Managing prostate cancer after proctocolectomy and ileal pouch-anal anastomosis: feasibility and outcomes of single-port transvesical robot-assisted radical prostatectomy.

INTRODUCTION: Patients with proctocolectomy and ileal pouch-anal anastomosis (PC-IPAA) face unique challenges in managing prostate cancer due to their hostile abdomens and heightened small bowel mucosa radiosensitivity. In such cases, external beam radiation therapy (EBRT) is contraindicated, and while brachytherapy provides a safer option, its oncologic effectiveness is limited. The Single-Port Transvesical Robot-Assisted Radical Prostatectomy (SP TV-RARP) offers promise by avoiding the peritoneal cavity. Our study aims to evaluate its feasibility and outcomes in patients with PC-IPAA. METHODS: A retrospective evaluation was done on patients with PC-IPAA who had undergone SP TV-RARP from June 2020 to June 2023 at a high-volume center. Outcomes and clinicopathologic variables were analyzed. RESULTS: Eighteen patients underwent SP TV-RARP without experiencing any complications. The median hospital stay was 5.7 h, with 89% of cases discharged without opioids. Foley catheters were removed in an average of 5.5 days. Immediate urinary continence was seen in 39% of the patients, rising to 76 and 86% at 6- and 12-month follow-ups. Half of the cohort had non-organ confined disease on final pathology. Two patients with ISUP GG3 and GG4 exhibited detectable PSA post-surgery and required systemic therapy; both had SVI, multifocal ECE, and large cribriform pattern. Positive surgical margins were found in 44% of cases, mostly Gleason pattern 3, unifocal, and limited. After 11.1 months of follow-up, no pouch failure or additional BCR cases were found. CONCLUSION: Patients with PC-IPAA often exhibit aggressive prostate cancer features and may derive the greatest benefit from surgical interventions, particularly given that radiation therapy is contraindicated. SP TV-RARP is a safe option for this group, reducing the risk of bowel complications and promoting faster recovery.

Long-Term Functional and Oncologic Outcomes Following Robotic Partial and Radical Nephrectomy: A Report from a Single Institution with up to 15 Years of Follow-Up.

Objective: To evaluate the long-term functional and oncologic outcomes after robotic partial nephrectomy (RAPN) and radical nephrectomy (RARN). Materials and Methods: A retrospective review was performed on 1816 patients who underwent RAPN and RARN at our institution between January 2006 and January 2018. Patients with long-term follow-ups of at least 5 years were selected. Exclusion criteria included patients with a previous history of partial or radical nephrectomy, known genetic mutations, and whose procedures were performed for benign indications. Statistical analysis was performed with results as presented. Results: A total of 769 and 142 patients who underwent RAPN and RARN, respectively, met our inclusion criteria. The duration of follow-up was similar after the two procedures with a median of ∼100 months. The 5- and 10-year chronic kidney disease (CKD) upstaging-free survivals were 74.5% and 65.9% after RAPN and 53% and 46.4% after RARN, respectively. Older age was identified as a potential predictor for CKD progression after RARN, whereas older age, higher body mass index, baseline renal function, and ischemia time were shown to predict CKD progression after RAPN. Renal cell carcinoma-related mortality rates for RAPN and RARN were equally 1.1%. No statistically significant differences were identified in the local recurrence, metastatic, and disease-specific survival between the two procedures. Conclusion: Compared with RARN, RAPN conferred a better CKD progression-free survival. Several factors were identified as potential predictors for clinically significant CKD progression both in the early and late postoperative phase. Long-term oncologic outcomes between the two procedures remained similarly favorable.

Single-Port Robotic Radical Prostatectomy Using Transvesical and Transperineal Access in Patients with a Hostile Abdomen.

