Insights into the photoactivatable CO releasing properties of dicarbonyl Ru(II) complex with 8-amino quinoline ligand: Experimental and theoretical studies.

Reaction between the polymeric [RuCl2(CO)2]n and the N,N-bidentate ligand, 8-amino-quinoline (Quin), in methanol, afforded the photoactivated CO releasing molecule with the formula of trans-(Cl,Cl)-[RuCl2(CO)2Quin]. In the presence of biomolecules or in solvents with varying polarity and coordinating abilities, the solvatochromic characteristics and dark stability were investigated. A new board band emerged in the visible spectrum during the illumination, and its position varies according to the type of solvent used, indicating the role of the solvent in controlling the nature of the CO-depleted species. Spectral methods were used in combination with density functional theory simulations to get insight into the local minimum structure and the electronic properties of the Ru(II) complex. The results of the myoglobin assay showed that within the first two hours of illumination, one of the two CO molecules was released. The cytotoxic properties of the Ru(II)-based complex were investigated against normal mice bone marrow stromal cells and malignant human acute monocytic leukaemia cells.

Metal-based carbon monoxide releasing molecules with promising cytotoxic properties.

Carbon monoxide, the "silent killer" gas, is increasingly recognised as an important signalling molecule in human physiology, which has beneficial biological properties. A particular way of achieving controlled CO administration is based on the use of biocompatible molecules that only release CO when triggered by internal or external factors. These approaches include the development of pharmacologically effective prodrugs known as CO releasing molecules (CORMs), which can supply biological systems with CO in well-regulated doses. An overview of transition metal-based CORMs with cytotoxic properties is here reported. The mechanisms at the basis of the biological activities of these molecules and their potential therapeutical applications with respect to their stability and CO releasing properties have been discussed. The activation of metal-based CORMs is determined by the type of metal and by the nature and features of the auxiliary ligands, which affect the metal core electronic density and therefore the prodrug resistance towards oxidation and CO release ability. A major role in regulating the cytotoxic properties of these CORMs is played by CO and/or CO-depleted species. However, several mysteries concerning the cytotoxicity of CORMs remain as intriguing questions for scientists.

Open versus minimally invasive nephroureterectomy in octogenarians: An analysis of surgical approach trends, outcomes, and survival analysis with propensity matching.

INTRODUCTION: Upper tract urothelial carcinoma (UTUC) is a rare disease accounting only for 5%-10% of urothelial carcinoma (UC). For localized high-risk disease, radical nephroureterectomy (RNU) is the standard of care. While minimally invasive (MIS) RNU has not been shown to decisively improve overall survival (OS) compared to open surgery, MIS RNU has been associated with reduced hospital length of stay (LOS), blood transfusion requirements and improved recovery, which are important considerations when treating older patients. The purpose of this study is to examine trends in surgical approach selection and outcomes of open vs. MIS RNU in patients aged ≥80 years. METHODS: Using the National Cancer Database (NCDB), patients aged ≥80 years who underwent open or MIS (either robotic or laparoscopic) RNU were identified from 2010 to 2019. Demographic, patient-related, and disease-specific factors associated with either open or MIS RNU were assessed using multivariate logistic regression models. Survival analysis was conducted using Kaplan-Meier plots and Cox-proportional hazard regression. Inverse probability of treatment weighting (IPTW) was utilized to adjust for confounding variables. Survival analysis was also conducted on the IPTW adjusted cohort using Kaplan-Meier plots and Cox-proportional hazard regression. RESULTS: 5,687 patients were identified, with 1,431 (25.2%) and 4,256 (74.8%) patients undergoing open and MIS RNU respectively. The proportion of RNU performed robotically has increased from 12.5% in 2010 to 50.4% in 2019. MIS was associated with a shorter hospital LOS (4.7 days versus 5.9 days, SMD 23.7%). Multivariate analysis revealed that MIS was associated with a significant reduction in 90-day mortality (OR: 0.571; 95%CI: 0.34-0.96, P = 0.033) and improved median OS (53.8 months [95%CI: 50.9-56.9] vs 42.35 months [95%CI: 38.6-46.8], P < 0.001) compared to open surgery. IPTW-adjusted survival analysis revealed improved median OS with MIS when compared to open surgery, with a survival benefit of 46.1 months (95%CI: 40.2-52.4 months) versus 37.7 months (95%CI: 32.6-46.5 months, P = 0.0034) respectively. IPTW-adjusted cox proportional hazard analysis demonstrated that MIS was significantly associated with reduced mortality (HR 0.76, 95%CI: 0.66-0.87, P < 0.001). CONCLUSION: In octogenarians undergoing RNU, MIS is associated with improved median OS and 90-day mortality.

