Sorafenib Neoadjuvant Therapy in the Treatment of High Risk Renal Cell Carcinoma

ObjectiveTo evaluate the clinical efficacy of sorafenib as preoperative neoadjuvant therapy in patients with high risk renal cell carcinoma (RCC).ResultsAmong the 18 patients there were 13 male and 5 female, with a median age of 54.6 years. The objective response rate (ORR) of the operation on the selected patients is very high (94.4%), including 4 cases (22.2%) of partial response (PR) and 13 cases (72.2%) of stable disease (SD). After preoperative sorafenib treatment, the average tumor size of the 18 patients decreased from 7.8 cm (ranging from 3.6 to 19.2 cm) to 6.2 cm (ranging from 2.4 to 16.8 cm), and the median value of average tumor CT value decreased from 61HU to 52 HU. Among the 5 patients who had IVC tumor thrombi, the grades of tumor thrombi in 2 patients who were grade II before sorafenib treatment became grade I and grade 0 respectively, 2 patients of grade III both became grade II.ConclusionPreoperative neoadjuvant therapy with sorafenib for high risk RCC patients can significantly decrease primary tumor volume as well as tumor thrombus, which could help the nephron-sparing surgery (NSS) or radical nephrectomy to be done successfully.     

Renal function outcomes after nephrectomy for kidney cancer in elderly patients

The kidneys are organs with multiple functions and essential to maintain life. Ablative procedures, such as nephrectomy, diminish nephron mass and can have a potentially negative impact on renal function. We investigated renal function outcome in patients who underwent nephrectomy for renal cell cancer with special emphasize on elderly patients. Data from 104 patients who underwent nephrectomy for kidney cancer in the Department of Urology, University Hospital Rijeka from January 2005 to December 2010 were retrospectively analyzed. All patients had a normal concentration of serum creatinine and a normal contralateral kidney before surgery. Renal function, as estimated by the glomerular filtration rate (eGFR), was determined before and after nephrectomy using the abbreviated Modification of Diet in Renal Disease equation. We compared the eGFR before and after nephrectomy in the patients of different age. The mean preoperative eGFR was 75.2 mL/min, and the mean postoperative eGFR was 52.7 mL/min (p < 0.0001). In the group of patients > or = 65 years old, the mean preoperative GFR was 69.2 mL/min, and the mean postoperative eGFR was 47.4 mL/min (p < 0.0001). Our data indicate that the eGFR significantly decreased after nephrectomy for kidney cancer. In elderly patients, diminished renal function following nephrectomy was more prominent.     

The Physiologic and Anesthetic Considerations in Elderly Patients Undergoing Robotic Renal Surgery

A number of patients are diagnosed with renal malignancies incidentally worldwide. Once a diagnosis of a renal malignancy is established, after a careful evaluation, patients can be offered a robotic nephrectomy or partial nephrectomy. We present a review of the physiologic and anesthetic considerations in elderly patients who are being considered for robotic renal surgery.Key words: Robotic partial nephrectomy, Robotic radical nephrectomy, Physiologic considerations, Anesthetic considerationsFrom the mid-1970s through the mid-1990s, the incidence of renal cell cancer (RCC) has risen by approximately 3% per annum in the United States¹ and 2.5% per annum in northern England.² The main reason for an increase in the incidence of RCC is the increased detection of early and pre-symptomatic tumors by routine radiologic imaging.² Urologists are now seeing more patients with RCC at early stages (T1) and offering these patients a robotic partial nephrectomy (RPN) or robotic radical nephrectomy (RRN) if the surgical expertise is available.³ A minimally invasive partial nephrectomy for small renal masses has been reported to show excellent functional and oncologic outcomes, with 5- to 10-year cancer-specific survival rates of 95% to 100%.⁴Many of the patients with newly diagnosed RCC are of advanced age and/or have some major comorbidity that often results in their poor performance status. It is envisaged that with an increase in life expectancy, urologists and urologic oncologists will see an increase in new referrals of RCC.⁵With the introduction of robotic renal surgery in the United Kingdom, it is likely that more patients will undergo an RRN/RPN over the next decade. Current literature supports the use of RPN in patients versus laparoscopic partial nephrectomy (LPN) due to a reduction in the warm ischemia time (WIT).⁶ This factor is of crucial importance in patients with a solitary kidney or patients with renal impairment undergoing a partial nephrectomy. The WIT reduces with RPN when compared with LPN.⁷We present a review of the important physiologic and anesthetic considerations in patients being considered for an RPN or RRN.     

