Intraoperative Frozen Section via Neurosafe During Robotic Radical Prostatectomy in the Era of Preoperative Risk Stratifications and Primary Staging With mpMRI and PSMA-PET CT: Is There a Perfect Candidate?

BACKGROUND: We aimed to analyze the effect of preoperative risk assessment including Ga-68 PSMA PET and multiparametric magnetic resonance imaging (mpMRI) on nerve sparing practices, positive surgical margin (PSM) rates and oncological outcomes based on a comparison between patients underwent RARP with and without Neurosafe (NS). METHODS: Patients underwent RARP with NS (RARP-NS) or without (RARP-only) NS retrospectively evaluated. Suspicion for extracapsular extension on mpMRI and/or Ga-68 PSMA PET was recorded as i(imaging)T3. NS was performed according to the Martini-Klinik technique. PSM at preserved bundle side were called PSM at region of interest (ROI) while the others were elsewhere. RESULTS: A total of 208 patients (90 in RARP-NS, 118 in RARP-only groups) were included. Preoperatively the RARP-only group showed significantly higher mean PSA (p = .01) and PIRADS 5 (p = .002) findings and had more D'Amico high risk (DAHR) patients (p = .08). The overall PSM rates for pT2 versus pT3 disease were 7.5% versus 21.6 and 15.6% versus 55% in RARP-NS and RARP-only groups, respectively. NS resulted in more bilaterally preserved bundles (81.1% vs. 66.3%) and less PSM at the ROI (3.3% vs. 23.4%) than RARP-only group. NS outperformed RARP-only in all clinical settings had its highest differential benefit in more bilateral nerve sparing and less PSM at ROI in patients with both DAHR and iT3 disease. BCR rates were 2.2% and 2.5% for RARP-NS and RARP only groups, respectively (p = .4). One patient in RARP-NS and 9 in RARP-only groups had PSA persistence (p = .02). CONCLUSION: RARP-NS led to more preserved bundles with less PSM. It was especially useful in DAHR patients with preoperative extracapsular extension suspicion in imaging simultaneously.

Diagnostic Performance of 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography to Monitor Treatment Response in Patients with Metastatic Prostate Cancer: The Concordance Between Biochemical Response and Prostate-specific Membrane Antigen Results.

BACKGROUND: Treatment response is traditionally monitored using prostate-specific antigen (PSA) and conventional imaging in patients with metastatic prostate cancer (mPCa). OBJECTIVE: To assess the diagnostic performance of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) when monitoring mPCa patients receiving systemic treatment and also to investigate the concordance between PSMA PET response according to the PSMA PET progression (PPP) criteria and biochemical response. DESIGN, SETTING, AND PARTICIPANTS: A total of 96 patients with 68Ga-PSMA-11 PET/CT-detected mPCa at baseline PSMA PET/CT (bPSMA) who underwent at least one follow-up scan after receiving systemic treatment were included in the study. PSA levels at bPSMA and follow-up PSMA PET (fPSMA) scans were recorded. The PPP criteria were used to define PSMA progression. Biochemical progression was defined as ≥25% increase in PSA. PSMA PET and PSA responses were dichotomized into progressive disease (PD) versus non-PD, and the concordance between PSA and PSMA responses was evaluated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The concordance between PSA and PSMA PET responses was presented using frequencies, percentages, and Cohen's kappa test. RESULTS AND LIMITATIONS: A total of 345 serial PSMA PET/CT (96 bPSMA and 249 fPSMA) scans were evaluated. The positivity rates of PSMA PET scans for PSA levels of <0.01, 0.01-0.2, 0.2-4, and >4 ng/ml were 55.6%, 75.0%, 100%, and 98.8%, respectively. PSA and PSMA responses showed moderate-to-high concordance (Cohen's κ = 0.623, p < 0.001). PSA-PSMA discordance was detected in 39 scans (17%). The most common cause of discordance was the discordant results between different metastatic lesions (16/28, 57.1%) in patients with PPP without PSA progression and local progression in prostate (n = 7/11, 63.6%) in patients with PSA progression without PPP. CONCLUSIONS: PSMA PET/CT showed very high detection rates of malignant lesions even at very low PSA values and showed significant concordance with PSA response when monitoring treatment response in patients receiving systemic treatment for mPCa. PATIENT SUMMARY: This study describes that prostate-specific membrane antigen positron emission tomography (PSMA PET), a new sensitive imaging tool, can detect malignant lesions even at very low prostate-specific antigen values when monitoring metastatic prostate cancer. The PSMA PET response and biochemical response showed significant concordance, and the reason for discordant results seems to be the different responses of metastatic lesions and prostatic lesions to systemic treatment.

