p53 and p16ink4a As Predictive and Prognostic Biomarkers for Nodal metastasis and Survival in A Contemporary Cohort of Penile Squamous Cell Carcinoma.

BACKGROUND: Human papilloma virus (HPV) infection is implicated in a proportion of invasive squamous cell carcinoma of the penis (PC). A subset of PC involves dysregulation of the p53 pathway. HPV in situ hybridization (ISH) and p16ink4a positivity are surrogate markers for HPV infection, and p53 immunohistochemistry (IHC) denotes abnormality in the p53 pathway. There remains an ambiguity with regard to the contribution of both the pathways in the prognosis of PC. We sought to analyze the clinicopathologic characteristics of a cohort of Indian PC patients with respect to p16 ink4a and p53 expression. PATIENTS AND METHODS: A cohort of 123 PC patients was studied for p16ink4aand p53IHC and HPVISH. The results of these biomarkers were correlated with various clinicopathologic parameters. RESULTS: p16ink4a and HPV ISH were positive in 47% and 53% of the tumors, respectively. The proportion of warty, basaloid, or mixed warty-basaloid tumor subtypes showed significant p16ink4apositivity (P < .0001) compared to other subtypes. Twenty-eight patients were dual negative (p53- /p16ink4a-), 32 were dual positive (p53+/p16ink4a+), 38 were p53+/p16ink4a-, and 25 were p53-/p16ink4a +. In patients where p16ink4a was negative, a p53-positive phenotype had a higher propensity for lymph node metastases (OR, 5.42; 95% CI, 1.75-16.80; P = .003). Similarly, p53 positivity dictates nodal involvement in the p16ink4a-positive subset of tumors (OR, 5.00; 95% CI, 1.23-20.17; P = .024). On multivariate analyses, pathologic subtypes (warty, warty-basaloid, and basaloid) (P < .0001), p16ink4aexpression (P < .0001), and absence of nodal metastasis (P < .0001) were significant predictors of improved overall (OS) and cancer specific survival (CSS). In Kaplan-Meier analysis, the OS was significantly longer in patients with p16ink4a + tumors (P < .0001), as was the CSS (P < .0001). Patients with dual positive tumors had a significantly higher OS (P < .001) and CSS (P = .012), in the entire cohort. In the node positive patients, dual positivity was associated with significantly higher OS (P < .0001); however, the median CSS for p53+/p16ink4a+tumors were not significantly different compared to p53- /p16ink4a- tumors (P = .064), although there was a trend towards improved CSS. CONCLUSIONS: There is a strong concordance between p16ink4aIHC and HPV ISH results. p16ink4a status is an independent predictor of survival (OS and CSS) in our cohort of PCs. p53 is a predictor of nodal metastasis irrespective of p16 status. Dual positive tumors have a significantly better outcome in comparison to dual negative tumors.

Management of superficial bladder carcinoma: time to rethink the treatment strategies in the era of orthotopic neo-bladder.

The objective of this study was to evaluate the recurrence and progression, on long-term follow-up, of patients with superficial bladder cancer managed with bladder sparing approach. A total of 48 patients with superficial bladder cancer, initially treated with bladder sparing approach between 1990 and 1992, were available for long-term follow-up ranging between 10 and 15 years; the remaining patients were lost to follow-up. All patients had undergone transurethral resection and adjuvant intravesical therapy. Recurrence was treated with resection and adjuvant therapy or radical cystectomy in cases of progression. Out of 48 study subjects, 11 had T1G1, 23 had T1G2 and 14 had T1G3 tumor. In the T1G1 group, 45.5% had recurrence. Four had single recurrence managed successfully with TURBT and intravesical therapy. One had multiple recurrences and underwent radiotherapy after the fifth recurrence. In the T1G2 group, 82.6% had recurrence and majority (60.8%) had multiple recurrences. Out of 14 cases with multiple recurrences, eight patients ultimately progressed to invasive bladder carcinoma and underwent radical cystectomy. Majority of these underwent ileal conduit because ileal neobladder could not be created due to severe fibrosis. All 14 patients with T1G3 had recurrence, of whom three (21.4%) had single recurrence. Out of the 11 other patients (78.6%) who had multiple recurrences, nine developed invasive bladder carcinoma and underwent radical cystectomy. Orthotopic neo-bladder could be performed only in one patient and the remaining had ileal conduit or Mainz pouch. We conclude that in the era of orthotopic neo-bladder offering good quality of life, radical cystectomy should be considered at the earliest opportunity in patients with aggressive superficial bladder cancer.

