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Sample records for del tumor renal

  1. Primary renal carcinoid tumor.

    PubMed

    Kanodia, K V; Vanikar, A V; Patel, R D; Suthar, K S; Kute, V B; Modi, P R; Trivedi, H L

    2013-09-01

    Primary renal carcinoid tumor is extremely rare and, therefore, its pathogenesis and prognosis is not well known. We report a primary renal carcinoid in a 26-year-old man treated by radical nephrectomy.

  2. Renal primitive neuroectodermal tumors.

    PubMed

    Bartholow, Tanner; Parwani, Anil

    2012-06-01

    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  3. Malignant renal tumors in children

    PubMed Central

    Sanchez, Thomas Ray; Wootton-Gorges, Sandra

    2015-01-01

    Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. PMID:28326263

  4. Ablative therapies for renal tumors

    PubMed Central

    Ramanathan, Rajan; Leveillee, Raymond J.

    2010-01-01

    Owing to an increased use of diagnostic imaging for evaluating patients with other abdominal conditions, incidentally discovered kidney masses now account for a majority of renal tumors. Renal ablative therapy is assuming a more important role in patients with borderline renal impairment. Renal ablation uses heat or cold to bring about cell death. Radiofrequency ablation and cryoablation are two such procedures, and 5-year results are now emerging from both modalities. Renal biopsy at the time of ablation is extremely important in order to establish tissue diagnosis. Real-time temperature monitoring at the time of radiofrequency ablation is very useful to ensure adequacy of ablation. PMID:21789083

  5. Primary renal primitive neuroectodermal tumor.

    PubMed

    Goel, V; Talwar, V; Dodagoudar, C; Singh, S; Sharma, A; Patnaik, N

    2015-01-01

    Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of primary renal PNET have been reported to date. Most literature about rPNET is isolated case reports. We report a case of rPNET in a 39-year-old male with a pre-operative diagnosis of renal cell carcinoma with renal vein thrombosis. The patient underwent radical nephrectomy with thrombolectomy, and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this tumor, prompt diagnosis and imparting effective chemotherapy regimen to the patient is required, and it is important to differentiate PNET from other small round-cell tumors because of different therapeutic approach.

  6. Tubulocystic Renal Cell Carcinoma: A Rare Renal Tumor

    PubMed Central

    Bindroo, Sandiya; Varshney, Neha; Mittal, Vijay

    2014-01-01

    Tubulocystic renal cell carcinoma of the kidney is a rare entity with less than one hundred cases reported so far. It was previously considered to have some similarities to various other renal cancers although this tumor has distinct macroscopic, microscopic and immuno-histochemical features. It is now a well-established entity in renal neoplastic pathology and has been recognized as a distinct entity in the 2012 Vancouver classification of renal tumors. This review aims to give an overview of tubulocystic renal cell carcinoma after extensive literature search using PubMed and CrossRef.

  7. Infrared spectroscopic imaging of renal tumor tissue

    NASA Astrophysics Data System (ADS)

    Šablinskas, Valdas; Urbonienė, Vidita; Ceponkus, Justinas; Laurinavicius, Arvydas; Dasevicius, Darius; Jankevičius, Feliksas; Hendrixson, Vaiva; Koch, Edmund; Steiner, Gerald

    2011-09-01

    Fourier transform infrared (FTIR) spectroscopic imaging has been used to probe the biochemical composition of human renal tumor tissue and adjacent normal tissue. Freshly resected renal tumor tissue from surgery was prepared as a thin cryosection and examined by FTIR spectroscopic imaging. Tissue types could be discriminated by utilizing a combination of fuzzy k-means cluster analysis and a supervised classification algorithm based on a linear discriminant analysis. The spectral classification is compared and contrasted with the histological stained image. It is further shown that renal tumor cells have spread in adjacent normal tissue. This study demonstrates that FTIR spectroscopic imaging can potentially serve as a fast and objective approach for discrimination of renal tumor tissue from normal tissue and even in the detection of tumor infiltration in adjacent tissue.

  8. Reflex Anuria After Renal Tumor Embolization

    SciTech Connect

    Kervancioglu, Selim Sirikci, Akif; Erbagci, Ahmet

    2007-04-15

    We report a case of reflex anuria after transarterial embolization of a renal tumor. Anuria developed immediately after embolization and resolved 74 hr following the procedure. We postulate that reflux anuria in our case was related to mechanoreceptors, chemoreceptors, or both, as these are stimulated by the occluded blood vessels, ischemia, and edema of the normal renal tissue of an embolized kidney.

  9. Radiofrequency ablation for renal tumors: our experience.

    PubMed

    Hiraoka, Kenji; Kawauchi, Akihiro; Nakamura, Terukazu; Soh, Jintetsu; Mikami, Kazuya; Miki, Tsuneharu

    2009-11-01

    To report our results of percutaneous radiofrequency ablation (RFA) for renal tumors and to assess predictors of therapeutic efficacy. Forty patients (median age 73 years) with renal tumors were treated with RFA under local or epidural anesthesia. All of them had high surgical risk or refused radical surgery. Tumors were punctured percutaneously using the Radionics Cool-tip RF System under computed tomography or ultrasonographic guidance. Median tumor diameter was 24 mm. After RFA, contrast-enhanced computed tomography or magnetic resonance imaging was performed within 1 month. Complete response (CR) was defined as no enhancement inside the tumor. Factors related to the outcome and to renal function were assessed. Median follow up was 16 months. CR was observed in 34 cases (85.0%). A significant difference in CR rate was observed between tumors < or =30 mm and those >30 mm. Outcomes tended to be better for tumors in the mid to lower kidney, and those away from the renal hilum. Recurrence was observed in one case (2.9%), but a CR was obtained again by additional RFA. Out of a total of 77 RFA procedures, complications occurred in only three cases (3.9%), and conservative treatment was possible in all cases. Serum creatinine levels 3 months after RFA did not differ from those before RFA. Percutaneous RFA is a safe and effective treatment for small renal tumors in patients with high surgical risk or who refuse radical surgery.

  10. Renal functional outcomes after surgery for renal cortical tumors

    PubMed Central

    Finkelstein, Julia B.; DeCastro, G. Joel; McKiernan, James M.

    2015-01-01

    Historically, radical nephrectomy represented the gold standard for the treatment of small (≤ 4cm) as well as larger renal masses. Recently, for small renal masses, the risk of ensuing chronic kidney disease and end stage renal disease has largely favored nephron-sparing surgical techniques, mainly partial nephrectomy. In this review, we surveyed the literature on renal functional outcomes after partial nephrectomy for renal tumors. The largest randomized control trial comparing radical and partial nephrectomy failed to show a survival benefit for partial nephrectomy. With regards to overall survival, surgically induced chronic kidney disease (GFR < 60 ml/min/ 1.73m2) caused by nephrectomy might not be as deleterious as medically induced chronic kidney disease. In evaluating patients who underwent donor nephrectomy, transplant literature further validates that surgically induced reductions in GFR may not affect patient survival, unlike medically induced GFR declines. Yet, because patients who present with a renal mass tend to be elderly with multiple comorbidities, many develop a mixed picture of medically, and surgically-induced renal disease after extirpative renal surgery. In this population, we believe that nephron sparing surgery optimizes oncological control while protecting renal function.

  11. Tumor Enucleation for Renal Cell Carcinoma

    PubMed Central

    Malkowicz, S. Bruce

    2015-01-01

    The increased number of small renal masses (SRMs) detected annually has led to a rise in the use of nephron-sparing surgery (NSS). These techniques aim to preserve the largest amount of healthy renal tissue possible while maintaining the same oncologic outcomes as radical nephrectomy (RN). Additionally, partial nephrectomy (PN) has been linked to a lower risk of chronic kidney disease, cardiovascular morbidity, and mortality when compared to RN. There has been continual progress toward resecting less renal parenchyma. While the predominant surgical method of performing NSS is through traditional PN, simple enucleation (SE) of the tumor has increased in popularity over recent years. SE is a technique that aims to preserve the maximal amount of renal parenchyma possible by utilizing the renal tumor pseudocapsule to bluntly separate the lesion from its underlying parenchyma, offering the smallest possible margin of excised healthy renal tissue. Several studies have demonstrated the oncological safety of SE compared with PN in the treatment of SRMs, with lower overall incidence of positive surgical margins. Additionally, SE has been shown to have similar 5- and 10-year progression-free and cancer-specific survival as PN. We present a review of the literature and an argument for SE to be a routine consideration in the treatment of all renal tumors amenable to NSS.

  12. Preoperative evaluation of renal artery in patients with renal tumor

    PubMed Central

    Zhu, Liangsong; Wu, Guangyu; Wang, Jianfeng; Huang, Jiwei; Kong, Wen; Chen, Yonghui; Xue, Wei; Huang, Yiran; Zhang, Jin

    2016-01-01

    Abstract To investigate the feasibility of the noncontrast-enhanced magnetic resonance angiography (NCE-MRA) to evaluate renal arteries before partial nephrectomy (PN). Retrospective analyzed 479 patients who underwent renal surgery between January 2013 and December 2015 with NCE-MRA or computed tomographic angiography (CTA) renal artery image reconstruction preoperative in our department. The renal artery reconstruction score (RARS) was based on the level of artery visualization in a 4-class criterion, and the R.E.N.A.L nephrometry score (R.E.N.A.L), arterial based complexity (ABC) were also analyzed. Of the 479 patients, the overall-lever RARS was 3.62, and the average in 2 groups was no significant difference (NCE-MRA vs CTA, P = 0.072). The performance of NCE-MRA in PN group was similar with CTA. Further comparison demonstrated that the efficiency of NCE-MRA in moderate- or low-degree tumor according to the R.E.N.A.L and ABC complexity less than 3S was equal to CTA. However, high degree (P < 0.001), 3S (P = 0.027), or 3H (P < 0.001) would affect the imaging of renal artery. Intragroup analysis showed that tumor complexity such as max tumor size (r = −o.351, P < 0.001), R.E.N.A.L (r = −0.439, P < 0.001), and ABC (r = −0.619, P < 0.001) were closely correlated with the NCE-MRA performance. The images of 2 sides of the kidney were compared in single person as well, which was meaningful for NCE-MRA patients only (NCE-MRA, P < 0.001; CTA, P = 0.182). The renal artery reconstruction performed by NCE-MRA is feasible and has a similar achievement in the PN potential recipients, with a lower side effect, and meets the requirements for making surgical decision. It has a broad application prospect in clinical practice; however, it still needs to further improve the ability in more complex tumors. PMID:27759632

  13. Renal Primitive Neuroectodermal Tumor: A Case Report.

    PubMed

    Yang, Cheng; Xu, Hanjiang; Zhou, Jun; Hao, Zongyao; Wang, Jianzhong; Lin, Changmin; Zhang, Li; Zhu, Xia; Liang, Chaozhao

    2015-12-01

    Primitive neuroectodermal tumor (PNET) is a malignant small round cell tumor and typically arises from bone or soft tissue in adolescents and young adults. Renal PNET is extraordinarily rare and exhibits highly aggressive biological behavior with poor prognosis.We present here a new case of renal PNET in a 31-year-old female. The patients were referred to our hospital because of left flank pain with nausea and vomiting for 1 week. A computed tomography scan revealed a 14.7 × 12.7 cm well-defined, unevenly mass lesion with both solid and cystic components and the tumor was not enhanced uniformly.A preoperative diagnosis of cystic renal cell carcinoma and urinary tract infection was made. The patient undergone anti-inflammatory therapy followed by a left radical nephrectomy. Taken with morphological pattern and immunohistochemical markers, a diagnosis of renal PNET was made. Two cycles of combined chemotherapy were executed. At the 14-month follow-up, no evidence of metastasis or recurrence was indicated.This case reminds clinicians that for adolescents and young adults with a suspicious renal mass, a diagnosis of renal PNET should be always considered. An initial surgery followed by radiotherapy and chemotherapy is suggested for the therapeutic management.

  14. Interpretation of male rat renal tubule tumors.

    PubMed Central

    Rodgers, I S; Baetcke, K P

    1993-01-01

    Based on an analysis of recent scientific studies, a Technical Panel of the U.S. Environmental Protection Agency's (EPA) Risk Assessment Forum recently advised EPA risk assessors against using information on certain male rat renal tubule tumors to assess human risk under conditions specified in a new Forum report. Risk assessment approaches generally assume that chemicals producing tumors in laboratory animals are a potential cancer hazard to humans. For most chemicals, including classical rodent kidney carcinogens such as N-ethyl-N-hydroxyethylnitrosamine, this extrapolation remains appropriate. Some chemicals, however, induce accumulation of alpha 2u-globulin (alpha 2u-g), a low molecular weight protein, in the male rat kidney. The alpha 2u-g accumulation initiates a sequence of events that appears to lead to renal tubule tumor formation. Female rats and other laboratory mammals administered the same chemicals do not accumulate low molecular weight protein in the kidney, and they do not develop renal tubule tumors. Because humans appear to be more like other laboratory animals than like the male rat, in this special situation, the male rat is not a good model for assessing human risk. The Forum report stresses the need for full scrutiny of a substantial set of data to determine when it is reasonable to presume that renal tumors in male rats are linked to a process involving alpha 2u-g accumulation and to select appropriate procedures for estimating human risks under such circumstances. PMID:7517352

  15. Renal tumors: diagnostic and prognostic biomarkers.

    PubMed

    Tan, Puay Hoon; Cheng, Liang; Rioux-Leclercq, Nathalie; Merino, Maria J; Netto, George; Reuter, Victor E; Shen, Steven S; Grignon, David J; Montironi, Rodolfo; Egevad, Lars; Srigley, John R; Delahunt, Brett; Moch, Holger

    2013-10-01

    The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants' responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary.

  16. Primary renal carcinoid tumor: A radiologic review

    PubMed Central

    Lamb, Leslie; Shaban, Wael

    2015-01-01

    Carcinoid tumor is the classic famous anonym of neuroendocrine neoplasms. Primary renal carcinoid tumors are extremely rare, first described by Resnick and colleagues in 1966, with fewer than a total of 100 cases reported in the literature. Thus, given the paucity of cases, the clinical and histological behavior is not well understood, impairing the ability to predict prognosis. Computed tomography and (occasionally) octreotide studies are used in the diagnosis and followup of these rare entites. A review of 85 cases in the literature shows that no distinctive imaging features differentiate them from other primary renal masses. The lesions tend to demonstrate a hypodense appearance and do not usually enhance in the arterial phases, but can occasionally calcify. Octreotide scans do not seem to help in the diagnosis; however, they are more commonly used in the postoperative followup. In addition, we report a new case of primary renal carcinoid in a horseshoe kidney. PMID:27186242

  17. Renal and adrenal tumors: Pathology, radiology, ultrasonography, therapy, immunology

    SciTech Connect

    Lohr, E.; Leder, L.D.

    1987-01-01

    Aspects as diverse as radiology, pathology, urology, pediatrics and immunology have been brought together in one book. The most up-do-date methods of tumor diagnosis by CT, NMR, and ultrasound are covered, as are methods of catheter embolization and radiation techniques in case of primarily inoperable tumors. Contents: Pathology of Renal and Adrenal Neoplasms; Ultrasound Diagnosis of Renal and Pararenal Tumors; Computed-Body-Tomography of Renal Carcinoma and Perirenal Masses; Magnetic Resonance Imaging of Renal Mass Lesions; I-125 Embolotherapy of Renal Tumors; Adrenal Mass Lesions in Infants and Children; Computed Tomography of the Adrenal Glands; Scintigraphic Studies of Renal and Adrenal Function; Surgical Management of Renal Cell Carcinoma; Operative Therapy of Nephroblastoma; Nonoperative Treatment of Renal Cell Carcinoma; Prenatal Wilms' Tumor; Congenital Neuroblastoma; Nonsurgical Management of Wilms' Tumor; Immunologic Aspects of Malignant Renal Disease.

  18. Primary renal carcinoid tumor: A rare cystic renal neoplasm

    PubMed Central

    Yoon, Jung-Hee

    2013-01-01

    We present the case of a 21-year-old man with an incidentally detected cystic renal mass. A well-defined, solid mass measuring approximately 8 cm x 6 cm with a cystic component was identified in the left kidney by abdominal multidetector computed tomography (CT) and ultrasonography. The mass was well-enhanced on the corticomedullary CT phase and washout of enhancement occurred on the nephrographic phase. The mass contained peripheral wall and septal calcifications in the cystic component. The lesion was resected and diagnosed as a primary renal carcinoid tumor. Primary carcinoid tumors of the kidney are extremely rare. This case is notable because of the rarity of this neoplasm and its unique radiologic and pathologic findings. A review of previously reported cases in the literature is also presented. PMID:24003360

  19. [Gastrointestinal stromal tumor and renal transplant].

    PubMed

    Seculini Patiño, Carina E; Tabares, Aldo H; Laborie, Maria V; Diller, Ana

    2017-01-01

    Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

  20. [Diagnosis and treatment of hydrocephalus-accompanied renal calculi complicated with renal tumor: 5 case reports].

    PubMed

    He, Chong-jun; Qin, Cai-peng; Li, Jian-xing; Xiong, Liu-lin; Xu, Qing-quan; Yang, Bo; Xu, Tao; Huang, Xiao-bo; Wang, Xiao-feng

    2014-08-18

    To investigate the diagnosis and treatment of renal pelvic tumor combined with renal urinary calculi and hydronephrosis. Five patients with renal pelvic tumor who underwent relief of the upper urinary obstruction were reviewed. One of the cases lost the opportunity of surgical therapy when pelvic tumor was detected at the advanced stage, and the other 4 cases had received surgery and were followed up. As pelvic tumor progresses rapidly after the renal blood flow is improved, and renal urinary calculi with hydronephrosis relieved; the patients with renal pelvic tumor need early diagnosis, aggressive treatment and close follow-up.

  1. Interpretation of male rat renal tubule tumors

    SciTech Connect

    Rodgers, I.S.; Baetcke, K.P.

    1993-12-01

    Based on an analysis of recent scientific studies, a Technical Panel of the U.S. Environmental Protection Agency`s (EPA) Risk Assessment Forum recently advised EPA risk assessors against using information on certain male rat renal tubule tumors to assess human risk under conditions specified in a new Forum report. Risk assessment approaches generally assume that chemicals producing tumors in laboratory animals are a potential cancer hazard to humans. For most chemicals, including classical rodent kidney carcinogens such as N-ethyl-N-hydroxyethylnitrosamine, this extrapolation remains appropriate. Some chemicals, however, induce accumulation of {alpha}{sub 2u}-globulin ({alpha}{sub 2u}-g), a low molecular weight protein, in the male rat kidney. The {alpha}{sub 2u}-g accumulation initiates a sequence of events that appears to lead to renal tubule tumor formation. Female rats and other laboratory mammals administered the same chemicals do not accumulate low molecular weight protein in the kidney, and they do not develop renal tubule tumors. Because humans appear to be more like other laboratory animals than like the male rat, in this special situation, the male rat is not a good model for assessing human risk. The Forum report stresses the need for full scrutiny of a substantial set of data to determine when it is reasonable to presume that renal tumors in male rats are linked to a process involving {alpha}{sub 2u}-g accumulation and to select appropriate procedures for estimating human risks under such circumstances. 92 refs.

  2. Small renal tumor with lymph nodal enlargement: A histopathological surprise

    PubMed Central

    Thottathil, Mujeeburahiman; Verma, Ashish; D’souza, Nischith; Khan, Altaf

    2016-01-01

    Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too. PMID:27453671

  3. Current standards of care and future directions for "high-risk" pediatric renal tumors: Anaplastic Wilms tumor and Rhabdoid tumor.

    PubMed

    Geller, James I

    2016-01-01

    'High risk' renal tumors of childhood generally includes anaplastic Wilms tumor, rhabdoid tumor, and metastatic renal sarcomas and carcinomas. In this review, the epidemiology, biology, treatment and prognosis of anaplastic Wilms tumor and rhabdoid tumor are presented. Future directions related to management of such cancers are discussed, with insights provided into possible clinical trials in development that consider integration of novel targeted therapies.

  4. Clear cell papillary renal cell carcinoma, renal angiomyoadenomatous tumor, and renal cell carcinoma with leiomyomatous stroma relationship of 3 types of renal tumors: a review.

    PubMed

    Hes, Ondrej; Compérat, Eva Maria; Rioux-Leclercq, Nathalie

    2016-04-01

    Renal angiomyoadenomatous tumor has been described in 2000, followed by description of clear cell papillary renal cell carcinoma in 2006. Discussions about possible relationship of both tumors were published since their description. The main differential diagnostic feature was considered presence/absence of fibroleiomyomatous stroma-relationship of renal angiomyoadenomatous tumor in stroma-rich tumors. However, it was shown that stroma is reactive and nonneoplastic by its nature and that all other histologic, immunohistochemical, and molecular-genetic features of both entities are identical. In upcoming World Health Organization classification of renal tumors (2016), both lesions are considered as a single entity (clear cell papillary renal cell carcinoma [CCPRCC]). Most published cases followed the benign/indolent clinical course. In addition, most tumors has normal status of VHL gene (methylation, LOH 3p, mutations); however, CCPRCC was referred in patients with VHL syndrome. Another issue covered by this review is possible relationship of CCPRCC and "renal cell carcinoma with leiomyomatous stroma" (RCCLS). Renal cell carcinoma with leiomyomatous stroma shows clear cell cytology and abundant leiomyomatous stroma. Some of RCCLS are positive for cytokeratin 7; some are negative. Similar situation exists for relation of RCCLS and VHL gene abnormalities. It is so far unclear whether any relation between CCPRCC and RCCLS exists. From all published studies, it seems that these tumors are less likely related to each other.

  5. Standardized Reporting of Microscopic Renal Tumor Margins: Introduction of the Renal Tumor Capsule Invasion Scoring System.

    PubMed

    Snarskis, Connor; Calaway, Adam C; Wang, Lu; Gondim, Dibson; Hughes, Ian; Idrees, Muhammad T; Kliethermes, Stephanie; Maniar, Viraj; Picken, Maria M; Boris, Ronald S; Gupta, Gopal N

    2017-01-01

    Renal tumor enucleation allows for maximal parenchymal preservation. Identifying pseudocapsule integrity is critically important in nephron sparing surgery by enucleation. Tumor invasion into and through the capsule may have clinical implications, although it is not routinely commented on in standard pathological reporting. We describe a system to standardize the varying degrees of pseudocapsule invasion and identify predictors of invasion. We performed a multicenter retrospective review between 2002 and 2014 at Indiana University Hospital and Loyola University Medical Center. A total of 327 tumors were evaluated following removal via radical nephrectomy, standard margin partial nephrectomy or enucleation partial nephrectomy. Pathologists scored tumors using our i-Cap (invasion of pseudocapsule) scoring system. Multivariate analysis was done to determine predictors of higher score tumors. Tumor characteristics were similar among surgical resection groups. Enucleated tumors tended to have thinner pseudocapsule rims but not higher i-Cap scores. Rates of complete capsular invasion, scored as i-Cap 3, were similar among the surgical techniques, comprising 22% of the overall cohort. Papillary histology along with increasing tumor grade was predictive of an i-Cap 3 score. A capsule invasion scoring system is useful to classify renal cell carcinoma pseudocapsule integrity. i-Cap scores appear to be independent of surgical technique. Complete capsular invasion is most common in papillary and high grade tumors. Further work is warranted regarding the relevance of capsular invasion depth as it relates to the oncologic outcome for local recurrence and disease specific survival. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Jade-1, a candidate renal tumor suppressor that promotes apoptosis.

    PubMed

    Zhou, Mina I; Foy, Rebecca L; Chitalia, Vipul C; Zhao, Jin; Panchenko, Maria V; Wang, Hongmei; Cohen, Herbert T

    2005-08-02

    Medical therapies are lacking for advanced renal cancer, so there is a great need to understand its pathogenesis. Most renal cancers have defects in the von Hippel-Lindau tumor suppressor pVHL. The mechanism by which pVHL protein functions in renal tumor suppression remains unclear. Jade-1 is a short-lived, kidney-enriched transcription factor that is stabilized by direct interaction with pVHL. Loss of Jade-1 stabilization by pVHL correlates with renal cancer risk, making the relationship between Jade-1 and renal cancer compelling. We report that Jade-1 expression was barely detectable in all tested renal cancer cell lines, regardless of VHL status. Strikingly, proteasome inhibitor treatment increased endogenous Jade-1 expression up to 10-fold. Jade-1 inhibited renal cancer cell growth, colony formation, and tumor formation in nude mice. Intriguingly, Jade-1 also affected the pattern of cell growth in monolayer culture and 3D culture. Jade-1 increased apoptosis by 40-50% and decreased levels of antiapoptotic Bcl-2. Antisense Jade-1-expressing cells confirmed these results. Therefore, Jade-1 may suppress renal cancer cell growth in part by increasing apoptosis. Jade-1 may represent a proapoptotic barrier to proliferation that must be overcome generally in renal cancer, perhaps initially by pVHL inactivation and subsequently by increased proteasomal activity. Therefore, Jade-1 may be a renal tumor suppressor.

  7. Jade-1, a candidate renal tumor suppressor that promotes apoptosis

    PubMed Central

    Zhou, Mina I.; Foy, Rebecca L.; Chitalia, Vipul C.; Zhao, Jin; Panchenko, Maria V.; Wang, Hongmei; Cohen, Herbert T.

    2005-01-01

    Medical therapies are lacking for advanced renal cancer, so there is a great need to understand its pathogenesis. Most renal cancers have defects in the von Hippel-Lindau tumor suppressor pVHL. The mechanism by which pVHL protein functions in renal tumor suppression remains unclear. Jade-1 is a short-lived, kidney-enriched transcription factor that is stabilized by direct interaction with pVHL. Loss of Jade-1 stabilization by pVHL correlates with renal cancer risk, making the relationship between Jade-1 and renal cancer compelling. We report that Jade-1 expression was barely detectable in all tested renal cancer cell lines, regardless of VHL status. Strikingly, proteasome inhibitor treatment increased endogenous Jade-1 expression up to 10-fold. Jade-1 inhibited renal cancer cell growth, colony formation, and tumor formation in nude mice. Intriguingly, Jade-1 also affected the pattern of cell growth in monolayer culture and 3D culture. Jade-1 increased apoptosis by 40-50% and decreased levels of antiapoptotic Bcl-2. Antisense Jade-1-expressing cells confirmed these results. Therefore, Jade-1 may suppress renal cancer cell growth in part by increasing apoptosis. Jade-1 may represent a proapoptotic barrier to proliferation that must be overcome generally in renal cancer, perhaps initially by pVHL inactivation and subsequently by increased proteasomal activity. Therefore, Jade-1 may be a renal tumor suppressor. PMID:16046545

  8. CD133+ Renal Progenitor Cells Contribute to Tumor Angiogenesis

    PubMed Central

    Bruno, Stefania; Bussolati, Benedetta; Grange, Cristina; Collino, Federica; Efrem Graziano, Manuela; Ferrando, Ugo; Camussi, Giovanni

    2006-01-01

    In the present study, we tested the hypothesis that resident progenitor cells may contribute to tumor vascularization and growth. CD133+ cells were isolated from 30 human renal carcinomas and characterized as renal resident progenitor cells on the basis of the expression of renal embryonic and mesenchymal stem cell markers. CD133+ progenitors differentiated into endothelial and epithelial cells as the normal CD133+ counterpart present in renal tissue. In the presence of tumor-derived growth factors, these cells were committed to differentiate into endothelial cells able to form vessels in vivo in SCID mice. Undifferentiated CD133+ progenitors were unable to form tumors when transplanted alone in SCID mice. When co-transplanted with renal carcinoma cells, CD133+ progenitors significantly enhanced tumor development and growth. This effect was not attributable to the tumorigenic nature of CD133+ progenitor cells because the same results were obtained with CD133+ cells from normal kidney. CD133+ progenitors contributed to tumor vascularization as the majority of neoformed vessels present within the transplanted tumors were of human origin and derived from the co-transplanted CD133+ progenitors. In conclusion, these results indicate the presence of a renal progenitor cell population in renal carcinomas that may differentiate in endothelial cells and favor vascularization and tumor growth. PMID:17148683

  9. Giant renal Angiomyolipoma masquerading as a Wilms tumor

    PubMed Central

    Dhua, Anjan Kumar; Ranjan, Abhishek; Agarwala, Sandeep; Bhatnagar, Veereshwar; Mathur, Sandeep R.; Devasenathipathy, Kandasamy

    2017-01-01

    Renal Angiomyolipoma (AML) is not commonly seen in the pediatric age group other than patients of tuberous sclerosis where in they can have renal AMLs within the first decade with bilateral in involvement. Diagnosis of renal AML can generally be made by the current radiological modalities in the appropriate clinical setting, but it can be mistaken for other tumors when it is large and has low-fat content. Herein we report a case of giant renal AML that was initially misdiagnosed as a Wilms tumor in a 12-year-old girl. PMID:28197035

  10. [Case of primary renal carcinoid tumor with hemorrhage].

    PubMed

    Kubota, Yasuaki; Seike, Kensaku; Maeda, Shinichi; Tashiro, Kazuhiro

    2010-04-01

    Carcinoid tumors are low-grade malignant tumors that arise from neuroendocrine cells. Primary renal carcinoid tumors are extremely uncommon. A 63-year-old woman presented with a right abdominal mass and fever. Abdominal computed tomography demonstrated a mass in the right kidney; the mass measured 120 mm in diameter and showed hemorrhage. The patient underwent an uneventful right radical nephrectomy, and histological appearance was typical of carcinoid tumor. Immunohistochemistry demonstrated strong cytoplasmic labeling for neuron-specific enolase and synaptophysin. Additional examinations of the gastrointestinal tract did not show any evidence of carcinoid tumors. The patient remains free from disease recurrence at 8 months after the operation. The prognosis for primary renal carcinoid tumor is relatively optimistic. Complete surgical excision is the only recommended treatment for localized renal carcinoid tumor.

  11. Carcinoid tumor with bilateral renal involvement in a child.

    PubMed

    Warrier, Raj P; Varma, Aditi Vian; Chauhan, Aman; Ward, Ken; Craver, Randal

    2011-12-01

    Carcinoid tumors are uncommon in children. Kidneys are rarely involved as they do not possess neuro-endocrine cells. Work up of painless hematuria after abdominal trauma in a 10-year-old boy revealed primary carcinoid tumors with metastasis to both kidneys. We were unable to find any previous reports of renal involvement by carcinoid tumor in children.

  12. Percutaneous renal cryoablation: prospective experience treating 120 consecutive tumors.

    PubMed

    Buy, Xavier; Lang, Hervé; Garnon, Julien; Sauleau, Erik; Roy, Catherine; Gangi, Afshin

    2013-12-01

    The purpose of this study was to evaluate the safety and efficacy of percutaneous renal cryoablation. A prospective nonrandomized evaluation of 120 renal tumors in 95 patients treated with percutaneous cryoablation because their condition did not allow surgery focused on tumor characteristics, complications, hospital course, treatment success based on MRI follow-up, and effect on renal function. The mean follow-up period was 28 months (range, 6-63 months). The mean tumor size was 26 mm (range, 10-68 mm), including 20 tumors larger than 40 mm. Ninety-one tumors were treated with CT and 29 with MRI guidance. Fifty-six tumors were anterior, and thermal protection of adjacent organs with carbodissection or hydrodissection was used in 55 cases. According to the Clavien-Dindo classification, five grade II complications and four grade III-V complications occurred. The technical success rate was 94%. Two tumors required a second session of cryoablation because of recurrence or residual tumor. Twelve months after treatment the overall survival was 96.7%, and the disease-free survival rate was 96.4%, including patients with recurrent genetic tumors. Renal function remained unchanged even in the subgroup of patients with a single kidney. Midterm follow-up shows that percutaneous renal cryoablation is an effective and safe alternative technique for patients whose condition does not allow surgery and that renal function is preserved. Cryoablation combined with percutaneous thermal protection techniques allows treatment of more complex tumors (large central tumors and tumors close to vulnerable structures). However, T1b and central tumors are associated with higher risk of incomplete treatment.

  13. Minimally Invasive Treatment of Small Renal Tumors: Trends in Renal Cancer Diagnosis and Management

    SciTech Connect

    Breen, David J. Railton, Nicholas J.

    2010-10-15

    Renal cell carcinoma is a common malignancy causing significant mortality. In recent years abdominal imaging, often for alternate symptomatology, has led the trend toward the detection and confirmation of smaller renal tumors. This has permitted the greater use of localized and nephron-sparing techniques including partial nephrectomy and image-guided ablation. This article aims to review the current role of image-guided biopsy and ablation in the management of small renal tumors. The natural history of renal cell carcinoma, the role of renal biopsy, the principles and procedural considerations of thermal energy ablation, and the oncological outcomes of these minimally invasive treatments are discussed and illustrated with cases from the authors' institution. Image-guided ablation, in particular, has changed the treatment paradigm and, by virtue of its increasingly evident efficacy and low morbidity, now favors the treatment of smaller tumors in patients previously unfit for surgery.

  14. [Metastatic renal tumor from oral floor cancer: a case report].

    PubMed

    Ishibashi, Yusuke; Hatakeyama, Shingo; Okamoto, Teppei; Suzuki, Yuichiro; Kudo, Shigemasa; Yoneyama, Takahiro; Koie, Takuya; Kamimura, Noritaka; Sakaki, Hirotaka; Kobayashi, Wataru; Kimura, Hiroto; Ohyama, Chikara

    2012-11-01

    A 61-year-old man with oral floor cancer (adenoid cystic carcinoma, T2N0M1) was treated with systemicc hemotherapy and radiation therapy at the department of dentistry and oral surgery in our hospital. He had three lung metastases and renal tumors detected by screening computed tomography. The oral floor cancer responded to the treatment to achieve partial response. However, lung and renal metastases did not respond to chemotherapy. Then, the patient was referred to our clinic to rule out the possibility of lung metastasis from renal cell carcinoma. Laparoscopic left nephrectomy was performed and pathological examination on the renal lesions revealed adenoid cystic carcinoma, which had identical histopathological features to the oral floor cancer. To our knowledge, this is the first report of metastatic renal tumor from oral floor cancer (adenoid cystic carcinoma).

  15. BRAF exon 15 mutations in pediatric renal stromal tumors: prevalence in metanephric stromal tumors.

    PubMed

    Marsden, Lily; Jennings, Lawrence J; Gadd, Samantha; Yu, Min; Perlman, Elizabeth J; Cajaiba, Mariana M

    2017-02-01

    Metanephric stromal tumors (MSTs) are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors, along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in MSTs and in other pediatric renal stromal tumors. In this study, 17 MSTs, 22 congenital mesoblastic nephromas, and 6 ossifying renal tumors of infancy were selected for BRAF exon 15 testing. Tumor genomic DNA was extracted from formalin-fixed paraffin-embedded tissue, followed by polymerase chain reaction amplification and Sanger dideoxy sequencing with primers flanking the BRAF exon 15 gene. BRAF exon 15 mutations were found in 11 (65%) of the 17 cases of MST, all corresponding to a thymidine-to-adenine substitution at codon 600 (BRAF V600E). All other renal stromal tumors tested were negative for BRAF exon 15 mutations. In conclusion, BRAF V600E mutations are encountered in most MSTs, supporting a link with other metanephric tumors and suggesting a clonal event possibly affecting primordial renal cells. In addition, BRAF V600E mutations have been associated with oncogene-induced senescence in other benign tumors, providing clues to the pathogenesis of metanephric neoplasms in keeping with their overall benign behavior. Our results also suggest a potential diagnostic use for BRAF exon 15 mutations in differentiating MSTs from other pediatric renal stromal tumors, particularly in limited samples.

  16. Uncommon renal tumors in children: A single center experience

    PubMed Central

    Mandal, Kartik Chandra; Mukhopadhyay, Madhumita; Barman, Shibsankar; Halder, Pankaj; Mukhopadhyay, Biswanath; Kumar, Rajarshi

    2016-01-01

    Aims: Scrutiny over the clinical behaviors, management, and the final outcome of some rare renal neoplasm in order to find out some hidden facts about these tumors which are playing an important role in the disease course and its management. Materials and Methods: Retrospective evaluation of uncommon (non-Wilms’) renal neoplasm in the pediatric population in a tertiary care center. Fifteen cases of uncommon renal tumors were treated in our institution over the last 5 years (January 2008 to December 2012). The cases were tabulated in the form of age, sex, mode of presentation, preoperative investigations, intraoperative grading, pathological type, postoperative management and the final outcome. The patients were followed up for 2 years (clinically every 3 months and ultrasonography abdomen in every 6 months for first 2 years) in order to see any evidence of recurrence and complications related to postoperative chemotherapy. Results: Out of 15 cases, four cases were clear cell sarcoma (CCS) (26.6%), three cases were rhabdoid tumor (20%), three cases were congenital mesoblastic nephroma (20%), two cases were multilocular cystic nephroma (13.3%), two cases were renal teratoma (13.3%), and one case of teratoid Wilms’ tumor (6.6%). There were two deaths (one CCS and one rhabdoid tumor) due to chemotherapy-related toxicity but no recurrence. Three patients were lost during postoperative follow-up; ten patients are doing well and getting a regular visit in the follow-up clinic. Conclusion: The clinical presentations of these uncommon renal tumors are similar to that of Wilms’ tumor. Thus, preoperative diagnosis is difficult even with modern imaging techniques. Some of these tumors (CCS, rhabdoid tumor) are rapidly progressing and have a poor outcome. Hence, early intervention in the form of complete surgical resection of the tumor (whenever possible) and postoperative chemo/radiotherapy are imperative for fruitful outcome. PMID:27046976

  17. Rapidly enlarging renal tumor during pregnancy: diagnostic and management dilemma

    PubMed Central

    Tiang, Kor Woi; Ng, Keng Lim; Vega-Vega, Antonio; Wood, Simon

    2014-01-01

    Urological tumors diagnosed during pregnancy are rare. However, the incidence seems to be increasing largely due to advancements in modern imaging techniques and improved antenatal care. The diagnosis and management of renal tumors during pregnancy poses a dilemma to clinicians. This case report highlights the challenges in managing a large chromophobe renal cell carcinoma in a young primigravida patient. Proper antenatal assessment, a multidisciplinary team approach and appropriate discussion with patient are important determinants to achieve the best clinical outcomes for both the mother and the baby.

  18. Spinal cord and bone metastasizing renal tumor of childhood.

    PubMed

    Arrotegui, J I; Barrios, C

    1995-01-01

    In recent reports on renal tumors of childhood with bone involvement neoplasms originally considered to be Wilms tumor have been assigned to new groups. After reviewing the literature, we knew that Wilms tumor rarely metastasizes in this way. Our case illustrates the unique biological feature of the rare, unfavorable histology Wilms tumor variant know as 'clear cell sarcoma of the kidney' (CCSK). Metastases to the spinal cord, as observed in our patient are distinctly unusual. To our knowledge, only two previous cases have been reported in the world literature.

  19. Hyperpolarized 13C MR Markers of Renal Tumor Aggressiveness

    DTIC Science & Technology

    2015-12-01

    such measures in order to distinguish between benign and RCC tumors in patients using the non - invasive rapid hyperpolarized 13C MRI. Review of...using RCC human cells to capture a range of aggressive renal tumors. And have shown using such a model several approaches to non -invasively assess...recent study reported that CHKA forms a complex with EGF receptor (EGFR) in a c-Src– dependent manner, and functions cooper- atively with EGFR and c-Src

  20. Renal and adrenal tumors in children.

    PubMed

    Zderic, Stephen A

    2004-08-01

    Survival rates for children with kidney tumors approach 90% for even the most advanced stages of disease, but the surgical management of large lesions remains challenging. With the development of additional chemotherapeutic regimens and the use of radiation therapy, survival rates have improved dramatically. The National Wilms' Tumor Study has conducted four long-term studies addressing how adjunctive therapy may be tailored optimally to maximize survival and minimize the exposure to chemotherapy and radiation therapy.

  1. Radio frequency ablation of small renal tumors:: intermediate results.

    PubMed

    Hwang, J J; Walther, M M; Pautler, S E; Coleman, J A; Hvizda, J; Peterson, James; Linehan, W M; Wood, B J

    2004-05-01

    With evolving radio frequency technology, the clinical application of radio frequency ablation (RFA) has been actively investigated in the treatment for small renal tumors. We present our intermediate patient outcomes after RFA. Since January 2001, 17 patients with a total of 24 hereditary renal tumors ranging from 1.2 to 2.85 cm were treated with RFA using the 200 W Cool-tip RF System (Radionics, Burlington, Massachusetts) under laparoscopic (9) or percutaneous (8) guidance and had a minimum 1-year followup. A percutaneous approach was considered unsuitable if kidney tumors were contiguous to bowel, ureter or large vessels. Treatment eligibility criteria included an average tumor diameter of less than 3.0 cm, tumor growth during 1 year and solid appearance with contrast enhancement (HU change greater than 20) on computerized tomography (CT). Postoperative followup consisted of CT with and without intravenous contrast, and renal function assessment at regular intervals. Median patient age was 38 years (range 20 to 51). At a median followup of 385 days (range 342 to 691), median tumor or thermal lesion diameter decreased from 2.26 to 1.62 cm (p = 0.0013), and only 1 lesion (4%), which was located centrally near the hilum, exhibited contrast enhancement (HU change greater than 10) on CT at 12 months. Of the 15 renal tumors ablated laparoscopically, 13 were in direct contact with the bowel and 2 were abutting the ureter, necessitating mobilization before RFA. Laparoscopic ultrasound was used to guide radio frequency electrode placement and monitor the ablation process in these cases. Operative time and intraoperative blood loss (mean +/- standard mean of error) were 243 +/- 29 minutes and 67 +/- 9 cc, respectively. In 1 patient whose ureter was adherent to the tumor a ureteropelvic junction obstruction developed after laparoscopic RFA, requiring open repair. At the minimum 1-year followup 23 of 24 ablated tumors lacked contrast uptake on CT, meeting our radiographic

  2. RADIO FREQUENCY ABLATION OF SMALL RENAL TUMORS: INTERMEDIATE RESULTS

    PubMed Central

    HWANG, J. J.; WALTHER, M. M.; PAUTLER, S. E.; COLEMAN, J. A.; HVIZDA, J.; PETERSON, JAMES; LINEHAN, W. M.; WOOD, B. J.

    2008-01-01

    Purpose With evolving radio frequency technology, the clinical application of radio frequency ablation (RFA) has been actively investigated in the treatment for small renal tumors. We present our intermediate patient outcomes after RFA. Materials and Methods Since January 2001, 17 patients with a total of 24 hereditary renal tumors ranging from 1.2 to 2.85 cm were treated with RFA using the 200 W Cool-tip RF System (Radionics, Burlington, Massachusetts) under laparoscopic (9) or percutaneous (8) guidance and had a minimum 1-year followup. A percutaneous approach was considered unsuitable if kidney tumors were contiguous to bowel, ureter or large vessels. Treatment eligibility criteria included an average tumor diameter of less than 3.0 cm, tumor growth during 1 year and solid appearance with contrast enhancement (HU change greater than 20) on computerized tomography (CT). Postoperative followup consisted of CT with and without intravenous contrast, and renal function assessment at regular intervals. Results Median patient age was 38 years (range 20 to 51). At a median followup of 385 days (range 342 to 691), median tumor or thermal lesion diameter decreased from 2.26 to 1.62 cm (p = 0.0013), and only 1 lesion (4%), which was located centrally near the hilum, exhibited contrast enhancement (HU change greater than 10) on CT at 12 months. Of the 15 renal tumors ablated laparoscopically, 13 were in direct contact with the bowel and 2 were abutting the ureter, necessitating mobilization before RFA. Laparoscopic ultrasound was used to guide radio frequency electrode placement and monitor the ablation process in these cases. Operative time and intraoperative blood loss (mean ± standard mean of error) were 243 ± 29 minutes and 67 ± 9 cc, respectively. In 1 patient whose ureter was adherent to the tumor a ureteropelvic junction obstruction developed after laparoscopic RFA, requiring open repair. Conclusions At the minimum 1-year followup 23 of 24 ablated tumors lacked

  3. Treatment of caval vein thrombosis associated with renal tumors.

    PubMed

    Jiménez-Romero, Carlos; Conde, María; de la Rosa, Federico; Manrique, Alejandro; Calvo, Jorge; Caso, Óscar; Muñoz, Carlos; Marcacuzco, Alberto; Justo, Iago

    2017-03-01

    Renal carcinoma represents 3% of all solid tumors and is associated with renal or inferior caval vein (IVC) thrombosis between 2-10% of patients, extending to right atrial in 1% of cases. This is a retrospective study that comprises 5 patients who underwent nephrectomy and thrombectomy by laparotomy because of renal tumor with IVC thrombosis level iii. Four patients were males and one was female, and the mean age was 57,2 years (range: 32-72). Most important clinical findings were hematuria, weight loss, weakness, anorexia, and pulmonary embolism. Diagnostic confirmation was performed by CT scanner. Metastatic disease was diagnosed before surgery in 3 patients. Suprahepatic caval vein and hepatic hilium (Pringle's maneouver) were clamped in 4 patients, and ligation of infrarrenal caval vein was carry out in one patient. Five patients developed mild complications (Clavien I/II). No patient died and the mean hospital stay was 8,6 days. All patients were treated with chemotherapy, and 3 died because distant metastasis, but 2 are alive, without recurrence, at 5 and 60 months, respectively. Nephrectomy and thrombectomy in renal tumors with caval thrombosis can be curative in absence of metastasis or, at less, can increase survival or quality of live. Then these patients must be treated in liver transplant units because major surgical and anesthesiologic expertise. Adjuvant treatment with tyrosin kinase inhibitors must be validate in the future with wider experiences. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Renal Tumors: Technical Success and Early Clinical Experience with Radiofrequency Ablation of 18 Tumors

    SciTech Connect

    Sabharwal, Rohan Vladica, Philip

    2006-04-15

    Purpose. To evaluate the feasibility, safety, and technical efficacy of image-guided radiofrequency ablation (RFA) for the treatment of small peripheral renal tumors and to report our early results with this treatment modality. Methods. Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal tumors. Indications included coexistent morbidity, high surgical or anesthetic risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten patients had CT-guided percutaneous RFA performed on an outpatient basis. One patient had open intraoperative ultrasound-guided RFA. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. With the exception of one patient with renal insufficiency who required gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks and then at 3, 6, 12 months, and every 12 months thereafter. Results. Fourteen (78%) of 18 tumors were successfully ablated with one session. Three of the remaining four tumors required two sessions for successful ablation. One tumor will require a third session for areas of persistent enhancement. Mean patient age was 72.82 {+-} 10.43 years. Mean tumor size was 1.95 {+-} 0.79 cm. Mean follow-up time was 10.91 months. All procedures were performed without any major complications. Conclusions. Our early experience with percutaneous image-guided radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and effective treatment of small peripheral renal tumors.

  5. A report of renal artery embolization for hematuria facilitating neoadjuvant chemotherapy in an unresectable malignant renal rhabdoid tumor.

    PubMed

    Sharma, Ruchika; Kitchen, Brenda J; Mody, Rajen; Chamdin, Aghiad; Bruch, Steven; Jasty, Rama

    2013-05-01

    Malignant rhabdoid tumor (MRT) of the kidney is a rare pediatric tumor characterized by its aggressive nature and chemoresistance. Our patient had MRT of the right kidney with tumor thrombus in the renal vein, inferior vena cava, and right atrium. He developed transfusion-resistant hematuria. This was successfully controlled with right renal artery embolization allowing completion of his neoadjuvant chemotherapy. He then underwent complete resection of the tumor and thrombus avoiding cardiopulmonary bypass.

  6. Management of Renal Tumors by Image-Guided Radiofrequency Ablation: Experience in 105 Tumors

    SciTech Connect

    Breen, David J. Rutherford, Elizabeth E.; Stedman, Brian; Roy-Choudhury, Shuvro H.; Cast, James E. I.; Hayes, Matthew C.; Smart, Christopher J.

    2007-09-15

    Aims. In this article we present our experience with radiofrequency ablation (RFA) in the treatment of 105 renal tumors. Materials and Methods. RFA was performed on 105 renal tumors in 97 patients, with a mean tumor size of 32 mm (11-68 mm). The mean patient age was 71.7 years (range, 36-89 years). The ablations were carried out under ultrasound (n = 43) or CT (n = 62) guidance. Imaging follow-up was by contrast-enhanced CT within 10 days and then at 6-monthly intervals. Multivariate analysis was performed to determine variables associated with procedural outcome. Results. Eighty-three tumors were completely treated at a single sitting (79%). Twelve of the remaining tumors were successfully re-treated and a clinical decision was made not to re-treat seven patients. A patient with a small residual crescent of tumor is under follow-up and may require further treatment. In another patient, re-treatment was abandoned due to complicating pneumothorax and difficult access. One patient is awaiting further re-treatment. The overall technical success rate was 90.5%. Multivariate analysis revealed tumor size to be the only significant variable affecting procedural outcome. (p = 0.007, Pearson {chi}{sup 2}) Five patients had complications. There have been no local recurrences. Conclusion. Our experience to date suggests that RFA is a safe and effective, minimally invasive treatment for small renal tumors.

  7. Management of renal tumors by image-guided radiofrequency ablation: experience in 105 tumors.

    PubMed

    Breen, David J; Rutherford, Elizabeth E; Stedman, Brian; Roy-Choudhury, Shuvro H; Cast, James E I; Hayes, Matthew C; Smart, Christopher J

    2007-01-01

    In this article we present our experience with radiofrequency ablation (RFA) in the treatment of 105 renal tumors. RFA was performed on 105 renal tumors in 97 patients, with a mean tumor size of 32 mm (11-68 mm). The mean patient age was 71.7 years (range, 36-89 years). The ablations were carried out under ultrasound (n = 43) or CT (n = 62) guidance. Imaging follow-up was by contrast-enhanced CT within 10 days and then at 6-monthly intervals. Multivariate analysis was performed to determine variables associated with procedural outcome. Eighty-three tumors were completely treated at a single sitting (79%). Twelve of the remaining tumors were successfully re-treated and a clinical decision was made not to re-treat seven patients. A patient with a small residual crescent of tumor is under follow-up and may require further treatment. In another patient, re-treatment was abandoned due to complicating pneumothorax and difficult access. One patient is awaiting further re-treatment. The overall technical success rate was 90.5%. Multivariate analysis revealed tumor size to be the only significant variable affecting procedural outcome. (p = 0.007, Pearson chi(2)) Five patients had complications. There have been no local recurrences. Our experience to date suggests that RFA is a safe and effective, minimally invasive treatment for small renal tumors.

  8. Renal arteriography

    MedlinePlus

    Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... an artery by a blood clot Renal artery stenosis Renal cell cancer Angiomyolipomas (noncancerous tumors of the ...

  9. Biomarkers of Renal Tumor Burden and Progression in TSC

    DTIC Science & Technology

    2013-09-01

    AD_________________ Award Number: W81XWH-10- 1 -0433 TITLE: Biomarkers of Renal Tumor Burden and...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...ADDRESS. 1 . REPORT DATE September 2013 2. REPORT TYPE Final 3. DATES COVERED 1 September 2010 - 31 August 2013 4. TITLE AND SUBTITLE 5a

  10. Management of pediatric renal tumor: Past and future trials of the Japan Wilms Tumor Study Group.

    PubMed

    Oue, Takaharu; Fukuzawa, Masahiro; Koshinaga, Tsugumichi; Okita, Hajime; Nozaki, Miwako; Chin, Motoki; Kaneko, Yasuhiko; Tanaka, Yukichi; Haruta, Masayuki; Tsuchiya, Kunihiko; Kuwajima, Shigeko; Takimoto, Tetsuya

    2015-10-01

    The Japan Wilms Tumor Study group (JWiTS) was founded in 1996 to improve outcomes for children with renal tumor in Japan, and a nationwide multicenter cooperative study was initiated thereafter. JWiTS-1 (1996-2005) was analyzed, and JWiTS-2 (2005-2014) is now under analysis; the following problems have been identified and used to decide future study protocol: (i) there has been a decline in survival rate for patients with rhabdoid tumor of the kidney (RTK) and new treatment strategies are required; (ii) the survival rate for bilateral Wilms tumors (BWT) has improved, but results for renal preservation are unsatisfactory; (iii) the prognosis of stage IV favorable nephroblastoma is very good, suggesting that the current protocols provide overtreatment, particularly for patients with lung metastasis; and (iv) no effective biological risk factors exist for predicting the outcome of Wilms tumor, and a study of the genetic changes of these tumors is necessary to determine biological markers for use in risk classification. To solve these issues, the development of a new risk classification of pediatric renal tumors is required. In addition, different study protocols should be developed according to the risk-based classification of the patients. Further, a new study protocol for BWT began in 2015, and new study protocols are being prepared for RTK, and for Wilms tumor with lung metastasis. In addition, an analysis of biological markers with regard to risk classification is to be performed. Furthermore, to create new protocols for patients with rare renal tumors, international collaboration with Children's Oncology Group and International Society of Pediatric Oncology is necessary.

  11. Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation.

    PubMed Central

    Terpe, H. J.; Störkel, S.; Zimmer, U.; Anquez, V.; Fischer, C.; Pantel, K.; Günthert, U.

    1996-01-01

    CD44 isoforms have been implicated in tumor progression and embryogenesis. Primary renal cell tumors (n = 100) of various histopathological differentiation and grading stages were analyzed for expression of CD44 isoforms in comparison with nonmalignant adult and fetal renal tissues. Evaluations were performed by immunohistochemistry using CD44 isoform-specific monoclonal antibodies and by reverse transcriptase polymerase chain reactions (RT-PCR). In the nonmalignant kidney no CD44 variant isoforms were detected. There was a significant increase in expression of CD44 standard (CD44s) and several variant isoforms (CD44v) in the course of tumor differentiation in clear cell carcinomas (n = 68) from stages G1 to G3 (P < 0.0001 for CD44s and isoforms containing CD44-6v, and P < 0.007 for those containing CD44-9v). Also, in chromophilic cell carcinomas (n = 13), CD44 isoform expression correlated with grading; ie, no CD44 expression was detected in G1 tumors, whereas in approximately 50% of the G2 tumors, CD44s, CD44-6v, and CD44-9v isoforms were present. Oncocytomas (n = 8), which are benign renal cell tumors, did not express CD44 isoforms, whereas invasive chromophobe cell carcinomas (n = 11) were positive for CD44s and CD44v isoforms. Transcript analyses by RT-PCR revealed that the upregulated isoforms in the carcinoma cells contained exons 8 to 10 and 3, 8 to 10 in combination from the variant region. In conclusion, expression of variant CD44 isoforms was strongly correlated with grading and appears to mediate a more aggressive phenotype to renal cell tumors. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:8579108

  12. Benign and tumor parenchyma metabolomic profiles affect compensatory renal growth in renal cell carcinoma surgical patients

    PubMed Central

    Rubinstein, Nimrod D.; Reznik, Ed; Shingarev, Roman; Juluru, Krishna; Akin, Oguz; Hsieh, James J.; Jaimes, Edgar A.; Russo, Paul; Susztak, Katalin; Coleman, Jonathan A.; Hakimi, A. Ari

    2017-01-01

    Background and objectives Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship. Design, setting, participants, and measurements Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG. Contra-lateral kidney volume fold-change within a 3.3 +/- 2.1 years follow-up interval was used as a surrogate for long-term CRG. Using a multivariable statistical model, we identified metabolites whose abundances significantly associate with CRG. Results Our analysis found 13 metabolites in the benign (e.g. L-urobilin, Variable Influence in Projection, VIP, score = 3.02, adjusted p = 0.017) and 163 metabolites in the malignant (e.g. 3-indoxyl-sulfate, VIP score = 1.3, adjusted p = 0.044) tissues that significantly associate with CRG. Benign/tumor fold change in metabolite abundances revealed three additional metabolites with that significantly positively associate with CRG (e.g. p-cresol sulfate, VIP score = 2.945, adjusted p = 0.033). At the pathway level, we show that fatty-acid oxidation is highly enriched with metabolites whose benign tissue abundances strongly positively associate with CRG, both pre-operatively and long term, whereas in the tumor tissue significant enrichment of dipeptides and benzoate (positive association), glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative associations) sub-pathways, were observed. Conclusion These data suggest that specific biological processes in the benign as well as in the tumor parenchyma strongly influence compensatory renal growth. PMID

  13. Calponin h1 expression in renal tumor vessels: correlations with multiple pathological factors of renal cell carcinoma.

    PubMed

    Islam, A H M Manjurul; Ehara, Takashi; Kato, Haruaki; Hayama, Masayoshi; Kobayashi, Shinya; Igawa, Yasuhiko; Nishizawa, Osamu

    2004-03-01

    We determined whether the architecture of renal tumor vessels is immunohistochemically different from that of normal renal vessels and related to the various pathological factors that affect prognosis of renal cell carcinoma (RCC). A total of 52 cases of primary RCC were selected. Tissues from radical nephrectomy specimens were stained with antibody to alpha-smooth muscle actin (alpha-SMA) and calponin h1. Immunostaining was evaluated semiqualitatively as 0-no staining to 3+-strong staining. Tumor cell proliferation was observed using proliferating marker Ki-67. Data were statistically compared with pathological factors, such as tumor size, histological pattern, growth pattern, cell type, nuclear grade, pathological stage and presence or absence of venous invasion. In normal renal tissues smooth muscle cells of the blood vessels showed strong immunoreactions with antibody to calponin h1 and alpha-SMA. Although alpha-SMA antibody showed similar strong immunoreactions in all types of renal tumor vessels, we observed qualitative alterations in the expression of calponin h1 in different types of RCCs. Strong to moderate immunoreactions with calponin h1 were observed in tumors with expansive growth and an alveolar pattern. Small tumors without venous invasion and chromophobe cell carcinomas also showed strong to moderate expression of calponin h1. Weak or absent expression of calponin h1 was observed significantly in infiltrating tumors, sarcomatous type, large, high grade and high stage tumors associated with significantly higher proliferating indexes. Our results strongly suggest that the renal tumor vessels are immunohistochemically different from normal renal vessels in respect to calponin h1 expression. We speculate that due to the decrease in or absence of calponin h1 tumor vessels do not develop adequate maturity to maintain vascular integrity. In addition, the distribution of calponin h1 significantly correlated with multiple pathological factors of RCC

  14. Increased risk of solid renal tumors in lithium-treated patients.

    PubMed

    Zaidan, Mohamad; Stucker, Fabien; Stengel, Bénédicte; Vasiliu, Viorel; Hummel, Aurélie; Landais, Paul; Boffa, Jean-Jacques; Ronco, Pierre; Grünfeld, Jean-Pierre; Servais, Aude

    2014-07-01

    Cystic kidney diseases and toxic interstitial nephritis may be complicated by renal tumors. Long-term lithium intake is associated with tubulointerstitial nephritis and renal cysts but to date such an association with tumors has not been determined. We evaluated this in a retrospective study to determine whether lithium-treated patients were at higher risk of renal tumors compared with lithium-free patients with chronic kidney disease (CKD), and to the general population. Over a 16-year period, 14 of 170 lithium-treated patients had renal tumors, including seven malignant and seven benign tumors. The mean duration of lithium exposure at diagnosis was 21.4 years. The renal cancers included three clear-cell and two papillary renal cell carcinomas, one hybrid tumor with chromophobe and oncocytoma characteristics, and one clear-cell carcinoma with leiomyomatous stroma. The benign tumors included four oncocytomas, one mixed epithelial and stromal tumor, and two angiomyolipomas. The percentage of renal tumors, particularly cancers and oncocytomas, was significantly higher in lithium-treated patients compared with 340 gender-, age-, and estimated glomerular filtration rate (eGFR)-matched lithium-free patients. Additionally, the Standardized Incidence Ratio of renal cancer was significantly higher in lithium-treated patients compared with the general population: 7.51 (95% confidence interval (CI) (1.51-21.95)) and 13.69 (95% CI (3.68-35.06)) in men and women, respectively. Thus, there is an increased risk of renal tumors in lithium-treated patients.

  15. Renal carcinoid tumor with liver metastasis followed up postoperatively for 9 years.

    PubMed

    Ouyang, BinShen; Ma, XiaoMei; Yan, HongZhu; He, Jin; Xia, ChunYan; Yu, HongYu

    2015-10-06

    We describe a case of renal carcinoid tumor with liver metastasis followed up postoperatively for 9 years. A 33-year-old man presented with left flank dull ache. On the abdominal computed tomography, a solid renal mass in the upper portion of the left kidney was detected. The patient had no other abnormal findings, such as suspected distant metastasis or lymph node metastasis. Radical nephrectomy was performed on 14/9/2005. Histological examination and immunohistochemical staining confirm primary renal carcinoid tumor. 9 years after radical nephrectomy, computed tomography of the abdomen demonstrated a 2 cm × 1.8 cm cyst mass in the right liver. Similar pathologic characteristics were found between the renal carcinoid tumor and liver tumor. We present a primary renal carcinoid tumor with liver metastasis 9 years after radical nephrectomy. With literature review, renal carcinoid tumors exhibit heterogenous behavior.

  16. CT and MRI Findings in a Rare Case of Renal Primitive Neuroectodermal Tumor

    PubMed Central

    Akkaya, Zehra; Peker, Elif; Gulpinar, Basak; Karadag, Hale; Erden, Ayse

    2016-01-01

    Summary Background Primary renal primitive neuroectodermal tumor/extraskeletal Ewing’s sarcoma (PNET/EES) is a very rare renal tumor. Case Report We report a case of primary renal PNET/EES of the kidney in an adult patient and describe its computed tomography and magnetic resonance imaging findings, including diffusion weighted images along with a review of the current medical literature. Conclusions Although very rare, a relatively large renal mass which shows very infiltrative growth pattern on CT and MR imaging and striking diffusion restriction should raise the suspicion of a renal primitive neuroectodermal tumor, in a young adult. PMID:27635170

  17. Clear cell renal cell tumors: Not all that is "clear" is cancer.

    PubMed

    Williamson, Sean R; Cheng, Liang

    2016-07-01

    Continued improvement of our understanding of the clinical, histologic, and genetic features of renal cell tumors has progressively evolved renal tumor classification, revealing an expanding array of distinct tumor types with different implications for prognosis, patient counseling, and treatment. Although clear cell renal cell carcinoma is unequivocally the most common adult renal tumor, there is growing evidence that some "clear cell" renal neoplasms, such as exemplified by multilocular cystic clear cell renal neoplasm of low malignant potential (formerly multilocular cystic renal cell carcinoma), do not have the same potential for insidious progression and metastasis, warranting reclassification as low malignant potential tumors or benign neoplasms. Still other novel tumor types such as clear cell papillary renal cell carcinoma have been more recently recognized, which similarly have shown a conspicuous absence of aggressive behavior to date, suggesting that these too may be recategorized as noncancerous or may be premalignant neoplasms. This importance for prognosis is increasingly significant in the modern era, in which renal masses are increasingly found incidentally by imaging techniques at a small tumor size, raising consideration for less aggressive management options guided by renal mass biopsy diagnosis, including imaging surveillance, tumor ablation, or partial nephrectomy.

  18. Chronic kidney disease in children with unilateral renal tumor.

    PubMed

    Cozzi, Denis A; Ceccanti, Silvia; Frediani, Simone; Schiavetti, Amalia; Cozzi, Francesco

    2012-05-01

    In patients who have undergone nephrectomy lower stage chronic kidney disease may develop, which is an independent risk factor for cardiovascular disease and overall mortality. We investigated whether the prevalence of lower stage chronic kidney disease is related to the amount of renal parenchyma excised in children with unilateral renal tumor. A total of 15 patients treated with nephrectomy and 10 treated with nephron sparing surgery were enrolled at a single academic center. The Kidney Disease Outcomes Quality Initiative guidelines were used to classify patients by chronic kidney disease stage based on estimated glomerular filtration rate values. The Modification of Diet in Renal Disease study equation and Schwartz equation were used in patients older and younger than 17 years, respectively. At a mean followup of more than 12 years 8 patients who had undergone nephrectomy and 1 treated with bilateral nephron sparing surgery presented with stage II chronic kidney disease (estimated glomerular filtration rate 60 to 89 ml/min/1.73 m(2)). Sequential measurements from diagnosis to 12 to 17 years postoperatively showed that stage II chronic kidney disease in patients who had undergone nephrectomy manifested as a negligible postoperative increase in mean ± SD estimated glomerular filtration rate (75.7 ± 25.5 vs 79.4 ± 3.9 ml/min/1.73 m(2), p = 0.6). Five of the 8 patients presented with stage II chronic kidney disease even before nephrectomy. The other 7 patients who had undergone nephrectomy and those treated with nephron sparing surgery presented with a significant postoperative increase in mean ± SD estimated glomerular filtration rate (81.1 ± 24 vs 102.3 ± 3 ml/min/1.73 m(2), p = 0.02, and 88.7 ± 2 vs 107.4 ± 14 ml/min/1.73 m(2), p = 0.005, respectively). A subset of children with unilateral renal tumor presents before and/or after nephrectomy, and not after nephron sparing surgery, with stage II chronic kidney disease, probably due to a reduced renal

  19. Clinical management of renal cell carcinoma with venous tumor thrombus.

    PubMed

    Agochukwu, Nnenaya; Shuch, Brian

    2014-06-01

    Venous invasion is common in advanced renal cell carcinoma (RCC) due to the unique biology of this cancer. The presence of a tumor thrombus often makes clinical management challenging. In this review, we detail specific preoperative, perioperative, and surgical strategies involving the care of the complex kidney cancer patient with venous tumor involvement. We performed a comprehensive review of selected peer-reviewed publications regarding RCC tumor thrombus biology, medical and surgical management techniques, and immediate and long-term outcomes. The perioperative management may require special imaging techniques, preoperative testing, very recent imaging, and consultation with other surgical services. There are various approaches to these patients as the clinical presentation, stage of disease, primary tumor size, level of thrombus, degree of venous occlusion, presence of bland thrombus, and primary tumor laterality influence management. Select patients with metastatic disease can do well with cytoreductive nephrectomy and thrombectomy. Those with localized disease have a high risk of recurrence; however, some patients can exhibit durable survival with surgery alone. The evolving surgical and medical treatments are discussed. Even when these surgeries are performed in high volume centers, significant perioperative complications are common and greater complications are seen with higher thrombus extent. If surgery is attempted, it is important for urologic oncologists to follow strict attention to specific surgical principles. These general principles include complete vascular control, avoidance of thrombus embolization, close hemodynamic monitoring, and institutional resources for caval resection/replacement and venous bypass if necessary.

  20. Lin28 sustains early renal progenitors and induces Wilms tumor.

    PubMed

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S; Zhu, Hao; Perez-Atayde, Antonio R; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q

    2014-05-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis.

  1. Renal Function Recovery after Nephrectomy or Nephron-Sparing Surgery in Children with Unilateral Renal Tumor.

    PubMed

    Cozzi, Denis A; Ceccanti, Silvia; Cozzi, Francesco

    2017-02-01

    Introduction Children with unilateral renal tumor (URT) and preoperative renal dysfunction (PRD) may benefit from nephron-sparing surgery (NSS). To test this hypothesis, we studied the outcome of baseline renal function after nephrectomy or NSS among children with URT. Materials and Methods Retrospective records review of children with URT who underwent nephrectomy (25 children) or NSS (11 children) at our institution. We analyzed the estimated glomerular filtration rate (eGFR) changes over time among patients, stratified by both preoperative renal function (with or without PRD) and surgical extent (NSS vs. nephrectomy). The primary end point was evaluation of compensatory recovery of preoperative eGFR after surgery. Only children older than 2 years at surgery were included in the study. Renal dysfunction was defined as an eGFR < 90 mL/min/1.73 m(2). Results After nephrectomy or NSS, patients with PRD presented, on average during adolescence, a significant increase in eGFR, whereas patients without PRD presented, on average during adolescence, a stable eGFR. However, after nephrectomy, 5 of 17 (29%) and 7 of 8 (87%) adolescent patients with baseline eGFR ≤ or > 100 mL/min/1.73 m(2), respectively, achieved or maintained two-kidney eGFR values (T-KEV) (p = 0.01). After NSS, four adolescent patients with PRD and seven without PRD achieved or maintained T-KEV. Conclusion The majority of children with URT and low baseline eGFR present with an impaired renal function recovery after nephrectomy and may benefit from NSS. Collaborative studies are needed to support present findings. Georg Thieme Verlag KG Stuttgart · New York.

  2. Obesity triggers enhanced MDSC accumulation in murine renal tumors via elevated local production of CCL2.

    PubMed

    Hale, Malika; Itani, Farah; Buchta, Claire M; Wald, Gal; Bing, Megan; Norian, Lyse A

    2015-01-01

    Obesity is one of the leading risk factors for developing renal cell carcinoma, an immunogenic tumor that is treated clinically with immunostimulatory therapies. Currently, however, the mechanisms linking obesity with renal cancer incidence are unclear. Using a model of diet-induced obesity, we found that obese BALB/c mice with orthotopic renal tumors had increased total frequencies of myeloid-derived suppressor cells (MDSC) in renal tumors and spleens by d14 post-tumor challenge, relative to lean counterparts. Renal tumors from obese mice had elevated concentrations of the known myeloid cell chemoattractant CCL2, which was produced locally by increased percentages of dendritic cells, macrophages, B cells, and CD45- cells in tumors. MDSC expression of the CCL2 receptor, CCR2, was unaltered by obesity but greater percentages of CCR2+ MDSCs were present in renal tumors from obese mice. Of note, the intracellular arginase levels and per-cell suppressive capacities of tumor-infiltrating and splenic MDSCs were unchanged in obese mice relative to lean controls. Thus, our findings suggest that obesity promotes renal tumor progression via development of a robust immunosuppressive environment that is characterized by heightened local and systemic MDSC prevalence. Targeted intervention of the CCL2/CCR2 pathway may facilitate immune-mediated renal tumor clearance in the obese.

  3. MUTATIONS IN THE VHL GENE FRIOM POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMORS

    EPA Science Inventory

    Potassium bromate (KBrO3) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO3 in F344 rats. ...

  4. MUTATIONS IN THE VHL GENE FRIOM POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMORS

    EPA Science Inventory

    Potassium bromate (KBrO3) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO3 in F344 rats. ...

