Special emphasis on bone health management in prostate cancer patients: a prospective longitudinal study

ABSTRACT Introduction: Use of androgen deprivation therapy (ADT) in carcinoma prostate (CaP) has deleterious effect on bone mineral density (BMD) leading to increase incidence of osteoporosis and skeletal-related events. We evaluated bone health status and impact of bone-directed therapy (BDT) and ADT on BMD in these patients from Jan 2015-Dec 2018. Materials and Method: Baseline bone health was assessed using Tc-99 MDP Bone scan/ DEXA scan for patients on ADT. Monthly zoledronic acid (ZA) was given to high-risk candidates (T-score ≤2.5 or previous hip/vertebral fracture) or Skel et al. metastatic patients who were receiving ADT. Baseline and follow-up (at 12-months) BMD using DEXA scan at various sites (spine, femur total, femur neck and radius) and subjective improvement in bony pain using Numeric Pain Rating Score after administration of ZA were compared. Results: A total of 96-patients of locally advanced and metastatic prostate cancer receiving ADT with or without BDT were included in the study cohort. Mean age of presentation was 68.4±15.61 years. Median serum PSA was 32.2±13.1ng/mL. There was significant improvement in mean BMD (T-score) in 64-patients post ZA therapy at 12-months (at femoral total, femoral neck and spine; 0.95, 0.79 and 0.68, respectively) (p <0.05) while there was significant deterioration in mean BMD at 12-months (at spine, femoral neck and femoral total; −0.77, −0.55 and −0.66, respectively) in 32 patients who did not receive ZA and were on ADT (p <0.05). Pain scores significantly decreased in patients after 12-months of ZA use (−2.92±2.16, p <0.01). Conclusion: Bone-directed therapy (Zoledronic acid) leads to both subjective and objective improvement in bone health of prostate cancer patients on ADT.

Special emphasis on bone health management in prostate cancer patients: a prospective longitudinal study.

INTRODUCTION: Use of androgen deprivation therapy (ADT) in carcinoma prostate (CaP) has deleterious effect on bone mineral density (BMD) leading to increase incidence of osteoporosis and skeletal-related events. We evaluated bone health status and impact of bone-directed therapy (BDT) and ADT on BMD in these patients from Jan 2015-Dec 2018. MATERIALS AND METHOD: Baseline bone health was assessed using Tc-99 MDP Bone scan/DEXA scan for patients on ADT. Monthly zoledronic acid (ZA) was given to high-risk candidates (T-score ≤2.5 or previous hip/vertebral fracture) or Skel et al. metastatic patients who were receiving ADT. Baseline and follow-up (at 12-months) BMD using DEXA scan at various sites (spine, femur total, femur neck and radius) and subjective improvement in bony pain using Numeric Pain Rating Score after administration of ZA were compared. RESULTS: A total of 96-patients of locally advanced and metastatic prostate cancer receiving ADT with or without BDT were included in the study cohort. Mean age of presentation was 68.4±15.61 years. Median serum PSA was 32.2±13.1ng/mL. There was significant improvement in mean BMD (T-score) in 64-patients post ZA therapy at 12-months (at femoral total, femoral neck and spine; 0.95, 0.79 and 0.68, respectively) (p < 0.05) while there was significant deterioration in mean BMD at 12-months (at spine, femoral neck and femoral total; -0.77, -0.55 and -0.66, respectively) in 32 patients who did not receive ZA and were on ADT (p < 0.05). Pain scores significantly decreased in patients after 12-months of ZA use (-2.92±2.16, p < 0.01). CONCLUSION: Bone-directed therapy (Zoledronic acid) leads to both subjective and objective improvement in bone health of prostate cancer patients on ADT.

Vulvar tuberculosis.

Genital tuberculosis (TB) in women is a chronic disease with low-grade symptoms. Genital tract tuberculosis is usually secondary to extragenital TB. The fallopian tubes are most commonly affected, and along with endometrial involvement, it causes infertility in such patients. Involvement of the cervix and the vulva is very rare. We present one such rare case of vulvar tuberculosis presented with a large ulcer diagnosed on histopathology and treated with antitubercular chemotherapy.

Genetic susceptibility of CYP1A1 gene and risk of pesticide exposure in prostate cancer.