PSA change after antibiotic treatment should not affect decisionmaking on performing a prostate biopsy.

BACKGROUND: To investigate the effect of antibiotic treatment on PSA when deciding on prostate biopsy. METHODS: A total of 206 patients with an elevated PSA level (2.5-30) were included. Mp-MRI could be done on 129 patients. Patients were given ciprofloxacin (500 mg, b.i.d. p.o.) for 4 weeks and PSA measurements were repeated. Systematic prostate biopsy was performed regardless of PSA changes on all patients. Additionally, cognitive biopsies were performed from PI-RADs III, IV, and V lesions. RESULTS: : Prostate cancer was detected in 36.4% of patients. 53.3% had Gleason score of 3+3, 46.7% had Gleason score ≥ 3+4. PSA values decreased in 56.3% and in 43.7% and remained the same or increased but cancer detection rates were not different: 34.5% vs. 38.9%, respectively (p = 0.514). PSA change in whole group was significant (6.38 ng/mL vs. 5.95 ng/mL, respectively (p = 0.01). No significant PSA decrease was observed in cancer patients (7.1 ng/mL vs. 7.05 ng/mL, p = 0.09), whereas PSA decrease was significant in patients with benign pathology (6.1 ng/mL vs. 5.5 ng/mL, p = 0.01). In patients with PI-RADs IV-V lesions, adenocarcinoma was present in 33.9% and 30.4% with or without PSA decrease, respectively (p = 0.209). Clinically significant cancer was higher in patients with after antibiotherapy PSA values >4 ng/mL regardless of PI-RADs grouping (p = 0.08). Addition of any PSA value to PI-RADs grouping did not have any significant effect on the detection of cancer. DISCUSSION: PSA change after antibiotic treatment has no effect in detecting cancer and should not delay performing a biopsy.

Fluorescence-guided extended pelvic lymphadenectomy during robotic radical prostatectomy.

We evaluated and described the impact of prostatic indocyanine green (ICG) injection on extended pelvic lymph node (LN) dissection (ePLND) in robotic-assisted radical prostatectomy (RARP). Between January 2019 and December 2021, we included consecutive 50 PCa patients who underwent ePLND during RARP with (n = 25) or without (n = 25) prostatic ICG injection. ICG injection was performed during abdominal port placement and robot docking. Pelvic LNs reflecting green color were initially excised and then the template was completed. The outcomes of two groups were compared. Overall, nine (36%) and five (20%) of the patients had metastatic LN involvement in the ICG and non-ICG groups, respectively. Of the 509 dissected LNs in the ICG group, 122 (23.9%) were fluorescence active. 20 LNs (3.9%) were metastatic in this group, 9 (45%) of which were ICG+. 408 LNs were resected on the non-ICG group with 8(1.9%) being metastatic. Eight (88.9%) of nine pN+ patients were florescent positive in the ICG group. Out of six patients with pN+ disease, Ga68 PSMA-PET/CT detected positive LNs preoperatively. In addition to preoperative Ga68 PSMA-PET/CT investigation, ICG-guided ePLND might increase identification and removal of metastatic LNs duirng RARP. Improvements in staging and oncologic outcomes may also be seen in intermediate- and high-risk patients.

Endopelvic Fascia Sparing Robotic Radical Cystectomy with Intracorporeal Studer Pouch with Balbay's Technique.

