Endovascular Therapy for Arteriogenic Erectile Dysfunction With a Novel Sirolimus-Eluting Stent.

BACKGROUND: Arteriogenic erectile dysfunction is a common disease oftentimes not satisfactory treatable with medical therapy. AIM: To assess the safety and clinical success rate of endovascular revascularization of erection-related arteries with the angiolite BTK stent in patients with arteriogenic erectile dysfunction. METHODS: A total of 100 consecutive men (61.8 ± 10 years) with atherosclerotic lesions in erection-related arteries agreed to participate and were included into a single-center all-comers registry. Endovascular therapy with angiolite BTK drug-eluting stents was performed on a total of 211 lesions. Patients received a baseline International Index of Erectile Function (IIEF)-15 questionnaire at first presentation and 3 and 12 months after stenting. An improvement by 4 points in the erectile function domain consisting of 6 questions (IIEF-6) was defined as minimal clinically important difference. A total of 24 patients with 52 stented arterial lesions underwent angiographic follow-up of the initially treated arterial side during secondary revascularization of the contralateral side (angiographic sub-study). OUTCOME: Clinical improvement of erections in 100 patients undergoing endovascular revascularization of erection-related arteries. RESULTS: No major adverse events occurred during endovascular revascularization or within 30 days thereafter. Technical success was achieved in all lesions and procedural success in all patients. At 1 year, 55 of 97 patients (56.7%) improved by at least 4 points in IIEF-6 score and thus achieved a clinically relevant improvement of erectile function.In the angiographic sub-study, arterial patency and binary restenosis were observed in 46 of 52 (88.5%) and in 8 of 52 (15.4%), respectively, after a mean follow-up of 9.6 ± 5.8 months. CLINICAL IMPLICATIONS: In patients with arteriogenic erectile dysfunction, endovascular therapy with a novel thin-strut sirolimus eluting stent is a safe and feasible treatment option. STRENGTHS & LIMITATIONS: This real-world arterial revascularization registry included patients with a multitude of risk factors for ED, thereby representing the heterogeneity in patients in the clinical practice, which is one of its strengths but also one of its weaknesses. Another strength was the focus being laid on analyzing outcomes of patients with arteriogenic ED using only a single endovascular device. Further studies are warranted to better define subgroups of patients with impaired clinical outcomes. CONCLUSION: Within the present all-comers registry, endovascular therapy of erectile dysfunction with the angiolite BTK stent was shown to be a safe and feasible treatment option resulting in clinical improvement rates comparable to earlier clinical trials although also showing that further research is warranted to define patient subgroups with particular benefits of endovascular therapy. Schönhofen J, Räber L, Knöchel J, et al. Endovascular Therapy for Arteriogenic Erectile Dysfunction With a Novel Sirolimus-Eluting Stent. J Sex Med 2021;18:315-326.

Frequency and anatomic distribution of arterial obstructions in patients with vasculogenic erectile dysfunction not responding to intracavernous prostaglandin.

Background: The extent of arterial disease in patients with erectile dysfunction (ED) non-responsive to intracavernosal injection of Alprostadil is of importance for therapeutic options. However, published evidence, in particular angiographically validated is scarce. Here we investigated arterial lesion patterns in this specific patient cohort by selective angiography. Patients and methods: A cohort of 239 patients received a clinical and duplex-sonographic workup for ED of suspected vascular origin. Duplex ultrasound of the cavernosal arteries was performed after intracavernosal injection of 10 µg Alprostadil. Consequently, standardized workup included grading of the erectile and determination of peak systolic velocity (PSV) and end-diastolic velocity (EDV) in both cavernosal arteries. PSV-values below 30 cm/sec indicated reduced arterial flow, whereas EDV-values above 15 cm/sec indicated a venous leak of the pudendal veins. All patients with suspected arterial ED based on duplex sonography underwent contrast-enhanced computed tomography. Endovascular therapy was carried out in ED patients not responsive or with significant side effects to PDE-5-inhibitors or Alprostadil by selective angiographic depiction of erection-related arteries. Results: 54 patients with a mean age of 61.2 (±9.8) years underwent angioplasty of erectionr elated arteries. Out of these 48/54 (89%) patients presented with an erection considered insufficient for penetration (E0-E3) subsequent to intracavernous application of 10 µg Alprostadil. 14/48 (29%) patients had bilateral arterial obstructions and 34/48 (71%) had unilateral disease. Commonly affected was the internal pudendal artery (n = 31, 65%), followed closely by the common penile artery (n = 30, 64%). The least affected arteries were the dorsal penile (n = 6, 13%), hypogastric (n = 4, 8%), common iliac (n = 4, 8%), cavernosal (n = 4, 8%), and inferior gluteal (n = 1, 2%) arteries. Conclusions: Arterial obstructions amenable to endovascular revascularization are frequent in patients non-responsive to intracavernosal prostaglandin administration. Therapeutic strategies in ED patients non-responsive to conservative measures should therefore consider endovascular treatment opportunities.

