Initial experience of the Versius robotic system in robot-assisted radical prostatectomy: a study of 58 cases.

Introduction: The study presents the initial outcomes of robot-assisted radical prostatectomies (RARPs) using the Versius robotic system in a urological centre with no prior robotic surgery experience. Material and methods: A retrospective analysis of 58 RARPs was conducted, including patients' parameters as well as Versius system performance. Results: The study involved 58 patients (average age 66.9 years). Median preoperative prostate specific antigen (PSA) was 9.8 ng/ml, with 48% having ISUP grade group ≥ 3 on biopsy and 25.8% showing extraprostatic extension on MRI. Median blood loss was 437 ml, with complications (10.3% Clavien-Dindo grade II and 4 grade III cases). One conversion to open surgery occurred (0.58%). Final pathology revealed 46.5% extraprostatic disease, and 25.8% had positive margins. Post-surgery, 96.5% had undetectable PSA at 6 weeks. Continence rates were 89.7% at 6 weeks, increasing to 91.3% at 12 months. Median catheter duration was 7.9 days, and the hospital stay was 4.5 days. Console time averaged 150.9 minutes, with a median operative time of 213 minutes. The Versius system reported medium priority alarms in 24.1% of operations, including 1266 alarms related to robotic arm clashes and 43 instrument swaps. One bedside unit exchange occurred with no console or robotic system failures. Conclusions: The Versius robotic system can be successfully introduced in a urological centre without prior robotic surgery experience. Our setup and operating room positioning are effective, safe, and reproducible. We encountered and resolved surgical and technical challenges. Further follow-up studies are needed to assess the system's performance.

Neoadjuvant Treatment in Muscle-Invasive Bladder Cancer: From the Beginning to the Latest Developments.

Urothelial carcinoma of the bladder is one of the most prevalent cancers worldwide, diagnosed as muscle invasive in 25% of cases. Although several studies have demonstrated an overall 5% absolute survival benefit at 5 years with cisplatin-based combination neoadjuvant treatment, administration of chemotherapy prior to radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC) patients is still a matter of debate. This may be due to the perceived modest survival benefit, cisplatin-based chemotherapy ineligibility, or fear of delaying potentially curative surgery in non-responders. However, immunotherapy and novel targeted therapies have shown to prolong survival in advanced disease and are under investigation in the neoadjuvant and adjuvant settings to reduce systemic relapse and improve cure rates. Genomic characterization of MIBC could help select the most effective chemotherapeutic regimen for the individual patient. Large cohort studies on neoadjuvant treatments with immune checkpoint inhibitors (ICIs) and molecular therapies, alone or combined with chemotherapy, are ongoing. In this review, we trace the development of neoadjuvant therapy in MIBC and explore recent advances that may soon change clinical practice.

Diverse PSMA expression in primary prostate cancer: reason for negative [68Ga]Ga-PSMA PET/CT scans? Immunohistochemical validation in 40 surgical specimens.

PURPOSE: The purpose of this study was to immunohistochemically validate the primary tumor PSMA expression in prostate cancer (PCa) patients imaged with [68Ga]Ga-PSMA PET/CT prior to surgery, with special consideration of PET-negative cases. METHODS: The study included 40 men with newly diagnosed treatment-naïve PCa imaged with [68Ga]Ga-PSMA I&T PET/CT as part of the diagnostic work-up prior to radical prostatectomy. All primary tumors were routinely stained with H&E. In addition, immunohistochemical staining of PSMA was performed and the immunoreactive score (IRS) was computed as semiquantitative measure. Subsequently, imaging findings were correlated to histopathologic results. RESULTS: Eighty-three percent (33/40) of patients presented focal uptake of [68Ga]Ga-PSMA I&T in the primary tumor in at least one prostate lobe. Among PSMA-PET positive patients, one-third had lymph node metastases (LNM) detected by post-operative histopathology, while in PET negative patients, only 1 out of 7 presented with regional LN involvement; PSMA-avid distant lesions, predominantly in bones, were observed in 15% and 0% of patients, respectively. The median IRS classification of PSMA expression in tumor tissue was 2 (range, 1-3) both in PSMA-PET positive and negative prostate lobes, with significantly different interquartile range: 2-3 vs. 2-2, respectively (p = 0.03). The median volume of PSMA-PET positive tumors was 5.4 mL (0.2-32.9) as compared to 1.6 mL (0.3-18.3) of PET-negative tumors (p < 0.001). There was a significant but weak correlation between SUVmax and percentage of PSMA-positive tumor cells (r = 0.46, p < 0.001). A total of 35/44 (~80%) lobes were positive in PSMA-PET imaging, when a cut-off percentage of PSMA-positive cells was ≥ 90%, while 19/36 (~53%) lobes with < 90% PSMA-positive cells were PSMA-PET negative. CONCLUSION: Positive [68Ga]Ga-PSMA I&T PET/CT scan of primary tumor of PCa results from a combination of factors, such as homogeneity and intensity of PSMA expression, tumor volume and grade, with a cutoff value of ≥ 90% PSMA-positive cells strongly determining PET-positivity. Focal accumulation of [68Ga]Ga-PSMA in the primary tumor may correlate positively with aggressiveness of prostate cancer, harboring higher risk of regional LN involvement and distant metastatic spread.

