados.

AIM: to study the expression of cyclin B1 and its possible relationship with the maximum SUV in FDG-PET and MIB1 expression in patients with NSCLC. MATERIALS AND METHODS: 49 patients (15 adenocarcinomas, 27 squamous cell carcinomas and 7 bronchoalveolar carcinomas) were included in this study; the immunohistochemical expression of cyclin B1 was determined using the tissue-array technique. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: cyclin B1 expression was detected in 40 out of 45 cases. The SUV values were higher (p=0.04) in the cyclin B1+ cases than in the negative cases (16.4+/-8.1 vs 10.9+/-6.2). Cyclin B1 expression and SUV values were not correlated with the clinical stage. The expression of cyclin B1+ correlated positively (p<0.0001) with that of MIB1. After univariate analysis, only the cellular proliferation was a prognostic factor (p=0.037). CONCLUSIONS: our results suggest that there is a direct correlation between cyclin B1 expression and max-SUV values in the PET of NSCLC patients. When the association of cyclin B1 with positive MIB1 is also considered, our results support the role of cell proliferation in FDG uptake by the tumour.

[The immunohistochemical expression of cyclooxygenase 2 is inversely associated with (18)F-FDG-PET SUV values in non-small-cell lung cancers. Initial results]. / La expresión inmunohistoquímica intensa de ciclooxigenasa 2 se asocia inversamente con los valores máximos de SUV en la (18)F-FDG-PET de pacientes afectados de carcinomas no microcíticos de pulmón. Relación con otros factores biológicos.

OBJECTIVE: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. MATERIAL AND METHOD: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 +/- 1.2 vs. 12.9 vs. 17.1 +/- 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. CONCLUSIONS: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression.

[The autoimmune hepatitis-primary biliary cirrhosis overlap syndrome: a case report]. / Síndrome overlap hepatitis autoinmune-cirrosis biliar primaria: a propósito de un caso.

The autoimmune hepatitis-primary biliary cirrhosis overlap syndrome is an entity characterized by clinical, analytical, immunological and histological manifestations of both entities. We present the case of a 26-year-old woman with a serious acute hepatitis that fulfills the diagnostic criteria of the overlap syndrome and that showed a satisfactory response to oral corticoid therapy.

Serum cytokeratins in alcoholic liver disease: contrasting levels of cytokeratin-18 and cytokeratin-19.

Serum cytokeratin (CK) levels are widely used as tumor markers. Serum levels of CK-18, a tumor marker also known as tissue polypeptide specific antigen (TPS), are increased in patients with alcoholic liver disease. Cytokeratin-18 is the main component of Mallory bodies, a hallmark of alcoholic hepatitis, which may also contain CK-19. Serum levels of CK-18 and CK-19, a tumor marker also known as CYtokeratin FRAgment 21-1 (CYFRA 21-1) were investigated in (a) heavy drinkers with alcoholic liver disease (n=15), (b) patients with malignancy (n=22), and (c) healthy controls (n=10). Serum levels of CYFRA 21-1 (CK-19) were markedly increased in patients with malignancy, but were similar in heavy drinkers and healthy controls. In contrast, serum levels of TPS (CK-18) in heavy drinkers were higher than those of healthy controls, and even tended to be higher than those of patients with malignancy. Both CK-19 and CK-18 levels were higher in cases of alcoholic hepatitis than in cases of fatty liver. Correlation with hepatocyte CK inclusions was stronger for serum TPS (CK-18) than for CYFRA 21-1 (CK-19). In conclusion, serum CYFRA 21-1 (CK-19) and TPS (CK-18) show a different pattern of increase that could reflect the composition of the altered hepatocyte CK network in alcoholic liver disease. Their usefulness as tumor markers, particularly that of serum TPS (CK-18), may be limited in patients with alcoholic liver disease.

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: a case report.

