[Myomectomy and uterine desarterialization as conservative treatment for uterine fibroids: Review of clinic case]. / Miomectomía y desarterialización uterina como tratamiento conservador de la miomatosis de grandes elementos: reporte de un caso.

BACKGROUND: Uterine fibroids are the most common gynecological tumors; the prevalence increases with age. They can cause symptoms (20-50%). Myomectomy is an alternative for women who wish to preserve their fertility, increased risk of blood loss and longer operative time. Since 2000, a significant number of surgeons have performed occlusion of uterine arteries prior to myomectomy successfully. CASE REPORT: We report the case of a 24-year-old patient, with a history of premature birth; and starts her condition after obstetric event with abnormal uterine bleeding and postcoital bleeding, accompanied by intense, oppressive and stabbing abdominal pain and increased ab-dominal volume. At physical examination an enlarged abdominal wall by a tumor involving, abdominal pain on palpation, at the gynecological examination: frankly enlarged uterus, about 25 x 20 cm, painful and tenderness. Prior to myomectomy, uterine externalization takes place and proceeds to dearterialization of uterine arteries under the García-González technique, removing the tumor without complications, with an estimated 100 cc bleeding. The bilateral uterine artery ligation, is one of the methods used to re-duce intraoperative blood loss. It is a quick, simple technique, whose theoretical basis is that 90% of the irrigation of the uterus comes from the uterine arteries.

Causes for an Incomplete Donation Process at a Tertiary Care Hospital.

INTRODUCTION: This study aims to identify the causes for the incomplete donation process at a tertiary care hospital. MATERIALS AND METHODS: A descriptive, retrospective study was performed; all potential donors reported to the Transplant Service within the period of 2005 to 2014 were included. Descriptive statistics were used across frequencies and proportions for categorical variables, central tendency, and dispersion for continuous variables. RESULTS: The total number of deaths reported at the University Hospital (HU) was 8472, of which 815 (n = 815) were reported to COETRA ("Consejo Estatal de Trasplantes"). Among organ or tissue donors, the main known cause of death was head trauma (HT) in 26% (72). Cardiac arrest (CA) as cause of death provided the largest number of donations (141, 57%); of these, 102 (41%) were male and 39 (16%) were female. In comparison, brain death (BD) provided 104 (43%); of these, 65 (27%) were male, and 39 (16%) were female. The age interval was with a higher donation rate was 45 to 49 y (BD 18, CA 22). Donation request was not performed in 359 patients because of medical contraindication 60% (215), rapid deterioration 18% (64), and incomplete donation process 8% (27). Of 452 organ requests, 207 were not accomplished, because of body integrity 28% (57), family disagreement 20% (42), and no acceptance of BE 13% (26). CONCLUSIONS: Opportunity areas: (1) Ensure the notification of all deaths to Transplant Department for identification of potential donors; (2) Reduce rapid deterioration and raise number of completed donation protocols; (3) Increase the donation rate.

Self-Management and Transition Readiness Assessment: Development, Reliability, and Factor Structure of the STARx Questionnaire.

INTRODUCTION: The Self-Management and Transition to Adulthood with Rx=Treatment (STARx) Questionnaire was developed to collect information on self-management and health care transition (HCT) skills, via self-report, in a broad population of adolescents and young adults (AYAs) with chronic conditions. METHODS: Over several iterations, the STARx questionnaire was created with AYA, family, and health provider input. The development and pilot testing of the STARx Questionnaire took place with the assistance of 1219 AYAs with different chronic health conditions, in multiple institutions and settings over three phases: item development, pilot testing, reliability and factor structuring. RESULTS: The three development phases resulted in a final version of the STARx Questionnaire. The exploratory factor analysis of the third version of the 18-item STARx identified six factors that accounted for about 65% of the variance: Medication management, Provider communication, Engagement during appointments, Disease knowledge, Adult health responsibilities, and Resource utilization. Reliability estimates revealed good internal consistency and temporal stability, with the alpha coefficient for the overall scale being .80. The STARx was developmentally sensitive, with older patients scoring significantly higher on nearly every factor than younger patients. CONCLUSION: The STARx Questionnaire is a reliable, self-report tool with adequate internal consistency, temporal stability, and a strong, multidimensional factor structure. It provides another assessment strategy to measure self-management and transition skills in AYAs with chronic conditions.

Patients' survival after free flap reconstructive surgery of head and neck squamous cell carcinoma: a retrospective multicentre study.

