Progression Free Survival, Overall Survival, and Relapse Rate in Endometrioid Ovarian Cancer and Synchronous Endometrial-Ovarian Endometrioid Cancer (SEO-EC): Results from a Large Retrospective Analysis.

Background and Objectives: We aimed to evaluate Progression Free Survival (PFS), Overall Survival (OS), and relapse rate in women affected by endometrioid ovarian cancer and synchronous endometrial-ovarian endometrioid cancer (SEO-EC). As secondary outcome, we assessed whether systematic pelvic and para-aortic lymphadenectomy could be considered a determinant of relapse rate in this population. Materials and Methods: We performed a retrospective analysis of women with diagnosis of endometrioid ovarian cancer or SEO-EC between January 2010 to September 2020, and calculated PFS, OS and relapse rate. Results: In almost all the patients (97.6%) who underwent systematic pelvic and para-aortic lymphadenectomy, there were no lymph node metastases confirmed by histology. We did not find a significant difference (p = 0.6570) for the rate of relapse in the group of women who underwent systematic pelvic and para-aortic lymphadenectomy (4/42; 9.5%) compared with the group of women who did not undergo the same procedure (1/21; 4.8%). During a median follow-up was 23 months, both PFS and OS were excellent. Conclusions: Women affected by early-stage low-grade endometrioid cancer and SEO-EC without apparent lymph node involvement at pre-operative imaging showed a very low rate of lymph node metastasis and similar relapse rate with or without lymphadenectomy.

Prognostic factors and surgical treatment in vulvar carcinoma: Single center experience.

AIM: Vulvar carcinoma represents 3-5% of all female genital cancers; the main surgical treatment is radical vulvectomy and inguinal lymphadenectomy. The aim of this study is to analyze prognostic factors in the patients underwent to primary surgery for vulvar carcinoma. METHODS: One hundred and eighteen cases of vulvar carcinoma underwent surgery between 2006 and 2016 at Operative Unit of Gynecology and Obstetrics of Cannizzaro Hospital (Catania, Italy) were retrospective analyzed. Risk factors for relapse (age, tumor size, FIGO stage, type of surgery, lymphadenectomy, margins status, metastatic nodes and radiotherapy) were evaluated by logistic regression. Univariate analysis of prognostic factors (age, tumor size, FIGO stage, metastatic inguinal nodes and type of surgery) was obtained by Cox proportional hazard model. Overall survival was calculated by Kaplan-Meier curves either for the entire population and for comparison between positive and negative variables (margin status, nodes and radiotherapy) with log-rank test to determine significance. Statistical significance was reached for P < 0.05. RESULTS: Type of surgery (radical local excision vs. radical vulvectomy) and positive inguinal nodes were identified as risk factors for relapse. Positive inguinal nodes and positive margins were identified as prognostic factors either for overall survival and disease specific survival; tumor size greater than 4 cm was identified as prognostic factors for overall survival. Overall survival was 38.4% and it was significantly higher in the patients with negative margins and nodes. CONCLUSIONS: Nodes status, resection margins, age and type of surgery represent prognostic factors have to be considered for adjuvant treatment in the patients affected from vulvar carcinoma.

Children Learn to Read: How Visual Analysis and Mental Imagery Contribute to the Reading Performances at Different Stages of Reading Acquisition.

Reading in alphabetic orthography requires analysis and recognition of specific attributes of visual stimuli, and generation, reactivation, and use of mental images of letters and words. This study evaluated the role of visual analysis and mental imagery in reading performances of students at different stages of reading acquisition. Reading "comprehension," "accuracy," and "speed," were analyzed. Participants were 90 children who attended primary school. Children were assessed in the first and third grade. The results highlighted that mental imagery and visual analysis influenced reading acquisition. These abilities are differently involved in the three dimensions of reading skill. The issues of this study have practical and educational applications. The early assessment of visual analysis and mental imagery skills and specific training on these abilities could contribute to facilitate reading acquisition. Strategies of intervention centered on visual imagery could increase reading performances in typically developing children and children at risk of learning difficulties.

A 10-year evaluation on adolescents with anxiety disorders: are they at risk of bipolarity?

