Francesco Porpiglia

Laparoscopic versus Open Partial Nephrectomy: Analysis of the Current Literature

OBJECTIVES To critically review the current scientific evidence about open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN) to define the current role of these techniques in the treatment of renal tumours. METHODS PubMed and Medline were searched for reports about OPN and LPN that were published from 1990 to 2007 and the most relevant papers were reviewed. RESULTS OPN is an established curative approach for the treatment of small renal tumours. LPN is challenging and the technique is still under development. The intermediate-term oncologic and functional outcomes of LPN are similar to those of OPN in experienced centres. However, the ischaemia time is longer in laparoscopy and a long learning curve is needed to decrease the risk of complications. In the first phase of a surgeons experience with LPN, a careful case selection based on the tumour growth pattern is required. CONCLUSION OPN is today the first treatment option for small renal tumours. LPN is technically challenging, but has been shown to achieve similar intermediate-term cancer cure and renal function results in centres with advanced laparoscopic expertise. Larger series with longer follow-up and prospective randomised studies are needed to confirm the safety and efficacy of LPN.

Effectiveness of nifedipine and deflazacort in the management of distal ureter stones

OBJECTIVES To evaluate the effectiveness of medical therapy during watchful waiting in patients with distal ureter stones. METHODS Ninety-six patients with radiopaque stones located in the distal tract of the ureter and with stone sizes of 1 cm or smaller were involved in the study. The patients were randomly divided into two groups. Group A (n = 48) received oral treatment with 30 mg of deflazacort daily (maximum 10 days) plus 30 mg of slow-release nifedipine daily (maximum 4 weeks). Group B (n = 48) underwent a wait-and-watch approach. Both groups of patients were allowed to use diclofenac on demand. Statistical analyses were carried out using Students t test, the chi-square test, and Fishers exact test. RESULTS The average stone size was 5.8 +/- 1.8 mm for group A and 5. 5 +/- 1.4 mm for group B. No statistically significant difference was found in stone size. Stone expulsion was observed in 38 (79%) of 48 patients in group A and in 17 (35%) of 48 patients in group B. The average expulsion time was 7 days (range 2 to 10) for group A and 20 days (range 10 to 28) for group B. A statistically significant difference was observed in both the expulsion rate and the expulsion time (P <0.05). The mean amount of sodium diclofenac used was 15 mg per patient for group A and 105 mg per patient for group B (P <0.05). CONCLUSIONS The medical treatment proved to be effective and safe, as demonstrated by the increased stone expulsion rate, decreased expulsion time, and reduced need for analgesic therapy.

Medical Therapy to Facilitate the Passage of Stones: What Is the Evidence?

CONTEXT Medical expulsive therapy (MET) for urolithiasis has gained increasing attention in the last years. It has been suggested that the administration of alpha-adrenoreceptor antagonists (alpha-blockers) or calcium channel blockers augments stone expulsion rates and reduces colic events. OBJECTIVE To evaluate the efficacy and safety of MET with alpha-blockers and calcium channel blockers for upper urinary tract stones with and without prior extracorporeal shock wave lithotripsy (ESWL). EVIDENCE ACQUISITION A systematic review of the literature was performed in Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews searched through 31 December 2008 without time limit. Efficacy and safety end points were evaluated in 47 randomised, controlled trials assessing the role of MET. Meta-analysis was conducted using Review Manager (RevMan) v.5.0 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). EVIDENCE SYNTHESIS Pooling of alpha-blocker and calcium channel blocker studies demonstrated a higher and faster expulsion rate compared to a control group (risk ratio [RR]: 1.45 vs 1.49; 95% confidence interval [CI]: 1.34-1.57 vs 1.33-1.66). Similar results have been obtained after ESWL (RR: 1.29 vs 1.57; 95% CI: 1.16-1.43 vs 1.21-2.04). Additionally, lower analgesic requirements, fewer colic episodes, and fewer hospitalisations were observed within treatment groups. CONCLUSIONS Pooled analyses suggest that MET with alpha-blockers or calcium channel blockers augments stone expulsion rates, reduces the time to stone expulsion, and lowers analgesia requirements for ureteral stones with and without ESWL for stones < or = 10 mm. There is some evidence that a combination of alpha-blockers and corticosteroids might be more effective than treatment with alpha-blockers alone. Renal stones after ESWL also seem to profit from MET. The vast majority of randomised studies incorporated into the present systematic review are small, single-centre studies, limiting the strength of our conclusions. Therefore, multicentre, randomised, placebo-controlled trials are needed.

