Management of endometrial cancer: issues and controversies.

Although endometrial cancer (EC) is the most common gynecologic cancer in developed countries, several aspects of its management are still controversial. In particular, the need to perform lymphadenectomy represents an important matter of discussion. Because of the discordant results in the literature, it is still not possible to draft any definitive conclusions regarding the therapeutic value of lymph node dissection. The present review discusses the role of lymphadenectomy in the setting of EC, risk factors for lymphatic spread, identification of patients at risk for lymph node dissemination, and the current evidence for adjuvant therapies in patients with positive nodes. Reasons for the difficulty in demonstrating any therapeutic value of pelvic and para-aortic lymphadenectomy are also discussed.

Concomitant chemoradiation treatment in selected Stage I endometrioid endometrial cancers.

PURPOSE OF INVESTIGATION: To evaluate chemotherapy with concomitant radiotherapy (RT) in "high risk" endometrial cancer (EC) patients. Furthermore to develop a new algorithm for management and treatment. MATERIALS AND METHODS: The study included 182 Stage I endometrioid EC patients who underwent definitive surgery after a first treatment. Stage, grade, ploidy DNA index, lymphovascular space involvement (LVSI), tumor diameter (TD), and p53 were considered to identify "high-risk" patients. Twenty-seven women received adjuvant concomitant chemoradiation (CR). Toxicity related to the CR treatment, disease free interval (DFI), and status of the patients were considered. RESULTS: Twenty-seven patients according to the present algorithm treatment were considered at "high risk". Median follow up was 43 months (range 16-68). Twenty-five (92%) patients completed CR treatment. Overall, grade 3/4 hematological toxicity was 18% while gastrointestinal toxicity was 15%. Four patients relapsed with a five-year rate of 14% of recurrences. CONCLUSIONS: Adjuvant concomitant CR is well tolerated and is a feasible regimen in "high risk" patients. The authors' new algorithm treatment could be used for management and further clinical studies.

Laparoendoscopic single-site surgery for the assessment of peritoneal carcinomatosis resectability in patients with advanced ovarian cancer.

PURPOSE OF INVESTIGATION: To evaluate the feasibility, safety, and effectiveness of laparoendoscopic single site surgery (LESS) for the assessment of peritoneal carcinomatosis resectability in patients with advanced stage ovarian cancer (AOC). MATERIALS AND METHODS: The authors retrospectively reviewed the medical records of patients affected by advanced stage ovarian cancer who underwent LESS for operative work-up. A standard cytoreductive laparotomy surgery (CRS) was performed. RESULTS: Fifty-two women affected by AOC underwent LESS for operative work-up. The peritoneal cancer score was completed in 49 (94%) patients by use of LESS; 34/37 (92%) patients considered with a resectable disease were effectively optimally debulked and 15/52 (28%) patients considered with an unresectable disease received before neoadjuvant chemotherapy (NACT) and then underwent surgery. CONCLUSION: LESS is feasible, safe, and is an alternative minimally invasive procedure to assess the resectability of AOC patients.

Outcome After Pneumonectomy in 17 Dogs and 10 Cats: A Veterinary Society of Surgical Oncology Case Series.

OBJECTIVE: To report the signalment, presenting clinical signs, surgical complications, histologic diagnosis, postoperative complications, and outcome of dogs and cats undergoing pneumonectomy. STUDY DESIGN: Retrospective case series; multicenter study. ANIMALS: Client-owned dogs (n=17) and cats (n=10). METHODS: Signalment, clinical signs, side affected, surgical data, preoperative diagnostic tests (including complete blood count, serum biochemistry, cytologic diagnosis, chest radiographs, and computed tomography), histologic diagnosis, surgical complications, adjunctive therapy, and date and cause of death were collected from records of dogs and cats that underwent pneumonectomy. Survival estimates and complication were assessed. RESULTS: Seventeen animals had a left-sided pneumonectomy performed (12 dogs, 5 cats) and 10 animals had a right-sided pneumonectomy (5 dogs, 5 cats). Fourteen animals were diagnosed with neoplasia (52%). The overall incidence of complications for dogs and cats were 76 and 80%, respectively, with major complications in 41 and 50%, respectively. Respiratory complications (persistent pleural effusion, oxygen dependence, persistent increased respiratory rate, or coughing) were the most frequent complications. No animals died or were euthanatized intraoperative or within the first 24 hours postoperative. One dog (6%) and 2 cats (20%) died, or were euthanatized in the first 2 weeks postoperative. CONCLUSION: Based on this case series, right and left pneumonectomy can be performed with low perioperative mortality in dogs and cats, with some animals experiencing prolonged survival.

