Prospective evaluation of a virtual urology outpatient clinic.

BACKGROUND: Outpatient department (OPD) clinics account for a significant proportion of healthcare expenditure. We report on a pilot study of a virtual outpatient clinic (VC) for urology patients as an alternative to a general urology clinic review. AIMS: The study aims to assess the safety and cost-effectiveness of a virtual clinic as an alternative to general OPD review. METHODS: A prospective study performed between March 2015 and December 2015 investigated the effectiveness of a VC in our institution. Eligible patients were recruited from general urology outpatient visits, from medical team members and from general practitioners (GP). Data recorded on each VC review included patient demographics, indication for referral to VC, outcome of VC and method of communication with the patient and their GP after the VC. RESULTS: Three hundred eighty-five patients were registered for the VC. Indications for referral included review of imaging results (n = 136), doctor or patient query (n = 112) and review of laboratory results (n = 67). Outcomes after VC review included general OPD follow-up (n = 134), discharge from urology care (n = 39), referral for urological intervention (n = 29) and referral for radiological investigation (n = 23). VC review prevented 217 OPD clinic visits, saved €17,360 and provided a failsafe mechanism for reviewing investigation results. Two patients booked for OPD review following VC review did not receive appointments. CONCLUSIONS: Virtual clinic is a safe and cost-effective alternative to general OPD review in appropriately selected patients.

The effect of Rapid Access Prostate Clinics on the outcomes of Gleason 7 prostate cancer: does earlier diagnosis lead to better outcomes?

INTRODUCTION: Rapid Access Prostate Clinics (RAPC) were introduced in Ireland by the National Cancer Control Programme bringing about expedited referral pathways and increased detection rates of prostate cancer. Lower Gleason (G) grade at diagnosis due to RAPC has been previously reported but grade at prostatectomy has not been assessed. The aim of this study was to assess the impact of RAPC on the outcomes of patients with G7 disease on radical prostatectomy (RP). METHODS: A retrospective analysis was carried out of all RPs performed over a 9-year period (2006-2014). Outcomes for G7 prostatectomies were compared before and after the introduction of the RAPC, with a further sub-analysis of G4 + 3 versus G3 + 4. The primary outcome was biochemical recurrence (BCR). Other outcomes were adjuvant/salvage radiotherapy, extra prostatic extension, positive surgical margins, seminal vesicle involvement and tumour stage. RESULTS: In total, 240 RPs were performed with 167 cases graded G7 (70 graded G4 + 3 and 97 graded G3 + 4). Since the introduction of RAPC the proportion of G4 + 3 compared to G3 + 4 has increased from 37.9 to 42%. There was no statistical difference in outcomes for G4 + 3 treated before and after the introduction of RAPC. G4 + 3 was associated with higher rates of BCR (24.4 vs. 0%, p < 0.0001, radiotherapy (41.1 vs. 4.8%, p < 0.0001) and worse histological features than G3 + 4. CONCLUSION: Despite the benefits in diagnosis of prostate cancer brought about by RAPC in Ireland, this has not translated to a lower grade for surgically treated patients. There has been no improvement in outcomes especially for higher grade G4 + 3 disease.

A Narrative Review on the Pathophysiology and Management for Radiation Cystitis.

Radiation cystitis is a recognised complication of pelvic radiotherapy. Incidence of radiation cystitis ranges from 23 to 80% and the incidence of severe haematuria ranges from 5 to 8%. High quality data on management strategies for radiation cystitis is sparse. Treatment modalities are subclassified into systemic therapies, intravesical therapies, and hyperbaric oxygen and interventional procedures. Short-term cure rates range from 76 to 95% for hyperbaric oxygen therapy and interventional procedures. Adverse effects of these treatment strategies are acceptable. Ultimately, most patients require multimodal treatment for curative purposes. Large randomised trials exploring emergent management strategies are required in order to strengthen evidence-based treatment strategies. Urologists encounter radiation cystitis commonly and should be familiar with diagnostic modalities and treatment strategies.

Peri-operative management in urinary diversion surgery: A time for change?

