Biomedical subjects

Dragan Golijanin

Publications and source records attributed to Dragan Golijanin.

14 recordsLinked to original sources

PubMed2006

Adult genitourinary sarcoma: the 25-year Memorial Sloan-Kettering experience.

PURPOSE: Urological sarcomas are rare. We describe a continued single institutional experience during 25 years. MATERIALS AND METHODS: The records from July 1977 to July 2003 were reviewed of all patients at our institution with sarcoma arising in the urinary tract or male genital system who were 16 years or older at diagnosis. RESULTS: The primary tumor site in 131 patients was the bladder in 20, the kidney in 26, paratesticular in 57, the prostate in 21 and other in 7. Median followup was 4.0 years. The most common histological subtypes were leiomyosarcoma in 29% of cases and liposarcoma in 26%. Median tumor size was 7 cm and 78% of lesions were high grade. Of the patients 28 (21%) presented with metastatic disease and their median survival was 1.4 years compared to 10.7 years in patients without metastatic disease (p < 0.0001). Disease specific survival was 56% and 42% at 5 and 10 years, respectively and median survival was 7.6 years. On univariate analysis unfavorable prognostic variables for disease specific survival were metastasis at presentation, high tumor grade, a lack of leiomyosarcoma and liposarcoma histological subtypes, prostate sarcoma and large tumor size, incomplete surgical resection and positive surgical margin. Patient sex, age and surgical margin status were not significant predictors. On multivariate analysis 2 variables remained significant predictors of disease specific survival, including tumor size (HR 1.1, 95% CI 1.02 to 1.17) and absent metastasis at diagnosis (HR 4.9, 95% CI 1.4 to 17.2). CONCLUSIONS: Predictors of disease specific survival include local disease at presentation, complete tumor resection and tumor grade, size, location and histological subtype. With adequate surgical treatment most patients who presented with primary disease and underwent complete surgical resection achieved prolonged disease specific survival.

Adolescent↗

PubMed2006

Robot-assisted radical prostatectomy in obese patients.

OBJECTIVES: Few centers perform extraperitoneal robot assisted radical prostatectomy. The average patient weight is increasing to the mildly obese. Little is known as to the difficulty-impact, obesity may have on robot-assisted extraperitoneal prostatectomy (RAP). We assess our own experience with obese patients undergoing RAP. MATERIALS AND METHODS: Information on 375 consecutive patients undergoing robot-assisted extraperitoneal prostatectomy by a single surgeon was gathered. Obesity is defined as having a body mass index (BMI) greater than 30 kg/m2. Patients with BMI >/= 30 were compared to those with BMI < 30. Specific comparators between the groups were: age, total operating time, estimated blood loss, total prostate specific antigen (PSA), specimen weight, pathological stage, grade and margin, complications, and functional outcomes. RESULTS: Sixty-seven men were identified as obese. When comparing the two groups, no statistically significant difference (p > .05) was noted in operative time (229 versus 217 min), blood loss (205 versus 175 ml), PSA, clinical and pathologic stages, specimen weight, and complications. 15% of non-obese patients had a positive margin compared to 12% of obese patients (p > .05). The 6-month continence rate in patients with a BMI >/= 30 was 92% versus 97% in patients with a BMI < 30. CONCLUSIONS: The extraperitoneal approach to performing a robot-assisted prostatectomy is not associated with increased morbidity in the obese patient. There were no statistically significant differences noted in oncological or functional outcomes between the two groups.

Adult↗

PubMed2005

Chemotherapy induces the expression of cyclooxygenase-2 in non-small cell lung cancer.