Reconstructive surgery versus nephrectomy in renal artery stenosis: comparison of effects on total and divided renal function and on blood pressure.

Twenty-six hypertensive patients with unilateral renal artery disease and normal overall renal function were treated surgically: eleven underwent arterial reconstruction and 15 unilateral nephrectomy. One year after operation there was similar reduction in blood pressure in each group (delta mean BP 45:3 mm Hg (p < 0.001) and 36.8 mm Hg (p < 0.001) respectively. contrary to previous reports, however, a small but significant improvement in overall renal function was observed in patients who underwent reconstructive surgery (delta mean serum creatinine--13.3 mumol/1 (p < 0.01); this was associated with a significant rise in para-aminohippurate (PAH) clearance in the operated kidney, while PAH clearance fell on the contralateral side. Overall renal function deteriorated in the patients who underwent unilateral nephrectomy (delta mean serum creatinine +22.7 mumol/1 (p < 0.01)). The latter was due partly to diminished clearance in the remaining kidney and partly to the loss of the excised kidney. The findings emphasise the superiority of renal artery reconstruction over nephrectomy in patients with renovascular hypertension.     

Blood Levels of Carbonic Anhydrase 9 Correlate with Clear Cell Renal Cell Carcinoma Activity

Introduction  Biomarkers for early detection of renal cell carcinoma (RCC) may help diagnose minimal residual disease in patients at risk for RCC, can guide anti-angiogenic therapy, or may help identify candidates for adjuvant treatment. In this study, we investigated whether blood levels of carbonic anhydrase 9 (CA9) correlate with RCC tumor burden and therefore disease activity. Methods  CA9 is a von Hippel–Lindau–hypoxia inducible factor target upregulated in clear cell RCC. We used an anti-CA9 antibody (M75)-based enzyme-linked immunosorbent assay test to measure CA9 levels in blood obtained before and after nephrectomy for clinically localized disease in patients with: (1) clear cell RCC, (2) papillary and chromophobe RCC or oncocytoma, or (3) benign kidney lesions, and we compared these samples to blood drawn from normal control individuals. Results  We observed a significant (p < 0.006) decrease in the blood levels of CA9, after nephrectomy for localized disease, in the majority of patients with clear cell RCC (57%). In contrast, patients with nonclear cell RCC, benign disease, or those having undergone debulking nephrectomy for metastatic disease did not have a decrease in CA9 blood levels after nephrectomy. Preliminary longitudinal follow up measurements of CA9 levels in a small group of patients indicated that rising CA9 levels may correlate with disease progression. Conclusions  Plasma CA9 levels correlate with disease activity in a subset of clear cell RCC patients and should be considered in future multiplex RCC biomarker development algorithms.     

肾嗜酸细胞腺瘤的诊疗分析（附47 例报告）

目的:分析肾嗜酸细胞腺瘤的临床特征,指导并提升诊疗水平。方法:回顾性分析47例肾嗜酸细胞腺瘤的临床资料,包括临床特点、影像表现、病理特征、治疗方法及预后等方面。结果:47例患者中43例因查体偶然发现,仅4例表现为患侧腰痛症状。术前影像诊断中1例考虑嗜酸细胞腺瘤,1例考虑腺瘤,2例CT与MRI报告不一致(CT与MRI各有1例诊断良性,具体类型不确定),其余43例均诊断为肾细胞癌(1例囊性肾癌)。27例行肾癌根治性切除术,16例行肾部分切除术,4例行微波或射频消融术。所有患者术后病理均诊断为肾嗜酸细胞腺瘤,随访4～179月,均无转移或复发。结论:肾嗜酸细胞腺瘤作为一种与肾细胞癌难相鉴别的良性肿瘤,因缺乏特异性表现,极易误诊为肾细胞癌,因此对肾肿瘤患者应尽可能选择保肾治疗方案。     

