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1.

INTRODUCTION

Giant condylomata acuminata (GCA) is a rare, locally invasive tumour that may undergo malignant transformation. It was first described a HPV-induced penile tumour which clinically resembled both a squamous cell carcinoma and condyloma acuminatum, often arising from a pre-existing warty lesion. We describe a case of peri-stomal GCA transformation into invasive squamous cell carcinoma (SCC), which is, to our knowledge, the first report of this in the literature.

PRESENTATION OF CASE

A 74 year old gentleman developed an acuminate, papillomatous peristomal eruption around a fifty year old ileostomy, with biopsies of the eruption showing reactive changes. Two years later, he developed ulcerating plaques affecting the previously papillomatous areas and an erythematous nodular lesion involving the superior part of the ileostomy and adjacent skin. Histological examination of the ileostomy lesion showed focal small islands of atypical squamous epithelium, and moderately differentiated invasive squamous cell carcinoma was shown in the excised tissue subsequently. Human papillomavirus (HPV type 16), p16 and p53 tumour suppressors were positive in the peri-stomal skin sample.

DISCUSSION AND CONCLUSIONS

Recurring, changing papillomatous lesions in the peristomal area should be reviewed with a high index of suspicion in relation to GCA tumours as they can progress to invasive squamous cell carcinomas.Abbreviations: GCA, giant condylomata acuminata; SCC, squamous cell carcinoma; HPV, human papillomavirus; UC, ulcerative colitis  相似文献   

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目的观察用i miqui mod治疗9例外生殖器尖锐湿疣的疗效及相关问题。方法5%i mqui mod霜睡前使用1次,每周3次,致疣体消失为止,疗程不超过16周。结果5例疣体在用药5周后完全消失,2例在6周后消失,2例在用药4周后改用电灼术去除疣体。患者均有局部药物不良反应,可耐受。2例治疗结束后2个月复发。结论I miqui mod可用于治疗外生殖器尖锐湿疣。  相似文献   

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PURPOSE: We evaluate the predictive value of urinary cytokine levels of interleukin (IL) 8 and 18 for response in patients receiving intravesical bacillus Calmette-Guerin (BCG) for prevention of recurrences of superficial bladder cancer and treatment of carcinoma in situ. MATERIALS AND METHODS: In 28 patients with superficial bladder cancer treated with BCG IL-8 expression in the urine during the first 6 hours after the first BCG instillation was determined. In 17 patients IL-18 levels were also evaluated during the first 12 hours after BCG instillation. IL-8 and 18 levels were determined by solid phase double ligand enzyme-linked immunosorbent assay. RESULTS: In 12 of the 28 patients assessed for IL-8 expression disease recurred after a median followup of 66 months. Median IL-8 expression during the first 6 hours for these patients was 851 ng. (range 232 to 8,497). Median IL-8 expression during the first 6 hours in patients without recurrence was 4,200 ng. (range 432 to 12, 232). Of 8 patients with a followup of greater than 36 months 7 (88%) had no recurrent disease and IL-8 levels greater than 4,000 ng. Patients secreting more than 4,000 ng. IL-8 into the urine after BCG have a significantly higher chance of remaining disease-free (p <0.05), and those with elevated IL-18 expression have a significantly longer disease-free survival (p <0.05). After a median followup of 23 months (range 7 to 93) 6 of the 17 patients assessed for IL-18 expression had treatment failure. Median IL-18 expression in those patients during the first 12 hours was 2,632 pg. (range 860 to 8,298). Median IL-18 expression during the first 12 hours in patients without recurrence was 12,258 pg. (range 1,727 to 151,495). CONCLUSIONS: In this study we confirmed the value of quantitative IL-8 expression in the urine during the first 6 hours after BCG instillation for superficial bladder cancer to predict freedom of disease. Furthermore, to our knowledge we report for the first time the potential value of IL-18 expression in the urine during the first 12 hours after BCG to predict freedom from disease. These findings may help improve the treatment of patients with superficial bladder cancer, especially by identifying those with a high risk of disease recurrence and progression after BCG therapy.  相似文献   

