VEGF-A/VEGF-B/VEGF-C expressions in non-hereditary, non-metastatic phaeochromocytoma.

Vascular endothelial growth factor (VEGF) is important in pathogenesis of different cancers. The aim of this study is to investigate the relationships between different VEGFs and clinicopathological factors in patients with phaeochromocytomas. Twenty patients (10 men; 10 women) with non-hereditary, non-metastatic phaeochromocytomas were examined for VEGF mRNA expressions by polymerase chain reaction. The expressions were correlated with the clinical and pathological factors of the patients. In addition, mouse double minute 2 (MDM2) expression in these tumours were studied by immunohistochemistry. High expressions of VEGF-A, VEGF-B, and VEGF-C mRNA were detected in 11 (55%), 9 (45%), and 9 (45%) of the tumours respectively. High expression of VEGF-A in phaeochromocytomas was significantly correlated with the tumour size (p=0.025) but did not correlate with patients' age, gender, and tumour laterality. Besides, there was a trend of VEGF-A expression correlated with MDM2 expression (p=0.064). On the other hand, expressions of VEGF-B and VEGF-C were not significantly correlated with tumour size, patients' age, gender, tumour laterality, and MDM2 expression. In addition, high expressions of VEGF-B and VEGF-A were associated with increase of tumour size (p=0.042). Co-expression of different VEGFs did not correlate with MDM2 expression. To conclude, there is a role for VEGF-A/VEGF-B/VEGF-C in the pathogenesis of non-hereditary, non-metastatic phaeochromocytomas.

Patients' perceptions following laparoscopic sleeve gastrectomy: Sorry or satisfied?

BACKGROUND AND OBJECTIVES: Laparoscopic sleeve gastrectomy (LSG) currently accounts for 70.1% of weight-loss surgeries in Australia, according to the Bariatric Surgery Registry. There are limited qualitative studies examining Australian patients' experiences. The aim of this study was to explore patients' perspectives following LSG, providing information for shared decision making. METHOD: Twenty-two patients one, two or three years post-LSG were recruited randomly. Qualitative data were collected through in-depth telephone interviews, and responses were analysed inductively. RESULTS: Three global themes were identified: 1) normality, 2) control and 3) ambivalence, with eight organising sub-themes: 1) weight, 2) physical changes and daily living enhancements, 3) exercise, 4) emotional responses, 5) eating behaviour, 6) societal influences, 7) body image and 8) relationships. DISCUSSION: LSG is generally associated with high levels of patient satisfaction, with physical and psychosocial benefits beyond metabolic improvements. The decision to undergo this elective procedure should be made with an understanding of the significant and permanent effects it has on patients' lives.

MicroRNA 183 family profiles in pheochromocytomas are related to clinical parameters and SDHB expression.

This study aims to examine the expression profiles of the miR-183 cluster (miR-96/182/183) in pheochromocytoma. Pheochromocytoma tissues were prospectively collected from 50 patients with pheochromocytoma. Expression of miR-183 cluster members and SDHB protein expression were analyzed in these tissues by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. The expression of miR-183 cluster members in pheochromocytomas was correlated with the clinical and pathological parameters of these patients. The expression levels of miR-183 cluster members were predominantly downregulated or deleted in pheochromocytoma. Low expression or deletion of miR-96 was predominantly noted in younger patients with pheochromocytoma (<50 years, P=.01). Female patients in the study group showed marked deletion of miR-182 (P=.05). Deletion of the cluster was also associated with SDHB protein expression in pheochromocytoma. Moreover, patients with low miR-183 cluster expression had a slightly better survival rate when compared with patients with high expression. To conclude, the findings indicate a role for miR-183 cluster members in the pathogenesis and clinical progression of pheochromocytoma.

Management of bariatric patients beyond the scalpel.

