[Provisional renal cell carcinoma subsets following the 2016 WHO classification].
Orv Hetil. 2020 Jan;161(3):83-94
Authors: Jenei A, Hes O, Kuthi L
Renal cell carcinoma (RCC) represents a heterogenous group of malignant tumors that originate from the kidney parenchyma. The different entities have their own specific epidemiological, morphological, immunohistochemical, genetic and clinical characteristics. The new WHO classification of renal tumors was published in 2016, and it takes all of these features together into account. Although in the past three years, several emerging subtypes have been described, these are not yet included in the current classification. In this review paper, these entities are summarized in details including the following emerging subsets: thyroid-like follicular carcinoma, ALK rearrangement-associated RCC, renal cell carcinoma with prominent smooth muscle stroma, fumarate hydratase-deﬁcient RCC, biphasic squamoid papillary RCC, eosinophilic solid and cystic RCC, atrophic kidney-like RCC, clear cell RCC with giant cells and emperipolesis, Warthin-like papillary RCC, low-grade oncocytic renal tumor (CD117-negative; CK7-positive), high-grade oncocytic renal tumor, TCEB1-mutated RCC and chromophobe RCC with neuroendocrine features. These entities are mostly diagnosed as RCC unclassified. The aim of this study is to introduce these subsets to the Hungarian pathologists, oncologists and urologists, to prompt diagnostic accuracy and to facilitate a collection along with a consecutive analysis of these cases. Orv Hetil. 2020; 161(3): 83-94.
PMID: 31928058 [PubMed - indexed for MEDLINE]
[Renal transplantation in urinary diversions].
Urologe A. 2020 Jan;59(1):27-31
Authors: Sikic D, Richterstetter M, Wullich B, Apel H
Renal transplantations in augmented bladders or urinary diversions are rare, accounting for only 1-2% of all renal transplantations. In most cases a dysfunctional lower urinary tract is the cause of end-stage renal disease in these patients; therefore recovery of the lower urinary tract is mandatory for long-term graft survival. Usually, urinary diversion is timed several months prior to renal transplantation. Beside renal transplantations into an ileum conduit, renal transplantations in continent urinary diversions have become increasingly popular. The most frequent complications are bacteriuria and urinary tract infections, which usually do not lead to graft loss when treated correctly with antibiotics. Long-term outcome of renal transplantations in urinary diversions is comparable to transplantations in healthy native bladders.
PMID: 31858164 [PubMed - indexed for MEDLINE]
Biomarkers for neoadjuvant checkpoint blockade response in urothelial cancer.
Nat Med. 2019 11;25(11):1650-1651
Authors: Ghatalia P, Plimack E
PMID: 31686037 [PubMed - indexed for MEDLINE]
Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial.
Nat Med. 2019 11;25(11):1706-1714
Authors: Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D
Antibodies targeting PD-1 or its ligand 1 PD-L1 such as atezolizumab, have great efficacy in a proportion of metastatic urothelial cancers1,2. Biomarkers may facilitate identification of these responding tumors3. Neoadjuvant use of these agents is associated with pathological complete response in a spectrum of tumors, including urothelial cancer4-7. Sequential tissue sampling from these studies allowed for detailed on-treatment biomarker analysis. Here, we present a single-arm phase 2 study, investigating two cycles of atezolizumab before cystectomy in 95 patients with muscle-invasive urothelial cancer (ClinicalTrials.gov identifier: NCT02662309). Pathological complete response was the primary endpoint. Secondary endpoints focused on safety, relapse-free survival and biomarker analysis. The pathological complete response rate was 31% (95% confidence interval: 21-41%), achieving the primary efficacy endpoint. Baseline biomarkers showed that the presence of preexisting activated T cells was more prominent than expected and correlated with outcome. Other established biomarkers, such as tumor mutational burden, did not predict outcome, differentiating this from the metastatic setting. Dynamic changes to gene expression signatures and protein biomarkers occurred with therapy, whereas changes in DNA alterations with treatment were uncommon. Responding tumors showed predominant expression of genes related to tissue repair after treatment, making tumor biomarker interpretation challenging in this group. Stromal factors such as transforming growth factor-β and fibroblast activation protein were linked to resistance, as was high expression of cell cycle gene signatures after treatment.
PMID: 31686036 [PubMed - indexed for MEDLINE]
Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Metastatic Cancer Post Solid Organ Transplantation: A Case Report and Review of the Literature.