Intravesical BCG treatment causes a long-lasting reduction of recurrence and progression in patients with high-risk non-muscle-invasive bladder cancer.

PURPOSE: To analyse if BCG treatment leads to long-term reduction of recurrence, progression, and cancer-specific mortality (CSM) in patients with high-risk NMIBC. MATERIALS AND METHODS: 140 patients with high-risk NMIBC were drawn from a population-based cohort of 538 patients with newly diagnosed bladder cancer in the Stockholm County between 1995 and 1996. Data were collected prospectively, and a final follow-up for recurrence, progression, and CSM was performed after 15 years. Patients that received BCG were compared with patients who did not receive BCG. Survival analysis was done with Kaplan-Meier estimates and Mantel-Cox log-rank test. Multivariable Cox proportional regression with stepwise selection was performed to verify the statistical significance of clinicopathological factors of prognostic importance. Results were displayed in Hazard ratios and a p < 0.05 was considered to be statistically significant. RESULTS: With a median follow-up of 100 months (2-182), 76 patients recurred; 50 progressed to muscle invasion; and 92 died of whom 38 died from bladder cancer. After 15-year follow-up, there was a statistically significant reduction in rate for recurrence (HR 0.40, p < 0.0001) and progression (HR 0.52, p = 0.038), but not for CSM, in patients that received BCG compared to those who did not. CONCLUSIONS: In this group, BCG in high-risk NMIBC patients reduced the long-term risk of recurrence and progression. The effect on CSM is yet to be clarified.

Robot-assisted radical cystectomy (RARC) with intracorporeal neobladder - what is the effect of the learning curve on outcomes?

OBJECTIVE: To evaluate the effect of the learning curve on operative, postoperative, and pathological outcomes of the first 67 totally intracorporeal robot-assisted radical cystectomies (RARCs) with neobladders performed by two lead surgeons at Karolinska University Hospital. PATIENTS AND METHODS: Between December 2003 and October 2012, 67 patients (61 men and six women) underwent RARC with orthotopic urinary diversion by two main surgeons. Data were collected prospectively on patient demographics, peri- and postoperative outcomes including operation times, conversion rates, blood loss, complication rates, pathological data and length of stay (LOS) for these 67 consecutive patients. The two surgeons operated on 47 and 20 patients, respectively. The patients were divided into sequential groups of 10 in each individual surgeon's series and assessed for effect of the learning curve. RESULTS: Patient demographics and clinical characteristics were similar in both surgeons' groups. The overall total operation times trended down in both surgeons' series from a median time of 565 min in the first group of 10 cases, to a median of 345 min in the last group for surgeon A (P < 0.001) and 413 to 385 min for surgeon B (not statistically significant). Risk of conversion to open surgery also decreased with a 30% conversion rate in the first group to zero in latter groups (P < 0.01). Overall complications decreased as the learning curve progressed from 70% in the first group to 30% in the later groups (P < 0.05), although major complications were not statistically different when compared between the groups. Patient demographics did not change over time. The mean estimated blood loss was unchanged across groups with increasing experience. The pathological staging, mean total lymph node yield and number of positive margins were also unchanged across groups. There was a decrease in LOS from a mean of 19 days in the first group to a mean (range) of 9 (4-78) days in the later groups, although the median LOS was unchanged and therefore not statistically significant. CONCLUSIONS: Totally intracorporeal RARC with intracorporeal neobladder is a complex procedure, but it can be performed safely, with a structured approach, at a high-volume established robotic surgery centre without compromising perioperative and pathological outcomes during the learning curve for surgeons. An experienced robotic team and mentor can impact the learning curve of a new surgeon in the same centre resulting in decreased operation times early in their personal series, reducing conversion rates and complication rates.