Laparoscopic and percutaneous ablative techniques in the treatment of renal cell carcinoma

Widespread use of computed tomography, ultrasound, and magnetic resonance imaging has led to an increase in detection of relatively small renal masses, and approaches to managing them have evolved in the last two decades. Indications for nephron-sparing surgery have expanded, and minimally invasive procedures, which can confer advantages over open surgery, are now available. Ablative techniques offer a combination of nephron-sparing and minimally invasive approaches. Ablative techniques include cryoablation, radiofrequency ablation (RFA), and high-intensity focused ultrasound (HIFU). Cryoablation and RFA have been relatively safe. HIFU has been associated with serious side effects in animal models, and is not yet acceptable for use in humans. Ablative techniques require long-term studies to confirm lasting efficacy. The best modality for tumor targeting, monitoring of therapy, and follow-up is still under investigation. Debate exists regarding the best method for ensuring adequate intraoperative tumor cryoablation. For minimally invasive ablative measures to gain a place as nephron-sparing approaches, they should show both equivalent efficacy and reduced morbidity relative to those of open partial nephrectomy. These techniques should currently be reserved for selected patients and should be compared to the evolving modality of laparoscopic partial nephrectomy.     

Synchronous RCC and TCC of the Kidney in a Patient With Multiple Recurrent Bladder Tumors

Development of concomitant renal TCC and RCC is an uncommon occurrence, yet many interesting issues can be addressed with this model. The possibility of misdiagnosing a renal TCC for an RCC, the options and importance of treating a retained ureteral stump after performing a radical nephrectomy for a renal TCC, and the risk of developing lower tract TCC in patients with upper tract TCC are some of the issues raised in this case review.     

Renal collecting duct carcinoma. Report of a case with cytologic findings on fine needle aspiration

BACKGROUND: Collecting duct carcinoma (CDC) of the kidney is a rare type of renal cell carcinoma (RCC) of collecting duct origin. Cytologic differentiation of CDC from conventional RCC is important because CDC has a poorer prognosis than the latter. CASE: A 60-year-old male incidentally demonstrated a left renal mass that was hypovascular by angiography. Fine needle aspiration (FNA) revealed numerous clusters of cells arranged in a tubular structure. The cells consisted of highly atypical cells having large nuclei with coarse or vesicular chromatin, prominent nucleoli and lacy or granular cytoplasm. Based on these findings, which were indicative of high grade RCC, he underwent left radical nephrectomy and lymphadenectomy. Histologic and immunohistochemical findings, including anti-high-molecular-weight cytokeratin (HMCK) antibody, confirmed the diagnosis of CDC. CONCLUSION: CDC should be added to the differential diagnosis when the result of cytologic examination of a renal mass is suggestive of high grade RCC. These features of FNA smears, together with HMCK immunohistochemistry, can be useful for the cytologic differential diagnosis of renal tumors.     

Ten-year survival analysis for renal carcinoma patients treated with an autologous tumour lysate vaccine in an adjuvant setting

About 30% of renal cell carcinomas (RCC) will develop recurrence after surgery. Despite evidence for a significantly improved survival by autologous tumour cell vaccination therapy, the procedure has not become standard. Between August 1993 and December 1996, 1,267 RCC patients undergoing radical nephrectomy in 84 German hospitals were subsequently treated by autologous tumour cell vaccination therapy. The study group comprised 692 patients with complete follow-up (stages pT2-3, pNx-2, M0 based on the TNM classification, 4th edition). Subsequent propensity-score matching according to 7 defined criteria with 861 control patients undergoing nephrectomy alone without adjuvant treatment at the Carl-Thiem-Hospital Cottbus, resulted in 495 matched pairs. Overall and stage-specific survival rates were analysed after a median follow-up of 131 months. The 5- and 10-year overall survival (OS) rates were 80.6 and 68.9% in the vaccine group and 79.2 and 62.1% in the control group (p = 0.066). Patients with pT3 stage RCC revealed 5- and 10-year OS rates of 71.3 and 53.6% in the study group and 65.4 and 36.2% in the control group (p = 0.022). In multivariable analysis, patients in the vaccine group showed a significantly improved survival both in the whole study group (HR = 1.28, p = 0.030) and in the subgroup presenting with pT3 stage tumours (HR = 1.67, p = 0.011). Adjuvant treatment with autologous vaccination therapy resulted in a significantly improved overall survival in pT3 stage RCC patients, suggesting benefit especially in this subgroup. However, controlled clinical trials integrating the recent TNM classification and further risk constellations are required to define additional patient groups that may derive benefit from this treatment.     