INTRODUCTION: Bowel preparation was established as part of the pre-operative course for patients undergoing ileal conduit formation since the late 1970's. Rationales for its use include reduction in infection and wound complications, technically easier anastomosis and earlier return to bowel function. However, recent reports have challenged this practice. Traditionally antibiotics were also administered for several days prior to surgery with the assumption that bacterial load was reduced. Modification of antibiotic protocols resulted from evidence-based findings. Furthermore, publications emphasizing the benefit of Enhanced Recovery Protocols/Programmes (ERP) have become contemporary. METHODS: An online multiple-choice questionnaire (via Monkey Survey) was administered to all consultant urologists in Ireland. This national cross-sectional study evaluated the use of bowel preparation and antibiotic prophylaxis prior to urinary diversion. In addition, we also assessed consultant urologists' awareness of ERP and their views on the introduction and implementation of such a national program. RESULTS: Of the 41 consultant urologists surveyed, 80.4% (n = 33) responded. 63.6% routinely used bowel preparation. Klean Prep was the most commonly used bowel preparation. 80.9% of urologists admit their patient's one-day pre-operatively for bowel preparation, with 87.8% using antibiotic prophylaxis at anesthesia induction, and 18.1% continuing the antibiotics for 24-48 h post-operatively. Although 74% of consultants are aware of ERP, only 66.6% are in favor of their national implementation. CONCLUSION: The majority of Irish urologists use bowel preparation prior to ileal conduit formation. Substantial recent evidence has emerged showing no difference in infective complications or anastomotic leakage when bowel preparation was not used. National guidelines would be beneficial regarding the use of bowel preparation, antibiotic prophylaxis and ERP for urinary diversion surgery.

Two hit hypothesis: an unusual complication following supra-pubic catheter insertion.

Osteomyelitis is an inflammation of the bone caused by an infection. Though bone is normally resistant to bacterial infection, events including trauma, presence of foreign bodies including prosthesis can act as a nidus for infection. Osteomyelitis is a rare but recognised complication of radiotherapy. Osteomyelitis of the pubis has scarcely been reported as a complication following urological procedures- prostatectomy, sling surgery and catheterisation. We report a rare complication of a gentleman post radiotherapy presenting with delayed osteomyelitis of the pubis following supra-pubic catheterisation.

Incidentalology: A developing urological sub-specialty.

OBJECTIVE: To identify the incidence and features of significant incidental findings discussed at our departmental multidisciplinary team meeting (MDM). The improved quality of radiological imaging has resulted in increased rates of incidental findings. Although some may be trivial, many have clinical significance and early diagnosis and treatment may be beneficial. METHODS: A retrospective analysis was performed of all cases discussed at the MDM between January 2012 and February 2013. Cases were divided into two groups--Group 1 consisted of patients whose initial imaging was performed for a urological presentation which resulted in a synchronous finding; Group 2 consisted of patients who were referred with a synchronous urological finding for discussion following investigation of an initial benign urological condition or a non-urological condition. RESULTS: 696 patients were discussed at 53 MDMs. 109 (15.7%) patients had incidental findings. 61 (56%) of these were in Group 1. 16 (26.2%) were synchronous malignant diagnoses, 25 (41%) were benign and 20 (32.8%) were indeterminate. 48 (44%) patients in Group 2 - 40 (83.3%) were renal in origin and 30 (75%) of these proceeded to surgery. The median tumour size was 3.2 cm (Range: 1.2 cm-10 cm). One patient had radio-frequency ablation. Two were referred for palliative care. Seven patients are under ongoing surveillance--the median size of these lesions is 3.6 cm (Range: 2.1 cm-8.3 cm). CONCLUSION: A substantial workload is generated from the investigation of incidental findings discussed at MDM--these now represent the majority of the caseload for renal cancer surgery.

Double trouble--ureteric obstruction due to bilateral urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) represents -5% of all urothelial carcinomas. Synchronous bilateral tumors are extremely rare with only 19 reports in the literature. Haematuria is the main presenting complaint. We report a case of synchronous bilateral tumors of the ureters in a gentleman with frank haematuria treated with staged aggressive resection.

A novel case of laparoscopic ureterolithotomy in a partial duplex ureteric collecting system: can open procedures still be justified in the minimally invasive era?

BACKGROUND: Impacted ureteric stones can pose a treatment challenge due to the high level of failure of ESWL and endourological approaches. Laparoscopic ureterolithotomy can provide a safe and successful alternative to these and open, invasive procedures. METHODS: Interval laparoscopic ureterolithtomy was carried out following placement of a percutaneous nephrostomy. This was performed through an trans-peritoneal approach with the ureterotomy closed by intracorporeal suturing and placement of a JJ stent without the need for an abdominal wound drain. CONCLUSION: Laparoscopic ureterolithotomy is a safe, minimally invasive method of managing large, impacted ureteric stones with minimal associated patient morbidity.

