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Sacral Neuromodulation Decreases Narcotic Requirements in Refractory Interstitial Cystitis
VOIDING FUNCTION, BLADDER PHYSIOLOGY AND PHARMACOLOGY, AND FEMALE UROLOGY
brachytherapy for localized prostate adenocarcinoma. Patients and physicians should consider these factors before a patient decides to undergo brachytherapy. Editorial Comment: What is this article doing in the section on voiding dysfunction? The authors have documented what many of us have observed in clinical practice (mostly, unfortunately, in retrospect). Patients choosing treatment for prostate cancer should be thoroughly screened for underlying voiding dysfunction and, if necessary, urodynamic studies performed to identify potential high risk patients considering brachytherapy. Those patients may be better served by an alternate mode of treatment. Alan J. Wein, M.D. Bladder Cancer in Patients With Spinal Cord Injuries K. SUBRAMONIAN, R. A. CARTWRIGHT, P. HARNDEN AND S. C. W. HARRISON, Department of Urology, Pinderfields Hospital, Wakefield and Leukaemia Research Fund Centre for Clinical Epidemiology at University of Leeds, Institute of Epidemiology and Department of Histopathology, St. James University Hospital, Leeds, United Kingdom BJU Int, 93: 739 –743, 2004 OBJECTIVE To evaluate the age-standardized incidence rate of bladder cancer in patients with spinal cord injury (SCI) and the overall risk for this population. PATIENTS AND METHODS We reviewed 1334 patients with SCI whose dates of SCI, or first attendance at our centre, were between 1940 and 1998. The length of follow-up was calculated for each patient and age-specific incidence rates of bladder cancer calculated using 5-year age bands. This was used to calculate the overall incidence rate, using direct standardization with the European standard population. The cancers were analysed histochemically to characterize the phenotype. RESULTS The 1324 patients contributed a total of 12 444 person-years of follow-up. There were four cases of bladder cancer, giving an age-standardized incidence rate of 30.7 per 100 000 person-years. Histochemistry showed areas were positive for cytokeratin 14, which was also positive in the undifferentiated areas. Immunohistochemical staining was positive for cytokeratin 14 and consistently negative for cytokeratin 20, suggesting a pure squamous phenotype. CONCLUSIONS The age-standardized incidence of invasive bladder cancer in patients in our SCI unit is not statistically different from that of the general population. However, the incidence of invasive bladder cancer in the present study appears to be lower than that reported in other series. Histochemical analysis confirmed a squamous cell phenotype in these tumours. Editorial Comment: The conclusion drawn from these data is at odds with those expressed in the other 8 series that the authors cite (table 2 in article) historically as studying the incidence of bladder cancer in patients with spinal cord injury. Of the 4 patients who had development of cancer in their series 3 had chronic indwelling catheters with a duration of catheterization of 18 to 32 years. In the series that the authors cite historically they calculated the interval since injury for the 60 tumors for which such data were available. The mean interval was 20 years (range 18.5 to 22), whereas in this study the length of followup was given as 22.3 years in those with cancer and 9.3 years in those without cancer. The diagnosis of cancer or no cancer was based on record review only, although the authors state that “it is our policy to investigate any patient with a long term catheter and symptoms suspicious of bladder cancer, using urine cytology, cystoscopy, and IVU.” From their data the authors conclude that “patients with SCI are unlikely to be at sufficiently greater risk of developing carcinoma of the bladder than the general population to warrant regular screening.” We will continue to screen those patients with long-term indwelling catheters. Alan J. Wein, M.D. Sacral Neuromodulation Decreases Narcotic Requirements in Refractory Interstitial Cystitis K. M. PETERS AND D. KONSTANDT, Department of Urology, William Beaumont Hospital, Royal Oak, Michigan BJU Int, 93: 777–779, 2004 OBJECTIVE To assess the efficacy of long-term sacral neuromodulation (InterStim, Medtronic Inc., Minneapolis, MN) in treating chronic pelvic pain associated with interstitial cystitis (IC, a symptom complex of urinary urgency, frequency and pelvic pain, often necessitating narcotics) refractory to standard therapy. PATIENTS AND METHODS Twenty-one patients (17 female, four male, mean age 45.5 years, range 17– 68) with refractory IC with chronic pelvic pain were reviewed retrospectively. In these patients a mean of six previous treatments for IC had failed. All patients had had cystoscopy and hydrodistension to confirm their diagnoses. All had a permanent InterStim device implanted by one surgeon (K.M.P.) between 2000 and 2002, after responding to a temporary test. Data were collected from chart reviews and patient questionnaires. Intramuscular morphine dose equivalents (MDEs) were calculated before and after implantation. RESULTS All 21 patients responded to the questionnaire; the mean (range) follow-up after implantation