Concurrent Bilateral Renal Angiomyolipoma and Renal Cell Carcinoma in a Patient With Tuberous Sclerosis Complex

Renal angiomyolipomas (AMLs) are often associated with tuberous sclerosis. These tumors are predominantly benign, although malignant forms do exist and are known to be associated with renal cell carcinoma. This case report describes a patient with tuberous sclerosis and massive bilateral AML. Total right nephrectomy was performed; histopathologic examination revealed the coexistence of AML and clear cell renal carcinoma in the same kidney. Because differentiation between renal cell carcinoma and AML with minimal or no fat component can be difficult, an accurate diagnosis is critical in the management of renal AML.Key words: Angiomyolipoma, Renal cell carcinoma, Tuberous sclerosisApproximately 80% of patients with tuberous sclerosis complex (TSC) develop renal angiomyolipoma (AML). Although often benign,^1,2 malignant AML and renal cell carcinoma (RCC) have also been reported in patients with TSC. The concurrence of renal AML and RCC in the same kidney has also been reported in patients with TSC and has been revealed on pathologic examination.Several criteria can be used to help predict malignancy in renal AML, such as tumor size, tumor size and necrosis, and atypical mitotic figures. We report a case of associated massive bilateral AML and RCC. We discuss the diagnosis and treatment of renal AML and emphasize the possibility of concurrent renal malignancies in patients with TSC.     

Interleukin-6 (IL-6) and C-reactive protein (CRP) concentration prior to total nephrectomy are prognostic factors in localized renal cell carcinoma (RCC)

Background

Radical nephrectomy is the gold standard for treatment of renal cell carcinoma (RCC), but even for localized disease the survival rates are still unsatisfactory. Identification of prognostic factorsl is the basis for future treatment strategies for an individual patient.

Aim

The aim of our study was to assess the usefulness of the concentration of IL-6 and CRP as prognostic factors in patients after nephrectomy due to localized RCC.

Materials and methods

Our prospective study included 89 patients (55 men and 34 women) who had been surgically treated for RCC. The examined group included patients with localized advanced disease (from T1 to T3) with no metastases in lymph nodes (N0), and with no distant metastases (M0). All patients had blood samples drawn three times during the study (one day before surgery, six days after surgery and 6 months after surgery) to evaluate the concentration of CRP and IL-6. In each patient RCC of the kidney was removed during radical nephrectomy. Statistical analysis was conducted using statistica v.7.0.

Results

Statistically significant relationships were found between the concentration of CRP before the operation and OS (p = 0.0001). CRP concentration at baseline was statistically significantly correlated with CSS (p = 0.0004). The level of IL-6 assessed before the surgery was significantly correlated with survival times such as OS (p = 0.0096) and CSS (p = 0.0002). The concentration of IL-6 and CRP measured 6 days after surgery and 6 months after surgery were not statistically significantly correlated with survival times.

Conclusions

Results of our study showed that elevated levels of IL-6 and CRP in peripheral blood before surgery of RCC were correlated with worse OS and CSS.     

Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma

ABSTRACT: We report two cases of gastrointestinal perforation (GIP) after radiotherapy in patients receiving tyrosine kinase inhibitor (TKI) for advanced renal cell carcinoma (RCC). Case 1 was a 61-year-old woman with lung metastases after a radical nephrectomy for a right RCC (cT3aN0M0) treated with interferon-alpha (OIF, 5 MIU, three times per week). She developed lytic metastases of the left femur and the left acetabulum. She was treated with palliative radiotherapy to the metastatic portion (3 Gy [MULTIPLICATION SIGN] 10 fractions), and 400 mg sorafenib twice per day plus continuing interferon alpha. She experienced sudden left lower abdominal pain after four weeks of treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. Case 2 was a 48-year-old man with lung, lymph node, and bone metastases after a radical nephrectomy for a right RCC (cT2N0M0), and was treated with 400 mg sorafenib twice per day. He developed lytic bone metastases of the lumbar vertebrae, which was treated with palliative radiotherapy to L2-4 (3 Gy [MULTIPLICATION SIGN] 10 fractions). He experienced sudden abdominal pain after two months of radiation treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. These cases underwent radiotherapy, and therefore this may be related to the radiosensitivity of TKI.     

Laparoscopic nephrectomy.

Since the first clinical operation in June 1990 laparoscopic nephrectomy for benign renal disease has become widely accepted. Although the laparoscopic operation takes much longer than open surgery, there are considerable reductions in the length of postoperative hospital stay and the time taken to return to normal activities and to full recovery. Major complications were relatively common in early operations, but with more experience morbidity has been reduced. Laparoscopic nephrectomy for malignant renal disease is still controversial, largely because of the fear of release of malignant tissue into the abdominal cavity during the morcellation and retrieval of the diseased kidney. To prevent this, the kidney is removed intact through a 5-7 cm incision. Long term follow up is needed, however, before we will know whether the laparoscopic procedure is effective in preventing recurrence of cancer. New developments have improved various technical aspects of the operation, but stringent assessment of new techniques is necessary so that the medical community can decide which procedures should become routine practice.     

肾细胞癌淋巴结转移预测指标的Logistic回归分析

目的：研究肾细胞癌淋巴结转移的危险因素,并建立Logistic回归模型。方法：2002年2月-2010年10月我院手术治疗的肾细胞癌163例,对其临床病理资料进行单因素和多因素的Logistic回归分析。结果：淋巴结转移的发生率为20．9％（34／163）。单因素分析显示：肿瘤大小、临床分期、Fuhrman核分级和贫血与肾细胞癌淋巴结转移的风险有关（P〈0．05）;多因素分析显示：肿瘤大小、临床分期和Fuhrman核分级是RCC淋巴结转移独立的风险因素。结论：肾细胞癌淋巴结转移的风险与肿瘤大小、临床分期和Fuhrman核分级有关,Logistic回归模型对于判断预后、指导术后治疗及随访方案的制订具有重要作用。     

肾嗜酸性细胞瘤的诊治体会（附11例报告）

目的：探讨肾嗜酸细胞瘤的诊断和治疗。方法：回顾分析我院2003．2009年间收治11例肾嗜酸细胞瘤的临床资料,结合文献对肾嗜酸细胞瘤的诊断及治疗进行复习讨论。结果：本组11例患者中,年龄为26—75岁,男性7例,女性4例。合并透明细胞癌者1例,术前误诊为肾上腺肿瘤者1例。7例行根治性肾切除术者,4例行肾部分切除术。术后随访11个月-7年未见肿瘤转移或复发。结论：肾嗜酸细胞瘤倾向于良性肾实质性肿瘤,临床表现无特异性,确诊需临床表现、影像学检查与病理学检查相结合。治疗首选保肾手术,但应注意并发恶性肿瘤的可能,加强随访。     

Risk of End-Stage Renal Disease after Cancer Nephrectomy in Taiwan: A Nationwide Population-Based Study