Antibiotic prophylaxis for transrectal ultrasound biopsy of the prostate in Ireland.

INTRODUCTION: Prostate cancer is the most common solid cancer affecting men in Ireland. Transrectal ultrasound (TRUS) biopsies of the prostate are routinely performed to diagnose prostate cancer. They are, in general, a safe procedure but are associated with a significant risk of infective complications ranging from fever, urinary tract infection to severe urosepsis. At present, there are no recommended national guidelines on the use of antibiotic prophylaxis to minimise the risk of infective complications post-TRUS biopsy. AIM: To review the antibiotic prophylaxis for TRUS biopsy used in Irish hospitals. METHOD: We used a standard telephone questionnaire to establish what antibiotic protocol is in use in each hospital. RESULTS: 40 hospitals were contacted, of which 29 perform TRUS biopsies. In the majority of hospitals, TRUS biopsies are carried out in the radiology department. All hospitals administer antibiotic prophylaxis but there is wide variation in the protocols used. There are five different antibiotics prescribed, ciprofloxacin being the most common. Treatment protocols vary from 1 to 10 days antibiotic cover post procedure. CONCLUSION: There is a lack of standardisation of antibiotic prophylaxis in Irish hospitals. There is a need for guidelines to clarify the most appropriate antibiotic, route of administration and duration of treatment.

Radical prostatectomy outcome when performed with PSA above 20 ng/ml.

Many centres currently do not offer radical prostatectomy (RP) to men with high-risk localised prostate cancer due to concerns regarding poor outcome, despite evidence to the contrary. We identified 18 men undergoing RP with serum PSA >20 ng/ml (high-risk by National Comprehensive Cancer Network definition) and minimum follow-up of 12 years (mean 13.5). Mean preoperative PSA was 37.0 ng/ml (Range 21.1-94.0). Prostatectomy pathology reported extracapsular disease in 16 (88.9%), positive surgical margins in 15 (83%) and positive pelvic lymph nodes in 5 (27.8%). Overall and cancer-specific survival at 5 and 10-years was 83.3%, 88.2%, 72% and 76.5% respectively. With complete follow-up 11 (61.1%) are alive, and 5 (27.8%) avoided any adjuvant therapy. Complete continence (defined as no involuntary urine leakage and no use of pads) was achieved in 60%, with partial continence in the remainder. We conclude that surgery for this aggressive variant of localised prostate cancer can result in satisfactory outcome.

The value of appropriate assessment prior to specialist referral in men with prostatic symptoms.

BACKGROUND: Referrals to Urology OPD of men with a likely diagnosis of BPH are common. AIMS: To review referrals to OPD of men with lower urinary tract symptoms (LUTS) to establish how many could have been managed without specialist assessment. METHODS: We reviewed records of 200 male patients referred to OPD with LUTS. We assessed whether the referral source had performed digital rectal examination (DRE), International Prostate Symptom Score (IPSS), Bother Score or PSA level. RESULTS: 74% of patients were referred by GPs. In 31.5% of cases DRE was performed prior to referral. One GP had completed an IPSS, none a Bother Score. 96% had a PSA checked before OPD. Ultimately, 88.5% of our patients were diagnosed with BPH. CONCLUSIONS: With better pre-assessment in the form of DRE, IPSS and Bother Score, allied to a PSA check, many patients with LUTS could be managed in a primary care setting.

Should patients with a pre-operative prostate-specific antigen greater than 15 ng/ml be offered radical prostatectomy?

BACKGROUND: Patients with prostate cancer with a pre-operative prostate-specific antigen (PSA) >15 ng/ml who undergo radical retropubic prostatectomy (RRP) generally do not have a good outcome, yet may have organ-confined cancer and should be offered the option of surgery. AIM: To assess the outcome of patients who underwent RRP with a pre-operative PSA >15 ng/ml. METHODS: Thirty-four patients, mean pre-operative PSA: 25.46 ng/ml (15.03-76.6) and mean Gleason score: 6.4 (5-9) were assessed. RESULTS: Two groups were identified. Group I: 41% (14/34) have no biochemical recurrence to mean follow up of 58 months (30-106). Mean PSA: 18.8 ng/ml (15.03-25.84). Mean Gleason score: 6.1 (5-7). Clinical stage: T1c in 80%. No patient had seminal vesicle or lymph node involvement. Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease to mean follow up of 66 months (36-98). Mean PSA: 28.9 ng/ml (15.28-76.6). Mean Gleason score: 6.7 (5-9). Clinical stage: T1c in 25%. Eleven patients had seminal vesicle (8) involvement or positive lymph nodes (3) or both (2). CONCLUSION: RRP seems feasible in patients whose pre-operative PSA is between 15 and 25 ng/ml with stage T1c, Gleason score < or = 7 and negative lymph node frozen section.