INCIDENCE OF SKELETAL COMPLICATIONS IN PATIENTS WITH BONE METASTATIC PROSTATE CANCER AND HORMONE REFRACTORY DISEASE: PREDICTIVE ROLE OF BONE RESORPTION AND FORMATION MARKERS EVALUATED AT BASELINE

PURPOSE We evaluated the incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease. We also assessed the predictive role of bone turnover markers determined at baseline. MATERIALS AND METHODS A total of 112 patients were consecutively enrolled in our study from July 1990 to July 1998 and followed until death or the last followup. Bone pain, disease extent in bone, serum prostate specific antigen, hemoglobin, and a panel of bone formation and resorption markers were assessed at baseline before any second line treatment. RESULTS Skeletal complications in 34 patients (30.3%, estimated yearly incidence 12.3%) involved vertebral deformity or collapse requiring spinal orthosis in 20 (17.9%), spinal cord compression in 7 (6.2%), pathological bone fracture in 10 (8.9%), symptomatic hypercalcemia in 1 (0.9%) and symptomatic hypocalcemia in 1 (0.9%). Median time to the evidence of the initial skeletal complication was 9.5 months. These adverse events did not influence overall survival. At baseline patients with eventual skeletal complications had greater bone pain (p = 0.02), a heavier tumor load in bone (p = 0.005), lower performance status (p = 0.05), and higher serum alkaline phosphatase (p <0.02) and urinary deoxypyridoline (p <0.05) than their counterparts. Multivariate analysis revealed that only urinary deoxypyridinoline was independently associated with the onset of these events (p <0.02). The scatterplot of urinary deoxypyridinoline values in patients with and without skeletal complications enabled us to detect a cutoff of 38 pM./mM. for predicting 51% of skeletal events with only an 8% false-positive rate. CONCLUSIONS Skeletal complications are common in patients with prostate cancer and hormone refractory disease. Bone loss is the major cause of onset. Baseline deoxypyridinoline at the cutoff point noted had moderate sensitivity but high specificity for predicting these adverse skeletal events.

Randomised Controlled Trial Comparing Laparoscopic and Robot-assisted Radical Prostatectomy

BACKGROUND The advantages of robot-assisted radical prostatectomy (RARP) over laparoscopic radical prostatectomy (LRP) have rarely been investigated in randomised controlled trials. OBJECTIVE To compare RARP and LRP in terms of the functional, perioperative, and oncologic outcomes. The main end point of the study was changes in continence 3 mo after surgery. DESIGN, SETTING, AND PARTICIPANTS From January 2010 to January 2011, 120 patients with organ-confined prostate cancer were enrolled and randomly assigned (using a randomisation plan) to one of two groups based on surgical approach: the RARP group and the LRP group. INTERVENTION All RARP and LRP interventions were performed with the same technique by the same single surgeon. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The demographic, perioperative, and pathologic results, such as the complications and prostate-specific antigen (PSA) measurements, were recorded and compared. Continence was evaluated at the time of catheter removal and 48 h later, and continence and potency were evaluated after 1, 3, 6, and 12 mo. The student t test, Mann-Whitney test, χ(2) test, Pearson χ(2) test, and multiple regression analysis were used for statistics. RESULTS AND LIMITATIONS The two groups (RARP: n=60; LRP: n=60) were comparable in terms of demographic data. No differences were recorded in terms of perioperative and pathologic results, complication rate, or PSA measurements. The continence rate was higher in the RARP group at every time point: Continence after 3 mo was 80% in the RARP group and 61.6% in the LRP group (p=0.044), and after 1 yr, the continence rate was 95.0% and 83.3%, respectively (p=0.042). Among preoperative potent patients treated with nerve-sparing techniques, the rate of erection recovery was 80.0% and 54.2%, respectively (p=0.020). The limitations included the small number of patients. CONCLUSIONS RARP provided better functional results in terms of the recovery of continence and potency. Further studies are needed to confirm our results.