Head and neck squamous cell carcinoma of the (HNSCC) represents approximately 5% of malignant tumours in Italy. HNSCC are commonly treated with surgery or radiotherapy, or a combination of such therapies. The objectives of treatment are maximum cure rate balanced with organ preservation, restoration of form and function, reduction of morbidities and improvement or maintenance of the patient's quality of life. Immediate reconstructive surgery: local, regional or free flaps are now widely advised in the treatment of these patients. Microsurgical transfer requires expertise, is time and resource consuming, and as a whole requires substantial costs. These considerations introduce some concerns about the wide or indiscriminate use of free flap reconstructive surgery. When considering cost-benefit outcomes of such treatment, the main objective is undoubtedly, survival. This data is underreported in the current literature, whereas functional outcomes of free flaps have been largely diffused and accepted. This study collects data from 1178 patients treated with free flap reconstructive surgery following ablation of HNSCC in a group of Italian tertiary hospitals, all members of the Head & Neck Group affiliated with the Italian Society of Microsurgery. According to many authors, free flap surgery for HNSCC seems to be a beneficial option for treatment even in terms of survival.

Head and neck soft tissue sarcomas: prognostic factors and outcome in a series of patients treated at a single institution.

BACKGROUND: Head and neck soft tissue sarcomas (STS) represent a rare disease. PATIENTS AND METHODS: One hundred and sixty-seven patients underwent surgery at our institution with an eradicating intent between 1990 and 2010. Local recurrence (LR), distant metastasis (DM) and disease-specific mortality (DSM) incidence were studied along with clinicopathological prognostic factors. RESULTS: Ten-year crude cumulative incidence (CCI) of LR, DM and DSM were 19%, 11% and 26%, respectively (median follow-up 66 months). Independent prognostic factors for DSM were tumor size (P < 0.001) and grade (P = 0.032), while surgical margins obtained a border-line significance (0.070); LR was affected by the tumor size (P = 0.001), while DM only by grade (P = 0.047). The median survival after LR and DM were 14 months and 7 months, respectively. Tumors sited in the paranasal sinus and supraclavicular region had the worst survival. CONCLUSIONS: Head and neck represent a very critical anatomical site for STS. Achievement of local disease control appears to be crucial, since even LR could be a life-threatening event.

Evidence for the participation of peripheral 5-HT2A, 5-HT2B, and 5-HT2C receptors in formalin-induced secondary mechanical allodynia and hyperalgesia.

The role of 5-HT2A/2B/2C receptors in formalin-induced secondary allodynia and hyperalgesia in rats was assessed. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia. Pre-treatment for five consecutive days with compound 48/80 (1, 3, 10, 10, and 10 µg/paw) prevented formalin-induced secondary allodynia and hyperalgesia. Ipsilateral, but not contralateral, peripheral pre-treatment (nmol/paw) with the 5-HT2 receptor agonist DOI (3-30), 5-HT (10-100) or fluoxetine (0.3-3) significantly increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. The pronociceptive effect of DOI (10 nmol/paw), 5-HT (100 nmol/paw) and fluoxetine (1 nmol/paw) was blocked by selective 5-HT2A (ketanserin), 5-HT2B (RS-127445), and 5-HT2C (RS-102221) receptor antagonists. Furthermore, ipsilateral pre-treatment (nmol/paw) with ketanserin (1, 10, and 100), RS-127445 (0.01, 0.1 and 1) or RS-102221 (1, 10 and 100) prevented while post-treatment reversed 1% formalin-induced secondary allodynia and hyperalgesia in both paws. In marked contrast, contralateral injection of the greatest tested dose of 5-HT2A/2B/2C receptor antagonists did not modify long-lasting secondary allodynia and hyperalgesia. These results suggest that 5-HT released from mast cells after formalin injection sensitizes primary afferent neurons via 5-HT2A/2B/2C receptors leading to the development and maintenance of secondary allodynia and hyperalgesia.

Role of EGFR family receptors in proliferation of squamous carcinoma cells induced by wound healing fluids of head and neck cancer patients.