OBJECTIVE: Anxiety disorders are the most frequent disorders comorbid with bipolar disorder (BD) often preceding the BD onset. The presence of comorbid anxiety in patients diagnosed with BD is associated with worsening of their BD symptoms, increased risky behaviour, decreased response to pharmacological treatment and deterioration in their quality of life and global functioning. The aim of this study was to investigate if anxiety disorders in adolescence could be considered as predictors of BD. METHODS: Adolescents with a primary anxiety disorder were recruited consecutively from the Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin. Subjects were evaluated for Axis I psychiatric disorders, family history and global functioning, and followed up on average 10 years later. RESULTS: A total of 29 patients (59.2%) were male and the mean age at the onset of anxiety disorder was 16.3 (±0.8). Ten years following recruitment, 11 (22.4%) patients fulfilled the criteria for BD. Of them, 10 (90.9%) had a family history of BD and four (36.4%) presented a comorbid substance use disorder. CONCLUSIONS: Our study shows that both family history of BD and substance use disorder, in adolescent patients with a primary anxiety disorder, should be considered as potential predictors of BD onset.

Dental plaque quantitation by light induced fluorescence technology in exclusive Electronic Nicotine Delivery Systems (ENDS) users.

OBJECTIVES: In comparison to conventional combustible cigarettes, Electronic Nicotine Delivery Systems (ENDS) including both e-cigarettes (ECs) and heated tobacco products (HTPs) significantly reduce exposure to toxic chemical emissions. However, their impact on dental plaque remains unclear. This study measures dental plaque in ENDS (ECs and HTPs) users using quantitative light-induced fluorescence (QLF) technology, comparing them with current, former, and never smokers. METHODS: This cross-sectional study compared dental plaque measurements using QLF technology (Q-ray cam™ Pro) among current smokers (≥10 cigarettes/day), former smokers (quit ≥6 months), never smokers, and exclusive ENDS users (quit ≥6 months). Dental plaque measurements were expressed as ΔR30 (total area of mature dental plaque) and ΔR120 (greater plaque thickness/maturation-calculus). The Simple Oral Hygiene (SOH) score was calculated by the QLF proprietary software. Statistical analyses including ANCOVA was performed by R version (4.2.3) with p < 0.05. RESULTS: A total 30 smokers, 24 former smokers, 29 never smokers, and 53 ENDS users were included. Current smokers had significantly higher ΔR30 and ΔR120 values compared to other groups (p < 0.001). ENDS users showed plaque levels similar to never and former smokers (p > 0.05) but significantly lower than current smokers (p < 0.01). Although ENDS users showed a lower SOH score than smokers, this difference was not statistically significant. Daily toothbrushing and mouthwash usage were significant covariates. CONCLUSION: ENDS users exhibited reduced accumulation of dental plaque and calculus compared with current smokers. CLINICAL SIGNIFICANCE: Exclusive ENDS use could less impact dental plaque accumulation compared to cigarette smoking. Further research is needed to confirm these findings and fully understand ENDS impact on dental plaque formation.

Awake laparoscopic cholecystectomy: A case report and review of literature.

BACKGROUND: Laparoscopic cholecystectomy (LC) is one of the most widely practiced surgical procedures in abdominal surgery. Patients undergo LC during general anaesthesia; however, in recent years, several studies have suggested the ability to perform LC in patients who are awake. We report a case of awake LC and a literature review. CASE SUMMARY: A 69-year-old patient with severe pulmonary disease affected by cholelithiasis was scheduled for LC under regional anaesthesia. We first performed peridural anaesthesia at the T8-T9 level and then spinal anaesthesia at the T12-L1 level. The procedure was managed in total comfort for both the patient and the surgeon. The intra-abdominal pressure was 8 mmHg. The patient remained stable throughout the procedure, and the postoperative course was uneventful. CONCLUSION: Evidence has warranted the safe use of spinal and epidural anaesthesia, with minimal side effects easily managed with medications. Regional anaesthesia in selected patients may provide some advantages over general anaesthesia, such as no airway manipulation, maintenance of spontaneous breathing, effective postoperative analgesia, less nausea and vomiting, and early recovery. However, this technique for LC is not widely used in Europe; this is the first case reported in Italy in the literature. Regional anaesthesia is feasible and safe in performing some types of laparoscopic procedures. Further studies should be carried out to introduce this type of anaesthesia in routine clinical practice.

Fosfomycin Pharmacokinetic Profile in Plasma and Urine and Quantitative Estimation in Prostate and Seminal Vesicles after One and Two Consecutive Doses of Oral Fosfomycin Trometamol in Healthy Male Volunteers.

