Evaluation of platelet distribution width as a diagnostic and prognostic biomarker in bladder neoplasm.

Aim: To evaluate the role of preoperative platelet distribution width (PDW) as a potential biomarker for distinguishing malignancy and tumor advantage of bladder neoplasm. Methods: The study included 210 subjects with bladder cancer, 76 subjects with urothelial papilloma and 132 healthy control subjects. Preoperative PDW along with other blood indices was evaluated. Results: PDW was higher in urothelial papilloma patients than that in bladder cancer patients (p < 0.001). Bladder cancer patients with advanced-stage disease exhibited lower PDW levels compared with patients with early stage disease. Conclusion: Reduced preoperative PDW level is an indicator of malignancy and advanced bladder cancer stages, suggesting it as a potential biomarker in bladder cancer diagnosis and prognosis.

Deletion of 14-3-3σ sensitizes mice to DMBA/TPA-induced papillomatosis.

The p53-inducible cell cycle regulator 14-3-3σ exhibits tumor suppressive functions and is highly expressed in differentiating layers of the epidermis and hair follicles. 14-3-3σ/SFN/stratifin is frequently silenced in human epithelial cancers, and experimental down-regulation of 14-3-3σ expression immortalizes primary human keratinocytes. In the repeated-epilation (ER) mouse model, a heterozygous nonsense mutation of 14-3-3σ causes repeated hair-loss, hyper-proliferative epidermis, and spontaneous development of papillomas and squamous cell carcinomas in aging mice. Therefore, loss of 14-3-3σ function might contribute to epithelial tumor development. Here, we generated mice with loxP sites surrounding the single 14-3-3σ exon which allowed Cre-mediated deletion of the gene. 14-3-3σ-deficient mice are viable, but demonstrate a permanently disheveled fur. However, histological analyses of the skin did not reveal obvious defects in the hair follicles or the epidermis. Deletion of 14-3-3σ did not enhance spontaneous epidermal tumor development, whereas it increased the frequency and size of DMBA/TPA-induced papillomas. In conclusion, 14-3-3σ is dispensable for normal epidermal homeostasis but critical for suppression of chemically-induced skin carcinogenesis. In addition, these results suggest that the ER mutation of 14-3-3σ is not equivalent to loss of 14-3-3σ, but may represent a gain-of-function variant, which does not reflect the organismal function of wild-type 14-3-3σ.

Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways.

Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra- and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low- to high-grade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, ß-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P=0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenoma-carcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.

Increased mitotic and proliferative activity are associated with worse prognosis in papillary tumors of the pineal region.

Papillary tumors of the pineal region are rare glial tumors located in the vicinity of the third ventricle, the clinical behavior of which is often aggressive. Little is known about the prognostic markers that might aid to identify patients at increased risk for recurrence. Therefore, the prognostic value of histopathologic and clinical features was examined in a series of 21 patients. Median age of the 12 male and 9 female patients was 35 years (range, 10 to 56 y). On histopathologic examination, all tumors were characterized by loose papillary structures and tumor cells forming broad perivascular pseudorosettes showing cytokeratin expression. In addition, tumors showed increased cellularity (n=4; 19%), nuclear pleomorphism (n=4; 19%), solid growth (n=11; 52%), necrosis (n=8; 38%), increased mitotic activity (≥3 mitoses per 10 high-power fields [n=10; 48%]), and increased proliferation (Ki67/MIB1 index ≥10% [n=8/20; 40%]). Gross total resection could be achieved in 13/21 patients (62%). Postoperatively, 13 patients received radiotherapy and 4 patients chemotherapy. Median recurrence-free survival was 66 months in 19 patients, for whom detailed follow-up information was available. Twelve patients (63%) experienced tumor progression. Three patients (16%) died of disease. Among the clinical and histopathologic features examined, only increased mitotic activity (52 [8 to 96] vs. 68 [66 to 70] mo [median [95% confidence interval]]) and proliferative activity (29 [0 to 64] vs. 67 [44 to 90] mo) were significantly associated with recurrence (P<0.05). Tumors of the 3 patients who had succumbed to disease showed increased mitotic and proliferative activity. In conclusion, increased mitotic and proliferative activities are associated with worse prognosis in papillary tumors of the pineal region.