Binding indocyanine green to human serum albumin potentially enhances the detection of sentinel lymph nodes. An initial step for facilitating the detection of first-station nodes in penile and other urological cancers.

Introduction: Surgical oncology strives to remove the primary cancer tumor together with its local lymphatic tissue. One of the techniques improving the staging of lymph nodes is sentinel node biopsy. The most common agent used in SNB is indocyanine green (ICG). Indocyanine green is characterized by its high affinity for human serum albumin (HSA). In practice, the visualization of the sentinel node is enhanced by attaching a relatively large carrier to the ICG molecule. The aim of this study was to investigate whether the covalent linking of ICG to a nanocolloid would extend the time of detection of the dye as it binds to HSA, assessed by fluorescence measurements in vitro. Material and methods: The influence of the molar concentration of ICG on its ability to form a complex with HSA was investigated. The dye luminescence was measured, with an increasing amount of dye in the presence of a constant concentration of HSA. The stability of the ICG:HSA complex was also investigated. Results: The binding of ICG and human protein in a solution ratio of 3 : 1 made it possible to detect the ICG luminescence with better and prolonged visibility. In the case of the two lowest ratios, complex formation was not observed. The use of ICG bound to a nanocolloid based on human serum albumin increases the luminescence of the HSA : ICG complex up to 98%. Conclusions: Properly selected proportions of human albumin protein and ICH allowed higher and longer luminescence to be achieved. Nevertheless, further studies are necessary to establish the optimal concentration ratio.

Fluorescence Imaging Using Methylene Blue Sentinel Lymph Node Biopsy in Melanoma.

INTRODUCTION: Fluorescence imaging of sentinel node biopsy in melanoma is a novel method. Both indocyanine green (ICG) and methylene blue (MB) have fluorescent properties. The aim of this study was to present, for the first time in a clinical series of patients, the possible usage of MB as a fluorescent dye for sentinel node biopsy during surgery for melanoma. MATERIAL AND METHODS: Twenty patients with skin melanoma, who were candidates for sentinel node biopsy were enrolled in our study. All patients underwent simultaneous use of standard nanocolloid and blue dye. Transcutaneous visualization of the sentinel node, visualization of lymphatic channels as well as sentinel node fluorescent visualization were all measured. We also performed calculations of Signal to Background ratios (SBR). RESULTS: In 15% (3/20) of patients, the fluorescent sentinel node was visible through the skin. The median SBR for the sentinel node visualization by fluorescence was 3.15 (range, 2.7-3.5). Lymphatic channels were visible in lymphatic tissue via fluorescence before visualization by the naked eye in 4 patients (20%). The median SBR ratio was 3.69 (range, 2.7-4.2). Sentinel nodes were visible by fluorescence in 13 cases (65%). The median SBR ratio was 2.49 (range, 1.5-5.7). No factors were found to be associated with fluorescent MB visualization of a sentinel node during biopsy. CONCLUSION: This is the first clinical study presenting the usefulness of fluorescent sentinel node biopsy in melanoma patients using MB as a fluorophore. Further studies are necessary to provide methods for its' clinical implementation.

