Validating a Novel Approach for Assessing Intraprostatic Hormone Concentrations through Prostate Biopsy.

BACKGROUND: Advances in chromatography and mass spectrometry have allowed us to develop a novel technique for measuring intraprostatic hormone concentrations directly on prostate needle biopsies, rather than using traditional punch excision. This has significant clinical implications as intraprostatic Dihydrotestosterone and testosterone levels could help monitor prostate growth, neoplasia and castration resistance. Methods : Patients undergoing radical cystoprostatectomy for bladder cancer were prospectively included. Each prostate specimen received one 90mg punch excision and six needle biopsies. Intraprostatic hormones were dosed through gas chromatography-mass spectrometry. Results : We included twenty patients, of which eleven were incidentally diagnosed with prostate cancer; four had ISUP 1 (20%) and seven had ISUP 2 (35%). The prostate biopsy technique was unable to obtain measures for testosterone, Delta-4- androsterone and androstenedione. Tissue concentrations of DHEA, DHT, E1 and E2 can be obtained with no significant difference from the reference established on a punch from a single biopsy core sample. CONCLUSIONS: Our study demonstrates that intraprostatic concentrations of DHEA, DHT, E1, and E2 can be measured without significant difference from the reference established on a single punch excision. This finding opens the way to research on the interactions between endocrinology and prostate oncogenesis and particularly on the mechanisms of resistance to hormone therapies in-vivo.

The impact of carcinoma in situ in ureteral margins during radical cystectomy: A case-controlled study.

BACKGROUND AND OBJECTIVE: The presence of carcinoma in situ (Cis) in association with bladder cancer is associated with a poor prognosis. However, the prognosis associated with the presence of Cis in ureteral margins (CUM) during radical cystectomy has been poorly defined. To assess the prognosis associated with the presence of Cis in ureteral margins in patients with pM0 bladder cancer who have not undergone neoadjuvant chemotherapy. MATERIALS AND METHODS: A retrospective case-control study was conducted between 2001 and 2016 using data from one academic center in France. From 1,450 radical cystectomies, 122 patients (case) who had CUM were matched according to age, sex, pTNM stage and urinary diversion method with a population sample of 122 patients (controls) who did not have Cis in ureteral margins during radical cystectomy. The survival analysis was performed by Kaplan-Meier using a (95%) CI. Multivariate Cox regression analysis was used to test the effect of CUM on cancer-specific survival. Recurrence-free survival was defined as a recurrence of urothelial carcinoma in the upper urinary tract. RESULTS AND LIMITATIONS: The mean follow-up period was 55.43 ± 39.6 months. The rate of Cis in the bladder in the CUM cases group was evaluated at 11.47%. The median overall and specific survival was inferior in the CUM cases group estimated at 43.3 [35.33-56.93] months, 52.43 [42.16-68.93] months respectively compared to the control group with a significant difference (P= 0.001, P= 0.0039). The cumulative probability of urothelial recurrence-free survival was decreased in the case group compared with the control group (63.9% vs. 92.6%, P = 0.0001). Multivariate analysis shown that urothelial recurrence was associated with CUM [(P <0.001), (HR adjusted =11.31), (95% CI): (3.38-37.77)] and the macroscopic appearance of the ureter (thickened, dilated) [(P= 0.003), (HR adjusted =4.62), (95% CI): (3.31-8.84)]. CONCLUSION: CUM is a poor prognostic factor that impacts cancer-specific survival and Recurrence-free survival. The presence of CUM has been independently associated with a significant increase in the risk of urothelial recurrence, and a decrease in both overall and specific survival. This supports the use of frozen section analysis to complete radical cystectomy without CUM.

[Usefulness of frozen section exams during radical cystectomy for urothelial carcinoma]. / Utilité des examens extemporanés lors de la cystectomie totale pour carcinome urothélial.