Background and Objectives: Robotic radical cystectomy (RARC) with intracorporeal urinary diversion is a technically complicated, time-consuming procedure. The aim of this study was to present the operative, pathological, oncological, and functional outcomes of patients who underwent endopelvic fascia sparing (EPFS) RARC with intracorporeal Studer pouch formation. To the best of our knowledge, this is first series in the literature that includes EPFS RARC. Methods: Between October 1, 2019 and April 30, 2022, 10 bladder cancer patients underwent EPFS RARC, bilateral extended pelvic lymph node dissection with intracorporeal Studer pouch reconstruction with Balbay's technique. Patient demographics, operative, and post-operative parameters were recorded. Results: Among 10 patients, 8 were male and 2 were female. Mean operative time, median estimated blood loss, and median duration of hospital stay was 530 minutes, 316 ml, and 8 days, respectively. One month postoperatively, the mean maximum flow, average flow rate, mean voided, and post-voided urine volume were 20.2 ml/sec, 4.4 ml/sec, 273.6 ml, and 3.5 ml, respectively. All of the patients were fully continent during day-time, three had mild night-time incontinence requiring pad use (both patients 1 pad per night). During a mean 11.5 months of follow up, zero patients died. One patient with a pathological, stage 4 tumor, had nodal recurrence at six months postoperatively. No distant metastasis were detected. Conclusion: Endopelvic fascia sparing RARC has very promising early functional results with safe oncological outcomes and low complication rates.

Genitalia Preserving Robotic Radical Cystectomy with Intracorporeal Studer Pouch Formation in the Female: Experience in 5 Cases.

We present operative, postoperative, oncologic and functional outcomes of genital tract sparing robot-assisted laparoscopic radical cystectomy, bilateral extended pelvic lymph node (LN) dissection and intracorporeal Studer pouch construction on five female patients with bladder cancer. One of the cases had concomitant nephroureterectomy performed due to a non-functioning kidney. Median patient age, mean operation time, median estimated blood loss and mean duration of hospital stay were 59 (39-78), 462 ± 25, 400 (50-970), 8.8 ± 2.5, respectively. Pathologic stages were pTis (n=1), pT1 (n=1), pT3 (n=1), pT4a (n=1) and pT4b (n=1). Mean LN yield was 32.4 ± 8.9. Positive surgical margins were detected in 2 patients with pT4 diseases. Only minor complications developed that were resolved with medical treatment. Two patients had no, 1 patient had mild, and 2 patients had moderate daytime incontinence. One patient had good, 3 patients had fair, and 1 had poor night-time incontinence. This complex robotic surgery can be performed safely with acceptable short-term surgical, oncological and functional outcomes.

Is elective cancer surgery feasible during the lock-down period of the COVID-19 pandemic? Analysis of a single institutional experience of 404 consecutive patients.

BACKGROUND: We aimed to assess the feasibility and short-term clinical outcomes of surgical procedures for cancer at an institution using a coronavirus disease 2019 (COVID-19)-free surgical pathway during the peak phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. MATERIALS AND METHODS: This was a single-center study, including cancer patients from all surgical departments, who underwent elective surgical procedures during the first peak phase between March 10 and June 30, 2020. The primary outcomes were the rate of postoperative SARS-CoV-2 infection and 30-day pulmonary or non-pulmonary related morbidity and mortality associated with SARS-CoV-2 disease. RESULTS: Four hundred and four cancer patients fulfilling inclusion criteria were analyzed. The rate of patients who underwent open and minimally invasive procedures was 61.9% and 38.1%, respectively. Only one (0.2%) patient died during the study period due to postoperative SARS-CoV2 infection because of acute respiratory distress syndrome. The overall non-SARS-CoV2 related 30-day morbidity and mortality rates were 19.3% and 1.7%, respectively; whereas the overall SARS-CoV2 related 30-day morbidity and mortality rates were 0.2% and 0.2%, respectively. CONCLUSIONS: Under strict institutional policies and measures to establish a COVID-19-free surgical pathway, elective and emergency cancer operations can be performed with acceptable perioperative and postoperative morbidity and mortality.

