Search

Traditionally, sensitivity to situational norms is understood as deriving from internal cognitive states that represent the rules for appropriate conduct. On an alternative view, norms are 'out there', in the practices and situations themselves, without being duplicated in the head. However, what does normativity look like when it is performed by people engaging with a concrete situation? A 'behaviour setting' offers a window onto these dynamics. This article presents an observational case study of normative coordination within a behaviour setting. Immersed in a scientific laboratory setting, the observations show how the normative demands of the overall behaviour setting can give shape to various places of action, or 'synomorphs', which invite the participants' activities. Responding to the different needs of each synomorph, in turn, maintains the behaviour setting. What connects these two reciprocal timescales of activity are the situationally sensitive activities of the participants. We end with several examples that bring such sensitivity to the interdependence of the norms of a behaviour setting to the fore. This article is part of the theme issue 'People, places, things, and communities: expanding behaviour settings theory in the twenty-first century'.

Background: Gastrointestinal severe adverse events such as ulceration and perforation have been reported for sodium or calcium polystyrene sulfonate and sevelamer. Howewer, their role in the pathogenesis is unclear. Chronic kidney disease is a well known risk factor, while the role of hypertension and/or diabetes is uncertain., Methods: A meta-analysis of the published literature was conducted to review the clinical features, risk factors and histopathological findings of patients who experienced gastrointestinal adverse events after administration of polystyrene sulfonate or sevelamer., Results: The meta-analysis indicated that patients were more likely to show necrosis and/or perforation when the resin used was polystyrene sulfonate compared to sevelamer (p < 0.001). Death was more likely in patients taking polystyrene sulfonate compared to sevelamer (p < 0.001)., Discussion: The results show that sevelamer is more likely to lead to inflammation or ulceration in the gastrointestinal tract than polystyrene sulfonate, which is more likely to be associated with severe gastrointestinal adverse events such as necrosis and/or perforation. Polystyrene sulfonate is significantly associated with death compared to sevelamer., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Background: Metastatic prostate adenocarcinoma is a rare event and there are few references to this topic. We report an unusual case of prostate cancer metastasis and review of contemporary literature. Moreover, we discuss the pathogenesis and the clinical aspects of this event., Case Presentation: A 70-year-old patient was admitted to the hospital for right scrotal pain. The ultrasound examination described an increase in testicular size, suggesting the possibility of orchiepididymitis. Past medical history reported a previous prostate adenocarcinoma. Inflammatory blood tests were normal. Importantly, PSA was 3.3 ng/ml. PET scan positivity in the scrotum raised suspicion of a relapse. Therefore, he underwent right orchiectomy., Conclusion: Although metastatic prostate adenocarcinoma is rare, a correct diagnosis is of paramount importance because the therapy changes accordingly. Patients who complain of scrotal pain need to be examined accurately. Although the most common cause behind this symptom is infectious, the patient's past medical history should be reviewed to exclude previous malignancies., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Introduction: The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab., Methods: Immunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor., Results: A positive association was found between NICD and Jag1 expression (p < 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823)., Discussion: These results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Negri, Bottarelli, Pedrazzi, Maddalo, Leo, Milanese, Sala, Lecchini, Campanini, Bozzetti, Zavani, Di Rienzo, Azzoni, Silini, Sverzellati, Gaiani, de’ Angelis and Gnetti.)

In this study, I will claim that we need to rearticulate the so-called "knowledge-to-action" (KTA) gap metaphor in clinical research as a discontinuity of practices. In clinical research, there is a significant delay between the production of research results and their application in policy and practice. These difficulties are normally conceptualized through the metaphor of the KTA gap between scientific knowledge and practical applications. I will advise that it is important to reformulate the terms of the problem, as they suggest the difficulty lies only in the results generated on one side (the laboratory), not reaching the other side (the clinic), and that crossing the gap requires us to simply optimize the transfer and exchange of knowledge. This perspective considers knowledge separate from the practices from which it was generated, making it into a thing that can be transported and transferred largely independently from the communities that produce or "possess" it. The paper then revises the terms of the problem, shifting the focus from knowledge understood as independent from practical circumstances to the situated practices of knowing. Knowledge will then be understood as enacted in practice, emerging as people interact recurrently in the context of established practices. When people coming from different domains and with different "ends-in-view" must coordinate, they have to deal with conceptual and practical tensions, different ways of doing things with their surroundings, and different normative practices. Considering that, the KTA gap will be revised, not as a gap between scientific results and their application in clinical practice, but as a discontinuity in how communities engage with their local contexts and what they perceive as relevant for their activities., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Di Rienzo.)