AIM: To determine the usefulness of the frozen section exams of lymph nodes dissection, ureteral and urethral section during radical cystectomy for urothelial carcinoma and define the impact on the surgical procedure. METHOD: A retrospective, single-center study of data collected from 182 patients who underwent radical cystectomy for an cT=3bN0M0 urothelial bladder cancer between 2016 and 2018. Bladder cancer extension was determined by thoracoabdominal CT with contrast enhancement and urography and an 18-FDG PET scanner. No patient received neoadjuvant chemotherapy. The diagnostic performance of the frozen section exams was related to final examinations. The impact of the result on the initial intervention was determined. RESULTS: The frozen section were positive in 29 lymph nodes dissections (15.9 %), 59 (16.6 %) ureteral and 20 (10.9 %) ureteral recessions. With lymph nodes exams, sensitivity, specificity and positive and negative predictive values were 93.5 %, 100 %, 100 %, and 98.7 %, respectively. With ureteral sections exams the same values were 91.5 %, 100 %, 100 %, and 98.4 % respectively. With urethral section exams, all the values were of 100 %. Finally, all the procedure has been modified for all patients with positive frozen section exam except one positive urethral section that did not give rise to radical urethrectomy. CONCLUSION: Frozen section exams were useful to the urologist during radical cystectomy for urothelial carcinoma. The performances of the frozen section exams carried out were excellent. The information of the urologist of the positive frozen section leeds to modify its management during the intervention in all the studied cases with the exception of one case.

[12-year history of radical surgery indications for the treatment of prostate cancer]. / Évolution sur 12 ans des indications de prostatectomie totale pour cancer.

AIM: To analyze the indications of radical prostatectomy and lymph node dissection retained during the last 12 years in an academic surgical center in the Paris region in order to ensure their adequacy in relation to the current clinical guidelines. METHOD: Monocentric retrospective study of prospectively collected data, between 2007 and 2019. Analysis of the clinical and pathological characteristics which were taken into account during multidisciplinary meeting discussion for the treatment decision, and comparison of their evolution over the four 3-year period corresponding to the clinical guideline updates. RESULTS: Two thousand eighty-eight consecutive patients treated by radical prostatectomy between 16/03/2007 and 17/03/2019 were included. The proportion of patients classified as low, intermediate or high risk according to D'Amico system was 13.2%, 80.8% and 6.0% respectively. An increase in the frequency of surgical treatment of high-risk cancers has been observed. At the same time, there has been a decrease in the frequency of prostatectomies to treat low-risk cancers. CONCLUSION: The indications for radical prostatectomy and lymph node dissection have evolved in line with the current clinical guidelines which were taken into consideration in a onco-urological multidisciplinary meeting. LEVEL OF EVIDENCE: 3.

[Does the delay from prostate biopsy to radical prostatectomy influence the risk of biochemical recurrence?] / Le delai entre biopsies de prostate et prostatectomie radicale influence-t-il le risque de recidive ?

INTRODUCTION: The influence of the delay between prostate biopsy and radical prostatectomy for patients with localized prostate cancer is controversial. The objective of this study was to establish a time limit between prostate biopsy and radical prostatectomy beyond which the risks of upgradging and biochemical recurrence (BCR) are increased. MATERIAL AND METHODS: Between January 2013 and January 2017, a retrospective analysis of the clinical, biological and histological data of 513 patients treated with radical prostatectomy for localized prostate cancer was performed in a single center. The primary endpoint was the assessment of the risk of BCR by the difference between post-biopsy USCF-CAPRA and post-surgical CAPRA-S scores. The secondary endpoint was the evaluation of the upgrading by the difference between the Gleason score on biopsy and on surgical specimen. The risks of BCR and upgrading were compared by Student test according to different delays between prostate biopsy and radical prostatectomy. The shortest delays for which a significant difference was found were reported. RESULTS: In this study, 513 patients were included. The median age at the time of the biopsy was 65 years (IQR: 60-69). The median preoperative PSA was 7.30ng/mL (IQR: 5.60-9.94). The median time between biopsy and surgery was 108 days (IQR: 86-141). For the entire cohort, the risk of BCR was significantly higher above a threshold of 90 days (P=0.039). No threshold was found for Gleason 6(3+3) patients. A 90-day threshold was found for Gleason 7(3+4) patients (P=0.038). Gleason patients≥8 had more upgrading beyond a 60-day threshold (P=0.040). CONCLUSION: Our study showed that after a 3 months delay, the risk of BCR was significantly higher for localized prostate cancer. It seemed possible to extend this period for low-risk patients, whereas it seemed necessary to keep it for intermediate-risks and to reduce it to 2 months for high-risks. LEVEL OF EVIDENCE: 4.

Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading.

BACKGROUND: To compare histological feature of prostate cancer (PCa) according androgenic status in patients who underwent radical prostatectomy (RP). METHODS: Between March 2007 and September 2013, we prospectively analysed 937 patients who were referred to our centre for RP. Clinical, pathological and biological data have been prospectively collected. Preoperative total testosterone (TT) and bioavailable testosterone (BT) serum determinations were carried out. The threshold for low serum testosterone was set at TT<3 ng/ml. Preoperative PSA value was registered. Gleason score (GS) and predominant Gleason pattern were determined in prostate biopsies and in prostate tissue specimens, crosschecked by two uro-pathologists. RESULTS: Nine hundred and thirty-seven consecutive patients were included. In all, 14.9% patients had low TT in the population. An exact match between biopsy and prostate specimens in GS grading was observed for 50.6% patients (n=474). Also, 40.9% of all patients were upgraded (n=383): 45.3% (n=63) in low serum testosterone patients and 40.1% (n=320) in normal serum testosterone patients. For prostate specimens, the proportion of patients with predominant Gleason pattern 4 was higher in patients with low TT compared with normal TT (41.7% vs 29.1%, P=0.0029). In all, 20.1% were upgraded from predominant Gleason pattern 3 on biopsies specimen to predominant Gleason 4 pattern on the prostate specimen in patients with low TT, whereas 11.6% were upgraded for normal TT patients (P=0.002). CONCLUSIONS: Low serum testosterone is an independent risk factor for predominant Gleason pattern 4 on prostate specimen after RP and for upgrading from low- to high-grade cancer between prostate needle biopsies and RP specimen. This observation should be taken into account in localised PCa management, especially for active surveillance or when a nerve-sparing approach is considered.

Value of positron emission tomography in diagnosing synchronous penile metastasis from urothelial bladder cancer.

Metastases to the penis are extremely rare events. Most frequently, penile metastases come from the urogenital system (bladder, prostate) or the rectum-sigmoid colon. Usually painful, penile lesions may be asymptomatic, making diagnosis more challenging. Hence, we report the adding value of (18)F-fludeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the detection of penile metastases originating from urothelial carcinoma of the bladder. Arguably, penile metastases must be considered as an advanced disease requiring essentially palliative care. Therefore, accurate staging of clinically localized muscle-invasive bladder cancer is crucial to avoid useless curative intent radical surgery.

Potential impact of 18F-FDG PET/CT on patients selection for neoadjuvant chemotherapy before radical cystectomy.

BACKGROUND: The detection of lymph node metastases in bladder cancer has a major impact on treatment decisions and patients prognosis. Due to limited value of conventional imaging, the place of molecular and functional imaging needs to be precised, particularly in the neoadjuvant setting. METHODS: From June 2011 to June 2013, 102 patients with clinically localized BCa were simultaneously staged with (18)F-FDG PET/CT before RC. This study assessed the diagnostic accuracy of (18)F-FDG PET/CT for the detection of metastases in normal-sized lymph nodes using extended pelvic lymph node dissection and histopathology as the reference standard. RESULTS: A total of 1211 LNs were examined histopathologically. Sixty-seven (5.5%) metastatic nodes were found in 26/102 patients (25.5%). Lymph node density was 22%. On patient-based analysis, sensitivity, specificity, predictive positive value (PPV), negative positive value (NPV) and accuracy for (18)F-FDG PET/CT were calculated as 50%, 96.2%, 80%, 86.2% and 85.3% respectively. On a field-based analysis, sensitivity, specificity, PPV, NPV and accuracy for (18)F-FDG PET/CT were calculated as 50.0%, 99.0%, 71.9%, 97.4%, and 96.5% respectively. The majority of missed metastases were micrometastasis <5 mm in long axis diameter. CONCLUSIONS: (18)F-FDG PET/CT improves diagnostic efficacy for lymph node staging in patients staged N0 with conventional cross-sectional imaging. (18)F-FDG PET/CT could be used as a surrogate marker for detection of metastases in non-enlarged pelvic lymph nodes and enhances management strategy guiding patients selection for neoadjuvant chemotherapy.

