Contemporary strategies for treating nonhereditary synchronous bilateral renal tumors and the impact of minimally invasive, nephron-sparing techniques

OBJECTIVES: As surgical technology and expertise advance, treatment strategies for patients with bilateral renal tumors will continue to shift toward methods that maximize preservation of renal function and maintain optimal oncologic outcomes while minimizing morbidity. Reports about such strategies are limited. We report the outcome of a contemporary cohort of patients treated for nonhereditary synchronous bilateral renal tumors at our institution to evaluate surgical strategies and newer techniques used during patient treatment. METHODS: From a surgical database, we identified 43 patients who met the criteria for nonhereditary, synchronous, bilateral renal tumors. Demographic characteristics, tumor pathology, renal function, surgical data, and outcomes were extracted from each patient's medical record. Computerized literature searches were performed to identify related articles for comparative purposes. RESULTS: Of the 43 patients, 36 (82%) were treated with staged procedures a median of 54 days apart. A total of 23 patients (53.3%) received bilateral nephron-sparing therapy, of whom 11 underwent a minimally invasive nephron-sparing approach. There was a median 28.0 ml/min decrease in creatinine clearance between initial preoperative levels and at last follow-up, with a median follow-up duration of 16 months, and no patient required dialysis. Of the 43 patients, 2 (4.7%) had local recurrences, and 1 (2.3%) had metastatic disease. CONCLUSION: These findings show a contemporary standard of care for treating patients with bilateral renal tumors, with more than half the patients undergoing bilateral nephron-sparing and nearly one third of patients receiving a minimally invasive nephron-sparing approach.     

Laparoscopic partial nephrectomy and minimally invasive nephronsparing surgery

Surgical extirpation remains the most effective therapy for renal cell carcinoma. The surgical management of renal masses has evolved away from radical nephrectomy and now includes nephron-sparing surgery for small tumors. Nephron-sparing surgery has similar cure rates and does not appear to compromise cancer control. As the detection of small renal masses by widespread abdominal imaging continues to increase, so will the demand for minimally invasive nephron-sparing procedures. Despite progress in surgical techniques, laparoscopic partial nephrectomy remains a technically challenging procedure. In this review, we discuss the challenges and recent advances in laparoscopic partial nephrectomy and other minimally invasive approaches to renal masses.     

Laparoscopic partial nephrectomy versus laparoscopic cryoablation for multiple ipsilateral renal tumors

BACKGROUND: Management of multiple ipsilateral renal tumors is a dilemma in clinical practice. The effects of minimally invasive nephron-sparing procedures in this group of patients have not been assessed. OBJECTIVE: To evaluate the technical feasibility and outcomes of laparoscopic partial nephrectomy (LPN) and laparoscopic cryoablation (LCA) for multiple ipsilateral renal tumors. DESIGN, SETTING, AND PARTICIPANTS: Between September 1999 and December 2006, 27 patients were treated with minimally invasive nephron sparing surgery (LPN or LCA) for synchronous multiple ipsilateral renal tumors in a single operating session at our institution. Fourteen patients with 28 tumors underwent LPN, and 13 patients with 31 tumors underwent LCA as the sole treatment modality. INTERVENTION: Medical records were retrospectively reviewed and data were collected. MEASUREMENTS: Demographic, intraoperative, postoperative, and intermediate-term follow-up data were compared between the two groups. RESULTS AND LIMITATIONS: Patients in the LPN group had fewer tumors (2 vs. 2.4, p=0.04) and larger dominant tumor size (3.6 vs. 2.5 cm, p=0.005) in the affected kidney and lower preoperative serum creatinine levels (1 vs. 1.4 mg/dl, p=0.02). Compared to the LCA group, patients in the LPN group had greater estimated blood loss (200 vs. 125 ml, p=0.02) and longer hospital stays (90 vs. 52.3h, p=0.02). There were no open conversions, and no kidneys were lost. Complication rate, renal functional outcomes, and intermediate-term cancer-specific survival rates were similar between the two groups. CONCLUSIONS: Both LPN and LCA are viable options for patients with multiple ipsilateral renal tumors in select patients. Renal functional outcomes, complication rates, and intermediate-term survival rates are comparable between the two groups in this small series.     

Robot-assisted retroperitoneal partial nephrectomy: technique and perioperative results

Abstract Growing evidence supports the use of nephron-sparing techniques for the management of appropriately selected renal masses up to 7?cm. Compared with the surgical standard of open partial nephrectomy, minimally invasive approaches have demonstrated equivalent cancer control with reduced patient morbidity. Robot assistance has the potential to provide patients and physicians greater access to minimally invasive nephron-sparing surgery. We describe a robot-assisted retroperitoneal approach for the management of posterior renal masses. Our early results suggest reduced perioperative morbidity with the ability to manage more complex tumors.     