The breast tumor resembling the tall cell variant of papillary thyroid carcinoma is a very unusual mammary carcinoma whose histologic and predominant nuclear features mimic a papillary thyroid carcinoma. We report the case of a 64-year-old woman who presented with a palpable nodule in the right breast. Fine needle aspiration disclosed abundant cellularity with isolated cells, sheets, and papillary formations of epithelial cells with nuclear grooves. Histologically, the neoplastic cells were arranged in a solid to papillary architecture, with follicular-like and cribriform areas. The cells were columnar to cuboidal with eosinophilic cytoplasm, clear chromatin, nuclear grooves, and occasional nuclear pseudoinclusions. Tumor cells were positive for cytokeratins, alpha and beta-estrogen receptors, progesterone receptor, androgen receptor, CEA, and bcl-2. We searched for BRAF mutations with negative results. Recognizing the cytologic and histologic characteristics of these peculiar mammary tumors that mimic thyroid carcinomas can avoid unnecessary clinical investigations.

Cell-cycle-associated markers and clinical outcome in human epithelial cancers: a tissue microarray study.

The development and progression of epithelial cancers are the result of an imbalance in signals promoting and inhibiting cellular proliferation and apoptosis. The aim of this study is to evaluate the expression of cell-cycle and apoptosis regulators and correlate them with clinical outcome in the most frequent carcinomas, in order to establish common prognostic biomarkers independent of cancer origin. Using tissue microarrays (TMAs), we have analysed the immuno-expression of Ki-67, Bcl-2, Bax, cyclin D1, cyclin D3, CDK1, CDK2, CDK6, p16, p21, and p27 in a series of 205 carcinomas of the large bowel, breast, lung and prostate (80, 73, 37 and 15 cases, respectively). By univariate analysis, positivity for p27, p16 and Bcl-2 was associated with better overall survival (P<0.0135, P<0.0442 and P<0.0001, respectively). The risk of mortality was 2.3-fold greater in patients without Bcl-2 expression. TMA immunohistochemical analysis identified a subset of epithelial cancers with overlapping alterations in cell-cycle checkpoints, apoptosis regulators and tumour suppressor pathways. We found that in most common epithelial cancers, regardless of origin, Bcl-2 appears to be the key biological factor influencing clinical behaviour.

Prospective histopathological analysis of hepatocellular carcinoma treated with percutaneous ethanol injection in patients on the waiting list for liver transplantation.

INTRODUCTION: Liver transplantation (LT) improves survival in selected patients suffering from hepatocellular carcinoma (HCC). Unfortunately, the long time lapse between indication and LT may cause tumor progression. Thus, percutaneous ethanol injection (PEI) has been proposed as adjuvant therapy of HCC in patients awaiting LT. The efficacy of PEI assessed using histopathological analysis of hepatectomy specimens has not been adequately evaluated. PATIENTS AND METHODS: Twenty-nine nodules of HCC in 27 patients (21 men; mean age, 58.1 +/- 7.3 years) listed for LT were treated with PEI. Pretreatment mean serum alpha-fetoprotein (AFP) was 11 +/- 13.4 ng/mL. Mean tumor diameter was 30.8 +/- 12.9 mm. Data from the explanted livers after transplantation included percentage tumor necrosis, presence of satellite and distant nodules, vascular invasion, tumor capsule, and grade of differentiation. RESULTS: Nineteen patients with 20 treated lesions underwent transplantation. The median interval PEI-LT was 3 months. Complete necrosis was observed in 13 nodules (65%). Satellite nodules were present in 10% of lesions. Previously unrecognized distant lesions were seen in 15.8% of patients. Only 1 nodule presented microscopic vascular invasion. Most HCC were well differentiated (90%), and completely encapsulated (80%). No tumor-related deaths occurred. Seventeen patients are alive and recurrence-free after a median follow-up of 15 months. CONCLUSIONS: PEI may achieve significant necrosis in cases of HCC awaiting LT. Nevertheless, previously unrecognized satellite and distant lesions may be observed. Further studies are needed to evaluate the influence of tumor necrosis on overall survival of these patients.

Doppler ultrasonography for the assessment of tumor necrosis after percutaneous ethanol injection prior to liver transplantation as adjuvant therapy of hepatocellular carcinoma.