The present Phase I study investigated, for the first time, fosfomycin pharmacokinetics in humans after two 3 g doses of fosfomycin trometamol administered 27 h apart, according to the dose regimen recommended for the prophylactic indication for transrectal prostate biopsy in adult men. Plasma, urine and seminal plasma concentrations were measured after one and two consecutive doses in 24 healthy men, representative of the target population of the prophylactic indication. Prostate and seminal vesicle concentrations were estimated based on seminal plasma concentrations using a one-step regression method. The exposure to fosfomycin was very similar in rate (Cmax, tmax) after one and two doses. The AUC showed a minimal increment. On average, the apparent volume of distribution was high (>100 L), and the mean clearance had an intermediate value. The total amount and dose fraction of fosfomycin excreted in urine showed a small increment after two doses. The renal clearance was about 5 L/h. The fosfomycin concentration in the prostate and seminal vesicles showed that the antibiotic increased on average after two consecutive doses. This result confirmed the ability of fosfomycin to distribute into the prostate and into seminal vesicles after one single dose and that a two consecutive dose regimen increases the antibiotic availability inside these peripheral tissues.

Pharmacokinetics and Safety of Single and Multiple Doses of Oral N-Acetylcysteine in Healthy Chinese and Caucasian Volunteers: An Open-Label, Phase I Clinical Study.

INTRODUCTION: Few studies have evaluated whether the pharmacokinetics of N-acetyl-cysteine (NAC) are different in Chinese and Caucasian individuals. METHODS: This single- and multiple-dose, single-centre, open-label, phase I clinical study was conducted in healthy adult volunteers. All participants received oral NAC 600-mg uncoated tablets, which were administered first as a single dose and, following a 48-h wash-out period, twice daily for 3 days. Blood and urine were collected after single- and multiple-dose NAC administration. Adverse event (AE) data were collected throughout the study. RESULTS: Fifteen Chinese and 15 Caucasian (mostly Italian) individuals (males 66.7%, mean age 36.8 years) participated in the study. Pharmacokinetic characteristics of NAC were similar in the two cohorts. Following both single- and multiple-dose administration, plasma concentration of NAC increased rapidly, reaching a peak at approximately 1.0 h. Maximum plasma concentration and extent of exposure were higher after multiple doses than after a single dose. The accumulation ratio was relatively consistent in both Chinese (mean ± standard deviation 1.5 ± 0.4) and Caucasian (1.4 ± 0.2) participants. The half-life was 15.4 h in Chinese and 18.7 h in Caucasian participants, and the fraction of NAC excreted in urine in the 36 h following administration was 3.7% in Chinese and 3.8% in Caucasian participants. Two Caucasian participants had a total of 3 AEs (headache, presyncope and dysmenorrhoea). No AEs occurred in Chinese participants. CONCLUSIONS: The pharmacokinetic characteristics of NAC are similar in healthy Chinese and Caucasian individuals after single and repeated administration. NAC has a favourable tolerability profile.

Pharmacokinetics and Safety of Rifamycin SV after Single and Multiple Doses of MMX® Modified Release Tablets in Healthy Male and Female Volunteers.

The primary objective of this single- and multiple-dose pharmacokinetic study was the investigation of rifamycin SV's pharmacokinetic profile in plasma and urine. All the 18 enrolled healthy men and post-menopausal women received modified release tablets containing 600 mg of the oral non-absorbable antibiotic, rifamycin SV, according to a multiple dose regimen: one tablet three times a day (daily intake: 1800 mg) for 14 consecutive days. Blood sampling and urine collection were performed up to 24 h post-dose after the first dose on Days 1 and 7. On average, on Day 1, Cmax,0-24 was 5.79 ± 4.24 ng/mL and was attained in a median time of 9 h. On Day 7, all the subjects had quantifiable levels of rifamycin SV in plasma at each sampling time. After a peak concentration attained 2 h post-dose (mean ± SD concentration: 10.94 ± 16.41 ng/mL), rifamycin SV decreased in plasma to levels similar to those of Day 1. The amounts of rifamycin SV excreted in urine paralleled the plasma concentration at the corresponding times. On Day 1, the total amount excreted in urine was 0.0013%, and was 0.0029% on Day 7. The study results confirmed those of the previous Phase I study: the systemic absorption of rifamycin SV was also proved negligible after 7 days of the 600 mg t.i.d. dose regimen of the newly formulated tablets, currently under development for the treatment of several small and large intestinal pathologies, including diarrhea-predominant irritable bowel syndrome, hepatic encephalopathy, and others. Registered at ClinicalTrials.gov with the identifier NCT02969252, last updated on 26JAN18.

