Evolution of Minimally Invasive Adrenal Surgery at a Tertiary Care Centre in Oman.

Objectives: This study aimed to review the case records and report the outcomes of open and laparoscopic adrenalectomy (LA) cases. Methods: This retrospective study included patients who underwent adrenal surgery from January 2010 to December 2020 at Sultan Qaboos University, Muscat, Oman. Demographic details, indications, surgical approaches, intra-operative data, complications, final pathology and outcome at the last follow-up were analysed. Results: A total of 52 patients underwent 61 adrenalectomies; six patients had a bilateral procedure while three patients had to undergo revision surgery resulting in a total of 55 individual procedures. Open adrenalectomy (OA) was performed on 11 patients and 44 patients underwent LA. Most patients (n = 27) were obese with a body mass index >30. Functional adenoma was excised in 36 patients with final diagnosis of Conn's syndrome in 15, pheochromocytoma in 13 and Cushing's syndrome in nine patients. Five patients had surgery for oncological indications. Non-functional adenoma was excised in 13 patients, with a mean size of 8.9 cm (range: 4-15 cm). The mean duration of surgery was less in laparoscopic procedure compared to open (199 versus 246 minutes). The mean estimated blood loss in LA was significantly less (108 versus 450 mL; P <0.05). Out of 55 procedures, only one patient developed Clavien-Dindo grade 2 complication. Conclusion: Both LA and OA were safely performed at the researchers' institution. There is a growing trend for LA, and with experience, the duration of surgery and estimated mean blood loss are demonstrating a positive trend.

Pathological, Oncologic and Functional Outcomes of a Prospective Registry of Salvage High Intensity Focused Ultrasound Ablation for Radiorecurrent Prostate Cancer.

PURPOSE: In this prospective registry we prospectively assessed the oncologic, functional and safety outcomes of salvage high intensity focused ultrasound for radiorecurrent prostate cancer. MATERIALS AND METHODS: A total of 81 men were prospectively recruited and evaluated at regular scheduled study visits to 6 months after high intensity focused ultrasound and thereafter as per standard of care. Transrectal ultrasound guided biopsy was performed at 6 months. The primary end point was absence or histological persistence of disease at 6-month biopsy. Secondary end points included quality of life, biochemical recurrence-free survival, overall survival, cancer specific survival and progression to androgen deprivation therapy. Survival analysis was performed according to the Kaplan-Meier method and multivariate analysis was performed using the log rank (Mantel-Cox) test. RESULTS: Mean ± SD prostate specific antigen before high intensity focused ultrasound was 4.06 ± 2.88 ng/ml. At 6 months 63 men underwent biopsy, of whom 22 (35%) had residual disease. At a mean followup of 53.5 ± 31.6 months median biochemical recurrence-free survival was 63 months. The 5-year overall and cancer specific survival rates were 88% and 94.4%, respectively. Nadir prostate specific antigen less than 0.5 ng/ml was a significant predictor of biochemical recurrence-free survival (p=0.014, 95% CI 1.22-5.87). I-PSS significantly increased (p <0.001) while IIEF-5 scores decreased and the SF-36 score did not change significantly. The rate of rectal fistulization and severe incontinence was 3.7% each. A total of 223 complications were recorded in the 180 days after high intensity focused ultrasound (Clavien-Dindo grade 1-195, grade II-20, grade III-7, grade IVa-1). CONCLUSIONS: Salvage high intensity focused ultrasound appears to be a viable treatment option for radiorecurrent prostate cancer, with acceptable morbidity.

Long-Term Oncologic Outcomes of Salvage Cryoablation for Radio-Recurrent Prostate Cancer.

PURPOSE: Management of localized radio-recurrent prostate cancer is not standardized, partly due to the absence of long-term data on oncologic control and the toxicity of various treatment modalities. We analyzed the long-term oncologic outcomes and morbidity of salvage cryoablation for radio-recurrent prostate cancer. MATERIALS AND METHODS: Patients undergoing salvage cryoablation for biopsy proven, localized radio-recurrent prostate cancer from 1995 to 2004 were prospectively accrued. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from a prospectively maintained database or via telephonic contact with the patient. The primary outcome was overall survival. Secondary outcomes were metastasis-free and biochemical disease-free survival. The Kaplan-Meier method was used for survival analysis and multivariable Cox regression analysis was performed. RESULTS: Of 187 patients 157 (84%) had records available for followup. Mean ± SD age was 69.4 ± 5.8 years and mean presalvage prostate specific antigen was 6.6 ± 5.7 ng/ml. Median followup was 117 months (IQR 55-154). Five and 10-year overall survival was 93% and 76%, respectively. Biochemical disease-free survival at 10 and 15 years was 35% and 22.6% whereas metastasis-free survival at 10 and 15 years was 86% and 71%, respectively. On multivariable analysis precryoablation and nadir prostate specific antigen values were significant predictors of metastasis-free and biochemical disease-free survival. Age at salvage cryoablation (p = 0.008) and nadir prostate specific antigen (p = 0.015) were significant predictors of overall survival. There were 157 Clavien-Dindo grade 1-2 and 22 grade 3 complications. CONCLUSIONS: A single center, long-term experience documented by a prospectively maintained database shows that cryoablation is a viable salvage option for radio-recurrent prostate cancer as it provides durable biochemical disease-free survival with acceptable morbidity.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry.