Multispectral Imaging Using Fluorescent Properties of Indocyanine Green and Methylene Blue in Colorectal Surgery-Initial Experience.

Introduction: Image-guided surgery is becoming a new tool in colorectal surgery. Intraoperative visualisation of different structures using fluorophores helps during various steps of operations. In our report, we used two fluorophores-indocyanine green (ICG), and methylene blue (MB)-during different steps of colorectal surgery, using one camera system for two separate near-infrared wavelengths. Material and methods: Twelve patients who underwent complex open or laparoscopic colorectal surgeries were enrolled. Intravenous injections of MB and ICG at different time points were administered. Visualisation of intraoperative ureter position and fluorescent angiography for optimal anastomosis was performed. A retrospective analysis of patients treated in our departments during 2020 was performed, and data about ureter injury and anastomotic site complications were collected. Results: Intraoperative localisation of ureters with MB under fluorescent light was possible in 11 patients. The mean signal-to-background ratio was 1.58 ± 0.71. Fluorescent angiography before performing anastomosis using ICG was successful in all 12 patients, and none required a change in position of the planned colon resection for anastomosis. The median signal-to-background ratios was 1.25 (IQR: 1.22-1.89). Across both centres, iatrogenic injury of the ureter was found in 0.4% of cases, and complications associated with anastomosis was found in 5.5% of cases. Conclusions: Our study showed a substantial opportunity for using two different fluorophores in colorectal surgery, whereby the visualisation of one will not change the possible quantification analysis of the other. Using two separate dyes during one procedure may help in optimisation of the fluorescent properties of both dyes when using them for different applications. Visualisation of different structures by different fluorophores seems to be the future of image-guided surgery, and shows progress in optical technologies used in image-guided surgery.

Challenging Visualization of Sentinel Lymph Nodes in Upper Urinary Tract Urothelial Carcinoma.

PURPOSE: The purpose of this study was to assess the possibility of detecting sentinel lymph nodes (SLNs) and to perform analysis of lymphatic outflow in patients with suspicion of upper tract urothelial carcinoma (UTUC) with the use of a radioisotope-based technique. METHODS: During 2018-2021, a prospective study was conducted on 19 patients with the suspicion of UTUC and for whom diagnostic ureterorenoscopy (URS) was planned. Technetium-99m (99mTc) nanocolloid radioactive tracer injection and a tumor biopsy were performed for staging procedures. Three-dimensional (3D) reconstruction and fusion of images were performed for better localization of lymph nodes (LNs). Detection of SLNs and the analysis of the radiotracer outflow was conducted with the use of single-photon emission-computed tomography/computed tomography (SPECT/CT) lymphangiography. RESULTS: The mean age of the patients was 73.4 years; 7 (36%) were male. Pathological staging from the biopsy was T0-8 (42%), Ta-7 (36%), T1-4 (21%). SLNs were detected in two of 19 cases (10%). In one patient a single SLN (5.3%) was visualized, and in another case (5.3%), multiple (double) radioactive lymph nodes were visualized. In 17 out of the 19 (89.5%) cases, no lymphatic outflow was observed, and out of these five cases (26.3%) of gravitational leakage of injected radiotracer to the retroperitoneal space was noted. CONCLUSIONS: We demonstrated that detection of SLNs in the upper urinary tract is possible yet challenging. Radiotracer injection in the upper urinary tract during ureterorenoscopy is difficult to perform, and the expected result of injection is unsatisfactory. Lymphatic outflow from the tumor site to the first LNs in our studied group of patients is visible in 10.5% of cases. SPECT/CT lymphangiography in cases of UTUC may provide valuable information about a patient's individual anatomy of the lymphatic system and the position of the first lymph nodes draining lymph with potential metastatic cells from the tumor.

Radionuclide-guided sentinel lymph node mapping in urachal cancer.