Dental management in pregnancy: recent trends.

This review analyzes the changes that occur during normal pregnancy and describes the main odontogenic infections, suggesting the actual best approach in dental management. Several studies support the hypothesis that periodontal disease is associated with preterm labour and other conditions complicating pregnancy, such as pre-eclampsia and fetal growth restriction. Appropriate dental care and prevention during pregnancy may reduce poor prenatal outcomes and eliminating risk factors. Dental examination before pregnancy is strongly suggested in order to act early on dental and periodontal diseases. Prevention means reducing the presence of bacterial plaque through professional hygiene sessions, education, and motivation to proper oral hygiene at home, education in proper nutrition, a balanced diet, and low intake of sugars. For these reasons, it is essential to have a more intense interdisciplinary collaboration between gynecologist and dentist in order to achieve an optimal women's health, during this particular time in their lives.

Pelvic arterial embolization for postpartum hemorrhage: long term results of a single center experience in 29,091 deliveries.

PURPOSE OF INVESTIGATION: To evaluate the rate of all postpartum hemorrhages (PPHs) treated with uterine embolization in a third level delivery center. MATERIALS AND METHODS: Since January 2008 to March 2014, 29,091 deliveries were registered in the present hospital in Bergamo, Italy. Among these deliveries, 2,002 cases (6.8%) of PPHs occurred. Seventy-three patients with severe obstetric hemorrhage underwent uterine artery embolization (UAE) (47 cases, 1.61/1,000 deliveries) or hysterectomy (26 cases, 0.89/1,000 deliveries). All identified cases were followed up by telephone on January 2015 in order to evaluate long term results. RESULTS: Embolization was performed successfully in 45 patients (95.7%). Two women underwent total abdominal hysterectomy: one patient for uterine atony and one for adherent placenta. In the follow up all the women interviewed reported the return of their menstrual cycle and 95.2% of women reported regular cycles. CONCLUSIONS: Embolization showed a success rate of 95.7%. For this reason, in the authors' opinion, it is the best choice as second line treatment of PPH, when patient is hemodynamically stable.

Otorrhagia and Nosebleed as first signs of Intravascular Absorption Syndrome During Hysteroscopy: From Bench to Bedside.

Hysteroscopic surgery is indicated for the treatment of several intrauterine diseases. The surgeon needs to be aware of, and know how to prevent, possible complications related to these procedures. In the case of operative hysteroscopy, the systemic effects of low-viscosity fluid uptake must be considered in order to prevent the complications in the patient. We report on two unusual clinical signs of intravascular absorption syndrome (IAS) that developed during an operative hysteroscopy with glycine 1.5% as the fluid of distension. Based on our experience, we recommend that practitioners reduce operating times, monitor fluid balances, check electrolytes and kinetic heart rates, and monitor for symptoms including otorrhagia and nosebleed, in order to identify and possibly prevent IAS due to an overload of low-viscosity fluids.

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC. METHODS: Thirteen women with EOC underwent cytoreductive surgery (CRS) and HIPEC, with CDDP and PTX. Blood, peritoneal perfusate and tissue samples were harvested to determine drug exposure by high-performance liquid chromatography and matrix-assisted laser desorption ionization imaging mass spectrometry (IMS). RESULTS: The mean maximum concentrations of CDDP and PTX in perfusate were, respectively, 24.8±10.4 µg ml(-1) and 69.8±14.3 µg ml(-1); in plasma were 1.87±0.4 µg ml(-1) and 0.055±0.009 µg ml(-1). The mean concentrations of CDDP and PTX in peritoneum at the end of HIPEC were 23.3±8.0 µg g(-1) and 30.1±18.3 µg(-1)g(-1), respectively. The penetration of PTX into the peritoneal wall, determined by IMS, was about 0.5 mm. Grade 3-4 surgical complications were recorded in four patients, five patients presented grade 3 and two patients presented grade 4 hematological complications. CONCLUSIONS: HIPEC with CDDP and PTX after CRS is feasible with acceptable morbidity and has a favorable pharmacokinetic profile: high drug concentrations are achieved in peritoneal tissue with low systemic exposure. Larger studies are needed to demonstrate its efficacy in patients with microscopic postsurgical residual tumours in the peritoneal cavity.