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PURPOSE: Stage T1 grade 3 transitional cell carcinoma of the bladder is associated with a high risk of tumor recurrence and progression. We report our experience with stage T1 grade 3 bladder tumors treated with bacillus Calmette-Guerin (BCG) therapy in the last 10 years. MATERIALS AND METHODS: We analyzed the outcome in 57 consecutive patients treated with intravesical BCG for stage T1 grade 3 bladder cancer between 1991 and 2001. After initial transurethral resection all patients received a 6-week course of BCG therapy consisting of 1 instillation weekly. All patients underwent systematic biopsies at the end of the first BCG course. Patients with negative biopsies received maintenance BCG therapy, consisting of intravesical instillations each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months after the first course. Patients with residual tumor received a second course of 6 weekly instillations. Time to tumor recurrence and progression, and the rate of patient survival were retrospectively analyzed. RESULTS: Median followup was 53 months (range 9 to 110). Minimum followup was 2 years in 36 cases (63.2%) and 5 years in 28 (49.1%). After the first BCG course 50 patients (87.7%) had no residual disease, while 7 (12.3%) had residual tumor. The recurrence and progression rates were 42.1% and 22.8%, respectively. The rate of delayed cystectomy was 14%. The rate of disease specific survival was 87.7%. CONCLUSIONS: Our study confirms that BCG therapy is effective conservative treatment for patients with stage T1 grade 3 bladder tumors.  相似文献   

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PURPOSE: We studied the cytolytic mechanism of nonstimulated, bacillus Calmette-Guerin (BCG) stimulated and interleukin (IL)-2 (Chiron Corp., Amsterdam, The Netherlands) stimulated peripheral blood mononuclear cells. MATERIALS AND METHODS: We inhibited the cytotoxicity of nonstimulated, BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells against various target cells using 3 monoclonal antibodies directed against the CD16 receptor of natural killer cells or alternatively monoclonal antibodies against the alpha and beta subunits of the IL-2 receptor complex (IL-2R). The main target cell was the poorly differentiated transitional cell line T24. RESULTS: Of the 3 anti-CD16 antibodies tested only CLB FcR-gran/1 effectively inhibited natural, IL-2 stimulated and BCG enhanced cytotoxicity. Cytotoxicity was also markedly diminished after depletion of CD16+CD56+/- cells with CLB FcR-gran/1. An hour of pretreatment with CLB FcR-gran/1 was enough to reduce significantly the level of cytotoxicity evoked by overnight stimulation with BCG or IL-2. Simultaneous administration of anti-IL-2Ralpha and anti-IL-2Rbeta significantly decreased the killing of target cells by BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells. CONCLUSIONS: Within the stimulation times chosen the same killing mechanisms seemed to explain the nonstimulated, BCG stimulated and IL-2 stimulated cytotoxicity with CD16 positive cells as central effectors. Anti-CD16 antibodies may deliver a target cell independent down-regulatory signal to natural killer cells or alternatively mimic a nonIg ligand and block the detection of the target cell.  相似文献   

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PURPOSE: Low dose bacillus Calmette-Guerin (BCG) for stage TaT1 transitional cell carcinoma of the bladder has been given in various studies with the aim of decreasing side effects while maintaining the same efficacy as full dose bacillus Calmette-Guerin. However, its application in clinical practice remains controversial. We examined the ablative activity and incidence of side effects of intravesical quarter dose BCG given for a papillary marker lesion of the bladder. MATERIALS AND METHODS: Included in our study were 44 patients with primary or recurrent, multiple but no more than 10 lesions of stage pTaT1, grades 1 to 2 transitional cell carcinoma of the bladder. Intravesical treatment begun 14 days after the complete transurethral resection of all visible tumors except 1 marker lesion no larger than 1 cm. consisted of instillations of 30 mg. Connaught strain BCG diluted in 50 ml. saline once weekly for 6 consecutive weeks. Two weeks after the last instillation any residual tumor was completely resected. In cases of complete disappearance of the marker lesion deep biopsy of the tumor area was done. Urine cytology was also performed. RESULTS: There was a complete response in 27 of the 44 patients (61%), no response in 12 (27%) and progression to carcinoma in situ in 1 (2%), while the response was not evaluable in 4. Local side effects included dysuria in 54% of cases and macroscopic hematuria in 39%. Neither BCG induced infection nor BCG sepsis was observed. CONCLUSIONS: Quarter dose BCG has a clear ablative effect on superficial bladder cancer with a 61% response rate. Phase III trials are now required to compare its efficacy and toxicity to those of full dose BCG.  相似文献   

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AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.  相似文献   

