Stress fracture of the ulna associated with bisphosphonate therapy and use of walking aid.

We report a case of a stress fracture of the ulna secondary to long-term bisphosphonate therapy and walking cane. Physicians need to have a high index of suspicion of stress fractures occurring in patients complaining of chronic upper limb pain if they are on bisphosphonate therapy and are using walking aids. Stress fractures of the upper extremities are rare and are usually associated with athletes; however, a few recent case reports have shown an association between stress fractures of the upper extremities and the use of walking aids. The association between increased incidence of upper extremity stress fractures and the use of both bisphosphonates and walking aids in patients has not been well studied, with only one previously reported case. Here, we report a case of a complete stress fracture of the ulna in a 77-year-old female, premorbidly ambulant with walking cane, on long-term bisphosphonates without any pre-existing medical conditions which could result in secondary causes of bone loss. Investigations did not reveal any causes of pathological fracture. This fracture is attributed to the use of long-term bisphosphonate therapy in conjunction with the use of a walking cane. This case highlights the importance of entertaining the possibility of such fractures occurring in any patient who is on bisphosphonate therapy presenting with stress fractures of the upper extremity.

Inhibition of angiogenic and non-angiogenic targets by sorafenib in renal cell carcinoma (RCC) in a RCC xenograft model.

BACKGROUND: It is widely recognised that sorafenib inhibits a range of molecular targets in renal cell carcinoma (RCC). In this study, we aim to use patient-derived RCC xenografts to delineate the angiogenic and non-angiogenic molecular targets of sorafenib therapy for advanced RCC (aRCC). METHODS: We successfully generated three patient RCC-derived xenografts in severe combined immunodeficient mice, consisting of three different RCC histological subtypes: conventional clear cell, poorly differentiated clear cell RCC with sarcomatoid changes, and papillary RCC. This study also used clear cell RCC cells (786-0/EV) harbouring mutant VHL to investigate the clonogenic survival of cells transfected with survivin sense and antisense oligonucleotides. RESULTS: All three xenografts retain their original histological characteristics. We reported that sorafenib inhibited all three RCC xenograft lines regardless of histological subtypes in a dose-dependant manner. Sorafenib-induced growth suppression was associated with not only inhibition of angiogenic targets p-PDGFR-ß, p-VEGFR-2, and their downstream signalling pathways p-Akt and p-ERK, cell cycle, and anti-apoptotic proteins that include cyclin D1, cyclin B1, and survivin but also upregulation of proapoptotic Bim. Survivin knockdown by survivin-specific antisense-oligonucleotides inhibited colony formation and induced cell death in clear cell RCC cells. CONCLUSION: This study has shed light on the molecular mechanisms of sorafenib in RCC. Inhibition of non-angiogenic molecules by sorafenib could contribute in part to its anti-tumour activities observed in vivo, in addition to its anti-angiogenic effects.

Nature of gram-negative rod antibiotic resistance during antibiotic rotation.

PURPOSE: The aim of this study was to characterize the evolution of gram-negative antibiotic resistance during a study of empiric antibiotic rotation. METHODS: We showed previously that quarterly rotation of a single antibiotic class is inferior to cycling two antibiotics per quarter for empiric treatment of gram-negative rod (GNR) infections, as evidenced by increased incidence of antibiotic-resistant GNR (rGNR) infections. Resistance patterns were examined by quantifying GNRs resistant to one or more of the following drug classes: Aminoglycosides, cephalosporins, carbapenems, fluoroquinolones, or piperacillin-tazobactam. For all rGNR isolates, the mean number of antibiotic classes to which an organism was resistant was calculated per quarter, as was the number of rGNR species. RESULTS: Single-antibiotic rotation (SAR) was associated with significant increases in the incidence of piperacillin-tazobactam (p < 0.0005) and cephalosporin (p = 0.003) resistance, reaching nearly 25% and 30% of rGNR isolates respectively, most notably during the quarter of designated cephalosporin use (VI). Multi-drug resistance emerged over time; resistant classes/resistant GNR isolates ranged from 1.2 in the dual-antibiotic rotation (DAR) to 1.9 in the SAR period (p = 0.02). Resistance was evident in an increasing number of unique GNR species. On average, 1.3 species were isolated per month in the DAR period and 3.0/month in the SAR period (p = 0.004), but proportionally, no single GNR species became significantly more resistant across time. Compared to only 5.8% in the DAR period, 29% noncompliance was observed in the SAR, with a six-fold increase in the use of nonscheduled empiric antibiotics due to the presence of an organism resistant to the scheduled rotation drug. CONCLUSIONS: A single-antibiotic rotation is associated with increased incidence and heterogeneity of resistant GNR isolates, as well as increased multiple-drug-class resistance. The attenuation of resistance observed in the single-antibiotic rotation may reflect the effect of unintended antibiotic heterogeneity driven by increasing resistance to the antibiotic class recommended for use each quarter. This suggests that reliance on a single antibiotic class for empiric treatment of GNR infection exerts sufficient pressure within the environment to encourage the development of diversified resistance, as well as cross-resistance over antibiotic classes, thus narrowing the availability of effective antibiotic treatment.

A nutrition support team led by general surgeons decreases inappropriate use of total parenteral nutrition on a surgical service.

