Perioperative Rates of Incidental Prostate Cancer after Aquablation and Holmium Laser Enucleation of the Prostate.

INTRODUCTION: Aquablation and holmium laser enucleation of the prostate (HoLEP) have evolved as established therapeutic options for men with benign prostatic obstruction (BPO). We sought to compare the rates of incidental prostate cancer (iPCa) after aquablation and HoLEP. METHODS: At our center, between January 2020 and November 2022, 317 men underwent aquablation, and 979 men underwent HoLEP for BPO. Histopathological assessment of resected tissue was conducted in all cases. If iPCa was detected, the Gleason score and percentage of affected tissue were assessed. Differences in important predictive factors for prostate cancer between study groups were accounted for by additional matched pairs analysis (with matching on age ± 1 year; PSA ± 0.5 ng/mL; and prostate volume ± 5 mL). RESULTS: Histopathology revealed iPCas in 60 patients (4.6%): 59 (6.03%) after HoLEP and 1 (0.3%) after aquablation (p = 0.001). Of 60 of incidental cancers, 11 had a Gleason score ≥7 (aquablation: 1/1 [100%]; HoLEP: 10/59 [16.9%]). The aquablation and HoLEP study groups differed in patient age, preoperative PSA, and prostate volume. Therefore, matched pairs analysis (aquablation: 132 patients; HoLEP: 132 patients) was conducted to improve comparability. Also after the matching procedure, significantly fewer iPCas were diagnosed after aquablation than HoLEP (aquablation: 0 [0%]; HoLEP: 6 [4.5%]; p = 0.015). CONCLUSION: Significantly fewer iPCas were identified after aquablation than HoLEP procedures. Histopathologic assessment of tissue after aquablation is feasible and may lead to the diagnosis of clinically significant iPCa. Therefore, histopathologic examination of the aquablation resective tissue should not be omitted.

The Dilemma of Misclassification Rates in Senior Patients With Prostate Cancer, Who Were Treated With Robot-Assisted Radical Prostatectomy: Implications for Patient Counseling and Diagnostics.

OBJECTIVES: There is a recent paradigm shift to extend robot-assisted radical prostatectomy (RARP) to very senior prostate cancer (PCa) patients based on biological fitness, comorbidities, and clinical PCa assessment that approximates the true risk of progression. Thus, we aimed to assess misclassification rates between clinical vs. pathological PCa burden. MATERIALS AND METHODS: We compared senior patients with PCa ≥75 y (n = 847), who were propensity score matched with younger patients <75 y (n = 3,388) in a 1:4 ratio. Matching was based on the number of biopsy cores, prostate volume, and preoperative Cancer of the Prostate Risk Assessment (CAPRA) risk groups score. Multivariable logistic regression models (LRMs) predicted surgical CAPRA (CAPRA-S) upgrade, which was defined as a higher risk of the CAPRA-S in the presence of lower-risk preoperative CAPRA score. LRM incorporated the same variables as propensity score matching. Moreover, patients were categorized as low-, intermediate-, and high-risk, preoperative and according to their CAPRA and CAPRA-S scores. RESULTS: Surgical CAPRA risk strata significantly differed between the groups. Greater proportions of unfavorable intermediate risk (39 vs. 32%) or high risk (30 vs. 28%; p < 0.001) were observed. These proportions are driven by greater proportions of International Society of Urological Pathology (ISUP) Gleason Grade Group 4 or 5 (33 vs. 26%; p = 0.001) and pathological tumor stage (≥T3a 54 vs. 45%; p < 0.001). Increasing age was identified as an independent predictor of CAPRA-S-based upgrade (age odds ratio [OR] 1.028 95% CI 1.02-1.037; p < 0.001). CONCLUSION: Approximately every second senior patient has a misclassification in (i.e., any up or downgrade) and each 4.5th senior patient specifically has an upgrade in his final pathology that directly translates to an unfavorable PCa prognosis. It is imperative to take such substantial misclassification rates into account for this sensitive PCa demographic of senior men. Future prospective studies are warranted to further optimize PCa workflow and diagnostics, such as to incorporate modern imaging, molecular profiling and implement these into biopsy strategies to identify true PCa burden.