BACKGROUND: Mounting evidence suggests that recurrence of resected head and neck squamous cell carcinomas (HNSCCs) is due to the outgrowth of unrecognized residual tumor cells as well as to the premalignant and/or precursor-field epithelial cells. We studied the impact of processes triggered by HNSCC surgery in stimulating both residual tumor cells [demonstrated to overexpress epidermal growth factor receptor (EGFR)], and premalignant cells surrounding the resected lesion. PATIENTS AND METHODS: EGFR expression/activation by immunohistochemistry/biochemistry and gene status by FISH were investigated in 23 primary HNSCCs and surrounding tissues. The ability to induce cell proliferation of wound healing drainages collected from 12 relapsed and 11 not relapsed patients was evaluated by a colorimetric assay in squamous cell carcinoma cell lines A431 (carrying EGFR amplification) and CAL27 (carrying three EGFR copies) in the presence/absence of EGFR therapeutic inhibitors. RESULTS: Primary tumors showed intermediate/high EGFR expression (91%), EGFR phosphorylation and EGFR-positive FISH (35%). Normal, metaplastic and dysplastic epithelium surrounding the resected tumor displayed EGFR overexpression. EGFR activation and gene amplification were observed in normal and dysplastic epithelium, respectively. Each tested wound healing drainage induced the cells to proliferate and the proliferation was significantly higher in relapsed compared with not relapsed HNSCC patients (P = 0.02 and P = 0.03). Anti-EGFR treatments inhibited the drainage-induced proliferation, with the highest inhibitory efficiency by cetuximab on A431 cells, while CAL27 cell growth was more efficiently inhibited by tyrosine kinase inhibitors. CONCLUSIONS: Surgery could favor the proliferation of cells showing EGFR overexpression/activation/amplification such as residual tumor cells and/or precursor-field epithelial cells already present after surgery. Treatment with anti-EGFR reagents inhibits wound-induced stimulation, according to the EGFR family status.

Role of peripheral and spinal 5-HT6 receptors according to the rat formalin test.

The present study assessed the possible pronociceptive role of peripheral and spinal 5-HT(6) receptors in the formalin test. For this, local peripheral administration of selective 5-HT(6) receptor antagonists N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)-benzenesulphonamide (SB-399885) (0.01-1 nmol/paw) and 4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfonamide hydrochloride (SB-258585) (0.001-0.1 nmol/paw) significantly reduced formalin-induced flinching. Local peripheral serotonin (5-HT) (10-100 nmol/paw) or 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride (EMD-386088) (0.01-0.1 nmol/paw; a selective 5-HT(6) receptor agonist) augmented 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of 5-HT (100 nmol/paw) or EMD-386088 (0.1 nmol/paw) was significantly reduced by SB-399885 or SB-258585 (0.1 nmol/paw). In contrast to peripheral administration, intrathecal injection of 5-HT(6) receptor antagonists SB-399885 and SB-258585 (0.1-10 nmol/rat) did not modify 1% formalin-induced nociceptive behavior. Spinal 5-HT (50-200 nmol/rat) significantly reduced formalin-induced flinching behavior during phases 1 and 2. Contrariwise, intrathecal EMD-386088 (0.1-10 nmol/rat) dose-dependently increased flinching during phase 2. The spinal pronociceptive effect of EMD-386088 (1 nmol/rat) was reduced by SB-399885 (1 nmol/rat) and SB-258585 (0.1 nmol/rat). Our results suggest that 5-HT(6) receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. Thus, 5-HT(6) receptors could be a target to develop analgesic drugs.

Decreased nitric oxide markers and morphological changes in the brain of arsenic-exposed rats.

Epidemiological studies demonstrate an association between chronic consumption of arsenic contaminated water and cognitive deficits, especially when the exposure takes place during childhood. This study documents structural changes and nitrergic deficits in the striatum of adult female Wistar rats exposed to arsenic in drinking water (3 ppm, approximately 0.4 mg/kg per day) from gestation, throughout lactation and development until the age of 4 months. Kainic acid injected animals (10mg/kg, i.p.) were also analyzed as positive controls of neural cell damage. Morphological characteristics of cells, fiber tracts and axons were analyzed by means of light microscopy as well as immunoreactivity to neuronal nitric oxide synthase (nNOS). As nitrergic markers, nitrite/nitrate concentrations, nNOS levels and expression of nNOS-mRNA were quantified in striatal tissue. Reactive oxygen species (ROS) and lipid peroxidation (LPx) were determined as oxidative stress markers. Arsenic exposure resulted in moderate to severe alterations of thickness, organization, surrounding space and shape of fiber tracts and axons, while cell bodies remained healthy. These anomalies were not accompanied by ROS and/or LPx increases. By contrast, except the expression of nNOS-mRNA, all nitrergic markers including striatal nNOS immunoreactivity presented a significant decrease. These results indicate that arsenic targets the central nitrergic system and disturbs brain structural organization at low exposure levels.

Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells.