The purpose of this study was to decrease the number of inappropriate orders for total parenteral nutrition (TPN) in surgical patients. From February 1999 through November 2000 and between July 2001 and June 2002, the surgeon-guided adult nutrition support team (NST) at a university hospital monitored new TPN orders for appropriateness and specific indication. In April 1999, the NST was given authority to discontinue inappropriate TPN orders. Indications, based on the American Society for Parenteral and Enteral Nutrition (ASPEN) standards, included short gut, severe pancreatitis, severe malnutrition/catabolism with inability to enterally feed > or =5 days, inability to enterally feed >50 per cent of nutritional needs > or =9 days, enterocutaneous fistula, intra-abdominal leak, bowel obstruction, chylothorax, ischemic bowel, hemodynamic instability, massive gastrointestinal bleed, and lack of abdominal wall integrity. The number of inappropriate TPN orders declined from 62/194 (32.0%) in the first 11 months of the study to 22/168 (13.1%) in the second 11 months (P < 0.0001). This number further declined to 17/215 (7.9%) in the final 12 months of data collection, but compared to the second 11 months, this decrease was not statistically significant (P = 0.1347). The involvement of a surgical NST was associated with a reduction in inappropriate TPN orders without a change in overall use.

Clinical experience and results of ESWL treatment for 3,093 urinary calculi with the Storz Modulith SL 20 lithotripter at the Singapore general hospital.

We study the outcome of 2,700 patients treated for 3,093 urinary calculi over a period of 60 months. All patients underwent Extracorporeal Shock Wave Lithotripsy (ESWL) treatment using the Storz Modulith SL20, predominantly on an outpatient basis (99.9% using intravenous pethidine for analgesia). The treatment outcome of 1,666 renal calculi and 1,427 ureteric calculi were analysed and stratified according to size and site. Follow-up status at 3 months was available for 91.8% of patients. For renal calculi, the overall success rate was 81% (re-treatment rate 29.7%). The majority of failures were stones larger than 2 cm and those situated in the lower pole of the renal calyces. The overall success rate for ureteric calculi is 85% with similar clearance rates throughout the ureter (re-treatment rate 22.8%). Failures were predominantly with stones larger than 2 cm. For the entire series, the morbidity rate requiring hospital admission was 2.9%, there was no mortality. The commonest cause for admission was for pain control (1.8%). To our knowledge, our experience with this lithotriptor is the largest to date. We have demonstrated that ESWL with Storz Modulith SL20 is safe, well tolerated and highly effective for the treatment of urolithiasis.

Calyceal diverticula. Ureteroscopic management.

In selected cases, RIRS management of calyceal diverticula and its related problems has been shown to be more efficacious than ESWL monotherapy and avoids the potential complications and discomfort of percutaneous and laparoscopic procedures. The advent of the Holmium laser energy source, with innovations such as the flexible ureteroscope and the tipless stone basket, have expanded the role of RIRS in the management of calyceal diverticula and associated problems. Presently, RIRS is the initial treatment choice for the management of low to moderate stone burdens that are contained in calyceal diverticula or trapped behind any narrowed intrarenal segment (e.g., infundibular stenosis). If repair of the stenotic segment is not successful, thereby excluding stone treatment, then under the same anesthesia, the patient undergoes a percutaneous antegrade renal surgery. The authors feel that the percutaneous approach as a first choice is more suitable for posteriorly located diverticula with a large stone burden. In selected cases of anteriorly located diverticula with large stone burdens, the laparoscopic approach is more expedient.

Simultaneous bilateral simple nephrectomy.

Bilateral simultaneous nephrectomy is a rare procedure usually performed for end-stage renal disease, most often because of persistent hypertension after renal transplantation. Four trocars generally are inserted, with a lower abdominal and a subcostal port being used by the surgeon. An intra-abdominal pressure of 8 to 10 mm Hg is used during the procedure. The first kidney is left in situ while the other one is being dissected. Unless there is infection or malignancy, a retrieval sac is not used. In our series of 13 cases, the operating times ranged from 240 to 390 minutes (mean 320 minutes), and the mean 125 mL. Surgical discharges criteria usually were met on postoperative day 1 or 2. Laparoscopic bilateral nephrectomy in a single session is feasible in nearly all properly selected cases, even in patients with previous abdominal surgery or peritoneal dialysis. The operation takes longer than open surgery and may have a higher complication rate, but recovery is faster.

The role of the bladder tumour antigen test in the management of gross haematuria.

BACKGROUND: The bladder tumour antigen (BTA) test has been found to be more sensitive than urine cytology for the detection of recurrent bladder cancer. We chose to evaluate the role of the bladder tumour antigen test in the management of gross haematuria on initial presentation. METHODS: A prospective analysis over a 3-month period of consecutive cases of gross haematuria was conducted. Routine investigations including intravenous urogram, flexible cystoscopy, urine cytology testing and BTA testing were performed. Results were correlated with the final diagnosis, and also with histology and tumour stage in the cases of malignant outcome. RESULTS: The prevalence of malignancy in our series was 25.5%. Sensitivity of the BTA test was 67% and specificity 66%. This was compared to cytology which yielded a sensitivity of 66% and specificity of 100%. There were 12 cases of falsely positive results on BTA testing, giving a positive predictive value of 40%. Four cases of falsely negative results were all from superficial tumours. CONCLUSION: In view of its poor sensitivity and positive predictive value, the BTA test has a limited role in the initial management of gross haematuria.

Vaginal bleeding as a presenting symptom of synovial sarcoma.

A case is reported of a woman who presented with bleeding from a vaginal extension of a synovial sarcoma. The patient was unaware of the primary tumor in the left thigh and histologically, the tumor resembled a carcinosarcoma. Awareness of the physical and radiologic findings allowed the correct pathologic diagnosis to be made. The manner of presentation of the tumor is believed to be unique.