BACKGROUND: Urachal cancer gives metastases through the lymph nodes (LNs). No lymphadenectomy scheme in the case of this cancer exist, yet it is proposed as a staging procedure. An assessment of lymphatic outflow from the tumor site with the use of single-photon emission computed tomography/computed tomography (SPECT/CT) lymphangiography is possible for staging purposes. OBJECTIVES: To perform the mapping of the LNs draining the lymph from urachal cancer with the use of radioisotope-based technique and to propose the lymphadenectomy template in case of urachal cancer. MATERIAL AND METHODS: A prospective study was conducted in 5 patients with urachal cancer. The 99m-technetium (Tc-99m)-nanocolloid was injected during a cystoscopy prior to the surgery. Lymphangiography was performed using SPECT/CT. A radioactive LNs analysis with the use of a hand-held gamma-ray detection probe was conducted during the surgery and the sentinel lymph node (SLN) biopsy procedure was performed. An additional lymphadenectomy containing the lymphatic basin of identified radioactive LNs was performed. RESULTS: In all cases lymphatic outflow from the urachal tumor to the LNs was present. Preoperative SPECT/CT allowed detecting the activity of the radiotracer in the common iliac region in all the studied patients. In 3 cases, bilateral lymphatic outflow, and in 2 cases, unilateral lymphatic outflow was observed. All preoperatively visualized LNs were found and excised with the use of a gamma-ray detection probe during a lymphadenectomy. In all cases, SLNs did not contain metastases. CONCLUSIONS: Mapping of the LNs draining the lymph from urachal cancer with the use of radiotracer is possible. Lymphatic outflow in the case of this cancer can be both unilateral and bilateral. No recommendations about the extension of lymphadenectomy are proposed. We recommend individual assessment and treatment based on additional knowledge about lymphatic outflow. This allows for minimally invasive yet targeted treatment as an SLN basin lymphadenectomy.

Methylene Blue-Current Knowledge, Fluorescent Properties, and Its Future Use.

Methylene blue is a fluorescent dye discovered in 1876 and has since been used in different scientific fields. Only recently has methylene blue been used for intraoperative fluorescent imaging. Here, the authors review the emerging role of methylene blue, not only as a dye used in clinical practice, but also as a fluorophore in a surgical setting. We discuss the promising potential of methylene blue together with the challenges and limitations among specific surgical techniques. A literature review of PubMed and Medline was conducted based on the historical, current and future usage of methylene blue within the field of medicine. We reviewed not only the current usage of methylene blue, but we also tried to grasp its' function as a fluorophore in five main domains. These domains include the near-infrared imaging visualization of ureters, parathyroid gland identification, pancreatic tumors imaging, detection of breast cancer tumor margins, as well as breast cancer sentinel node biopsy. Methylene blue is used in countless clinical procedures with a relatively low risk for patients. Usage of its fluorescent properties is still at an early stage and more pre-clinical, as well as clinical research, must be performed to fully understand its potentials and limitations.

68Ga-PSMA I&T PET/CT for primary staging of prostate cancer.

PURPOSE: The present study is based on a retrospective analysis of Gallium-68 (68Ga)-labelled prostate-specific membrane antigen (68Ga-PSMA I&T) PET/CT performed in newly diagnosed, treatment-naïve prostate cancer (PCa) patients prior to definitive treatment. METHODS: A total of 82 men were included in the study and were imaged with 68Ga-PSMA I&T PET/CT to assess the distribution of PSMA-avid disease for staging purposes (11 with low-risk, 32 with intermediate-risk, and 39 with high-risk PCa). Forty patients (20 with intermediate- and 20 with high-risk disease) underwent subsequent radical prostatectomy with extended pelvic lymph node dissection which allowed for correlation of imaging findings with histopathologic data. RESULTS: PSMA-positive disease was detected in 83% of patients with 66/82 (80.5%) primary tumours being visualized. PSMA-avid lymph nodes were recorded in 17/82 patients (20.7%, 3 with intermediate-risk and 14 with high-risk PCa); distant disease was found in 14/82 subjects (17.1%, 2 with intermediate-risk and 12 with high-risk PCa). No extraprostatic disease was found in low-risk PCa. SUVmax of primary tumours showed a weak but significant correlation with serum PSA values (r = 0.51, p < 0.001) and Gleason scores (GSC; r = 0.35, p = 0.001), respectively. In correlation with histopathology, calculated per-region sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of lymph node metastases were 35.0%, 98.4%, 63.6%, 95.0%, and 93.0%, respectively. CONCLUSIONS: In patients with initial diagnosis of intermediate- and high-risk prostate cancer, 68Ga-PSMA I&T PET/CT emerges as a relevant staging procedure by identifying nodal and/or distant metastases. Due to the low prevalence of extraprostatic disease, its value seems to be limited in low-risk disease.