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VOIDING FUNCTION, BLADDER PHYSIOLOGY AND PHARMACOLOGY, AND FEMALE UROLOGY
was 15.4 (7.4 –23.1) months. Eighteen patients used chronic narcotics before the InterStim and 20 reported moderate or marked improvement in pain afterward. The mean MDE decreased from 81.6 to 52.0 mg/day (36%) after implantation (P ⫽ 0.015). Four of 18 patients stopped all narcotics after InterStim implantation. CONCLUSIONS Sacral neuromodulation decreases narcotic requirements and subjective pelvic pain in patients with refractory IC. Further decreases in MDE are anticipated as dose reductions continue in patients who improved. Editorial Comment: Since no one knows what interstitial cystitis really is or how sacral modulation really works, the results seem a perfect match! Although “patients selected treatment by sacral nerve modulation for the urgency and frequency aspects of their disease. . . [and] pain was monitored as a secondary variable,” unfortunately, there are no data with respect to the results on the urgency and frequency aspect of the symptomatology reported by these patients. Apparently the only patients who had a permanent implant were those who responded to a temporary test. One wonders how many patients were tested to find these 21. Of the 21 patients 20 were reported as having “moderate to marked improvement in pain” after the procedure. The authors also add, “it has been our experience that sacral nerve stimulation does not ‘cure’ the symptoms of IC. If the generator is switched off the symptoms will return.” Although it may make no difference with respect to the conclusions, it would be optimal to figure out a nonharmful way of doing a study with this technology in these patients using a double-blind placebo methodology. The intricacies of such a study are more than just those that initially come to mind. Alan J. Wein, M.D. Antiproliferative Factor, Heparin-Binding Epidermal Growth Factor-Like Growth Factor, and Epidermal Growth Factor in Men With Interstitial Cystitis Versus Chronic Pelvic Pain Syndrome S. KEAY, C.-O. ZHANG, T. CHAI, J. WARREN, K. KOCH, D. GRKOVIC, H. COLVILLE AND R. ALEXANDER, Division of Infectious Diseases, Department of Medicine and Section of Urology, Department of Surgery, University of Maryland School of Medicine, and Research Service and Section of Urology, Veterans Affairs Maryland Health Care System, Baltimore, Maryland Urology, 63: 22–26, 2004 Objectives. To determine whether men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have urine markers previously described for patients with interstitial cystitis (IC; presence of antiproliferative factor [APF] activity, decreased levels of heparin-binding epidermal growth factor-like growth factor [HB-EGF], and increased levels of epidermal growth factor). Methods. Clean catch urine specimens were collected from 41 symptomatic patients with CP/CPPS, 36 asymptomatic men without bladder disease who served as the control group, and 24 men with IC. APF activity was determined by 3H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and epidermal growth factor levels were determined by enzyme-linked immunosorbent assay. Results. Men with CP/CPPS did not differ significantly from asymptomatic controls for any of the three markers tested (P ⬎0.49). In contrast, APF activity was present significantly more often and HB-EGF levels were significantly lower in the urine specimens from men with IC than in the specimens from controls or patients with CP/CPPS (P ⬍0.00001 for all four comparisons). Although the epidermal growth factor levels also tended to be higher in the urine from patients with IC than in the urine from controls, the difference did not reach statistical significance (P ⫽ 0.06). Conclusions. These findings indicate that at least two of the urine biomarkers previously identified in women with IC (presence of APF activity and decreased levels of HB-EGF) are also found in men with IC, but not in men with CP/CPPS. This finding suggests that IC and CP/CPPS may be two different disorders with distinct pathophysiologies. It also confirms the utility of the presence of APF activity and HB-EGF levels as markers for IC in men, as well as in women, with this disorder. Editorial Comment: Keay et al deserve an immense amount of credit for pursuing this line of research. Assuming that the final diagnoses are accurate, this is an important article. However, the authors realistically state that “future studies are warranted to determine prospectively whether APF and HB-EGF assays can be used to distinguish between men with IC and men with CP/CPPS III at the time of initial presentation, and whether these markers correlate with voiding symptoms and clinical findings.” Alan J. Wein, M.D.
brachytherapy for localized prostate adenocarcinoma. Patients and physicians should consider these factors before a patient decides to undergo brachytherapy. Editorial Comment: What is this article doing in the section on voiding dysfunction? The authors have documented what many of us have observed in clinical practice (mostly, unfortunately, in retrospect). Patients choosing treatment for prostate cancer should be thoroughly screened for underlying voiding dysfunction and, if necessary, urodynamic studies performed to identify potential high risk patients considering brachytherapy. Those patients may be better served by an alternate mode of treatment. Alan J. Wein, M.D. Bladder Cancer in Patients With Spinal Cord Injuries K. SUBRAMONIAN, R. A. CARTWRIGHT, P. HARNDEN AND S. C. W. HARRISON, Department of Urology, Pinderfields Hospital, Wakefield and Leukaemia Research Fund Centre for Clinical Epidemiology at University of Leeds, Institute of Epidemiology and Department of Histopathology, St. James University Hospital, Leeds, United Kingdom BJU Int, 93: 739 –743, 2004 OBJECTIVE To evaluate the age-standardized incidence rate of bladder cancer in patients with spinal cord injury (SCI) and the overall risk for this population. PATIENTS AND METHODS We reviewed 1334 patients with SCI whose dates of SCI, or first attendance at our centre, were between 1940 and 1998. The length of follow-up was calculated for each patient and age-specific incidence rates of bladder cancer calculated using 5-year age bands. This was used to calculate the overall incidence rate, using direct standardization with the European standard population. The cancers were analysed histochemically to characterize the phenotype. RESULTS The 1324 patients contributed a total of 12 444 person-years of follow-up. There were four cases of bladder cancer, giving an age-standardized incidence rate of 30.7 per 100 000 person-years. Histochemistry showed areas were positive for cytokeratin 14, which was also positive in the undifferentiated areas. Immunohistochemical staining was positive for cytokeratin 14 and consistently negative for cytokeratin 20, suggesting a pure squamous phenotype. CONCLUSIONS The age-standardized incidence of invasive bladder cancer in patients in our SCI unit is not statistically different from that of the general population. However, the incidence of invasive bladder cancer in the present study appears to be lower than that reported in other series. Histochemical analysis confirmed a squamous cell phenotype in these tumours. Editorial Comment: The conclusion drawn from these data is at odds with those expressed in the other 8 series that the authors cite (table 2 in article) historically as studying the incidence of bladder cancer in patients with spinal cord injury. Of the 4 patients who had development of cancer in their series 3 had chronic indwelling catheters with a duration of catheterization of 18 to 32 years. In the series that the authors cite historically they calculated the interval since injury for the 60 tumors for which such data were available. The mean interval was 20 years (range 18.5 to 22), whereas in this study the length of followup was given as 22.3 years in those with cancer and 9.3 years in those without cancer. The diagnosis of cancer or no cancer was based on record review only, although the authors state that “it is our policy to investigate any patient with a long term catheter and symptoms suspicious of bladder cancer, using urine cytology, cystoscopy, and IVU.” From their data the authors conclude that “patients with SCI are unlikely to be at sufficiently greater risk of developing carcinoma of the bladder than the general population to warrant regular screening.” We will continue to screen those patients with long-term indwelling catheters. Alan J. Wein, M.D. Sacral Neuromodulation Decreases Narcotic Requirements in Refractory Interstitial Cystitis K. M. PETERS AND D. KONSTANDT, Department of Urology, William Beaumont Hospital, Royal Oak, Michigan BJU Int, 93: 777–779, 2004 OBJECTIVE To assess the efficacy of long-term sacral neuromodulation (InterStim, Medtronic Inc., Minneapolis, MN) in treating chronic pelvic pain associated with interstitial cystitis (IC, a symptom complex of urinary urgency, frequency and pelvic pain, often necessitating narcotics) refractory to standard therapy. PATIENTS AND METHODS Twenty-one patients (17 female, four male, mean age 45.5 years, range 17– 68) with refractory IC with chronic pelvic pain were reviewed retrospectively. In these patients a mean of six previous treatments for IC had failed. All patients had had cystoscopy and hydrodistension to confirm their diagnoses. All had a permanent InterStim device implanted by one surgeon (K.M.P.) between 2000 and 2002, after responding to a temporary test. Data were collected from chart reviews and patient questionnaires. Intramuscular morphine dose equivalents (MDEs) were calculated before and after implantation. RESULTS All 21 patients responded to the questionnaire; the mean (range) follow-up after implantation
