Image-Guided Precision Medicine in the Diagnosis and Treatment of Pheochromocytomas and Paragangliomas.

In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis and treatment pose several challenges for clinicians due to their inherent complexity, and they require management by multidisciplinary teams. The conventional concepts of medical imaging are currently undergoing a paradigm shift, thanks to developments in radiomic and metabolic imaging. However, despite active research, clinical relevance of these new parameters remains unclear, and further multicentric studies are needed in order to validate and increase widespread use and integration in clinical routine. Use of AI in PPGLs may detect changes in tumor phenotype that precede classical medical imaging biomarkers, such as shape, texture, and size. Since PPGLs are rare, slow-growing, and heterogeneous, multicentric collaboration will be necessary to have enough data in order to develop new PPGL biomarkers. In this nonsystematic review, our aim is to present an exhaustive pedagogical tool based on real-world cases, dedicated to physicians dealing with PPGLs, augmented by perspectives of artificial intelligence and big data.

Survival analysis and prognostic factors of retroperitoneal liposarcoma curative surgery in a single centre. Analysis of adjacent organ invasion between imaging and definitive histopathology.

INTRODUCTION: Retroperitoneal liposarcoma (RPL) is a rare primary mesenchymal tumour that develops in retroperitoneal adipose tissue. Unlike the majority of published series, this homogeneous cohort focuses on RPL. The main purpose of this study is to evaluate the overall and recurrence-free survival of RPLs who underwent excision surgery and the prognostic factors involved. PATIENTS AND METHODS: A total of 82 patients from a single centre, who underwent curative surgery for histologically confirmed retroperitoneal liposarcoma between 2008 and 2020, were analysed in the study. Compartmental surgical excision was advised as per the guidelines. The primary endpoints were 5 years of overall survival and recurrence-free survival. Predictable tumour invasion of adjacent organs, based on a pre-operative CT scan, was also investigated to test the correlation between pre-operative imaging and pathological data. RESULTS: Median follow-up was 61.6 months. Five year overall survival was 71.9% [95% CI: 59.8; 80.9] and 5 year recurrence-free survival was 49% [95% CI: 36.4; 60.5]. Following multivariable analysis, the factors influencing overall survival were tumour rupture and onset of severe complications (Dindo-Clavien grade ≥3). Factors influencing recurrence-free survival were neoadjuvant radiotherapy and tumour rupture. A significant correlation (p < 0.05) was found between predicted invasion based on a CT scan of the colon, spleen, adrenal gland, posterior abdominal wall and diaphragm, and pathological invasion. CONCLUSIONS: Curative compartmental surgery remains the gold standard treatment for RPL. This study, highlights the fact that the quality of the surgical excision is a crucial factor in patient prognosis.

Adrenalectomy for Pheochromocytoma: Complications and Predictive Factors of Intraoperative Hemodynamic Instability.

BACKGROUND: Surgery is the treatment of choice for pheochromocytoma. However, this surgery carries a risk of hemodynamic instability (HDI). The aim of this study was to report complications associated with this procedure, to identify risk factors for HDI during surgery, and its impact on postoperative outcomes. METHODS: The charts of all patients who underwent adrenalectomy for pheochromocytoma in two academic centers between 2006 and 2020 were retrospectively reviewed. The primary outcome was HDI defined by a systolic blood pressure >160 mmHg or a mean blood pressure <60 mmHg intraoperatively. The secondary outcomes of interest were the total duration of HDI, the occurrence of intraoperative arrhythmia, perioperative cardiovascular events, and postoperative complications. RESULTS: 205 patients were included. HDI occurred intraoperatively in 155 patients (75.6%) but only 6 (3.2%) experienced arrhythmia. Thirty-eight postoperative complications were reported (18.6%) but only nine were ≥3 according to Clavien-Dindo (4.4%). There were 10 postoperative cardiovascular events (5.7%). Patients with intraoperative HDI had higher rates of postoperative complications (21.3% vs 10%; P = .07), major postoperative complications (5.8% vs 0%; P = .12) and cardiovascular events (6.5% vs 0%; P = .12). Factors associated with intraoperative HDI in univariate analysis were age (OR = 8.14; P = .006), high blood pressure preoperatively (OR = 2.16; P = .04), tumor size (OR = 15.83; P = .0001), and urinary normetanephrine level (OR = 9.33; P = .04). DISCUSSION: In multidisciplinary centers, the overall morbidity of adrenalectomy for pheochromocytoma is low. HDI during adrenalectomy for pheochromocytoma is highly prevalent but rarely associated with major cardiovascular events. There might be a link between HDI and postoperative cardiovascular events.