Transitional cell tumours of the lacrimal drainage apparatus.

BACKGROUND: Tumours of the lacrimal drainage apparatus (LDA) are very rare, but can be life-threatening. Seventy percent of lacrimal sac tumours are of epithelial origin, and transitional cell tumours represent an interesting sub-group of these epithelial tumours. METHODS: A retrospective review of cases of LDA transitional cell tumours co-managed at the Royal National Throat Nose and Ear Hospital and Moorfields Eye Hospital, London. RESULTS: Twenty cases of transitional cell tumours of the LDA were identified, comprising 10 transitional cell papillomas (TCPs) and 10 transitional cell carcinomas (TCCs). All cases were resected through a modified lateral rhinotomy approach. Limited resection of orbital fat with preservation of orbital functions was required for 2 cases of TCC. Fractionated external beam radiotherapy was administered in 7 cases of TCC. The mean follow up was 80 months (range 11 months-16 years). Recurrences were detected in 4 cases, which were managed by further surgery. Two cases have been lost to follow-up, but the 18 other patients are currently alive and disease free. CONCLUSION: A favourable outcome can be achieved with transitional cell tumours of the LDA when an optimum management plan is followed.

Intraductal papillary neoplasm of the bile duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma. IPNBs are mainly found in patients from Far Eastern areas, where hepatolithiasis and clonorchiasis are endemic. According to the immunohistochemical profiles of the mucin core proteins, IPNBs are classified into four types: pancreaticobiliary, intestinal, gastric, and oncocytic. Approximately 40%-80% of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma, suggesting that IPNB is a disease with high potential for malignancy. It is difficult to make an accurate preoperative diagnosis because of IPNB's low incidence and the lack of specificity in its clinical manifestation. The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation. Simultaneous proximal and distal bile duct dilation can be detected in some cases, which has diagnostic significance. Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions. However, pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion. Surgical resection is the major treatment. Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved. Staging, histologic subtype, curative resection and lymph node metastasis are factors affecting long-term survival.

Biliary papillomatosis in three Caucasian patients in a Western centre.

INTRODUCTION: Biliary papillomatosis (BP) is a rare condition with a strong potential for malignant transformation and cases from Western centres are sparse.(1) We discuss the presentation, investigation and management of this condition in three Caucasian patients and present a review of the existing literature on BP. PATIENTS AND METHODS: The case notes of three Caucasian patients with BP who presented to our tertiary referral centre were reviewed. Their case histories, investigations and managements are presented. A search of MEDLINE, PubMed and Cochrane databases was performed to review relevant literature around BP. DISCUSSION: BP is a rare condition characterised by multiple papillary adenomas involving the biliary tree which lead to recurrent attacks of cholangitis. It is a low-grade neoplasm with high malignant potential and should be regarded as a pre-malignant lesion.

Enhancement of tongue carcinogenesis in Hras128 transgenic rats treated with 4-nitroquinoline 1-oxide.

Transgenic rats carrying human c-Ha-ras proto-oncogene (Hras128 rats) have been shown to be highly susceptible to induction of tumors. We have found an early induction of tongue tumors in Hras128 rats treated with 4-nitroquinoline 1-oxide (4NQO). 4NQO was administered to the Hras128 and wild-type Sprague-Dawley (SD) rats for 4 and 8 weeks, respectively. The experiment was terminated at 14 (Hras128 rats) and 28 (SD rats) weeks. Either during or after treatment with 4NQO, dysplastic hyperplasia, papilloma and squamous cell carcinoma were found on the tongue of both Hras128 and wild-type rats, with a higher incidence and multiplicity in Hras128 rats. Treatment of the Hras128 rats with 4NQO significantly increased cell proliferation in the tumor compared to the control rats. In the tongue tumors of the Hras128 rats, there was a significant increase in the mRNA expression levels of cyclin D1 and COX2. To examine whether this experimental system is useful for screening of the candidate agents for cancer preventive effect, nimesulide, a selective COX2 inhibitor, was tested in the present model. Nimesulide significantly decreased total multiplicity of tongue lesions compared to the control rats. Treatment of Hras128 rats with nimesulide caused a significant decrease in the levels of mRNA expression of cyclin D1 and COX2 in the tumor. Therefore, the current 4NQO-induced Hras128 rat tongue carcinogenesis model provides a simple and rapid system for investigating carcinogenesis process and evaluating the effect of possible cancer preventive agents for human tongue cancer.