Tips and tricks for intracorporeal robot-assisted urinary diversion.

Since 2003, Karolinska University Hospitals have performed totally intracorporeal robotic-assisted radical cystectomy (RARC) in carefully selected patients. As our technique has evolved, the proportion of patients undergoing RARC has progressively increased. Whilst open radical cystectomy remains the gold standard, several high-volume centres have now demonstrated that RARC is both feasible and safe. RARC comprises three stages: radical cystectomy, extended lymph node dissection and urinary diversion. The majority of centres in the United States currently perform RARC utilizing an extracorporeal approach for the urinary diversion stage, perceiving this to be a more accessible option with a reduced risk of complications. We assess the evidence for this perception, reviewing the literature and reporting the functional outcomes and complication rates for a totally intracorporeal RARC approach. We also describe our technique for both intracorporeal orthotopic neobladder and intracorporeal ileal conduit, identifying the potential hazard steps and the 'tips and tricks' to optimize outcomes.

Microsomal prostaglandin E synthase 1 determines tumor growth in vivo of prostate and lung cancer cells.

There is strong evidence for a role of prostaglandin E(2) (PGE(2)) in cancer cell proliferation and tumor development. In PGE(2) biosynthesis, cyclooxygenases (COX-1/COX-2) convert arachidonic acid to PGH(2), which can be isomerized to PGE(2) by microsomal PGE-synthase-1 (MPGES-1). The human prostate cancer cell line DU145 expressed high amounts of MPGES-1 in a constitutive manner. MPGES-1 expression also was detectable in human prostate cancer tissues, where it appeared more abundant compared with benign hyperplasia. By using shRNA, we established stable and practically complete knockdown of MPGES-1, both in DU145 cells with high constitutive expression and in the non-small cell lung cancer cell line A549, where MPGES-1 is inducible. For microsomes prepared from knockdown clones, conversion of PGH(2) to PGE(2) was reduced by 85-90%. This resulted in clear phenotypic changes: MPGES-1 knockdown conferred decreased clonogenic capacity and slower growth of xenograft tumors (with disintegrated tissue structure) in nude mice. For DU145 cells, MPGES-1 knockdown gave increased apoptosis in response to genotoxic stress (adriamycin), which could be rescued by exogenous PGE(2). The results suggest that MPGES-1 is an alternative therapeutic target in cancer cells expressing this enzyme.

Age at surgery, educational level and long-term urinary incontinence after radical prostatectomy.

OBJECTIVE: To identify predictors for long-term urinary leakage after radical prostatectomy. PATIENTS AND METHODS: A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. Urinary leakage was defined as use of two or more pads per day. RESULTS: Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence. CONCLUSIONS: In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. Other predictors are low educational level, salvage radiation therapy and respiratory disease. Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme.

Robotic-assisted reconstructive urology.

PURPOSE OF REVIEW: The use of robotic surgery in reconstructive urology has steadily increased since the year 2000. Articles in the MEDLINE database (from January 2000 to May 2011) identified using the Boolean search: robotic or robot-assisted and reconstructive surgery and urology. In addition, the reference lists of previously published articles on robotic-assisted reconstructive surgery were checked for additional studies. This review will summarize the current advances in robotic-assisted reconstructive urology. RECENT FINDINGS: Even though many advocate the introduction of robot-assisted technique in reconstructive urology, relatively few studies have been published. Researchers do report shorter hospital stays and less blood loss than are reported for patients operated on with open reconstructive techniques and also report acceptable short-term outcomes. SUMMARY: The current literature shows that complex robot-assisted urological reconstructive surgical procedures may be used for both children and adults. With appropriate experience, this technique offers the expected advantages of decreased blood loss and transfusion rate, reduced analgesic requirements, and early hospital discharge in comparison with the open approach. However, robotic-assisted reconstructive urologic surgery needs to be evaluated in larger randomized studies with long-term follow-up.

Diagnostic random bladder biopsies: reflections from a population-based cohort of 538 patients.