1217
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VOIDING FUNCTION, BLADDER PHYSIOLOGY AND PHARMACOLOGY, AND FEMALE UROLOGY
was 15.4 (7.4 –23.1) months. Eighteen patients used chronic narcotics before the InterStim and 20 reported moderate or marked improvement in pain afterward. The mean MDE decreased from 81.6 to 52.0 mg/day (36%) after implantation (P ⫽ 0.015). Four of 18 patients stopped all narcotics after InterStim implantation. CONCLUSIONS Sacral neuromodulation decreases narcotic requirements and subjective pelvic pain in patients with refractory IC. Further decreases in MDE are anticipated as dose reductions continue in patients who improved. Editorial Comment: Since no one knows what interstitial cystitis really is or how sacral modulation really works, the results seem a perfect match! Although “patients selected treatment by sacral nerve modulation for the urgency and frequency aspects of their disease. . . [and] pain was monitored as a secondary variable,” unfortunately, there are no data with respect to the results on the urgency and frequency aspect of the symptomatology reported by these patients. Apparently the only patients who had a permanent implant were those who responded to a temporary test. One wonders how many patients were tested to find these 21. Of the 21 patients 20 were reported as having “moderate to marked improvement in pain” after the procedure. The authors also add, “it has been our experience that sacral nerve stimulation does not ‘cure’ the symptoms of IC. If the generator is switched off the symptoms will return.” Although it may make no difference with respect to the conclusions, it would be optimal to figure out a nonharmful way of doing a study with this technology in these patients using a double-blind placebo methodology. The intricacies of such a study are more than just those that initially come to mind. Alan J. Wein, M.D. Antiproliferative Factor, Heparin-Binding Epidermal Growth Factor-Like Growth Factor, and Epidermal Growth Factor in Men With Interstitial Cystitis Versus Chronic Pelvic Pain Syndrome S. KEAY, C.-O. ZHANG, T. CHAI, J. WARREN, K. KOCH, D. GRKOVIC, H. COLVILLE AND R. ALEXANDER, Division of Infectious Diseases, Department of Medicine and Section of Urology, Department of Surgery, University of Maryland School of Medicine, and Research Service and Section of Urology, Veterans Affairs Maryland Health Care System, Baltimore, Maryland Urology, 63: 22–26, 2004 Objectives. To determine whether men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have urine markers previously described for patients with interstitial cystitis (IC; presence of antiproliferative factor [APF] activity, decreased levels of heparin-binding epidermal growth factor-like growth factor [HB-EGF], and increased levels of epidermal growth factor). Methods. Clean catch urine specimens were collected from 41 symptomatic patients with CP/CPPS, 36 asymptomatic men without bladder disease who served as the control group, and 24 men with IC. APF activity was determined by 3H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and epidermal growth factor levels were determined by enzyme-linked immunosorbent assay. Results. Men with CP/CPPS did not differ significantly from asymptomatic controls for any of the three markers tested (P ⬎0.49). In contrast, APF activity was present significantly more often and HB-EGF levels were significantly lower in the urine specimens from men with IC than in the specimens from controls or patients with CP/CPPS (P ⬍0.00001 for all four comparisons). Although the epidermal growth factor levels also tended to be higher in the urine from patients with IC than in the urine from controls, the difference did not reach statistical significance (P ⫽ 0.06). Conclusions. These findings indicate that at least two of the urine biomarkers previously identified in women with IC (presence of APF activity and decreased levels of HB-EGF) are also found in men with IC, but not in men with CP/CPPS. This finding suggests that IC and CP/CPPS may be two different disorders with distinct pathophysiologies. It also confirms the utility of the presence of APF activity and HB-EGF levels as markers for IC in men, as well as in women, with this disorder. Editorial Comment: Keay et al deserve an immense amount of credit for pursuing this line of research. Assuming that the final diagnoses are accurate, this is an important article. However, the authors realistically state that “future studies are warranted to determine prospectively whether APF and HB-EGF assays can be used to distinguish between men with IC and men with CP/CPPS III at the time of initial presentation, and whether these markers correlate with voiding symptoms and clinical findings.” Alan J. Wein, M.D.