INTRODUCTION: Percutaneous ethanol injection (PEI) is considered to be a curative treatment for hepatocellular carcinoma (HCC). The imaging technique of choice for the assessment of local response after PEI has not been well defined, but helical computerized tomography (hCT) has been recommended. The aim of this study was to assess the accuracy of Doppler ultrasonography (US) for evaluation of tumor necrosis after PEI. PATIENTS AND METHODS: Twenty-one patients with single HCC listed for liver transplantation underwent multisession US-guided PEI. Liver Doppler US was done at the 4th week after PEI. Complete response was defined as the absence of any intratumoral Doppler signal. The liver was analyzed in transplant recipients during the follow-up. Complete pathological response was defined as necrosis > or = 90% of total tumor volume. Histological and sonographic findings were compared. RESULTS: Twelve patients underwent transplantation (9 men, mean age 60 +/- 5.2 years). Nine of these (75%) showed a complete ultrasonographic response. In the explanted liver, complete necrosis was present in 6 nodules, and incomplete necrosis was seen in the remaining 6 cases. In comparison with histology, Doppler US showed values of sensitivity, specificity, positive predictive values, and negative predictive values of 50%, 100%, 100%, and 60%, respectively. Overall accuracy was 75%. CONCLUSIONS: In our series, Doppler US showed low sensitivity but high specificity in the assessment of HCC necrosis after PEI. The ultrasonographic finding of complete response requires hCT for confirmation, but the presence in Doppler US of neoplastic viable tissue is enough to indicate a further cycle of PEI.

Prolonged survival after liver transplantation for Hodgkin's disease-induced fulminant liver failure.

A 30-year-old male with a past history of nodular lymphocyte predominance Hodgkin's disease in apparent complete remission for two years received a liver transplantation because of fulminant liver failure. Histopathological examination of the explanted liver showed massive infiltration by Hodgkin's disease. In spite of a nodal recurrence of Hodgkin's disease, the patient is alive and in excellent general condition six years after liver transplantation.

Primary anaplastic large cell lymphoma of the central nervous system.

Central nervous system (CNS) involvement is extremely rare in anaplastic large cell lymphoma (ALCL), and in children only isolated cases have been reported, mainly as secondary CNS involvement. A case of fatal primary ALCL of the brain in a 13-year-old white boy is reported. Magnetic resonance imaging of the brain showed decreased absorption in T1- and T2-weighted image showed a hyperintense signal in the right parietal lobe and 2 masses in the right frontal lobe. A frontal lobe biopsy showed a pleomorphic neoplasm diffusely infiltrating the brain parenchyma and composed of large cells with bizarre, often polylobated or horseshoe-shaped nuclei. Immunohistochemical stains showed diffuse strong positivity for CD30, anaplastic lymphoma kinase protein (ALK-1), p80, leucocyte common antigen, CD45RO (UCHL1), and focal staining for epithelial membrane antigen. Immunostainings for cytokeratins, monocyte-macrophage, and B-cell markers were negative. Epstein-Barr virus latent membrane protein was not detected. To the best of our knowledge, there is only 1 case of primary ALCL of the brain in childhood previously reported in the literature. Before the biopsy, both cases were clinically misdiagnosed as mycobacterial CNS infection. Therefore, primary ALCL should also be included in the differential diagnosis when a mycobacterial CNS infection is suspected in pediatric patients; a careful cytological evaluation of the cerebrospinal fluid or cerebral biopsy are essential for an accurate diagnosis.

Liver-cell adenomas with heavy iron deposition.

We report 3 unusual cases of liver cell adenomas with some uncommon features, corresponding to 3 women aged 45, 37, and 41 years, respectively. The diagnosis was incidental in 2 cases, and the third presented with abdominal pain. Radiologic findings were consistent with liver-cell adenoma, but gross examination failed to reveal the lesion until 24 hours of formalin fixation in 2 cases. Histopathological examination showed a striking deposition of iron pigment. In fact, Pearl's stain was the best way to visualize the limits of the neoplasm, which were irregular (pseudo-infiltrative). There was no evidence of other architectural or cytologic features suggesting an alternative diagnosis, particularly liver-cell carcinoma. Follow-up ranged from 9 months to 6 years and all patients are free of disease.

Hepatoma in a 40-year old male with hereditary hemochromatosis in the absence of cirrhosis. Implications of molecular diagnosis.