Percutaneous ultrasound-guided radiofrequency ablation of recurrent renal cell carcinoma in renal allograft after partial nephrectomy

Percutaneous thermal ablation is increasingly being studied in the treatment of renal tumors. Because radiofrequency ablation is a minimally invasive and nephron-sparing procedure, it is ideally suited for patients with a single kidney, multiple tumors, or contraindications to conventional surgery. We report on a patient with recurrent renal cell carcinoma in a transplanted kidney that was successfully treated with percutaneous ultrasound-guided radiofrequency ablation.     

Outlining the limits of partial nephrectomy

Amongst nephron-sparing modalities, partial nephrectomy (PN) is the standard of care in the treatment of renal cell carcinoma (RCC). Despite the increasing utilization of PN, particularly propagated by robot-assisted, minimally invasive approaches for small renal masses (SRMs), the limits of PN appear to be also evolving. In this review, we sought to address the tumour stage beyond which PN may be oncologically perilous. While the evidence supports PN in the treatment of tumours < pT2a, PN may have a role in advanced or metastatic RCC. Other scenarios wherein PN has limited utility are also explored, including anatomical or surgical factors that dictate the difficulty of the case, such as prior renal surgery. Lastly, we discuss the emerging role of molecular biomarkers, specifically epigenetics, to aid in the risk stratification of SRMs and to select tumours optimally suited for PN.     

肾细胞癌多中心病灶的研究

目的：探讨肾细胞癌多中心病灶的发病率及相关因素。方法：102例肾癌根治术标本，间隔3mm分层切开检查切面；假包膜外20mm范围及肾门组织连续切片检查包膜完整性及镜下多中心灶。统计分析，计数资料比较采用χ^2检验，相关检验采用多元Logistic回归分析。结果：多中心灶发生率为15．7％，原发灶直径≤4cm组为4．9％，＞4cm组为23．0％，差别有显著性意义（P＝0．014）。血管浸润和包膜完整性为多中心灶的显著相关因素（P＝0．017，0．006）。结论：对侧肾正常时保肾手术应限于直径＜4cm的肾癌，绝对指征的病例可放宽至7cm。血管浸润及假包膜不完整者，多中心灶发生率增高，术后须密切随访。     

Where are the limits of elective nephron- sparing surgery in renal cell carcinoma?

OBJECTIVES: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is still controversial. The presented study was performed to determine limitations for NSS regarding to multifocality and to characterize the biological importance of these small tumor lesions. METHODS: In 372 patients who underwent radical nephrectomy for RCC consecutively, nephrectomy specimens were investigated by using 3-mm parenchyma sections regarding to local tumor spread and multifocality. To characterize multifocal tumors, we performed cytogenetic and molecular genetic investigations. RESULTS: Serial sections of 372 nephrectomy specimens revealed a total of 92 multifocal tumors in 61 specimens (16.4%). The correlation between tumor size and multifocality is shown as follows: tumor diameter 1-20 mm: 12.5%; 21-30 mm: 23.4%; 31-40 mm: 10.2%; >40 mm: 16.7%. The mean diameter of the multifocal tumors was 8.8x9.1x6.1 mm and the mean distance to the primary tumor was 26.4 mm (5-84 mm). Using cytogenetic and molecular genetic analysis, in nearly one third of all cases a concordance of chromosomal aberrations in primary and secondary tumors was found. CONCLUSIONS:Multifocality of renal cell carcinoma occurs independently from primary tumor size. The evidence of structural and/or numeric aberrations, found in additional tumor foci, obviously is an argument for their malignant potential. This findings have to be considered in preparation of nephron-sparing surgery for patients with renal cell carcinoma.     

Leiomyomas of the kidney: emphasis on conservative diagnosis and treatment

Leiomyomas are benign mesenchymal tumors that rarely occur in the kidney. We present the reports of three renal leiomyomas diagnosed and treated at our institution during the past 10 years. On the basis of our experience, preoperative diagnosis may be possible through image-guided percutaneous biopsy, and conservative treatment with either expectant management or minimally invasive nephron-sparing surgery should always be considered.     