Heterogeneity of contemporary grade group 4 prostate cancer in radical prostatectomy specimens.

PURPOSE: The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. METHODS: From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. RESULTS: Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM. CONCLUSIONS: Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence.

Complete Transurethral Resection before Radical Cystectomy May Improve Oncological Outcomes.

OBJECTIVES: The objective of this study was to assess the impact of complete transurethral resection of bladder tumors (TURBTs) before radical cystectomy on pathological and oncological outcomes of patients with muscle-invasive bladder cancer (MIBC) and high-risk non-MIBC. MATERIALS AND METHODS: The charts of all patients who underwent radical cystectomy for bladder cancer in 2 academic departments of urology between 1996 and 2016 were retrospectively reviewed. Patients were divided into 2 groups according to the completeness of the last endoscopic resection before radical cystectomy: macroscopically complete transurethral resection (complete) or macroscopically incomplete transurethral resection (incomplete). The primary end point was the recurrence-free survival (RFS). Secondary end points included cancer-specific survival (CSS) and rates of pT0 and downstaging. RESULTS: Out of 486 patients included for analysis, the TURBT immediately preceding radical cystectomy was considered macroscopically complete in 253 patients (52.1%) and incomplete in 233 patients (47.9%). In multivariate analysis, macroscopically complete TURBT was the strongest predictor of both pT0 disease (OR = 3.1; p = 0.02) and downstaging (OR = 7.1; p < 0.0001). After a median follow-up of 41 months, macroscopically complete TURBT was associated with better RFS (5-year RFS: 57 vs. 37%; p < 0.0001) and CSS (5-year CSS: 70.8 vs. 54.5%; p = 0.002). In multivariate analysis adjusting for multifocality, weight of endoscopic resection specimen, cT4 stage on preoperative imaging, interval between endoscopic resection and radical cystectomy, neoadjuvant chemotherapy, pT stage, and associated carcinoma in situ, macroscopically complete endoscopic resection remained the main predictor of better RFS (HR = 0.4; p = 0.0003) and the only preoperative factor associated with CSS (HR = 0.5; p = 0.01). CONCLUSION: A macroscopically complete TURBT immediately preceding radical cystectomy may improve pathological and oncological outcomes in patients with MIBC and high-risk MIBC.

Weight-loss with activation of brown fat: Suspect pheochromocytoma.

INTRODUCTION: Excess catecholamine stimulates heat production in brown adipose tissue (BAT). Activation of BAT can be detected in patients presenting pheochromocytoma. CASE STUDY: A 58-year-old female patient sought medical advice due to 13 kg weight loss over 2 years accompanied by sweating and high blood pressure. Thoracic-abdominal-pelvic CT-scan revealed a solid 40 mm mass in the left adrenal compartment with peri-adrenal nodules and a solid 80 mm mass at the lower end of the right kidney. 18FDG-PET scan exhibited intense uptake in the supraclavicular, intercostal, mediastinal, peri-renal, mesenteric, iliac and inguinal spaces. Renal tumor with locoregional infiltration and remote metastases was initially considered. Diagnosis of pheochromocytoma was subsequently confirmed by a 10-fold increase in urinary catecholamine, metanephrine and normetanephrine levels. Left adrenalectomy confirmed the diagnosis of pheochromocytoma, with 3 lymph-node metastases in the adjacent adipose tissue surrounded by brown fat. The patient was clinically asymptomatic with normal blood pressure at 3 months post-surgery. A weight gain of 6 kg was recorded, with normalisation of catecholamines/metanephrine/normetanephrine levels. Bilateral peri-renal infiltration (including the right renal mass) disappeared on CT-scan, and TEP-18-FDG no longer showed hypermetabolism. Recurrent mediastinal metastases were diagnosed 6 months after surgery. CONCLUSION: Brown fat activation may mislead diagnosis of pheochromocytoma, suggesting multi-metastatic extra-adrenal tumor, if clinicians are not aware of it.

Assessing the extirpative quality of a radical prostatectomy technique: categorisation and mapping of technical errors.

OBJECTIVE: To examine the extirpative quality of an open radical prostatectomy (RP) technique by first categorising and mapping all intraprostatic incisions into benign tissue and then determining a cumulative technical error rate given by all intraprostatic incisions into benign and malignant tissue. PATIENTS AND METHODS: We performed a retrospective review of prospectively collected data relating to 1065 men with clinically localised prostate cancer who underwent open retropubic RP (70.6% nerve-sparing surgery [NSS]) by a single surgeon (January 2005 to December 2011). We recorded all intraprostatic incisions: (i) iatrogenic positive surgical margins (PSMs), (ii) deep or superficial benign capsular incisions (BCIs), (iii) incisions into benign prostate glands at the prostate apex or bladder neck (benign glandular tissue incisions [BGTIs]), and determined incision location, length and nature (solitary/multiple). We evaluated: (i) associations between benign incisions, NSS and PSMs, (ii) significant predictors for PSM risk by multivariate analysis, (iii) postoperative biochemical recurrence (BCR)-free survival (Kaplan-Meier method). RESULTS: Intraprostatic incision rates were 2.3% pT2 PSMs, 6.0% BCIs and 5.4% BGTIs. There were slight variations in rate over time and with NSS technique. Benign incisions were located as follows: 46.8% right posterolateral, 37.5% left posterolateral, and 15.7% bilateral for BCIs; 58.6% bladder neck and 41.4% apical for BGTIs. The median (range) incision length, for solitary and multiple incisions respectively, was 4 (1-13) and 9 (2-25) mm for BCIs and 1 (1-5) and 2 (2-6) mm for BGTIs. BCI rate, but not BGTI rate, was significantly associated with NSS (P = 0.004) and PSM (P = 0.005), and increased PSM risk 3.6-fold. A PSM increased BCR risk two-fold (odds ratio 2.078, 95% confidence interval 1.383-3.122). BCR-free survival decreased significantly even for short PSMs (<1 mm; P < 0.001). CONCLUSIONS: Although the pT2 PSM rate was low (2.3%), the cumulative technical error rate (patients with at least one pT2 PSM, BCI or BGTI) was five-fold higher (12.5%). Categorising and mapping intraprostatic incisions is a tool surgeons can use in self-audits to identify areas of potential improvement, reduce errors, and improve surgical skills.

Conventional versus automated implantation of loose seeds in prostate brachytherapy: analysis of dosimetric and clinical results.

PURPOSE: To review the clinical outcome of I-125 permanent prostate brachytherapy (PPB) for low-risk and intermediate-risk prostate cancer and to compare 2 techniques of loose-seed implantation. METHODS AND MATERIALS: 574 consecutive patients underwent I-125 PPB for low-risk and intermediate-risk prostate cancer between 2000 and 2008. Two successive techniques were used: conventional implantation from 2000 to 2004 and automated implantation (Nucletron, FIRST system) from 2004 to 2008. Dosimetric and biochemical recurrence-free (bNED) survival results were reported and compared for the 2 techniques. Univariate and multivariate analysis researched independent predictors for bNED survival. RESULTS: 419 (73%) and 155 (27%) patients with low-risk and intermediate-risk disease, respectively, were treated (median follow-up time, 69.3 months). The 60-month bNED survival rates were 95.2% and 85.7%, respectively, for patients with low-risk and intermediate-risk disease (P=.04). In univariate analysis, patients treated with automated implantation had worse bNED survival rates than did those treated with conventional implantation (P<.0001). By day 30, patients treated with automated implantation showed lower values of dose delivered to 90% of prostate volume (D90) and volume of prostate receiving 100% of prescribed dose (V100). In multivariate analysis, implantation technique, Gleason score, and V100 on day 30 were independent predictors of recurrence-free status. Grade 3 urethritis and urinary incontinence were observed in 2.6% and 1.6% of the cohort, respectively, with no significant differences between the 2 techniques. No grade 3 proctitis was observed. CONCLUSION: Satisfactory 60-month bNED survival rates (93.1%) and acceptable toxicity (grade 3 urethritis<3%) were achieved by loose-seed implantation. Automated implantation was associated with worse dosimetric and bNED survival outcomes.

Retroperitoneoscopic adrenalectomy: comparison of retrograde and antegrade approach among a series of 279 cases.

