[Effectiveness and tolerability of celecoxib in outpatient department practice]. / Efficacia e tollerabilità del celecoxib nella pratica clinica ambulatoriale.

OBJECTIVES: Object of this work is to evaluate activity and tolerance of Celecoxib in out-patient's department practice. PATIENTS AND METHODS: In this study we enlisted 46 patients, affected by pain of inflammatory or degenerative origin; any of them ever did continued therapy with NSAIDs before. We administered 200 mg daily dose of Celecoxib for at least three months. Each patient has been evaluated by the Visual Analogic Score (VAS) Scale before and after the therapy. RESULTS: The data We obtained agree with those of multicenter studies like CLASS. Celecoxib had similar efficacy respect with traditional NSAIDs, with good control of pain in both osteoarthrosic and arthritic pain (p < 0.000). Not good results were obtained for control of acute-onset pain. In our population We didn't find side-effects different from those included in the technical-form of the drug. The only patient who complained of epigastric pain did not stop the treatment, because the symptom resolved with assumption of the drug during meals. CONCLUSIONS: By the analysis of the results We consider Celecoxib useful for the control of pain in the treatment of osteoarthrosis and autoimmune diseases like Rheumatoid Arthritis. Anyway, treatment with Celecoxib (as with all Coxib-family drugs) should be reserved for long-lasting treatments in patients at risk for gastrointestinal bleeding.

Site of origin of epithelial ovarian cancer: the endometriosis connection.

To investigate the left- and right-sided distribution of ovarian malignant surface epithelial tumours, data were collected on 209 women undergoing first-line surgery for Stage I and II disease. Considering the unilateral cancers, the observed proportion of left-sided lesions was 35/54 (65%) in the endometrioid, 20/45 (44%) in the serous, 19/35 (54%) in the clear cell, 13/29 (45%) in the mucinous, 2/8 (25%) in the mixed, and 2/5 (40%) in the undifferentiated histological type group. The proportion of left-sided unilateral endometrioid cancers was significantly different from the expected 50% (chi2(1), 4.74, P = 0.03) and very similar to that previously observed for benign endometriotic cysts, constituting further evidence in favour of a possible development of endometrioid cancers from the latter lesions.

Lateral distribution of nonendometriotic benign ovarian cysts.

To investigate the left- and right-sided distribution of nonendometriotic benign ovarian cysts, data were collected on 406 women undergoing first-line surgery for tumours with various histotypes. Considering the unilateral cysts, the observed proportion of left lesions was 65/129 (50.4%) in the serous, 38/79 (48.1%) in the mucinous, 59/134 (44.0%) in the dermoid, 11/21 (52.4%) in the parovarian, and 3/7 (42.9%) in the miscellaneous cysts group, without significant differences from the expected 50%. This contrasts with the finding of a significantly more frequent development of endometriomas on the left ovary, and suggests that the pathogenesis of endometriotic and nonendometriotic cysts is different.

Is ureteral endometriosis an asymmetric disease?

Six cases of endometriosis obstructing the left ureter were observed among 1,054 consecutive patients undergoing surgery in an eight-year period. In addition, 125 women with ureteral endometriosis (left-sided, n = 66; right-sided, n = 40; bilateral, n = 19) were described in 62 articles identified in a systematic review of the English language literature between 1980 and 1998. Considering only the patients with unilateral ureteral endometriosis and combining the published figures with those of our surgical series, the observed proportion of left lesions (72/112, 64%; 95% CI 55% to 73%) was significantly different from the expected proportion of 50% (chi2(1), 9.14, P = 0.002). The lateral asymmetry found in the location of ureteral endometriosis is compatible with the menstrual reflux theory and with the anatomical differences of the left and right hemipelvis.

Primary malignant melanoma of the vagina: case report.