PURPOSE: To determine the effect of taxane-based chemotherapy on intratumoral levels of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Lung specimens obtained at the time of surgery were used to measure levels of COX-2 and PGE(2) in tumors and adjacent nontumorous tissues in three subsets of NSCLC patients who underwent: (A) surgical resection only (n = 16); (B) surgical resection after preoperative taxane-based chemotherapy (n = 13); or (C) surgical resection after preoperative chemotherapy coadministered with the selective COX-2 inhibitor, celecoxib 400 mg bid (n = 17). RESULTS: Levels of intratumoral PGE(2) were nearly 3-fold higher among patients who received preoperative chemotherapy compared with those treated by surgery alone (P < 0.001). This difference was abrogated by the addition of celecoxib to preoperative chemotherapy (P < 0.001). Amounts of intratumoral COX-2 were approximately 3-fold higher in groups of patients who received preoperative chemotherapy with celecoxib (P < 0.0001) or without celecoxib (P < 0.001), compared with the group who underwent surgical resection only. Importantly, statistically significant positive correlations between COX-2 and PGE(2) were observed in the surgery only (r = 0.502, P = 0.047) and preoperative chemotherapy groups (r = 0.740, P = 0.004); this correlation was abrogated when celecoxib was given with chemotherapy (r = 0.005, P = 0.98). CONCLUSIONS: Treatment with chemotherapy led to increased amounts of COX-2 and PGE(2) in NSCLC. Cotreatment with celecoxib abrogated the increase in levels of PGE(2) but not COX-2 induced by chemotherapy. Importantly, these results clearly show that levels of a pharmacologic target (i.e., COX-2) can be affected by both the intrinsic molecular properties of a tumor and therapy.

Adult↗

PubMed2005

Urothelial cancer of the renal pelvis in percutaneous nephrolithotomy patients.

INTRODUCTION: The association between staghorn calculus of the kidney long-standing and urothelial tumors of the renal pelvis is well documented. We describe 3 patients with urothelial cancer in a kidney who underwent percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Retrospective analysis of our series of more than 500 PCNLs revealed 3 patients in whom urothelial cancer of the renal pelvis was diagnosed during or following percutaneous stone removal. Preoperative assessment included IVP, renal sonography and renal scan using DTPA in all 3 patients, and CT in 2 patients. Imaging did not raise the suspicion of a neoplastic lesion. RESULTS: All patients had a long history of urolithiasis and urinary infections. No patient was diagnosed preoperatively. One patient was diagnosed postoperatively, when a CT demonstrated a renal lesion. The second patient underwent simple nephrectomy due to a non-functioning kidney, and the tumor was found on pathological analysis. In the third patient, biopsies were taken from a suspicious-looking tissue in the renal pelvis during the PCNL session. All patients had transitional cell carcinoma: 1 associated with sarcomatoid features and 1 with squamous carcinoma. They all died from metastatic disease 2-19 months after the diagnosis of urothelial cancer. CONCLUSIONS: The preoperative diagnosis of urothelial cancer in patients with staghorn stones is difficult due to the existing stone and inflammation. Since the prognosis of urothelial cancer is extremely poor, biopsies of the renal pelvis, obtained directly through the nephroscope during the PCNL session, may be the only key for early diagnosis and treatment. A high index of suspicion should be raised when patients suffering from infected staghorn calculi are encountered, and such intraoperative biopsies should be considered.

Aged↗

PubMed2004

Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis.

PURPOSE: Prostaglandin E2 (PGE2) promotes malignant growth. Cyclooxygenase (COX) catalyzes the synthesis of PGH2, which is converted, in turn, by microsomal prostaglandin E synthase (mPGES-1) to PGE2. One strategy for inhibiting carcinogenesis is to prevent PGE2 production in premalignant and malignant tissues. It is important, therefore, to determine whether enzymes involved in PGE2 biosynthesis are deregulated in neoplasia. The main purpose of this study was to determine whether amounts of COX-2 or mPGES-1 were increased in intraepithelial neoplasia or squamous cell carcinoma (SCC) of the penis. Because human papillomavirus (HPV) has been linked to the development of penile SCC, a secondary objective was to determine whether COX-2 was overexpressed in SCC arising in an HPV16 transgenic mouse. EXPERIMENTAL DESIGN: Immunohistochemistry and immunoblotting were used to evaluate the expression of COX-2 and mPGES-1 in benign and malignant lesions including metastases to lymph nodes. Amounts of intratumoral PGE2 were quantified by enzyme immunoassay. Reverse transcription-PCR was used to determine the expression of each of the four known receptors (EP(1-4)) for PGE2. RESULTS: Immunohistochemistry demonstrated increased expression of COX-2 and mPGES-1 in dysplasia, carcinoma in situ, invasive SCC, and metastases to lymph nodes. Immunoblot analysis confirmed that COX-2 and mPGES-1 were consistently overexpressed in SCC. PGE2 and all four of the PGE2 receptor subtypes were detected in each of the tumor samples. Elevated levels of COX-2 were also detected in SCC arising in an HPV16 transgenic mouse. CONCLUSIONS: Increased amounts of COX-2 and mPGES-1 were detected in penile intraepithelial neoplasia and carcinoma. These findings provide the basis for evaluating whether inhibiting COX-2 will be useful in the prevention or treatment of penile SCC.