  5. Preserving Renal Function through Partial Nephrectomy Depends on Tumor Complexity in T1b Renal Tumors

    PubMed Central

    2017-01-01

    This study aimed to determine patients with T1b renal cell carcinoma (RCC) who could benefit from partial nephrectomy (PN) and method to identify them preoperatively using nephrometry score (NS). From a total of 483 radical nephrectomy (RN)-treated patients and 40 PN-treated patients who received treatment for T1b RCC between 1995 and 2010, 120 patients identified through 1:2 propensity-score matching were included for analysis. Probability of chronic kidney disease (CKD) until postoperative 5-years was calculated and regressed with respect to the surgical method and NS. Median follow-up was 106 months. CKD-probability at 5-years was 40.7% and 13.5% after radical and PN, respectively (P = 0.005). While PN was associated with lower risk of CKD regardless of age, comorbidity, preoperative estimated renal function, the effect was observed only among patients with NS ≤ 8 (P < 0.001) but not in patients with NS ≥ 9 (P = 0.746). Percent operated-kidney volume reduction and ischemia time were similar between the patients with NS ≥ 9 and ≤ 8. In the stratified Cox regression accounting for the interaction observed between the surgical method and the NS, PN reduced CKD-risk only in patients with NS ≤ 8 (hazard ratio [HR], 0.054; P = 0.005) but not in ≥ 9 (HR, 0.996; P = 0.994). In T1b RCC with NS ≥ 9, the risk of postoperative CKD was not reduced following PN compared to RN. Considering the potential complications of PN, minimally invasive RN could be considered with priority in this subgroup of patients. PMID:28145654

  6. Nephron-sparing surgery for renal tumor: a choice of treatment in an allograft kidney.

    PubMed

    Ribal, M J; Rodriguez, F; Musquera, M; Segarra, J; Guirado, L; Villavicencio, H; Alcaraz, A

    2006-06-01

    The incidence of de novo malignancies is an accepted complication of organ transplantation. Renal cell carcinoma (RCC) was 4.6% of cancers occurring de novo in organ allograft recipients compared with 3% in the general population. Less than 10% of these renal cancers affected the renal allograft. Among patients developing a renal tumor in the kidney allograft, transplant nephrectomy reduced the quality of life. For these patients for whom preservation of renal function is a relevant clinical consideration, partial nephrectomy may be considered the choice for treatment. Fifteen cases have been reported regarding conservative surgery on kidney transplant tumors. Herein we have reported three cases of renal masses in well-functioning kidney transplants that were successfully treated with nephon-sparing surgery. Our experience demonstrated that in selected patients, nephron-sparing surgery on a renal allograft represents a feasible approach for tumor removal with preservation of graft function.

  7. Composite renal cell carcinoma with clear cell renal cell carcinomatous and carcinoid tumoral elements: a first case report.

    PubMed

    Bressenot, A; Delaunay, C; Gauchotte, G; Oliver, A; Boudrant, G; Montagne, K

    2010-02-01

    Renal endocrine tumours are extremely rare, and carcinoid tumoral elements in renal cell carcinoma have never been reported. This is the first report of a composite renal cell carcinoma containing a clear cell renal cell carcinoma associated with carcinoid tumoral elements, in a patient with synchronous metastatic disease. In the absence of specific radiological and clinical manifestations, typical morphological features as well as an immunostaining profile of neuroendocrine differentiation were identified by microscopy. Secondary nodal and liver localisations were characterised by carcinoid elements only. Despite antiangiogenic therapy, liver metastasis progressed, suggesting that adjuvant therapy cannot be based on the presence of the clear cell renal cell carcinoma component. In this context, extensive tissue sampling is recommended to reveal the endocrine component that is the most aggressive element of such a composite carcinoma.

  8. Ossifying renal tumor of infancy: findings at ultrasound, CT and MRI.

    PubMed

    Lee, Sang Hwan; Choi, Young Hun; Kim, Woo Sun; Cheon, Jung-Eun; Moon, Kyung Chul

    2014-05-01

    A 4-month-old boy presented with persistent gross hematuria. At ultrasonography, a 3.5-cm echogenic mass with posterior shadowing and tumor vascularity was detected within the right renal pelvis. Precontrast CT showed a slightly hyperattenuating mass in the renal pelvis. At MRI the mass was heterogeneously hypointense on T2-weighted images and isointense on T1-weighted images. Contrast-enhanced CT and MRI both revealed peripheral enhancement of the mass. A histological diagnosis of ossifying renal tumor of infancy was made after open pyelostomy and tumor enucleation. We suggest that ossifying renal tumor of infancy should be considered when a mass with posterior acoustic shadowing and tumor vascularity on US, hyperattenuation on precontrast CT and hypointensity on T2-weighted MRI is seen within the renal pelvis of an infant with hematuria.

  9. [Renal carcinoid tumor presenting as bladder tamponade: a case report and review of the Japanese cases].

    PubMed

    Kajita, Yoichiro; Megumi, Yuzuru; Okabe, Tatsushiro

    2005-07-01

    A 65-year-old man presented with sudden onset of gross hematuria and urinary retention. Computed tomographic scan (CT) showed a cystic multilocular enhancing lesion (9 cm in diameter) at the left renal hilum causing thinning and lateral displacement of the left renal parenchyma. Left hydronephrosis and a renal calculi were observed. We performed radical nephrectomy suspecting a cystic renal cell carcinoma. Microscopic examination and immunohistochemical studies confirmed the diagnosis of the carcinoid tumor. The tumor cells were fully positive for neuron-specific enolase and keratin, and partially positive for chromogranin-A. One of the resected lymph nodes was positive for metastasis. Additional gastrointestinal tract examinations for carcinoid tumor were negative. However, he was concurrently diagnosed with poorly differentiated prostate cancer and hormonal therapy was started. He is free of recurrent carcinoid tumor nine months postoperatively. This case is the 31st report of renal carcinoid tumors in Japan.

  10. Angiomyolipoma with hypertension mimicking a malignant renal tumor.

    PubMed

    Springer, Alexander M; Saxena, Amulya K; Willital, Günter H

    2002-09-01

    A 13-month-old girl with a unilateral renal angiomyolipoma causing severe hypertension is reported. The differential diagnosis of renal masses, a review of the literature, and the diagnostic algorithm for renal masses used at our center are presented.

  11. Percutaneous irreversible electroporation of a renal tumor: Anesthetic management.

    PubMed

    de la Flor-Robledo, M; Solís-Muñoz, P; Sanjuán-Álvarez, M; Abadal-Villayandre, J M; Asensio-Merino, F

    2016-01-01

    Percutaneous irreversible electroporation (IRE) is a novel tumour ablation method. The application of short and high-voltage electrical pulses to the target lesion induces alterations in cell membrane permeability, finally causing tumour cell death. The extremely high-voltage that is needed in this technique requires the surveillance and management of an experienced anaesthesiologist, as it involves a significant risk of complications, such as cardiac arrhythmias or seizures. The case is presented of a 66 year-old patient diagnosed with a renal adenocarcinoma, and who received without intention-to-cure IRE under general anaesthesia. This case represents the first time this type of technique is used in Spain. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Study of molecule variations in renal tumor based on confocal micro-Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhuang, Zhengfei; Li, Ning; Guo, Zhouyi; Zhu, Meifang; Xiong, Ke; Chen, Sijin

    2013-03-01

    Confocal micro-Raman spectroscopy-a valuable analytical tool in biological and medical field of research-allows probing molecular vibrations of samples without external labels or extensive preparation. We employ confocal micro-Raman spectroscopy to characterize renal tumors and normal tissue. Results show that Raman peaks of the renal tumor at 788 and 1087 cm-1, which belong to νs and νas stretching, respectively, have an obvious increase. At the same time, the ratio of I855/I831 in renal tumor tissue is 1.39±0.08, while that in normal renal tissue is 2.44±0.05 (p<0.01). This means that more tyrosine conformation transform from "buried" to "exposed" in the presence of cancer. Principal component analysis is used to classify the Raman spectra of renal tumor tissue and normal tissue.

  13. New percutaneous ablative modalities in nephron-sparing surgery of small renal tumors

    NASA Astrophysics Data System (ADS)

    de Riese, Werner T. W.; Nelius, Thomas; Aronoff, David R.; Mittemeyer, Bernhard T.

    2004-07-01

    Renal tumors are increasingly detected on abdominal imaging studies. Standard treatment of small renal tumors includes partial or radical nephrectomy, done either open or laparoscopically. Several in situ ablative techniques to treat small renal lesions are currently in various phases of evolution. All involve imparting destructive energy to the tumor while minimizing injury to adjacent normal tissue. Cryotherapy (CryoT), radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFUS) and high-intensity radiation (HIR) are all being evaluated as tools to ablate renal tumors. The goal with these modalities is to minimize the blood loss, tissue manipulation, and morbidity associated with excisional approaches. Animal studies have shown that large, reproducible lesions can be ablated in normal kidney tissue by these new techniques. Studies of human renal tissue response to RFA are just beginning. Ex vivo studies reveal large, reproducible controlled lesions in normal renal tissue, similar to animal studies. In vivo studies have shown no significant toxicity, while efficacy is currently under evaluation. Preliminary clinical studies in humans have revealed that renal tumors are slow to regress after treatment, but about 75% of these small renal tumors appeared well treated. Mixed responses have been observed in the remaining cases. This paper presents a concise review of efficacy, advantages and disadvantages of these new minimal invasive techniques and their possible clinical implication in the future.

  14. Primary nephrectomy and intraoperative tumor spill: report from the Children's Oncology Group (COG) renal tumors committee.

    PubMed

    Gow, Kenneth W; Barnhart, Douglas C; Hamilton, Thomas E; Kandel, Jessica J; Chen, Mike K S; Ferrer, Fernando A; Price, Mitchell R; Mullen, Elizabeth A; Geller, James I; Gratias, Eric J; Rosen, Nancy; Khanna, Geetika; Naranjo, Arlene; Ritchey, Michael L; Grundy, Paul E; Dome, Jeffrey S; Ehrlich, Peter F

    2013-01-01

    Initial Children's Oncology Group (COG) management for Wilms' tumor (WT) consists of primary nephroureterectomy with lymph node sampling. While this provides accurate staging to define further treatment, it may result in intraoperative spill (IOS), which is associated with higher recurrence rates and therefore requires more intensive therapy. The purpose of this study is to determine current rates and identify factors which may predispose a patient to IOS. The study population was drawn from the AREN03B2 renal tumor banking and classification study of the Children's Oncology Group. All children with a first time occurrence of a renal mass were eligible for the study. At the time of enrollment and prior to risk stratification, the institution is required to submit operative notes, pathology specimens, a chest computed tomography scan (CT), and a contrast-enhanced CT or magnetic resonance imaging (MRI) of the abdomen and pelvis for central imaging review. These data are then used to determine an initial risk classification and therapeutic protocol eligibility. Patients who had a unilateral nephroureterectomy for favorable histology WT underwent further review to assure data accuracy and to clarify details regarding the spill. Analyses were performed using chi square and logistic regression. Odd ratios (OR) are shown with 95% confidence intervals. There were 1,131 primary nephrectomies for unilateral WT with an IOS rate of 9.7% with an additional 1.8% having possible tumor spill during renal vein or IVC tumor thrombectomy. IOS correlated with diameter (>12 cm, p<0.0001) and laterality (right, p=0.0414). Simple logistic regression indicated that IOS increased 2.7% [p=0.0240, OR 1.027 (1.004, 1.052)] with each 1 cm increase in diameter (3 - 21 cm) and 4.7% [p=0.0147 OR 1.047 (1.009, 1.086)] with each 100 g increase in weight (80 - 1800 g). Multiple logistic regression indicated that laterality [right p=0.048, OR 1.46 (1.004, 2.110)] and weight (p=0.03, OR 1.039 (1

  15. Modification of Antitumor Immunity and Tumor Microenvironment by Resveratrol in Mouse Renal Tumor Model.

    PubMed

    Chen, Liang; Yang, Sixing; Liao, Wenbiao; Xiong, Yunhe

    2015-06-01

    Renal cell carcinoma (RCC) microenvironment plays critical roles in antitumor immune response. Resveratrol exhibits a direct antitumor effect in various tumor models. However, the immunomodulatory effect of resveratrol on RCC microenvironment is unknown. In this study, we found that administration of low dose of resveratrol inhibits Renca tumor growth and its inhibition effect depends on CD8(+) T cells. Moreover, the proportion of regulatory T cells is decreased, while the proportion of myeloid-derived suppressor cells does not alter after resveratrol treatment. More importantly, massive amount of activated CD8(+) T cells accumulates in tumor microenvironment in the resveratrol-treated group and shows increased cytotoxicity, as indicated by a higher expression of Fas ligand. We also found that resveratrol switches the expression of T-helper (Th) 2 cytokines such as interleukin (IL)-6 and IL-10 to Th 1 cytokines with dominance of interferon (IFN)-γ, which increases the expression of Fas in Renca cells. Furthermore, we found resveratrol down-regulates angiogenesis along with decreased level of vascular endothelial growth factor in tumor microenvironment. Our results strongly suggest that resveratrol might be used for RCC immunotherapy through modulating tumor microenvironment.

  16. CA9 as a molecular marker for differential diagnosis of cystic renal tumors.

    PubMed

    Li, Guorong; Bilal, Issam; Gentil-Perret, Anne; Feng, Gang; Zhao, An; Peoc'h, Michel; Genin, Christian; Tostain, Jacques; Gigante, Marc

    2012-01-01

    CA9 is proven to be a powerful marker for clear cell renal cell carcinoma. The studies on CA9 have been limited to solid renal cell carcinomas (RCC). We have conducted a study of CA9 expression in renal cystic tumors. The purpose of the present study was to extend the utility of CA9 for cystic renal tumors. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to detect CA9 expression in cystic renal tumors. Forty-three cystic renal tumors (22 benign and 21 malignant) were included for the immunohistochemical staining. Thirty-six patients with a cystic renal mass (20 malignant and 16 benign cystic tumors) were studied to measure CA9 level in the fluid by ELISA. Sixteen cysts (9 malignant and 7 benign cysts) were subjected both to immunohistochemistry and CA9 measurement in the fluid. Using immunohistochemical staining, all the benign cystic renal tumors including the 18 simple cyst and 4 benign multilocular cystic nephromas did not express CA9. All 13 cystic clear cell RCC were scored as strong staining for CA9. For 8 multilocular clear cell RCC, 7 were scored as strong staining for CA9 and the other one was negative. There was a significant difference in positive percentage (P < 0.001) between the 2 groups of malignant and benign cysts. For the 16 benign cysts, the mean concentration of CA9 in the fluid of cyst was 162 ± 133 pg/ml (median: 0 pg/ml; range: 0-2140 pg/ml). For the 20 malignant renal cystic tumors, the mean concentration of CA9 in the fluid of cyst was 2043 ± 62 pg/ml (median: 2,140 pg/ml; range: 1,112-2,140 pg/ml). There was a significant difference in mean concentration of CA9 between the two groups of malignant and benign cysts (P < 0.001). The presence or absence of CA9 expression measured by immunohistochemistry and ELISA test was concordant in 14 out of 16 cases (88%). Malignant cystic renal tumors expressed strongly CA9 while the benign renal cysts did not express CA9. CA9 can be detected in the fluid of malignant

  17. CT of acquired cystic kidney disease and renal tumors in long-term dialysis patients

    SciTech Connect

    Levine, E.; Grantham, J.J.; Slusher, S.L.; Greathouse, J.L.; Krohn, B.P.

    1984-01-01

    The kidneys of long term dialysis patients frequently demonstrate multiple small acquired cysts and renal cell tumors on pathologic examination. The original kidneys of 30 long-term dialysis patients and six renal transplant patients were evaluated by computed tomography to determine the incidence of these abnormalities. Among dialysis patients, 43.3% had diffuse bilateral cysts, while 16.7% had occasional cysts (fewer than five per kidney), and 40% showed no renal cysts. Seven solid renal tumors were detected in four dialysis patients with renal cysts. Acquired cystic kidney disease tends to result in renal enlargement, is more common in patients who have been maintained on dialysis for prolonged periods, and may lead to spontaneous renal hemorrhage. The six transplant patients showed no evidence of renal cysts, and all had markedly shrunken kidneys. Acquired cystic disease and renal cell tumors in the original kidneys of dialysis patients may be due to biologically active substances that are not cleared effectively by dialysis but that are removed by normally functioning transplant kidneys.

  18. Review of renal carcinoid tumor with focus on clinical and pathobiological aspects.

    PubMed

    Kuroda, N; Tanaka, A; Ohe, C; Mikami, S; Nagashima, Y; Inoue, K; Shuin, T; Taguchi, T; Tominaga, A; Alvarado-Cabrero, I; Petersson, F; Brunelli, M; Martignoni, G; Michal, M; Hes, O

    2013-01-01

    Renal carcinoid tumor is a rare neoplasm. In this article, we review this neoplasm with a focus on clinical and pathobiological aspects. The majority of patients present in the fourth to seventh decades, but there is no gender predilection. Clinically, patients with renal carcinoid tumor frequently present with abdominal, back or flank pain. This tumor is occassionally associated with horseshoe kidney and/or mature cystic teratoma located in the kidney. Macroscopically, these tumors are well demarcated with a lobulated appearance and yellow or tan-brown color cut surface. Microscopically, these tumors are composed of monomorphic round to polygonal cells with granular amphophilic to eosinophilic cytoplasm. Tumor cells are arranged in trabecular, ribbon-like, gyriform, insular, glandular and solid patterns. The nuclei are round to oval and with evenly distributed nuclear chromatin, frequently with a "salt and pepper"-pattern. Immunohistochemically, tumor cells demonstrate immuno-labeling for chromogranin A and synaptophysin. Ultrastructurally, the neoplastic cells contain abundant dense core neurosecretory granules. In previous genetic studies, abnormalities of chromosomes 3 or 13 have been reported. The clinical behavior of renal carcinoid tumors is variable, but is more indolent than most renal cell carcinomas. Further investigations are warranted in order to elucidate the critical genetic abnormalities responsible for the pathogenesis of this rare entity in renal neoplastic pathology.

  19. Clear Cell Papillary Renal Cell Carcinoma and Renal Angiomyoadenomatous Tumor – Two Variants of a Morphologic, Immunohistochemical and Genetic Distinct Entity of Renal Cell Carcinoma

    PubMed Central

    Deml, Karl-Friedrich; Schildhaus, Hans-Ulrich; Compérat, Eva; von Teichman, Adriana; Storz, Martina; Schraml, Peter; Bonventre, Joseph V.; Fend, Falko; Fleige, Barbara; Nerlich, Andreas; Gabbert, Helmut Erich; Gaβler, Nikolaus; Grobholz, Rainer; Hailemariam, Seife; Hinze, Raoul; Knüchel, Ruth; Lhermitte, Benoit; Nesi, Gabriella; Rüdiger, Thomas; Sauter, Guido; Moch, Holger

    2015-01-01

    Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary renal cell carcinoma (pRCC). It is a matter of controversy whether their morphologic, immunophenotypic and molecular features allow the definition of a separate renal carcinoma entity. The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT. We investigated 28 ccpRCC and 9 RAT samples by immunohistochemistry using 25 markers. VHL gene mutations and allele losses were investigated by Sanger sequencing and fluorescence in situ hybridization (FISH). Clinical follow-up data were obtained for a subset of the patients. No tumor recurrence or tumor-related death was observed in any of the patients. Immunohistochemistry and molecular analyses led to the reclassification of three tumors as ccRCC and TFE3 translocation carcinomas. The immunohistochemical profile of ccpRCC and RAT samples was very similar but not identical, differing from both ccRCC and pRCC. Especially, the parafibromin and hKIM-1 expression exhibited differences in ccpRCC/RAT compared with ccRCC and pRCC. Genetic analysis revealed VHL mutations in 2/27 (7%) and 1/7 (14%) ccpRCC and RAT samples, respectively. FISH analysis disclosed a 3p loss in 2/20 (10 %) ccpRCC samples. ccpRCC and RAT have a specific morphologic and immunohistochemical profile but they share similarities with the more aggressive renal tumors. Based on our results, we regard ccpRCC/RAT as a distinct entity of renal cell carcinomas. PMID:25970683

  20. Renal Carcinoid Tumor Metastatic to the Uvea, Medial Rectus Muscle, and the Contralateral Lacrimal Gland.

    PubMed

    Kiratli, Hayyam; Uzun, Salih; Tarlan, Berçin; Ateş, Deniz; Baydar, Dilek Ertoy; Söylemezoğlu, Figen

    2015-01-01

    Renal carcinoid tumor is an exceedingly rare malignancy. A 57-year-old man with a renal carcinoid tumor discovered after metastasizing to intraocular and bilateral orbital structures is described. The patient presented with a blind painful OS and a right superotemporal subconjunctival mass. Imaging studies revealed a large left intraocular tumor, a mass in the left medial rectus muscle, and right lacrimal gland enlargement. The OS was enucleated, and incisional biopsies were performed from the other 2 lesions. Histopathological studies demonstrated metastatic neuroendocrine tumor with chromogranin and synaptophysin positivity. Systemic work up revealed a right renal mass and multiple hepatic metastatic lesions. Radical nephrectomy was performed, and octreotide, capecitabine, and temozolomide were administered. Removal of the primary tumor and the eye that had no prospect for useful vision and further treatment with octreotide, capecitabine, and temozolomide provided a disease progression-free period of 24 months and allowed the patient to function normally.

  1. [Tumor of upper urinary tract in renal polycystic disease].

    PubMed

    Rabii, Redouane; el Mejjad, Amine; Fekak, Hamid; Querfani, Baderdine; Joual, Abdenbi; el Mrini, Mohamed

    2003-09-01

    Upper urinary tract tumours are exceptional in the context of renal polycystic disease. The authors report the case of Mrs B. F., 56 years old, who presented with left loin pain associated with haematuria. Clinical examination was normal and ultrasound examination revealed bilateral renal polycystic disease with a mass in the left renal sinus. CT urography showed a tumour arising from the renal pelvis suggestive of an upper urinary tract tumour. The laboratory assessment revealed normal renal function and normal urine cytology. Treatment consisted of radical nephroureterectomy with resection of a bladder cuff. Histological examination revealed a urothelial tumour of the renal pelvis with negative surgical margins. In the light of this case, the authors discuss the diagnostic difficulties and specificities, the treatment and the outcome of this unusual clinical association.

  2. Loss of heterozygosity and SOSTDC1 in adult and pediatric renal tumors

    PubMed Central

    2010-01-01

    Background Deletions within the short arm of chromosome 7 are observed in approximately 25% of adult and 10% of Wilms pediatric renal tumors. Within Wilms tumors, the region of interest has been delineated to a 2-Mb minimal region that includes ten known genes. Two of these ten candidate genes, SOSTDC1 and MEOX2, are particularly relevant to tumor development and maintenance. This finding, coupled with evidence that SOSTDC1 is frequently downregulated in adult renal cancer and regulates both Wingless-Int (Wnt)- and bone morphogenetic protein (BMP)-induced signaling, points to a role for SOSTDC1 as a potential tumor suppressor. Methods To investigate this hypothesis, we interrogated the Oncomine database to examine the SOSTDC1 levels in adult renal clear cell tumors and pediatric Wilms tumors. We then performed single nucleotide polymorphism (SNP) and sequencing analyses of SOSTDC1 in 25 pediatric and 36 adult renal tumors. Immunohistochemical staining of patient samples was utilized to examine the impact of SOSTDC1 genetic aberrations on SOSTDC1 protein levels and signaling. Results Within the Oncomine database, we found that SOSTDC1 levels were reduced in adult renal clear cell tumors and pediatric Wilms tumors. Through SNP and sequencing analyses of 25 Wilms tumors, we identified four with loss of heterozygosity (LOH) at 7p and three that affected SOSTDC1. Of 36 adult renal cancers, we found five with LOH at 7p, two of which affected SOSTDC1. Immunohistochemical analysis of SOSTDC1 protein levels within these tumors did not reveal a relationship between these instances of SOSTDC1 LOH and SOSTDC1 protein levels. Moreover, we could not discern any impact of these genetic alterations on Wnt signaling as measured by altered beta-catenin levels or localization. Conclusions This study shows that genetic aberrations near SOSTDC1 are not uncommon in renal cancer, and occur in adult as well as pediatric renal tumors. These observations of SOSTDC1 LOH, however, did not

  3. Suprarenal inferior vena cava filter placement prior to transcatheter arterial embolization (TAE) of a renal cell carcinoma with large renal vein tumor thrombus: Prevention of pulmonary tumor emboli after TAE

    SciTech Connect

    Hirota, Shozo; Matsumoto, Shinnichi; Ichikawa, Satoshi; Tomita, Masaru; Koshino, Tukasa; Sako, Masao; Kono, Michio

    1997-03-15

    To prevent embolization of necrotic renal vein tumor after transcatheter embolization of a left renal cell carcinoma, we placed a suprarenal Bird's nest inferior vena cava filter. The patient tolerated the procedure well and had extensive tumor infarction including the tumor thrombus on 6-month follow-up computed tomography.

  4. Compensatory renal growth and function in postnephrectomized patients with Wilms tumor

    SciTech Connect

    Walker, R.D.; Reid, C.F.; Richard, G.A.; Talbert, J.L.; Rogers, B.M.

    1982-02-01

    The objective of this study was to determine whether or not renal growth and function were adversely affected in the remaining kidneys of patients who had undergone nephrectomy for Wilms tumor. These patients received chemotherapy and some radiotherapy (tumoricidal agents which might affect the remaining kidney). Renal growth was compared between the treatment groups and normal renal growth. Hypertrophy did occur and did not appear to be affected by subsequent treatment. Renal function was minimally altered in all treatment groups irrespective of the type of treatment.

  5. Left adrenal tumor extending into the renal vein: surgical management with ipsilateral kidney preservation.

    PubMed

    Doerfler, Arnaud; Vaudreuil, Lionel; Le Gal, Sophie; Lebreton, Gil; Tillou, Xavier

    2015-08-04

    If single adrenal metastasis surgery is well admitted, no recommendation exists about the management of a renal vein tumor thrombus, even though the actual consensual attitude consists in a nephrectomy associated to an adrenalectomy. We report, here, the case of a 74-year-old man with a suspected adrenal metastasis of a lung carcinoma associated with a left adrenal and renal vein tumor thrombus treated by adrenalectomy and renal vein thrombectomy and ipsilateral kidney sparing. The postoperative computed tomography scan showed no thrombus in the left renal vein. Doppler ultrasound performed 1 month after adrenalectomy proved a good left renal vein flux. At 36 months of follow-up, the patient is alive without signs of recurrence. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2015.

  6. Left adrenal tumor extending into the renal vein: surgical management with ipsilateral kidney preservation

    PubMed Central

    Doerfler, Arnaud; Vaudreuil, Lionel; Le Gal, Sophie; Lebreton, Gil; Tillou, Xavier

    2015-01-01

    If single adrenal metastasis surgery is well admitted, no recommendation exists about the management of a renal vein tumor thrombus, even though the actual consensual attitude consists in a nephrectomy associated to an adrenalectomy. We report, here, the case of a 74-year-old man with a suspected adrenal metastasis of a lung carcinoma associated with a left adrenal and renal vein tumor thrombus treated by adrenalectomy and renal vein thrombectomy and ipsilateral kidney sparing. The postoperative computed tomography scan showed no thrombus in the left renal vein. Doppler ultrasound performed 1 month after adrenalectomy proved a good left renal vein flux. At 36 months of follow-up, the patient is alive without signs of recurrence. PMID:26242191

  7. Renal mass biopsy using Raman spectroscopy identifies malignant and benign renal tumors: potential for pre-operative diagnosis.

    PubMed

    Liu, Yufei; Du, Zhebin; Zhang, Jin; Jiang, Haowen

    2017-05-30

    The accuracy of renal mass biopsy to diagnose malignancy can be affected by multiple factors. Here, we investigated the feasibility of Raman spectroscopy to distinguish malignant and benign renal tumors using biopsy specimens. Samples were collected from 63 patients who received radical or partial nephrectomy, mass suspicious of cancer and distal parenchyma were obtained from resected kidney using an 18-gauge biopsy needle. Four Raman spectra were obtained for each sample, and Discriminant Analysis was applied for data analysis. A total of 383 Raman spectra were eventually gathered and each type of tumor had its characteristic spectrum. Raman could separate tumoral and normal tissues with an accuracy of 82.53%, and distinguish malignant and benign tumors with a sensitivity of 91.79% and specificity of 71.15%. It could classify low-grade and high-grade tumors with an accuracy of 86.98%. Besides, clear cell renal carcinoma was differentiated with oncocytoma and angiomyolipoma with accuracy of 100% and 89.25%, respectively. And histological subtypes of cell carcinoma were distinguished with an accuracy of 93.48%. When compared with final pathology and biopsy, Raman spectroscopy was able to correctly identify 7 of 11 "missed" biopsy diagnoses. These results suggested that Raman may serve as a promising non-invasive approach in the future for pre-operative diagnosis.

  8. Effect of Stereotactic Body Radiotherapy on the Growth Kinetics and Enhancement Pattern of Primary Renal Tumors.

    PubMed

    Sun, Maryellen R M; Brook, Alexander; Powell, Michael F; Kaliannan, Krithica; Wagner, Andrew A; Kaplan, Irving D; Pedrosa, Ivan

    2016-03-01

    The objective of our study was to assess the growth rate and enhancement of renal masses before and after treatment with stereotactic body radiotherapy (SBRT). This retrospective study included all patients with renal masses who underwent SBRT during a 5-year period. Orthogonal measurements of renal masses were obtained on pre- and posttreatment CT or MRI. Pre- and posttreatment growth rates were compared for renal mass diameter and volume using the t test. Pre- and posttreatment tumor enhancement values were compared for tumors that underwent multiphasic contrast-enhanced MRI. Forty patients underwent SBRT for the treatment of 41 renal tumors: clear cell renal cell carcinomas (RCCs) (n = 16), papillary RCCs (n = 6), oncocytic neoplasms (n = 8), unclassified RCCs (n = 2), urothelial carcinoma (n = 1), and no pathologic diagnosis (n = 8). The mean maximum tumor diameter before treatment was 3.9 cm (range, 1.6-8.3 cm). Three hundred thirty-eight pre- and posttreatment imaging studies were analyzed: 214 MRI studies and 124 CT studies. The mean pre- and posttreatment lengths of observation were 416 days (range, 2-1800 days) and 561 days (83-1366 days), respectively. The mean pretreatment tumor growth rate of 0.68 cm/y decreased to -0.37 cm/y post treatment (p < 0.0001), and the mean tumor volume growth rate of 21.2 cm(3)/y before treatment decreased to -5.35 cm(3)/y after treatment (p = 0.002). Local control-defined as less than 5 mm of growth-was achieved in 38 of 41 (92.7%) tumors. The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 showed progression in one tumor (2.4%), stability in 31 tumors (75.6%), partial response in eight tumors (19.5%), and complete response in one tumor (2.4%). No statistically significant change in tumor enhancement was shown (mean follow-up, 142 days; range, 7-581 days). Renal tumors treated with SBRT show statistically significant reductions in growth rate and tumor size after treatment but do not show statistically significant

  9. Characterization of a splice-site mutation in the tumor suppressor gene FLCN associated with renal cancer.

    PubMed

    Bartram, Malte P; Mishra, Tripti; Reintjes, Nadine; Fabretti, Francesca; Gharbi, Hakam; Adam, Alexander C; Göbel, Heike; Franke, Mareike; Schermer, Bernhard; Haneder, Stefan; Benzing, Thomas; Beck, Bodo B; Müller, Roman-Ulrich

    2017-05-12

    Renal cell carcinoma is among the most prevalent malignancies. It is generally sporadic. However, genetic studies of rare familial forms have led to the identification of mutations in causative genes such as VHL and FLCN. Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors. Using Sanger sequencing we identify a heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient suffering from renal cell carcinoma. Furthermore, both tumor DNA and DNA from a metastasis are analyzed regarding this mutation. The pathogenic effect of the sequence alteration is confirmed by minigene assays and the biochemical consequences on the protein are examined using TALEN-mediated transgenesis in cultured cells. Here we describe an FLCN mutation in a 55-year-old patient who presented himself with progressive weight loss, bilateral kidney cysts and renal tumors. He and members of his family had a history of recurrent pneumothorax during the last few decades. Histology after tumor nephrectomy showed a mixed kidney cancer consisting of elements of a chromophobe renal cell carcinoma and dedifferentiated small cell carcinoma component. Subsequent FLCN sequencing identified an intronic c.1177-5_-3delCTC alteration that most likely affected the correct splicing of exon 11 of the FLCN gene. We demonstrate skipping of exon 11 to be the consequence of this mutation leading to a shift in the reading frame and the insertion of a premature stop codon. Interestingly, the truncated protein was still expressed both in cell culture and in tumor tissue, though it was strongly destabilized and its subcellular localization differed from wild-type FLCN. Both, altered protein stability and subcellular localization could be partly reversed by blocking proteasomal and lysosomal degradation. Identification of disease-causing mutations in BHD syndrome requires the

  10. [Conservative surgical treatment of renal carcinoma. Personal experience with 29 surgical excisions of tumors].

    PubMed

    Villani, U; Pastorello, M

    1991-03-01

    From 1980 to 1988, elective conservative surgery (tumorectomy by enucleo-resection) was performed for renal cell carcinoma at stage I in 29 patients. An accurate preoperative renal investigation was carried out to identify the exact extension of the tumor and to study all the parenchimal situation, through IVP, ultrasound, CT scanning and, particularly, conventional selective angiography. The operative technique employed was: lymphadenectomy, peri-pararenal fat extirpation, in situ tumor enucleation by circular incision of the renal capsule and blunt dissection of the renal parenchyma with 2 cm safety margin to the tumor; multiple biopsies in the "bed" of resection for histopathologic peroperative evaluation; careful examination of the pseudocapsule and surrounding renal tissue; hemostasis. Follow-up was 10-113 months (mean 40,34 months). 2 of 29 patients died for progression of disease (at 52nd and 16yh month from surgery, 2/29 died for non-neoplastic reasons; 25/29 pts are living without local recurrences or distant metastases. In the same period (1980-1988), radical nephrectomy was performed for renal tumors at stage I in 34 patients. In an average observation period of 49,67 months, 2/34 patients died for progression of disease; 3/34 pts died for non-neoplastic reasons. 1/34 patient is living with pulmonar metastases and 28/34 are living without evidence of cancer. From this study we have got the conclusion that elective renal-sparing excision of the tumor (with macro-micro examination of the abscission surfaces) should be considered as a curative treatment in the case of low stage single tumors smaller than 7 cm, peripherally located in renal cortex, with unbroken pseudocapsule.

  11. Tubulocystic carcinoma of the kidney: a new entity among renal tumors.

    PubMed

    Azoulay, Sandy; Vieillefond, Annick; Paraf, François; Pasquier, Dominique; Cussenot, Olivier; Callard, Patrice; Sibony, Mathilde

    2007-11-01

    Tubulocystic carcinoma is a tumor entity, which is not yet included in the WHO-classification of renal tumors. We report a series of 11 cases of this tumor, 6 of which were examined in by immunohistochemistry using a panel of five antibodies (CK7, CK34betaE12, CK19, CD10 and P504S). All patients were men. Each had renal tumor stage of pT1N0M0, with a diameter of 1.7 to 7 cm (mean, 3.3 cm). None of the patients presented with recurrence or metastases. Grossly, tumors were microcystic masses with a bubble-wrap appearance. Histological features included cysts and small tubules, separated by delicate septa and lined by flat to columnar or hobnail cells. The cyst and tubule epithelium showed immunohistochemical characteristics of both proximal and distal tubules. Tubulocystic carcinoma is a distinctive kidney tumor, with noteworthy macroscopic and microscopic characteristics, which can be distinguished from other cystic kidney tumors, including cystic nephroma, multilocular cystic renal cell carcinoma and some solid tumors with extensive cystic changes. More cases are needed to ascertain its prognosis. Tubulocystic carcinoma should be considered as a new subtype of renal cell carcinoma in the next revision of the WHO classification.

  12. Folliculin Contributes to VHL Tumor Suppressing Activity in Renal Cancer through Regulation of Autophagy

    PubMed Central

    Kellner, Emily; Mikhaylova, Olga; Yi, Ying; Sartor, Maureen A.; Medvedovic, Mario; Biesiada, Jacek; Meller, Jarek; Czyzyk-Krzeska, Maria F.

    2013-01-01

    Von Hippel-Lindau tumor suppressor (VHL) is lost in the majority of clear cell renal cell carcinomas (ccRCC). Folliculin (FLCN) is a tumor suppressor whose function is lost in Birt-Hogg-Dubé syndrome (BHD), a disorder characterized by renal cancer of multiple histological types including clear cell carcinoma, cutaneous fibrofolliculoma, and pneumothorax. Here we explored whether there is connection between VHL and FLCN in clear cell renal carcinoma cell lines and tumors. We demonstrate that VHL regulates expression of FLCN at the mRNA and protein levels in RCC cell lines, and that FLCN protein expression is decreased in human ccRCC tumors with VHL loss, as compared with matched normal kidney tissue. Knockdown of FLCN results in increased formation of tumors by RCC cells with wild-type VHL in orthotopic xenografts in nude mice, an indication that FLCN plays a role in the tumor-suppressing activity of VHL. Interestingly, FLCN, similarly to VHL, is necessary for the activity of LC3C-mediated autophagic program that we have previously characterized as contributing to the tumor suppressing activity of VHL. The results show the existence of functional crosstalk between two major tumor suppressors in renal cancer, VHL and FLCN, converging on regulation of autophagy. PMID:23922894

  13. The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

    PubMed

    Golovastova, Marina O; Tsoy, Larisa V; Bocharnikova, Anna V; Korolev, Dmitry O; Gancharova, Olga S; Alekseeva, Ekaterina A; Kuznetsova, Ekaterina B; Savvateeva, Lyudmila V; Skorikova, Elena E; Strelnikov, Vladimir V; Varshavsky, Vladimir A; Vinarov, Andrey Z; Nikolenko, Vladimir N; Glybochko, Peter V; Zernii, Evgeni Yu; Zamyatnin, Andrey A; Bazhin, Alexandr V; Philippov, Pavel P

    2016-07-01

    The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

  14. Renal Mass Biopsy to Guide Treatment Decisions for Small Incidental Renal Tumors: A Cost-effectiveness Analysis1

    PubMed Central

    Gervais, Debra A.; Hartman, Rebecca I.; Harisinghani, Mukesh G.; Feldman, Adam S.; Mueller, Peter R.; Gazelle, G. Scott

    2010-01-01

    Purpose: To evaluate the effectiveness, cost, and cost-effectiveness of using renal mass biopsy to guide treatment decisions for small incidentally detected renal tumors. Materials and Methods: A decision-analytic Markov model was developed to estimate life expectancy and lifetime costs for patients with small (≤4-cm) renal tumors. Two strategies were compared: renal mass biopsy to triage patients to surgery or imaging surveillance and empiric nephron-sparing surgery. The model incorporated biopsy performance, the probability of track seeding with malignant cells, the prevalence and growth of benign and malignant tumors, treatment effectiveness and costs, and patient outcomes. An incremental cost-effectiveness analysis was performed to identify strategy preference under a willingness-to-pay threshold of $75 000 per quality-adjusted life-year (QALY). Effects of changes in key parameters on strategy preference were evaluated in sensitivity analysis. Results: Under base-case assumptions, the biopsy strategy yielded a minimally greater quality-adjusted life expectancy (4 days) than did empiric surgery at a lower lifetime cost ($3466), dominating surgery from a cost-effectiveness perspective. Over the majority of parameter ranges tested in one-way sensitivity analysis, the biopsy strategy dominated surgery or was cost-effective relative to surgery based on a $75 000-per-QALY willingness-to-pay threshold. In two-way sensitivity analysis, surgery yielded greater life expectancy when the prevalence of malignancy and propensity for biopsy-negative cancers to metastasize were both higher than expected or when the sensitivity and specificity of biopsy were both lower than expected. Conclusion: The use of biopsy to guide treatment decisions for small incidentally detected renal tumors is cost-effective and can prevent unnecessary surgery in many cases. © RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10092013/-/DC1 PMID

  15. Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma

    PubMed Central

    Ambrosio, Maria R.; Rocca, Bruno J.; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T.; Tripodi, Sergio A.; Tosi, Piero

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551

  16. Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

    PubMed

    Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

  17. Tumor heterogeneity as a rationale for a multi-epitope approach in an autologous renal cell cancer tumor vaccine

    PubMed Central

    Wittke, Stefan; Baxmann, Susann; Fahlenkamp, Dirk; Kiessig, Stephan T

    2016-01-01

    Purpose An autologous tumor vaccine already used successfully in the immune therapy of renal cell carcinoma was investigated in detail. The evaluation of potential tumor markers should allow for the assessment of potency according to pharmaceutical regulations. Methods A panel of 36 tumor-associated antigens and cellular marker proteins was characterized in a total of 133 tumor cell lysates by methods such as ELISA, Western blots, and topological proteomics. The induction of tumor-associated antigen-specific antibodies was demonstrated by immunization in mice. Results Tumor heterogeneity was demonstrated: none of the tumor-associated antigens investigated were detectable in each tumor lysate. In parallel, the coincidental presence of potential danger signals was shown for HSP-60 and HSP-70. The presence of both antigen and danger signal allowed a successful induction of an immune response in a murine model. Conclusion The verified tumor heterogeneity indicates the need for a multi-epitope approach for the successful immunotherapy in renal cell carcinoma. PMID:26889089

  18. The diagnostic value of cytokeratins expression in the renal parenchyma tumors.

    PubMed

    Alexa, Aurora; Baderca, Flavia; Lighezan, Rodica; Izvernariu, D; Raica, M

    2010-01-01

    Renal carcinomas are a heterogeneous group of tumors, difficult to classify and identify precisely. Since their prognosis depends very much upon their type, precise diagnosis might mean the difference between therapeutic success and patient death. Cytokeratins are particularly useful for the identification of the epithelial nature of the tumors, because their expression is maintained even in poorly differentiated tumors. Monoclonal cytokeratins such as CK7 and CK20 stain different components of the renal tubular system and are a useful duo for the identification of the origin of the different tumors that might arise in the kidney. Along with polyclonal cytokeratins such as AE1/AE3 and high molecular weight cytokeratin antibodies (34betaE12, Cam 5.2), epithelial membrane antigen (EMA) and vimentin, they are included in every diagnostic panel for renal tumors. We have selected 138 renal parenchyma tumor specimens, performed morphological diagnosis and then stained them with polyclonal cytokeratin antibody AE1/AE3, and monoclonal antibodies to CK7 and CK20. AE1/AE3 was expressed in 61.7% of the renal parenchyma tumors, with high intensity and percentage of positive cases in the papillary carcinomas (100%), and with rare and weakly positive cells in chromophobic cells carcinomas, clear cells carcinomas and sarcomatous carcinomas. CK7 was positive in 68% of the renal parenchyma tumors, with positive reaction in 100% of the cases of chromophobic cells and sarcomatous carcinomas. Clear cells carcinomas had the less percentage of positive cells, whereas papillary carcinomas were positive in seven out of eight cases. No difference in the staining pattern was noticed between type I and type II papillary carcinomas. CK20 was negative in all cases studied.

  19. Microwave ablation of renal tumors: state of the art and development trends.

    PubMed

    Floridi, Chiara; De Bernardi, Irene; Fontana, Federico; Muollo, Alessandra; Ierardi, Anna Maria; Agostini, Andrea; Fonio, Paolo; Squillaci, Ettore; Brunese, Luca; Fugazzola, Carlo; Carrafiello, Gianpaolo

    2014-07-01

    In the last decades an increased incidence of new renal tumor cases has been for clinically localized, small tumors <2.0 cm. This trend for small, low-stage tumors is the reflection of earlier diagnosis primarily as a result of the widespread and increasing use of non-invasive abdominal imaging modalities such as ultrasound, computerized tomography, and magnetic resonance imaging. Renal tumors are often diagnosed in elderly patients, with medical comorbidities whom the risk of surgical complications may pose a greater risk of death than that due to the tumor itself. In these patients, unsuitable for surgical approach, thermal ablation represents a valid alternative to traditional surgery. Thermal ablation is a less invasive, less morbid treatment option thanks to reduced blood loss, lower incidence of complications during the procedure and a less long convalescence. At present, the most widely used thermal ablative techniques are cryoablation, radiofrequency ablation and microwave ablation (MWA). MWA offers many benefits of other ablation techniques and offers several other advantages: higher intratumoral temperatures, larger tumor ablation volumes, faster ablation times, the ability to use multiple applicators simultaneously, optimal heating of cystic masses and tumors close to the vessels and less procedural pain. This review aims to provide the reader with an overview about the state of the art of microwave ablation for renal tumors and to cast a glance on the new development trends of this technique.

  20. Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer.

    PubMed

    Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina

    2016-12-01

    Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormalities arising in the setting of known renal cell carcinoma, particularly late in the course of disease. This is frequently associated with internal jugular vein thrombi, which should be evaluated with an abnormal thyroid. Thyroglobulin levels are usually normal in such patients.

  1. Successful Repeated Peptide Receptor Radionuclide Therapies in Renal Neuroendocrine Tumor With Osseous Metastasis.

    PubMed

    Yordanova, Anna; Mayer, Karin; Essler, Markus; Ahmadzadehfar, Hojjat

    2016-12-01

    Renal neuroendocrine tumor (NET) is an extremely rarely occurring disease. The sporadic reports in the literature are mostly case reports, or less commonly small studies. In cases of metastatic disease from renal NET, there are no established therapies. We are reporting our experience with a patient with extensive osseous infiltration of a renal NET, who was successfully treated with peptide receptor radionuclide therapy (PRRT) using Lu-DOTATATE. In a period of 10 years, the patient underwent in total 12 cycles of PRRT with a cumulative dose of 81 GBq. All therapies were unproblematic and well tolerated.

  2. Case Report of Percutaneous Tract Seeding of Renal Pelvic Tumor: 8-Year Journey

    PubMed Central

    2016-01-01

    Abstract A 58-year-old female presented with renal colic and was found to have renal transitional cell carcinoma at the time of percutaneous surgery. She developed percutaneous tract seeding that clinically presented as subcutaneous skin nodules. After local treatment with surgical excision and radiation treatment, the patient developed retroperitoneal recurrence 5 years later. Percutaneous tract seeding is rare. There is no general consensus on prevention of tract seeding during percutaneous resection of renal urothelial tumors. Various recommendations from the literature are discussed. PMID:27868102

  3. Radio-frequency ablation of small renal tumors: minimum follow up of 1 year

    NASA Astrophysics Data System (ADS)

    Patel, Vipul; Thaly, Rahul; Shah, Ketul

    2007-02-01

    OBJECTIVE: With the increased utility of complex imaging modalities small renal tumors are being diagnosed with rising frequency. We performed radiofrequency ablation to treat tumors less than 4cm in size using a combination of temperature, impedance, ultrasound and laparoscopic guidance. In this article we reviewed the outcome of radiofrequency ablation of renal tumors at one year at our institution. MATERIALS AND METHODS: Over a three-year period 75 patients with a total of 93 renal tumors underwent radiofrequency ablation. Average patient age was 64.5 years with ASA of 2.9. Indications for nephron sparing were imperative in 33 (solitary kidney 21, renal insufficiency 12). Seventeen patients had significant co-morbidities with ASA score of 3 or more and were thought to be poor candidates for nephrectomy or partial nephrectomy. Five were Jehovah's Witness patients. Average tumor size was 3.2 cm (1.5-4.0). 60% of the tumors were exophytic and 40% deep. Radiofrequency ablation was performed via a transperitoneal approach using the single pronged 3cm Cool tip electrode (Radionics Inc). Tumor was isolated laparoscopically. Prior to ablation the lesions were biopsied. Ablation was performed using both laparoscopic and real-time ultrasound imaging of the boarders of the tumor. During ablation impedance and temperature monitoring was performed. For each tumor two separate ablations were performed at perpendicular angles, the first ablation was for 6 minutes and the second for 3 minutes. The center and periphery of the tumor was monitored to insure that the temperature rose above 70 degrees Celsius. Patients were followed at three-month intervals with triple phase CT scan or MRI to evaluate efficacy of the ablation. Our criteria for recurrent tumor were growth or enhancement of the lesion. RESULTS: Average operative time was 109 minutes with and average EBL of <25cc. Mean hospital stay was 1.4 days. At average follow up of 19.2 months (range 2-24), one lesion showed

  4. Combined MRI and Fluoroscopic Guided Radiofrequency Ablation of a Renal Tumor

    SciTech Connect

    Fotiadis, Nikolas I.; Sabharwal, Tarun; Gangi, Afshin; Adam, Andreas

    2009-01-15

    Percutaneous CT- and ultrasound-guided radiofrequency ablation of renal cell carcinoma (RCC) has been shown to have very promising medium-term results. We present a unique case of recurrent RCC after partial nephrectomy in a patient with a single kidney and impaired renal function. This tumor could not be visualized either with CT or with ultrasound. A combination of magnetic resonance imaging and fluoroscopic guidance was used, to the best of our knowledge for the first time, to ablate the tumor with radiofrequency. The patient was cancer-free and off dialysis at 30-month follow up.

  5. Brown tumor: clinical findings of secondary hyperparathyroidism in patients with renal osteodystrophy.

    PubMed

    Silva, Mairaira Teles Leão E; Cedraz, Juliana Silva Barros; Pontes, Caetano Guilherme Carvalho; Trento, Cleverson Luciano; Brasileiro, Bernardo Ferreira; Piva, Marta Rabello; Pereira, Fabiano Alvim

    2017-01-01

    A brown tumor, or osteoclastoma, is a nonneoplastic bony lesion associated with hyperparathyroidism and directly related to increased levels of parathyroid hormone. These tumors result from excessive osteoclastic activity. This article presents 3 cases of brown tumor localized in facial bones. The lesions were the result of secondary hyperparathyroidism associated with chronic renal failure. The patients were two 42-year-old men and a 39-year-old woman. All patients had been treated systemically by hemodialysis for more than 10 years. This article highlights the importance of proper diagnosis and management of dental patients presenting with a brown tumor.

  6. Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

    SciTech Connect

    Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.; Lichtenberg, T.

    1984-01-01

    Having noted an increased serum level of TPA and CEA in patients with renal carcinoma the authors extended these studies by using a larger number of tumor markers. In 15 patients (11 men and 4 women after menopause) aged 33 to 74 years who had renal carcinoma, among them 3 with tumor metastases, the serum concentration of TPA, CA 12-5, CEA, AFP, ferritin, prolactin, ..beta..-HCG, and ..beta../sub 2/-microglobulin was measured by radioimmunoassay. Monoclonal antibodies were used in the determination of serum CA 12-5 and CEA. In all patients surgical treatment, irradiation, or cytostatic therapy had not been performed. In serum the normal range was exceeded by TPA in 7 patients, CA 12-5 in 3, CEA and AFP in one each, ferritin in 12, prolactin in 2, and ..beta../sub 2/-microglobulin in 10 patients. In one man serum prolactin was reduced. Serum ..beta..-HCG was normal in all patients. According to these results serum ferritin, TPA, and ..beta../sub 2/-microglobulin are of great value as tumor markers in patients with renal carcinoma. In several patients the increase of serum ..beta../sub 2/-microglobulin may be ascribed partly to deterioration of renal function. As no consistent patterns of tumor markers in serum were observed it is recommended to determine several tumor markers and not only one of them during the follow-up of patients. Radioimmunoassays for measuring the serum level of tumor markers, especially ferritin, TPA, and ..beta../sub 2/-microglobulin, may considerably assist in the management of patients with renal carcinoma by providing early information about tumor recurrence or metastases.

  7. Clinicopathological study on thyroid follicular carcinoma-like renal tumor related to serious hypertension

    PubMed Central

    Wang, Hui; Yu, Jianpeng; Xu, Zhonghua; Li, Gang

    2017-01-01

    Abstract Rationale: Thyroid carcinoma-like tumor of the kidney (TLFCK) is an extremely rare variant of renal cell carcinoma. Most cases were incidentally found, while we report the first case of TLFCK presented with hypertension. Patient concerns: A 25-year-old woman was admitted to our hospital presenting with hypertension for ∼20 months, without gross hematuria, weight loss, and flank pain. Diagnoses: Imaging studies revealed a right renal mass with multiple calcifications. Histologically, the tumor had striking follicles with dense, colloid-like material resembling thyroid follicular carcinoma while the tumor cells were negative for thyroid markers (thyroglobulin and thyroid transcription factor-1). Interventions: The patient successfully underwent nephron sparing surgery with an uneventful recovery. Outcomes: Hypertension returned to normal without any medication interference. Two years after surgery, the patient is still in good health without recurring disease or related hypertension. Lessons: Recognition of the cytomorphological features of TLFCK can avoid misdiagnosis of this renal tumor as a metastatic carcinoma and the objective of surgical management is to remove the tumor and preserve renal function. PMID:28328844

  8. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4

    SciTech Connect

    Golumbek, P.T.; Lazenby, A.J.; Levitsky, H.I.; Jaffee, L.M.; Baker, M.; Pardoll, D.M. ); Karasuyama, Hajime )

    1991-11-01

    The generation of antigen-specific antitumor immunity is the ultimate goal in cancer immunotherapy. When cells from a spontaneously arising murine renal cell tumor were engineered to secrete large doses of interleukin-4 (IL-4) locally, they were rejected in a predominantly T cell-independent manner. However, animals that rejected the IL-4-transfected tumors developed T cell-dependent systemic immunity to the parental tumor. This systemic immunity was tumor-specific and primarily mediated by CD8{sup +} T cells. Established parental tumors could be cured by the systemic immune response generated by injection of the genetically engineered tumors. These results provide a rationale for the use of lymphokine gene-transfected tumor cells as a modality for cancer therapy.

  9. Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats

    PubMed Central

    Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L.; He, Yongcheng; Wang, Niansong; Liang, Mingyu

    2016-01-01

    Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13BN26 rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13BN26 rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7–8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

  10. Fish oil supplementation reduces cachexia and tumor growth while improving renal function in tumor-bearing rats.

    PubMed

    Coelho, Isabela; Casare, Fernando; Pequito, Danielle C T; Borghetti, Gina; Yamazaki, Ricardo K; Brito, Gleisson A P; Kryczyk, Marcelo; Fernandes, Luiz Claudio; Coimbra, Terezila M; Fernandez, Ricardo

    2012-11-01

    The objective of the present work was to study the renal function of healthy and tumor-bearing rats chronically supplemented with fish oil (FO), a source of n-3 polyunsaturated fatty acids. Weanling male rats were divided in two groups, one control (C) and another orally supplemented for 70 days with FO (1 g/kg body weight). After this time, half the animals of each group were injected in the right flank with a suspension of Walker 256 tumor cells (W and WFO). The W group had less proteinemia reflecting cachectic proteolysis, FO reversed this fact. Tumor weight gain was also reduced in WFO. Glomerular filtration rate (GFR) was not different in FO or W compared to C, but was higher in WFO. Renal plasma flow (RPF) was higher in the FO supplemented groups. The W group had lower plasma osmolality than the C group, but FO supplementation resulted in normalization of this parameter. Fractional sodium excretion (FE(Na+)) of FO rats was similar to C. Proximal Na(+) reabsorption, evaluated by lithium clearance, was similar among the groups. Urinary thromboxane B(2) (TXB(2)) excretion was lower in the supplemented groups. The number of macrophages in renal tissue was higher in W compared to C rats, but was lower in WFO rats compared to W rats. In conclusion, FO supplementation resulted in less tumor growth and cachexia, and appeared to be renoprotective, as suggested by higher RPF and GFR.

  11. Renal Cell Carcinoma: Comparison of RENAL Nephrometry and PADUA Scores with Maximum Tumor Diameter for Prediction of Local Recurrence after Thermal Ablation.

    PubMed

    Maxwell, Aaron W P; Baird, Grayson L; Iannuccilli, Jason D; Mayo-Smith, William W; Dupuy, Damian E

    2017-05-01

    Purpose To evaluate the performance of the radius, exophytic or endophytic, nearness to collecting system or sinus, anterior or posterior, and location relative to polar lines (RENAL) nephrometry and preoperative aspects and dimensions used for anatomic classification (PADUA) scoring systems and other tumor biometrics for prediction of local tumor recurrence in patients with renal cell carcinoma after thermal ablation. Materials and Methods This HIPAA-compliant study was performed with a waiver of informed consent after institutional review board approval was obtained. A retrospective evaluation of 207 consecutive patients (131 men, 76 women; mean age, 71.9 years ± 10.9) with 217 biopsy-proven renal cell carcinoma tumors treated with thermal ablation was conducted. Serial postablation computed tomography (CT) or magnetic resonance (MR) imaging was used to evaluate for local tumor recurrence. For each tumor, RENAL nephrometry and PADUA scores were calculated by using imaging-derived tumor morphologic data. Several additional tumor biometrics and combinations thereof were also measured, including maximum tumor diameter. The Harrell C index and hazard regression techniques were used to quantify associations with local tumor recurrence. Results The RENAL (hazard ratio, 1.43; P = .003) and PADUA (hazard ratio, 1.80; P < .0001) scores were found to be significantly associated with recurrence when regression techniques were used but demonstrated only poor to fair discrimination according to Harrell C index results (C, 0.68 and 0.75, respectively). Maximum tumor diameter showed the highest discriminatory strength of any individual variable evaluated (C, 0.81) and was also significantly predictive when regression techniques were used (hazard ratio, 2.98; P < .0001). For every 1-cm increase in diameter, the estimated rate of recurrence risk increased by 198%. Conclusion Maximum tumor diameter demonstrates superior performance relative to existing tumor scoring systems and

  12. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    PubMed Central

    Costa, Vera L; Henrique, Rui; Ribeiro, Franclim R; Pinto, Mafalda; Oliveira, Jorge; Lobo, Francisco; Teixeira, Manuel R; Jerónimo, Carmen

    2007-01-01

    Background Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. Methods A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Results Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007), PTGS2 (p = 0.002), and RASSF1A (p = 0.0001). CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively), whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004). RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035). In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031) and nuclear grade (p = 0.022), respectively. Conclusion The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses. PMID:17645803

  13. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors.

    PubMed

    Costa, Vera L; Henrique, Rui; Ribeiro, Franclim R; Pinto, Mafalda; Oliveira, Jorge; Lobo, Francisco; Teixeira, Manuel R; Jerónimo, Carmen

    2007-07-23

    Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007), PTGS2 (p = 0.002), and RASSF1A (p = 0.0001). CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively), whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004). RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035). In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031) and nuclear grade (p = 0.022), respectively. The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

  14. Morphologic evidence that analgesic-induced kidney pathology contributes to the progression of tumors of the renal pelvis.

    PubMed

    Stewart, J H; Hobbs, J B; McCredie, M R

    1999-10-15

    Whether phenacetin-containing analgesics cause renal pelvic tumors by virtue of the weak mutagenicity of phenacetin, or indirectly through local effects of analgesic-induced renal papillary scarring, is debated. Because phenacetin consumption ceased in New South Wales, Australia in 1975, cases of renal pelvic carcinoma seen 14-15 years later (many of which were associated with long-standing analgesic-induced renal papillary pathology) provided an opportunity to examine the temporal relation between phenacetin exposure and those histologic characteristics of the tumors and adjacent renal tissue that may implicate analgesics in their etiology. The authors conducted a "blinded" histopathologic review of tumors of the renal pelvis and adjacent noncancerous renal tissue from 100 cases for which epidemiologic data regarding risk factor exposure (specifically phenacetin-containing analgesics, tobacco, infection, and kidney stones) had been obtained in a population-based case-control study from New South Wales in 1989 and 1990. A history of consumption of phenacetin-containing analgesics was associated strongly with the presence and severity of diffuse renal papillary scarring, and less strongly with papillary calcification. The histologic grade of the renal pelvic tumors tended to rise significantly with consumption of phenacetin-containing analgesics in a dose-dependent fashion and with the degree of papillary scarring, but was not related to smoking. In multivariate analysis it was the degree of papillary scarring (to a greater extent than the amount of phenacetin consumption) that was associated significantly and strongly with a higher histologic grade. Only diffuse papillary calcification was associated significantly with squamous change in the renal pelvic tumors. Based on the results of the current study, the authors conclude that 1) in phenacetin-related tumors of the renal pelvis, the presence and severity of analgesic-induced renal papillary scarring correlates

  15. Correlation between loss of renal function and loss of renal volume after partial nephrectomy for tumor in a solitary kidney.

    PubMed

    Sharma, Nidhi; O'Hara, Jerome; Novick, Andrew C; Lieber, Michael; Remer, Erick M; Herts, Brian R

    2008-04-01

    We assessed the correlation between reduced renal function and parenchymal volume following partial nephrectomy. In 21 of 42 patients with tumors in a solitary kidney who were enrolled in a study measuring function before and after surgery underwent computerized tomography, and measurement of the glomerular filtration rate and estimated glomerular filtration rate (the latter at baseline and 2 to 6 months) before and after surgery. A segmentation algorithm was used to measure renal parenchymal volume. The percent of renal parenchymal volume loss was correlated with the percent loss in glomerular filtration rate using the Pearson correlation coefficient. Mean +/- SD net preoperative volume was 284 +/- 67 cc (range 179 to 413) and mean net postoperative volume was 240 +/- 61 cc (range 119 to 346) with an absolute functional volume loss of between 5 and 160 cc. The average percent of parenchymal volume loss was 15% (range -2% to 47%). The mean loss of the measured glomerular filtration rate 3 days postoperatively was 33.9% (range -70.7% to 74.4%) and the estimated glomerular filtration rate 2 to 6 months postoperatively was 19.7 % (-6.0% to 45.5%). There was a low degree of correlation between the percent volume loss and the percent measured glomerular filtration rate loss at 3 days (r = 0.28, p = 0.22). However, there was a moderate degree of correlation between the percent volume loss and the percent estimated glomerular filtration rate loss at 2 to 6 months (r = 0.48, p = 0.03). In patients with partial nephrectomy the renal parenchymal volume loss correlates best with the renal function loss several months after surgery. Estimates of volume loss may be useful for predicting postoperative renal function when planning partial nephrectomy in patients with a solitary kidney.

  16. What meralgia paresthetica can hide: renal tumor as an infrequent cause.

    PubMed

    Ramírez Huaranga, Marco Aurelio; Ariza Hernández, Andrés; Ramos Rodríguez, Claudia Carolina; González García, Jesús

    2013-01-01

    Meralgia paresthetica is a mononeuropathy of the femoral cutaneous nerve with characteristic findings, usually secondary to injury or compression, being most common in the inguinal area. Exceptional cases associated with compressions caused by abdominal or pelvic tumors have been published, so it is always advisable to extend the study with imaging tests. We present a case associated with a renal tumor. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  17. Percutaneous radiofrequency ablation of renal tumors in high-risk patients: 10 years' experience.

    PubMed

    Alguersuari, A; Mateos, A; Falcó, J; Criado, E; Fortuño, J R; Guitart, J

    2016-01-01

    To retrospectively evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) done to treat renal tumors in patients with high surgical risk or with the risk of developing multiple renal tumors in the medium term at our center over a period of 10 years. Between 2005 and 2015, we used RFA to treat 89 T1a or T1b tumors in 87 patients (mean age, 73.7±10.87 years) with high surgical risk. We excluded patients treated with radiofrequency and embolization or microwave ablation. The tumors treated were clear cell carcinomas (43.6%), papillary renal carcinomas (17.2%), chromophobe renal cell carcinomas (10.3%), cystic tumors (2.2%), and an angiomyolipoma (1.1%). The mean size of the tumors was 2.6cm. Computed tomography and/or ultrasonography were used to guide the procedure. We analyzed the relation between the efficacy of the procedure and patients' age, the type of needle, the source of the patients, the size and location of the tumor, and the number of sessions required to achieve ablation. We recorded all complications. The RFA procedure was completed in all patients. The mean follow-up period was 32.1 months. The efficacy was 93.7%. A single session was sufficient in 87.5% of patients; 8% required two sessions and 4.5% required three sessions. The only factor associated with worse efficacy was the size of the tumor (p=0.03). The rate of complications was 5.6%. RFA is efficacious and safe, with results comparable to those reported in the literature. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Photothermal Ablation of in Situ Renal Tumor by PEG-IR780-C13 Micelles and Near-Infrared Irradiation.

    PubMed

    Qiu, Xuefeng; Xu, Linfeng; Zhang, Yanting; Yuan, Ahu; Wang, Kaikai; Zhao, Xiaozhi; Wu, Jinhui; Guo, Hongqian; Hu, Yiqiao

    2016-03-07

    PEG-IR780-C13 micelles have been demonstrated to be a novel photothermal agent with tumor-targeting property. This study was designed to explore the feasibility of applying PEG-IR780-C13 micelles and near-infrared (NIR) irradiation for thermal ablation of renal tumor by using an in situ tumor model. In addition, the potential thermal injury to normal renal tissue was evaluated. PEG-IR780-C13 micelles were intended to accumulate in renal tumor after systemic delivery. In vitro results revealed that PEG-IR780-C13 micelles were uptaken by RENCA cells mainly through caveola-mediated endocytosis and mainly distributed in late endosomes and lysosomes. Upon NIR irradiation, PEG-IR780-C13 micelles generated heat effectively both in vitro and in vivo, exhibiting a promising photothermal therapeutic property. The photothermal effect of PEG-IR780-C13 micelles could effectively destroy RENCA cells in vitro and adequately inhibit growth of in situ renal tumor in vivo. Meanwhile, PEG-IR780-C13 micelles mediated photothermal therapy (PTT) resulting in only limited injury to normal renal tissue surrounding tumor sites. Our data indicated that PEG-IR780-C13 micelles mediating PTT could generate tumor-specific heat for destruction of renal tumor in a minimally invasive way, providing a novel strategy for thermal ablation of renal tumor.

  19. Review of renal tumors associated with Birt-Hogg-Dubé syndrome with focus on clinical and pathobiological aspects.

    PubMed

    Kuroda, N; Furuya, M; Nagashima, Y; Gotohda, H; Kawakami, F; Moritani, S; Ota, S; Hora, M; Michal, M; Hes, O; Nakatani, Y

    2014-06-01

    Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder characterized by clinical features of skin lesions, pulmonary lesions and renal tumor. The gene responsible for this syndrome is located on chromosome 17p11.2 and designated as FLCN. In this article, we review renal tumors associated with BHDS with a focus on clinical and pathobiological aspects. Renal tumors often occur multifocally or bilaterally in the imaging analyses or gross examination. Histological examination of renal tumors includes a variety of subtypes such as hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear cell RCC and papillary RCC. The histologic discordance in multiple tumors seems to be characteristic of this syndrome. Oncocytosis is observed histologically in about half of the cases. Several investigations have elucidated that folliculin may be involved in the mammalian target of rapamycin (mTOR) pathway recently. Renal tumors composed of clear cells may behave in an aggressive fashion. However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and oncocytoma behave mostly in an indolent fashion.

  20. Tumor doubling time of renal cell carcinoma measured by CT: collaboration of Japanese Society of Renal Cancer.

    PubMed

    Ozono, Seiichiro; Miyao, Noriomi; Igarashi, Tatsuo; Marumo, Ken; Nakazawa, Hayakazu; Fukuda, Momokuni; Tsushima, Tomoyasu; Tokuda, Noriaki; Kawamura, Juichi; Murai, Masaru

    2004-02-01

    This study was conducted to examine the natural history of renal cell carcinoma (RCC). Inclusion criteria were the following: (1) patients who received diagnostic imaging of the kidney (CT, MRI) at two points in time before the diagnosis of RCC or patients who were followed, without treatment, after a diagnosis of RCC; and (2) patients in whom changes in tumor size were followed by the same modality of diagnostic imaging and who did not receive any treatment which could exert anti-tumor activity on the primary or metastatic lesions. The tumor doubling time (DT) and the growth rate of maximum tumor diameter (R) were determined. DT was calculated using the equation DT = (T - T(0)) x log2/logV - logV(0) (where T - T(0) indicates the length of time between two measurements and V(0) and V denote the tumor volume at two points of measurement). R was calculated using the equation R = (phi - f(0))/(T - T(0)) x 100 (where phi(0) and f indicate the maximum diameter at two points). Fifty-six cases registered with the Japanese Society of Renal Cancer were included in the evaluation. DT was 603.1 +/- 510.1 days, which did not correlate with V(0). R was 0.263 +/- 0.346 cm/day x 100. In cases where the tumor diameter was >/=4 cm, a significant correlation was noted between f(0) and R. Elucidation of the natural history of RCC will contribute to facilitation of differential diagnosis and determination of optimum therapeutic strategy.

  1. Graded activation of the MEK1/MT1-MMP axis determines renal epithelial cell tumor phenotype

    PubMed Central

    Mahimkar, Rajeev; Alfonso-Jaume, Maria Alejandra; Cape, Leslie M.; Dahiya, Rajvir; Lovett, David H.

