A rare histopathological spiradenocylindroma: a case report.

Background: Spiradenocylindroma is an extremely rare entity composed by two distinct neoplasms in one lesion: spiradenoma and cylindroma. It may arose solitary or multiple, sporadic or familial and often affect the scalp. Surgical removal is curative and histopathological examination is mandatory for diagnosis. Aim: The aim of this article is to define the clinical features of spiradenocylindroma and its importance in the differential diagnoses of head and neck tumors. Case presentation: A 58 years-old female with a preauricolar painless, tender nodule presented to our attention. The patient under-went ultrasonography and MRI, which showed a non-specific cystic lesion. Surgery was performed and histopathological examination revealed a spiradenocylindroma. A 3-years disease-free follow-up was achieved. Conclusion: Spiradenocylindroma is often misdiagnosed and, in our study, we highlight its role in the differential diagnoses of head and neck masses.

Multiple synchronous bilateral neoplasms of the parotid glands.

Abstract: In this paper we report the rare case of a patient who came to our attention with three synchronous Warthin tumours affecting both the right and left parotid glands. The patient was a 68-year-old female, heavy smoker, with a seven-year history of painless growing nodules in both pre-auricular areas. Left-sided subtotal parotidectomy and contralateral superficial parotidectomy were performed at two differ-ent surgical times. Multiple, simultaneous and bilateral Warthin tumours represent a rare pathological entity of the salivary glands. Careful preoperative examination and radiological evaluation of the salivary glands are critical for the early diagnosis of bilateral synchronous tumours.

Advantages of temporal muscle flap with no fascia in oral reconstruction after tumor removal.

ABSTRACT: Temporalis Muscle Flap is known to be a first choice rotational flap for oral reconstruction even though a few postoperative complications were reported in Literature. Among these, fascia necrosis may prolong recovery, increase discomfort and elevate sanitary cost. The aim of the study is to report the advantages of temporalis muscle flap without deep fascia in the reconstruction of the maxilla. The study group comprised seven patients aged between 43 and 64 years who underwent oral surgical reconstruction with TMF with no fascia. Reconstruction with the temporalis muscle flap was done in the same time of demolitive surgery and the same surgeon performed all the surgeries. In no case, TMF was covered with slough and this permitted to all our patients to undergo an easier rehabilitation with a low number of medications. Our experience showed that removing the fascia from TMF is a safe procedure that strongly decreased time of oral healing and improves patient comforts.

Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.

One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.

Polymorphic acetylation of hydralazine.

The acetylation of hydralazine has been studied in hypertensive patients undergoing maintenance therapy with the drug. The patients were acetylator phenotyped with sulfamethazine. Using gas-liquid chromatography and high-pressure liquid chromatography, hydralazine and two of its acetylated metabolites, methyltriazolophthalazine (MTP) and 3-hydroxymethyltriazolophthalazine (HOMTP), have been determined in the 0- to 24-hr urine. The excretion of hydralazine and HOMTP but not MTP was found to be related to the acetylator phenotype. The metabolic ratio HOMTP: hydralazine showed a bimodal distribution and the average ratio for slow acetylators (1.6) was lower than the ratio in rapid acetylators (14.9). It is concluded that hydralazine is polymorphically acetylated in man. The acetylated metabolite HOMTP was not, however, the major metabolite reported previously.

Effect of dose on acetylator phenotype distribution of hydralazine.

The effect of dose on acetylator phenotype distribution of hydralazine has been determined, The acetylated metabolites methyltriazolophthalazine (MTP) and 3-hydroxymethyltriazolophthalazine (3-OHMTP) and acid-labile hydralazine (HP) were determined in the 0- to 24-hr urine of patients receiving various doses. The difference between the mean value for the ration 3-OHMTP:HP in the rapid and slow acetylators varied with dose, the greatest difference being after a 200 mg (100 mg twice daily) dose. The distribution of the ratio became less clearly bimodal at lower doses, with overlap between phenotypes occurring at doses of 100 mg (50 mg twice daily) or less. The most effective dose for discriminating between acetylator phenotypes was found to be 200 mg (100 mg twice daily).

Selective endothelin A receptor antagonists. 3. Discovery and structure-activity relationships of a series of 4-phenoxybutanoic acid derivatives.