68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging Before Radical Prostatectomy: Central Review of Imaging and Comparison with Histopathology of Extended Lymphadenectomy.

BACKGROUND: Results from prospective trials have shown higher accuracy of prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) in detection of lymph node metastasis (LNM) compared to conventional imaging. OBJECTIVE: To evaluate the accuracy of 68Ga-PSMA-11 PET/CT for LNM detection in patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS: Between June 2014 and November 2020, 96 patients with 68Ga-PSMA PET/CT for primary staging underwent RP and extended PLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The results from 68Ga-PSMA PET/CT were compared with histologic data from primary PLND in 96 patients. All 68Ga-PSMA PET/CT scans were centrally reviewed. RESULTS AND LIMITATIONS: Of 96 patients, 15.6% (n = 15) harbored LNMs. The median prostate-specific antigen at 68Ga-PSMA PET/CT was 8.0 ng/ml (interquartile range 5.5-11.7). The majority of patients had intermediate- (52.1%) or high-risk disease (41.7%). Biopsy grade group 4 and 5 was present in 22.9% and 15.6%, respectively. The 68Ga-PSMA PET/CT scans identified eight of 15 patients (53.3%) as LN-positive (true positive). The calculated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68Ga-PSMA PET/CT in the detection of LNM were 53.3%, 98.8%, 88.9%, 92.0%, and 91.7%, respectively. The per-patient sensitivity and specificity in the detection of LNMs larger than 2 mm were 61.5% and 98.8%, respectively. The main limitation is the retrospective design of the study. CONCLUSIONS: 68Ga-PSMA PET/CT is accurate in lymph node staging and the results support its use for primary staging of prostate cancer. PATIENT SUMMARY: We compared prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) findings with histopathology results after extended lymph node dissection and showed that it is accurate in detecting lymph node metastases. Our results support the use of PSMA PET/CT for primary staging of prostate cancer.

Feasibility, safety and efficacy of argon beam coagulation in robot-assisted partial nephrectomy for solid renal masses ≤ 7 cm in size.

One of the most important steps of the partial nephrectomy (PN) is hemostatic control of tumor bed which also effects the warm ischemia time (WIT). Argon beam coagulation (ABC) for decades is a well-known method for surface controls during major open surgical sites. This study aimed to compare peri- and postoperative relevant parameters in patients with ABC or internal renorrhaphy (IR) during robot-assisted partial nephrectomy (RAPN). One hundred seventy patients with ≤ 7 cm tumors, who underwent RAPN at our institutions, were included in this retrospective study. Tumor bed was controlled by either IR or by ABC after closing isolated overt collecting system defects. No additional IR was performed in patients with ABC. Estimated blood loss (EBL), WIT, estimated glomerular filtration rate (eGFR) change, on- vs. off-clamp procedure as well as Clavien-Dindo > 2 complications in both groups were compared. Eighty-seven (51.1%) patients had ABC and 83 (48.9%) had IR as their tumor bed control method. Tumor size, side and RENAL nephrometry score in both groups were similar. Mean warm ischemia time (WIT) was 20.8 min in ABC group and 23.8 min in IR group (p = 0.03). In 4-7 cm tumors, WIT was 19.9 min in ABC group while 26.6 min in IR group (p = 0.026). eGFR change from baseline and EBL favored ABC in entire cohort as well as in 4-7 cm tumors with statistical significance. There were more off-clamp procedures with ABC in ≤ 4 cm tumors. No ABC specific complications were observed. Within 2 years of follow-up, no patient developed recurrences. The control of the tumor base with ABC during RAPN shortens the warm ischemia times significantly compared to IR. Besides, ABC had better EBL and GFR changes outcomes. With close monitoring of intra-abdominal pressure and frequent venting, disturbing complications of ABC could completely be avoided. ABC was found to be feasible, safe and effective during RAPN.

Gut hormones and gut microbiota: implications for kidney function and hypertension.