Palladium(II) Complexes of 4-Phenyl-3-thiosemicarbazone Ligands: Insights Into Cytotoxic Properties and Mode of Cell Death.

Reactions between sodium tetrachloropalladate and 2- (or 4-) substituted 4-phenyl-3-thiosemicarbazone ligands (HLR), with various electron-donating and electron-withdrawing substituents (R = OCH3, NO2, and Cl), afford square-planar complexes of the general formula [Pd(LR)2]. Ground-state geometry optimization and the vibrational analysis of cis- and trans-isomers of the complexes were carried out to get an insight into the stereochemistry of the complexes. Natural bond orbital analysis was used to analyze how the nature of the substituent affects the natural charge of the metal center, the type of hybridization, and the strength of the M-N and M-S bonds. Using spectrophotometry, the stability of the complexes, and their DNA binding abilities were assessed. The Pd(II) complexes showed moderate cytotoxicity against MCF-7 and Caco-2 cell lines, two of the assessed malignant cell lines, resulting in all known cell death types, including early apoptotic bodies and late apoptotic vacuoles as well as evident necrotic bodies.

Long-term clinical evaluation of laparoscopic management of large hiatal hernias.

BACKGROUND: Large hiatal hernias (LHH) account for 5-10% of all hiatal hernias. Surgery of LHH should be associated with low rates of postoperative complications and recurrences, to guarantee a favorable quality of life (QoL). Data on long-term results of laparoscopic repair of LHH are lacking. The objective of our study is to evaluate the long-term clinical outcomes of laparoscopic LHH management in a high-volume experienced center. METHODS: Patients who had undergone elective laparoscopic repair of LHH between January 1992 and December 2008 at the Center of Minimally Invasive Surgery of the Department of Surgical Sciences, University of Turin, Italy were included. Preoperative and intraoperative data were collected from patients' charts. Patients were clinically evaluated at long-term postoperative follow-up to assess control of symptoms, degree of satisfaction with surgery, and QoL. RESULTS: At mean follow-up of 240 months (range 168-348), 81 patients were available for clinical evaluation. Severe heartburn was reported by six patients (7.4%), while severe post-prandial epigastric pain by three (3.7%). Recurrent coughing episodes were described by six patients (7.4%), while occasional mild episodes of transient dysphagia by 13 (16%). No gas bloat detected. Proton Pump Inhibitors were taken by 22 patients (27.2%) to control symptoms. The Modified Italian Gastroesophageal Reflux Disease-Health Related Quality of Life (MI-GERD-HRQL) score decreased significantly from 40 to 7 (P<0.0001) postoperatively. Satisfaction was achieved in 76 patients (93.8%) with an average satisfaction index of 8.6 (IQR 8-10). CONCLUSIONS: Laparoscopic LHH repair is effective when performed in a specialized center, with long-lasting significant improvements of symptoms and QoL.

Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd(II) complexes.

A series of Pd(II) complexes of the general formula [PdX(NNS)] (X = Cl, Br, I, NCS and phenyl-tetrazole-thiolato; NNS = 2-quinolinecarboxyaldehyde-N4-phenylthiosemicarbazone) was tested against four malignant cell lines for their antiproliferative properties and the outcomes were compared to those seen in normal mouse splenocytes. Various auxiliary ligands were substituted in order to investigate the impact of the character of the ligand on the cytotoxicity of this class of Pd(II) complexes. The iodo complex was the most cytotoxic compound towards the Caco-2 cell line in this study. The improved apoptosis and necrosis cell modes were in accordance with the fragmentation results of DNA, which revealed increased fragmentation terminals, especially in isothiocyanate and tetrazole-thiolato complexes. After 24 hours, at half the IC50 of each complex, the complex-treated cells exhibited considerable genotoxicity when compared to the corresponding non-treated control especially in the case of isothiocyanate and tetrazole-thiolato complexes.

