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.

[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.

Laparoscopic right adrenalectomy after liver transplantation.

To our knowledge, laparoscopic right adrenalectomy has not been previously reported after orthotopic liver transplantation. The aim of this report is to demonstrate the feasibility of the laparoscopic approach in this technically challenging situation, and to outline some considerations unique to this clinical setting.

Genetic epidemiology of non-insulin-dependent diabetes mellitus (NIDDM) in north India: distribution of Gm and Km allotypes in 'Punjabis'.

Non-insulin dependent diabetes mellitus (NIDDM) is becoming endemic to modernizing and urbanizing populations all over the globe. The data on Gm and Km allotypes in the 'Punjabis' (n = 165) from north India show an interesting association with NIDDM. Differences between diabetic and control samples for the Km allele frequency distribution approach significance (p = 0.0897). The observed phenotypic diversity in the Gm system in diabetics indicates genetic heterogeneity in the disease group. A significant decrease (or absence) of phenotype Gm1,3,17; ;5,21 (p = 0.0119), and presence of phenotype Gm1,2,3,17; ;5,21 (p = 0.0158) in diabetics may constitute a risk factor for this disorder in 'Punjabis'.

The use of adenosine for repair of penetrating cardiac injuries: a novel method.

The use of intravenous administration of adenosine to expedite cardiorrhaphy in penetrating cardiac trauma by inducing temporary asystole is described. It is quicker, more effective, and safer than the traditional methods.

Coronary-pulmonary steal syndrome.

The development of an internal thoracic artery-pulmonary artery fistula after operation is a rare entity of no clear etiology. We report a patient who underwent coronary bypass reoperation, presented 3 years later with angina on exertion, and upon investigation was found to have an internal thoracic artery-pulmonary artery fistula. This patient was managed conservatively.

Early and follow-up angiography in minimally invasive coronary bypass without mechanical stabilization.

BACKGROUND: This study was undertaken to assess the early and late outcome of coronary anastomosis constructed on a beating heart without the help of mechanical stabilization. METHODS: All consecutive patients (51) from January 1996 to September 1997 who had bypass done by one surgeon using a left minithoracotomy (39) or median sternotomy (12) on a beating heart with occlusive local snares without mechanical stabilization underwent follow-up angiography early (100%) (within 6 hours) and late (63.5%) at a mean of 9.6+/-4.48 months (range, 3.3 to 19.1 months). RESULTS: The cumulative late patency was 95.4% (83 of 87 patients), with two early and two late occlusions. There was no early or late mortality or perioperative myocardial infarction. Two patients (3.9%) developed recurrent angina. Four anastomotic irregularities (4 of 32 patients, 12.6%) have cleared up on follow-up angiography. There was no evidence of late stenosis at the snare sites used for local occlusion. CONCLUSIONS: Minimally invasive coronary bypass is safe and effective. Early angiographic abnormalities should be interpreted with caution and we could not demonstrate any long-term deleterious effects of local snaring.

Minimally invasive coronary artery bypass: a series with early qualitative angiographic follow-up.

BACKGROUND: Notwithstanding the advantages offered by minimally invasive coronary bypass, valid concerns have been raised about the technical accuracy of the distal anastomoses that can be fashioned on a beating heart. The main objective of our study was to undertake early and complete qualitative angiographic graft analysis in all patients undergoing this procedure. METHODS: All enrolled patients (25) from January to October 1996 who had bypass done by one surgeon via left minithoracotomy (19) or median sternotomy (6) on a beating heart underwent postoperative angiography within 4 to 6 hours. These angiograms were then reviewed for qualitative analysis and compared with a similar series done under conventional cardioplegic arrest. RESULTS: There was 97.5% graft patency (28/29) and no anastomotic occlusions. One internal thoracic artery was damaged. There was no mortality and no perioperative myocardial infarctions. All patients are alive and symptom free. The follow-up is 100% complete and ranges from 15 days to 11 months. Of the 26 anastomoses that could be assessed, 21 (81%) were grade A and 5 (19%) were grade B. In comparison, 24/25 (96%) of the anastomoses fashioned on an arrested heart by the same surgeon were grade A (p = 0.175). CONCLUSIONS: Minimally invasive coronary bypass can be carried out effectively and safely in a select group of patients, and the development of stabilizing devices and proper instrumentation should further improve results.

Left anterior descending endarterectomy and internal thoracic artery bypass for diffuse coronary disease.