Animals↗

PubMed2004

Microsomal prostaglandin E synthase-1 is overexpressed in inflammatory bowel disease. Evidence for involvement of the transcription factor Egr-1.

Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the conversion of cyclooxygenase-derived prostaglandin (PG) H(2) to PGE(2). Increased amounts of mPGES-1 were detected in inflamed intestinal mucosa from patients with inflammatory bowel disease (IBD). Treatment with tumor necrosis factor (TNF)-alpha stimulated mPGES-1 transcription in human colonocytes, resulting in increased amounts of mPGES-1 mRNA and protein. The inductive effect of TNF-alpha localized to the GC box region of the mPGES-1 promoter. Binding of Egr-1 to the GC box region of the mPGES-1 promoter was enhanced by treatment with TNF-alpha. Notably, increased Egr-1 expression and binding activity were also detected in inflamed mucosa from IBD patients. Treatment with TNF-alpha induced the activities of phosphatidylcholine-phospholipase C (PC-PLC) and protein kinase (PK) C and enhanced NO production. A pharmacological approach was used to implicate PC-PLC --> PKC --> NO signaling as being important for the induction of mPGES-1 by TNF-alpha. TNF-alpha also enhanced guanylate cyclase activity and inhibitors of guanylate cyclase activity blocked the induction of mPGES-1 by TNF-alpha. YC-1, an activator of guanylate cyclase, induced mPGES-1. Overexpressing a dominant negative form of PKG blocked TNF-alpha-mediated stimulation of the mPGES-1 promoter. Taken together, these results suggest that overexpression of mPGES-1 in IBD is the result of Egr-1-mediated activation of transcription. Moreover, TNF-alpha induced mPGES-1 by stimulating PC-PLC --> PKC --> NO --> cGMP --> PKG signal transduction pathway.

Blotting, Northern↗

PubMed2004

Bladder cancer as a prognostic factor for upper tract transitional cell carcinoma.

PURPOSE: Upper tract transitional cell carcinoma (UTTCC) is a relatively rare tumor. Overall 5-year disease specific survival is in the range of 16.5% to 95% depending on stage. In this study we evaluated predictors associated with disease recurrence and disease specific survival. MATERIALS AND METHODS: We report on 129 patients with a median age of 68 years who underwent nephroureterectomy for UTTCC between July 1989 and June 2002. A total of 67 patients had primary UTTCC and 62 had previous (52) or synchronous (10) transitional cell carcinoma of the bladder (BTCC). Medical records were reviewed and analyzed for possible prognostic predictors (primary tumor stage, grade, multifocality, carcinoma in situ, symptoms and signs at presentation, sex, and history of smoking). Disease specific survival and freedom from bladder recurrence were assessed with the Kaplan-Meier method, and differences between the groups were compared using the log rank test. The Cox proportional hazards regression model was used to assess the significance of each predictor. RESULTS: Disease specific death was reported for 44 patients. In a multivariate analysis using previous BTCC as a predictor (categorized as superficial, invasive or none), primary disease stage and history of BTCC were associated with disease specific survival (p = 0.001 and p = 0.018). History of BTCC grouped the patients into distinct populations in terms of disease specific survival and freedom from bladder recurrence. CONCLUSIONS: This study demonstrates that a history of BTCC (invasive or superficial) has an adverse effect on the prognosis of patients diagnosed with UTTCC independent of primary tumor stage.

Adult↗

PubMed2004

Laparoscopic nephrectomy for infected, obstructed and non-functioning kidneys.