The determinants of bootstrap financing in crises: evidence from entrepreneurial ventures in the COVID-19 pandemic.

Bootstrap financing refers to measures that entrepreneurial ventures undertake to preserve liquidity (e.g., reducing expenses, collecting receivables, delaying payments, preselling). Prior research shows that bootstrap financing is an important enabler for the growth of resource-constrained early-stage ventures. However, little is known about the use of bootstrap financing in crises, during which the preservation of liquidity is particularly salient. We investigate the determinants of bootstrap financing in the 2020 COVID-19 crisis using a sample of 17,046 German entrepreneurial ventures. We formulate hypotheses about the determinants of bootstrap financing from a necessity, human capital, and opportunity cost perspective. Among others, our results show that the severity of the crisis for the venture, the level of private consumption, and self-employment experience are positively associated with an increased use of bootstrap financing measures. Our study contributes to the literature on bootstrap financing and illuminates how entrepreneurial ventures maintain liquidity in crises. Plain English Summary Economic downturns or crises often lead to financial distress for ventures. To survive such tumultuous times, ventures need to preserve their liquidity. Bootstrap financing refers to measures that entrepreneurial ventures take to preserve liquidity (like sending payment reminders, paying invoices later, reducing tax advances, reducing commercial rent). Because little is known about how bootstrap financing is used during crises, we investigate how it was used during the COVID-19 crisis. Our study builds on a survey of 17,046 German entrepreneurial ventures and self-employed individuals. We find that the use of bootstrap financing is positively related to how severe the crisis was for the venture along with the level of private consumption and self-employment experience of the venture's owner. In contrast, a negative association exists with private liquidity, business liquidity, how long before the owner retires, and part-time self-employment. The positive association between self-employment experience and bootstrap financing indicates that targeted entrepreneurship education programs or webinars should focus on inexperienced entrepreneurs so that these individuals are prepared to use bootstrapping methods to maintain liquidity during crises.

Robot-Assisted Nerve-Sparing Excision of a Symptomatic Obturator Nerve Schwannoma: A Case Report.

Reports in the literature have presented the feasibility of a minimally invasive resection of retroperitoneal or pelvic schwannomas. However, there are only a few reports in the literature about a robot-assisted nerve-sparing approach towards obturator schwannomas. We present a case of a concomitant excision of a symptomatic obturator nerve schwannoma in a patient undergoing robot-assisted radical prostatectomy with pelvic lymphadenectomy. The patient complained about an ongoing, low-grade sensory dysfunction in the left proximal thigh area, without loss of muscular function. A preoperative pelvic MRI incidentally showed a thickening of the left obturator nerve of about 1 cm. During pelvic lymphadenectomy, the thickening was identified, an axial incision was made to the nerve sheath, and a small tumor mass (9 mm x 5 mm x 3 mm) was excised, thereby decompressing the nerve fibers and simultaneously preserving the continuity of the obturator nerve. The nerve sheath was closed using a 7-0 monofilament suture. Frozen section biopsy that was undertaken during the surgical procedure excluded the presence of a malignancy. There were no intra- or postoperative complications. Postoperatively, the patient described a temporary sensory dysfunction of the left inner-thigh area, which regressed completely. The histopathological result confirmed a benign schwannoma of the obturator nerve. In experienced hands, the robot-assisted approach appears safe and feasible as a technique to excise a schwannoma of the obturator nerve, without the need to proceed to a full nerve resection.

Correction: Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts.

Since the publication of this paper, the authors noticed that Amar Ahmad was not credited as contributing equally to the paper. He should be considered as a joint first author with Lorenzo Dutto. In addition, the author Ashwin Sridhar was incorrectly listed as Ashwin Shridhar, and the author Gregory L. Shaw was incorrectly listed as Gregory Shaw. The correct names are listed above.

Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts.