BACKGROUND: Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. PATIENTS AND METHODS: Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. RESULTS: PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. CONCLUSIONS: PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Assessment of histopathological features of needle biopsy in recurrent prostate cancer following salvage high-intensity focused ultrasound.

INTRODUCTION: Local recurrence of prostate cancer (PCa) following radiotherapy may be treated with curative intent using salvage high-intensity focused ultrasound (s-HIFU). The interpretation of needle core biopsy specimens following s-HIFU is a daunting task, even for experienced pathologists. We describe various histopathological features encountered in biopsy specimens following whole-gland s-HIFU in one of the largest descriptive studies to date. METHODS: Fifty-five patients with biopsy-proven localized radio-recurrent PCa underwent s-HIFU and transrectal ultrasound (TRUS)-guided prostatic needle biopsies at 180 days post-treatment. All biopsies were reviewed by two genitourinary pathologists. RESULTS: PCa was detected in 11 (24%) biopsies. Radiation therapy-associated changes were identified in all cases. Additional findings included extensive coagulative stromal necrosis (100%), smudgy chromatin of cancer nuclei (82%), and markedly enlarged bizarre nuclei in the residual cancer (55%). Gleason grade assignment was possible in 10 (91%) of these biopsies and concordance of Gleason grading between pre- and post-therapy specimens was observed in six (60%) cases. CONCLUSIONS: The histological interpretation of needle biopsies following salvage HIFU is challenging and requires an understanding of the histopathological changes associated with this procedure in both tumoural and non-tumoural prostatic tissue. Accurate interpretation of the morphological changes following s-HIFU is instrumental for optimization of clinical decision-making and treatment planning in recurrent PCa.

Ileal conduit: standard urinary diversion for elderly patients undergoing radical cystectomy.

PURPOSE: Ileal conduit (IC) is the most frequent urinary diversion (UD) performed after radical cystectomy (RC). We reviewed the literature to investigate the factors influencing the choice of this diversion and its complications. METHODS: A literature search (PubMed) was performed for all English language publications on UDs performed for treatment of bladder cancer from 1950 to 2015. The literature review was focused on studies reporting outcome of IC and its comparison with other types of UDs. RESULTS: IC is the most common UD performed in elderly patients undergoing RC for bladder cancer. Long-term studies looking at the change in renal function after UD report a universal decline in the glomerular filtration rate; however, this decline in renal function is the least for IC. There is a significant morbidity of RC (20-56 %), which can be attributed to patient factors, surgical technique and hospital volume. Modern concepts of bowel preparation, postoperative nutrition, early enteral feeding and involvement of stoma therapists have helped improve the outcomes. The quality of life is preserved, and in many including elderly, it may be improved with IC UD. CONCLUSIONS: IC is the most commonly performed UD following radical cystectomy. It is associated with acceptable morbidity and has the lowest reoperation rates as compared to continent diversion. It is also the procedure of choice for most patients' elderly patients as well as patients with limited dexterity, poor motivation, anatomical restrictions and poor renal function. Studies measuring HRQOL report excellent patient acceptability, especially in the elderly population.

Comparative morbidity of ablative energy-based salvage treatments for radio-recurrent prostate cancer.

