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1.
Ann Surg Oncol ; 2020 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32623609

RESUMO

BACKGROUND: Reoperation rates following breast-conserving surgery (BCS) range from 10 to 40%, with marked surgeon and institutional variation. OBJECTIVE: The aim of this study was to identify factors associated with intraoperative margin re-excision, evaluate for any differences in local recurrence based on margin re-excision and determine reoperation rates with use of intraoperative margin analysis. PATIENTS AND METHODS: We analyzed consecutive patients with ductal carcinoma in situ (DCIS) or invasive breast cancer who underwent BCS at our institution between 1 January 2005 and 31 December 2016. Routine intraoperative frozen section margin analysis was performed and positive or close margins were re-excised intraoperatively. Univariate analysis was used to compare margin status and the Kaplan-Meier method was used to compare recurrence. Multivariable logistic regression was utilized to analyze factors associated with re-excision. RESULTS: We identified 3201 patients who underwent BCS-688 for DCIS and 2513 for invasive carcinoma. Overall, 1513 (60.2%) patients with invasive cancer and 434 (63.1%) patients with DCIS had close or positive margins that underwent intraoperative re-excision. Margin re-excision was associated with larger tumor size in both groups. The permanent pathology positive margin rate among all patients was 1.2%, and the 30-day reoperation rate for positive margins was 1.1%. Five-year local recurrence rates were 0.6% and 1.2% for patients with DCIS and invasive cancer, respectively. There was no difference in recurrence between patients with and without intraoperative margin re-excision (p = 0.92). CONCLUSION: Both DCIS and invasive carcinoma had similar rates of intraoperative margin re-excision. Although intraoperative margin re-excision was common, the reoperation rate was extremely low and there was no difference in recurrence between those with or without intraoperative re-excision.

2.
Urol Oncol ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32624422

RESUMO

OBJECTIVE: We evaluated the natural history and long-term outcomes of incidentally detected prostate cancer (PCa) at radical cystectomy (RC) for bladder cancer (BCa). PATIENTS AND METHODS: We identified 1,640 male patients who underwent RC between 1992 and 2012. Patients were stratified as clinically insignificant and clinically significant PCa, based on Grade Group (GG) 1 and ≥2, respectively. Survival was assessed using the Kaplan-Meier method. RESULTS: There were 329 (20%) patients with incidentally detected PCa at RC: 245 (15%) GG1, 52 (3.2%) GG2, 20 (1.2%) GG3, 6 (0.4%) GG4, and 6 (0.4%) GG5. Median follow-up among survivors was 9.6 years (interquartile range 7.5-13.3), during which time 253 patients died, of whom 127 died of BCa and 1 died of PCa. Nine patients experienced biochemical recurrence (BCR), 4 underwent salvage PCa therapies, and 2 developed PCa metastases. Patients with clinically significant PCa were significantly more likely to experience BCR (6% vs. 1.6%; P = 0.04) and had shorter median time to BCR (1.8 vs. 10.4 years; P = 0.01) than those with clinically insignificant PCa. No patients with BCR had greater than pT2N0 BCa or positive BCa margins. Ten-year PCa-specific survival, BCa-specific survival, other cause-specific survival, and overall survival were 99%, 57%, 63%, and 35%, respectively. CONCLUSIONS: In a large RC series, we note a 20% rate of incidental PCa, the majority of which are clinically insignificant. On long-term follow-up, we determined that BCR and PCa mortality are extremely rare events among these patients. Pending validation, future guidelines may consider omission of PCa surveillance for some patients with incidental PCa at RC.

3.
Arch Pathol Lab Med ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32589068

RESUMO

CONTEXT.­: Controversies and uncertainty persist in prostate cancer grading. OBJECTIVE.­: To update grading recommendations. DATA SOURCES.­: Critical review of the literature along with pathology and clinician surveys. CONCLUSIONS.­: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.