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Although laser is effective in the treatment of genital condylomata, patients with extensive lesions frequently require more than one treatment. The present study was undertaken to investigate whether the cure rate achieved by a single laser treatment could be improved by adding topical 5% 5-fluorouracil (5-FU). Twenty patients with extensive genital condylomata were treated with laser alone. Twenty patients comparable to the first group in age, number, size, and distribution of the condylomata were treated by laser and 5-FU. The first application of 5% 5-FU cream was carried out at the end of the laser treatment by the surgeon in the operating room. The patients were instructed to apply 5-FU cream once weekly to the vulva and once every two weeks to the vagina by using an applicator filled to one-third with 5-FU cream. Seven patients (35%) without 5-FU were found to have persistent condylomata at the first follow-up examination eight to 12 weeks after the single laser treatment. Two additional patients were noted to have disease six and nine months after laser treatment. The combination of laser and 5-FU failed in two cases (10%), both identified at the first visit. The difference is statistically significant (P less than .025, chi-square test). Two patients exposed to 5-FU experienced chemical vulvitis. It is concluded that the combination of a single laser treatment and 5-FU has acceptable side effects and results in a higher cure rate than a single laser treatment without 5-FU.  相似文献   

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One hundred and one female patients with vulvar condylomata acuminata were treated with the argon laser. Most were managed under regional or general anesthesia because of the large size and extent of the warts. Ten patients were lost to follow-up after the first session. Of 91 other patients, 78 (86%) were free of lesions on follow-up examinations after one or two treatments. The 13 other patients had recurrent lesions: seven patients underwent three laser sessions; four required four sessions, and 2 others required five and six sessions, respectively. These results were comparable with those achieved with the carbon dioxide laser.  相似文献   

14.
The limits of bacillus Calmette-Guerin for carcinoma in situ of the bladder   总被引:3,自引:0,他引:3  
PURPOSE: Historically carcinoma in situ of the bladder has been treated with radical cystectomy based on the aggressive and potentially invasive nature of this disease. The introduction in the late 1970s of intravesical bacillus Calmette-Guerin (BCG) has made this therapy the gold standard in the management of carcinoma in situ. Cases that are refractory or resistant to BCG therapy are a management dilemma with various available treatment options. MATERIALS AND METHODS: A comprehensive literature review of the current management of carcinoma in situ of the bladder was performed using MEDLINE, a review of current urology journals and abstracts from recent urology meetings. Data focused on BCG resistant carcinoma in situ of the bladder and current approaches in use for refractory disease. RESULTS: Complete and durable response rates have been reported in more than 70% of patients with carcinoma in situ who are treated with intravesical BCG. To our knowledge the optimal therapeutic regimen has not been established, although extended periods of treatment beyond the originally described 6-week course have not been shown to improve complete response rates. Prolonged administration of BCG is associated with adverse side effects. Various prognostic indicators of recurrence and progression exist that may identify a subset of cases unlikely to respond favorably to a conservative approach, including carcinoma in situ with associated stage T1 bladder lesions, diffuse and multifocal carcinoma in situ, multiple recurrences with intravesical therapy and extravesical involvement. Current molecular markers may also predict the response of carcinoma in situ to therapy. Treatment options available for BCG refractory carcinoma in situ of the bladder include intravesical chemotherapy, combined immuno-chemotherapy and radical cystectomy. Intravesical valrubicin and oral bropirimine have been shown to induce a complete response rate of 21% to 50%, although data on long-term followup are forthcoming. Radical cystectomy remains effective therapy for aggressive carcinoma in situ of the bladder. CONCLUSIONS: The current management of carcinoma in situ of the bladder is ill defined due to the variable natural history and unpredictable response of this disease to therapy. Controversy exists as to the optimal treatment of carcinoma in situ of the bladder since different forms of carcinoma in situ may exist that complicate therapeutic decisions for appropriate therapy. Some tumor characteristics are associated with more aggressive behavior and may be predictive of treatment outcome.  相似文献   

15.
尖锐湿疣是由人乳头瘤病毒(HPV)-6,11型感染所致的皮肤黏膜的良性增生,是性传播疾病中较为常见的一种疾病。一直以来,尖锐湿疣都有着较高的复发率,对其复发因素的探究一直是个热点,但迄今为止,其复发的原因仍不清楚拉。。为探讨尖锐湿疣的复发因素,笔者对杭州市第六人民医院皮肤性病科就诊的120例尖锐湿疣患者的资料进行了回顾性分析。  相似文献   