Robotic nephrectomy for central renal tumors with intraoperative evaluation of tumor histology

Patients undergoing nephrectomy for central renal tumors suspicious for renal cell carcinoma (RCC) may carry a small risk of having transitional cell carcinoma (TCC) on final pathology, even in the absence of filling defects or abnormal cytology. We describe outcomes in such patients undergoing robotic nephrectomy for suspected RCC, with intraoperative specimen assessment to guide completion ureterectomy if TCC is present. Between September 2010 and August 2015, ten patients had central renal masses suspicious for RCC, which were not amenable to nephron-sparing surgery. Patients underwent a four-arm robotic nephrectomy technique using a GelPOINT^® access port. Following hilar ligation, the ureter was divided between adjacent hem-o-lok clips, placed in an endocatch bag, and extracted through the GelPOINT incision for the frozen section analysis. If intraoperative assessment confirmed TCC, a robotic completion ureterectomy and a bladder cuff excision were performed. Of the ten patients with central tumors who underwent robotic nephrectomy for suspected RCC, four (40 %) had TCC on the frozen section analysis and underwent completion ureterectomy. Five patients had RCC, and one patient had an oncocytoma. Mean age was 63.1 years (49–76) and mean tumor size was 4.0 cm (1.9–7.6). Mean operating time was 246 min (135–328). All patients had negative margins. Mean length of stay was 2.5 days. No recurrences were documented at median 8.5 months follow-up. For patients undergoing robotic nephrectomy for central renal tumors, intraoperative specimen evaluation can help determine the need for minimally invasive completion ureterectomy.     

Open partial nephrectomy: current review

Partial nephrectomy (PN) is increasingly considered the gold standard treatment for localized renal cell carcinomas (RCCs) where technically feasible. The advantage of nephron-sparing surgery lies in preservation of parenchyma and hence renal function. However, this advantage is counterbalanced with increased surgical risk. In recent years with the popularization of minimally invasive partial nephrectomy (laparoscopic and robotic), the contemporary role of open PN (OPN) has changed. OPN has several advantages, particularly in complex patients such as those with a solitary kidney, multi-focal tumors, and significant surgical history, as well as providing improved application of renoprotective measures. As such, it is a technique that remains relevant in current urology practice. In this article we discuss the evidence, indications, operative considerations and surgical technique, along with the role of OPN in contemporary nephron-sparing surgery.     

Watchful waiting for small renal masses

Small renal masses (SRMs; < 4 cm in diameter) account for most renal tumors treated today. Incidental early detection of SRMs by abdominal imaging results in favorable grade and stage migration to renal cell carcinoma, and also increases detection of benign renal tumors. As a result, most SRMs manifest indolent biological behavior with excellent prognosis. Despite the increased use of minimally invasive laparoscopic surgery, nephron-sparing techniques, and percutaneous ablation therapy, selected patients are managed by initial active surveillance, reserving therapy for progression. Older patients and those with competing risks due to medical comorbidities are excellent candidates for active surveillance; their risk of early progression due to growth or metastases appears to be low. Active surveillance should not be recommended for younger, healthier patients until prognostic factors are better defined. Needle core use for improved histopathologic characterization of SRMs should be considered before recommending treatment.     

Ablative techniques for the management of kidney cancer

For lesions smaller than 4 cm, nephron-sparing surgery has been shown to be oncologically equivalent to radical nephrectomy, albeit with the advantage of preservation of overall renal function. As such, partial nephrectomy became the first-line treatment option for localized, small renal masses. Minimally invasive options associated with limited morbidity--such as probe-ablative procedures--are, however, being investigated in selected patients for whom invasive, nephron-sparing surgery (whether laparoscopic or open) is undesirable. The main probe-ablative techniques being investigated as alternatives to partial nephrectomy are cryoablation, radiofrequency ablation, and high-intensity focused ultrasound. Advances in imaging, ablative system technologies, and early evidence that in situ tumor ablation can yield comparable results to those achieved with tumor resection in selected cases, have sparked significant interest in these minimally invasive techniques.     

How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery?