BACKGROUND: Active surveillance is recommended for insignificant prostate cancer (PCa). Tools exist to identify suitable candidates using clinical variables. We aimed to develop and validate a novel risk score (NRS) predicting which patients are harbouring insignificant PCa. METHODS: We used prospectively collected data from 8040 consecutive unscreened patients who underwent radical prostatectomy between 2006 and 2016. Of these, data from 2799 patients with Gleason 3 + 3 on biopsy were used to develop a multivariate model predicting the presence of insignificant PC at radical prostatectomy (ERSPC updated definition3: Gleason 3 + 3 only, index tumour volume < 1.3 cm3 and total tumour volume < 2.5 cm3). This was used to develop a novel risk score (NRS) which was validated in an equivalent independent cohort (n = 441). We compared the accuracy of existing predictive tools and the NRS in these cohorts. RESULTS: The NRS (incorporating PSA, prostate volume, age, clinical T Stage, percent and number of positive biopsy cores) outperformed pre-existing predictive tools in derivation and validation cohorts (AUC 0.755 and 0.76, respectively). Selection bias due to analysis of a surgical cohort is acknowledged. CONCLUSIONS: The advantage of the NRS is that it can be tailored to patient characteristics and may prove to be valuable tool in clinical decision-making.

Non-invasive predictors of survival in cardiac amyloidosis.

BACKGROUND: Patients with cardiac amyloidosis (CA) have increased mortality. AIMS: Clinical, electrocardiographic, and echocardiographic parameters were assessed for risk-stratification of CA. METHODS AND RESULTS: CA was confirmed by endomyocardial biopsy in 59 patients (54.8+/-1.2 years) with light-chain (n = 43) or transthyretin amyloidosis (n = 16). Six patients without CA served as controls (NCA). Clinical symptoms, electrocardiographic, and echocardiographic parameters were analyzed for prognostic significance. Of the patients with light-chain amyloidosis, 14 died and 2 underwent heart transplantation. 1-/3-year survival was 68%/63%. Survival depended on left ventricular function (LV-EF), LV mass, radius/wall thickness, septum thickness, low voltage pattern (LVP), conduction delay, NYHA class, and stem cell transplantation. A multivariate model only contained LV-EF and LVP; the beneficial effect of stem cell transplantation was cancelled out as this treatment was withheld in patients with highest cardiac risk. Survival was most limited if both risk factors occurred. Cardiac involvement in transthyretin amyloidosis showed better survival (2 deaths, 1-/3-year survival 91%/83%). Analysis of prognostic risk factor utility in all amyloid patients (light-chain and transthyretin) again revealed LVP and LV-EF, and aetiology of amyloidosis as independent survival parameters. CONCLUSION: Prognosis of CA is poor, but aetiology of amyloid, LVP, and LV-EF allows identification of patients at highest risk of death, who may require individual treatment approaches (heart transplantation prior to causative therapy).

Complexity analysis of placental blood flow in normal and high-risk pregnancies.

Various strategems of complexity analysis of microvascular blood flow were carried out in several fields of medicine in the past, as such as angiology, ophthalmology and neurology. The introduction of colour-angio-mode, a special form of colour coded Doppler sonography, now makes possible to perform complexity analysis of the placental blood displacement even in the absence of information about hydrodynamic details such as directionality, velocity profile and number of displaced blood cells. Algorithms were developed which allows to extract information concerning the time averaged power of phonon-erythrocytes collision events (from the square of the frequencies of back scattered ultrasound recorded during 166 ms) in 20,000 to 40,000 regions of interest. The obtained values are being displayed as false coloured pixels on a video-screen, we succeeded to obtain quantitative data about displacement rates.In cross-sectional and longitudinal studies we generated typical diagrams displaying the "occurrence rate" of various powers of displacement over time. By this mode of display contour plots can be generated, showing a large amount of low intensity pixels and a small amount of high intensity pixels representing the parenchymatous blood flow inside the placenta. As was to be expected, interdependencies between the placental blood flow and the maternal and fetal heart rates as well as the maternal breathing can be found. While there was only limited influence of maternal and fetal heart rate on the placental blood flow, maternal breathing showed striking influence. Surprisingly, during expiration the power of placental blood movement was decreased, and there was a marked increase during inspiration. In cases of severe intrauterine growth retardation, colour pixel intensities were seen to transiently vanish during end-expiration. The power of placental blood displacement was marked increased subsequent to reducing maternal hematocrit during hemodilution therapy by infusion of artificial colloids. These interdependencies could be confirmed by ex vivo examinations perfusing and percolating the placenta after birth in a hemodynamic model. Additionally, we found interdependencies between fetal and maternal blood displacement inside the placenta. By modelling the decrease of fetal inotropic power in the ex vivo examinations, increase in the power of maternal blood displacement in the intervillous space. The two types of placental blood flow are known to be determined by many factors. While it is currently impossible to measure all these parameters determining an parenchymatous blood flow, it is possible to obtain useful informations about the physiologic and pathophysiologic changes of placental blood flow using colour-angio-mode as a tool of complexity analysis based on the distribution of local blood displacement. This new knowledge can help to understand clinically relevant changes in the individual patient as well their underlying causes.