Traditional cuvette-based enzyme studies lack spatial information and do not allow real-time monitoring of the effects of modulating enzyme functions in vivo. In order to probe the realistic timescales of steric modifications in enzyme-substrate complexes and functional binding-unbinding kinetics in living cells without losing spatial information, it is imperative to develop sensitive imaging strategies that can report enzyme kinetics in real time over a wide dynamic range of timescales. Here we present a multi-photon excitation-based, ultra-fast photon detection using a streak camera and Laguerre expansion-based fast deconvolution approach for achieving high spatio-temporal resolution in monitoring real-time enzyme kinetics in single cells. In particular, we report spatially resolved, nanosecond-scale fluorescence dynamics associated with binding-unbinding kinetics of endogenous metabolic co-factor nicotinamide adenine dinucleotide with enzymes in intact living cells. By monitoring real-time kinetics of NAD(P)H-enzyme kinetics in primary hepatocytes isolated from young and aged mouse models, we observed that the mechanism of inhibition of mitochondrial respiration at complex I site is mediated by redistribution of free and protein-bound nicotinamide adenine dinucleotide pools and that this equilibrium redistribution is affected by age-related modifications in mitochondrial function. We describe unique advantages of Laguerre deconvolution algorithm in comparison with conventional lifetime analysis approaches. Non-invasive monitoring of metabolic dysfunctions in intact animal models is an attractive strategy for gaining insight into the dynamics of tissue metabolism in health and in various metabolic syndromes such as cancer, diabetes and aging-induced metabolic dysfunctions. Besides the example demonstrated above, we envisage that the proposed method can find applications in a variety of other situations where intensity-based approaches fall short owing to spectroscopic artefacts.

Review of 346 patients with free-flap reconstruction following head and neck surgery for neoplasm.

We present our 14-year experience of free tissue transfer following surgery for head and neck neoplasm. We evaluated 346 patients mean age 57 years, 65% had squamous cell carcinoma; the most frequent sites were oral cavity and mandible (168) craniomaxillo facial region (94) pharynx +/- cervical oesophagus and oropharyngostomes (84). In 327 (95%) cases the reconstruction was a success. Flap revision was necessary in 29 (8.4% of total) and recovery was successful in 10/29. Nine patients (2.6%) died perioperatively. Poor preoperative condition, previous treatment, and requirement for vein graft were significantly associated with increased risk of major complications after surgery. Cosmetic and functional outcomes were assessed on 1-10 scales: 69 and 77% of patients, respectively, had cosmetic and functional results in the 7-10 range, indicating successful outcome. Overall survival probabilities, estimated on 338 patients with malignant disease, were 53% at 2 years and 32% at 5 years. Most patients, but not all, had advanced disease stage, and 188 (54%) had recurrent disease. Hence, overall survival rates are acceptable and justify the use of complex reconstruction procedures in such patients.

Prediction of TP53 status for primary cisplatin, fluorouracil, and leucovorin chemotherapy in ethmoid sinus intestinal-type adenocarcinoma.

PURPOSE: To assess the role of TP53 status in predicting pathologic complete remission after primary chemotherapy in patients with ethmoidal intestinal-type adenocarcinoma (ITAC). PATIENTS AND METHODS: Thirty patients with ethmoidal ITAC enrolled onto a phase II study received chemotherapy with cisplatin, fluorouracil, and leucovorin (PFL) followed by surgery and radiation. On surgical specimens, absence of viable tumor cells was defined as pathologic complete remission (pCR). TP53 status/p53 function, analyzed on pretreatment biopsies, were retrospectively correlated with pathologic results and patient outcome. RESULTS: Twelve patients achieved a pCR; 18 patients did not (overall response rate, 40%). In patients with wild-type (wt) TP53 or functional p53 protein, the pCRs were 83% and 80%, respectively; in patients with mutated TP53 or impaired p53 protein, pCRs were 11% and 0%, respectively (P < or = .0001). At a median 55-month follow-up, all pCR patients were disease-free; 44% of nonresponding patients experienced relapse (P = .0061). CONCLUSION: The results indicate the existence of two genetic ITAC subgroups, defined by differences in TP53 mutational status or protein functionality, that strongly influence pathologic response to primary chemotherapy and, ultimately, prognosis. PFL seems to be highly effective in terms of pCR and disease-free survival in the presence of a wt or a still-efficient p53 protein, even when encoded by a mutated TP53 gene (eg, early-stop codon mutation), but ineffective in ITACs carrying a disabled p53 protein. Whether this model is extensible to other head and neck cancers needs appropriate investigation.

Craniotomies without burr holes using an oscillating saw.

