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

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

Individualization of tacrolimus administration in renal transplant recipients: Pharmacokinetic and pharmacogenetic approach

Tacrolimus remains the centerpiece of the maintenance treatment scheme in renal transplant recipients. Both its narrow therapeutic window and its highly pharmacokinetic variance may lead to overtreatment and toxicity or insufficient treatment and transplant rejection, conditions that are usually seen in clinical practice. Our aim was to determine the impact of patient characteristics, drug-to-drug interactions and genotype (presence of CYP3A5*1 and CYP3A5*3) on the kinetics of tacrolimus in renal transplant recipients. Our patient population consisted of 40 renal transplant recipients. CYP3A5 genotyping was performed based on the following procedures: DNA extraction from blood, polymerase chain reaction and accordingly, restriction fragment length polymorphism. Statistical analysis was performed with Student’s t-test or Mann-Whitney test, according to the presence of normality of the studied parameters, linear regression analysis and general linear model-repeated measures. The frequency of CYP3A5*3/*3 genotype was 87.5% (35/40) whereas the frequency of the CYP3A5*1/*3 genotype was 12.5% (5/40). No individual homozygote for CYP3A5*1 was detected. CYP3A5*1 variant was associated with significant lower tacrolimus dose adjusted concentration. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution. Timepoint, in contrast with gender, had a statistically significant impact on tacrolimus kinetics. No statistically significant difference was observed in tacrolimus kinetics during the coadministration of omeprazole or statin. Statistically significant decrease in serum cholesterol was observed after the initiation of statin whilst renal and hepatic function remained unchanged. No skeletal muscle abnormalities were reported during the coadministration of statin. Pharmacokinetic and pharmacogenetic approach can be used to elucidate genetic and epigenetic factors that influence tacrolimus kinetics and thus, they can contribute to dose individualization.Το tacrolimus παραμένει ο ακρογωνιαίος λίθος στην ανοσοκατασταλτική αγωγή που λαμβάνουν οι ασθενείς με μεταμόσχευση νεφρού. Το στενό θεραπευτικό παράθυρο και η σημαντική ενδοϋποκειμενική και διϋποκειμενική διακύμανση της κινητικής του εκθέτει τον ασθενή στον κίνδυνο υπερδοσολογίας και πιθανής εμφάνισης τοξικότητας ή υποδοσολογίας και κινδύνου απόρριψης του μοσχεύματος. Σκοπός της παρούσας διδακτορικής διατριβής ήταν η φαρμακοκινητική και η φαρμακογενετική προσέγγιση με στόχο την εξατομίκευση της χρήσης του tacrolimus σε ασθενείς με μεταμόσχευση νεφρού. Τον πληθυσμό μελέτης αποτέλεσαν 40 ασθενείς με μεταμόσχευση νεφρού της Νεφρολογικής Κλινικής του Πανεπιστημιακού Γενικού Νοσοκομείου Πατρών. Η γονοτύπιση αφορούσε στην ανεύρεση του CYP3A5*1 και *3 αλληλομόρφου και πραγματοποιήθηκε με τη μεθοδολογία της απομόνωσης DNA από λευκά αιμοσφαίρια περιφερικού αίματος των ασθενών, την αλυσιδωτή αντίδραση πολυμεράσης για τον πολλαπλασιασμό του τμήματος ενδιαφέροντος και την ανάλυση πολυμορφισμού περιοριστικών θραυσμάτων. Για τη στατιστική ανάλυση, χρησιμοποιήθηκαν το Student’s t-test ή τo Mann-Whitney test, ανάλογα με το εάν οι μεταβλητές ακολουθούσαν κανονική ή όχι κατανομή, η μέθοδος της γραμμικής παλινδρόμησης και η μέθοδος των γενικευμένων γραμμικών μοντέλων-ανάλυση επαναλαμβανόμενων μετρήσεων. Η συχνότητα του CYP3A5*3/*3 και CYP3A5*1/*3 γονοτύπου ήταν 87,5% (35/40) και 12,5% (5/40), αντίστοιχα. Δεν ανευρέθησαν ομοζυγώτες για το CYP3A5*1 αλληλόμορφο. Ανεδείχθη συσχέτιση του CYP3A5*1 με χαμηλότερες προβλεπόμενες τιμές της προσαρμοσμένης στη δόση συγκέντρωσης και υψηλότερες προβλεπόμενες τιμές του όγκου κατανομής του υπό μελέτη φαρμάκου. Οι ασθενείς που έφεραν το CYP3A5*1 αλληλόμορφο απαιτούσαν υψηλότερες δόσεις tacrolimus για την επίτευξη της επιθυμητής συγκέντρωσης στο αίμα σε σχέση με τους ομοζυγώτες για το CYP3A5*3 νωρίς αλλά και στην απώτερη φάση μετά τη μεταμόσχευση. Η επίδραση της χρονικής στιγμής, δηλαδή του χρόνου μετά τη μεταμόσχευση, στην κινητική του tacrolimus ήταν σημαντική ενώ δεν ανεδείχθη σημαντική επίδραση του φύλου. Δεν ανευρέθη ανάγκη για πιο τακτικό έλεγχο από το σύνηθες της συγκέντρωσης του tacrolimus σε μεταμοσχευμένους νεφρούw που δεν εκφράζουν το CYP3A5 και λαμβάνουν ομεπραζόλη ή στατίνη (ατορβαστατίνη, σιμβαστατίνη, πραβαστατίνη ή φλουβαστατίνη). Η ασφάλεια και η αποτελεσματικότητα των στατινών διατηρήθηκε κατά τη συγχορήγηση με tacrolimus. Η φαρμακοκινητική και η φαρμακογενετική προσέγγιση αναδεικνύουν τις γενετικές και επιγενετικές εκείνες παραμέτρους που επηρεάζουν την κινητική του tacrolimus και συμβάλλουν στην εξατομίκευση της χορήγησής του

