Addressing recurrent hypoglycaemia through thoracic surgical intervention: understanding Doege-Potter syndrome, a rarity in syndromes.

Doege-Potter syndrome (DPS), a rare paraneoplastic phenomenon characterised by non-islet cell tumour hypoglycaemia (NICTH), presents clinicians with intricate diagnostic and therapeutic challenges. This comprehensive review consolidates current understanding, clinical presentations, diagnostic modalities, therapeutic interventions, and emerging trends in managing DPS. The pathophysiology of DPS revolves around dysregulated insulin-like growth factors (IGF), particularly IGF-2, produced by mesenchymal tumours, notably solitary fibrous tumours (SFT). Clinical manifestations encompass recurrent hypoglycaemic episodes, often distinct from typical hypoglycaemia, with implications for insulin and counterregulatory hormone levels. Diagnosis necessitates a multidisciplinary approach integrating biochemical assays, imaging studies, and histopathological confirmation of the underlying neoplasm. Surgical resection remains the cornerstone of treatment, complemented by adjunctive therapies to manage persistent hypoglycaemia. Prognosis is influenced by successful tumour resection and long-term surveillance for recurrence. A patient-centred approach, incorporating supportive services and multidisciplinary care, is essential for optimal outcomes in individuals affected by DPS.

Secondary aortoenteric fistula: a narrative review of the view of the surgeon.

Aortoenteric fistula (AEF) is defined as the abnormal communication between the aorta and the gastrointestinal tract. AEFs are divided into primary and secondary usually after abdominal aortic aneurysm (AAA) recovery and are a rare but quite dangerous cause of gastrointestinal bleeding that the general surgeon may face during his/her career. Secondary AEF was first described in 1953 to a 44-year-old woman 3 months after an AAA operation. This review presents the role of the surgeon in the management of secondary aortoenteric fistulas. AEFs are a rare but fatal gastrointestinal bleeding cause that the general surgeon may be asked to manage. Diagnosis requires the combination of strong clinical suspicion and the presence of a history of AAA surgery. Although a vascular surgery case, general surgeons play a role in choosing the technique of restoring the intestinal tract, which seems to be significantly related to subsequent morbidity and mortality.

Demographic and clinical characteristics of patients with varicose veins in Albania: a retrospective, single-centre analysis.

Introduction: Chronic venous disease (CVD) constitutes a frequently underdiagnosed pathological condition that progressively diminishes patients' quality of life and imposes an escalating strain on healthcare resources. This study aims to comprehensively investigate the epidemiological landscape of varicose vein disease, examining age group distributions, gender patterns, residence influences, marital status correlations, weight considerations, educational impacts, and various aspects related to varicose veins. Material and methods: This was a single-centre retrospective analysis, in Albania from May 2018 to September 2023. Data were collected retrospectively through hospital records. Data collection involved administering a structured questionnaire to study participants, categorically organised into three sections. The first section focused on collecting demographic information, the second section involved self-perception of identifying risk factors associated with varicose veins, and the final section included inquiries about the history of variceal surgery. Results: The CEAP classification distribution in our cohort revealed a predominant presence of C2 (varicose veins) in 53.3% of patients, followed by C3 (oedema) at 29.2%, and C4 (changes in skin and subcutaneous tissue secondary to CVD) at 10.5%, whereas C5 (healed venous ulcer) and C6 (active venous ulcer) were less frequent. Based on the body mass index (BMI) scale, data from patients indicated that 9.7% were in the category of underweight, 54.8% had a normal BMI, and 35.5% were categorised as overweight. Conclusions: The study's thorough exploration of patient perspectives, risk factors, and treatment choices contributes to a holistic understanding of varicose vein management, emphasising the importance of personalised approaches that account for demographic variations and individual beliefs.

Assessment of stone ablation rate using the Moses technology modes with different energy and pulse settings: An experimental study.