    2011-01-01

    Activation of Raf/Ras/mitogen-activated protein kinase (MEK)/mitogen-activated protein kinase signaling and elevated expression of membrane type-1 matrix metalloproteinase (MT1-MMP) are associated with von Hippel–Lindau gene alterations in renal cell carcinoma. We postulated that the degree of MEK activation was related to graded expression of MT1-MMP and the resultant phenotype of renal epithelial tumors. Madin Darby canine kidney epithelial cells transfected with a MEK1 expression plasmid yielded populations with morphologic phenotypes ranging from epithelial, mixed epithelial/mesenchymal to mesenchymal. Clones were analyzed for MEK1 activity, MT1-MMP expression and extent of epithelial–mesenchymal transition. Phenotypes of the MDCK-MEK1 clones were evaluated in vivo with nu/nu mice. Tissue microarray of renal cell cancers was quantitatively assessed for expression of phosphorylated MEK1 and MT1-MMP proteins and correlations drawn to Fuhrman nuclear grade. Graded increases in the MEK signaling module were associated with graded induction of epithelial–mesenchymal transition of the MDCK cells and induction of MT1-MMP transcription and synthesis. Inhibition of MEK1 and MT1-MMP activity reversed the epithelial–mesenchymal transition. Tumors generated by epithelial, mixed epithelial/mesenchymal and mesenchymal MDCK clones demonstrated a gradient of phenotypes extending from well-differentiated, fully encapsulated non-invasive tumors to tumors with an anaplastic morphology, high Fuhrman nuclear score, neoangiogenesis and invasion. Tumor microarray demonstrated a statistically significant association between the extent of phosphorylated MEK1, MT1-MMP expression and nuclear grade. We conclude that graded increases in the MEK1 signaling module are correlated with M1-MMP expression, renal epithelial cell tumor phenotype, invasive activity and nuclear grade. Phosphorylated MEK1 and MT1-MMP may represent novel, and mechanistic, biomarkers for the assessment of renal

  2. Graded activation of the MEK1/MT1-MMP axis determines renal epithelial cell tumor phenotype.

    PubMed

    Mahimkar, Rajeev; Alfonso-Jaume, Maria Alejandra; Cape, Leslie M; Dahiya, Rajvir; Lovett, David H

    2011-12-01

    Activation of Raf/Ras/mitogen-activated protein kinase (MEK)/mitogen-activated protein kinase signaling and elevated expression of membrane type-1 matrix metalloproteinase (MT1-MMP) are associated with von Hippel-Lindau gene alterations in renal cell carcinoma. We postulated that the degree of MEK activation was related to graded expression of MT1-MMP and the resultant phenotype of renal epithelial tumors. Madin Darby canine kidney epithelial cells transfected with a MEK1 expression plasmid yielded populations with morphologic phenotypes ranging from epithelial, mixed epithelial/mesenchymal to mesenchymal. Clones were analyzed for MEK1 activity, MT1-MMP expression and extent of epithelial-mesenchymal transition. Phenotypes of the MDCK-MEK1 clones were evaluated in vivo with nu/nu mice. Tissue microarray of renal cell cancers was quantitatively assessed for expression of phosphorylated MEK1 and MT1-MMP proteins and correlations drawn to Fuhrman nuclear grade. Graded increases in the MEK signaling module were associated with graded induction of epithelial-mesenchymal transition of the MDCK cells and induction of MT1-MMP transcription and synthesis. Inhibition of MEK1 and MT1-MMP activity reversed the epithelial-mesenchymal transition. Tumors generated by epithelial, mixed epithelial/mesenchymal and mesenchymal MDCK clones demonstrated a gradient of phenotypes extending from well-differentiated, fully encapsulated non-invasive tumors to tumors with an anaplastic morphology, high Fuhrman nuclear score, neoangiogenesis and invasion. Tumor microarray demonstrated a statistically significant association between the extent of phosphorylated MEK1, MT1-MMP expression and nuclear grade. We conclude that graded increases in the MEK1 signaling module are correlated with M1-MMP expression, renal epithelial cell tumor phenotype, invasive activity and nuclear grade. Phosphorylated MEK1 and MT1-MMP may represent novel, and mechanistic, biomarkers for the assessment of renal cell

  3. Ketorolac: safe and effective analgesia for the management of renal cortical tumors with partial nephrectomy.

    PubMed

    Diblasio, Christopher J; Snyder, Mark E; Kattan, Michael W; Russo, Paul

    2004-03-01

    Ketorolac has demonstrated advantages as a supplement to opioid based analgesia in several surgical settings, including donor nephrectomy. To our knowledge there has been no published data to date on the use of ketorolac in patients undergoing partial nephrectomy. We compared analgesia with ketorolac and opioids to analgesia with opioids alone with regard to pain control, postoperative recovery and effects on renal function in patients with renal cortical tumors surgically managed by partial nephrectomy. Records for 154 patients treated with partial nephrectomy for renal cortical tumors were retrospectively analyzed. Clinicopathological variables examined were age, gender, medication use, comorbidity profile, operation side, estimated blood loss, hospital stay, operative duration, American Society of Anesthesiologists class, histopathology results, perioperative transfusion status, ischemia type (warm vs cold vs none), duration of renal artery cross clamping, tumor size and intraparenchymal location, pathological stage and perioperative complications. Postoperative duration to the initiation of solid diet, discontinuation of patient controlled analgesia and overall pain control were assessed. Serum creatinine was measured during the preoperative period, and at 1, 3 or greater and 30 or greater days postoperatively. Patients who received ketorolac demonstrated superior postoperative recovery with an earlier return to solid diet and earlier discontinuation of patient controlled analgesia. Treatment groups were similar with respect to changes in serum creatinine, blood loss, transfusion rates and complication rates. Ketorolac was not associated with an increased risk of acute renal failure. Ketorolac is a safe and effective supplement to opioid based analgesia for pain control after partial nephrectomy.

  4. Pseudo-vascular tumor in a renal flow study

    SciTech Connect

    Elgazzar, A.H.; Fernandez-Ulloa, M.; Powers, G.T.

    1985-03-01

    A case in which, for the first time, the superior mesenteric artery caused an appearance mimicking vascular tumor on a kidney radionuclide angiogram (RNA) obtained posteriorly, is reported. A subsequent contrast arteriogram showed that the superior mesenteric artery caused that appearance and confusion with possible vascular tumor on RNA. No similar cases with mesenteric blush simulating vascular tumor have been found in the literature. Mesenteric blushes on RNAs obtained posteriorly have been described only in cases of kidney agenesis and post-nephrectomy. This pattern should be kept in mind when interpreting RNAs to avoid subjecting patients to invasive diagnostic procedures.

  5. Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

    SciTech Connect

    Mellas, J.; Hammerman, M.R.

    1986-03-01

    We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na/sup +/-H/sup +/ exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using (/sup 14/C)-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 ..gamma.. phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular (Na/sup +/) > intracellular (Na/sup +/), was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na/sup +/-H/sup +/ exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells.

  6. UBE2QL1 is Disrupted by a Constitutional Translocation Associated with Renal Tumor Predisposition and is a Novel Candidate Renal Tumor Suppressor Gene

    PubMed Central

    Wake, Naomi C; Ricketts, Christopher J; Morris, Mark R; Prigmore, Elena; Gribble, Susan M; Skytte, Anne-Bine; Brown, Michael; Clarke, Noel; Banks, Rosamonde E; Hodgson, Shirley; Turnell, Andrew S; Maher, Eamonn R; Woodward, Emma R

    2013-01-01

    Investigation of rare familial forms of renal cell carcinoma (RCC) has led to the identification of genes such as VHL and MET that are also implicated in the pathogenesis of sporadic RCC. In order to identify a novel candidate renal tumor suppressor gene, we characterized the breakpoints of a constitutional balanced translocation, t(5;19)(p15.3;q12), associated with familial RCC and found that a previously uncharacterized gene UBE2QL1 was disrupted by the chromosome 5 breakpoint. UBE2QL1 mRNA expression was downregulated in 78.6% of sporadic RCC and, although no intragenic mutations were detected, gene deletions and promoter region hypermethylation were detected in 17.3% and 20.3%, respectively, of sporadic RCC. Reexpression of UBE2QL1 in a deficient RCC cell line suppressed anchorage-independent growth. UBE2QL1 shows homology to the E2 class of ubiquitin conjugating enzymes and we found that (1) UBE2QL1 possesses an active-site cysteine (C88) that is monoubiquitinated in vivo, and (2) UBE2QL1 interacts with FBXW7 (an F box protein providing substrate recognition to the SCF E3 ubiquitin ligase) and facilitates the degradation of the known FBXW7 targets, CCNE1 and mTOR. These findings suggest UBE2QL1 as a novel candidate renal tumor suppressor gene. PMID:24000165

  7. Partial and Radical Nephrectomy for Unilateral Synchronous Multifocal Renal Cortical Tumors

    PubMed Central

    Mano, Roy; Kent, Matthew; Larish, Yaniv; Winer, Andrew G.; Chevinsky, Michael S.; Hakimi, A. Ari; Sternberg, Itay A.; Sjoberg, Daniel D.; Russo, Paul

    2016-01-01

    Objective To evaluate clinicopathologic characteristics and treatment outcomes of patients undergoing partial (PN) or radical nephrectomy (RN) for unilateral synchronous multifocal renal tumors. Methods We retrospectively reviewed medical records for 128 patients with non-metastatic unilateral synchronous multifocal renal tumors who underwent surgical resection at our institution from 1995 to 2012. Five patients with hereditary renal cell carcinoma were excluded. Differences between patient and tumor characteristics from the two nephrectomy groups were evaluated. Outcomes in terms of recurrence-free survival, overall survival, and chronic kidney disease upstaging were estimated using Kaplan-Meier methods. The log-rank test was used for group comparisons. Results The study cohort included 78 PN patients (63%) and 45 RN patients (37%); 17/95 planned PN (18%) were converted to RN. Tumor diameter and R.E.N.A.L. nephrometry scores were greater in RN patients (p<0.0001 and p=0.0002, respectively). Pathological stage T3 was seen in 40% of RN patients and 10% of PN patients (p=0.0002). Histologic concordance was apparent in 60/123 patients (49%). Median follow-up for patients alive without a recurrence was 4 years. Five-year recurrence-free survival was 98% for PN and 85% for RN. Five-year overall survival was 96% for PN and 86% for RN (p=0.5). Five-year freedom from chronic kidney disease upstaging was 74% for PN, and 55% for RN (p=0.11). Conclusion Partial nephrectomy for the treatment of unilateral synchronous multifocal renal tumors with favorable characteristics was associated with a low recurrence rate. These findings suggest PN is an appropriate management strategy for this group of carefully selected patients. PMID:25872696

  8. Microwave ablation versus partial nephrectomy for small renal tumors: intermediate-term results.

    PubMed

    Guan, Wei; Bai, Jian; Liu, Jihong; Wang, Shaogang; Zhuang, Qianyuan; Ye, Zhangqun; Hu, Zhiquan

    2012-09-01

    Prospective randomized comparison of intermediate-term outcomes of patients with small renal tumors who were treated with partial nephrectomy (PN) or microwave ablation. Of 102 selected patients with solitary small renal tumors who had prospectively completed at least 2 years of follow-up since December 2004, randomizedly, 54 had either open (19) or laparoscopic (35) PN and 48 had laparoscopic (28) or open (20) microwave ablation. Patient and tumor characteristics, surgical data, complications, histologic and oncologic data, and functional data of the two approaches were compared. Patients in microwave ablation group and PN group matched for age, sex, American Society of Anesthesiologists score, body mass index, and tumor size and were respectively followed for median 32 and 36 months. Surgical and hospitalization times were comparable in both groups. Estimated blood loss, complication rates, and decline of postoperative renal function were significantly less in the microwave ablation group (P = 0.0002, P = 0.0187, and P = 0.0092, respectively). The decrease in estimated glomerular filtration rate at the last available follow-up was similar in both groups (P = 1.0000). There were no disease-specific deaths. Kaplan-Meier estimates of overall local recurrence-free survival at 3 years were 91.3% for microwave ablation and 96.0% for PN (P = 0.5414); the respective numbers for renal cell carcinomas were 90.4 and 96.6% (P = 0.4650). Microwave ablation can be also safely and efficiently done for patients with small renal tumors. This intermediate analysis showed that microwave ablation provides favorable results compared to PN. However, longer term data are still needed. Copyright © 2012 Wiley Periodicals, Inc.

  9. CT-Guided Microwave Ablation of 45 Renal Tumors: Analysis of Procedure Complexity Utilizing a Percutaneous Renal Ablation Complexity Scoring System.

    PubMed

    Mansilla, Alberto V; Bivins, Eugene E; Contreras, Francisco; Hernandez, Manuel A; Kohler, Nathan; Pepe, Julie W

    2017-02-01

    To develop a scoring system that stratifies complexity of percutaneous ablation of renal tumors. Analysis was performed of 36 consecutive patients (mean age, 64 y; range, 30-89 y) who underwent CT-guided microwave (MW) ablation of 45 renal tumors (mean tumor diameter, 2.4 cm; range, 1.2-4.0 cm). Technical success and effectiveness were determined based on intraprocedural and follow-up imaging studies. The RENAL score and the proposed percutaneous renal ablation complexity (P-RAC) score were calculated for each tumor. Technical success was 93.3% (n = 42). Biopsy of 38 of 45 renal tumors revealed 23 renal cell carcinomas. Median follow-up period was 9.7 months (range, 2.9-46.8 months). There were no tumor recurrences. One major complication, ureteropelvic junction stricture, occurred (2.6%). The P-RAC score was found to differ statistically from the RENAL score (t = 3.754, df = 44, P = .001). A positive correlation was found between the P-RAC score and number of antenna insertions (r = .378, n = 45, P = .011) and procedure duration (r = .328, n = 45, P = .028). No correlation was found between the RENAL score and number of MW antenna insertions (r = .110, n = 45, P = .472) or procedure duration (r = .263, n = 45, P = .081). Hydrodissection was significantly more common in the P-RAC high-complexity category than in low-complexity category (χ(2) = 12.073, df = 2, P = .002). The P-RAC score may be useful in stratifying percutaneous renal ablation complexity. Further studies with larger sample sizes are necessary to validate the P-RAC score and to determine if it can predict risk of complications. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  10. The use of immunohistochemical expression of SF-1 and EMA in distinguishing adrenocortical tumors from renal neoplasms.

    PubMed

    Enriquez, Miriam L; Lal, Priti; Ziober, Amy; Wang, Liping; Tomaszewski, John E; Bing, Zhanyong

    2012-03-01

    Steroidogenic factor -1 (SF-1) is an orphan member of the nuclear hormone receptor superfamily, and is considered to play an important role in the differentiation of steroidogenic tissues. In this study, we compared the immunohistochemical stains of SF-1 and epithelial membrane antigen (EMA) in non-neoplastic adrenal tissue, and adrenal and renal tumors using tissue microarrays (TMAs). The adrenal tissue array included 19 cases of normal adrenal cortex, 22 cases of adrenal adenoma, and 20 cases of adrenal cortical carcinoma. The renal tissue array included 20 cases of each of the following types of renal cell carcinoma: clear cell, papillary, and chromophobe. In addition, 20 cases of renal oncocytoma were also included in the study. SF-1 showed positive staining in all cases (100%) of normal adrenal cortex and adrenal cortical adenoma, and in 18 (90%) cases of adrenocortical carcinoma. In renal tumors, SF-1 showed negative stains in all of oncocytoma, papillary, and chromophobe renal cell carcinoma. Only 3 out of 20 cases of clear cell renal cell carcinoma showed weak positivity in approximately 10% of tumor cells. EMA stained positively in 85%, 95%, 100%, and 95% of clear cell, papillary, chromophobe renal cell carcinomas, and oncocytomas, respectively. EMA was completely negative in the adrenal TMAs. In conclusion, SF-1 and EMA may be helpful in the differentiation of adrenal tumors from renal tumors in difficult cases.

  11. Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of ADAM17.

    PubMed

    Franovic, Aleksandra; Robert, Isabelle; Smith, Karlene; Kurban, Ghada; Pause, Arnim; Gunaratnam, Lakshman; Lee, Stephen

    2006-08-15

    Malignancy is a manifestation of acquired defects in regulatory circuits that direct normal cell proliferation and homeostasis. Most of these circuits operate through cell autonomous pathways, whereas others potentially involve the neighboring microenvironment. We report that the metalloprotease ADAM17 plays a pivotal role in several acquired tumor cell capabilities by mediating the availability of soluble transforming growth factor-alpha, an epidermal growth factor receptor (EGFR) ligand, and thus the establishment of a key autocrine signaling pathway. Silencing of ADAM17 in human renal carcinoma cell lines corrects critical features associated with cancer cells, including growth autonomy, tumor inflammation, and tissue invasion. Highly malignant renal carcinoma cancer cells fail to form in vivo tumors in the absence of ADAM17, confirming the essential function of this molecule in tumorigenesis. These data show that ligand shedding is a crucial step in endogenous EGFR activation and endorse prospective therapeutic strategies targeting ADAM17 in human cancer.

  12. A collision tumor of papillary renal cell carcinoma and oncocytoma: case report and literature review.

    PubMed

    Goyal, Rajen; Parwani, Anil V; Gellert, Lan; Hameed, Omar; Giannico, Giovanna A

    2015-11-01

    The most common renal neoplasms include clear cell, chromophobe, and papillary renal cell carcinomas (PRCCs) and oncocytomas. While lesions containing hybrid features of different tumor types, such as hybrid oncocytic tumors, have been well documented in the literature, the finding of a collision tumor of two distinct tumor types- PRCC and oncocytoma-is extremely rare. We present a case of PRCC associated with an oncocytoma. Our discussion includes a review of the available literature on this rare type of collision tumor. Prosection of a partial nephrectomy performed in a 78-year-old man for painless gross hematuria and nocturia revealed a 6.4 × 5 × 3.6-cm well-delineated orange to yellow-tan mass harboring a white-tan 1 × 0.9 × 0.9-cm mass. Histologic diagnosis of PRCC associated with an oncocytoma was rendered. By immunohistochemistry, focal CK7 expression was present in the oncocytoma, while strong diffuse positive CK7 expression was present in the PRCC component. Fluorescence in situ hybridization (FISH) revealed trisomy 17 in 39.3% of PRCC tumor nuclei but no significant chromosomal aberration in oncocytoma. In view of this and previously reported cases, thorough sectioning and examination, especially in large oncocytomas, is recommended to exclude the presence of an associated malignancy. To our knowledge, trisomy 17 by FISH has not been previously reported in these extremely rare tumors. Copyright© by the American Society for Clinical Pathology.

  13. The diagnostic value of EMA expression in the renal parenchyma tumors.

    PubMed

    Alexa, Aurora; Baderca, Flavia; Lighezan, Rodica; Zăhoi, Delia Elena; Izvernariu, D

    2011-01-01

    Renal parenchyma tumors are a heterogeneous group of malignancies that are difficult to diagnose and classify. Immunohistochemistry begun to be routinely used for the diagnosis of these tumors. Panels of antibodies are developed for the diagnostic assessment of these tumors, which include cytokeratins, epithelial membrane antigen and vimentin. Epithelial membrane antigen (EMA) is expressed by most of the tumor cell types. Forty-seven specimens of renal parenchyma tumors were studied immunohistochemically for the expression of EMA. In the majority of the cases, clear cells carcinoma was positive for EMA (25/33, 75.70%). All of the papillary carcinomas were positive, with different staining patterns between the two subtypes. The two cases of chromophobe cells carcinomas were intensely positive with a granular cytoplasmic staining pattern. The mixed epithelial-stromal tumor was negative for EMA in both of the components. Out of the three cases of sarcomatoid carcinomas, one was negative, one was weakly positive (+1) and the last was positive (+2). Intensely positive normal tubes were caught by the tumor proliferation in the negative case and in the negative stained areas of the weakly positive case.

  14. Improving needle biopsy accuracy in small renal mass using tumor-specific DNA methylation markers.

    PubMed

    Chopra, Sameer; Liu, Jie; Alemozaffar, Mehrdad; Nichols, Peter W; Aron, Manju; Weisenberger, Daniel J; Collings, Clayton K; Syan, Sumeet; Hu, Brian; Desai, Mihir; Aron, Monish; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning; Siegmund, Kimberly D

    2017-01-17

    The clinical management of small renal masses (SRMs) is challenging since the current methods for distinguishing between benign masses and malignant renal cell carcinomas (RCCs) are frequently inaccurate or inconclusive. In addition, renal cancer subtypes also have different treatments and outcomes. High false negative rates increase the risk of cancer progression and indeterminate diagnoses result in unnecessary and potentially morbid surgical procedures. We built a predictive classification model for kidney tumors using 697 DNA methylation profiles from six different subgroups: clear cell, papillary and chromophobe RCC, benign angiomylolipomas, oncocytomas, and normal kidney tissues. Furthermore, the DNA methylation-dependent classifier has been validated in 272 ex vivo needle biopsy samples from 100 renal masses (71% SRMs). In general, the results were highly reproducible (89%, n=70) in predicting identical malignant subtypes from biopsies. Overall, 98% of adjacent-normals (n=102) were correctly classified as normal, while 92% of tumors (n=71) were correctly classified malignant and 86% of benign (n=29) were correctly classified benign by this classification model. Overall, this study provides molecular-based support for using routine needle biopsies to determine tumor classification of SRMs and support the clinical decision-making.

  15. Prognostic significance of MST1R dysregulation in renal cell tumors

    PubMed Central

    Pires-Luís, Ana S; Vieira-Coimbra, Márcia; Ferreira, Maria João; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Antunes, Luís; Dias, Paula C; Lobo, Francisco; Oliveira, Jorge; Graça, Inês; Henrique, Rui; Jerónimo, Carmen

    2016-01-01

    Macrophage stimulating 1 receptor (MST1R) is a C-MET proto-oncogene family receptor tyrosine kinase. Promoter methylation patterns determine transcription of MST1R variants as hypermethylation of a region upstream of transcription start site (TSS) is associated with lack of MST1R long transcript (MST1R long) and expression of a short transcript with oncogenic potential. Thus, we aimed to investigate MST1R variant transcript regulation in renal cell tumors (RCT) and assess their prognostic potential. We found, in a series of 120 RCT comprising the four main subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma), that higher methylation levels close to TSS were associated with total MST1R expression levels (MST1R total) in primary tumors (p=0.049) and renal cancer cell lines. After demethylating treatment, MST1R long/MST1R total ratio increased, as expected, in two renal cell carcinoma cell lines tested. However, in primary tumors with hypermethylation upstream of TSS, a decrease in MST1R long/MST1R total ratio was not detected, although higher expression ratio of nuclear factor-κB was apparent. Furthermore, survival analysis demonstrated that MST1R long/MST1R total ratio was independently associated with shorter disease-specific and disease-free survival, whereas MST1R total expression associated with shorter disease-specific survival. In conclusion, although promoter methylation patterns seem to determine MST1R global transcription regulation in renal cell carcinoma, other mechanisms might contribute to deregulate MST1R variant expression in RCT. Nevertheless, MST1R total expression and MST1R long/MST1R total ratio modulate the biological and clinical aggressiveness of renal cell carcinoma, as depicted by its prognostic significance, a finding that requires validation in a larger independent series. PMID:27648366

  16. A Molecular Analysis of Tumor Margins by MALDI Mass Spectrometry in Renal Carcinoma

    PubMed Central

    Oppenheimer, Stacey R.; Mi, Deming; Sanders, Melinda E.; Caprioli, Richard M.

    2010-01-01

    The rate of tumor recurrence post resection suggests that there are underlying molecular changes in nearby histologically normal tissue that go undetected by conventional diagnostic methods that utilize contrast agents and histochemistry. MALDI MS is a molecular technology that has the specificity and sensitivity to monitor and identify molecular species indicative of these processes. The current study utilizes this technology to assess molecular distributions within a tumor and adjacent normal tissue in clear cell renal cell carcinoma biopsies. Results indicate that the histologically normal tissue adjacent to the tumor expresses many of the molecular characteristics of the tumor. Proteins of the mitochondrial electron transport system are examples of such distributions. This work demonstrates the utility of MALDI MS for the analysis of tissue biopsies in the elucidation of molecular processes in the tumor microenvironment. PMID:20141219

  17. Exploiting natural anti-tumor immunity for metastatic renal cell carcinoma.

    PubMed

    Murphy, Katherine A; James, Britnie R; Guan, Yue; Torry, Donald S; Wilber, Andrew; Griffith, Thomas S

    2015-01-01

    Clinical observations of spontaneous disease regression in some renal cell carcinoma (RCC) patients implicate a role for tumor immunity in controlling this disease. Puzzling, however, are findings that high levels of tumor infiltrating lymphocytes (TIL) are common to RCC. Despite expression of activation markers by TILs, functional impairment of innate and adaptive immune cells has been consistently demonstrated contributing to the failure of the immune system to control RCC. Immunotherapy can overcome the immunosuppressive effects of the tumor and provide an opportunity for long-term disease free survival. Unfortunately, complete response rates remain sub-optimal indicating the effectiveness of immunotherapy remains limited by tumor-specific factors and/or cell types that inhibit antitumor immune responses. Here we discuss immunotherapies and the function of multiple immune system components to achieve an effective response. Understanding these complex interactions is essential to rationally develop novel therapies capable of renewing the immune system's ability to respond to these tumors.

  18. Exploiting natural anti-tumor immunity for metastatic renal cell carcinoma

    PubMed Central

    Murphy, Katherine A; James, Britnie R; Guan, Yue; Torry, Donald S; Wilber, Andrew; Griffith, Thomas S

    2015-01-01

    Clinical observations of spontaneous disease regression in some renal cell carcinoma (RCC) patients implicate a role for tumor immunity in controlling this disease. Puzzling, however, are findings that high levels of tumor infiltrating lymphocytes (TIL) are common to RCC. Despite expression of activation markers by TILs, functional impairment of innate and adaptive immune cells has been consistently demonstrated contributing to the failure of the immune system to control RCC. Immunotherapy can overcome the immunosuppressive effects of the tumor and provide an opportunity for long-term disease free survival. Unfortunately, complete response rates remain sub-optimal indicating the effectiveness of immunotherapy remains limited by tumor-specific factors and/or cell types that inhibit antitumor immune responses. Here we discuss immunotherapies and the function of multiple immune system components to achieve an effective response. Understanding these complex interactions is essential to rationally develop novel therapies capable of renewing the immune system's ability to respond to these tumors. PMID:25996049

  19. Familial papillary renal cell tumors and subsequent cancers: a nationwide epidemiological study from Sweden.

    PubMed

    Czene, Kamila; Hemminki, Kari

    2003-04-01

    Familial risks in papillary renal cell carcinoma and association with second primary malignancies were studied using the nationwide Swedish Family Cancer Data Base. Cancer data obtained from the Swedish Cancer Registry from 1961 to 1998 included 1,733 cases of papillary renal cell carcinoma. The standardized incidence ratio was used to measure cancer risk. Only 5 families were identified in which a parent had papillary renal cell carcinoma and an offspring had kidney cancer (nonsignificant SIR 1.51 for offspring). Discordant tumor sites associated with papillary renal cell carcinoma in the 2 generations were the upper aerodigestive tract and bladder (SIR 2.53, 95% CI 1.08 to 4.58 and 2.14, 95% CI 1.02 to 3.68, respectively). There was an overall increase in the risk of second primary malignancies of the lung, prostate and bladder and for non-Hodgkin's lymphoma and leukemia in patients with papillary renal cell carcinoma. The risk for a second primary tumor of the bladder associated with papillary renal cell carcinoma during the followup of 1 to 10 years was about 15 times higher than that associated with adenocarcinoma, which is the most common histological type of kidney cancer. The SIR was significantly higher in females than in males (59.67, 95% CI 40.23 to 82.94 versus 18.76, 95% CI 14.51 to 23.56). In addition to the familial association of these 2 cancer sites, the high risk of a second primary cancer of the bladder in patients with papillary renal cell carcinoma may reflect a common genetic alteration.

  20. Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

    PubMed Central

    Pires-Luís, Ana Sílvia; Vieira-Coimbra, Márcia; Vieira, Filipa Quintela; Costa-Pinheiro, Pedro; Silva-Santos, Rui; Dias, Paula C; Antunes, Luís; Lobo, Francisco; Oliveira, Jorge; Gonçalves, Céline S; Costa, Bruno M; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of 3 genes—SMYD2, SETD3, and NO66—was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity [area under curve (AUC) = 0.959], and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC = 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness. PMID:26488939

  1. Raised serum levels of cachectin/tumor necrosis factor alpha in renal allograft rejection

    PubMed Central

    1987-01-01

    A sensitive radioimmunoassay was used for monitoring serum levels of endogenous cachectin/tumor necrosis factor alpha (TNF) in 10 renal transplant recipients. Acute allograft rejections were associated with marked elevations of circulating TNF. The peak levels of TNF (median 140 pg/ml) were in the same concentration range as previously reported in parasitic infections. The results show that the release of TNF into circulation is an early event in renal allograft rejection and that raised levels of TNF in man can also be induced by noninfectious stimuli. PMID:3309124

  2. Histotype differentiation of hypo-echoic renal tumors on CEUS: usefulness of enhancement homogeneity and intensity.

    PubMed

    Lu, Qing; Xue, Li-yun; Huang, Bei-jian; Wang, Wen-ping; Li, Cui-xian

    2015-08-01

    The purpose of this study is to evaluate qualitative and quantitative analysis of contrast-enhanced ultrasound (CEUS) in differential diagnoses of hypo-echoic renal tumor histotypes. Our study cohort comprised 103 clear cell renal cell carcinomas (ccRCCs), 24 papillary renal cell carcinomas (pRCCs), 28 chromophobe renal cell carcinomas (cRCCs), and 34 angiomyolipomas (AMLs), hypo-echoic on ultrasound, and imaged between January 2011 and December 2013. Enhancement homogeneity and tumor-to-cortex intensity ratio (TOC ratio) were retrospectively analyzed. Overall, heterogeneous enhancement was more common in ccRCCs than AMLs, pRCCs, and cRCCs. TOC ratio showed the trend ccRCC > AML > pRCC = cRCC. Similar trends were seen in tumors <4 cm. Using heterogeneous enhancement or TOC ratio >107.5% to differentiate ccRCC from other histotypes, the sensitivity, specificity, positive and negative predictive values were 93.1%, 74.5%, 84.8%, and 87.5%, respectively. Tumors >4 cm exhibited considerable overlap in enhancement homogeneity among different histotypes. TOC ratios were similar between homo- and heterogeneously enhancing tumors for ccRCCs and for pRCCs and cRCCs, but higher in homogeneously enhancing than heterogeneously enhancing AMLs. In homo- and heterogeneously enhancing tumors, TOC ratios followed the trends ccRCCs > AMLs > pRCCs = cRCCs and ccRCCs > AMLs = pRCCs = cRCCs, respectively. With TOC ratio >105.81% and >72.37% to differentiate homo- and heterogeneously enhancing ccRCCs from other histotypes in tumors >4 cm with same enhancement homogeneity, the sensitivity, specificity, positive and negative predictive values were 70.0%, 85.7%, 70.0%, 85.7%, and 91.7%, 94.4%, 95.7%, 89.5%, respectively. CEUS homogeneity and TOC ratio are helpful in differential diagnosis of hypo-echoic renal tumor histotypes. Diameter and enhancement homogeneity should be considered when deciding the diagnostic TOC ratio cutoff.

  3. Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

    PubMed

    Kuroda, Naoto; Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro-omi; Ota, Satoshi; Michal, Michal; Hes, Ondrej; Nakatani, Yukio

    2014-06-01

    In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors.

  4. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  5. Mini-flank supra-12th rib incision for open partial nephrectomy for renal tumor with RENAL nephrometry score ≥10: an innovation of traditional open surgery.

    PubMed

    Wang, Hang; Sun, Li-an; Wang, Yiwei; Xiang, Zhuoyi; Zhou, Lin; Guo, Jianming; Wang, Guomin

    2015-04-01

    The skill of supra-12th rib mini-flank approach for open partial nephrectomy (MI-OPN) provides an advanced operative method for renal tumor. Compared with laparoscopic and robotic surgery, it may be a feasible selection for the complex renal tumors. We describe our techniques and results of MI-OPN in complex renal tumors with high RENAL nephrometry score (RENAL nephrometry score ≥10). Fifty-five patients diagnosed with renal tumors between January 2009 and July 2013 were included in this study. Eligibility criteria comprised of patients with complex renal tumor (RENAL score ≥10) being candidates for partial nephrectomy (PN). All patients received MI-OPN and all surgeries were performed by a single urologist. The preoperative workup comprised of medical history, physical examination, and routine laboratory tests. Serum creatinine was recorded preoperatively and 2 to 3 months after operation. Operative time, ischemia time, blood loss, operative and postoperative complications, renal function, and pathology parameters were recorded. MI-OPN was successfully performed in all cases. Mean tumor size was 4.7 cm (range: 2.5-8.1). Mean warm ischemia time was 28.1 minutes (range: 21-39), mean operative time was 105 minutes (range: 70-150) and mean estimated blood loss was 68 mL (range: 10-400). Mean postoperative hospital stay was 6.5 days (range: 5-12). Postoperative complications were found in 3 patients (5.5%). The mean pre- and postoperative serum creatinine levels were 76.2 μmol/L (range: 47-132) and 87.1 μmol/L (range: 61-189) with significant difference (P = 0.004). The mean pre- and postoperative estimated glomerular filtration rate (eGFR) were 91.5 (range: 34-133) and 82.5 (range: 22-126.5), respectively with significant difference (P = 0.024). In an average follow-up of 19.9 months (range: 8-50), no local recurrence or systemic progression occurred. In conclusion, MI-OPN can combine the benefits of both minimal invasive and traditional open

  6. MicroRNA-23b* targets proline oxidase, a mitochondrial tumor suppressor protein in renal cancer

    PubMed Central

    Liu, W; Zabirnyk, O; Wang, H; Shiao, Y-H; Nickerson, M L; Khalil, S; Anderson, L M; Perantoni, A O; Phang, J M

    2010-01-01

    Proline oxidase (POX) is a novel mitochondrial tumor suppressor, which can suppress proliferation and induce apoptosis through the generation of reactive oxygen species (ROS) and decreasing hypoxia inducible factor (HIF) signaling. Recent studies have demonstrated the absent expression of POX in human cancer tissues, including renal cancer. However, the mechanism for the loss of POX remains obscure. No genetic or epigenetic variation of POX gene was found. Here, we identified the up-regulated miR-23b* in renal cancer as an important regulator of POX. Ectopic overexpression of miR-23b* in normal renal cells resulted in striking down-regulation of POX, while POX expression increased markedly when endogenous miR-23b* was knocked down by its antagomirs in renal cancer cells. Consistent with POX-mediated tumor suppression pathway, these antagomirs induced ROS, inhibited HIF signaling and increased apoptosis. Furthermore, we confirmed the regulation of miR-23b* on POX and its function in the DLD1 Tet-off POX cell system. Using a luciferase reporter system, we verified the direct binding of miR-23b* to POX mRNA 3′UTR. In addition, pairs of human renal carcinoma and normal tissues showed the negative correlation between miR-23b* and POX protein expression, providing its clinical corroboration. Taken together, our results suggested miR-23b*, by targeting POX, could function as an oncogene; decreasing miR-23b* expression may prove to be an effective way of inhibiting kidney tumor growth. PMID:20562915

  7. MDCT imaging following nephrectomy for renal cell carcinoma: Protocol optimization and patterns of tumor recurrence

    PubMed Central

    Coquia, Stephanie F; Johnson, Pamela T; Ahmed, Sameer; Fishman, Elliot K

    2013-01-01

    The purpose of this pictorial essay is to review the common and uncommon sites of renal cell carcinoma recurrence throughout the body by examining their appearances on computerized tomography (CT). CT imaging protocols will be discussed. The sites of recurrence have been categorized into 4 groups: chest and mediastinum, abdomen and pelvis, musculoskeletal, and neurological. For each site of recurrence, a representative CT image correlate with discussion is provided. The unique CT appearance of renal cell carcinoma recurrence and how it can be used in lesion detection will be discussed. Renal cell carcinoma recurrences are hypervascular like the primary tumor, which can aid in not only lesion detection but also in some cases, differentiation from other primary tumors. Through CT case review of various sites of recurrence, lesions are shown to be easily seen on arterial phase while sometimes being nearly inconspicuous on venous or delayed phases. Coronal and sagittal reconstructions can also improve diagnostic sensitivity. CT is the most commonly used imaging tool for surveillance of renal cell carcinoma recurrence after nephrectomy. Knowledge of sites of recurrence as well as the utility of arterial phase imaging and multiplanar reconstructions will aid in optimizing detection of disease recurrence. PMID:24349648

  8. Fifteen-year experience with renal cell carcinoma with associated venous tumor thrombus.

    PubMed

    Nooromid, Michael J; Ju, Mila H; Havelka, George E; Kozlowski, James M; Kundu, Shilajit D; Eskandari, Mark K

    2016-10-01

    For patients with renal cell carcinoma with venous tumor thrombus (VTT), the importance of the extent of the VTT on survival has inconsistent published results. The aim of the study was to evaluate the prognostic value of the VTT on morbidity and mortality of our patients with renal cell carcinoma. This was a single institution review of all patients who underwent resection of renal cell carcinoma with VTT over a 15-year period. Thirty-seven patients (26 men, 11 women) with a mean age of 61 years were analyzed. The majority of the cohort were of Neves level II (n = 19), while 8 were of Neves 0 (only renal vein) or I, and 10 were of Neves III (extending into retrohepatic cava) or IV (extending supradiaphragmatically). When compared with Neves 0-II patients, there were more Neves III-IV patients with operative time >3 hours (70% vs 30%), blood loss >2,000 mL (70% vs 33%), and intensive care unit stay longer than one day (60% vs 30%) (P ≤ .05 each). Mean follow-up was 58 months. The overall 5-year survival was 71%, and all 10 patients with Neves III-IV had survived since the operation. We found advanced tumor thrombus involvement did not impact long-term survival; however, cases with suprahepatic VTT had increased operative time, blood loss, and duration of hospital stay. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. [Renal and upper urinary tract tumors: what the nephrologist should know].

    PubMed

    Gigante, Margherita; Cicione, Raffaele Ivan; Ranieri, Elena

    2010-01-01

    Urinary tract carcinomas are among the most common malignancies and are derived from neoplastic transformation of the urothelium. They can be located in the lower (bladder, urethra) or upper (pyelocaliceal cavities, ureter) urinary tract. Urothelial carcinomas are the fourth most common cancer type after prostate or breast cancer, lung cancer, and colorectal cancer. Bladder cancer accounts for 90-95% of urothelial carcinomas and it is the most common malignancy of the urinary tract. Renal cancer also belongs to the urothelial carcinomas and is a relatively uncommon solid tumor, accounting for about 3% of all adult malignancies, although its incidence is on the rise. The most common histological subtype, renal cell carcinoma (RCC), is a clear cell carcinoma that makes up approximately 70-80% of all renal neoplasms and appears to be the only histological subtype that is partially responsive to immunotherapeutic approaches. The current review gives an overview of upper urinary tract tumors and renal cancer, in particular RCC, highlighting issues related to its molecular pathogenesis and the new immunotherapeutic approaches.

  10. A Survey of Mesenchyme-related Tumors of the Rat Kidney in the National Toxicology Program Archives, with Particular Reference to Renal Mesenchymal Tumor.

    PubMed

    Hard, Gordon C; Seely, John Curtis; Betz, Laura J

    2016-08-01

    In order to harmonize diagnostic terminology, confirm diagnostic criteria, and describe aspects of tumor biology characteristic of different tumor types, a total of 165 cases of mesenchyme-related tumors and nephroblastomas of the rat kidney were reexamined from the National Toxicology Program (NTP) Archives. This survey demonstrated that renal mesenchymal tumor (RMT) was the most common spontaneous nonepithelial tumor in the rat kidney, also occurring more frequently in the NTP studies than nephroblastoma. Renal sarcoma was a distinct but very rare tumor entity, representing a malignant, monomorphous population of densely crowded, fibroblast-like cells, in which, unlike RMT, preexisting tubules did not persist. Nephroblastoma was characterized by early death of affected animals, suggesting an embryonal origin for this tumor type. Male and female rats were equally disposed to developing RMT, but most of the cases of nephroblastoma occurred in female rats and liposarcoma occurred mostly in male rats. This survey confirmed discrete histopathological and biological differences between the mesenchyme-related renal tumor types and between RMT and nephroblastoma. Statistical analysis also demonstrated a lack of any relationship of these renal tumor types to test article administration in the NTP data bank.

  11. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.

    PubMed Central

    Herman, J G; Latif, F; Weng, Y; Lerman, M I; Zbar, B; Liu, S; Samid, D; Duan, D S; Gnarra, J R; Linehan, W M

    1994-01-01

    Mutational inactivation and allelic loss of the von Hippel-Lindau (VHL) gene appear to be causal events for the majority of spontaneous clear-cell renal carcinomas. We now show that hypermethylation of a normally unmethylated CpG island in the 5' region provides another potentially important mechanism for inactivation of the VHL gene in a significant portion of these cancers. This hypermethylation was found in 5 of 26 (19%) tumors examined. Four of these had lost one copy of VHL while one retained two heavily methylated alleles. Four of the tumors with VHL hypermethylation had no detectable mutations, whereas one had a missense mutation in addition to hypermethylation of the single retained allele. As would be predicted for the consequence of methylation in this 5' CpG island, none of the 5 tumors expressed the VHL gene. In contrast, normal kidney and all tumors examined with inactivating VHL gene mutations but no CpG island methylation had expression. In a renal cell culture line, treatment with 5-aza-2'-deoxycytidine resulted in reexpression of the VHL gene. These findings suggest that aberrant methylation of CpG islands may participate in the tumor-suppressor gene inactivations which initiate or cause progression of common human cancers. Images PMID:7937876

  12. Transplantation of human renal cell carcinoma into NMRI nu/nu mice. III. Effect of irradiation on tumor acceptance and tumor growth

    SciTech Connect

    Otto, U.; Huland, H.; Baisch, H.; Kloeppel, G.

    1985-07-01

    Irradiation of human renal cell carcinoma before radical tumor nephrectomy resulted in a significantly lower acceptance rate (1 of 7) in nude mice than for nonirradiated tumors (all of 13). The tumor tissue was transplanted into NMRI nu/nu mice immediately after nephrectomy. In this experimental system the authors demonstrated the reduced vitality of human tumor cells after irradiation. In a second series of experiments, 3 morphologically different human renal cell carcinomas were irradiated at various doses after establishment in nude mice. The irradiated tumor tissue was transplanted to the next passage. The morphology, proliferation rate and growth of these tumors were compared with those of nonirradiated controls. Radiation effect was dose dependent in the responding tumor types. The characteristics correlated with radiosensitivity were high proliferation rate (measured by flow cytometry), low cytologic grading and fast growth rate in the nude mice.

  13. CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer.

    PubMed

    Min, B; Park, H; Lee, S; Li, Y; Choi, J-M; Lee, J Y; Kim, J; Choi, Y D; Kwon, Y-G; Lee, H-W; Bae, S-C; Yun, C-O; Chung, K C

    2016-07-14

    The multifunctional enzyme transglutaminase 2 (TG2) primarily catalyzes cross-linking reactions of proteins via (γ-glutamyl) lysine bonds. Several recent findings indicate that altered regulation of intracellular TG2 levels affects renal cancer. Elevated TG2 expression is observed in renal cancer. However, the molecular mechanism underlying TG2 degradation is not completely understood. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase. Previous studies reveal that CHIP deficiency mice displayed a reduced life span with accelerated aging in kidney tissues. Here we show that CHIP promotes polyubiquitination of TG2 and its subsequent proteasomal degradation. In addition, TG2 upregulation contributes to enhanced kidney tumorigenesis. Furthermore, CHIP-mediated TG2 downregulation is critical for the suppression of kidney tumor growth and angiogenesis. Notably, our findings are further supported by decreased CHIP expression in human renal cancer tissues and renal cancer cells. The present work reveals that CHIP-mediated TG2 ubiquitination and proteasomal degradation represent a novel regulatory mechanism that controls intracellular TG2 levels. Alterations in this pathway result in TG2 hyperexpression and consequently contribute to renal cancer.

  14. Expression of Pax2 in Human Renal Tumor-Derived Endothelial Cells Sustains Apoptosis Resistance and Angiogenesis

    PubMed Central

    Fonsato, Valentina; Buttiglieri, Stefano; Deregibus, Maria Chiara; Puntorieri, Valeria; Bussolati, Benedetta; Camussi, Giovanni

    2006-01-01

    The transcription factor Pax2 is known to play a key role during renal development and to act as an oncogene favoring renal tumor growth. We recently showed that endothelial cells derived from human renal carcinomas display abnormal characteristics of survival and angiogenic properties. In the present study we found that renal tumor-derived endothelial cells, but not normal endothelial cells, expressed Pax2 protein and mRNA. To down-regulate Pax2 expression, we transfected tumor-derived endothelial cells with an anti-sense PAX2 vector whereas we transfected normal human microvascular endothelial cells with a sense PAX2 vector to induce Pax2 expression. The inhibition of Pax2 expression in tumor-derived endothelial cells induced an increase in tumor suppressor PTEN expression and a decrease in Akt phosphorylation. In addition, decreased apoptosis resistance, adhesion, invasion, and in vitro and in vivo angiogenesis were observed. Conversely, Pax2 induction in normal endothelial cells conferred to these cells a proinvasive, proangiogenic phenotype similar to that of tumor-derived endothelial cells. These results indicate that Pax2 is involved in renal tumor angiogenesis and its expression may antagonize that of the PTEN tumor suppressor gene, affecting the Akt-survival pathway and promoting angiogenesis. PMID:16436683

  15. Percutaneous Renal Tumor Ablation: Radiation Exposure During Cryoablation and Radiofrequency Ablation

    SciTech Connect

    McEachen, James C.; Leng, Shuai; Atwell, Thomas D.; Tollefson, Matthew K.; Friese, Jeremy L.; Wang, Zhen; Murad, M. Hassan; Schmit, Grant D.

    2016-02-15

    IntroductionOnce reserved solely for non-surgical cases, percutaneous ablation is becoming an increasingly popular treatment option for a wider array of patients with small renal masses and the radiation risk needs to be better defined as this transition continues.Materials and MethodsRetrospective review of our renal tumor ablation database revealed 425 patients who underwent percutaneous ablation for treatment of 455 renal tumors over a 5-year time period. Imparted radiation dose information was reviewed for each procedure and converted to effective patient dose and skin dose using established techniques. Statistical analysis was performed with each ablative technique.ResultsFor the 331 cryoablation procedures, the mean DLP was 6987 mGycm (SD = 2861) resulting in a mean effective dose of 104.7 mSv (SD = 43.5) and the mean CTDI{sub vol} was 558 mGy (SD = 439) resulting in a mean skin dose of 563.2 mGy (SD = 344.1). For the 124 RFA procedures, the mean DLP was 3485 mGycm (SD = 1630) resulting in a mean effective dose of 50.3 mSv (SD = 24.0) and the mean CTDI{sub vol} was 232 mGy (SD = 149) resulting in a mean skin dose of 233.2 mGy (SD = 117.4). The difference in patient radiation exposure between the two renal ablation techniques was statistically significant (p < 0.001).ConclusionBoth cryoablation and RFA imparted an average skin dose that was well below the 2 Gy deterministic threshold for appreciable sequela. Renal tumor cryoablation resulted in a mean skin and effective radiation dose more than twice that for RFA. The radiation exposure for both renal tumor ablation techniques was at the high end of the medical imaging radiation dose spectrum.

  16. Short Term Clinical Outcome after Laparoscopic Cryoablation of the Renal Tumor < or = 3.5 cm.

    PubMed

    Polascik, T J; Nosnik, I; Mayes, J M; Mouraviev, V

    2007-12-01

    Between September 2000 and September 2006, 26 patients underwent primary laparoscopic cryosurgical procedures (28) for an organ-confined renal tumor(s). In one case, cryosurgery was done sequentially on both kidneys. All patients had been carefully selected based on the following criteria: tumor size < or = 3.5 cm, the absence of local and systemic spread on cross-sectional computed tomography (CT) or magnetic resonance imaging (MRI), and the ability to tolerate general anesthesia. A pure laparoscopic approach was employed using third generation cryotechnology (Galil Medical Inc., Plymouth Meeting, USA). Patients were followed by serial CT or MRI scan, creatinine level, and physical examination at least every six months after cryotherapy. The mean patient age was 64 years (range: 44-79) and the mean follow-up was 20.9 +/- 17.2 months. The median tumor size was 2.0 cm (range: 1-3.5 cm). Only one patient required a blood transfusion and one patient developed a transient ileus. The median length of stay was 2.0 days (range: 0-9 days). The median change in creatinine was 0.1 mg/dl (range:-0.4 to 1.8). No patient was converted to open surgery. No evidence of recurrence or progression was found in all patients, and overall survival rate was 100%. Laparoscopic renal cryoablation of the small renal tumor is a safe procedure with minimal complications. Although there were no recurrences with short term follow-up, further long term study is needed to verify its efficacy.

  17. Histotripsy and metastasis: Assessment in a renal VX-2 rabbit tumor model

    NASA Astrophysics Data System (ADS)

    Styn, Nicholas R.; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2012-10-01

    Histotripsy is a non-invasive, pulsed ultrasound technology where controlled cavitation is used to homogenize targeted tissue. We sought to assess the possibility that histotripsy may increase metastatic spread of tumor by quantifying the number of lung metastasis apparent after histotripsy treatment of aggressive renal VX-2 tumor compared to nontreated controls. VX-2 tumor was implanted in the left kidneys of 28 New Zealand White rabbits. Twenty rabbits were treated with histotripsy (day 13 after implantation) while 8 served as controls. All rabbits underwent left nephrectomy (day 14) and then were euthanized (day 19). This study was powered to detect a doubling in metastatic rate. Homogenized tumor was seen in all treated nephrectomy specimens. Whole-mount, coronal lung sections were viewed to calculate number and density of metastases. Viable tumor was present in all 28 lungs examined. Histology confirmed fractionation of tumor in all treatment rabbits. There was not a statistical difference in total lung metastases (88.7 vs. 72.5; p=0.29) or metastatic density (8.9 vs. 7.0 mets/cm2; p=0.22) between treated and control rabbits. Further investigation is planned to validate these results in the VX-2 model and to assess metastatic rates in less aggressive tumors treated with histotripsy.

  18. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    PubMed Central

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff; Pedersen, Magnus; Hansen, Morten; Svane, Inge Marie

    2015-01-01

    Personalized cancer immunotherapy based on infusion of T cells holds the promise to specifically target a patient’s individual tumor. Accumulating evidence indicates that the T cells mediating these tumor regressions after cancer immunotherapies may primarily target patient-specific mutations expressed by the patients’ tumors and that the presence of these “neo-antigen” specific T-cells may be related to a high number of mutations in the tumor. In melanoma, treatment with autologous tumor-infiltrating lymphocytes (TILs) can mediate durable complete responses. Previous trials investigating TIL therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe the major advances in the characterization and application of TIL therapy for patients with RCC and OC. PMID:26308285

  19. Treatment of renal tumors by percutaneous ultrasound-guided radiofrequency ablation using a multitined electrode: effectiveness and complications.

    PubMed

    del Cura, Jose L; Zabala, Rosa; Iriarte, Jose I; Unda, Miguel

    2010-03-01

    Radiofrequency ablation (RFA) is a minimally aggressive, therapeutic alternative for renal tumors. It can be an alternative to nephrectomy in patients with previous nephrectomy, bilateral tumors, von Hippel-Lindau disease, or small renal carcinomas and in those with contraindications for surgery. To assess the effectiveness of the treatment of renal tumors by RFA in the short and medium term and to identify the possible complications and the factors that determine therapeutic success. A retrospective review of patients with renal tumors treated with RFA between May 2005 and December 2008 was performed in a tertiary academic hospital. Patients were selected among those with previous nephrectomy, bilateral neoplasms, von Hippel-Lindau disease, surgical risk, comorbidity, advanced age, or patient's refusal to surgery. Tumors with evidence of extrarenal extension were excluded. Patients were followed up for 10-50 mo using computed tomography and magnetic resonance imaging. Ultrasound-guided RFA was performed on 65 tumors (range: 1.2-5.3 cm) of 58 patients using multitined electrodes. Incomplete ablation rate, therapeutic success rate, and complications rate. Therapeutic success was achieved in 59 of 65 tumors (91%): 53 in a single session, 5 in two sessions, and 1 in three sessions. A significant relationship was observed between size and growth pattern of the tumor and both therapeutic success and incomplete ablation rates. Therapeutic success in tumors >5 cm was 60%. Complications were detected in 10 patients (13%); 5% were considered major complications. Limitations include the lack of pathologic studies to confirm a complete ablation and the lack of a control group to compare with the results of those who underwent nephrectomy. RFA is safe and effective in renal tumors. Corticomedullary lesions and tumors >3 cm have greater possibility of incomplete ablation. In tumors >5 cm, RFA has a significant failure rate. 2009 European Association of Urology. Published by

  20. Local tumor irradiation augments the response to IL-2 therapy in a murine renal adenocarcinoma.

    PubMed

    Younes, E; Haas, G P; Dezso, B; Ali, E; Maughan, R L; Kukuruga, M A; Montecillo, E; Pontes, J E; Hillman, G G

    1995-10-15

    We have previously demonstrated that local tumor irradiation effectively enhanced the therapeutic effect of IL-2 therapy on pulmonary metastases from a murine renal adenocarcinoma, Renca. Irradiation with 300 rad to the left lung only, followed by systemic IL-2 therapy, results in increased tumor reduction in both lungs, suggesting that radiation enhances the systemic effect of immunotherapy. In this study, we show that irradiation of the tumor-bearing organ is essential for the combined effect of both modalities. This effect is radiation dose-dependent as increases in the radiation dosage result in greater tumor reduction in the irradiated field as well as systemically in nonirradiated fields when combined with immunotherapy. We find that irradiation has a direct inhibitory effect on Renca cell growth in vitro. Irradiation of Renca cells also causes an upregulation in H-2Kd class I MHC antigen detectable at 300 rad and more pronounced with 800 rad. By in vivo selective depletion of lymphocyte subsets, we demonstrate the involvement of Lyt-2+ and L3T4+ T cell subsets and AsGM1+ cells, including NK cells, in the antitumor effect mediated by tumor irradiation and IL-2 therapy. Immunohistochemistry studies, performed on lung sections, showed a significant infiltration of CD3+ T cells and macrophages in the tumor nodules following treatment with tumor irradiation and IL-2 therapy. Our studies indicate that the mechanism of interaction between tumor irradiation and immunotherapy may include radiation-induced alterations in the tumor growth and antigenicity which may enhance or trigger an anti-tumor response elicited by IL-2 and mediated by T cells, AsGM1+ cells, and macrophages.

  1. Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

    PubMed

    Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

    2017-07-21

    Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.Modern Pathology advance online publication, 21

  2. Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers

    PubMed Central

    Senchenko, Vera N.; Pronina, Irina V.; Khodyrev, Dmitry S.; Kudryavtseva, Anna V.; Krasnov, George S.; Gerashchenko, Ganna V.; Chashchina, Larisa I.; Kazubskaya, Tatiana P.; Kondratieva, Tatiana T.; Lerman, Michael I.; Angeloni, Debora; Braga, Eleonora A.; Kashuba, Vladimir I.

    2015-01-01

    The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently affected in different types of cancer. The objective of our study was to expand our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its inactivation. In this study, several experimental approaches were used: tumor growth analyses and apoptosis assays in vitro and in SCID mice, expression and methylation assays and other. With the use of the small cell lung cancer cell line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed that the suppression can be realized through the induction of apoptosis and, possibly, associated with the inhibition of angiogenesis. In addition, for the first time, high methylation frequencies have been observed in both intronic (32-39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas, including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in 83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor stage and grade have been revealed for SCC, ADC and ccRCC. The association between the decrease of the SEMA3B mRNA level and hypermethylation of the promoter and the intronic CpG-islands has been estimated in renal primary tumors (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in ccRCC. The frequency of this effect was high in both lung (92-95%) and renal (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We conclude that aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression. PMID:25961819

  3. Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers.

    PubMed

    Loginov, Vitaly I; Dmitriev, Alexey A; Senchenko, Vera N; Pronina, Irina V; Khodyrev, Dmitry S; Kudryavtseva, Anna V; Krasnov, George S; Gerashchenko, Ganna V; Chashchina, Larisa I; Kazubskaya, Tatiana P; Kondratieva, Tatiana T; Lerman, Michael I; Angeloni, Debora; Braga, Eleonora A; Kashuba, Vladimir I

    2015-01-01

    The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently affected in different types of cancer. The objective of our study was to expand our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its inactivation. In this study, several experimental approaches were used: tumor growth analyses and apoptosis assays in vitro and in SCID mice, expression and methylation assays and other. With the use of the small cell lung cancer cell line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed that the suppression can be realized through the induction of apoptosis and, possibly, associated with the inhibition of angiogenesis. In addition, for the first time, high methylation frequencies have been observed in both intronic (32-39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas, including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in 83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor stage and grade have been revealed for SCC, ADC and ccRCC. The association between the decrease of the SEMA3B mRNA level and hypermethylation of the promoter and the intronic CpG-islands has been estimated in renal primary tumors (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in ccRCC. The frequency of this effect was high in both lung (92-95%) and renal (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We conclude that aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression.

  4. Real-Time MRI-Guided Cryoablation of Small Renal Tumors at 1.5 T

    PubMed Central

    Ahrar, Kamran; Ahrar, Judy U.; Javadi, Sanaz; Pan, Li; Milton, Denái R.; Wood, Christopher G.; Matin, Surena F.; Stafford, R. Jason

    2014-01-01

    Objectives Real-time magnetic resonance imaging (MRI)-guided cryoablation has been investigated in open MRI systems with low magnetic fields (0.2–0.5 T). More advanced imaging techniques and faster imaging rates are possible at higher magnetic fields which often require a closed-bore magnet design. However, there is very little experience with real-time interventions in closed-bore 1.5 T MRI units. Herein, we report our initial experience with real-time MRI-guided cryoablation of small renal tumors using a prototype balanced steady-state free precession (bSSFP) imaging sequence in a closed-bore 1.5-T MRI system. Materials and Methods From August 2008 to April 2012, 18 patients underwent MRI-guided cryoablation of small renal tumors. A 1.5-T cylindrical MRI scanner with a 125 cm × 70 cm bore and a prototype bSSFP sequence (BEAT IRTTT) were used to guide the placement of 17-gauge cryoprobes in real time. Ice ball formation was monitored every 3 minutes in one or more imaging planes. Each ablation consisted of 2 freeze-thaw cycles. Contrast-enhanced MRI was performed after the second active thaw period. Follow-up consisted of clinical evaluation and renal protocol computed tomography (CT) or MRI performed at 1, 6, 12, 18, and 24 months and annually thereafter. Results During the study period, we successfully ablated 18 tumors in 18 patients in 18 sessions. The mean tumor size was 2.2 cm (median, 2 cm; range: 1.2–4.4 cm). The number of cryoprobes used per patient was determined based on tumor size. The mean number of cryoprobes used per patient was 3 (median, 3 cryoprobes; range, 2–4 cryoprobes). Fifty-six cryoprobes, 9 biopsy needles, and 2 hydrodissection needles were successfully placed under real time MRI guidance using BEAT IRTTT sequence. Hydrodissection under MRI guidance was successfully performed in 4 patients. In each patient, contrast-enhanced MRI performed after the second active thaw period revealed a sharply defined avascular zone surrounding the

  5. Molecular sub-classification of renal epithelial tumors using meta-analysis of gene expression microarrays.

    PubMed

    Sanford, Thomas; Chung, Paul H; Reinish, Ariel; Valera, Vladimir; Srinivasan, Ramaprasad; Linehan, W Marston; Bratslavsky, Gennady

    2011-01-01

    To evaluate the accuracy of the sub-classification of renal cortical neoplasms using molecular signatures. A search of publicly available databases was performed to identify microarray datasets with multiple histologic sub-types of renal cortical neoplasms. Meta-analytic techniques were utilized to identify differentially expressed genes for each histologic subtype. The lists of genes obtained from the meta-analysis were used to create predictive signatures through the use of a pair-based method. These signatures were organized into an algorithm to sub-classify renal neoplasms. The use of these signatures according to our algorithm was validated on several independent datasets. We identified three Gene Expression Omnibus datasets that fit our criteria to develop a training set. All of the datasets in our study utilized the Affymetrix platform. The final training dataset included 149 samples represented by the four most common histologic subtypes of renal cortical neoplasms: 69 clear cell, 41 papillary, 16 chromophobe, and 23 oncocytomas. When validation of our signatures was performed on external datasets, we were able to correctly classify 68 of the 72 samples (94%). The correct classification by subtype was 19/20 (95%) for clear cell, 14/14 (100%) for papillary, 17/19 (89%) for chromophobe, 18/19 (95%) for oncocytomas. Through the use of meta-analytic techniques, we were able to create an algorithm that sub-classified renal neoplasms on a molecular level with 94% accuracy across multiple independent datasets. This algorithm may aid in selecting molecular therapies and may improve the accuracy of subtyping of renal cortical tumors.

  6. Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma

    PubMed Central

    Sirintrapun, Sahussapont J.; Geisinger, Kim R.; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L.; Ghazalpour, Anatole; Bender, Ryan P.; Gatalica, Zoran

    2014-01-01

    Abstract Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the

  7. Inflammatory myofibroblastic tumor of renal pelvis presenting with iterative hematuria and abdominal pain: A case report

    PubMed Central

    WU, SHUIQING; XU, RAN; ZHAO, HUASHENG; ZHU, XUAN; ZHANG, LEI; ZHAO, XIAOKUN

    2015-01-01

    Inflammatory myofibroblastic tumor (IMT) is a rare type of mesenchymal tumor, which may affect various organs. The preferential site for IMT in the genitourinary system is the urinary bladder, while the presence of IMT in the kidney, and particularly in the renal pelvis, is rare. In the present report, the case of a 43-year-old man who was admitted to the Department of Urology of The Second Xiangya Hospital of Central South University (Changsha, China) in July 2012, with complaints of iterative gross hematuria and abdominal pain unresponsive to antibiotics is described. Computed tomography and magnetic resonance imaging indicated a slightly enhanced mass in the left renal pelvis of 1.5 cm in diameter. On request of the patient, a left nephrectomy was then performed, based on a suspected diagnosis of renal pelvic carcinoma. However, analysis of the intraoperative fast-frozen section exhibited proliferation of compact spindle cells, suggesting IMT. Therefore, further ureterectomy was avoided, and the patient remained in healthy condition thereafter. PMID:26788220

  8. Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma

    PubMed Central

    Bousquet, Guilhem; Bouchtaoui, Morad El; Leboeuf, Christophe; Battistella, Maxime; Varna, Mariana; Ferreira, Irmine; Plassa, Louis-François; Hamdan, Diaddin; Bertheau, Philippe; Feugeas, Jean-Paul; Damotte, Diane; Janin, Anne

    2015-01-01

    Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs. In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53-expressing tumor cells and TP53 gene abnormalities. We identified TP53 gene alterations in primary tumors, metastases and xenografts. Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived. Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC. Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC. PMID:26002555

  9. Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma.

    PubMed

    Bousquet, Guilhem; El Bouchtaoui, Morad; Leboeuf, Christophe; Battistella, Maxime; Varna, Mariana; Ferreira, Irmine; Plassa, Louis-François; Hamdan, Diaddin; Bertheau, Philippe; Feugeas, Jean-Paul; Damotte, Diane; Janin, Anne

    2015-08-07

    Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs. In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53-expressing tumor cells and TP53 gene abnormalities.We identified TP53 gene alterations in primary tumors, metastases and xenografts. Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived.Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC. Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC.

  10. Single center comparison of laparoscopic cryoablation and CT-guided percutaneous cryoablation for renal tumors.

    PubMed

    Derweesh, Ithaar H; Malcolm, John B; Diblasio, Christopher J; Giem, Andrew; Rewcastle, John C; Wake, Robert W; Patterson, Anthony L; Gold, Robert

    2008-11-01

    Cryoablation has demonstrated therapeutic effectiveness for selected renal tumors. We compared our perioperative and short-term outcomes of laparoscopic (LAP) v percutaneous (PERC) renal cryoablation. Thirty-four patients (18 men/16 women) underwent a LAP and 26 patients (19 men/7 women) underwent a PERC procedure between September1998 and January 2007. LAP cryoablation was performed transperitoneally with ultrasonographic monitoring. PERC cryoablation was performed with CT guidance. Follow-up imaging was obtained at regular intervals. Mean follow-up was 25 months. Average age (years) was 67.0 for the LAP and 69.7 for the PERC procedure (P = 0.307). Mean body mass index (kg/m(2)) was 29.8 for those undergoing LAP and 28.7 for those undergoing PERC procedures (P = 0.543). Mean tumor size (cm) was 2.9 for LAP patients and 3.1 for PERC patients (P = 0.432). Anterior tumors comprised 61.7% of LAP and 15.4% of PERC procedures (P < 0.001). Posterior tumors comprised 32.4% of LAP and 65.4% of PERC procedures (P = 0.01). Mean procedure time (minutes) was 165.7 for LAP and 106.6 for PERC procedures (P < 0.001). Hospital stay (days) was 2.6 for those undergoing LAP and 1.8 for those undergoing PERC procedures (P < 0.001). Both LAP patients (82.4%) and PERC patients (19.2%) needed postoperative narcotics (P < 0.001). Atelectasis developed in 70.6% of LAP patients and 34.6% of PERC patients (P = 0.005). Residual enhancement was seen in 11.5% of PERC patients and 2.9% of LAP patients (P = 0.192). Complications developed in 14.7% of LAP patients and 26.9% of PERC patients (P = 0.248). 1-year, 2-year, and 3-year disease-specific survival for the two groups was 100%. Tumor size > 4 cm and endophytic location were significantly associated with residual enhancement. LAP and PERC renal cryoablation have similar short-term outcomes. Significantly more anterior tumors were approached laparoscopically and significantly more posterior tumors were approached percutaneously. The PERC

  11. Bilateral renal tumors in an adult man with Smith-Magenis syndrome: The role of the FLCN gene.

    PubMed

    Dardour, Leila; Verleyen, Pieter; Lesage, Karl; Holvoet, Maureen; Devriendt, Koen

    2016-10-01

    Smith-Magenis syndrome (SMS) is a contiguous-gene disorder most commonly caused by a deletion of chromosome 17p11.2. We report a 57 year-old man with SMS who presents bilateral renal tumors. This is most likely related to haploinsufficiency of FLCN gene, located in the deleted region, and a known tumor suppressor gene. Haploinsufficiency of FLCN causes Birt-Hogg-Dubé syndrome (BHDS), characterized by pulmonary cysts, renal and skin tumors. The present observation suggests that the follow-up of patients with SMS should also focus on possible manifestations of BHDS.

  12. Tumor necrosis factor alpha promoter polymorphism in posttransplantation diabetes mellitus of renal transplant recipients.

    PubMed

    Kao, C-C; Lian, J-D; Chou, M-C; Chang, H-R; Yang, S-F

    2010-11-01

    Posttransplantation diabetes mellitus (PTDM) is a major complication in renal transplant recipients. Some studies have demonstrated that tumor necrosis factor alpha (TNF-α) expression and its genetic polymorphism are associated with diabetes mellitus. We investigated this association in Asian renal transplant recipients. Polymerase chain reaction-restriction-fragment length polymorphism was used to measure TNF-α G-238A and G-308A gene polymorphisms among 241 nonposttransplantation diabetic subjects and 73 PTDM patients. PTDM patients showed higher values of body weight and body mass index (BMI) than the non-PTDM group. However, no significant association was observed between TNF-α G-238A and TNF-α G-308A polymorphisms with PTDM incidence, gender, age at transplantation, follow-up duration, BMI, or type of immunosuppression. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Nondisjunction reduplication of chromosome 3 is not a common mechanism in the development of human renal cell tumors.

    PubMed

    Kovacs, G; Wilkens, L; Papp, T

    1988-01-01

    Because of the recurrent loss of regions of the chromosome 3 short arm in renal cell carcinomas, a chromosomal mechanism for the expression of recessive cancer genes has been implicated in the development of this type of tumor. Nondisjunction and subsequent reduplication of a mutant chromosome is one of the presumed mitotic mechanisms leading to the expression of recessive cancer genes. Using variant fluorescence at the centromeric region of chromosome 3 and a restriction fragment length polymorphism on chromosome 3p, we found chromosome 3 heteromorphism in the constitutional cells of 14 of 15 patients with renal tumors showing two normal chromosomes 3. This heteromorphism was maintained in each tumor. Therefore, the mechanism of nondisjunction and reduplication in the development of homozygosity for a mutant chromosome 3 in renal tumors remains questionable.

  14. The Nephrologist’s Tumor: Basic Biology and Management of Renal Cell Carcinoma

    PubMed Central

    Hu, Susie L.; Chang, Anthony; Perazella, Mark A.; Okusa, Mark D.; Jaimes, Edgar A.

    2016-01-01

    Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel–Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist’s tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist’s tumor. PMID:26961346

  15. Robotic partial nephrectomy for renal cell carcinomas with venous tumor thrombus.

    PubMed

    Abaza, Ronney; Angell, Jordan

    2013-06-01

    To describe the first report of robotic partial nephrectomies (RPNs) for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Partial nephrectomy for RCC extending into the renal vein has been described in limited fashion, but such a complex procedure has not previously been reported in minimally-invasive fashion. We demonstrate the feasibility of robotic nephron-sparing surgery despite vein thrombi and the results of the initial four highly-selected patients to have undergone this novel procedure. Two patients underwent RPN for RCC with VTT involving intraparenchymal vein branches, and 2 others had VTT involving the main renal vein. Mean patient age was 65 years (range 50-74 years). Mean tumor size was 7.75 cm (range 4.3-12.8 cm) with mean RENAL (radius, exophytic/endophytic, nearness to collecting system, anterior/posterior, and location) nephrometry score of 9.75 (range 8-12). Mean warm ischemia time was 24.2 minutes (range 19-27 minutes) and mean estimated blood loss was 168.8 mL (range 100-300 mL). No patients required transfusion, and there were no intraoperative complications. No patients required conversion to open or standard laparoscopic surgery. All 4 patients were discharged home on the first postoperative day. A single postoperative complication occurred in 1 patient who was readmitted with an ileus that resolved spontaneously. All patients had negative surgical margins. Two patients developed metastatic disease on surveillance imaging. RPN in patients with VTT is safe and feasible in selected patients. Given the risk of metastatic disease in patients with pathologic stage T3a RCC, the role of nephron sparing requires further evaluation such that radical nephrectomy remains the standard of care. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Evaluation of three-dimensional printing for laparoscopic partial nephrectomy of renal tumors: a preliminary report.

    PubMed

    Zhang, Yi; Ge, Hong-wei; Li, Ning-chen; Yu, Cheng-fan; Guo, Hong-feng; Jin, Shi-hua; Liu, Jin-shun; Na, Yan-qun

    2016-04-01

    To investigate the impact of three-dimensional (3D) printing on the surgical planning, potential of training and patients' comprehension of minimally invasive surgery for renal tumors. Patients of a T1N0M0 single renal tumor and indicated for laparoscopic partial nephrectomy were selected. CT data were sent for post-processing and output to the 3D printer to create kidney models with tumor. By presenting to experienced laparoscopic urologists and patients, respectively, the models' realism, effectiveness for surgical planning and training, and patients' comprehension of disease and procedure were evaluated with plotted questionnaires (10-point rating scales, 1-not at all useful/not at all realistic/poor, 10-very useful/very realistic/excellent). The size of resected tumors was compared with that on the models. Ten kidney models of such patients were fabricated successfully. The overall effectiveness in surgical planning and training (7.8 ± 0.7-8.0 ± 1.1), and realism (6.0 ± 0.6-7.8 ± 1.0) were reached by four invited urologists. Intraoperative correlation was advocated by the two performing urologists. Patients were fascinated with the demonstration of a tactile "diseased organ" (average ≥ 9.0). The size deviation was 3.4 ± 1.3 mm. Generating kidney models of T1N0M0 tumors with 3D printing are feasible with refinements to be performed. Face and content validity was obtained when those models were presented to experienced urologists for making practical planning and training. Understandings of the disease and procedure from patients were well appreciated with this novel technology.