BACKGROUND: The etiology of prostate cancer (PCa) is multi-factorial including environmental and genetic factors. Present study evaluates the association between level of pesticides, stress level and CYP1A1 gene polymorphism with PCa patients. METHODS: A case control study was conducted with 102 PCa patients and age match symptomatic (n= 107) and asymptomatic benign prostatic hyperplasia (BPH, n= 70) patients. Pesticide level was characterized by Gas Chromatography. The oxidative stress and scavenging mechanisms were determined by biochemical method. Two polymorphisms of CYP1A1 gene, rs4646903 and rs1048943, were analyzed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism and allele specific PCR method. RESULTS: Higher level of pesticide namely beta-hexachlorocyclohexane (ß-HCH), Malathion, Chlorpyrifos and Fenvalerate were found in PCa group (all p value: < 0.05). Kruskal Wallis H test depicted that level of ß-HCH and Malathion significantly correlated with higher grade of PCa (all p< 0.05). The PCa Patients with simultaneously low antioxidant activity and high stress level tended to suffer worst clinical outcomes. Dominant model of rs4646903 and rs1048943 suggested that substitution is associated with a higher risk of PCa (OR: 2.2, CI: 1.6-3.8, p: 0.009 and OR: 1.95, CI: 1.1-3.4, p: 0.026; respectively) and this risk was also influenced by smoking and pesticide exposure. CONCLUSION: Environmental and genetic factors are reported to raise risk; person with high level of these pesticides especially in high risk genotype might be more susceptible to PCa.

Prospective randomized comparison of repairing vesicovaginal fistula with or without the interposition flap: Result from a tertiary care Institute in Northern India.

OBJECTIVE: Assessment of results of repairing vesicovaginal fistula (VVF) with or without the use of interposition flaps. MATERIAL AND METHODS: This prospective randomized study was conducted between January 2012 to December 2017 in the Department of Urology, King George's Medical University, Lucknow, India. Obstetric and gynecological simple fistula of ≤4 cm were included for evaluation. Those with complex or complicated fistula or fistula due to malignancy were excluded. Patients were divided into two groups (group 1 and group 2) depending upon route of repair i.e., transvaginal or transabdominal, respectively, as per the characteristics and location of the fistula. These two groups of patients were randomized into two subgroups (1A, 1B and 2A, 2B) based on the inclusion or omission of the interposition flap during fistula repair. Perioperative and postoperative parameters (blood loss, mean operating time, hospital stay, and requirement of analgesics) and success rates of fistula repair were compared. All complications that occurred in the postoperative period till the last follow-up appointment were recorded. The Clavien-Dindo Classification was used to stratify the complications. RESULTS: Fifty-seven patients underwent transvaginal repair in group 1 (29 with Martius flap: group 1A; 28 without Martius flap: group 1B), while 69 patients underwent transabdominal repair in group 2 (35 with interposition flap: group 2A; 34 without flap: group 2B). Blood loss, mean operating time, hospital stay, and the requirement of analgesics were comparable between each subgroup-1A versus 1B and 2A versus 2B, respectively. The overall success rate of repair across all groups was 96.04% (121/126). The success rate was 93.1% in transvaginal repair with Martius flap versus 96.43% in transvaginal repair with no flap (p=1.0). Success rate was 97.1% in transabdominal repair with an omental flap versus 97.06% in without an omental flap (p=1.0). Mean follow-up period was 39.6 months (range: 6-68 months). Out of 29 patients with Martius flap interposition, 9 (31.03%) of them reported a significantly reduced sensation on the labia majora. Of these 9 patients, 5 reported numbness while the remaining 4 experienced pain as compared to the patients in subgroup IB, who did not report any altered sensation in the labia. (p=0.0019). CONCLUSION: The success rates are similar in simple VVF repair (fistula size less than 4 cm) irrespective of the use of interposition flaps. However, overall morbidities following repair with the interposition flap are higher when compared with repair without interposition flap, either by the transvaginal or by the transabdominal route.

Squamous cell carcinoma of skin due to prolonged indwelling percutaneous nephrostomy catheter.

