Hypoxemia of the lower limbs during robot-assisted radical prostatectomy in Trendelenburg position.

Objectives: The objective of this study is to assess frequency and risk factors for intraoperative hypoxemia of the lower limbs during robot-assisted radical prostatectomy (RARP). Trendelenburg position during RARP may contribute to hypoxemia and compartment syndrome (CS) of the lower limbs as a major but rare complication. Patients and methods: This prospective study included patients undergoing RARP for prostate cancer. Preoperative calculation of the ankle-brachial-index (ABI) was performed. Peripheral oxygen saturation (SpO2) at the toes was routinely measured. Occurrence of SpO2 levels of <90% was defined as hypoxemic events and treated immediately. Blood pressure, intraabdominal pressure, SpO2 of the upper limb and surgery time were monitored in case of hypoxemia. A multivariable logistic regression model was performed with age, BMI, nicotine abuse, MAP, comorbidities as covariates and hypoxemia of the lower limbs as the outcome. Results: A total of 207 patients were included. Among these, 126 patients had ABI measurements with 10.6% having an abnormal ABI value. One, two or at least three events of lower limb hypoxemia occurred intraoperatively in 19.7%, 14.8% and 16.9%, respectively. In 20 events, surgical instruments were affecting vascular perfusion by compression. None of the covariates were statistically significant associated with lower limb hypoxemia. No patient developed a compartment syndrome. Conclusion: Decrease in oxygen saturation of the lower extremities was observed frequently during RARP, without revealing any risk factors for its occurrence. Routine oximetry leads to an early detection of hypoxemia of the lower extremities, giving the anaesthesiologist and surgeon the opportunity to make adequate adjustments (increasing blood pressure and ending iliac vessel compression).

Urgent Endovascular Aortic Repair Requiring Coverage of the Left Subclavian Artery.

BACKGROUND: Evaluation of the optimal left subclavian artery (LSA) management during thoracic endovascular aortic repair (TEVAR) involving the distal aortic arch in an urgent setting. METHODS: A total of 52 patients with acute aortic syndromes underwent TEVAR (March 2017 to May 2021) requiring proximal landing in the distal aortic arch. Decision for partial or complete LSA ostial endograft coverage, with or without additional bypassing, was made depending upon the aortic pathology and vascular anatomy. We focused on the patency of the circle of Willis and the unilateral dominance of one carotid or a vertebral artery: 35% underwent complete (complete LSA group) and 17% partial LSA coverage (partial LSA group), whereas in 48% the LSA was reached only by the bare springs of the endograft (control group). A total of 22% of the complete LSA group underwent LSA bypass before TEVAR, whereas 11% underwent cerebrospinal fluid drainage. Endpoints were 30-day and 1-year mortality, stroke, spinal cord ischemia (SCI), and malperfusion. RESULTS: Technical success was achieved in 96%. The endograft length was 171 ± 34 (complete LSA group) versus 151 ± 22 (partial LSA group) versus 181 ± 52 mm (control group), covering 6 ± 2 versus 5 ± 1 versus 7 ± 2 intercostal arteries. The 30-day mortality, stroke and SCI rates did not differ. One patient with arm malperfusion underwent LSA bypass post-TEVAR. After 1 year, aortic interventions occurred in 6 (complete LSA group) versus 22 (partial LSA group) versus 13% (control group). One-year mortality (0 vs. 0 vs. 8%), stroke (6 vs. 0 vs. 4%), and SCI (0 vs. 0 vs. 4%) were similar between groups. CONCLUSION: With an adequate analysis of vascular anatomy, coverage of the LSA for TEVAR is safe and may offer results similar to TEVAR starting distal to the LSA.

Functional outcome after radical prostatectomy in 1313 patients: A single-center study.