Objectives: To compare lithotripsy ablation rate with the Moses modes versus conventional pulse modes when using the Holmium:Yttrium-Aluminum-Garnet (Ho:YAG) laser. Methods: The Lumenis® Pulse P120H Holmium Laser System and a 365 µm Moses D/F/L fiber were used to assess stone ablation rate in conventional Short and Long Pulse as well as Moses Contact and Distance at 10 W (0.5Jx20Hz and 2Jx5Hz) and 60 W (1Jx60Hz and 2Jx30Hz). Hard and soft phantom stones were formed, and all tests were conducted in a custom experimental configuration installed in a saline-filled bath. The laser was delivered up to 3 kJ of total energy. The fragmentation pattern was assessed via photographs in each cohort. Results: The time to reach the target energy was 5 min and 50 s in all 10 W and 60 W trials, respectively. In both stone types, ablation was more effective when high-power, high-energy and Moses Distance was utilized. In soft stones, the lowest ablation rate was detected in the Long Pulse modality in all power, energy and frequency settings. Overall, when dusting settings (high-frequency, low-energy) were used, a deeper single cavitation was observed rather than small cavitations. Conclusions: The most effective pulse modality as evaluated via stone ablation rate depends on the stone hardness as well as energy and frequency settings. In both hard and soft stones, ablation is more effective when 60 W (2Jx30Hz) power settings and Moses Distance are used. Tailored laser settings in terms of energy and frequency could be set for each case scenario.

High-power Holmium:Yag lithotripsy in bladder urolithiasis: Is it safe and effective? A combined clinical and experimental study.

Objective: To evaluate the efficacy and safety of Holmium: Yttrium-Aluminum-Garnet (Ho:YAG) laser in bladder lithotripsy using high-power settings > 100 W. Materials and Methods: A combined experimental and clinical study was conducted. The Quanta Cyber: Ho 150 with a 550 µm Quanta optical fiber was utilized in all set-ups. Ablation rates for soft and hard artificial stones were tested in vitro using 100 W and 20 W power settings. In the experiment, a porcine bladder was used. The optical fiber was inserted through a rigid cystoscope, whilst a K-type thermocouple was inserted in the bladder dome. The tested high-power settings were 152 W, 120 W and 105 W. In every trial, the lasing time was over 60 s. In the clinical study, 35 patients underwent transurethral high-power bladder lithotripsy. Laser settings were set between 100 W and 150 W. Results: Stone mass (stone weight) was significantly lower after stone ablation independently of the stone type or the laser settings. Significantly higher mass decrease and ablation rate were detected in high-power compared to low-power settings. In the experiment, the highest temperature recorded was 32°C at 152 W. At 120 W and 105 W, the peak temperatures didn't reach 30°C. In the clinical study, a stone-free rate of 100% and a mean operative time of 43 ± 18 min were reported. All patients stayed in the hospital for one day except for one who presented minor hematuria. Additional complications did not occur. Conclusion: Ho:YAG laser lithotripsy > 100 W is an effective, fast and safe modality for the treatment of bladder calculi.

Novel Robotic Platforms for Robot-Assisted Laparoscopic Surgery in Urology: A Narrative Review.

Robot-assisted surgery (RAS) has been integrated into clinical practice to overcome several limitations of conventional open or laparoscopic surgery. After the expiration of the long key patent period of Intuitive Surgical, various robotic systems (RSs) have been developed aiming at improving certain characteristics of the first robotic platform, the Da Vinci RS. This narrative review provides an overview of the current RSs used in urology along with the initial results from their application in urologic procedures. Nine robotic platforms are being analyzed regarding their unique characteristics as well as their efficacy, safety, feasibility, and outcomes in urologic, oncological, or non-oncological operations. The main barrier to the wide application of RAS has been the increased cost that refers to both acquisition and maintenance costs. Besides, the health inequality resulting from the lack of expert robotic surgeons and the difficulty of performing robot-assisted procedures in provincial hospitals should be overcome. However, large properly designed comparative studies are required to establish the role of newly introduced RSs. In addition, urologists should keep abreast of new developments and research in robot-assisted urologic procedures.

Challenges and pitfalls in the perioperative management of mediastinal mass syndrome: an up-to-date review.

The perioperative management of patients undergoing mediastinal mass operations presents a persistent challenge across multiple clinical specialties. General anesthesia administration further increases the risk of perioperative cardiorespiratory decompensation. The interdisciplinary team plays a crucial role in ensuring a safe perioperative period. However, due to the rarity and variability of mediastinal mass syndromes, specific management protocols are lacking. This review aims to outline the multitude of challenges and pitfalls encountered during perioperative management in patients with the mediastinal mass syndrome. We describe diagnostic evaluation, preoperative optimization, intraoperative considerations, and postoperative care strategies, emphasizing the paramount significance of a multidisciplinary approach and personalized treatment plans. Preoperative multidisciplinary discussions, meticulous anesthetic management, and well-established protocols for emergency situations are pivotal to ensuring patient safety. Healthcare providers involved in the care of patients with mediastinal mass syndrome must grasp these challenges and pitfalls, enabling them to deliver safe and effective perioperative management.