Substitution urethroplasty for anterior urethral strictures: buccal versus lingual mucosal graft.

AIM: To compare the results of substitution urethroplasty and donor site morbidity between buccal mucosal graft (BMG) and lingual mucosal graft (LMG). PATIENTS AND METHODS: Patients who underwent single-stage dorsal onlay free oral mucosal graft substitution urethroplasty by Barbagli's technique between January 2004 and August 2008 were included in this study. Patients who underwent buccal (cheek, lip) mucosal graft urethroplasty were included in group I and those who underwent LMG urethroplasty (tongue) were included in group II. All patients underwent complete evaluation of the stricture including inspection of the oral cavity. Exclusion criteria were stricture length <3 cm and complex strictures which required a multistage procedure. RESULTS: The results of urethroplasty were similar in both groups in terms of blood loss, duration of postoperative hospitalization, complications encountered at urethroplasty site, mean postoperative Q(max) and mean postoperative AUA symptom score. Early slurring of speech complications was seen in group II, but not in group I. The long-term complications of persistent oral discomfort, perioral numbness and tightness of the mouth were seen only in group I. CONCLUSION: LMG urethroplasty is a good substitute for BMG urethroplasty with equally good results of urethroplasty with lower donor site morbidity.

Dorsal onlay lingual mucosal graft urethroplasty for urethral strictures in women.

OBJECTIVE: To describe the technique and results of dorsal onlay lingual mucosal graft (LMG) urethroplasty for the definitive management of urethral strictures in women. PATIENTS AND METHODS: In all, 15 women (mean age 42 years) with a history suggestive of urethral stricture who had undergone multiple urethral dilatations and/or urethrotomy were selected for dorsal onlay LMG urethroplasty after thorough evaluation, from October 2006 to March 2008. After a suprameatal inverted-U incision, the dorsal aspect of the urethra was dissected and urethrotomy was done at the 12 o'clock position across the strictured segment. Tailored LMG harvested from the ventrolateral aspect of the tongue was then sutured to the urethrotomy wound over an 18 F silicone catheter. RESULTS: The preoperative mean maximum urinary flow rate of 7.2 mL/s increased to 29.87 mL/s, 26.95 mL/s and 26.86 mL/s with a 'normal' flow rate curve at 3, 6 and 12 months follow-up, respectively. One patient at the 3-month follow-up had submeatal stenosis and required urethral dilatation thrice at monthly intervals. At the 1-year follow-up, none of the present patients had any neurosensory complications, urinary incontinence, or long-term functional/aesthetic complication at the donor site. CONCLUSION: LMG urethroplasty using the dorsal onlay technique should be offered for correction of persistent female urethral stricture as it provides a simple, safe and effective approach with durable results.

Neo-bladder vaginal fistula: an unusual complication after orthotopic urinary diversion.

Development of neo-bladder vaginal fistula is not an unknown complication after cystectomy and orthotopic urinary diversion in females. Compared to native bladder, the wall of the neo-bladder is much thinner that may render it vulnerable to fistulization. Injury to the vagina during cystectomy is the most important predisposing factor. Herein, we present a case of neo-bladder vaginal fistula and discuss the potential surgical and clinical factors contributing to its occurrence as well as the treatment options available.

Our experience with genitourinary fistulae.