OBJECTIVE: The object of this study is to describe a new method for performing craniotomies which obviates the need for burr holes, improves bony reconstruction, and reduces post-operative cosmetic deformities. Moreover, this technique provides excellent exposure of skull base structures and dural venous sinuses. METHODS: Craniotomies in varied locations are created with the use of a micro-oscillating saw and chisel. No burr holes are used and reconstruction with plates and screws is unnecessary. RESULTS: We initially applied our technique to approaches to the anterior skull base with combined craniofacial tumour resections. We have since performed over 2000 craniotomies of any size and shape in all supratentorial locations using the oscillating saw. CONCLUSIONS: We have found that our method creates better cosmetic results than standard techniques and is safer for craniotomies spanning dural venous sinuses. With experience, operating time was significantly reduced and costs were lowered because reconstruction with fixation devices was not needed.

Adenocarcinoma of ethmoid sinus: an occupational disease.

Sinonasal tumours, particularly those of ethmoidal origin, are rare neoplasms, of which adenocarcinoma is the most frequent histotype in Europe. The association between sinonasal malignancies and exposure to wood or leather dusts has been widely documented, however, the precise tumour site and histology has seldom been reported. In the present study, exposure to wood or leather dusts was investigated in 499 patients diagnosed with sinonasal tumours, who were treated at the Head and Neck Surgery Department of the National Cancer Institute of Milan, Italy, between 1987 and 2001. The original tumour site and histology were carefully assessed. Of the 499 patients evaluated, 249 had ethmoidal tumours; 124 of which adenocarcinomas, affecting 115 males; 9 females. Of the males with adenocarcinoma, 90.4% had been exposed to wood or leather dusts; 16.3% of these had only been exposed for a short time and long before onset of the disease (median exposure 11 years; median latency 31 years). Of the remaining 125 patients with ethmoidal tumours other than adenocarcinomas, only 2 (1.6%) had ever been exposed to these dusts. Non-ethmoidal sinonasal tumours were seen in 250 cases; 17 of these (6.8%) were adenocarcinomas; no exposure to wood or leather dusts was reported in any of these patients. Ethmoid proved to be the sinonasal site affected by adenocarcinomas induced by exposure to wood or leather dusts. Even brief exposure, which may have occurred a very long time before onset of the disease, seems to be sufficient to increase the incidence of this tumour type. No significant correlation was observed between exposure and either non-ethmoidal sinonasal neoplasms or ethmoidal tumours other than adenocarcinomas.

Primary chemotherapy followed by anterior craniofacial resection and radiotherapy for paranasal cancer.

BACKGROUND: To study prospectively the activity of primary chemotherapy with cisplatin, fluorouracil and leucovorin (PFL) in patients with paranasal cancer receiving surgery and postoperative radiotherapy. PATIENTS AND METHODS: Forty-nine patients, previously untreated, with resectable paranasal carcinoma were enrolled. PFL (leucovorin 250 mg/m2/day for 5 days as a 120 h continuous infusion (c.i.), 5-fluorouracil 800 mg/m2/day from day 2 as a 96 h c.i. and cisplatin 100 mg/m2 day 2 q 3 weeks) was planned for five courses. RESULTS: Thirty-two patients (65%) completed three or more chemotherapy courses. Two deaths from thrombotic events were observed after the first cycle. Eight cardiac toxicities were recorded during chemotherapy causing treatment discontinuation. Objective response to PFL was observed in 21 patients [43%; 95% confidence interval (CI) 29% to 58%], including four complete responses (CRs) (8%; 95% CI 2% to 20%) and 17 partial responses (PRs) (35%). Pathological complete remission (pCR) was achieved in eight of 49 patients (16%). At 3 years, overall survival was 69% and event-free survival 57%. Overall and event-free survival in patients achieving pCR is 100%. CONCLUSIONS: PFL is active in paranasal cancer. Patients who attain a pathological complete remission have a favorable prognosis. Cardiovascular complications represent the limiting toxicity. Primary chemotherapy combined with surgery-sparing treatment approaches deserves further investigation.

Primary high-grade mucoepidermoid carcinoma of the minor salivary glands with cutaneous metastases at diagnosis.

Mucoepidermoid carcinoma (MEC) represents 15% of all salivary glands malignancies. Metastatic disease at diagnosis is observed in less than 5% of the cases. The lung is the most commonly involved site. This is the first reported case of high-grade MEC of the salivary gland with skin metastases at diagnosis. This feature was associated with a chemoresistant and aggressive behaviour. Differential diagnosis between metastatic MEC and primary skin MEC is essential for therapeutic management and prognosis.