Governance forms drivers in bio-pharmaceutial inter-firm relationships

Since the first theoretical papers on Transaction Cost Economy, several studies have addressed the problem of designing governance forms in inter-firm relationship. Scholars have deeply investigated the problem and several theories have been proposed to face with it. The biopharmaceutical industry is one of the most interesting testbed for understanding dynamics and rationality of governance forms in IFRs; indeed, in this industry the advent of the biotechnology has not been disruptive as in other industries, so that the new comers, the biotech companies, and the incumbents, the pharmaceutical ones, have incurred in several types of IFRs such as licencing agreements, non equity alliances, equity alliances and mergers and acquisitions. Thus, several papers have tried to investigate what kind of drivers influence the choice of the governance form in this industry, but most of them have focused on general characteristics of inter-firm agreements, such as the investment specificity, the number of prior ties, the technology distance and so forth. Differently from other researchs, in this paper, we focus on specific characteristics of IFRs in the biopharma industry and we build a theoretical framework consisting of 13 drivers that are able to influence the governance mode of IFRs in this industry. We test our theoretical framework through an explorative empirical analysis. Even if more confirmative empirical analysis is needed, the empirical results evidence the validity of the theoretical framework proposed in this paper and provide some interesting managerial implications

Comparison of Sexual Function in Transsexual Women Who Underwent Sex Reassignment Surgery by Two Different Techniques

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Factors predictive of shockwave lithotripsy failure for ureteral stones: Why we need to hurry

Background: The Aims of This Study Are to Evaluate The Prognostic Factors of Extracorporeal Shockwave Lithotripsy In Patients With Ureteric Stones, and to Identify Which Patients Might Directly Benefit of An Endoscopic Treatment. Methods: We Performed a Prospective Study From January 2013 and July 2016 On Patients With Single Ureteric Stone and Undergoing Extracorporeal Shockwave Lithotripsy (Swl). We Divided Patients Into Two Groups: First Group (Success Group) Included Cases Resolved With Swl Only, and a Second Group (Failure Group) Including Patients With Stone Not Resolved By Swl and Requiring An Endoscopic Treatment. We Evaluated Age, Weight, Height, Body Mass Index, Stone Size, Hydronephrosis, Laterality, Location, Days Elapsed From Onset of Symptoms to Swl and Stone Density When Computed Tomography Was Performed. In Case of Stone Fragments >4 Mm, The Procedure Was Repeated Up to a Maximum of Three Times. Swl Was Considered As Failed If Patients Had a Residual Stone of Any Size After a Follow-Up of 3 Months or If a Complication Occurred. Results: 274 Patients Completed Follow-Up and Were Enrolled In The Study. Mean Age Was 53.22 Years (Standard Deviation: 13.98). Swl Overall Success Rate Was 84.3% (231 Patients Successfully Treated With Shockwaves) and Failure Rate Was 15.7% (43 Patients Underwent Auxiliary Endoscopic Procedure). At The Univariate Analysis, We Observed a Statistically Significant Difference for Hydronephrosis (P=0.006), Time Elapsed From Symptoms Onset (P=0.013), Patients\u2019 Age (P=0.06) and Mean Stone Density (0.023). In The Multivariate Logistic Regression, Patients\u2019 Age (or: 1.517), and Time Elapsed From Obstruction to Swl (or: 3.005) Were Independent Predictive Factors for Swl Failure. Furthermore, Moderate and Severe Hydronephrosis Seemed to Be Independent Predictive Factors for Swl Failure, Presenting An or of 2.451 and 4.207 Respectively. High Stone Density Resulted to Be a Predictive Factor for Swl Failure (or: 2.293 If Density Was Higher Than 1100 Hounsfield Units). Conclusions: We Report a Large Series of Patients Undergone Primary Swl for Ureteric Stones. Our Data Demonstrated The Role of Hydronephrosis, Time Elapsed From Obstruction Onset to Treatment and Stone Density As Independent Predictive Factors of Swl Failure

S9-Fibronectin, EGF-R, HB-EGF:biomarkers of urothelial damage during intravesical adjuvant therapy?