  17. Association between residential proximity to environmental pollution sources and childhood renal tumors.

    PubMed

    García-Pérez, Javier; Morales-Piga, Antonio; Gómez, José; Gómez-Barroso, Diana; Tamayo-Uria, Ibon; Pardo Romaguera, Elena; Fernández-Navarro, Pablo; López-Abente, Gonzalo; Ramis, Rebeca

    2016-05-01

    Few risk factors for childhood renal tumors are well established. While a small fraction of cases might be attributable to susceptibility genes and congenital anomalies, the role of environmental factors needs to be assessed. To explore the possible association between residential proximity to environmental pollution sources (industrial and urban areas, and agricultural crops) and childhood renal cancer, taking into account industrial groups and toxic substances released. We conducted a population-based case-control study of childhood renal cancer in Spain, including 213 incident cases gathered from the Spanish Registry of Childhood Tumors (period 1996-2011), and 1278 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the respective subject's residences to the 1271 industries, the 30 urban areas with ≥75,000 inhabitants, and the agricultural crops located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. Excess risk (OR; 95%CI) of childhood renal tumors was observed for children living near (≤2.5km) industrial installations as a whole (1.97; 1.13-3.42) - particularly glass and mineral fibers (2.69; 1.19-6.08), galvanization (2.66; 1.14-6.22), hazardous waste (2.59; 1.25-5.37), ceramic (2.35; 1.06-5.21), surface treatment of metals (2.25; 1.24-4.08), organic chemical industry (2.22; 1.15-4.26), food and beverage sector (2.19; 1.18-4.07), urban and waste-water treatment plants (2.14; 1.07-4.30), and production and processing of metals (1.98; 1.03-3.82) -, and in the proximity of agricultural crops (3.16; 1.54-8.89 for children with percentage of crop surface ≥24.35% in a 1-km buffer around their residences). Our study provides some epidemiological evidence that living near certain industrial areas and agricultural crops

  18. Carcinoid tumor associated with adjacent dysplastic columnar epithelium in the renal pelvis: A case report and literature review.

    PubMed

    Kim, Sung Sun; Choi, Chan; Kang, Taek Won; Choi, Yoo Duk

    2016-01-01

    Carcinoid tumors are well documented in the pulmonary and gastrointestinal systems, but very rare in the urinary tract, especially in the renal pelvis. We report on a 60-year-old female patient who presented with left flank pain and fever. Abdominal computed tomography demonstrated a heterogeneously enhancing mass in the left renal pelvis and a stone at the left proximal ureter. Multiple parenchymal lesions were also observed, which were identified as uneven caliectasis displaying air-fluid levels and renal parenchymal atrophy. The patient underwent simple nephro-ureterectomy. Macroscopically, a polypoid mass was observed in the renal pelvis. Microscopically, the tumor revealed acinar, tubular, and solid pattern and was composed of small, monotonous and hyperchromatic cells. Lining epithelia in renal pelvis and ureter revealed columnar epithelia with dysplastic change. The tumor cells were positive for chromogranin A, synaptophysin, CD56, and focally positive for cytokeratin. Immunohistochemical staining of synaptophysin and chromogranin A highlighted the neuroendocrine cells in the columnar epithelium. Ki-67 (1:50; MIB-1) labeling index was less than 1% in the area with highest uptake. We report here a case of carcinoid tumor of the renal pelvis that was associated with adjacent dysplastic columnar epithelium. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  19. Skull Base Clear Cell Carcinoma, Metastasis of Renal Primary Tumor: A Case Report and Literature Review

    PubMed Central

    Sepúlveda, Ilson; Platin, Enrique; Klaassen, Rodrigo; Spencer, M. Loreto; García, Cesar; Alarcón, Ricardo; Ulloa, David

    2013-01-01

    We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program. PMID:24019781

  20. Extracting tumor tissue immune status from expression profiles: correlating renal cancer prognosis with tumor-associated immunome.

    PubMed

    Teltsh, Omri; Porgador, Angel; Rubin, Eitan

    2015-10-20

    Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative for prognosis prediction. However, evaluating the expression of immune-associated genes within cancer biopsy is subject to significant inconsistencies related to the sampling methodology. Here, we present immFocus, a method for extracting immune signals from total RNA sequencing of tumor biopsies, intended for immunity depiction and prognosis evaluation. It is based on reducing the variation which biopsy preparation adds to the apparent expression levels of immune genes. We employed immFocus to normalize gene expression with an immune index using data obtained from renal clear cell carcinoma biopsies. Genes that became less variable due to normalization were found to be preferentially immune-related. Moreover, immune-related genes tended to become more prognostic due to the normalization. These results demonstrate, for the first time, that whole transcriptome sequencing can be used for interrogation of a cancer immunome and for advancing immune-based prognosis.

  1. Primary Renal Rhabdomyosarcoma in an Adolescent With Tumor Thrombosis in the Inferior Vena Cava and Right Atrium

    PubMed Central

    Lin, Wei-Ching; Chen, Jeon-Hor; Westphalen, Antonio; Chang, Han; Chiang, I-Ping; Chen, Cheng-Hong; Wu, Hsi-Chin; Lin, Chien-Heng

    2016-01-01

    Abstract Although the second peak of the age distribution of rhabdomyosarcoma (RMS) is at adolescence, renal RMS is extremely rare at this age group. This tumor is indistinguishable from other renal tumors based on clinical and imaging findings, and the diagnosis relies on histology and immunohistochemical staining. We report a unique case of adolescent renal RMS associated with tumor thrombus extending into the inferior vena cava (IVC) and right atrium. An 18-year-old female adolescent presented with shortness of breath and palpitations, associated with right flank discomfort, and hematuria. A pleomorphic-type renal RMS with Budd–Chiari syndrome and arrhythmia induced by IVC and RA thrombosis was diagnosed. Despite complete tumor resection, the patient developed multiple lung metastases a month after surgery. Chemotherapy was recommended, but the patient declined. She died within a year of the initial operation. Adolescent renal RMS is rare and associated with poor outcome. Early aggressive multimodal therapy seems to be appropriate, in particular, in the presence of tumor thrombosis. PMID:27227946

  2. [Renal tumors: The International Society of Urologic Pathology (ISUP) 2012 consensus conference recommendations].

    PubMed

    Rioux-Leclercq, Nathalie; Ferran, Algaba; Mahul, Amin; Argani, Pedram; Billis, Athanase; Bonsib, Stephen; Cheng, Liang; Cheville, John; Eble, John; Egevad, Lars; Epstein, Jonathan; Grignon, David; Hes, Ondrej; Humphrey, Peter; Magi-Galluzzi, Cristina; Martignoni, Guido; McKenney, Jesse; Merino, Maria; Moch, Holger; Montironi, Rodolfo; Netto, George; Reuter, Viktor; Samaratunga, Hemamali; Shen, Steven; Srigley, John; Tamboli, Pheroze; Tan, Puay Hoon; Tickoo, Satish; Trpkov, Kiril; Zhou, Ming; Delahunt, Brett; Comperat, Eva

    2014-12-01

    During the last 30 years many advances have been made in kidney tumor pathology. In 1981, 9 entities were recognized in the WHO Classification. In the latest classification of 2004, 50 different types have been recognized. Additional tumor entities have been described since and a wide variety of prognostic parameters have been investigated with variable success; however, much attention has centered upon the importance of features relating to both stage and grade. The International Society of Urological Pathology (ISUP) recommends after consensus conferences the development of reporting guidelines, which have been adopted worldwide ISUP undertook to review all aspects of the pathology of adult renal malignancy through an international consensus conference to be held in 2012. As in the past, participation in this consensus conference was restricted to acknowledged experts in the field. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Anti-tumor effects of AMT in the renal cell carcinoma model.

    PubMed

    Caballero, Marcello; Scheele, Jürgen; Zirrgiebel, Ute; Esser, Norbert; Schächtele, Christoph; Soltau, Jens; Rentschler, Jochen; Diergarten, Klaus; Drevs, Joachim

    2010-01-01

    Auron-Misheil-Therapy (AMT) is a defined but unique combination of approved pharmaceuticals. It consists of insulin, chlorpheniramine and an aqueous camomile extract, and it has been successfully applied clinically in late-stage cancer patients. The purpose of this study was to elucidate the anti-tumor efficacy of AMT in a validated murine renal cell carcinoma animal model (RENCA). There were two independent studies; each animal group consisted of 16 mice. During a 6-week pretreatment period, vehicle (group A) and AMT (1.6 mg/kg/d) (group B) were administered once daily in a 5 days/week schedule either intramuscularly or subcutaneously. Tumor challenge at day 0 was followed by a 3-week treatment period (either vehicle or AMT once daily intramuscularly for 21 days consecutively). In study 2 the AMT dosage was increased up to 4-fold by doubling individual doses and switching to a twice daily schedule. The injections were all intramuscular. With the exception of group D, a six-week pretreatment period preceded the tumor challenge at day 0. Tumor challenge was followed by a 3-week treatment period (vehicle, AMT at either 3.2 mg/kg/d) (group A) or 6.4 mg/kg/d (group B), or AMT0, an AMT preparation which does not stimulate IL-6 secretion (6.4 mg/kg/d, group C) continuously for 21 days. AMT administration for group D (6.4 mg/kg/d) was limited to the treatment period from day 1 to 21. All mice were sacrificed 21 days after tumour transplantation. AMT administration was safe and well tolerated, and significantly reduced primary tumor volume in pretreated animals. The effective route of application was intramuscular, with dose escalation resulting in an improved anti-tumor effect. This is the first demonstration of a significant anti-tumorigenic effect of AMT in a validated tumor model.

  4. Biodistribution and radioimmunoscintigraphy studies of renal cell carcinoma using tumor-preferential monoclonal antibodies and F(ab')2 fragments

    SciTech Connect

    Chiou, R.K. )

    1989-12-01

    The in vivo localization of renal cell carcinoma-preferential monoclonal antibodies A6H, D5D, and C5H was evaluated and the biodistribution of F(ab')2 antibody fragments of A6H and the intact Mab were compared in over 100 nude mice. A6H localized well to most renal cell carcinoma xenografts studied; the median tumor to blood ratios ranged from 6.4 to 11.5 for various xenografts. C5H also localized well to most renal cell carcinoma xenografts tested. However, D5D did not localize well to renal cell carcinoma xenografts in vivo despite its highly restrictive in vitro reactivity. The F(ab')2 fragments of A6H produced higher tumor to blood ratios, which probably resulted from fast clearance of the fragments from the circulation. Preliminary results showed that indium-111 labeling may further improve imaging.

  5. Integrin-linked kinase (ILK) expression correlates with tumor severity in clear cell renal carcinoma.

    PubMed

    Engelman, Míriam de Fátima Brasil; Grande, Rogério Mendes; Naves, Marcelo Andery; de Franco, Marcello Fabiano; de Paulo Castro Teixeira, Vicente

    2013-01-01

    Integrin-linked kinase (ILK) is an unique intracellular serine/threonine kinase and adapter protein. When dysregulated, it has been associated with increased cell proliferation, anchorage-independent cell growth, evasion of apoptosis, angiogenesis, invasion of surrounding tissues, downregulation of E-cadherin expression, nuclear translocation of β-catenin and metastasis, all features of tumoral malignancy. The objective of the present work was to evaluate the expression of ILK in clear cell renal carcinomas (CCRC) as a possible prognostic indicator. ILK immunoexpression was evaluated in a tissue microarray (TMA) with 45 human CCRCs. In addition, the apoptotic and proliferative indices and the immuno-expression of β-catenin and E-cadherin were also evaluated. E-cadherin expression was significantly decreased in tumors with positive ILK expression in relation to those with negative immunoexpression (p = 0.011). ILK immunostaining was significantly increased in high-grade in comparison to low-grade CCRCs (p = 0.0008). ILK expression was also associated with increased proliferative index (p = 0.020), tumor size >7.0 cm (p = 0.018) and with renal vein and capsule invasion (p = 0.003 and p = 0.00). Finally, tumors stage I and II (noninvasive) presented significantly reduced ILK immunoexpression when compared to stage III (locally invasive) (p = 0.0028). ILK immunoexpression in CCRC increases with loss of intercellular adhesion, nuclear grading, increased proliferative index and Robson stage. Altogether, our data suggest a possible role for ILK in the progression of CRCC.

  6. A murine model of K-ras and β-catenin induced renal tumors express high levels of E2F1 and resemble human Wilms Tumor

    PubMed Central

    Yi, Yajun; Polosukhina, Dina; Love, Harold D.; Hembd, Austin; Pickup, Michael; Moses, Harold L.; Lovvorn, Harold N.; Zent, Roy; Clark, Peter E.

    2016-01-01

    Background Wilms tumor (WT) is the most common renal neoplasm of childhood. We previously showed that restricted activation of the WNT/β-catenin pathway in renal epithelium late in kidney development is sufficient to induce small primitive neoplasms with features of epithelial WT. Metastatic disease progression required simultaneous addition of an activating mutation of the oncogene K-RAS. Here, we sought to define the molecular pathways activated in this process and their relationship to human renal malignancies. Methods Affymetrix expression microarray data from murine kidneys with activation of K-ras, Ctnnb1 (β-catenin), or both restricted to renal epithelium were analyzed and compared to publically available expression data from normal and neoplastic human renal tissue. Target genes were verified by immunoblot and immunohistochemistry. Results Mouse kidney tumors with activation of K-ras and Ctnnb1 and human renal malignancies have similar mRNA expression signatures and are associated with activation of networks centered on β-catenin and TP53. Up-regulation of WNT/β-catenin targets (MYC, Survivin, FOXA2, Axin2, Cyclin D1) was confirmed by immunoblotting. K-RAS/β-catenin murine kidney tumors were more similar to human WT than other renal malignancies and demonstrated activation of a TP53 dependent network of genes including the transcription factor E2F1. Up-regulation of E2F1 was confirmed in both murine and human WT samples. Conclusions Simultaneous activation of K-RAS and β-catenin in embryonic renal epithelium leads to neoplasms similar to human WT associated with activation of TP53 and up-regulation of E2F1. Further studies to evaluate the role of TP53 and E2F1 in human WT are warranted. PMID:25934441

  7. Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross-sectional and longitudinal study.

    PubMed

    Cozzi, Denis A; Ceccanti, Silvia; Frediani, Simone; Mele, Ermelinda; Cozzi, Francesco

    2013-09-01

    Mild-to-moderate renal function loss may be an independent risk factor for cardiovascular disease and overall mortality. As in adults with renal carcinoma nephrectomy is associated with an high risk for moderate renal function loss, we aimed to assess the renal function adaptation over a long period of time in children with unilateral renal tumor (URT). Seventy-two children who underwent surgery for URT were enrolled in this study. Glomerular filtration rate was estimated (eGFR) with the Modification of Diet in Renal Study or the Schwartz equation, as appropriate for the age. Twelve patients treated by nephron-sparing surgery (Group A) and 42 treated by nephrectomy (Group B) had an age between 2 and 30 years; 18 patients treated by nephrectomy had an age between 33 and 51 years (Group C). At cross-sectional follow-up 8% patients of Group A, 42% of Group B and 78% of Group C presented a mild-to-moderate renal function. The longitudinal data stratified by post-operative intervals showed that patients of Group C presented a significant progressive decrease in mean ± standard deviation eGFR (88.1 ± 22.6 during the third decade after surgery vs. 66.6 ± 15.6 ml/min/1.73 m(2) during the fifth decade after surgery; P = 0.02). The longitudinal data stratified by age showed that patients with an age between 45 and 54 years presented a mean eGFR significantly lower than that expected for the physiological renal function decline with aging (P = 0.001). Aging is associated with a mild-to-moderate renal function loss in many adult patients following nephrectomy during childhood for URT. Copyright © 2013 Wiley Periodicals, Inc.

  8. Healthcare resource use and costs associated with renal impairment in US patients with bone metastases from solid tumors.

    PubMed

    Qian, Yi; Arellano, Jorge; Bhowmik, Debajyoti; Thomson, Erin; Smith, David M; Hechmati, Guy; Song, Xue

    2017-04-01

    Introduction During cancer progression, more than half of patients develop renal insufficiency, including chronic kidney disease. The primary and secondary objectives of this study were to estimate healthcare resource use and costs, respectively, associated with renal impairment in patients with bone metastases from solid tumors in the United States. Methods and materials This was a retrospective, observational cohort study conducted using administrative claims data for individuals with solid tumors and bone metastases. Control patients were matched to renal impairment patients using propensity scores (ratio up to 3:1) based on demographics, clinical characteristics, and baseline costs. Average per-patient per-year healthcare resource utilization and costs (total costs and cost components; 2013 dollars) were reported. Results In total, 2616 renal impairment patients were matched to 7211 control patients. Renal impairment patients had greater healthcare resource use compared with controls, including a greater mean number of hospital admissions (4.4 versus 2.1), longer average stay per hospital admission (7.4 versus 6.5 days), as well as greater mean number of physician office visits (22.9 versus 18.8), emergency department visits (3.1 versus 2.0), and hospital-based outpatient visits (18.8 versus 16.0) compared with control patients. Total costs were > $50,000 higher among renal impairment patients ($142,267 versus $88,839; P < 0.001), with hospital costs accounting for $72,557 for renal impairment patients, and $27,858 for control patients ( P < 0.001). Conclusion The healthcare resource use and costs associated with renal impairment in patients with bone metastases from solid tumors is high; efforts to reduce renal impairment in this population, including the potential avoidance of nephrotoxic agents, are warranted.

  9. Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups.

    PubMed

    de Velasco, Guillermo; Miao, Diana; Voss, Martin H; Hakimi, A Ari; Hsieh, James J; Tannir, Nizar M; Tamboli, Pheroze; Appleman, Leonard J; Rathmell, W Kimryn; Van Allen, Eliezer M; Choueiri, Toni K

    2016-10-01

    Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared with patients with favorable or intermediate risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here, we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole-exome transcriptome data in renal cell carcinoma patients (n = 54) included in The Cancer Genome Atlas who ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by the MSKCC risk group, nor was the expression of cytolytic genes-granzyme A and perforin-or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis revealed that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. Cancer Immunol Res; 4(10); 820-2. ©2016 AACR.

  10. Tumor-to-tumor metastasis: report of two cases of renal cell carcinoma metastasizing to microcystic serous cystadenoma of the pancreas.

    PubMed

    Shah, Lopa; Tiesi, Gregory; Bamboat, Zubin; McCain, Donald; Siegel, Andrew; Mannion, Ciaran

    2015-02-01

    Metastatic cancer to the pancreas accounts for less than 2% of all pancreatic malignancies. In contrast to other metastatic tumors, renal cell carcinoma (RCC) has a propensity to metastasize as a solitary pancreatic lesion. While symptomatic patients may present with obstructive jaundice, abdominal pain, or gastrointestinal bleeding, the diagnosis of metastatic pancreatic involvement is often made in asymptomatic patients, during follow-up evaluation in the aftermath of an initial diagnosis of renal cell carcinoma. Microcystic serous cystadenoma of the pancreas is an uncommon pancreatic exocrine neoplasm that morphologically resembles conventional (clear cell) RCC, in so far as both tumors are characterized by neoplastic cells with clear cytoplasm, relatively uniform nuclei and scant associated tumor stroma. Herein, we report 2 immunohistochemically confirmed cases of unsuspected metastatic RCC to the pancreas, with the metastatic tumor in each case confined to a preexisting microcystic serous cystadenoma of the pancreas.

  11. A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer

    PubMed Central

    Berlato, Chiara; Khan, Moddasar N.; Thompson, Richard; Maniati, Eleni; Montfort, Anne; Jangani, Maryam; Canosa, Monica; Kulbe, Hagen; Hagemann, Urs B.; Duncan, Alexander R.; Fletcher, Laura; Wilkinson, Robert W.; Powles, Thomas; Quezada, Sergio A.; Balkwill, Frances R.

    2017-01-01

    Elevated expression of the chemokine receptor CCR4 in tumors is associated with poor prognosis in several cancers. Here, we have determined that CCR4 was highly expressed in human renal cell carcinoma (RCC) biopsies and observed abnormal levels of CCR4 ligands in RCC patient plasma. An antagonistic anti-CCR4 antibody had antitumor activity in the RENCA mouse model of RCC. CCR4 inhibition did not reduce the proportion of infiltrating leukocytes in the tumor microenvironment but altered the phenotype of myeloid cells, increased NK cell and Th1 cytokine levels, and reduced immature myeloid cell infiltrate and blood chemokine levels. In spite of prominent changes in the myeloid compartment, the anti-CCR4 antibody did not affect RENCA tumors in T cell–deficient mice, and treatment with an anti–class II MHC antibody abrogated its antitumor activity. We concluded that the effects of the anti-CCR4 antibody required the adaptive immune system and CD4+ T cells. Moreover, CCL17-induced IFN-γ production was reduced when Th1-polarized normal CD4+ T cells were exposed to the CCR4 ligand, evidencing the involvement of CCR4 in Th1/Th2 regulation. The anti-CCR4 antibody, alone or in combination with other immune modulators, is a potential treatment approach to human solid cancers with high levels of CCR4-expressing tumor-infiltrating leukocytes and abnormal plasma CCR4 ligand levels. PMID:28134623

  12. Genomics of chromophobe renal cell carcinoma: implications from a rare tumor for pan-cancer studies

    PubMed Central

    Rathmell, Kimryn W.; Chen, Fengju; Creighton, Chad J.

    2015-01-01

    Chromophobe Renal Cell Carcinoma (ChRCC) is a rare subtype of the renal cell carcinomas, a heterogenous group of cancers arising from the nephron. Recently, The Cancer Genome Atlas (TCGA) profiled this understudied disease using multiple data platforms, including whole exome sequencing, whole genome sequencing (WGS), and mitochondrial DNA (mtDNA) sequencing. The insights gained from this study would have implications for other types of kidney cancer as well as for cancer biology in general. Global molecular patterns in ChRCC provided clues as to this cancer's cell of origin, which is distinct from that of the other renal cell carcinomas, illustrating an approach that might be applied towards elucidating the cell of origin of other cancer types. MtDNA sequencing revealed loss-of-function mutations in NADH dehydrogenase subunits, highlighting the role of deregulated metabolism in this and other cancers. Analysis of WGS data led to the discovery of recurrent genomic rearrangements involving TERT promoter region, which were associated with very high expression levels of TERT, pointing to a potential mechanism for TERT deregulation that might be found in other cancers. WGS data, generated by large scale efforts such as TCGA and the International Cancer Genomics Consortium (ICGC), could be more extensively mined across various cancer types, to uncover structural variants, mtDNA mutations, themes of tumor metabolic properties, as well as noncoding point mutations. TCGA's data on ChRCC should continue to serve as a resource for future pan-cancer as well as kidney cancer studies, and highlight the value of investigations into rare tumor types to globally inform principals of cancer biology. PMID:25859550

  13. POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMOR IS INDEPENDENT OF CODING REGION MUTATIONS IN THE VON HIPPEL- LINDAU GENE

    EPA Science Inventory

    Potassium bromate (KBr03) is a rat renal carcinogen and a major drinking water disinfection by-product from ozonization. While KBr03 is a human nephro- and neuro-toxicant, its carcinogenicity in humans is unknown. Clear cell renal tumors, the common form of human renal carcinomas...

  14. POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMOR IS INDEPENDENT OF CODING REGION MUTATIONS IN THE VON HIPPEL- LINDAU GENE

    EPA Science Inventory

    Potassium bromate (KBr03) is a rat renal carcinogen and a major drinking water disinfection by-product from ozonization. While KBr03 is a human nephro- and neuro-toxicant, its carcinogenicity in humans is unknown. Clear cell renal tumors, the common form of human renal carcinomas...

  15. [Vancouver classification of renal tumors: Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)].

    PubMed

    Kristiansen, G; Delahunt, B; Srigley, J R; Lüders, C; Lunkenheimer, J-M; Gevensleben, H; Thiesler, T; Montironi, R; Egevad, L

    2015-05-01

    The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics.

  16. Natural history of untreated renal cell carcinoma with venous tumor thrombus.

    PubMed

    Reese, Adam C; Whitson, Jared M; Meng, Maxwell V

    2013-10-01

    The natural history of untreated renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is poorly characterized. We aimed to describe the natural history of this disease, and to identify prognostic factors associated with disease-specific survival. We identified patients in the Surveillance, Epidemiology, and End Results (SEER) database with untreated renal cell carcinoma and venous tumor thrombi. Disease-specific median and 1-year survival rates were determined, and disease-free survival curves were plotted using the Kaplan-Meier method. Multivariable Cox regression analyses were performed to identify factors associated with disease-specific and overall survival in this patient group. Of 2,265 patients with RCC and VTT, 390 (17%) underwent no treatment; 278 (71%) patients died during follow-up; of these, 243 deaths (87%) were due to RCC. Median and 1-year disease-specific survival for this group was 5 months and 29%, respectively. On multivariable analysis, the extent of tumor thrombus (HR 1.7 for T3c vs. T3b, 95% CI 1.0-2.7) and the presence of metastases (HR 3.1 for M+ vs. M0, 95% CI 1.7-5.5) were most strongly associated with disease-specific mortality. Prognosis is poor for the majority of untreated patients with RCC and VTT. Supradiaphragmatic thrombi and distant metastases are adverse prognostic factors in this patient group. This information is important when counseling patients as to the risk and benefits of surgical vs. nonoperative management of RCC and VTT. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Targeted contrast-enhanced ultrasound imaging of angiogenesis in an orthotopic mouse tumor model of renal carcinoma.

    PubMed

    Wei, Shuping; Fu, Ninghua; Sun, Yu; Yang, Zhijian; Lei, Li; Huang, Pengfei; Yang, Bin

    2014-06-01

    Previous studies have reported that microbubbles bearing targeting ligands to molecular markers of angiogenesis can be successfully detected by ultrasound imaging in various animal models of solid cancer. In the present study, we sought to investigate the activity of microbubbles targeted to vascular endothelial growth factor receptor 2 (VEGFR2) in an orthotopic model of renal cell carcinoma (RCC). Microbubbles conjugated to an anti-VEGFR2 antibody (MBV) were compared with microbubbles conjugated to an isotype control antibody (MBC) or naked microbubbles (MBN). An orthotopic mouse model of human RCC was established by surgically implanting an established tumor within the renal capsule in mice. Tumor growth and blood flow were verified by B-mode and color Doppler ultrasound imaging. VEGFR2 expression within the tumor and renal parenchyma was detected by immunohistochemistry. The duration of contrast enhancement of MBV was much longer than those of MBN and MBC when assessed over 10 min. The baseline-subtracted contrast intensity within the tumor was higher for MBV than for MBC and MBN (p < 0.01). Additionally, the contrast intensity for MBV was significantly higher in the tumor region than in normal parenchyma (p < 0.01). Microbubbles targeting VEGFR2 exhibit suitable properties for imaging angiogenesis in orthotopic models of renal cell carcinoma, with potential applications in life science research and clinical medicine. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  18. Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - A Systematic Review with Description of Type, Frequency, Risk Factors and Management.

    PubMed

    Vollherbst, Dominik; Bertheau, Robert; Kauczor, Hans-Ulrich; Radeleff, Boris Alexis; Pereira, Philippe L; Sommer, Christof-Matthias

    2017-03-01

    Background Radiofrequency ablation (RFA) is an established treatment for small renal tumors. The objective of this review is to systematically assess the type, frequency, risk factors and management of treatment failure after image-guided percutaneous RFA of renal tumors. Method 10 studies (967 patients, 1033 tumors) with a mean/median follow-up of ≥ 30 months were systematically identified and analyzed. Results and Conclusion Image-guided percutaneous RFA of localized renal tumors is very effective. The most common type of treatment failure is residual unablated tumor (5.9 %), followed by local tumor progression (4.7 %). De novo tumors in the kidneys occur in 1.3 % of cases and extra-renal metastases in 2.0 %. Local tumor progression, de novo tumors in the kidneys and extra-renal metastases occur predominantly later than 12 months after initial RFA. Tumor size > 3 cm and central tumor location are the major risk factors for treatment failure. In the case of treatment failure, repeated RFA shows high success rates (86.3 % for residual unablated tumors and 87.5 % for local tumor progression). Key Points: · Treatment failure can be subdivided into residual unablated tumor and local tumor progression.. · Residual unablated tumor occurs in 5.9 % of cases.. · Local tumor progression occurs in 4.7 % of cases.. · Tumor size and location are the major risk factors for treatment failure.. · Repeated RFA is effective and commonly used for management.. Citation Format · Vollherbst D, Bertheau R, Kauczor H et al. Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - A Systematic Review with Description of Type, Frequency, Risk Factors and Management. Fortschr Röntgenstr 2017; 189: 219 - 227.

  19. PO-60 - Renal tumors with extensive vascular disease: management challenges in a pediatric series from the Hospital for Sick Children.

    PubMed

    Zamperlini-Netto, G; Zanette, A; Wehbi, E; Williams, S; Grant, R M; Brandao, L R

    2016-04-01

    Venous thrombotic events (VTE) are becoming more and more common in children, particularly in the hospital setting. To date, 1 in 200 children admitted to tertiary pediatric hospitals are now being recognized to develop VTE. Amongst those patients with an identified thrombotic occlusion, pediatric patients diagnosed with renal tumors have long been recognized, but their ideal management in the instances of vascular invasion remains controversial. We describe the clinical behavior of patients diagnosed with renal tumors and extra renal vascular involvement at The Hospital for Sick Children in Toronto, Canada. A retrospective analysis was conducted in patients diagnosed from 1990 to 2012. Data collected included: age, gender, symptoms at presentation, staging, pathology report, radiological evidence of intravascular thrombus [i.e. renal veins (RV), inferior vena cava (IVC) and right atrium (RA)], intraoperative findings, therapeutic protocol implemented and anticoagulation; for outcomes, tumor and/or thrombus recurrence, thromboembolic phenomena [i.e. pulmonary embolism (PE)] and survival. Of 299 patients with renal tumors identified, 292 were included: Wilms (219), Renal Cell Carcinoma (RCC, 29), Clear Cell Sarcoma of the Kidney (CCSK, 12), others (32). The median age of the group was 4.53years (4days - 18 years). Extra renal vascular disease was identified in 29 patients, with a median age 7.05years (0.6-16 years; p=0.03), including Wilms tumors (22/219, 10%), RCC (2/29, 7%), CCSK (1/12, 8.3%) and others (4/32, 12.5%; p=0.01). Vascular involvement comprised exclusive evidence of RV disease (7), IVC disease (19; 15 infra-hepatic), RA disease (3) and PE (5).Treatment escalation because of vascular disease included neo-adjuvant chemotherapy (12; Wilms [11], RCC [1]), intraoperative cavectomy/ thrombectomy (1; Wilms), and cavotomies (11 Wilms [7], RCC [1], CCSK [1], PNET [1], sarcoma [1]). Four patients were placed under cardiopulmonary bypass. Anticoagulation was

  20. [Current status of alternative therapies renal function at the Instituto Mexicano del Seguro Social].

    PubMed

    Méndez-Durán, Antonio; Ignorosa-Luna, Manuel Humberto; Pérez-Aguilar, Gilberto; Rivera-Rodríguez, Francisco Jesús; González-Izquierdo, José Jesús; Dávila-Torres, Javier

    2016-01-01

    Introducción: el IMSS realiza de manera sistemática la actualización de datos de los pacientes en terapias sustitutivas de la función renal (TSFR) mediante un registro electrónico denominado: Censo de administración de pacientes con Insuficiencia Renal Crónica (CIRC), cuyo objetivo es conocer la prevalencia de pacientes con insuficiencia renal crónica y el comportamiento de las TSFR en el IMSS. Métodos: estudio retrospectivo, incluye 212 hospitales de segundo nivel con programas de diálisis, pacientes pediátricos y adultos. Datos obtenidos del CIRC de enero a diciembre de 2014, cédulas numeral y nominal de diálisis peritoneal (DP) y hemodiálisis (HD). Se identifica prevalencia de pacientes y terapias por delegación, distribución por género y edad, causa de la enfermedad renal, la morbilidad y mortalidad. Resultados: 55 101 pacientes, de los cuales fueron 29 924 masculinos (54 %) y 25 177 femeninos (46 %); edad promedio 62.1 años (rng: 4 a 90); pensionados 20 387 (36.9 %). Las causas de la insuficiencia renal fueron: diabetes 29 054 (52.7 %), hipertensión arterial 18 975 (34.4%), glomerulopatías crónicas 3951 (7.2 %), riñones poliquísticos 1142 (2.1 %), congénitos 875 (1.6 %), y otras 1104 (2 %). La HD se otorgó en 41 % de los pacientes y la DP al 59 % restante; el costo anual fue de 5 608 290 622 pesos. Conclusiones: la prevalencia incrementada de diabetes mellitus e hipertensión arterial repercuten en el inicio de una TSFR, las cuales muestran un panorama financiero catastrófico para el Instituto.

  1. Modification of the tumor microenvironment as a novel target of renal cell carcinoma therapeutics.

    PubMed

    Finke, James H; Rayman, Pat A; Ko, Jennifer S; Bradley, Judy M; Gendler, Sandra J; Cohen, Peter A

    2013-01-01

    To move forward with immunotherapy, it is important to understand how the tumor microenvironment generates systemic immunosuppression in patients with renal cell carcinoma (RCC) as well as in patients with other types of solid tumors. Even though antigen discovery in RCC has lagged behind melanoma, recent clinical trials have finally authenticated that RCC is susceptible to vaccine-based therapy. Furthermore, judicious coadministration of cytokines and chemotherapy can potentiate therapeutic responses to vaccine in RCC and prolong survival, as has already proved possible for melanoma. Although high-dose interleukin 2 immunotherapy has been superseded as first-line therapy for RCC by promiscuous receptor tyrosine kinase inhibitors (rTKIs) such as sunitinib, sunitinib itself is a potent immunoadjunct in animal tumor models. A reasonable therapeutic goal is to unite antiangiogenic strategies with immunotherapy as first-line therapy for RCC. This strategy is equally appropriate for testing in all solid tumors in which the microenvironment generates immunosuppression. A common element of RCC and pancreatic, colon, breast, and other solid tumors is large numbers of circulating myeloid-derived suppressor cells (MDSCs), and because MDSCs elicit regulatory T cells rather than vice versa, gaining control over MDSCs is an important initial step in any immunotherapy. Although rTKIs like sunitinib have a remarkable capacity to deplete MDSCs and restore normal T-cell function in peripheral body compartments such as the bloodstream and the spleen, such rTKIs are effective only against MDSCs, which are engaged in phospho-STAT3-dependent programming (pSTAT3+). Unfortunately, rTKI-resistant pSTAT3- MDSCs are especially apt to arise within the tumor microenvironment itself, necessitating strategies that do not rely exclusively on STAT3 disruption. The most utilitarian strategy to gain control of both pSTAT3+ and pSTAT3- MDSCs may be to exploit the natural differentiation pathway

  2. Neutrophil Chemokines Secreted by Tumor Cells Mount a Lung Antimetastatic Response during Renal Cell Carcinoma Progression

    PubMed Central

    López-Lago, Miguel A.; Posner, Shai; Thodima, Venkata J.; Molina, Ana M.; Motzer, Robert J.; Chaganti, RSK

    2012-01-01

    The mechanism by which renal cell carcinoma (RCC) colonizes the lung microenvironment during metastasis remains largely unknown. To investigate this process, we grafted human RCC cells with varying lung metastatic potential in mice. Gene expression profiling of the mouse lung stromal compartment revealed a signature enriched for neutrophil-specific functions that was induced preferentially by poorly metastatic cells. Analysis of the gene expression signatures of tumor cell lines showed an inverse correlation between metastatic activity and the levels of a number of chemokines, including CXCL5 and IL8. Enforced depletion of CXCL5 and IL8 in these cell lines enabled us to establish a functional link between lung neutrophil infiltration, secretion of chemokines by cancer cells, and metastatic activity. We further show that human neutrophils display a higher cytotoxic activity against poorly metastatic cells compared to highly metastatic cells. Together, these results support a model in which neutrophils recruited to the lung by tumor-secreted chemokines build an antimetastatic barrier with loss of neutrophil chemokines in tumor cells acting as a critical rate-limiting step during lung metastatic seeding. PMID:22665059

  3. Craniofacial brown tumor as a result of secondary hyperparathyroidism in chronic renal disease patient: A rare entity

    PubMed Central

    Verma, Pradhuman; Verma, Kanika Gupta; Verma, Dinesh; Patwardhan, Nitin

    2014-01-01

    Brown tumors are erosive bony lesions caused by rapid osteoclastic activity and peritrabecular fibrosis due to primary or secondary hyperparathyroidism resulting in a local destructive phenomenon. The differential diagnosis based on histological examination is only presumptive. Clinical, radiological and laboratory data are necessary for definitive diagnosis. Here, we report a very rare case of brown tumor involving maxilla and mandible, which is the result of secondary hyperparathyroidism in 30-year-old female patient with chronic renal disease. PMID:25328310

  4. Optical-resolution photoacoustic microscopy of the metabolic rate of oxygen in a mouse renal tumor model

    NASA Astrophysics Data System (ADS)

    Yeh, Chenghung; Hu, Song; Liang, Jinyang; Li, Lei; Soetikno, Brian; Lu, Zhi Hong; Sohn, Rebecca E.; Maslov, Konstantin; Arbeit, Jeffrey M.; Wang, Lihong V.

    2015-03-01

    We propose using noninvasive longitudinal optical-resolution photoacoustic microscopy (L-ORPAM) to quantify blood flow flux, oxygen saturation (sO2), and thereby the metabolic rate of oxygen (MRO2), for a renal tumor model in the same mouse over weeks to months. Experiments showed that the sO2 difference between the artery and vein decreased greatly due to the arteriovenous shunting effect during tumor growth. Moreover, hypermetabolism was exhibited by an increase in MRO2.

  5. Does a venous tumor thrombus exclude renal transitional cell carcinoma? Implications for neo-adjuvant treatment strategies.

    PubMed

    Huber, Johannes; Teber, Dogu; Hatiboglu, Gencay; Popeneciu, Valentin; Jakobi, Hildegard; Hallscheidt, Peter; Pahernik, Sascha; Hohenfellner, Markus

    2014-02-01

    A venous tumor thrombus (VTT) is well-known in renal cell carcinoma, but we experienced a series of five patients with VTT due to renal transitional cell carcinoma (TCC). Our study aimed to determine the incidence and clinical relevance of this entity. From our prospectively-maintained tumor database, we identified 102 patients with renal TCC according to postoperative histology and analyzed the incidence of VTT in renal TCC from 1990 to 2010. Five out of 102 patients with TCC (5%) had a VTT. None of these five patients experienced gross haematuria and we presumed correct diagnosis preoperatively in one out of five patients. Univariate analysis revealed that TNM stage and resection status were inferior in the VTT group. All five patients from the VTT group died from their disease, with a median survival of 8.9 months. With regard to all diagnosed VTT, the effective incidence of vena cava involvement in RCC was 48-fold higher than in renal TCC. A VTT is very suggestive of renal cell carcinoma. However, before neo-adjuvant treatment, the diagnosis should be assured whenever there is doubt.

  6. A rare case of TFE-related pigmented renal tumor with overlapping features between melanotic Xp11 translocation renal cancer and Xp11 renal cell carcinoma with melanotic features.

    PubMed

    Cardili, Leonardo; Wrublevsky Pereira, Gregório; Viana, Cristiano Ribeiro

    2017-02-16

    In recent years, an increasing number of TFE3 rearrangement-associated tumors with melanotic features have been reported as primary neoplasm in different anatomical sites, including the kidney. Melanotic Xp11 translocation renal cancer (MXTRC) and Xp11 renal cell carcinoma with melanotic features (XRCCM) have been proposed to be main categories for pigmented lesions in the microophthalmia-associated transcription factor (MiTF/TFE3) family of renal tumors that may show variable degrees of melanocytic differentiation. Herein we report a rare case of TFE3-related pigmented renal tumor showing unusual immunoexpression of cytokeratins (AE1/AE3) and renal cell carcinoma markers (RCC, CD10). Cathepsin-K and Vimentin were diffusely positive whereas melanocytic markers (HMB-45 and Melan-A) displayed weak and patchy expression. We found no labelling for PAX-8, muscle markers (desmin, smooth muscle actin, muscle-specific actin and caldesmon) and S-100. TFE3 fusion was confirmed by break-apart fluorescence in situ hybridization (FISH). This case corroborates previous evidence for overlap in the TFE3-associated cancer family and illustrates that it may not be possible to set a clear cutoff between epithelial (XRCCM) and mesenchymal (MXTRC) subgroups.

  7. Why should survivors of childhood renal tumor and others with only one kidney be denied the chance to play contact sports?

    PubMed

    Spreafico, Filippo; Terenziani, Monica; van den Heuvel-Eibrink, Marry M; Pritchard-Jones, Kathy; Levitt, Gill; Graf, Norbert; Bergeron, Christophe; Massimino, Maura

    2014-04-01

    Over the last few decades advances in the treatment of childhood and young adult cancer have greatly improved survival. As a result most children diagnosed with Wilms' tumor (the most common renal tumor in childhood) or other renal tumors become long-term survivors, living with surgically solitary kidneys. As physical activity is gaining credibility as a therapy enhancing well-being, encouraging cancer survivors do exercise during adolescence and adulthood is advisable. Discussing current evidence-based information would help to provide a framework for the harmonization of guidelines for sport participation of childhood and young adult renal tumor survivors.

  8. Tumor necrosis factor-α: regulation of renal function and blood pressure

    PubMed Central

    Garvin, Jeffrey L.

    2013-01-01

    Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that becomes elevated in chronic inflammatory states such as hypertension and diabetes and has been found to mediate both increases and decreases in blood pressure. High levels of TNF-α decrease blood pressure, whereas moderate increases in TNF-α have been associated with increased NaCl retention and hypertension. The explanation for these disparate effects is not clear but could simply be due to different concentrations of TNF-α within the kidney, the physiological status of the subject, or the type of stimulus initiating the inflammatory response. TNF-α alters renal hemodynamics and nephron transport, affecting both activity and expression of transporters. It also mediates organ damage by stimulating immune cell infiltration and cell death. Here we will summarize the available findings and attempt to provide plausible explanations for such discrepancies. PMID:23515717

  9. The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies. 1984.

    PubMed

    Neri, Giovanni; Martini-Neri, Maria Enrica; Katz, Ben E; Opitz, John M

    2013-11-01

    The ensuing paper by Professor Giovanni Neri and colleagues was originally published in 1984, American Journal of Medical Genetics 19:195–207. The original article described a new family with a condition that the authors designated as the Perlman syndrome. This disorder, while uncommon, is an important multiple congenital anomaly and dysplasia syndrome; the causative gene was recently identified. This paper is a seminal work and is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al. [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed. © 2013 Wiley Periodicals, Inc.

  10. Comparing renal function preservation after laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for clinical T1a renal tumor: using a 3D parenchyma measurement system.

    PubMed

    Zhu, Liangsong; Wu, Guangyu; Huang, Jiwei; Wang, Jianfeng; Zhang, Ruiyun; Kong, Wen; Xue, Wei; Huang, Yiran; Chen, Yonghui; Zhang, Jin

    2017-05-01

    To compare the renal function preservation between laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy. Data were analyzed from 246 patients who underwent laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for solitary cT1a renal cell carcinoma from January 2013 to July 2015. To reduce the intergroup difference, we used a 1:1 propensity matching analysis. The functional renal parenchyma volume preservation were measured preoperative and 12 months after surgery. The total renal function recovery and spilt GFR was compared. Multivariable logistic analysis was used for predictive factors for renal function decline. After 1:1 propensity matching, each group including 100 patients. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation had a smaller decrease in estimate glomerular filtration rate at 1 day (-7.88 vs -20.01%, p < 0.001), 3 months (-2.31 vs -10.39%, p < 0.001), 6 months (-2.16 vs -7.99%, p = 0.015), 12 months (-3.26 vs -8.03%, p = 0.012) and latest test (-3.24 vs -8.02%, p = 0.040), also had better functional renal parenchyma volume preservation (89.19 vs 84.27%, p < 0.001), lower decrease of the spilt glomerular filtration rate (-9.41 vs -17.13%, p < 0.001) at 12 months. The functional renal parenchyma volume preservation, warm ischemia time and baseline renal function were the important independent factors in determining long-term functional recovery. The laparoscopic radio frequency ablation assisted tumor enucleation technology has unique advantage and potential in preserving renal parenchyma without ischemia damage compared to conventional laparoscopic partial nephrectomy, and had a better outcome, thus we recommend this technique in selected T1a patients.

  11. A novel grading system for clear cell renal cell carcinoma incorporating tumor necrosis.

    PubMed

    Delahunt, Brett; McKenney, Jesse K; Lohse, Christine M; Leibovich, Bradley C; Thompson, Robert Houston; Boorjian, Stephen A; Cheville, John C

    2013-03-01

    Grading of renal cell carcinoma (RCC) has prognostic significance, and there is recent consensus by the International Society of Urological Pathology (ISUP) that for clear cell and papillary RCC, grading should primarily be based on nucleolar prominence. Microscopic tumor necrosis also predicts outcome independent of tumor grading. This study was undertaken to assess whether the incorporation of microscopic tumor necrosis into the ISUP grading system provides survival information superior to ISUP grading alone. Data on 3017 patients treated surgically for clear cell RCC, 556 for papillary RCC, and 180 for chromophobe RCC were retrieved from the Mayo Clinic Registry. Median follow-up periods were 8.9, 9.7, and 8.5 years, respectively. Four proposed grades were defined: grade 1: ISUP grade 1+ISUP grade 2 without necrosis; grade 2: ISUP grade 2 with necrosis+ISUP grade 3 without necrosis; grade 3: ISUP grade 3 with necrosis+ISUP grade 4 without necrosis; grade 4: ISUP grade 4 with necrosis or sarcomatoid/rhabdoid tumors. There was a significant difference in survival between each of the grades for clear cell RCC, and the concordance index was superior to that of ISUP grading. The proposed grading system also outperformed the ISUP grading system when cases were stratified according to the TNM stage. Similar results were not obtained for papillary RCC or chromophobe RCC. We conclude that grading for clear cell RCC should be based on nucleolar prominence and necrosis, that ISUP grading should be used for papillary RCC, and that chromophobe RCC should not be graded.

  12. The mechanism of local tumor irradiation combined with interleukin 2 therapy in murine renal carcinoma: histological evaluation of pulmonary metastases.

    PubMed

    Dezso, B; Haas, G P; Hamzavi, F; Kim, S; Montecillo, E J; Benson, P D; Pontes, J E; Maughan, R L; Hillman, G G

    1996-09-01

    We have demonstrated that tumor irradiation enhanced the therapeutic effect of interleukin 2 (IL-2) on pulmonary metastases from a murine renal adenocarcinoma, Renca. To investigate the mechanism of interaction between tumor irradiation and IL-2 therapy, we have histologically evaluated the effects of each therapy alone or in combination on Renca pulmonary metastases. Following treatment of established lung metastases with irradiation and IL-2 therapy, lung sections were processed for H&E or immunohistochemical staining. We found that tumor irradiation or IL-2 therapy locally induced vascular damage, resulting in multifocal hemorrhages and mononuclear cell mobilization in the lung tissue. This effect was amplified in lungs treated with the combined therapy. Immunohistochemistry showed that irradiation produced a macrophage influx into irradiated tumor nodules, and systemic IL-2 therapy induced T-cell infiltration in tumor nodules. Lungs treated with the combined therapy exhibited massive macrophage, T-cell, and natural killer cell mobilization in disintegrating tumor nodules and in the lung tissue. This combined therapy caused a decrease in the number of proliferating tumor cells and an increase in the number of apoptotic cells, which were more marked than with either therapy alone. We suggest that the macrophages mobilized by radiation-induced tissue injury could play a role in phagocytosis of apoptotic tumor cells, processing and presenting of tumor antigens for a systemic immune response activated by IL-2. Tumor destruction may result from the concomitant action of activated T cells, natural killer cells, and macrophages infiltrating the tumor nodules.

  13. Immunohistochemical characterization of renal tumors in patients with Birt-Hogg-Dubé syndrome.

    PubMed

    Iribe, Yasuhiro; Kuroda, Naoto; Nagashima, Yoji; Yao, Masahiro; Tanaka, Reiko; Gotoda, Hiroko; Kawakami, Fumi; Imamura, Yoshiaki; Nakamura, Yasushi; Ando, Midori; Araki, Akinobu; Matsushima, Jun; Nakatani, Yukio; Furuya, Mitsuko

    2015-03-01

    Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder associated with a germline mutation of folliculin (FLCN). The affected families are at a high risk for developing multiple renal cell carcinomas (RCC). Little is known about the immunostaining patterns of mutant FLCN-associated RCCs. We investigated 32 RCCs obtained from 17 BHD patients. The studied tumors included chromophobe RCCs (n = 15), hybrid oncocytic/chromophobe tumors (HOCT) (n = 14) and clear cell RCCs (n = 3). Almost all chromophobe RCCs and HOCTs revealed positive staining for S100A1, Ksp-cadherin and CD82. They stained either focally or diffusely for CK7, and were negative for CA-IX. All clear cell RCCs were positively stained for CA-IX and negative for CK7. These data confirmed that mutant FLCN-associated oncocytic and clear cell RCCs exhibited generally similar immunostaining patterns compared to their sporadic counterparts. Frequent positive staining for S100A1, Ksp-cadherin and CD82 in chromophobe RCCs and HOCTs indicated that these two types were relatively similar rather than distinctively different in their patterns of immunoreactivity. Characteristic peri-nuclear halos and polygonal cells with clear cytoplasm, which often misleads pathologists into the diagnosis of clear cell RCC, should be carefully examined using an immunohistochemical panel including CA-IX, Ksp-cadherin, CD82 and CK7.

  14. The coexistence of hypercalcemia and hypoglycemia in a patient with a renal tumor and B cell lymphoma.

    PubMed

    Soutelo, Jimena; Moldes, Sofía; Frisone, Cielo; Salvá, Laura; Agostinis, Cecilia; Faraj, Gabriel

    2017-01-01

    Paraneoplastic syndromes are a heterogeneous group of malignant diseases caused by events which involve endocrine, immune and metabolic aspects and whose symptoms vary according to the substance produced and the primary tumor. Hypercalcemia is a frequent complication in cancer patients. Prognosis of cancer patients with hypercalcemia is usually poor. A factor called parathyroid hormone related peptide, whose actions are similar to those of the parathyroid hormone, is thought to be the most common cause of malignancy associated hypercalcemia. Non-islet hypoglycemic cell tumor consists of a rare syndrome characterized by the presence of a solid tumor and severe fasting hypoglycemia determined by an insulin-independent pathway. We report a case of a 59-year-old-man with a renal tumor and a T-cell rich large B cell lymphoma who was hospitalized due to severe hypercalcemia and hypoglycemia. The laboratory examination reported hypercalcemia with inhibited PTH and hypoglycemia with inhibited insulin secretion, arriving to the conclusion of tumoral peptide production. He received denosumab and corticoid therapy. The patient died one month later despite initial improvement after medical treatment. While a single paraneoplastic manifestation may be expected in most tumors, the coexistence of two or more of them is rare, except in hepatocellular carcinomas, and it has not yet been described in renal tumors.

  15. Papillary renal cell carcinoma: correlation of tumor grade and histologic characteristics with clinical outcome.

    PubMed

    Cornejo, Kristine M; Dong, Fei; Zhou, Amy G; Wu, Chin-Lee; Young, Robert H; Braaten, Kristina; Sadow, Peter M; Nielsen, G P; Oliva, Esther

    2015-10-01

    Histologic prognostic parameters in papillary renal cell carcinoma (PRCC) are unclear. The aims were to review the clinicopathological features of PRCC, including Fuhrman grade and International Society of Urological Pathology (ISUP) nucleolar grade, and to identify parameters that may be independent prognostic indicators. PRCCs in patients treated by nephrectomy were retrieved from the pathology files from 1984 to 2010. Parameters studied included tumor multifocality, size, PRCC type (1 or 2), Fuhrman grade, ISUP nucleolar grade, presence of necrosis, lymphovascular invasion, and stage at presentation. Cancer-specific survival (CSS) and overall survival (OS) were used as prognostic measures. Of 154 PRCCs, 112 (73%) were type 1, and 42 (27%), type 2. A total of 125 patients were male, and 29, female, with ages from 26 to 86 (mean, 62.7) years. Fuhrman grade was 1 in 8 (5%), 2 in 95 (62%), 3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. ISUP nucleolar grade was 1 in 47 (31%), 2 in 56 (36%), 3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. Mean follow-up interval was 73.9 months (0.13-222 months). ISUP nucleolar grade was a significant predictor of both CSS and OS in univariate (CSS, P = .001; OS, P = .004) and multivariate (CSS, P = .04; OS, P = .008) analyses, whereas Fuhrman grade was only predictive of CSS in univariate (P = .001) and multivariate (P = .04) analyses. Only ISUP nucleolar grade and lymphovascular invasion were independently prognostic for CSS and OS in univariate and multivariate analyses. Therefore, the ISUP nucleolar grade appears to be superior in predicting survival in patients with PRCC. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Population based analysis of survival in patients with renal cell carcinoma and venous tumor thrombus.

    PubMed

    Whitson, Jared M; Reese, Adam C; Meng, Maxwell V

    2013-02-01

    To identify prognostic factors for renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and determine the significance of thrombus level on survival. Patients within the Surveillance, Epidemiology, and End Results (SEER) database with RCC and VTT were identified and included if managed surgically. The Kaplan-Meier method and Cox regression analyses were performed to identify factors associated with disease-specific survival. A total of 1,875 patients met the inclusion criteria. One-year survival for patients undergoing surgery was 60% for patients with metastases and 90% for those without. Factors associated with worse survival included larger tumor size (HR 1.2, 95% CI 1.0-1.4), medullary, collecting duct, or sarcomatoid histology (HR 2.2, 95% CI 1.5-3.3), Fuhrman grade 3 (HR 2.2, 95% CI 1.5-3.3) or grade 4 (HR 2.9, 95% CI 1.8-4.5) tumors, positive lymph nodes (HR 1.5, 95% CI 1.0-2.0), and metastases (HR 3.5, 95% CI 2.6-4.8). Thrombus level above the diaphragm (T3c) was not significantly associated with worse survival (HR 1.4, 95% CI 0.8-2.5). In this large, population-based study of patients with RCC and VTT, we identify several disease-specific factors strongly associated with cancer-specific mortality. After controlling for adverse prognostic factors, thrombus level was not associated with worse outcome. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. [Presurgical treatment of axitinib reduced operation risk by downsizing the vena cava tumor thrombus in advanced renal cell carcinomas: two case reports].

    PubMed

    Hamada, Akihiro; Yamasaki, Toshinari; Negoro, Hiromitsu; Kobayashi, Takashi; Terada, Naoki; Sugino, Yoshio; Matsui, Yoshiyuki; Inoue, Takahiro; Kamba, Tomomi; Yoshimura, Koji; Ogawa, Osamu

    2014-12-01

    In cases of advanced renal cell carcinoma with inferior vena cava (IVC) thrombus, surgical resection of both tumor and thrombus contributes to the improvement of patient's prognosis, but the risk of perioperative complication is still high. We experienced two cases of advanced renal tumors with IVC tumor thrombus down-sized by presurgical treatment of axitinib. Axitinib treatment showed a marked tumor reduction effect without any severe adverse event. We could remove both tumor and thrombus without perioperative complications. In these two cases, downsizing of IVC thrombus enabled us to reduce the extent of the surgery.

  18. A human novel gene DERPC on 16q22.1 inhibits prostate tumor cell growth and its expression is decreased in prostate and renal tumors.

    PubMed Central

    Sun, Mei; Ma, Lanfeng; Xu, Linda; Li, Jia; Zhang, Wei; Petrovics, Gyorgy; Makarem, Mazen; Sesterhenn, Isabell; Zhang, Mei; Blanchette-Mackie, E. Joan; Moul, Judd; Srivastava, Shiv; Zou, Zhiqiang

    2002-01-01

    BACKGROUND: Deletion of chromosome 16q is frequently associated with diverse tumors. Numerous studies strongly suggest the presence of one or more tumor suppressor genes on chromosome 16q22 to 16qter including the widely studied cadherin gene family. However, the specific tumor suppressor genes residing in this region need better definition and characterization. MATERIAL AND METHODS: Standard molecular biology approaches have been used to clone and characterize the DERPC cDNA and its protein product on chromosome 16q22.1. Northern blotting was used to define the expression pattern in a multiple human tissue blots. DERPC expression was examined in multi-tumor array (Clontech, CA, USA) dot blot as well as in laser capture microdissection (LCM) derived prostate cancer (CaP) specimens by quantitative RT-PCR. Western blot analysis and a fluorescent microscopy were used to characterize the molecular size and the cellular location of green fluorescent protein (GFP)-tagged DERPC fusion proteins. A colony formation assay was conducted to determine the effects of DERPC expression on tumor cell growth. RESULTS: A novel gene DERPC (Decreased Expression in Renal and Prostate Cancer) was identified and characterized. DERPC encoded a strong basic, proline- and glycine-rich nuclear protein. DERPC was ubiquitously expressed, with abundant expression in kidney, skeletal muscle, testis, liver, ovary, and heart and moderate expression in prostate. DERPC expression was reduced in renal (67%) and prostate tumors (33%). Expression of DERPC has inhibitory potential on CaP cell growth. Further, overexpression of DERPC in LNCaP cells caused alterations of nuclear morphology. CONCLUSION: This study suggests that decreased expression of DERPC may be implicated in tumorigenesis of renal and CaPs. PMID:12477976

  19. Tumor infiltrating CD8(+) T lymphocyte count is independent of tumor TLR9 status in treatment naïve triple negative breast cancer and renal cell carcinoma.

    PubMed

    Mella, Mikko; Kauppila, Joonas H; Karihtala, Peeter; Lehenkari, Petri; Jukkola-Vuorinen, Arja; Soini, Ylermi; Auvinen, Päivi; Vaarala, Markku H; Ronkainen, Hanna; Kauppila, Saila; Haapasaari, Kirsi-Maria; Vuopala, Katri S; Selander, Katri S

    2015-06-01

    Toll-like receptor 9 (TLR9) is a cellular DNA-receptor of the innate immune system that is widely expressed in cancers. We demonstrated that low tumor TLR9 expression predicts poor disease-specific survival in triple negative breast cancer (TNBC) and renal cell carcinoma (RCC). We hypothesized that this is because TLR9 expression affects tumor immunophenotype. To begin to test this, we compared the number of tumor infiltrating CD8(+) T lymphocytes with TLR9 expression in treatment naïve breast cancer (n = 197) and RCC (n = 94) cohorts with known TLR9 expression status. CD8(+) T lymphocyte counts were assayed with image analysis after immunohistochemistry (IHC). Tumor TLR9 expression was not correlated with CD8(+) T cell counts in breast cancer or RCC. CD8(+) T cell counts were significantly associated with tumor proliferation index in TNBC, but not in non-TNBC. CD8(+) T cell counts were also significantly associated with tumor grade in non-TNBC, but not in TNBC. In RCC, CD8(+) T cell counts were significantly associated with tumor stage. CD8(+) T cell counts were significantly associated with prognosis in TNBC and RCC, but the presence of CD8(+) T cells in these tumors had opposite effects on disease-specific survival: High CD8(+) counts were associated with better prognosis in TNBC and worse prognosis in RCC. Among TNBC patients, those with low tumor TLR9 and low CD8(+) T cell counts had the poorest prognosis (log-rank p = 0.0002 vs. high tumor TLR9 and high CD8(+) T cell count). In conclusion, pre-treatment tumor TLR9 status is not associated with tumor infiltrating CD8(+) T lymphocytes in TNBC or RCC. The combination of TLR9 and CD8(+) TIL count might be a novel composite prognostic marker in TNBC.

  20. Contribution of magnetic resonance imaging to prenatal differential diagnosis of renal tumors: report of two cases and review of the literature.

    PubMed

    Linam, L E; Yu, X; Calvo-Garcia, M A; Rubio, E I; Crombleholme, T M; Bove, K; Kline-Fath, B M

    2010-01-01

    Enlargement of a kidney on prenatal imaging is usually due to hydronephrosis or cystic renal disease, and much less often results from solid tumors such as mesoblastic nephroma, Wilms' tumor, nephroblastomatosis, renal sarcoma, and angiomyolipoma. All can be diagnosed by ultrasound. Magnetic resonance imaging is useful not only in confirming the presence of a renal mass, but also in the evaluation of the contralateral kidney for subtle abnormalities. We present one case each of Wilms' tumor and mesoblastic nephroma, both detected on antenatal ultrasound and further studied with fetal magnetic resonance imaging. Copyright (c) 2010 S. Karger AG, Basel.

  1. Clinical and histopathological effects of presurgical treatment with sunitinib for renal cell carcinoma with inferior vena cava tumor thrombus at a single institution.

    PubMed

    Ujike, Takeshi; Uemura, Motohide; Kawashima, Atsunari; Nagahara, Akira; Fujita, Kazutoshi; Miyagawa, Yasushi; Nonomura, Norio

    2016-11-01

    To evaluate the clinical and histopathological effects of presurgical treatment with sunitinib on inferior vena cava (IVC) tumor thrombus. Between 2010 and 2014, we treated seven patients with renal cell carcinoma and IVC tumor thrombus presurgically with sunitinib. We retrospectively evaluated primitive tumor size, the level of tumor thrombus according to Novick's classification, its distance above the renal vein, thrombus diameter at its widest segment, and histopathological change after sunitinib treatment. Three patients were diagnosed histologically. Percutaneous biopsy of the renal mass before sunitinib treatment was performed in two patients. One patient was diagnosed after sunitinib treatment following nephrectomy. The primitive tumors shrank upon sunitinib therapy in four cases; however, although the caval thrombus was downstaged (from level II to I) in one patient, the level of caval thrombus did not change in five patients and increased in one patient (from level III to IV). We evaluated the histopathological effects in two patients. In one patient, the IVC tumor thrombus was mostly replaced with necrotic tissue, but its thrombus level was not downstaged. In the other patient, the IVC tumor thrombus was downstaged, but tumor thrombus was not replaced with necrotic tissue and viable tumor cells remained. Presurgical treatment with sunitinib for renal cell carcinoma with IVC tumor thrombus appears to have limited effect on IVC tumor thrombus, in contrast to its effects on primitive tumor shrinkage. In the absence of evidence of presurgical benefits from prospective studies, this treatment may not be systematically advisable.

  2. Fulminant Buddchiari syndrome caused by renal primitive neuroectodermal tumor with inferior vena cava thrombus extending to atrium.

    PubMed

    Mete, Uttam K; Singh, Dig Vijay; Bhattacharya, Anish; Kakkar, Nandita

    2015-01-01

    Primitive neuroectodermal tumors (PNET) of the kidney are rare, the diagnosis usually being made at histopathology. A young female presented with a massive right renal mass with features of hepatic dysfunction. Computed tomography scan of the abdomen revealed a large tumor of right kidney with tumor thrombus extending from inferior vena cava (IVC) to right atrium with features suggesting Buddchiari syndrome (BCS). Needle biopsy of mass showed a round cell neoplasm and positive staining for neuron specific enolase and minimum inhibitory concentration-2 on immunohistochemistry. She was managed with neo-adjuvant chemotherapy, surgery and adjuvant chemotherapy. To the best of our knowledge this is the first case of renal PNET with inferior IVC tumor thrombus extending to right atrium with BCS. We suggest that renal PNET should be kept in mind as a differential diagnosis in young adults presenting with a large kidney mass extending to IVC that shows evidence of necrosis on imaging, which may be associated with BCS as in index case.

  3. A Mathematical Method to Calculate Tumor Contact Surface Area: An Effective Parameter to Predict Renal Function after Partial Nephrectomy.

    PubMed

    Hsieh, Po-Fan; Wang, Yu-De; Huang, Chi-Ping; Wu, Hsi-Chin; Yang, Che-Rei; Chen, Guang-Heng; Chang, Chao-Hsiang

    2016-07-01

    We proposed a mathematical formula to calculate contact surface area between a tumor and renal parenchyma. We examined the applicability of using contact surface area to predict renal function after partial nephrectomy. We performed this retrospective study in patients who underwent partial nephrectomy between January 2012 and December 2014. Based on abdominopelvic computerized tomography or magnetic resonance imaging, we calculated the contact surface area using the formula (2*π*radius*depth) developed by integral calculus. We then evaluated the correlation between contact surface area and perioperative parameters, and compared contact surface area and R.E.N.A.L. (Radius/Exophytic/endophytic/Nearness to collecting system/Anterior/Location) score in predicting a reduction in renal function. Overall 35, 26 and 45 patients underwent partial nephrectomy with open, laparoscopic and robotic approaches, respectively. Mean ± SD contact surface area was 30.7±26.1 cm(2) and median (IQR) R.E.N.A.L. score was 7 (2.25). Spearman correlation analysis showed that contact surface area was significantly associated with estimated blood loss (p=0.04), operative time (p=0.04) and percent change in estimated glomerular filtration rate (p <0.001). On multivariate analysis contact surface area and R.E.N.A.L. score independently affected percent change in estimated glomerular filtration rate (p <0.001 and p=0.03, respectively). On ROC curve analysis contact surface area was a better independent predictor of a greater than 10% change in estimated glomerular filtration rate compared to R.E.N.A.L. score (AUC 0.86 vs 0.69). Using this simple mathematical method, contact surface area was associated with surgical outcomes. Compared to R.E.N.A.L. score, contact surface area was a better predictor of functional change after partial nephrectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Differences in Renal Tumor Size Measurements for Computed Tomography Versus Magnetic Resonance Imaging: Implications for Patients on Active Surveillance.

    PubMed

    Khan, Irtaza; Beksac, Alp Tuna; Paulucci, David J; Abaza, Ronney; Eun, Daniel D; Bhandari, Akshay; Badani, Ketan K

    2017-08-11

    To evaluate and compare the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in predicting the final pathologic tumor size of partial nephrectomy specimens. We analyzed a multi-institutional database of 807 patients who underwent robotic partial nephrectomy for a cT1a renal mass from 2006 to 2016. Patients who had a solitary tumor with complete data on the baseline imaging modality and the tumor size (baseline and pathologic) (n = 349) were included for analysis. Baseline tumor size evaluated by both imaging modalities, in addition to the difference between the measurements and final pathologic tumor size (cm) measurements, was compared between patients who received a baseline CT (n = 276, 79.1%) and those who received an MRI (n = 73, 20.9%). There were no statistically significant differences between any baseline characteristics and receipt of a CT versus MRI. In multivariable analysis adjusting for confounders, there was no significant difference in the baseline tumor size between patients receiving an MRI and those receiving a CT (2.3 versus 2.6 cm; β = -0.13; 95% confidence interval [CI] = -0.33 to 0.07; P = .208). Tumor size on imaging was smaller from final pathology by 0.43 cm on average (P = .002). Measurement error for the measured baseline versus actual pathologic tumor size did not significantly differ for patients receiving an MRI versus those receiving a CT (0.38 versus 0.44 cm; β = -0.06; 95% CI = -0.16 to 0.04; P = .232). Baseline renal tumor size measurements were not significantly different for CT scan and MRI. Choice of imaging modality can be based on doctor and patient preference, including cost and exposure to radiation.

  5. Biochemical characterization of human renal tumors by in vitro nuclear magnetic resonance

    NASA Astrophysics Data System (ADS)

    Tosi, M. R.; Tugnoli, V.; Bottura, G.; Lucchi, P.; Battaglia, A.; Giorgianni, P.

    2001-05-01

    This study reports an in vitro magnetic resonance spectroscopy characterization of healthy renal parenchyma, renal cell carcinomas and oncocytomas. In vitro 1H NMR measurements allow in-depth biochemical characterization of human healthy and neoplastic renal tissues. Some metabolites with an osmotic activity are considered markers of physiological renal function. Moreover, the HPLC technique was applied to investigate the amino acidic profile of these tissues: some amino acids appear to have statistic significance.

  6. Tumor thrombus in a retroaortic left renal vein and incidental right circumcaval ureter.

    PubMed

    Pinsk, R; Nemcek, A A; Fitzgerald, S W

    1992-01-01

    The authors describe computed tomographic (CT) and magnetic resonance (MR) imaging of coexistent anomalies of the inferior vena cava and renal venous system. These were particularly relevant due to the presence of a renal neoplasm which invaded an anomalous renal vein.

  7. Tumor Necrosis on Magnetic Resonance Imaging Correlates with Aggressive Histology and Disease Progression in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Beddy, Peter; Genega, Elizabeth M; Ngo, Long; Hindman, Nicole; Wei, Jesse; Bullock, Andrea; Bhatt, Rupal S; Atkins, Michael B; Pedrosa, Ivan

    2015-01-01

    Purpose To correlate the magnetic resonance imaging (MRI) features of clear cell renal cell carcinoma (ccRCC) with the histopathological features and disease progression. Material and Methods IRB approval for this retrospective study was obtained; patient consent was not required. The initial staging MRIs of 75 patients with histologically confirmed ccRCC were retrospectively reviewed. The imaging was assessed by two radiologists for the presence of tumor necrosis, cystic degeneration, intracellular fat, hemorrhage, retroperitoneal collaterals and renal vein thrombosis. Quantitative analysis for the MRI presence of intracellular lipid within tumors was performed. MRI findings were correlated with histopathologic findings of clear cell percentage, alveolar and tubular growth pattern and disease progression. Statistical associations were evaluated with non-parametric univariable analyses and multivariable logistic regression models. Results Correlation between MRI and histopathologic features was performed in 75 patients whereas follow-up data was available for progression analysis in 68 patients. The presence of tumor necrosis, retroperitoneal collaterals and renal vein thrombosis on MRI were significantly associated with low percentage of tumor cells with clear cytoplasm (p<0.01) and with metastatic disease at presentation or disease progression (p<0.01). At multivariable analysis, necrosis remained as the only feature statistically associated with disease progression (p=0.03, adjusted odds ratio=27.7, CI 95%=1.4–554.7 for reader one and p=0.02, adjusted odds ratio=29.3, CI 95%=1.7–520.8 for reader two). Conclusion Necrosis in ccRCC on MRI correlates with the histopathological finding of lower percentage of tumor cells with clear cytoplasm and is a poor prognostic indicator irrespective of tumor size. PMID:24145001

  8. Intratumor Heterogeneity of Perfusion and Diffusion in Clear-Cell Renal Cell Carcinoma: Correlation With Tumor Cellularity.