Application of methylene blue as an improvement of the injection technique of botulinum toxin A in the treatment of refractory idiopathic overactive bladder: prospective, single-blind (patient-blind), randomized trial.

INTRODUCTION: Refractory idiopathic overactive bladder (RIOAB) is a common condition with a significant negative impact on quality of life. Intravesical injection of botulinum toxin A (BTX-A) is widely used as an intervention for these cases. In the standard method the drug solution is colorless. The addition of dye such as methylene blue (MB) facilitates visualization during the procedure and may have a beneficial effect. AIM: To evaluate the injection of BTX-A with the addition of methylene blue (MB) against a standard method in the treatment of RIOAB. MATERIAL AND METHODS: In this 1-center, single-blinded, randomized controlled trial, we recruited 80 patients with RIOAB. A total of 39 were assigned to injection into the bladder wall of 100 U BTX-A with MB (in 9.5 ml normal saline + 0.5 ml MB), and 41 were assigned to BTX-A 100 U alone (in 10 ml normal saline). Cystoscopy with a submucosal injection of the solution was performed systematically, including the bladder triangle. Participants were assessed 6 and 12 weeks after the treatment using a Likert scale and OABSS questionnaire. RESULTS: Significant improvement was similar (result of 1 or 2 on the Likert scale) and was achieved in 66.7% and 69.2% after 6 weeks and in 63.9% and 64.1% after 12 weeks in the BTX-A + MB group and only-BTX-A group, respectively. There was a significant difference between the two groups (p = 0.049) in the total number of patients with complications: 2 (5.6%) vs. 9 (23.1%). CONCLUSIONS: The addition of MB to BTX for treatment of RIOAB patients does not influence treatment efficacy, while it limits the risk of complications.

Laparoscopic sacrocolpopexy for neovaginal prolapse in a patient after male-to-female sex reassignment surgery.

INTRODUCTION: Male / female sex reassignment surgery is performed on transsexuals, and includes removal of the male external genitalia, and creation of the neovagina from the skin of the penis, usually allowing sexual intercourse (1, 2). The incidence of the prolapse of the neovagina is not known; however, such complication is observed relatively rarely (3, 4). the long-term outcomes of prolapse treatment in transsexual patients are not available in the literature. The purpose of this study was to demonstrate laparoscopic sacrocolpopexy to repair a neovagina prolapse in a patient after male-to-female sex reassignment surgery. MATERIALS AND METHODS: In september 2013, a laparoscopic repair was performed on a 44-year-old woman who presented a neovaginal prolapse of pelvic organ prolapse quantification (pop-q) stage iii, twenty one years after sex reassignment surgery. This condition caused painful or even indisposed intercourse. in may 2013, the patient underwent unsuccessful vaginal treatment with the suturing device. Before the initial surgery, the patient was examined with cystoscopy, urodynamics and microbiology; no pathologies were found. laparoscopic repair of the neovaginal prolapse followed the principles described previously in the natural female (5). In the supine lithotomy position, a standard multiport laparoscopic sacrocolpopexy was performed with the use of the polypropylene mesh (Artisyn® y-shaped mesh, ethicon, inc somerville, nj.) and coated polyglactin sutures. The following steps were applied: exposure of the anterior and posterior neovaginal walls; suturing the bifurcated end of the mesh to the neovagina; longitudinal incision of the parietal peritoneum and creation of a tunnel for the mesh; fixation of the proximal end of the mesh to the promontorium; and closure of the parietal peritoneum over the mesh that was placed retroperitoneally. The draining tube was left for 24 hours. RESULTS: The operation was completed successfully, with no blood loss or complications. The operative time was 115 minutes. The patient was discharged on the 2nd postoperative day. In a four-year follow-up, the patient presented significant improvement of symptoms, a small prolapse of approximate pop-q stage i, and declared performing satisfying intercourse. CONCLUSIONS: Laparoscopic sacrocolpopexy with the use of a polypropylene mesh to repair a neovaginal prolapse in transsexuals seems to be a valuable alternative to other procedures. Further observations and evaluation of a greater number of patients will be necessary to assess the actual value of the method.

