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.

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.

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.

Hypothermic preservation of lung allograft inhibits cytokine-induced chemoattractant-1, endothelial leucocyte adhesion molecule, vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 expression.

Organ dysfunction is a major clinical problem after lung transplantation. Prolonged cold ischaemia and reperfusion injury are believed to play a central role in this complication. The influence of cold preservation on subsequent warm reperfusion was studied in an isolated, ventilated and perfused rat lung. Rat lungs were flushed with cold Perfadex-solution and stored at 4 degrees C for different time periods. Thereafter lungs were perfused and ventilated for up to 3 h. Physiological parameters, production of inflammatory mediators and leucocyte infiltration were measured before and after perfusion. Lungs subjected to a cold ischaemia time of up to 6 h showed stable physiological conditions when perfused for 3 h. However, cold-ischaemia time beyond 6 h resulted in profound tissue oedema, thereby impairing ventilation and perfusion. Warm reperfusion and ventilation per se induced a strong inflammatory response, as demonstrated by a significant up-regulation of chemokines and adhesion molecules (cytokine-induced chemoattractant-1, intracellular adhesion molecule and endothelial leucocyte adhesion molecule), accompanied by enhanced leucocyte infiltration. Although the up-regulation of inflammatory mediators was blunted in lungs that were subjected to cold ischaemia, this did not influence leucocyte infiltration. In fact, cold ischaemia time correlated with leucocyte sequestration. Although cold preservation inhibits the expression of inflammatory mediators it does not affect leucocyte sequestration during warm reperfusion. Cold preservation might cause impairment of the endothelial barrier function, as evidenced by tissue oedema and profound leucocyte infiltration.

Imaging findings after minimally invasive nephron-sparing renal therapies.

With the trend towards minimally invasive and nephron-sparing surgery for renal masses, laparoscopic partial nephrectomy and energy ablative techniques have become common approaches to treat low-stage tumours. Complications following such techniques are occasional, especially for ablation techniques. This review illustrates the imaging of these complications and of tumour recurrence, with the conclusion that imaging plays an important role in their diagnosis, and in the infrequent situation that intervention is needed, helps to plan subsequent management.

[Laparoscopic partial nephrectomy: technique and outcomes]. / Nefrectomía parcial laparoscópica: técnica y resultados.

The indication of laparoscopic partial nephrectomy (LPN) has evolved considerably, and the technique is approaching established status at our institution. Over the past 5 years, the senior author has performed more than 450 laparoscopic partial nephrectomies at the Cleveland Clinic. Herein we present our current technique, review contemporary data and oncological outcomes of LPN.

Nefrectomía parcial laparoscópica: técnica y resultados / Laparoscopic partial nephrectomy: technique and outcomes

La indicación de la Nefrectomía Parcial Laparoscópica (NPL) ha evolucionado considerablemente y la técnica se está convirtiendo en una opción establecida en nuestro centro. En los últimos 5 años, el autor principal ha realizado más de 450 nefrectomías parciales laparoscópicas en la Clínica Cleveland. Presentamos seguidamene nuestra técnica y revisamos los datos actuales y los resultados oncológicos de la NPL

The indication of laparoscopic partial nephrectomy (LPN) has evolved considerably, and the technique is approaching established status at our institution. Over the past 5 years, the senior author has performed more than 450 laparoscopic partial nephrectomies at the Cleveland Clinic. Herein we present our current technique, review contemporary data and oncological outcomes of LPN

Laparoscopic radical cystectomy with intracorporeal ileal conduit diversion: five cases with a 2-year follow-up.