Contemporary Trends of Holmium Laser Enucleation of the Prostate Utilization in the United States: A Comprehensive Analysis Using the National Surgical Quality Improvement Program Database (2011-2020).

Introduction: The most recent American Urological Association (AUA) Guidelines advocated laser enucleation of the prostate (LEP) as a size-independent surgical option for benign prostatic hyperplasia (BPH). Despite its endorsement by AUA and the growing body of evidence supporting its safety and efficacy, the utilization of LEP remains limited in the United States. This study aimed to evaluate the utilization trends and perioperative outcomes of LEP compared with other surgical procedures used for BPH management. Methods: A retrospective cohort analysis was performed using American College of Surgeons National Surgical Quality Improvement Program data from 2011 to 2020. Patients undergoing prostatectomy for BPH were identified using specific current procedural terminology (CPT) codes. Baseline demographic data, preoperative risk factors, and postoperative outcomes were collected. Multivariable logistic regression was employed to assess predictors of holmium laser enucleation of the prostate (HoLEP) utilization and postoperative complications. Results: Out of 8,415,549 patients, 95,144 underwent prostatectomy for BPH. Procedures included HoLEP 5305 cases, transurethral resection of the prostate (TURP) 57,803 cases, repeated TURP (re-TURP) 5549 cases, photoselective vaporization of the prostate (PVP) 23,739 cases, and simple prostatectomy 2748 cases. HoLEP utilization showed a gradual increase, from 4.8% in 2015 to 7.6% in 2020. Multivariable regression revealed that HoLEP selection significantly increased from 2016 to 2020 (odds ratio [OR]: 1.251, p < 0.001), and there was less likelihood of HoLEP selection for African American patients (OR: 0.752, p < 0.001). HoLEP had significantly lower complication rates, including urinary tract infections, blood transfusions, 30-day readmission, and reoperation. Conclusion: Despite underutilization, the adoption of HoLEP has slightly increased since 2015, rising from 4.8% in 2015 to 7.6% in 2020. The underutilization could be attributed to a lack of availability and the steep learning curve.

Interruptions in bladder cancer care during the COVID-19 public health emergency.

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.

Estrogen/estrogen receptor activation protects against DEN-induced liver fibrosis in female rats via modulating TLR-4/NF-kß signaling.

AIM: Men are more susceptible to liver fibrosis (LF) than women. However, the underlying molecular mechanism, especially the role of estrogen/estrogen receptor (ER) activation in this sexual dimorphism is unclear. Therefore, the aim of the current study was to investigate the impact and the underlying molecular mechanisms of estrogen/ER activation on diethyl nitrosamine (DEN)-induced LF. MAIN METHODS: Thirty ovariectomized (OVX) female rats were randomly allocated into five groups (n = 6), and received no treatment, diethyl nitrosamine (DEN), DEN/fulvestrant, DEN/silymarin or DEN/estradiol benzoate (EB). In addition, three sham groups received no treatment, DEN or DEN/fulvestrant, and one control group that neither ovariectomized nor treated. Directly after treatment, liver injury biomarkers were measured. In addition, hepatic tissue hydroxyproline, TNF- α, TGF- ß, and IL-10 were evaluated. Expression of NF-kß, CD68 (a marker for macrophage infiltration), ER-ß and TLR-4 were measured. Finally, liver tissue histopathology was assessed. KEY FINDINGS: Ovariectomy aggravates DEN-induced LF, as it significantly elevated all liver tissue injury biomarkers. This effect has become even worse after blocking ER by fulvestrant, indicating a protective role of estrogen/ER activation against DEN-induced LF. Inhibition of TLR-4/NF-kß signaling pathway contributed to this protective effect, as estrogen deprivation or blocking of ER significantly activates this pathway during the onset of LF. While administration of EB or silymarin (selective ER-ß activator) improved LF indices and deactivated this pathway. SIGNIFICANCE: These results provide new insight into the pivotal role of estrogen/ER activation via modulation of TLR-4/NF-kß, in the alleviation of LF pathogenesis.