Effect of human papilloma virus expression on clinical course of laryngeal papilloma.

CONCLUSION: Our observations suggest that human papilloma virus (HPV) 6/11 is the main causative agent of laryngeal papilloma and that detection of active HPV DNA expression may be helpful in identifying patients with aggressive recurrent laryngeal papilloma. OBJECTIVES: HPV is assumed to be the main causative agent of this disease. We investigated the expression of the entire genotype of HPV in cases of laryngeal papilloma and correlated their expression with the clinical course of the disease. SUBJECTS AND METHODS: Seventy cases of laryngeal papilloma were evaluated for the presence of the HPV genome by in situ hybridization (ISH) using wide-spectrum HPV DNA probe. Specific types of HPV infection were determined by DNA ISH using type-specific HPV DNA probes (HPV 6, 11, 16, 18, 31, 33). Separate analyses were conducted comparing viral types, frequency of recurrences and duration of disease-free periods. RESULTS: We detected HPV DNA in 40 of the 70 laryngeal papilloma cases (57%). In particular, HPV DNA was detected in 75% of the juvenile types. There were significant associations between HPV and laryngeal papilloma (p<0.01). Among the HPV-positive cases, major specific types were HPV 6/11 (97%). Significant associations were also noted between viral expression and clinical course.

Hypoxia increases intensity of epidermal papillomatosis in roach Rutilus rutilus.

Hypoxia, which occurs frequently in aquatic ecosystems and is mainly due to increasing eutrophication can cause severe environmental stress in fish. We investigated experimentally the hypothesis that hypoxia could be one of the environmental stress factors that can induce papillomatosis in fish. Male roach Rutilus rutilus exposed to periodic oxygen deficiency and accompanied temperature increases (OT group) showed the highest increase in the intensity of papillomatosis, as measured by the number of scales covered by papillomatosis tumors. The second highest increase in disease intensity was among male roach exposed to periodical temperature increases. The incidence of such tumors was lowest in the control group, which was exposed to neither hypoxia nor increased temperature. The mortality of fish during the 17 d experiment was highest and the condition factor was lowest in the OT group, indicating this group experienced a higher level of stress. The apparent interaction of hypoxia and temperature suggests that these environmental stressors are among the multifactorial elements leading to papillomatosis in roach. Furthermore, these results provide experimental evidence to indicate that hypoxia may contribute to tumor development in fish.

Management of low grade papillary bladder tumors.

PURPOSE: We evaluated the management and treatment outcomes of low grade papillary bladder tumors. MATERIALS AND METHODS: We evaluated 215 patients diagnosed with low grade and noninvasive papillary bladder tumors, and followed them every 6 months with flexible cystoscopy for 6 to 10 or more years. Tumor recurrence was treated with transurethral resection or outpatient cystoscopic fulguration. RESULTS: Of the 215 patients 143 (67%) had at least 1 recurrence (positive cystoscopy). With a median followup of 8 years tumor recurrences averaged 6.2 (range 1 to 19) requiring 0.34 transurethral resections per year or 1 transurethral resection every 3 years, or 0.61 fulgurations or 1 fulguration approximately every 2 years. There were 17 patients (8%) who had progression in grade or stage and 1 patient (0.5%) died of bladder cancer. Patients most likely to have recurrence had multiple tumors, low grade (TaLG) carcinoma or tumor at first followup cystoscopy. CONCLUSIONS: Surveillance cystoscopy at 6-month intervals coupled with outpatient fulguration controls recurrent tumors and reduces the therapeutic burden for patients diagnosed with low grade papillary bladder tumors.

Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas.