INTRODUCTION: Our objective was to analyze the incidence, etiopathology, diagnosis and therapeutic aspects of the genitourinary fistula in an Indian population. METHODS: This is a retrospective analysis of the genitourinary fistulae repaired at the Department of Urology, Institute of Medical Sciences, Banaras Hindu University, between January 1990 and December 2006. The surgical approach varied in each patient. Interposition grafts or flaps were used as and when required. The main outcomes analyzed were the incidence, etiology, surgical approaches, accessory procedure required, need for tissue interposition, cure rate per repair and overall success rate. RESULTS: Out of 558 cases, 403 were vesicovaginal, 84 ureterovaginal, 43 urethrovaginal and 28 vesicouterine fistulae. The most common etiology was obstructed labor (72.2%), followed by hysterectomy. The transvaginal route was preferred for repair wherever possible. The transabdominal route was adopted for the repair of supratrigonal vesicovaginal, ureterovaginal and vesicouterine fistulae and if bladder augmentation was required. Conservative management was successful in 1.9% of the vesicovaginal fistulae and in 8 cases of ureterovaginal fistula. The remaining cases were managed surgically with excellent results. CONCLUSION: Genitourinary fistulae are not life-threatening but are socially debilitating. Surgical repair provides the definitive cure, but expectant treatment can be tried in selective patients.

Lingual mucosal graft urethroplasty for anterior urethral strictures.

OBJECTIVE: To evaluate the effectiveness of a lingual mucosal graft (LMG) urethroplasty for anterior urethral strictures and the donor site complications. METHODS: A total of 30 patients underwent urethroplasty for anterior urethral strictures using dorsal on-lay of a LMG from March 2006 to December 2006. Most patients had balanitis xerotica obliterans as the etiology. The mean stricture length was 10.2 cm (range 3.7-16.5). Postoperatively, all patients underwent pericatheter urethrography at 3 weeks, followed by retrograde urethrography with micturating cystourethrography, and uroflowmetry at 3 and 6 months. Repeat uroflowmetry was done as, and when, required. RESULTS: The mean period of follow-up was 9 months (range 4-12). The overall success rate was 83.3%. The mean peak flow rate increased postoperatively from 4.36 mL/s to 35.5 mL/s at 3 months and 25.06 mL/s at 6 months of follow-up. One patient developed repeat stricture at the anastomotic site, and 4 patients developed recurrent meatal stenosis. CONCLUSIONS: The results of LMG urethroplasty were comparable to that of buccal mucosal graft urethroplasty. LMG is easy to harvest. Most importantly, the donor site complications were minimal without any functional or esthetic deficiency.

Relook TURBT in superficial bladder cancer: its importance and its correlation with the tumor ploidy.

OBJECTIVE: To evaluate various prognostic factor predictors of residual growth in Relook transurethral resection of bladder tumor (TURBT) in superficial bladder cancer. Also, to evaluate the role of Relook TURBT along with the ploidy for prediction of recurrence and stage progression in these patients. MATERIAL AND METHODS: Fifty patients with superficial bladder cancer underwent TURBT after complete evaluation. Ploidy of the tumor specimen was evaluated by flow cytometry. After 4 to 6 weeks of initial TURBT, these patients underwent Relook TURBT. Final treatment was given after the results of the histological evaluation of these specimens. Patients who underwent bladder sparing treatment were followed-up. RESULTS: Of the patients, 28.5% had residual tumor in Relook TURBT. Growth was found to be at the same site in 66.7% and at a different site 33.3%; 75% had single while 25% had multiple residual growth. Residual malignant tissue had a statistically significant correlation with size of the tumor (>3 cm), appearance (solid tumor), number (>3), grade (high), and multiple previous resections. Overall, the up-migration of stage and grade leads to change in treatment in 41.6%; 5 underwent radical cystectomy and 1 opted for radiotherapy; in 2 patients, intravesical BCG was given. In follow-up of mean 11.5 months, 16.6% had recurrence. Presence of residual growth in Relook TURBT along with number, size, morphology, and multiple previous resections were found to have significant correlation with the recurrence in these patients. Ploidy and grade of the tumor were not found to have correlation. CONCLUSIONS: Multiple, more than 3 cm, solid high grade tumor with > 3 previous resections were predictors of presence of residual tumor in Relook TURBT. Presence of residual growth is a significant risk factor for recurrence. Ploidy was not found to be significantly correlated with recurrence.