Analysis of the inter- and intravillous placental blood circulation in high-risk pregnancies before and after the hemodilution therapy using the colour-angio-mode.

OBJECTIVE: The aim of the study was to examine the efficiency of a hemodilution (HD) therapy on the inter- and intravillous placental blood circulation in high-risk pregnancies by applying the colour-angio-mode (CAM). PATIENTS AND METHODS: 24 patients were examined who had fetal growth retardation and/or pathological Doppler results. In all cases the hematocrit was >36%. The patients were given 500 ml Ringer solution and 500 ml HAES 10% intravenously per day; maternal heart rate and blood pressure were measured continuously. Prior to and after the therapy the same area of the placenta was examined using CAM; histograms demonstrating the distribution of the intensity values and summation values of the color pixels were calculated. RESULTS: In 14 patients the fetal outcome was good. The histograms showed in 11/14 cases an increase of low intensity values indicating an improvement of the placental circulation. The summation value of the color pixels as measured by CAM was significantly increased after the therapy in these cases (p = 0.022). In 10 patients the fetal outcome was unfavorable. The histograms showed a decrease of the intensity values in 6/10 cases. There was no significant change in the summation values of the color pixels after the therapy (p = 0.139). CONCLUSIONS: CAM sonography demonstrated for the first time a local effect of the HD therapy within the placenta. In the positive case the placental blood circulation will improve and the pregnancy develops favourably (responder). In the negative case there is no change of the placental blood circulation and pregnancy must be terminated due to a pathological fetal heart rate tracing, fetal growth failure or hypertensive disorders (nonresponder).

Correlation of Doppler velocimetry findings in twin pregnancies including course of pregnancy and fetal outcome.

OBJECTIVE: Subject of the study was the significance of umbilical artery Doppler velocimetry findings for the further course of pregnancy and fetal outcome in cases of twin pregnancies. METHODS: In 206 cases of twin pregnancy, the umbilical artery was examined using Doppler velocimetry in the median 9 days prior to delivery, and the result was correlated with the further course of pregnancy and fetal outcome. 174 pregnancies showed normal Doppler findings of the umbilical artery (group A), 32 twin pregnancies showed pathological Doppler findings of at least one twin (group B). The median of the maternal age and the parity between the groups were not different. RESULTS: In group B (pathological Doppler findings), intrauterine growth retardation and pre-eclampsia occurred 5 times more often than in group A (normal Doppler findings). The total rate of cesarean sections was not different between the study populations; the rate of deliveries by cesarean section in group B was significantly increased by a factor of 2.4 due to a pathological CTG. The median birth weight and the gestational age at birth were significantly lower in group B (1,660 g; 35 weeks) as compared to group A (2,460 g; 37 weeks; p<0.001). In group B, the rate of premature deliveries up to reaching the 34th week of gestation was 3. 4 times higher; the rate of SGA newborns was 6.3 times higher. Perinatal mortality was increased by a factor of 1.5 in group B compared to group A. CONCLUSION: The Doppler velocimetry findings have considerable effects on the further course of a multiple pregnancy. In case of pathological Doppler findings, early hospitalization and close monitoring of the pregnancy should be performed. In cases of additional pathological findings (maternal illness, pathological Doppler findings of fetal blood vessels), termination of the pregnancy has to be considered.

Doppler sonographic findings for hypertension in pregnancy and HELLP syndrome.