Percutaneous nephrostomy (PCN) catheter placement is a commonly performed procedure in the urological practice for various indications like percutaneous nephrolithotomy, pyonephrosis, infected hydronephrosis and after failed attempt of ureteric stenting. The nephrostomy catheter is usually associated with low complication and morbidity rate, but prolonged indwelling nephrostomy tube may be hazardous in some cases. We hereby report a case of squamous cell carcinoma of skin around the PCN, which was attributed to chronic inflammation and persistent irritation from a long-term neglected indwelling nephrostomy catheter for last 3 years. The patient was managed with wide local excision of skin carcinoma and ureterocalicostomy for pelviureteric junction stricture. The authors report the first documented case with aforementioned presentation.

Diagnostic utility of GATA3 immunohistochemical expression in urothelial carcinoma.

AIMS: This study aims to explore the utility of GATA binding protein 3, a zinc finger transcription factor, expression in genitourinary carcinoma, especially urothelial carcinoma. SETTINGS AND DESIGN: It is a prospective study where 74 consecutive cases of urothelial carcinoma along with 10 cases each of prostatic adenocarcinoma (PC) and conventional clear cell renal cell carcinoma were included between August 2016 and January 2017. METHODS AND MATERIALS: All the cases were histopathologically evaluated and immunohistochemically stained for GATA binding protein 3. Only nuclear positivity was considered as positive. Immunoreactivity score for GATA expression was calculated based on the staining intensity as well as percentage. STATISTICAL ANALYSIS USED: The statistical analysis was done using Statistical Package for Social Sciences Version 15.0 statistical analysis software. P value of <0.05 was considered statistically significance. RESULTS: GATA3 expressions were seen in 77% of the cases of urothelial carcinoma, whereas none of the clear cell renal cell carcinoma and prostatic adenocarcinoma cases was GATA3 positive. GATA3 expression significantly correlated with histological grade and muscle invasion with a weaker or negative expression in high-grade muscle invasive tumor as compared to low-grade and noninvasive neoplasm. Significantly weaker expression of GATA3 was found in cases with severe nuclear pleomorphism, mitosis >10/10 hpf, presence of necrosis, and tumor-infiltrating lymphocytes. No significant change in the status of GATA3 expression was seen in follow-up cases between initial Transurethral resection of bladder tumor (TURBT) and post-recurrence TURBT or radical cystectomy specimens. CONCLUSIONS: GATA3 as a sensitive and specific marker for urothelial carcinoma can be effectively used to exclude other genitourinary malignancies, PC, and renal cell carcinoma, at metastatic site. This marker can also be effectively used in predicting the probable grade and invasion in biopsy material with poor morphological characteristics, thereby helping in appropriate management in such cases.

Implications of the Fracture Risk Assessment Algorithm for the assessment and improvement of bone health in patients with prostate cancer: A comprehensive review.

OBJECTIVE: Maintaining the optimum bone health is one of the important concerns in patients with prostate cancer, but it usually remains neglected. Failure to screen these patients is detrimental to both the length and the quality of life. The estimation of bone mineral density (BMD) and more recently the World Health Organization's fracture risk assessment (FRAX) algorithm in appropriate patients is recommended by several specialty organizations/associations at the time of instituting androgen deprivation therapy (ADT) for metastatic and high-risk individuals. It provides a 10-year risk evaluation of hip and major osteoporotic fractures (MOF). Using this web-based new investigating tool, candidates at high risk of fractures can be predicted more accurately according to clinical risk factors (CRF) alone or in combination with the femoral neck BMD. The FRAX application for senile osteoporosis has been studied and reviewed extensively, but no systematic review has ever been conducted for assessing the implication of FRAX in prostate cancer. This review article will give insight about the validity, role, and utility of this investigating tool in clinical practice for fracture risk assessment in these individuals. MATERIAL AND METHODS: This systematic review was carried out as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and Cochrane review principles. We searched the PubMed, Cochrane database of systematic reviews, and the EMBASE electronic database until December 2018 using the medical subject heading terms prostate cancer and FRAX. RESULTS: A total of nine studies meet the inclusion criteria and were included in the review. These studies enrolled a total of 3704 patients (sample size range, 78-1220) of localized, metastatic, castration resistant prostate cancer with or without ADT and/or on photon or radiotherapy. The factors that influenced FRAX included age, ethnicity, baseline BMD, duration of ADT, presence of CRF, and measurement methods (CRF, with/without BMD, computed tomography based). An advanced age and duration of ADT were the most robust risk factors. A 10-year MOF and hip fracture risk estimation was higher when the femoral neck BMD was not incorporated in the FRAX measurement. Despite several well-known strengths of using FRAX in the fracture risk assessment of suitable candidates with prostate cancer, several risk factors such as the mode/duration of ADT, mode of radiotherapy, Vitamin D levels, bone remodeling markers, and recent/recurrent fractures need to be incorporated in the FRAX calculator for improving the predictive ability. In contrast to senile osteoporosis with a longer life expectancy, the fracture risk in patients with prostate cancer need to be measured more frequently and for a shorter time. Therefore, models like Garvan calculator with both 5- and 10-year risk estimates have to be developed for these patients. Additionally, its utilization is of limited value in the presence of recurrent fractures or falls. CONCLUSION: The FRAX algorithm is beneficial in identifying patients who require early intervention or bone-directed therapy as an early step to decrease skeletal-related events and other morbidity. Several risk factors need to be added for improving the FRAX predictive value. This model is still underutilized in the clinical practice and increasing the awareness among treating physicians will help in optimizing the bone health and the quality of life of this important population subgroup.