Background: Chest drainage systems are affected by intra and inter-observer variability and poor sensibility in detecting minimal or apparent air leaks., Objectives: Overcome intra and inter-observer variability in detecting air leaks., Methods: After surgery, a single apical chest tube was connected to the Drentech™ PalmEVO device and air leaks were checked twice a day by observation of both bubbles-in-the-chamber and digital data., Results: On a total of 624 observations, disagreement between digital and traditional systems was recorded in 60(9.6%) cases. In 25(21.4%) patients, a disagreement was recorded. Overall, the digital evaluation influenced clinical management in 13(52%). In 10(40%) patients with temporary discordant features, the presence of high pleural fluid output led to a progressive final concordance., Conclusions: Disagreement between traditional and digital systems in checking air leaks is not negligible. Digital systems could give advantages in making an objective assessment of air leaks, standardizing the timing of chest tube removal., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To explore the safety and feasibility of photo-selective vaporization of the prostate (PVP) with GreenLight XPS 180 Watt laser (GL-180- W XPS) combined with other surgical procedures., Material and Methods: Data on patients in whom GL-180-W XPS was performed to relieve lower urinary tract symptoms/ benign prostatic hyperplasia (LUTS/BPH) symptoms were extracted from a multi-institutional database (2011-2016). Patients were stratified into two groups. In the first all patients who had GL-180-W XPS with a concomitant procedure during the same surgical session were included as cases while those who underwent GL-180-W XPS PVP only were included as control., Results: A total of 487 patients were included. Fifty-eight (11.9%) patients underwent concomitant procedures. Multivariable linear regression models failed to find an association between concomitant procedures and longer laser time (p = 0.4). Similarly, multivariable linear regression models failed to find an association between concomitant procedures and laser time even when the analyses were repeated and stratified into endoscopic (p = 0.6) and open/laparoscopic (p = 0.4) procedures. Multivariable logistic regression models failed to demonstrate any association between concomitant procedures and early complications (OR:1.39, CI: 0.379-2.44, p = 0.2), late complications (OR:1.84, CI:0.78-3.98; p = 0.1) and acute urinary retention (OR:1.84, CI:0.78-3.98; p = 0.1). When the analyses were repeated and the concomitant procedures stratified into endoscopic and open/laparoscopic ones, they yielded virtually the same results., Conclusions: GL-180-W XPS PVP could be safely performed in concomitant endoscopic or open/laparoscopic surgery. These results should be taken into consideration in the counseling of the patient who might choose to undergo simultaneous procedures.

Problem: The influence of fetal sex on immune responses in multifetal pregnancies remains incompletely elucidated. The a2 isoform of vacuolar adenosine triphosphatase (a2V) is expressed on the cell membrane of maternal lymphoid cells and contributes to down-regulation of pro-inflammatory immune responses during gestation. The association between fetal sex and a2V expression on peripheral blood mononuclear cells (PBMCs) from mothers with twin gestations was assessed., Method of Study: Patients in this prospective study were 93 women with twin pregnancies in their mid-second or early third trimester-27 with two male, 30 with two female and 36 with one male and one female fetus. PBMCs were isolated and a2V was measured by ELISA in cell lysates. Demographic and clinical data were subsequently obtained and correlations between a2V and fetal sex, birthweight and pregnancy outcome were assessed by the Mann-Whitney and Spearman rank correlation tests., Results: The mean a2V level was highest when both fetuses were male (2.0 ng/mL) and lowest when both were female (1.5 ng/mL; P = 0.0184). Only when both fetuses were female did the a2V concentration negatively correlate with birthweight of the 1st (P = 0.0011) and 2nd (P = 0.0044) born fetus and with gestational age at delivery (P = 0.0018). There were no associations between a2V and these outcomes in male only or mixed twin pregnancies., Conclusion: We conclude that the a2V-mediated regulation of maternal immunity during twin pregnancies is influenced by fetal sex., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

