José Valbuena

Anatomic hepatectomy as a definitive treatment for hepatolithiasis: a cohort study

BACKGROUND Treatment requirements in hepatolithiasis may vary and may involve a multidisciplinary approach. Surgical resection has been proposed as a definitive treatment. OBJECTIVES This study aimed to evaluate the clinical results of anatomic liver resection among Chilean patients with hepatolithiasis. METHODS An historical cohort study was conducted. Patients who underwent hepatectomy as a definitive treatment for hepatolithiasis from January 1990 to December 2010 were included. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded. Preoperative, operative and postoperative variables were evaluated. RESULTS A total of 52 patients underwent hepatectomy for hepatolithiasis. The mean ± standard deviation patient age was 49.8 ± 11.8 years (range: 24-78 years); 65.4% of study subjects were female. A total of 75.0% of subjects had a history of previous cholecystectomy. The main presenting symptom was abdominal pain (82.7%). Hepatic involvement was noted in the left lobe in 57.7%, the right lobe in 34.6% and bilaterally in 7.7% of subjects. The rate of postoperative clearance of the biliary tree was 90.4%. Postoperative morbidity was 30.8% and there were no postoperative deaths. Three patients had recurrence of hepatolithiasis, which was associated with Carolis disease in two of them. Overall 5-year survival was 94.5%. CONCLUSIONS Anatomic liver resection is an effective treatment in selected patients with hepatolithiasis and is associated with low morbidity and no mortality. At longterm follow-up, anatomic hepatectomy in these patients was associated with a lower rate of recurrence.

Loss of Expression of Reprimo, a p53-induced Cell Cycle Arrest Gene, Correlates with Invasive Stage of Tumor Progression and p73 Expression in Gastric Cancer.

Reprimo (RPRM), a downstream effector of p53-induced cell cycle arrest at G2/M, has been proposed as a putative tumor suppressor gene (TSG) and as a potential biomarker for non-invasive detection of gastric cancer (GC). The aim of this study was to evaluate the epigenetic silencing of RPRM gene by promoter methylation and its tumor suppressor function in GC cell lines. Furthermore, clinical significance of RPRM protein product and its association with p53/p73 tumor suppressor protein family was explored. Epigenetic silencing of RPRM gene by promoter methylation was evaluated in four GC cell lines. Protein expression of RPRM was evaluated in 20 tumor and non-tumor matched cases. The clinical significance of RPRM association with p53/p73 tumor suppressor protein family was assessed in 114 GC cases. Tumor suppressor function was examined through functional assays. RPRM gene expression was negatively correlated with promoter methylation (Spearman rank r = -1; p = 0.042). RPRM overexpression inhibited colony formation and anchorage-independent growth. In clinical samples, RPRM gene protein expression was detected in 75% (15/20) of non-tumor adjacent mucosa, but only in 25% (5/20) of gastric tumor tissues (p = 0.001). Clinicopathological correlations of loss of RPRM expression were significantly associated with invasive stage of GC (stage I to II-IV, p = 0.02) and a positive association between RPRM and p73 gene protein product expression was found (p<0.0001 and kappa value = 0.363). In conclusion, epigenetic silencing of RPRM gene by promoter methylation is associated with loss of RPRM expression. Functional assays suggest that RPRM behaves as a TSG. Loss of expression of RPRM gene protein product is associated with the invasive stage of GC. Positive association between RPRM and p73 expression suggest that other members of the p53 gene family may participate in the regulation of RPRM expression.

