Association of an organ transplant-based approach with a dramatic reduction in postoperative complications following radical nephrectomy and tumor thrombectomy in renal cell carcinoma.

OBJECTIVES: Our aim was to determine whether using an organ transplant-based(TB) approach reduces postoperative complications(PCs) following radical nephrectomy(RN) and tumor thrombectomy(TT) in renal cell carcinoma(RCC) patients with level II-IV thrombi. METHODS: A total of 390(292 non-TB/98 TB) IRCC-VT Consortium patients who received no preoperative embolization/IVC filter were included. Stepwise linear/logistic regression analyses were performed to determine significant multivariable predictors of intraoperative estimated blood loss(IEBL), number blood transfusions received, and overall/major PC development within 30days following surgery. Propensity to receive the TB approach was controlled. RESULTS: The TB approach was clearly superior in limiting IEBL, blood transfusions, and PC development, even after controlling for other significant prognosticators/propensity score(P < .000001 in each case). Median IEBL for non-TB/TB approaches was 1000 cc/300 cc and 1500 cc/500 cc for tumor thrombus Level II-III patients, respectively, with no notable differences for Level IV patients(2000 cc each). In comparing PC outcomes between non-TB/TB patients with a non-Right-Atrium Cranial Limit, the observed percentage developing a: i) PC was 65.8%(133/202) vs. 4.3%(3/69) for ECOG Performance Status(ECOG-PS) 0-1, and 84.8%(28/33) vs. 25.0%(4/16) for ECOG-PS 2-4, and ii) major PC was 16.8%(34/202) vs. 1.4%(1/69) for ECOG-PS 0-1, and 27.3%(9/33) vs. 12.5%(2/16) for ECOG-PS 2-4. Major study limitation was the fact that all TB patients were treated by a single, experienced, high volume surgeon from one center (non-TB patients were treated by various surgeons at 13 other centers). CONCLUSIONS: Despite this major study limitation, the observed dramatic differences in PC outcomes suggest that the TB approach offers a major breakthrough in limiting operative morbidity in RCC patients receiving RN and TT.

Is imperative partial nephrectomy feasible for kidney cancer with venous thrombus involvement? Outcomes of 42 cases and matched pair analysis with a large radical nephrectomy cohort.

BACKGROUND: Radical nephrectomy (RN) with/without (±) thrombus excision (ThE) is the undisputed standard treatment for kidney cancer (KC) with renal or caval thrombus (Th). However, partial nephrectomy (PN) ± ThE may be considered in rare cases due to imperative (I) indications. OBJECTIVE: To evaluate the efficacy of IPN ± ThE and to compare it with RN ± ThE for KC with Th. DESIGN, SETTING, AND PARTICIPANTS: Records of 2,549 patients undergoing surgery for KC with Th at 24 institutions between 1971 and 2014 were retrospectively reviewed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were overall survival (OS) and cancer specific survival (CSS), renal function variation after surgery and complications. Secondary outcomes were predictors of OS and CSS for IPN cases. To reduce bias IPN group was matched with RN using a propensity score with greedy algorithm on the basis of age, gender, tumor size, TNM, and histology. RESULTS AND LIMITATIONS: Forty-two patients underwent IPN ± Th. All thrombi were ≥level I; 5 patients experienced Clavien ≥ 3 complications with 2 complications-related deaths. At 27.3 (interquartile range: 7.1-47.7) months OS and CSS were 54.8% and 78.6%, respectively whereas at 9.7 (interquartile range: 1.4-43.7) months eGFR change was -17.3 ± 27.0ml/min. On univariate analysis tumour size, preoperative eGFR, transfusions, hospital stay, high serum creatinine, operating time, complications, lymphadenectomy, and metastases related to an increased risk of death. After matching (n = 38 per arm) no significant differences were present except for tumor necrosis (IPN = 39.5%; 15.8%; P = 0.01), thrombus level (P = 0.02), so as for operating time (P = 0.27), perioperative transfusions (P = 0.74) and complications (P = 0.35). A 5-year OS and CSS for IPN were 57.9% and 73.7%, respectively with no significant differences with RN (OS = 63.2, P = 0.611; CSS = 68.4, P>0.99). After 14.9 months creatinine and eGFR changes were (+0.4 ± 0.6mg/dl and -23.2 ± 37.3ml/min; P = 0.2879). CONCLUSIONS: In selected cases due to imperative indications PN ± ThE is a complex procedure and may be an alternative to RN ± ThE for KC with Th yielding noninferior oncological outcomes, functional outcomes, and complications. Further studies are needed to determine the role of PN ± ThE for KC with Th.