With these recommendations the Interdisciplinary Urinalysis Group (GIAU) aims to stimulate the following aspects : improvement and standardization of the post analytical approach to physical, chemical and morphological urine examination (ECMU); emphasize the value added to ECMU by selection of clinically significant parameters, indication of analytical methods, of units of measurement, of reference values; improvement of interpretation of dip stick urinalysis with particular regard to the reconsideration of the diagnostic significance of the evaluated parameters together with an increasing awareness of the limits of sensitivity and specificity of this analytical method. Accompanied by the skills to propose and carry out in-depth investigations with analytical methods that are more sensitive and specific;increase the awareness of the importance of professional skills in the field of urinary morphology and their relationships with the clinicians. through the introduction, in the report, of descriptive and interpretative comments depending on the type of request, the complexity of the laboratory, the competence of the pathologist;implement a policy of evaluation of the analytical quality by using, in addition to traditional internal and external controls, a program for the evaluation of morphological competence. The hope is to revalue the enormous potential diagnostic of ECMU, implementing a urinalysis on personalized diagnostic needs that each patient brings with it., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Background: Several gray areas and controversies exist concerning the management of pulmonary ground-glass opacities (GGOs), and there is a lack of consensus among clinicians on this topic. One of the main aims of the Italian Society of Thoracic Surgery is to promote education and research, so we decided to perform a survey on this topic to estimate current trends in practice in a large sample of thoracic surgeons., Methods: A total of 160 thoracic surgeons responded, namely, completed our questionnaire (response rate, 53%; 160 of 302). The survey was composed of 36 questions divided into six subsections: (1) demographic characteristics of the respondents; (2) terminology and taxonomy; (3) radiologic and radiometabolic evaluation; (4) diagnostic approach and indications for surgery; (5) surgical management; and (6) radiologic surveillance., Results: We observed some divergence of opinion regarding the definition of mixed GGOs, the role of 18F fluorodeoxyglucose positron emission tomography and computed tomography scans, indications for nonsurgical biopsy, intraoperative techniques for localizing GGOs, indications for surgery, extension of lung resection and lymph node dissection according to the radiologic scenario, use of intraoperative frozen section analysis, and radiologic surveillance of pure GGOs., Conclusions: This topic warrants more investigation in the future. An upcoming consensus conference of Italian Society of Thoracic Surgery experts (also open to experts in other specialties) could provide updated indications for GGO management based on the literature, expert opinions, and the results of the present survey., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The expertise curve of video-assisted thoracoscopic surgery (VATS) lobectomies still stirs debate and controversy both because of the number of procedures to carry out and of the evaluation of the learning threshold. The purpose of our study was the examination of the variables related to the learning curve of the video-assisted approach, to establish what may be an expression of the technical maturity of the surgeon., Methods: The National Register for VATS lobectomy built in 2013 was used to collect data from 65 Thoracic Surgery Units. Out of more than 3,700 patients enrolled, only information from Units with ≥100 VATS lobectomies were retrospectively analysed. Unpaired Student's t -tests, Fisher's exact tests, Pearson's χ 2 were applied as needed. Cumulative summative analysis and one-way ANOVA were used to identify the expertise curve of VATS lobectomy., Results: Ten institutions contributed a total of 1,679 patients, who were divided into three uniform groups according to the chronological sequence of surgery. The length of utility incision, the number of dissected lymph nodes and the operative time were not statistically significant (P=0.999, P=0.972 and P=0.307, respectively) among groups. Conversion to thoracotomy and postoperative air leaks occurred in 125 (7.44%) and 109 (6.49%) patients, gradually declined in Group 3 with statistical significance (P=0.048 and P=0.00086)., Conclusions: The conversion rate and the percentage of air leaks seem to define the expertise of VATS lobectomy, being linked to the ability to manage more complicated surgical cases or intraoperative adverse events., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed., Methods: From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method., Results: Overall, median OS, CSS, and RFS were 29 (95 % CI 18-39), 48 (95 % CI 19-78), and 22 (95 % CI 17-27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21-7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00-1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95-6.63, p < 0.0001) with tumor size ≥5 cm (HR: 1.85, 95 % CI 0.88-3.88, p = 0.10) experienced a worse RFS., Conclusions: In selected surgically treated SCLC, the long-term survival may be stratified according to the node-spreading pattern.