Doppler examinations of the umbilical artery, both uterine arteries, and the fetal middle cerebral artery were performed in the third trimester in 18 patients with pregnancy induced hypertension, 52 patients with preeclampsia, and 32 patients with HELLP syndrome and the results were correlated with the parameters fetal outcome. For 74% of the patients this was the first pregnancy, in 93% of the cases a cesarean section was necessary; 66% of the newborn babies were dystrophic and 90% of them were born prematurely. The blood flow in one uterine artery was restricted in 95% of all 102 pregnant women, only 5% did not show any pathological findings. A pathological blood flow was observed on Doppler sonography in the umbilical artery in 70% of the group and 39% showed a pathologically increased perfusion of the fetal middle cerebral artery. The average birth weights and gestational ages in the study group were markedly reduced in comparison with healthy pregnant women (pregnancy induced hypertension: 1620 g/35 weeks; preeclampsia: 1660 g/34 weeks; HELLP syndrome: 1160 g/31 weeks, respectively). The lowest values for average birth weight and gestational age occurred when all four investigated blood vessels showed pathological Doppler findings: 1180 g/31 weeks (0 to 1 pathological vascular findings: 2780 g/38 weeks; 2 pathological vascular findings: 1845 g/34.5 weeks; 3 pathological vascular findings: 1330 g/31 weeks). This Doppler study underlines the importance of examining four blood vessels: the uterine, the umbilical, and the fetal middle cerebral arteries for a complete analysis of the fetoplacental hemodynamics. On account of the severely impaired hemodynamics observed in the placentas of our patients with hypertensive diseases in pregnancy or HELLP syndrome, we believe the early diagnosis of these disorders by Doppler sonography and an early start of therapy to be essential.

Antenatal visualization of vascular anastomoses in monochorionic twins using color Doppler sonography: the protective function of these anastomoses and the phenomenon of interference beating.

This report concerns the antenatal visualization and velocimetry of an arterioarterial and a venovenous anastomosis in a monochorionic twin pregnancy using color Doppler sonography. The phenomenon of 'interference beating' occurs when two flow velocity waveforms are superimposed in one blood vessel. This characteristic image can be generated antenatally to confirm the existence of a vascular communication. We were able to reveal these anastomoses postnatally using the dye injection technique.

Comparison of Doppler sonographic examinations of the umbilical and uterine arteries in high-risk pregnancies.

OBJECTIVE: To determine the value of Doppler ultrasonographic examinations of the uterine artery in high-risk collectives and their importance as compared to examinations of the umbilical artery. METHODS: In 142 patients with fetal growth retardation (birth weight <10th percentile) and/or pre-eclampsia/HELLP syndrome (as defined by ACOG criteria), the umbilical artery and the uterine arteries were examined bilaterally using a 3.5/5-MHz color Doppler system (Acuson 128). The patients were assigned to six groups according to the Doppler findings (uterine artery unilaterally/bilaterally normal/pathologic and umbilical artery normal/pathologic). For each group, the median of the birth weight and the gestational age at delivery was determined and the frequency of occurrence of complications was calculated. RESULTS: In cases with pathologic results in all three vessels, the median gestational age at delivery and the median birth weight were significantly lower than in all other subgroups. Of the cases with pathologic findings in the umbilical artery only, 6% had pre-eclampsia/HELLP syndrome. However, this complication developed in 90% of the cases with pathologic findings in both uterine arteries. If only the umbilical artery was examined (and not the uterine arteries) the Doppler results were normal in 40 (28%) of the patients in our high-risk group, thus incorrectly simulating undisturbed placental hemodynamics. CONCLUSIONS: Examination of both uterine arteries is an indispensable element of Doppler examination to assess placental performance and risk to the fetus.

Predictive value of a single CTG, ultrasound and Doppler examination to diagnose acute and chronic placental insufficiency in multiple pregnancies.