Estrogen Attenuates Diethylnitrosamine-Induced Hepatocellular Carcinoma in Female Rats via Modulation of Estrogen Receptor/FASN/CD36/IL-6 Axis.

This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The levels of liver injury serum biomarkers, liver content of interleukin-6 (IL-6), relative liver weight and distortion of liver histological pictures were significantly increased in ovariectomized (OVX) rats and SHAM rats that received DEN alone and were further exaggerated when DEN was combined with fulvestrant (F) compared to non-DEN treated rats. The OVX rats showed higher insults than SHAM rats. The tapering impact on these parameters was clear in OVX rats that received estradiol benzoate (EB), silymarin (S) or orlistat (ORS). The immunohistochemistry and/or Western blot analysis of liver tissues showed a prominent increase in fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) expressions in OVX and SHAM rats who received DEN and/ or F compared to SHAM rats. In contrast to S, treatment of OVX rats with EB mitigated DEN-induced expression of FASN and CD36 in liver tissue, while ORS improved DEN-induced expression of FASN. In conclusion, the protective effect against HCC was mediated via estrogen receptor alpha (ER-α) which abrogates its downstream genes involved in lipid metabolism namely FASN and CD36 depriving the tumor from survival vital energy source. In addition, ORS induced similar mitigating effect against DEN-induced HCC which could be attributed to FASN inhibition and anti-inflammatory effect. Furthermore, S alleviated DEN-induced HCC, independent of its estrogenic effect.

Impact of rural residence on the presentation, management and survival of patients with non-metastatic muscle-invasive bladder carcinoma.

PURPOSE: To assess the impact of rural and remote residence on the receipt of guidelines-recommended treatment, quality of treatment and overall survival (OS) in patients with non-metastatic muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: Patients with MIBC were identified using National Cancer Database. Patients were classified into three residential areas. Logistic regression models were used to assess associations between geographic residence and receipt of radical cystectomy (RC) or chemoradiation therapy (CRT). Models were fitted to assess quality benchmarks of RC and CRT. RESULTS: We identified 71,395 patients. Of those 58,874 (82.5%) were living in Metro areas, 8,534 (11.9%) in urban-rural adjacent (URA), and 3,987 (5.6%) in urban-rural remote to metro area (URR). URR residence was significantly associated with poor OS compared to URA and Metro residence (HR 0.87, 95% CI 0.81-0.94 and HR 0.90, 95% CI 0.87-0.93, p<0.001). There was no difference in the likelihood of receiving RC and CRT among different residential areas. Among patients who underwent RC; individuals living in URR were less likely to receive neoadjuvant chemotherapy and adequate lymph node dissection, and had a higher probability of positive surgical margin than those living in metro areas. For those who received CRT; individuals living in Metro areas were more likely to receive concomitant systemic therapy compared to URR. CONCLUSIONS: Rural residence is associated with lower OS for MIBC patients and less likelihood of meeting quality benchmarks for RC and CRT. This data should be used to guide further health policy and allocation of resources for rural population.

Microsurgery in the Sickle Cell Trait Population: Can it Be Safely and Successfully Performed?

Free-tissue transfer reconstruction in patients with sickle cell anemia risks failure due to polymerization of sickle hemoglobin within the flap microcirculation. However, outcomes vary, as the amount of polymerization is dependent on factors such as disease phenotype/diagnosis, degree of hypoxia, and intracellular dehydration. Most of the literature focuses on patients with sickle cell disease, which produces higher concentrations of sickle hemoglobin and, therefore, is a contraindication to microvascular reconstruction. Fewer reports describe microsurgery in patients with sickle cell trait (SCT) who carry the heterozygous phenotype. Here, we present a case in which a patient with SCT underwent microsurgical breast reconstruction with deep inferior epigastric perforator free-tissue transfer. The 52-year-old woman had previously experienced a failed alloplastic-based reconstruction after radiation therapy for breast cancer. In our case, clinical and Doppler examinations demonstrated that arterial and venous anastomoses had remained patent; so the patient was discharged on postoperative day 4. Blistering developed on postoperative day 8, and by day 15 there was partial necrosis of the inferior-lateral aspect of the deep inferior epigastric perforator flap. Debridement and closure resolved the issue, and at 5 months postprocedure, the flap remained well-perfused and well-incorporated. This case, presented here with patient consent, reports a successful outcome of microsurgical reconstruction in a patient with SCT. It expands the limited evidence to support the safety and feasibility of autologous surgical interventions for patients with the heterozygous phenotype of sickle cell anemia.

