Harry Nisen

Laparoscopic versus open nephrectomy for renal cell carcinoma

Laparoscopic radical nephrectomy has become a well-standardized and reproducible, but technically demanding procedure. It is rapidly replacing the traditional open technique in radical nephrectomy with T1-2 tumours. Open operation will mainly be reserved for T3 tumours. Nephron-sparing surgery will play a major role in small (<4 cm) peripheral tumours. Open technique is still the standard for NSS, but with the refined techniques, laparoscopy may be soon coming.

Papillary renal cell cancer is strongly associated with simple renal cysts.

Introduction: The purpose of this study was to evaluate the prevalence of simple renal cysts (SRCs) in patients with renal neoplasia. Patients and Methods: The study population consisted of 482 patients who underwent partial or radical nephrectomy for kidney tumour between 2006 and 2010. Prevalence of cysts was evaluated retrospectively on a preoperative CT or MRI scan. Results: SRCs are more prevalent in patients with papillary renal cell cancer (RCC) than patients with clear cell RCC. All obese (BMI ≥30) patients in our study population had SRCs. Conclusions: This is the first study to show an association between SRCs and papillary RCC.

Hand-assisted laparoscopic versus open partial nephrectomy in patients with T1 renal tumor: Comparative perioperative, functional and oncological outcome

Abstract Objective: Studies comparing hand-assisted laparoscopic partial nephrectomy (HALPN) and open partial nephrectomy (OPN) for T1 kidney tumors are scarce. This study investigated the perioperative, functional and oncological outcomes of these methods. Materials and methods: A prospective institutional kidney tumor register was used to identify patients between January 2006 and May 2014 undergoing HALPN (n = 139) or OPN (n = 165) for tumors 7 cm or smaller with non-absolute indication for nephron-sparing surgery. The outcomes were compared using univariate and multivariate statistical methods. Results: HALPN and OPN groups were similar with regard to tumor characteristics but HALPN patients were 2 years younger (p = 0.001) and had less comorbidity. Fewer intraoperative complications were encountered in HALPN than in OPN patients (7.2% vs 12.7%, p = 0.043). HALPN patients had less all-grade postoperative 30 day complications than OPN patients (27% vs 41%, p = 0.037), but there was no significant difference in Clavien 3–5 complications. Glomerular filtration rate 3 months after operation was lower in the HALPN than in the OPN group (7.1 ± 12.7% vs 10.0 ± 12.4%, p = 0.054). There was no difference in overall survival or recurrence-free survival during the median follow-up of 35 months. Conclusions: HALPN is a feasible method to achieve equal perioperative, functional and oncological outcomes compared to OPN in patients with tumors 7 cm or smaller in diameter.

PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease

Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down‐regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up‐regulated and nephrin mislocalized in podocytes of obese Zucker diabetic fatty (ZDF) rats that have altered renal function. In cultured podocytes, PACSIN2 and nephrin colocalize and interact. We show that nephrin is endocytosed in PACSIN2‐positive membrane regions and that PACSIN2 overexpression increases both nephrin endocytosis and recycling. We identify rabenosyn‐5, which is involved in early endosome maturation and endosomal sorting, as a novel interaction partner of PACSIN2. Interestingly, rabenosyn‐5 expression is increased in podocytes in obese ZDF rats, and, in vitro, its overexpression enhances the association of PACSIN2 and nephrin. We also show that palmitate, which is elevated in diabetes, enhances this association. Collectively, PACSIN2 is up‐regulated and nephrin is abnormally localized in podocytes of diabetic ZDF rats. In vitro, PACSIN2 enhances nephrin turnover apparently via a mechanism involving rabenosyn‐5. The data suggest that elevated PACSIN2 expression accelerates nephrin trafficking and associates with albuminuria.—Dumont, V., Tolvanen, T. A., Kuusela, S., Wang, H., Nyman, T. A., Lindfors, S., Tienari, J., Nisen, H., Suetsugu, S., Plomann, M., Kawachi, H., Lehtonen, S. PACSIN2 accelerates nephrin trafficking and is up‐regulated in diabetic kidney disease. FASEB J. 31, 3978–3990 (2017). www.fasebj.org—Dumont, Vincent, Tolvanen, Tuomas A., Kuusela, Sara, Wang, Hong, Nyman, Tuula A., Lindfors, Sonja, Tienari, Jukka, Nisen, Harry, Suetsugu, Shiro, Plomann, Markus, Kawachi, Hiroshi, Lehtonen, Sanna PACSIN2 accelerates nephrin trafficking and is up‐regulated in diabetic kidney disease. FASEB J. 31, 3978–3990 (2017)

Renal tumour anatomical characteristics and functional outcome after partial nephrectomy

Abstract Objective. Anatomical features of renal tumours may be useful in predicting glomerular filtration rate (GFR) after partial nephrectomy. In this study, anatomical classification systems (ACSs) were compared to predict changes in renal function after surgery. Materials and methods. A group of 294 patients with T1 renal tumours receiving partial nephrectomy between January 2006 and June 2013 were identified from the institutional kidney tumour database. Preoperative images from computed tomography or magnetic resonance imaging were reviewed to assess diameter, PADUA (preoperative aspects and dimensions used for an anatomical) classification score, RENAL (radius, exophytic/endophytic properties of the tumour, nearness of tumour deepest portion to the collecting system or sinus, anterior/posterior descriptor and location relative to polar lines) nephrometry score, centrality index (C index) and renal tumour invasion index (RTII). GFR was estimated using the Modification of Diet in Renal Disease equation preoperatively and 3 months after operation. Linear and logistic regression were applied as statistical methods. Results. Mean tumour diameter was 3.0 ± 2.2 cm (range 1.0–7.0 cm). GFR was 85 ± 22 ml/min/1.73 m² before the operation and 77 ± 21 ml/min/1.73 m² (–8% change) 3 months after the operation. In univariate linear regression, the percentage change in GFR was weakly but statistically significantly associated with surgical approach (p = 0.04), indication for nephron sparing (p = 0.02), preoperative GFR (p < 0.001), PADUA (p = 0.02), RENAL (p = 0.01) and RTII (p = 0.003). In multivariate logistic regression analysis among patients with tumours 3 cm or larger, PADUA (odds ratio 1.55, p = 0.021) and RTII (odds ratio 3.87, p = 0.037) predicted at least a 20% reduction in GFR. Conclusions. Renal tumour ACSs may be clinically useful in predicting changes in renal function after partial nephrectomy in patients with larger tumours. The performance of RTII is equal to that of other ACSs in predicting changes in GFR.

Contemporary treatment of renal tumors: a questionnaire survey in the Nordic countries (the NORENCA-I study)

Abstract Objective: The five Nordic countries comprise 25 million people, and have similar treatment traditions and healthcare systems. To take advantage of these similarities, a collaborative group (Nordic Renal Cancer Group, NORENCA) was founded in 2015. Materials and methods: A questionnaire of 17 questions on renal tumor management and surgical education was designed and sent to 91 institutions performing renal tumor surgery in 2015. The response rate was 68% (62 hospitals), including 28 academic, 25 central and nine district hospitals. Hospital volume was defined as low (LVH: < 20 operations), intermediate (IVH: 20–49 operations), high (HVH: 50–99) and very high (VHVH: ≥ 100). Descriptive statistics were performed. Results: Fifteen centers were LVH, 16 IVH, 21 HVH and 10 VHVH. Of all 3828 kidney tumor treatments, 55% were radical nephrectomies (RNs), 37% partial nephrectomies (PNs) and 8% thermoablations. For RN and PN, the percentages of open, laparoscopic and robotic approaches were 47%, 40%, 13% and 47%, 20%, 33%, respectively. The mean complication rate (Clavien–Dindo 3–5) was 4.9%, and 30 day mortality (TDM) was 0.5%. The median length of hospital stay was 4 days. Training with a simulator, black box or animal laboratory was possible in 48%, 74% and 21% of institutions, respectively. Conclusions: Despite some differences between countries, the data suggest an overall general common Nordic treatment attitude for renal tumors. Furthermore, the data demonstrate high adherence to international standards, with a high proportion of PN and acceptable rates for major complications and TDM.