The third in this series of papers describes our further progress into the discovery of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of diseases in which a pathophysiological role for endothelin has been implicated. These include hypertension, ischemic diseases, and atherosclerosis. In earlier publications we have outlined the discovery and structure-activity relations of two moderately potent series of nonpeptide ETA receptor antagonists. In this paper, we describe how a pharmacophore model for ETA receptor binding was developed which enabled these two series of compounds to be merged into a single class of 4-phenoxybutanoic acid derivatives. The subsequent optimization of in vitro activity against the ETA receptor led to the discovery of (R)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]-4-(2-methylphenyl)b utanoi c acid (12m). This compound exhibits low-nanomolar binding to the ETA receptor and a greater than 1000-fold selectivity over the ETB receptor. Data are presented to demonstrate that 12m is orally bioavailable in the rat and is a functional antagonist in vitro and in vivo of ET-1-induced vasoconstriction.

RP 64477: a potent inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase with low systemic bioavailability.

RP 64477 (N-butyl-3-(p-decyloxybenzamido)-4-(methylthio)benzamide) has been shown to be a potent inhibitor of the cholesterol esterifying enzyme Acyl-coenzyme A:cholesterol O-acyltransferase (EC 2.3.1.26; ACAT) in intestinal, hepatic, adrenal, and arterial tissue preparations obtained from a range of animal species. Drug concentrations producing 50% inhibition of enzyme activity (IC50 values) ranged from 14-283 nM. Inhibition by RP 64477 in a rabbit intestinal enzyme preparation was shown to be non-competitive with respect to the substrate oleoyl-CoA. In whole cell assays using human intestinal (CaCo-2), hepatic HepG2) and monocytic (THP-1) cell lines, RP 64477 inhibited ACAT activity with IC50s of 113, 503, and 180 nM, respectively. RP 64477 (0.03% w/w by diet) reduced significantly cholesterol absorption in cholesterol/cholic acid-fed rats from 94+/- 8% to 65 +/- 4%. In cholesterol-fed rabbits, cholesterol absorption was reduced from 72 +/- 5% to 50 +/-5% and 44 +/- 5% at dose levels of 10 and 30 mg kg-1 b.i.d., respectively. Plasma cholesterol levels were reduced dose-dependently in both cholesterol/cholic-acid-fed rats and cholesterol-fed rabbits. Neither cholesterol absorption nor plasma cholesterol levels were reduced significantly in animals maintained on standard laboratory diets. Pharmacokinetic studies indicated that RP 64477 were very poorly absorbed following oral administration to rats. Plasma levels of drug were < 2 ng mL-1 following a dose of 2000 mg kg-1 p.o.. When radiolabelled RP 64477 was administered orally, limited absorption was indicated by the overwhelming elimination of radioactivity in the faces (96.4% of administered material) coupled with low renal clearance (0.6% of dose) and biliary excretion (0.05% of dose). In conclusion, this work shows that RP 64477 is a potent inhibitor of ACAT obtained from a range of animal species and man. Inhibition of cholesterol absorption and hypocholesterolaemic activity has been demonstrated in rats and rabbits maintained on diets supplemented with cholesterol. Pharmacokinetic studies indicate low systemic exposure to RP 64477 as a result of limited absorption of this drug.

Genotype distribution of estrogen receptor-alpha gene polymorphisms in Italian women with surgical uterine leiomyomas.

OBJECTIVE: To explore a possible association between estrogen receptor-alpha (ER-alpha) gene polymorphisms and development of uterine leiomyomas. DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): 119 women with clinically and surgically diagnosed uterine leiomyomas. INTERVENTION(S): Therapeutic hysterectomy. MAIN OUTCOME MEASURE(S): Frequency and distribution of ER-alpha gene polymorphisms. RESULT(S): No statistically significant differences between controls and patients in the allele frequency and genotype distribution were found when Pvu II and Xba I restriction polymorphism sites were analyzed separately. When the two ER-alpha gene polymorphisms were analyzed in combination, five major genotypes were recognized in controls or patients; the frequency differed slightly but not significantly between groups. CONCLUSION(S): The Pvu II and Xba I polymorphisms in the ER-alpha gene do not produce different risks of developing uterine leiomyomas.

Serum levels of soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) in patients with cervical cancer.