Recently, attention has been drawn to papillary neoplasm of the pancreatobiliary systems. In the pancreas, the disease entity of intraductal papillary mucinous neoplasm (IPMN-P) is widely recognized. In contrast, the pathological characteristics of biliary papillary tumors, such as biliary papilloma(tosis) and papillary cholangiocarcinoma, have not yet been well documented. In this study, we compared the pathological features and post-operative prognosis among biliary papillary tumors (10 cases of biliary papilloma(tosis) and 22 cases of papillary cholangiocarcinoma), conventional non-papillary cholangiocarcinoma (15 cases), and IPMN-P (31 cases). Macroscopically, all biliary papillary tumors were characterized by the prominent intraductal papillary proliferation, and macroscopic mucin-hypersecretion was seen in 9 of 32 cases (28%). Histologically, biliary papillary tumors consisted of three types of tumor cells (pancreaticobiliary, intestinal and gastric types), whereas only the pancreaticobiliary type was observed in non-papillary cholangiocarcinoma. Immunohistochemically, biliary papillary tumors were characterized by the common expression of MUC2, CDX2 and cytokeratin 20. In addition, biliary papillary tumors could be associated with two types of invasive lesions: tubular adenocarcinoma (9 cases) and mucinous carcinoma (5 cases). Patients with tubular adenocarcinoma had a poor prognosis compared to non-invasive papillary tumor or papillary tumor with mucinous carcinoma. These pathological characteristics and the survival status of biliary papillary tumors were different from those of non-papillary cholangiocarcinoma, and rather closely resembled those of IPMN-P. In conclusion, biliary papillary tumors may be the biliary counterpart (intraductal papillary neoplasm of the bile duct) of IPMN-P.

[Differentiated thyroid carcinoma in young people].

OBJECTIVE: To investigate the factors that influence survival of the patients with differentiated thyroid carcinoma in young people and evaluate the efficiency of unilateral lobectomy plus isthmectomy with therapeutic cervical lymph node dissection and postoperative TSH (thyroid stimulating hormone) suppressive therapy. METHODS: One hundred and thirty-one patients under 30 years old with differentiated thyroid carcinoma treated in this hospital (14 cases no more than and 117 cases more than 16 years) from Jan. 1st, 1985 to Dec. 31st, 1997 were retrospectively reviewed. One hundred and twenty-eight patients were received only surgery and TSH suppressive therapy, and 3 patients received chemotherapy or radiotherapy because of the progressive metastasis in necks or mediastina. A multivariate analysis was performed in these patients by the Cox proportional hazard model. RESULTS: The mean follow-time (x +/- s) of all patients were (140.86 +/- 43.76) months, with range from 20 to 229 months; Ninety-eight patients followed more than 10 years. Ten patients died of thyroid cancer. The overall 10-year survival rate was 97.18%. The 10-year survival rate for patients < or = 16 years of age and > 16 years were 75.97% and 96.57% respectively (P = 0. 0006). The 10-year survival rate for women and men were 94.91% and 93.69% respectively (P = 0.5261). The 10-year survival rates of patients with papillary thyroid carcinoma and follicular thyroid carcinoma were 93.77% and 96. 55% respectively (P = 0.8137). For patients with tumor size of < or = 1 cm, 1-4 cm and >4 cm the survival rate was 100.0%, 96.40%, and 80.67% respectively (P = 0. 0589). The 10-year survival rates of patients with or without lymph node metastasis were 88.37% and 100. 0% respectively (P = 0.0313). For patients of with or without distant metastasis, The survival rate was 96.64% or 60.00% (P = 0.0000). The 10-year survival rates with or without recurrence were 86. 67% and 95.48% respectively (P = 0. 5681). Using multivariate analysis, risk factors that independently influence survival were distant metastasis, tumor size and age. CONCLUSIONS: The distant metastasis, tumor size and age at diagnosis were the independent factors influencing survival significantly. The status of lymph node metastasis may have certain effect on the prognosis. Unilateral lobectomy plus isthmectomy with a therapeutic cervical lymph node dissection followed by postoperative TSH suppressive therapy is a favourable model to children and young adults with DTC without distant metastasis, but to the patients with distant metastasis, their prognosis of this therapy model is disappointing.