Influence of Obesity and Type 2 Diabetes Mellitus on the Pharmacokinetics of Tramadol After Single Oral Dose Administration.

BACKGROUND AND OBJECTIVES: The number of overweight, obese and diabetic patients is constantly increasing. Metabolic disorders may affect the pharmacokinetics of drugs, e.g., by altering the activity of cytochrome P450 (CYP) isoenzymes. Tramadol is a commonly used analgesic metabolised mainly via CYP2D6 to its active metabolite, O-desmethyltramadol. The aim of the study was to assess the influence of overweight, obesity and type 2 diabetes mellitus on tramadol and O-desmethyltramadol pharmacokinetics. METHODS: All patients received a single oral dose (100 mg) of tramadol. The plasma concentrations of tramadol and O-desmethyltramadol were measured with the validated high-performance liquid chromatography method with fluorescence detection. The pharmacokinetic parameters of tramadol and O-desmethyltramadol were calculated by non-compartmental methods. RESULTS: After nephrectomy, the patients were divided into four groups-a control group (n = 12, mean [SD] age 61 [14] years, body mass index (BMI) 22 [2] kg/m2, CLcr (creatinine clearance) 74 [30] mL/min); an overweight group (n = 15, mean [SD] age 63 [11] years, BMI 27 [1] kg/m2, CLcr 81 [35] mL/min); an obese group (n = 12, mean [SD] age 57 [8] years, BMI 33 [4] kg/m2, CLcr 113 [51] mL/min); and an obese and diabetic group (n = 9, mean [SD] age 64 [10] years, BMI 33 [4] kg/m2, CLcr 87 [35] mL/min). Apart from the time to first occurrence of maximal concentration (tmax), there were no significant differences in the pharmacokinetic parameters of tramadol and O-desmethyltramadol among the groups. Moreover, there were no significant differences in the O-desmethyltramadol/tramadol ratios among the four groups of patients after nephrectomy. CONCLUSIONS: No significant differences were found in the pharmacokinetics of tramadol and O-desmethyltramadol, indicating that the opioid can be administered to overweight, obese and diabetic patients without dosage adjustment.

Can the evolution of male contraception lead to a revolution? Review of the current state of knowledge.

INTRODUCTION: Great advances in medical research concerning methods of contraception have been achieved in recent years, however, more than 25% of couples worldwide still rely on condoms - a method with poor efficacy. Even though there is a spectrum of 11 different contraceptive methods for women, there are only 4 commonly used by men (condoms, periodic abstinence, withdrawal and vasectomy). In this review, advances and present, state-of-the-art, both hormonal and non-hormonal male contraceptive methods will be presented and evaluated. Potential novel targets that warrant greater research will be highlighted. MATERIAL AND METHODS: A comprehensive literature search without a time limit was performed using the Medline database on May 2017. The terms 'male contraception' in conjunction with 'reversible inhibition of sperm under guidance' (RISUG), 'hormonal', 'non-hormonal', 'vasectomy' or 'testosterone' were used. The articles were limited to those published in English, Polish or French. RESULTS: There are various contraceptives currently available to regulate male fertility. Vasectomy is still the most effective permanent form of male contraceptive with a failure rate lower than 1%. Reversible, non hormonal methods of male contraception, like reversible inhibition of sperm under guidance, are very promising and close to being introduced into the market. In regards to hormonal contraception research, the use of testosterone injections has been widely studied yet they often harbor undesirable side effects and require further development. CONCLUSIONS: Despite continuous efforts worldwide, it seems that another several years of research is needed to provide safe, effective and affordable male contraceptives which will allow both men and women to participate fully in family planning.

Overactive bladder treatment: application of methylene blue to improve the injection technique of onabotulinum toxin A.