Complications of Laparoscopic Surgery for Renal Masses: Prevention, Management, and Comparison with the Open Experience

CONTEXT The initial excitement about the laparoscopic treatment of renal masses has been tempered by concerns related to increased operative time, technical complexity, and the suitability of laparoscopic approaches to oncologic surgery. OBJECTIVE To provide a comprehensive review of intraoperative and postoperative complications and their prevention and management during laparoscopic surgery of renal tumors. EVIDENCE ACQUISITION A literature review of the Medline and Google Scholar databases was performed, searching for renal cell carcinoma, renal mass, laparoscopy, laparoscopic radical nephrectomy, open radical nephrectomy, laparoscopic partial nephrectomy, open partial nephrectomy, laparoscopic cryoablation, laparoscopic radiofrequency ablation, complications, intra-operative, and post-operative. English-language articles published between 1990 and 2008 were reviewed. EVIDENCE SYNTHESIS Laparoscopic radical nephrectomy (LRN), whether transperitoneal or retroperitoneal, can be performed safely. The overall complication rate is low and does not significantly differ from that of the open experience. Laparoscopic partial nephrectomy (LPN), in contrast, is a technically challenging procedure. Although the intermediate oncologic outcomes are comparable to those of the open experience, there are concerns related to warm ischemia time, and there is a risk of major complications such as urinary leakage and hemorrhage requiring transfusion. Laparoscopic-assisted ablative therapies (cryotherapy and radiofrequency) are being performed more commonly for the treatment of small exophytic renal lesions with a low complication rate and intermediate oncologic outcomes similar to LRN and LPN. CONCLUSIONS Complications associated with the laparoscopic management of renal masses vary among the different procedures and with surgeon experience. The rate of complication appears to be similar to that of open surgery.

Prospective evaluation of mitotane toxicity in adrenocortical cancer patients treated adjuvantly

Toxicity of adjuvant mitotane treatment is poorly known; thus, our aim was to assess prospectively the unwanted effects of adjuvant mitotane treatment and correlate the findings with mitotane concentrations. Seventeen consecutive patients who were treated with mitotane after radical resection of adrenocortical cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory evaluation, monitoring of mitotane concentrations, and a hormonal work-up at baseline and every 3 months till ACC relapse or study end (December 2007). Mitotane toxicity was graded using NCI CTCAE criteria. All biochemical measurements were performed at our center and plasma mitotane was measured by an in-house HPLC assay. All the patients reached mitotane concentrations >14 mg/l and none of them discontinued definitively mitotane for toxicity; 14 patients maintained consistently elevated mitotane concentrations despite tapering of the drug. Side effects occurred in all patients but were manageable with palliative treatment and adjustment of hormone replacement therapy. Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS than aldosterone. Mitotane induced either perturbation of thyroid function mimicking central hypothyroidism or, in male patients, inhibition of testosterone secretion. The discrepancy between salivary and serum cortisol, as well as between total and free testosterone, is due to the mitotane-induced increase in hormone-binding proteins which complicates interpretation of hormone measurements. A low-dose monitored regimen of mitotane is tolerable and able to maintain elevated drug concentrations in the long term. Mitotane exerts a complex effect on the endocrine system that may require multiple hormone replacement therapy.

