Risk of second primary malignancies following a diagnosis of cutaneous malignant melanoma or nonmelanoma skin cancer in Alberta, Canada from 1979 to 2009.

BACKGROUND: Recent studies have revealed geographical variations with respect to the risk of second primary malignancies (SPMs) following cutaneous malignant melanoma (CMM) and nonmelanoma skin cancer (NMSC). OBJECTIVES: To provide the largest analysis of the risk of SPM following skin cancers in Canada and to detect associations that may shed light on common pathogeneses between linked malignancies. METHODS: Relative risks for development of SPMs following a diagnosis of CMM or NMSC were calculated via a retrospective analysis of data retrieved from the Alberta Cancer Registry (ACR) from 1979 to 2009. RESULTS: From 1979 to 2009, 85,967 NMSC and 6884 CMM incident cases were recorded in the ACR. In total 19,869 SPMs were identified following a primary NMSC (7709 cutaneous and 12,160 noncutaneous), while 1437 SPMs (908 cutaneous and 529 noncutaneous) followed CMM. Patients with a previous history of skin cancer had a 60% increased risk of developing an SPM compared with those without [observed/expected ratio (O/E) 1.6, 95% confidence interval (CI) 1.6-1.7; P < 0.001]. Thirty and 10 different SPMs were significantly identified to follow a diagnosis of NMSC and CMM, respectively. Patients under the age of 40 years with a prior history of CMM had a marked increased expectancy for SPM [O/E 5.6, 95% CI 4.5-7.0; P < 0.001). CONCLUSIONS: Further studies are warranted to identify environmental and molecular connections among linked cutaneous and noncutaneous malignancies, which may lead to earlier detection of related neoplasms via expanded screening protocols and development of shared treatment regimens. Heightened surveillance for the development of SPMs in patients with CMM under the age of 40 years should be considered.

Reasons and predictive factors for discontinuation of PDE-5 inhibitors despite successful intercourse in erectile dysfunction patients.

This study was aimed to identify characteristics of ED patients who discontinued PDE5i despite successful intercourse. Data were collected using a questionnaire from 34 urologic clinics regardless of the effect (success or failure) of PDE5i treatment by visiting the clinics (717), e-mail (64) or post (101) for 882 ED patients who had previously taken any kind of PDE5i on demand four or more times. Discontinuation of PDE5i was defined if the patient had never taken PDE5i for the previous 1 year despite successful intercourse. Of the 882 patients, 485 were included in the final analysis. Difference in the socio-demographic, ED- and partner-related data between the continuation and discontinuation group and factors influencing discontinuation of the PDE5i were analyzed. Among 485 respondents (mean age, 53.6), 116 (23.9%) had discontinued PDE5i use despite successful intercourse. Most common reasons for the discontinuation were 'reluctant medication-dependent intercourse' (31.0%), 'spontaneous recovery of erectile function without further treatment' (30.2%), and 'high cost' (26.7%). In multiple logistic regression analysis, independent factors influencing discontinuation of the drug were cause of ED (psychogenic), short duration of ED, low education (⩽ middle school), and religion (Catholic). In partner-related compliance, only partner's religion (Catholic) was a significant factor.

Clinicopathological comparisons of index and second primary melanomas in paediatric and adult populations.

BACKGROUND: The high incidence of cutaneous melanoma globally has sparked interest in the features associated with second primary melanomas (SPMs). OBJECTIVES: To identify differences and similarities between index and second primary melanomas while comparing the absolute and relative risk of subsequent melanoma development in paediatric and adult patients. METHODS: A retrospective analysis of patients diagnosed with invasive malignant melanoma from 1973 to 2008 inclusive was completed with data obtained from the Surveillance, Epidemiology and End Results (SEER) database. RESULTS: In total, 208,289 patients were diagnosed with invasive melanoma in the SEER database from 1973 to 2008, with subsequent primary melanomas diagnosed in 6888 (3.3%). The incidence of SPMs increased with increasing age of diagnosis of the patient's first melanoma. However, the relative risk of developing a subsequent melanoma was nearly double for patients diagnosed with their first melanoma at the age of 19 years and younger compared with patients greater than the age of 19 years. Compared with a patient's initial invasive melanoma, 44% of the subjects had a different melanoma subtype with their subsequent melanoma. SPMs were located in a different anatomical site from the index malignancy in 55% of patients. Nodular melanomas were more common as index melanomas compared with SPMs. CONCLUSIONS: Although invasive cutaneous melanoma is primarily a malignancy of adulthood, the heightened relative risk of SPMs in the paediatric population calls for careful long-term scrutiny in this latter population following an index melanoma diagnosis.