Primary vaginal melanoma is a very rare gynecological malignant tumor (less than 150 reported cases to-date). Prognosis is poor in spite of treatment. Due to the fact that only small groups of patients have been compared, conservative treatment has usually been recommended. In recent times, radical pelvic surgery has appeared to improve the chances of survival. We present an unusual case of primitive melanoma of the upper-third of the vagina with urethral and urinary bladder infiltration in a 47-year-old woman. Treatment consisted of preliminary pelvic bilateral lymphadenectomy, anterior exenteration, and urinary bladder reconstruction according to the Bricker technique. Four months after surgical treatment, liver metastases were found. Chemotherapy was initiated consisting of 8 cycles every 21 days of fotemustine 100 mg/m2 (day 1) and dacarbazine (DTIC) 250 mg/m2 (days 2-5). Interferon alpha-2-b, 3 MU thrice weekly, for the whole period of chemotherapy, was also administered. The patient is in partial remission one year after surgical treatment.

Diagnostic phase antibody response to the human papillomavirus type 16 E2 protein is associated with successful treatment of genital HPV lesions with systemic interferon alpha-2b.

BACKGROUND AND OBJECTIVE: Systemic interferon alpha-2b treatment reduces relapses of genital human papillomavirus (HPV) lesions in some but not all females. The aim of the present study was to investigate possible predictive pretreatment factors for the outcome of therapy. MATERIAL AND METHODS: HPV DNA status and HPV antibody response were evaluated in 100 randomized patients treated with laser ablation and systemic interferon alpha-2b or placebo, and followed up to 6 months. RESULTS: Overall, adjuvant therapy with systemic interferon-alpha did not differ from placebo. However, detectable diagnostic phase levels of serum antibodies to e.g. HPV16 open reading frame (ORF) E2 derived peptide 141EEASVTVVEGQVDYY155 predicted 10-fold difference in the risk of recurrence of HPV infection following adjuvant interferon alpha-2b therapy as compared with placebo (odds ratio, OR, 0.5, 95% confidence interval (CI), 0.1-2.3; OR, 4.6, 95% CI 0.5-41, respectively). This trend was statistically significant in the whole study population (2P < 0.05), and in patients with high viral load (2P < 0.01). CONCLUSIONS: Evaluation of the E2 antibody responses may help to identify women with genital HPV lesions who respond to systemic interferon alpha-2b treatment.

Type 1 cytokine response and treatment outcome of genital HPV lesions.

OBJECTIVES: To determine the role of type 1 cytokines as predictors of response to treatment of genital HPV lesions with laser ablation with or without adjuvant systemic interferon alpha 2b (IFN-alpha). METHODS: Measurement of serum interleukin 2 (IL-2), IL-2 soluble receptor alpha (sIL-2 alpha), interferon gamma, and human papilloma virus (HPV) DNA in patients undergoing treatment of genital HPV lesions with carbon dioxide laser and systemic IFN-alpha. A randomised, placebo controlled study of 92 cases with 6 months of follow up. RESULTS: High IL-2/sIL-2 alpha was associated with 60% to 70% protection against recurrences both in the IFN-alpha and placebo groups (OR = 0.4, 90%, CI 0.1-2.5; OR = 0.3, 90% CI 0.0-1.8, respectively). Diagnostic phase serum IL-2 predicted favourable outcome (OR = 0.2, 90% CI 0.0-1.0) in women with high load of HPV DNA or HPV 16/18 DNA regardless of the adjuvant therapy. CONCLUSIONS: Serum IL-2 determinations may identify women with good prognosis following laser ablation of genital HPV lesions.

Human T helper cell epitopes overlap B cell and putative cytotoxic T cell epitopes in the E2 protein of human papillomavirus type 16.