OBJECTIVES: To assess the impact of urinary continence and erectile function on the quality of life in men undergoing radical prostatectomy (RP) for prostate cancer (PC), we analyzed the preoperative and 1-year postoperative outcomes of five functional domains and their influencing factors. PATIENTS AND METHODS: In this prospective study, all patients undergoing open or robot-assisted RP between Febuary 2017 and March 2020 in a single academic center were included. Patient-reported outcomes were assessed pre- and 12 months postoperatively using the Expanded Prostate Index Composite (EPIC-26) survey, evaluating continence, irritative/obstructive micturition, gastrointestinal symptoms, sexuality, and overall vitality. We examined the impact of RP on sexual function and urinary continence using multivariable logistic regression models, accounting for patient and tumor characteristics. RESULTS: Overall, 1313 consecutive patients gave consent for study participation and completed both surveys. The median age was 66 years (IQR: 60-70). The majority of patients (n = 601, 46%) had an intermediate risk PC. Robotic RP was performed in 71.6% and nerve-sparing technique in 81% of the cases. The median pre- versus postoperative scores were the following: urinary continence 100 (IQR: 91.8-100) versus 85.5 (64.8-100), irritative micturition 87.5 (IQR: 75-100) versus 93.8 (IQR: 87.5-100), gastrointestinal symptoms the same with 100 (IQR: 95.8-100), vitality 95 (IQR: 80-100) versus 90 (IQR: 75-100), and erectile function 65.3 (IQR: 38.8-87.5) versus 22.2 (IQR: 12.5-48.7), respectively. Age (p < 0.001), risk classification (p = 0.002), and nerve-sparing surgery (p = 0.016) were associated with good sexual function (EPIC-26 score ≥60), while only age (p = 0.001) was statistically significantly associated with good urinary continence (EPIC-26 score ≥80). CONCLUSION: Non-modifiable factors such as age and PC risk classification impact urinary continence and sexual function after RP. Nevertheless, urologic surgeons should further focus on improving nerve-sparing techniques, the only modifiable variable, to reduce the surgery's negative impact on urinary continence and sexual function.

Association between Operative Time and Short-Term Radical Cystectomy Complications.

INTRODUCTION: The aim of this study was to examine the relationship between duration of surgical intervention and postoperative complications in radical cystectomy (RC). We hypothesized that the complication rate increases with longer operative time. METHODS: We analyzed the National Surgical Quality Improvement Program database 2011-2017 to identify all patients who underwent RC. Clinicodemographic characteristics, operative time, and perioperative complications using the Clavien-Dindo Classification (CDC) were abstracted. We fit a generalized linear model with linear splines for operative time to analyze if the relationship between operative time and probability of complication changed over time. RESULTS: A total of 10,520 RC patients were identified with a mean operative time of 5.5 h (standard deviation 2.03). In 55% and 18.2%, any complication and major complications (CDC ≥3) occurred within 30 days postoperatively, respectively. The spline regression model for any complication showed an almost linear relationship between the complication rate and operative time, ranging from 55% at 2.5 h to 82% at 10 h. For major complications, the model revealed the inflection point (knot) at 4.5 h, which corresponds to the lowest complication rate with 15%. Operative times at the extremes of the distribution had higher complication rates: 17.5% if <2.5 h and 28% if >10 h. DISCUSSION/CONCLUSION: Operative time of RC is associated with postoperative complications. Though many factors impact the duration of surgery, surgeries that lasted between 4 and 5 h had trend toward the lowest complication rates. Attention to factors impacting operative time may allow surgeons to identify strategies for optimizing surgical care and reducing complications after RC.

Immune checkpoint inhibitor monotherapy is associated with less cardiac toxicity than combination therapy.

BACKGROUND: Treatment options for many cancers include immune checkpoint inhibitor (ICI) monotherapy and combination therapy with impressive clinical benefit across cancers. We sought to define the comparative cardiac risks of ICI combination and monotherapy. METHODS: We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac ADRs (cADRs), such as carditis, heart failure, arrhythmia, myocardial infarction, and valvular dysfunction, related to ICI therapy. To explore possible relationships, we used the reporting odds ratio (ROR) as a proxy of relative risk. A lower bound of a 95% confidence interval of ROR &gt; 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance. RESULTS: We found 2278 cADR for ICI monotherapy and 353 for ICI combination therapy. Combination therapy was associated with significantly higher odds of carditis (ROR 6.9, 95% CI: 5.6-8.3) versus ICI monotherapy (ROR 5.0, 95% CI: 4.6-5.4). Carditis in ICI combination therapy was fatal in 23.4% of reported ADRs, compared to 15.8% for ICI monotherapy (P = 0.058). CONCLUSIONS: Using validated pharmacovigilance methodology, we found increased odds of carditis for all ICI therapies, with the highest odds for combination therapy. Given the substantial risk of severe ADR and death, clinicians should consider these findings when prescribing checkpoint inhibitors.

Are work relative value units correlated with operative duration of common surgical procedures?