Objectives: Our aim was to investigate whether advanced maternal age (≥40years) still impairs the outcome of twin pregnancies after assisted reproductive techniques (ART)., Study Design: The retrospective observational study evaluated 430 nulliparous dichorionic diamniotic twin pregnancies conceived with ART. The population was divided into women <40 years old (Group A, n=265) and ≥40 years old (Group B, n=165)., Results: Gestational diabetes mellitus and gestational hypertension/preeclampsia were significantly more frequent in nulliparous twin pregnancies after ART ≥40years compared to <40years (p=0.021 and p<0.001, respectively). In univariate analysis of twin pregnancies after ART, there was only a trend of higher incidence of total preterm birth (PB) rate within mother aged ≥40 years old (p=0.104). However, Group A showed higher rate of spontaneous preterm birth (SPB) <37 weeks, whereas Group B showed significantly higher rate of iatrogenic PB <37 weeks of gestation (p=0.023 and p=0.001, respectively). For delivery <32 weeks of gestation, the rate of SPB in Group A was significantly higher (p=0.002). A higher incidence of PB was observed in Group B after heterologous treatment (p<0.001). Despite this, the absolute prevalence of PB in the entire population is higher in Group A, both after autologous (22.5%) and heterologous (25%) ART treatment, than in Group B (10.1% vs 21.4%)., Conclusions: Our data indicate that nulliparous twin pregnancies conceived with ART in mothers ≥40 years old did not show significantly higher incidence of PB, even if an increased rate of iatrogenic PB <37 weeks is showed., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: Air leakage represents a major problem in lung surgery. Absorbable fibrin sealant patch (AFSP), a collagen sponge coated with human fibrinogen and thrombin, can be used as an adjunct to primary stapling or suturing. This study compared the efficacy of AFSP with manual suturing after primary stapling., Methods: This was a prospective, multicenter, randomized study. Patients undergoing lobectomy, bilobectomy, anatomical segmentectomy for lung cancer or wedge resection for pulmonary metastasis with air leakage grade 1 or 2 according to Macchiarini scale after stapler suture were randomized to receive AFSP or standard surgical treatment (ST). The primary endpoint was the reduction of intraoperative air leakage intensity. Duration of postoperative air leakage and number of days until removal of last chest drain were secondary endpoints. Safety was recorded for all patients., Results: A total of 346 patients were enrolled in 14 centres, 179 of whom received AFSP and 167 ST. Intraoperative air leak intensity was reduced in 90.5% of AFSP patients and 82% of ST patients (P=0.03). A significant reduction in postoperative air leakage duration was observed in the AFSP group (P=0.0437). The median number of days until removal of last drainage was 6 (3-37) in the AFSP group and 7 (2-27) in the ST (P=0.38). Occurrence of adverse events was comparable in both groups., Conclusion: AFSP was more efficacious than standard ST as an adjunct to primary stapling in reducing intraoperative air leakage intensity and duration of postoperative air leakage in patients undergoing pulmonary surgery. AFSP was well tolerated.

Background: Myostatin is a negative regulator of skeletal muscle mass. We recently demonstrated that myostatin expression is upregulated in an experimental model of cancer cachexia, suggesting that modulations of this pathway might play a pathogenic role in cancer-related muscle wasting. The present study was designed to investigate whether myostatin signaling is modulated in the muscle of non-weight-losing (nWL) patients with lung and gastric cancer., Methods: Myostatin signaling was studied in muscle biopsies obtained during surgical procedure from nWL patients affected by gastric (n=16) or lung (n=17) cancer. Western blotting was applied to test both the total expression of myostatin and the expression of phosphorylated form of GSK-3beta and Smad2/3., Results: In patients with gastric cancer, the expression of both myostatin and phosphorylated GSK-3beta (p-GSK3β) were significantly increased. By contrast, in patients with lung cancer, myostatin levels were comparable to controls, whereas the expression of p-GSK3β significantly decreased in patients with disease stage III/IV., Conclusions: Myostatin signaling is altered in nWL cancer patients. Different tumor types may give rise to different patterns of molecular changes within the muscle, which occur even before cachexia becomes clinically apparent.