Transplant Proc. 2019 Nov;51(9):3053-3058
Authors: Wong K, Shen J, D'Ambruoso S, Stefanoudakis D, Drakaki A
Immunotherapy is expanding its role in cancer therapy, and in various tumor types it has now become the frontline treatment. Though generally better tolerated than traditional chemotherapy, its mechanism of activating the immune system results in a unique set of adverse reactions that maybe disastrous in the setting of post solid organ transplantation. We herein describe a case report of a patient who was post-renal transplant, developed metastatic, relapsed, refractory renal cell carcinoma, and was successfully treated with nivolumab for 6 cycles while maintaining renal graft function. We also reviewed the published case reports of immunotherapy administered in the post-renal transplantation setting.
PMID: 31627918 [PubMed - indexed for MEDLINE]
Cutaneous Metastasis as a Presenting Feature of Renal Adenocarcinoma in a Renal Transplant Recipient: A Case Report.
Transplant Proc. 2019 Nov;51(9):3072-3073
Authors: Basic-Jukic N, Mesar I, Kirincich J
Cutaneous metastases of urological malignancies are a rare phenomenon. We present a case of a renal transplant recipient who presented with skin nodule 12 years posttransplant. Pathohistologic evaluation revealed metastasis from the renal adenocarcinoma. The patient was treated with temsirolimus and later with sorafenib; however, he died 13 months after the initial presentation with a functional renal allograft.
PMID: 31611123 [PubMed - indexed for MEDLINE]
Multiple Primary Malignancies: The First Case of a Combination of a Gastrointestinal Stromal Tumor and Renal Cell Carcinoma in a Kidney Transplant Recipient.
Transplant Proc. 2019 Nov;51(9):3070-3071
Authors: Juric I, Basic-Jukic N
There is limited data on multiple primary malignancies in the kidney transplant population. Gastrointestinal stromal tumors (GISTs) are rare tumors in kidney transplant recipients, with only 5 cases reported in the literature to date. GIST patients are at an increased risk for developing additional malignancies, with other histologic types of gastrointestinal tract malignancies being the most frequent and other types of malignancies rare. There is evidence in the literature suggesting an association between GIST and renal cell carcinomas. We report on the first case of a GIST and a renal cell carcinoma in a kidney transplant recipient and in other solid organ transplant recipients.
PMID: 31611119 [PubMed - indexed for MEDLINE]
Immunotherapy and urothelial carcinoma: An overview and future prospectives.
Crit Rev Oncol Hematol. 2019 Nov;143:46-55
Authors: Pierantoni F, Maruzzo M, Gardi M, Bezzon E, Gardiman MP, Porreca A, Basso U, Zagonel V
BACKGROUND: Urothelial carcinoma (UC) is a common malignancy with a high mortality rate when metastatic. Traditionally, systemic therapy consisted in platinum-based regimens as first-line, with Taxanes or Vinflunine as further lines. Recently, checkpoint inhibitors (CPIs) immunotherapy has emerged as a new therapeutic option.
METHODS: We searched in Medline, Pubmed and ClinicalTrial.gov databases for the relevant literature, reviewing the results of published trials and the design of ongoing studies involving CPIs in UC.
RESULT: Strong evidence supports the use of CPIs after failure of Cisplatin-based chemotherapy, although no predictive parameter is available so far. Expression of Programmed-Death-1-Ligand has given conflicting results, and is currently indicated only for the selection of Cisplatin-ineligible patients who should receive CPIs.
CONCLUSION: The therapeutic landscape of UC is rapidly changing due to the availability of CPIs. Neoadjuvant trials with CPIs and trials combining two CPIs are promising and will further expand the use of immunotherapy.
PMID: 31476551 [PubMed - indexed for MEDLINE]
Microwave Ablation of Renal Cell Carcinoma of the Transplanted Kidney: Two Cases.
Cardiovasc Intervent Radiol. 2019 Nov;42(11):1653-1657
Authors: Favi E, Raiteri M, Paone G, Alfieri CM, Ferraresso M
Thermal ablative techniques have been increasingly recognized as a valuable alternative to graftectomy and nephron-sparing surgery for the treatment of small neoplasms arising in the transplanted kidney. However, long-term efficacy and safety data are still lacking. In particular, current experience with microwave ablation is limited to a very recent single-centre series of three cases. We herein report two microwave ablations of renal cell carcinoma of the kidney allograft. The procedures were successfully performed under ultrasound guidance with complete tumour necrosis, no peri-operative complications, and preserved renal function. No recurrences were observed after 3 years of follow-up.
PMID: 31388701 [PubMed - indexed for MEDLINE]
Radiomics analysis of multiparametric MRI for the preoperative evaluation of pathological grade in bladder cancer tumors.
Eur Radiol. 2019 Nov;29(11):6182-6190
Authors: Wang H, Hu D, Yao H, Chen M, Li S, Chen H, Luo J, Feng Y, Guo Y
OBJECTIVES: To develop and validate an MRI-based radiomics strategy for the preoperative estimation of pathological grade in bladder cancer (BCa) tumors.