Knowledge and Attitudes of Medical and Nursing Students in a Greek University Regarding Sexually Transmitted Diseases.

AIMS AND OBJECTIVES: the present study aimed to assess the knowledge and attitudes of medical and nursing students at the University of Patras, western Greece, regarding sexually transmitted infections (STIs), sexual behavior and STI prevention measures, as well as the level of future healthcare professionals' education. METHOD: A descriptive, cross-sectional study was conducted. A total of 231 medical and nursing students (n = 106 medical, and n = 125 nursing) completed and returned the pre-tested study questionnaire. RESULTS: Most participants (77.5%) were females and46.1% were in the age group of 18-21 years. Syphilis, HIV/AIDS, and Hepatitis B were regarded as STIs by 65.8% of them. Medical students could predominantly list the widely known STIs compared to nursing students (p = 0.004). Regarding HIV/AIDS, 72.7% of the respondents reported that it is transmitted sexually and through blood transfusion. However, medical students were better informed than nursing students (p = 0.001). Medical students as well as students in the final year of their studies were found to be better informed about the vaccines available to prevent STIs. Regarding the question about what constitutes a risky sexual behavior, 71.4% answered sexual intercourse without the use of condom and 18.6% indicated having sex with an unknown partner. Most participants (69.7%) were satisfied with the education provided by their institution and no statistically significant difference was observed between medical and nursing students. Almost all students (97.8%) agreed that the course/subject of sex education must be included in school programs. CONCLUSIONS: A comprehensive analysis of knowledge and attitudes of Greek medical and nursing students regarding STIs, prevention measures and education level was conducted. The results of the present study could assist in the development of targeted training courses that can improve healthcare professionals' knowledge and ability to manage STIs.

Endoscopic enucleation of the prostate with Thulium Fiber Laser (ThuFLEP). A retrospective single-center study.

PURPOSE: The aim of the present, retrospective study was to describe our initial experience and early outcomes of Thulium Fiber Laser enucleation of the prostate (ThuFLEP) with the use of the FiberDust™ (Quanta System, Samarate, Italy) in patients with benign prostate hyperplasia. METHODS: From June 2022 to April 2023, all patients who underwent endoscopic enucleation of the prostate at Urology Department of the University Hospital of Patras were included. A single surgeon utilizing the same standardized operative technique performed all the surgeries. The primary endpoints included the uneventful completion of the operation, the surgical time and any minor or major complication observed intra- or post-operatively. RESULTS: Twenty patients with benign prostate hyperplasia were treated with ThuFLEP. All the surgeries were completed successfully and uneventfully. The enucleation phase of the operation was completed in a mean time of 45±9.1 min, while the average time needed for the morcellation was 17.65±3.42 min. No significant complications were observed intra- or post-operatively. The average hemoglobin drop was calculated to be 0.94±0.71 g/dL. CONCLUSIONS: All the operations were successfully and efficiently completed with the use of the FiberDust™ (Quanta System, Samarate, Italy) in ThuFLEP. Significant blood loss or major complications were not observed.

How long do we need to reach sufficient expertise with the avatera® robotic system?

PURPOSE: To investigate the learning curve in four basic surgical skills in laparoscopic and robotic surgeries, and evaluate the approximate time needed to reach sufficient expertise in performing these tasks with the avatera® system. METHODS: Twenty urology residents with no previous experience in dry-lab and robotic surgery were asked to complete four basic laparoscopic tasks (peg transfer, circle cutting, needle guidance, and suturing) laparoscopically and robotically. All participants were asked to complete the tasks first after watching the Uroweb educational material and, second, after undertaking a 2-hour training in robotic and laparoscopic dry-lab. Thereafter, all trainees continued to undertake 2-hour training programs until being able to complete the tasks with the avatera® robot at the desired time. Paired t test and one-way ANOVA test were used to analyze time differences between the groups. RESULTS: Time needed to complete all tasks either robotically or laparoscopically was significantly less in the second compared to the first attempt for all Groups in each Task. In the robotic dry-lab, time needed to complete the tasks was significantly less than in the laparoscopic dry-lab. A significant effect of previous laparoscopic experience of the participants on the training time needed to achieve most of the goal times was detected. CONCLUSION: The results of the study highlight the role of previous laparoscopic experience in the training time needed to achieve the performance time goals and demonstrate that the learning curve of basic surgical skills using the avatera® system is steeper than the laparoscopic one.