Immunohistochemical assessment of Ki-67 in the differential diagnosis of adrenocortical tumors

OBJECTIVES To evaluate the utility of Ki-67 immunohistochemical analysis in the differential diagnosis between benign and malignant adrenocortical neoplasms. METHODS Tissue specimens were obtained from 37 patients referred to our institute from 1990 to 1999. The indications for adrenalectomy were adrenal-dependent Cushing syndrome (n = 9), hyperandrogenism (n = 1), mineralocorticoid excess (n = 8), and nonfunctioning adrenal masses (n = 19). The histologic diagnosis was cortical adenoma in 26 of 37 patients and cortical carcinoma in the remainder. Normal adrenal glands were obtained from subjects who underwent radical nephrectomy because of initial renal carcinoma. Immunohistochemical analysis was performed using the monoclonal antibody anti-Ki-67 (clone MIB-1). The Ki-67 labeling index was expressed as the number of positive cells per 1000 cells.Results. The average Ki-67 expression was 2.0 per thousand +/- 1.2 per thousand (SD) in normal adrenal glands, 11.3 per thousand +/- 16.0 per thousand in adenomas, and 185.8 per thousand +/- 60.3 per thousand in carcinomas (P <0.0001). A threshold value of the Ki-67 labeling index between 70 per thousand and 90 per thousand reliably separated adenoma from carcinoma. A significant inverse correlation was found between Ki-67 expression and overall survival in patients with adrenal carcinoma (r = -0.74, P = 0.009). CONCLUSIONS Immunohistochemical assessment of the nuclear antigen Ki-67 can be useful in the differential diagnosis between adrenocortical adenoma and carcinoma. High levels of Ki-67 seem to indicate patients with adrenocortical cancer with a worse prognosis.

Robotic versus laparoscopic adrenalectomy: a systematic review and meta-analysis.

CONTEXT Over the last decade, robot-assisted adrenalectomy has been included in the surgical armamentarium for the management of adrenal masses. OBJECTIVE To critically analyze the available evidence of studies comparing laparoscopic and robotic adrenalectomy. EVIDENCE ACQUISITION A systematic literature review was performed in August 2013 using PubMed, Scopus, and Web of Science electronic search engines. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. EVIDENCE SYNTHESIS Nine studies were selected for the analysis including 600 patients who underwent minimally invasive adrenalectomy (277 robot assisted and 323 laparoscopic). Only one of the studies was a randomized clinical trial (RCT) but of low quality according to the Jadad scale. However, the methodological quality of included nonrandomized studies was relatively high. Body mass index was higher for the laparoscopic group (weighted mean difference [WMD]: -2.37; 95% confidence interval [CI], - 3.01 to -1.74; p<0.00001). A transperitoneal approach was mostly used for both techniques (72.5% of robotic cases and 75.5% of laparoscopic cases; p=0.27). There was no significant difference between the two groups in terms of conversion rate (odds ratio [OR]: 0.82; 95% CI, 0.39-1.75; p=0.61) and operative time (WMD: 5.88; 95% CI, -6.02 to 17.79; p=0.33). There was a significantly longer hospital stay in the conventional laparoscopic group (WMD: -0.43; 95% CI, -0.56 to -0.30; p<0.00001), as well as a higher estimated blood loss (WMD: -18.21; 95% CI, -29.11 to -7.32; p=0.001). There was also no statistically significant difference in terms of postoperative complication rate (OR: 0.04; 95% CI, -0.07 to -0.00; p=0.05) between groups. Most of the postoperative complications were minor (80% for the robotic group and 68% for the conventional laparoscopic group). Limitations of the present analysis are the limited sample size and including only one low-quality RCT. CONCLUSIONS Robot-assisted adrenalectomy can be performed safely and effectively with operative time and conversion rates similar to laparoscopic adrenalectomy. In addition, it can provide potential advantages of a shorter hospital stay, less blood loss, and lower occurrence of postoperative complications. These findings seem to support the use of robotics for the minimally invasive surgical management of adrenal masses.

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy

CONTEXT A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. OBJECTIVE To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). EVIDENCE ACQUISITION A literature review was conducted. EVIDENCE SYNTHESIS Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. CONCLUSIONS Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. PATIENT SUMMARY In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes.