Is primary endoscopic puncture of ureterocele a long-term effective procedure?

Background/Purpose: For more than a decade, endoscopic puncture of ureterocele has been recommended as an initial and, in the majority of the patients, as a definitive procedure. This study evaluates the long-term effectiveness of primary endoscopic puncture of ureterocele. Methods: Over the last 18 years (1984 through 2001), 52 patients (median age 3 months) underwent primary endoscopic puncture of ureterocele. The median follow-up was 9 years (6 months to 18 years). Antenatal ultrasound scan detected hydronephrosis and led to the postnatal diagnosis of ureterocele in 12 (23%) children, whereas in the remaining 40 (77%) children the diagnosis was made on investigation for urinary tract infection (UTI). The ureterocele presented as a part of renal duplication in 48 (92%) patients and a single system in 4 (8%). Forty-four (92%) of the patients with duplication presented with non- or poorly functioning upper poles. Vesicoureteric reflux (VUR) was seen in the lower moiety of the ipsilateral kidney in 31 and in 18 of the contralateral kidney comprising 49 renal refluxing units (RRU). Results: Complete decompression of the ureterocele was achieved in 48 (92%) patients after the first endoscopic puncture. Four (8%) patients required a second puncture of ureterocele. Nine (17%) of the 52 patients underwent nephrectomy for a nonfunctioning kidney. Ten (19%) patients required upper pole partial nephrectomy owing to nonfunctioning upper pole. Twenty-nine (59%) of the 49 RRU showed spontaneous resolution of VUR. Sixteen (33%) RRU underwent endoscopic correction of VUR. One required ureteric reimplantation. The remaining 4 (8%) are maintained on prophylactic antibiotics. Five (10%) patients had VUR in the upper pole moieties after ureterocele puncture. Conclusions: Our data suggest that primary endoscopic puncture of ureteroceles is a simple, long-term, effective, and safe procedure avoiding complete reconstruction in the majority of the patients. J Pediatr Surg 38:116-119.     

Hypercalciuria in patients with CLCN5 mutations

Hypercalciuria is regarded as a characteristic symptom of Dent disease, an X-linked recessive tubulopathy characterized by low molecular weight (LMW) proteinuria, nephrocalcinosis/nephrolithiasis, and progressive renal failure due to mutations in the CLCN5 gene. As the presence of hypercalciuria may affect the decision to consider a CLCN5 mutation in the differential diagnosis, the phenotypic spectrum and the relative frequency of hypercalciuria in patients with CLCN5 mutations was determined. We assessed renal calcium excretion in 34 male patients with proven CLCN5 mutations, who had been referred because of LMW proteinuria and at least one additional symptom of Dent disease. Hypercalciuria was defined as renal calcium excretion exceeding 0.1 mmol/kg per day. Data obtained were compared with all series of CLCN5-positive patients identified by a systematic literature survey. In 7 of our 19 families, at least 1 affected male had normal calcium excretion. Hypercalciuria was observed in 22 of 31 patients tested (71%) compared to 85 of 90 (94.4%) in series from Europe and North America and 74.4% from Japan. LMW proteinuria was present in all CLCN5-positive patients; 25% of the patients in European and North American series, 45% of the Japanese, and 41% in the present series had only two of the four principal symptoms of Dent disease. Therefore, a CLCN5 mutation should be considered irrespective of the presence of hypercalciuria in a patient with LMW proteinuria and one additional symptom of Dent disease.     

Impact of Prostate-specific Antigen (PSA) Screening Trials and Revised PSA Screening Guidelines on Rates of Prostate Biopsy and Postbiopsy Complications

Background

Prostate biopsy and postbiopsy complications represent important risks of prostate-specific antigen (PSA) screening. Although landmark randomized trials and updated guidelines have challenged routine PSA screening, it is unclear whether these publications have affected rates of biopsy or postbiopsy complications.

Clusterin knockdown using the antisense oligonucleotide OGX-011 re-sensitizes docetaxel-refractory prostate cancer PC-3 cells to chemotherapy

OBJECTIVES

To characterize changes in secretory clusterin (sCLU) expression in prostate cancer cells after treatment with docetaxel and to determine whether sCLU knockdown can re‐introduce chemosensitivity in a docetaxel‐resistant, androgen‐independent human prostate cancer model.

PATIENTS AND METHODS

A tissue microarray was constructed for 84 radical prostatectomy (RP) specimens from a multicentre Phase II trial of neoadjuvant combined androgen ablation and docetaxel (CUOG‐P01a) and assessed for changes in the expression of the cytoprotective chaperone sCLU. The human prostate cancer cell line PC‐3 was repeatedly exposed to docetaxel chemotherapy in vitro, and a docetaxel‐resistant cell subline (PC‐3dR) was developed and analysed.

RESULTS

sCLU levels were significantly higher in RP specimens treated with neoadjuvant combined androgen ablation and docetaxel than in untreated specimens. Similarly, sCLU expression increased 2.5‐fold in the newly developed docetaxel‐refractory PC‐3dR cell line compared with parental PC‐3 cells. There was a dose‐dependent and sequence‐specific decrease in sCLU levels in PC‐3dR cells using OGX‐011, an antisense oligonucleotide against human sCLU. OGX‐011 and small‐interference RNA both chemosensitized PC‐3dR cells to docetaxel and mitoxantrone in vitro and apoptotic rates in PC‐3dR cells were significantly increased when OGX‐011 was combined with docetaxel. In vivo, growth of PC‐3dR xenografts in nude mice was synergistically inhibited by OGX‐011 combined with paclitaxel or mitoxantrone (by 76% and 44% compared with their mismatch controls, respectively).

CONCLUSION

The present findings indicate that targeted knockdown of sCLU enhances the effects of cytotoxic chemotherapy in docetaxel‐refractory cells, and provide preclinical proof of principle for clinical trials testing OGX‐011 in second‐line chemotherapy regimens for patients with docetaxel‐refractory prostate cancer.     

Value of Laparoscopic Appendectomy in the Elderly Patient

Background  Acute appendicitis (AA) in elderly patients (60 years of age and older) is a challenging problem associated with significant morbidity and mortality when perforation is present. We hypothesized that laparoscopic appendectomy (LA) would enable an earlier correct diagnosis and have advantages in elderly patients. Methods  We performed a retrospective review of patients who underwent laparoscopic appendectomy for suspected AA. Data of elderly patients were compared to data of younger patients (18 to <60 years of age). Results  Fifty-four LA were performed in elderly patients and 423 in younger patients. Patients over the age of 60 years had more co-morbidities and required more frequent use of anticoagulants. Preoperative imaging (ultrasound or computerized tomography) was significantly more frequent in elderly patients (36% versus 15%), and was associated with a higher rate of confirmation of acute appendicitis (78% versus 55%), which allowed a decrease in the rate of negative surgical explorations to 4.1% in elderly patients compared to 10.2% in younger patients. Complicated appendicitis and conversions were more frequent in the elderly patients. This resulted in prolonged operative time and longer hospital stay for this group. The overall complication rate was equivalent in the two groups, without differences in the occurrence either of infectious complications or of complications related to surgical site. There were no deaths following appendectomy in our series. Conclusions  Laparoscopic appendectomy is safe in the elderly population and is not associated with any increase in morbidity. The high incidence of complicated appendicitis in elderly patients affects operative time and length of hospital stay following laparoscopic appendectomy, and it can also lead to an increased rate of conversion to an open procedure. Use of preoperative abdominal computerized tomography scan is mandatory in elderly patients to provide an early diagnosis and to decrease unnecessary surgical exploration when acute appendicitis is suspected.     

Multiple arterial revascularization using the tangential K-graft technique

The tangential K graft is a comfortable surgical technique aiming to increase cardiac surgeons' versatility in performing multiple arterial grafting using only two arterial conduits. One end of the free graft--either the right internal thoracic artery (RITA) or the radial artery (RA)--is attached to a marginal circumflex branch. Its other end is anastomosed end to side to a diagonal branch. After the left internal thoracic artery (LITA) is attached to the left anterior descending coronary artery, a wide-open side-to-side LITA to free RITA or RA anastomosis--resembling the letter K--is constructed.     

A novel bioartificial liver with culture of porcine hepatocyte aggregates under simulated microgravity

An extracorporeal bioartificial liver device could provide vital support to patients suffering from acute liver failure. We designed a novel, customized bioreactor for use as a bioartificial liver (patent pending). The Innsbruck Bioartificial Liver (IBAL) contains aggregates of porcine hepatocytes grown under simulated microgravity. The culture vessel rotates around its longitudinal axis and is perfused by two independent circuits. The circuit responsible for exchange of plasma components with the patient consists of a dialysis tube winding spirally around the internal wall of the culture vessel. IBAL was evaluated in vitro. Viability tests showed sufficient viability of hepatocytes for up to 10 days. Cytologic examination of samples from the bioreactor showed liver cell aggregates. These were also examined by electron microscopy. A number of biochemical parameters were analyzed. In conclusion, cell culture is possible for at least 10 days in the IBAL system, organoid hepatocyte aggregates are formed and synthetic activity of the hepatocytes was demonstrated.     

Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station.

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01). CONCLUSIONS: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.     

Transplantation of the RPE in AMD

The retinal pigment epithelium (RPE) maintains retinal function as the metabolic gatekeeper between photoreceptors (PRs) and the choriocapillaries. The RPE and Bruch's membrane (BM) suffer cumulative damage over lifetime, which is thought to induce age-related macular degeneration (AMD) in susceptible individuals. Unlike palliative pharmacologic treatments, replacement of the RPE has a curative potential for AMD. This article reviews mechanisms leading to RPE dysfunction in aging and AMD, laboratory studies on RPE transplantation, and surgical techniques used in AMD patients. Future strategies using ex vivo steps prior to transplantation, BM prosthetics, and stem cell applications are discussed. The functional peculiarity of the macular region, epigenetic phenomena leading to an age-related shift in protein expression, along with the accumulation of lipofuscin may affect the metabolism in the central RPE. Thickening of BM with age decreases its hydraulic conductivity. Drusen are deposits of extracellular material and formed in part by activation of the alternative complement pathway in individuals carrying a mutant allele of complement factor H. AMD likely represents an umbrella term for a disease entity with multifactorial etiology and manifestations. Presently, a slow progressing (dry) non-neovascular atrophic form and a rapidly blinding neovascular (wet) form are discerned. No therapy is currently available for the former, while RPE transplantation and promising (albeit non-causal) anti-angiogenic therapies are available for the latter. The potential of RPE transplantation was demonstrated in animal models. Rejection of allogeneic homologous transplants in patients focused further studies on autologous sources. In vitro studies elucidated cell adhesion and wound healing mechanisms on aged human BM. Currently, autologous RPE, harvested from the midperiphery, is being transplanted as a cell suspension or a patch of RPE and choroid in AMD patients. These techniques have been evaluated from several groups. Autologous RPE transplants may have the disadvantage of carrying the same genetic information that may have led to AMD manifestation. An intermittent culturing step would allow for in vitro therapy of the RPE, its rejuvenation and prosthesis of BM to improve the success RPE transplants. Recent advances in stem cell biology when combined with lessons learned from studies of RPE transplantation are intriguing future therapeutic modalities for AMD patients.