Impact of lymph node dissection at the time of radical nephrectomy with tumor thrombectomy on oncological outcomes: Results from the International Renal Cell Carcinoma-Venous Thrombus Consortium (IRCC-VTC).

OBJECTIVES: To study the effect of lymph node dissection (LND) at the time of nephrectomy and tumor thrombectomy on oncological outcomes in patients with renal cell carcinoma (RCC) and tumor thrombus. PATIENTS AND METHODS: The records of 1,978 patients with RCC and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1985 to 2014 at 24 centers were analyzed. None of the patients had distant metastases. Extent and pathologic results of LND were compared with respect to cancer-specific survival (CSS). Multivariable Cox regression models were used to quantify the effect of multiple covariates. RESULTS: LND was performed in 1,026 patients. In multivariable analysis, the presence of LN metastasis, the number of positive LNs, and LN density were independently associated with cancer-specific mortality (CSM). Clinical node-negative (cN-) disease was documented in 573 patients, 447 of them underwent LND with 43 cN- patients (9.6%) revealing positive LNs at pathology. LN positive cN- patients showed significantly better CSS when compared to LN positive cN+ patients. In multivariable analysis, positive cN status in LN positive patients was a significant predictor of CSM (HR, 2.923; P = 0.015). CONCLUSIONS: The number of positive nodes harvested during LND and LN density was strong prognostic indicators of CSS, while number of removed LNs did not have a significant effect on CSS. The rate of pN1 patients among clinically node-negative patients was relatively high, and LND in these patients suggested a survival benefit. However, only a randomized trial can determine the absolute benefit of LND in this setting.

Profiling microRNA from nephrectomy and biopsy specimens: predictors of progression and survival in clear cell renal cell carcinoma.

OBJECTIVE: To identify microRNA (miRNA) characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer-specific survival (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue. MATERIALS AND METHODS: RNA was isolated from nephrectomy and kidney biopsy specimens (n = 156 and n = 46, respectively). Samples were grouped: benign, non-progressive, and progressive ccRCC. MiRNAs were profiled by microarray and validated by quantitative reverse transcription-polymerase chain reaction. Biomarker signatures were developed to predict cancer status in nephrectomy and biopsy specimens. CSS was examined using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Microarray analysis revealed 20 differentially expressed miRNAs comparing non-progressive with progressive tumours. A biomarker signature validated in nephrectomy specimens had a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and ccRCC specimens. A second signature differentiated non-progressive vs progressive ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b-5p, and -223-3p were associated with CSS. CONCLUSION: This study identified miRNAs differentially expressed in ccRCC samples; as well as those correlating with CSS. Biomarkers identified in this study have the potential to identify patients who are likely to have progressive ccRCC, and although preliminary, these results may aid in differentiating aggressive and indolent ccRCC based on biopsy specimens.

MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype.

The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3-T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease.

Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival.

BACKGROUND: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. METHODS: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. RESULTS: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. CONCLUSIONS: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc.

Endovascular Removal of Intracardiac Thrombus Prior to Radical Nephrectomy and Inferior Vena Cava Thrombectomy.

We report a case of a 54-year-old patient with a T3c renal mass with intracardiac extension of the thrombus to the level of the pulmonary valve. The patient was not a candidate for cardiopulmonary bypass due to recent pulmonary embolism. Under transesophageal echocardiogram guidance, the intracardiac thrombus was removed percutaneously via transvenous mechanical thrombectomy. The patient was effectively downstaged to T3b and underwent successful radical nephrectomy and inferior vena cava thrombectomy without the use of cardiopulmonary bypass.

Cardiopulmonary Bypass has No Significant Impact on Survival in Patients Undergoing Nephrectomy and Level III-IV Inferior Vena Cava Thrombectomy: Multi-Institutional Analysis.

PURPOSE: The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. MATERIALS AND METHODS: We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. RESULTS: Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. CONCLUSIONS: In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass.

Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy.

PURPOSE: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.

A non-invasive miRNA based assay to detect bladder cancer in cell-free urine.