Activation of T helper cells is a prerequisite for the function of cytotoxic T lymphocytes (CTL) and the maturation of the B cell response. Because epitopes recognized by each of these cells may overlap, we scanned the E2 protein of human papillomavirus (HPV) type 16 to identify the T helper cell epitopes. Four major T helper cell epitopes (mapping between aa:s 11-25, 141-155, 191-205 & 231-245) and adjacent human B cell epitopes were found. The first peptide-defined epitope (RLNV) 11CQDKILTHYENDSTD25 overlapped five putative HLA-I (A1, A2, A0205, A3 & A11) binding motifs (CQDKILTHY, RLNVCQDKI, NVCQDKIL, RLNVCQDK & RLNVCQDK). This epitope is also part of an N-terminal alpha-helix which may form four HLA-II (DR2, DR4, DR7 & DR8) specific agretopes for structures recognizable by the T cell receptor (e.g. KILT). The second epitope 141EEASVTVVEGOVDYY155 (GLYY) overlapped the putative HLA-A1 & HLA-Bw37 binding motifs (VVEGQVDYY/QVDYYGLYY and EEASVTVV), and two HLA-II (DR1 & DR3) specific agretopes. The third and fourth epitopes were not associated with more than one putative CTL epitope each. Only the first epitope shared considerable aa-homology with corresponding regions of other genital HPV types.

A colposcopic scoring system for grading cervical lesions.

Colposcopic scoring systems have been used for distinguishing low-risk from high-risk cervical lesions. We studied 159 HPV DNA positive patients (7 with HPV 6/11, 51 with HPV 16/18, 52 with HPV31/33/35, 25 with mixed HPV types, and 24 with untypable HPV) (mean age 25.7 years, SD 7.4), and 69 age matched HPV-DNA negative control, patients, drawn from the same clinical setting. A dot-blot hybridization technique (ViraPap and VyraType, Digene Diagnostics, MD, USA) was used for HPV DNA hybridizations types 6/11, 16/18, and 31/33/35. Each patient underwent cytologic and colposcopic evaluation at four-month intervals. A colposcopic score for grading cervical lesions was used. It included features of lesion borders, tone of acetowhitening, and vascular atypia. Each feature was graded using three categories, so that an increasing score would be associated with gradually more severe lesions. The mean follow-up time was 12.2 months (SD 8.7) for the cases, and 12.8 months (SD 6.9) for the controls. The study end point was defined as the presence of cytologic changes consistent with CIN, in which case colposcopically directed biopsy and endocervical curettage were performed. The mean colposcopic score derived from the features of ATZ was 4.9 in the HPV DNA positive patients and 4.3 in the HPV DNA negative patients. The mean colposcopic score was 3.3 for those with HPV 6/11, 4.5 for HPV 16/18, 5.3 for HPV 31/33/35, 5.0 for mixed HPV types, and 4.0 for untypable HPV.(ABSTRACT TRUNCATED AT 250 WORDS)

Vulvar and vaginal colposcopic pictures of human papillomavirus infection.

The recognition of both overt and subclinical vulvar HPV infection has become increasingly important. However, although molecular biological evidence has indicated a strong link between HPVs and cancer, clinical or epidemiological evidence is still not fully convincing. We studied 159 HPV DNA positive patients, using a dot blot hybridization technique (ViraPap and ViraType, Digene Diagnostics. USA), and 69 randomly selected HPV negative controls drawn from the same clinical setting, at the outpatient clinic, Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland. Seven patients had HPV 6/11, 51 had HPV 16/18, 52 had HPV 31/33/35 25 had more than one of the three HPV DNA groups ("mixed"), and 24 had untypable HPV DNA. Cases and controls were examined at four month intervals. The mean follow-up time was 12.2 months (SD 8.7) for the cases, and 12.8 (SD 6.9) for the controls. Although vulvar or vaginal abnormalities (acetowhite epithelium, squamous papillomatosis, filaments, satellite lesions, fissure, papules, or exophytic condylomas) were more commonly seen in the cases than in the controls, the difference was significant only for exophytic condylomas. In conclusion, colposcopy is not a good predictor of HPV infection and should not be used as an HPV screening test. HPV DNA hybrodization did not help more than the histopathologic findings in the diagnosis, but allowed the recognition of high-risk patients. The role of an accurate colposcopic examination with target biopsies remains essential.