Introduction: Prostate cancer diagnosis and treatment is challenging in surgically complex patients. Radical prostatectomy can be performed without peritoneal entry using novel single-port (SP) transperineal (TP) and transvesical (TV) approaches. We sought to examine the outcomes of radical prostatectomy using novel TP and TV approaches in patients with extensive prior abdominal surgeries. Materials and Methods: From 2019 to 2023, 51 patients with extensive prior abdominal surgeries were identified who underwent TP (18) and SP TV (33) robotic radical prostatectomy. Indications included history of various surgeries with open laparotomy, including J-pouch reconstruction (22, 43%), active stoma (14, 27%), and open bowel resection (9, 18%). In all patients, 12/51 (24%) had a history of incisional hernia repair with mesh. A retrospective analysis was performed. Results: All cases were completed without open conversion, bowel injuries, or blood transfusions. Length of stay was 5.6 hours for TV and 22 hours for TP. No opioids were prescribed in 91% of TV vs 56% of TP. One intraoperative complication (ureteral injury) occurred in a patient undergoing the TP approach. Postoperative complications were noted in 14/51 (27%), including 10/18 (56%) TP vs 4/33 (12%) TV. High-grade complications (Clavien 3) occurred in three patients (6%, all TP). Pathologic staging showed pT3 in 26/51 (17 TV vs 9 TP), while the remainder were pT2. Biochemical recurrences were noted in four patients (8%, three TV and one TP). Immediate continence was noted in 30% of TV patients. Long-term continence after 12 months was 92% in TV and 67% in TP. Conclusions: In patients with extensive prior abdominal surgeries, radical prostatectomy is feasible using a TP or TV approach. No bowel injuries or open conversion were observed. The SP TV approach offers advantages of shorter hospital stay, shorter catheter duration, less opioid use, fewer complications, and improved continence recovery.

Complications of single-port robot-assisted radical prostatectomy: multi-institutional analysis from the Single-Port Advanced Research Consortium (SPARC).

OBJECTIVE: To evaluate the perioperative complications of single-port robot-assisted radical prostatectomy (SP-RARP). PATIENTS AND METHODS: A retrospective review was performed on the prospectively maintained, Institutional Review Board-approved, multi-institutional Single-Port Advanced Research Consortium (SPARC) database. A total of 1103 patients were identified who underwent three different approaches of SP-RARP between 2019 and 2022 using the purpose-built SP robotic platform. In addition to baseline clinical, perioperative outcomes, this study comprehensively analysed for any evidence of intraoperative complication, as well as postoperative complication and readmission within 90 days of the respective surgery. RESULTS: Of the 244, 712, and 147 patients who underwent transperitoneal, extraperitoneal, and transvesical SP-RARP, respectively, intraoperative complications were noted in five patients (0.4%), all of which occurred during the transperitoneal approach. Two patients had bowel serosal tears, two had posterior button-holing of the bladder necessitating repair, and one patient had an obturator nerve injury. Postoperative complications were noted in 143 patients (13%) with major complications (Clavien-Dindo Grade ≥III) only identified in 3.7% of the total cohort. The most common complications were lymphocele (3.9%), acute urinary retention (2%), and urinary tract infection (1.9%). The 90-day re-admission rate was 3.9%. CONCLUSION: The SP-RARP is a safe and effective procedure with low complication and readmission rates regardless of the approach. These results are comparable to current multi-port RARP literature.

First 100 cases of transvesical single-port robotic radical prostatectomy.

Objective: To describe the surgical technique and report the early outcomes of the transvesical (TV) approach to single-port (SP) robot-assisted radical prostatectomy. Methods: All procedures were performed at a single center by one surgeon. We identified the first 100 consecutive patients with clinically localized prostate cancer that underwent SP TV robot-assisted radical prostatectomy using the da Vinci SP robotic surgical system. Data were collected prospectively and analyzed with descriptive statistics. The primary outcomes assessed were postoperative urinary continence, rate of biochemical recurrence, and sexual function. Results: All procedures were performed without extra ports or conversion. The median age was 62.1 years and 49.0% of the patients had abdominal surgery history. The preoperative median prostate-specific antigen value and prostate volume were 5.0 ng/mL and 33.0 mL, respectively. There were no intraoperative complications. The median operative time and estimated blood loss were 212.5 min and 100.0 mL, respectively. A total of 92.0% of patients were discharged within 24.0 h, with an overall median length of stay of 5.6 h. Only 4.0% of patients required opioid prescriptions at discharge. The median Foley catheter duration was 3 days. Positive margins were present in 15.0% of cases. Median follow-up was 10.4 months. Continence rate was immediate after Foley removal in 49.0% of cases, 65.0% at 2 weeks, 77.4% at 6 weeks, 94.1% at 6 months, and 98.9% at 1 year. One case of biochemical recurrence (1.0%) was noted 3 months after surgery. Conclusion: The SP TV approach for radical prostatectomy cases is a safe and feasible technique for patients with clinically localized prostate cancer. This technique offers advantages of short hospital stay, minimal narcotic use postoperatively, and promising early return of urinary continence, without compromising oncologic outcomes.