OBJECTIVE: The aim of this study was to test the addition of methylene blue (MB) to onabotulinum toxin A (BTX-A) solution in overactive bladder (OAB) treatment, as a means of facilitating observation of the injection site and assessing the distribution of the drug under the bladder mucosa during injection. Pharmacological interactions between BTX-A and MB were also evaluated. MATERIALS AND METHODS: The study was conducted between December 2014 and April 2016 on 30 patients: six males and 24 females (median age 57.7, range 23-80 years) diagnosed with OAB, who qualified for intravesical BTX-A injection. Each received 100 IU of BTX-A (Botox®; Allergan), dissolved in 9.5 ml of 0.9% NaCl with the addition of 0.5 ml of MB. Cystoscopy with submucosal injection of the solution was performed systematically, including the bladder triangle. For pharmacological evaluation, quantitative determination of MB was performed on a capillary electrophoresis system with diode array detection. RESULTS: In the course of 600 injections, the addition of MB facilitated the observation of the procedure; the exact distribution of the solution could not be observed in only 43 injections in seven patients. The range of distribution of the drug varied from 1 to 2.5 cm. Pharmacological evaluation based on visual observations and experiments showed that pharmaceutical interactions do not occur between MB and this commercially available formulation of BTX-A. CONCLUSIONS: Applying a coloured solution of BTX-A significantly facilitates observation of the procedure and assessment of drug distribution. There are no pharmaceutical interactions between MB and BTX-A.

Tetraspanin CD151 mediates communication between PC3 prostate cancer cells and osteoblasts.

Invasion and migration of cancer cells are crucial for the formation of secondary lesions. These require activation of signalling cascades modulated by the number of regulatory molecules. One such molecule is CD151, a member of evolutionary conserved tetraspanin family. CD151 is involved in cell adhesion, motility and cancer progression due to formation of complexes with laminin-binding integrins and regulation of growth factor receptors function (e.g. HGFR, TGFßR, EGFR). Recent studies point to correlation between CD151 expression and high tumour grade in prostate cancer (PCa). Herein, we investigated a possible role of CD151 in communication between PC3 cancer cells and either cancer-associated fibroblasts (CAFs) or osteoblasts, an interplay which is significant for metastasis. The analysis showed that although CAFs strongly enhanced both migration and invasion of PC3 prostate cancer cells, the effect was not dependent on CD151. On the other hand, CD151 was found to promote 3D migration as well as invasive growth in response to osteoblasts-secreted growth factors. Obtained data revealed that knockdown of CD151 abolished activation of pro-migratory/pro-survival kinases (i.e FAK, Src, HSP27) triggered by osteoblasts, along with expression of matrix metalloproteinase-13. This suggests that CD151 participates in communication between PC3 cells and bone microenvironment and the process can be considered as a significant step of PCa progression and metastasis.

THE EFFECT OF TOTAL AND PARTIAL NEPHRECTOMY ON THE PHARMACOKINETICS OF INTRAVENOUS PARACETAMOL IN HUMANS.

Paracetamol is one of the most common analgesic and antipyretic drugs. Recently intravenous paracetamol has been widely used to treat moderate postoperative pain. Surgery is the main method of treatment of renal cancer. Total or partial nephrectomy can be performed, depending on the size and location of the tumor. Pharmacokinetics of drugs may depend on the type of surgery. The aim of the study was to compare the postinfusion pharmacokinetics of paracetamol in patients after total nephrectomy (TN) and nephron sparing surgery (NSS).The research was carried out on two groups of patients after nephrectomy: total (TN n = 37; mean [SD], age, 60.4 [10.9] years; BMI, 26.5 [3.8] kg/m2; creatinine clearance, Cl, 80.9 [37.1] mL/min) and nephron sparing surgery (NSS n = 17; 57.9 [16.5] years; BMI, 29.5 [5.3] kg/m2; Cl, 97.6 [27.8] mL/min). The patients were treated with paracetamol (PerfalganO Bristol-Myers Squibb) at an intravenous dose of 1.000 mg, which was infused for 15 minutes after surgery. The concentrations of paracetamol in the patients' plasma were determined by the HPLC method with UV detection (X = 261 run). The main pharmacokinetic parameters of paracetamol in the TN vs. NSS group were as follows: C.. 29.08 [17.39] vs. 27.54 [15.70] pg/mL (p = 0.6692); AUC5, 29.24 [13.86] vs. 34.85 [14.28] pg.h/mL (p = 0.2896); AUMC5,,,, 47.58 [26.08] vs. 62.02 [27.64] pg-h/mL (p = 0.1345); to. 2.34 [0.96] vs. 1.93 [0.50] h (p = 0.1415), respectively. In both groups the exposure to paracetamol was comparable. The t1/2 after nephron sparing surgery was shorter than after total nephrectomy. Therefore, these patients may demand more frequent drug administration. In the NSS group the C. of the analgesic was considerably reduced in men.

