Haem oxygenase 1 expression is associated with prognosis in cholangiocarcinoma patients and with drug sensitivity in xenografted mice.

OBJECTIVE: Haem oxygenase-1 (HO-1) plays important roles in cytoprotection and tumour growth. Cholangiocarcinoma (CCA) is a deadly malignancy with very poor prognosis. The role of HO-1 in tumour progression in CCA up to now has been relatively unexplored, thus, its possible therapeutic implications in CCA have been investigated here. MATERIALS AND METHODS: HO-1 expression in tumour tissues from 50 CCA patients was determined by immunohistochemical analysis and its association with survival time was evaluated using the Kaplan-Meier method. Its role in CCA cells in vitro was evaluated by transwell and wound healing assays and suppression of HO-1 expression by siRNA. Effects of HO-1 inhibition on gemicitabine (GEM)-mediated tumour suppression was evaluated in nude mice xenografted with CCA cells. RESULTS: HO-1 expression was inversely associated with median overall survival time. Hazard ratio of patients with high HO-1 expression was 2.42 (95% CI: 1.16-5.08) with reference to low expression and HO-1 knock-down expression inhibited transwell cell migration. Suppression of HO-1 by Zn-protoporphyrin (ZnPP) enhanced cytotoxicity to GEM in CCA cells, validated in CCA xenografts. Treatment with GEM and ZnPP almost completely arrested tumour growth, whereas treatment with only a single reagent, retarded it. Tumour inhibition was associated with reduction in expression of Ki-67 and microvascular density, and enhanced p53 and p21 immunohistochemical staining. CONCLUSION: High HO-1 expression was associated with poor prognosis of CCA. Synergistic role of HO-1 inhibition in chemotherapy of CCA is a promising insight for treatment of this tumour and warrants further investigation.

De novo lupus nephritis in a renal transplanted child: a case report.

De novo lupus nephritis (LN) is a rare complication in renal transplantation recipients. We present the clinical manifestations of de novo LN in a 12-year-old boy who received a cadaveric renal transplant. The cause of end-stage renal disease was prune belly syndrome with renal dysplasia. His immunosuppressive drugs included tacrolimus, mycophenolate sodium, and prednisolone. After 3 years of treatment, he developed nephrotic syndrome (NS) without other symptoms of systemic lupus erythematosus (SLE). The renal pathology of the transplanted kidney showed suspicious acute cellular rejection and LN World Health Organization class IV-G (A/C). Antinuclear antibody was positive, but anti-dsDNA and anti-Smith were negative. The serum complements were initially normal. Pulse methylprednisolone was given and the dosages of all immunosuppressive drugs increased; notwithstanding, his edema and hypoalbuminemia worsened. Repeated biopsy of the transplanted kidney was done. A full-house pattern was documented under immunofluorescent examination which confirmed LN WHO class IV-G (A/C) without evidence of rejection. He then developed macrophage-associated hemophagocytic syndrome and cytomegalovirus pneumonia. He ultimately developed pulmonary hemorrhage and died owing to severe pneumonia. De novo LN should be considered in renal transplant recipients with new onset of NS despite there not being any other clinical manifestations of SLE.

Downregulation of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) is associated with enhanced expression of matrix metalloproteinases and cholangiocarcinoma metastases.

BACKGROUND: Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has been implicated in the attenuation of tumor metastasis by negatively regulating metalloproteinase (MMP) levels. RECK gene expression is downregulated in many solid tumors, with this downregulation being associated with poor prognosis. This study evaluated the role of RECK in cholangiocarcinoma (CCA). METHODS: The expression of RECK, MMP-2, and MMP-9 in paraffin sections of hamster and human CCA specimens was analyzed by immunohistochemistry. Functional analysis of RECK was performed in RECK small interfering (si) RNA knockdown CCA cell lines. The effect of aspirin on RECK status and function was evaluated using Western blotting, gelatin zymography, invasion and proliferation assays, and PhosphoELISArray analysis of Ras downstream mediators. RESULTS: Hamster tissues showed high RECK expression in hyperplastic biliary duct epithelia, low RECK expression in precancerous lesions, and no RECK expression in CCA. In human specimens, RECK was highly expressed in normal biliary cells, whereas intrahepatic CCA showed low levels of expression. Downregulation of RECK was correlated with tumor metastasis (P < 0.01) and shorter patient survival (P < 0.02). RECK expression levels were inversely correlated with MMP-2 and MMP-9 expression (P < 0.05). SiRNA RECK-depleted M139 CCA cells exhibited increased MMP-2/-9 gelatinase activities and invasiveness. Aspirin (500 µM) demonstrated myriad effects in human CCA cell lines, including growth suppression, reduced phosphorylation of Akt/Erk/c-Jun, elevation of RECK expression, inhibition of MMP-2/MMP-9 activity, and enhanced invasiveness. CONCLUSIONS: RECK functions as a metastasis suppressor in CCA; upregulation of RECK expression could provide a potential therapy to improve the prognosis of this type of cancer.

Granulomatous, hepatolithiasis and hepatomegaly caused by Capillaria hepatica infection: first case report of Thailand.