Overexpression of p73 as a Tissue Marker for High-Risk Gastritis

Purpose: Histologic assessment of high-risk gastritis for the development of gastric cancer is not well defined. The identification of tissue markers together with the integration of histologic features will be required for this assessment. Experimental Design: Matched tumor/nontumor adjacent mucosa (NTAM) of 91 early gastric cancer and 148 chronic gastritis cases were evaluated for histologic characteristics (atrophy, intestinal metaplasia, chronic inflammation, polymorphonuclear infiltration, and Helicobacter pylori) by the Sydney System. Atrophy risk assessment was also evaluated by the Operative Link on Gastritis Assessment (OLGA) staging system. Eight tissue markers (BRCA1, HSP90, STAT1, FHIT, EGFR, p73, p53, p16INK4a) and EBV were also evaluated by tissue microarray/immunohistochemistry/in situ hybridization platform. Data were analyzed by contingency tables (2 × 2) using Fishers exact two-tailed test (P < 0.001) and integrated by Significance Analysis of Microarrays (SAM) and clustering analysis. Results: Histologically, NTAM have severe intestinal metaplasia/chronic inflammation and severe atrophy assessed by Sydney and OLGA staging systems. H. pylori infection was similar in both groups, and EBV was found only in 5.5% of the tumor samples. Overexpression of p73 was higher in NTAM (50.5%) than in chronic gastritis (10.8%; P < 0.0001). Integration of histologic features and tissue markers showed that overexpression of p73, severe atrophy, and OLGA stage 4 were the most relevant features in NTAM. Clustering analysis correctly assigned NTAM and control cases (P < 0.0001). Conclusions: Overexpression of p73 should be considered for the assessment of high-risk chronic gastritis. SAM allows the integration of histology and tissue markers for this assessment. Clin Cancer Res; 16(12); 3253–9. ©2010 AACR.

Florid reactive lymphoid hyperplasia (lymphoma-like lesion) of the uterine cervix

Lymphoma-like lesion (LLL) of the female genital tract is an older term in the literature that describes a florid reactive lymphoid proliferation that can be misinterpreted as lymphoma. Multiple causes of LLL have been suggested but most cases remain unexplained. We describe the clinicopathologic features of 6 patients with LLL involving the uterine cervix. Five patients presented with abnormal Papanicolaou test (Pap smear), and 3 patients had a biopsy procedure performed prior to detection of LLL in a loop electrosurgical excision procedure (LEEP). In each specimen, surface epithelial erosion was associated with a superficial, polymorphous lymphoid infiltrate with numerous scattered large cells, without cellular necrosis or sclerosis. Squamous dysplasia was present in 4 patients. Immunohistochemical studies revealed a mixed population of B- and T-lymphoid cells. T-cells were more numerous but B-cells and formed aggregates or sheets in areas. The large cells were predominantly B-cells positive for CD20 and negative for CD3 in all cases. CD30 was positive 3 cases, and Epstein-Barr virus-encoded RNA was positive in 3 cases. Assessment for clonality in 1 patient using polymerase chain reaction (PCR) methods revealed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements. At last clinical follow-up there was no evidence of progressive or systemic disease. We conclude that LLL of the cervix has a number of etiologies and that a prior surgical procedure, present in 3 patients in this study, is another possible etiology. As has been reported by others, monoclonal IgH gene rearrangements can be detected in this entity which has a benign clinical course.

Sarcoma histiocítico cutáneo: Reporte de un caso

El sarcoma histiocitico (SH), anteriormente designado como linfoma histiocitico verdadero, es una neoplasia maligna que muestra caracteristicas morfologicas e inmunofenotipicas de diferenciacion histiocitica. Frecuentemente, se presenta con enfermedad clinicamente avanzada y curso agresivo. Muchas inconsistencias en su terminologia y criterios diagnosticos han complicado su reconocimiento y caracterizacion. Se ha documentado en ganglios linfaticos, piel y sitios extranodales; con aproximadamente 29 casos reportados con compromiso cutaneo. Histologicamente, la lesion consiste en una proliferacion difusa de celulas grandes epiteloideas con marcado pleomorfismo. Reportamos un paciente de 78 anos que presenta una lesion nodular en la piel y partes blandas de la frente. Despues de una extensa evaluacion clinica y patologica, se demuestra que se trata de un SH. Se revisan las caracteristicas clinico patologicas y se discute el diagnostico diferencial, que incluye neoplasias que frecuentemente presentan compromiso cutaneo tales como melanoma, linfomas de celulas grandes y carcinomas. El SH es un diagnostico de exclusion que requiere una evaluacion clinica y patologica extensa, que incluye estudios inmunofenotipicos, y en algunos casos tecnicas moleculares. Este caso corresponde al primer caso reportado en nuestro pais.