The pretreatment serum levels of the soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) were retrospectively measured in 54 patients with cervical cancer and in 55 patients with benign uterine disease as controls. Serum mean (+/- standard deviation) concentrations of both p55 and p75 sTNFr were higher in patients with cervical cancer than in controls (2.6+/-1.3 vs 1.9+/-0.7 ng/ml, p<0.0001, and, respectively, 7.8+/-4.3 vs 5.9+/-3.0 ng/ml, p=0.009). Both receptor levels were significantly higher in patients with stage IIb-IV than in those with stage I-IIa cervical cancer or with cervical intraepithelial neoplasia (CIN) 3. Among the 31 patients with stage I-IIa disease who underwent initial surgery, the preoperative serum p55 and p75 sTNFr values correlated neither with the common prognostic variables nor with the clinical outcome. In conclusion, serum p55 and p75 sTNFr levels are significantly elevated in patients with cervical cancer. However, the serum measurement of these soluble receptors seems to be of limited clinical value for the management of patients with this malignancy.

Determination of serum levels of different cytokeratins in patients with uterine malignancies.

Tissue polypeptide antigen (TPA), TPS, Cyfra 21-1, Cytokeratins 8-18 (CTKRS 8-18), SCC and CA 125 were measured in blood samples drawn at diagnosis from 43 patients with endometrial cancer, 47 with cervical cancer, 11 with cervical intraepithelial neoplasia (CIN), and 236 with benign uterine disease as controls. The cut-off values for all antigens were chosen at the 95th percentile of the standard Gaussian variate of controls; these limits were 98 U/L for TPA, 127 U/L for TPS, 1.6 ng/mL for Cyfra 21-1, 1.2 ng/mL for CTKRS 8-18, 48 U/mL for CA 125, and 2.8 ng/mL for SCC. TPA had the same sensitivity as SCC for squamous cell carcinoma of the cervix (42%) and a higher sensitivity than CA 125 for endometrial cancer (40% vs 12% respectively). TPA was more sensitive than TPS for both cervical (40% vs 13%) and endometrial cancer (40% vs 21%). TPA and SCC had a higher sensitivity than Cyfra 21-1 (34%) and CTKRS 8-18 (27%) for squamous cell carcinoma of the cervix. In conclusion, as for soluble cytokeratin fragments, the serum TPA seems to be the most reliable marker for the management of cervical and endometrial cancer.

Serum interleukin-6 levels in uterine malignancies. Preliminary data.

Interleukin-6 (IL-6) was measured with an enzyme-immunoassay in blood samples drawn at diagnosis from 37 patients with endometrial cancer, 36 with cervical cancer, 9 with cervical intraepithelial neoplasia (CIN) and 68 with benign uterine disease. The minimal detectable dose of IL-6 was 3 pg/mL. Detectable serum IL-6 levels were found in 9% of patients with benign uterine diseases, 11% of patients with CIN, 44% of patients with cervical cancer and 11% of patients with endometrial cancer. As regards cervical cancer, serum IL-6 levels > 3 pg/mL were found in 36.0% of 25 patients with stage Ib-IIa disease and in 64% of 11 patients with stage IIb-IV disease. As regards endometrial cancer, serum detectable IL-6 levels were observed in 0% of 30 patients with stage I-II disease and in 57% of 7 patients with stage III-IV disease (p = 0.0005). These preliminary data suggest that IL-6 may be involved in the progression of uterine malignancies.

Serum CYFRA 21-1 assay in squamous cell carcinoma of the cervix.