OBJECTIVE: To assess whether diagnostic random bladder biopsies and the detection of concomitant carcinoma in situ (CIS) have an impact on the frequency of intravesical bacille Calmette-Guérin (BCG) instillations or radical cystectomy; and whether this affects the cancer-specific survival in patients with pTaG3 or pT1G1-G3 transitional cell carcinoma of the urinary bladder. MATERIAL AND METHODS: A population-based cohort of 538 patients with newly diagnosed bladder cancer was prospectively registered in the Stockholm County during 1995 and 1996 and followed for more than 5 years. RESULTS: Random biopsies were recommended in all patients but the decision to take biopsies was made by the treating urologist and hence performed in 326 out of 538 patients (61%), which revealed concomitant CIS in 47 patients(14%). Sixty out of 103 (58%) patients with pTaG3 or pT1G1-G3 tumours, in whom random biopsies were performed, received intravesical BCG compared with five out of 22 patients (23%) where random biopsies were not taken (p = 0.004). Moreover, 23 out of 103 patients (22%) with pTaG3 or pT1G1-G3 tumours in whom random biopsies were performed underwent radical cystectomy compared with none out of 22 patients (0%) without random biopsies (p = 0.013). The Cox proportional hazard ratio for death due to bladder cancer in patients with pTaG3 or pT1G1-G3 tumours among patients not having versus having undergone random biopsies was 2.5 (95% confidence interval 1.1-5.6). CONCLUSION: Patients diagnosed in Stockholm in 1995 or 1996 with pTaG3 or pT1G1-G3 bladder tumours having undergone random bladder biopsies more frequently underwent BCG treatment and radical cystectomy and had higher cancer-specific survival than patients who did not undergo random biopsies.

Does extended lymphadenectomy preclude laparoscopic or robot-assisted radical cystectomy in advanced bladder cancer?

PURPOSE OF REVIEW: Open radical cystectomy with an appropriate bilateral lymph node dissection (LND) is currently the standard treatment for patients with muscle-invasive bladder cancer. Approximately 25% of patients with stages T1-T4 N0 M0 harbour metastatic lymph nodes at the time of radical cystectomy. Results from open high volume radical cystectomy series suggest that a more extended LND provides the best survival outcomes and the lowest local recurrence rates. Currently, there is controversy whether laparoscopic or robot-assisted extended LND at radical cystectomy is technically feasible and whether it can provide oncological control equivalent to open LND series at the time of radical cystectomy. RECENT FINDINGS: Laparoscopic LND is technically demanding and requires prolonged operation time. Most studies to date indicate that fewer nodes are removed than with an open approach, putting a question mark to this surgical approach from an oncological point of view. Limited data on lymph node yield using a robot-assisted approach are available; however, several series found similar results as in open series. SUMMARY: At present, there is no conclusive evidence showing that laparoscopic LND gives similar results than open LND. Robot-assisted LND is still in its learning curve and more patient series are needed.

Incidental findings during computed tomographic angiography diagnostic work-up in patients with arteriogenic erectile dysfunction.

AIM: To analyse the incidental findings during computed tomographic angiography (CTA) diagnostic work-up in patients with arteriogenic erectile dysfunction (ED). PATIENTS AND METHODS: The medical records of all patients with suspected arteriogenic ED were entered into a database. Risk factors and underlying comorbidities were also collected. Pathological CTA findings were extracted from the CT readings and entered into the database. Incidental findings on CTA were classified as those requiring immediate medical treatment, requiring deferred medical treatment or of no clinical importance. RESULTS: A total of 200 patients underwent CTA for suspected arteriogenic ED. Mean patient age was 59.6 ± 11.7 years. Of these, 181 patients (90.5%) had obstructions of erection-related arteries. In 168 patients (84.0%), CTA showed multiple incidental pathological findings. Eighty-five of 200 patients (42.5%) exhibited incidental findings requiring immediate further medical workup and/or treatment: coronary artery calcification was diagnosed in 75/200 (37.5%), aorto-iliac aneurysms in 8/200 (4%) of patients and incidentally detected embolism in 1/200 patient. Pancreatic and liver tumours were less frequent (incidence 1.5% and 1%, respectively). Incidental findings requiring deferred medical workup and/or treatment were detected in 175/200 patients (87.5%). The findings with the highest prevalence were liver steatosis followed by colon diverticulosis and prostate hyperplasia. Findings of little to no clinical importance were reported in 117 (58.5%) patients. These included uncomplicated renal cysts, spinal degeneration and renal vascular anomalies. Almost every second patient presenting with ED had an incidental finding which required immediate treatment. CONCLUSIONS: Incidental findings not directly related to ED were common among patients undergoing CTA scans for suspected arterial obstructions. Coronary artery calcification was the leading finding requiring further medical workup and/or treatment. Thus, the benefit of CTA investigations extends beyond the anatomic description of arterial obstructions of erection-related arteries.