Low Risk of Postoperative Hernia Following Single-port Robot-assisted Radical Prostatectomy: A Report From the Single-port Advanced Research Consortium (SPARC).

OBJECTIVE: To evaluate the risk of postoperative hernia following different approaches of single-port robot-assisted radical prostatectomy (SP-RARP). METHODS: A retrospective review was performed on patients who underwent SP-RARP between February 2019 and December 2022. Demographic and clinical information was collected from the multi-institutional, prospectively-maintained Single-Port Advanced Research Consortium (SPARC) database. Data were analyzed using IBM Statistical Packaging for Social Sciences (SPSS) version 29.0 with descriptive statistics as presented. RESULTS: A total of 1103 patients were identified, consisting of 244 (22.1%), 712 (64.6%), and 147 (13.3%) cases performed via transperitoneal, extraperitoneal (EP), and transvesical (TV) approaches, respectively. During a median follow-up time of 11 months (interquartile range 5.7-17.1 months), only two cases of incisional hernia were reported. Both cases occurred following transperitoneal SP-RARP with one patient requiring surgical repair. There remains no evidence of postoperative hernia following EP and TV SP-RARP at the completion of our review. CONCLUSION: SP-RARP was associated with low risk for postoperative hernia. The risk was lower following TV and EP SP-RARP where the peritoneum is preserved.

The Transition Toward Opioid-sparing Outpatient Radical Prostatectomy: A Single Institution Experience With Three Contemporary Robotic Approaches.

OBJECTIVE: To evaluate for differences in the perioperative and early postoperative outcomes between three different contemporary approaches of robotic radical prostatectomy (RARP), namely Single-Port (SP) Transvesical (TV), SP Extraperitoneal (EP), and Multi-Port (MP) Transperitoneal (TP). METHODS: Retrospective review was performed on 865 consecutive patients with localized prostate cancer who underwent SP-TV, SP-EP, and MP-TP RARP. SP-TV and SP-EP RARP were performed using the purpose-built SP robotic platform. All procedures were performed by a single, experienced robotic surgeon. Demographics, perioperative, and early postoperative data were collected from the prospectively-maintained database. Statistical analysis was performed with descriptive statistics as presented. RESULTS: All SP cases were completed without any need for conversion or additional ports. When compared with MP-TP RARP, both SP-EP and SP-TV RARP were associated with significantly reduced length of stay (median, SP-TV 5.07 vs SP-EP 5.1 vs MP-TP 26.6 hours, P = <.05) and with most patients being discharged within 24 hours (SP-TV 92.3% vs SP-EP 84.6% vs MP-TP 30.4%, P = <.05). Postoperative analgesia requirements were significantly reduced following SP-TV RARP with 95% did not require opioid analgesia after discharge, as opposed to 77.6% and 12.1% of patients in the SP-EP and MP-TP RARP cohorts, respectively (P = <.05). Additionally, SP-TV RARP demonstrated the added benefit of a shorter Foley catheter duration of 4 days with an earlier return of urinary continence. CONCLUSION: The localization of RARP, as facilitated by the SP robotic platform, provided the opportunity for enhanced postoperative recovery resulting in decreased length of admission and postoperative pain, which allowed for increasing adoption of opioid-sparing outpatient prostatectomy.

Holmium Laser Enucleation of the Prostate vs Transvesical Single-port Robotic Simple Prostatectomy for Large Prostatic Glands.

OBJECTIVE: To compare the perioperative outcomes of transvesical single-port robotic simple prostatectomy (SP-RASP) and holmium laser enucleation of the prostate (HoLEP). MATERIALS AND METHODS: A retrospective review was performed of patients undergoing SP-RASP and HoLEP from 2019 to 2022 with preoperative prostatic volume (PPV) >80 cm3. Percent of prostate adenoma removed (%PAR) was estimated by specimen weight normalized by PPV. Univariate analysis was performed using chi-square, Fisher exact, and Wilcoxon rank-sum tests. A subgroup analysis with 1:1 matching for PPV was also performed. RESULTS: A total of 50 SP-RASP and 90 HoLEP cases were analyzed. The median (interquartile range) PPV was 169 (128-244)cm3 for SP-RASP and 129 (100-150)cm3 for HoLEP, (P < .01). The median (interquartile range) %PAR was 57(44-68) for SP-RASP vs 51(42-62) for HoLEP (P = .10). Overall, 11(12%) HoLEP and 5(10%) SP-RASP patients experienced complications (P = .51). Same-day discharge occurred in 24(48%) SP-RASP vs 7(8%) HoLEP patients (P < .01). Median foley catheter duration was longer in SP-RASP (6 vs 1 day, P < .01) and trial of void was successful at first attempt in >94% (P = .68). Transient de novo incontinence was reported in 24(28%) HoLEP vs 2(5%) SP-RASP (P < .01). No differences in voiding parameters were observed at latest follow up. Subgroup postmatched analysis revealed analogous findings. CONCLUSION: SP-RASP and HoLEP have similar favorable perioperative outcomes for management of large prostatic adenomas. SP-RASP may be considered in patients unwilling to accept the risk of transient incontinence and in those with unfavorable urethral access, large bladder stone burden, or diverticula.

