Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.

Robotic-assisted laparoscopic repair of rectovesical fistula after Hartmann's reversal procedure.

The case is of a 59-year-old male with history of severe ischemic colitis following emergent intervention for a ruptured infrarenal aortic aneurysm who subsequently underwent left hemicolectomy, partial proctectomy, and Hartmann colostomy. The patient later underwent reversal of the Hartmann colostomy with diverting ileostomy. The surgery was complicated by a right ureteral and posterior bladder injury that resulted in a large rectovesical fistula involving the right hemitrigone and right ureteral orifice. An attempt to repair the rectovesical fistula at an outside facility was unsuccessful. Then, he underwent a robotic-assisted laparoscopic repair of rectovesical fistula, including simple prostatectomy, excision of rectovesical fistulous tract, rectal closure, peritoneal and omental flap interposition, bladder neck reconstruction, vesicourethral anastomosis and right ureteral reimplantation. There were no intraoperative or postoperative complications, and the patient was discharged at postoperative day 4; cystoscopy at 6-week follow-up demonstrated a successful closure of the fistula, at which time the ureteral stents were removed.

Robotic uterine-sparing vesicovaginal fistula repair.

INTRODUCTION AND HYPOTHESIS: The objective was to describe a technique for the robotic repair of complex vesicovaginal fistula (VVF) with uterine preservation. METHODS: From 2015 to 2017, two patients underwent the procedure. Following placement of the patient in the lithotomy position, catheterization of the fistulous tract and laparoscopic omental harvesting is performed. Then, the robotic system is docked. A transverse incision was made in the peritoneum above the uterus was made to provide access to the bladder, the uterus is mobilized, and a cystotomy is performed to identify the structures. Subsequently, the cystotomy is extended toward the fistulous tract, the plane between the organs is dissected to proceed with the vaginal closure, the vagina is closed, the omental flap is interposed, and the bladder is closed. RESULTS: Mean operative time (OT) was 219 min. Mean estimated blood loss (EBL) was 75 ml. One of the patients had an intraoperative cervix canal injury that was identified and repaired. The postoperative course was uneventful, and the mean length of hospital stay (LOS) was 1 day. A mean follow-up of 17 (±9.89) months showed no recurrence at cystoscopy or imaging evaluation. CONCLUSIONS: Uterine-sparing VVF repair is feasible and safe. More studies are needed to assess equivalence compared with other procedures.

Overall survival and oncological outcomes after partial nephrectomy and radical nephrectomy for cT2a renal tumors: A collaborative international study from the French kidney cancer research network UroCCR.

BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results. METHOD: A retrospective international multicenter study was conducted in the frame of the French kidney cancer research network (UroCCR). We considered all patients aged≥18 years who underwent surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm) between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS). Comparison between PN and RN was realized after an adjustment by propensity score considering predefined confounding factors: age, sex, tumor size, pT stage of the TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of 267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and 88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2% after PN and 91.0% and 85.0% after RN. No significant difference between groups was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05, P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50-2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a stage kidney tumors. The risk of recurrence is probably more related to prognostic factors than the surgical technique. The decision to perform a PN should depend on technical feasibility rather than tumor size, both to imperative and elective situation. LEVEL OF EVIDENCE: 4.

Live surgery: highly educational or harmful?

PURPOSE: Live surgery (LS) is considered a useful teaching opportunity. The benefits must be balanced with patient safety concerns. To evaluate the rate of complications of a series of urologic LS performed by experts during the Congress Challenge in Laparoscopy and Robotics (CILR). METHODS: We present a large, multi-institution, multi-surgeon database that derives from 12 CILR events, from 2004 to 2015 with a total of 224 cases. Radical prostatectomy (RP) was the most common procedure and a selection of complex cases was noted. The primary measure was postoperative complications and use of a Postoperative Morbidity Index (PMI) to allow quantitative weighing of postoperative complications. RESULTS: From 12 events, the number of cases increased from 11 in 2004 to 27 in 2015 and a total of 27 surgeons. Of 224 cases (164 laparoscopic and 60 robotic), there were 26 (11.6%) complications: 5 grade I, 5 grade II, 3 grade IIIa, 12 grade IIIb and 1 grade V, the latter from laparoscopic cystectomy. Analysis of PMI was 23 times higher from cystectomy compared to RP. CONCLUSIONS: In the setting of live surgery, the overall rate of complications is low considering the complexity of surgeries. The PMI is not higher in more complex procedures, whereas RP seems very safe.