BACKGROUND: The risk and efficacy of using an arterial conduit to bypass an endarterectomized coronary artery remain incompletely defined. To address this question we analyzed retrospectively 74 patients from 1989 to 1994 in whom bypass grafting using the left internal thoracic artery to an endarterectomized left anterior descending artery was performed. METHODS: There were 60 men and 14 women with a mean age of 60.1 +/- 8.6 years. Of this cohort, 55 patients (74.3%) had a previous infarction, 18 (24.3%) were diabetic, and 5 (6.7%) had reoperations; 25 patients (34%) had a totally occluded left anterior descending artery and the average ejection fraction was 45%. Each patient had 2.95 +/- 0.52 grafts with 48 patients (65%) requiring multiple endarterectomies. The average length of the endarterectomized segment was 3.1 +/- 1.6 cm. Average anoxia time was 49 +/- 13 minutes. Postoperatively 19 patients (25.6%) required intraaortic balloon and 18 (24.3%) required inotropic support. Perioperative infarction in the left anterior descending artery distribution occurred in 5 patients (6.7%). RESULTS: There were 3 (4.0%) early and 4 (5.4%) late deaths at a mean follow-up of 36 +/- 16 months. Recurrent angina was present in 9 patients (14.7%). Actuarial 5-year survival was 84.5%. Angiographic follow-up obtained in 23 patients (37.4%) demonstrated 74% anastomotic patency, with good distal run-off in 13 (65%). The anterior segmental wall motion was preserved. CONCLUSIONS: The use of the left internal thoracic artery bypass and adjunctive left anterior descending artery endarterectomy to expand the scope of myocardial revascularization in carefully selected circumstances appears to be beneficial.

Needlescopic urology: incorporating 2-mm instruments in laparoscopic surgery.

OBJECTIVES: To report the initial experience with incorporation of needlescopic (2 mm) instruments and optics in various therapeutic minimally invasive urologic procedures. METHODS: Needlescopic techniques were used to successfully perform a variety of urologic surgeries including adrenalectomy, nephrectomy, renal cyst marsupialization, orchiopexy, lymphocele marsupialization, and pelvic lymph node dissection. RESULTS: To date we have performed 42 needlescopic procedures in 39 patients (14 female and 25 male) ranging in age from 8 months to 87 years (mean 46.6 years). Three procedures were converted to conventional laparoscopy and one to open surgery, yielding a needlescopic success rate of 90.5%. Surgical times averaged 132 minutes and blood loss averaged 67 mL. Procedures were performed on an outpatient basis in 33.3% of cases, and 94.9% of patients were discharged home within 23 hours. The overall complication and conversion rate was 14.3% and there was no mortality. CONCLUSIONS: Our initial experience is quite promising. In select patients, needlescopic urologic surgery is feasible and safe, and may reduce postoperative pain, hospital stay, and recovery time, and improve cosmesis. Further evaluation of, and improvement in, 2-mm instrumentation and optical technology is needed.

Extra-anatomic renal revascularization in patients with renal artery stenosis and abdominal aortic occlusion.

Thirteen patients with atherosclerotic renal artery stenosis and total abdominal aortic occlusion underwent extra-anatomic surgical renal revascularization without aortic replacement. Renal artery stenosis was present unilaterally (n = 2), bilaterally (n = 7), or in a solitary kidney (n = 4). Surgical renal revascularization was indicated for treatment of severe hypertension in all patients and for preservation of renal function in 10 patients. The level of abdominal aortic occlusion was suprarenal (n = 3), perirenal (n = 2), or infrarenal (n = 8). All patients had extensive collateral vascular supply to the lower extremities with absent (n = 7) or mild (n = 6) claudication. Surgical renal revascularization was achieved with hepatorenal bypass (n = 6), mesenterorenal bypass (n = 4), or splenorenal bypass (n = 3). None of the patients underwent concomitant aortic replacement. There were no operative deaths. Postoperatively, hypertension was improved in 10 patients, unchanged in 2 patients, and worse in 1 patient. Renal function was improved in 8 patients, stable in 2 patients, and worse in 3 patients. After surgical renal revascularization, no patient required aortic replacement, while 1 patient underwent extra-anatomic revascularization of the lower extremities. We conclude that some patients with renal artery stenosis and abdominal aortic occlusion can be managed by surgical renal revascularization alone without a more extensive and potentially hazardous aortic replacement. In these patients, extra-anatomic techniques can allow safe and successful surgical renal revascularization while avoiding surgery on the diseased aorta.

Initial experience with retroperitoneoscopic nephroureterectomy: use of a double-balloon technique.

OBJECTIVES: To report the initial experience with retroperitoneoscopic nephroureterectomy for symptomatic, end-stage vesicoureteral reflux. METHODS: Two patients underwent a nephroureterectomy by a four-port retroperitoneal laparoscopic approach. In 1 patient, a double-balloon technique was used to dissect the pelvic extraperitoneal space and gain access to the juxtavesical ureter. In the second patient, the distal ureter was mobilized with routine laparoscopic dissection techniques. RESULTS: Operative time was 6 and 5.5 hours, respectively, and mean hospital stay was 4 days. Mean patient follow-up is 17.5 months. CONCLUSIONS: The technique of retroperitoneoscopic nephroureterectomy is in evolution; until now, a major concern has been the inadequate access to the distal ureter through a completely retroperitoneoscopic approach. Described herein is a double-balloon technique that significantly facilitates dissection of the juxtavesical ureter during a retroperitoneal laparoscopic nephroureterectomy.