The efficiency of excretory urography to detect upper urinary tract tumors after cystectomy for urothelial cancer.

PURPOSE: We determined the efficiency of routine excretory urography for detecting tumor recurrence in the upper urinary tract after cystectomy and urinary diversion for bladder cancer. MATERIALS AND METHODS: We evaluated 322 patients who underwent cystectomy and urinary diversion, and had undergone routine followup, including regular excretory urography 1, 2, 3, 5, 7 and 10 years after cystectomy. RESULTS: Upper urinary tract recurrence was found in 15 of the 322 patients (4.7%) patients. Eight of 15 cases were detected by routine excretory urography, resulting in a low efficiency of 0.75% (8 of 1,064 studies) for this method. The remaining 7 recurrences were detected as a result of symptoms such as macrohematuria or flank pain occurring between routine followup examinations. Patients were at up to 10 times higher risk for recurrence in the upper urinary tract if they had positive distal ureteral resection margins or a history of upper urinary tract tumors. Although the incidence of recurrence in the upper urinary tract increased 1.8-fold in patients with pTa/pT1 tumors, it remained relatively low at 8.4%. CONCLUSIONS: The incidence of recurrence in the upper urinary tract a median of 49 months (range 12 to 220) after cystectomy for transitional cell carcinoma was 4.7%. Because only half of these cases were detected by routine excretory urography, this should be limited to patients at high risk with a history of upper urinary tract tumors or positive ureteral margins. In the future other techniques, eg cytology of voided urine or new markers, should be evaluated to replace excretory urography for routine followup of patients after cystectomy for transitional cell carcinoma of the bladder.

Early Recurrence Patterns Following Totally Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section (ERUS) Scientific Working Group.

Recurrence following radical cystectomy often occurs early, with >80% of recurrences occurring within the first 2 yr. Debate remains as to whether robot-assisted radical cystectomy (RARC) negatively impacts early recurrence patterns because of inadequate resection or pneumoperitoneum. We report early recurrence patterns among 717 patients who underwent RARC with intracorporeal urinary diversion at nine different institutions with a minimum follow-up of 12 mo. Clinical, pathologic, radiologic, and survival data at the latest follow-up were collected. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method, and Cox regression models were built to assess variables associated with recurrence. RFS at 3, 12, and 24 mo was 95.9%, 80.2%, and 74.6% respectively. Distant recurrences most frequently occurred in the bones, lungs, and liver, and pelvic lymph nodes were the commonest site of local recurrence. We identified five patients (0.7%) with peritoneal carcinomatosis and two patients (0.3%) with metastasis at the port site (wound site). We conclude that unusual recurrence patterns were not identified in this multi-institutional series and that recurrence patterns appear similar to those in open radical cystectomy series. PATIENT SUMMARY: In this multi-institutional study, bladder cancer recurrences following robotic surgery are described. Early recurrence rates and locations appear to be similar to those for open radical cystectomy series.

[11C]Acetate positron emission tomography-computed tomography imaging of prostate cancer lymph-node metastases correlated with histopathological findings after extended lymphadenectomy.