INTRODUCTION: We compared the morbidity of whole gland salvage ablation using cryotherapy (CRYO) and high-intensity focused ultrasound (HIFU) for radio recurrent prostate cancer at a single centre over a 17-year period. METHODS: Patients were divided in 3 cohorts. Group 1 included the first 65 patients treated with CRYO (1995-1998); Group 2 included the last 65 patients treated with CRYO (2002-2004), and Group 3 included 65 patients treated with HIFU (2006-2011). We analyzed the complications reported within at least 90 days of treatment or up to the last follow-up. RESULTS: We tallied Clavien grade complications. For Groups 1, 2 and 3, we recorded the following Clavien I-II complications: 78, 49 and 13, respectively. For Clavien grade IIIa, 2, 5 and 4 for Groups 1, 2 and 3, respectively. For Clavien grade IIIb, 8, 2 and 3 for Groups 1, 2 and 3, respectively. Clavien grade II complications were statistically higher in Group 1 versus Group 2 (p = 0.005) and in Group 2 versus Group 3 (p = 0.0001). The rate of mild-moderate incontinence was significantly higher in the CRYO group compared to the HIFU cohort (p ≤ 0.05). The rate of urinary retention was significantly higher in Group 2 compared to Group 3 (p = 0.0005). The rates of severe incontinence (range: 1.5%-5%), need for surgical intervention (uniform at 1.5%), and recto-urethral fistulae (range: 1.5%-3%) were not statistically different. CONCLUSIONS: CRYO was associated with higher overall morbidity. The morbidity during the early experience with HIFU was lower than both subgroups of CRYO. This may reflect the advancement of technology or cumulative learning experience.

Systematic methods for measuring outcomes: How they may be used to improve outcomes after Radical cystectomy.

In the era of managed healthcare, the measuring and reporting of surgical outcomes is a universal mandate. The outcomes should be monitored and reported in a timely manner. Methods for measuring surgical outcomes should be continuous, free of bias and accommodate variations in patient factors. The traditional methods of surgical audits are periodic, resource-intensive and have a potential for bias. These audits are typically annual and therefore there is a long time lag before any effective remedial action could be taken. To reduce this delay the manufacturing industry has long used statistical control-chart monitoring systems, as they offer continuous monitoring and are better suited to monitoring outcomes systematically and promptly. The healthcare industry is now embracing such systematic methods. Radical cystectomy (RC) is one of the most complex surgical procedures. Systematic methods for measuring outcomes after RC can identify areas of improvements on an ongoing basis, which can be used to initiate timely corrective measures. We review the available methods to improve the outcomes. Cumulative summation charts have the potential to be a robust method which can prompt early warnings and thus initiate an analysis of root causes. This early-warning system might help to resolve the issue promptly with no need to wait for the report of annual audits. This system can also be helpful for monitoring learning curves for individuals, both in training or when learning a new technology.

Dovitinib: rationale, preclinical and early clinical data in urothelial carcinoma of the bladder.

INTRODUCTION: Bladder cancer (BC) is the third and fifth cancer in men in terms of incidence and mortality in the US. Overexpression and mutations of fibroblast growth factor receptor 3 (FGFR3) are frequently found in BC and can represent a very interesting therapeutic target. Different FGFR3-targeted strategies have been investigated through in vitro and in vivo settings, including FGFR3 tyrosine kinase inhibitors such as dovitinib . AREAS COVERED: The authors review the data that provide a scientific rationale for FGFR3-targeted therapy in BC. They also provide an evaluation of the currently available in vitro and in vivo data on the use of dovitinib in BC patients. EXPERT OPINION: The development and progression of BC rely on a very complex signaling network that involves many different receptors aside from FGFR3 and VEGFR2. The involved signaling network can also be very different from one BC to the other, and can also evolve through time in the same patient. Inhibiting only one single target may thus not be sufficient to achieve a complete downstream oncogenic signaling blockage. Additionally, in vitro data on the use of neutralizing monoclonal antibodies targeting FGFR3 show that it can be a more efficient strategy to reach the same goal, with the potential advantage of less toxicity.

Three-year outcomes of recovery of erectile function after open radical prostatectomy with sural nerve grafting.

INTRODUCTION: Optimal oncologic control of higher stage prostate cancers often requires sacrificing the neurovascular bundles (NVB) with subsequent postoperative erectile dysfunction (ED), which can be treated with interposition graft using sural nerve. AIMS: To examine the long term outcome of sural nerve grafting (SNG) during radical retropubic prostatectomy (RRP) performed by a single surgeon. METHODS: Sixty-six patients with clinically localized prostate cancer and preoperative International Index of Erectile Function (IIEF) score >20 who underwent RRP were included. NVB excision was performed if the risk of side-specific extra-capsular extension (ECE) was >25% on Ohori' nomogram. SNG was harvested by a plastic surgeon, contemporaneously as the urologic surgeon was performing RRP. IIEF questionnaire was used pre- and postoperatively and at follow-up. MAIN OUTCOME MEASURES: Postoperative IIEF score at three years of men undergoing RRP with SNG. Recovery of potency was defined as postoperative IIEF-EF domain score >22. RESULTS: There were 43 (65%) unilateral SNG and 23 (35%) bilateral SNG. Mean surgical time was 164 minutes (71 to 221 minutes).The mean preoperative IIEF score was 23.4+1.6. With a mean follow-up of 35 months, 19 (28.8%) patients had IIEF score >22. The IIEF-EF scores for those who had unilateral SNG and bilateral SNG were 12.9+4.9 and 14.8+5.3 respectively. History of diabetes (P=0.001) and age (P=0.007) negatively correlated with recovery of EF. 60% patients used PDE5i and showed a significantly higher EF recovery (43% vs. 17%, P=0.009). CONCLUSIONS: SNG can potentially improve EF recovery for potent men with higher stage prostate cancer undergoing RP. The contemporaneous, multidisciplinary approach provides a good quality graft and expedited the procedure without interrupting the work-flow.