Investigation of clinical interaction between omeprazole and tacrolimus in CYP3A5 non-expressors, renal transplant recipients

Paraskevi F Katsakiori1, Eirini P Papapetrou2, Dimitrios S Goumenos3, George C Nikiforidis4, Christodoulos S Flordellis1Departments of 1Pharmacology, 3Internal Medicine-Nephrology, 4Medical Physics, School of Medicine, University of Patras, Rion, Greece; 2Center for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USABackground: As proton pump inhibitors share CYP3A4 enzyme with tacrolimus for their hepatic elimination, they potentially affect its pharmacokinetics, most prominently in patients with CYP2C19 or CYP3A5 gene mutations. Our aim was to investigate the impact of omeprazole on tacrolimus pharmacokinetics in CYP3A5 non-expressors, kidney transplant recipients.Methods: Twelve patients (five males/seven females) were observed for 175 ± 92.05 days. Omeprazole (20 mg pos) was administrated for 75.83 ± 45.17 days. Immunosuppressant regimen consisted of tacrolimus (n = 12), methylprednisolone (n = 10), mycophenolate mofetil (n = 11), azathioprine (n = 1), and everolimus (n = 2). Patient’s body weight, coadministered drugs, and tacrolimus trough levels were monitored. Aspartate and alanine aminotransferase, γ-glutamyltransferase, and bilirubin were used for evaluating hepatic function. Tacrolimus kinetics were estimated with daily dose, concentration, dose adjusted concentration, and volume of distribution with and without coadministration of omeprazole. CYP3A5 genotyping was performed with PCR followed by restriction fragment length polymorphism analysis. Statistical analysis was performed with Prism 4 software (GraphPad Software, Inc).Results: No statistically significant difference was observed in tacrolimus kinetics and hepatic function during coadministration of omeprazole.Conclusion: Our results let us propose that there is no need for more frequent therapeutic drug monitoring of tacrolimus when coadministrated with omeprazole in CYP3A5 nonexpressors, though prospective studies with more patients and longer observation period are needed to confirm these findings.Keywords: CYP3A5, omeprazole, renal transplantation, tacrolimu

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

Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach

<p><b>Background:</b> The aim of our study was to determine the impact of CYP3A5*1 and CYP3A5*3 on the kinetics of tacrolimus in renal transplant recipients.</p> <p><b>Material and methods: </b>Forty kidney recipients were selected to participate. Maintenance scheme consisted of tacrolimus, a purine inhibitor and a steroid. CYP3A5 genotyping was performed with PCR and RFLP. Pharmacokinetic model was developed with Linear Regression and General Linear Model repeated measures approach. The impact of sex, CYP3A5*1 allele, age at transplantation, hepatic and renal function on tacrolimus kinetics was examined.</p> <p><b>Results:</b> The frequency of CYP3A5*3/*3 and CYP3A5*1/*3 genotype was 35/40 and 5/40, respectively. No CYP3A5*1/*1 was detected. CYP3A5*1 variant was associated with significant lower TAC dose adjusted concentration at 3, 6, 12 and 36 months after transplantation. Hepatic and renal function showed a significant effect on tacrolimus dose adjusted concentration 3 months after transplantation (p=0.000 and 0.028, respectively). Sex did not show a significant impact on tacrolimus kinetics. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution.</p> <p><b>Conclusion:</b> We proved that CYP3A5*1 carriers need higher tacrolimus dose than CYP3A5*3 homozygotes to achieve the target blood concentration.</p

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