Renal Tumor Invasion Depth and Diameter are the Two Most Accurate Anatomical Features Regarding the Choice of Radical Versus Partial Nephrectomy

Background and Aims: To evaluate simple tumor characteristics (renal tumor diameter and parenchymal invasion depth) compared with more complex classifications, that is, Renal Tumor Invasion Index (RTII) and Preoperative Aspects and Dimensions Used for an Anatomical classification, in predicting the type of nephrectomy (radical vs partial) performed. Material and Methods: A total of 915 patients who had undergone either partial nephrectomy (n = 388, 42%) or radical nephrectomy (n = 527, 58%) were identified from the Helsinki University Hospital kidney tumor database between 1 January 2006 and 31 December 2014. Tumor maximum diameter and depth of invasion into the parenchyma were estimated from computed tomography or magnetic resonance imaging images and compared with Preoperative Aspects and Dimensions Used for an Anatomical and Renal Tumor Invasion Index. Logistic regression and receiver operating curves were used to compare the parameters at predicting the type of nephrectomy. Results and conclusion: All the anatomical variables of receiver operating curve/area under the curve analyses were significant predictors for the type of nephrectomy. Parenchymal invasion (area under the curve 0.91; 95% confidence interval, 0.89–0.93), RTII (area under the curve 0.91; 95% confidence interval, 0.89–0.93), and diameter (area under the curve 0.91; 95% confidence interval, 0.89–0.93) performed significantly better than Preoperative Aspects and Dimensions Used for an Anatomical classification (area under the curve 0.88; 95% confidence interval, 0.85–0.89). In multivariable analysis, invasion depth was the best predictor of nephrectomy type (percentage correct, 85.6%). Addition of one anatomic parameter into the model of non-anatomical cofactors improved the accuracy of the model significantly, but the addition of more parameters did not. Parenchymal invasion depth and tumor diameter are the most accurate anatomical features for predicting the nephrectomy type. All potential anatomical classification systems should be tested against these two simple characteristics.

Clonal heterogeneity influences drug responsiveness in renal cancer assessed by ex vivo drug testing of multiple patient-derived cancer cells: Subclone-specific therapeutic approach for renal cancer

Renal cell cancer (RCC) has become a prototype example of the extensive intratumor heterogeneity and clonal evolution of human cancers. However, there is little direct evidence on how the genetic heterogeneity impacts on drug response profiles of the cancer cells. Our goal was to determine how genomic clonal evolution impacts drug responses. Finding from our study could help to define the challenge that clonal evolution poses on cancer therapy. We established multiple patient‐derived cells (PDCs) from different tumor regions of four RCC patients, verified their clonal relationship to each other and to the uncultured tumor tissue by genome sequencing. Furthermore, comprehensive drug‐sensitivity testing with 460 oncological drugs was performed on all PDC clones. The PDCs retained many cancer‐specific copy number alterations and mutations in driver genes such as VHL, PBRM1, PIK3C2A, KMD5C and TSC2 genes. The drug testing highlighted vulnerability in the PDCs toward approved RCC drugs, such as the mTOR‐inhibitor temsirolimus, but also novel sensitivities were uncovered. The individual PDC clones from different tumor regions in a patient showed distinct drug–response profiles, suggesting that genomic heterogeneity contributes to the variability in drug responses. Studies of multiple PDCs from a patient with cancer are informative for elucidating cancer heterogeneity and for the determination on how the genomic evolution is manifested in cancer drug responsiveness. This approach could facilitate tailoring of drugs and drug combinations to individual patients.

Use of venous-thrombotic-embolic (vte) prophylaxis in patients undergoing surgery for renal tumors in nordic countries (the norenca-ii study)

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