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.

The alpha1 subunit of the sodium pump could represent a novel target to combat non-small cell lung cancers.

With an overall 5 year survival rate as low as 15% for non-small cell lung cancer (NSCLC), even with surgical intervention and the use of newer molecules in adjuvant chemotherapy, there is an urgent need for new biological targets and associated novel anti-cancer agents. The present study was undertaken to evaluate the potential of the Na(+)/K(+)-ATPase alpha1 subunit as a novel target in NSCLC and revealed that alpha1 expression is markedly higher in a significant proportion of NSCLC clinical samples compared to normal lung tissue. Furthermore, reduction in alpha1 expression in A549 NSCLC cells by anti-alpha1 siRNA resulted in markedly impaired proliferation and migration of these cancer cells. Finally, of three cardenolides investigated, UNBS1450, which is known to bind to Na(+)/K(+)-ATPase and displays potent anti-tumour activity in vivo in experimental models of human NSCLCs, is the most potent inhibitor of Na(+)/K(+)-ATPase isozymes (alpha1beta1, alpha2beta1 and alpha3beta1), most strikingly of alpha1beta1. This was reflected in the compound's more potent anti-proliferative activity in all NSCLC cell lines evaluated (A549, Cal-12T, NCI-H727 and A427); the first three of which over-express alpha1. The marked impairment in A549 NSCLC cell proliferation and migration, and resulting similar morphology following anti-alpha1 siRNA or UNBS1450 treatment, was associated with features of abnormal cytokinesis, mediated in the case of UNBS1450 by disorganization of the actin cytoskeleton. Collectively these data strongly suggest that targeting the Na(+)/K(+)-ATPase alpha1 using specific cardenolides could represent a novel means to combat certain NSCLCs.

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 macrophage colony-stimulating factor (M-CSF) levels in patients with epithelial ovarian cancer.

The preoperative macrophage colony-stimulating factor (M-CSF) levels were measured in serum samples from 56 patients with epithelial ovarian cancer and 68 patients with benign ovarian disease who had undergone laparotomy. M-CSF values were significantly higher in the former (median, range: 2.18, 0.70-10.00 ng/ml versus 1.19, 0.17-5.54 ng/ml, P < 0.0001), and were not significantly related to stage, histology, grade of differentiation, age, and residual disease after first surgery. M-CSF concentrations were also measured in 163 serum samples drawn from patients with stage III-IV epithelial ovarian cancer at different times since the first surgery. M-CSF values were higher in the 81 samples from patients with clinically evident disease than in the 82 samples from patients with no clinical evidence of disease (median, range: 2.13, 0.60-10.00 ng/ml versus 1.05, 0.40-10.00 ng/ml, P < 0.0001). M-CSF levels before second-look laparotomy were similar in the 18 patients who showed persistent disease at surgical reevaluation and in the 11 patients who achieved pathological complete response (median, range: 1.26, 0.70-3.27 ng/ml versus 0.94, 0.46-4.23 ng/ml, P = NS). M-CSF concentrations were raised (> or = 1.70 ng/ml) only in 1 (14.3%) of the 7 samples from patients with clinically evident disease and serum CA125 < 35 U/ml, and only in 5 (38.5%) of the 13 samples from patients with positive second-look findings and serum CA125 < 35 U/ml. In conclusion, serum M-CSF levels correlated with the clinical status of disease in patients with epithelial ovarian cancer. However, the concomitant determination of serum M-CSF seems to add little to the CA125 assay alone in the monitoring of patients with this malignancy.

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.

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%).

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.

Prothrombin fragment F1+2 and thrombin-antithrombin III complex (TAT) plasma levels in patients with gynecological cancer.

The pretreatment plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III complex (TAT) were measured in 56 consecutive patients with gynecological cancer and in 33 apparently healthy volunteer nonpregnant women as control. Prothrombin fragment F1+2 concentrations were significantly elevated in the 18 patients with ovarian cancer (median, 3.2 nmol/ liter; range, 0.9-17.0 nmol/liter, P < 0.0001), in the 24 patients with cervical cancer (median, 1.7 nmol/liter; range, 0.6-15.0 nmol/ liters, P < 0.0001), and in the 14 patients with endometrial cancer (median, 1.5 nmol/liter; range, 0.6-3.0 nmol/liter, P = 0.036) when compared to controls (median, 1.0 nmol/liter; range, 0. 1 -2.1 nmol/ liter). Similarly, TAT levels were significantly higher in patients with ovarian cancer (median, 5.3 microgram /ml; range, 1.3-65.0 microgram/ml , P < 0.0001), cervical cancer (median, 3.8 microgram/ml; range, 2.1 - 11.0 microgram / ml, P < 0.0001), and endometrial cancer (median, 2.7 microgram/ml; range, 1.9-19.0 microgram /ml, P = 0.008) when compared to controls (median, 2.2 microgram/ml; range, 1.0-5.0 microgram/ml). Prothrombin fragment F1+2 levels correlated with TAT levels (r = 0.659, P < 0.0001). Among ovarian cancer patients, prothrombin fragment F1+2 and TAT concentrations correlated with FIGO stage (III-IV versus 1, P = 0.01 and P = 0.003, respectively) and CA 125 levels (P 0.02 and P < 0.0001, respectively). The present data confirmed the occurrence of hemostasis activation in patients with gynecological cancer, and in particular in those with ovarian cancer.