RNA from cell-free urine was analyzed in an attempt to identify a microRNA (miRNA) profile that could be used as a non-invasive diagnostic assay to detect the presence of urothelial carcinoma of the bladder (UCB) and provide a discriminatory signature for different stages of progression. In addition, the presence of specific miRNAs co-isolating with urinary extracellular vesicles/exosomes was investigated. RNA was isolated from cell-free urine of patients diagnosed with UCB (TaG1, T1G3, ≥T2, CIS) and control patients (healthy control and UCB patients with no evidence of disease). MiRNAs were profiled by qRT-PCR array on pooled samples within each group. Validation of the miRNAs was performed on individual samples using qRT-PCR. Extracellular vesicles were isolated via ultracentrifugation. 236 miRNAs were detected in at least one of the pooled samples. Seven of the miRNAs validated on individual samples had significantly higher levels in the cancer group. A panel of miRNAs discriminated between cancer and cancer-free patients with a sensitivity of 88% and specificity of 78%, (AUC=88.8%). We recorded a sensitivity of 80% for TaG1, 95% for T1G3, 90% for ≥T2 with specificity of 77% for healthy controls and 80% for no evidence of disease. Select miRNAs were detected in extracellular vesicles of UCB patients and healthy controls, albeit at different levels. Utilizing this non-invasive assay, we identified miRNA capable of detecting UCB and distinguishing different stages of progression, providing evidence that miRNA profiling in cell-free urine holds promise for the development of valuable clinical diagnostic tools.

Lessons learned from the International Renal Cell Carcinoma-Venous Thrombus Consortium (IRCC-VTC).

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.

Impact of histologic subtype on cancer-specific survival in patients with renal cell carcinoma and tumor thrombus.

BACKGROUND: Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE: We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS: Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS: In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.

MicroRNA Profile to Predict Gemcitabine Resistance in Bladder Carcinoma Cell Lines.

MicroRNAs (miRNA) are small, noncoding RNAs with important regulatory roles in development, differentiation, cell proliferation, and death as well as the complex process of acquired drug resistance. The goal of this study was to identify specific miRNAs and their potential protein targets that confer acquired resistance to gemcitabine in urothelial carcinoma of the bladder (UCB) cell lines. Gemcitabine-resistant cells were established from 6 cell lines following exposure to escalating concentrations of the drug and by passaging cells in the presence of the drug over a 2- to 3-month period. Differential miRNA expression was identified in a microarray format comparing untreated controls with resistant cell lines, representing the maximum tolerated concentration, and results were validated via qRT-PCR. The involvement of specific miRNAs in chemoresistance was confirmed with transfection experiments, followed by clonogenic assays and Western blot analysis. Gemcitabine resistance was generated in 6 UCB cell lines. Microarray analysis comparing miRNA expression between gemcitabine-resistant and parental cells identified the differential expression of 66 miRNAs. Confirmation of differential expression was recorded via qRT-PCR in a subset of these miRNAs. Within this group, let-7b and let-7i exhibited decreased expression, while miR-1290 and miR-138 displayed increased expression levels in gemcitabine-resistant cells. Transfection of pre-miR-138 and pre-miR-1290 into parental cells attenuated cell death after exposure to gemcitabine, while transfection of pre-miR-let-7b and pre-miR-let-7i into the resistant cells augmented cell death. Mucin-4 was up-regulated in gemcitabine-resistant cells. Ectopic expression of let-7i and let-7b in the resistant cells resulted in the down-regulation of mucin-4. These results suggest a role for miRNAs 1290, 138, let-7i, and let-7b in imparting resistance to gemcitabine in UCB cell lines in part through the modulation of mucin-4. Alterations in these miRNAs and/or mucin-4 may constitute a potential therapeutic strategy for improving the efficacy of gemcitabine in UCB.

A review of contemporary data on surgically resected renal masses--benign or malignant?