Background: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is under discussion in the urological literature. The main problem of NSS is the multifocality of RCC. The presented study was preformed to assess the accuracy of pre-and intraoperative ultrasound (US), and computerized tomography (CT) in determination of tumor size and detection of multifocal lesions.Materials and methods: Tumor size was measured by preoperative US and CT and compared with the tumor diameters in gross sections of the neoplastic kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy specimen, and the results were correlated with preoperative US and CT on the one hand, and the ex situ sonography of the nephrectomized kidney on the other hand.Results: US and CT show similar results in the determination of the tumor size. In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this regard.Conclusions: In preparation for nephron-sparing surgery of renal cell carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound can safely predict multifocal lesions of renal cell carcinoma.CommentaryLocal tumor recurrence following nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) may be due to incomplete resection of the primary tumor, occult multicentric disease or the development of a new primary or metastatic focus of RCC in the renal remnant. The risk of multicentric disease in RCC has been evaluated and debated extensively in the literature. RCC generally occurs as a discrete focal lesion rather than an infiltrative process which is seen in carcinoma of the prostate. At issue is whether the molecular events that give rise to malignant transformation affect a discrete segment of the kidney or a broader segment of the renal tubular epithelium. A high incidence of multicentric RCC has been reported in patients with germ line mutations such as those that exist in von Hippel Lindau disease and other forms of hereditary RCC suggesting a global predisposition to malignant degeneration throughout the entire renal parenchyma.The incidence of multicentricity in sporadic RCC has been less clear. Emerging cytogenetic and molecular data suggest that satellite lesions may occasionally arise from the same malignant clone as their corresponding primary lesion and may therefore represent biologically significant intra-renal metastasises. A recent review of published studies comprising over 1100 cases of sporadic RCC indicated an aggregate incidence of 15.2% of tumor multifocality (range 6.5%–28%)[1]. It is important to remember that these studies represent a diverse group of patients and that RCC is in fact a heterogenous group of tumors. The risk of multicentricity is not equal in all patients and appears to be related to other prognostic variables such as tumor histology, stage and grade. For example, papillary RCC is known to be associated with a higher incidence of multifocality than the more common clear cell variant. The risk of multifocal disease also increases with larger tumors, particularly those that extend beyond the renal capsule (pT3+). Finally, some microfocal tumors are of unknown biological significance such as the finding of satellite adenomas. Of importance when considering relative indications for elective NSS is the incidence of multifocality when the primary or index tumor is ⩽ 4 cm. A recent review of the literature indicated that the incidence of multifocality in this setting is approximately 5%.The most worrisome implication of multifocal RCC is that this will predispose to an increased risk of local tumor recurrence following NSS. Although this potential risk must be considered, the relationship between multifocality and local recurrence is neither linear or predictable as suggested by the low overall local recurrence rates reported following NSS in several large series. In nearly 1800 cases of NSS reported in the literature to date, the risk of local tumor recurrence has ranged from 0–10% and is clearly lowest among patients undergoing elective NSS for small (⩽ 4 cm) low stage lesions [1]. The true biologic significance of multicentric renal tumors and their implication for NSS therefore remain to be fully elucidated.[1] Uzzo RG, Novick AC. Nephron-sparing surgery for renal tumors: indications, techniques and outcomes. J Urol 2001;166:6–18.Andrew C. Novick, M.D.     

Perioperative Complications of Robot-Assisted Partial Nephrectomy

The incidence of renal cell carcinoma continues to increase with utilization of diagnostic abdominal imaging with migration towards a proportionally greater detection of small renal masses (SRM). Robot-assisted partial nephrectomy (RAPN) has become an attractive minimally invasive treatment modality for SRM’s due to the technical advantages and shortened learning curve compared to laparoscopic partial nephrectomy (LPN) while preserving comparable perioperative outcomes. With advances in ablative approaches for stage I renal cell carcinoma (RCC) and controversy surrounding the role of extirpative surgery for SRM’s, systematic understanding of the complications associated with RAPN has become even more imperative. This review aims to summarize and evaluate the contemporary literature, compile reported intraoperative complications, describe conventional and nephron-sparing surgery (NSS) specific postoperative complications, and assess factors associated with an increased likelihood for perioperative complications following RAPN.     

How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery?

BACKGROUND: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is under discussion in the urological literature. The main problem of NSS is the multifocality of RCC. The presented study was performed to asses the accuracy of pre- and intraoperative ultrasound (US), and computerized tomography (CT) in determination of tumor size and detection of multifocal lesions. MATERIALS AND METHODS: Tumor size was measured by preoperative US and CT and compared with the tumor diameters in gross sections of the neoplastic kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy specimen, and the results were correlated with preoperative US and CT on the one hand, and the ex situ sonography of the nephrectomized kidney on the other hand. RESULTS: US and CT show similar results in the determination of the tumor size. In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this regard. CONCLUSIONS: In preparation for nephron-sparing surgery of renal cell carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound can safely predict multifocal lesions of renal cell carcinoma.     

The impact of renal surgery on global renal function and non-oncologic morbidity

Nephron preservation has been increasingly prioritized in the treatment of small renal tumors. Radical nephrectomy is now understood as a risk factor for development of chronic kidney disease, which is known to increase the risk of cardiovascular events and all-cause mortality. Indications for nephron-sparing surgery (NSS) have broadened from solitary kidney, bilateral tumors, and hereditary tumor syndromes to essentially all small renal tumors. Laparoscopic NSS has demonstrated excellent cancer control as well as good functional preservation despite the need for warm ischemia. There has been ongoing debate regarding safe parameters for warm ischemia, which are thought to vary with patient factors. Focal ablative therapies have been developed for use in high-risk surgical candidates (eg, radiofrequency ablation, cryoablation) to minimize renal and other treatment-related morbidity. Emphasis on minimally invasive approaches and advances in preventing renal dysfunction and other morbidity after NSS will guide the future of these therapies.     