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PURPOSE: We investigated the efficacy of the recombinant bacillus Calmette-Guerin subunit protein vaccine Mpt-64 for inducing cytokine production and suppressing orthotopic bladder tumor growth in mice. MATERIALS AND METHODS: One mycobacteria candidate gene (Mpt-64) was cloned and ligated into eukaryotic expression vectors. The induction and efficiency of Mpt-64 protein expression were detected using Western blotting. Various doses of Mpt-64 proteins were instilled intravesically 6 times in 2 weeks after intravesical implantation of MBT-2 tumor cells in chemical injured urothelium. Systemic cytokine responses, tumor growth and cumulative survival rates were monitored. RESULTS: In vitro expression of recombinant Mpt-64 subunit protein was efficient in our system. Mice treated with 100 and 200 microg Mpt-64 subunit proteins significantly inhibited orthotopic MBT-2 tumor growth in C3H/HeN mice compared with that in control and 50 microg treatment groups in terms of the tumor taking rate, bladder tumor burden and mortality rate. Meanwhile, marked increased serum interferon-gamma with a limited but significant increase in serum interleukin-2 was observed in mice treated with 100 and 200 microg Mpt-64 proteins compared with control and 50 microg treated groups. CONCLUSIONS: A highly immunopotent recombinant Mpt-64 subunit protein of bacillus Calmette-Guerin was produced and it elicited immune responses with a high serum interferon-gamma level, inhibited orthotopic tumor growth and prolonged survival in tumor bearing mice. Thus, intravesical immunogenic therapy using recombinant Mpt-64 protein may be an alternative bacillus Calmette-Guerin regimen for superficial bladder cancer.  相似文献   

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PURPOSE: We assessed the safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients. MATERIALS AND METHODS: We retrospectively reviewed the charts of 697 patients treated with bacillus Calmette-Guerin instillations at our institution from 1991 to 2004. In 24 patients (3.5%) an underlying comorbidity directly affecting the immune system was diagnosed before bacillus Calmette-Guerin administration or steroids were administered at least 6 weeks before and at the time of bacillus Calmette-Guerin instillations. The immunosuppressive effect of steroids was assessed by the percent of lymphocytes. End points were the bacillus Calmette-Guerin response at 6 months, defined as normal cystoscopy, cytology and biopsy when available, and treatment related toxicity. RESULTS: Four patients (17%) had active lymphoma or chronic lymphocytic leukemia during bacillus Calmette-Guerin administration and 21 (88%) had a concurrent condition for which oral steroids (11), inhaled steroids (14) or oral and inhaled steroids (4) were administered. Patients treated with oral steroids had a lower percent of lymphocytes than patients treated with inhaled steroids and 15 age matched patients with high risk superficial bladder cancer and no steroid treatment (12.3% vs 17.5% and 18.6%, respectively). The overall bacillus Calmette-Guerin response rate at 6 months was 58%. Ten of the 24 patients had disease recurrence and 3 had disease progression at a median followup of 63.5 months (IQR 19.5, 89). One patient treated with oral steroids had self-limited febrile disease and worsening of myalgia 48 hours after his third bacillus Calmette-Guerin cycle. No other systemic adverse event following bacillus Calmette-Guerin therapy was recorded and all patients completed scheduled treatments. CONCLUSIONS: Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. The bacillus Calmette-Guerin response rate at 6 months and the side effects profile associated with bacillus Calmette-Guerin therapy in these patients were comparable to those in patients with no evidence of immunosuppression. Further studies are warranted to assess the safety and efficacy of bacillus Calmette-Guerin instillations in critically immunocompromised patients.  相似文献   

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Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To determine the influence of gender on the outcome of patients with high‐risk non‐muscle‐invasive bladder cancer treated with intravesical bacille Calmette‐Guérin (BCG) therapy, as the role of hormone status in the pathogenesis of urothelial carcinoma and the response to treatment remains subject to debate.

PATIENTS AND METHODS

We reviewed 1021 consecutive patients (756 men and 265 women) who were treated with induction BCG between 1978 and 2006 for multiple or recurrent high‐grade Ta, T1, and/or carcinoma in situ (CIS) bladder cancer. All patients had ≥5 years of follow‐up. The endpoints of initial response to BCG and the time to disease recurrence and progression were correlated with gender using Kaplan‐Meier methods and multivariate Cox regression models.

RESULTS

Men were significantly more likely to present with high grade (P = 0.003) tumours and with CIS (P < 0.001), while age and clinical stage at presentation were similar between men and women. There was no significant difference in the initial response to BCG by gender, as 593/756 (78.4%) men and 219/265 (82.6%) women had no evidence of disease at 6 months after BCG treatment (P = 0.14). The median time to recurrence after BCG therapy was also similar for men and women (20 vs 21 months, P = 0.51). Likewise, there was no evidence of a significant association between gender and the risk of disease progression after BCG therapy, such that the 5‐year estimated freedom from progression was 77% and 82%, respectively, for men and women (P = 0.08). Moreover, on a multivariate analysis controlling for patient age and tumour stage, grade and CIS, gender was not associated with the risk of recurrence (hazard ratio 0.94, 95% confidence interval 0.79–1.11; P = 0.44) or progression (1.18, 0.85–1.63; P = 0.33) after BCG. When the outcomes for women treated with BCG were stratified by age <50 years (the median age of menopause in the USA) vs ≥50 years, again there were no differences in the risk of tumour recurrence (P = 0.95) or progression (P = 0.35).