BACKGROUND: Obesity management in general practice sometimes involves referral of patients for bariatric surgery. Integral to the success of long-term weight loss maintenance is supporting the patient's psychological, nutritional and exercise needs. OBJECTIVE: This article is written to equip general practitioners (GPs) to manage the comprehensive needs, before and after bariatric surgery, of patients who are obese. DISCUSSION: The number of patients undergoing bariatric surgery in Australia has increased significantly in the past few years. Pre-operative and postoperative management of this intervention presents a challenge for GPs. In this article we provide guidance around psychological, nutritional and exercise interventions, to equip GPs in managing patients who are obese. Access to allied health providers is not always available for patients, so this article is co-written with allied health colleagues who share their expertise as a resource for GPs.

Silent genetic alterations identified by targeted next-generation sequencing in pheochromocytoma/paraganglioma: A clinicopathological correlations.

AIMS: The goal of this pilot study was to develop a customized, cost-effective amplicon panel (Ampliseq) for target sequencing in a cohort of patients with sporadic phaeochromocytoma/paraganglioma. METHODS: Phaeochromocytoma/paragangliomas from 25 patients were analysed by targeted next-generation sequencing approach using an Ion Torrent PGM instrument. Primers for 15 target genes (NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, MEN1, KIF1Bß, EPAS1, CDKN2 & PHD2) were designed using ion ampliseq designer. Ion Reporter software and Ingenuity® Variant Analysis™ software (www.ingenuity.com/variants) from Ingenuity Systems were used to analysis these results. RESULTS: Overall, 713 variants were identified. The variants identified from the Ion Reporter ranged from 64 to 161 per patient. Single nucleotide variants (SNV) were the most common. Further annotation with the help of Ingenuity variant analysis revealed 29 of these 713variants were deletions. Of these, six variants were non-pathogenic and four were likely to be pathogenic. The remaining 19 variants were of uncertain significance. The most frequently altered gene in the cohort was KIF1B followed by NF1. Novel KIF1B pathogenic variant c.3375+1G>A was identified. The mutation was noted in a patient with clinically confirmed neurofibromatosis. Chromosome 1 showed the presence of maximum number of variants. CONCLUSIONS: Use of targeted next-generation sequencing is a sensitive method for the detecting genetic changes in patients with phaeochromocytoma/paraganglioma. The precise detection of these genetic changes helps in understanding the pathogenesis of these tumours.

A prospective observational study of the effect of critical illness on ultrastructural and microscopic morphology of duodenal mucosa.

OBJECTIVE: Disturbed intestinal barrier function due to 'leaky' tight junctions may cause secondary sepsis via paracellular translocation across the gut wall. Our objective was to describe the effects of critical illness on duodenal morphology and ultrastructure. DESIGN, SETTING AND PARTICIPANTS: Prospective observational study of 12 mechanically ventilated critically ill patients in an intensive care unit and 15 control participants in an outpatient endoscopy suite. INTERVENTION: We took six endoscopic biopsy samples of the duodenum from each participant for analysis by electron and light microscopy. MAIN OUTCOME MEASURES: Our primary outcome was tight junction morphology, examined with electron microscopy. Secondary outcomes were microvillus length and density, vascular endothelium morphology and mitochondrial density and morphology, examined with electron microscopy, and morphology examined with light microscopy. RESULTS: We observed no abnormalities of tight junction ultrastructure in either group. There was a tendency towards shorter microvilli in the critically ill group: mean length in critically ill patients, 1.17 µm (interquartile range [IQR], 1.05-1.60 µm) v mean length in control patients, 1.58 µm (IQR, 1.30-1.72 µm); P = 0.07. There was a tendency towards less dense microvilli in the critically ill group: mean density in critically ill patients, 7.29 microvilli/µm (IQR, 6.83-8.05 microvilli/µm) v mean density in control patients, 8.23 microvilli/µm (IQR, 7.34-9.11 microvilli/µm); P = 0.07. Vascular endothelium appeared normal in all critically ill patients and abnormal in one control participant. Abnormal mitochondrial morphology was noted in one critically ill patient and one control participant, and no differences were seen in mitochondrial density. Using light microscopy, we saw more apoptotic cells in the critically ill patients (P = 0.018), but villus height, crypt depth and lymphocyte density were normal. CONCLUSIONS: We did not detect any morphological abnormalities of duodenal tight junctions in critically ill patients. Our results should be interpreted with caution because of the small sample population, but our observations challenge the concept that paracellular translocation facilitates secondary sepsis.