Intravesical chemotherapy and immunotherapy with BCG represent the standard therapy to prevent recurrence after transurethral resection (TUR) of non-muscle invasive bladder cancer (NMI-BC). Maintenance for at least one year is considered the best regimen. Noteworthy, a relevant number of patients do not complete the planned treatment due to local toxicity of the drug given intravesically1, 2. A major challenge for the urologists is to identify an early urothelial damage biomarker to prevent severe local toxicity requiring treatment interruption and to improve patient's compliance. The preliminary purpose of our research was to verify the possible correlation between urothelial damage induced by intravesical treatment and the expression of potential biomarkers in urine or bladder washing solution. Fibronectin (FN), Epidermal Growth Factor-Receptor (EGF-R) and Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) have been preliminary investigated. The urinary HB-EGF expression in patients with interstitial cystitis has been already analyzed by some studies3, 4, 5 The biomarkers trend during therapy with hyaluronic acid and chondroitin sulphate solution will be investigated. Materials and Methods: we collected 50 ml urine and bladder washing solution during intravesical therapy in 55 patients after NMI-BC TUR and in 10 healty controls for a total of 200 samples. After centrifugation, total cellular RNA was isolated from the cell pellett using miRNeasy Mini Kit (Qiagen®) according to the manufacturer's instructions. We investigated FN and EGF-R gene expression by Real Time quantitative PCR. Finally, the abundance of HB-EGF in urine samples was measured using Enzyme-linked immunosorbent assay (ELISA) (Abcam®) following manufacturer's instructions. Results: The FN gene expression levels in NMI-BC compared with controls were increased 4.7 fold while EGF-R levels were decreased 0.9 fold. In the patients in whom local toxicity due to intravesical therapy was clinically relevant, the FN gene expression levels were increased 5.82 fold, and the EGF-R one was decreased 0.88 fold. In contrast patients before starting therapy or with a good tolerance showed gene expression levels increased 1.9 fold for FN and 1.1 fold for EGF-R. In patients receiving hyaluronic acid and chondroitin sulphate solution to treat the severe vesical toxicity the average FN gene expression levels were decreased from 3 to 0.6 fold, with concomitant symptomatic improvement. HB-EGF protein levels in urine in patients receiving intravesical chemo or immunotherapy were increased 1.2 fold compared to controls and remained unchanged during therapy. No fold change was detected in patients treated with hyaluronic acid and chondroitin sulphate solution. Our preliminary data will be updated in the final presentation. Statistical analysis is ongoing. Conclusion: EGF-R gene expression in the bladder washing solution and HB-EGF levels in urine did not show significant fold change in relation to urothelial damage compared to controls. Preliminarly, FN gene expression in bladder washing solution showed an overexpression during urothelial damage and decrease after therapy with hyaluronic acid and chondroitin sulphate solution in correlation to symptoms relief

COMPLIANCE WITH ONE YEAR MAINTENANCE INTRAVESICAL BCG IN PATIENTS AFFECTED BY T1G3 BLADDER CANCER

Introduction: BCG maintenance for at least one year is the best regimen for prevention of recurrence and progression in high risk non muscle invasive bladder cancer (NMIBC), undergoing conservative approach. Noteworthy, a relevant number of patients do not complete the planned treatment interruption. Study aim was to analyze retrospectively the reasons of treatment. Patients and Methods: Consecutive patients affected by T1G3 BC, undergoing BCG maintenance for one year, according to the SWOG schedule (3 weekly instillations at 3, 6, 12 months) were included in this study. Connaught BCG (81 mg/50 ml) was given starting 1430 days after TUR. If toxicity occurred, treatment was postponed up to two weeks. No dose reduction was considered. The patients’ compliance with the treatment was analyzed. Results: Out of 160 patients, 148 (92.5%) completed the induction cycle. In 10 (6.3%) more patients a recurrence was detected. In 15 (9.4%) patients induction only was planned due to personal difficulties. In 123 patients (76.8%) maintenance for one year was planned. However, 8 patients never started and 67 (54.4%) completed only one year maintenance: 6 (4.8%) interrupted for toxicity and 9 (7,3%) for recurrence. Compliance decreased from 84.5% at 3 to 57,7% at 12 months, 56 (45.6%) patients not completing one-year. In particular 109 patients (83.8%) completed the maintenance at 3 and 88 (67.2%) at 6 months. Noteworthy, mild grade I BCG toxicity, not requiring therapy on urologists’ opinion, was recorded in 91 (74%) out of 123 patients in whom maintenance was planned. Main limit was the retrospective nature of the study. Conclusion: Maintenance interruption was due to moderate-severe toxicity in only 5% of the patients. The poor patient’s compliance was probably multifactorial, partially related to grade I toxicity, not taken into appropriate account by the urologists. A correct and periodical counselling with the patients undergoing BCG maintenance regimen could ameliorate the compliance to BCG