A tracheal perforation was discovered after Nd-YAG laser thermal ablation (LTA) of a thyroid nodule. The LTA is a relatively new method of treatment of thyroid nodules, which consists of delivering laser energy into the thyroid by means of two optical fibres. The patient presented with a multinodular goitre and initially refused surgery, then underwent an LTA of a thyroid nodule. Fifty days after the procedure she started to have symptoms related to a tracheal stenosis and, after tracheoscopy, a tracheal perforation was diagnosed and she underwent a total thyroidectomy plus tracheal repair. The results of the histological examination revealed a goitre with a focal area of papillary carcinoma. This particular complication is likely the first of its kind to be described after the LTA of a thyroid nodule.

The surgery of the cervico-thoracic inlet is a challenge for the thoracic surgeon. Several authors have described different approaches - with different degrees of invasiveness - to this anatomical area. We used the transmanubrial osteomuscular sparing approach described by Grünenwald and Spaggiari for six patients with five different indications: 1) left anterior Pancoast tumor; 2) glomus tumor originating from the inferior trunk (C8-T1 roots) of the right brachial plexus; 3) T1 vertebral tumor; 4) right internal jugular chain, Pirogoff confluence and subclavian artery metastatic lymph nodes from thyroid carcinoma; 5) chondrosarcoma of the first left rib. The results have been satisfactory from a surgical point of view, considering that the approach gave a good exposure of the operative field (especially at the cervical level), without cosmetic problems or functional limitations. In our experience, the transmanubrial osteomuscular sparing approach is a valid technique for the treatment of several kinds of tumors of the cervico-thoracic inlet, giving a good exposure of the operative field. In the case of anterior Pancoast tumors, the upper lobectomy may necessitate a further axillary thoracotomy, when fissural adherences are present.

We report a technical modification of the classic transmanubrial osteomuscular sparing approach described by Grünenwald and Spaggiari for the treatment of a T1 vertebral tumor. The goal of the surgical treatment for spinal tumors of the cervico-thoracic area is to excise the vertebral tumor, reconstruct the spinal column, and place an internal fixation device to achieve immediate stabilization. The procedure was necessary for treating a patient who presented with an invasion of T1 vertebral body by multiple myeloma with initial neurological symptoms of epidural spinal cord compression. This approach requires a multidisciplinary team, essentially composed by the thoracic surgeon, who performs the anatomical dissection of the cervico-thoracic area, and the neurosurgeon, who performs the vertebrectomy and placement of a titanium prosthesis (Harm's cage). The operation was successful; the follow-up 6 months after the surgical procedure is normal.

Background: Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1-4 and 7-10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1-4 and 7-10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance., Results: A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33-62%). Median duration of response was 23 weeks (range, 6-70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression., Conclusions: The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects., (Copyright 2002 American Cancer Society.)

Purpose: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non-small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG)., Patients and Methods: From April 1997, patients with locally advanced or metastatic NSCLC, an age of < or = 70 years, and an Eastern Cooperative Oncology Group performance status < or = 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m(2), gemcitabine 1,000 mg/m(2), and vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m(2) on days 1 and 29 and vinorelbine 30 mg/m(2)/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival., Results: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P <.01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen., Conclusion: The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.