Analysis of anastomotic urethroplasty for pelvic fracture urethral distraction defect: Decadal experience from a high-volume tertiary care center.

CONTEXT: Pelvic fracture urethral distraction defect (PFUDD) may be challenging for the treating urologist. Anastomotic urethroplasty is the established surgical procedure for the treatment of PFUDD. Few studies in literature focus purely on PFUDD, and majority of the studies include anterior urethral stricture as well. The period of these studies is relatively short. We conducted a retrospective analysis of patients who underwent primary or redo anastomotic urethroplasty for PFUDD over a period of 12 years at a tertiary care center in northern India. AIMS: The aim is to study anastomotic urethroplasty for pelvic fracture urethral distraction defect with regard to long-term success rate and complications. SETTINGS AND DESIGN: This was a retrospective study. Subjects and. METHODS: This retrospective study was conducted in the Department of Urology, King George's Medical University, Lucknow, India, from August 2004 to July 2016. All patients who underwent progressive perineal anastomotic repair of PFUDD were included in this study. Demographic findings, type of pelvic fracture, length of distraction defect as per retrograde urethrography (RUG) and micturating cystourethrography, any history of erectile dysfunction in the preoperative or postoperative phase, and urinary incontinence in postoperative phase were analyzed. Decision regarding catheter removal was taken after pericatheter RUG at 4 weeks. Follow-up was done at 3 and 6 months in postoperative period. RESULTS: A total of 226 anastomotic repairs were done in 221 patients. Of the 221 patients, 51 (23%) were redo urethroplasty. The mean age of patients was 27.6 years. The mean length of distraction defect was 2.7 cm. The mean duration of hospital stay was 6 days. Primary urethroplasty was successful in 163 (93.14%) of 175 patients and redo urethroplasty in 44 (86.27%) of 51 patients. Out of 165 patients, 18 (10.9%) patients reported occasional incontinence while 6 (3.63%) patients reported mild incontinence. CONCLUSIONS: Anastomotic urethroplasty is the definitive procedure for PFUDD. Our success rate for primary deferred anastomotic urethroplasty is 93.14% and for redo anastomotic urethroplasty is 86.27%.

Outcomes of patients with Fournier's Gangrene: 12-year experience from a tertiary care referral center.