OBJECTIVES: Work relative value units (wRVUs) quantify physician workload. In theory, higher wRVU assignments for procedures recognize an increase in complexity and time required to complete the procedure. The fairness of wRVU assignment is debated across specialties, with some surgeons arguing that reimbursement may be unfairly low for longer, more complex cases. For this reason, we sought to assess the correlation of wRVUs with operative time in commonly performed surgeries. STUDY DESIGN: We analyzed the National Surgical Quality Improvement Program database, selecting the 15 most performed surgical procedures across specialties in a 90-day global period, using Current Procedural Terminology codes. METHODS: Calculation and comparison of mean operative time and mean wRVUs were performed for each of the 15 procedures. Cases with missing values for wRVUs or operative time and cases with an operative time of less than 15 minutes were excluded. The Spearman correlation coefficient was calculated to evaluate the strength of correlation between operative duration and wRVUs. RESULTS: A total of 1,994,394 patients met criteria for analysis. The lowest mean wRVU was 7.78 (95% CI, 7.77-7.78) for inguinal hernia repair; the highest was 43.50 (95% CI, 43.37-43.60) for pancreatectomy. The shortest mean operative time was 51.0 (95% CI, 50.8-51.1) minutes for appendectomy; the longest was for pancreatectomy at 324.6 (95% CI, 323.2-326.0) minutes. The Spearman correlation coefficient was 0.81. CONCLUSIONS: In our analysis, we found a strong correlation between operative duration and wRVU assignment. Thus, the reimbursement of physicians depending on wRVUs is fair for the most commonly performed surgical procedures across specialties.

Nephrotoxicity of immune checkpoint inhibitor therapy: a pharmacovigilance study.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy has demonstrated impressive clinical benefits across cancers. However, adverse drug reactions (ADRs) occur in every organ system, often due to autoimmune syndromes. We sought to investigate the association between ICI therapy and nephrotoxicity using a pharmacovigilance database, hypothesizing that inflammatory nephrotoxic syndromes would be reported more frequently in association with ICIs. METHODS: We analyzed VigiBase, the World Health Organization pharmacovigilance database, to identify renal ADRs (rADRs), such as nephritis, nephropathy and vascular disorders, reported in association with ICI therapy. We performed a disproportionality analysis to explore if rADRs were reported at a different rate with one of the ICI drugs compared with rADRs in the entire database, using an empirical Bayes estimator as a significance screen and defining the effect size with a reporting odds ratio (ROR). RESULTS: We found 2341 rADR for all examined ICI drugs, with a disproportionality signal solely for nephritis [ROR = 3.67, 95% confidence interval (CI) 3.34-4.04]. Examining the different drugs separately, pembrolizumab, nivolumab and ipilimumab + nivolumab combination therapy had significantly higher reporting odds of nephritis than the other ICI drugs (ROR = 4.54, 95% CI 3.81-5.4; ROR = 3.94, 95% CI 3.40-4.56; ROR 3.59, 95% CI 2.71-4.76, respectively). CONCLUSIONS: Using a pharmacovigilance method, we found increased odds of nephritis when examining rADRs associated with ICI therapy. Pembrolizumab, nivolumab and a combination of ipilimumab + nivolumab showed the highest odds. Clinicians should consider these findings and be aware of the increased risk of nephritis, especially in patients treated with pembrolizumab, when administering ICI therapy.

Surgical Complications Requiring Intervention in Open versus Minimally Invasive Radical Prostatectomy.

INTRODUCTION: Injuries to surrounding structures during radical prostatectomy (RP) are rare but serious complications. However, it remains unknown if injuries to intestines, rectum, or vascular structures occur at different rates depending on the surgical approach. METHODS: We compared the frequency of these outcomes in open RP (ORP) and minimally invasive RP (MIS-RP) using the national American College of Surgeons National Surgical Quality Improvement Program database (2012-2017). Along with important metrics of clinical and surgical outcomes, patients were identified as undergoing surgical repair of small or large bowel, vascular structures, or hernias based on Current Procedural Terminology codes. RESULTS: In our propensity matched analysis, a total of 13,044 patients were captured. Bowel injury occurred more frequently in ORP than in MIS-RP (0.89 vs. 0.26%, p < 0.01). By intestinal segment, rectal and large bowel injuries were more common in ORP than MIS-RP (0.41 vs. 0.11% and 0.31 vs. 0.05%, both p < 0.01). However, there was no statistically significant difference between the groups for small bowel injury (0.17 vs. 0.11%, p = 0.39). Vascular injury was more common in MIS-RP (0.18 vs. 0.08%, p = 0.08). Hernias requiring repair were only identified in the MIS-RP group (0.12%). CONCLUSION: When considering surgical approach, rectal and large bowel injuries were more common in ORP, while vascular injuries and hernia repair were more common in MIS-RP. Our findings can be used in counseling patients and identifying risk factors and strategies to reduce these complications.

