Re-operation for hyperparathyroidism

INTRODUCTION: Re-operation for hyperparathyroidism (HPT) represents a challenge for experienced endocrine surgeons. The present study reviews the technical and pathological factors for failure of initial surgery and identifies strategies to approach re-operative parathyroidectomy. METHODS: Clinical details, operation notes, pathology, localization studies and complications for re-operative cases performed by three surgeons were reviewed. RESULTS: Over a 10-year period there were 40 re-operative cases with a 98% success rate. There were 31 patients with primary HPT, 21 with persistent primary (PP) and 10 with recurrent primary (RP). Multigland disease (MGD) was present in 19 of the 31 (61%) primary HPT cases. The culprit gland was ectopic in 14 cases, at a normal location in 10 and there was regrowth at previously excised sites or remnant disease in 10. There were nine patients with secondary HPT, four with persistent secondary (PS) and five with recurrent secondary (RS). The culprit gland was ectopic in five, at a normal location in four and regrowth at a previously excised site in two. Pre-operative investigations were employed in all cases and the most helpful were sestamibi scan (S) and selective venous sampling (SVS) for parathyroid hormone (PTH) concentration. True positive localizations for S was in 20 of 34 cases (59%), SVS in seven of nine (78%), computed tomography (CT) in seven of 17 (41%) and ultrasound scan (USS) in 10 of 28 (36%). CONCLUSIONS: Re-operative parathyroidectomy can be performed by experienced surgeons with a very high success rate and minimal complications.     

Raloxifene acutely suppresses ventricular myocyte contractility through inhibition of the L-type calcium current

1. The selective oestrogen (ER) receptor modulator, raloxifene, is widely used in the treatment of postmenopausal osteoporosis, but may also possess cardioprotective properties. We investigated whether it directly suppresses myocyte contractility through Ca(2+) channel antagonism in a similar way to 17beta-oestradiol. 2. Cell shortening and Ca(2+) transients were measured in single guinea-pig ventricular myocytes field-stimulated (1 Hz, 37 degrees C) in a superfusion chamber. Electrophysiological recordings were performed using single electrode voltage-clamp. 3. Raloxifene decreased cell shortening (EC(50) 2.4 microm) and the Ca(2+) transient amplitude (EC(50) 6.4 microm) in a concentration-dependent manner. At a concentration of 1 microm, raloxifene produced a 33+/-2% (mean+/-s.e.m) and 24+/-2% reduction, respectively (P<0.001, n=14 for both parameters). 4. These inhibitory actions were not observed in myocytes that had been incubated with the specific antagonist, ICI 182,780 (10 microm) (n=11). 5. Raloxifene (1 microm) shortened action potential durations at 50 and 90% repolarisation (P<0.05 and <0.001, respectively; n=27) and decreased peak L-type Ca(2+) current by 45%, from -5.1+/-0.5 pA/pF to -2.8+/-0.3 pA/pF (P<0.001, n=18). 6. Raloxifene did not significantly alter sarcoplasmic reticulum Ca(2+) content, as assessed by integrating the Na(+)/Ca(2+) exchanger currents following rapid caffeine application. 7. The present study provides evidence for direct inhibitory actions of raloxifene on ventricular myocyte contractility, mediated through Ca(2+) channel antagonism.     

Acute actions of 3 alpha-hydroxy-tibolone on factors influencing contraction in guinea-pig ventricular myocytes

We investigated whether one of the main estrogenic metabolites of the postmenopausal agent, tibolone (Org OD14), exerts direct cardiac actions in a similar way to 17beta-estradiol. 3alpha-OH-tibolone (40 microM) decreased both cell shortening and Ca2+ transient amplitude of field-stimulated (1 Hz, 37 degrees C) guinea-pig ventricular myocytes. These effects were still observed in cells that had been incubated with the specific estrogen receptor antagonist, ICI 182,780 (C(32)H(47)F(5)O(3)S), suggesting an estrogen receptor-independent mechanism of action. In addition, 3alpha-OH-tibolone inhibited the L-type Ca2+ current and shortened action potential durations (APD). This mechanism may contribute to a potential cardiovascular action of tibolone.     

Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray

To identify genes that are differentially expressed in human esophageal squamous cell carcinoma (ESCC), we have developed a cDNA microarray representing 34 176 clones to analyse gene expression profiles in ESCC. A total of 77 genes (including 31 novel genes) were downregulated, and 15 genes (including one novel gene) were upregulated in cancer tissues compared with their normal counterparts. Immunohistochemistry and Northern blot analysis were carried out to verify the cDNA microarray results. It was revealed that genes involved in squamous cell differentiation were coordinately downregulated, including annexin I, small proline-rich proteins (SPRRs), calcium-binding S100 proteins (S100A8, S100A9), transglutaminase (TGM3), cytokeratins (KRT4, KRT13), gut-enriched Krupple-like factor (GKLF) and cystatin A. Interestingly, most of the downregulated genes encoded Ca(2+)-binding or -modulating proteins that constitute the cell envelope (CE). Moreover, genes associated with invasion or proliferation were upregulated, including genes such as fibronectin, secreted protein acidic and rich in cystein (SPARC), cathepsin B and KRT17. Functional analysis of the alteration in the expression of GKLF suggested that GKLF might be able to regulate the expression of SPRR1A, SPRR2A and KRT4 in ESCC. This study provides new insights into the role of squamous cell differentiation-associated genes in ESCC initiation and progression.     