Vesicourethral Anastomosis in Transvesical Single-Port Robotic Radical Prostatectomy: A Technical Description and Perioperative Outcomes.

Objective: To describe the technical evolution and perioperative outcomes of vesicourethral anastomosis (VUA) in transvesical (TV) single-port robot-assisted radical prostatectomy (SP-RARP). Materials and Methods: A retrospective review was performed on 189 patients who underwent TV SP-RARP by a single surgeon using the purpose-built SP robotic platform. VUA was completed from within the bladder using two unidirectional V-loc sutures in a continuous, semicircular manner with greater emphasis posteriorly. The most recent 20 cases of TV SP-RARP were selected to evaluate the anastomosis technique and to compare the perioperative outcomes with the first 20 cases of TV SP-RARP performed at our institution. Demographic and clinical data were collected from the prospectively maintained database and statistical analysis was performed. Results: VUA was effectively completed in all cases using the aforementioned technique without any suture breaks, need for conversion, or evidence of intraoperative complication, including urine leak. Marked improvement in the learning curve was observed, which translated to significant reduction in the number of VUA sutures (median: 13 vs 15, p < 0.05) and faster anastomosis time (median: 19.1 vs 33.5 minutes, p < 0.05). The number of anastomotic sutures did not correlate with the prostatectomy specimen weight or volume, especially with both being significantly greater in the latest cases (median weight: 45.1 vs 37.6 g, p < 0.05; median volume: 40.9 vs 36.2 mL, p < 0.05). Postoperative outcomes were favorable with immediate continence achieved in 51.3% of our total cohort and with no patients demonstrating evidence of bladder neck contracture. Conclusion: We provided a detailed technical description of VUA in TV SP-RARP. The improved maneuverability of the SP robotic platform allowed for unique movements to facilitate suture placements from within the confined space of the bladder. The learning curve of a single surgeon was shown in our study, which resulted in notable reduction in the number of sutures, faster anastomosis time, and improved perioperative outcomes.

Single-port Transvesical Robot-assisted Radical Prostatectomy: The Surgical Learning Curve of the First 100 Cases.

OBJECTIVE: To determine the number of cases required to reach plateau performance. METHODS: We performed a single-surgeon review of the first 100 consecutive procedures. All procedures were performed using the da Vinci single-port robotic system between November 2020 and March 2022. Time was used as the measure of the learning curve (LC). Relevant surgical steps were considered separately for detailed analysis. Data were collected retrospectively and analyzed through the cumulative sum method and moving average graphing. A comparative analysis was done between subgroups of 20 consecutive cases for perioperative outcomes. RESULTS: All cases were completed successfully, without extra ports or conversion. The LC for prostate excision showed initial exponential improvement and reached plateau at case 28. Vesicourethral anastomosis time gradually shortened over time, with a clear inflection point at case 10. Total operative time rapidly improved and plateaued early to 213.0 minutes. Robot-docking and undocking, achieving hemostasis, wound closure, and intraoperative idle times were consistent throughout the series. Estimated blood loss decreased significantly after the first 20 cases (from median of 135.0-88.0 mL, P = .03). CONCLUSION: In our early experience, the LC for single-port transvesical robot-assisted radical prostatectomy suggests that performance improved after 10-30 cases in the hands of an experienced robotic surgeon.

Single Port Versus Multiport Robot-assisted Simple Prostatectomy: A Multi-institutional Study From the Single-port Advanced Research Consortium (SPARC).