Nonpapillary Prone Endoscopic Combined Intrarenal Surgery (ECIRS): Five-Year Experience and Outcomes from a High-Volume Center.

Endoscopic combined intrarenal surgery (ECIRS) provides simultaneous retrograde and percutaneous access to the upper urinary tract. The purpose of this study is to present revised data, tips and tricks, and technique modifications arising from our five-year experience with ECIRS. The data of 62 patients who underwent nonpapillary prone ECIRS from January 2019 to November 2023 were prospectively collected. All cases were performed in the prone position. Inclusion criteria were complex stone cases with stones in multiple calyces requiring either multiple accesses or multiple sessions to achieve stone-free status. Patients' mean age was 54.4 ± 12.39 years, while the mean stone size was 39.03 ± 13.93 mm. The mean operative time was 51.23 ± 17.75 min. Primary and final stone-free rates were 83.8% and 90.3%, respectively. In total, nine patients presented with postoperative complications, which were all Grade II ones. The holmium-YAG laser type during retrograde lithotripsy was associated with significantly shorter operative times compared to the thulium fiber laser. Nonpapillary prone ECIRS is a feasible, safe, and efficient approach for patients with specific stone and anatomy characteristics. The implementation of more, higher-evidence studies is of utmost importance so that safer conclusions can be drawn.

IDEAL-D Phase 0 Evaluation of the Avatera System in Robot-Assisted Prostate, Bladder and Renal Surgery.

Purpose: To evaluate the utilization of novel Avatera system in urological operations according to the IDEAL-D framework recommendations for high-risk invasive surgical devices. Materials and Methods: Three surgeons attempted to perform 23 upper and lower urinary tract operations on human cadavers and in live porcine models using the Avatera system. Total operative time and the duration of the substeps were evaluated. Surgical performance was assessed with the Global Evaluative Assessment of Robotic Skills (GEARS) score. Suturing was rated using the technical checklist for the assessment of suturing in robotic surgery. Attending surgeons rated their satisfaction with the Avatera system on a scale of 1-5. Results and Limitation: Seventeen out of 18 operations performed on cadavers were completed, while one pyeloplasty was discontinued. All five operations performed in porcine models were completed. Although 1 pig was euthanized on the fifth postoperative day, its symptoms were unrelated to surgery. Mean GEARS and Suturing scores in the upper urinary tract were 29 ± 0.7 and 29.5 ± 0.95, respectively, and in the lower urinary 28.5 ± 1.2 and 29.5 ± 0.5, respectively. Surgeons' satisfaction was high or very high for all procedures. Conclusions: The Avatera system was associated with good surgical performance and high surgeons' satisfaction rates. All urological procedures performed were shown to be feasible, with comparable risks to other robot-assisted surgery systems.

Robot-assisted radical prostatectomy using the avatera system™: a prospective pilot study.

BACKGROUND: Robot-assisted radical prostatectomy is a minimally invasive, safe procedure preferred in the management of localized prostate cancer. In this study, we present our initial experience with the avatera™ system (avateramedical GmbH, Jena, Germany) in robot-assisted radical prostatectomy. METHODS: A total of fourteen patients underwent robot-assisted radical prostatectomy using this newly introduced system in our department from June 2022 to October 2022. The primary endpoints of the study were the time and the successful completion of the operation, the hemoglobin drop and the presence of complications. The pathologic tumor stage and the presence of positive surgical margins were also recorded. Follow-up of the patients for the functional outcomes over a period of 3 months took place. RESULTS: The completion of all the surgeries was successful. The median draping and docking times were 9.5 minutes (7-13) and 10 minutes (5-40), respectively. The median console time was 103.5 minutes (90-121). No conversion to laparoscopic or open prostatectomy was necessary. The median hemoglobin drop was 1.95 g/dL (0.3-2.7), while positive surgical margins were present in two patients postoperatively. No major complications or need for transfusion were noticed. Six months after the procedure, 78.6% of the participants were continent while 77.7% of the nerve-sparing patients reported erections adequate for intercourse. CONCLUSIONS: All the operations were completed successfully without major complications or significant blood loss. The functional outcomes were acceptable according to the literature. Based on the early outcomes, robot-assisted radical prostatectomy with the avatera™ system (avateramedical GmbH) could be considered feasible, safe, and efficient.

Replicating Florence Intracorporeal Neobladder Technique in Laparoscopic Radical Cystectomy: A Retrospective Study.

OBJECTIVE: To evaluate retrospectively the feasibility of Florence robotic intracorporeal neobladder technique in laparoscopic radical cystectomy. METHODS: Fourteen patients with muscle-invasive bladder cancer underwent laparoscopic radical cystectomy and Florence robotic intracorporeal neobladder between September 2021 and February 2023. Patients' characteristics, pathology data, perioperative outcomes, postoperative complications, and follow-up data were collected. RESULTS: All operations were successfully completed laparoscopically. The median total operative time was 343 minutes, and the median estimated blood loss was 169.5 mL. No intraoperative complications were observed. The median hospitalization time was 7days, while the median time to regular diet was 3days. Clavien Dindo Grade < III complications appeared in five patients within 30days postoperation. No other complications were noted over the 90days follow-up. Organ-confined disease was confirmed in 11 patients and locally advanced disease in three patients. At 3months follow-up, eight and four patients were daytime and night-time continent, respectively. CONCLUSION: Replicating Florence robotic intracorporeal neobladder in laparoscopic radical cystectomy is safe, feasible, and repeatable, based on the encouraging perioperative, oncological, and functional outcomes of our study. However, further prospective studies on a larger scale are required to prove its long-term results.

Feasibility study of a novel robotic system for transperitoneal partial nephrectomy: An in vivo experimental animal study.

PURPOSE: To evaluate the safety and feasibility of partial nephrectomy with the use of the novel robotic system in an in vivo animal model. METHODS: Right partial nephrectomy was performed in female pigs by a surgical team consisting of one surgeon and one bedside assistant. Both were experienced in laparoscopic surgery and trained in the use of the novel robotic system. The partial nephrectomies were performed using four trocars (three trocars for the robotic arms and one as an assistant trocar). The completion of the operations, set-up time, operation time, warm ischemia time (WIT) and complication events were recorded. The decrease in all variables between the first and last operation was calculated. RESULTS: In total, eight partial nephrectomies were performed in eight female pigs. All operations were successfully completed. The median set-up time was 19.5 (range, 15-30) minutes, while the estimated median operative time was 80.5 minutes (range, 59-114). The median WIT was 23.5 minutes (range, 17-32) and intra- or postoperative complications were not observed. All variables decreased in consecutive operations. More precisely, the decrease in the set-up time was calculated to 15 minutes between the first and third attempts. The operative time was reduced by 55 minutes between the first and last operation, while the WIT was decreased by 15 minutes during the consecutive attempts. No complications were noticed in any operation. CONCLUSIONS: Using the newly introduced robotic system, all the advantages of robotic surgery are optimized and incorporated, and partial nephrectomies can be performed in a safe and effective manner.

Robot-assisted pyeloplasty for ureteropelvic junction obstruction: initial experience with the novel avatera system.

PURPOSE: This pilot study was designed to interpret the technically specific features of the avatera robotic system and present our initial experience with this novel platform in robot-assisted pyeloplasty (RAP). METHODS: A single-center prospective study was conducted including all patients who underwent RAP with the avatera robotic system from June 2022 to October 2022 in our Department. Transperitoneal robot-assisted dismembered pyeloplasty was performed in all cases. The trocar placement and the surgical technique were similar in all patients. The successful completion of the procedures, operation time (including draping, docking and console time), decrease in hemoglobin postoperatively, and presence of any complications were the study's primary endpoints. RESULTS: In total, nine patients underwent RAP using the avatera system. All procedures were successfully completed. The draping of the robotic unit was completed in a median time of 10 min (range 7-15), while the median docking time was 17 min (range 10-24). The median console time was 88 min (range 78-116) and no complications were noticed. The median hemoglobin drop was calculated to 0.7 g/dL (range 0.4-1). During the mean follow-up of 9.33 ± 2.78 months, no late postoperative complications were noticed. CONCLUSION: The early outcomes of the use of the novel avatera system in RAP are presented. All operations were successfully completed with safety and efficacy, without complications or significant blood loss.

Automatic quantitative analysis of in-stent restenosis using FD-OCT in vivo intra-arterial imaging.

PURPOSE: A new segmentation technique is implemented for automatic lumen area extraction and stent strut detection in intravascular optical coherence tomography (OCT) images for the purpose of quantitative analysis of in-stent restenosis (ISR). In addition, a user-friendly graphical user interface (GUI) is developed based on the employed algorithm toward clinical use. METHODS: Four clinical datasets of frequency-domain OCT scans of the human femoral artery were analyzed. First, a segmentation method based on fuzzy C means (FCM) clustering and wavelet transform (WT) was applied toward inner luminal contour extraction. Subsequently, stent strut positions were detected by utilizing metrics derived from the local maxima of the wavelet transform into the FCM membership function. RESULTS: The inner lumen contour and the position of stent strut were extracted with high precision. Compared to manual segmentation by an expert physician, the automatic lumen contour delineation had an average overlap value of 0.917 ± 0.065 for all OCT images included in the study. The strut detection procedure achieved an overall accuracy of 93.80% and successfully identified 9.57 ± 0.5 struts for every OCT image. Processing time was confined to approximately 2.5 s per OCT frame. CONCLUSIONS: A new fast and robust automatic segmentation technique combining FCM and WT for lumen border extraction and strut detection in intravascular OCT images was designed and implemented. The proposed algorithm integrated in a GUI represents a step forward toward the employment of automated quantitative analysis of ISR in clinical practice.

Percutaneous trans-hepatic bilateral biliary stenting in Bismuth IV malignant obstruction.

AIM: To investigate the clinical efficiency of percutaneous trans-hepatic bilateral biliary metallic stenting for the management of Bismuth IV malignant obstructive disease. METHODS: Our hospital's database was searched for all patients suffering from the inoperable malignant biliary obstruction Bismuth IV, and treated with percutaneous bilateral trans-hepatic placement of self-expandable nitinol stents. The indication for percutaneous stenting was an inoperable, malignant, symptomatic, biliary obstruction. An un-correctable coagulation disorder was the only absolute contra-indication for treatment. Bismuth grading was performed using magnetic resonance cholangiopancreatography. Computed tomography evaluation of the lesion and the dilatation status of the biliary tree was always performed prior to the procedure. All procedures were performed under conscious sedation. A single trans-hepatic track technique was preferred (T-configuration stenting) and a second, contra-lateral trans-hepatic track (Y-configuration stenting) was used only in cases of inability to access the contra-lateral lobe using a single track technique. The study's primary endpoints were clinical success, defined as a decrease in bilirubin levels within 10 d and patient survival rates. Secondary endpoints included peri-procedural complications, primary and secondary patency rates. RESULTS: A total of 35 patients (18 female, 51.4%) with a mean age 69 ± 13 years (range 33-88) were included in the study. The procedures were performed between March 2000 and June 2008 and mean time follow-up was 13.5 ± 22.0 mo (range 0-96). The underlying malignant disease was cholangiocarcinoma (n = 10), hepatocellular carcinoma (n = 9), pancreatic carcinoma (n = 5), gastric cancer (n = 2), bile duct tumor (n = 2), colorectal cancer (n = 2), gallbladder carcinoma (n = 2), lung cancer (n = 1), breast cancer (n = 1) or non-Hodgkin lymphoma (n = 1). In all cases, various self-expandable bare metal stents with diameters ranging from 7 to 10 mm were used. Stents were placed in Y-configuration in 24/35 cases (68.6%) using two stents in 12/24 patients and three stents in 12/24 cases (50%). A T-configuration stent placement was performed in 11/35 patients (31.4%), using two stents in 4/11 cases (36.4%) and three stents in 7/11 cases (63.6%). Follow-up was available in all patients (35/35). Patient survival ranged from 0 to 1763 d and the mean survival time was 168 d. Clinical success rate was 77.1% (27/35 cases), and peri-procedural mortality rate was 5.7% (2/35 patients). Biliary re-obstruction due to stent occlusion occurred in 25.7% of the cases (9/35 patients), while in 7/11 (63.6%) one additional percutaneous re-intervention due to stent occlusion resulting in clinical relapse of symptomatology was successfully performed. In the remaining 4/11 patients (36.4%) more than 1 additional reintervention was performed. The median decrease of total serum bilirubin was 60.5% and occurred in 81.8% of the cases (27/33 patients). The median primary and secondary patency was 105 (range 0-719) and 181 d (range 5-1763), respectively. According to the Kaplan-Meyer survival analysis, the estimated survival rate was 73.5%, 47.1% and 26.1% at 1, 6 and 12 mo respectively, while the 8-year survival rate was 4.9%. Major and minor complication rates were 5.7% (2/35 patients) and 17.1% (6/35 patients), respectively. CONCLUSION: Percutaneous bilateral biliary stenting is a safe and clinically effective palliative approach in patients suffering from Bismuth IV malignant obstruction.