In vitro cytotoxicity of Mn(I) and Ru(II) carbonyls with a diphenyl pyridyl phosphine coligand towards leukaemia.

Human acute monocytic leukaemia cells were tested under both dark and light conditions for their susceptibility to Mn(I) and Ru(II) carbonyl complexes with a diphenyl pyridyl phosphine coligand. The Ru(II) complex (IC50 = 7.13 ± 0.8 µM) displayed higher outstanding potency against leukaemia than the Mn(I) analogue (54.58 ± 4.1 µM) in the dark and both complexes were completely harmless to healthy mouse bone marrow cells.

Effect of autologous bone marrow derived mesenchymal stem cells in treatment of rheumatoid arthritis.

INTRODUCTION: Chronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advancements in the management of RA, adverse side effects and ineffective treatments remain a problem. Effective treatment is usually hampered by financial issues. As a result, less expensive medications that reduce both inflammation and bone resorption are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA. AIM OF THE STUDY: This study aimed to examine the anti-arthritic effect of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides (Os), and human placental extract (HPE), individually and combined, on an RA model, using Complete Freund's adjuvant (CFA)-induced arthritis in rats. MATERIALS AND METHODS: In female rats, RA was induced by injecting CFA in the paw of the hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via the intraperitoneal route. A complete blood count (CBC), erythrocyte sedimentation rate (ESR), serum cortisol, urea, uric acid, and other biochemical parameters were measured to determine the safety and efficacy of the different treatments. Histopathological analysis of bone sections was carried out. RESULTS: Combining oligosaccharides and HPE therapy with the infusion of rat-bone marrow MSCs had beneficial antiarthritic and anti-inflammatory effects in CFA-induced arthritis in rats: overall such triple therapy significantly reduced serum levels of IL-6, IL-10, and TNF-alpha in comparison with all other combinations (all P > 0.05). Meanwhile, the triple therapy did not have negative effects on levels of CBC, serum cortisol, ESR, and liver enzymes (all NS) as well as on renal functions (NS). Also, the histopathological analysis showed significant improvements in the healing and remodelling of osteoporotic lesions in arthritic rats. As shown by counting apoptotic cells as a histopathological substitute for measuring apoptotic or regeneration markers, the lowest count was found in the group treated with a triple therapy of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides, and HPE. CONCLUSION: The combination of rat MSCs, oligosaccharides, and HPE has the potential to be an effective treatment for rheumatoid arthritis.

Volumetric Analysis of Renal Masses as Predictors of Partial Nephrectomy Outcomes.

Objective: To examine the role of endophytic tumor volume (TV) assessment (endophycity) on perioperative partial nephrectomy (PN) outcomes. Patients and Methods: Retrospective review of 212 consecutive laparoscopic and open partial nephrectomies from single institution using preoperative imaging and 1-year follow-up. Demographics, comorbidities, RENAL nephrometry scores, and all peri- and postoperative outcomes were recorded. Volumetric analysis performed using imaging software, independently assessed by two blinded radiologists. Univariate and multivariate statistical analysis were completed to assess predictive value of endophycity for all clinically meaningful outcomes. Results: Among those undergoing minimally invasive surgery (MIS), lower tumor endophycity was associated with higher likelihood of trifecta outcome (negative surgical margin, <10% decline in estimated glomerular filtration rate, the absence of complications) irrespective of max tumor size. For MIS, estimated blood loss increased with greater tumor endophycity regardless of tumor size. Among those who underwent open partial nephrectomy, lower tumor endophycity was associated with trifecta outcomes for tumors >4 cm only. On multivariate analysis with log-scaled odds ratios (OR), tumor endophycity and total kidney volume had the strongest correlation with tumor-related complications (OR = 3.23, 2.66). The analysis identified that tumor endophycity and TV on imaging were inversely correlated with of trifecta outcomes (OR = 0.53 for both covariates). Conclusions: Volumetric assessment of tumor endophycity performed well in identifying PN outcomes. As automated imaging software improves, volumetric analysis may prove to be a useful adjunct in preoperative planning and patient counseling.