OBJECTIVE: To assess the feasibility and intermediate-term outcome of laparoscopic radical cystectomy (LRC) with ileal conduit urinary diversion in patients with organ-confined muscle-invasive carcinoma of the urinary bladder, the entire procedure undertaken intracorporeally only using laparoscopic techniques. PATIENTS AND METHODS: Five patients (four men and one woman) underwent LRC with intracorporeal ileal conduit diversion in February 2000, using a six-port transperitoneal technique. LRC, ileal conduit exclusion, restoration of ileo-ileal continuity, and bilateral stented uretero-ileal anastomoses were completed intracorporeally in all patients. The follow-up data up to 2 years are reported. RESULTS: All procedures were completed laparoscopically with no open conversion or intraoperative complications. The mean duration of surgery was 7.5 h; the blood loss was 360 mL and no patient required perioperative blood transfusion. The mean (range) hospital stay was 7 (6-22) days; the specimen weight was 225-400 g. The surgical margins of the bladder specimen were negative in each patient. One patient developed intestinal obstruction after surgery, requiring a diverting ileostomy for 12 weeks. At a follow-up of 2 years, two patients died, both from unrelated causes (myocardial infarction and septicaemia from pulmonary infection in one each). The three surviving patients are asymptomatic with normal upper tracts and no evidence of local recurrence or metastatic disease. CONCLUSION: LRC with ileal conduit diversion undertaken completely intracorporeally is a feasible option for muscle-invasive organ-confined carcinoma of the urinary bladder, with good outcomes over a 2-year follow-up.

Laparoscopic radical nephrectomy in 100 patients: a single center experience from the United States.

BACKGROUND: The objective of the current study was to report a single-surgeon, single-center experience with 100 consecutive laparoscopic radical nephrectomies with intact specimen extraction, with the aim of evaluating the oncologic adequacy of the laparoscopic dissection from a technical standpoint and various parameters including the learning curve. METHODS: Of the 140 laparoscopic radical nephrectomies performed at the study institution since August 1997, the initial 100 are evaluated herein. To evaluate the technical oncologic adequacy, comparison was made with 40 contemporary open radical nephrectomy specimens with regard to detailed radiologic (computed tomography scan) and pathologic data. RESULTS: In the 100 patients studied (with a mean tumor size of 5.1 cm), the mean surgical time was 2.8 hours, the blood loss was 212 mL, the specimen weight was 554.3 g, and the hospital stay was 1.6 days. Complications occurred in 14 patients (14%) and were major in 3 (3%) and minor in 11 (11%). Two patients (2%) were converted to open surgery. There was no perioperative mortality. Over a mean follow-up of 16.1 months, there was no local or port site recurrence reported; 2 patients developed metastatic disease with 1 death occurring at 11 months. When evaluating the learning curve in the initial 50 versus the second 50 patients, a shorter surgical time (P = 0.02) appeared to be the only significant variable. On multivariate analyses, the only variables found to impact on surgical time were specimen weight (P < 0.001) and chronologic time period of surgery (P = 0.05). All laparoscopic specimens were extracted intact; surgical margins were negative for tumor in all 100 patients. All detailed radiologic and histopathologic parameters evaluated were nearly identical between the laparoscopic and open surgery groups. CONCLUSIONS: Laparoscopic radical nephrectomy with intact specimen extraction currently is a routine, effective, and efficacious treatment option for patients with T1-T3aN0M0 renal tumors. Although no long-term data were available as of last follow-up, the negative surgical margins achieved routinely in the current series provide encouraging surrogate evidence of the technical efficacy of laparoscopy from an oncologic standpoint. As such, at the study institution, laparoscopic radical nephrectomy with intact specimen extraction currently is the standard-of-care for patients with T1-3aN0M0 renal tumors measuring < or = 10-12 cm in size.

Robotic laparoscopic surgery: a comparison of the DA Vinci and Zeus systems.

OBJECTIVES: To evaluate two currently available robotic surgical systems in performing various urologic laparoscopic procedures in an acute porcine model. METHODS: Robotic laparoscopic surgery was performed in 14 swine. Data were compared between the da Vinci Robotic System and the Zeus Robotic System. RESULTS: During laparoscopic nephrectomy, the da Vinci System (n = 6) had a significantly shorter total operating room time (51.3 versus 71.6 minutes; P = 0.02) and actual surgical time (42.1 versus 61.4 minutes; P = 0.03) compared with the Zeus System (n = 5). However, the blood loss and adequacy of surgical dissection were comparable between the two groups. For laparoscopic adrenalectomy, the da Vinci System (n = 5) had a shorter actual surgical time (12.2 versus 26.0 minutes; P = 0.006) than did the Zeus System (n = 5). For laparoscopic pyeloplasty, the da Vinci System had a shorter total operating room time (61.4 versus 83.4 minutes; P = 0.10) and anastomotic time (44.7 versus 66.4 minutes; P = 0.11). During pyeloplasty anastomosis, the total number of suture bites per ureter was 13.0 for the da Vinci System (n = 6) and 10.8 for the Zeus System (n = 6). The complications included an adrenal parenchymal tear each during a da Vinci System-based left adrenalectomy and a Zeus System-based right adrenalectomy. An inferior vena caval tear during a Zeus System-based right adrenalectomy occurred in 1 case, which was suture-repaired telerobotically. CONCLUSIONS: Robotic laparoscopic procedures can be performed effectively using either the da Vinci or Zeus System. In this limited study, the learning curve and operative times were shorter and the intraoperative technical movements appeared inherently more intuitive with the da Vinci System. Additional clinical experience is necessary.

Missed acute ascending aortic dissection.

We describe a patient who presented with classic symptoms and signs of acute aortic dissection that escaped detection despite state-of-the-art imaging techniques. We review the pertinent literature concerning the diagnosis of acute dissection of the ascending aorta and describe the types of dissection that might be missed with conventional diagnostic techniques. Repeated efforts should be made to diagnose aortic dissection even though initial studies may be negative in patients with clinical evidence of dissection.

Laparoscopic cross-trigonal Cohen ureteroneocystostomy: novel technique.

PURPOSE: We describe a novel technique of laparoscopic transvesical cross-trigonal Cohen anti-reflux ureteroneocystostomy. MATERIALS AND METHODS: A 10, an 11 and a 32-year-old patient with symptomatic unilateral vesicoureteral reflux underwent laparoscopic cross-trigonal ureteral reimplantation. Two 5 mm. balloon tip ports were suprapubically inserted into the bladder. Using a transurethral resectoscope with a Collins knife a 4 to 5 cm. cross-trigonal submucosal trough was created from the refluxing ureteral orifice to the contralateral side of the bladder. The refluxing ureteral orifice and intramural ureter were completely mobilized intravesically, advanced transtrigonally and secured to the detrusor muscle at the apex of the trough with 3 deep interrupted sutures. The elevated mucosal flaps of the trough were suture approximated over the ureter to create a submucosal tunnel. All suturing was performed by freehand laparoscopic technique. RESULTS: Operative time was between 2.5 and 4.5 hours and blood loss was 10 to 50 cc. Adequate submucosal trough creation, ureteral extravesical mobilization and intravesical advancement, and bladder mucosal flap reapproximation were done to create a submucosal tunnel in all cases. Satisfactory transtrigonal anchoring of the neoureteral orifice to the detrusor muscle and mucosa was achieved with 3 stitches. Hospital stay was 2, 2 and 1 days in the 3 cases, and the Foley catheter remained in place for 3, 1 and 1 week, respectively. At 6 months reflux had resolved in 2 patients, while in 1 grade II reflux persisted, which was improved from grade IV preoperatively. All patients have remained infection-free without antibiotics. CONCLUSIONS: Laparoscopic transvesical cross-trigonal antireflux ureteral reimplantation is technically feasible. Intravesical laparoscopic suturing is possible. Potential advantages include a decreased hospital stay, decreased narcotic requirement and better cosmesis. Further experience is necessary to refine the technical nuances and evaluate outcomes compared to the open technique.

Laparoscopic bladder flap ureteral reimplantation: survival porcine study.