OBJECTIVE: To compare the results of retroperitoneal laparoscopic adrenalectomy using the antegrade and retrograde approach. MATERIALS AND METHODS: We performed an analysis of a single-center series of 279 retroperitoneal laparoscopic adrenalectomies from 1996 to 2010. We compared 172 cases performed with an antegrade approach and 107 with a retrograde approach without dissection of the renal hilum and initial control of the adrenal vein in comparable populations. RESULTS: The operative time was shorter in the group treated with the retrograde technique, 101±51 vs 140±40 minutes, respectively (Student's t test, P<.001). Blood loss was similar in both groups, 85±224 vs 80±126 mL, respectively (P=NS). Hemodynamic instability was defined as the maximal systolic blood pressure minus the minimal systolic blood pressure divided the maximal systolic blood pressure. It was lower in the group who underwent the retrograde technique (32.7 vs 37.6 mL; Student's t test, P=.005) with a lower perioperative consumption of ephedrine (2.2 vs 5.1 mg, P=.004) and atropine (0.09 vs 0.22 mg, P=.026). No difference was found between the 2 groups in the frequency of perioperative complications or postoperative mortality (1 death in each group of causes unrelated to the surgery). CONCLUSION: Retroperitoneal laparoscopic adrenalectomy using a retrograde approach is a safe and reproducible technique. It makes it possible to perform adrenalectomy without dissection of the renal hilum, with a reduction in the operative time. The good hemodynamic stability observed with this technique makes it very attractive for the treatment of pheochromocytoma.

Erectile function after permanent 125I prostate brachytherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: To analyze erectile function in men treated by prostate brachytherapy (PB) for localized prostate cancer. MATERIAL AND METHODS: Of a series of 270 sexually active men treated by PB, 241 (89%), mean age 65 yr (range, 43-80 yr), participated in a study on erectile function that was evaluated using the International Index of Erectile Function 5-item (IIEF-5) questionnaire before implantation and by postal survey after a mean follow-up of 36 months (range, 6-70 months). RESULTS: After PB, 27 patients (11%) had no erectile dysfunction (ED), 36 (15%) had mild ED, 58 (24%) had mild to moderate ED, 24 (10%) had moderate ED, 53 (22%) had severe ED and 43 (18%) were not sexually active. In patients with a preimplant IIEF score >12 (cut-off for intercourse with penetration), 73% had a deterioration of erectile function by at least one class after PB. Risk factors for ED after PB were age, preimplant IIEF score and prostate volume. Median time to ED onset was 16 months and was shorter with androgen deprivation (p = 0.007), diabetes (p = 0.03) and age over 55 (p = 0.01). CONCLUSIONS: Following PB, the majority of patients progressively develop or major ED after a free interval that may last several months. SUPPORT: Ligue Nationale contre le Cancer, France.

OBJET: Etude de la fonction érectile chez les hommes traités par curiethérapie pour un cancer localisé de la prostate. MATÉRIELS ET MÉTHODES: A partir de 270 hommes sexuellement actifs, traités par curiethérapie, 241 (89%), moyenne d'âge 65 ans (entre, 43­80 ans), acceptaient de participer à l'étude de la fonction érectile après curiethérapie. Cette étude menée par le questionnaire validé IIEF 5 (International Index of Erectile Function 5-item), évaluait la fonction érectile avant curiethérapie, et en moyenne 36 mois (entre 6-70mois) après la curiethérapie de prostate. L'enquête était faite par envoi postal. RÉSULTATS: Après la curiethérapie, 27 patients (11%) n'avaient pas de dysfonction érectile, 36 (15%) avaient une dysfonction très modérée, 58 (24%) entre très modérée et modérée, 24 (10%) modérée, 53 (22%) avaient une dysfonction érectile sévère et 43 (18%) n'étaient plus sexuellement actifs. Parmi les patients ayant un score IIEF avant curiethérapie >12 (score moyen permettant une pénétration pendant l'acte sexuelle), 73% avait une détérioration de leur fonction érectile d'au moins une classe IIEF. Les facteurs de risque de la dysfonction érectile après curiethérapie étaient: l'âge, le score IIEF avant curiethérapie et le volume de la prostate. La période moyenne pour déclencher une dysfonction érectile après curiethérapie était de 16 mois. Cette période se réduisait lorsque les patients étaient sous hormonothérapie (p = 0.007), avaient du diabète (p = 0.03) et étaient âgés de plus de 55 ans (p = 0.01). CONCLUSIONS: Après curiethérapie, la majorité des patients développaient progressivement une dysfonction érectile plusieurs mois après la curiethérapie. SOUTIEN: Ligue Nationale contre le Cancer, France.