CONCLUSION

These data suggest that the outcomes of men and women with high risk non‐muscle‐invasive urothelial carcinoma treated with BCG are similar. As such, further studies are required to determine the clinical relevance of preclinical evidence that has suggested a potential role for sex steroids in the pathophysiology of bladder cancer.  相似文献   

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PURPOSE: The standard approach to treatment for patients with high risk Ta, Tis, or T1 bladder cancer that persists or recurs after bacillus Calmette-Guerin is radical cystectomy in medically fit patients. Maintenance bacillus Calmette-Guerin has been shown in both SWOG (Southwest Oncology Group) and EORTC (European Organization for Research and Treatment of Cancer) studies to reduce the probability of disease worsening events. As new drugs come on line and experience with maintenance and combination immunotherapy increases, there may be a tendency to delay definitive local therapy and thereby expose patients to a higher risk of progression to invasive and potentially metastatic disease. We explored a large prospective data set from the SWOG 8507 randomized trial of maintenance bacillus Calmette-Guerin to better understand this risk and specifically to assess the impact of timing of recurrence on survival. MATERIALS AND METHODS: The database includes 501 evaluable patients who were treated with induction bacillus Calmette-Guerin and then were randomized to maintenance bacillus Calmette-Guerin or observation. Recurrence patterns were defined as early (less than 12 months following randomization) or late (12 or more months after randomization). Patients were identified who underwent cystectomy at any time after induction bacillus Calmette-Guerin. All patients were followed for life for determination of vital status. Outcome measure of overall survival was assessed using Kaplan-Meier analysis and adjustment for covariates was done with proportional hazards models. Survival was defined from date of randomization to death from any cause. RESULTS: A total of 501 patients were randomized after induction bacillus Calmette-Guerin, of whom 251 had recurrence and 229 died. Of the patients who died 59% had recurrence following randomization. Early recurrence was not associated with a higher risk of death compared to late recurrence (p=0.68). There was no evidence that bacillus Calmette-Guerin affected the relationship of timing of relapse and survival. There was no difference in progression to T2 or greater between early and late recurrence (38 of 117, 32% vs 34 of 134, 25%; p=0.21). Cystectomy was performed infrequently as 56 of 251 patients who had recurrence underwent the operation. Patients who had early recurrence had a slightly higher cystectomy rate than those with late recurrence (32 of 117, 27% vs 24 of 134, 18%; p=0.07). Among 394 patients with no evidence of disease at randomization those who underwent cystectomy for T2 or greater disease had a higher risk of death compared to patients who underwent cystectomy for Tis or T1 disease (HR 1.76; 95% CI 0.77, 4.00; p=0.18). CONCLUSIONS: There was no association of the timing of recurrence after induction bacillus Calmette-Guerin on long-term survival probability. When patients had early recurrence there was a slightly higher probability of cystectomy but not progression to muscle invasive cancer. When cystectomy was performed the 5-year postoperative survival probability was lower than that reported in contemporary series.  相似文献   

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PURPOSE: We conducted a prospective, double-blind study with a crossover design of intravesical bacillus Calmette-Guerin (BCG) and dimethyl sulfoxide to determine whether patients with classic and nonulcer interstitial cystitis, respectively, might benefit from either regimen. MATERIALS AND METHODS: A total of 21 patients, including 11 with classic and 10 with nonulcer interstitial cystitis, randomly underwent treatments with intravesical BCG or dimethyl sulfoxide and, if not improved, were treated with the other substance after a washout period. All 21 patients were evaluated with symptom questionnaires, including a visual analog pain scale and voiding diaries. RESULTS: Regardless of regimen, there was no improvement in maximal functional capacity. There was a reduction in urinary frequency following dimethyl sulfoxide treatment but only in the classic subtype (p <0.05), whereas no reduction was seen following BCG in either subtype. A substantial pain decrease was noted in classic (p <0.05) as well as nonulcer (p <0.05) interstitial cystitis following dimethyl sulfoxide. CONCLUSIONS: Intravesical BCG has been presented as a promising new option for treatment of interstitial cystitis. We failed to demonstrate benefit from this treatment. Dimethyl sulfoxide had no positive effect on maximal functional capacity but resulted in a significant reduction in pain and urinary frequency, although only in patients with classic interstitial cystitis.  相似文献   

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