A randomized clinical trial of lidocaine jelly for prevention of inadvertent retrograde stone migration during pneumatic lithotripsy of ureteral stone.

PURPOSE: We studied the efficacy of lidocaine jelly instillation proximal to the ureteral stone during intracorporeal lithotripsy using a semirigid ureteroscope for the prevention of retrograde migration and improvement in stone-free rate. MATERIALS AND METHODS: From November 2006 to September 2007, 50 patients with 5 to 18 mm ureteral stones undergoing ureteroscopic removal using pneumatic lithotripsy were randomized into 2 groups. Group 1 (25 patients) had lidocaine jelly instilled proximal to the stone before and after fragmentation, and group 2 was the control group (25 patients). Ureteroscopy was performed using an 8 or 6.4Fr semirigid ureteroscope. A 5Fr ureteral stent was advanced beyond the stone. Lidocaine jelly (2 ml) was instilled and lithotripsy was performed with a Swiss LithoClast . A 5Fr ureteral catheter was left in place for 24 hours. Patients were followed at 24 hours with plain x-ray of the kidneys, ureters and bladder, and at 2 weeks with noncontrast enhanced computerized tomography of the kidneys, ureters and bladder. RESULTS: The 2 groups were comparable with regard to age and stone size. Stone or stone fragment migration occurred in 4% and 28% of patients in groups 1 and 2, respectively, and this difference was statistically significant (p = 0.002). At 2 weeks followup with imaging the stone-free rate was 96% and 72% in groups 1 and 2, respectively, and this difference was also statistically significant (p = 0.045). Although the mean operative time was slightly longer in the treatment group (33.56 +/- 13 vs 35.84 +/- 12.5 minutes) the difference was not significant (p = 0.450). CONCLUSIONS: Lidocaine jelly instillation proximal to ureteral calculi during lithotripsy is an effective method of preventing retrograde stone displacement as well as significantly improving the stone-free rate.

Separate submission of standard lymphadenectomy in 6 packets versus en bloc lymphadenectomy in bladder cancer.

INTRODUCTION: Our aim was to evaluate detection of nodal metastasis during radical cystectomy with standard pelvic lymph node dissection versus en bloc lymphadenectomy for the treatment of bladder cancer. MATERIALS AND METHODS: Hospital records of a total of 77 patients with radical cystectomy and either standard pelvic lymph node dissection or en bloc lymphadenectomy were reviewed. Nodal dissection specimens during standard lymphadenectomy were sent for pathology examination in 6 separate containers marked as external iliac, internal iliac, and obturator groups from both sides. En bloc dissection specimens were sent in 2 containers marked as the right and the left pelvic nodes. Clinical and pathological findings of these two groups were compared in terms of the number of dissected lymph nodes, number of nodes with metastasis, lymph node density, and clinical outcomes. RESULTS: There were 34 patients with standard lymph node dissection and 43 with en bloc lymphadenectomy (anterior pelvic exenteration). Age, sex, duration of the disease, number of transurethral resections prior to cystectomy, pathological grade at cystectomy, and stage of the primary tumor were comparable in the two groups of patients. The median numbers of nodes removed per patient were 15.5 (range, 4 to 48) and 7.0 (range, 1 to 24) in those with standard and en bloc lymphadenectomy, respectively (P < .001). Nodal involvement was detected in 10 (29.4%) and 9 (20.9%) patients, respectively (P = .43). CONCLUSION: Although nodal involvement was not significantly different between the two groups, standard lymphadenectomy submitted in 6 different containers significantly improved the nodal yield over en bloc resection. Obturator nodes were the most commonly involved nodes in our study.

Surgical ligation of scrotal varicocele for male factor infertility is a valid option of treatment.