[Malignant transformation of a juvenile papilloma in a 11 year old boy]. / Maligne Entartung einer juvenilen Kehlkopfpapillomatose bei einem 11-jährigen Jungen.

BACKGROUND: The juvenile laryngeal papilloma is the most common benign neoplasm in children. Often the entity shows an elongated recurrent course of disease with an expansion into the tracheo-bronchial system. Sporadic malignant transformation in adults with a papilloma was reported after treatment with radiotherapy alone or in combination with the intake of additional toxins (e. g. nicotine). Similar reports of a malignant transformation of juvenile papillomas without additional risk factors is very rarely reported. CASE REPORT: We report about an 11 year old boy, who suffered from a juvenile laryngeal papilloma. The multiple laser surgical procedures and a therapy with interferon resulted in a short-term remissions. A tracheotomy was inevitable. Seven months after the first diagnosis of the papilloma a regional metastatic squamous cell carcinoma was found. In spite of combined radiotherapy and chemotherapy the boy died 11 months later. CONCLUSIONS: The spontaneous malignant transformation of a juvenile papilloma in a squamous cell carcinoma is extremely rare. The surgical intervention as well the radiotherapy and chemotherapy using interferon was unsuccessful due to the high grade of malignancy. In view of the very short time interval between first diagnosis of juvenile papilloma and the subsequent malignant transformation, one must consider either the potential presence of a very aggressive form of papilloma or alternative two coincident independent diseases.

Use of interferon-alpha in recurrent respiratory papillomatosis: 20-year follow-up.

OBJECTIVES: The aim of this study was analysis of the results of use of interferon-alpha (IFN-alpha) in patients with recurrent respiratory papillomatosis (RRP) and correlation of the results with human papillomavirus (HPV) type. METHODS: A multicenter prospective series (42 patients from 22 hospitals) yielded 20 years of follow-up of patients with RRP and HPV typing who were treated with IFN-alpha in doses of 3 MU/m2 3 times per week. RESULTS: During long-term follow-up (mean +/- SD, 172 +/- 36.8 months), the rate of event-free survival evaluated by Kaplan-Meier analysis was 42.8%, and the overall survival rate was 82.6%. The HPV typing revealed an association of HPV 11 with a more aggressive disease course (64% of HPV 11 patients versus 24% of HPV 6 patients), a lower incidence of long-term response to IFN-alpha therapy (14% of HPV 11 patients versus 64% of HPV 6 patients), and a higher incidence of malignant transformation and mortality during follow-up (36% and 24%, respectively, of HPV 11 patients versus 0% of HPV 6 patients). CONCLUSIONS: The obtained results revealed maximal effectiveness of IFN-alpha therapy in RRP patients with HPV 6 as compared with HPV 11. The association of HPV 11 with a worse long-term response to IFN-alpha therapy and a higher incidence of malignant transformation and mortality is clinically important and indicates the necessity of HPV typing in RRP patients after the first biopsy.

High co-prevalence of genogroup 1 TT virus and human papillomavirus is associated with poor clinical outcome of laryngeal carcinoma.

BACKGROUND: The aetiology and factors leading to the progression of laryngeal cancer are still unclear. Although human papillomavirus (HPV) has been suggested to play a role, reports concerning the effect of HPV infection on tumour development are controversial. Recently, transfusion transmitted virus (TTV) was suggested to play a role in certain infections as a causative or coinfecting agent. AIMS: To investigate whether the development and progression of laryngeal squamous cell carcinoma is associated with coinfection with TTV and HPV. METHODS: The prevalence of TTV and HPV was investigated using the polymerase chain reaction in tissue samples from 40 healthy individuals, 10 patients with recurrent papillomatosis, five patients with papillomatosis with malignant transformation, and 25 patients with laryngeal carcinoma. The obtained prevalence data were compared and analysed statistically. RESULTS: In the 11 patients with carcinoma who had metastasis or relapse there was a high rate of coinfection with genogroup 1 TTV and HPV (eight of 11), whereas in the 14 without tumour progression no coinfection was found. Coinfection was associated with significantly lower tumour free survival in patients with carcinoma (p < 0.001). Furthermore, four of five patients who had papillomatosis with malignant transformation were coinfected with genogroup 1 TTV and HPV. CONCLUSIONS: Although the nature of cooperation between HPV and TTV needs to be investigated further, coinfection with genogroup 1 TTV and HPV appears to be associated with poor clinical outcome in laryngeal cancer.