Delayed Thoracodorsal Artery Perforator Free Flap for Calcaneal Degloving Injury Reconstruction.

The thoracodorsal artery perforator (TDAP) flap has a long vascular pedicle that is ideal for lower extremity reconstruction, but it generally relies on the presence of a dominant septocutaneous perforator vessel. Surgical delay optimizes flap survival by creating relative ischemia to augment perforator vessels. In this report, we describe the use of a delayed free TDAP flap in the setting of an absent dominant perforator vessel for the reconstruction of a calcaneal degloving injury. A 22-year-old actively smoking patient with a body mass index of 33.5 presented with a nonhealing left heel wound with overlying necrotic changes after traumatic degloving injury. The entire weight-bearing portion of the calcaneal fat pad and the flanking regions were debrided. The TDAP flap was elevated, revealing three small thoracodorsal artery perforators. Given that a dominant perforator was absent, the flap was surgically delayed. Free-tissue transfer occurred 8 days later. This operation was conducted entirely in left lateral decubitus with simultaneous wound preparation and flap harvest. The flap was elevated on two perforators to elongate the pedicle's length and inset to cover exposed calcaneus and pad the heel. Six months postoperatively, the patient is doing well without flap compromise or ulceration. The TDAP flap is a versatile microsurgical tool, and surgical delay extends the utility of this flap when a dominant septocutaneous perforator is unavailable. Recipient site debridement may occur simultaneously with the TDAP delay procedure. Importantly, only one position is required for flap elevation, microsurgical anastomosis, and insetting, thus obviating intraoperative repositioning.

Robot-assisted retroperitoneal lymph node dissection: a systematic review of perioperative outcomes.

OBJECTIVE: To assess the safety and feasibility of robot-assisted retroperitoneal lymph node dissection (R-RPLND) and to compare the perioperative outcomes of R-RPLND with open RPLND (O-RPLND), as RPLND forms an integral part of the management of testis cancer and R-RPLND is a minimally invasive treatment option for this disease. MATERIALS AND METHODS: The PubMed® , Scopus® , Cochrane Central Register of Controlled Trials, and Web of Science™ databases were searched for studies reporting perioperative outcomes of primary and post-chemotherapy R-RPLND and studies comparing R-RPLND with O-RPLND. RESULTS: The search yielded 42 articles describing R-RPLND, including five comparative studies. The systematic review included 4222 patients (single-arm studies, n = 459; comparative studies, n = 3763). Of 459 patients in the single-arm studies, 271 underwent primary R-RPLND and 188 underwent post-chemotherapy R-RPLND. For primary R-RPLND, the operative time ranged from 175 to 540 min and the major complication rate was 4.1%. For post-chemotherapy R-RPLND, the operative time ranged from 134 to 550 min and the major complication rate was 8.5%. The conversion rate to open surgery was 2.2% in primary R-RPLND and 9.0% in post-chemotherapy R-RPLND. In comparison with O-RPLND, R-RPLND was associated with a lower transfusion rate (14.5% vs 0.9%, P < 0.001) and a lower complication rate (18.5% vs 7.8%, P = 0.002). CONCLUSION: Robot-assisted RPLND has acceptable perioperative outcomes in both the primary and post-chemotherapy settings but a notable rate of conversion to open surgery in the post-chemotherapy setting. Compared with O-RPLND, R-RPLND is associated with a lower transfusion rate and fewer overall complications. Given the potential impact of selection bias, the optimal patient selection criteria for R-RPLND remain to be elucidated.

Revisiting current National Comprehensive Cancer Network (NCCN) high-risk prostate cancer stratification: a National Cancer Database analysis.