OBJECTIVE: To compare robot-assisted simple prostatectomy intraoperative and postoperative.ßoutcomes between single-port (SP) and multiport (MP) robotic systems in a multi-institutional setting. METHODS: We analyzed all-consecutive robot-assisted simple prostatectomy cases done in 5 centers from January 2017 to October 2022. Data were analyzed with descriptive statistics and compared with appropriate tests depending on the type of variable and distribution. Statistical significance was considered when P.ß<.05. RESULTS: A total of 405 cases were analyzed:.ß249 and 156 were MP and SP, respectively. Operative times were similar between groups (P.ß=.ß.62). Estimated blood loss during surgery was significantly lower with the SP robot (P.ß<.001). Postoperatively, the SP approach required a significantly shorter hospital stay, less use of opioids, and a shorter duration of Foley catheter (P.ß<.001). There was no significant difference between the post-operative Clavien-Dindo ...3 complication rate (P.ß=.ß.30). The 30-day readmission rate of MP (10.8%) was significantly higher than for SP (0%) (P.ß<.001). De novo urge incontinence was more common in the MP group (P.ß=.ß.02). CONCLUSION: The SP robotic approach to simple prostatectomy is advantageous when it comes to postoperative comfort for patients. Specifically, it requires a shorter hospital stay, less use of opioids, and a shorter Foley catheter duration.

Minimally-Invasive Radical Nephrectomy and Left-Sided Level II Caval Thrombectomy: A New Combined Technique.

OBJECTIVE: To present a combined multiport robotic and open approach for left radical nephrectomy and inferior vena cava thrombectomy in patients with a primary left renal mass and level II inferior vena cava (IVC) tumor thrombus. METHODS: A 69-year-old female was diagnosed with an 8.9cm left renal neoplasm with level II IVC thrombus. She was placed in the left-side-up flank position. The descending colon was mobilized and the left gonadal vein was identified. The left renal vein was identified and fully dissected. The left renal artery was dissected and stapled. The kidney was dissected and left detached with exception of the renal vein. The robot was undocked and the patient was positioned supine. Through a supra-umbilical midline incision, the ascending colon and duodenum were mobilized medially. The right renal vein and IVC were identified and dissected to the level of hepatic veins. The IVC was clamped using a Satinsky clamp. The right renal artery and vein remained patent during thrombectomy. The IVC was opened, the thrombus was evacuated, and IVC was closed. Clamps were removed and the kidney was removed. RESULTS: Operative time was 405 minutes. IVC clamp time was 14 minutes. Estimated blood loss was 500cc. Recovery was uncomplicated. Length of stay was 4 days. Pathology showed clear cell carcinoma with negative margins. CONCLUSION: IVC thrombectomy is challenging on left sided tumors. Combining a robotic and open technique together is feasible and allows a smaller supra-umbilical midline incision compared to standard open incision.

Single-port Robotic Transvesical Partial Prostatectomy for Localized Prostate Cancer: Initial Series and Description of Technique.

BACKGROUND: Partial prostatectomy has been described as an alternative to focal therapy for the management of localized low- and intermediate-risk prostate cancer. OBJECTIVE: To describe early outcomes and technique for single-port (SP) transvesical partial prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed for nine patients with low-volume, localized, low- to intermediate-risk prostate cancer (Gleason ≤7) undergoing SP transvesical partial prostatectomy replicating the inclusion criteria for focal therapy by a single surgeon from November 2020 to March 2022. SURGICAL PROCEDURE: The daVinci SP access port was inserted percutaneously into the bladder and pnuemovesicum was achieved. The camera, robotic instruments, assistant port, and flexible suction tubing were introduced through the access port. The Koelis transrectal ultrasound with preoperative prostate magnetic resonance imaging fusion was used for intraoperative guidance. MEASUREMENTS: Demographic information, intraoperative variables, and postoperative outcomes were collected in an institutional review board-approved database, and a descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: All cases were completed without requiring extra ports or conversion. No intraoperative complications were noted, and all patients were discharged on the day of surgery. Pathology showed Gleason scores of 3 + 3 = 6 in one case, 3 + 4 = 7 in seven cases, and 4 + 3 = 7 in one case, all with negative intraoperative margin assessment. At 6 wk, the median prostate-specific antigen was 0.5 and the median Sexual Health Inventory for Men score was 17.5 from 23 preoperatively. All patients were continent at 6 wk. The limitations include a small number of patients, short follow-up, and single-surgeon experience. CONCLUSIONS: We demonstrated the feasibility of the SP robotic transvesical partial prostatectomy. Early functional outcomes show impressive time to continence and erectile function. Continued follow-up will evaluate long-term oncologic outcomes. PATIENT SUMMARY: We performed partial prostatectomies in selected patients as an alternative to focal therapy using a novel transvesical single-port approach. Our approach was safe and feasible, with fewer complications and promising initial return to continence and erectile function.