Since laparoscopic nephrectomy was introduced by Clayman et al, it has been doubted whether it should be employed in patients with extensive perirenal fibrosis. In this series, 20 consecutive patients underwent laparoscopic nephrectomy for obstructed, infected, non-functioning kidneys. Preoperative assessment included urine cultures, abdominal sonography, intravenous pyelography, computerized tomography and a renal scan. Laparoscopic nephrectomies were performed using either the transperitoneal or the retroperitoneal approach.Patients' mean age was 52 years (range 20-77, SD = 15.2). Three patients underwent previous open surgery on the same kidney and 15 had percutaneous nephrostomies. The etiology of obstruction was stone disease in 15 cases, uretero-pelvic junction obstruction (3), iatrogenic ureteral injury (1), and infected multicystic kidney (1). Mean operative time was 224 minutes (range 140-325, SD = 57). Conversion to open surgery was necessary in one patient due to splenic injury. Mean hospital stay was 3 days (range 2-6, SD = 1). Laparoscopic nephrectomy was feasible in cases of severe perirenal fibrosis, with an acceptable rate of complications, and may be considered in patients with obstructed, infected, and non-functioning kidneys.

Adult↗

PubMed2003

Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma.

Elevated levels of prostaglandin E(2) (PGE(2)) occur in head and neck squamous cell carcinoma (HNSCC) and have been associated with a poor prognosis. Recently, an inducible microsomal prostaglandin E synthase-1 (mPGES) was identified. This enzyme converts the cyclooxygenase product prostaglandin H(2) (PGH(2)) to PGE(2). Given the apparent significance of PGE(2) in carcinogenesis, it is important to elucidate the mechanisms that account for increased amounts of PGE(2) in HNSCC. By immunoblot analysis, mPGES was overexpressed in 11 of 14 (79%) cases of HNSCC compared with adjacent normal tissue. Immunohistochemistry localized mPGES expression to neoplastic epithelial cells. Cell culture was used to determine whether cellular transformation was associated with increased amounts of mPGES. Levels of mPGES protein and mRNA were markedly elevated in HNSCC cell lines (1483 and Ca9-22) versus a nontumorigenic oral epithelial cell line (MSK-Leuk1). Interestingly, treatment of MSK-Leuk1 cells with PGE(2) caused both dose- and time-dependent stimulation of cell growth. Each of the four known receptors for PGE(2) (E-prostanoid receptor subtypes 1-4) was detected in head and neck squamous mucosa. Taken together, these results suggest that overexpression of mPGES contributes to the increased levels of PGE(2) found in HNSCC. Additional studies will be needed to determine whether this enzyme is a bona fide target for anticancer therapy.

Blotting, Western↗

PubMed2003

Orthotopic urinary diversion after cystectomy for bladder cancer: implications for cancer control and patterns of disease recurrence.

PURPOSE: The impact of orthotopic urinary diversion on the quality of cystectomy and ensuing cancer control has not been adequately studied. We analyzed our experience with this clinical problem. MATERIALS AND METHODS: The records of 214 patients who underwent cystectomy and orthotopic diversion for bladder cancer were retrospectively evaluated and compared with those of 269 treated with an ileal conduit. Analyzed end points included overall and cancer specific survival. We specifically assessed the patterns of relapse and their association with pathological findings at cystectomy in the neobladder group. RESULTS: No cancer specific survival difference was identified in the neobladder and ileal conduit cohorts when adjusting for pathological stage. Patterns of relapse in 62 of the 214 patients with a neobladder (29%) included local recurrence in 23 (11%), distant recurrence in 19 (9%), and combined local and distant recurrence in 18 (8%). Urethral recurrence was rare (2%). Of 10 patients (4.6%) diagnosed with upper tract recurrence 6 and 4 initially had relapse in the ureteroenteric anastomosis and renal pelvis, respectively. Five of the 6 patients with anastomotic relapse had evidence of disease in the intramural or juxtavesical ureter that was removed en bloc with the cystectomy specimen. Only 1 patient required neobladder takedown after such anastomotic recurrence. CONCLUSIONS: These results indicate that neobladders do not compromise the quality of preceding cystectomy or interfere with management in the presence of local or distant disease relapse. Our data suggest that involvement of the intramural or juxtavesical ureteral segment at cystectomy irrespective of surgical margin status may identify patients at higher risk for anastomotic recurrence, which is associated with an ominous prognosis.