    PubMed

    Yuan, Qing; Kapur, Payal; Zhang, Yue; Xi, Yin; Carvo, Ingrid; Signoretti, Sabina; Dimitrov, Ivan E; Cadeddu, Jeffrey A; Margulis, Vitaly; Brugarolas, James; Madhuranthakam, Ananth J; Pedrosa, Ivan

    2016-12-01

    Magnetic resonance imaging (MRI) has the potential to noninvasively provide information about the tumor microenvironment. A correlation between arterial spin-labeled (ASL) MRI and tumor vasculature has been previously demonstrated; however, its correlation with tumor cellularity is unknown. We sought to assess intratumor heterogeneity of perfusion and diffusion in vivo in clear-cell renal cell carcinoma (ccRCC) using MRI and to correlate these findings with tumor vascularity and cellularity at histopathology. Twenty-three ccRCC patients underwent ASL and diffusion-weighted MRI before surgery after signing an informed consent in this prospective institutional review board-approved, HIPAA (Insurance Portability and Accountability Act)-compliant study. Quantitative ASL perfusion and diffusion were measured in 2 areas within the same tumor with high and low perfusion. Microvessel density (MVD) on CD31 and CD34 immunostains and tumor cellularity in anatomically coregistered tissue samples were correlated to MRI measurements (Spearman; P < .05 statistically significant). ASL perfusion (P < .0001), CD31 MVD (P = .02), CD34 MVD (P = .04), and cellularity (P = .002) from high and low perfusion areas were significantly different across all tumors. There were positive correlations between tumor cellularity and CD31 MVD (ρ = 0.350, P = .021), CD31 and CD34 MVD (ρ = 0.838, P < .0001), ASL perfusion and cellularity (ρ = 0.406, P = .011), and ASL perfusion and CD31 MVD (ρ = 0.468, P = .003), and a negative correlation between tissue diffusion coefficient and cellularity (ρ = -0.316, P = .039). Tumor areas with high ASL perfusion exhibit higher cellularity and MVD compared to areas with low perfusion in the same tumor. A positive correlation between tumor vascularity and cellularity in ccRCC is newly reported. A negative correlation between tumor diffusion and cellularity is confirmed. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Investigations on the presence of papova virus in certain forms of human cancer. Note I. Renal tumors and melanomas.

    PubMed

    Stoian, M; Dumitrescu, S M; Athanasiu, P; Nastac, E

    1980-01-01

    Within the framework of their research concerns regarding the presence of papova viruses in the human population of Romania, as well as the relationship between these viruses and certain forms of human cancer, the authors undertook an electron microscopic study of 4 renal tumors and 6 melanomas. No viral particles could be made evident in any of the sections examined. Viral SV-40 antigen was detected by indirect immunofluorescence reaction in kidney sections from a nephrosis case considered as control.

  10. Role of Tumor Necrosis Factor Alpha in Disease Using a Mouse Model of Shiga Toxin-Mediated Renal Damage ▿

    PubMed Central

    Lentz, Erin K.; Cherla, Rama P.; Jaspers, Valery; Weeks, Bradley R.; Tesh, Vernon L.

    2010-01-01

    Mice have been extensively employed as an animal model of renal damage caused by Shiga toxins. In this study, we examined the role of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) in the development of toxin-mediated renal disease in mice. Mice pretreated with TNF-α and challenged with Shiga toxin type 1 (Stx1) showed increased survival compared to that of mice treated with Stx1 alone. Conversely, mice treated with Stx1 before TNF-α administration succumbed more quickly than mice given Stx1 alone. Increased lethality in mice treated with Stx1 followed by TNF-α was associated with evidence of glomerular damage and the loss of renal function. No differences in renal histopathology were noted between animals treated with Stx1 alone and the TNF-α pretreatment group, although we noted a sparing of renal function when TNF-α was administered before toxin. Compared to that of treatment with Stx1 alone, treatment with TNF-α after toxin altered the renal cytokine profile so that the expression of proinflammatory cytokines TNF-α and interleukin-1β (IL-1β) increased, and the expression of the anti-inflammatory cytokine IL-10 decreased. Increased lethality in mice treated with Stx1 followed by TNF-α was associated with higher numbers of dUTP-biotin nick end labeling-positive renal tubule cells, suggesting that increased lethality involved enhanced apoptosis. These data suggest that the early administration of TNF-α is a candidate interventional strategy blocking disease progression, while TNF-α production after intoxication exacerbates disease. PMID:20605983

  11. Characterization of pancreatic islet cell tumors and renal tumors induced by a combined treatment of streptozotocin and nicotinamide in male SD rats.

    PubMed

    Kato, Yuki; Masuno, Koichi; Fujisawa, Kae; Tsuchiya, Noriko; Torii, Mikinori; Hishikawa, Atsuko; Izawa, Takeshi; Kuwamura, Mitsuru; Yamate, Jyoji

    2017-09-05

    We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37-45 weeks after the treatment with STZ (50 or 75mg/kg, i.v.) and NA (350mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas. Most STZ/NA-induced carcinomas were characterized by well-differentiated tumor cells with/without local invasion into the surrounding tissues, and weak proliferative activity. No outcome such as distance metastasis and death was noted. All of the ICTs strongly expressed insulin, part of which had hormone productivity; however there were no hypoglycemia-related clinical signs such as convulsion in these rats 36 weeks after the treatment. These results suggested that rat ICTs induced STZ/NA have small impact on biological activity or prognosis. STZ/NA treatment significantly increased of focal proliferative lesions in the kidney, liver and adrenal glands other than pancreatic islets. Of the STZ/NA-induced kidney tumors, more than 60% were renal cell adenomas, and many of them were basophilic type. The incidence of eosinophilic or clear cell type of tumors was less than 10%, respectively. Immunohistochemical analyses revealed that many of the STZ/NA-induced basophilic type of renal tumors were derived from proximal tubules, whereas the clear cell and eosinophilic types were derived from collecting tubules. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors

    ClinicalTrials.gov

    2016-04-14

    Childhood Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Clear Cell Sarcoma of the Kidney; Papillary Renal Cell Carcinoma; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Renal Wilms Tumor; Stage II Renal Cell Cancer; Stage II Renal Wilms Tumor; Stage III Renal Cell Cancer; Stage III Renal Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Renal Wilms Tumor

  13. Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.

    PubMed

    Liśkiewicz, Arkadiusz D; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin-Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska-Szypułka, Halina

    2016-02-19

    Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

  14. Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis

    PubMed Central

    Liśkiewicz, Arkadiusz D.; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin–Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska–Szypułka, Halina

    2016-01-01

    Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/−) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth. PMID:26892894

  15. Correlation of CT imaging features and tumor size with Fuhrman grade of clear cell renal cell carcinoma.

    PubMed

    Oh, Saelin; Sung, Deuk Jae; Yang, Kyung Sook; Sim, Ki Choon; Han, Na Yeon; Park, Beom Jin; Kim, Min Ju; Cho, Sung Bum

    2017-03-01

    Background Identification of clinical features to determine the aggressive potential of tumors is highly warranted to stratify patients for adequate treatment. Computed tomography (CT) imaging features of clear cell renal cell carcinoma (ccRCC) may contribute to personalized risk assessment. Purpose To assess the correlation between CT imaging features and Fuhrman grade of ccRCC, and to identify the predictors of high Fuhrman grade in conjunction with tumor size. Material and Methods CT scans of 169 patients with 173 pathologically proven ccRCCs were retrospectively reviewed in consensus by two radiologists for the presence of intratumoral necrosis and intratumoral cyst and tumor size. Histologic grade was classified as either low (Fuhrman grade I or II) or high (Fuhrman grade III or IV). Statistical significance was evaluated by using univariate, multivariate regression, receiver operating characteristic (ROC) curve, and Spearman correlation analyses. Results On CT, 20 of the 173 tumors had intratumoral cysts, 60 had intratumoral necrosis, and 93 showed entirely solid tumors. The odds of high grade were higher with intratumoral necrosis and entirely solid tumor than with intratumoral cyst ( P < 0.03). Intratumoral necrosis showed a significantly high odds ratio of 25.73 for high Fuhrman grade. The ROC curve showed a threshold tumor size of 36 mm to predict high Fuhrman grade for overall tumors (area under the ROC curve, 0.70). In ccRCCs with intratumoral necrosis or cyst, tumor size did not significantly correlate with Fuhrman grade. Conclusion Intratumoral necrosis on CT was a strong and independent predictor of biologically aggressive ccRCCs, irrespective of tumor size.

  16. Differing Von Hippel Lindau Genotype in Paired Primary and Metastatic Tumors in Patients with Clear Cell Renal Cell Carcinoma

    PubMed Central

    Vaziri, Susan A. J.; Tavares, Emmanuel J.; Golshayan, Ali R.; Rini, Brian I.; Aydin, Hakan; Zhou, Ming; Sercia, Linda; Wood, Laura; Ganapathi, Mahrukh K.; Bukowski, Ronald M.; Ganapathi, Ram

    2012-01-01

    In sporadic clear cell renal cell carcinoma (CCRCC), the von Hippel Lindau (VHL) gene is inactivated by mutation or methylation in the majority of primary (P) tumors. Due to differing effects of wild-type (WT) and mutant (MT) VHL gene on downstream signaling pathways regulating angiogenesis, VHL gene status could impact clinical outcome. In CCRCC, comparative genomic hybridization analysis studies have reported genetic differences between paired P and metastatic (M) tumors. We thus sequenced the VHL gene in paired tumor specimens from 10 patients to determine a possible clonal relationship between the P tumor and M lesion(s) in patients with CCRCC. Using paraffin-embedded specimens, genomic DNA from microdissected samples (>80% tumor) of paired P tumor and M lesions from all 10 patients, as well as in normal tissue from 6 of these cases, was analyzed. The DNA was used for PCR-based amplification of each of the 3 exons of the VHL gene. Sequences derived from amplified samples were compared to the wild-type VHL gene sequence (GenBank Accession No. AF010238). Methylation status of the VHL gene was determined using VHL methylation-specific PCR primers after DNA bisulfite modification. In 4/10 (40%) patients the VHL gene status differed between the P tumor and the M lesion. As expected, when the VHL gene was mutated in both the P tumor and M lesion, the mutation was identical. Further, while the VHL genotype differed between the primary tumor in different kidneys or multiple metastatic lesions in the same patient, the VHL germline genotype in the normal adjacent tissue was always wild-type irrespective of the VHL gene status in the P tumor. These results demonstrate for the first time that the VHL gene status can be different between paired primary and metastatic tissue in patients with CCRCC. PMID:22655276

  17. Tumor Vascularity in Renal Masses: Correlation of Arterial Spin-Labeled and Dynamic Contrast Enhanced MR Imaging Assessments

    PubMed Central

    Zhang, Yue; Kapur, Payal; Yuan, Qing; Xi, Yin; Carvo, Ingrid; Signoretti, Sabina; Dimitrov, Ivan; Cadeddu, Jeffrey A.; Margulis, Vitaly; Muradyan, Naira; Brugarolas, James; Madhuranthakam, Ananth J.; Pedrosa, Ivan

    2015-01-01

    Objective To investigate potential correlations between perfusion by arterial spin-labeled (ASL) magnetic resonance imaging (MRI) and dynamic contrast enhanced (DCE) MRI derived quantitative measures of vascularity in renal masses >2 cm and to correlate these with microvessel density (MVD) in clear cell renal cell carcinoma (ccRCC). Methods Informed written consent was obtained from all patients before imaging in this HIPAA-compliant, IRB-approved, prospective study. 36 consecutive patients scheduled for surgery of a known renal mass >2 cm underwent 3T ASL and DCE MRI. ASL measures (PASL) of mean, peak, and low perfusion areas within the mass were correlated to DCE-derived Ktrans, Kep, and Ve in the same locations using a region of interest analysis. MRI data were correlated to MVD measures in the same tumor regions in ccRCC. Spearman correlation was used to evaluate the correlation between PASL and DCE-derived measurements, and MVD. P<0.05 was considered statistically significant. Results Histopathologic diagnosis was obtained in 36 patients (25 men; mean age 58 ±12 years). PASL correlated with Ktrans (ρ=0.48, P=0.0091 for the entire tumor and ρ=0.43, P=0.03 for the high flow area, respectively) and Kep (ρ=0.46, P=0.01 for the entire tumor and ρ=0.52, P=0.008 for the high flow area, respectively). PASL (ρ=0.66, P=0.0002), Ktrans (ρ=0.61, P=0.001), and Kep (ρ=0.64, P=0.0006) also correlated with MVD in high and low perfusion areas in ccRCC. Conclusions PASL correlate with the DCE-derived measures of vascular permeability and flow, Ktrans and Kep, in renal masses >2cm in size. Both measures correlate to MVD in clear cell histology. MICROABSTRACT Arterial spin labeling (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) have been proposed to quantitatively assess vascularity in renal cell carcinoma (RCC). However there are intrinsic differences between these two imaging methods, such as the relative contribution of vascular permeability

  18. Tumor Vascularity in Renal Masses: Correlation of Arterial Spin-Labeled and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Assessments.

    PubMed

    Zhang, Yue; Kapur, Payal; Yuan, Qing; Xi, Yin; Carvo, Ingrid; Signoretti, Sabina; Dimitrov, Ivan; Cadeddu, Jeffrey A; Margulis, Vitaly; Muradyan, Naira; Brugarolas, James; Madhuranthakam, Ananth J; Pedrosa, Ivan

    2016-02-01

    Arterial spin-labeled (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) have been proposed to quantitatively assess vascularity in renal cell carcinoma (RCC). However, there are intrinsic differences between these 2 imaging methods, such as the relative contribution of vascular permeability and blood flow to signal intensity for DCE MRI. We found a correlation between ASL perfusion and the DCE-derived volume transfer constant and rate constant parameters in renal masses > 2 cm in size and these measures correlated with microvessel density in clear cell RCC. The objective of this study was to investigate potential correlations between perfusion using arterial spin-labeled (ASL) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE) MRI-derived quantitative measures of vascularity in renal masses > 2 cm and to correlate these with microvessel density (MVD) in clear cell renal cell carcinoma (ccRCC). Informed written consent was obtained from all patients before imaging in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, prospective study. Thirty-six consecutive patients scheduled for surgery of a known renal mass > 2 cm underwent 3T ASL and DCE MRI. ASL perfusion measures (PASL) of mean, peak, and low perfusion areas within the mass were correlated to DCE-derived volume transfer constant (K(trans)), rate constant (Kep), and fractional volume of the extravascular extracellular space (Ve) in the same locations using a region of interest analysis. MRI data were correlated to MVD measures in the same tumor regions in ccRCC. Spearman correlation was used to evaluate the correlation between PASL and DCE-derived measurements, and MVD. P < .05 was considered statistically significant. Histopathologic diagnosis was obtained in 36 patients (25 men; mean age 58 ± 12 years). PASL correlated with K(trans) (ρ = 0.48 and P = .0091 for the entire tumor and ρ = 0.43 and P = .03 for the

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

    PubMed

    Tilki, Derya; Hu, Brian; Nguyen, Hao G; Dall'Era, Marc A; Bertini, Roberto; Carballido, Joaquín A; Chandrasekar, Thenappan; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Gontero, Paolo; Gonzalez, Javier; Haferkamp, Axel; Hohenfellner, Markus; Huang, William C; Koppie, Theresa M; Linares, Estefania; Lorentz, C Adam; Mandel, Philipp; Martinez-Salamanca, Juan I; Master, Viraj A; Matloob, Rayan; McKiernan, James M; Mlynarczyk, Carrie M; Montorsi, Francesco; Novara, Giacomo; Pahernik, Sascha; Palou, Juan; Pruthi, Raj S; Ramaswamy, Krishna; Rodriguez Faba, Oscar; Russo, Paul; Shariat, Shahrokh F; Spahn, Martin; Terrone, Carlo; Thieu, William; Vergho, Daniel; Wallen, Eric M; Xylinas, Evanguelos; Zigeuner, Richard; Libertino, John A; Evans, Christopher P

    2015-02-01

    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. 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. 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. 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. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. RhoB Acts as a Tumor Suppressor That Inhibits Malignancy of Clear Cell Renal Cell Carcinoma

    PubMed Central

    Ma, Xin; Zhang, Peng; Gao, Yu; Fan, Yang; Pang, Haigang; Gong, Huijie; Shen, Donglai; Gu, Liangyou; Zhang, Yu

    2016-01-01

    This study aims to investigate the biological role of RhoB in clear cell renal cell carcinoma (ccRCC). The expression of RhoB was examined in specimens of patients and cell lines by Western blot and Immunohistochemistry. The correlation between RhoB expression and clinicopathologic variables was also analyzed. The effects of RhoB on cell proliferation, cell cycle, cell apoptosis, and invasion/migration were detected by over-expression and knockdown of RhoB level in ccRCC cells via plasmids and RNAi. The results showed that RhoB was low-expressed in ccRCC surgical specimens and cell lines compared with adjacent normal renal tissues and normal human renal proximal tubular epithelial cell lines (HKC), and its protein expression level was significantly associated with the tumor pathologic parameter embracing tumor size(P = 0.0157), pT stage(P = 0.0035), TNM stage(P = 0.0024) and Fuhrman tumor grade(P = 0.0008). Further, over-expression of RhoB remarkably inhibited the cancer cell proliferation, colony formation and promoted cancer cell apoptosis, and aslo reduced the invasion and migration ability of ccRCC cells. Interestingly, up-regulation of RhoB could induce cell cycle arrest in G2/M phase and led to cell cycle regulators(CyclineB1,CDK1) and pro-apoptotic protein(casp3,casp9) aberrant expression. Moreover, knockdown of RhoB in HKC cells promoted cell proliferation and migration. Taken together, our study indicates that RhoB expression is decreased in ccRCC carcinogenesis and progression. Up-regulation of RhoB significantly inhibits ccRCC cell malignant phenotype. These findings show that RhoB may play a tumor suppressive role in ccRCC cells, raising its potential value in futural therapeutic target for the patients of ccRCC. PMID:27384222

  1. Percutaneous RF Thermal Ablation of Renal Tumors: Is US Guidance Really Less Favorable Than Other Imaging Guidance Techniques?

    SciTech Connect

    Veltri, Andrea Garetto, Irene; Pagano, Eva; Tosetti, Irene; Sacchetto, Paola Fava, Cesare

    2009-01-15

    The purpose of this study was to compare our experience with ultrasound (US)-guided percutaneous radiofrequency thermal ablation (RFA) of renal tumors with results of CT-guided and MRI-guided series in the current literature. Of 90 consecutive renal tumors treated with RFA in 71 patients, 87 lesions were ablated under US guidance. We performed a retrospective analysis of clinical outcome and safety. Results were then compared to published case series where CT and MRI guidances were used exclusively. In our series we had a major complication rate of 4.6%, whereas in CT- and MRI-based series it was 0-12% (mean, 2.2%) and 0-8.3% (mean, 4.1%), respectively. During follow-up (1-68 months; mean, 24 months) technical effectiveness was 89.7%, while it was between 89.5% and 96% in CT-guided series and between 91.7% and 100% in MRI-guided series. The size of successfully treated lesions (28 mm) was lower than that of partially-ablated lesions (36 mm; p = 0.004) and only central lesion location proved to be a negative prognostic factor (p = 0.009); in CT-guided series, positive prognostic factors were exophytic growth and size {<=}3 cm. 'Tumor-specific' 2-year survival was 92% in our series, 90-96% in CT-guided series, and not reported in MRI-guided series. In conclusion, despite common beliefs, US guidance in RFA of renal tumors is not less favorable than other guidance techniques. Thus the interventional radiologist can choose his or her preferred technique taking into account personal experience and available equipment.

  2. Skin-to-tumor Distance Predicts Treatment Failure of T1A Renal Cell Carcinoma Following Percutaneous Cryoablation.

    PubMed

    Vernez, Simone L; Okhunov, Zhamshid; Kaler, Kamaljot; Youssef, Ramy F; Dutta, Rahul; Palvanov, Arkadiy; Shah, Paras; Osann, Kathryn; Siegel, David N; Lobko, Igor; Kavoussi, Louis; Clayman, Ralph V; Landman, Jaime

    2017-06-23

    To determine the impact of skin-to-tumor (STT) distance on the risk for treatment failure following percutaneous cryoablation (PCA). We retrospectively reviewed patients who underwent PCA with documented T1a recurrent renal cell carcinoma (RCC) at 2 academic centers between 2005 and 2015. Patient demographics, tumor characteristics, and perioperative and postoperative course variables were collected. Additionally, we measured the STT distance by averaging the distance from the skin to the center of the tumor at 0°, 45°, and 90° on preoperative computed tomography imaging. We identified 86 patients with documented T1a RCC. The mean age at the time of surgery was 69 years (range: 37-91 years), and the mean tumor size was 2.7 cm (range: 1.0-4.0 cm). With a mean follow-up of 24 months (range: 3-63 months), 11 (12.8%) treatment failures occurred. Patients with treatment failure had significantly higher mean STT distance than those without: 11.0 cm (range: 6.3-20.1 cm) compared to 8.4 cm (range: 4.4-15.2 cm), respectively (P = .002). STT distance was an independent predictor of treatment failure (odds ratio: 1.32, 95% confidence interval: 1.04-1.69, P = .029). STT distance greater than 10 cm had a fourfold increased risk of tumor treatment failure (odds ratio: 4.43, 95% confidence interval: 1.19-16.39, P = .018). Tumor size, R.E.N.A.L. Nephrometry score, and number of cryoprobes placed were not associated with treatment failure. STT, an easily measured preoperative variable, may inform the risk of RCC treatment failure following PCA. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Linker stability influences the anti-tumor activity of acetazolamide-drug conjugates for the therapy of renal cell carcinoma

    PubMed Central

    Neri, Dario

    2016-01-01

    Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas. A comparative evaluation of four dipeptides revealed that SMDCs featuring valine-citrulline and valine-alanine linkers exhibited greater serum stability and superior therapeutic activity, compared to the counterparts with valine-lysine or valine-arginine linkers. The most active products substantially inhibited tumor growth over a prolonged period of time, in a tumor model for which sunitinib and sorafenib do not display therapeutic activity. However, complete tumor eradication was not possible even after ten intravenous injection. Macroscopic near-infrared imaging procedures confirmed that ligands had not lost the ability to selectively localize at the tumor site at the end of therapy and that the neoplastic masses continued to express CAIX. The findings are of mechanistic and of therapeutic significance, since CAIX is a non-internalizing membrane-associated antigen, which can be considered for targeted drug delivery applications in kidney cancer patients. PMID:27890855

  4. External validation of the Arterial Based Complexity (ABC) scoring system in renal tumors treated by minimally invasive partial nephrectomy.

    PubMed

    Gu, Liangyou; Ma, Xin; Li, Hongzhao; Yao, Yuanxin; Xie, Yongpeng; Chen, Luyao; Gao, Yu; Zhang, Xu

    2017-09-01

    To assess the role of the Arterial Based Complexity (ABC) scoring system in predicting clinically relevant outcomes of a minimally invasive partial nephrectomy (MIPN). We retrospectively reviewed 350 consecutive patients who underwent a MIPN between 2013 and 2014. Tumor complexity was evaluated according to the ABC scoring system. Complications, surgical, and renal outcomes were recorded. There were respectively 36 (10.3%), 229 (65.4%), 43 (12.3%), and 42 (12.0%) patients in category 1, 2, 3S, 3H. Multivariate regression showed category assignment was associated with warm ischemia time (P < 0.001), estimated blood loss (P = 0.001), and operative time (P = 0.032). On multivariate analyses, tumor size was the only independent predictor of overall (P = 0.035) and minor (P = 0.032) complications, but ABC category failed to predict complications (P > 0.05 for all). For renal function, ABC category failed to predict postoperative estimated glomerular filtration rate at 1 day and 6 months (P > 0.05 for both). In MIPN, the ABC scoring system predicted a prolonged warm ischemia time and operative time, and an added estimated blood loss. This scoring system was not a predictor for the occurrence of complications and postoperative renal function. © 2017 Wiley Periodicals, Inc.

  5. High risk of development of renal cell tumor in end-stage kidney disease: the role of microenvironment.

    PubMed

    Nagy, Anetta; Walter, Eva; Zubakov, Dmitry; Kovacs, Gyula

    2016-07-01

    End-stage renal disease (ESRD) and acquired cystic renal disease (ACRD) are associated with high risk of development of renal cell tumors (RCT) displaying unusual phenotype and genotype. The underlying molecular mechanism is not yet known. To explore the molecular microenvironment, we have established the expression profile of ESRD/ACRD kidneys. RNA extracted from normal and ESRD/ACRD kidneys and distinct types of RCT was subjected to Affymetrix HG U133 micro array analysis. A gene expression signature indicated cancer-related biological processes in the remodeling of ESRD/ACRD kidneys. Quantitative RT-PCR studies confirmed a specific gene signature including a functional group of inflammatory cytokines and also cytokeratins associated with stem cell characteristics of epithelial cells. Several of the signature genes including the SCEL were expressed in ESRD/ACRD-associated papillary RCT as well. Immunohistological analysis confirmed the expression of CXCL8 and its receptor CXCR2 as well as the expression of SCEL in hyperplastic tubular, cystic, and papillary structures and RCTs in ESRD/ACRD kidney. Our data indicates that ESRD/ACRD is a novel disease and the inflammatory microenvironment altered plasticity, and stem cell characteristics of epithelial cells may be associated with the high risk of tumor development.

  6. Multimodality Imaging Characteristics of the Common Renal Cell Carcinoma Subtypes: An Analysis of 544 Pathologically Proven Tumors

    PubMed Central

    Fu, Winnie; Huang, Guan; Moloo, Zaahir; Girgis, Safwat; Patel, Vimal H; Low, Gavin

    2016-01-01

    Objectives: The objective of this study was to define the characteristic imaging appearances of the common renal cell carcinoma (RCC) subtypes. Materials and Methods: The Institutional Review Board approval was obtained for this HIPAA-compliant retrospective study, and informed consent was waived. 520 patients (336 men, 184 women; age range, 22–88 years) underwent preoperative cross-sectional imaging of 544 RCCs from 2008 to 2013. The imaging appearances of the RCCs and clinical information were reviewed. Data analysis was performed using parametric and nonparametric statistics, descriptive statistics, and receiver operating characteristic analysis. Results: The RCC subtypes showed significant differences (P < 0.001) in several imaging parameters such as tumor margins, tumor consistency, tumor homogeneity, the presence of a central stellate scar, T2 signal intensity, and the degree of tumor enhancement. Low T2 signal intensity on magnetic resonance imaging (MRI) allowed differentiation of papillary RCC from clear cell and chromophobe RCCs with 90.9% sensitivity and 93.1% specificity. A tumor-to-cortex ratio ≥1 on the corticomedullary phase had 98% specificity for clear cell RCC. Conclusion: The T2 signal intensity of the tumor on MRI and its degree of enhancement are useful imaging parameters for discriminating between the RCC subtypes while gross morphological findings offer additional value in RCC profiling. PMID:28123840

  7. Selective arterial embolization of symptomatic and asymptomatic renal angiomyolipomas: a retrospective study of safety, outcomes and tumor size reduction

    PubMed Central

    Bardin, Florian; Chevallier, Olivier; Bertaut, Aurélie; Delorme, Emmanuel; Moulin, Morgan; Pottecher, Pierre; Di Marco, Lucy; Gehin, Sophie; Mourey, Eric; Cormier, Luc; Mousson, Christiane; Midulla, Marco

    2017-01-01

    Background Angiomyolipoma (AML) is the most common renal benign tumor. Treatment should be considered for symptomatic patients or for those at risk for complications, especially retroperitoneal bleeding which is correlated to tumor size, grade of the angiogenic component and to the presence of tuberous sclerosis complex (TSC). This study reports our single-center experience with the use of selective arterial embolization (SAE) in the management of symptomatic and asymptomatic renal AMLs. Methods In this retrospective mono-centric study, all demographic and imaging data, medical records, angiographic features, outpatient charts and follow-up visits of patients who underwent prophylactic or emergency SAE for AMLs between January 2005 and July 2016 were reviewed. Tumor size and treatment outcomes were assessed at baseline and after the procedure during follow-up. Computed tomography (CT), magnetic resonance imaging (MRI) or ultrasonography was used to evaluate AML shrinkage. Renal function was measured pre- and post-procedure. Results Twenty-three patients (18 females, 5 males; median age, 45 years; range, 19–85 years) who underwent SAE either to treat bleeding AML (n=6) or as a prophylactic treatment (n=17) were included. Overall, 34 AMLs were embolized. TSC status was confirmed for 6 patients. Immediate technical success rate was 96% and 4 patients benefitted from an additional procedure. Major complications occurred in 3 patients and minor post-embolization syndrome (PES) in 14 patients. The mean AML size reduction rate was 26.2% after a mean follow-up was 20.5 months (range, 0.5–56 months), and only non-TSC status was significantly associated with better shrinkage of tumor (P=0.022). Intralesional aneurysms were significantly more frequent in patients with hemorrhagic presentation (P=0.008). There was no change in mean creatinine level after SAE. Conclusions SAE is a safe and effective technique to manage renal AMLs as a preventive treatment as well as in

  8. Age, Gender and R.E.N.A.L. Nephrometry Score do not Improve the Accuracy of a Risk Stratification Algorithm Based on Biopsy and Mass Size for Assigning Surveillance versus Treatment of Renal Tumors.

    PubMed

    Osawa, Takahiro; Hafez, Khaled S; Miller, David C; Montgomery, Jeffrey S; Morgan, Todd M; Palapattu, Ganesh S; Weizer, Alon Z; Caoili, Elaine M; Ellis, James H; Kunju, Lakshmi P; Wolf, J Stuart

    2016-03-01

    A previously published risk stratification algorithm based on renal mass biopsy and radiographic mass size was useful to designate surveillance vs the need for immediate treatment of small renal masses. Nonetheless, there were some incorrect assignments, most notably when renal mass biopsy indicated low risk malignancy but final pathology revealed high risk malignancy. We studied other factors that might improve the accuracy of this algorithm. For 202 clinically localized small renal masses in a total of 200 patients with available R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, hilar tumor touching main renal artery or vein and location relative to polar lines) nephrometry score, preoperative renal mass biopsy and final pathology we assessed the accuracy of management assignment (surveillance vs treatment) based on the previously published risk stratification algorithm as confirmed by final pathology. Logistic regression was used to determine whether other factors (age, gender, R.E.N.A.L. score, R.E.N.A.L. score components and nomograms based on R.E.N.A.L. score) could improve assignment. Of the 202 small renal masses 53 (26%) were assigned to surveillance and 149 (74%) were assigned to treatment by the risk stratification algorithm. Of the 53 lesions assigned to surveillance 25 (47%) had benign/favorable renal mass biopsy histology while in 28 (53%) intermediate renal mass biopsy histology showed a mass size less than 2 cm. Nine of these 53 masses (17%) were incorrectly assigned to surveillance in that final pathology indicated the need for treatment (ie intermediate histology and a mass greater than 2 cm or unfavorable histology). Final pathology confirmed a correct assignment in all 149 masses assigned to treatment. None of the additional parameters assessed improved assignment with statistical significance. Age, gender, R.E.N.A.L. nephrometry score, R.E.N.A.L. score components and nomograms

  9. A renal epithelioid angiomyolipoma/perivascular epithelioid cell tumor with TFE3 gene break visualized by FISH.

    PubMed

    Ohe, Chisato; Kuroda, Naoto; Hes, Ondrej; Michal, Michal; Vanecek, Tomas; Grossmann, Petr; Tanaka, Yukichi; Tanaka, Mio; Inui, Hidekazu; Komai, Yoshihiro; Matsuda, Tadashi; Uemura, Yoshiko

    2012-12-01

    We present a case of renal epithelioid angiomyolipoma (eAML)/perivascular epithelioid cell tumor (PEComa) with a TFE3 gene break visible by fluorescence in situ hybridization (FISH). Histologically, the tumor was composed of mainly epithelioid cells forming solid arrangements with small foci of spindle cells. In a small portion of the tumor, neoplastic cells displayed nuclear pleomorphism, such as polygonal and enlarged vesicular nuclei with prominent nucleoli. Marked vascularity was noticeable in the background, and perivascular hyaline sclerosis was also seen. Immunohistochemically, neoplastic cells were diffusely positive for α-smooth muscle actin and melanosome in the cytoplasm. Nuclei of many neoplastic cells were positive for TFE3. FISH analysis of the TFE3 gene break using the Poseidon TFE3 (Xp11) Break probe revealed positive results. Reverse transcriptase-polymerase chain reactions (RT-PCR) for ASPL/TFE3, PRCC/TFE3, CLTC/TFE3, PSF/TFE3, and NonO/TFE3 gene fusions all revealed negative results. This is the first reported case of renal eAML/PEComa with a TFE3 gene break, and it has unique histological findings as compared to previously reported TFE3 gene fusion-positive PEComas. Pathologists should recognize that PEComa with TFE3 gene fusion can arise even in the kidney.

  10. Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL-/- clear cell renal carcinoma.

    PubMed

    Gao, Wenhua; Li, Wei; Xiao, Tengfei; Liu, Xiaole Shirley; Kaelin, William G

    2017-01-31

    Most clear cell renal carcinomas (ccRCCs) are initiated by somatic inactivation of the VHL tumor suppressor gene. The VHL gene product, pVHL, is the substrate recognition unit of an ubiquitin ligase that targets the HIF transcription factor for proteasomal degradation; inappropriate expression of HIF target genes drives renal carcinogenesis. Loss of pVHL is not sufficient, however, to cause ccRCC. Additional cooperating genetic events, including intragenic mutations and copy number alterations, are required. Common examples of the former are loss-of-function mutations of the PBRM1 and BAP1 tumor suppressor genes, which occur in a mutually exclusive manner in ccRCC and define biologically distinct subsets of ccRCC. PBRM1 encodes the Polybromo- and BRG1-associated factors-containing complex (PBAF) chromatin remodeling complex component BRG1-associated factor 180 (BAF180). Here we identified ccRCC lines whose ability to proliferate in vitro and in vivo is sensitive to wild-type BAF180, but not a tumor-associated BAF180 mutant. Biochemical and functional studies linked growth suppression by BAF180 to its ability to form a canonical PBAF complex containing BRG1 that dampens the HIF transcriptional signature.

  11. Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions1

    PubMed Central

    Azzi, Sandy; Gallerne, Cindy; Romei, Cristina; Le Coz, Vincent; Gangemi, Rosaria; Khawam, Krystel; Devocelle, Aurore; Gu, Yanhong; Bruno, Stefania; Ferrini, Silvano; Chouaib, Salem; Eid, Pierre; Azzarone, Bruno; Giron-Michel, Julien

    2015-01-01

    Intrarenal interleukin-15 (IL-15) participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15) isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC) to peritumoral (ptumTEC), tumoral (RCC), and cancer stem cells (CSC/CD105+). RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα) chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15) isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα). This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105+, where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105+ from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa) displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, “apparently normal” ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral “preneoplastic” environment committed to favor tumor progression. PMID:26152359

  12. Radiation dose during CT-guided percutaneous cryoablation of renal tumors: Effect of a dose reduction protocol.

    PubMed

    Levesque, Vincent M; Shyn, Paul B; Tuncali, Kemal; Tatli, Servet; Nawfel, Richard D; Olubiyi, Olutayo; Silverman, Stuart G

    2015-11-01

    To estimate and compare the radiation dose using a standard protocol and that of a dose reduction protocol in patients undergoing CT-guided percutaneous cryoablation of renal tumors. An IRB-approved, HIPAA-compliant retrospective study of 97 CT-guided cryoablation procedures to treat a solitary renal tumor in each of 97 patients (64 M, 33 F; range 31-84 yrs) was performed. Fifty patients were treated using a standard dose protocol (kVp=120, mean mAs=180, monitoring scans every 3 min during freezes), and an additional 47 patients were treated using a dose reduction protocol (kVp=100, mean mAs=100, monitoring scans less frequently than every 3 min during freezes). Multiple Wilcoxon Mann-Whitney (rank-sum) tests were used to compare dose-length product (DLP) between the two groups. Fisher's exact test was used to compare technique effectiveness at 12 months post ablation between the two groups. Median DLP for the standard protocol group was 4833.5 mGy*cm (range, 1667-8267 mGy*cm); median DLP for the dose reduction group was 2648 mGy*cm (range, 850-7169 mGy*cm), significantly less than that of the standard protocol group (p<0.01). The technique effectiveness for the dose reduction group was not significantly different from that of the standard protocol group at 12 month follow up (p=0.434). The radiation dose during percutaneous CT-guided cryoablation of renal tumors was substantial in both the standard and the dose reduction groups; however, it was significantly lower with the protocol change that reduced dose parameters and decreased the number of CT scans. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Laparoscopic Radiofrequency Ablation Combined with Surgical Excision for Exophytic Renal Angiomyolipoma: A Novel Technique Based on Tumor Vasculature Features of Enhancing Renal Masses Toward Hilar Off-Clamping Nephron-Sparing Surgery.

    PubMed

    Xiong, Wei; Ran, Qing; Du, Yangchun; Lv, Ji; Chen, Fang; Zhong, Shan; Guo, Pu; Dou, Ke; Sun, Minghan

    2017-08-01

    Symptomatic angiomyolipoma (AML) and asymptomatic AML larger than 4 cm in size are usually treated with nephron-sparing surgery or transarterial embolization. We used radiofrequency ablation to treat the vascular pedicle of exophytic AML with low R.E.N.A.L. nephrometry score and investigated its feasibility for hilar off-clamping nephron-sparing surgery. Contrast-enhanced computed tomography (CT) showed enhanced, well-defined lipomatous tumors with a maximum diameter of 4-8 cm in the kidney of 15 patients. Results indicated that the exophytic tumors featured in the enlarged tumor vasculatures extended into the parenchyma of the involved kidney. The patients underwent radiofrequency ablation by using a Cool-tip™ probe placed into the root of the AML mass from different directions under laparoscopic ultrasonography guidance. After sealing the vascular pedicle of the tumor, the bloodless tumors were resected en bloc without renal hilar clamping or suturing the resection defect of the kidney. All patients underwent the procedure smoothly, and no perioperative complications occurred. The contrast-enhanced CT scan showed small defects in the contrast-enhanced renal parenchyma at third month after the procedure, and the decrease in function of the treated kidneys was <10% during the 12-month follow-up. Our initial experience suggests that sealing the tumor vessels by radiofrequency ablation based on the tumor vasculature features of a renal mass is an alternative to hilar clamping in laparoscopic nephron-sparing surgery. Laparoscopic radiofrequency ablation and tumor excision are a definitive and safe minimally invasive procedure that allows the successful removal of exophytic sporadic AML mass with low R.E.N.A.L. nephrometry score.

  14. Identification of patient-specific and tumor-shared T cell receptor sequences in renal cell carcinoma patients.

    PubMed

    Massa, Chiara; Robins, Harlan; Desmarais, Cindy; Riemann, Dagmar; Fahldieck, Corinna; Fornara, Paolo; Seliger, Barbara

    2017-02-03

    A major requirement for cancer immunotherapy is the development of biomarkers for prognosis and for monitoring therapy response. In an attempt to evaluate the immune response of renal cell carcinoma (RCC) patients, tumor lesions and / or blood samples from 12 RCC patients underwent deep T cell receptor (TCR) sequencing. Despite the low number of samples, different TCR distribution patterns could be detected. Most of the RCC patients presented "patient-specific" TCR sequences, and those clonotypes were present at higher frequency in tumor lesions suggesting a specific extravasation from the blood. Comparison among the tumor samples revealed also "patient-shared" TCR patterns. Indeed, a central core of 16 different TCRs were shared by 3 patients, whereas other 6 patients shared between 4 and 6 TCR sequences, with two sub-groups sharing 12 to 17 different clonotypes. The relative frequencies of shared clonotypes were very different varying from < 1% to a maximum of 37% of the total TCR repertoire. These data confirm the presence of tumor-specific TCR within the cancer tissue and suggest the existence of shared epitopes among different patients that might be used as targets for tumor immunotherapy.

  15. Prognostic Factors for Renal Cell Carcinoma Subtypes Diagnosed According to the 2016 WHO Renal Tumor Classification: a Study Involving 928 Patients.

    PubMed

    Kuthi, Levente; Jenei, Alex; Hajdu, Adrienn; Németh, István; Varga, Zoltán; Bajory, Zoltán; Pajor, László; Iványi, Béla

    2017-07-01

    The morphotype and grade of renal cell carcinoma (RCC) in 928 nephrectomies were reclassified according to the 2016 WHO classification in order to analyze the distribution and outcomes of RCC subtypes in Hungary, to assess whether microscopic tumor necrosis is an independent prognostic factor in clear cell RCC, and to study whether a two-tiered grading (low/high) for clear cell and papillary RCC provides similar prognostic information to that of the four-tiered ISUP grading system. 83.4% of the cohort were clear cell, 6.9% papillary, 4.5% chromophobe, 2.3% unclassified, 1.1% Xp11 translocation, 1.1% clear cell papillary, 0.3% collecting duct and 0.1% mucinous tubular and spindle cell RCCs. RCC occurred in 16 patients with end-stage kidney disease and none of them displayed features of acquired cystic kidney disease-associated RCC. The 5-year survival rates were as follows: chromophobe 100%, clear cell papillary 100%, clear cell low-grade 96%, papillary type 1 92%, clear cell high-grade 63%, papillary type 2 65%, unclassified 46%, Xp11 translocation 20%, and collecting duct 0%. The 5-year survival rates in low-grade and high-grade papillary RCC were 95% and 59%, respectively. In clear cell RCC, only the grade, the stage and the positive surgical margin proved to be independent prognostic factors statistically. Overall, papillary RCC occurred relatively infrequently; microscopic tumor necrosis in clear cell RCC did not predict the outcome independently of the tumor grading; and the assignment of clear cell and papillary RCCs into low-grade or high-grade tumors was in terms of survival no worse than the ISUP grading.

  16. A Rare Renal Epithelial Tumor: Mucinous Cystadenocarcinoma Case Report and Review of the Literature

    PubMed Central

    Tepeler, Abdulkadir; Erdem, Mehmet Remzi; Kurt, Omer; Topaktas, Ramazan; Kilicaslan, Isin; Armağan, Abdullah; Önol, Şinasi Yavuz

    2011-01-01

    Primary renal mucinous cystadenocarcinoma is a very rare lesion of kidney which originates from the metaplasia of the renal pelvic uroepithelium. Only one case with primary mucinous cystadenocarcinoma has been reported in the English literature. We report second case of mucinous cystadenocarcinoma which was radiologically classified as type-IIF Bosniak cyst in peripheral localization. We aimed to present this extreme and unusual entity with its radiological, surgical, and pathologic aspects under the light of literature. PMID:22110514

  17. Contralateral adrenal metastasis from renal cell carcinoma with tumor thrombus in the adrenal vein: a case report

    PubMed Central

    Muśko, Natalia; Kozikowski, Mieszko; Nyk, Łukasz; Borówka, Andrzej; Dobruch, Jakub

    2015-01-01

    A 64-year-old woman presented with contralateral right adrenal metastasis with adrenal vein thrombus, which was diagnosed many years after left nephrectomy with adrenalectomy due to renal cell cancer. The patient underwent right adrenalectomy with adrenal vein tumor thrombectomy for treatment. The pathologic examination confirmed metastatic clear cell carcinoma. The remote but existing risk of developing contralateral adrenal metastasis (CAM) after primary radical nephrectomy supports the idea of sparing the adrenal gland in suitable patients who undergo radical nephrectomy. Contralateral adrenal metastasis from RCC is a rare finding with the potential benefit of cure after resection. Care must be taken in preoperative diagnostics, as this metastasis is capable of causing inferior vena cava tumor thrombus via the suprarenal venous route. According to our knowledge, our case is the second similar entity described in literature so far. PMID:26807301

  18. Acute spontaneous tumor lysis in anaplastic large T-cell lymphoma presenting with hyperuricemic acute renal failure.

    PubMed

    Hsu, Hsiang-Hao; Huang, Chiu-Ching

    2004-01-01

    Acute spontaneous tumor lysis (ASTL) syndrome, an extremely rare disease, requires prompt recognition and aggressive management because it is fulminant at its outset, associated with severe metabolic derangement, and potentially reversible. We describe an unusual case in which spontaneous tumor lysis occurred in anaplastic large T-cell lymphoma associated with acute uric acid nephropathy, persistent oliguria, and shock. This case contrasts markedly with previously reported cases of ASTL syndrome, which developed mainly in the pathologic type of Burkitt lymphoma. To our knowledge, this is the first reported occurrence of ASTL syndrome associated with anaplastic large T-cell type lymphoma. This report also chronicles our successful experience with continuous renal replacement therapy in the presence of compromised hemodynamic status.

  19. Sarcomatoid carcinoma of the renal pelvis with giant cell tumor-like features: case report with immunohistochemical findings.

    PubMed

    Acikalin, Mustafa Fuat; Kabukcuoglu, Sare; Can, Cavit

    2005-02-01

    Sarcomatoid transitional cell carcinoma is a rare entity, in which a malignant, overtly epithelial component coexists with areas having a sarcoma-like appearance. Histological distinction of sarcomatoid carcinomas from carcinosarcomas is often difficult and immunohistochemistry is a helpful diagnostic adjunct in the correct diagnosis. In the present report, we describe an uncommon case of sarcomatoid transitional cell carcinoma of the renal pelvis, associated with giant cell tumor-like features. Immunoperoxidase staining for cytokeratin was positive in spindle cell component, indicating an epithelial origin. The carcinomatous component showed a diffuse membranous reactivity for E-cadherin, whereas the reactivity was sporadic and weaker in the sarcomatoid component, suggesting that the decrease of E-cadherin expression might be associated with the acquisition of sarcomatous morphology. Osteoclast-like multinucleated giant cells were positive for CD68 and negative for p53 oncoprotein, suggesting that they represent a non-neoplastic component that is reactively induced in the tumor stroma.

  20. Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng.

    PubMed

    Yousef, Mokhtar I; Hussien, Hend M

    2015-04-01

    Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of solid tumors, while its usage is limited due to its nephrotoxicity. The present study was undertaken to examine the effectiveness of ginseng to ameliorate the renal nephrotoxicity, damage in kidney genomic DNA, tumor necrosis factor-α, interleukin 6, tumor suppressor P53, histological changes and oxidative stress induced by cisplatin in rats. Cisplatin caused renal damage, including DNA fragmentation, upregulates gene expression of tumor suppressor protein p53 and tumor necrosis factor-α and IL-6. Cisplatin increased the levels of kidney TBARS, xanthine oxidase, nitric oxide, serum urea and creatinine. Cisplatin decreased the activities of antioxidant enzymes (GST, GPX, CAT and SOD), ATPase and the levels of GSH. A microscopic examination showed that cisplatin caused kidney damage including vacuolization, severe necrosis and degenerative changes. Ginseng co-treatment with cisplatin reduced its renal damage, oxidative stress, DNA fragmentation and induced DNA repair processes. Also, ginseng diminished p53 activation and improved renal cell apoptosis and nephrotoxicity. It can be concluded that, the protective effects of ginseng against cisplatin induced-renal damage was associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes.

  1. Evaluation of putative renal cell carcinoma markers PAX-2, PAX-8, and hKIM-1 in germ cell tumors: a tissue microarray study of 100 cases.

    PubMed

    Sangoi, Ankur R; McKenney, Jesse K; Brooks, James D; Bonventre, Joseph V; Higgins, John P

    2012-10-01

    In a subset of cases, metastatic renal cell carcinoma can demonstrate significant morphologic overlap with germ cell neoplasms, making accurate diagnosis challenging. In such cases, immunohistochemistry is often used as an adjunct diagnostic tool. Expression of the putative renal cell carcinoma markers PAX-2, PAX-8, and hKIM-1 has been reported in a small series of certain germ cell tumors, raising doubt about their specificity for renal cell carcinoma. To further characterize these markers, we evaluated PAX-2, PAX-8, and hKIM-1 staining in 100 germ cell tumors using tissue microarrays. PAX-2 and PAX-8 staining was identified in 50% and 25% of yolk sac tumors (respectively), with hKIM-1 staining identified in 48% of embryonal carcinomas and 50% of yolk sac tumors. All other germ tumor cells (notably including 62 seminomas) were negative for all 3 markers, in contrast to prior reports of PAX-8 reactivity in seminoma. This study indicates that PAX-2, PAX-8, and hKIM-1 should be used cautiously in distinguishing renal cell carcinoma from nonseminomatous germ cell neoplasia and also adds to the growing list of nonrenal tumors that express these 3 markers.

  2. Expression and clinical value of the soluble major histocompatibility complex class I-related chain A molecule in the serum of patients with renal tumors.

    PubMed

    Zhao, Y-K; Jia, C-M; Yuan, G-J; Liu, W; Qiu, Y; Zhu, Q-G

    2015-06-29

    We investigated the expression and clinical value of the soluble major histocompatibility complex class I-related chain A (sMICA) molecule in the serum of patients with renal tumors. Sixty patients diagnosed with renal tumors were enrolled in the experimental group, whereas 20 healthy volunteers served as the control group. The sMICA levels were measured via enzyme-linked immunosorbent assay, and the results were analyzed in combination with data from pathol-ogy examination. The experimental group had a statistically significant higher sMICA level (P < 0.05) than the control group. The sMICA level was higher in patients with malignant tumors than in those with be-nign tumors. We also observed a positive relationship among different tumor-node-metastasis (TNM) pathological stages with more advanced diseases exhibiting higher sMICA levels. As a tumor-associated antigen, MICA has a close relationship with renal tumorigenesis and immune es-cape. Our results indicated that sMICA levels were related to tumor pathol-ogy, TNM stage, and metastasis. Therefore, sMICA might be a potential marker for tumor characteristics, prognosis, and recurrence prediction.

  3. Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

    PubMed Central

    von Roemeling, Christina A.; Marlow, Laura A.; Radisky, Derek C.; Rohl, Austin; Larsen, Hege E.; Wei, Johnny; Sasinowska, Heather; Zhu, Heng; Drake, Richard; Sasinowski, Maciek; Tun, Han W.; Copland, John A.

    2014-01-01

    Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression. Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 ‘hits’ that contribute to ccRCC cell proliferation. Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC. PMID:24979721

  4. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma12

    PubMed Central

    Arias-González, Laura; Moreno-Gimeno, Inmaculada; del Campo, Antonio Rubio; Serrano-Oviedo, Leticia; Valero, María Llanos; Esparís-Ogando, Azucena; de la Cruz-Morcillo, Miguel Ángel; Melgar-Rojas, Pedro; García-Cano, Jesús; Cimas, Francisco José; Hidalgo, María José Ruiz; Prado, Alfonso; Callejas-Valera, Juan Luis; Nam-Cha, Syong Hyun; Giménez-Bachs, José Miguel; Salinas-Sánchez, Antonio S; Pandiella, Atanasio; del Peso, Luis; Sánchez-Prieto, Ricardo

    2013-01-01

    Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas. PMID:23730213

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

    PubMed

    Mager, Rene; Daneshmand, Siamak; Evans, Christopher P; Palou, Joan; Martínez-Salamanca, Juan I; Master, Viraj A; McKiernan, James M; Libertino, John A; Haferkamp, Axel; Haferkamp, Axel; Capitanio, Umberto; Carballido, Joaquín A; Chantada, Venancio; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Evans, Christopher P; Gontero, Paolo; González, Javier; Hohenfellner, Markus; Huang, William C; Koppie, Theresa M; Libertino, John A; Espinós, Estefanía Linares; Lorentz, Adam; Martínez-Salamanca, Juan I; Master, Viraj A; McKiernan, James M; Montorsi, Francesco; Novara, Giacomo; O'Malley, Padraic; Pahernik, Sascha; Palou, Joan; Moreno, José Luis Pontones; Pruthi, Raj S; Faba, Oscar Rodriguez; Russo, Paul; Scherr, Douglas S; Shariat, Shahrokh F; Spahn, Martin; Terrone, Carlo; Tilki, Derya; Vázquez-Martul, Dario; Donoso, Cesar Vera; Vergho, Daniel; Wallen, Eric M; Zigeuner, Richard

    2016-11-01

    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. 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. 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. 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. © 2016 Wiley Periodicals, Inc.

  6. Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

    ClinicalTrials.gov

    2016-11-28

    Adult Renal Wilms Tumor; Beckwith-Wiedemann Syndrome; Childhood Renal Wilms Tumor; Diffuse Hyperplastic Perilobar Nephroblastomatosis; Hemihypertrophy; Stage I Renal Wilms Tumor; Stage II Renal Wilms Tumor; Stage III Renal Wilms Tumor; Stage IV Renal Wilms Tumor; Stage V Renal Wilms Tumor

  7. Energy stress-induced lncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development.

    PubMed

    Xiao, Zhen-Dong; Han, Leng; Lee, Hyemin; Zhuang, Li; Zhang, Yilei; Baddour, Joelle; Nagrath, Deepak; Wood, Christopher G; Gu, Jian; Wu, Xifeng; Liang, Han; Gan, Boyi

    2017-10-04

    The roles of long non-coding RNAs in cancer metabolism remain largely unexplored. Here we identify FILNC1 (FoxO-induced long non-coding RNA 1) as an energy stress-induced long non-coding RNA by FoxO transcription factors. FILNC1 deficiency in renal cancer cells alleviates energy stress-induced apoptosis and markedly promotes renal tumor development. We show that FILNC1 deficiency leads to enhanced glucose uptake and lactate production through upregulation of c-Myc. Upon energy stress, FILNC1 interacts with AUF1, a c-Myc mRNA-binding protein, and sequesters AUF1 from binding c-Myc mRNA, leading to downregulation of c-Myc protein. FILNC1 is specifically expressed in kidney, and is downregulated in renal cell carcinoma; also, its low expression correlates with poor clinical outcomes in renal cell carcinoma. Together, our study not only identifies FILNC1 as a negative regulator of renal cancer with potential clinical value, but also reveals a regulatory mechanism by long non-coding RNAs to control energy metabolism and tumor development.FoxO are commonly down-regulated transcription factors and tumor suppressors in renal cell cancer (RCC). Here, the authors show that upon energy stress FoxOs induce the expression of the long non-coding RNA FILNC1, which inhibits survival of RCC by downregulating c-Myc and c-Myc-dependent metabolic rewiring.

  8. Germline mutations in the VHL tumor suppresssor gene are similar to somatic VHL aberrations in sporadic renal cell carcinoma

    SciTech Connect

    Whaley, J.M.; Naglich, J.; Gelbert, L.

    1994-09-01

    A candidate gene for von Hippel Lindau disease was recently identified that led to the isolation of a partial cDNA clone with extended open reading frame without significant homology to known genes or obvious functional motifs, except for an acidic pentamer repeat domain. To further characterize the functional domains of the VHL gene and assess its involvement in hereditary and non-hereditary tumors, we performed mutation analyses and studied its expresssion in normal and tumor tissue. We identified germline mutations in 39% of VHL disease families. Moreover, 33% of sporadic RCCs, and all (6/6) sporadic RCC cell lines analyzed, showed mutations within the VHL gene. Both germline and somatic mutations included deletions, insertions, splice site mutations, missense and nonsense mutations, all of which clustered at the 3{prime} end of the corresponding partial VHL cDNA open reading frame including an alternatively-spliced exon of 123 nucleotides in length, suggesting functionally important domains encoded by the VHL gene in this region. Over 180 sporadic tumors of other types have shown no detectable base changes within the presumed coding sequence of the VHL gene to date. We conclude that the gene causing VHL has an important and specific role in the etiology of sporadic renal cell carcinomas, acts as a recessive tumor suppressor gene, and appears to encode important functional domains within the 3{prime} end of the known open reading frame.

  9. Small renal masses: The molecular markers associated with outcome of patients with kidney tumors 7 cm or less

    NASA Astrophysics Data System (ADS)

    Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Pikalova, L. V.

    2016-08-01

    The investigation of molecular mechanisms of tumor cell behavior in small renal masses is required to achieve the better cancer survival. The aim of the study is to find molecular markers associated with outcome of patients with kidney tumors 7 cm or less. A homogenous group of 20 patients T1N0M0-1 (mean age 57.6 ± 2.2 years) with kidney cancer was selected for the present analysis. The content of transcription and growth factors was determined by ELISA. The levels of AKT-mTOR signaling pathway components were measured by Western blotting analysis. The molecular markers associated with unfavorable outcome of patients with kidney tumors 7 cm or less were high levels of NF-kB p50, NF-kB p65, HIF-1, HIF-2, VEGF and CAIX. AKT activation with PTEN loss also correlated with the unfavorable outcome of kidney cancer patients with tumor size 7 cm or less. It is observed that the biological features of kidney cancer could predict the outcome of patients.

  10. Concordance of Pathologic Features Between Metastatic Sites and the Primary Tumor in Surgically Resected Metastatic Renal Cell Carcinoma.

    PubMed

    Psutka, Sarah P; Cheville, John C; Costello, Brian A; Stewart-Merrill, Suzanne B; Lohse, Christine M; Leibovich, Bradley C; Boorjian, Stephen A; Thompson, R Houston

    2016-10-01

    To evaluate the concordance of pathologic features in metastatic renal cell carcinoma (RCC) between the primary nephrectomy and metastasectomy specimens. Primary nephrectomy (n = 454) and matched metastasectomy specimens (n = 680) from patients treated between 1970 and 2009 for RCC were re-reviewed by 1 urologic pathologist in a blinded fashion. RCC histologic subtype, grade, coagulative necrosis, and the presence of sarcomatoid differentiation were compared between the primary and the metastatic tumor with kappa statistics. Concordance with the primary tumor was observed for subtype in 647 (95%, kappa = 0.71) of the metastases, for grade in 411 (60%, kappa = 0.35), necrosis in 460 (68%, kappa = 0.32), and sarcomatoid differentiation in 643 (95%, kappa = 0.60). Upgrading was observed in 100%, 63%, and 13% of patients with grades 1, 2, and 3 primary tumors, respectively (no patient had a grade 1 metastatic lesion). Metastatic tumors treated with metastasectomy within 30 days of nephrectomy (n = 145) had similar rates of concordant subtype, necrosis, and sarcomatoid differentiation to those undergoing metastasectomy beyond 30 days from nephrectomy (P >.05 for all), but had higher rates of concordant grade (71% vs 58%, P = .003). Pre-metastasectomy exposure to systemic targeted or immunotherapy was not associated with a change in concordance of histopathologic features. Among 454 surgically managed metastatic RCC patients, we observed a high degree of concordance for histologic subtype and sarcomatoid differentiation, and varying degrees of discordance for grade and coagulative tumor necrosis, between primary and metastatic tumors. Further investigation is warranted to understand the biologic and therapeutic implications of these observations. Published by Elsevier Inc.

  11. Occasional diagnosis of synchronous renal cell carcinoma during staging of other primary tumors.

    PubMed

    Piccinini, L; Luppi, G; Zoboli, A; Torricelli, P

    1996-01-01

    Synchronous renal cell cancer (RCC) associated with primary neoplasms of other organs or tissues represents a rare diagnostic report during life. Recently, the widespread use of new diagnostic techniques (echography, computed tomography and magnetic resonance imaging) has permitted diagnosis of clinically silent RCC. We report 6 RCC cases occasionally diagnosed during initial staging of a primary cancer of other organs: 1 rhinopharyngeal carcinoma, 1 gastric cancer, 1 Waldenström's disease, 1 non-Hodgkin's lymphoma, 2 breast cancer, RCC was clinically silent in all patients. The diagnostic problems related to a report of a renal mass in patients with neoplastic disease at other sites and the consequent therapeutic implications are discussed.

  12. Tumor size is associated with compensatory hypertrophy in the contralateral kidney after radical nephrectomy in patients with renal cell carcinoma.

    PubMed

    Park, Bong Hee; Sung, Hyun Hwan; Jeong, Byong Chang; Seo, Seong Ii; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Jeon, Hwang Gyun

    2016-06-01

    To assess the association between tumor size and postoperative compensatory hypertrophy of the contralateral kidney estimated with preoperative and postoperative CT in patients with renal cell carcinoma (RCC). We prospectively identified 728 patients who underwent radical nephrectomy for RCC between 2012 and 2014. Contrast-enhanced CT was done within 3 months preoperatively and 1 year postoperatively. A tissue segmentation tool program with CT images was used to estimate kidney volume. We divided patients into three groups according to tumor size (A: ≤4 cm, B: 4-7 cm, C: >7 cm). Preoperative and postoperative volumetric kidney parameters were compared and multivariable linear regression model was used to analyze predictors associated with postoperative compensatory hypertrophy. The preoperative median contralateral kidney volume was significantly larger in group C than in groups A and B (A: 170.3, B: 176.9, C: 186.8 mL, p < 0.05); the median tumor-side renal parenchymal volume was smaller in group C than in the other groups (A: 168.4, B: 171.1, C: 139.0 mL, p < 0.001). However, the postoperative median contralateral kidney volume among the three groups was not significantly different; the median contralateral kidney volume change after surgery was significantly larger in groups A and B than in group C (A: 37.8, B: 37.5, C: 27.4 mL, p < 0.05). Tumor size (≤7 cm) (p = 0.001) and male gender (p < 0.001) were significantly correlated with increased contralateral kidney volume on multivariable analysis. Tumor size showed the strongest positive association with postoperative contralateral kidney volume (A vs. C, partial regression coefficient = 10.6; B vs. C, partial regression coefficient = 10.5). Tumor size (≤4 or 4-7 cm) and male gender are significant factors associated with compensatory hypertrophy after surgery.

  13. Radiofrequency Ablation of Renal Tumors with an Expandable Multitined Electrode: Results, Complications, and Pilot Evaluation of Cooled Pyeloperfusion for Collecting System Protection

    SciTech Connect

    Rouviere, Olivier Badet, Lionel; Murat, Francois Joseph; Marechal, Jean Marie; Colombel, Marc; Martin, Xavier; Lyonnet, Denis; Gelet, Albert

    2008-05-15

    The objective of this study was to retrospectively evaluate the results of radiofrequency ablation (RFA) of renal tumors with an impedance-based system using an expandable multitined electrode. Twenty-two patients (30 tumors) were treated with RFA over a 7-year period, percutaneously (16 tumors) or intraoperatively (14 tumors). Follow-up imaging was performed at 1-3, 6, and 12 months and yearly thereafter. Twenty-seven of 30 tumors (19/22 patients) showed no residual tumor on the first imaging control. Two residual tumors were successfully ablated by a second RFA procedure. Our mean follow-up period was 35 months (range, 3-84 months). Two tumors that had been completely ablated based on imaging criteria recurred 11 and 48 months after RFA. One was treated by partial nephrectomy. The other one was not treated because the patient developed bone metastases. One patient had nephrectomy because of an RFA-induced ureteropelvic junction stricture. Nine patients (11 sessions) had a pyeloperfusion of cooled saline during RFA. None developed symptomatic complications, even though in three patients the ablation zone extended to the closest calyx (3-5 mm from the tumor). We conclude that RFA of renal tumors is promising, but serious complications to the collecting system must be taken into consideration. Prophylactic per-procedural cooling of the collecting system is feasible but needs further assessment.

  14. Radiofrequency ablation of renal tumors with an expandable multitined electrode: results, complications, and pilot evaluation of cooled pyeloperfusion for collecting system protection.

    PubMed

    Rouvière, Olivier; Badet, Lionel; Murat, François Joseph; Maréchal, Jean Marie; Colombel, Marc; Martin, Xavier; Lyonnet, Denis; Gelet, Albert

    2008-01-01

    The objective of this study was to retrospectively evaluate the results of radiofrequency ablation (RFA) of renal tumors with an impedance-based system using an expandable multitined electrode. Twenty-two patients (30 tumors) were treated with RFA over a 7-year period, percutaneously (16 tumors) or intraoperatively (14 tumors). Follow-up imaging was performed at 1-3, 6, and 12 months and yearly thereafter. Twenty-seven of 30 tumors (19/22 patients) showed no residual tumor on the first imaging control. Two residual tumors were successfully ablated by a second RFA procedure. Our mean follow-up period was 35 months (range, 3-84 months). Two tumors that had been completely ablated based on imaging criteria recurred 11 and 48 months after RFA. One was treated by partial nephrectomy. The other one was not treated because the patient developed bone metastases. One patient had nephrectomy because of an RFA-induced ureteropelvic junction stricture. Nine patients (11 sessions) had a pyeloperfusion of cooled saline during RFA. None developed symptomatic complications, even though in three patients the ablation zone extended to the closest calyx (3-5 mm from the tumor). We conclude that RFA of renal tumors is promising, but serious complications to the collecting system must be taken into consideration. Prophylactic per-procedural cooling of the collecting system is feasible but needs further assessment.

  15. Metastatic renal cell carcinoma, with a radiographically occult primary tumor, presenting in the operative site of a thoracic meningioma: long-term follow-up: Case report.

    PubMed

    Heary, Robert F; Agarwal, Nitin; Barrese, James C; Barry, Maureen T; Baisre, Ada

    2014-10-01

    Lesions metastatic to the site of a meningioma resection from a different primary tumor are rare. Metastasis of a tumor without a known primary tumor is also rare. Metastasis of a renal cell carcinoma, without an identifiable primary tumor, to the bed of a meningioma resection has not been previously reported. The authors describe the case of a 54-year-old man who presented with decreased sensory and motor function in the lower extremities. He underwent T3-5 laminectomies and gross-total removal of an intradural, extramedullary meningioma. The postoperative course was uneventful, and the patient regained full neurological function. After a 3-year period, he developed progressive upper thoracic pain and lower-extremity paresthesias. Imaging studies showed an epidural mass at the T2-4 levels and what appeared to be blastic involvement of the T2-4 vertebrae. A metastatic workup was negative. Emergency revision laminectomies yielded a fibrous, nonvascular mass. Neuropathology was consistent with metastatic renal cell carcinoma. After 6 months, the patient's symptoms of pain and paresthesias recurred. Repeat excision, with decompression of the spinal cord, revealed tumor cells morphologically and immunophenotypically similar to those obtained from the prior surgery. Cytogenetic analysis confirmed the presence of metastatic renal cell carcinoma. A novel case of an epidural metastatic renal cell carcinoma, of unknown primary origin, in the same operative bed of a previously resected intradural, extramedullary meningioma of the thoracic spine is reported.

  16. Honokiol inhibits c-Met-HO-1 tumor-promoting pathway and its cross-talk with calcineurin inhibitor-mediated renal cancer growth.

    PubMed

    Balan, Murugabaskar; Chakraborty, Samik; Flynn, Evelyn; Zurakowski, David; Pal, Soumitro

    2017-07-19

    Honokiol (HNK) is a small molecule with potent anti-inflammatory and anti-tumorigenic properties; yet the molecular targets of HNK are not well studied. Hyperactivation of the receptor tyrosine kinase c-Met and overexpression of the cytoprotective enzyme heme oxygenase-1 (HO-1) play a critical role in the growth and progression of renal cell carcinoma (RCC). Interestingly, the calcineurin inhibitor (CNI) cyclosporine A (CsA), an immunosuppressant used to prevent allograft rejection, can also increase the risk of RCC in transplant patients. We studied the potential role of c-Met signaling axis on CNI-induced renal tumor growth and tested the anti-tumor efficacy of HNK. Importantly, CNI treatment promoted c-Met induction and enhanced c-Met-induced Ras activation. We found that HNK treatment effectively down-regulated both c-Met phosphorylation and Ras activation in renal cancer cells. It inhibited the expression of both c-Met- and CNI-induced HO-1, and promoted cancer cell apoptosis. In vivo, HNK markedly inhibited CNI-induced renal tumor growth; and it decreased the expression of phospho-c-Met and HO-1 and reduced blood vessel density in tumor tissues. Our results suggest a novel mechanism(s) by which HNK exerts its anti-tumor activity through the inhibition of c-Met-Ras-HO-1 axis; and it can have significant therapeutic potential to prevent post-transplantation cancer in immunosuppressed patients.