Squamous cell carcinoma antigen (SCC) is the best known marker for squamous cell carcinoma of the cervix as well as of the lung, oesophagus, head and neck and anal canal. Elevated levels of cytokeratin 19-fragments (CYFRA 21-1) have recently been detected in a large proportion of patients with non small cell cancer of the lung, and in particular of those with squamous cell carcinoma. Serum levels of CYFRA 21-1 (cut-off = 1.06 ng/mL) and SCC (cut-off = 2 ng/mL) were measured in blood samples collected before treatment from 15 patients with cervical intraepithelial neoplasia (CIN), 56 patients with cervical cancer, 48 patients with endometrial cancer, and 361 patients with benign uterine diseases. Serum CYFRA 21-1 values in patients with CIN were superimposable on those detected in patients with benign uterine diseases. Conversely, serum CYFRA 21-1 levels were higher in patients with cervical cancer (p < 0.05) and in patients with endometrial cancer (p < 0.05) than in those with benign uterine diseases. There was no significant difference in serum CYFRA 21-1 levels between cervical and endometrial cancer, and, as regards cervical cancer, there was no significant difference in antigen values between squamous cell carcinoma and adenocarcinoma. Among patients with squamous cell carcinoma of the cervix, CYFRA 21-1 values correlated with FIGO stage (stage IIb-IV vs stage Ib-IIa, p = 0.0303). Elevated CYFRA 21-1 levels were found in 20.0% of patients with CIN, in 41.7% of patients with squamous cell carcinoma of the cervix, in 62.5% of patients with adenocarcinoma of the cervix, in 45.8% of patients with endometrial cancer, and in 13% of patients with benign uterine diseases. Serum SCC was more sensitive than serum CYFRA 21-1 for both early and advanced squamous cell carcinoma of the cervix; these preliminary data seem to show that serum CYFRA 21-1 is of limited value for the management of patients with this malignancy.

Recurrence patterns in patients with early stage cervical cancer treated with radical hysterectomy and external pelvic irradiation.

One hundred and fifty patients with clinical FIGO stage IB-II cervical cancer who underwent radical surgery followed by external pelvic irradiation between 1978 and 1991 were reviewed. Until June 1994, 28 (18.7%) patients developed recurrent disease. Seventeen (60.7%) of them experienced a pelvic failure, 7 (25.0%) an extrapelvic failure and 4 (14.3%) both a pelvic and an extrapelvic failure. The median time to recurrence was 16 months for patients with pelvic failure (range = 4-50 months), 27 months for those with extrapelvic failure (range = 6-49 months), and 21 months for those with both pelvic and extrapelvic failure (range u 8-56 months). Recurrence rates were significantly related to surgical-pathologic stage, tumor size and lymph node status, but not to histologic type. An extrapelvic recurrence, alone or associated with a pelvic failure, was found in 0.9% of 117 patients with negative lymph nodes, 6.2% of 16 patients with one or two positive lymph nodes, and 52.9% of 17 patients with three or more positive lymph nodes, (p = 0.0001). It is worth noting that 9 (81.8%) out of the 11 patients who developed extrapelvic recurrences had three or more involved lymph nodes. The number of positive lymph nodes (p = 0.0001) and the tumor size (p = 0.0046) were independent prognostic variables for disease-free survival.

Analysis of treatment failures in patients with early-stage uterine leiomyosarcoma.

This retrospective study aimed to investigate the treatment failures in 26 patients with stages I-II uterine leiomyosarcoma (> or = 10 mitoses per 10 high-power field (HPF) who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy +/- adjuvant external pelvic irradiation. Thirteen (50%) patients developed recurrent disease, after a median time of 10 months from surgery (range = 4-72 months). Recurrence was pelvic in 3 (23%) patients, extrapelvic in 9 (69%) patients, and both pelvic and extrapelvic in 1 (8%) patient. Disease-free survival was better for premenopausal than for postmenopausal patients (p = 0.002) and for patients with < 20 mitoses per 10 HPF than for those with > or = 20 mitoses per 10 HPF (p = 0.006). In conclusion, patients with early-stage disease who had undergone locoregional treatment experienced a high recurrence rate. Most of the treatment failures were extrapelvic. Multicentric randomized trials on the role of adjuvant chemotherapy are advocated.

The measurement of plasma D-dimer (DD) levels in the follow-up of patients with ovarian cancer.

Peripheral blood samples for the measurement of DD and CA 125 were drawn from 39 patients with ovarian cancer at different times from first surgery. Both median DD and CA 125 levels were significantly higher in the 20 samples drawn from patients with clinically evident disease than in the 37 samples from patients without clinical evidence of disease (477 vs 300 ng/ml p = 0.006, and 66 vs 11 U/ml, p < 0.0001, respectively). DD levels did not correlate with CA 125 levels. The sensitivity, specificity and diagnostic accuracy of the tests in the assessment of clinical disease status were as follows: 65%, 62% and 63% for DD (cut-off = 416 ng/ml); 70%, 92% and 84% for CA 125 (cut-off = 35 U/ml); 90%, 59% and 70% for DD "or" CA 125; and 45%, 95% and 77% for DD "and" CA 125. DD levels correlated with the clinical course of disease in ovarian cancer patients. However, the concomitant determination of DD and CA 125 did not improve the reliability of CA 125 assay alone in the follow-up of these patients.