Aged↗

PubMed2003

Outcome analysis of tunica vaginalis flap for the correction of recurrent urethrocutaneous fistula in children.

PURPOSE: Urethrocutaneous fistula is the most common (2% to 10%) complication of hypospadias surgery. The correction of such fistula is associated with a 10% to 40% failure rate. The key measure to ensure a successful repair is separation of the suture lines in the urethra and skin, using well vascularized elastic tissue. If the dartos fascia is unavailable and local penile skin is fibrotic as a result of previous operations, a tunica vaginalis flap may be considered. We report our experience with tunica vaginalis flap as an adjunct to fistula repair. MATERIALS AND METHODS: We used tunica vaginalis flap for the repair of recurrent urethrocutaneous fistulas in 14 children with a mean age of 7.6 years (range 3 to 15). All patients had undergone previous hypospadias repairs and previous attempts to close the fistula had failed. The mean number of fistulas per patient was 1.6 (range 1 to 4), and the locations were perineal (1), penoscrotal (3), midshaft (10), and subcoronal (8). The mean number of failed previous closures with local penile skin flaps was 2.4 (range 1 to 5). Surgery was initiated by injecting povidone solution via the urethral meatus to identify all fistulas. Calibration or cystoscopy excluded distal urethral strictures. Surgery was performed using a microscope and fistulas were closed primarily in 12 patients and with an onlay island flap in 2. The urethral suture line was covered with a flap of tunica vaginalis, which was harvested through a small scrotal incision and mobilized via a subcutaneous tunnel into the penis. The testis was then fixed to the scrotum. A urethral stent with or without suprapubic catheter drainage provided urinary diversion for 2 to 7 days. RESULTS: The repair was successful in all patients. During a mean followup of 44 months (range 8 to 60) there was no evidence of recurrent fistulas or urethral strictures. Penile cosmesis was excellent, and all parents reported a straight penis when erected. No postoperative complications were encountered in the testicles. CONCLUSIONS: Repair of recurrent urethrocutaneous fistulas with a tunica vaginalis flap is highly effective regardless of fistula location. This flap is easy to mobilize and provides excellent coverage of the urethral suture line. It is a simple procedure with no complications to the testicles.

Adolescent↗

PubMed2003

Carcinoma in a bladder diverticulum: presentation and treatment outcome.

PURPOSE: In this retrospective review we characterize the outcomes of patients treated for transitional cell carcinoma in a bladder diverticulum. MATERIALS AND METHODS: Between 1986 and 2001, 39 patients were treated for tumors in a bladder diverticulum. All patients underwent initial transurethral resection of the tumor. Based on cystoscopic evaluation, bimanual examination and computerized tomography findings, tumors were classified as superficial (Ta, Tis), superficially invasive confined to diverticulum (T1) or extra diverticular (T3+). Patients with superficial or superficially invasive disease were treated either conservatively with repeat transurethral resection, or with partial or radical cystectomy. Patients with extra diverticular extension were treated with partial or radical cystectomy when amenable to surgical extirpation. Predictors of outcome were assessed by univariate and multivariate analyses. End point was overall and disease-specific survival. RESULTS: Of our cohort of 39 patients 13 (33%) presented with superficial disease, 13 (33%) with superficially invasive tumors and 13 (33%) with invasive (extra diverticular) disease. Actuarial 5-year disease specific survival for the cohort was 72 +/- 5.4%. Significant differences in 5-year disease specific survival were observed among patients presenting with superficial tumors (83 +/- 9%), superficially invasive tumors (67 +/- 7%) and extra diverticular disease (45 +/- 14%). Of the patients presenting with T1 tumors the primary mode of treatment did not correlate with outcome. In a multivariate model clinical staging was the only independent predictor of outcome and concomitant carcinoma in situ reached borderline significance. CONCLUSIONS: Our data support a conservative approach for tumors confined to the bladder diverticulum, provided complete removal is feasible and close surveillance ensues.

Adult↗

PubMed2002

Evaluation of urine CYFRA 21-1 for the detection of primary and recurrent bladder carcinoma.