A T-helper cell epitope overlaps a major B-cell epitope in human papillomavirus type 18 E2 protein.

Cultivated CD4+ T-helper cells from two patients with cervical adenocarcinoma showed responses to a peptide EKTGILTVTYHSETQRTK derived from an E2 protein of human papillomavirus type 18 (HPV 18), but not to a corresponding HPV 16 peptide (HKSAIVTLTYDSEWQRDQ). Serum antibodies in the HPV 18 peptide were also demonstrated in these patients. The GILT motif resembles a common pattern present in many T-cell epitopes, and is located at the beginning of an 11-amino acid-long A-helix structure close to the carboxyterminal end of HPV 18 E2. We conclude that two epitopes (a T-helper cell epitope and a B-cell epitope) overlap in the HPV 18 E2.

Intralesional recombinant alpha 2B interferon in the treatment of human papillomavirus-associated cervical intraepithelial neoplasia.

Twenty-four patients with human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN); of whom 13 had CIN 1, 8 had CIN 2, and 3 had CIN 3; were treated with recombinant alpha 2b interferon (IFN) by intraperilesional injections. The dosage given was 3 x 10(6) international units per day, 3 days per week for 3 weeks. In situ hybridization was carried out for HPV types 6/11 and 16/18. One year after treatment, complete response was observed in 8 (33%) cases, partial regression in 14 (58%) cases, persistence in 2 (8%) cases (in which case traditional surgical therapy was performed), and progression in none of the cases. Adverse effects (asthenia, fever, chills, and headache) were observed in 20 (83%) cases. None of the patients had myelodepression. Intraperilesional treatment of HPV-associated CIN with recombinant alpha 2B IFN does not appear to be a valid substitute for traditional treatment, but it could be considered in certain cases when surgery is not advised.

Invasive cervical carcinoma in patients aged 35 or younger.

There has been concern that invasive cervical carcinoma is more aggressive in young women. We studied retrospectively 36 patients who were less than 35 years old (mean age 30.8 years, range 22-35 years, SD 3.6), and 36 controls (mean age 59.4 years, range 40-72 years, SD 9.5), treated for invasive cervical carcinoma between 1976 and 1986. Histologically 31 (86%) were squamous cell carcinomas and 5 (14%) were adenocarcinomas both in the patients aged 35 years or younger and in the control group. Clinical findings and rates of pelvic lymph nodes metastases were comparable in both groups. Compared to controls, patients aged 35 or younger had longer intervals from diagnosis to recurrence (20.3 months vs. 9.0 months), longer intervals from recurrence to death (15.3 months vs. 7.0 months), and longer intervals from diagnosis to death (39.6 months vs 20.0 months). There was no difference between the groups in the 5-year survival (75% vs. 81%). In conclusion, we found no evidence that the overall clinical behaviour of invasive cervical cancer is more aggressive in young women.

Human papillomavirus infection of the female genital tract: correlation of HPV DNA with cytologic, colposcopic, and natural history findings.

Although molecular biology evidence suggests a strong link between HPVs and anogenital neoplasias, evidence from clinical studies is still less convincing. Thus, the recognition of both overt and subclinical HPV infection has become increasingly important. We studied the correlation between HPV DNA and cytologic, colposcopic and natural history findings in a defined group of women. The study population consisted of 150 HPV DNA positive cases (mean age 25.7 years, SD 7.4) and 69 randomly selected HPV DNA negative controls (mean age 27.3 years, SD 7.9) enrolled in an ongoing study of the natural history of genital HPV infections. All cases and controls had normal cervicovaginal cytology at the enrollment. A commercial dot-blot technique hybridization test (Virapap and Viratype, Digene Diagnostics, USA) was used for HPV DNA testing of cervicovaginal scrapes. Five percent of the patients had HPV 16/18, 31% had HPV 31/33/35, 15% had more than one of the three HPV DNA groups ("mixed"), and 15% had untypable HPV DNA. Cases and controls were followed by repeat examinations every 4th month. The mean follow-up time was 12.2 months (SD 8.7) for the cases, and 12.8 months (SD 6.9) for the controls. The study endpoint was defined as the presence of cytologic changes consistent with CIN. The overall prevalence of atypical transformation zone (ATZ) findings was 45% in the controls and 56% in the cases, with no significant differences between the specific HPV DNA groups. Although vulvar or vaginal abnormalities (acetowhite epithelium, squamous papillomatosis, filaments, satellite lesions, fissures, papules or exophytic condylomas) were more commonly seen in the cases than in the controls, the difference was significant only for condylomas and fissures.(ABSTRACT TRUNCATED AT 250 WORDS)