Comparison of comorbidity indices for prediction of morbidity and mortality after major surgical procedures.

BACKGROUND: Assessing perioperative risk is essential for surgical decision-making. Our study compares the accuracy of comorbidity indices to predict morbidity and mortality. METHODS: Analyzing the National Surgical Quality Improvement Program, 16 major procedures were identified and American Society of Anesthesiologists (ASA), Charlson Comorbidity Index and modified Frailty Index were calculated. We fit models with each comorbidity index for prediction of morbidity, mortality, and prolonged length of stay (pLOS). Decision Curve Analysis determined the effectiveness of each model. RESULTS: Of 650,437 patients, 11.7%, 6.0%, 17.0% and 0.75% experienced any, major complication, pLOS, and mortality, respectively. Each index was an independent predictor of morbidity, mortality, and pLOS (p < 0.05). While the indices performed similarly for morbidity and pLOS, ASA demonstrated greater net benefit for threshold probabilities of 1-5% for mortality. CONCLUSIONS: Models including readily available factors (age, sex) already provide a robust estimation of perioperative morbidity and mortality, even without considering comorbidity indices. All comorbidity indices show similar accuracy for prediction of morbidity and pLOS, while ASA, the score easiest to calculate, performs best in prediction of mortality.

Impact of high-intensity local treatment on overall survival in stage IV upper tract urothelial carcinoma.

OBJECTIVES: To investigate the impact of high-intensity local treatment (LT) on overall survival (OS) in patients with stage IV upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Within the National Cancer Database, we identified 7,357 patients diagnosed with stage IV UTUC from 2004 to 2015. Patients who underwent high-intensity LT, defined as radical surgery of the primary tumor, were compared with those who did not. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Weighted survival analyses were used to test the association between high-intensity LT and OS. Multivariable Cox model was used to assess for independent predictors of OS. Sensitivity analysis was used to account for possible biases. RESULTS: Among stage IV patients, 10.6% (n = 779) had locally advanced disease (T4), 32.6% (n = 2,399) had node-positive disease (N+) and 56.8% (N = 4,179) had distant metastases (M+). Fewer than half of the patients underwent high-intensity LT (n = 2,908, 39.5%) while the remainder did not. On IPTW-adjusted survival analysis, high-intensity LT was associated with a prolonged OS (11.17 months [IQR, 5.19 to 24.28] months vs. 6.18 months [IQR, 2.27 to 14.49], P ≤ 0.001). A similar benefit was seen on adjusted survival analyses for each stage IV subgroup, defined according to TNM characteristics. The survival benefit was confirmed at sensitivity analysis. CONCLUSION: High-intensity LT in balanced cohorts of patients with stage IV UTUC is associated with prolonged OS including those with locally advanced (T4), node-positive (N+) or distant metastases (M+).

Systematic Review of Time to Definitive Treatment for Intermediate Risk and High Risk Prostate Cancer: Are Delays Associated with Worse Outcomes?

PURPOSE: Prostate cancer is most commonly an indolent disease, especially when detected at a localized stage. Unlike other tumors that may benefit from timely receipt of definitive therapy, it is generally accepted that treatment delays for localized prostate cancer are acceptable, especially for low risk prostate cancer. Since treatment delay for intermediate risk and high risk disease is more controversial, we sought to determine if delays for these disease states negatively impacted oncological outcomes. MATERIALS AND METHODS: We conducted a systematic review of the literature with searches of Medline, EMBASE and the Cochrane Database of Systematic Reviews from inception to June 30, 2020. General study characteristics as well as study population and delay information were collected. The outcomes of interest extracted included biochemical recurrence, pathological features (positive surgical margins, upgrading, extracapsular extension, and other pathological features), cancer specific survival and overall survival. RESULTS: After identifying 1,793 unique references, 24 manuscripts met criteria for data extraction, 15 of which were published after 2013. Based on our review, delays up to 3 months are safe for all localized prostate cancer and are not associated with worse oncological outcomes. Some studies identified worse oncological outcomes as a result of delays beyond 6 to 9 months. However, these studies are counterbalanced by others finding no statistically significant association with delays up to 12 months. Studies that did find worse outcomes as a result of delays identified a higher risk of biochemical recurrence and worse pathological outcomes but not worse cancer specific or overall survival. CONCLUSIONS: Definitive treatment for intermediate risk and high risk prostate cancer can be delayed up to 3 months without any oncological consequences. Some evidence suggests that there is a higher risk of biochemical recurrence and worse pathological outcomes associated with delays beyond 6 to 9 months. To date, there are no reports of worse cancer specific survival or overall survival as a result of delayed treatment for intermediate risk and high risk prostate cancer.