Validation of the European Society of Urogenital Radiology scoring system for prostate cancer diagnosis on multiparametric magnetic resonance imaging in a cohort of repeat biopsy patients.

BACKGROUND: Wide variations in acquisition protocols and the lack of robust diagnostic criteria make magnetic resonance imaging (MRI) detection of prostate cancer (PCa) one of the most challenging fields in radiology and urology. OBJECTIVE: To validate the recently proposed European Society of Urogenital Radiology (ESUR) scoring system for multiparametric MRI (mpMRI) of the prostate. DESIGN, SETTING, AND PARTICIPANTS: An institutional review board-approved multicentric prospective study; 129 consecutive patients (1514 cores) referred for mpMRI after at least one set of negative biopsies. INTERVENTION: Transfer of mpMRI-suspicious areas on three-dimensional (3D) transrectal ultrasound images by 3D elastic surface registration; random systematic and targeted cores followed by core-by-core analysis of pathology and mpMRI characteristics of the core locations. The ESUR scores were assigned after the procedure on annotated Digital Imaging and Communications in Medicine archives. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships between ESUR scores and biopsy results were assessed by the Mann-Whitney U test. The Yates correction and Pearson χ(2) tests evaluated the association between categorical variables. A teaching set was randomly drawn to construct the receiver operating characteristic curve of the ESUR score sum (ESUR-S). The threshold to recommend biopsy was obtained from the Youden J statistics and tested in the remaining validation set in terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS AND LIMITATIONS: Higher T2-weighted, dynamic weighted imaging and dynamic contrast-enhanced ESUR scores were observed in areas yielding cancer-positive cores. The proportion of positive cores increased with the ESUR-S aggregated in five increments (ESUR-S 3-5: 2.9%; ESUR-S 6-8: 11.1%; ESUR-S 9-10: 38.2%; ESUR-S 11-12: 63.4%; and ESUR-S 13-15: 83.3%; p<0.0001). A threshold of ESUR-S ≥ 9 exhibited the following characteristics: sensitivity: 73.5%; specificity: 81.5%; positive predictive value: 38.2%; negative predictive value: 95.2%; and accuracy: 80.4%. Although the study was not designed to compare repeat biopsy strategies, more targeted cores than random systematic cores were found to be positive for cancer (36.3% compared with 4.9%, p<0.00001). CONCLUSIONS: In the challenging situation of repeat biopsies, the ESUR scoring system was shown to provide clinically relevant stratification of the risk of showing PCa in a given location.

Ejaculatory function after permanent 125I prostate brachytherapy for localized prostate cancer.

PURPOSE: Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent (125)I prostate brachytherapy for localized prostate cancer. PATIENTS AND METHODS: Of 270 sexually active men with localized prostate cancer treated with permanent (125)I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain. RESULTS: Of the 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p < .0001). The latter finding was correlated with age (p < .001) and the preimplant International Index of Erectile Function score (p < .001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p < .001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p < .0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001). CONCLUSION: Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.

[Partial nephrectomy by selective renal parenchymal clamping using a new clamp]. / Néphrectomie partielle par clampage parenchymateux sélectif utilisant un nouveau clamp.

OBJECTIVE: To study the results of open partial nephrectomy by selective renal parenchymal clamping using a new renal parenchyma clamp, the Réniclamp. MATERIAL AND METHODS: Partial nephrectomy was performed in 37 patients using the Réniclamp for an imperative indication in 7 patients (solitary kidneys) and an elective indication in 30 patients. The tumour was situated in a pole in 22 cases and on the lateral border of the kidney in 15 cases. The mean tumour diameter was 29 mm (range: 10 - 60 mm). RESULTS: The mean operating time was 147 minutes and the mean clamping time was 25 minutes. Mean blood loss was 191 cc (range : 50-450 cc) and no patient required blood transfusion. No cases of slipping of the clamp or renal parenchymal lesion due to the clamp were observed. COMPLICATIONS: A urinary fistula treated by endoscopy and obstructive clot of the upper urinary tract, which required endoscopic treatment and selective embolisation. The surgical margins were negative in every case. CONCLUSION: Partial nephrectomy by selective renal parenchymal clamping is an alternative to the pedicle clamping technique in almost every case of renal tumour except for central renal lesions. Réniclamp distributes the pressure homogeneously, avoiding damage to the parenchyma due to excess pressure on the proximal part of the clamp and bleeding due to insufficient pressure on the distal part of the clamp.