Pelvic lymph node metastases in cervical cancer: comparison of lymphography, inspection, radiography, and histologic examination of lymph nodes.

Lymphangiography is commonly performed in the pretreatment evaluation of patients with cervical carcinoma, but its value is controversial. The purpose of this report is to determine the reliability of lymphography in the indication of metastatic pelvic lymph nodes by comparing data from preoperative lymphangiography, inspection of lymph nodes during laparotomy, radiography of surgically removed lymph nodes, and postoperative histologic report. Twenty-one patients (mean age 51.1 years, SD 14.5) with cervical cancer FIGO stages I b to II b were enrolled in this study. They all underwent Wertheim's radical hysterectomy with pelvic lymphadenectomy. With reference to histologic report this series included 8 squamous carcinomas (38%), 10 adenocarcinomas (48%) and 3 sarcomas (14%). Seven patients (33%) had a positive preoperative lymphangiography, in 9 patients (43%) lymph nodes were considered positive at the inspection during laparotomy, postoperative radiography of the lymph nodes was considered probably positive in 7 patients (33%) and positive in 2 patients (10%), histologic report was positive for lymphonodal metastases in 4 patients (19%). A total of 335 lymph nodes were studied, and with reference to the evaluated methods (lymphangiography, inspection, radiography, histology), 1 positive method was found in 40 lymph nodes (12%), 2 positive methods in 6 lymph nodes (2%), 3 or 4 positive methods in none of the lymph, nodes, and 4 negative methods in 289 lymph nodes (86%). Histologic report was positive in 4 lymph nodes (1%). Lymphangiography in the pretreatment evaluation in cases of cervical carcinoma is not reliable in indicating possible metastatic lymph nodes. It remains a useful exam fixation to be routinely performed.

Uterine cervix carcinoma diagnosed during puerperium. Case report.

The Authors describe a case of invasive uterine cervix squamous carcinoma in a 30 year old woman, diagnosed soon after delivery. They point out the rarity of the tumor during puerperium and illustrate its clinico-pathological aspects.

[Intralesional therapy using recombinant interferon alpha 2 B in lesions of the uterine cervix caused by human papilloma virus]. / Terapia intralesionale con interferone alfa 2 B ricombinante in lesioni della cervice uterina da human papilloma virus (HPV).

A clinical study on 20 patients with uterine cervix Human Papilloma Virus (HPV) lesions treated with intralesional recombinant alpha 2b interferon (3 millions I.U.) three times a week for three weeks where possible, is presented. After one year from treatment, lesions were cured or stabilized in 18 Patients (90%); progression was observed in 2 patients (10%) for which reason traditional surgical therapy was performed.

[Embryonal carcinoma of the ovary. Anatomo-clinical aspects and presentation of a case]. / Carcinoma embrionale dell'ovaio. Aspetti anatomo-clinici e presentazione di un caso.

A case of ovarian embryonic carcinoma in a 25 year old patient hospitalized in the Gynecological Department of the National Cancer Institute, Naples, is described. After a general introduction the clinical condition of the patient is discussed with emphasis on the histological aspects of the neoplasm.

Uterine carcinosarcoma. Case report.

The authors describe the clinical and pathologic features of uterine carcinosarcoma. In the case of a 45 year old patient the rarity of this double tumor is pointed out.