BackgroundThe conclusions of population-based studies examining the risk of developing end-stage renal disease (ESRD) after nephrectomy among patients with renal cell carcinoma (RCC) remain inconclusive. In this study, we sought to examine whether patients with RCC undergoing radical nephrectomy (RN) have higher risk of ESRD compared to those undergoing partial nephrectomy (PN).MethodsNationwide population-based retrospective cohort of 7670 patients with RCC who underwent RN or PN between 2000 and 2011 as recorded in the Taiwan National Health Insurance in-patient claims data were analyzed. The primary outcome of interest was the occurrence of ESRD requiring regular renal hemodialysis. Multivariable Cox proportional hazard regression model was performed to assess the risk.FindingsThe median follow-up for the post-propensity matched cohort (1212 PN and 2424 RN) was 48 months. Seventy patients (2.9%) developed ESRD among those who underwent RN, for an incidence rate of 6.9 cases per 1000 person-years. In contrast, only 23 patients (1.9%) developed ESRD among patients who underwent PN, for an incidence rate of 5.5 cases per 1000 person-years. Despite the higher incidence rate of ESRD among RN, the aIRR (RN/PN) was 1.26 (95% CI 0.78-2.01), which was not statistically significant.ConclusionsThis Taiwan nationwide population-based study suggests that patients with RCC undergoing RN do not have significantly higher risk of developing ESRD compared to those undergoing PN.     

肾脏巨大血管平滑肌脂肪瘤合并结节性硬化1 例报告并文献复习

目的:总结肾脏巨大血管平滑肌脂肪瘤合并结节性硬化的临床及组织病理特点,探讨其诊疗方法及预后情况.方法:回顾性分析1例罕见的肾脏巨大血管平滑肌脂肪瘤合并结节性硬化的临床特征、组织病理学特点以及诊断、治疗方法,同时复习近年来的国内外相关文献.结果:患者于我院行剖腹探查,右肾巨大肿瘤切除术,术后病理示血管平滑肌脂肪瘤.手术后患者恢复良好,症状明显改善,肝肾功能正常.术后3个月复查CT:左肾区与术前比无变化,右肾区未见肿瘤复发.结论:对于巨大肾脏血管平滑肌脂肪瘤合并结节性硬化的患者,手术治疗仍可作为可选择的治疗方法,但其远期预后仍待观察.     

Laparoscopic radical nephrectomy: morcellate or leave intact? Definitely morcellate!

Eleven years after the first laparoscopic radical nephrectomy (LRN), which was performed with morcellation, the best approach to the procedure remains controversial. Concerns include tumor seeding, recurrence, accuracy of staging, histopathological diagnosis, and longer surgery time. Enclosing the kidney in an impermeable sac prior to morcellation helps prevent seeding. Pathological review of morcellated LRN specimens has been shown to be as accurate as that of intact specimens. Ten-year survival data for LRN with morcellation are not available yet, but 5-year rates are as good as those for open nephrectomy. The utility of morcellation in LRN is supported by the results of clinical practice.     

Nephron-sparing Management of Upper Tract Urothelial Carcinoma

Upper tract urothelial carcinoma (UTUC) is a relatively rare tumor, but is characterized by high rates of recurrence, morbidity, and mortality. Choice of treatment modality is generally influenced by lesion size, grade, and focality. Radical nephroureterectomy with bladder cuff excision is the gold-standard management of UTUC, although an organ-sparing approach may be beneficial in selected patients. Conservative endoscopic management of UTUC in appropriate patients has a favorable impact on quality of life and health care costs when compared with patients who progress to dialysis-dependent renal failure. Careful ureteroscopic surveillance following endoscopic management of UTUC is essential.Key words: Upper tract urothelial carcinoma, Tumor grade, Nephron-sparing endoscopic treatment, Topical adjuvant chemo-immunotherapy, Oncologic outcomesUpper tract urothelial carcinoma (UTUC) accounts for < 5% of all cases of urothelial neoplasia, but is a very morbid disease, with recurrence rates up to 90%^1–9 and 5-year survival rates ranging from 30% to 60%.¹⁰ Radical nephroureterectomy (NU) with bladder-cuff excision has been the traditional treatment for UTUC because of its high rate of recurrence. However, given the morbidity of nephrectomy and the risk of developing chronic kidney disease (CKD) or dialysis-dependent renal failure, as well as the risk of contralateral tumors,^11–14 a nephron-sparing approach may be preferable in selected patients.