Dorsal onlay lingual mucosal graft urethroplasty: Comparison of two techniques.

OBJECTIVES: To compare the results of two different techniques of dorsal onlay lingual mucosal graft (LMG) urethroplasty for anterior urethral strictures. METHODS: Thirty patients underwent dorsal onlay LMG urethroplasty by Barbagli's technique (group I) and 25 through a ventral sagittal urethrotomy approach (group II). All of the patients were followed up with a pericatheter urethrography at 3 weeks, retrograde urethrography with micturating cystourethrography and uroflowmetry at 3, 6 and 12 months. RESULTS: Mean follow up was 22 months and 13 months in group I and II, respectively. The mean peak flow rate increased from 4.2 mL/s preoperatively to 35.5, 25.06 and 25 mL/s at 3, 6, and 12 months, respectively, in group I and from 7.8 mL/s to 34.2, 28.4 and 26.2 mL/s at 3, 6 and 12 months, respectively, in group II. Five patients in group I and two patients in group II had an anastomotic stricture at 12 months. Meatal narrowing was seen in five patients in group I and three patients in group II. The overall success rate was 83.4% and 76.6% in group I and 90% and 80% in group II at 6 and 12 months, respectively. One patient had chordee in group I and no patient had chordee in group II. There was a shorter operative time and less blood loss in group II. CONCLUSIONS: Dorsal onlay LMG urethroplasty through a ventral sagittal approach is better than the Barbagli's technique in terms of results and complications.

Genito-urinary polyps: summary of the 10-year experiences of a single institute.

OBJECTIVE: We present a large series of polyps situated in various parts of the urinary tract in adults, including 12 cases of fibroepithelial polyps, four cases of eosinophilic cystitis, three cases of benign prostatic epithelial polyp, and one case of transitional cell carcinoma presenting as a bladder polyp. MATERIAL AND METHODS: Data on 23 patients with polyps in the urinary tract treated in our department from December 1995 to December 2005 were reviewed. The characteristics of the patients, disease, and treatment modalities were recorded. RESULTS: Of the 23 patients treated in our institute during the study period, seven had polyps in the ureter, eight had polyps in the bladder, and eight had polyps in the urethra. Twenty-one patients underwent endoscopic resection of the polyps, and two patients were managed conservatively with medical therapy. Twenty-two polyps were benign (fibroepithelial polyps, benign prostatic epithelial proliferations, eosinophilic cystitis), and in one patient transitional cell carcinoma presented as a bladder polyp. Postoperative recovery was excellent. Mild hematuria manifested in two patients during the perioperative period, but there was no recurrence in the follow-up period. Two patients with a urethral polyp managed with endoscopic resection developed urethral stricture during the postoperative period and required repeated urethral dilatations during the follow-up period. CONCLUSION: The presence of polyps in the urinary tract is rare. The treatment of choice is endoscopic resection, and the prognosis of these patients is excellent.

Lingual mucosal graft substitution urethroplasty for anterior urethral strictures: our technique of graft harvesting.

OBJECTIVE: To describe our technique of lingual mucosal graft harvesting for substitution urethroplasty and the complications encountered at the donor site. METHODS: Twenty-eight patients who underwent lingual mucosal graft urethroplasty between May 2006 and March 2007 were included in this study. TECHNIQUE: The site of the graft harvest is the lateral mucosal lining of the tongue. Graft harvesting is started from the posterior landmark of the graft on the left side of the tongue. It is continued across the tip of the tongue to the other side if lengthier graft is required. The graft harvesting site is simultaneously closed with continuous running suture using 4-0 polyglactin suture to achieve immediate and good homeostasis. RESULTS: Mean duration of follow up was 4.2 months. Average length of harvested graft was 6.5 cm. Mean harvesting time was 18 min. At the first postoperative day, 92% patients experienced pain at donor site and 24% had slurring of speech. By third postoperative day, >70% were free of pain and four had slurring of speech. By sixth postoperative day, none of the patient suffered pain. All the patients were able to resume oral fluid within 24 h, eat soft solid diet in 48-72 h and return to normal diet after 4-5 days of surgery. No patient suffered from difficulty in opening the mouth, salivation disturbances, peri-oral numbness or difficulty in protrusion of tongue. CONCLUSION: Lingual mucosal graft harvesting is a simple procedure, provides lengthy graft and is associated with minimal donor site complications.