Trends in incidence of nonmelanoma skin cancers in Alberta, Canada, 1988-2007.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common malignancy affecting caucasian populations and has been seeing global increases in incidence for decades. OBJECTIVES: The objective of this study was to determine trends in incidence of NMSC in Alberta, Canada from 1988 to 2007. METHODS: A retrospective analysis of patients from Alberta diagnosed with NMSC from 1988 to 2007 inclusive was conducted with data retrieved from the Alberta Cancer Registry (ACR). Sex-, age- and anatomical location-specific incidence rates and trends were examined. RESULTS: From 1988 to 2007, there were 66 192 basal cell carcinomas, 19 959 invasive squamous cell carcinomas (SCC) and 12 494 in situ SCC. ACR coding for the 2007 data was not completed at the time of this study; hence, data from this year were not included in the trend analyses. Incidence of NMSC in women has been stable since 2000 [annual percentage change (APC) 0.08, P = 0.88] and has declined in men since 2001 (APC -1.28, P = 0.026). BCC incidence has been stable since 2000 (APC -0.80, P = 0.09). In situ and invasive SCC also showed a trend towards stabilization in 2000 (APC 0.36, P = 0.77) and 1995 (APC 0.01, P = 0.98), respectively. NMSC primarily affects the elderly and is rarely seen in individuals before the age of 40 years. Although the head and neck region was the location most often involved with NMSC (71.1%), it revealed a stabilizing trend, whereas most other anatomical regions demonstrated an increasing NMSC incidence rate. CONCLUSIONS: NMSC incidence in Alberta has stabilized in women and declined in men. As 95-99% of NMSC occurs in patients aged 40 years or older, and with its increased frequency in traditionally clothed areas, the authors recommend regular complete skin examinations starting at 40 years of age.

Ineffectiveness of sun awareness posters in dermatology clinics.

BACKGROUND: Although sun awareness posters have been used in doctors' offices and clinics for decades to promote sun protective behaviour, there is no evidence of their usefulness. OBJECTIVES: To investigate whether sun awareness posters lead to inquiry of skin cancer and sun protection measures. METHOD: Patients considered at risk for skin cancer seen at a dermatology clinic were randomly asked to complete a questionnaire designed to assess the effectiveness of three different sun awareness posters placed in patient rooms. The posters were selected on the basis of their catchy slogan and eye-appealing images, and included those featuring parental interest, sex appeal and informative advice. RESULTS: Only half of the patients noticed the posters (50.6%). The poster with sex appeal garnered the most attention (67.8%), followed by the informative poster (49.2%) and the parental interest poster (35.8%) (P < 0.001). Although patients who noticed the sun awareness poster inquired about cutaneous cancers and sun protection practices twice as often as those who did not notice the poster, only one-tenth of such inquiries were attributed to the poster ( approximately 5% of the target population). As reported in the questionnaire, the posters themselves were less effective than the advice of physicians in influencing patient attitudes towards sun protection measures. CONCLUSION: Organizations that produce and disseminate posters should consider beyond focus groups when they design their posters and should consider field testing their products to ensure that they are reaching the targeted audience and are having the expected beneficial effect, otherwise their posters are simply decorative.

Ganglioneuroblastoma presenting as dilated cardiomyopathy.

We report an unusual presentation of ganglioneuroblastoma with features of dilated cardiomyopathy in a 22 month old girl. She was admitted with cardiomegaly; during echocardiography a suspicious abdominal mass was detected by chance. Further imaging studies, including abdominal ultrasonography and spiral computed tomography, revealed a solid mass originating in the right adrenal gland. Metabolic studies and pathological findings were compatible with ganglioneuroblastoma. Following tumour removal and supportive therapy for cardiomyopathy, her clinical condition and laboratory findings improved. Although ganglioneuroblastoma with features of dilated cardiomyopathy is rare, because neurogenic tumours may be involved in its development, measurement of catecholamines in children with dilated cardiomyopathy is strongly recommended.

Multicenter study of the treatment of erectile dysfunction with transurethral alprostadil (MUSE) in Korea.

A Korean multicenter study was conducted to assess the effectiveness of transurethral alprostadil with MUSE in 334 subjects with chronic erectile dysfunction (ED) who were enrolled in 21 clinical centers. Patients with psychogenic impotence comprised about 30% of subjects. Intraurethral alprostadil was titrated in a stepwise fashion in the clinics from 250 to 500 or 1000 mcg based on erectile response and tolerability. The erectile responses were evaluated using an erection assessment scale (score of 1-5). The dose that produced a maximal penile response of score 5 (full rigid erection) or 4 (full tumescence, partial rigidity) was selected for home treatment. Patients who showed partial erection (score of 3) with 1000 mcg were also included in the home-treatment group. In-clinic phase: 198 men (59.3%) had maximal penile responses of score 4 or 5. The rate of maximal responses was not related to patient age, etiology or duration of the ED. A total of 228 (68.3%) men progressed to home treatment. The overall level of comfort of the transurethral alprostadil was rated as uncomfortable or very uncomfortable in 12%. Home phase: During the two-month period of home treatment, 178 (78.1%) men had successful sexual intercourse at least once, and 78.2% of administrations (1976) resulted in successful intercourse. The main causes of drop-out were insufficient erectile response in 27 men (11.8%), adverse reactions (mostly penile or urethral pain) in 7 (3.1%) or both in 7 (3.1%). In conclusion, transurethral alprostadil could be a suitable treatment option for patients with ED regardless of age and etiology of ED. Efficacy in an Asian population (Korea) is comparable to that reported previously in Caucasians.

Clinical study of SS-cream in patients with lifelong premature ejaculation.

OBJECTIVES: To investigate the clinical efficacy of SS-cream, the topical agent made from the extracts of nine natural products for the treatment of premature ejaculation, we performed a double-blind, randomized, placebo-controlled Phase III clinical study of patients with lifelong premature ejaculation in three medical centers. METHODS: One hundred six patients (mean age 38.7 +/- 0.61 years) completed this study. The ejaculatory latency measured by stopwatch and sexual satisfaction ratio of both partner and patient were investigated twice in the screening period and once after each treatment (1 placebo 0.20 g and 5 SS-cream 0.20 g for a total of six treatments). Patients were instructed to apply the cream on the glans penis 1 hour before sexual intercourse in a double-blind randomized fashion. Clinical efficacy was compared with the prolongation of ejaculatory latency and improvement of the sexual satisfaction ratio before and after each treatment. RESULTS: In the screening period, the mean ejaculatory latency was assessed at 1.37 +/- 0.12 minutes, and neither the patients nor their partners were satisfied with their sexual lives. After treatment, the mean ejaculatory latency was prolonged to 2.45 +/- 0.29 minutes in the placebo group and 10.92 +/- 0.95 minutes in the SS-cream group. The clinical efficacy of placebo and SS-cream as judged by an ejaculatory latency time prolonged more than 2 minutes was 15.09% and 79.81%, respectively. The improvement of sexual satisfaction to a grade higher than effective was 19.81% and 82.19%, respectively, for placebo and SS-cream. Of 530 trials of SS-cream, 98 (18.49%) resulted in a sense of mild local burning and mild pain. No adverse effect on sexual function or partner and no systemic side effects were observed. CONCLUSIONS: According to these results, SS-cream is effective and safe in the treatment of premature ejaculation, with mild local side effects.

IGF-I and TGF-beta2 have a key role on regeneration of nitric oxide synthase (NOS)-containing nerves after cavernous neurotomy in rats.

The molecular mechanism of nitric oxide synthase (NOS)-containing nerve regeneration is still unknown. It is believed that growth factors are involved in this phenomenon. We investigated the change of NOS containing nerve fibers and the mRNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, TGF-beta3, vascular endothelial growth factor (VEGF), endothelial NOS (eNOS) and neuronal NOS (nNOS) on the penis after cavernous nerve neurotomy in rats. Male rats were divided into four groups: (1) sham operation (n = 14); (2) unilateral neurotomy of a 5 mm segment of the cavernous nerve (n = 21); (3) unilateral neurotomy with growth hormone (n = 14); and (4) bilateral neurotomy (n = 21). Electrostimulation of the intact cavernous nerve or pelvic ganglion were performed at one, three and six months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and immunohistochemistry were used to identify NOS in the penis. The gene expression for growth factors, eNOS and nNOS were investigated in corporal tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). One month after neurotomy, both unilateral and bilateral neurotomy groups showed significant decreases in NOS-containing nerve fibers on the dorsal and intracavernosal nerves on the side of neurotomy. Significantly lower mRNA expression of nNOS, IGF-I and TGF-beta2, higher mRNA expression of eNOS and VEGF189 were shown in these groups. At three months, the number of NOS-containing nerve fibers in the unilateral neurotomy group increased only slightly, while the GH-treated group showed a significant increase. At six months, those in the intracavernosal nerve only increased in a significant amount (P < 0.0001), however mRNA expression of nNOS, IGF-I and TGF-beta2 showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dorsal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvic ganglion stimulation. In the unilateral neurotomy group at six months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regeneration derived from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater maximal intracavernosal pressure and a shorter latency period at six months than at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta2 may play a key role in the regeneration of nNOS-containing nerve fibers in the dorsal and intracavernosal nerves, and eNOS increases temporarily in the intracavernous involving VEGF189 after unilateral cavernous nerve injury.

The role of growth factor on regeneration of nitric oxide synthase (NOS)--containing nerves after cavernous neurotomy in the rats.

Nitric oxide synthase (NOS) containing nerve regeneration can be seen six months after unilateral cavernous nerve neurotomy in rats. However, its molecular mechanism is still unknown. It is believed that growth factors are involved in this phenomenon. In this study we investigated the change of NOS containing nerve fibers and the RNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha, TGF-beta 1, TGF-beta 2. TGF-beta 3 and NOS on the penis after cavernous nerve neurotomy in rats. Male rats were divided into three groups: (1) sham operation (N = 10); (2) unilateral neurotomy of a 5 mm segment of the cavernous nerve (N = 15); and (3) bilateral neurotomy (n = 15). Electrostimulation of the intact cavernous nerve or pelvic ganglion was performed at one, three and six months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was used to identify NOS in the penile nerve fibers. The gene expression for growth factors and bNOS was investigated in corporal tissue by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. One month after neurotomy, both unilateral and bilateral neurotomy groups showed a significant decrease in NOS-containing nerve fibers on the dorsal and intracavernosal nerves on the side of neurotomy, and a significantly lower mRNA expression of bNOS, IGF-I and TGF-beta 2. At three months, the number of NOS-containing nerve fibers in the unilateral neurotomy group increased only slightly but at six months those in the intracavernosal nerve increased in a significant amount (P < 0.0001), however mRNA expression of bNOS, IGF-I and TGF-beta 2 showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dorsal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvic ganglion stimulation. In the unilateral neurotomy group at six months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regeneration derives from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater maximal intracavernosal pressure and a shorter latency period at six months than at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta 2 may play a key role in regeneration of NOS-containing nerve fibers in the dorsal and intracavernosal nerves after unilateral cavernous nerve injury.

Growth hormone enhances regeneration of nitric oxide synthase-containing penile nerves after cavernous nerve neurotomy in rats.

PURPOSE: As growth hormone has been reported to improve nerve regeneration, we studied the effect of rat growth hormone (GH) on the regeneration of nitric oxide synthase (NOS)-containing penile nerves and the neurons in the pelvic ganglia after unilateral cavernous nerve neurotomy in rats. MATERIALS AND METHODS: Male rats were divided into three groups: sham operation (n = 14); unilateral neurotomy of a 5 mm. segment of the cavernous nerve (n = 14) with subsequent injection of buffer solution only; and unilateral neurotomy with GH injection (n = 14). Electrostimulation of the intact cavernous nerve was performed at 1 and 3 months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was used to identify NOS in penile nerve fibers of the mid-shaft segment and in neurons of the pelvic ganglia. RESULTS: One month after unilateral neurotomy, both the buffer alone and GH-treated groups showed a significant decrease in NOS-containing nerve fibers in the dorsal and intracavernosal nerves on the side of neurotomy. At 3 months, the number of NOS-containing nerve fibers in the buffer alone group did not increase, while the GH-treated group showed a significant increase. In the GH-treated group at 3 months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of neurotomy (p <0.034), indicating that the regeneration derives from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the GH-treated group revealed a greater maximal intracavernosal pressure and a shorter latency period at 3 months than in those given buffer alone. CONCLUSIONS: Our results show that GH injection significantly enhances the regeneration of NOS-containing fibers in the dorsal and intracavernosal nerves after unilateral cavernous nerve injury. We believe that GH administration may present a new and more physiologic approach to the treatment of erectile dysfunction after radical pelvic surgery.