OBJECTIVE: To clearly define the proportions of benign vs malignant histologic findings in resected renal masses through an in-depth review of the contemporary medical data to assist in preoperative risk assessment. MATERIALS AND METHODS: PubMed and select oncology congresses were searched for publications that identify the histologic classification of resected renal masses in a representative sample from the contemporary data: [search] incidence AND (renal cell carcinoma AND benign); incidence AND (renal tumor AND benign); percentage AND (renal cell carcinoma AND benign); limit 2003-2011. RESULTS: We identified 26 representative studies meeting the inclusion criteria and incorporating 27,272 patients. The frequency of benign tumors ranged from 7% to 33%, with most studies within a few percentage points of the mean (14.5% ± 5.2%, median 13.9%). Clear cell renal cell carcinoma occurred in 46% to 83% of patients, with a mean of 68.3% (median 61.3; SD = 11.9%). An inverse relationship between tumor size and benign pathologic features was identified in 14 of 19 (74%) studies that examined an association between tumor size and pathologic characteristics. A statistically significant correlation between clear cell renal cell carcinoma and tumor size was identified in 13 of 19 studies (63%). The accuracy of preoperative cross-sectional imaging was low in the 2 studies examining computed tomography (17%). CONCLUSION: Benign renal tumors represent ∼15% of detected surgically resected renal masses and are more prevalent among small clinical T1a lesions. Noninvasive preoperative differentiation between more and less aggressive renal masses would be an important clinical advance that could allow clinicians greater diagnostic confidence and guide patient management through improved risk stratification.

Temporary targeted renal blood flow interruption using a reverse thermosensitive polymer to facilitate bloodless partial nephrectomy: a swine survival study.

UNLABELLED: What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. OBJECTIVE: To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. MATERIALS AND METHODS: A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion of segmental or subsegmental arteries and was compared with main renal artery clamping with hilar clamps. The resection site was randomized for each swine. Laboratory studies were performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine, repeat angiography was performed with emphasis on the site of previous flow interruption. Gross and microscopic examination of kidney, liver, lung, heart, skeletal muscle was later performed, and the vessel that had supported the previous plug was examined. RESULTS: All animals survived. No abnormal chemistry or haematology results were encountered over the 6 weeks. There were no surgical complications in either group. Using angiography we found 100% patency of vessels that had been occluded with the polymer 6 weeks previously for PN. The only gross or microscopic abnormalities were related to the renal resection and scar formation, and were similar in the two groups. CONCLUSION: Targeted flow interruption with the RTP added no additional risk to PN while allowing bloodless resection and uninterrupted flow to untargeted renal tissue.

Targeted endovascular temporary vessel occlusion with a reverse thermosensitive polymer for near-bloodless partial nephrectomy: comparison to standard surgical clamping techniques.

PURPOSE: To determine whether reversible blood flow interruption to a randomly chosen target region of the kidney may be achieved with the injection of a reverse thermoplastic polymer through an angiographic catheter, thereby facilitating partial nephrectomy without compromising blood flow to the remaining kidney or adding risks beyond those encountered by the use of hilar clamping. METHODS: Fifteen pigs underwent partial nephrectomy after blood flow interruption by vascular cross-clamping or injection of polymer (Lumagel™) into a segmental artery. Five animals were euthanized after surgery (three open and two laparoscopic resection, cross-clamping n = 2), and 10 (open resection, cross-clamping n = 4) were euthanized after 6 weeks' survival. Blood specimens were obtained periodically, and angiogram and necropsy were performed at 6 weeks. RESULTS: Selective renal ischemia was achieved in all cases. Surgical resection time averaged 9 and 24.5 min in the open and laparoscopic groups, respectively. Estimated blood loss was negligible with the exception of one case where an accessory renal artery was originally overlooked. Reversal of the polymer to a liquid state was consistent angiographically and visually in all cases. Time to complete flow return averaged 7.4 and 2 min for polymer and clamping, respectively. Angiography at 6 weeks revealed no evidence of vascular injury. Laboratory data and necropsies revealed no differences between animals undergoing vascular clamping or polymer injection. CONCLUSION: Lumagel was as effective as vascular clamping in producing a near bloodless operative field for partial nephrectomy while maintaining flow to the uninvolved portion of the affected kidney.

Temporary targeted hemostasis to facilitate bloodless partial nephrectomy.