Time-related effects of enzymatic disaggregation on model human lung carcinomas.

Enzyme cocktails used to prepare tumor cell suspensions may influence yield, viability, and cytology, thus time-related cocktail effects on model human lung carcinomas were examined. A549, NCI-H125, and NCI-H460 carcinomas were completely disaggregated at 25 degrees C over 2 h with either (mg/ml) collagenase/DNAase (C/D, 1/0.1), collagenase/hyaluronidase/DNAse (C/H/D, 1/0, 1/0.1), or polymyxa protease/DNAse (PP/D, 3/0.1). Trypan blue viabilities, total yields, viable yields, and flow cytometric percent tumor cells (TC) were measured every 20-30 min (n = 4-7 per tumor type). The final percentages of TC, mononuclear cells (MN), polymorphonuclear cells (PMN), lymphocytes, and necrotic cells were determined by cytology (n = 4-5 per tumor type). The time-dependent measurements showed that 1) disaggregation was progressive and complete with all cocktails; 2) viability was stable or increasing with all cocktails; 3) percent TC was stable for all cocktails, but lower for PP/D than C/D in final suspensions; and 4) PP/D gave lower final total yields, higher final viabilities, but the same final viable yields as the C cocktails, suggesting selective elimination of dead cells by PP/D. Final cytology measurements showed that PP/D gave a lower percent MN and a higher percent PMN than C cocktails. Cocktail effects may importantly influence cell suspension properties.

Dose-related doxorubicin effect in an orthotopic secondary lung cancer screen.

Lung cancer is the leading cause of cancer-related death of both sexes in the United States and promises to be a major problem in the world community for decades. We are developing an orthotopic (organ specific) secondary screening system to measure the uptake and efficacy of new lung cancer agents. The elements of the system are: (1) orthotopic growth of a model human lung cancer (NCI-H460 large cell carcinoma) in the right caudal lobe of the nude rat; (2) 1-hr ex vivo pulmonary perfusion treatment of the tumor-bearing lungs; and (3) soft agar clonogenic assay of the enzymatically disaggregated tumor cells. This study characterizes dose-response aspects of the system. Perfusion of tumor-bearing lungs with 0, 1, 10, and 100 micrograms/ml doxorubicin resulted in a dose-related reduction in surviving fraction from 1.01 +/- 0.41 to 0.019 +/- 0.006 (P < 0.05) without significant treatment-related increases in lung weight or perfusion pressure. Tumor and lung drug levels were also dose-related, with lung levels exceeding tumor levels at all doses. The tumor drug level at the 100 micrograms/ml dose was 62 +/- 16 ng/mg. There was a strong negative correlation between the measured tumor drug level and surviving fraction in the clonogenic assay (R2 = 0.47, P = 0.0005). This new screening system is capable of demonstrating dose-related uptake and tumoricidal activity of doxorubicin on an orthotopic, model human large cell lung carcinoma. It may be useful for the secondary screening of agents active against human lung cancer.

Secondary screening system for preclinical testing of human lung cancer therapies.

The National Cancer Institute has instituted a primary screening system for testing new agents against cultured cancer cell lines. The purpose of this study was to determine the feasibility of using a nude rat orthotopic (organ-specific) human lung cancer model system as an in vivo secondary screen for general evaluation of new anticancer agents and therapies active against lung cancer. To make this determination, we tested whether this system allows measurement of uptake and tumoricidal activity of anticancer therapies. Tumor-bearing lungs from 53 Rowett nude rats with orthotopically implanted human large-cell undifferentiated lung carcinoma (NCI-H460) were perfused ex vivo for 1 hour with or without each of two anticancer modalities. Lungs were perfused with blood-free perfusate alone (untreated control), perfusate with 100 micrograms/mL doxorubicin (treated positive control), or perfusate with lymphokine-activated killer cells plus human recombinant interleukin-2 (LAK/rIL-2). Weight gain during perfusion was the criterion used to quantitate lung injury. Treatment efficacy was measured by clonogenic assay after enzymatic disaggregation of the perfused tumors. Doxorubicin levels in the tumor and in the uninvolved lung were measured by high-performance liquid chromatography. Both treatment groups showed only slight increases in lung weight compared with that in the untreated control group, suggesting good lung tolerance of the procedure. Lung and tumor levels of doxorubicin were 320 +/- 21 ng/mg of tissue and 32 +/- 5 ng/mg of tissue (means +/- SE), respectively. Clonogenic assay demonstrated a fivefold to 10-fold reduction in the surviving fraction of tumor cells with doxorubicin but no change with LAK/rIL-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracellular flush solution that contains blood, mannitol, albumin, and prostacyclin protects rat lungs from six hours of ischemia.

We have used an isolated rat lung model to compare the quality of preservation of different flush techniques with each other and with topical cooling alone. Lung injury was assessed by recording lung weights after reperfusion after 4 and 6 hours of ischemia. The flush solutions studied were intracellular (Collins-Sacks), traditional extracellular, extracellular with low potassium plus dextran, and extracellular containing blood, mannitol, albumin, and prostacyclin (Wallwork's solution). Flushing with Wallwork's solution before both 4 and 6 hours of ischemia gave superior protection from lung edema after reperfusion over all the other methods.

Irradiated nude rat model for orthotopic human lung cancers.

The development of improved animal models for biological and preclinical studies of human lung cancer is important because lung cancer is the leading cause of cancer death in the United States. To determine whether the Rowett nude rat could serve as an orthotopic (organ-specific) model of this disease, nude rats (CR: NIH-RNU), with and without 500 rads of prior gamma-irradiation, were implanted intrabronchially with 10(7) cultured cells from 3 human lung cancer lines. Without irradiation, the NCI-H460 large-cell undifferentiated carcinoma had a 54% take-rate, whereas the NCI-H125 adenosquamous carcinoma and A549 adenocarcinoma had take-rates of 7 and 33%, respectively; irradiation increased the respective take-rates to 100, 83, and 90%. In irradiated rats, tumor age versus weight measurements showed progressive growth for all three tumors, with growth rates in the order: NCI-H460 greater than A549 greater than NCI-H125, requiring approximately 3, 5, and 9 weeks, respectively, for average tumor sizes to exceed 500 mg. The small-cell carcinoma cell line NCI-H345 was implanted only into irradiated rats and resulted in more slowly growing tumors. Histopathological study showed all model tumor types to have histological characteristics consistent with the clinical tumors from which the cell lines were derived. Each tumor type had a different growth pattern, with some of the the A549- and NCI-H125-derived tumors metastasizing to contralateral lung and/or regional lymph nodes. There was no evidence for immunological rejection in irradiated, tumor-bearing rats. Nonirradiated, implanted rats without gross tumor exhibited peribronchiolar mononuclear cell infiltration with or without fibrosis, suggesting prior immunological rejection. The successful orthotopic growth of these 4 human lung cancer cell lines in irradiated nude rats suggests that this model could be useful for biological and preclinical studies of human lung cancer, both in intact rats and via ex vivo perfusion of their tumor-bearing lungs.

Interleukin 1 pretreatment decreases ischemia/reperfusion injury.

Hearts isolated from rats treated 36 hr before with interleukin 1 (IL-1) had increased glucose-6-phosphate dehydrogenase (G6PD) activity and decreased hydrogen peroxide levels and injury after global ischemia (I, 20 min)/reperfusion (R, 40 min) compared with hearts from untreated rats. Hearts isolated from rats treated 6 hr earlier with IL-1 also had increased polymorphonuclear leukocytes (PMN), H2O2 levels, and oxidized glutathione (GSSG) contents compared with hearts from untreated rats. Depletion of circulating blood PMN by prior treatment with vinblastine prevented both early (from treatment 6 hr before study) IL-1-induced increases in myocardial PMN accumulation, H2O2 levels, and GSSG contents and late (from treatment 36 hr before study) increases in myocardial G6PD activity and protection against I/R. Our results indicate that IL-1 pretreatment causes an early (6 hr after IL-1 treatment) myocardial PMN accumulation and most likely an H2O2-dependent oxidative stress, which contributes to late (36 hr after IL-1 treatment) increases in myocardial G6PD activity and decreases in I/R injury.