[Prognostic impact of tumors localized at the prostatic apex]. / Impact pronostique des tumeurs localisées à l'apex prostatique.

OBJECTIVE: The apex is a particular region of the prostate in its surgical dissection and pathological analysis. We sought to evaluate the prognostic value of the apical localization of prostate tumors. METHOD: From 1988 to 2010, data pre- (age, clinical stage, preoperative PSA, biopsy Gleason score) and postoperative (prostate weight, pathologic stage TNM 2010, Gleason score, margin status) of 2765 total prostatectomies were collected prospectively. These data were compared according to existence or absence of tumor at the apex. The prognostic impact of tumor at the apex on biochemical recurrence-free survival (PSA>0.2 ng/mL) has been studied in univariate and multivariate models. RESULTS: One thousand eight hundred seventeen tumors had a location at the apex (65.7%). In univariate analysis, there was a significant difference in the clinical stage, the biopsy and pathological Gleason score, the result of curage, the pathological stage and the margin status between apical tumors and others. With a mean decline of 34.6 months, 502 patients had a biochemical recurrence (18.1%). Disease-free survival at 10 years was 60.7% for tumor at the apex versus 65.9% in other cases. The location at the apex was significantly associated with biochemical recurrence on univariate analysis (P=0.01). After adjustment for clinical and pathological stage, PSA level, Gleason score and surgical margins, the apex was not anymore a pejorative independent predictor (P=0.0087). CONCLUSION: The existence of tumor in the prostatic apex was associated with more aggressive tumoral criteria and was an independent and pejorative predictor of biochemical recurrence-free survival at 10 years in univariate analysis. The apical localization could be an additional argument in the decision of adjuvant therapy after prostatectomy.

Dexamethasone-netilmicin: a new ophthalmic steroid-antibiotic combination. Efficacy and safety after cataract surgery.

PURPOSE: The purpose of this study was to evaluate both efficacy and safety of a new ophthalmic steroid-antibiotic fixed combination containing dexamethasone and netilmicin in the postsurgical management of cataract surgery. METHODS: In total, 223 patients were randomly treated with dexamethasone 1 mg/ml plus netilmicin 3 mg/ml (n=148), or dexamethasone 1 mg/ml plus tobramycin 3 mg/ml (n=75, TOBRADEX) four times in a day for 7+/-1 days starting immediately after surgery. Efficacy (anterior chamber (AC) inflammation, conjunctival hyperaemia, corneal and lid oedema, ocular infection, pain, photophobia and tearing) and safety (burning, stinging, blurred vision, intraocular pressure, and visual acuity) were analysed in the operated eye after 1 and 7+/-1 days. A follow-up visit was performed at day 14+/-2. The extent of AC inflammation, measured by slit-lamp according to a standard scoring system, was used as primary efficacy parameter. RESULTS: At the primary end point (day 7) both fixed combinations were equally effective in reducing postoperative inflammation. The safety profile of the dexamethasone/netilmicin combination was excellent with no evidence of poor local tolerance or adverse reaction. CONCLUSIONS: A new fixed combination of dexamethasone and netilmicin was effective and safe in controlling ocular inflammation after cataract surgery.

Taylor's method: a therapeutic alternative for perforated gastroduodenal ulcer.