Minimally invasive nephron-sparing surgery (MINSS) for renal tumours part I: laparoscopic partial nephrectomy

OBJECTIVES: To review the evolution and current status of extirpative methods (laparoscopic partial nephrectomy [LPN]) of minimally invasive nephron-sparing surgery (MINSS) for renal tumors. METHODS: The English language literature of the past 10 yr was reviewed by using the National Library of Medicine database and the following keywords: kidney, laparoscopic partial nephrectomy, minimally invasive, nephron-sparing surgery, renal, and tumor. Over 275 papers were identified. Of these, 55 papers were selected for this review on the basis of their contribution in advancing the field with regards to (1) evolution of concepts, (2) development and refinement of techniques, and (3) intermediate- and long-term clinical outcomes of LPN. RESULTS: Open partial nephrectomy (OPN) is the reference standard for nephron-sparing surgery against which all MINSS techniques should be measured. With available skills for time-sensitive intracorporeal suturing, LPN provides perioperative results and long-term oncologic and functional outcomes comparable to the reference standard, with significantly decreased patient morbidity. The initial 5-yr data of 50 patients has just become available, and shows overall and cancer-specific survival of 84% and 100%, respectively. As global experience with this technique increases, data need to be prospectively accrued, and long-term cancer cure rates should be compared with the reference standard. CONCLUSIONS: As of this writing, the technique and global acceptance of LPN is evolving, although it remains restricted by the complexity of laparoscopic renal reconstruction. In expert hands, cancer cure and renal function outcomes are similar to OPN.     

Nephron-sparing surgery for renal cell carcinoma--is tumor size a suitable parameter for indication?

Objectives. Because patients with small renal cell carcinomas (RCC) are being treated by nephron-sparing surgery with increased frequency, a generally accepted parameter giving additional information as to which kind of tumor is suitable for this treatment is urgently required. Methods. In a retrospective analysis of 245 patients who underwent radical nephrectomy for RCC, we investigated whether tumor size could provide the necessary information. We analyzed the association of tumor size with pTNM classification, grade, and the findings of the flow cytometric analysis of the DNA content analyzing the DNA index (DI). Results. Stage pT1 was found in 23 patients (9.4%), pT2 in 100 (40.8%), pT3 in 109 (44.5%), and pT4 in 13 patients (5.3%). Grade 1 was found in 87 patients (35.5%), grade 2 in 120 (49.0%), and grade 3 in 38 patients (15.5%). A low DI was found in 71%, a moderately increased DI in 20%, and a high DI in 9%. Lymph node metastases were detected in 14% and distant metastases in 22%. Closer examination of the tumors less than 2.5 cm (n = 23) revealed a significantly lower incidence (P <0.001) of infiltration of the renal capsule (n = 0) than in the rest of the group. Positive lymph nodes or distant metastases could not be found in this subgroup. A multifocal appearance of RCC was detected in only 2 (8.7%) of the 23 patients; it was detected in 67 (30.2%) of the 222 patients in the rest of the group. None of the 23 patients had grade 3 tumors (P <0.05). Fifty-two percent of the tumors were grade 1 and 48% grade 2. None of the 23 had a high DI; a moderately increased DI was found in 1 patient and a low DI in 22 of the 23 patients. Detailed examination of the tumors between 2.5 and 4 cm (n = 29) revealed an infiltration of the renal capsule in 11 (38%); lymph node metastases were found in 2 (6.9%) and metastases in 4 (13.8%). A multifocal appearance was found in 4 (13.9%) of the 29 patients; grade 3 tumors were detected in 3 (10.3%) of 29 patients, grade 2 tumors in 12 (41.4%), and grade 1 tumors in 14 (48.3%). In this subgroup, a high DI was found in 14% (not significant). The examination of tumors larger than 4 cm in size revealed worse results in the pTNM classification, grade, and flow cytometric results. Conclusions. Only tumors smaller than 2.5 cm should be considered suitable for nephron-sparing surgery in patients eligible for elective surgery. In patients in whom nephron-sparing surgery is imperative, even tumors between 2.5 and 4 cm appear to be suitable. In patients requiring extensive resection, however, the risk of local recurrence seems to be higher because of the higher incidence of multifocality.