[Interest using 3D ultrasound and MRI fusion biopsy for prostate cancer detection]. / Quel est l'intérêt de l'échographie 3D et fusion d'image IRM pour la détection du cancer de la prostate ?

INTRODUCTION: The strategic therapy for prostate cancer depends on histo-pronostics data, which could be upgraded by obtaining targeted biopsies (TB) with MRI (magnetic resonance imagery) fusion 3D ultrasound. OBJECTIVES: To compare diagnostic yield of image fusion guided prostate biopsy using image fusion of multi-parametric MRI (mpMRI) with 3D-TRUS. MATERIALS AND METHODS: Between January 2010 and April 2013, 179 consecutive patients underwent outpatient TRUS biopsy using the real-time 3D TRUS tracking system (Urostation™). These patients underwent MRI-TRUS fusion targeted biopsies (TB) with 3D volume data of the MRI elastically fused with 3D TRUS at the time of biopsy. RESULTS: A hundred and seventy-three patients had TBs with fusion. Mean biopsy core per patient were 11.1 (6-14) for SB and 2.4 (1-6) for TB. SBs were positive in 11% compared to 56% for TB (P<0.001). TB outperformed systematic biopsy(SB) in overall any cancer detection rate, detection of clinically significant cancer (58% vs. 36%), cancer core length (6.8mm vs. 2.8mm), and cancer rate per core (P<0.001). In multivariable logistic regression, with TB we have more chance to find a clinically significant cancer (OR:3.72 [2-6.95]). When both TRUS and MRI are positive, there is 2.73 more chance to find a clinically significant cancer. CONCLUSION: MR/TRUS elastic fusion-guided biopsies outperform systematic random biopsies in diagnosing clinically significant cancer. Ability of interpretation of real-time TRUS is essential to perform the higher level of MR/US fusion and should be use for active surveillance. LEVEL OF PROOF: 4.

An oral lesion as the primary clinical manifestation of sarcoidosis.

An oral lesion as the first clinical presentation of sarcoidosis is extremely rare. We present the case of a 39-year-old woman who was referred to the oral and maxillofacial surgery department with a persistent asymptomatic nodular lesion in the hard palate. This was located adjacent to a grossly carious upper first molar and a provisional diagnosis of chronic periapical granuloma was made. An incisional biopsy of the lesion was carried out, which unexpectedly revealed the presence of a non-caseating granulomatous inflammatory reaction. A referral was sent to the respiratory medicine team and a diagnosis was later confirmed of stage II sarcoidosis. This case report highlights the need for clinicians to be aware of all possible causes of oral lesions, including rare manifestations of underlying systemic disease.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma.

BACKGROUND: Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC). METHODS: Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft. RESULTS: We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis. CONCLUSIONS: Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.

Acoustic radiation force impulse elastography of the spleen in healthy dogs of different ages.

OBJECTIVES: To determine the elastographic characteristics of splenic parenchyma in clinically healthy dogs of various ages in order to establish preliminary qualitative and quantitative standards/reference intervals for this technique. MATERIALS AND METHODS: Thirty three healthy dogs categorized as young, adult and elderly were used. Splenic echotexture, echogenicity, size and ages were assessed with B-mode ultrasonography. Using qualitative elastography, the spleen (head, body and tail) was examined for homogeneity and presence of deformities. Shear velocities in different splenic segments were then quantitatively evaluated. RESULTS: All splenic segments visualised with the B-mode ultrasonography appeared normal. Different splenic segments examined with qualitative elastography were free of any detectable malformations and the images appeared as homogeneous dark areas. The mean shear velocity values were 2 · 32 m/s for head, 2 · 16 m/s for body and 2 · 25 m/s for tail of the spleen (P = 0 · 40), and they did not vary between the different age groups (P > 0 · 05). CLINICAL SIGNIFICANCE: Quantitative and qualitative ARFI elastography of the spleen in clinically healthy dogs differing in age could be easily performed, and it may aid in the diagnosis and evaluation of splenic abnormalities routinely assessed in veterinary practice with B-mode ultrasonography.