Relative bioavailability and pharmacokinetics of two oral formulations of docosahexaenoic acid/eicosapentaenoic acid after multiple-dose administration in healthy volunteers.

OBJECTIVES: To assess the comparative pharmacokinetic profile and bioavailability of docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) after multiple-dose administration of a new oral formulation (test formulation) and a commercially available reference formulation in healthy subjects. METHODS: Forty-eight healthy subjects received a 28-day oral treatment with DHA/EPA in the form of either the test or the reference product according to an open-label, randomized, parallel-group design. Both formulations were given t.i.d. at 8-h intervals at a dose of 3.0 g/day. Steady-state DHA and EPA concentrations in plasma and lysed whole blood were measured by gas-liquid chromatography at baseline and after 7, 14, 21 and 28 days of treatment. Kinetic parameters were compared both after subtraction of baseline concentrations and by using baseline concentrations as a covariate. RESULTS: For both DHA and EPA, plasma and RBC concentrations measured from day 7 to day 28 were significantly higher than at baseline and did not differ significantly between the two products. On day 28 the plasma DHA concentration on average doubled the baseline level after administration of test and reference product, while there was a 10-fold increase in EPA plasma concentration. When the assessment was performed using baseline values as covariate, test-to-reference ratios for area under the curve (AUCss(0-8)) and for peak concentration (Css(max)) after the last administration on day 28 met bioequivalence criteria (i.e., 90% confidence intervals within 0.80-1.25 for AUCss(0-8) ratios, and within 0.75-1.33 for Css(max) ratios). When the assessment was conducted after subtraction of baseline values, the 90% confidence intervals for Css(max) ratios were within the bioequivalence range, whereas the intervals for AUCss(0-8) ratio were borderline for bioequivalence. CONCLUSION: The two formulations tested were similarly effective in increasing DHA and EPA concentrations in plasma and lysed whole blood, and showed comparable bioavailability for both active components.

Laparo-endoscopic "Rendezvous" to treat cholecysto-choledocolithiasis: Effective, safe and simplifies the endoscopist's work.

AIM: To investigate our clinical experience with combined laparo-endoscopic Rendezvous (RV) for the treatment of patients affected by gallstones and common bile duct (CBD) stones and especially to study the never evaluated opinion of the endoscopist concerning the difficulty of the intraoperative endoscopic procedure during the RV in comparison with standard endoscopic retrograde cholangio-pancreatography (ERCP). METHODS: Eighty consecutive patients affected by cholecystolithiasis and diagnosed or suspected CBD stones were treated with a standardized "tailored" RV. The relevant technical features, the feasibility, the effectiveness in stone clearance, the safety but also the simple evaluation of difficulty and agreement of the endoscopist were analyzed with a questionnaire. RESULTS: The feasibility was 97.5% and the effectiveness 100% concerning CBD clearance and solution of coexisting problems at the papilla. Minor morbidity was 3.3%, the operating time was prolonged by a mean of 14 min, the mean hospital stay was 3.8 d and only one stone's recurrence occurred. The endoscopist evaluated the procedure to be simpler than standard ERCP-ES in 81.2% of the cases. CONCLUSION: Simultaneous RV carries high effectiveness and safety at least comparable to those reported for other options. The endoscopist is very often satisfied with this approach because of the minimization of some steps of the endoscopic procedure and avoidance of relevant iatrogenic risk factors. If the mandatory collaboration between surgeons and endoscopists is guaranteed, this approach can often be preferable for the patient, the surgeon, the endoscopist and the hospital.

Pharmacokinetics and Pharmacodynamics of Follicle-Stimulating Hormone in Healthy Women Receiving Single and Multiple Doses of Highly Purified Human Menotrophin and Urofollitrophin.