Hepatocarcinoma is a poor-prognosis complication of hereditary hemochromatosis (HH). It occurs with a frequency rate of 10-20%. It is usually diagnosed during the 6th or 7th decade of life, and it appears almost exclusively in association with liver cirrhosis or in the presence of other known risk factors such as HBV or HCV. We present a case of hepatocarcinoma in a 40-year-old male with a long history of ethanol abuse of more than 100 g/day. The patient was studied through familial HH screening, and firstly diagnosed of HH on the base of biochemical blood tests. Subsequently, a C282Y mutation--homozygous--was identified. Studies performed on the patient did not suggest liver cirrhosis. Serology for HBV and HCV was negative. Concurrently, the patient presented an isolated liver lesion of 4 cm in segment 6 of the right lobe. Imaging techniques suggested an hepatoma. A surgical resection of the tumor by right hepatectomy was performed. The diagnosis of HH, complicated by hepatoma, on a non-cirrhotic liver was confirmed. After 2 years of post-surgery follow-up, a period during which the patient underwent treatment including periodic phlebotomies, he remains asymptomatic and with no signs of tumor recurrence.

[Renal amyloidosis as initial clinical manifestation of Crohn's disease]. / Amiloidosis renal como manifestación clínica inicial de la enfermedad de Crohn.

We present a 20-year-old man with oligosymptomatic Crohn's disease of the terminal ileum complicated by chronic renal insufficiency due to secondary amyloidosis. Definitive diagnosis of Crohn's disease was established 7 years after the onset of the renal disease as a result of symptoms of intestinal obstruction requiring surgery. The affected colonic segment was removed and histopathological examination of the surgical specimen confirmed the diagnosis of Crohn's disease without identifying intestinal amyloidosis. Despite the surgical intervention and the absence of recurrence of inflammatory bowel disease, renal insufficiency steadily progressed, and the patient required kidney transplantation. The patient's subsequent course was excellent and no recurrence of intestinal or renal disease was observed after 8 years of follow-up.

[Intraventricular arachnoid cyst in the adult]. / Quiste aracnoideo intraventricular en el adulto.

INTRODUCTION: Intracranial arachnoid cysts are benign, congenial cystic lesions found in infancy. The commonest sites are the lateral fissure and the posterior fossa. Exceptionally they may be found in the ventricular system. CLINICAL CASE: We describe a 69 year old patient with a clinical history of headache and tingling of the face for 24 hours. Diagnosis of a lateral ventricle arachnoid cyst was made on computerized tomography and magnetic resonance. Treatment was surgical with excision of the wall of the cyst and the communication with the ventricle. CONCLUSION: We review 14 cases previously described (9 adults and 5 children), analyzing their clinical and radiological features, type of treatment given and the different theories proposed as to pathogenesis.

[Inflammatory pseudotumor of the spleen. Review and a new case report]. / Pseudotumor inflamatorio del bazo. Revisión y aportación de un nuevo caso.

Splenic inflammatory pseudotumour has been defined as a benign tumour reactive lesion with unspecified reparative or inflammatory alterations. It is a mimicking tumour often confused with other pathologies, primarily, lymphoproliferative disorders. Though its aetiology remains unknown, these tumours are often associated to infectious agents such as the Epstein-Barr virus. We describe a case of a 29 year-old patient with a history of infectious mononucleosis, followed by fever, weight loss, and splenomegaly. Splenectomy detected a homogeneous, whitish 2 cm node diagnosed as splenic inflammatory pseudotumour. The clinical features and diagnosis of this disorder are discussed in relation to the histopathological findings.

[Smooth muscle tumor of the lower lip. A report of a case of rapid growing and increased mitotic activity]. / Tumor de músculo liso de labio inferior. Reseña de un caso de rápido crecimiento y elevada actividad mitósica.

Smooth-muscle tumors are not often found in the oral cavity. The tumors found usually are benign tumors of the angioleiomyoma type. We report a new case of oral smooth-muscle tumor, in the lower lip of a 74-year-old woman. Immunohistochemistry and electron microscopic study confirmed the nature of the lesion. Although some mitoses were visible, the outcome has been favorable.

Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?

INTRODUCTION: Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences. AIM: To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT). METHOD: We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011. RESULTS: Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704). CONCLUSIONS: Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.