  17. Epigenetic inactivation of the candidate tumor suppressor gene ASC/TMS1 in human renal cell carcinoma and its role as a potential therapeutic target

    PubMed Central

    Liu, Qianling; Jin, Jie; Ying, Jianming; Cui, Yun; Sun, Mengkui; Zhang, Lian; Fan, Yu; Xu, Ben; Zhang, Qian

    2015-01-01

    This study investigated the epigenetic alteration and biological function of the pro-apoptotic gene ASC/TMS1 in renal cell carcinoma. ASC/TMS1 was downregulated in five out of six RCC cell lines. A significant downregulation was also detected in sixty-seven paired renal tumors compared with adjacent non-cancerous tissues. The downregulation of ASC/TMS1 was correlated with promoter hypermethylation and could be restored with demethylation treatment. Re-expression of ASC/TMS1 in silenced RCC cell lines inhibited cell viability, colony formation, arrested cell cycle, induced apoptosis, suppressed cell invasion and repressed tumorigenicity in SCID mice. The antitumorigenic function of ASC/TMS1 in renal cancer was partially regulated by activation of p53 and p21 signaling. In addition, restoration of ASC/TMS1 sensitizes RCC cells to DNA damaging agents. Knockdown of ASC/TMS1 reduced DNA damaging agents-induced p53 activation and cell apoptosis. Moreover, ASC/TMS1 hypermethylation was further detected in 41.1% (83/202) of RCC tumors, but only 12% in adjacent non-cancerous tissues. ASC/TMS1 methylation was significantly correlated with higher tumor nuclear grade. In conclusion, ASC/TMS1 is a novel functional tumor suppressor in renal carcinogenesis. ASC/TMS1 tumor specific methylation may be a useful biomarker for designing improved diagnostic and therapeutic strategies for RCC. PMID:26093088

  18. Formation of Renal Cysts and Tumors in Vhl/Trp53-Deficient Mice Requires HIF1α and HIF2α.

    PubMed

    Schönenberger, Désirée; Harlander, Sabine; Rajski, Michal; Jacobs, Robert A; Lundby, Anne-Kristine; Adlesic, Mojca; Hejhal, Tomas; Wild, Peter J; Lundby, Carsten; Frew, Ian J

    2016-04-01

    The von Hippel-Lindau (VHL) tumor suppressor gene is inactivated in the majority of clear cell renal cell carcinomas (ccRCC), but genetic ablation of Vhl alone in mouse models is insufficient to recapitulate human tumorigenesis. One function of pVHL is to regulate the stability of the hypoxia-inducible factors (HIF), which become constitutively activated in the absence of pVHL. In established ccRCC, HIF1α has been implicated as a renal tumor suppressor, whereas HIF2α is considered an oncoprotein. In this study, we investigated the contributions of HIF1α and HIF2α to ccRCC initiation in the context of Vhl deficiency. We found that deleting Vhl plus Hif1a or Hif2a specifically in the renal epithelium did not induce tumor formation. However, HIF1α and HIF2α differentially regulated cell proliferation, mitochondrial abundance and oxidative capacity, glycogen accumulation, and acquisition of a clear cell phenotype in Vhl-deficient renal epithelial cells. HIF1α, but not HIF2α, induced Warburg-like metabolism characterized by increased glycolysis, decreased oxygen consumption, and decreased ATP production in mouse embryonic fibroblasts, providing insights into the cellular changes potentially occurring in Vhl mutant renal cells before ccRCC formation. Importantly, deletion of either Hif1a or Hif2a completely prevented the formation of renal cysts and tumors in Vhl/Trp53 mutant mice. These findings argue that both HIF1α and HIF2α exert protumorigenic functions during the earliest stages of cyst and tumor formation in the kidney. Cancer Res; 76(7); 2025-36. ©2016 AACR.

  19. Outcomes After Cryoablation Versus Partial Nephrectomy for Sporadic Renal Tumors in a Solitary Kidney: A Propensity Score Analysis.

    PubMed

    Bhindi, Bimal; Mason, Ross J; Haddad, Mustafa M; Boorjian, Stephen A; Leibovich, Bradley C; Atwell, Thomas D; Weisbrod, Adam J; Schmit, Grant D; Thompson, R Houston

    2017-09-26

    While partial nephrectomy (PN) is considered the standard approach for a tumor in a solitary kidney, percutaneous cryoablation (PCA) is emerging as an alternative nephron-sparing option. To compare outcomes between PCA and PN for tumors in a solitary kidney. Patients who underwent PCA or PN between 2005 and 2015 for a single primary renal tumor in a solitary kidney were identified using Mayo Clinic Registries. Exclusion criteria were inherited tumor syndromes and salvage procedures. PCA and PN. To achieve balance in baseline characteristics, we used inverse probability of treatment weighting (IPTW) based on propensity to receive treatment. The risk of having a post-treatment complication and percent drop in estimated glomerular filtration rate (eGFR), as well as the risks of local/ipsilateral recurrence, distant metastasis, and cancer-specific mortality, were compared between groups using logistic, linear, and Fine-and-Gray competing risk regression models. The cohort included 118 patients (PCA: 54; PN: 64) with a median follow-up of 47 mo (interquartile range 18, 74). In unadjusted analyses, PCA was associated with a lower risk of complications (15% vs 31%; odds ratio [OR]=0.38; 95% confidence interval [CI] 0.15, 0.96; p=0.04). However, upon accounting for baseline differences with IPTW adjustment, there was no longer a significant difference in the risk of complications (28% vs 29%; OR=0.95; 95% CI 0.53, 1.69; p=0.9). There were no significant differences between PCA and PN in percentage drop in eGFR at discharge (mean: 11% vs 16%; β=-5%; 95% CI -13, 3; p=0.2) or at 3 mo (12% vs 9%; β=3%; 95% CI -3, 10; p=0.3). Likewise, no significant differences were noted in local recurrence (HR=0.87; 95% CI 0.38, 1.98; p=0.7), distant metastases (HR=0.60; 95% CI 0.30, 1.20; p=0.2), or cancer-specific mortality (HR=1.13; 95% CI 0.32, 3.98; p=0.8). Limitations include the sample size, given the relative rarity of renal masses in solitary kidneys. Our study found no

  20. Percutaneous Cryoablation of Metastatic Renal Cell Carcinoma for Local Tumor Control: Feasibility, Outcomes, and Estimated Cost-effectiveness for Palliation

    PubMed Central

    Bang, Hyun J.; Littrup, Peter J.; Goodrich, Dylan J.; Currier, Brandt P.; Aoun, Hussein D.; Heilbrun, Lance K.; Vaishampayan, Ulka; Adam, Barbara; Goodman, Allen C.

    2013-01-01

    Purpose To assess complications, local tumor recurrences, overall survival (OS), and estimates of cost-effectiveness for multisite cryoablation (MCA) of oligometastatic renal cell carcinoma (RCC). Materials and Methods A total of 60 computed tomography- and/or ultrasound-guided percutaneous MCA procedures were performed on 72 tumors in 27 patients (three women and 24 men). Average patient age was 63 years. Tumor location was grouped according to common metastatic sites. Established surgical selection criteria graded patient status. Median OS was determined by Kaplan–Meier method and defined life-years gained (LYGs). Estimates of MCA costs per LYG were compared with established values for systemic therapies. Results Total number of tumors and cryoablation procedures for each anatomic site are as follows: nephrectomy bed, 11 and 11; adrenal gland, nine and eight; paraaortic, seven and six; lung, 14 and 13; bone, 13 and 13; superficial, 12 and nine; intraperitoneal, five and three; and liver, one and one. A mean of 2.2 procedures per patient were performed, with a median clinical follow-up of 16 months. Major complication and local recurrence rates were 2% (one of 60) and 3% (two of 72), respectively. No patients were graded as having good surgical risk, but median OS was 2.69 years, with an estimated 5-year survival rate of 27%. Cryoablation remained cost-effective with or without the presence of systemic therapies according to historical cost comparisons, with an adjunctive cost-effectiveness ratio of $28,312–$59,554 per LYG. Conclusions MCA was associated with very low morbidity and local tumor recurrence rates for all anatomic sites, with apparent increased OS. Even as an adjunct to systemic therapies, MCA appeared cost-effective for palliation of oligometastatic RCC. PMID:22538119

  1. Clinical and oncological outcomes in Chinese patients with renal cell carcinoma and venous tumor thrombus extension: single-center experience.

    PubMed

    Chen, Xiaonan; Li, Shijie; Xu, Zhenqun; Wang, Kefeng; Fu, Donghui; Liu, Qiang; Wang, Xia; Wu, Bin

    2015-02-04

    To evaluate the clinical and oncological outcomes and to identify prognostic factors for survival in Chinese patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). A total of 86 patients who underwent nephrectomy and tumor thrombectomy for RCC and venous tumor thrombus extension from 2003 to 2013 were included in this retrospective study. The records of these patients were reviewed. Kaplan-Meier analysis was used to determine cancer-specific survival (CSS). Prognostic factors for CSS were identified by univariate and multivariate analyses using the Cox proportional hazards regression mode. All patients in this cohort received radical nephrectomy and tumor thrombectomy. Median follow-up period was 27.0 months (range 3-111). No patients died intraoperatively, and the complication rate was 36.0%. The 1-, 3-, and 5-year CSS rates for all patients were 93.0%, 70.9%, and 58.1%, respectively, and those for patients without distant metastasis at presentation were 95.3%, 82.6%, and 68.6%, respectively. Multivariate Cox regression analysis showed that lymph node invasion, distant metastasis at presentation, and invasion of the inferior vena cava (IVC) wall were the independent prognostic factors for CSS in all patients. For patients without distant metastasis, tumor grade, lymph node invasion, and perinephric fat invasion were significantly associated with CSS on multivariate analysis. Survival rates for patients with RCC and VTT were still poor. Our results indicated that lymph node invasion, distant metastasis at presentation, and invasion of the IVC wall were independent negative prognostic factors.

  2. Clear cell renal cell carcinoma: a comparative study of histological and chromosomal characteristics between primary tumors and their corresponding metastases.

    PubMed

    Dagher, Julien; Kammerer-Jacquet, Solène-Florence; Dugay, Frédéric; Beaumont, Marion; Lespagnol, Alexandra; Cornevin, Laurence; Verhoest, Grégory; Bensalah, Karim; Rioux-Leclercq, Nathalie; Belaud-Rotureau, Marc-Antoine

    2017-07-01

    Clear cell renal cell carcinoma (ccRCC) has a poor prognosis with a 50% risk of metastases. Little is known about the phenotypic and molecular profiles of metastases regarding their corresponding primary tumors. This study aimed to screen phenotypic and genotypic differences between metastases and their corresponding primary tumors. We selected four cases with available frozen material. The histological, immunohistochemical (VEGFA, CD31, SMA, Ki67, p53, PAR-3), FISH (VHL gene), next-generation sequencing (VHL and c-MET genes), multiplex ligation-dependent probe amplification, and array-(comparative genomic hybridization) CGH analyses were realized. Metastases were nodal, hepatic (synchronous), adrenal, and pulmonary (metachronous). High-grade tumor cells were significantly more frequent in metastases (p = 0.019). Metastases and high-grade zones of primary tumors shared similar characteristics compared to low-grade zones: a lower microscopic vascular density (43.5 vs 382.5 vessels/mm(2); p = 0.0027), a higher expression of VEGF (73 vs 10%, p = 0.045), Ki67 (37.6 vs 8.3%; p = 0.011), and p53 (54 vs 10.6%; p = 0.081), and a cytoplasmic and membranous PAR-3 staining. Metastases exhibited more chromosomal imbalances than primary tumors in total (18.75 ± 6.8; p = 0.044) with more genomic gains (13.5 ± 7; p = 0.013). The loss of chromosome 9 and gain of Xq were found in both primary tumors and metastases but gains of loci or chromosomes 2p, 3q, 5, 8q, 12, and 20 were only found in metastases. The VHL gene status was similar in each tumor couple. Although metastases and primary tumors share common histological features, this study highlights chromosomal differences specific to metastases which could be involved in ccRCC metastatic evolution.

  3. Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions.

    PubMed

    Azzi, Sandy; Gallerne, Cindy; Romei, Cristina; Le Coz, Vincent; Gangemi, Rosaria; Khawam, Krystel; Devocelle, Aurore; Gu, Yanhong; Bruno, Stefania; Ferrini, Silvano; Chouaib, Salem; Eid, Pierre; Azzarone, Bruno; Giron-Michel, Julien

    2015-06-01

    Intrarenal interleukin-15 (IL-15) participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15) isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC) to peritumoral (ptumTEC), tumoral (RCC), and cancer stem cells (CSC/CD105(+)). RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα) chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15) isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα). This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105(+), where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105(+) from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa) displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, "apparently normal" ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral "preneoplastic" environment committed to favor tumor progression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Tumor-associated macrophages mediate immunosuppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 pathway.

    PubMed

    Daurkin, Irina; Eruslanov, Evgeniy; Stoffs, Taryn; Perrin, George Q; Algood, Chester; Gilbert, Scott M; Rosser, Charles J; Su, Li-Ming; Vieweg, Johannes; Kusmartsev, Sergei

    2011-10-15

    Renal cell carcinoma (RCC), the most common human kidney cancer, is frequently infiltrated with tumor-associated macrophages (TAM) that can promote malignant progression. Here, we show that TAMs isolated from human RCC produce substantial amounts of the proinflammatory chemokine CCL2 and immunosuppressive cytokine IL-10, in addition to enhanced eicosanoid production via an activated 15-lipoxygenase-2 (15-LOX2) pathway. TAMs isolated from RCC tumors had a high 15-LOX2 expression and secreted substantial amounts of 15(S)-hydroxyeicosatetraenoic acid, its major bioactive lipid product. Inhibition of lipoxygenase activity significantly reduced production of CCL2 and IL-10 by RCC TAMs. In addition, TAMs isolated from RCC were capable of inducing in T lymphocytes, the pivotal T regulatory cell transcription factor forkhead box P3 (FOXP3), and the inhibitory cytotoxic T-lymphocyte antigen 4 (CTLA-4) coreceptor. However, this TAM-mediated induction of FOXP3 and CTLA-4 in T cells was independent of lipoxygenase and could not be reversed by inhibiting lipoxygenase activity. Collectively, our results show that TAMs, often present in RCCs, display enhanced 15-LOX2 activity that contributes to RCC-related inflammation, immunosuppression, and malignant progression. Furthermore, we show that TAMs mediate the development of immune tolerance through both 15-LOX2-dependent and 15-LOX2-independent pathways. We propose that manipulating LOX-dependent arachidonic acid metabolism in the tumor microenvironment could offer new strategies to block cancer-related inflammation and immune escape in patients with RCC.

  5. βIII-tubulin overexpression is linked to aggressive tumor features and shortened survival in clear cell renal cell carcinoma.

    PubMed

    Quaas, Alexander; Rahvar, Amir-Hossein; Burdelski, Christoph; Koop, Christina; Eichelberg, Christian; Rink, Michael; Dahlem, Roland; Schlomm, Thorsten; Tsourlakis, Maria Christina; Simon, Ronald; Minner, Sarah; Sauter, Guido; Steurer, Stefan

    2015-10-01

    βIII-tubulin (TUBB3) is a microtubule component overexpression of which is found in many solid cancer types, often linked to poor patient prognosis, and has been suggested to predict failure of microtubule-targeting chemotherapeutics. This study was designed to determine prevalence and prognostic impact of TUBB3 expression in kidney cancers. A tissue microarray (TMA) containing more than 1,200 renal tumors was analyzed by immunohistochemistry. TUBB3 expression varied markedly between the different histological subtypes and was more frequent in 105 papillary cancers (75.2 %, p < 0.0001), 38 oncocytomas (52.6 %, p < 0.0001), and 22 chromophobic carcinomas (36.4 %, p = 0.1221) than in 555 clear cell RCC (16.4 %). In clear cell cancers, strong TUBB3 positivity was linked to high Fuhrman grade (p < 0.0001), advanced stage (0.002), nodal metastases (p = 0.0433), hematogenous metastases (p = 0.0016), and shortened overall survival (p < 0.0001). Associations with outcome and tumor phenotype were inversely for papillary RCC, where TUBB3 immunostaining was linked to low tumor stage (p = 0.0012) and prolonged survival (p = 0.0043). TUBB3 expression levels and their effects are strikingly different between ccRCC and papillary RCC. These differences may be caused by differences in VHL function between these RCC subtypes, because VHL (like TUBB3) is another strong regulator of microtubule function.

  6. Tumor-suppressing effects of microRNA-429 in human renal cell carcinoma via the downregulation of Sp1

    PubMed Central

    Wu, Deyao; Niu, Xiaobing; Pan, Huixing; Zhou, Yunfeng; Zhang, Zichun; Qu, Ping; Zhou, Jian

    2016-01-01

    MicroRNA (miR)-429 has been frequently reported to be downregulated in various tumors, including renal cell carcinoma (RCC), nasopharyngeal carcinoma, Ehrlich ascites tumor cells, gastric cancer, non-small cell lung cancer and endometrial endometrioid carcinoma. The present study investigated the effects of miR-429 on human RCC A498 and 786-O cells. Following transfection of cells with miR-429 mimics and scrambled control, MTT, cell migration, cell invasion and luciferase assays were performed. In addition, western blotting was performed in order to assess the expression of specificity protein 1 (Sp1), which was predicted to be a target of miR-429 by TargetScan. The present results revealed that miR-429 inhibited cell proliferation, migration and invasion of 786-O and A498 cells. In addition, the present results demonstrated that miR-429 overexpression downregulated Sp1 protein expression, which provides evidence that miR-429 may directly target Sp1 in RCC. These results suggest that miR-429 may be investigated for use as a predictive marker for early detection of tumor metastasis and blocking RCC cells from becoming invasive. PMID:27698878

  7. Benign nodal lesions mimicking metastases from pediatric renal neoplasms: a report of the National Wilms' Tumor Study Pathology Center.

    PubMed

    Weeks, D A; Beckwith, J B; Mierau, G W

    1990-12-01

    Regional lymph node status is a key factor in the staging of pediatric renal tumors on the National Wilms' Tumor Study (NWTS). A review of cases entered on the NWTS has uncovered a number of cases where benign lymph node findings were mistaken for metastases. Most frequently, this was due to the presence of complexes of epithelial cells and Tamm-Horsfall protein within nodal sinuses. The epithelial cells were derived from damaged nephrons, usually resulting from obstruction by tumor. Another epithelial pseudometastic lesion, intranodal squamous epithelial cells, was found to originate from metaplastic calyceal urothelium. Benign mesothelial or coelomic inclusions similar to those previously described in pelvic and periaortic lymph nodes of adult females were found in nodes of four patients, including two boys, who are, to our knowledge, the first to be described with this finding. Other sources of confusion included protrusion of lymphoid follicles or germinal centers into nodal sinuses, thick endothelial cells of postcapillary venules mimicking epithelial tubules, nodal megakaryocytes resembling anaplastic nuclear changes, and histiocytic granulomas. Immunocytochemical methods were useful in evaluating some of these phenomena. Recognition of these pseudometastatic lesions is essential in order to avoid unnecessary and potentially hazardous therapeutic intensification.

  8. [Design of radiolabeled antibody fragments for tumor-selective radioactivity localization--brush border enzyme-sensitive bond to decrease renal accumulation of radioactivity].

    PubMed

    Mukai, Takahiro; Fujioka, Yasushi; Arano, Yasushi; Saji, Hideo

    2003-08-01

    Nonspecific renal radioactivity localization constitutes a problem in targeted imaging and therapy with radiolabeled antibody fragments. Based on the idea that the renal radioactivity levels should be reduced if radiolabeled compounds excreted in the urine are released from antibody fragments by tubular brush border enzymes, 3'-iodohippuryl N epsilon-maleoyl-L-lysine (HML) was designed as a radioiodination reagent for antibody fragments; the glycyl-lysine sequence in HML is a substrate for a brush border enzyme and m-iodohippuric acid is released by cleavage of the linkage. In normal mice, HML-conjugated Fab demonstrated low renal radioactivity levels from early postinjection times. Directly radioiodinated Fab showed migration of radioactivity from the membrane to the lysosomal fraction of the renal cells from 10 to 30 min postinjection. On the other hand, the majority of the radioactivity was detected only in the membrane fraction after injection of HML-conjugated Fab. In tumor-bearing mice, HML-conjugated Fab showed a marked decrease in renal radioactivity localization without impairing the tumor accumulation. These findings indicate that HML is a useful reagent for reducing the renal radioactivity levels of antibody fragments.

  9. Caval thrombus in conjunction with renal tumors: indication for surgery and technical details.

    PubMed

    González, J; Ciancio, G

    2014-11-01

    Patients with locally advanced renal cell carcinoma require an aggressive surgical approach, as this strategy represents the only hope for curing the disease. Selection of the appropriate surgical technique to treat these cases is essential in order to achieve the best outcomes. This process usually entails a tailored approach centered on the individual disease features. This article reviews the indications and provides a technical description for each of the surgical steps commonly used to address the multiple possible scenarios in this context.

  10. Renal, hepatic, pulmonary and adrenal tumors induced by prenatal inorganic arsenic followed by dimethylarsinic acid in adulthood in CD1 mice

    PubMed Central

    Tokar, Erik J.; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2012-01-01

    Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33–35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal. PMID:22230260

  11. miR-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B

    PubMed Central

    Ding, Meng; Zhong, Jinsha; Zhang, Chen-Yu; Ge, Jingping; Wang, Junjun; Zhang, Chunni

    2016-01-01

    The incidence and mortality rate of renal cell carcinoma (RCC) have been significantly increasing; however, the mechanisms involved in RCC development and progression are unclear. In this study, we found that miR-28-5p was decreased in RCC tumor specimens and several renal carcinoma cell lines. By using a combination of luciferase reporter assays and western blotting, we identified RAP1B, a Ras-related small GTP-binding oncoprotein implicated in a variety of tumors, as a direct target of miR-28-5p in RCC. The RAP1B protein level was increased in RCC tumor specimens and renal carcinoma cell lines, and this was inversely correlated with miR-28-5p expression. In vitro gain-of-function and loss-of-function studies in human renal carcinoma cell lines, demonstrated that miR-28-5p suppressed cell proliferation and migration by directly inhibiting RAP1B, and this effect was reversed by co-transfection with RAP1B. In addition, the stable overexpression of miR-28-5p inhibited tumor cell proliferation in vivo. This newly identified miR-28-5p/RAP1B axis provides a novel mechanism for the pathogenesis of RCC, and molecules in this axis may serve as potential biomarkers and therapeutic targets for RCC. PMID:27729617

  12. A proposal of post-operative nomogram for overall survival in patients with renal cell carcinoma and venous tumor thrombus.

    PubMed

    Gu, Liangyou; Wang, Zihuan; Chen, Luyao; Ma, Xin; Li, Hongzhao; Nie, Wenyuan; Peng, Cheng; Li, Xintao; Gao, Yu; Zhang, Xu

    2017-06-01

    To identify the predictors of overall survival (OS) and create a post-operative prognostic model for patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). The study cohort included patients with RCC and VTT that underwent full surgical resection between 2006 and 2016. Univariate and multivariate analyses were used to determine the prognostic factors of OS. A nomogram was developed and internally calibrated by bootstrap resampling method. A total of 185 patients were identified, including patients with thrombus present in the renal vein (109 patients, 58.9%), infrahepatic inferior vena cava (IVC; 68 patients, 36.8%), and suprahepatic IVC (8 patients, 4.3%). After a median follow-up of 30.2 months (interquartile range, 12.1-48.4 months), 63 (34.1%) patients died. Independent prognostic factors for OS included histological subtype, collecting system invasion, metastasis at surgery, De Ritis ratio (AST/ALT), and serum albumin. Independently predictive variables were used to create a nomogram, which achieved a concordance index of 0.75 for OS. For patients with RCC and VTT, the developed and internally validated post-operative nomogram can be used to select patients who may benefit from aggressive surveillance regimens or adjuvant therapy clinical trials. © 2017 Wiley Periodicals, Inc.

  13. Candidate tumor suppressor and pVHL partner Jade-1 binds and inhibits AKT in renal cell carcinoma.

    PubMed

    Zeng, Liling; Bai, Ming; Mittal, Amit K; El-Jouni, Wassim; Zhou, Jing; Cohen, David M; Zhou, Mina I; Cohen, Herbert T

    2013-09-01

    The von Hippel-Lindau (VHL) tumor suppressor pVHL is lost in the majority of clear-cell renal cell carcinomas (RCC). Activation of the PI3K/AKT/mTOR pathway is also common in RCC, with PTEN loss occurring in approximately 30% of the cases, but other mechanisms responsible for activating AKT at a wider level in this setting are undefined. Plant homeodomain protein Jade-1 (PHF17) is a candidate renal tumor suppressor stabilized by pVHL. Here, using kinase arrays, we identified phospho-AKT1 as an important target of Jade-1. Overexpressing or silencing Jade-1 in RCC cells increased or decreased levels of endogenous phospho-AKT/AKT1. Furthermore, reintroducing pVHL into RCC cells increased endogenous Jade-1 and suppressed endogenous levels of phospho-AKT, which colocalized with and bound to Jade-1. The N-terminus of Jade-1 bound both the catalytic domain and the C-terminal regulatory tail of AKT, suggesting a mechanism through which Jade-1 inhibited AKT kinase activity. Intriguingly, RCC precursor cells where Jade-1 was silenced exhibited an increased capacity for AKT-dependent anchorage-independent growth, in support of a tumor suppressor function for Jade-1 in RCC. In support of this concept, an in silico expression analysis suggested that reduced Jade-1 expression is a poor prognostic factor in clear-cell RCC that is associated with activation of an AKT1 target gene signature. Taken together, our results identify 2 mechanisms for Jade-1 fine control of AKT/AKT1 in RCC, through loss of pVHL, which decreases Jade-1 protein, or through attenuation in Jade-1 expression. These findings help explain the pathologic cooperativity in clear-cell RCC between PTEN inactivation and pVHL loss, which leads to decreased Jade-1 levels that superactivate AKT. In addition, they prompt further investigation of Jade-1 as a candidate biomarker and tumor suppressor in clear-cell RCC.

  14. Candidate tumor suppressor and pVHL partner Jade-1 binds and inhibits AKT in renal cell carcinoma

    PubMed Central

    Zeng, Liling; Bai, Ming; Mittal, Amit K.; El-Jouni, Wassim; Zhou, Jing; Cohen, David M.; Zhou, Mina I.; Cohen, Herbert T.

    2013-01-01

    The von Hippel-Lindau tumor suppressor pVHL (VHL) is lost in the majority of clear-cell renal cell carcinomas (RCCs). Activation of the PI3K/AKT/mTOR pathway is also common in RCC, with PTEN loss occurring in ~30% of the cases, but other mechanisms responsible for activating AKT at a wider level in this setting are undefined. Plant homeodomain protein Jade-1 (PHF17) is a candidate renal tumor suppressor stabilized by pVHL. Here using kinase arrays we identified phospho-AKT1 as an important target of Jade-1. Overexpressing or silencing Jade-1 in RCC cells increased or decreased levels of endogenous phospho-AKT/AKT1. Further, reintroducing pVHL into RCC cells increased endogenous Jade-1 and suppressed endogenous levels of phospho-AKT, which colocalized with and bound to Jade-1. The N-terminus of Jade-1 bound both the catalytic domain and the C-terminal regulatory tail of AKT, suggesting a mechanism through which Jade-1 inhibited AKT kinase activity. Intriguingly, RCC precursor cells where Jade-1 was silenced exhibited an increased capacity for AKT-dependent anchorage-independent growth, in support of a tumor suppressor function for Jade-1 in RCC. In support of this concept, an in silico expression analysis suggested that reduced Jade-1 expression is a poor prognostic factor in clear-cell RCC that is associated with activation of an AKT1 target gene signature. Taken together, our results identify two mechanisms for Jade-1 fine control of AKT/AKT1 in RCC, through loss of pVHL, which decreases Jade-1 protein, or through attenuation in Jade-1 expression. These findings help explain the pathologic cooperativity in clear-cell RCC between PTEN inactivation and pVHL loss, which leads to decreased Jade-1 levels that superactivate AKT. Additionally, they prompt further investigation of Jade-1 as a candidate biomarker and tumor suppressor in clear-cell RCC. PMID:23824745

  15. [Differences in sports participation for children and adolescents with solitary kidney due to renal tumors across Europe. Time for harmonization].

    PubMed

    Spreafico, F; Terenziani, M; Ardissino, G; Calegari, M; Catania, S; Massimino, M

    2015-02-01

    As a result of advances in treatment, almost 90% of children diagnosed with Wilms tumor became long-term survivors, and have a sustainable quality of life. These patients' involvement in sports during their childhood is hopefully increasing too. The cornerstone of renal tumor cure remains radical nephrectomy, however, so survivors live with a solitary kidney. In most European countries and the USA, the involvement in sports of children with a solitary kidney depends on a responsible physician saying a "qualified yes", pending individual assessment. Unlike the case in the rest of Europe, in Italy having only one kidney automatically disqualifies an individual wishing to participate in any organized "competitive" sports carrying some risk of renal trauma, including basketball, soccer and sometime volleyball. This absolute restriction is based on ad hoc Ministerial rulings concerning "Health protection in sport activities". But available data do not seem to support such an absolute limitation on participation in sports based exclusively on the fact of having a single kidney. The sport-specific incidence of kidney injuries has been estimated at 2.3 injuries per million male athlete/exposures for basketball (2.5 for females), and 2.6 for soccer (6.0 for girls). Kidney injuries are significantly more rare than head or spine injuries. This article aims to provide Italian sport medicine specialists and policy-makers with the necessary background so that the current, over-protective "unquestionably no" response can be reconsidered, and converted into a still well-founded, more permissive attitude to the sports activities suitable for any children with a solitary normal kidney.

  16. The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth

    PubMed Central

    2009-01-01

    Background Human clear cell renal cell carcinoma (CRCC) remains resistant to therapies. Recent advances in Hypoxia Inducible Factors (HIF) molecular network led to targeted therapies, but unfortunately with only limited clinical significance. Elucidating the molecular processes involved in kidney tumorigenesis and resistance is central to the development of improved therapies, not only for kidney cancer but for many, if not all, cancer types. The oncogenic PI3K/Akt, NF-kB and MAPK pathways are critical for tumorigenesis. The sonic hedgehog (SHH) signaling pathway is crucial to normal development. Results By quantitative RT-PCR and immunoblot, we report that the SHH signaling pathway is constitutively reactivated in tumors independently of the von Hippel-Lindau (VHL) tumor suppressor gene expression which is inactivated in the majority of CRCC. The inhibition of the SHH signaling pathway by the specific inhibitor cyclopamine abolished CRCC cell growth as assessed by cell counting, BrdU incorporation studies, fluorescence-activated cell sorting and β-galactosidase staining. Importantly, inhibition of the SHH pathway induced tumor regression in nude mice through inhibition of cell proliferation and neo-vascularization, and induction of apoptosis but not senescence assessed by in vivo studies, immunoblot and immunohistochemistry. Gli1, cyclin D1, Pax2, Lim1, VEGF, and TGF-β were exclusively expressed in tumors and were shown to be regulated by SHH, as evidenced by immunoblot after SHH inhibition. Using specific inhibitors and immunoblot, the activation of the oncogenic PI3K/Akt, NF-kB and MAPK pathways was decreased by SHH inhibition. Conclusions These findings support targeting SHH for the treatment of CRCC and pave the way for innovative and additional investigations in a broad range of cancers. PMID:20015350

  17. Early Significant Tumor Volume Reduction After Radiosurgery in Brain Metastases From Renal Cell Carcinoma Results in Long-Term Survival

    SciTech Connect

    Kim, Wook Ha; Kim, Dong Gyu; Han, Jung Ho; Paek, Sun Ha; Chung, Hyun-Tai; Park, Chul-Kee; Kim, Chae-Yong; Kim, Yong Hwy; Kim, Jin Wook; Jung, Hee-Won

    2012-04-01

    Purpose: To retrospectively evaluate survival of patients with brain metastasis from renal cell carcinoma (RCC) after radiosurgery. Patients and Methods: Between 1998 and 2010, 46 patients were treated with radiosurgery, and the total number of lesions was 99. The mean age was 58.9 years (range, 33-78 years). Twenty-six patients (56.5%) had a single brain metastasis. The mean tumor volume was 3.0 cm{sup 3} (range, 0.01-35.1 cm{sup 3}), and the mean marginal dose prescribed was 20.8 Gy (range, 12-25 Gy) at the 50% isodose line. A patient was classified into the good-response group when the sum of the volume of the brain metastases decreased to less than 75% of the original volume at a 1-month follow-up evaluation using MRI. Results: As of December 28, 2010, 39 patients (84.8%) had died, and 7 (15.2%) survived. The overall median survival time was 10.0 {+-} 0.4 months (95% confidence interval, 9.1-10.8). After treatment, local tumor control was achieved in 72 (84.7%) of the 85 tumors assessed using MRI after radiosurgery. The good-response group survived significantly longer than the poor-response group (median survival times of 18.0 and 9.0 months, respectively; p = 0.025). In a multivariate analysis, classification in the good-response group was the only independent prognostic factor for longer survival (p = 0.037; hazard ratio = 0.447; 95% confidence interval, 0.209-0.953). Conclusions: Radiosurgery seems to be an effective treatment modality for patients with brain metastases from RCC. The early significant tumor volume reduction observed after radiosurgery seems to result in long-term survival in RCC patients with brain metastases.

  18. Can diffusion-weighted magnetic resonance imaging of clear cell renal carcinoma predict low from high nuclear grade tumors.

    PubMed

    Parada Villavicencio, Carolina; Mc Carthy, Robert J; Miller, Frank H

    2017-04-01

    To assess the diagnostic performance of the apparent diffusion coefficient (ADC) in predicting the Fuhrman nuclear grading of clear cell renal cell carcinomas (ccRCC). A total of 129 patients who underwent partial and radical nephrectomies with pathology-proven ccRCC were retrospectively evaluated. Histopathological characteristics and nuclear grades were analyzed. In addition, conventional magnetic resonance imaging (MRI) features were assessed in consensus by two radiologists to discriminate nuclear grading. ADC values were obtained from a region of interest (ROI) measurement in the ADC maps calculated from diffusion-weighted imaging (DWI) using b values of 50, 500, and 800 s/mm(2). The threshold values for predicting and differentiating low-grade cancers (Fuhrman I-II) from high grade (Fuhrman III-IV) was obtained using binary logistic regression. The ADC cut-off value for differentiating low- and high-grade tumors was determined using classification analysis. Significant associations (P < 0.001) were found between nuclear grading, conventional MR features, and DWI. Hemorrhage, necrosis, perirenal fat invasion, enhancement homogeneity, and cystic component were identified as independent predictors of tumor grade. High-grade ccRCC had significantly lower mean ADC values compared to low-grade tumors. An ADC cut-off value of 1.6 × 10(-3) mm(2)/s had an optimal predictive percentage of 65.5% for low-grade tumors above this threshold and 81% for high-grade ccRCC below this threshold. Overall predictive accuracy was 70.5%. The addition of ADC values to a model based on MRI conventional features demonstrates increased sensitivity and high specificity improving the distinguishing accuracy between both high-grade and low-grade ccRCC.

  19. Investigation of Renal Cell Carcinoma by Contrast-Enhanced Ultrasound- Predictive Value of Time Intensity Curve Analysis in Establishing Local Tumor Invasion and Stage: A Pilot Study.

    PubMed

    Tamas-Szora, Attila; Socaciu, Mihai; Crișan, Nicolae; Dobrotă, Florentin; Prunduș, Paul; Bungărdean, Cătălina; Buruian, Mircea; Coman, Ioan; Opincariu, Iulian; Badea, Radu

    2015-07-01

    Contrast-enhanced ultrasound (CEUS) allows for real-time examination of signal intensity changes in a region of interest (ROI) and quantification of contrast agent kinetics. This study assessed the predictive ability of time-intensity curve (TIC) parameters for local tumor invasion and T stage of renal cell carcinoma (RCC). Renal tumors in 41 patients were examined by CEUS. Thirty-two met the inclusion criteria, with a total of 33 tumors (27 clear cell, 4 chromophobe, and 2 papillary type I). Nineteen (57.6%) tumors were included in group A (stages pT1 and pT2) and 14 (42.4%) in group B (stage pT3). ROIs were established as: whole tumor (TuW); tumor area with the highest signal intensity (TuMAX) and renal cortex (Ref). The TIC param­eters for each ROI were calculated as below: peak signal intensity, time to peak (TTP), rise time (RT), and mean transit time (MTT). They were analyzed as a whole value for each ROI and as a ratio between the different ROIs. There were significant differences between the tumors invading and not invading the renal sinus fat for TTP (TuW/Ref) [0.98 (0.67-1.25) vs. 1.18 (1.08-1.3), P < .05]. For differentiation between groups A and B, the following ratios were proven as predictors by univariate regression analysis: TTP (TuMAX/TuW); MTT (Tu­MAX/TuW); RT (TuMAX/TuW) (P = .03, P = .01 and P = .02, respectively). The value derived from the Receiver Operating Characteristic (ROC) curve for RT (TuMAX/TuW) was 0.8 with sensitivity = 78.6%, specificity = 89.5%, and cutoff value of > 0.91. TIC parameters were predictors of locally noninvasive and invasive RCC.

  20. A Pharmacokinetic and Safety Study of Trebananib, a Fc-Fusion Peptibody, in Patients with Advanced Solid Tumors and Varying Degrees of Renal Dysfunction.

    PubMed

    Wu, Benjamin; Lewis, Lionel D; Harvey, R Donald; Rasmussen, Erik; Gamelin, Erick; Sun, Yu-Nien; Friberg, Gregory; Koyner, Jay L; Dowlati, Afshin; Maitland, Michael L

    2017-01-11

    Clearance of trebananib (AMG 386), a 64 kD anti-angiogenic peptibody, has been associated with estimated glomerular filtration rate (eGFR). We prospectively evaluated trebananib pharmacokinetics and safety/tolerability in advanced solid tumor patients with varying degrees of renal function. Patients were assigned to normal renal function, mild, moderate, or severe renal dysfunction cohorts based on eGFR, received trebananib 15 mg/kg IV weekly, and underwent week 1 and week 5 pharmacokinetic and weekly safety assessments. For 28 patients, trebananib clearance decreased from normal renal function (1.52 mL/hr/kg), to mild (1.20 mL/hr/kg), moderate (0.79 mL/hr/kg), and severe (0.53 mL/hr/kg) renal dysfunction (P ≤ 0.001). Treatment-related adverse events showed no association with clearance. Trebananib clearance was proportional to eGFR and unrelated to pretreatment protein excretion. These data confirm a role for renal clearance of a recombinant peptibody with molecular weight < 69 kD and support a longer dosing interval for patients with severe renal dysfunction. This article is protected by copyright. All rights reserved.

  1. An uncommon and insidious presentation of renal cell carcinoma with tumor extending into the inferior vena cava and right atrium: a case report.

    PubMed

    Lu, Hou Tee; Chong, Jen Lim; Othman, Norliza; Vendargon, Simon; Omar, Shamsuddin

    2016-05-03

    Renal cell carcinoma is a potentially lethal cancer with aggressive behavior and it tends to metastasize. Renal cell carcinoma involves the inferior vena cava in approximately 15% of cases and it rarely extends into the right atrium. A majority of renal cell carcinoma are detected as incidental findings on imaging studies obtained for unrelated reasons. At presentation, nearly 25% of patients either have distant metastases or significant local-regional disease with no symptoms that can be attributed to renal cell carcinoma. A 64-year-old Indian male with a past history of coronary artery bypass graft surgery, congestive heart failure, and diabetes mellitus complained of worsening shortness of breath for 2 weeks. Incidentally, a transthoracic echocardiography showed a "thumb-like" mass in his right atrium extending into his right ventricle through the tricuspid valve with each systole. Abdomen magnetic resonance imaging revealed a heterogenous lobulated mass in the upper and mid-pole of his right kidney with a tumor extending into his inferior vena cava and right atrium, consistent with our diagnosis of advanced renal cell carcinoma which was later confirmed by surgical excision and histology. Radical right nephrectomy, lymph nodes clearance, inferior vena cava cavatomy, and complete tumor thrombectomy were performed successfully. Perioperatively, he did not require cardiopulmonary bypass or deep hypothermic circulatory arrest. He had no recurrence during the follow-up period for more than 2 years after surgery. Advanced extension of renal cell carcinoma can occur with no apparent symptoms and be detected incidentally. In rare circumstances, atypical presentation of renal cell carcinoma should be considered in a patient presenting with right atrial mass detected by echocardiography. Renal cell carcinoma with inferior vena cava and right atrium extension is a complex surgical challenge, but excellent results can be obtained with proper patient selection, meticulous

  2. Bone Metastasis in Renal Cell Carcinoma is Preprogrammed in the Primary Tumor and Caused by AKT and Integrin α5 Signaling.

    PubMed

    Haber, Tobias; Jöckel, Elke; Roos, Frederik C; Junker, Kerstin; Prawitt, Dirk; Hampel, Christian; Thüroff, Joachim W; Brenner, Walburgis

    2015-08-01

    Bone metastasis develops in 30% of all patients with renal cell carcinoma. We elucidated the mechanisms that lead to and predict bone metastasis of renal cell carcinoma. Nine renal cell carcinoma primary cell lines and 30 renal cell carcinoma tissue specimens (normal and tumor tissue) were collected from 3 patients with no metastasis and 10 with lung or bone metastasis within 5 years after nephrectomy. Cell migration was analyzed in a Boyden chamber and proliferation was assessed by bromodeoxyuridine incorporation. Adhesion to fibronectin, and collagen I and IV was determined after cell staining. The expression and/or activity of cellular signaling molecules was quantified by Western blot. Compared to renal cell carcinoma cells from patients without metastasis, the migration of cells from patients with bone metastasis was enhanced 13.5-fold (p = 0.034), and adhesion to fibronectin and collagen I was enhanced 5.8-fold and 6.1-fold (p = 0.002 and 0.014, respectively). In general proliferation was decreased in metastasizing cells. In accordance with these results we detected higher activity of AKT (p = 0.011) and FAK (p = 0.054), higher integrin α5 expression (p = 0.052) and lower PTEN expression in primary cells from patients with bone metastasis compared to nonmetastasizing cells. An almost similarly altered expression pattern was also observed in the renal cell carcinoma tissue specimens and the normal renal tissue of patients with bone metastasis. We describe evidence that molecular predispositions determine the potential for bone metastasis to develop in renal cell carcinoma, which may serve as prognostic markers after initial tumor detection. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Experiences in US-Guided Percutaneous Radiofrequency Ablation of 44 Renal Tumors in 31 Patients: Analysis of Predictors for Complications and Technical Success

    SciTech Connect

    Veltri, Andrea Calvo, Amedeo; Tosetti, Irene; Pagano, Eva; Genovesio, Andrea; Virzi, Valentina; Ferrando, Ugo; Fontana, Dario; Gandini, Giovanni

    2006-10-15

    Purpose. Preliminary clinical studies have shown the feasibility, safety, and efficacy of radiofrequency thermal ablation (RFA) of renal tumors, but only a few have analyzed the prognostic factors for technical success and there are no long-term results. Our objective was to statistically evaluate our mid-term results of percutaneous US-guided RFA in order to define predictors for complications and technical success. Methods. We selected for treatment 44 tumors in 31 patients (24 with renal cell carcinoma, 7 with hereditary tumors, 15 with a solitary kidney), up to 5 cm in diameter. Results. Eight adverse events occurred; 3 (6.8%) were major complications, successfully treated with interventional radiology procedures in 2 cases. Exophytic extension of the tumor was protective against complications (p 0.040). Technical success was obtained in 38 lesions after one RFA session and in 39 (89%) after one more session, when possible. At the end of treatment, central extension was the only negative predictor for technical success (p = 0.007), while neither size >3 cm (p = 0.091) nor other prognostic factors were statistically significant. Conclusion. US-guided percutaneous RFA can be proposed for non-central renal tumors up to 5 cm, also in patients without surgical contraindications, thanks to a low incidence of complications and a high success rate. Randomized controlled trials versus surgery are now needed to investigate long-term comparative results.

  4. Nano-encapsulation of plitidepsin: in vivo pharmacokinetics, biodistribution, and efficacy in a renal xenograft tumor model.

    PubMed

    Oliveira, Hugo; Thevenot, Julie; Garanger, Elisabeth; Ibarboure, Emmanuel; Calvo, Pilar; Aviles, Pablo; Guillen, Maria Jose; Lecommandoux, Sébastien

    2014-04-01

    Plitidepsin is an antineoplasic currently in clinical evaluation in a phase III trial in multiple myeloma (ADMYRE). Presently, the hydrophobic drug plitidepsin is formulated using Cremophor®, an adjuvant associated with unwanted hypersensitivity reactions. In search of alternatives, we developed and tested two nanoparticle-based formulations of plitidepsin, aiming to modify/improve drug biodistribution and efficacy. Using nanoprecipitation, plitidepsin was loaded in polymer nanoparticles made of amphiphilic block copolymers (i.e. PEG-b-PBLG or PTMC-b-PGA). The pharmacokinetics, biodistribution and therapeutic efficacy was assessed using a xenograft renal cancer mouse model (MRI-H-121 xenograft) upon administration of the different plitidepsin formulations at maximum tolerated multiple doses (0.20 and 0.25 mg/kg for Cremophor® and copolymer formulations, respectively). High plitidepsin loading efficiencies were obtained for both copolymer formulations. Considering pharmacokinetics, PEG-b-PBLG formulation showed lower plasma clearance, associated with higher AUC and Cmax than Cremophor® or PTMC-b-PGA formulations. Additionally, the PEG-b-PBLG formulation presented lower liver and kidney accumulation compared with the other two formulations, associated with an equivalent tumor distribution. Regarding the anticancer activity, all formulations elicited similar efficacy profiles, as compared to the Cremophor® formulation, successfully reducing tumor growth rate. Although the nanoparticle formulations present equivalent anticancer activity, compared to the Cremophor® formulation, they show improved biodistribution profiles, presenting novel tools for future plitidepsin-based therapies.

  5. Radiofrequency Ablation in Combination with Embolization in Metachronous Recurrent Renal Cancer in Solitary Kidney after Contralateral Tumor Nephrectomy

    SciTech Connect

    Gebauer, Bernhard Werk, Michael; Lopez-Haenninen, Enrique; Felix, Roland; Althaus, Peter

    2007-07-15

    Purpose. To evaluate the feasibility and safety of minimally invasive, percutaneous techniques in metachronous recurrent renal cell cancers (RCCs) in solitary kidneys. Methods. In 4 patients, recurrent RCC was treated by radiofrequency ablation (RFA) (RITA, StarBurst) alone, and in 2 patients by RFA in combination with superselective transarterial particle-lipiodol embolization using 3 Fr microcatheters. RFA was guided by computed tomography in 5 patients, and by magnetic resonance imaging in 1 patient. Mean tumor diameter was 26.7 mm (range 10-45 mm). All interventions were technically successful; during follow-up 1 patient developed recurrent RCC, which was retreated by RFA after embolization. Results. No major peri- or postprocedural complications occurred. Changes in creatinine (pre- vs. post-intervention, 122 vs. 127 {mu}mol/l) and calculated creatinine clearance (pre- vs. post-intervention, 78 vs. 73 ml/min) after ablation were minimal. Conclusion. In single kidneys, percutaneous, minimally invasive techniques are safe and feasible. In large tumors, or where there are adjacent critical structures, we prefer a combination of embolization and thermal ablation (RFA)

  6. Study of Kidney Tumors in Younger Patients

    ClinicalTrials.gov

    2016-11-18

    Clear Cell Sarcoma of the Kidney; Congenital Mesoblastic Nephroma; Diffuse Hyperplastic Perilobar Nephroblastomatosis; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Wilms Tumor; Stage II Renal Cell Cancer; Stage II Wilms Tumor; Stage III Renal Cell Cancer; Stage III Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Wilms Tumor; Stage V Wilms Tumor

  7. Tumor suppressive microRNA-1285 regulates novel molecular targets: Aberrant expression and functional significance in renal cell carcinoma

    PubMed Central

    Yoshino, Hirofumi; Yamasaki, Takeshi; Yamada, Yasutoshi; Nohata, Nijiro; Fuse, Miki; Nakagawa, Masayuki; Enokida, Hideki

    2012-01-01

    MicroRNAs (miRNA) are non-coding RNAs, approximately 22 nucleotides in length, which function as post-transcriptional regulators. A large body of evidence indicates that miRNAs regulate the expression of cancer-related genes involved in proliferation, migration, invasion, and metastasis. The aim of this study was to identify novel cancer networks in renal cell carcinoma (RCC) based on miRNA expression signatures obtained from RCC clinical specimens. Expression signatures revealed that 103 miRNAs were significantly downregulated (< 0.5-fold change) in RCC specimens. Functional screening (cell proliferation assays) was performed to identify tumor suppressive activities of 20 downregulated miRNAs. Restoration of mature miRNAs in cancer cells showed that 14 miRNAs (miR-1285, miR-206, miR-1, miR-135a, miR-429, miR-200c, miR-1291, miR-133b, miR-508-3p, miR-360-3p, miR-509-5p, miR-218, miR-335, miR-1255b and miR-1285) markedly inhibited cancer cell proliferation, suggesting that these miRNAs were candidate tumor suppressive miRNAs in RCC. We focused on miR-1285 because it significantly inhibited cancer cell proliferation, invasion, and migration following its transfection. We addressed miR-1285-regulated cancer networks by using genome-wide gene expression analysis and bioinformatics. The data showed that transglutaminase 2 (TGM2) was directly regulated by miR-1285. Silencing of the target gene demonstrated significant inhibition of cell proliferation and invasion in the RCC cells. Furthermore, immunohistochemistry showed that TGM2 expression levels in RCC specimens were significantly higher than those in normal renal tissues. Downregulation of tumor suppressive miR-1285, which targets oncogenic genes including TGM2, might contribute to RCC development. Thus, miR-1285 modulates a novel molecular target and provides new insights into potential mechanisms of RCC oncogenesis. PMID:22294552

  8. High incidence of loss of heterozygosity in breast tumors from carriers of the BRCA2 999del5 mutation.

    PubMed

    Ingvarsson, S; Geirsdottir, E K; Johannesdottir, G; Sigbjörnsdóttir, B I; Eiriksdottir, G; Ragnarsson, G; Agnarsson, B A; Gudmundsson, J; Jonasson, J G; Sigurdsson, A; Egilsson, V; Barkardottir, R B

    1998-10-01

    Germ-line mutation in the BRCA2 gene confers an increased risk of breast cancer. An elevation of additional genetic defects in tumors of patients with germ-line mutation in the BRCA2 gene compared with sporadic breast tumors has been reported. To evaluate the nature of the difference, we did detailed mapping of chromosomes 1p, 3p, 6q, 11, 13q, 16q, 17, and 20q, using microsatellite markers. We found that the frequency of loss of heterozygosity was similar at some chromosomal regions in the BRCA2 999del5 and sporadic tumors but significantly different at others. These others include chromosomal arms 3p, 6q, 11p, 11q, 13q, and 17p. Loss of heterozygosity mapping suggests that the same chromosome regions are involved in both tumor groups but at elevated frequencies in BRCA2 999del5 tumors. This higher frequency of genetic aberrations could pinpoint genes that selectively promote tumor progression in individuals predisposed to breast cancer due to the BRCA2 999del5 germ-line mutation. Accumulation of somatic genetic changes during tumor progression may follow a specific and more aggressive pathway of chromosome damage in these individuals.

  9. Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model

    PubMed Central

    Borgna, Vincenzo; Villegas, Jaime; Burzio, Verónica A.; Belmar, Sebastián; Araya, Mariela; Jeldes, Emanuel; Lobos-González, Lorena; Silva, Verónica; Villota, Claudio; Oliveira-Cruz, Luciana; Lopez, Constanza; Socias, Teresa; Castillo, Octavio; Burzio, Luis O.

    2017-01-01

    Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma. PMID:28620146

  10. Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model.

    PubMed

    Borgna, Vincenzo; Villegas, Jaime; Burzio, Verónica A; Belmar, Sebastián; Araya, Mariela; Jeldes, Emanuel; Lobos-González, Lorena; Silva, Verónica; Villota, Claudio; Oliveira-Cruz, Luciana; Lopez, Constanza; Socias, Teresa; Castillo, Octavio; Burzio, Luis O

    2017-07-04

    Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.

  11. Renal vein thrombosis

    MedlinePlus

    ... the kidneys. Possible Complications Complications may include: Acute renal failure (especially if thrombosis occurs in a dehydrated child) ... Saunders; 2012:chap 34. Read More Acute kidney failure Arteriogram Blood ... embolus Renal Tumor Review Date 5/19/2015 Updated by: ...

  12. Tumor-associated macrophages subvert T-cell function and correlate with reduced survival in clear cell renal cell carcinoma

    PubMed Central

    Dannenmann, Stefanie Regine; Thielicke, Julia; Stöckli, Martina; Matter, Claudia; von Boehmer, Lotta; Cecconi, Virginia; Hermanns, Thomas; Hefermehl, Lukas; Schraml, Peter; Moch, Holger; Knuth, Alexander; van den Broek, Maries

    2013-01-01

    Although malignant cells can be recognized and controlled by the immune system, in patients with clinically apparent cancer immunosurveillance has failed. To better understand local immunoregulatory processes that impact on cancer progression, we correlated intratumoral immunological profiles with the survival of patients affected by primary clear cell renal cell carcinoma (ccRCC). A retrospective analysis of 54 primary ccRCC samples for 31 different immune response-related transcripts, revealed a negative correlation of CD68 (a marker of tumor-associated macrophages, TAMs) and FOXP3 (a marker of regulatory T cells, Tregs) with survival. The subsequent analysis of 12 TAM-related transcripts revealed an association between the genes coding for CD163, interferon regulatory factor 4 (IRF4) and fibronectin 1 (FN1), all of which have been linked to the M2 TAM phenotype, with reduced survival and increased tumor stage, whereas the opposite was the case for the M1-associated gene coding for inducible nitric oxide synthetase (iNOS). The M2 signature of (CD68+) TAMs was found to correlate with CD163 expression, as determined in prospectively collected fresh ccRCC tissue samples. Upon co-culture with autologous tumor cells, CD11b+ cells isolated from paired blood samples expressed CD163 and other M2-associated proteins, suggesting that the malignant cells promote the accumulation of M2 TAMs. Furthermore, the tumor-associated milieu as well as isolated TAMs induced the skewing of autologous, blood-derived CD4+ T cells toward a more immunosuppressive phenotype, as shown by decreased production of effector cytokines, increased production of interleukin-10 (IL-10) and enhanced expression of the co-inhibitory molecules programmed death 1 (PD-1) and T-cell immunoglobulin mucin 3 (TIM-3). Taken together, our data suggest that ccRCC progressively attracts macrophages and induces their skewing into M2 TAMs, in turn subverting tumor-infiltrating T cells such that immunoregulatory

  13. Tumor-associated macrophages subvert T-cell function and correlate with reduced survival in clear cell renal cell carcinoma.

    PubMed

    Dannenmann, Stefanie Regine; Thielicke, Julia; Stöckli, Martina; Matter, Claudia; von Boehmer, Lotta; Cecconi, Virginia; Hermanns, Thomas; Hefermehl, Lukas; Schraml, Peter; Moch, Holger; Knuth, Alexander; van den Broek, Maries

    2013-03-01

    Although malignant cells can be recognized and controlled by the immune system, in patients with clinically apparent cancer immunosurveillance has failed. To better understand local immunoregulatory processes that impact on cancer progression, we correlated intratumoral immunological profiles with the survival of patients affected by primary clear cell renal cell carcinoma (ccRCC). A retrospective analysis of 54 primary ccRCC samples for 31 different immune response-related transcripts, revealed a negative correlation of CD68 (a marker of tumor-associated macrophages, TAMs) and FOXP3 (a marker of regulatory T cells, Tregs) with survival. The subsequent analysis of 12 TAM-related transcripts revealed an association between the genes coding for CD163, interferon regulatory factor 4 (IRF4) and fibronectin 1 (FN1), all of which have been linked to the M2 TAM phenotype, with reduced survival and increased tumor stage, whereas the opposite was the case for the M1-associated gene coding for inducible nitric oxide synthetase (iNOS). The M2 signature of (CD68(+)) TAMs was found to correlate with CD163 expression, as determined in prospectively collected fresh ccRCC tissue samples. Upon co-culture with autologous tumor cells, CD11b(+) cells isolated from paired blood samples expressed CD163 and other M2-associated proteins, suggesting that the malignant cells promote the accumulation of M2 TAMs. Furthermore, the tumor-associated milieu as well as isolated TAMs induced the skewing of autologous, blood-derived CD4(+) T cells toward a more immunosuppressive phenotype, as shown by decreased production of effector cytokines, increased production of interleukin-10 (IL-10) and enhanced expression of the co-inhibitory molecules programmed death 1 (PD-1) and T-cell immunoglobulin mucin 3 (TIM-3). Taken together, our data suggest that ccRCC progressively attracts macrophages and induces their skewing into M2 TAMs, in turn subverting tumor-infiltrating T cells such that

  14. Tumor Necrosis Adds Prognostically Significant Information to Grade in Clear Cell Renal Cell Carcinoma: A Study of 842 Consecutive Cases From a Single Institution.

    PubMed

    Khor, Li-Yan; Dhakal, Hari P; Jia, Xuefei; Reynolds, Jordan P; McKenney, Jesse K; Rini, Brian I; Magi-Galluzzi, Cristina; Przybycin, Christopher G

    2016-09-01

    Tumor necrosis has been shown to be an independent predictor of adverse outcome in renal cell carcinoma. A modification of the International Society of Urological Pathology (ISUP) grading system for renal cell carcinomas has recently been proposed, which incorporates the presence of tumor necrosis into grade. The investigators proposing this system found that necrosis added significant prognostic information to ISUP grade. We attempted to describe our experience with the effect of tumor necrosis in relationship to nuclear grade by reviewing the slides from a large consecutive series of localized clear cell renal cell carcinomas from our institution and obtaining long-term clinical follow-up information (overall survival). Of the 842 clear cell renal cell carcinomas reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and 140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. Five hundred and forty-seven (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%) were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2 months (range 0.12 to 273.6), and 310 (36.8%) patients died. On univariable analysis, there was no significant difference in outcome for tumors of ISUP grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade 4 and necrosis were significant predictors of overall survival on multivariable analysis. When the recently proposed modified grading system incorporating tumor necrosis was applied to our data, there was no significant difference in overall survival between patients with modified grade 1 tumors and those with modified grade 2 tumors (P=0.31); however, there was a statistically significant difference between patients with modified grade 1 or 2 tumors and those with modified grade 3 tumors (P=0.04),and a substantial difference in outcome between those with modified grade 3 and modified grade 4 tumors (P<0.001). When a recursive partitioning approach

  15. Expression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependent

    PubMed Central

    2010-01-01

    Background Cell-surface glycoproteins play critical roles in cell-to-cell recognition, signal transduction and regulation, thus being crucial in cell proliferation and cancer etiogenesis and development. DPP IV and NEP are ubiquitous glycopeptidases closely linked to tumor pathogenesis and development, and they are used as markers in some cancers. In the present study, the activity and protein and mRNA expression of these glycoproteins were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytomas (RO). Methods Peptidase activities were measured by conventional enzymatic assays with fluorogen-derived substrates. Gene expression was quantitatively determined by qRT-PCR and membrane-bound protein expression and distribution analysis was performed by specific immunostaining. Results The activity of both glycoproteins was sharply decreased in the three histological types of renal tumors. Protein and mRNA expression was strongly downregulated in tumors from distal nephron (ChRCC and RO). Moreover, soluble DPP IV activity positively correlated with the aggressiveness of CCRCCs (higher activities in high grade tumors). Conclusions These results support the pivotal role for DPP IV and NEP in the malignant transformation pathways and point to these peptidases as potential diagnostic markers. PMID:20459800

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

    PubMed

    Tornberg, S V; Kilpeläinen, T P; Järvinen, P; Visapää, H; Järvinen, R; Taari, K; Nisén, H

    2017-09-01

    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. 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. 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

  17. Other paradigms: growth rate constants and tumor burden determined using computed tomography data correlate strongly with the overall survival of patients with renal cell carcinoma.

    PubMed

    Stein, Wilfred D; Huang, Hui; Menefee, Michael; Edgerly, Maureen; Kotz, Herb; Dwyer, Andrew; Yang, James; Bates, Susan E

    2009-01-01

    In solid tumors, where curative therapies still elude oncologists, novel paradigms are needed to assess the efficacy of new therapies and those already approved. We used radiologic measurements obtained in patients with metastatic renal cell carcinoma enrolled in a phase II study of the epothilone B analog, ixabepilone (Ixempra), to address this issue. Using a novel 2-phase mathematical equation, we used the radiologic measurements to estimate the concomitant rates of tumor regression and growth (regression and growth rate constants). Eighty-one patients were enrolled on the ixabepilone trial at the time of this analysis. Growth rate constants were determined using computed tomography measurements obtained exclusively while a patient was enrolled on study. The growth rate constants of renal cell carcinomas treated with ixabepilone were significantly reduced compared with those of tumors in patients who received placebo in a previous trial. Furthermore, a correlation with overall survival was found for both the growth rate constant and the initial tumor burden; and this correlation was even stronger when both the growth rate constant and the initial tumor burden were combined. The readily amenable mathematical model described herein has potential applications to many tumor types that can be assessed with imaging modalities. Because the growth rate constant seems to be a surrogate for survival, assessment could aid in the evaluation of relative efficacies of different therapies and perhaps in assessing the potential individual benefit of an experimental therapy.

  18. The Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor Cediranib (Recentin; AZD2171) Inhibits Endothelial Cell Function and Growth of Human Renal Tumor Xenografts

    SciTech Connect

    Siemann, Dietmar W. Brazelle, W.D.; Juergensmeier, Juliane M.

    2009-03-01

    Purpose: The goal of this study was to examine the therapeutic potential of the vascular endothelial growth factor (VEGF) signaling inhibitor cediranib in a human model of renal cell carcinoma (Caki-1). Methods and Materials: The effects of cediranib treatment on in vitro endothelial cell function (proliferation, migration, and tube formation), as well as in vivo angiogenesis and tumor growth, were determined. Results: In vitro, cediranib significantly impaired the proliferation and migration of endothelial cells and their ability to form tubes, but had no effect on the proliferation of Caki-1 tumor cells. In vivo, cediranib significantly reduced Caki-1 tumor cell-induced angiogenesis, reduced tumor perfusion, and inhibited the growth of Caki-1 tumor xenografts. Conclusions: The present results are consistent with the notion that inhibition of VEGF signaling leads to an indirect (i.e., antiangiogenic) antitumor effect, rather than a direct effect on tumor cells. These results further suggest that inhibition of VEGF signaling with cediranib may impair the growth of renal cell carcinoma.

  19. The expression of FOXL2 in pancreatic, hepatobiliary, and renal tumors with ovarian-type stroma.

    PubMed

    Westerhoff, Maria; Tretiakova, Maria; Hart, John; Gwin, Katja; Liu, Xiuli; Zhou, Ming; Yeh, Matthew M; Antic, Tatjana

    2014-05-01

    FOXL2, a gene encoding a member of the fork-head-winged-helix family of transcription factors, is one of the earliest expressed genes during female gonadal development. It is expressed in normal ovarian stroma and ovarian neoplasms with granulosa cell lineage. Nonovarian tumors such as pancreatic mucinous cystic neoplasms (PMCs), hepatobiliary cystadenomas (HBCs), and mixed epithelial and stromal tumor of the kidney (MEST) have ovarian-type stroma. Immunohistochemical staining with FOXL2, estrogen receptor, and progesterone receptor was performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear immunohistochemical positivity in the tumor stroma. All cases of PMC and HBC demonstrated nuclear reactivity for FOXL2 in the subepithelial stromal cells. Ninety percent of MEST demonstrated nuclear FOXL2 positivity. Estrogen receptor nuclear positivity was demonstrated in 57% of PMC, 77% of HBC, and 80% of MEST. Progesterone receptor nuclear positivity was present in 67% of PMC, 100% of HBC, and 90% of MEST. Clinical information was available for 37 patients. Seventy-eight percent of the patients had a history of obesity, heavy alcohol use, or hormone-related therapy. The 2 male patients had histories significant for morbid obesity and chronic alcoholism. FOXL2 is expressed from the early stages of ovarian development and has been shown to be mandatory for normal ovarian function. We have shown that it is also expressed in the aberrant ovarian-type stroma characteristic of PMC, HBC, and MEST. Most of such patients, including the rare male patients, have risk factors for hormonal abnormalities such as obesity and hormonal replacement therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Interleukin 10-expressing B cells inhibit tumor-infiltrating T cell function and correlate with T cell Tim-3 expression in renal cell carcinoma.

    PubMed

    Cai, Chen; Zhang, Jin; Li, Minyu; Wu, Zhen-Jie; Song, Ken H; Zhan, Tina W; Wang, Lin-Hui; Sun, Ying-Hao

    2016-06-01

    Renal cell carcinoma is among the leading causes of cancer-related death and was found to induce IL-10. We started by focusing on IL-10-secreting cells in tumor-infiltrating lymphocytes in renal cell carcinoma patients and observed that both CD3(+) T cells and CD19(+) B cells contributed to an elevated IL-10 expression. We then focused on IL-10-expressing B cells, and found that compared to non-IL-10-producing B cells, the IL-10-expressing B cells had significantly lower levels of CD19 and CD20 expression, a lack of IgM and IgD expression, while the level of CD27 was elevated. Moreover, culturing under unstimulated conditions resulted in higher antibody production by these IL-10-producing B cells than their peripheral blood counterparts, which strongly suggested that they are plasmablast-differentiating cells. Both IgA and IgG subtypes were found but IgA had a higher relative abundance in the tumor-infiltrating fraction. We then observed inverse correlations between the frequency of IL-10-producing B cells and pro-inflammatory cytokine-producing T cells and T cell proliferation. The expression of T cell exhaustion marker Tim-3, however, was upregulated in patients with high frequencies of IL-10-producing B cells. Moreover, supernatant from tumor B cells suppressed T cell inflammation. In addition, frequencies of IL-10-producing tumor-infiltrating B cells were inversely correlated with resected tumor size, and were higher in later stage tumors. Together, our data demonstrated that IL-10-producing B cells had plasmablast-differentiating phenotype, and could contribute to T cell immunosuppression in renal cell carcinoma.

  1. A rare case of regression of brown tumors of tertiary hyperparathyroidism after parathyroidectomy and renal transplant: A 5-year follow-up

    PubMed Central

    Noleto, José Wilson; Ramos, Ivana Alencar Svenson; Rocha, Julierme Ferreira; Garcia, Idelmo Rangel; Salvador Roberto, Berthiene M.

    2016-01-01

    Tertiary hyperparathyroidism (HPT) is a rare condition that affects patients with secondary HPT, which develop hyperplasia of the parathyroid glands, thus causing an increase in parathyroid hormone levels. Bone alterations are the main consequences of this condition including the development of osteolytic lesions called brown tumor. This article reports an unusual case of brown tumors located in the maxilla and mandible in a 19-year-old man with chronic renal failure with hyperplasia of the parathyroid glands. The lesions regressed approximately 5 months after the parathyroidectomy. At this same time, the patient underwent renal transplant. The patient was followed for 5 years, showing improvement in overall clinical status. There was also improvement of the results of laboratory tests and the pattern of trabecular bone. The correct diagnosis of oral lesions was of great relevance for the conservative treatment could have been chosen. PMID:27563621

  2. [Cost comparison of open and robot-assisted partial nephrectomy in treatment of renal tumor].

    PubMed

    Abd El Fattah, V; Chevrot, A; Meusy, A; Mercier, G; Wagner, L; Soustelle, L; Boukaram, M; Thuret, R; Costa, P; Droupy, S

    2016-04-01

    Robot-assisted partial nephrectomy rapidly took on among urologists, even though studies showing its superiority over other techniques are still scarce and its costs hard to evaluate, especially in the French medical system. To evaluate the cost overrun of robot-assisted partial nephrectomy compared to that of open partial nephrectomy. From January 2010 to December 2013, 77 patients underwent a partial nephrectomy, 46 of which by robot-assisted laparoscopy and the remaining 31 by lombotomy. The two groups were similar in composition. Economic data regarding the staff, the consumables and the premises involved have been analyzed. Costs are significantly higher in the NPR group (9253.21 euros vs. 7448.42 euros) due to higher consumable expenses as well as the costs pertaining to the amortization and maintenance of the robot. Yet, that difference tends to diminish as the duration of the experiment increases. No significant difference was found in warm ischemia times, operation duration and renal function a month after the operation. On the other hand, patients from the NPR group spent a significantly smaller amount of time in recovery room (159 minutes vs. 205 minutes, P=0.004), presented fewer complications and were discharged faster (6.1 days vs. 8.1 days, P=0.04). To be profitable for the hospital in the French GHS system, robot-assisted partial nephrectomy must take place in a complex where at least 300 robot-assisted interventions are performed annually, in the framework of a hospitalization lasting four days or less, the use of a single needle holder and no systematic use of a haemostatic agent. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Classification models for clear cell renal carcinoma stage progression, based on tumor RNAseq expression trained supervised machine learning algorithms

    PubMed Central

    2014-01-01

    Background Clear-cell Renal Cell Carcinoma (ccRCC) is the most- prevalent, chemotherapy resistant and lethal adult kidney cancer. There is a need for novel diagnostic and prognostic biomarkers for ccRCC, due to its heterogeneous molecular profiles and asymptomatic early stage. This study aims to develop classification models to distinguish early stage and late stage of ccRCC based on gene expression profiles. We employed supervised learning algorithms- J48, Random Forest, SMO and Naïve Bayes; with enriched model learning by fast correlation based feature selection to develop classification models trained on sequencing based gene expression data of RNAseq experiments, obtained from The Cancer Genome Atlas. Results Different models developed in the study were evaluated on the basis of 10 fold cross validations and independent dataset testing. Random Forest based prediction model performed best amongst the models developed in the study, with a sensitivity of 89%, accuracy of 77% and area under Receivers Operating Curve of 0.8. Conclusions We anticipate that the prioritized subset of 62 genes and prediction models developed in this study will aid experimental oncologists to expedite understanding of the molecular mechanisms of stage progression and discovery of prognostic factors for ccRCC tumors. PMID:25374611

  4. Classification models for clear cell renal carcinoma stage progression, based on tumor RNAseq expression trained supervised machine learning algorithms.

    PubMed

    Jagga, Zeenia; Gupta, Dinesh

    2014-01-01

    Clear-cell Renal Cell Carcinoma (ccRCC) is the most- prevalent, chemotherapy resistant and lethal adult kidney cancer. There is a need for novel diagnostic and prognostic biomarkers for ccRCC, due to its heterogeneous molecular profiles and asymptomatic early stage. This study aims to develop classification models to distinguish early stage and late stage of ccRCC based on gene expression profiles. We employed supervised learning algorithms- J48, Random Forest, SMO and Naïve Bayes; with enriched model learning by fast correlation based feature selection to develop classification models trained on sequencing based gene expression data of RNAseq experiments, obtained from The Cancer Genome Atlas. Different models developed in the study were evaluated on the basis of 10 fold cross validations and independent dataset testing. Random Forest based prediction model performed best amongst the models developed in the study, with a sensitivity of 89%, accuracy of 77% and area under Receivers Operating Curve of 0.8. We anticipate that the prioritized subset of 62 genes and prediction models developed in this study will aid experimental oncologists to expedite understanding of the molecular mechanisms of stage progression and discovery of prognostic factors for ccRCC tumors.