Thymoma associated with hypogammaglobulinaemia and pure red cell aplasia

Thymomas are neoplasias that begin in the thymus and develop in the anterior mediastinum. They are commonly associated with a variety of systemic and autoimmune disorders, such as pure red cell aplasia, hypogammaglobulinaemia, pancytopaenia, collagen diseases, and, most commonly, myasthenia gravis. The presence of inter-current infections, especially diarrhoea and pneumonia, in the presence of lymphocyte B depletion and hypogammaglobulinaemia is known as Good’s syndrome and may affect up to 5% of patients with thymoma. While anaemia is present in 50%–86% of patients with Good’s syndrome, only 41.9% of cases present pure red cell aplasia. Concomitance of these two conditions has only been rarely studied. We report on the case of a 55-year-old man diagnosed with advanced thymoma, who, during the progression of his disease, developed signs and symptoms suggesting Good’s syndrome and pure red cell aplasia. We also performed a brief review of the literature concerning this association, its clinical characteristics, and treatment.

Granulomatosis linfomatoide cerebral primaria en paciente VIH positivo: Caso clínico

We report a 34-years-old male, with a history of hepatitis B and human immunodeficiency virus (HIV) infection that was admitted to the hospital with malaise, weight loss, frontal behavior and chest pain. Imaging studies showed two frontal cortical/subcortical nodules. A stereotactic cerebral biopsy showed reactive gliosis and a prominent atypical angiocentric and angiodestructive lymphoid infiltrate containing large pleomorphic CD20 and EBV-positive cells consistent with Lymphomatoid granulomatosis. Other studies were negative. The patient was lost from follow up.We report a 34-years-old male, with a history of hepatitis B and human immunodeficiency virus (HIV) infection that was admitted to the hospital with malaise, weight loss, frontal behavior and chest pain. Imaging studies showed two frontal cortical/subcortical nodules. A stereotactic cerebral biopsy showed reactive gliosis and a prominent atypical angiocentric and angiodestructive lymphoid infiltrate containing large pleomorphic CD20 and EBV-positive cells consistent with Lymphomatoid granulomatosis. Other studies were negative. The patient was lost from follow up.

Early-Onset EBV-Positive Post-transplant Plasmablastic Lymphoma Arising in a Liver Allograft A Case Report and Literature Review

We report a case of a 51-year-old man who received a cadaveric liver allograft for autoimmune and hepatopulmonary syndrome. The patient was admitted with symptoms of progressive vomiting and diarrhea 16 months after transplantation. Laboratory studies showed abnormal liver functions, and abdominal magnetic resonance imaging (MRI) showed a 76-mm heterogeneous mass in the liver. Histological examination showed a malignant lymphoid neoplasm with plasmablastic features. Plasmablastic lymphoma (PL) is rare in the post-transplantation period. To the best of our knowledge, only 25 well-documented cases of posttransplant PL, including ours, have been described.

Leucemia de células velludas en el embarazo: Caso clínico

Hairy cell leukemia (HCL) is a rare chronic B cell lymphoproliferative disorder that affects mostly men. It usually presents with pancytopenia, splenomegaly and bone marrow infiltration, without lymphadenopathy. Diagnosis is based on the presence of mononuclear cells with cytoplasmic projections in a blood smear, the typical bone marrow infiltration pattern and the immunophenotypic profile. HCL occurs seldom in young women and even more exceptionally during pregnancy. We report a 31-year-old woman in whom a splenomegaly was detected during routine prenatal care. Pancytopenia with 25% of hairy cells was found in her blood count. The patient was subjected to an open splenectomy and had an uneventful pregnancy. After two years of follow up, she has a normal blood count and has not required chemotherapy.

Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer

Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors. In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies. In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05). The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%). Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.