Fluorescent Versus Radioguided Lymph Node Mapping in Bladder Cancer.

INTRODUCTION: The aim of the study was to compare 2 methods of the sentinel lymph node biopsy (SLNB) procedure in bladder cancer: we applied technetium radiocolloid (RadCol) detected by a gamma ray detection probe, and indocyanine green (ICG) detected by a near-infrared fluorescent (NIRF) camera. MATERIAL AND METHODS: The SLNB was performed on 50 patients using the RadCol and the ICG, followed by a lymphadenectomy and a pathologic examination. RESULTS: In the analyzed group of 47 patients (3 patients were excluded owing to the lack of lymphatic drainage from the tumor), the SLNB was performed using the 2 methods. The ICG with a NIRF-guided camera detected all sentinel lymph nodes (SLNs) in 46 cases, whereas RadCol detected them in 45 cases. In 12 (25.6%) of 47 patients, the ICG-fluorescent method revealed more SLNs than the RadCol method. In 8 (17%) patients, the SLNs revealed in the ICG fluorescence were metastatic. In 3 (6.4%) patients, we found SLNs outside the standard lymphadenectomy template, but a histopathologic examination showed they were negative for cancer. In 3 (6.4%) patients, the SLNs detected by both methods were negative for cancer, but other resected lymph nodes revealed metastases. CONCLUSION: Our study shows that SLNB procedure with the RadCol or the ICG method is useful for the evaluation of lymph nodes in bladder cancer. The new ICG fluorescent technique with a NIRF camera system is safe, enables live view of the results of the procedure, and does not create additional costs. However, it highlights more lymph nodes than the radioactive method.

Radio-Guided Lymph Node Mapping in Bladder Cancer Using SPECT/CT and Intraoperative γ-Probe Methods.

PURPOSE: Lymph outflow from bladder tumor differs between individuals, making the prediction of the metastatic landing sites difficult. A "blind" template of lymphadenectomy has been tested as a solution to this problem. We believe that it is feasible to find methods enabling more precise lymph nodes (LNs) evaluation. The aims of our study were to evaluate the possibility of LNs mapping in case of muscle invasive bladder cancer (MIBC) and to compare the 2 methods of their detection. PATIENTS AND METHODS: Our study group consisted of 38 cN0 MIBC patients. Lymph nodes mapping was performed by SPECT/CT lymphoscintigraphy using Tc-nanocolloid, followed by intraoperative verification with γ-ray probe. Lymph nodes with increased radiotracer uptake (hot spots) were removed, and then pelvic LNs dissection was conducted. Lymph nodes resected as hot spots and LNs resected with lymphadenectomy were separately examined by a pathologist. RESULTS: An average of 3 hot spots (range, 1-5) were identified in each case. For 36 of 38 patients, both preoperative SPECT/CT and intraoperative γ-probe evaluation results were obtained. Ninety-five percent of hot spots were found distally and caudally to the uretero-iliac crossing; 5% were found proximal. Lymph nodes outside the pelvic LNs dissection area did not contain metastases. In 2 patients, metastases were found in LNs without increased radiotracer uptake, and the observed hot spots contained no metastases. CONCLUSIONS: Radio-guided LNs mapping in case of MIBC is feasible. Preoperative detection of hot spots using SPECT/CT and intraoperative γ-ray detection probe gives similar results.