A non-stress test, an ultrasound biometry (biparietal and abdominal diameter) and a Doppler sonography blood flow measurement (fetal descending aorta, umbilical artery and fetal middle cerebral artery) were performed in the third trimester of 130 multiple pregnancies. These three methods were compared in terms of their prognostic value for fetal growth retardation (81 from 263 children; defined as weight at birth < 10 percentile) and a pathological "fetal outcome" (76 from 263 children, defined as 5-min-Apgar < 8, umbilical artery-pH < 7.20 and transfer to neonatal intensive care unit). Fetal growth retardation could best be predicted by means of the Doppler results for all three blood vessels ("total Doppler result") (sensitivity of 75.9%). Doppler results for all three blood vessels showed the best result in predicting a pathological "fetal outcome"; the sensitivity was 60.3%. The biometric examinations with ultrasound and the non-stress test produced worse results compared to Doppler sonography. Doppler velocimetry of only one blood vessel showed worse results compared to Doppler velocimetry of more than one blood vessel. Doppler sonography should be performed as a routine test for all multiple pregnancies. More intensive pregnancy surveillance is urgently recommended with pathological findings.

Critical comparison of indices and threshold values for assessing placenta performance using Doppler ultrasound.

To determine the most appropriate index and an optimal cutoff value for obstetric Doppler ultrasound, the umbilical and uterine arteries of 467 patients were examined during the third trimester using an Acuson 128 color Doppler system. Doppler ultrasound detection of chronic placental insufficiency with fetal growth retardation and acute placental insufficiency with subpartal asphyxia were selected as criteria. A birth weight below the 10th percentile (using Hohenauer's percentiles) was taken as the parameter for the former and a 5-minute Apgar score of < 8 for the latter criterion. For each artery, two risk groups were studied: 103 patients with chronic and 27 patients with acute placental insufficiency. Using EROC curves, the prediction of chronic and acute placental insufficiency was computed for six Doppler indices (maximum systolic, mean [TAMX] and maximum end-diastolic velocities, S/D ratio, RI, PI) and 10 threshold values per index (the 1st to 50th percentiles for the qualitative indices and the 50th to 99th percentiles for the quantitative indices). The following results were obtained: (1) the development of chronic placental insufficiency was predicted best in Doppler examinations of the umbilical artery by calculating the PI with the 60th percentile as the threshold value, and in examinations of the uterine artery by determining the S/D ratio with the 90th percentile; 2nd (2) acute placental insufficiency was predicted best by calculating the mean blood flow velocity (TAMX) in the umbilical artery, with the 50th percentile as the ideal cutoff value; in examinations of the uterine artery the best results were obtained by determining the S/D ratio with the 90th percentile as cutoff value. Three conclusions may be drawn from the results: (1) taken overall, the qualitative Doppler parameters (S/D ratio, RI, PI) are superior to the quantitative parameters (maximum systolic, mean [TAMX] and maximum end-diastolic velocity) in the detection of both chronic and acute placental insufficiency; (2) in Doppler examinations of the umbilical artery the optimal threshold value is in the region of the 60th, and in examinations of the uterine artery in the region of the 90th, percentile; and (3) chronic placental insufficiency was detected better than the acute form; examinations of the umbilical artery yielded more explicit data than those of the uterine artery.

Development of quantitative Doppler indices for uteroplacental and fetal blood flow during the third trimester.

The aim of our study was to describe the development of uteroplacental and fetal blood flow during the third trimester. Doppler examination was carried out on 393 uncomplicated pregnancies with uncomplicated term delivery. Using a pulsed color Doppler, we calculated the maximum systolic, mean and maximum end-diastolic velocity after correcting the angle of insonation. Patients under tocolysis or other medication influencing blood flow parameters were excluded from this cross-sectional study. Summarizing the results gained by Doppler ultrasound investigation of the uteroplacental and fetal blood vessels, we created quantiles as quantitative Doppler indices for the maximum systolic, mean (TAMX = time averaged maximum velocity) and maximum end-diastolic velocity. The following conclusions could be drawn: (1) resistance to the blood flow in the maternal portion of the placenta does not change during the third trimester; (2) resistance to the blood flow on the fetal side of the placenta decreases up to week 42 of gestation; (3) cerebral vascular resistance decreases constantly up to gestational week 42; and (4) vascular resistance to the blood flow of the kidney decreases only slightly during the third trimester. This study offers clinically important values for quantitative Doppler flow velocimetry for the first time. We hope that our findings improve the usefulness of Doppler ultrasound as a diagnostic tool in obstetrical management.