Effect of epidermal papillomatosis on survival of the freshwater fish Rutilus rutilus.

Epidermal papillomatosis occurs in several marine and freshwater fish species. Previously, papillomatosis has been shown to induce mortality in juvenile carp. We studied the effect of epidermal papillomatosis on the survival of adult male roach Rutilus rutilus by caging naturally diseased, marked (by us) fish in the field. Within the constraints of the experimental design, there was no difference in survival between healthy, slightly diseased and heavily diseased fish. Therefore, we conclude that the possible effect of epidermal papillomatosis on the mortality of wild roach is relatively minor.

Apoptotic index: use in predicting recurrence in breast cancer patients.

Apoptosis maintains tissue homeostasis through its ability to control cell population and has been extensively studied in human cancers. Relation of apoptosis to prognosis is still controversial. In this study, we analyzed the prognostic significance of apoptotic and mitotic indices (AI & MI) using hematoxylin and eosin stained slides by light microscopy in breast cancer patients. In our study, apoptotic index was significantly associated with predicting relapse free survival (RFS), distant recurrence free survival (DRFS) and overall survival (OS) with lesions having higher apoptotic index showing poor prognosis. Our results also point out that quantitation of apoptotic index by simple light microscopy as a routine practice along with histological diagnosis, could provide additional prognostic information in patients who are at high risk of developing recurrence with breast cancers.

Choroid plexus tumors in children and young adults: report of 16 consecutive cases.

Choroid plexus tumors are rare intraventricular tumors, and they represent 2-4% of brain tumors in children. This single-institution retrospective study involves 16 consecutive choroid plexus tumors: 13 papillomas and 3 carcinomas. Tumor locations were the lateral ventricles in 13 cases, the third ventricle in 2 cases and the fourth ventricle in 1 case. The mean age at presentation was 3.1 years. Two patients died of perioperative blood loss. Five-year survival was 85% with papillomas and 33% with carcinomas. None of the papillomas recurred after total tumor resection, and the functional outcome in long-term survivors after papilloma surgery was excellent in 92% of the cases. Two of the carcinoma patients had disseminated disease. Fifty percent of the patients had persistent hydrocephalus after tumor resection, and these required cerebrospinal fluid diversion.

The cost of juvenile-onset recurrent respiratory papillomatosis.

OBJECTIVE: To assess the medical costs and the number of quality-adjusted life years lost owing to juvenile-onset recurrent respiratory papillomatosis (JORRP). DESIGN: We examined hospital and physician charges for JORRP surgical procedures in Maryland in 1994 adjusting for inflation and the cost-charge ratio. Centers for Disease Control and Prevention data on treatment intensity for JORRP were augmented with a review of treatment records for 18 patients with JORRP. Sensitivity analyses were performed. To illustrate the application of our cost estimates, we compare the costs of JORRP to the costs of the surgical procedures that would be necessary to prevent it. RESULTS: We find that the present value at birth of the cost of a single case of JORRP is $201,724 (range, $61,822-$474,334). The annual cost for a single case of JORRP is $57,996 (range, $32,407-$94,114). The annual cost of JORRP in the United States is between $40 million and $123 million depending on the prevalence. Cesarean section (CS) for women with condyloma has been suggested as a potential strategy to prevent JORRP, but its efficacy remains to be determined. Our results suggest that if only 1% of the CSs actually prevented JORRP, this strategy would be a cost-effective means to prevent JORRP. CONCLUSIONS: Studies to reduce the uncertainty surrounding the efficacy of CS and the effect of both CS and JORRP on families need to precede consideration of a policy of CS for women with clinically evident genital condyloma. Patients should be kept thoroughly informed about the role of CS for the prevention of JORRP and the nature of the remaining uncertainties.