A novel anti-ageing mechanism for retinol: induction of dermal elastin synthesis and elastin fibre formation.

Dermal elastic fibres are extracellular matrix protein complexes produced by fibroblasts and involved in skin elasticity. Elastin fibres decrease with age as a result of reduced synthesis and increased degradation, resulting in skin sagging and reduced skin elasticity. In this study, we show that retinol (ROL), known to enhance dermal collagen production, is also enhancing elastin fibre formation. ROL induced elastin gene expression and elastin fibre formation in cultured human dermal fibroblasts. Topical treatment of cultured human skin explants with a low dose (0.04%) of ROL increased mRNA and protein levels of tropoelastin and of fibrillin-1, an elastin accessory protein, as documented by QPCR and immunohistochemistry staining. Luna staining confirmed the increased elastin fibre network in the ROL-treated skin explants, as compared with untreated controls. These data demonstrate that ROL exerts its anti-ageing benefits not only via enhanced epidermal proliferation and increased collagen production, but also through an increase in elastin production and assembly.

Learning in human neural networks on microelectrode arrays.

This paper describes experiments involving the growth of human neural networks of stem cells on a MEA (microelectrode array) support. The microelectrode arrays (MEAs) are constituted by a glass support in which a set of tungsten electrodes are inserted. The artificial neural network (ANN) paradigm was used by stimulating the neurons in parallel with digital patterns distributed on eight channels, then by analyzing a parallel multichannel output. In particular, the microelectrodes were connected following two different architectures, one inspired by the Kohonen's SOM, the other by the Hopfield network. The output signals have been analyzed in order to evaluate the possibility of organized reactions by the natural neurons.f The results show that the network of human neurons reacts selectively to the subministered digital signals, i.e., it produces similar output signals referred to identical or similar patterns, and clearly differentiates the outputs coming from different stimulations. Analyses performed with a special artificial neural network called ITSOM show the possibility to codify the neural responses to different patterns, thus to interpret the signals coming from the network of biological neurons, assigning a code to each output. It is straightforward to verify that identical codes are generated by the neural reactions to similar patterns. Further experiments are to be designed that improve the hybrid neural networks' capabilities and to test the possibility of utilizing the organized answers of the neurons in several ways.

Determination of the non-enzymatic glycation of hemoglobin by isoelectrofocusing of its globin chains.

Micro cation exchange chromatography determination of HbA1c does not provide a complete picture of Hb glycation, for it does not determine all the glycated forms of hemoglobin. For the determination of total glycation, we describe here a rod IEF method, which allows the simultaneous quantitation of glycation on alpha and beta globin chains. The method exhibits good sensitivity; it is not affected by artifacts deriving from temperature, hypertriglyceridemia, Hb variants or labile HbA1 (aldiminic Hb). The results obtained indicate that in a normal population approximately 18% of the beta chain and 8% of the alpha chain are glycated. These mean percentages increase in the diabetic to 28% and 12%, respectively. The beta chain is glycated on both valine and lysine residues, while the alpha chain is glycated only on the latter. HbA1 values from micro cation exchange chromatography are significantly related to both alpha and beta glycation. Thus, valinic or lysinic glycation have roughly the same clinical significance.

A prospective randomized study comparing intramuscular progesterone and 17alpha-hydroxyprogesterone caproate in patients undergoing in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To compare the effectiveness of i.m. P and 17alpha-hydroxyprogesterone caproate (17-HPC) for luteal phase support, in patients undergoing IVF-ET cycles. DESIGN: Prospective, randomized study. SETTING: Patients undergoing IVF-ET in our Centers. PATIENT(S): The inclusion criteria were the use of GnRH down-regulation and aged <40 years. INTERVENTION(S): A total of 300 cycles were randomly treated with either 17-HPC (341 mg every 3 days) or P (50 mg daily). MAIN OUTCOME MEASURE(S): The outcomes of IVF in both study groups were evaluated for biochemical pregnancy, miscarriage, clinical pregnancy, and ongoing pregnancy. RESULT(S): No difference was found in the main outcome parameters considered. CONCLUSION(S): Although the results of the study encourage the use of 17-HPC for luteal phase support in patients undergoing IVF-ET program, more studies are necessary to support the hypothesis that it can replace i.m. P-in-oil.

Effect of 2,2,2-trifluoroethanol on capillary zone electrophoretic peptide separations.