BACKGROUND/AIMS: In the context of actual trends towards an efficient and less aggressive therapy of peptic ulcer, it seems that Taylor's method, in selected cases of perforated gastroduodenal ulcers (PGDU), comes again into attention. The aim of this study was to present our 16 years' experience with Taylor's treatment as an efficient option for sealed perforated ulcers, and to highlight the indications and advantages of this method. METHODOLOGY: A retrospective study, and prospective since 1990, was carried out on a series of 64 patients out of 592 (10%) diagnosed with PGDU between 1987 and 2003. The patients were carefully evaluated, particularly looking for clinical, laboratory and imaging diagnosis factors, indicating potential candidates for conservative approach: short history, hydropneumoperitoneum in small amount on admission. Two thirds of the patients presented in the Emergency Unit less than 12 hours from the onset of the symptoms. The diagnosis of PGDU was established by corroborating the obvious symptoms and abdominal signs with erect chest X-ray and ultrasonography (US) of the abdomen. The efficiency of Taylor's method, consisting of nasogastric aspiration, fluids resuscitation, parenteral broad spectrum antibiotics and antisecretory drugs, was assessed by meticulous repeated physical examinations, dynamics of WBC (white blood cell) and US. In case of failure, this method remained as a part of preoperative treatment. RESULTS: The method was successful in 57 out of 64 (89%) cases of perforated peptic ulcer disease, selected from the 592 cases admitted with perforated peptic ulcer following the clinical and imaging criteria previously mentioned. The presence of pneumoperitoneum certifies the diagnosis of PGDU, but the amount of peritoneal fluid assessed by US predicts the success of the procedure. Seven patients developed complications (10.9%), mainly intraabdominal abscesses and only four of them needed surgical drainage. The mortality was nil. After discharge all patients were referred to gastroenterologists for monitoring the medical treatment and no recurrence was encountered. CONCLUSIONS: The Taylor's method is a reliable alternative in selected cases of perforated gastroduodenal ulcers, the main advantage being the avoidance of anesthetic and surgical stress with their potential morbidity and mortality.

[The assessment of empiric antibiotherapy in acute secondary peritonitis]. / Evaluarea tratamentului antibiotic empiric în peritonitele acute secundare de cauza, digestiva.

UNLABELLED: The adequate use of antibiotics, according to the international guidelines of antimicrobial therapy, is, in addition to surgery, an important part of the management of intra-abdominal infections. The aim of the study was to assess the efficacy of empiric antibiotherapy in acute peritonitis of digestive cause. MATERIAL AND METHODS: A retrospective study was carried out on a series of 75 cases of acute peritonitis, admitted in the IIIrd Surgical Unit, in the period 2003-2005. Perforated duodenal ulcer was the cause of diffuse peritonitis in 46 % of the cases, followed by acute appendicitis (31%) and traumatic perforation of the small bowel (11 %). The most frequent bacteria encountered was E. coli (62 %), while Klebsiella, Enterobacter and Acinetobacter were present in nearly 8% of the cases. Ertapenem as single agent was preferred in 36.8% of the patients and an association of third generation cephalosporins or aminoglycoside with metronidazole in 33.4%. RESULTS: the efficiency of the treatment was assessed in regard to clinical (fever) and laboratory (leucocytosis) data, the duration of treatment and hospital stay. The outcome was appreciated as good in almost 73% of the patients treated with ertapenem, and 52% respectively for combined therapy. CONCLUSION: the authors recommend the use of penems as monotherapy in the empiric treatment of acute peritonitis following digestive perforation.

[Necrotizing fasciitis]. / Fasciita necrozanta.

The management of a right foot necrotizing fasciitis and severe sepsis in an old diabetic patient is presented. The early and aggressive surgery, adequate antibiotherapy and correction of organic disfunction (cardio-circulatory, renal, respiratory) eliminated the vital risk and resulted in a satisfactory morpho-functional recovery of the foot.

[Acute surgical pathology in elderly patients]. / Aspecte ale chirurgiei de urgenta la pacientul vârstnic.

The consequence of demographic aging is an increase of surgical pathology of the elderly, concerning both number and complexity of the cases. To asses the nature of geriatric surgical pathology and the effect of co-morbidities on surgical outcome, a retrospective study was carried out on a series of 401 patients aged over 75, treated in the IIIrd Surgical Unit in the period 2002-2003. 132 patients were admitted as acute cases and 94 of them were operated: 62 required immediate surgery and 32 required delayed operations. According to the nature of the diseases, benign surgical conditions were encountered in majority of the cases (78 cases). The diagnostics requiring immediate operations were: complicated hernias, perforated peptic ulcer, lower limb acute ischemia. Delayed emergency operations were performed for: acute cholecystitis, biliary lithiasis with angiocholitis and complicated gastric cancer. Cardiovascular pathology was recorded as the most frequent co-morbidity. Hospital mortality rate of 32.9% resulted mainly from cases with mesenteric infarction and generalized peritonitis, as well as from delayed emergencies such as complicated gastric and colon cancer. The most frequent causes of death following surgery were: cardiac failure, sepsis and multiple organ failure.