BACKGROUND AND OBJECTIVE: Highly purified human menotrophin and urofollitrophin preparations obtained from human urine via a novel patented purification method have been tested over a timeframe of 14 years in the studies presented in this article. The objective of the studies was to investigate the pharmacokinetics and the pharmacodynamics of follicle-stimulating hormone (FSH) after single subcutaneous and intramuscular doses and multiple subcutaneous doses of the tested preparations in healthy fertile pituitary-suppressed women. DESIGNS: We performed five open, randomised, crossover, single-dose bioequivalence and/or bioavailability studies and one open, multiple-dose, pharmacokinetics and pharmacodynamics study. STUDY SUBJECTS AND TREATMENTS: The six studies included 121 healthy fertile women taking their usual combined oral contraceptives for 3 months before the study: Study 1: 300 international units (IU) of highly purified menotrophin as single subcutaneous and intramuscular doses. Study 2: 300 IU of highly purified menotrophin (test formulation vs. comparator) as single subcutaneous doses. Study 3: 300 IU of highly purified urofollitrophin (hp-FSH) (test formulation vs. comparator) as single subcutaneous doses. Study 4: 300 IU (2 × 150 IU vs. 4 × 75 IU) of hp-FSH as single subcutaneous doses. Study 5: 225 and 445 IU of hp-FSH as single subcutaneous doses. Study 6: daily 225 IU of hp-FSH as subcutaneous doses for 5 consecutive days. MAIN OUTCOME MEASURES: The main outcome measures were the FSH pharmacokinetic parameters, estradiol concentrations, and the number and size of the follicles. RESULTS: FSH after single subcutaneous and intramuscular injections of menotrophin or urofollitrophin attained a systemic peak (maximum) concentration (C max) that was on average consistent throughout the first four studies and ranged from 4.98 to 7.50 IU/L. The area under the plasma concentration-time curve (AUC) from administration to the last observed concentration time t (AUCt) ranged from 409.71 to 486.16 IU/L·h and the elimination half-life (t ½) ranged from 39.02 to 53.63 h. After multiple doses of urofollitrophin (225 IU) for 5 days, FSH attained a mean C max of 14.93 ± 2.92 IU/L and had an AUC during the time interval τ between two consecutive doses at steady state (AUCτ) of 322.59 ± 57.92 IU/L·h, which was similar to the mean AUCt after a single subcutaneous dose of 225 IU of urofollitrophin in study 5 (306.82 ± 68.37 IU/L·h). CONCLUSIONS: In our studies, the intramuscular and subcutaneous routes of menotrophin were equivalent; both menotrophin and urofollitrophin were bioequivalent to their marketed reference; FSH kinetic parameters following injection of urofollitrophin were dose proportional and independent from the administered concentration; and multiple doses of FSH increased estradiol levels and enhanced growth of follicles with a good dose-response correlation. Local tolerability was excellent throughout the six studies.

[Blunt liver trauma: efficacy of non-operative management]. / I traumi chiusi del fegato: efficacia del trattamento conservativo.

All haemodynamically stable patients with blunt abdominal trauma can be managed conservatively by non-operative management which is the treatment of choice in 80% of liver trauma. Non-operative management, when feasible, yields very good results in terms of survival, need for blood transfusions, morbidity and reduction of hospital stay. The Authors retrospectively analyse their recent experience with liver trauma. Of 53 patients with blunt liver trauma, 36 underwent surgical treatment whereas 17 haemodynamically stable patients received non-operative management. After CT scans, all patients on non-operative management underwent haemodynamic monitoring, US and blood examinations. A percentage of 47.1 % had a > or = grade III trauma. The mortality and morbidity rates were 0% and no blood transfusions were needed. The efficacy of non-operative management was 100% and none of the patients needed subsequent surgical treatment. Our clinical experience demonstrates that non-operative management is feasible and effective even for higher grade traumas, but always requires strict clinical, haemodynamic and US monitoring and careful patient selection. Current progress in the field and recent evidence reported in the literature indicate the likelihood of further developments and more widespread utilisation of non-operative management in liver trauma.

Recombinant filgrastim (BK0023) pharmacodynamics and pharmacokinetics after single and multiple escalating doses in an equivalence study in healthy men.