Increased blood pressure (BP) and chronic kidney disease are two leading risk factors for cardiovascular disease. Increased sodium intake is one of the most important risk factors for development of hypertension. Recent data have shown that gut influences kidney function and BP by variety of mechanisms. Various hormones and peptides secreted from gut such as gastrin, glucocorticoids, Glucagon-like peptide-1 impact on kidney function and BP especially influencing sodium absorption from gut. These findings stimulate scientist to find new therapeutic options such as tenapanor for treatment of hypertension by blocking sodium absorption from gut. The gastrointestinal tract is also occupied by a huge community of microbes (microbiome) that under normal condition has a symbiotic relationship with the host. Alterations in the structure and function of the gut microbiota have been shown to play a key role in the pathogenesis and complications of numerous diseases including hypertension. Based on these data, in this review, we provide a summary of the available data on the role of gut and gut microbiota in regulation of BP and kidney function.

The role of sodium intake in nephrolithiasis: epidemiology, pathogenesis, and future directions.

The prevalence of nephrolithiasis has doubled over the last decade and the incidence in females now approaches that of males. Since dietary salt is lithogenic, a purported mechanism common to both genders is excess dietary sodium intake vis-a-vis processed and fast foods. Nephrolithiasis has far-reaching societal implications such as impact on gross domestic product due to days lost from work (stone disease commonly affects working adults), population-wide carcinogenic diagnostic and interventional radiation exposure (kidney stone disease is typically imaged with computed tomographic imaging and treated under imaging guidance and follow-up), and rising healthcare costs (surgical treatment will be indicated for a number of these patients). Therefore, primary prevention of kidney stone disease via dietary intervention is a low-cost public health initiative with massive societal implications. This primer aims to establish baseline epidemiologic and pathophysiologic principles to guide clinicians in sodium-directed primary prevention of kidney stone disease.

Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival.

BACKGROUND AND AIMS: Endostatin, generated from collagen XVIII, and endorepellin, possess dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. Few data on endostatins are available for patients with chronic kidney disease (CKD). We tested whether serum endostatin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. MATERIALS AND METHOD: A total of 519 CKD pre-dialysis patients were included. Baseline plasma endostatin levels were measured in all patients. All included patients were followed-up (time-to-event analysis) until occurrence of death, fatal or nonfatal CVEs. Fatal and nonfatal CVE including death, stroke, and myocardial infarction were recorded prospectively RESULTS: The mean age of the patients was 52.2±12.3years. There were 241 (46.4%) males, 111 (21.4%) had diabetes, 229 (44.1%) were smokers and 103 (19.8%) had a previous CVE. After a median follow-up of 46months, 46 patients died and 172 had a new CVE. In the univariable Cox survival analysis, higher endostatin levels were associated with a higher risk for both outcomes. However, after adjusting for traditional (age, gender, smoking status, diabetes, systolic blood pressure, HDL and total cholesterol) and renal-specific (eGFR, proteinuria and hsCRP) risk factors, endostatin levels remained associated only with the CVE outcome (HR=1.88, 95% CI 1.37-2.41 for a 1 SD increase in log endostatin values). CONCLUSION: Endostatin levels are independently associated with incident CVE in CKD patients, but show limited prediction abilities for all-cause mortality and CVE above traditional and renal-specific risk factors.

Novel Masters of Erythropoiesis: Hypoxia Inducible Factors and Recent Advances in Anemia of Renal Disease.

Anemia seen in patients with chronic kidney disease is a particular form of 'anemia of chronic disease'. Although multifactorial in origin, erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. Subsequent clinical observations revealed that these ESA hyporesponsive patients often had increased systemic inflammation as a consequence of their comorbidities. Use of high ESA doses to overcome this ESA hyporesponsiveness posed some concerns regarding associated adverse events of therapy and increased mortality in this special patient population. Recognizing the pivotal roles of hypoxia inducible factors (HIFs) in orchestrating elements of erythropoiesis opened new avenues in the management of renal anemia. Several phase 1 and 2 studies confirmed the results of early experimental studies supporting the beneficial role of augmenting HIFs for erythropoiesis. In this review, we describe the physiologic functions of HIF in erythropoiesis with special emphasis on interactions with iron and hepcidin metabolism and inflammation.