Cyclooxygenase-2 pathway correlates with vascular endothelial growth factor expression and tumor angiogenesis in hepatitis B virus-associated hepatocellular carcinoma

Evidence indicates that cyclooxygenase (COX)-2-derived prostaglandins (PGs) contribute to tumor growth by inducing angiogenesis. We investigated the role of COX-2 in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). COX-2 and vascular endothelial growth factor (VEGF) expressions were examined by immunohistochemistry in 24 HBV-associated HCC. Tumor micro-vessel density (MVD) was assessed using CD34 immunohistochemistry. Hep3B HCC cell line, which carries integrated HBV genome, was stably transfected with human COX-2 cDNA. COX-2 and VEGF expressions were determined by Western blot while PG level was determined by ELISA. The effects of PGs on VEGF expression were also investigated. Expression of COX-2 and VEGF in HCC cells were observed in 19 (79%) and 16 (67%) cases, respectively. Well-differentiated HCC expressed COX-2 more strongly than less-differentiated HCC (p<0.001). COX-2 expression was found to correlate with VEGF expression and MVD (p=0.003 and 0.004, respectively). COX-2 overexpressing Hep3B clone had higher VEGF expression as compared to non-COX-2 expressing clone and parental cells. Treatment of the COX-2 overexpressing cells with a COX-2-selective inhibitor, NS-398 (10 microM), decreased PGE2 level and attenuated VEGF expression. Addition of PGE2 (10 microM) and the stable analog of PGI2, carbaprostacyclin (5 microM), to Hep3B cells also increased VEGF expression. Up-regulation of COX-2 correlates with VEGF expression and tumor angiogenesis in HBV-associated HCC. Moreover, COX-2 up-regulates VEGF expression in HCC cells, possibly via PGs production. Selective inhibition of COX-2 may block HCC associated angiogenesis and thus provides a rational approach for treatment of this malignancy.     

Cytomegalovirus infection of the nasopharynx

This report describes a case of cytomegalovirus (CMV) infection of the nasopharynx. A 47 year old man presented with a nasopharyngeal mass of one month's duration. The patient had a history of pneumonia one month previously. Sinus computed tomography incidentally picked up a nasopharyngeal mass. The initial biopsy showed lymphoid hyperplasia. Repeated nasopharyngoscopy showed a prominent central nasopharyngeal mass without ulceration. Histology of the nasopharyngeal biopsy revealed several enlarged epithelial cells with characteristic CMV cytopathic changes. An immunohistochemical study, using a monoclonal IgG antibody against a CMV antigen, confirmed CMV infection. The patient's nasopharyngeal mass decreased in size gradually on follow up. To the best of our knowledge, this is the first reported case of CMV infection of the nasopharynx in the English literature. This disease entity should be considered in those patients presenting with nasopharyngeal mass, biopsy negative for malignancy, and no underlying immunosuppression or immunodeficiency.     

Congenital orbito-palpebral cyst in a case of Fraser syndrome

A seven-year-old girl was referred to our clinic with absent eyelids and a mass which was gradually increasing in size from the right orbit. The child was diagnosed to have Fraser syndrome (cryptophthalmos, abnormal genitalia, mental deficiency, renal agenesis and abnormal ears). On examination, there was cryptophthalmos and a cystic swelling arising from the right orbit. The cyst was removed. On gross examination, there was a posterior eyeball with normal optic nerve. Placed in the anterior part of the eyeball was a cyst measuring about 2 cm in diameter filled with a yellow-coloured fluid. The cavity of the eyeball was communicating with the cyst. The cyst wall was lined by a single layer of epithelium. The posterior eyeball had well developed sclera, choroid, retina and optic nerve. There have been many reports of cryptophthalmos in Fraser syndrome. The most common eye deformity described with cryptophthalmos is microphthalmia or anophthalmia. To the author's knowledge, there is one other report of cystic eyeball with cryptophthalmos in the literature. The cyst seems to be due to a surface ectodermal anomaly, rather than a neuro-ectodermal anomaly where there is failure of invagination of the primary optic cup during development. The cyst wall in those cases has inverted retinal elements. In our case, differentiation of retinal elements was present in the posterior eyeball. The abnormality seemed to lie in the derivatives of surface ectoderm, namely the eyelids and the anterior segment structures.     

Multislice computed tomography angiography in pediatric liver transplantation

BACKGROUND: Preoperative delineation of any vascular anomalies offers planning for possible alteration of surgical procedures, especially in pediatric recipients undergoing living-related liver transplantation. PURPOSE: We assess the efficacy of three-dimensional (3D) multislice computed tomography (CT) angiography in the hope of replacing conventional angiography as the pretransplant evaluation of the hepatic vascular system for potential recipients of liver transplantation. METHODS: 3D CT angiography was performed in 38 children with biliary atresia. Conventional angiography was also performed in the first 15 patients. Twelve patients underwent living-related liver transplantation. The findings on 3D CT angiography were compared with conventional angiography and operative findings. RESULTS: 3D CT angiography was successfully performed in 37 pediatric patients. All findings of 3D CT angiography on hepatic artery, portal vein, and inferior vena cava paralleled those of catheter angiography and operative findings. Four patients were unsuitable to receive living grafts because of pathologic insults of the hepatic artery (one patient) and the portal vein (three patients). Three patients were advised to undergo a venous graft for portal anastomoses. Eight patients demonstrated portosystemic shunts that may require closure. CONCLUSION: 3D CT angiography proves to be a better tool in the demonstration of the vascular system and identification of pathologic insults in pediatric patients. It is superior to conventional angiography because it is less invasive, more convenient, and more efficient in providing thorough preoperative information that would have a major impact on patient selection and surgical planning.