BACKGROUND AND OBJECTIVES: The new filgrastim formulation, BK0023, whose synthesis method is patented, was tested in a phase I clinical study that was aimed at investigating the pharmacodynamic and pharmacokinetic equivalence and the safety of BK0023 in healthy male subjects. METHODS: Single and multiple escalating doses were administered to healthy male volunteers according to a double-blind, randomised, two-way crossover design. Thirty-two subjects received subcutaneous filgrastim 2.5 µg/kg/day for 7 consecutive days in each period, 36 subjects received 5 µg/kg/day for 7 days in each period, and 22 subjects received 10 µg/kg/day for 5 days. Absolute neutrophil count (ANC) and CD34+ cell count were measured in whole blood as primary and secondary pharmacodynamic parameters. Filgrastim concentrations were measured in serum to calculate the primary pharmacokinetic parameters. RESULTS: The maximum ANC and the area under the curve of the ANC after the first dose and to the end of treatment satisfied the equivalence criterion (95 % confidence intervals within 85-115 or 85-117 % in case of log-transformation). At all three dose regimens, BK0023 was also bioequivalent to the reference product in terms of pharmacokinetic profile of serum filgrastim. The frequency of the treatment-emergent adverse events did not differ significantly between treatments, with the most frequent untoward effects being back and bone pain. CONCLUSIONS: Equivalence could be established using both the baseline-adjusted values and the original unadjusted values. The tested formulation at all three dose regimens was also bioequivalent to the reference product in terms of pharmacokinetic profile.

Preclinical and clinical phase I studies of a new recombinant Filgrastim (BK0023) in comparison with Neupogen®.

BACKGROUND: Filgrastim or methionyl-granulocyte colony-stimulating factor (Met-G-CSF), is a recombinant therapeutic protein widely used to treat severe neutropenia caused by myelosuppressive drugs in patients with nonmyeloid malignancies. In addition to its role in the regulation of granulopoiesis, treatment with G-CSF is considered the standard approach to mobilize CD34 positive (CD34+) mononuclear cells for reconstituting hemopoietic ability for bone marrow transplantation. An intended biosimilar filgrastim (coded BK0023) was produced in GMP conditions by E.coli fermentation according to an original recombinant process and showed physico-chemical properties and purity profile similar to Neupogen®, a commercial preparation of filgrastim. The aim of the present study was to demonstrate the comparability of BK0023 to Neupogen® in terms of both in vitro biological activities and in vivo toxicology, pharmacokinetics and pharmacodynamics. METHODS: Cell proliferation and radioligand binding assays were conducted in NFS-60 cells to compare the biological activity and functional interaction with the G-CSF receptor in vitro, while preclinical in vivo studies, including pharmacokinetics and pharmacodynamics after repeated dose were performed in normal and neutropenic rats. A phase I study was carried out in healthy male volunteers treated by multiple-dose subcutaneous administration of BK0023 and Neupogen® to evaluate their pharmacodynamic effects as well as their pharmacokinetic and safety profile and to demonstrate their pharmacodynamic equivalence and pharmacokinetic bioequivalence. RESULTS: The results reported in this work demonstrate that BK0023 is comparable in terms of biological activity, efficacy and safety to Neupogen®. CONCLUSIONS: BK0023 has the same pharmacokinetic profile, efficacy and safety as the reference commercial filgrastim Neupogen® and therefore could be further developed to become a convenient option to treat neutropenia in oncological patients.

Laparoscopic Reversal of Hartmann's Procedure: State of the Art 20 Years after the First Reported Case.

Introduction. Aim of the present work is to review the literature to point out the role of laparoscopic reversal of Hartmann procedure. Material and Methods. Number of patients, age, sex, etiology, Hinchey classification, interval between procedure and reversal, position of the first trocars, mean operative time (min), number and causes of conversion, length of stay, mortality, complications, and quality of life were considered. Results. 238 males (52.4%) and 216 females (47.6%) between 38 and 67 years were analyzed. The etiology was diverticulitis in 292 patients (72.1%), carcinoma in 43 patients (10.6%), and other in 70 patients (17.3%). Only 7 articles (22.6%) reported Hinchey classification. The interval between initial procedure and reversal was between 50 and 330 days. The initial trocar was open positioned in 182 patients (43.2%) through umbilical incision, in 177 patients (41.9%) in right upper quadrant, and in 63 patients (14.9%) in colostomy site. The operative time was between 69 and 285 minutes. A total of 83 patients (12.1%) were converted and the causes were reported in 67.4%. The length of stay was between 3 and 12 days. 5 patients (0.7%) died. The complications concern 112 cases (16.4%). Conclusion. The laparoscopic Hartmann's reversal is safer and achieves faster positive results.

Pressor response to oral tyramine and monoamine oxidase inhibition during treatment with ralfinamide (NW-1029).