The multiple layers of signaling selectivity at protease-activated receptors.

The Protease-Activated Receptors (PARs) are G-protein-coupled receptors (GPCRs) characterized by a unique mechanism of activation. They carry built in their extended N-terminal structure their own activating agonist, in the form of a cryptic tethered ligand, unmasked by an irreversible proteolytic cleavage. Besides, PARs display several other particular properties, that converge and create interacting and intertwined layers of molecular processes regulating receptor's selective signaling with important biological and pharmacological consequences. These include the operation of multiple proteases, co-factors and protease inhibitors expressed in many types of cells and tissues, creating a dynamic balance between activators and inhibitors of PAR function in a tissue specific way. Membrane microdomain compartmentalization and allosteric modulation through intermolecular interactions between PARs adds further complexity to the receptor signaling and desensitization. Furthermore, molecular components interacting with thrombin and PARs take on new roles. In particular, activated protein C (APC) forms a significant negative feedback loop for thrombin with anticoagulant properties. In addition, APC exerts anti-inflammatory and direct neuroprotective effects in vivo and in vitro. This has informed the pharmacological dissection of anticoagulant from the anti-inflammatory and neuroprotective actions of APC and the generation of engineered APC mutations with diminished risk of serious bleeding, while preserving the cytoprotective effects of APC on cells. Even more important, these advances have made possible a paradigm shift, away from a "neurocentric" and towards a "vasculo-neuronal-inflammatory model of action", which supports novel pharmacological strategies targeting multiple disease mechanisms.

Tacrolimus and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: An interaction study in CYP3A5 non-expressors, renal transplant recipients.

OBJECTIVES: Atherosclerosis is a significant factor affecting long-term outcome in renal transplant recipients. Studies have been conducted to determine the pharmacogenomic pathways involved in statin efficacy, efficiency, and adverse effect likelihood. However, little is known about the influence of statins on tacrolimus kinetics. The aim of this study was to investigate possible pharmacological interactions between tacrolimus and statins in CYP3A5 non-expressors, renal transplant recipients. MATERIALS AND METHODS: Twenty-four patients, treated with tacrolimus (n=24), methylprednisolone (n=24), and mycophenolate mofetil (n=19)/azathioprine (n=1)/everolimus (n=4), participated in the study. After an observation time of 112±36 days, statins, namely, atorvastatin (n=12), simvastatin (n=8), pravastatin (n=2), or fluvastatin (n=2), were administered for additional 101±34 days. DNA was extracted from whole blood sample and polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for CYP3A5 genotyping. Student's t-test and Mann-Whitney test were used to test the significance of difference in variables that passed or did not pass Kolmogorov's normality test, respectively. RESULTS: No statistically significant difference was observed in tacrolimus daily dose, concentration, concentration/dose ratio, and volume of distribution before and during the administration of statins. Statistically significant decrease in serum cholesterol was observed after initiation of statins. Renal and hepatic function remained unchanged and no skeletal muscle abnormalities were reported. CONCLUSIONS: The results of this study show that tacrolimus and statins do not interact in terms of efficacy, efficiency, and adverse effect likelihood. No significant clinical interaction or effect was observed, even with the use of atorvastatin or simvastatin, which are metabolized by CYP3A4 such as tacrolimus.