  5. Tumor Control Outcomes Following Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases from Renal Cell Carcinoma

    PubMed Central

    Zelefsky, Michael J; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei, Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

    2014-01-01

    Purpose To report tumor local progression-free outcomes following treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Methods and Materials Between 2004 and 2010, a total of 105 lesions from renal cell carcinomas were treated with either SD-IGRT to prescription doses of 18–24 Gy (median, 24 Gy) or hypofractionation (3 or 5 fractions) with prescription doses ranging between 20 and 30 Gy. The median follow-up was 12 months (range, 1–48 months). Results The overall 3-year actuarial local progression-free survival (LPFS) for all lesions was 44%. The 3-year LPFS for those who received high single-dose (24 Gy; n = 45), low single-dose (< 24 Gy; n = 14), and hypofractionation regimens (n = 46) were 88%, 21%, and 17%, respectively (high single dose versus low single dose, p = 0.001; high single dose versus hypofractionation, p < 0.001). Multivariate analysis revealed the following variables as significant predictors of improved LPFS: dose of 24 Gy compared with lower dose (p = 0.009), and single dose versus hypofractionation (p = 0.008). Conclusion High-dose SD-IGRT is a non-invasive procedure resulting in high probability of local tumor control for metastatic renal cell cancers, generally considered radioresistant according to classical radiobiological ranking. PMID:21596489

  6. Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

    SciTech Connect

    Zelefsky, Michael J.; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

    2012-04-01

    Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

  7. Influence of tumor size on oncological outcomes of pathological T3aN0M0 renal cell carcinoma treated by radical nephrectomy

    PubMed Central

    Li, Hongzhao; Gu, Liangyou; Li, Xintao; Gao, Yu; Xie, Yongpeng

    2017-01-01

    Objective To evaluate the prognostic significance of tumor size in pathological T3aN0M0 renal cell carcinoma (RCC) treated by radical nephrectomy. Materials and methods Patients who underwent radical nephrectomy for sporadic RCC with pathological T3aN0M0 RCC at our institution between January 2006 and June 2015 were identified. The entire cohort was divided into two groups according to the cutoff of tumor size obtained from receiver operating characteristic (ROC) curve. Clinicopathological variables were retrospectively collected and compared. Kaplan-Meier analysis and multivariate Cox regression were conducted to evaluate the effect of tumor size on survival outcomes. Results 163 pT3aN0M0 RCC patients were included with a median follow-up period of 31 months. The optimal cutoff for tumor size was 7 cm according to the ROC curve. 90 cases (55.2%) presented tumors which measured 7 cm or less, and 73 cases (44.8%) showed tumor size greater than 7 cm. Patients with larger tumors tended to exhibit higher rates of symptoms and higher Fuhrman grades; they also indicated more necrosis features, and were more likely to invade the collecting system and renal vein. Compared with patients who exhibited tumor size of≤7 cm, those with tumor size>7 cm were associated with shorter estimated five-year cancer-specific survival (CSS, 46.6% versus 75.0%, P = 0.003) and five-year recurrence-free survival (RFS, 35.6% versus 62.7%, P = 0.011). Multivariate Cox analysis revealed that tumor size was retained as an independent factor for CSS (HR = 2.506, 95% CI 1.169–5.373, P = 0.018). Conclusions The tumor size significantly affected the survival outcomes of pT3aN0M0 RCC treated by radical nephrectomy, and a cutoff size of 7 cm can help enhance the prognostic discrimination. Thus, the tumor size may be considered in the future TNM classification of stage pT3a. PMID:28288191

  8. Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.

    PubMed

    Furuya, Mitsuko; Hong, Seung-Beom; Tanaka, Reiko; Kuroda, Naoto; Nagashima, Yoji; Nagahama, Kiyotaka; Suyama, Takahito; Yao, Masahiro; Nakatani, Yukio

    2015-03-01

    Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN). The affected families have a high risk for developing multiple renal cell carcinomas (RCC). Diagnostic markers that distinguish between FLCN-related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non-metastatic B (GPNMB) between FLCN-related RCCs and sporadic renal tumors (n = 62). The expression of GPNMB was also evaluated by quantitative RT-PCR. Histopathological analysis revealed that the most frequent histological type was chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.

  9. Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt–Hogg–Dubé syndrome

    PubMed Central

    Furuya, Mitsuko; Hong, Seung-Beom; Tanaka, Reiko; Kuroda, Naoto; Nagashima, Yoji; Nagahama, Kiyotaka; Suyama, Takahito; Yao, Masahiro; Nakatani, Yukio

    2015-01-01

    Birt–Hogg–Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN). The affected families have a high risk for developing multiple renal cell carcinomas (RCC). Diagnostic markers that distinguish between FLCN-related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non-metastatic B (GPNMB) between FLCN-related RCCs and sporadic renal tumors (n = 62). The expression of GPNMB was also evaluated by quantitative RT-PCR. Histopathological analysis revealed that the most frequent histological type was chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD. PMID:25594584

  10. Pediatric Renal Neoplasms.

    PubMed

    Ranganathan, Sarangarajan

    2009-03-01

    Renal tumors in childhood consist of a diverse group of tumors ranging from the most common Wilms' tumor, to the uncommon and often fatal rhabdoid tumor. Diagnosis is based on morphologic features and aided by ancillary techniques such as immunohistochemistry and cytogenetics. Molecular techniques have helped identify a group of pediatric renal cell carcinomas that have specific translocations, called translocation-associated carcinomas. Differential diagnosis of the various tumors is discussed. Pathogenesis and nephroblastomatosis, the precursor lesions of Wilms tumor, also are discussed briefly, as are the handling of these tumor specimens and prognostic factors. Copyright © 2009 Elsevier Inc. All rights reserved.

  11. [Renal leiomyoma. Case report].

    PubMed

    Joual, A; Guessous, H; Rabii, R; Benjelloun, M; Benlemlih, A; Skali, K; el Mrini, M; Benjelloun, S

    1999-01-01

    The authors report a case of renal leiomyoma observed in a 56-year-old man. This cyst presented in the from of loin pain. Computed tomography revealed a homogeneous renal tumor. Treatment consisted of radical nephrectomy. Histological examination of the specimen showed benign renal leiomyoma.

  12. Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins.

    PubMed

    Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Espada, Joaquín Diego; Colavita, Juan Pablo Melana; Brandan, Nora Cristina; Torres, Adriana Mónica; Aguirre, María Victoria

    2016-10-01

    Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-xL, and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-xL overexpression was concomitant with the enhancement of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their

  13. Pío del Río-Hortega: A Visionary in the Pathology of Central Nervous System Tumors

    PubMed Central

    Ramon y Cajal Agüeras, Santiago

    2016-01-01

    The last 140 years have seen considerable advances in knowledge of central nervous system tumors. However, the main tumor types had already been described during the early years of the twentieth century. The studies of Dr. Pío del Río Hortega have been ones of the most exhaustive histology and cytology-based studies of nervous system tumors. Río Hortega's work was performed using silver staining methods, which require a high level of practical skill and were therefore difficult to standardize. His technical aptitude and interest in nervous system tumors played a key role in the establishment of his classification, which was based on cell lineage and embryonic development. Río Hortega's approach was controversial when he proposed it. Current classifications are not only based on cell type and embryonic lineage, as well as on clinical characteristics, anatomical site, and age. PMID:26973470

  14. Pío del Río-Hortega: A Pioneer in the Pathology of Central Nervous System Tumors.

    PubMed

    Ramon Y Cajal Agüeras, Santiago

    2016-01-01

    The last 140 years have seen considerable advances in knowledge of central nervous system tumors. However, the main tumor types had already been described during the early years of the twentieth century. The studies of Dr. Pío del Río Hortega have been ones of the most exhaustive histology and cytology-based studies of nervous system tumors. Río Hortega's work was performed using silver staining methods, which require a high level of practical skill and were therefore difficult to standardize. His technical aptitude and interest in nervous system tumors played a key role in the establishment of his classification, which was based on cell lineage and embryonic development. Río Hortega's approach was controversial when he proposed it. Current classifications are not only based on cell type and embryonic lineage, as well as on clinical characteristics, anatomical site, and age.

  15. A new method using multiphoton imaging and morphometric analysis for differentiating chromophobe renal cell carcinoma and oncocytoma kidney tumors

    NASA Astrophysics Data System (ADS)

    Wu, Binlin; Mukherjee, Sushmita; Jain, Manu

    2016-03-01

    Distinguishing chromophobe renal cell carcinoma (chRCC) from oncocytoma on hematoxylin and eosin images may be difficult and require time-consuming ancillary procedures. Multiphoton microscopy (MPM), an optical imaging modality, was used to rapidly generate sub-cellular histological resolution images from formalin-fixed unstained tissue sections from chRCC and oncocytoma.Tissues were excited using 780nm wavelength and emission signals (including second harmonic generation and autofluorescence) were collected in different channels between 390 nm and 650 nm. Granular structure in the cell cytoplasm was observed in both chRCC and oncocytoma. Quantitative morphometric analysis was conducted to distinguish chRCC and oncocytoma. To perform the analysis, cytoplasm and granules in tumor cells were segmented from the images. Their area and fluorescence intensity were found in different channels. Multiple features were measured to quantify the morphological and fluorescence properties. Linear support vector machine (SVM) was used for classification. Re-substitution validation, cross validation and receiver operating characteristic (ROC) curve were implemented to evaluate the efficacy of the SVM classifier. A wrapper feature algorithm was used to select the optimal features which provided the best predictive performance in separating the two tissue types (classes). Statistical measures such as sensitivity, specificity, accuracy and area under curve (AUC) of ROC were calculated to evaluate the efficacy of the classification. Over 80% accuracy was achieved as the predictive performance. This method, if validated on a larger and more diverse sample set, may serve as an automated rapid diagnostic tool to differentiate between chRCC and oncocytoma. An advantage of such automated methods are that they are free from investigator bias and variability.

  16. Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

    PubMed Central

    Mitsunari, Kensuke; Miyata, Yasuyoshi; Watanabe, Shin-Ichi; Asai, Akihiro; Yasuda, Takuji; Kanda, Shigeru; Sakai, Hideki

    2017-01-01

    Fps/Fes related (Fer) is a non-receptor tyrosine kinase that is expressed in fibroblasts, immune cells and endothelial cells. Fer serves an important pathological role in cell survival, angiogenesis and the immune system. However, the pathological role of Fer expression in the stromal cells surrounding renal cell carcinoma (RCC) has not been previously investigated. In the present study, immunohistochemical analysis of Fer was performed using the formalin-fixed tissue samples of 152 patients with RCC. The proliferative and apoptotic indices were used to represent the percentage of proliferation marker protein Ki-67- and cleaved caspase-3-positive cells, respectively. The microvessel density was defined as the number of cluster of differentiation (CD) 31-positively stained vessels/mm2. In addition, CD57+ and CD68+ cells were counted using semi-quantification of natural killer (NK) cells and macrophages. Fer expression in stromal cells was negatively associated with Fuhrman grade, pathological tumor stage and metastasis (P<0.001). Fer expression in stromal cells was negatively associated with CD68+ macrophage density, whereas it was positively associated with CD57+ NK cell density. Kaplan-Meier estimators indicated that decreased stromal Fer expression was a predictive marker of decreased cause-specific survival rate (P<0.001). Furthermore, low expression of Fer was identified as being an independent marker of decreased cause-specific survival using multivariate analysis (hazard ratio, 7.4; 95% confidence interval, 1.7–33.0; P<0.001). The results of the present study suggested that low Fer expression in stromal cells is associated with increased malignant aggressiveness and decreased survival in patients with RCC. CD57+ NK cell and CD68+ macrophage regulation in cancer-stromal tissue is considered to affect RCC pathology. PMID:28356966

  17. Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma

    PubMed Central

    He, Hai-Tao; Xu, Mu; Kuang, Ye; Han, Xiao-Yun; Wang, Ming-Qi; Yang, Qing

    2016-01-01

    Background Accumulating evidence suggests long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of cancers. However, their functions in chromophobe renal cell carcinoma (chRCC) are not fully understood. Methods We analyzed the expression profiles of lncRNA, microRNA, and protein-coding RNA, along with the clinical information of 59 primary chRCC patients collected from The Cancer Genome Atlas database to identify lncRNA biomarkers for prognosis. We also constructed an lncRNA–microRNA–mRNA coexpression network (competitive endogenous RNAs network) by bioinformational approach. Results One hundred and forty-two lncRNAs were found to be differentially expressed between the cancer and normal tissues (fold change ≥1.5, P<0.001). Among them, 12 lncRNAs were also differentially expressed with the corresponding clinical characteristics (fold change ≥1.5, P<0.01). Besides, 7 lncRNAs (COL18A1-AS, BRE-AS1, SNHG7, TMEM51-AS1, C21orf62-AS1, LINC00336, and LINC00882) were identified to be significantly correlated with overall survival (log-rank P<0.05). A competitive endogenous RNA network in chRCC containing 16 lncRNAs, 18 miRNAs, and 168 protein-coding RNAs was constructed. Conclusion Our results identified specific lncRNAs associated with chRCC progression and prognosis, and presented competing endogenous RNA potential of lncRNAs in the tumor. PMID:27799788

  18. Individual Bromodomains of Polybromo-1 Contribute to Chromatin Association and Tumor Suppression in Clear Cell Renal Carcinoma.

    PubMed

    Porter, Elizabeth G; Dykhuizen, Emily C

    2017-02-17

    The architecture of chromatin is governed, in part, by ATP-dependent chromatin remodelers. These multiprotein complexes contain targeting domains that recognize post-translational marks on histones. One such targeting domain is the bromodomain (BD), which recognizes acetyl-lysines and recruits proteins to sites of acetylation across the genome. Polybromo1 (PBRM1), a subunit of the Polybromo-associated BRG1- or hBRM-associated factors (PBAF) chromatin remodeler, contains six tandem BDs and is frequently mutated in clear cell renal cell carcinoma (ccRCC). Mutations in the PBRM1 gene often lead to the loss of protein expression; however, missense mutations in PBRM1 have been identified and tend to cluster in the BDs, particularly BD2 and BD4, suggesting that individual BDs are critical for PBRM1 function. To study the role of these six BDs, we inactivated each of the six BDs of PBRM1 and re-expressed these mutants in Caki2 cells (ccRCC cells with the loss of function mutation in PBRM1). Four of the six BDs abrogated PBRM1 tumor suppressor function, gene regulation, and chromatin affinity with the degree of importance correlating strongly to the rate of missense mutations in patients. Furthermore, we identified BD2 as the most critical for PBRM1 and confirmed BD2-mediated association to histone H3 peptides acetylated at lysine 14 (H3K14Ac), validating the importance of this specific acetylation mark for PBRM1 binding. From these data, we conclude that four of the BDs act together to target PBRM1 to sites on chromatin; when a single BD is mutated, PBRM1 no longer controls gene expression properly, leading to increased cell proliferation.

  19. Ossifying renal tumor of infancy: report of a case with positive WT-1 immunohistochemistry and high mitotic index and review of the literature.

    PubMed

    Vaillancourt, Benoit; Oligny, Luc Laurier; Déry, Julie; Franc-Guimond, Julie; Bouron-Dal Soglio, Dorothee

    2016-08-30

    Ossifying renal tumor of infancy (ORTI) is a rare, benign pediatric tumor of the kidney. Since first reported by Chatten in 1980, 23 cases have been published. Previous authors have argued that ORTI might originate from nephrogenic rests, thereby sharing a pathogenic relationship with Wilms' tumor (WT). ORTI is characterized histologically by a population of polygonal osteoblast-like cells around an osteoid core and densely cellular component of blastemal-like or spindle cells. While the immunohistochemical profile of the cellular components has been reported, to the best of our knowledge the status of WT1 expression has only been reported once, where it showed negative marking. Mitoses have been described only sporadically in this neoplasm. We report on a case of ORTI with positive WT1 immunohistochemical marking and numerous mitoses. This case highlights a possible pitfall for misdiagnosing ORTI as a WT and provides additional insight into its pathogenesis.

  20. Age- and Tumor Subtype–Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

    PubMed Central

    Hogervorst, Frans; van Hien, Richard; Cornelissen, Sten; Broeks, Annegien; Adank, Muriel A.; Meijers, Hanne; Waisfisz, Quinten; Hollestelle, Antoinette; Schutte, Mieke; van den Ouweland, Ans; Hooning, Maartje; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; Arndt, Volker; Bermisheva, Marina; Bogdanova, Natalia V.; Bolla, Manjeet K.; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Dunning, Alison M.; Fasching, Peter A.; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G.; Haeberle, Lothar; Hall, Per; Hillemanns, Peter; Hopper, John L.; Jakubowska, Anna; John, Esther M.; Jones, Michael; Khusnutdinova, Elza; Knight, Julia A.; Kosma, Veli-Matti; Kristensen, Vessela; Lee, Andrew; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Margolin, Sara; Meindl, Alfons; Milne, Roger L.; Muranen, Taru A.; Newcomb, Polly A.; Offit, Kenneth; Park-Simon, Tjoung-Won; Peto, Julian; Pharoah, Paul D.P.; Robson, Mark; Rudolph, Anja; Sawyer, Elinor J.; Schmutzler, Rita K.; Seynaeve, Caroline; Soens, Julie; Southey, Melissa C.; Spurdle, Amanda B.; Surowy, Harald; Swerdlow, Anthony; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Trentham-Dietz, Amy; Vachon, Celine; Wang, Qin; Whittemore, Alice S.; Ziogas, Argyrios; van der Kolk, Lizet; Nevanlinna, Heli; Dörk, Thilo; Bojesen, Stig; Easton, Douglas F.

    2016-01-01

    Purpose CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. Patients and Methods CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. Results Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center–based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10−20). The OR was higher for estrogen receptor (ER)–positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10−21]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10−4). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. Conclusion These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into

  1. ZBRK1, a novel tumor suppressor, activates VHL gene transcription through formation of a complex with VHL and p300 in renal cancer.

    PubMed

    Chen, Ke; Yu, Gan; Gumireddy, Kiranmai; Li, Anping; Yao, Weimin; Gao, Lu; Chen, Shuliang; Hao, Jun; Wang, Ji; Huang, Qihong; Xu, Hua; Ye, Zhangqun

    2015-03-30

    Inactivation or mutation of the VHL gene causes various tumors, including clear cell renal cell carcinoma (ccRCC). In the present study, we identified ZBRK1 as a novel VHL interacting protein by yeast two-hybrid screening, and found a single ZBRK1-binding site located in the VHL promoter region. Ectopic expression of ZBRK1 increases transcriptional activity of the VHL, whereas the depletion of endogenous ZBRK1 by shRNA leads to reduction of VHL expression. We also demonstrate that the inhibition of VEGF transcription by ZBRK1 overexpression is dependent on VHL/HIF pathway. Moreover, VHL is confirmed to serve as a bridge component for the association of ZBRK1 and p300, which leads to an increase in ZBRK1 transcriptional activity in the VHL promoter. We further provide striking evidences that ZBRK1 acts as a tumor suppressor in renal carcinoma by a variety of in vitro and in vivo assays, and ZBRK1 may represent a molecular marker to distinguish patients with ccRCC at high risk from those with a better survival prognosis. Taken together, these findings suggest that ZBRK1 suppresses renal cancer progression perhaps by regulating VHL expression.

  2. ZBRK1, a novel tumor suppressor, activates VHL gene transcription through formation of a complex with VHL and p300 in renal cancer

    PubMed Central

    Gumireddy, Kiranmai; Li, Anping; Yao, Weimin; Gao, Lu; Chen, Shuliang; Hao, Jun; Wang, Ji; Huang, Qihong; Xu, Hua; Ye, Zhangqun

    2015-01-01

    Inactivation or mutation of the VHL gene causes various tumors, including clear cell renal cell carcinoma (ccRCC). In the present study, we identified ZBRK1 as a novel VHL interacting protein by yeast two-hybrid screening, and found a single ZBRK1-binding site located in the VHL promoter region. Ectopic expression of ZBRK1 increases transcriptional activity of the VHL, whereas the depletion of endogenous ZBRK1 by shRNA leads to reduction of VHL expression. We also demonstrate that the inhibition of VEGF transcription by ZBRK1 overexpression is dependent on VHL/HIF pathway. Moreover, VHL is confirmed to serve as a bridge component for the association of ZBRK1 and p300, which leads to an increase in ZBRK1 transcriptional activity in the VHL promoter. We further provide striking evidences that ZBRK1 acts as a tumor suppressor in renal carcinoma by a variety of in vitro and in vivo assays, and ZBRK1 may represent a molecular marker to distinguish patients with ccRCC at high risk from those with a better survival prognosis. Taken together, these findings suggest that ZBRK1 suppresses renal cancer progression perhaps by regulating VHL expression. PMID:25749518

  3. Update on Renal Mass Biopsy.

    PubMed

    Haifler, Miki; Kutikov, Alexander

    2017-04-01

    Renal masses are diagnosed with an increasing frequency. However, a significant proportion of these masses are benign, and the majority of malignant tumors are biologically indolent. Furthermore, renal tumors are often harbored by the elderly and comorbid patients. As such, matching of renal tumor biology to appropriate treatment intensity is an urgent clinical need. Renal mass biopsy is currently a very useful clinical tool that can assist with critical clinical decision-making in patients with renal mass. Yet, renal mass biopsy is associated with limitations and, as such, may not be appropriate for all patients.

  4. A Trial of PT2977 Tablets In Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-12-22

    Advanced Solid Tumors; Solid Tumor; Solid Carcinoma; Solid Tumor, Adult; ccRCC; RCC, Clear Cell Adenocarcinoma; RCC; Kidney Cancer; Clear Cell Renal Cell Carcinoma; Renal Cell Carcinoma, Metastatic; Renal Cell Carcinoma Recurrent; Renal Cell Carcinoma, Clear Cell Adenocarcinoma

  5. Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure.

    PubMed

    Kornhauser, Carlos; Dubey, Luis-Antonio; Garay, M-Eugenia; Pérez-Luque, Elva-Leticia; Malacara, Juan-Manuel; Vargas-Origel, Arturo

    2002-05-01

    Acute renal failure (ARF) in neonates may occur after renal ischemia. Growth factors participate in the tubular regeneration process. Insulin-like growth factor-1 (IGF-1) is produced in the kidney during the recovery phase of ARF. Tumor necrosis factor-alpha (TNFalpha) may play a role in renal apoptosis. We examined serum and urinary IGF-1 and TNFalpha in neonates with or without ARF after asphyxia, in order to assess their possible use as markers of renal damage and recovery. We studied 20 full-term asphyxiated neonates, 10 with ARF and 10 without ARF, and compared them with 13 normal newborns for 7 days after birth. Blood urea, creatinine, pH, base deficit, and serum and urine IGF-1 and TNFalpha were assessed. Neonates with ARF had more-severe acidosis than patients without ARF. All patients had lower serum IGF-1 values immediately after birth than control children. Serum IGF-1 remained low in the ARF patients. The initial urinary IGF-1 was higher in all patients compared with control newborns, and remained elevated for the rest of the study only in the ARF neonates. Serum and urinary TNFalpha concentrations were similar for all healthy and diseased neonates. Measurement of serum and urinary IGF-1 levels in ARF neonates might be of additional value for clinical assessment of ARF.

  6. MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma

    SciTech Connect

    Wang, Xinsheng; Jiang, Fuquan; Song, Haitao; Li, Xu; Xian, Jiantao; Gu, Xinquan

    2016-02-12

    Sperm-associated antigen 9(SPAG9), as a well-recognized oncogene protein, has a critical effect on renal cell carcinoma (RCC) progression. Our study tried to explore the mediator of miR-200a-3p, a tumor suppressing miRNA on SPAG9 expression and renal cell proliferation and apoptosis. We found the expression of miR-200a-3p was significantly lower in RCC specimens. Based on in vitro assays, we found miR-200a-3p significantly inhibit cancer cell proliferation by inducing apoptosis. In addition, our study uncovered that miR-200a-3p directly regulates oncogenic SPAG9 in 786-O and ACHN cells. Silencing of SPAG9 resulted in significantly decreased in the growth and the cell cycle of the renal cancer cell lines. Understanding of oncogenic SPAG9 regulated by miR-200a-3p might be beneficial to reveal new therapeutic targets for RCC. - Highlights: • MiR-200a-3p is downregulated in renal cell carcinoma. • MiR-200a-3p regulates cell proliferation through inducing apoptosis. • MiR-200a-3p is involved in cell cycle regulation. • SPAG9 is a potential target of miR-200a-3p.

  7. Associations between Tumor Vascularity, Vascular Endothelial Growth Factor Expression and PET/MRI Radiomic Signatures in Primary Clear-Cell–Renal-Cell-Carcinoma: Proof-of-Concept Study

    PubMed Central

    Yin, Qingbo; Hung, Sheng-Che; Wang, Li; Lin, Weili; Fielding, Julia R.; Rathmell, W. Kimryn; Khandani, Amir H.; Woods, Michael E.; Milowsky, Matthew I.; Brooks, Samira A.; Wallen, Eric. M.; Shen, Dinggang

    2017-01-01

    Studies have shown that tumor angiogenesis is an essential process for tumor growth, proliferation and metastasis. Also, tumor angiogenesis is an important prognostic factor of clear cell renal cell carcinoma (ccRCC), as well as a factor in guiding treatment with antiangiogenic agents. Here, we attempted to find the associations between tumor angiogenesis and radiomic imaging features from PET/MRI. Specifically, sparse canonical correlation analysis was conducted on 3 feature datasets (i.e., radiomic imaging features, tumor microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression) from 9 patients with primary ccRCC. In order to overcome the potential bias of intratumoral heterogeneity of angiogenesis, this study investigated the relationship between regional expressions of angiogenesis and VEGF, and localized radiomic features from different parts within the tumors. Our study highlighted the significant strong correlations between radiomic features and MVD, and also demonstrated that the spatiotemporal features extracted from DCE-MRI provided stronger radiomic correlation to MVD than the textural features extracted from Dixon sequences and FDG PET. Furthermore, PET/MRI, which takes advantage of the combined functional and structural information, had higher radiomics correlation to MVD than solely utilizing PET or MRI alone. PMID:28256615

  8. Associations between Tumor Vascularity, Vascular Endothelial Growth Factor Expression and PET/MRI Radiomic Signatures in Primary Clear-Cell-Renal-Cell-Carcinoma: Proof-of-Concept Study.

    PubMed

    Yin, Qingbo; Hung, Sheng-Che; Wang, Li; Lin, Weili; Fielding, Julia R; Rathmell, W Kimryn; Khandani, Amir H; Woods, Michael E; Milowsky, Matthew I; Brooks, Samira A; Wallen, Eric M; Shen, Dinggang

    2017-03-03

    Studies have shown that tumor angiogenesis is an essential process for tumor growth, proliferation and metastasis. Also, tumor angiogenesis is an important prognostic factor of clear cell renal cell carcinoma (ccRCC), as well as a factor in guiding treatment with antiangiogenic agents. Here, we attempted to find the associations between tumor angiogenesis and radiomic imaging features from PET/MRI. Specifically, sparse canonical correlation analysis was conducted on 3 feature datasets (i.e., radiomic imaging features, tumor microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression) from 9 patients with primary ccRCC. In order to overcome the potential bias of intratumoral heterogeneity of angiogenesis, this study investigated the relationship between regional expressions of angiogenesis and VEGF, and localized radiomic features from different parts within the tumors. Our study highlighted the significant strong correlations between radiomic features and MVD, and also demonstrated that the spatiotemporal features extracted from DCE-MRI provided stronger radiomic correlation to MVD than the textural features extracted from Dixon sequences and FDG PET. Furthermore, PET/MRI, which takes advantage of the combined functional and structural information, had higher radiomics correlation to MVD than solely utilizing PET or MRI alone.

  9. Hepatic and renal metallothionein concentrations in Commerson's dolphins (Cephalorhynchus commersonii) from Tierra del Fuego, South Atlantic Ocean.

    PubMed

    Cáceres-Saez, Iris; Polizzi, Paula; Romero, Belén; Dellabianca, Natalia A; Ribeiro Guevara, Sergio; Goodall, R Natalie P; Cappozzo, H Luis; Gerpe, Marcela

    2016-07-15

    The Commerson's dolphin is the most common endemic odontocete of subantarctic waters of Tierra del Fuego, Argentina incidentally caught in fishing nets. The species is classified as "Data Deficient" by the IUCN. Metallothioneins (MTs) are considered as suitable biomarkers for health and environmental monitoring. The aims of the study were to assess MT concentrations in the liver and kidney of bycaught specimens. Moreover, correlations with Zn, Se, Cd, Ag and Hg, and the molar ratios of MT:metals were estimated to evaluate if there is an indication of their respective protective role against metal toxicity in tissues. Hepatic and renal MT concentrations were similar, ranging from 11.6 to 29.1nmol·g(-1) WW, and Kidney/Liver ratios ranging from 0.73 to 1.93 corresponded to normal ranges. Results suggest that MTs are related to physiological ranges for the species. This information constitutes the first MT report on Commerson's dolphins and possibly considered as baseline for species' conservation.

  10. A Novel Tumor Antigen and Foxp3 Dual-Targeting Tumor Cell Vaccine Enhances the Immunotherapy in a Murine Model of Renal Cell Carcinoma

    DTIC Science & Technology

    2014-10-01

    DATES COVERED t 4. TITLE AND SUBTITLE A Novel Tumor Antigen and Foxp3 Dual-Targeting Tumor Cell Vaccine 5a. CONTRACT NUMBER Enhances the...past year I have generated Foxp3-over expressing RENCA cells, as the source of candidate dual targeting tumor cells vaccine . We have performed...controlled vaccine therapy in RENCA model in three different schedules. When applied in a pre- vaccine schedule, RENCA and RENCA Foxp3 tumor cell vaccine

  11. Oncolytic virotherapy with an armed vaccinia virus in an orthotopic model of renal carcinoma is associated with modification of the tumor microenvironment.

    PubMed

    Fend, Laetitia; Remy-Ziller, Christelle; Foloppe, Johann; Kempf, Juliette; Cochin, Sandrine; Barraud, Luc; Accart, Nathalie; Erbs, Philippe; Fournel, Sylvie; Préville, Xavier

    2016-02-01

    Oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. We have constructed a vaccinia virus (WR strain) deleted for thymidine kinase (TK) and ribonucleotide reductase (RR) genes that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. We evaluated this construct (VV-FCU1) in the orthotopic model of renal carcinoma (RenCa). Systemic administration of VV-FCU1 resulted in orthotopic tumor growth inhibition, despite temporary expression of viral proteins. VV-FCU1 treatment was associated with an infiltration of tumors by CD8(+) T lymphocytes and a decrease in the proportion of infiltrating Tregs, thus modifying the ratio of CD8(+)/CD4(+) Treg in favor of CD8(+)cytotoxic T cells. We demonstrated that VV-FCU1 treatment prolonged survival of animals implanted with RenCa cells in kidney. Depletion of CD8(+) T cells abolished the therapeutic effect of VV-FCU1 while depletion of CD4(+) T cells enhanced its protective activity. Administration of the prodrug 5-fluorocytosine (5-FC) resulted in a sustained control of tumor growth but did not extend survival. This study shows the importance of CD4(+) and CD8(+) T cells in vaccinia virus-mediated oncolytic virotherapy and suggests that this approach may be evaluated for the treatment of human renal cell carcinoma.

  12. Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations.

    PubMed

    Figel, Ainhoa-M; Brech, Dorothee; Prinz, Petra U; Lettenmeyer, Ulrike K; Eckl, Judith; Turqueti-Neves, Adriana; Mysliwietz, Josef; Anz, David; Rieth, Nicole; Muenchmeier, Niklas; Buchner, Alexander; Porubsky, Stefan; Siegert, Sabine I; Segerer, Stephan; Nelson, Peter J; Noessner, Elfriede

    2011-07-01

    Tissue dendritic cells (DCs) may influence the progression of renal cell carcinoma (RCC) by regulating the functional capacity of antitumor effector cells. DCs and their interaction with T cells were analyzed in human RCC and control kidney tissues. The frequency of CD209(+) DCs in RCCs was found to be associated with an unfavorable T(H)1 cell balance in the tissue and advanced tumor stages. The CD209(+) DCs in RCC were unusual because most of them co-expressed macrophage markers (CD14, CD163). The phenotype of these enriched-in-renal-carcinoma DCs (ercDCs) could be reiterated in vitro by carcinoma-secreted factors (CXCL8/IL-8, IL-6, and vascular endothelial growth factor). ErcDCs resembled conventional DCs in costimulatory molecule expression and antigen cross-presentation. They did not suppress cognate cytotoxic T-lymphocyte function and did not cause CD3ζ down-regulation, FOXP3 induction, or T-cell apoptosis in situ or in vitro; thus, they are different from classic myeloid-derived suppressor cells. ErcDCs secreted high levels of metalloproteinase 9 and used T-cell crosstalk to increase tumor-promoting tumor necrosis factor α and reduce chemokines relevant for T(H)1-polarized lymphocyte recruitment. This modulation of the tumor environment exerted by ercDCs suggests an immunologic mechanism by which tumor control can fail without involving cytotoxic T-lymphocyte inhibition. Pharmacologic targeting of the deviated DC differentiation could improve the efficacy of immunotherapy against RCC. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. A divide-and-conquer strategy in tumor sampling enhances detection of intratumor heterogeneity in routine pathology: A modeling approach in clear cell renal cell carcinoma.

    PubMed

    Lopez, José I; Cortes, Jesús M

    2016-01-01

    Intratumor heterogeneity (ITH) is an inherent process in cancer development which follows for most of the cases a branched pattern of evolution, with different cell clones evolving independently in space and time across different areas of the same tumor. The determination of ITH (in both spatial and temporal domains) is nowadays critical to enhance patient treatment and prognosis. Clear cell renal cell carcinoma (CCRCC) provides a good example of ITH. Sometimes the tumor is too big to be totally analyzed for ITH detection and pathologists decide which parts must be sampled for the analysis. For such a purpose, pathologists follow internationally accepted protocols. In light of the latest findings, however, current sampling protocols seem to be insufficient for detecting ITH with significant reliability. The arrival of new targeted therapies, some of them providing promising alternatives to improve patient survival, pushes the pathologist to obtain a truly representative sampling of tumor diversity in routine practice. How large this sampling must be and how this must be performed are unanswered questions so far.  Here we present a very simple method for tumor sampling that enhances ITH detection without increasing costs. This method follows a divide-and-conquer (DAC) strategy, that is, rather than sampling a small number of large-size tumor-pieces as the routine protocol (RP) advises, we suggest sampling many small-size pieces along the tumor. We performed a computational modeling approach to show that the usefulness of the DAC strategy is twofold: first, we show that DAC outperforms RP with similar laboratory costs, and second, DAC is capable of performing similar to total tumor sampling (TTS) but, very remarkably, at a much lower cost. We thus provide new light to push forward a shift in the paradigm about how pathologists should sample tumors for achieving efficient ITH detection.

  14. A divide-and-conquer strategy in tumor sampling enhances detection of intratumor heterogeneity in routine pathology: A modeling approach in clear cell renal cell carcinoma

    PubMed Central

    Lopez, José I.; Cortes, Jesús M.

    2016-01-01

    Intratumor heterogeneity (ITH) is an inherent process in cancer development which follows for most of the cases a branched pattern of evolution, with different cell clones evolving independently in space and time across different areas of the same tumor. The determination of ITH (in both spatial and temporal domains) is nowadays critical to enhance patient treatment and prognosis. Clear cell renal cell carcinoma (CCRCC) provides a good example of ITH. Sometimes the tumor is too big to be totally analyzed for ITH detection and pathologists decide which parts must be sampled for the analysis. For such a purpose, pathologists follow internationally accepted protocols. In light of the latest findings, however, current sampling protocols seem to be insufficient for detecting ITH with significant reliability. The arrival of new targeted therapies, some of them providing promising alternatives to improve patient survival, pushes the pathologist to obtain a truly representative sampling of tumor diversity in routine practice. How large this sampling must be and how this must be performed are unanswered questions so far.  Here we present a very simple method for tumor sampling that enhances ITH detection without increasing costs. This method follows a divide-and-conquer (DAC) strategy, that is, rather than sampling a small number of large-size tumor-pieces as the routine protocol (RP) advises, we suggest sampling many small-size pieces along the tumor. We performed a computational modeling approach to show that the usefulness of the DAC strategy is twofold: first, we show that DAC outperforms RP with similar laboratory costs, and second, DAC is capable of performing similar to total tumor sampling (TTS) but, very remarkably, at a much lower cost. We thus provide new light to push forward a shift in the paradigm about how pathologists should sample tumors for achieving efficient ITH detection. PMID:27127618

  15. Possible roles of tumor necrosis factor-α and angiotensin II type 1 receptor on high glucose-induced damage in renal proximal tubular cells.

    PubMed

    Takao, Toshihiro; Horino, Taro; Matsumoto, Reiko; Shimamura, Yoshiko; Ogata, Koji; Inoue, Kousuke; Taniguchi, Yoshinori; Taguchi, Takafumi; Terada, Yoshio

    2015-02-01

    Recent studies have identified that high glucose-induced renal tubular cell damage. We previously demonstrated that high glucose treatment induced oxidative stress in human renal proximal tubular epithelial cells (RPTECs), and angiotensin II type 1 (AT1) receptor blockers reduce high glucose-induced oxidative stress in RPTEC possibly via blockade of intracellular as well as extracellular AT1 receptor. However, exact roles of tumor necrosis factor (TNF)-α and AT1 receptor on high glucose-induced renal tubular function remain unclear. N-acetyl-beta-glucosaminidase (NAG), concentrations of TNF-α/angiotensin II and p22(phox) protein levels after high glucose treatment with or without AT1 receptor blocker or thalidomide, an inhibitor of TNF-α protein synthesis, were measured in immortalized human renal proximal tubular epithelial cells (HK2 cells). AT1 receptor knockdown was performed with AT1 receptor small interfering RNA (siRNA). High glucose treatment (30 mM) significantly increased NAG release, TNF-α/angiotensin II concentrations in cell media and p22(phox) protein levels compared with those in regular glucose medium (5.6 mM). Candesartan, an AT1R blocker, showed a significant reduction on high glucose-induced NAG release, TNF-α concentrations and p22(phox) protein levels in HK2 cells. In addition, significant decreases of NAG release, TNF-α concentrations and p22(phox) protein levels in HK2 cells were observed in high glucose-treated group with thalidomide. AT1R knockdown with siRNA markedly reversed high glucose, angiotensin II or TNF-α-induced p22(phox) protein levels in HK2 cells. TNF-α may be involved in high glucose-induced renal tubular damage in HK2 cells possibly via AT1 receptor signaling.

  16. Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature.

    PubMed

    Sun, Ke; You, Qihan; Zhao, Ming; Yao, Hongtian; Xiang, Hua; Wang, Lijun

    2013-01-01

    Primary carcinoid tumor arising in a mature teratoma of the horseshoe kidney is exceptionally rare and only 4 such cases have been reported in the world literature to date. The simultaneous occurrence of different subtypes of renal cell carcinoma (RCC) or RCC coexistence with non-RCC neoplasms from the same kidney is unusual and infrequently reported. Herein we report a case of primary carcinoid tumor arising within mature teratoma, concurrent with a clear cell RCC in the horseshoe kidney of a 37-year-old man. Histologically, both the carcinoid tumor and clear cell RCC demonstrated the characteristic morphology in their classic forms. In addition to the carcinoid tumor, the mature teratoma consisted of variably sized, large cystic spaces lined by cytologically bland mucinous columnar epithelium, pseudostratified columnar epithelium, ciliated epithelium and mature smooth muscle fibers were also identified within the cystic wall. Furthermore, foci of round, small nodules composed of mature prostatic acinus were noted in the teratoma which was confirmed by exhibiting strong immunoreactivity for prostate specific antigen. The present case serves to expand the histologic component that may be encountered in the mature terotoma of the kidney and further broadens the spectrum of primary tumors occurring in the horseshoe kidney.

  17. Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature

    PubMed Central

    Sun, Ke; You, Qihan; Zhao, Ming; Yao, Hongtian; Xiang, Hua; Wang, Lijun

    2013-01-01

    Primary carcinoid tumor arising in a mature teratoma of the horseshoe kidney is exceptionally rare and only 4 such cases have been reported in the world literature to date. The simultaneous occurrence of different subtypes of renal cell carcinoma (RCC) or RCC coexistence with non-RCC neoplasms from the same kidney is unusual and infrequently reported. Herein we report a case of primary carcinoid tumor arising within mature teratoma, concurrent with a clear cell RCC in the horseshoe kidney of a 37-year-old man. Histologically, both the carcinoid tumor and clear cell RCC demonstrated the characteristic morphology in their classic forms. In addition to the carcinoid tumor, the mature teratoma consisted of variably sized, large cystic spaces lined by cytologically bland mucinous columnar epithelium, pseudostratified columnar epithelium, ciliated epithelium and mature smooth muscle fibers were also identified within the cystic wall. Furthermore, foci of round, small nodules composed of mature prostatic acinus were noted in the teratoma which was confirmed by exhibiting strong immunoreactivity for prostate specific antigen. The present case serves to expand the histologic component that may be encountered in the mature terotoma of the kidney and further broadens the spectrum of primary tumors occurring in the horseshoe kidney. PMID:24228123

  18. [Therapeutic efficacy of dendritic cells pulsed by autologous tumor cell lysate in combination with CIK cells on advanced renal cell carcinoma].

    PubMed

    Wang, Hui; Feng, Fang; Zhu, Mingao; Wang, Roushu; Wang, Xiaoping; Wu, Ying; Zhuang, Zhixiang

    2015-01-01

    To investigate the clinical efficacy of dendritic cells (DCs) sensitization by autologous tumor cell lysate in combination with cytokine-induced killer (CIK) cells on patients with advanced renal cell carcinoma and detect their immune functions and adverse effects. The study analyzed retrospectively 82 patients with advanced renal cell carcinoma admitted in our department from January 2011 to December 2013. Peripheral blood mononuclear cells (PBMCs) were isolated from the above patients. Adherent cells were cultured to produce DCs. The DCs were pulsed with autologous tumor cell lysate (Ag) to produce Ag-DC. T lymphocytes were cultured to prepare CIK. The Ag-DC was co-cultured with CIK to produce Ag-DC-CIK vaccine, and then the phenotypes of the DCs and the secretion of IL-12 were evaluated. CIK cell proliferation was determined, too. The 41 patients received the immunotherapy of Ag-DC-CIK, and the other 41 patients received CIK cell therapy alone. After 2 cycles of treatment, the changes of T cell subtypes and cytokines released in the peripheral blood were evaluated. The therapeutic outcomes were evaluated with the help of imageology. The adverse effects were also observed. Compared with the DCs alone, DCs pulsed with autologous tumor cell lysates expressed significantly surface molecules CD11c, CD83, CD86 and HLA-DR, and the release of IL-12 significantly increased. CIK cell proliferation was significantly enhanced after co-cultured with the Ag-DC. Meanwhile, the percentages of CD3⁺CD8⁺ cells and CD3⁺CD56⁺ cells went up significantly compared with the controls. Clinical responses of the Ag-DC-CIK treatment group were much better than those of the control group. No severe adverse effects were seen in the two groups. DCs derived from PBMCs of advanced renal cell carcinoma patients harboring the autologous tumor cell antigens can differentiate into mature DCs, which facilitate the proliferation of CIK cells. Ag-DC-CIK vaccine improves the immune status of

  19. BRCA1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1

    PubMed Central

    Drost, Rinske; Dhillon, Kiranjit K.; van der Gulden, Hanneke; van der Heijden, Ingrid; Brandsma, Inger; Cruz, Cristina; Chondronasiou, Dafni; Castroviejo-Bermejo, Marta; van der Burg, Eline; Wientjens, Ellen; Pieterse, Mark; Klijn, Christiaan; Klarenbeek, Sjoerd; Loayza-Puch, Fabricio; Elkon, Ran; van Deemter, Liesbeth; Rottenberg, Sven; van de Ven, Marieke; Dekkers, Dick H.W.; Demmers, Jeroen A.A.; Agami, Reuven; Balmaña, Judith; Taniguchi, Toshiyasu; Bouwman, Peter

    2016-01-01

    Heterozygous germline mutations in breast cancer 1 (BRCA1) strongly predispose women to breast cancer. BRCA1 plays an important role in DNA double-strand break (DSB) repair via homologous recombination (HR), which is important for tumor suppression. Although BRCA1-deficient cells are highly sensitive to treatment with DSB-inducing agents through their HR deficiency (HRD), BRCA1-associated tumors display heterogeneous responses to platinum drugs and poly(ADP-ribose) polymerase (PARP) inhibitors in clinical trials. It is unclear whether all pathogenic BRCA1 mutations have similar effects on the response to therapy. Here, we have investigated mammary tumorigenesis and therapy sensitivity in mice carrying the Brca1185stop and Brca15382stop alleles, which respectively mimic the 2 most common BRCA1 founder mutations, BRCA1185delAG and BRCA15382insC. Both the Brca1185stop and Brca15382stop mutations predisposed animals to mammary tumors, but Brca1185stop tumors responded markedly worse to HRD-targeted therapy than did Brca15382stop tumors. Mice expressing Brca1185stop mutations also developed therapy resistance more rapidly than did mice expressing Brca15382stop. We determined that both murine Brca1185stop tumors and human BRCA1185delAG breast cancer cells expressed a really interesting new gene domain–less (RING-less) BRCA1 protein that mediated resistance to HRD-targeted therapies. Together, these results suggest that expression of RING-less BRCA1 may serve as a marker to predict poor response to DSB-inducing therapy in human cancer patients. PMID:27454287

  20. Tumor

    MedlinePlus

    ... excessively in the body. Normally, the body controls cell growth and division. New cells are created to replace ... room for healthy replacements. If the balance of cell growth and death is disturbed, a tumor may form. ...

  1. [Spinal cord infarction following radical nephrectomy using extracorporeal circulation for renal cell carcinoma with tumor thrombus in the inferior vena cava and right atrium: a case report].

    PubMed

    Sumino, Yasuhiro; Sato, Fuminori; Mimata, Hiromitsu

    2010-07-01

    A 51 year-old man admitted to our hospital for macroscopic hematuria and right abdominal mass. CT demonstrated a large hypervascular mass and tumor thrombus in the inferior vena cava and right atrium. We diagnosed right renal cancer (stage III), and he underwent radical nephrectomy and resection of tumor thrombus with extracorporeal circulation. Operative time was 9 hours. Time for extracorporeal circulation was 119 minutes, and it took 60 minutes for intraoperative balloon occlusion of descending aorta in order to arrest hemorrhage. Pathological diagnosis was clear cell carcinoma of the kidney (pT3c, N0, M0). Four days after surgery, paraplegia was evident, and a diagnosis of spinal cord infarction was made based on neurologic examination and MRI findings. In cases with such a surgery requiring extracorporeal circulation, preoperative meeting with cardiologists and anesthetists is indispensable in order to fully understand the possible complications. Especially, to keep a careful watch and prepare for spinal cord ischemia is mandatory.

  2. Sunitinib treatment for multifocal renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (NET) in patient with Von Hippel-Lindau disease. Case Report.

    PubMed

    Babinska, Anna; Studniarek, Michał; Świątkowska-Stodulska, Renata; Sworczak, Krzysztof

    2015-12-01

    Von Hippel-Lindau disease (VHL) is an autosomal, dominant, hereditary disease occurring in approximately one in 36,000 births. VHL disease produces a variety of tumors and cysts in the central nervous system and visceral organs. Surgical management, when possible, improves prognosis and extends patient's life. When surgery is impossible, treatment with tyrosine kinase inhibitors demonstrates encouraging response rates. We present a 60-year old patient with coexistence of multifocal renal cell carcinomas (RCC) and pancreatic neuroendocrine tumor (NET) in VHL disease, who received Sunitinib as the best option of treatment. Progression - free survival time is over 4 years. Regarding her acceptable tolerance for tyrosine kinase inhibitors, medical treatment is continued. RCC and pancreatic NET associated with VHL are responsive to Sunitinib for prolonged periods of time. Tyrosine kinase inhibitors treatment for patients with multiple neoplasms associated with VHL disease may too be considered. Sunitinib showed acceptable toxicity.

  3. Comparison of the tumor-seeking agent Tc-99m(V) dimercaptosuccinic acid and the renal imaging agent Tc-99m dimercaptosuccinic acid in humans

    SciTech Connect

    Ohta, H.; Ishii, M.; Yoshizumi, M.; Endo, K.; Sakahara, H.; Nakajima, T.; Yomoda, I.; Masuda, H.; Horiuchi, K.; Hata, N.

    1985-03-01

    Being aware of the ideal nuclear properties of Tc-99m, interest has been focused on the design of the (+5) oxidation state Tc-99m(V) dimercaptosuccinic acid (Tc(V)-DMSA) as a tumor-seeking agent. Tc-99m(V) DMSA holds a TcO4(3-) core and, like PO4(3-), has excellent characteristics for tumor uptake, but has a different distribution than the well-known renal scanning agent, Tc-99m DMSA. The differences in chemical behavior of Tc-99m(V) DMSA and Tc-99m DMSA are discussed. Three cases in which neoplasms were studied with Tc-99m(V) DMSA and Tc-99m DMSA are presented. Tc-99m DMSA and Tc-99m(V) DMSA, having a common ligand and tracer but, with the metal ion core in a different oxidation state, the uptake characteristics are altered markedly.

  4. Surgical treatment of renal cell carcinoma: Can morphological features of inferior vena cava tumor thrombus on computed tomography or magnetic resonance imaging be a prognostic factor?

    PubMed

    Choi, Don Kyoung; Jeon, Hwang Gyun; Jeong, Chang Wook; Kwak, Cheol; Song, Cheryn; Chung, Jinsoo; Hong, Sung Kyu; Hong, Sung-Hoo; Seo, Seong Il

    2017-02-01

    To evaluate the impact of morphological features of inferior vena cava thrombus on the overall survival and cancer-specific survival (cancer-specific survival of patients with renal cell carcinoma). We retrospectively analyzed the records of 156 renal cell carcinoma patients with inferior vena cava thrombus who underwent radical nephrectomy and thrombectomy from 1998 to 2013 at five tertiary centers. Inferior vena cava thrombi were classified as spherical (type I) and spiculated (type II) according to morphological features on computed tomography or magnetic resonance imaging. Multivariate cox regression models were used to quantify the impact of prognostic factors on overall survival and cancer-specific survival. Type I was found in 29 patients (18.6%), and type II in 127 patients (81.4%). Median follow up was 38.2 months (interquartile range 12-57). Demographic characteristics were not significantly different, except for the cranial thrombus height (P = 0.003). On multivariate analysis, Eastern Cooperative Oncology Group performance score, clinical tumor size, distant metastasis, histologic subtype, thrombus morphology and remnant venous thrombus significantly affected overall survival in pNany Many patients (all P < 0.05). Among the pNO /X MO patients, clinical tumor size, histologic subtype, thrombus morphology and remnant venous thrombus significantly affected overall survival (all P < 0.05). In terms of cancer-specific survival, Eastern Cooperative Oncology Group performance score, clinical tumor size, distant metastasis, histologic subtype and thrombus morphology significantly affected cancer-specific survival in pNany Many patients (all P < 0.05). In patients with pNO /X MO , body mass index, clinical tumor size, histological subtype, thrombus morphology and remnant venous thrombus significantly affected cancer-specific survival (all P < 0.05). Clinical tumor size, histological subtype, and thrombus morphology are independent predictors of overall survival

  5. In vivo and in vitro studies on renal uptake of radiolabeled affibody molecules for imaging of HER2 expression in tumors.

    PubMed

    Altai, Mohamed; Varasteh, Zohreh; Andersson, Karl; Eek, Annemarie; Boerman, Otto; Orlova, Anna

    2013-04-01

    Affibody molecules (6-7 kDa) are a new class of small robust three-helical scaffold proteins. Radiolabeled subnanomolar anti-HER2 affibody ZHER2:342 was developed for imaging of HER2 expression in tumors, and a clinical study has demonstrated that the (111)In- and (68)Ga-labeled affibody molecules can efficiently detect HER2 expressing metastases in breast cancer patients. However, a significant renal accumulation of radioactivity after systemic injection of a radiolabeled anti-HER2 affibody conjugate is observed. The aim of this study was to investigate the mechanism of renal reabsorption of anti-HER2 affibody at the molecular level. Renal accumulation of radiolabeled anti-HER2 affibody molecules was studied in a murine model and in vitro using opossum-derived proximal tubule (OK) cells. It was found that kidney reabsorption of affibody molecule was not driven by megalin/cubilin. Amino acids in the target-binding side of affibody molecule were involved in binding to OK cells. On OK cells, two types of receptors for anti-HER2 affibody molecule were found: KD1=0.8 nM, Bmax1=71,500 and KD2=9.2 nM, Bmax2=367,000. The results of the present study indicate that affibody molecule and other scaffold-based targeting proteins with a relatively low kidney uptake can be selected using in vitro studies with tubular kidney cells.

  6. PGRMC1 Is a Novel Potential Tumor Biomarker of Human Renal Cell Carcinoma Based on Quantitative Proteomic and Integrative Biological Assessments

    PubMed Central

    Wang, Xixi; Zhang, Peng; Lu, Weiliang; Yu, Yamei; Deng, Shi; Yang, Hanshuo; Zhu, Hongxia; Xu, Ningzhi; Liang, Shufang

    2017-01-01

    Progesterone receptor membrane component 1 (PGRMC1) is widely observed with an elevated level in multiple human cancers. However, the roles of PGRMC1 in renal cancer are not clear and merit further study. In this report, we made a systematic, integrative biological assessment for PGRMC1 in renal cell carcinoma (RCC) by a quantitative proteomic identification, immunohistochemical detection, and its clinic pathologic significance analysis. We found that PGRMC1 abundance is increased by 3.91-fold in RCC tissues compared with its autologous para-cancerous tissues by a quantitative proteome identification. To validate the proteomic result with more confidence, 135 clinic RCC tissues were recruited to measure PGRMC1 abundance by immunohistochemical staining, and 63.7% RCC samples (n = 86) showed a higher abundance of PGRMC1 than the noncancerous counterparts. And the elevated PGRMC1 level was related to the tumor malignancy degree and overall survival of RCC patients. Meanwhile the average serum PGRMC1 concentration for RCC patients (n = 18) was significantly increased by 1.67 fold compared with healthy persons. Moreover an exogenous elevated abundance of PGRMC1 by plasmid transfections significantly enhanced cell proliferation of renal cancer cells in vitro. Our findings demonstrate PGRMC1, which promotes RCC progression phenotypes in vitro and in vivo, is a novel potential biomarker and therapeutic target for RCC. PMID:28107520

  7. Chemically exacerbated chronic progressive nephropathy not associated with renal tubular tumor induction in rats: an evaluation based on 60 carcinogenicity studies by the national toxicology program.

    PubMed

    Melnick, Ronald L; Burns, Kathleen M; Ward, Jerrold M; Huff, James

    2012-08-01

    Chronic progressive nephropathy (CPN) is a common age-related degenerative-regenerative disease of the kidney that occurs in both sexes of most strains of rats. Recently, claims have been made that enhanced CPN is a mode of action for chemically induced kidney tumors in male rats and that renal tubular tumors (RTTs) induced by chemicals that concomitantly exacerbate CPN are not relevant for human cancer risk assessments. Although CPN is an observable histopathological lesion that may be modified by diet, the etiology of this disease and the mechanisms for its exacerbation by chemicals are unknown, and it fails to meet fundamental principles for defining carcinogenic modes of action and human relevance. Our comprehensive evaluation of possible relationships between exacerbated CPN and induction of RTTs in 58 carcinogenicity studies, conducted by the National Toxicology Program, in male and 11 studies in female F344 rats using 60 chemicals revealed widespread inconsistency in the claimed association. Because the proposed hypothesis lacks evidence of biological plausibility, and due to inconsistent relationships between exacerbated CPN and kidney tumor incidence in carcinogenicity studies in rats, dismissing the human relevance of kidney tumors induced by chemicals that also exacerbate CPN in rats would be wrong.

  8. Oxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma.

    PubMed

    Kusmartsev, Sergei; Eruslanov, Evgeniy; Kübler, Hubert; Tseng, Timothy; Sakai, Yoshihisa; Su, Zhen; Kaliberov, Sergei; Heiser, Axel; Rosser, Charles; Dahm, Philip; Siemann, Dietmar; Vieweg, Johannes

    2008-07-01

    Metastatic renal cell carcinoma (RCC) associates with overproduction of vascular endothelial growth factor (VEGF) due to the mutation/inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. Herein we demonstrate that implantation of human RCC tumor cells into athymic nude mice promotes the appearance of VEGF receptor 1 (VEGFR1)/CD11b double-positive myeloid cells in peripheral blood. Avastin-mediated VEGF neutralization was capable of significantly reducing the numbers of circulating VEGFR1+ myeloid cells. Conversely, up-regulation of VEGFR1 by myeloid cells could also be achieved in vitro by coculturing bone marrow cells with RCC-conditioned medium or by short-term exposure of naive myeloid cells to oxidative stress. Treatment of myeloid cells with H2O2, lipid peroxidation product 4-hydroxy-2(E)-nonenal, or an inhibitor of thioredoxin reductase all resulted in increased expression of VEGFR1. Furthermore, after exposure to oxidative stress, myeloid cells acquire immunosuppressive features and become capable of inhibiting T cell proliferation. Data suggest that tumor-induced oxidative stress may promote both VEGFR1 up-regulation and immunosuppressive function in bone marrow-derived myeloid cells. Analysis of tumor tissue and peripheral blood from patients with metastatic RCC revealed that VEGFR1+ cells can be also found in cancer patients. Restoration of immunocompetence in metastatic RCC patients by pharmacological elimination of VEGFR1+ cells may have a significant impact on the therapeutic efficacy of cancer vaccines or other immune-based therapies.

  9. Spontaneous peripheral T-cell responses toward the tumor-associated antigen cyclin D1 in patients with clear cell renal cell carcinoma.

    PubMed

    Dannenmann, Stefanie R; Hermanns, Thomas; Bransi, Ali; Matter, Claudia; von Boehmer, Lotta; Stevanovic, Stefan; Schraml, Peter; Moch, Holger; Knuth, Alexander; van den Broek, Maries

    2013-11-01

    Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples. We analyzed the blood of patients with HLA-A2(+) ccRCC for the presence of CD8(+) T cells specific for TAA-derived HLA-A2-restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with Cyclin D1-positive tumors. Cyclin D1-specific CD8(+) T cells secreted TNF-α, IFN-γ, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8(+) T cells in the blood of these patients with ccRCC. The high frequency (43%) of Cyclin D1 overexpression and the presence of functional cyclin D1-specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies.

  10. Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc

    SciTech Connect

    Liu, Yongchao; Yin, Bingde; Zhang, Changcun; Zhou, Libin; Fan, Jie

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer This study is the first to test the let-7a/c-myc loop in renal cell carcinoma cell lines. Black-Right-Pointing-Pointer Let-7a down-regulated c-myc in three renal cell carcinoma cell lines. Black-Right-Pointing-Pointer c-myc target genes were down-regulated because of the let-7a-mediated down-regulation of c-myc. Black-Right-Pointing-Pointer The let-7a/c-myc loop has a significant function in renal cell carcinoma cell lines. -- Abstract: Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.

  11. Erythropoietin is a JAK2 and ERK1/2 effector that can promote renal tumor cell proliferation under hypoxic conditions.

    PubMed

    Miyake, Makito; Goodison, Steve; Lawton, Adrienne; Zhang, Ge; Gomes-Giacoia, Evan; Rosser, Charles J

    2013-09-03

    Erythropoietin (EPO) provides an alternative to transfusion for increasing red blood cell mass and treating anemia in cancer patients. However, recent studies have reported increased adverse events and/or reduced survival in patients receiving both EPO and chemotherapy, potentially related to EPO-induced cancer progression. Additional preclinical studies that elucidate the possible mechanism underlying EPO cellular growth stimulation are needed. Using commercial tissue microarray (TMA) of a variety of cancers and benign tissues, EPO and EPO receptor immunohistochemical staining was performed. Furthermore using a panel of human renal cells (Caki-1, 786-O, 769-P, RPTEC), in vitro and in vivo experiments were performed with the addition of EPO in normoxic and hypoxic states to note phenotypic and genotypic changes. EPO expression score was significantly elevated in lung cancer and lymphoma (compared to benign tissues), while EPOR expression score was significantly elevated in lymphoma, thyroid, uterine, lung and prostate cancers (compared to benign tissues). EPO and EPOR expression scores in RCC and benign renal tissue were not significantly different. Experimentally, we show that exposure of human renal cells to recombinant EPO (rhEPO) induces cellular proliferation, which we report for the first time, is further enhanced in a hypoxic state. Mechanistic investigations revealed that EPO stimulates the expression of cyclin D1 while inhibiting the expression of p21cip1 and p27kip1 through the phosphorylation of JAK2 and ERK1/2, leading to a more rapid progression through the cell cycle. We also demonstrate an increase in the growth of renal cell carcinoma xenograft tumors when systemic rhEPO is administered. In summary, we elucidated a previously unidentified mechanism by which EPO administration regulates progression through the cell cycle, and show that EPO effects are significantly enhanced under hypoxic conditions.

  12. Erythropoietin is a JAK2 and ERK1/2 effector that can promote renal tumor cell proliferation under hypoxic conditions

    PubMed Central

    2013-01-01

    Background Erythropoietin (EPO) provides an alternative to transfusion for increasing red blood cell mass and treating anemia in cancer patients. However, recent studies have reported increased adverse events and/or reduced survival in patients receiving both EPO and chemotherapy, potentially related to EPO-induced cancer progression. Additional preclinical studies that elucidate the possible mechanism underlying EPO cellular growth stimulation are needed. Methods Using commercial tissue microarray (TMA) of a variety of cancers and benign tissues, EPO and EPO receptor immunohistochemical staining was performed. Furthermore using a panel of human renal cells (Caki-1, 786-O, 769-P, RPTEC), in vitro and in vivo experiments were performed with the addition of EPO in normoxic and hypoxic states to note phenotypic and genotypic changes. Results EPO expression score was significantly elevated in lung cancer and lymphoma (compared to benign tissues), while EPOR expression score was significantly elevated in lymphoma, thyroid, uterine, lung and prostate cancers (compared to benign tissues). EPO and EPOR expression scores in RCC and benign renal tissue were not significantly different. Experimentally, we show that exposure of human renal cells to recombinant EPO (rhEPO) induces cellular proliferation, which we report for the first time, is further enhanced in a hypoxic state. Mechanistic investigations revealed that EPO stimulates the expression of cyclin D1 while inhibiting the expression of p21cip1 and p27kip1 through the phosphorylation of JAK2 and ERK1/2, leading to a more rapid progression through the cell cycle. We also demonstrate an increase in the growth of renal cell carcinoma xenograft tumors when systemic rhEPO is administered. Conclusions In summary, we elucidated a previously unidentified mechanism by which EPO administration regulates progression through the cell cycle, and show that EPO effects are significantly enhanced under hypoxic conditions. PMID

  13. Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma

    SciTech Connect

    Whaley, J.M.; Naglich, J.; Gelbert, L.; Laidlaw, J.; Seizinger, B.R.; Kley, N.; Hsia, Y.E.; Lamiell, J.M.; Green, J.S.; Collins, D.

    1994-12-01

    von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome predisposing to multifocal bilateral renal cell carcinomas (RCCs), pheochromocytomas, and pancreatic tumors, as well as angiomas and hemangioblastomas of the CNS. A candidate gene for VHL was recently identified, which led to the isolation of a partial cDNA clone with extended open reading frame, without significant homology to known genes or obvious functional motifs, except for an acidic pentamer repeat domain. To further characterize the functional domains of the VHL gene and assess its involvement in hereditary and nonhereditary tumors, we performed mutation analyses and studied its expression in normal and tumor tissue. The authors identified germline mutations in 39% of VHL disease families. Moreover, 33% of sporadic RCCs and all (6/6) sporadic RCC cell lines analyzed showed mutations within the VHL gene. Both germ-line and somatic mutations included deletions, insertions, splice-site mutations, and missense and nonsense mutations, all of which clustered at the 3{prime} end of the corresponding partial VHL cDNA open reading frame, including an alternatively spliced exon 123 nt in length, suggesting functionally important domains encoded by the VHL gene in this region. Over 180 sporadic tumors of other types have shown no detectable base changes within the presumed coding sequence of the VHL gene to date. We conclude that the gene causing VHL has an important and specific role in the etiology of sporadic RCCs, acts as a recessive tumor-suppressor gene, and appears to encode important functional domains within the 3{prime} end of the known open reading frame.

  14. Expression Levels of PIWI-interacting RNA, piR-823, Are Deregulated in Tumor Tissue, Blood Serum and Urine of Patients with Renal Cell Carcinoma.

    PubMed

    Iliev, Robert; Fedorko, Michal; Machackova, Tana; Mlcochova, Hana; Svoboda, Marek; Pacik, Dalibor; Dolezel, Jan; Stanik, Michal; Slaby, Ondrej

    2016-12-01

    Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting for about 3% of adult malignancies. P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of naturally occurring, short non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. There were preliminary data published indicating that piR-823 expression is deregulated in circulating tumor cells and tumor tissue in gastric and kidney cancer, respectively. In our study, we analyzed piR-823 levels in 588 biological specimens: tumor tissue (N=153), adjacent renal parenchyma (N=121), blood serum (N=178) and urine (N=20) of patients undergoing nephrectomy for RCC; and in blood serum (N=101) and urine (N=15) of matched healthy controls. Expression levels of piR-823 were determined in all biological specimens by quantitative real-time polymerase chain reaction, compared in patients and controls, and correlated with clinicopathological features of RCC. We identified a significant down-regulation of piR-823 in tumor tissue [p<0.0001, area under the curve (AUC)=0.7945]. On the contrary in blood serum and urine, the expression of piR-823 was significantly higher in patients with RCC compared to healthy individuals (p=0.0005, AUC=0.6264 and p=0.0157, AUC=0.7433, respectively). We further observed higher levels of piR-823 in tumor tissue to be associated with shorter disease-free survival of patients (p=0.0186) and a trend for higher piR-823 levels in serum to be associated with advanced clinical stages of RCC (p=0.0691). There were no other significant associations of piR-823 levels in any type of biological specimen with clinicopathological features of RCC. piR-823 is down-regulated in tumor tissue, but positively correlated with worse outcome, indicating its complex role in RCC pathogenesis. In blood serum, piR-823 is up-regulated, but with unsatisfactory analytical performance. Preliminary data indicate the promising

  15. Effect of Tumor Complexity and Technique on Efficacy and Complications after Percutaneous Microwave Ablation of Stage T1a Renal Cell Carcinoma: A Single-Center, Retrospective Study.

    PubMed

    Klapperich, Marki E; Abel, E Jason; Ziemlewicz, Timothy J; Best, Sara; Lubner, Meghan G; Nakada, Stephen Y; Hinshaw, J Louis; Brace, Christopher L; Lee, Fred T; Wells, Shane A

    2017-07-01

    Purpose To evaluate the effects of tumor complexity and technique on early and midterm oncologic efficacy and rate of complications for 100 consecutive biopsy-proved stage T1a renal cell carcinomas (RCCs) treated with percutaneous microwave ablation. Materials and Methods This HIPAA-compliant, single-center retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety-six consecutive patients (68 men, 28 women; mean age, 66 years ± 9.4) with 100 stage T1a N0M0 biopsy-proved RCCs (median diameter, 2.6 cm ± 0.8) underwent percutaneous microwave ablation between March 2011 and June 2015. Patient and procedural data were collected, including body mass index, comorbidities, tumor histologic characteristics and grade, RENAL nephrometry score, number of antennas, generator power, and duration of ablation. Technical success, local tumor progression, and presence of complications were assessed at immediate and follow-up imaging. The Kaplan-Meier method was used for survival analyses. Results Technical success was achieved for all 100 tumors (100%), including 47 moderately and five highly complex RCCs. Median clinical and imaging follow-up was 17 months (range, 0-48 months) and 15 months (range, 0-44 months), respectively. No change in estimated glomerular filtration rate was noted after the procedure (P = .49). There were three (3%) procedure-related complications and six (6%) delayed complications, all urinomas. One case of local tumor progression (1%) was identified 25 months after the procedure. Three-year local progression-free survival, cancer-specific survival, and overall survival were 88% (95% confidence interval: 0.52%, 0.97%), 100% (95% confidence interval: 1.0%, 1.0%), and 91% (95% confidence interval: 0.51%, 0.99%), respectively. Conclusion Percutaneous microwave ablation is an effective and safe treatment option for stage T1a RCC, regardless of tumor complexity. Long-term follow-up is needed

  16. Recurrent renal giant leiomyosarcoma

    PubMed Central

    Öziş, Salih Erpulat; Gülpınar, Kamil; Şahlı, Zafer; Konak, Baha Burak; Keskin, Mete; Özdemir, Süleyman; Ataoğlu, Ömür

    2016-01-01

    Primary renal leiomyosarcomas are rare, aggressive tumors. They constitute 1–2% of adult malignant renal tumors. Although leiomyosarcomas are the most common histological type (50–60%) of renal sarcomas, information on renal leiomyosarcoma is limited. Local or systemic recurrences are common. The radiological appearance of renal leiomyosarcomas is not specific, therefore renal leiomyosarcoma cannot be distinguished from renal cell carcinoma by imaging methods in all patients. A 74-year-old female patient presented to our clinic complaining of a palpable mass on the right side of her abdomen in November 2012. The abdominal magnetic resonance imaging revealed a mass, 25 × 24 × 23 cm in size. Her past medical history revealed that she has undergone right radical nephrectomy in 2007, due to a 11 × 12 × 13 cm renal mass that was then reported as renal cell carcinoma on abdominal magnetic resonance imaging, but the pathological diagnosis was low-grade renal leiomyosarcoma. The most recent follow-up of the patient was in 2011, with no signs of local recurrence or distant metastases within this four-year period. The patient underwent laparotomy on November 2012, and a 35 cm retroperitoneal mass was excised. The pathological examination of the mass was reported as high-grade leiomyosarcoma. The formation of this giant retroperitoneal mass in 1 year can be explained by the transformation of the lesion’s pathology from low-grade to a high-grade tumor. PMID:27436926

  17. A Novel Tumor Antigen and Foxp3 Dual Targeting Tumor Cell Vaccine Enhances the Immunotherapy in a Murine Model of Renal Cell Carcinoma

    DTIC Science & Technology

    2015-12-01

    mature DCs. Immuno-fluorescent staining and flow cytometry have been performed to phenotype resulted DCs (Figure 1). Result showed that 89.3% of live... staining and flow cytometry. Live cells were gated and percentage of CD11c positive DCs was determined. B. DCs were gated, and mouse H2 (MHC) or CD86 (co...performed immunofluorescence staining and flow cytometry to access the composition in the tumor infiltrates (tumor microenvironment). Test of CD4 cells

  18. HAVCR/KIM-1 activates the IL-6/STAT-3 pathway in clear cell renal cell carcinoma and determines tumor progression and patient outcome.