Ralfinamide, an original Na(+) channel blocker developed for the treatment of chronic pain, inhibits monoamineoxidase-B with no apparent effect on monoamineoxidase-A. To evaluate the pressor response to oral tyramine under fasting conditions during treatment with ralfinamide in healthy normotensive subjects. Ten women and 10 men aged 52.9 ± 5.5, sensitive to the oral tyramine pressor effect in the dose range 200-400 mg, received ralfinamide 320 mg daily during 7 days of confinement. Starting on day 5, ascending doses of tyramine 50, 100 and 200 mg were daily administered to subjects, who had responded to 200 mg at screening, and 100, 200 and 400 mg to the 400 mg responders. Vital parameters were monitored. The systolic blood pressure peak (ΔSBP), the time to achieve the peak (Δt) and the area under the pressure curve (over baseline) were calculated. ΔSBP ≥ 30 mmHg were measured for one subject with tyramine 200 mg and for 11 subjects with 400 mg, whilst ΔSBP was <30 mmHg for eight subjects at all the tested doses. ΔSBP, Δt and AUC after co-treatment with ralfinamide and tyramine were not significantly different from those measured after tyramine alone. Ralfinamide did not potentiate the pressor response to single oral doses of tyramine from 50 to 400 mg. These preliminary results give an evidence for the specificity of ralfinamide for MAO-B in comparison with MAO-A, analogously to the observations previously done for safinamide. Dietary tyramine restrictions may not be necessary in neuropathic pain patients receiving ralfinamide as a therapy.

Comparison of two entry methods for laparoscopic port entry: technical point of view.

Laparoscopic entry is a blind procedure and it often represents a problem for all the related complications. In the last three decades, rapid advances in laparoscopic surgery have made it an invaluable part of general surgery, but there remains no clear consensus on an optimal method of entry into the peritoneal cavity. The aim of this paper is to focus on the evolution of two used methods of entry into the peritoneal cavity in laparoscopic surgery.

Pressor response to oral tyramine during co-administration with safinamide in healthy volunteers.

The aim of this study was to evaluate the pressor response to oral tyramine during repeated administration of oral safinamide in healthy volunteers. Twelve females and eight males aged 52.7 ± 4.9 years entered the study. An oral tyramine screening test was conducted to select subjects sensitive to the tyramine pressor effect on systolic blood pressure (SBP) in the dose range of 200-400 mg. Safinamide 300 mg was then administered once daily under fasting conditions. Starting on day 5 (safinamide pharmacokinetic steady state), single ascending doses of tyramine were co-administered daily: 50, 100 and 200 mg were administered on days 5, 6 and 7, respectively. Vital parameters were monitored by telemetry. No SBP increase ≥30 mmHg over baseline was observed when tyramine was co-administered with safinamide. Less than one third of the 400 mg responders reported SBP increases between 22 and 27 mmHg, which were below the threshold of 30 mmHg over baseline. SBP increases, as well as time interval to pressor response measured after co-treatment with safinamide and tyramine 200 mg, were not significantly different from those measured after administration of oral tyramine 200 mg alone. Safinamide 300 mg, administered o.d. under fasting conditions, does not change the tyramine pressor response as evaluated at steady state after 6-7 days of treatment as compared with the effect of tyramine administered alone. Safinamide, which inhibits monoamine oxidase (MAO)-B, does not affect oral tyramine metabolism mediated mostly by the intestinal MAO-A.

Laparoscopic excision of a case of percutaneous cystohepatic fistula in a patient affected by polycystic disease of the liver: point of technique.

A 76-year-old man affected by autosomal-dominant polycystic kidney disease was admitted for a 2-year history of purulent leakage from a cutaneous orifice present in the right hypochondrium. The patient was submitted to a percutaneous aspiration of a big symptomatic cyst in the right liver about 3 years earlier in another hospital. Shortly, an orifice with purulent leakage appeared in his hypochondrium. Two years later, the patient came under our observation. Computed tomography scan showed a polycystic liver with a fistula from a hepatic cyst to the skin. A laparoscopic approach was chosen to dissect the fistulous tract from its liver bed and then a cutaneous incision was performed to resect the en-block fistulous tract and skin containing the cutaneous orifice. Cystocutaneous fistula, as in our patient, is not reported yet; the laparoscopic approach allows treatment in the presence of a fistula and, as in our case, of hepatic cysts.