This is the first case report in Thailand of a Capillaria hepatica infection causing a granulomatous hepatic lesion, bile duct dilatation, hepatolithiasis and hepatomegaly. The patient's chief complaint was abdominal pain with fever and chills. Imaging of the liver revealed a 3-cm mass in the postero-inferior sub-segment of the right lobe of the liver with bile duct dilatation. Right hepatectomy and cholecystectomy were performed. Gross pathology of the right hepatectomy revealed focal intrahepatic duct dilatation with prominent periductal fibrosis. The histopathological section revealed chronic inflammation and some granuloma formation surrounding the bile ducts, generalized portal infiltration, prominence of eosinophils and hepatolithiasis. Histopathotogical section revealed oblique sections of C. hepatica egg (size 35.4+/-6.38 microm in width) and brown amorphous pigment.

Cytokine expression in hamsters experimentally infected with Opisthorchis viverrini.

The cytokine mRNA expression of IL-12, IFN-gamma, TGF-beta, IL-4, and IL-10 were investigated in spleen, liver and mesenteric lymph nodes (MLN) in hamsters experimentally infected with Opisthorchis viverrini. Animals were infected with 5, 25 or 100 metacercariae (Mc) and examined by RT-PCR and real-time PCR at 2 weeks, 2 and 6 months after infection. The cytokine expression was compared using HPRT. The IL-12 was significantly expressed at 2 weeks in the liver of the 5- and 25-Mc-infected groups. It is correlated with the inflammation intensity found in the liver at the same time. The production of IFN-gamma was not increased. The significant increase in expression of IL-10 was observed in the 6-month group in the spleen, which may suppress the Th1 and lead to a Th2 response. The IL-4 and TGF-beta expressions in MLN were significantly increased, and correlated with the dose of infection, especially in the 6-month groups. The TGF-beta level in MLN was 15-fold higher than in the uninfected control, compared to a twofold increase in spleen and liver. Because this parasite resides in the bile duct, the regulatory cytokine levels of mucosal immunity were enhanced more than those in systemic immunity. These results indicate the predominance of Th2 responses in chronic O. viverrini infection, and the high level of TGF-beta may inhibit the immune functions, which allows the parasites to evade host immune response.

Insulinoma in childhood.

A 9-year-old boy with convulsions is herein described. He was diagnosed and treated for epilepsy and insufficient adrenal function for four years with no response. Hypoglycemia from hyperinsulinism was found and the source of the hyperinsulinism was a tumor of the tail of the pancreas--located by computerized tomographic scan and magnetic resonance imaging. Distal pancreatectomy was performed with good results. Histology of the tumor showed islet cell tumors with capsular invasion. For this type of patient, long-term follow-up should include: prevention of metastasis or recurrence, and testing for multiple endocrine neoplasia type 1.

Imprint cytology from a childhood case of metastatic papillary thyroid carcinoma.

A 9-year-old girl with a history of a palpable multinodular hard mass in the right lobe of the thyroid gland was biopsied. On diagnosis of a papillary carcinoma, total thyroidectomy and right radical neck dissection were performed. Examination of frozen sections demonstrated metastasis in the right but not the left cervical lymph nodes. Imprint cytology revealed small papillary sheets of neoplastic cells with a high proportion of cytoplasmic inclusions and a few nuclear grooves. These nuclear details allowed a specific diagnosis of metastatic papillary thyroid carcinoma. Papillary thyroid carcinoma can be easily diagnosed by imprint cytology. In places such as small and country hospitals that do not have pathology laboratories, it can also be used successfully as an alternative to frozen section histology. The efficiency, simplicity and rapidity of this method make it a very useful procedure.

Cytologic diagnosis of Cryptococcus neoformans in HIV-positive patients.

OBJECTIVE: To present experience with the cytologic diagnosis of pulmonary cryptococcosis in bronchial washings and bronchoalveolar lavage in human immunodeficiency virus (HIV)-positive patients in Thailand. STUDY DESIGN: The study group consisted of 54 HIV-positive patients admitted to the Faculty of Medicine, Srinagarind Hospital, during the period January 1992-June 1994. Bronchial washing and bronchoalveolar lavage specimens were studied for Cryptococcus neoformans by routine Papanicolaou and special staining methods. RESULTS: The Cryptococcus organism, an encapsulated yeast with a clear halo on Papanicolaou-stained smears, was found both extracellularly and in histiocytes in 4 of 54 (7.4%) cases. A definitive diagnosis was confirmed by positive staining of the capsular mucopolysaccharides with periodic acid-Schiff and Mayer's mucicarmine stain and of the cell wall with methenamine silver. Lung biopsy was performed in one case and revealed cryptococcosis. CONCLUSION: This study underscores the usefulness of cytologic screening in the detection of this opportunistic pulmonary infection. The cytopathologist and cytotechnologist should be alert for the presence of Cryptococcus in cytologic specimens from HIV-positive patients.

Neonatal melioidosis: a report of 5 cases.

Melioidosis, caused by Pseudomonas pseudomallei, occurs in tropical areas and is diagnosed mostly in adults. In Khon Kaen, a province of northeast Thailand, five cases of infantile melioidosis were managed at Srinagarind Hospital. The patient's specimens were submitted to microbiologic and serologic examination for P. pseudomallei demonstrated by indirect hemagglutination. Possible modes of transmission such as environment, perinatal exposure and venereal transmission were investigated.