OBJECTIVE: To extend previous robotic-assisted techniques developed in the swine model to studies of laparoscopic and open partial nephrectomy conducted in pigs and calves, designed to encompass vessel diameters similar to those encountered in humans. Lumagel (Pluromed, Woburn, MA), a nontoxic polymer, can be administered intra-arterially under fluoroscopic guidance to obtain a bloodless operative field during partial nephrectomy while maintaining normal circulation to uninvolved renal tissue. METHODS: A total of 10 animals (7 pigs and 3 calves) underwent flow interruption to the kidney, 2 with cross-clamping of the main renal artery, the remaining with Lumagel. Other than the first pig and calf, all the animals then underwent partial nephrectomy. RESULTS: Using Lumagel, targeted blood flow interruption was achieved and circulation to the uninvolved renal tissue was maintained. Hemostasis lasted for ≥30 minutes. The surgical resection time averaged 11 minutes (range 10-13) and 23.3 minutes (range 9-40) in the open and laparoscopic groups, respectively. The estimated blood loss was negligible, with the exception of 2 cases, 1 in which an error in angiographic assessment led to an unoccluded vessel near the resection site and a second case in which a guidewire was inadvertently passed through a vessel. The interval to complete flow return, as determined by direct visualization of the kidney and its corresponding angiogram, averaged 7 and 2.5 minutes for Lumagel and arterial clamping, respectively. CONCLUSION: Lumagel provides reliable and reproducible intraluminal blood flow interruption and flow restoration in both main and segmental renal arteries. By providing blood-free resection, the techniques described could facilitate partial nephrectomy without global renal ischemia.

Nonclamping partial nephrectomy: towards improved nephron sparing.

Ischemia-reperfusion injury caused by vascular clamping contributes to the decline in glomerular filtration rate following partial nephrectomy. Ischemia is the main modifiable factor that determines postoperative kidney function, and it is likely that a harmless duration of ischemia does not exist. Each additional minute of warm ischemia increases the odds of acute renal failure, severe chronic kidney disease (CKD) and end-stage renal disease. Our experience comparing partial nephrectomy with and without clamping in solitary kidneys suggests that renovascular clamping is the only statistically significant determinant of postoperative renal dysfunction. Studies comparing partial nephrectomy with and without clamping demonstrate that ischemia is associated with a risk of acute renal failure, advanced CKD, and renal replacement therapy. Oncologic outcomes and complications in partial nephrectomy without clamping are similar to those with clamping. Even in complex lesions, partial nephrectomy without vascular clamping is preferable when feasible.

Novel ZEB1 expression in bladder tumorigenesis.

UNLABELLED: What's known on the subject? and What does the study add? Epithelial-mesenchymal transition (EMT) is involved in tumor progression where the underlying cellular changes associated with EMT have been identified in in vitro models and confirmed in a limited number of in vivo studies. ZEB1, which targets E-cadherin repression, is a transcriptional regulator that has been implicated in EMT, and is associated with uterine and colorectal cancers. Regulation of ZEB1 expression has been shown to involve different microRNAs (miRNAs), identifying a potential role for miRNA in EMT. In the present study we have identified novel expression of ZEB1 in bladder tumours and shown a role for ZEB1 in enhanced migration and invasion potential in in vitro assays. Confirmation of ZEB1 expression in bladder tumours was shown in tissue microarrays (TMAs). OBJECTIVE: To evaluate ZEB1 expression in bladder tumorigenesis and define a possible role for this transcription factor in urothelial carcinomas of the bladder (UCBs). MATERIALS AND METHODS: Five hundred and fifty-eight samples were assembled in 10 tissue microarrays (TMAs; 263 non-muscle-invasive Ta/T1/Tis, 295 muscle-invasive T2-T4). All tumours were transitional cell carcinomas (TCCs) and processed for immunohistochemistry to assess nuclear ZEB1 expression. Expression levels of ZEB1 were modulated in bladder carcinoma cell lines CUBIII or UM-UC-3 after forced expression or shRNA knockdown, respectively. Protein expression levels were determined using western blot analysis and transfectants were assessed for migration and invasion potential in standard in vitro assays. RESULTS: Nuclear ZEB1 expression was recorded in 22.8% of non-muscle-invasive UCBs and 21.7% of muscle-invasive UCBs, including 24.1% grade I/II and 21.1% grade III tumours, and absent in normal bladder mucosa. No significant correlation was observed for tumour stage and grade, nodal involvement, vascular invasion, metastasis and overall or cancer-specific survival. The introduction or knockdown of ZEB1 expression in bladder carcinoma cell lines showed enhanced or reduced migration and invasive potential, respectively. Changes in ZEB1 expression were accompanied by altered microRNA (miRNA) expression underlying events linked to epithelial-mesenchymal transition (EMT). CONCLUSION: The results in the present study showed novel expression of ZEB1 in bladder cancer in the absence of a link to clinical variables of change, including metastasis and survival. However, in vitro assays showed enhanced or reduced migration and invasion after the introduction or reduction of ZEB1, respectively, in transfected bladder cell lines. Modulation in expression of ZEB1 was closely linked to changes in the miR-200 family along with alternative known prognostic indicators of bladder tumour progression.