Corrosion at the neck-stem junction as a cause of metal ion release and pseudotumour formation.

We present a series of 35 patients (19 men and 16 women) with a mean age of 64 years (36.7 to 75.9), who underwent total hip replacement using the ESKA dual-modular short stem with metal on-polyethylene bearing surfaces. This implant has a modular neck section in addition to the modular head. Of these patients, three presented with increasing post-operative pain due to pseudotumour formation that resulted from corrosion at the modular neck-stem junction. These patients underwent further surgery and aseptic lymphocytic vaculitis associated lesions were demonstrated on histological analysis. Retrieval analysis of two modular necks showed corrosion at the neck-stem taper. Blood cobalt and chromium levels were measured at a mean of nine months (3 to 28) following surgery. These were compared with the levels in seven control patients (three men and four women) with a mean age of 53.4 years (32.1 to 64.1), who had an identical prosthesis and articulation but with a prosthesis that had no modularity at neck-stem junction. The mean blood levels of cobalt in the study group were raised at 50.75 nmol/l (5 to 145) compared with 5.6 nmol/l (2 to 13) in control patients. Corrosion at neck-stem tapers has been identified as an important source of metal ion release and pseudotumour formation requiring revision surgery. Finite element modelling of the dual modular stem demonstrated high stresses at the modular stem-neck junction. Dual modular cobalt-chrome hip prostheses should be used with caution due to these concerns.

The relationship between vitamin D and chemotherapy-induced toxicity - a pilot study.

BACKGROUND: There are anecdotal data that lower levels of vitamin D may be associated with increased levels of toxicity in individuals receiving chemotherapy; we therefore wished to investigate this further. METHODS: From a cohort of over 11 000 individuals, we included those who had vitamin D levels (serum 1,25(OH)(2)D3) measured before and during chemotherapy. They were analysed for side effects correlating Chemotherapy Toxicity Criteria with vitamin D levels, normalising data for general markers of patient health including C-reactive protein and albumin. RESULTS: A total of 241 (2% of the total cohort) individuals entered the toxicity analysis. We found no overall difference in toxicity effects experienced by patients depending on whether they were vitamin D depleted or had sufficient levels (P=0.78). CONCLUSION: This pilot study suggests routine vitamin D measurement during treatment does not appear to be necessary in the management of chemotherapy-induced toxicity.

[A novel technique for distal ureterectomy and bladder cuff excision]. / Nueva técnica para la ureterectomía distal y excisión de manguito vesical.

INTRODUCTION: We describe a novel endoscopic approach and provide a literature review for the "en bloc" dissection of the distal ureter and bladder cuff during laparoscopic radical nephroureterectomy using a transvesical single port approach under pneumovesicum. MATERIALS AND METHODS: The procedure was performed in an 80-year old male with a history of gross hematuria due to left renal pelvic TCC and no history of prior bladder TCC. Laparoscopic radical nephroureterectomy was performed and the ureter was dissected down to the bladder and clipped. A single-port device was inserted transvesically and pneumovesicum established. A full thickness incision of the bladder around the ureter was performed with progressive intravesical mobilization of the distal ureter. Subsequently, a water-tight closure of the bladder defect was achieved. The distal ureter, together with the bladder cuff, was then delivered en bloc laparoscopically with the specimen. RESULTS: The operating time (LESS radical nephroureterectomy, RPLND, and bladder cuff excision) was 6hours and 15minutes. The bladder cuff time was 45minutes. There were no intra or postoperative complications and the catheter was removed after 6 days. Histopathological analysis showed kidney-invasive papillary urothelial cancer, pT3 pN0 (0/7) G3. CONCLUSION: The distal ureter and bladder cuff techniques have not yet been standardized. Management of the bladder cuff with a single port is feasible. Additional studies are needed to identify the best approach for management of the distal ureter at the time of laparoscopic nephroureterectomy.