The use of 2,2,2-trifluoroethanol-water mixtures for peptide separations by capillary zone electrophoresis (CZE) displays some advantages over aqueous solutions. First, the increase in viscosity reduces and stabilizes the running current and facilitates heat dispersion, with a consequent improvement in the number of theoretical plates. Second, the decrease in the dielectric constant leads to a modification of the dissociation constants of the ionizable groups. The consequence is a change in selectivity that, for several favourable peptide pairs, provides an increase in resolution. Third, the interaction trifluoroethanol with the peptide modifies the Stokes radius in a manner strongly dependent on the peptide sequence. This can also be utilized for an increase in CZE performance. Fourth, the structural properties of 2,2,2-trifluoroethanol are particularly useful for an improvement in the separation of large apolar peptides. Finally, the use of trifluoroethanol strongly stabilizes the capillary coating.

A new approach for the treatment of bacterial vaginosis: use of polyhexamethylene biguanide. A prospective, randomized study.

BACKGROUND: Bacterial vaginosis (BV) is the most common vulvovaginal infection and represents the 35% of all the infections occurring in women in the reproductive age. It is well recognised that serious forms of BV can induce several complications among women undergoing gynaecologic or obstetric surgery, having pelvic inflammatory diseases, temporary or absolute infertility, miscarriage and abortion. At present, the clinical treatment of choice of BV is the use of systemic or local (gel or cream) metronidazole and clindamycin, though systemic use has some limitations due to side-effects and contraindications. Polyhexamethylene biguanide (PHMB) is a new bi-biguanide compound having a broad spectrum activity and low toxicity, that have been successfully utilized in ophthalmology and dentistry. Aim of this study was to evaluate the efficacy and tolerability of a single-dose vaginal administration of a PHMB vaginal gel in the treatment of BV in comparison to clindamycin vaginal cream. METHODS: One-hundred and ten patients affected by BV were treated with PHMB vaginal gel in single administration or clindamycin vaginal cream 1 daily administration for 7 days. RESULTS: We demonstrated the therapeutic efficacy of mono-dose administration of a vaginal solution containing PHMB in BV treatment; this efficacy is similar to the one shown in antibiotic therapy. Furthermore, this product was well tolerated by all treated patients. CONCLUSIONS: Mono-dose PHMB treatment should be regarded as the therapy of choice for BV, using clindamycin and metronidazole only for relapses treatment.

Determination of the post-translational modifications of salivary acidic proline-rich proteins.

Human salivary acidic proline-rich proteins were analyzed by electrospray-ion trap mass spectrometry and by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. All acidic-PRP isoforms share a common N-terminal region, which contains a pyroglutamic acid residue at the N-terminus, and two phosphorylation sites on Ser 8 and 22. At the same time, HPLC-MS spectra revealed isoforms of PRP-1 and PRP-3 having a different number of phosphoserine residues, namely, a mono-phosphorylated form of PRP-1 and PRP-3 and a tri-phosphorylated form of PRP-1. The analysis of the masses of tryptic digests suggested that the third phosphate residue should be located on Ser 17. Another protein with a mass of 30,923 amu was detected along the HPLC pattern and MS data of its tryptic digest suggested that it corresponds to the dimer of Pa, the isoform of PRP-1 with a substitution Arg-Cys at 103 position. Finally, structural identification is pending for another post-translational modification of acidic-PRP that provides an increase of 111-114 amu.

Atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and histology.

OBJECTIVE: A new terminology for cytologic diagnosis of cervical lesions has been introduced by Bethesda System. This includes: 1) Atypical squamous cells of undetermined significance (ASCUS), 2) Low-grade squamous intraepithelial lesion (LSIL), 3) High-grade squamous intraepithelial lesion (HSIL), 4) squamo-cellular carcinoma. The aim of this study was to assess the correlation between the colpocytologic test (Pap psmear), the histologic response and colposcopy. METHODS: We re-examined the cytologic results of 447 patients who underwent routine cytologic tests, with a diagnosis of various grades of atypia, from ASCUS to HSIL. A histologic test was carried out on a colposcopic basis in 210 cases and cytologic results were correlated with the histologic and colposcopic pictures. RESULTS: For ASCUS the histology was positive in 19.1% (31/163) of cases and negative in 10.4% of the colposcopically positive cases (17/163), while in the remaining 70.5% (115/163) the colposcopy resulted negative. In LSIL with the presence of human papillomavirus (HPV) the histologic findings, confirmed the cytologic result in 35.8% (48/134) while in the group of cervical intraepithelial neoplasia (CIN I) results corresponded in 40.6% (41/101). In high squamous intraepithelial lesions there was an histologic confirmation in 59.2% (29/49). CONCLUSIONS: The data obtained indicate an increase in positive histology results from the types of low grade (ASCUS-LSIL) to those of a high grade (HSIL). Our results indicate that the presence of ASCUS should be assessed colposcopically and histologically, where indicated.