Gallbladder torsion: a diagnostic challenge.

80-year-old female presented with clinical findings suggestive of acute cholecystitis. Intraoperatively we discovered a dusky gallbladder with gangrenous patches and gallbladder torsion with 270 degrees clockwise rotation along the longitudinal axis. Gallbladder torsion is a rare cause of acute cholecystitis with less than 500 cases published in the literature. Gallbladder torsion should be included in the list of differential diagnoses in patients suspected of having acute cholecystitis especially when there are inconsistencies between clinical features and imaging. It is worth noting that 3-dimensional reconstructed CT may be useful in preoperative diagnosis of gallbladder torsion.

Staged laparoscopic sleeve gastrectomy followed by Roux-en-Y gastric bypass for morbidly obese patients: a risk reduction strategy.

BACKGROUND: In our centre laparoscopic Roux-en-Y gastric bypass (LRYGBP) is the most effective weight loss surgical procedure performed. However, LRYGBP may be associated with higher risk of peri- and postoperative complications in contrast to a purely restrictive procedure to justify this procedure on all comers. Laparoscopic sleeve gastrectomy (LSG) as a staged procedure may be an alternate risk reduction strategy. The aim of this study is to report on the short-term outcomes of LSG, the effect on operative risk reduction and resolution of comorbidities. METHODS: A prospective review of 138 patients who underwent consecutive LSG from November 2004 to November 2006 was performed. Data were collected on all patients who attended the three to six monthly clinical follow-up and/or the patient questionnaire. Data collection included demographics, degree of weight reduction, postoperative complications, and changes in comorbidities. RESULTS: Median BMI was 50.60 kg/m(2) (33-82). Of the patients, 46.38% had a BMI >or=50 kg/m(2). The overall median postoperative excess weight loss (EWL) was 43.26%, 31.08% at 6 months, 54.50% at 12 months, 51.47% at 18 months and 46.05% at 24 months. Of the patients, 39% had resolution of type 2 diabetes mellitus, 48% had resolution of dyslipidemia, 29% in hypertension, 52% in obstructive sleep apnea. Complication rate was 5.07% and four patients needed further surgical intervention. The mortality rate was zero. CONCLUSION: LSG does minimize postoperative complication rates significantly on high-risk patients and achieves effective short-term weight loss with resolutions in comorbidities. Additional studies are required to evaluate LSG as a stand-lone procedure.

Laparoscopic inguinal hernia repair without mesh fixation, early results of a large randomised clinical trial.

BACKGROUND: A new persistent groin pain is reported by a significant number of patients following laparoscopic totally extraperitoneal hernia repair (TEP). Mesh fixation has been implicated as a possible cause, but is widely considered essential for mesh stabilization and early recurrence prevention. This study investigates whether any association exists between mesh fixation by metal tacks and the incidence of new groin pain or early hernia recurrence. METHODS: A prospective multicenter double-blinded randomised trial was conducted between December 2004 and January 2006. Standardized TEP repair was performed with a rectangular 10 x 15cm polypropylene mesh. Hernia were randomized to either mesh fixation by metal tacks or left entirely unfixated. Clinical review by physical examination was performed by a separate blinded surgeon after a minimum of six months, with another review planned after two years. The incidence of new groin pain and recurrence were compared. RESULTS: Five hundred herniae in 360 patients were entered into the study. At the first wave of clinical follow-up (median eight, range 6-13 postoperative months) a new pain was reported by 38 versus 23% (p = 0.003), occurring at least once a week in 22 versus 15% (p = 0.049), or several times per week in 16 versus 8% (p = 0.009) for fixated versus unfixated repairs, respectively. Patients with bilateral repairs were five times more likely to report the unfixated side being more comfortable (p = 0.006). There was one recurrence in the fixated group (1/247) whilst none have yet occurred in the unfixated group. Fixation increased operative costs by approximately 375 AUD. CONCLUSION: Mesh fixation in TEP is associated with increased operative cost and chronic pain but no difference in the risk of hernia recurrence at six months was observed.

Laparoscopic gastric resection for benign and malignant conditions: lessons learned from 35 consecutive cases.