Oral complications after lingual mucosal graft harvest for urethroplasty.

BACKGROUND: The aim of this study was to assess the complications at donor site after lingual mucosal graft harvesting for urethroplasty. METHODS: From March 2006 to December 2006, 30 patients of anterior urethral stricture underwent lingual mucosal graft urethroplasty. The site of the harvest graft was lateral mucosal lining of the tongue. Donor site complications, that is, pain, slurring of speech, pain during speech, salivatory changes and difficulty in protrusion of tongue were noted. RESULTS: The mean (range) age of patients was 36.2 years (22-52 years). The mean (range) stricture length was 8.4 cm (4.8-16 cm) and graft length was 8.5 cm (4.2-16.2 cm). Mean duration of follow up was 3.8 months. At the first postoperative day, 90% of the patients experienced pain at donor site and 20% had slurring of speech. Pain was mild to discomforting in 80% and distressing to horrible in 13% of the patients. By third postoperative day, two-thirds were pain free, one-thirds had mild pain only and none had slurring of speech. By day 6 of surgery, all patients were pain free. Six per cent of the patients reported numbness over ventral aspect of anterior half of tongue, which persisted in the first follow up and subsided by second follow up. There was no bleeding, haematoma or infection at donor site. All patients were able to resume oral fluid within 24 h, eat soft solid diet in 48-72 h and return to normal diet after 4-5 days of surgery. No patient complained of difficulty in opening the mouth, salivation disturbances, perioral numbness or difficulty in protrusion of tongue. No long-term functional or aesthetic complications were reported. CONCLUSION: Lingual mucosal graft harvesting is feasible, provides a long graft, is easy to carry out and is the least morbid procedure.

Xanthogranulomatous pyelonephritis: our experience with review of published reports.

BACKGROUND: The aim of this study was to analyse the cases of xanthogranulomatous pyelonephritis with review of published reports. METHODS: We retrospectively reviewed all nephrectomy specimens during February 1995 to January 2006. We found 26 cases of xanthogranulomatous pyelonephritis. We prepared a chart of these cases consisting of preoperative symptoms, laboratory findings, radiological imaging results and preoperative diagnosis. Open nephrectomy was carried out in all cases. RESULTS: Age group of the patients was 6-65 years and male : female ratio was 1.6:1. Twenty-two patients presented to us with intermittent high-grade fever, 21 with flank pain, 18 with loin mass, 2 with haematuria and 1 was detected during screening of vague gastrointestinal symptoms. Twenty-five patients had pyuria and only 10 had sterile urine culture. In all patients, only one kidney was affected. All patients had renal calculi 10-42 mm in size with bilaterally enlarged kidneys. Ipsilateral kidney was enlarged because of hydronephrosis or pyonephrosis in all cases and contralateral kidney was enlarged because of compensatory hypertrophy in 13 cases. Ipsilateral kidney had severely compromised renal function in all cases. Associated psoas abscess was present in one and tuberculosis in another. CONCLUSION: Xanthogranulomatous pyelonephritis is a relatively rare entity that is associated with obstruction, stones and infection of the urinary tract. Late presentation leads to loss of renal parenchyma. It cannot be differentiated preoperatively with renal tumours (renal cell carcinoma and Wilms' tumour), pyonephrosis, infected hydronephrosis and renal lymphoma. Nephrectomy and antibiotics are the treatment of choice.