A Transition Toward a Faster Recovery in Single-Port Transvesical Simple Prostatectomy.

Objectives: To present the updated technique and evaluate the perioperative and postoperative outcomes of single-port transvesical simple prostatectomy (SP TVSP) Patients and Methods: Forty-two consecutive patients with benign prostatic hyperplasia indicated for surgery underwent SP TVSP in a single institution. Through direct suprapubic bladder access, the SP robot was docked. Prostatic enucleation was performed using the prostatic capsule as a landmark. Then a complete vesicourethral mucosal advancement flap was accomplished. Demographics, perioperative, and postoperative data were prospectively collected. Mean follow-up period was 12 months. Results: All procedures were effectively performed with no conversion, additional port placement, or intraoperative complication. The median prostatic volume was 170 cc. Ninety-five percent of the patients did not require opioids analgesia after discharge. Excluding planned admissions, 92% (21/23 patients) were discharged after a median (interquartile range) of 4.6 (4.1-5.7) hours after surgery. The median Foley catheter duration for all cohort was 7 days, and decreased to 3 days after technique adjustment for the last 19 consecutive patients. The median international prostate symptom score decreased from 23 before surgery to 2.5 after surgery. All patients had a significant postoperative improvement in maximum flow rate with a 200% improvement over baseline (19 vs 6.5 mL/sec). Conclusion: In our initial series, SP TVSP allows for favorable perioperative and early postoperative outcomes including low complication same-day discharge, short Foley catheter stay, minimal opioids use, and quick recovery.

Delaying Cancer Cases in Urology during COVID-19: Review of the Literature.

PURPOSE: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting hospital systems and the availability of resources for surgical procedures. Our aim is to provide guidance for urologists to help prioritize urological cancer surgeries. MATERIALS AND METHODS: We reviewed published literature on bladder cancer, upper tract urothelial carcinoma, penile cancer, testis cancer, prostate cancer, renal cancer and adrenal cancer. RESULTS: For muscle invasive bladder cancer delays should be less than roughly 10 weeks and neoadjuvant chemotherapy should be considered. Patients with nonmuscle invasive bladder cancer should be counseled appropriately based on risk and intravesical therapies can continue. Upper tract urothelial carcinoma should also be treated with minimal delays for high risk patients, especially with ureteral tumors. Surgery for T1 renal cancers when indicated can be delayed until adequate resources are available. Patients with T2 renal cancer should be considered for early surgery if there are unfavorable preoperative characteristics. Higher stage renal tumors should be considered for early surgery. An early multidisciplinary approach is recommended for metastatic renal cancers. High risk prostate cancer may need preferential treatment and consideration of neoadjuvant hormonal therapy. Penile cancer can have worse sexual or oncologic outcomes with prolonged surgical delay. Likewise, adrenal cancer is aggressive and needs early surgical treatment. Testicular cancer should be treated in a timely manner with surgery or chemotherapy, as indicated. CONCLUSIONS: This review should further assist urologists in recognizing patients with potentially aggressive tumor biology that warrants early treatment.

Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.

The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

Mass-spectrometric profiling of porphyrins in complex biological samples with fundamental, toxicological, and pharmacological applications.

Rapid, high-throughput, and quantitative evaluations of biological metabolites in complex milieu are increasingly required for biochemical, toxicological, pharmacological, and environmental analyses. They are also essential for the development, testing, and improvement of new commercial chemical products. We demonstrate the application of ultra-high performance liquid chromatography-mass spectrometry (uHPLC-MS), employing an electrospray ionization source and a high accuracy quadrupole time-of-flight mass analyzer, for the identification and quantification of a series of porphyrin derivatives in liver: a matrix of particular relevance in toxicological or pharmacological testing. Exact mass is used to identify and quantify the metabolites. Chromatography enhances sensitivity and alleviates potential saturation issues by fanning out the contents of a complex sample before their injection into the spectrometer, but is not strictly necessary for the analysis. Extraction and sample treatment procedures are evaluated and matrix effects discussed. Using this method, the known mechanism of action of a well-characterized porphyrinogenic agent was verified in liver extracts from treated rats. The method was also validated for use with bacterial cells. This exact-mass method uses workhorse instruments available in many laboratories, providing a highly flexible alternative to existing HPLC- and MS/MS-based approaches for the simultaneous analysis of multiple compounds in biological media.