OBJECTIVE: The aim of this study was to determine the efficacy of combined [(11)C]acetate positron emission tomography and computed tomography ([(11)C]acetate-PET/CT) in regional lymph-node staging in patients with prostate cancer (PCa). MATERIAL AND METHODS: [(11)C]Acetate-PET/CT was performed in 19 PCa patients who subsequently underwent extended pelvic lymph-node dissection (ePLND). The [(11)C]acetate-PET/CT results were compared with the surgical and histopathological findings from 13 defined lymph-node regions. RESULTS: [(11)C]Acetate-PET/CT was true-positive for lymph-node metastases in nine patients, false-positive in three, false-negative in one patient and true-negative in six. The patient-by-patient-based sensitivity was 90% and the specificity 67%, the positive predictive value (PPV) was 75% and the negative predictive value (NPV) 86%. From a total of 114 nodal regions (mean 5.9 regions per patient), 484 lymph nodes (mean 25.5 nodes per patient) were removed and evaluated histopathologically. Forty-six lymph nodes from 24 out of 114 (21%) nodal regions were positive for PCa metastasis. The nodal-region-based sensitivity of [(11)C]acetate-PET/CT was 62%, specificity was 89%, PPV 62% and NPV 89%. CONCLUSION: [(11)C]Acetate-PET/CT detects PCa lymph-node metastases with high patient-by-patient-based sensitivity but low specificity, and low nodal-region-based sensitivity but high specificity. Its limited ability to detect microscopic lymph-node involvement makes ePLND essential in all patients diagnosed with positive nodes on [(11)C]acetate-PET/CT.

Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

PURPOSE: Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. MATERIALS AND METHODS: All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. RESULTS: BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. CONCLUSIONS: Our results suggest that the investigated polymorphisms influence patient response to BCG-treatment and thus may serve as possible markers for identification of BCG-failures.

Pilot study of adoptive immunotherapy with sentinel node-derived T cells in muscle-invasive urinary bladder cancer.

OBJECTIVE: The aim of this study was to determine by computed tomography (CT) whether treatment with tumor-draining lymph-node-derived expanded autologous T lymphocytes results in objective responses and/or improved survival in patients with metastatic urinary bladder cancer (UBC) and to record the toxicity of the treatment. MATERIALS AND METHODS: Eighteen patients with metastatic UBC were prospectively selected from two centers. The preoperative staging was T2-T4bN1-2 and/or M0-M1 or MX. Tumor-draining lymph nodes were harvested at intended cystectomy for the extraction of T lymphocytes. This was followed by expansion of the T lymphocytes in a cell culture, and subsequent reinfusion of these autologous tumor-specific T lymphocytes. Responses to therapy were evaluated by CT scans according to Response Evaluation Criteria In Solid Tumors (RECIST) and clinical follow-up, according to the research protocol. RESULTS: Nine out of 18 patients were treated. Treatment was feasible and safe. In two out of nine immunologically treated patients, objective responses were detected in terms of diminished or obliterated nodal metastases. When excluding three patients with disseminated osseous metastases plus one with a T4b tumor left in situ, a success rate of two out of six treated patients was seen. The two responders had survival times of 35 and 11 months, respectively. No toxicity was recorded. CONCLUSIONS: Infusion of expanded autologous tumor-specific T lymphocytes is feasible and safe, and objective responses according to RECIST were recorded. One objective responder to immunotherapy displayed notably long overall survival.

A comparative study of tissue ω-6 and ω-3 polyunsaturated fatty acids (PUFA) in benign and malignant pathologic stage pT2a radical prostatectomy specimens.

OBJECTIVE: To analyze different polyunsaturated fatty acid (PUFA) tissue levels in malignant compared with benign prostatic tissue from the same prostate specimens. MATERIALS AND METHODS: Fresh frozen benign and malignant prostatic tissue was obtained from radical prostatectomy specimens in 49 men with pathologic stage pT2a prostate cancer. Histopathologic examination confirmed that all tissues from each prostate being analyzed were either completely benign or almost totally malignant. The PUFA composition in these tissues was determined by gas-liquid chromatography on a capillary column. The relative amount of each PUFA (% of total fatty acids) was quantified by integrating the area under the peak and dividing the result by the total area of all fatty acids. RESULTS: Tissue levels of dihomo-γ-linolenic acid, (C20:3w6), an ω-6 PUFA and a major precursor of ω-6 PUFA metabolites, were significantly higher in malignant compared with benign tissues (P = 0.002). Tissue levels of the downstream ω-6 metabolites, arachidonic acid (AA) (20:4ω6), and adrenic acid, (22:4ω6), were significantly lower in cancer tissues, (P < 0.0001 and P = 0.013, respectively). Overall, the total levels of ω-6 PUFA were lower in cancer (P = 0.001). CONCLUSION: We found that the ω-6 PUFA AA and adrenic acid are decreased in malignant prostatic tissues compared with benign tissues from the same prostates. These findings provide additional evidence that dietary fat is associated with prostatic carcinogenesis.