BACKGROUND: The urinary concentration of soluble cytokeratin 19 fragments, measured by the CYFRA 21-1 assay, may be used for the noninvasive, early detection of bladder carcinoma. METHODS: This prospective study examined urine samples from 325 patients. The authors included 152 patients who presented with hematuria or irritative voiding symptoms (Group 1), 107 patients who were under surveillance after undergoing transurethral resection of bladder carcinoma (Group 2), 46 patients with urinary tract pathology other than bladder carcinoma (Group 3), and 20 healthy participants (Group 4). The urine concentration of CYFRA 21-1 was measured by an immunoradiometric assay. The patients in Groups 1 and 2 underwent cytoscopy and urine cytopathology. Biopsies were obtained if a tumor was seen on cytoscopy or if there was a suspicion of carcinoma in situ (CIS). RESULTS: The optimal cut-off concentration for the detection of primary bladder tumors, 4.9 microg/L, resulted in a sensitivity of 79.3% and a specificity of 88.6%. The optimal threshold for the detection of recurrent bladder tumors (excluding patients who had been treated with intravesical bacillus Calmette-Guerin [BCG]), 4.04 microg/L, resulted in a sensitivity of 76.2% and a specificity of 84.2%. There was no significant advantage for centrifugation of the urine samples or for determination of the creatinine concentration in the urine samples. The CYFRA 21-1 assay of urine samples provided a three-fold greater sensitivity compared with the sensitivity of cytology for detecting Grade 1 transitional cell tumors. CYFRA 21-1 detected 91.9% of Grade 3 tumors, 100% of CIS, and 92.8% of invasive bladder tumors (T2 or higher classification). The CYFRA 21-1 assay detected all tumors that had positive cytology with the exception of only one tumor. Conversely, the assay identified 71% of primary tumors and 65% of recurrent tumors that were missed by cytopathology. Urinary stones, infection, and previous intravesical BCG immunotherapy caused many false positive results. CONCLUSIONS: The urinary CYFRA 21-1 assay is a useful test for the noninvasive detection of bladder carcinoma and for surveillance of patients who were not treated previously with BCG. It may be used in combination with urine cytology and bladder ultrasound. Multi-institutional trials are required to compare the accuracy as well as the cost of this combination of tests with cystoscopy.

Adolescent↗

PubMed2002

Primary and postoperative retroperitoneal fibrosis-experience with 18 cases.

OBJECTIVES: Retroperitoneal fibrosis (RPF) is an uncommon disease complicated by ureteral entrapment. Its etiology includes several medications, periaortic inflammation, abdominal and retroperitoneal operations, radiotherapy, and malignancy. We present 18 patients, 14 of whom developed RPF after surgery and radiotherapy. METHODS: During the past 12 years, we treated 7 women and 11 men. The diagnosis was based on intravenous urography, retrograde pyelography, and computed tomography features. Computed tomography-guided or intraoperative biopsies were taken to differentiate benign from malignant fibrosis. In all patients, percutaneous stent nephrostomies or internal stents were inserted before surgery. The operation included ureterolysis with an omental flap or ureteral reimplantation. Follow-up included renal function tests, intravenous urography, and computed tomography. RESULTS: The mean patient age was 57.3 years (range 36 to 85). Fourteen patients developed RPF after abdominal or retroperitoneal surgery. Three had primary RPF and one malignant RPF due to metastatic disease. Six patients also underwent radiotherapy. The mean time between the insults to the diagnosis of RPF was 18.6 months (range 1 to 96). Ten patients had bilateral obstruction. Fourteen patients underwent surgery and four were treated with stenting only. Of the 14 patients who underwent surgery, 10 had a normal intravenous urogram postoperatively and 4 had decreased function of the formerly obstructed kidney. In 1 patient, re-entrapment of the ureter appeared owing to pelvic recurrence of tumor. At last follow-up, 1 patient waits with stents. The mean follow-up time was 22 months (range 4 to 52). CONCLUSIONS: The etiology of RPF varies. The unique feature of our series was the high incidence of patients who developed RPF after surgery and radiotherapy to the retroperitoneum. Nephrostomy drainage and ureteral stenting facilitated surgery. Ureterolysis combined with wrapping the ureter with an omental flap or re-implantation ensured good anatomic and functional results.

Adult↗