"Stand-up" urologic endoscopy.

OBJECTIVES: To report the advantages of performing diagnostic and therapeutic urologic endoscopic procedures with the urologic surgeon in the standing-up position. METHODS: Our 25-year institutional experience with more than 10,000 cases of transurethral ablation of the prostate and other urologic endoscopic procedures, performed by the urologist in the standing-up position, was examined. A questionnaire of all 55 of our former urology residents was carried out to determine current practice trends. RESULTS: We have noted no drawbacks from performing transurethral surgery in the standing-up position. Ninety-two percent of the respondents believe that the standing-up position was more comfortable for endoscopic surgery than the sitting-down position. CONCLUSIONS: the standing-up technique of transurethral surgery minimizes positional stresses on the urologist's cervical and thoracic spine while optimizing endoscopic visualization and maneuverability. We recommend it in preference to the conventional sitting-down technique.

Transperitoneal nephrectomy for benign disease of the kidney: a comparison of laparoscopic and open surgical techniques.

OBJECTIVE: The objective of this study was to compare the results of laparoscopic nephrectomy for benign disease to open surgical nephrectomy for benign disease. METHODS: Twenty consecutive patients undergoing laparoscopic nephrectomy for benign disease were compared with 23 patients undergoing open surgical nephrectomy for benign disease and with 29 patients undergoing a donor nephrectomy. Data were collected in the following areas: patient age, anesthetic risk, operative time, estimated blood loss, postoperative time to resume oral intake, parenteral analgesics, oral analgesics, hospital stay, complications, and convalescence. Information was obtained through chart review, telephone interviews, and mailed questionnaires. RESULTS: Compared with open surgical nephrectomy, laparoscopic nephrectomy resulted in a statistically significant longer operative time; however, it afforded a statistically significant decrease in postoperative ileus (open group), hospital stay (both groups), oral analgesics (donor group), and convalescence (both groups). The incidence of complications was 15 percent in the laparoscopic group and 0 percent in the two open surgical groups; the majority of complications occurred during the initial seven laparoscopic procedures. CONCLUSIONS: Laparoscopic nephrectomy is a more time-consuming procedure than open surgical nephrectomy. Also, early in one's experience with this technique, the complication rate is higher than with open surgery. However, despite the newness of the technique, it results in significant benefits to the patient: decreased postoperative pain, shorter hospitalization, and more rapid convalescence.

Laparoscopic renal cryoablation: initial clinical series.

OBJECTIVES: To present the technique and short-term results of retroperitoneal laparoscopic renal cryoablation. METHODS: Ten patients underwent laparoscopic renal cryoablation of 11 exophytic renal tumors ranging in size from 1.5 to 3 cm identified on computed tomography. Tumors were located at the upper (3), middle (5), or lower (3) pole of the kidney. Three patients had a solitary kidney. A 3-port retroperitoneal laparoscopic approach was used to create renal cryolesions. Puncture cryoablation was performed with a 4.8-mm cryoprobe. Real-time, endoscopic, steerable, color Doppler ultrasound was used to monitor the evolving cryolesion. All patients have completed a minimum follow-up of 3 months (mean 5.5, range 3 to 9). RESULTS: Cryoablation was technically successful in all 10 patients (11 tumors). Under ultrasound guidance, the ice ball was intentionally created up to 1 cm beyond the tumor edge with the aim of achieving negative margins. Mean surgical time was 2.4 hours, cryoablation (double freeze-thaw) time 12.9 minutes, cryoprobe tip temperature -186 degrees C, and blood loss 75 mL. Systemic temperature remained unaltered. Hospital stay was less than 23 hours in 9 of 10 patients. Follow-up magnetic resonance imaging at 1 day and 1, 2, and 3 months identified the punched-out, nonenhancing, spontaneously resorbing, renal cryolesion. Follow-up biopsies of the cryoablated tumor site were negative for cancer in the 3 patients who have undergone the biopsy. CONCLUSIONS: The initial series of laparoscopic renal cryoablation is presented. The retroperitoneoscopic approach, by avoiding the peritoneal cavity, minimizes the chances of the bowel coming in contact with the evolving cryolesion, and the potential sequelae thereof. Laparoscopic renal cryoablation is currently developmental and long-term data are awaited. Nevertheless, it is potentially an attractive addition to available nephron-sparing surgical techniques.