The impact of smoking on radical cystectomy complications increases in elderly patients.

BACKGROUND: Smoking, the most common risk factor for bladder cancer (BC), is associated with increased complications after radical cystectomy (RC), poorer oncologic outcomes, and higher mortality. The authors hypothesized that the effect of smoking on the probability of major complications increases with increasing age among patients who undergo RC. METHODS: The authors analyzed the American College of Surgeons National Surgical Quality Improvement Program database (2011-2017), identified all patients undergoing RC using Current Procedural Terminology codes, and formed two groups according to smoking status (active smoker and nonsmoker [included former and never-smokers]). Patient characteristics and 30-day postoperative complications using the Clavien-Dindo Classification (CDC) were assessed. A multivariable logistic regression model was constructed that included age, sex, race, body mass index, operative time, comorbidities, chemotherapy status, and type of diversion with major complications (CDC ≥III) as the outcome variable, and explored the interaction between age and smoking status. RESULTS: A total of 10,528 patients underwent RC, including 22.8% who were active smokers. The authors identified an interaction between age and smoking status (P = .045). Older patients were found to experience a stronger smoking effect than younger patients with regard to the probability of major complications. The risk of a major complication was the same for 50-year-old nonsmokers and smokers, but it increased from 17.8% to 21.7% for 70-year-old nonsmokers and smokers, respectively (P < .001). CONCLUSIONS: Up to 20% of patients who undergo RC are active smokers, and these individuals have an increased risk of major complications. The effect of smoking is stronger with increasing age; the difference with regard to complications for smokers versus nonsmokers was found to increase substantially, wherein older smokers are at an especially high risk of complications.

Interdisciplinary Comparison of PADUA and R.E.N.A.L. Scoring Systems for Prediction of Conversion to Nephrectomy in Patients with Renal Mass Scheduled for Nephron Sparing Surgery.

PURPOSE: We examined interdisciplinary variability using 2 established preoperative nephrometry scores to predict conversion to nephrectomy in patients with a renal mass who were scheduled for partial nephrectomy. MATERIALS AND METHODS: A total of 229 consecutive candidates for partial nephrectomy were included in this study at a single institution between January 2013 and May 2017. Patient, tumor and treatment characteristics were assessed. The PADUA (preoperative aspects and dimensions used for an anatomical) score and the R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) score were independently calculated by board certified radiologists and urological residents using computerized tomography or magnetic resonance imaging. Statistical analyses were done with the κ statistic, ROC curves, and univariable and multivariable binary logistic regression analyses. RESULTS: Partial nephrectomy was performed in 198 of the 229 cases (86.5%) while 31 (13.5%) were converted to nephrectomy. The prevalent tumor stage was pT1a, noted in 94 of the 229 cases (41.1%), and the predominant histological entity was clear cell carcinoma, found in 128 (55.9%). Radiologist and urologist interdisciplinary comparison of the PADUA and R.E.N.A.L. scores revealed a κ of 0.40 and 0.56, respectively. ROC curve analyses demonstrated a higher AUC predicting conversion to nephrectomy using the PADUA score by the urologist and the radiologist (0.79 and 0.782) compared to that of the R.E.N.A.L. score (0.731 and 0.766, respectively). Using a cutoff of 10 or greater the PADUA score determined by the urologist had 81% sensitivity and 71% specificity, and it was independently associated with conversion to nephrectomy (OR 10.98, p<0.001). CONCLUSIONS: Our results indicate higher prediction of conversion to nephrectomy when using the PADUA score compared to the R.E.N.A.L. score. Calculation of the PADUA and the R.E.N.A.L. score by physicians without specialized radiological training is feasible and might achieve comparable results to predict conversion to nephrectomy compared to the gold standard provided by board certified radiologists. This information is helpful if nephrometry scores are not regularly included in the radiology report.