Cellular and biochemical mechanisms, risk factors and management of preterm birth: state of the art.

Preterm birth (PTB) is usually defined as a delivery before 37 completed weeks or 259 days of gestation. World Health Organization estimates a worldwide incidence of PTB of 9.6%. Infants born preterm are at higher risks than infants born at term for mortality, and acute and chronic morbidity. Major causes of PTB are the following: spontaneous preterm labor with intact membranes (50%), labor induction or caesarean delivery for maternal or fetal indications (30%), and preterm premature rupture of membranes or PPROM (20%). The aim of this review is to analyze this medical condition, focusing on cellular and biochemical mechanisms, maternal risk factors and role of inflammation and infections in preterm premature rupture of membranes (PPROM) and PTB. Moreover we will discuss about the proper therapeutic strategies for its management. Although different methods have been introduced to predict the advent of preterm labour in asymptomatic women, possibilities for real primary prevention are rare. An early estimation of potential risk factors is pivotal in the secondary prevention of PTB. Finally most efforts so far have been tertiary interventions. These measures have reduced perinatal morbidity and mortality. Advances in primary and secondary care will be needed to prevent prematurity-related illness in infants and children.

A cultured human neural network operates a robotic actuator.

The development of bio-electronic prostheses, hybrid human-electronics devices and bionic robots has been the aim of many researchers. Although neurophysiologic processes have been widely investigated and bio-electronics has developed rapidly, the dynamics of a biological neuronal network that receive sensory inputs, store and control information is not yet understood. Toward this end, we have taken an interdisciplinary approach to study the learning and response of biological neural networks to complex stimulation patterns. This paper describes the design, execution, and results of several experiments performed in order to investigate the behavior of complex interconnected structures found in biological neural networks. The experimental design consisted of biological human neurons stimulated by parallel signal patterns intended to simulate complex perceptions. The response patterns were analyzed with an innovative artificial neural network (ANN), called ITSOM (Inductive Tracing Self Organizing Map). This system allowed us to decode the complex neural responses from a mixture of different stimulations and learned memory patterns inherent in the cell colonies. In the experiment described in this work, neurons derived from human neural stem cells were connected to a robotic actuator through the ANN analyzer to demonstrate our ability to produce useful control from simulated perceptions stimulating the cells. Preliminary results showed that in vitro human neuron colonies can learn to reply selectively to different stimulation patterns and that response signals can effectively be decoded to operate a minirobot. Lastly the fascinating performance of the hybrid system is evaluated quantitatively and potential future work is discussed.

Current trends in the treatment of Ewing's sarcoma.

The authors analyse the results obtained in the treatment of Ewing's sarcoma by comparing the period previous to the use of chemotherapy with the more recent one involving the use of antiblastic drugs. Thirty-one patients with Ewing's sarcoma were divided into three groups according to the type of treatment used. The first group included 11 patients treated either by surgery or high dosage radiation (7000-8000 rads); the second group included 9 patients treated by radiation plus polychemotherapy; finally, the third group included 11 patients treated by surgery (excision in 5 localizations and segmental resection in the remaining 6), associated with polychemotherapy and low dosage radiotherapy. The results in the first group were discouraging as none of the patients survived five years; there was a low survival rate (33%) for the second group, partly due to the fact that there were 4 localizations in the pelvis, a site with a notoriously unfavourable prognosis; the third group had the highest percentage (55%) of long-term disease-free patients. Thus, in agreement with what is reported in the literature, the most radical surgery possible, associated with polychemotherapy and low-dose radiotherapy, currently seems to be the best treatment.

[Supra- and intercondylar fractures of the distal meta-epiphysis of the humerus in adults: prognosis and therapy]. / Fratture sovra ed intercondiloidee della meta-epifisi distale dell'omero nell'adulto: prognosi e terapia.

Based on the results obtained in a group of 43 patients, the indications and results of the treatment of supra- and intercondylar fractures of the distal meta-epiphysis of the humerus during adult age are discussed. The treatment methods used are described. The results of surgical and nonsurgical treatment are analysed.