BACKGROUND: High-risk prostate cancer includes heterogenous populations with variable outcomes. This study aimed to compare the prognostic ability of individual high-risk factors, as defined by National Comprehensive Cancer Network (NCCN) risk stratification, in prostate cancer patients undergoing radical prostatectomy. METHODS: We queried the National Cancer Database from 2004 to 2018 for patients with non-metastatic high-risk prostate cancer who underwent radical prostatectomy and stratified them as Group H1: Prostate specific antigen (PSA) > 20 ng/ml alone, Group H2: cT3a stage alone and Group H3: Gleason Grade (GG) group 4/5 as per NCCN guidelines. The histopathological characteristics and rate of adjuvant therapy were compared between different groups. Inverse probability weighting (IPW)-adjusted Kaplan-Meier curves were utilized to compare overall survival (OS) in group H1 and H2 with H3. RESULTS: Overall, 61,491 high-risk prostate cancer patients were identified, and they were classified into Group H1 (n = 14,139), Group H2 (n = 2855) and Group H3 (n = 44,497). Compared to group H1 or H2, pathological GG group > 3 (p < 0.001), pathological stage pT3b or higher (p < 0.001), lymph nodal positive disease (pN1) (p < 0.001) and rate of adjuvant therapy (p < 0.001) were significantly in Group H3. IPW-adjusted Kaplan-Meier curves showed significantly better 5-year OS in group H1 compared to group H3 [95.1% vs 93.3%, p < 0.001] and group H2 compared to group H3 [94.4% vs 92.9%, p < 0.001]. CONCLUSION: PSA > 20 ng/ml or cT3a stage in isolation have better oncologic and survival outcomes compared to GG > 3 disease and sub-stratification of 'High-risk' category might lead to better patient prognostication.

A comparative analysis of radical cystectomy with perioperative chemotherapy, chemoradiation therapy, or systemic therapy in patients with clinically advanced node-positive bladder cancer (cN2/N3).

Introduction: The management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer. Materials and methods: A retrospective analysis of the National Cancer Database for patients with stage IIIB urothelial bladder cancer was done from 2004-2019. Patients were classified as Group A: Those who received RC-PLND with perioperative chemotherapy, Group B: Those who received CRT, and Group C: Those who received only ST alone. The primary outcome was overall survival (OS). Inverse probability weighting (IPW)-adjusted Kaplan Meier curves were utilized to compare overall survival (OS) and cox multivariate regression analysis was used to identify predictors for OS. Results: Overall, 2,575 patients were identified. They were classified into Group A (n=1,278), Group B (n=317) and Group C (n=980). Compared to Group B, patients in Group A were younger (SMD=19.6%), had lower comorbidities (SMD=18.2%), had higher income (SMD=31.5%), had private insurance (SMD= 26.7%), were treated at academic centres (SMD=29.3%) and had higher percentage of N2 disease (SMD=31.1%). Using IPW-adjusted survival analysis, compared to Group C, the median OS was significantly higher in Group A (20.7 vs 14.2 months, p<0.001) and Group B (19.7 vs 14.2 months, p<0.001) but similar between Group A and Group B (20.9 vs 19.7 months, p=0.74). Both surgery (HR=0.72 (0.65-0.80), p<0.001) and CRT (0.70 (0.59-0.82), p<0.001) appeared to be independent predictors for OS on cox-regression analysis. The major limitations include bias due to retrospective analysis and non-assessment of cancer-specific survival. Conclusion: In stage IIIB bladder cancer with advanced lymph nodal disease, both RC and CRT offer equivalent survival benefits and are superior to systemic therapy alone.

Evaluation of cytotoxic properties of two fluorescent fac-Re(CO)3 complexes bearing an N,N-bidentate benzimidazole coligand.

The reaction between 1H-benzimidazol-2-ylmethyl-(N-aryl)amine derivatives (LR) and [ReBr(CO)5] afforded octahedral Re(i) complexes of the general formula of [ReBr(CO)3LR] (R = 4-Cl and 4-COOCH3). The Re(i) complexes were screened for their potential cytotoxicity against three malignant cell lines and one normal cell line of different origins. The solvatochromic characteristics of the complexes were examined by UV/vis. spectroscopy with the aid of time-dependent density functional theory calculations. Strong autofluorescence emission can be seen in the two Re(i) complexes between 460 and 488 nm. They appeared to accumulate inside intercellular connections and surrounding cellular membranes. The substances gathered also, along the cell membrane, waiting for their entry. The mode of cell death staining and the DNA fragmentation analysis revealed that the 4-Cl complex showed increased apoptotic changes in the MCF-7, and the Caco-2 cell line, while the HepG2 cell line showed little apoptotic changes.