OBJECTIVE: To highlight changing trends of the clinical spectrum, and compare the management options and predictors of Fournier's gangrene (FG) outcomes in a tertiary care referral center. MATERIAL AND METHODS: This study included patients with FG between August 2005 and July 2017. Patients were classified as "responders" and "nonresponders." We compared the baseline characteristics, clinical spectrum, biochemical data, management modalities, outcomes, and FG severity index (FGSI) and age-adjusted Charlson Comorbidity Index (ACCI) between responders and nonresponders. RESULTS: We studied 72 patients and further divided them to responders (60 patients) and non-responders (12 patients). All were males; the mean age was 56.27+19.27 years (range, 47-85 years). The most common complaints were perineal discomfort (n=62; 86.1%) and fever (n=48; 66.7%). FG originated from the penoscrotal region in 64 patients (88.8%) and perineal region in 8 patients. Diabetes mellitus was the most common comorbidity (36%). The mean duration of the presentation was 10.19 days (range, 7-30 days). Sixteen patients underwent split skin grafting. The mortality rate was 8.3%. Nonresponders had distinct findings relative to responders: advanced age (71.5±7.17 vs. 53.23±19.85 years; p=0.00); high blood sugar (245.83±116.26 vs. 139.06±35.64 mg/dL; p<0.01); leukocytosis (27166.67±10295.75 vs. 10558.4±3130.64 cumm; p<0.01); elevated serum creatinine (3.78±1.43 vs. 1.38±1.00; p<0.01); hyponatremia (127.33±11.84 vs. 137.33±3.42 meq/l; p<0.01), elevated international normalized ratios (1.66±0.28 vs. 1.32±0.07; p<0.01); and high FGSI (9.83±1.11 vs. 6.46±1.68;p<0.01) and ACCI scores (6.33±0.49 vs. 5±0.82; p<0.01). On univariate and multivariate regression analysis, raised blood sugar and deranged international normalized ratios at presentation were significantly associated with decreased response to treatment (p<0.05). CONCLUSION: An advanced age, diabetes mellitus, renal impairment, leukocytosis, altered sensorium, shock at presentation, deranged international normalized ratios, and high FGSI and ACCI scores can be used as predictors for poor response. FG risk scores adequately characterize the severity and prognosis of FG, but clinician's judgement is vital. The management comprises of a multidisciplinary approach, including parenteral antibiotics, urgent surgical debridement, and comorbidities optimization.

Medullary sponge kidney and Caroli's disease in a patient with stricture urethra: look for the hidden in presence of the apparent.

Caroli's disease is a rare congenital disorder with incidence rate of approximately 1 in 1 000 000 population. Renal anomalies which may be associated with Caroli's disease include medullary sponge kidney (MSK), cortical cysts, adult recessive polycystic kidney disease and rarely autosomal dominant polycystic kidney disease. Exact incidence of MSK in patients of Caroli's disease is not known. There are only a handful of reported cases of this association in literature. We hereby report a case of Caroli's disease with MSK with nephrocalcinosis. He presented to primary health centre with symptoms of urethral stricture due to lichen sclerosus et atrophicus and was managed with repeated co-axial dilatation but was never evaluated for underlying chronic renal insufficiency due to MSK. The thorough clinical examination and proper evaluation is important in patient of urethral stricture with underlying chronic renal insufficiency to avoid delayed diagnosis, management and related complications.

Large anterior urethral calculus masquerading as periurethral abscess.

Urethral calculus causes variety of symptoms from simple dysuria to acute urinary retention. The diagnosis is many times not easy. A plain X-ray of the pelvis may aid in diagnosis. Due to variety of symptomatic presentations sometimes it is not the first diagnosis that comes to one's mind. Management is by removal of the calculus via various methods ranging from endoscopic to open surgery. We present the case of an adult male, who was initially thought to have periurethral abscess due to stricture urethra but during investigations was found to have urethral calculus as the cause for his symptoms.

Acute mechanical duodenal obstruction due to giant hydronephrosis: an unusual cause of acute abdomen.

Giant hydronephrosis (GH) is a rare clinical entity with about 600 cases and defined as the adult renal pelvis containing greater than 1 L of fluid, or at least 1.6% of the body weight or kidney occupying the hemiabdomen. The pelvic-ureteric junction (PUJ) obstruction is the most frequent cause of GH. We thus report a case of massive abdominal distension due to GH secondary to PUJ obstruction who presented with acute duodenal obstruction due to extrinsic compression and was managed with percutaneous nephrostomy followed by open nephrectomy.

Gossypiboma masquerading as nephrocutaneous fistula.

Nephrocutaneous fistula is a rare complication of surgical procedures involving the kidney. Fistula formation is also a complication seen in gossypiboma. We present the case of a patient who was initially suspected to have nephrocutaneous fistula after open pyelolithotomy. Later while undergoing open resection of fistula, he was found to have a retained surgical sponge (gossypiboma) near the lower pole of kidney. Gossypiboma is a term used for mass formed around a surgical sponge accidentally left in the body. It is most of the times not diagnosed by radiological imaging and thus results in unnecessary investigations to rule out other causes for the patient's symptoms. Having a high index of suspicion may lead to an earlier diagnosis. But the prevention of gossypiboma is of the utmost importance. A meticulous approach while operating by the surgeon and operating rooms staff is very important in doing so.