OBJECTIVE: To evaluate the role of surgical ligation of scrotal varicocele for treatment of male factor infertility. METHODS: We studied 60 patients who presented with infertility and were also found to have scrotal varicocele. Patients with other probable causes contributing to infertility were excluded. Diagnosis was made by clinical examination and scrotal ultrasonography. All the patients underwent either laparoscopic varicocelectomy or open retroperitoneal high ligation of the testicular veins. Operative time and hospital stay was recorded. All patients were evaluated for postoperative improvement of semen parameters and development of any postoperative complication. The results were analyzed by commercially available software. RESULTS: During the study period 5 patients were lost to follow up and were excluded. The rest of patients (n=55) were young, with age ranging from 20-35 years (Mean age 27.8 years, SD +/- 4.38). All patients had unilateral left sided varicocele; two patients (3.6%) had grade I varicocele, 21 patients (38.2%) had grade II varicocele and 32 patients (58.2%) had grade III varicocele. Statistically significant improvement in sperm density (p value < 0.05), sperm activity (p value < 0.05) and sperm morphology (p value < 0.05) was observed after the surgical ligation. The mean operative time was 54.88 minutes (SD + 13). The mean hospital stay in laparoscopic procedure was 33.4 (SD + 15.3). Minor complications were noted in 13 patients and included superficial wound infection in 3 patients, 6 patients exhibited testicular pain and persistence of varicocele in 4 patients. CONCLUSION: Surgical ligation of scrotal varicocele is asafe and effective mode of treatment of male factor infertility in selected population.

Extracorporeal shock wave lithotripsy with a transportable electrohydraulic lithotripter: experience with >300 patients.

OBJECTIVE: To review a multicentre experience of using a transportable lithotripter (STS-T, Medstone, Inc, Aliso Viejo, CA. USA) for treating patients with urolithiasis in all parts of the urinary tract. PATIENTS AND METHODS: In all, 326 patients with a total of 370 stones were treated as outpatients with the STS-T lithotripter. All patients received a single shock wave lithotripsy treatment and were followed after 4-6 weeks in the outpatient clinic, the primary endpoint being to determine the efficacy (as defined by the stone-free rate). Secondary objectives included establishing a database of patient demographic information, stone characteristics, stone location, procedural endpoints, and complication rates. RESULTS: In all there were 370 procedures, with a mean of 2394 shocks administered at an energy level of 24 kV. The mean treatment time was 51 min, excluding anaesthesia-induction time. The mean stone aggregate size was 8.2 mm; 62% of the stones were in the kidney while 38% were in various locations in the ureter. Of the treated stones, 90% had definite or probable evidence of fragmentation. The overall stone-free rate after one treatment with the STS-T was 52.8%. Of patients with residual fragments, most (61%) had fragments of <4 mm in aggregate diameter. The overall complication rate was 3.8%, the most common complication being postoperative pain. CONCLUSION: The Medstone STS-T lithotripter was an effective device for treating urolithiasis in all parts of the urinary tract. This system had a high margin of safety, as shown by the low complication rate. With no apparent sacrifice of efficacy compared to first-generation or fixed (not transportable) second-generation devices, the Medstone STS-T represents an important advance in the development of a truly transportable lithotripter.

Hand-assisted laparoscopic renal surgery: hand-port incision complications.

BACKGROUND AND PURPOSE: Hand-assisted laparoscopic (HAL) renal surgery is an accepted standard of practice. We report our complications at the hand port-site incision in various HAL urologic procedures. PATIENTS AND METHODS: Data and follow-up were complete for 54 patients who underwent HAL nephrectomy. HAL partial nephrectomy, or HAL nephroureterectomy at our institution from October 2001 to April 2003. A retrospective review of the patients' charts was performed to identify the incidence of postoperative hand port-site complications. The mean patient age was 59 years, and the mean follow-up was 5.4 months. RESULTS: Five complications were observed in four patients (9.3%). One patient had a superficial wound infection (1.9%) and an incisional hernia (1.9%) that was surgically repaired. One patient had a superficial incisional breakdown that healed well after conservative measures. One obese patient with severe chronic obstructive pulmonary disease eviscerated through his hand-port incision after a coughing spell. This was repaired operatively, and the patient healed well with the aid of an abdominal binder. One patient developed an enterocutaneous fistula at her hand-port site that healed well after both operative and conservative management. CONCLUSIONS: The technique of HAL renal surgery is safe and effective. Complications associated with the hand-port incision exist, and as they become better defined, the surgeon may take extra steps toward their recognition and prevention.