PURPOSE: The bladder or Boari flap is a useful technique for ureteroneocystostomy when the distal ureter is too short to reach the bladder without undue tension. We report our experience with laparoscopic Boari flap ureteroneocystostomy in the chronic porcine model. MATERIALS AND METHODS: Six female farm pigs underwent unilateral laparoscopic Boari bladder flap ureteroneocystostomy. Refluxing direct ureteral reimplantation was performed in the initial 3 animals. In the next 3 animals a submucosal tunnel was formed to achieve nonrefluxing ureteroneocystostomy into the Boari flap. The animals were sacrificed 6 weeks after surgery. At sacrifice ascending cystography, ipsilateral antegrade pyelography and autopsy examination of the ureteroneocystostomy site was performed. RESULTS: No intraoperative or postoperative complications were noted. Average operative time was 140 minutes. Postoperatively serum creatinine and hemoglobin were normal in all pigs. All 3 animals with direct ureteroneocystostomy into the Boari flap had free reflux into the kidney and all 3 with a submucosal tunnel reimplant had no reflux on ascending cystography and free drainage on antegrade pyelography. Autopsy confirmed a patent anastomotic site in all 6 cases. CONCLUSIONS: Laparoscopic ureteroneocystostomy using the Boari bladder flap technique is feasible. Our survival porcine model confirms the successful application of the refluxing and nonrefluxing technique of ureteral reimplantation. Clinical application of the technique has the potential to decrease patient morbidity associated with traditional open surgery.

Laparoscopic renal cryoablation: impact on renal function and blood pressure.

OBJECTIVES: To evaluate the renal function and blood pressure outcomes after laparoscopic renal cryotherapy. Laparoscopic renal cryoablation is a developmental minimally invasive modality for the treatment of renal neoplasms. After cryotherapy, a segment of renal parenchyma is rendered ischemic/necrotic and left in situ. It is currently unknown whether this may trigger renin overproduction and thus renin-mediated hypertension. METHODS: Data are presented for 22 of 56 treated patients, each of whom completed a minimum follow-up of 6 months. The data were obtained from patient charts, phone interviews, and/or questionnaires. These results were statistically compared over time by paired t tests. RESULTS: The mean follow-up was 20.6 months. No significant differences were found between the preoperative and most recent postoperative serum creatinine (sCr) levels (1.13 and 0.91 mg/dL, respectively), systolic and diastolic blood pressure values (135.6 versus 131.2 mm Hg and 78 versus 72.7 mm Hg, respectively), or in the estimated creatinine clearance (P <0.05). The number or dose of antihypertensive medications did not change during the follow-up period for any patient. In 3 patients with a solitary kidney, the blood pressure and sCr values remained unchanged (mean preoperative sCr 1.43 mg/dL and mean postoperative sCr after a minimum of 6 months 1.33 mg/dL). CONCLUSIONS: Laparoscopic renal cryoablation did not have a deleterious impact on renal function or blood pressure during a mean follow-up of 20.6 months.

Familial torticollis with polydactyly: manifestation in three generations.

Familial transmission of congenital muscular torticollis (CMT) has been reported in the literature, and postaxial polydactyly has been frequently reported in familial cases, but, to our knowledge, familial CMT with postaxial polydactyly has not been described. In this article, we report a rare case of CMT with postaxial polydactyly in 3 generations of a family and suggest an autosomal-dominant pattern of inheritance in these cases.

Current role of laparoscopic adrenalectomy.

OBJECTIVE: Laparoscopic adrenalectomy is now a standard procedure for the vast majority of patients with surgical adrenal disease. Herein, we evaluate various techniques employed during laparoscopic adrenalectomy, and assess the current role of laparoscopic adrenalectomy, and possible future developments. MATERIALS AND METHODS: We reviewed large series of reports presenting the results of laparoscopic transperitoneal and retroperitoneal adrenalectomy and we compared the data of different series and authors, adding our experience. RESULTS: Laparoscopic adrenalectomy is a safe, reproducible and effective procedure with low complication rates. With increasing worldwide experience, the indications for laparoscopic adrenalectomy are expanding. When retrospectively compared to open surgery, laparoscopic adrenalectomy is superior in terms of postoperative pain, hospital stay, return to normal activity and complications. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and effective option for most surgical adrenal pathologies. Moreover, laparoscopic adrenalectomy is associated with a superior patient tolerance profile. It is safe to say that today, laparoscopy must be considered the first choice procedure for excision of benign surgical adrenal lesions.