PRELIMINARY DATA ON PSA CHANGES DURING INTRAVESICAL THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

Introduction/Aim: Many factors can cause an increase of PSA independently from the presence of prostate cancer . The objective was to evaluate the fluctuation of the serum levels of PSA during adjuvant intravesical chemotherapy or immunotherapy. An increase of PSA due to intravesical BCG and up to 3 months later has been reported (1). Patients and Methods: Patients treated with intravesical chemotherapy or immunotherapy for non- muscle invasive bladder cancer (NMIBC) were entered in the study. Serum samples were collected before starting intravesical therapy, during therapy (within 3rd and 6th instillation) and 30 days after the end of the 6-week induction regimen and during maintenance regimen when given. Patients with urinary tract infections, history of chronic prostatitis, elevated PSA before starting intravesical therapy, palpable prostate nodule or prostate cancer were not included. Results: Forty-five patients were studied, 34 receiving chemotherapy and 11 BCG. Thirty-three patients completed the induction regimen and in 12 more patients the research is ongoing. Out of the 33 evaluable patients, 23 received chemotherapy (mitomycin or epirubicin), while 10 immunotherapy (BCG Connaught). The pre-induction PSA mean level was 2.9 ng/ml.We observed a median PSA increase of 33,5% (p<0.0001) during therapy, in 18 (54.5%) patients. Twelve patients (36.3%) showed a median PSA decrease of 31.4% (p=0.3638). In two patients only (6%) PSA remained unchanged.We also observed a median increase of serum PSA levels of 87.4% at one month after the end of induction regimen. No significant difference between serum PSA level fluctuations induced by chemotherapy or BCG was detected: median increases during therapy and 30 days after the end were 91.7% and 149, 7% and 91.7% and 133% respectively (p<0.001). Discussion and Conclusion: Our preliminary study shows a clinically relevant increase of serum PSA levels in men undergoing both adjuvant intravesical BCG or chemotherapy. We confirm the results of the few studies reporting the increase of PSA during intravesical therapy with BCG or chemotherapy (2). The above mentioned variations should be considered when selecting patients undergoing prostate biopsy

Studio pilota sul valore predittivo dei livelli plasmatici di 9 fattori angiogenetici nella selezione di pazienti candidati alla biopsia prostatica

To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients' selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels ( 654 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A potential cut-off level was computed. Fifty patients were entered. Median PSA was 6.8 ng/mL. A prostate nodule was palpable in 18 (36%) patients. The median number of biopsy cores was 12. Prostate cancer was detected in 25 (50%) and ASAP and PIN in 2 more patients (4%) respectively. Among the 9 considered biomarkers, only leptin showed an interesting diagnostic performance with an AUC of 0.781, at a cut-off value of 2.11 ng/mL, demonstrating a sensitivity of 78%, a specificity of 77% and a positive predictive value of 85%. Main limitations of our study are the exploratory design and the criteria adopted for patients' selection determining a detection rate for prostate cancer above the usual range. Leptin only, in our preliminary study, shows promising diagnostic accuracy for the selection of patients candidate to prostate biopsy. Further studies are required to confirm its diagnostic value and its relation with BMI