    PubMed

    Cuadros, Thaïs; Trilla, Enric; Sarró, Eduard; Vilà, Maya R; Vilardell, Jordi; de Torres, Inés; Salcedo, Mayte; López-Hellin, Joan; Sánchez, Alex; Ramón y Cajal, Santiago; Itarte, Emilio; Morote, Juan; Meseguer, Anna

    2014-03-01

    Renal cell carcinoma (RCC), the third most prevalent urological cancer, claims more than 100,000 lives/year worldwide. The clear cell variant (ccRCC) is the most common and aggressive subtype of this disease. While commonly asymptomatic, more than 30% of ccRCC are diagnosed when already metastatic, resulting in a 95% mortality rate. Notably, nearly one-third of organ-confined cancers treated by nephrectomy develop metastasis during follow-up care. At present, diagnostic and prognostic biomarkers to screen, diagnose, and monitor renal cancers are clearly needed. The gene encoding the cell surface molecule HAVCR1/KIM-1 is a suggested susceptibility gene for ccRCC and ectodomain shedding of this molecule may be a predictive biomarker of tumor progression. Microarray analysis of 769-P ccRCC-derived cells where HAVCR/KIM-1 levels have been upregulated or silenced revealed relevant HAVCR/KIM-1-related targets, some of which were further analyzed in a cohort of 98 ccRCC patients with 100 month follow-up. We found that HAVCR/KIM-1 activates the IL-6/STAT-3/HIF-1A axis in ccRCC-derived cell lines, which depends on HAVCR/KIM-1 shedding. Moreover, we found that pSTAT-3 S727 levels represented an independent prognostic factor for ccRCC patients. Our results suggest that HAVCR/KIM-1 upregulation in tumors might represent a novel mechanism to activate tumor growth and angiogenesis and that pSTAT-3 S727 is an independent prognostic factor for ccRCC.

  19. Primary Tumor Characteristics Are Important Prognostic Factors for Sorafenib-Treated Patients with Metastatic Renal Cell Carcinoma: A Retrospective Multicenter Study

    PubMed Central

    Kim, Sohee; Nam, Byung-Ho; Lee, Sang Eun; Seo, Ill Young; Kim, Tae Nam; Hong, Sung-Hoo; Kwon, Tae Gyun; Seo, Seong Il; Song, Kanghyon; Kwak, Cheol

    2017-01-01

    We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients. PMID:28271073

  20. The impact of histology on clinicopathologic outcomes for patients with renal cell carcinoma and venous tumor thrombus: a matched cohort analysis.

    PubMed

    Kaushik, Dharam; Linder, Brian J; Thompson, R Houston; Eisenberg, Manuel S; Lohse, Christine M; Cheville, John C; Leibovich, Bradley C; Boorjian, Stephen A

    2013-07-01

    To evaluate the impact of tumor histology on clinicopathologic outcomes for patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). We identified 807 patients with RCC and VTT who underwent nephrectomy at our institution between 1970 and 2008. All pathologic specimens were re-reviewed by a single urologic pathologist. Patients with non-clear cell RCC (non-ccRCC, n = 56) were matched 1:2 to patients with clear cell RCC (ccRCC) VTT based on symptoms at presentation, regional lymph node involvement, distant metastases, tumor thrombus level, nuclear grade, and sarcomatoid differentiation. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. The 56 patients with non-ccRCC VTT included 26 papillary, 11 chromophobe, 5 collecting duct tumors, and 14 RCCs not otherwise specified. Compared to unmatched patients with ccRCC VTT (n = 751), patients with non-ccRCC VTT presented with larger tumor size (P = .02), higher nuclear grade (P = .04), and more frequent sarcomatoid differentiation (P <.001) and lymph node invasion (P <.001). However, when patients with non-ccRCC were matched to patients with ccRCC, no significant differences were noted with regard to 5-year metastases-free survival (41% vs 34%, P = .24) or cancer-specific survival (25% vs 27%, P = .97). Non-ccRCC VTT is associated with a high rate of adverse pathologic features. Nevertheless, when matched to patients with ccRCC, patients with non-ccRCC VTT did not have increased rate of recurrence or adverse survival. Aggressive surgical resection represents the mainstay of treatment in these cases, whereas continued efforts to optimize a multimodal management approach to such patients remain necessary. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Trends in the use of partial nephrectomy for cT1 renal tumors: Analysis of a 10-yr European multicenter dataset.

    PubMed

    Simone, G; De Nunzio, C; Ferriero, M; Cindolo, L; Brookman-May, S; Papalia, R; Sperduti, I; Collura, D; Leonardo, C; Anceschi, U; Tuderti, G; Misuraca, L; Dalpiaz, O; Hatzl, S; Lodde, M; Trenti, E; Pastore, A L; Palleschi, G; Lotrecchiano, G; Salzano, L; Carbone, A; De Cobelli, O; Tubaro, A; Schips, L; Zigeuner, R; Tostain, J; May, M; Guaglianone, S; Muto, G; Gallucci, M

    2016-11-01

    Although extensively addressed in US registries, the utilization rate of Partial Nephrectomy has been poorly addressed in European settings. Our aim is to evaluate the impact of hospital volume on the use of PN for cT1 renal tumors. 2526 patients with cT1N0M0 renal tumors treated with either PN or radical nephrectomy at 10 European centres in the last decade were included in the analysis. Joinpoint regression analysis was used to identify significant changes over time in linear slope of the trend for each center. The correlation between yearly caseload and the slopes was assessed with the non-parametric Spearman test. Coincident pairwise tests and regression analyses were used to generate and compare the trends of high-volume (HV), mid-volume (MV) and low-volume (LV) groups. Yearly caseload was significantly associated with increased use of PN (R = 0.69, p = 0.028). The utilization rate of PN was stable at LV centres (p = 0.67, p = 0.7, p = 0.76, for cT1, cT1a, and cT1b tumors, respectively), while increased significantly at MV (p = 0.002, 0.0005 and 0.007, respectively) and HV centers (all p < 0.0001). Regression analysis confirmed the trends for HV and MV as significantly different from those observed in LV centres (all p ≤ 0.002) and highlighted significant differences also between MV and HV centres (all p ≤ 0.03). We confirmed the association between caseload and the use of PN for cT1 tumors. Our findings suggest that a minimum caseload might turn the tide also in LV centres while a selective referral to HV centers for cT1b tumors should be considered. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Preoperative Gamma-Glutamyltransferase Is Associated with Cancer-Specific Survival and Recurrence-Free Survival of Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus

    PubMed Central

    Luo, Cheng; Xu, Ben; Fan, Yu; Yu, Wei

    2017-01-01

    Introduction. To evaluate the prognostic significance of preoperative gamma-glutamyltransferase (GGT) on the subgroup of nonmetastatic renal cell carcinoma (RCC) with venous tumor thrombus. Materials and Methods. We retrospectively reviewed the institutional database and collected the medical data of 156 patients with nonmetastatic RCC with venous tumor thrombus between March 2004 and December 2014. Kaplan-Meier and Cox regression analyses were applied to determine the prognostic factors for cancer-specific survival (CSS) and recurrence-free survival (RFS). Results. The median value and optimal cutoff point of preoperative GGT were 23.0 and 37.5 IU/L, respectively. In the entire cohort, 67 (42.9%) patients experienced disease recurrence, and 46 (29.5%) patients died. Kaplan-Meier analysis revealed that the CSS and RFS rates were lower in patients with preoperative GGT ≥ 37.5 IU/L than in those with preoperative GGT < 37.5 IU/L. Multivariate Cox proportional hazard analysis demonstrated that high preoperative GGT was significantly associated with shorter CSS (hazard ratio [HR]: 2.115; 95% CI: 1.164–3.843; p = 0.014) and RFS (HR: 1.955; 95% CI: 1.166–3.276; p = 0.011), after adjusting other covariates. Conclusions. Preoperative GGT can serve as an independent prognostic biomarker of nonmetastatic RCC patients with venous tumor thrombus. Further prospective study is warranted to confirm our results. PMID:28168196

  3. Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response.

    PubMed

    Li, Bo; Gao, Yong-Ju; Wu, Xin-Yu; Cui, Jing; Long, Ye; Xu, Jun-Ling; Ding, De-Gang

    2017-09-01

    The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

  4. Sunitinib pretreatment improves tumor-infiltrating lymphocyte expansion by reduction in intratumoral content of myeloid-derived suppressor cells in human renal cell carcinoma.

    PubMed

    Guislain, Aurelie; Gadiot, Jules; Kaiser, Andrew; Jordanova, Ekaterina S; Broeks, Annegien; Sanders, Joyce; van Boven, Hester; de Gruijl, Tanja D; Haanen, John B A G; Bex, Axel; Blank, Christian U

    2015-10-01

    Targeted therapy with sunitinib, pazopanib or everolimus has improved treatment outcome for patients with metastatic renal cell carcinoma patients (RCC). However, despite considerable efforts in sequential or combined modalities, durable remissions are rare. Immunotherapy like cytokine therapy with interleukin-2, T cell checkpoint blockade or adoptive T cell therapies can achieve long-term benefit and even cure. This raises the question of whether combining targeted therapy with immunotherapy could also be an effective treatment option for RCC patients. Sunitinib, one of the most frequently administered therapeutics in RCC patients has been implicated in impairing T cell activation and proliferation in vitro. In this work, we addressed whether this notion holds true for expansion of tumor-infiltrating lymphocytes (TILs) in sunitinib-treated patients. We compared resected primary RCC tumor material of patients pretreated with sunitinib with resection specimen from sunitinib-naïve patients. We found improved TIL expansion from sunitinib-pretreated tumor digests. These TIL products contained more PD-1 expressing TIL, while the regulatory T cell infiltration was not altered. The improved TIL expansion was associated with reduced intratumoral myeloid-derived suppressor cell (MDSC) content. Depletion of MDSCs from sunitinib-naïve RCC tissue-digest improved TIL expansion, proving the functional relevance of the MDSC alteration by sunitinib. Our in vivo results do not support previous in vitro observations of sunitinib inhibiting T cell function, but do provide a possible rationale for the combination of sunitinib with immunotherapy.

  5. Impact of Microscopic Wall Invasion of the Renal Vein or Inferior Vena Cava on Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor Thrombus: A Multi-institutional Analysis from the International Renal Cell Carcinoma-Venous Thrombus Consortium.

    PubMed

    Rodriguez Faba, Oscar; Linares, Estefania; Tilki, Derya; Capitanio, Umberto; Evans, Christopher P; Montorsi, Francesco; Martínez-Salamanca, Juan I; Libertino, John; Gontero, Paolo; Palou, Joan

    2017-02-09

    Microscopic vein invasion (MVI), with local destruction and invasion of the endothelium by tumor, is of controversial predictive value in renal cell carcinoma (RCC). To assess the impact of venous extension and wall invasion in RCC on survival. Data for 1023 RCC patients with vena cava thrombus treated with radical nephrectomy and complete tumor thrombectomy were collected within a prospectively maintained international consortium (1995-2012). The Kaplan-Meier method and univariable and multivariable Cox regression analyses were used to assess the impact of MVI on cancer-specific survival (CSS). The main two variables of interest were microscopic renal vein wall invasion (MRVI) and microscopic vena cava wall invasion (MVCI). MRVI was found in 725 cases (70.9%) and MVCI in 230 (22.5%). Patients with MRVI had larger tumors (p=0.005), longer hospital stay (p<0.001), higher clinical stage 0.039), higher Fuhrman grade (p=0.028), and more frequent fat invasion. Presence of MVCI was associated with larger tumors (p<0.001), longer hospital stay (p<0.001), higher clinical stage (p<0.001), lymph node involvement (p=0.045), higher Fuhrman grade (p<0.001), and higher thrombus level (p<0.001). With median follow-up of 52 mo, overall 5-yr CSS was 57.4%. Multivariable analysis showed that presence of MRVI was an independent factor related to CSS (hazard ratio 2.24, 95% confidence interval 1.24-3.59, p=0.006). The main limitation was the inability to report MVI percentages. Patients with MRVI experience significantly worse survival outcomes after radical nephrectomy and tumor thrombectomy. Consideration of MRVI at final pathology is appropriate to improve decision-making for risk-adapted follow-up. The behavior of locally advanced renal cell carcinoma (RCC) depends on clinical and pathologic factors. Analysis revealed that RCC patients with microscopic renal vein wall invasion experience significantly worse cancer-specific survival. Copyright © 2017 European Association of

  6. PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation and tumor development in renal distal tubules of rats and men.

    PubMed

    Ribback, Silvia; Cigliano, Antonio; Kroeger, Nils; Pilo, Maria G; Terracciano, Luigi; Burchardt, Martin; Bannasch, Peter; Calvisi, Diego F; Dombrowski, Frank

    2015-05-30

    Activation of the PI3K/AKT/mTOR pathway is a crucial molecular event in human clear cell renal cell carcinoma (ccRCC), and is also upregulated in diabetic nephropathy. In diabetic rats metabolic changes affect the renal distal tubular epithelium and lead to glycogen-storing Armanni-Ebstein lesions (AEL), precursor lesions of RCC in the diabetes induced nephrocarcinogenesis model. These lesions resemble human sporadic clear cell tubules (CCT) and tumor cells of human ccRCC.Human sporadic CCT were examined in a collection of 324 nephrectomy specimen, in terms of morphologic, metabolic and molecular alterations, and compared to preneoplastic CCT and RCC developed in the rat following streptozotocin-induced diabetes or N-Nitrosomorpholine administration. Diabetic and non-diabetic rats were subjected to the dual PI3K/mTOR inhibitor, NVP/BEZ235.Human sporadic CCT could be detected in 17.3% of kidney specimens. Human and rat renal CCT display a strong induction of the PI3K/AKT/mTOR pathway and related metabolic alterations. Proteins involved in glycolysis and de novo lipogenesis were upregulated. In in vivo experiments, dual inhibition of PI3K and mTOR resulted in a reduction of proliferation of rat diabetes related CCT and increased autophagic activity.The present data indicate that human sporadic CCT exhibit a pattern of morphologic and metabolic alterations similar to preneoplastic lesions in the rat model. Activation of the PI3K/AKT/mTOR pathway in glycogenotic tubuli is a remarkable molecular event and suggests a preneoplastic character of these lesions also in humans.

  7. Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma.

    PubMed

    Incorvaia, Lorena; Bronte, Giuseppe; Bazan, Viviana; Badalamenti, Giuseppe; Rizzo, Sergio; Pantuso, Gianni; Natoli, Clara; Russo, Antonio

    2016-04-19

    The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC).This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition.Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC.

  8. Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients.

    PubMed

    Liu, Shijie; Tian, Zuhong; Zhang, Lei; Hou, Shuang; Hu, Sijun; Wu, Junshen; Jing, Yuming; Sun, Huimin; Yu, Fei; Zhao, Libo; Wang, Ruoxiang; Tseng, Hsian-Rong; Zhau, Haiyen E; Chung, Leland W K; Wu, Kaichun; Wang, Hao; Wu, Jason Boyang; Nie, Yongzhan; Shao, Chen

    2016-09-13

    Circulating tumor cells (CTCs) have emerged as promising tools for noninvasive cancer detection and prognosis. Most conventional approaches for capturing CTCs use an EpCAM-based enrichment strategy, which does not work well in cancers that show low or no expression of EpCAM, such as renal cell carcinoma (RCC). In this study, we developed a new set of cell surface markers including CA9 and CD147 as alternative CTC-capture antigens specifically designed for RCC patients. We showed that the expression of both CA9 and CD147 was prevalent in a RCC patient cohort (n=70) by immunohistochemical analysis, with both molecules in combination covering 97.1% of cases. The NanoVelcro platform combined with CA9-/CD147-capture antibodies demonstrated significantly higher efficiency for capturing both CTC-mimicking renal cancer cells and RCC CTCs in peripheral blood, compared to the conventional EpCAM-based method. Using immunofluorescence cytological validation at the single-cell level, we were able to identify bona fide CTCs in RCC patient blood following the well-accepted criteria in our CTC-capture system. We further demonstrated a significant association of CTC numbers as well as the CTC expression status of Vimentin, a mesenchymal marker, with disease progression, including pathologic features and clinical staging. These results provide new insights into developing novel, effective targets/approaches for capturing CTCs, making CTCs a valuable tool for improved cancer detection, prognosis and treatment in RCC.

  9. Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients

    PubMed Central

    Hou, Shuang; Hu, Sijun; Wu, Junshen; Jing, Yuming; Sun, Huimin; Yu, Fei; Zhao, Libo; Wang, Ruoxiang; Tseng, Hsian-Rong; Zhau, Haiyen E.; Chung, Leland W.K.; Wu, Kaichun; Wang, Hao; Wu, Jason Boyang; Nie, Yongzhan; Shao, Chen

    2016-01-01

    Circulating tumor cells (CTCs) have emerged as promising tools for noninvasive cancer detection and prognosis. Most conventional approaches for capturing CTCs use an EpCAM-based enrichment strategy, which does not work well in cancers that show low or no expression of EpCAM, such as renal cell carcinoma (RCC). In this study, we developed a new set of cell surface markers including CA9 and CD147 as alternative CTC-capture antigens specifically designed for RCC patients. We showed that the expression of both CA9 and CD147 was prevalent in a RCC patient cohort (n=70) by immunohistochemical analysis, with both molecules in combination covering 97.1% of cases. The NanoVelcro platform combined with CA9-/CD147-capture antibodies demonstrated significantly higher efficiency for capturing both CTC-mimicking renal cancer cells and RCC CTCs in peripheral blood, compared to the conventional EpCAM-based method. Using immunofluorescence cytological validation at the single-cell level, we were able to identify bona fide CTCs in RCC patient blood following the well-accepted criteria in our CTC-capture system. We further demonstrated a significant association of CTC numbers as well as the CTC expression status of Vimentin, a mesenchymal marker, with disease progression, including pathologic features and clinical staging. These results provide new insights into developing novel, effective targets/approaches for capturing CTCs, making CTCs a valuable tool for improved cancer detection, prognosis and treatment in RCC. PMID:27494883

  10. Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma

    PubMed Central

    Badalamenti, Giuseppe; Rizzo, Sergio; Pantuso, Gianni; Natoli, Clara; Russo, Antonio

    2016-01-01

    The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition. Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC. PMID:26872372

  11. Clinicians’ Real World Perceptions of Pre-Nephrectomy Diagnostic Biopsy Performance as a Driver of Reduction in Unnecessary Surgeries in Renal Tumors

    PubMed Central

    Augustine, Lauren; Sanden, Mats O.; Wassman, E. Robert

    2015-01-01

    Operative removal of oncocytomas is generally unnecessary, but not infrequent in the context of renal masses. The infrequent use of pre-nephrectomy biopsies is a function of historical limitations of histopathological differential diagnosis in this setting. Assessment of clinicians’ receptiveness to a novel molecular diagnostic approach to this challenge was undertaken by means of a survey vehicle administered to 102 practicing urologists and pathologists who met inclusion criteria related to their actual clinical activity. Survey results supported the previously reported observations on misdiagnosis with urologists’ reported rates of 25% inconclusive results, and an additional 17% disagree with the final surgical diagnosis. The self-reported rate of 9% for pre-operative biopsies was comparable to prior reports, but 39% of urologists who are not currently performing pre-operative biopsies expressed interest in introducing them into their practice for this purpose with an improved diagnostic. Almost all urologists (94%) felt it important not to resect benign oncocytomas and 62% indicated they would use a test which improved the ability to sub-type renal tumors pre-operatively. The level of performance benchmark of the unidentified prototypic microRNA-based diagnostic as reported previously in the literature was deemed sufficient to change care in these cases by 73%. Overall they predicted a 38% rate of biopsies and resulting increases in decisions to forgo nephrectomy or to perform only partial nephrectomy. Pathologists also expressed support for the use of this technology in the context of inadequate specimens and for improved sub-typing of these tumors in inconclusive cases.

  12. Nonfunctioning Juxtaglomerular Cell Tumor

    PubMed Central

    Sakata, Ryoko; Shimoyamada, Hiroaki; Yanagisawa, Masahiro; Murakami, Takayuki; Makiyama, Kazuhide; Nakaigawa, Noboru; Inayama, Yoshiaki; Ohashi, Kenichi; Nagashima, Yoji; Yao, Masahiro; Kubota, Yoshinobu

    2013-01-01

    The juxtaglomerular cell tumor (JGCT) is a rare renal tumor characterized by excessive renin secretion causing intractable hypertension and hypokalemia. However, asymptomatic nonfunctioning JGCT is extremely rare. Here, we report a case of nonfunctioning JGCT in a 31-year-old woman. The patient presented with a left renal tumor without hypertension or hypokalemia. Under a clinical diagnosis of renal cell carcinoma, radical nephrectomy was performed. The tumor was located in the middle portion adjacent to the renal pelvis, measuring 2 cm in size. Pathologically, the tumor was composed of cuboidal cells forming a solid arrangement, immunohistochemically positive for renin. Based on these findings, the tumor was diagnosed as JGCT. In cases with hyperreninism, preoperative diagnosis of JGCT is straightforward but difficult in nonfunctioning case. Generally, JGCT presents a benign biological behavior. Therefore, we should take nonfunctioning JGCT into the differential diagnoses for renal tumors, especially in younger patients to avoid excessive surgery. PMID:23607027

  13. The epigenetic modifier CHD5 functions as a novel tumor suppressor for renal cell carcinoma and is predominantly inactivated by promoter CpG methylation

    PubMed Central

    Du, Zhenfang; Li, Lili; Huang, Xin; Jin, Jie; Huang, Suming; Zhang, Qian; Tao, Qian

    2016-01-01

    Renal cell carcinoma (RCC) is the most common urological cancer with steadily increasing incidence. A series of tumor suppressor genes (TSGs) have been identified methylated in RCC as potential epigenetic biomarkers. We identified a 1p36.3 TSG candidate CHD5 as a methylated target in RCC through epigenome study. As the role of CHD5 in RCC pathogenesis remains elusive, we further studied its expression and molecular functions in RCC cells. We found that CHD5 was broadly expressed in most normal genitourinary tissues including kidney, but frequently silenced or downregulated by promoter CpG methylation in 78% of RCC cell lines and 44% (24/55) of primary tumors. In addition, CHD5 mutations appear to be rare in RCC tumors through genome database mining. In methylated/silenced RCC cell lines, CHD5 expression could be restored with azacytidine demethylation treatment. Ectopic expression of CHD5 in RCC cells significantly inhibited their clonogenicity, migration and invasion. Moreover, we found that CHD5, as a chromatin remodeling factor, suppressed the expression of multiple targets including oncogenes (MYC, MDM2, STAT3, CCND1, YAP1), epigenetic master genes (Bmi-1, EZH2, JMJD2C), as well as epithelial-mesenchymal transition and stem cell markers (SNAI1, FN1, OCT4). Further chromatin immunoprecipitation (ChIP) assays confirmed the binding of CHD5 to target gene promoters. Thus, we demonstrate that CHD5 functions as a novel TSG for RCC, but is predominantly inactivated by promoter methylation in primary tumors. PMID:26943038

  14. CD8+ T-cell clones specific for the 5T4 antigen target renal cell carcinoma tumor-initiating cells in a murine xenograft model.

    PubMed

    Tykodi, Scott S; Satoh, Shoko; Deming, Janise D; Chou, Jeffrey; Harrop, Richard; Warren, Edus H

    2012-09-01

    The tumor antigen 5T4 is frequently expressed at high levels on renal cell carcinoma (RCC) and other epithelial carcinomas. Surveys of normal tissues demonstrate abundant 5T4 expression on placental trophoblast cells with limited expression elsewhere. 5T4 is the target for a therapeutic cancer vaccine (MVA-5T4) that elicits 5T4-specific serological, proliferative, and cytotoxic T lymphocyte (CTL) responses. However, the antitumor activity of 5T4-specific CTL has not been extensively characterized. CD8 T cells from HLA-A2 healthy donors (n=4) or RCC patients (n=2) were stimulated in vitro with the HLA-A2-binding nonamer peptides 5T417-25 or 5T497-105 and screened by flow cytometry with specific tetramers (TET). CD8/TET T-cell clones specific for 5T417-25 or 5T497-105 peptide were isolated from 4/6 and 1/4 donors, respectively. A subset of clones specific for 5T417-25 was cytolytic for MVA-5T4-infected HLA-A2 EBV-transformed lymphoblastoid cell line target cells and for constitutively HLA-A2-expressing and 5T4-expressing RCC tumor cell lines (including A498 RCC). In a xenoengraftment assay, the coinoculation of a representative 5T417-25-specific CTL clone with A498 RCC tumors cells into immune-deficient mice completely prevented growth of A498 tumors. Taken together, these data demonstrate high-avidity CD8 CTL able to recognize the naturally processed 5T417-25 epitope on RCC tumor cells including putative tumor-initiating cells are present in peripheral blood of both healthy donors and RCC patients. CD8T-cell immunity targeting 5T417-25 is therefore of substantial interest both as a potential target for further development of vaccination or adoptive cellular immunotherapy and for immune monitoring studies in association with nonspecific immunotherapies.

  15. Redefining pT3 renal cell carcinoma in the modern era: a proposal for a revision of the current TNM primary tumor classification system.

    PubMed

    Margulis, Vitaly; Tamboli, Pheroze; Matin, Surena F; Meisner, Matthew; Swanson, David A; Wood, Christopher G

    2007-06-15

    The 2002 American Joint Committee on Cancer (AJCC) tumor classification for renal cell carcinoma (RCC) does not take into account concomitant venous invasion and extrarenal tumor extension (ERE). In the current study, the authors evaluated the prognostic significance of venous tumor thrombus (VTT) and its extent, the presence and location of ERE, and a combination of both features on survival after the surgical management of patients with pathologic T3 (pT3) RCC. With Institutional Review Board approval, the institutional nephrectomy database of 3470 patients treated at the University of Texas M. D. Anderson Cancer Center from 1990 to 2006 was searched for pT3 RCC patients who were treated with partial or radical nephrectomy. Patients with nonmetastatic, lymph node-negative RCC and a minimum follow-up of 6 months were included in the analysis. A total of 419 patients with pT3N0/NxM0 RCC and a mean follow-up of 40.8 months met the study inclusion criteria. In multivariate Cox regression analyses, the 2002 AJCC primary tumor classification was not found to be an independent predictor of cancer-specific mortality. A total of 211 patients with ERE only (50.4%) and 72 patients with VTT only (17.2%) were found to have a similar risk of death from RCC (hazards ratio [HR] of 1.018; P = .957), whereas 136 patients harboring both features (32.5%) were found to be significantly more likely to die from RCC (HR of 2.660; P < .001). The authors proposed a new primary tumor classification in which they grouped patients with both ERE and VTT (which was found to be an independent predictor of cancer-specific survival) into a separate staging category, and demonstrated improved prognostic ability when compared with the 2002 AJCC classification (c indexes of 0.625 vs 0.580, respectively). The prognostic accuracy of the 2002 AJCC pT3 tumor classification can be improved by subclassifying patients with ERE only and those with VTT only into a prognostic category that is separate from

  16. Renal oncocytoma: new observations

    SciTech Connect

    Quinn, M.J.; Hartman, D.S.; Friedman, A.C.; Sherman, J.L.; Lautin, E.M.; Pyatt, R.S.; Ho, C.K.; Csere, R.; Fromowitz, F.B.

    1984-10-01

    Renal oncocytomas are uncommon, benign tumors that can be treated by local incision or heminephrectomy; their preoperative differentiation from renal cell carcinoma, treated by radical nephrectomy, would be invaluable. A particularly important finding, a central scar, not stressed in previous reports, is frequently demonstrated by CT examination. The authors evaluated radiographic studies of 18 pathologically confirmed cases of oncocytoma and compared findings with results of CT, sonography, and angiogrpahy studies of 18 renal cell carcinoma cases. Oncocytomas can be suggested if a stellate scar is identified within an otherwise homogeneous tumor on ultrasound (US) and CT; if the mass appears homogeneous but no scar is present, angiography should be performed.

  17. Chromophobe cell renal carcinoma.

    PubMed

    Megumi, Y; Nishimura, K

    1998-01-01

    Chromophobe cell renal carcinoma is a recently established subtype of renal cell carcinoma. Herein we report a case of chromophobe cell renal carcinoma in a 67-year-old male patient who occasionally underwent computed tomography. In a microscopic study with hematoxylin and eosin stain, clear eosinophilic cytoplasm, and a moderately atypical nucleus were observed. And it was stained positively by Hale's colloidal iron. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. From these results, this tumor was pathologically diagnosed as chromophobe cell renal carcinoma.

  18. Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance

    PubMed Central

    Zhang, Xiao-Dong; Luo, Zhentao; Chen, Jie; Song, Shasha; Yuan, Xun; Shen, Xiu; Wang, Hao; Sun, Yuanming; Gao, Kai; Zhang, Lianfeng; Fan, Saijun; Leong, David Tai; Guo, Meili; Xie, Jianping

    2015-01-01

    Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall Au29–43(SG)27–37 nanoclusters (<2 nm) with a naturally-occurring peptide (e.g., glutathione or GSH) as the protecting shell. The GSH-coated Au29–43(SG)27–37 nanoclusters can escape the RES absorption, leading to a good tumor uptake (~8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au29–43(SG)27–37 nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy. PMID:25727895

  19. Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance

    NASA Astrophysics Data System (ADS)

    Zhang, Xiao-Dong; Luo, Zhentao; Chen, Jie; Song, Shasha; Yuan, Xun; Shen, Xiu; Wang, Hao; Sun, Yuanming; Gao, Kai; Zhang, Lianfeng; Fan, Saijun; Leong, David Tai; Guo, Meili; Xie, Jianping

    2015-03-01

    Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall Au29-43(SG)27-37 nanoclusters (<2 nm) with a naturally-occurring peptide (e.g., glutathione or GSH) as the protecting shell. The GSH-coated Au29-43(SG)27-37 nanoclusters can escape the RES absorption, leading to a good tumor uptake (~8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au29-43(SG)27-37 nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.

  20. Comprehensive Evaluation of Prostate-Specific Membrane Antigen Expression in the Vasculature of Renal Tumors: Implications for Imaging Studies and Prognostic Role.

    PubMed

    Spatz, Sophia; Tolkach, Yuri; Jung, Klaus; Stephan, Carsten; Busch, Jonas; Ralla, Bernhard; Rabien, Anja; Feldmann, Georg; Brossart, Peter; Bundschuh, Ralph A; Ahmadzadehfar, Hojjat; Essler, Markus; Toma, Marieta; Müller, Stefan C; Ellinger, Jörg; Hauser, Stefan; Kristiansen, Glen

    2017-08-18

    Prostate-specific membrane antigen (PSMA) is expressed by endothelium of many tumors. The aim of the study was to find a rationale for PSMA-based imaging and to investigate the prognostic role of vascular PSMA expression in patients with renal cell carcinoma (RCC). Two-hundred fifty seven patients with RCC were included with a median follow-up exceeding 10.0 years. PSMA expression on the tumor vessels was detected by immunohistochemistry. Vascular expression of FOLH1-gene (PSMA) mRNA was investigated in clear-cell RCC (ccRCC) and papillary RCC (pRCC) using The Cancer Genome Atlas (TCGA) data. Endothelial PSMA protein expression was higher in ccRCC than in pRCC and chromophobe RCC. Higher grade, higher stage, metastatic and lethal ccRCCs showed higher PSMA expression in tumor vessels. In both univariate and multivariate analysis intensity of endothelial PSMA protein expression (positive vs. negative) was significantly associated with overall survival. TCGA-based analyses confirm the prognostic role of vascular expression of FOLH1-mRNA and support the utility of PSMA-based imaging in ccRCC, but not in pRCC. We provide a rationale for further development of PSMA-targeted imaging in ccRCC. The prognostic role of PSMA was shown both at the protein (ccRCC) and mRNA-levels (ccRCC and pRCC). Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

    PubMed

    Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

    2016-09-01

    To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

  2. Repurposing the anti-malarial drug artesunate as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation of tumor growth, metastasis, and angiogenesis

    PubMed Central

    Lim, Sharon; Lee, Se Jeong; Lim, Joung Eun; Nam, Do-Hyun; Joo, Kyeung Min; Jeong, Byong Chang; Jeon, Seong Soo; Choi, Han Yong; Lee, Hye Won

    2015-01-01

    Despite advances in the development of molecularly targeted therapies, metastatic renal cell carcinoma (RCC) is still incurable. Artesunate (ART), a well-known anti-malarial drug with low toxicity, exhibits highly selective anti-tumor actions against various tumors through generation of cytotoxic carbon-centered free radical in the presence of free iron. However, the therapeutic efficacy of ART against metastatic RCC has not yet been fully elucidated. In the analysis on a dataset from The Cancer Genome Atlas (TCGA) (n = 469) and a tissue microarray set from Samsung Medical Center (n = 119) from a cohort of patients with clear cell RCC (ccRCC), up-regulation of transferrin receptor 1 (TfR1), which is a well-known predictive marker for ART, was correlated with the presence of distant metastasis and an unfavorable prognosis. Moreover, ART exerted potent selective cytotoxicity against human RCC cell lines (Caki-1, 786-O, and SN12C-GFP-SRLu2) and sensitized these cells to sorafenib in vitro, and the extent of ART cytotoxicity correlated with TfR1 expression. ART-mediated growth inhibition of human RCC cell lines was shown to result from the induction of cell cycle arrest at the G2/M phase and oncosis-like cell death. Furthermore, ART inhibited cell clonogenicity and invasion of human RCC cells and anti-angiogenic effects in vitro in a dose-dependent manner. Consistent with these in vitro data, anti-tumor, anti-metastatic and anti-angiogenic effects of ART were also validated in human 786-O xenografts. Taken together, ART is a promising novel candidate for treating human RCC, either alone or in combination with other therapies. PMID:26426994

  3. Upregulation of Far Upstream Element-Binding Protein 1 (FUBP1) Promotes Tumor Proliferation and Tumorigenesis of Clear Cell Renal Cell Carcinoma

    PubMed Central

    Duan, Junyao; Bao, Xu; Ma, Xin; Zhang, Yu; Ni, Dong; Wang, Hanfeng; Zhang, Fan; Du, Qingshan; Fan, Yang; Chen, Jianwen; Wu, Shengpan; Li, Xintao; Gao, Yu

    2017-01-01

    Objective The far upstream element (FUSE)-binding protein 1 (FUBP1) is a transactivator of human c-myc proto-oncogene transcription, with important roles in carcinogenesis. However, the expression pattern and potential biological function of FUBP1 in clear cell renal cell carcinoma (ccRCC) is yet to be established. Methods FUBP1 expression was detected in ccRCC tissues and cell lines by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The correlations of FUBP1 mRNA expression levels with clinicopathological factors were evaluated. The biological function of FUBP1 during tumor cell proliferation was studied by MTS, colony formation, and soft-agar colony formation. The effects of FUBP1 on cell cycle distribution and apoptosis were analyzed by flow cytometry. Western blot analysis was used to identify the potential mechanism of FUBP1 regulating cell cycle and apoptosis. Results The levels of FUBP1 mRNA and protein expression were upregulated in human ccRCC tissues compared with adjacent noncancerous tissues. High levels of FUBP1 mRNA expression were associated with higher tumor stage and tumor size. FUBP1 knockdown inhibited cell proliferation and induced cell cycle arrest and apoptosis. Meanwhile, the expression levels of c-myc and p21 mRNA were correlated with that of FUBP1 mRNA. Conclusions FUBP1 acts as a potential oncogene in ccRCC and may be considered as a novel biomarker or an attractive treatment target of ccRCC. PMID:28076379

  4. Improving the prognostic value of disease specific Graded Prognostic Assessment (ds-GPA) model for renal cell carcinoma by incorporation of Cumulative Intracranial Tumor Volume (CITV).

    PubMed

    Ali, Mir Amaan; Hirshman, Brian R; Wilson, Bayard; Schupper, Alexander J; Joshi, Rushikesh; Proudfoot, James A; Goetsch, Steven J; Alksne, John F; Ott, Kenneth; Aiyama, Hitoshi; Nagano, Osamu; Carter, Bob S; Chiang, Veronica; Serizawa, Toru; Yamamoto, Masaaki; Chen, Clark C

    2017-07-25

    We tested the prognostic value of cumulative intracranial tumor volume (CITV) in the context of ds-GPA model for renal cell carcinoma (RCC) patients with brain metastasis (BM) treated with stereotactic radiosurgery (SRS). Patient and tumor characteristics were collected from RCC cohorts with newly BM who underwent SRS. Univariable and multivariable logistic regression model was used to test the prognostic value of CITV, Karnofsky Performance Score (KPS), and the number of BM. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to assess whether CITV improved the prognostic utility of RCC ds-GPA. In univariable logistic regression models, CITV, KPS, and the number of BM independently associated with RCC patient survival. In a multivariable Cox proportional hazard model, the association between CITV and survival remained robust after controlling for KPS and the number of BM (P=.042). The incorporation of the cumulative intracranial tumor volume (CITV) into the RCC ds-GPA model (consisting of KPS and number of BM) improved prognostic accuracy with NRI>0 of 0.3156 (95% CI: 0.0883-0.5428, P=.0065) and integrated discrimination improvement (IDI) of 0.0151 (95% CI: 0.0036-0.0277, P=.0183). These findings were validated in an independent cohort of 107 SRS-treated RCC BM patients. CITV is an important prognostic variable in SRS-treated RCC patients with BM. The prognostic value of the ds-GPA scale for RCC brain metastasis was enhanced by the incorporation of CITV. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Repurposing the anti-malarial drug artesunate as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation of tumor growth, metastasis, and angiogenesis.

    PubMed

    Jeong, Da Eun; Song, Hye Jin Jin; Lim, Sharon; Lee, Se Jeong Jeong; Lim, Joung Eun; Nam, Do-Hyun; Joo, Kyeung Min; Jeong, Byong Chang; Jeon, Seong Soo; Choi, Han Yong; Lee, Hye Won

    2015-10-20

    Despite advances in the development of molecularly targeted therapies, metastatic renal cell carcinoma (RCC) is still incurable. Artesunate (ART), a well-known anti-malarial drug with low toxicity, exhibits highly selective anti-tumor actions against various tumors through generation of cytotoxic carbon-centered free radical in the presence of free iron. However, the therapeutic efficacy of ART against metastatic RCC has not yet been fully elucidated. In the analysis on a dataset from The Cancer Genome Atlas (TCGA) (n = 469) and a tissue microarray set from Samsung Medical Center (n = 119) from a cohort of patients with clear cell RCC (ccRCC), up-regulation of transferrin receptor 1 (TfR1), which is a well-known predictive marker for ART, was correlated with the presence of distant metastasis and an unfavorable prognosis. Moreover, ART exerted potent selective cytotoxicity against human RCC cell lines (Caki-1, 786-O, and SN12C-GFP-SRLu2) and sensitized these cells to sorafenib in vitro, and the extent of ART cytotoxicity correlated with TfR1 expression. ART-mediated growth inhibition of human RCC cell lines was shown to result from the induction of cell cycle arrest at the G2/M phase and oncosis-like cell death. Furthermore, ART inhibited cell clonogenicity and invasion of human RCC cells and anti-angiogenic effects in vitro in a dose-dependent manner. Consistent with these in vitro data, anti-tumor, anti-metastatic and anti-angiogenic effects of ART were also validated in human 786-O xenografts. Taken together, ART is a promising novel candidate for treating human RCC, either alone or in combination with other therapies.

  6. Leiomyoma Arising from Mullerian Remnant, Mimicking Ovarian Tumor in a Woman with MRKH Syndrome and Unilateral Renal Agenesis.

    PubMed

    Girma, Wubishet; Woldeyes, Wondimagegnehu

    2015-10-01

    Leiomyoma with secondary changes arising from Mullerian remnant may mimic ovarian tumor in women with Mayer-Rockitansky-Kuster-Hauser (MRKH) syndrome in patients with pelvic mass and urologic abnormalities. The patient was a 40 years old known case of MRKH, presented with lower abdominal pain and swelling for over one year. On physical examination, large pelvic mass (about 15cm by 10cm) was found and a diagnosis of ovarian tumor was made by imaging which also showed absent right kidney. Finally, the mass was found to be a big leiomyoma with areas of hyaline, edematous and cystic degenerations. Although leiomyoma arising from rudimentary Mullerian bulb is a rare condition, it should be considered in differential diagnosis of pelvic mass in patients with MRKH. Possibility of urologic abnormalities should also be considered in these patients and appropriate work up per local context should be made.

  7. Renal Artery Embolization

    PubMed Central

    Sauk, Steven; Zuckerman, Darryl A.

    2011-01-01

    Renal artery embolization (RAE) is an effective minimally invasive alternative procedure for the treatment of a variety of conditions. Since the 1970s when RAE was first developed, technical advances and growing experience have expanded the indications to not only include treatment of conditions such as symptomatic hematuria and palliation for metastatic renal cancer, but also preoperative infarction of renal tumors, treatment of angiomyolipomas, vascular malformations, medical renal disease, and complications following renal transplantation. With the drastically improved morbidity associated with this technique in part due to the introduction of more precise embolic agents and smaller delivery catheters, RAE continues to gain popularity for various urologic conditions. The indications and techniques for renal artery embolization are reviewed in the following sections. PMID:23204638

  8. Tumor Genetic Analyses of Patients with Metastatic Renal Cell Carcinoma and Extended Benefit from mTOR Inhibitor Therapy

    PubMed Central

    Voss, Martin H.; Hakimi, A. Ari; Pham, Can G.; Brannon, A. Rose; Chen, Ying-Bei; Cunha, Luis F.; Akin, Oguz; Liu, Han; Takeda, Shugaku; Scott, Sasinya N.; Socci, Nicholas D.; Viale, Agnes; Schultz, Nikolaus; Sander, Chris; Reuter, Victor E.; Russo, Paul; Cheng, Emily H.; Motzer, Robert J.; Berger, Michael F.; Hsieh, James J.

    2014-01-01

    Purpose Rapalogs are allosteric mTOR inhibitors and approved agents for advanced kidney cancer. Reports of clonal heterogeneity in this disease challenge the concept of targeted monotherapy, yet a small subset of patients derives extended benefit. Our aim was to analyze such outliers and explore the genomic background of extreme rapalog sensitivity in the context of intratumor heterogeneity. Experimental Design We analyzed archived tumor tissue of five RCC patients, who previously achieved durable disease control with rapalogs (median duration 28 months). DNA was extracted from spatially separate areas of primary tumors and metastases. Custom target capture and ultra-deep sequencing was used to identify alterations across 230 target genes. Whole exome sequence analysis was added to investigate genes beyond this original target list. Results Five long-term responders contributed 14 specimens to explore clonal heterogeneity. Genomic alterations with activating effect on mTOR signaling were detected in 11 of 14 specimens, offering plausible explanation for exceptional treatment response through alterations in two genes (TSC1, MTOR). In two subjects, distinct yet functionally convergent alterations activated the mTOR pathway in spatially separate sites. In one patient, concurrent genomic events occurred in two separate pathway components across different tumor regions. Conclusions Analysis of outlier cases can facilitate identification of potential biomarkers for targeted agents, and we implicate two genes as candidates for further study in this class of drugs. The previously reported phenomenon of clonal convergence can occur within a targetable pathway which might have implications for biomarker development beyond this disease and this class of agents. PMID:24622468

  9. Computed tomography of renal oncocytoma

    SciTech Connect

    Levine, E.; Huntrakoon, M.

    1983-10-01

    Renal oncocytoma is a relatively rare tumor that has an excellent prognosis and usually may be treated adequately by local resection. Preoperative differentiation from renal cell carcinoma, which requires radical nephrectomy, is thus of importance. The computed tomographic (CT) and pathologic features of three incidentally-detected renal oncocytomas were compared with those of six renal cell carcinomas of comparable size. Renal cell carcinoma appears on CT as a solid mass that generally has an indistinct interface with normal renal parenchyma, a lobulated contour, and a nonhomogeneous pattern of contrast enhancement. These features correlate with the pathologic findings of an irregular tumor margin and the frequent presence of tumor hemorrhage and necrosis. Oncocytoma, on the other hand, generally has a distinct margin, a smooth contour, and a homogeneous appearance on contrast-enhanced CT scans. These findings correlate with a smooth tumor margin and absence of tumor hemorrhage and necrosis on pathologic examination. These features are not pathognomonic of oncocytoma, as angiographic evidence suggests that renal cell carcinoma may show both distinct margination and a homogeneous blush in 6% of cases. However, their demonstration by CT should alert radiologists and surgeons to the possibility that a renal mass may be an oncocytoma. Such a presumptive diagnosis then can lead to a surgical approach that allows for renal-conserving surgery.

  10. A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

    ClinicalTrials.gov

    2017-08-17

    Ewing Sarcoma; Gastrointestinal Tumor; Germ Cell Tumor; Hepatic Tumor; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Clear Cell Carcinoma; Renal Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma

  11. Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma.

    PubMed

    Hirata, Hiroshi; Hinoda, Yuji; Nakajima, Koichi; Kawamoto, Ken; Kikuno, Nobuyuki; Ueno, Koji; Yamamura, Soichiro; Zaman, Mohd S; Khatri, Gaurav; Chen, Yi; Saini, Sharanjot; Majid, Shahana; Deng, Guoren; Ishii, Nobuhisa; Dahiya, Rajvir

    2011-04-15

    The functional significance of Wnt antagonist DKK1 has not been investigated in renal cell carcinoma (RCC). Therefore, we hypothesized that DKK1 may be a tumor suppressor gene and is epigenetically silenced, thus decreased DKK1 may cause progression of RCC. To assess the function of DKK1, we established stable DKK1 transfected cells and monitored them regarding cell viability, colony formation, apoptosis, cell cycle, and invasive capability. RCC cell lines had decreased levels of DKK1, which were increased after treatment with 5-Aza-2'-deoxycytidine and trichostatin A. In chromatin immunoprecipitation assay, the level of dimethyl H3K9 and trimethyl H3K27 was decreased after 5-Aza-2'-deoxycytidine/trichostatin A treatment in RCC cell lines. Increased methylation was also associated with higher pathological stages in primary RCC tissues. T-cell factor/lymphoid enhancer factor activity and nuclear beta-catenin expression were not changed in DKK1 transfectants. Also the expression of cyclinD1 and c-Myc was not changed in DKK1 transfectants. These results suggest that DKK1 may not be involved in the beta-catenin dependent pathway. We also evaluated the expression of various related genes. Cleaved caspase3, p53, p21 and puma expression were significantly upregulated in the DKK1 transfected cells. The population of apoptotic cells was increased in stable DKK1 cells and tumor growth suppression was also observed in nude mice with DKK1 transfected cells. In conclusion, this is the first report to show that DKK1 expression is epigenetically silenced in kidney cancer and its reexpression induces apoptosis and cell cycle arrest in RCC.

  12. Phase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat in advanced renal cell carcinoma and other solid tumors

    PubMed Central

    Zibelman, Matthew; Wong, Yu-Ning; Devarajan, Karthik; Malizzia, Lois; Corrigan, Alycia; Olszanski, Anthony J.; Denlinger, Crystal S.; Roethke, Susan K.; Tetzlaff, Colleen H.; Plimack, Elizabeth R.

    2015-01-01

    Background Drugs inhibiting the mammalian target of rapamycin (mTOR) are approved in the treatment of renal cell carcinoma (RCC), but resistance inevitably emerges. Proposed escape pathways include increased phosphorylation of Akt, which can be down regulated by histone deacetylase (HDAC) inhibitors. We hypothesized that co-treatment with the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat may abrogate resistance in RCC. Methods This phase 1 study evaluated the co-administration of ridaforolimus and vorinostat in patients with advanced solid tumors. The primary objective was to determine the maximum tolerated dose (MTD) in RCC patients. Although all solid tumors were allowed, prior cytotoxic chemotherapy was limited to 1 regimen. Using a modified 3+3 dose escalation design, various dose combinations were tested concurrently in separate cohorts. Efficacy was a secondary endpoint. Results Fifteen patients were treated at one of three dose levels, thirteen with RCC (10 clear cell, 3 papillary). Dosing was limited by thrombocytopenia. The MTD was determined to be ridaforolimus 20mg daily days 1–5 with vorinostat 100mg BID days 1–3 weekly, however late onset thrombocytopenia led to a lower recommended phase II dose: ridaforolimus 20mg daily days 1–5 with vorinostat 100mg daily days 1–3 weekly. Two patients, both with papillary RCC, maintained disease control for 54 and 80 weeks, respectively. Conclusions The combination of ridaforolimus and vorinostat was tolerable at the recommended phase II dose. Two patients with papillary RCC experienced prolonged disease stabilization, thus further study of combined HDAC and mTOR inhibition in this population is warranted. PMID:26091915

  13. Breast cancer metastatic to the kidney with renal vein involvement.

    PubMed

    Nasu, Hatsuko; Miura, Katsutoshi; Baba, Megumi; Nagata, Masao; Yoshida, Masayuki; Ogura, Hiroyuki; Takehara, Yasuo; Sakahara, Harumi

    2015-02-01

    The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

  14. Molecular imaging of late somatostatin receptor-positive metastases of renal cell carcinoma in the pancreas by 68Ga DOTATOC PET/CT: a rare differential diagnosis to multiple primary pancreatic neuroendocrine tumors.

    PubMed

    Peter, Luisa; Sänger, Jörg; Hommann, Merten; Baum, Richard Paul; Kaemmerer, Daniel

    2014-08-01

    Ga somatostatin receptor PET/CT, currently the most sensitive imaging modality for well-differentiated neuroendocrine tumors, is based on the molecular imaging of somatostatin receptors (SSTRs) that are expressed in different tumor entities such as neuroendocrine neoplasms, lymphomas, meningiomas, or renal cell cancer (RCC). Most neuroendocrine neoplasms show a high expression of SSTR subtypes 2A and 5, whereas the overexpression of SSTR2A in RCC is mainly seen in peritumoral vessels. Here we report a case with strongly SSTR-positive pancreatic lesions detected by Ga DOTATOC PET/CT, which histologically turned out to be ultralate metastases of a RCC.

  15. Renal primitive neuroectodermal tumor as a second malignancy after chemotherapy and radiation for Non-Hodgkin's Lymphoma--treatment-related or just poor old bad luck?: A case report.

    PubMed

    de Menezes, Jean-Louis; Patil, Hitendra M; Kannan, R; Pradhan, Sultan A

    2015-01-01

    Peripheral primitive neuroectodermal tumor (PNET) is a rare histology to be found in primary tumors of the kidney. There are less than a hundred cases reported in the English literature. Most of these have been diagnosed after surgery for a renal neoplasm diagnosed on imaging. PNET has rarely been reported as a second malignancy, and has never been reported as a second malignancy after non-Hodgkin's lymphoma (NHL). Herein, we present our case of a 38-year-old female who developed a second malignancy in the kidney after the treatment for NHL.

  16. Renal tubular and adrenal medullary tumors in the 2-year rat study with canagliflozin confirmed to be secondary to carbohydrate (glucose) malabsorption in the 15-month mechanistic rat study.

    PubMed

    De Jonghe, Sandra; Johnson, Mark D; Mamidi, Rao N V S; Vinken, Petra; Feyen, Bianca; Lammens, Godelieve; Proctor, Jim

    2017-09-12

    During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet. Canagliflozin-dosed rats on standard diet showed presence of basophilic renal tubular tumors (6/90) and an increased incidence of adrenal medullary hyperplasia (35/90), which was fully prevented by feeding a glucose-free diet (no RTT's; adrenal medullary hyperplasia in ≤5/90). These data further confirm that kidney and adrenal medullary tumors in the 2-year rat study were secondary to carbohydrate (glucose) malabsorption and were not due to a direct effect of canagliflozin on these target tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Primary Renal Primitive Neuroectodermal Tumor/Ewing’s Sarcoma Imaging and Pathologic Findings of a Patient with a Nine Year, Eight Month Disease Free Period: Case Report and Review of Literature

    PubMed Central

    Zokalj, Ivan; Igrec, Jasminka; Plesnar, Antonio

    2016-01-01

    Introduction Primitive neuroectodermal tumor (PNET)/Ewing’s sarcoma (EWS) belongs to a family of neoplasms that are presumed to originate from the neuroectodermal crest. PNET/EWSs are highly aggressive malignancies that usually present in the form of bone or soft tissue masses and usually affect adolescents and young adults. Primary PNET/EWS of the kidney is very rare. Case Presentation We present the case of a 32-year-old female patient with primary renal PNET/EWS diagnosed nine years and eight months earlier. The patient presented with acute flank pain in the left lumbar region, hematuria, and episodes of high body temperature of 40°C. Abdominal ultrasound (US) and subsequently performed computed tomography (CT) revealed a large renal mass of heterogenous structure. The kidney tumor had central necrotic hypodense areas and strongly peripherally enhanced solid parts on postcontrast CT images. Immunohistochemistry revealed positivity for CD99 and neuron-specific enolase (NSE). Tumor cells were negative for CD3, CD 20, chromogranin, synaptophysin, vimentin, and neurofilament. Reverse transcription polymerase change reaction (RT-PCR) revealed EWS/FL1 translocation type 2. The patient underwent nephrectomy and polychemotherapy. The follow-up nine years and eight months after the diagnosis showed no evidence of tumor. Conclusions PNET/EWS should be included in the differential diagnosis of renal tumors in symptomatic young adults. Patients with localised PNET/EWS treated with a combination of surgery and chemotherapy have an excellent chance of long-term survival, as in the case we have presented. PMID:27703957

  18. Transarterial embolization (TAE) as add-on to percutaneous radiofrequency ablation (RFA) for the treatment of renal tumors: Review of the literature, overview of state-of-the-art embolization materials and further perspective of advanced image-guided tumor ablation.

    PubMed

    Sommer, C M; Pallwein-Prettner, L; Vollherbst, D F; Seidel, R; Rieder, C; Radeleff, B A; Kauczor, H U; Wacker, F; Richter, G M; Bücker, A; Rodt, T; Massmann, A; Pereira, P L

    2017-01-01

    Percutaneous radiofrequency ablation (RFA) for the treatment of stage I renal cell carcinoma has recently gained significant attention as the now available long-term and controlled data demonstrate that RFA can result in disease-free and cancer-specific survival comparable with partial and/or radical nephrectomy. In the non-controlled single center trials, however, the rates of treatment failure vary. Operator experience and ablation technique may explain some of the different outcomes. In the controlled trials, a major limitation is the lack of adequate randomization. In case reports, original series and overview articles, transarterial embolization (TAE) before percutaneous RFA was promising to increase tumor control and to reduce complications. The purpose of this study was to systematically review the literature on TAE as add-on to percutaneous RFA for renal tumors. Specific data regarding technique, tumor and patient characteristics as well as technical, clinical and oncologic outcomes have been analyzed. Additionally, an overview of state-of-the-art embolization materials and the radiological perspective of advanced image-guided tumor ablation (TA) will be discussed. In conclusion, TAE as add-on to percutaneous RFA is feasible and very effective and safe for the treatment of T1a tumors in difficult locations and T1b tumors. Advanced radiological techniques and technologies such as microwave ablation, innovative embolization materials and software-based solutions are now available, or will be available in the near future, to reduce the limitations of bland RFA. Clinical implementation is extremely important for performing image-guided TA as a highly standardized effective procedure even in the most challenging cases of localized renal tumors.

  19. Recurrent deletion of the short arm of chromosome 3 in human renal cell carcinoma: shift of the c-raf 1 locus.

    PubMed

    Teyssier, J R; Henry, I; Dozier, C; Ferre, D; Adnet, J J; Pluot, M

    1986-12-01

    A cytogenetic study performed on 6 human renal cell carcinomas after short-term culture on extracellular matrix with serum-free medium showed aneuploidy without structural changes in 2 tumors and a rearrangement of the short arm of chromosome 3 in 4 tumors, including deletions and a translocation involving the 3p14 and 3p21 bands. Chromosomal in situ hybridization with a c-raf 1 probe demonstrated that in 2 renal cancers with del3(p14 or 21) the cellular oncogene had shifted from 3p25 to 3p14 as a result of an interstitial deletion.

  20. Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma

    PubMed Central

    KUROZUMI, AKIRA; KATO, MAYUKO; GOTO, YUSUKE; MATSUSHITA, RYOSUKE; NISHIKAWA, RIKA; OKATO, ATSUSHI; FUKUMOTO, ICHIRO; ICHIKAWA, TOMOHIKO; SEKI, NAOHIKO

    2016-01-01

    Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that microRNA-26a (miRNA-26a) and microRNA-26b (miRNA-26b) were significantly reduced in cancer tissues. To date, few reports have provided functional analyses of miR-26a or miR-26b in renal cell carcinoma (RCC). The aim of the present study was to investigate the functional significance of miR-26a and miR-26b in RCC and to identify novel miR-26a/b-mediated cancer pathways and target genes involved in RCC oncogenesis and metastasis. Downregulation of miR-26a or miR-26b was confirmed in RCC clinical specimens. Restoration of miR-26a or miR-26b in RCC cell lines (786-O and A498) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analysis and luciferase reporter assays showed that lysyl oxidase-like 2 (LOXL2) and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were directly regulated by these miRNAs. Moreover, downregulating the PLOD2 gene significantly inhibited cell migration and invasion in RCC cells. Thus, our data showed that two genes promoting metastasis, LOXL2 and PLOD2, were epigenetically regulated by tumor-suppressive microRNAs, miR-26a and miR-26b, providing important insights into the molecular mechanisms of RCC metastasis. PMID:26983694

  1. Multi-disciplinary surgical approach to the management of patients with renal cell carcinoma with venous tumor thrombus: 15 year experience and lessons learned.

    PubMed

    Gayed, Bishoy A; Youssef, Ramy; Darwish, Oussama; Kapur, Payal; Bagrodia, Aditya; Brugarolas, James; Raj, Ganesh; DiMaio, J Michael; Sagalowsky, Arthur; Margulis, Vitaly

    2016-07-19

    The management of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. We report our 15 year experience in the management of patients with RCC with VTT utilizing a multidisciplinary team approach, highlighting improved total and specifically Clavien III-V complication rates. We reviewed the records of 146 consecutive patients who underwent radical nephrectomy with venous thrombectomy between 1998 and 2012. Data on patient history, staging, surgical techniques, morbidity, and survival were analyzed. Additionally, complication rates between two surgical eras, 1998-2006 and 2006-2012, were assessed. The study included 146 patients, 97 males (66 %), and a median age of 61 years (range, 24-83). Overall complications rate was 53 %, high grade complications (Clavien III -V) occurred in 10 % of patients. Most importantly, there was a lower incidence of overall and high grade complications (45 % and 8 %, respectively) in the last 6 years compared to the earlier surgeries included in the study (67 % and 13 % respectively) [p = .008 and .03, respectively). 30 day postoperative mortality was 2.7 %. 5 year overall survival (5Y- OS) and 5 year cancer specific survival (5Y- CSS) were 51 % and 40 %, respectively. Metastasis was the only independent predictor factor for CSS (HR 3.8, CI 1.9-7.6 and p < .001) and OS (HR 2.6, CI 1.5-4.7 and p = .001) in all patients. Our data suggest that patients with RCC and VTT can be treated safely utilizing a multidisciplinary team approach leading to a decrease in complication rates.

  2. Multiple oncocytomas and renal carcinoma

    SciTech Connect

    Velasquez, G.; Glass, T.A.; D'Souza, V.J.; Formanek, A.G.

    1984-01-01

    Renal oncocytoma, although rare, is being diagnosed more frequently, and criteria to differentiate it from other tumors have been described. Multiple oncocytomas have been reported, but an association between multiple oncocytomas and renal carcinoma in the same kidney has not been described. The authors report a case with two oncocytomas and a renal carcinoma in the right kidney as well as a right adrenal adenoma.

  3. Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

    ClinicalTrials.gov

    2017-02-17

    Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors

  4. Tubulocystic Renal Cell Carcinoma: A Great Imitator

    PubMed Central

    Banerjee, Indraneel; Yadav, Sher Singh; Tomar, Vinay; Yadav, Suresh; Talreja, Shyam

    2016-01-01

    Tubulocystic renal cell carcinoma (TCRC) is a rare renal tumor. Patients are usually asymptomatic; it is usually detected incidentally, during imaging studies for Bosniak type III and type IV renal cysts. These tumors rarely metastasize. The role of targeted therapy in such rare tumors is still controversial. We report a case of TCRC initially presented as a Bosniak type II renal cyst and was discovered ultimately to be a metastatic disease. This type of presentation might broaden our understanding of this rare disease. PMID:27601972

  5. Renal masses presenting 25 and 50 years following blunt renal trauma.

    PubMed

    Pruthi, R S; Issa, M M; Kabalin, J N; Terris, M K

    1998-10-01

    The long-term consequences of blunt renal trauma are not well described. We report on 2 patients with a history of blunt renal trauma who presented with radiographically detected renal masses suspicious for renal tumor. Both patients suffered blows to the kidney during boxing matches followed by flank pain and hematuria. The injuries occurred 25 and 50 years prior to the detection of renal masses. Subsequent nephrectomy and histopathological evaluation revealed benign dystrophic renal tissue. These presentations represent probable long-term sequelae of blunt renal trauma.

  6. Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma.

    PubMed

    Motzer, Robert J; Hutson, Thomas E; Hudes, Gary R; Figlin, Robert A; Martini, Jean-Francois; English, Patricia A; Huang, Xin; Valota, Olga; Williams, J Andrew

    2014-10-01

    Sunitinib is a first-line advanced renal cell carcinoma (RCC) standard of care. In a randomized phase II trial comparing sunitinib treatment schedules, separate exploratory biomarker analyses investigated the correlations of efficacy with selected serum, germ line single-nucleotide polymorphism (SNP), or tumor markers. Advanced RCC patients received first-line sunitinib 50 mg/day on the approved 4-week-on-2-week-off schedule (n = 146) or 37.5 mg/day continuous dosing (n = 146). The following correlation analyses were performed: (1) response evaluation criteria in solid tumors-defined tumor response with serum soluble protein levels via two distinct multiplex (n < 1,000) platforms; (2) response and time-to-event outcomes with germ line SNPs in vascular endothelial growth factor (VEGF)-A and VEGF receptor (VEGFR)3 genes; and (3) response and time-to-event outcomes with tumor immunohistochemistry status for hypoxia-inducible factor 1-alpha (HIF-1α) and carbonic anhydrase-IX or tumor Von Hippel-Lindau (VHL) gene inactivation status. Lower baseline angiopoietin-2 (Ang-2) and higher baseline matrix metalloproteinase-2 (MMP-2) levels were identified by both platforms as statistically significantly associated with tumor response. There were no significant correlations between VEGF-A or VEGFR3 SNPs and outcomes. Progression-free survival was longer for HIF-1α percent of tumor expression groups 0-2 (HIF-1α low) versus 3-4 (HIF-1α high; p = 0.034). There were no significant correlations between outcomes and each VHL inactivation mechanism [mutation (86% of VHL-inactive patients), methylation (14%), and large deletion (7%)] or mechanisms combined. Serum Ang-2 and MMP-2 and tumor HIF-1α were identified as relevant baseline biomarkers of sunitinib activity in advanced RCC, warranting further research into their prognostic versus predictive value.

  7. Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors

    ClinicalTrials.gov

    2016-10-13

    Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Rhabdoid Tumor; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Germ Cell Tumors; Ewings Sarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcoma; Osteosarcoma; Rhabdomyosarcoma

  8. Renal autotransplantation: current perspectives.

    PubMed

    Stewart, B H; Banowsky, L H; Hewitt, C B; Straffon, R A

    1977-09-01

    Autotransplantation, with or without an extracorporeal renal operation, has been done 39 times in 37 patients. Indications for the procedure included several ureteral injury in 4 patients, failed supravesical diversion in 2, renal carcinoma in a solitary kidney in 1, renovascular hypertension in 1 and donor arterial reconstruction before renal transplantation in 29. Success was obtained in all but 2 procedures, both of which involved previously operated kidneys with severe inflammation and adhesions involving the renal pelvis and pedicle. Based on our experience and a review of currently available literature we believe that renal autotransplantation and extracorporeal reconstruction can provide the best solution for patients with severe renovascular and ureteral disease not correctable by conventional operative techniques. The technique can be of particular value in removing centrally located tumors in solitary kidneys and in preparing donor kidneys with abnormal arteries for renal transplantation. The role of autotransplantation in the management of advanced renal trauma and calculus disease is less clear. A long-term comparison of patients treated by extracorporeal nephrolithotomy versus conventional lithotomy techniques will be necessary before a conclusion is reached in these disease categories.

  9. Renal autotransplantation: current perspectives.

    PubMed

    Stewart, B H; Banowsky, L H; Hewitt, C B; Straffon, R A

    1976-01-01

    Autotransplantation, with or without an extracorporeal renal operation, has been done 39 times in 37 patients. Indications for the procedure included severe ureteral injury in 4 patients, failed supravesical diversion in 2, renal carcinoma in a solitary kidney in 1, renovascular hypertension in 1 and donor arterial reconstruction before renal transplantation in 29. Success was obtained in all but 2 procedures, both of which involved previously operated kidneys with severe inflammation and adhesions involving the renal pelvis and pedicle. Based on our experience and a review of currently available literature we believe that renal autotransplantation and extracorporeal reconstruction can provide the best solution for patients with severe renovascular and ureteral disease not correctable by conventional operative techniques. The technique can be of particular value in removing centrally located tumors in solitary kidneys and in preparing donor kidneys with abnormal arteries for renal transplantation. The role of autotransplantation in the management of advanced renal trauma and calculus disease is less clear. A long-term comparison of patients treated by extracorporeal nephrolithotomy versus conventional lithotomy techniques will be necessary before a conclusion is reached in these disease categories.

  10. Contemporary Renal Cell Cancer Epidemiology

    PubMed Central

    Chow, Wong-Ho; Devesa, Susan S.

    2010-01-01

    We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to TCE has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the VHL gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers. PMID:18836333

  11. The scintigraphic pattern of renal angiomyolipoma

    SciTech Connect

    Jaikishen, P.; Oster, Z.H.; Atkins, H.L. )

    1990-03-01

    The patterns of renal and gallium scintigraphy in a patient with renal angiomyolipoma are presented. Renal study with Tc-99m DTPA demonstrated a photopenic area in the flow and delayed images. Ga-67 citrate imaging did not show any evidence of increased activity. Although this pattern is also seen in renal cysts, scintigraphy seems to be valuable in the evaluation of angiomyolipoma. It helps differentiate it from renal carcinoma or renal abscess (which may be gallium avid), especially when the tumor is characterized by a paucity of adipose tissue and complicated by hemorrhage, in which case CT and ultrasonographic patterns are not diagnostic.

  12. Tumor-specific loss of 11p15. 5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma

    SciTech Connect

    Henry, I.; Grandjouan, S.; Couillin, P.; Barichard, F.; Huerre-Jeanpierre, C.; Glaser, T.; Philip, T.; Lenoir, G.; Chaussain, J.L.; Junien, C. )

    1989-05-01

    The authors have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), they investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, the data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both.

  13. Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

    ClinicalTrials.gov

    2016-04-11

    Ewing's Sarcoma; Osteosarcoma; Astrocytoma; Atypical Teratoid/Rhabdoid Tumor; Ependymoma; Germ Cell Tumor; Glioma; Medulloblastoma; Rhabdoid Tumor; Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Rhabdomyosarcoma

  14. [Primary renal angiosarcoma].

    PubMed

    Costero-Barrios, Cesáreo B; Oros-Ovalle, Cuauhtémoc

    2004-01-01

    The twenty-fourth case of primary renal angiosarcoma is described, according to the available international literature, this present in a 71-year-old male, a mechanic by trade, without carcinogenic antecedents. Hematuria, pain in flank, and left-side tumoral mass of approximately 20 cm in diameter located in kidney by computerized axial tomography (CT) constituted manifestations. A left nefrectomy was performed. No metastasis was found. The tumor replaced 4/5 of the organ and weighed 1145 g. It showed angiomatous structure with atypical proliferation of endothelial cells in a sinusoldal trauma and anastomosatic vascular channels that invaded neighboring parenchymal and capsule. Tymorous cells were positive for CD31 and CD34 and negative for cytokeratins, S100 and HMB 45 proteins. The patient was subjected to treatment with chemotherapy and radiotherapy (lineal accelerator), but 12 months after surgery he presented retroperitonal tumoral relapse and hepatic metastasis. Diagnostic differentiation with benign vascular tumors is pointed out, as well as carcinomas and sarcomas that showed an outstanding angiomatous component, both primary and/or secondary. Primary renal angiosarcoma exposes the multiplicity of localizations that it is capable of with a tumor of this type, as well as renal parenquimatous capacity to be the seat of a great variety of neoplasias.

  15. The impact of tumor size on the efficacy of monoclonal antibody-targeted radiotherapy: studies using a nude mouse model with human renal cell carcinoma xenografts

    SciTech Connect

    Chiou, R.K. )

    1991-07-01

    Monoclonal antibody (Mab)-targeted radiotherapy is a unique approach in cancer therapy. Multiple factors affect the success of treatment. Internal radiation dosimetry and mini-dose Mab-targeted radiotherapy studies reveal that tumor size affects the efficacy of treatment. For tumors with calculated weight greater than 400 mg., intravenous administration of 131I-labeled A6H or A6H-C5H combination delivers significantly less tumor radiation dose (2070 +/- 580 cGy/100 microCi) than those for tumors of weight less than 200 mg. (5260 +/- 2460 cGy/100 microCi). In the mini-dose (an average of 73 to 86 microCi) Mab-targeted radiotherapy study of 109 mice with small tumors (six, 12, or 19 days after implantation), tumors 12 days after implantation (approximately 60 mg. in weight) showed regression in all mice and in 62% of mice gross tumor elimination was observed. In contrast, mini-dose therapy at day 19 (tumor weights approximately 170 mg.) resulted in tumor regression and tumor elimination rates of 33% and 17% respectively. These studies suggest that Mab-targeted radiotherapy is more suitable for treating small tumors.