METHODS: A primary cohort of 70 patients (31 high-grade BCa and 39 low-grade BCa) with BCa were retrospectively enrolled. Three sets of radiomics features were separately extracted from tumor volumes on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps. Two sets of multimodal features were separately generated by the maxout and concatenation of the above mentioned single-modality features. Each feature set was subjected to a two-sample t test and the least absolute shrinkage and selection operator (LASSO) algorithm for feature selection. Multivariable logistic regression (LR) analysis was used to obtain five corresponding radiomics models. The diagnostic abilities of the radiomics models were evaluated using receiver operating characteristic (ROC) curve analysis and compared using the DeLong test. Validation was performed on a time-independent cohort containing 30 consecutive patients.
RESULTS: The areas under the ROC curves (AUCs) of single-modality T2WI, DWI, and ADC models in the training cohort were 0.7933 (95% confidence interval [CI] 0.7471-0.8396), 0.8083 (95% CI 0.7565-0.8601), and 0.8350 (95% CI 0.7924-0.8776), respectively. Both multimodality models achieved higher AUCs (maxout 0.9233, 95% CI 0.9001-0.9466; concatenation 0.9233, 95% CI 0.9001-0.9466) than single-modality models. The AUCs of the maxout and concatenation models in the validation cohort were 0.9186 and 0.9276, respectively.
CONCLUSIONS: The MRI-based multiparametric radiomics approach has the potential to be used as a noninvasive imaging tool for preoperative grading of BCa tumors. Multicenter validation is needed to acquire high-level evidence for its clinical application.
KEY POINTS: • Multiparametric MRI may help in the preoperative grading of BCa tumors. • The Joint_Model established from T2WI, DWI, and ADC feature subsets demonstrated a high diagnostic accuracy for preoperative prediction of pathological grade in BCa tumors. • The radiomics approach has the potential to preoperatively assess tumor grades in BCa and avoid subjectivity.
PMID: 31016445 [PubMed - indexed for MEDLINE]
Assessment of the extracellular volume fraction for the grading of clear cell renal cell carcinoma: first results and histopathological findings.
Eur Radiol. 2019 Nov;29(11):5832-5843
Authors: Adams LC, Jurmeister P, Ralla B, Bressem KK, Fahlenkamp UL, Engel G, Siepmann S, Wagner M, Hamm B, Busch J, Makowski MR
OBJECTIVES: To assess the potential of T1 mapping-based extracellular volume fraction (ECV) for the identification of higher grade clear cell renal cell carcinoma (cRCC), based on histopathology as the reference standard.
METHODS: For this single-center, institutional review board-approved prospective study, 27 patients (17 men, median age 62 ± 12.4 years) with pathologic diagnosis of cRCC (nucleolar International Society of Urological Pathology (ISUP) grading) received abdominal MRI scans at 1.5 T using a modified Look-Locker inversion recovery (MOLLI) sequence between January 2017 and June 2018. Quantitative T1 values were measured at different time points (pre- and postcontrast agent administration) and quantification of the ECV was performed on MRI and histological sections (H&E staining).
RESULTS: Reduction in T1 value after contrast agent administration and MR-derived ECV were reliable predictors for differentiating higher from lower grade cRCC. Postcontrast T1diff values (T1diff = T1 difference between the native and nephrogenic phase) and MR-derived ECV were significantly higher for higher grade cRCC (ISUP grades 3-4) compared with lower grade cRCC (ISUP grades 1-2) (p < 0.001). A cutoff value of 700 ms could distinguish higher grade from lower grade tumors with 100% (95% CI 0.69-1.00) sensitivity and 82% (95% CI 0.57-0.96) specificity. There was a positive and strong correlation between MR-derived ECV and histological ECV (p < 0.01, r = 0.88). Interobserver agreement for quantitative longitudinal relaxation times in the T1 maps was excellent.
CONCLUSIONS: T1 mapping with ECV measurement could represent a novel in vivo biomarker for the classification of cRCC regarding their nucleolar grade, providing incremental diagnostic value as a quantitative MR marker.
KEY POINTS: • Reduction in MRI T1 relaxation times after contrast agent administration and MR-derived extracellular volume fraction are useful parameters for grading of clear cell renal cell carcinoma (cRCC). • T1 differences between the native and the nephrogenic phase are higher for higher grade cRCC compared with lower grade cRCC and MRI-derived extracellular volume fraction (ECV) and histological ECV show a strong correlation. • T1 mapping with ECV measurement may be helpful for the noninvasive assessment of cRCC pathology, being a safe and feasible method, and it has potential to optimize individualized treatment options, e.g., in the decision of active surveillance.
PMID: 30887194 [PubMed - indexed for MEDLINE]