Serum levels of soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) in endometrial cancer.

The pretreatment serum levels of the soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) were retrospectively measured in 38 patients with endometrial cancer and 55 patients with benign uterine diseases as controls. Serum p55 and p75 sTNFr levels were significantly higher in patients with endometrial cancer (median = 2.4 ng/ml, range = 1.4-6.8 ng/ml, and median = 7.1 ng/ml, range = 2.5-19.5 ng/ml, respectively) than in controls (median = 1.7 ng/ml, range = 0.5-4.0 ng/ml, p < 0.0001, and median = 5.2 ng/ml, range = 2.6-21.9 ng/ml, p = 0.03, respectively). In the former, serum p55 and p75 sTNFr values correlated with the extent of disease (stage III-IV versus I-II: p = 0.04 and p = 0.03, respectively). Among the 23 patients with stage I endometrial cancer who underwent initial surgery, the preoperative serum levels of both receptors correlated with the histologic grade and myometrial invasion but not with the clinical outcome. In conclusion, a stage-dependent release of the soluble receptors for TNF into the bloodstream occurs in patients with endometrial cancer.

Preoperative serum intercellular adhesion molecule-1 (ICAM-1) and E-selectin (endothelial cell leukocyte adhesion molecule, ELAM-1) in patients with epithelial ovarian cancer.

The serum levels of intercellular adhesion molecule-1 (ICAM-1) and E-Selectin (endothelial cell leukocyte adhesion molecule, ELAM-1) were retrospectively measured in serum samples drawn at diagnosis from 66 patients with epithelial ovarian cancer and 128 patients with benign ovarian masses. The preoperative serum ICAM-1 levels were higher in the former group (p < 0.0001), while serum E-Selectin concentrations were similar in the two groups (p = NS). Among patients with epithelial ovarian cancer, neither serum ICAM-1 nor E-selectin levels correlated with FIGO stage and with histologic type. The serum assay of ICAM-1 and E-Selectin seems to have limited value in the management of patients with epithelial ovarian cancer.

Treatment of obstetric and gynecologic infections with meropenem: comparison with imipenem/cilastatin.

The aim of this study was to compare the clinical and bacteriologic efficacy of meropenem with imipenem/cilastatin in the treatment of obstetric and gynecologic infections. This was a controlled, multicenter, randomized study with two parallel groups and a follow-up period of up to 4 weeks. A total of 105 hospital in-patients requiring antibacterial parenteral therapy were enrolled, 52 in the meropenem group and 53 in the imipenem/cilastatin group. Both drugs were administered at 0.5 g every 8 hours, by slow intravenous infusion over 20-30 minutes; for meropenem the administration by intravenous bolus injection (over approximately 5 minutes) was allowed. The mean duration of therapy was 5 days for both treatments. At the end of treatment, all 46 evaluable patients in the meropenem treatment group had a satisfactory clinical response, while in the imipenem/cilastatin group 5/49 patients were clinical failures. The difference between the treatment groups in clinical response was statistically significant (100% vs 89.8%; p=.026). A similar result was seen in the intention-to-treat analysis (98% vs 84.6%; p=0.017). Both treatments were well tolerated, but fewer meropenem patients experienced treatment-related adverse events in comparison with imipenem/cilastatin (11.5% vs 15.1%).

Metabolism and disposition studies with a [35S]-labelled growth promotor: bis(N1-methyl-N2-methylsulphonyl) guanidinylethyl] disulphide.

The disposition and metabolism of the [35S]-labelled growth promotor bis[N1-methyl- N2-methylsulphonyl) guanidinylethyl] disulphide was studied in the rat following oral administration. There was rapid and significant absorption of drug-derived products evidenced by maximum concentrations for plasma and the majority of sampled tissues at 1 h post dose, and extensive renal clearance, with greater than 62% of dose voided in urine in 12 h. Analysis of urine revealed that the administered compound had been completely metabolised to five metabolites of which the two major products have been characterised. A metabolic pathway involving reductive cleavage of the disulphide bond, followed by S-methylation and sulphoxidation would appear to be involved in the biotransformation of the compound.