INTRODUCTION: Despite significant advances in laparoscopy, gastric surgery is still generally carried out by conventional open techniques. The aim of the study was to report the short- and medium-term outcomes of gastric surgery when carried out laparoscopically for a variety of benign and malignant conditions. METHODS: A retrospective review was carried out for all patients who underwent a laparoscopic gastric resection between January 2000 and September 2006. Follow up was carried out at the private consulting rooms and by telephone interview. RESULTS: Thirty-five consecutive laparoscopic gastric resection were carried out in 31 patients for a variety of benign lesions, six early gastric cancer and 13 adenocarcinomas. The totally intracorporeal laparoscopic procedures included four total, eight distal and 21 partial gastrectomies. There were two open conversions (6%). There was one in-hospital mortality (3%) and one non-fatal anastomotic leak. Median operative duration and length of stay were 75, 205 and 252 min and 5, 6.5 and 8 days for laparoscopic partial, distal and total gastrectomy, respectively. After malignant resections, there were six recurrences; however, 15 patients remained disease-free at up to 60 months follow up. CONCLUSION: Laparoscopic gastric resection is feasible with good short- and medium-term results and may be an appropriate treatment option in selected cases.

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.

A comparative study of the inhibitory effects of interleukin-1 receptor antagonist following administration as a recombinant protein or by gene transfer.

Anakinra, the recombinant form of IL-1 receptor antagonist (IL-1Ra), has been approved for clinical use in the treatment of rheumatoid arthritis as the drug Kineret trade mark, but it must be administered daily by subcutaneous injection. Gene transfer may offer a more effective means of delivery. In this study, using prostaglandin E2 production as a measure of stimulation, we quantitatively compared the ability of anakinra, as well as that of IL-1Ra delivered by gene transfer, to inhibit the biologic actions of IL-1beta. Human synovial fibroblast cultures were incubated with a range of doses of anakinra or HIG-82 cells genetically modified to constitutively express IL-1Ra. The cultures were then challenged with recombinant human IL-1beta either simultaneously with addition of the source of IL-1Ra or 24 hours later. In a similar manner, the potencies of the two sources of IL-1Ra were compared when human synovial fibroblasts were challenged with IL-1beta produced constitutively by genetically modified cells. No significant difference in inhibitory activity was observed between recombinant protein and IL-1Ra provided by the genetically modified cells, under static culture conditions, even following incubation for 4 days. However, under culture conditions that provided progressive dilution of the culture media, striking differences between these methods of protein delivery became readily apparent. Constitutive synthesis of IL-1Ra by the genetically modified cells provided sustained or increased protection from IL-1 stimulation over time, whereas the recombinant protein became progressively less effective. This was particularly evident under conditions of continuous IL-1beta synthesis.

The effect of metallic radial head arthroplasty on radiocapitellar joint contact area.

OBJECTIVE: This study determined the effect of metallic radial head arthroplasty on radiocapitellar joint contact area. DESIGN: The contact area of eight intact radiocapitellar joints was assessed during simulated compressive loading. Subsequently, the same experiments were repeated after reconstruction with three different radial head implant sizes. BACKGROUND: There has been an increasing use of metal radial head implants relative to silicone implants. However, the contact characteristics with the metal reconstruction have not been determined. METHODS: A 100 N compressive load was applied to the radiocapitellar joint at three different flexion angles for the native joint and three different sizes of a metal head implant. An impression material was employed to quantify joint contact area. RESULTS: Following metallic radial head arthroplasty, the contact area decreased by approximately two-thirds relative to the native radiocapitellar joint (P<0.001). Smaller implant sizes resulted in slightly larger contact areas (P<0.05). In addition, contact area decreased as joint flexion angle increased (P<0.04). CONCLUSIONS: Selection of radial head implant size is likely not a significant factor with regard to contact area mechanics of the radiocapitellar articulation. RELEVANCE: The effect of radial head implant size on the contact area produced with the native capitellum is not known. This study shows that the design or selection of a metallic radial head implant from the viewpoint of size is likely not an important factor with regard to minimizing joint contact stresses.