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.

Preoperative evaluation of D-dimer and CA 125 levels in differentiating benign from malignant ovarian masses.

Plasma levels of D-dimer (DD) and CA 125 were measured preoperatively in 121 patients with ovarian masses submitted to laparotomy. DD and CA 125 levels were higher in the 56 patients with epithelial ovarian cancer than in the 65 patients with benign ovarian disease (P < 0.0001). The logistic regression procedure showed that both DD assay (cutoff 416 ng/ml) and CA 125 assay (cutoff 65 U/ml) were significant predictive variables for malignancy (P = 0.0001). The concordance between predicted probabilities and observed responses was 75.7% for DD, 72.1% for CA 125, and 90.8% for Dd and CA 125. It is worth noting that DD was increased ( > 416 ng/ml) in 73% of FIGO stage I patients, whereas CA 125 was above 65 U/ml in only 33.3%. Sensitivity, specificity, positive predictive value, and negative predictive value of the tests in differentiating benign from malignant ovarian masses were as follows: 76.8, 93.8, 91.5, and 82.4%, respectively, for CA 125; 94.6, 76.9, 77.9, and 94.3%, respectively, for the combination CA 125 or DD; and 73.2, 100.0, 100.0, and 81.3%, respectively, for the combination CA 125 and DD. The combination CA 125 and DD seems to be a useful diagnostic tool to differentiate benign from malignant ovarian masses. Elevated preoperative levels of both antigens are invariably associated with a postsurgical diagnosis of epithelial ovarian cancer.

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.

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.

Ultrasonographic bone characteristics during normal pregnancy: longitudinal and cross-sectional evaluation.

OBJECTIVE: We evaluated the pattern of bone density during pregnancy by radiation-free ultrasonographic densitometry. STUDY DESIGN: In a longitudinal study we measured bone mineral density in a group of 10 normal primiparous women, from the fourteenth to the thirty-eighth weeks of pregnancy. In a cross-sectional study bone mineral density was determined in a group of 85 normal primiparous women, in different weeks of pregnancy. RESULTS: In the longitudinal study ultrasonographic bone density was stable in the first part of pregnancy, whereas a significant (p < 0.05) decrease was evidenced during the third trimester. A negative correlation between bone density and weeks of pregnancy (p < 0.0001) was evidenced in the cross-sectional study. CONCLUSION: During physiologic pregnancy the calcium mobilization from the maternal bone stores to accomplish the fetal needs can cause a significant decrease in maternal bone density in the last trimester of gestation.

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.

Serum levels of tumor necrosis factor (TNF), soluble receptors for TNF (55- and 75-kDa sTNFr), and soluble CD14 (sCD14) in epithelial ovarian cancer.

The preoperative serum levels of tumor necrosis factor (TNF), soluble receptors for TNF (55- and 75-kDa sTNFr), and soluble CD14 (sCD14) were retrospectively measured in 66 patients with epithelial ovarian cancer and in 59 patients with benign ovarian masses. The preoperative serum TNF and sCD14 levels were higher in patients with epithelial ovarian cancer than in those with benign ovarian disease (P = 0.001 and P < 0.0001, respectively). Among patients with advanced malignancy, preoperative serum TNF and sCD14 correlated with neither the common prognostic variables nor the clinical outcome of patients. The preoperative serum 55- and 75-kDa sTNFr levels were higher in patients with epithelial ovarian cancer than in those with benign ovarian disease (P < 0.0001 and P = 0.02, respectively). Among patients with advanced malignancy, preoperative serum 55- and 75-kDa sTNFr correlated with FIGO stage (IV vs III, P = 0.008 and P = 0.01, respectively) and with the clinical outcome of patients. Among patients followed after surgery and chemotherapy for advanced epithelial ovarian cancer, 55- and 75-kDa sTNFr levels were significantly higher in the samples drawn from patients with clinical evidence of disease when compared to those from patients without clinical evidence of disease; conversely, TNF and sCD14 levels were similar in the two groups. In conclusion, the preoperative serum levels of TNF, 55- and 75-kDa sTNFr, and sCD14 were significantly higher in patients with epithelial ovarian cancer than in those with benign ovarian disease. The measurement of serum TNF and sCD14 seemed to be of limited clinical value for the management of patients with advanced epithelial ovarian cancer. Conversely, the assay of serum 55- and 75-kDa sTNFr might have a potential clinical relevance, for both prognostic purposes and assessment of disease status.

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.

Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer.

High levels of IL-6 were found in 50% of 114 patients with primary ovarian cancer. IL-6 sensitivity was lower than that of CA 125, and the combination of both assays did not increase the sensitivity of CA 125 alone. However, elevated IL-6 serum levels were correlated with a poor prognosis since patients with low IL-6 levels had a better survival than patients with high IL-6 levels (P = 0.0009). Multivariate analysis revealed that IL-6 positivity has an independent value.