Purpose: To determine the maximum-tolerated dose of gemcitabine when combined with a fixed dose of vinorelbine in the treatment of non-small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the activity of this combination., Patients and Methods: Sixty-eight patients with stage IIIB/IV NSCLC were treated with vinorelbine at fixed dose of 30 mg/m(2) intravenously and gemcitabine at increasing dose levels from 800 to 1,500 mg/m(2) intravenously on days 1 and 8 every 3 weeks., Results: In phase I, dose-limiting toxicity occurred at the dosage of 1,500 mg/m(2) gemcitabine, with three of five patients developing grade 4 thrombocytopenia. In phase II, with gemcitabine at 1,200 mg/m(2), 19 (36%) of 52 assessable patients responded. Objective response was observed in 11 (39%) of 28 patients with stage IIIB disease and in eight (33%) of 24 patients with stage IV. The median time to progression was 29 weeks (range, 2 to 41 weeks; 35 weeks and 16 weeks for stages IIIB and IV, respectively), and median survival was 54 weeks (range, 2 to 84+ weeks; 63 weeks and 42 weeks for stages IIIB and IV, respectively). One-year survival was 64% for patients with stage IIIB disease and 29% for those with stage IV. Clinical benefit response was observed in 29 (59%) of 49 assessable patients. Grade 4 leukopenia and thrombocytopenia were uncommon (6% and 8% of cases, respectively); however, grade 3/4 leukothrombocytopenia occurred more frequently in patients aged more than 70 years (52% and 24%, respectively)., Conclusion: The combination of vinorelbine and gemcitabine is effective and tolerable in the treatment of NSCLC, thus deserving randomized trials with cisplatin combination regimens.

Surgical therapy of lung metastases nowadays is an established procedure. The operation's purpose is the radical and therefore potential curative resection. Beside there are diagnostic and palliative indications. Beside there are diagnostic and palliative indications. Median sternotomy is the standard approach for revision of both lungs even in unilateral seeming disease. Preoperative staging is not reliable concerning number and extension of metastases. From 1972 to 1991 843 operations for lung metastases were carried out in 729 patients in the surgical department of the "Thoraxklinik Heidelberg-Rohrbach". 30-day-mortality amounted to 2.9%, 5-year-survival-rate was 33% overall from date of metastases resection. The best results were achieved in testicular cancer with 67% 5-years-survival-rate, poorest survival was observed in melanomas with 12% 3-years-survival. Beside the primary tumor and partly dependent on it several prognostic factors were relevant: radicality, sarcoma vs carcinoma in favour of carcinomas, disease-free interval, type of resection, thoracic lymphnode involvement. As figured out by multivariate analysis the prognostic influence of the factors varies considerably due to the kind of primary tumor. Surgery of lung metastases is part of an interdisciplinary oncological therapeutical concept and offers a prolonged survival to most of the patients and the possibility of cure to some. Even if prolongation of life is not feasible an improved quality and therefore a good palliation is obtained.

2', 4'-Dimethylbenzamiloride (DMB), an inhibitor of Na(+)-Ca++ antiporter dose-dependently (10-100 microM) inhibited Na(+)-dependent 45Ca++ efflux from brain synaptosomes. This compound was also able to stimulate basal release of [3H]DA from superfused TIDA neurons. Another amiloride analogue, 5-N-methyl-N-guanidinocarbonylmethylamiloride (MGCMA, 100-300 microM), which lacks of inhibitory properties on the Na(+)-Ca++ antiporter, failed to modify basal [3H]DA release from TIDA neurons. In addition, when the antiporter operates as a Ca(++)-influx pathway, DMB dose-dependently inhibited Na(+)-dependent 45Ca++ uptake in brain synaptosomes, whereas it did not prevent K(+)-induced 45Ca++ uptake, which reflets the activation of voltage-operated Ca++ channels. Finally DMB inhibited ouabain-induced [3H]DA release, which depends on the activation of the Na(+)-Ca++ exchanger due to the inhibition of the Na+/K(+)-ATPase pump.

Hashimoto's thyroiditis is an autoimmune disease characterized by the presence of thyroid autoantibodies and frequent coexistence of other autoimmune disorders. The object of our research was to examine the peripheral blood and fine-needle cytology modifications in patients with this disease during therapy with Timopentina. Our results suggested a possible therapeutic effect of Timopentina, as an alternative to traditional cortisone treatment.

Effects of amethopterin (MTX) on lymphoid tissue of rabbit appendix have been evaluated. The drug caused an evident depletion of lymphoid cells. This finding suggested the relevance of cytotoxicity in the mechanism of immune suppression. Discontinuation of drug treatment demonstrated a tendency toward the reorganization of the lymphoid tissue.