4.
Urol Oncol ; 38(7): 640.e13-640.e22, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32402769

RESUMO

OBJECTIVES: The optimal management approach for synchronous bilateral renal masses is unknown, particularly regarding surgical sequencing of bilateral partial nephrectomy (PN). We evaluated the impact of simultaneous vs. staged bilateral PN on renal functional, perioperative, and oncologic outcomes. PATIENTS AND METHODS: We reviewed our institutional nephrectomy registry to identify patients who underwent simultaneous or staged (within 6 months) bilateral PN for nonmetastatic bilateral synchronous solid renal masses between 1980 and 2015. Short-term and long-term renal function changes were assessed at 3 and 12 months, respectively. Perioperative outcomes were pooled across staged surgeries by taking the sum of each outcome. Local recurrence-free, distant metastases-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method. Outcomes were compared by surgical sequencing approach. A sensitivity analysis was performed that grouped approaches by preoperative intent. RESULTS: Among the 107 patients studied, 77 (72%) underwent simultaneous and 30 (28%) underwent staged PN. The majority of PN were performed by open approach. Clinicopathologic features were similar between groups. Patients who underwent simultaneous PN had lower mean short-term (-6% vs. -24%, P = 0.015) and median long-term (-4% vs. -22%, P < 0.001) reduction in eGFR vs. staged PN, respectively. Furthermore, patients with simultaneous PN had lower pooled length of stay (median 6 vs. 8 days, P < 0.001), rate of urine leak (3% vs. 17%, P = 0.018), and rate of high-grade complications (8% vs. 23%, P = 0.044), relative to staged PN, respectively. However, on sensitivity analysis, only differences in long term reduction in estimated glomerular filtration rate and length of stay remained. There were no significant differences in oncologic outcomes between groups. CONCLUSIONS: Our results suggest that when technically feasible, simultaneous PN yields comparable outcomes vs. staged PN, offering a reasonable surgical sequencing approach for patients presenting with bilateral synchronous renal masses.

5.
Int J Urol ; 27(7): 618-622, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32424856

RESUMO

OBJECTIVES: To evaluate the timing and distribution of first renal cell carcinoma metastasis after nephrectomy stratified by nodal status. METHODS: We evaluated patients treated with nephrectomy for sporadic, unilateral renal cell carcinoma between 1970 and 2011 who subsequently developed distant metastasis to three or fewer sites. Site-specific metastases-free 2-year survival rates were estimated using the Kaplan-Meier method. Associations of nodal status with time to metastasis were evaluated using multivariable Cox regression models. RESULTS: A total of 1049 patients met the inclusion criteria (135 pN1, 914 pN0/x patients). The median time to identification of first distant metastasis for pN1 patients was 0.4 years (interquartile range 0.2-1.1 years) versus 2.2 years (interquartile range 0.6-6.0 years) in pN0/x patients. The most common site of metastasis was to the lung, but this occurred earlier in pN1 patients (median 0.3 years vs 2.0 years). pN1 was associated with significantly lower site-specific 2-year metastases-free survival when compared with pN0/x for lung (37% vs 70%, P < 0.001), bone (63% vs 87%, P < 0.001), non-regional lymph nodes (60% vs 96%, P < 0.001) and liver metastases (79% vs 91%, P < 0.001). On multivariable analysis, pN1 status remained significantly associated with lung, bone, and non-regional lymph node (all P < 0.001) metastases, but it was no longer associated with liver metastases (P = 0.3). CONCLUSIONS: pN1 nodal status in M0 patients treated with nephrectomy for renal cell carcinoma is associated with more frequent early metastasis to sites conferring poor prognosis when compared with pN0/x. Our findings highlight the importance of rigorous, early surveillance though the multimodal use of a comprehensive history, physical, laboratory and radiological studies, as outlined in societal guidelines.

6.
World Neurosurg ; 139: 12-19, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32251827

RESUMO

BACKGROUND: Ewing-like sarcoma with capicua transcriptional repressor (CIC) rearrangement is a unique class of undifferentiated round cell sarcomas characterized by CIC-double homeobox 4 gene fusion. Despite showing great histologic resemblance to Ewing sarcomas, they have proved to be a distinct pathological entity from the immunohistochemistry and genetic examinations and the response to treatment. We have presented a case of CIC-rearranged Ewing-like sarcoma with cerebral metastasis managed with operative resection and gamma knife radiosurgery. CASE DESCRIPTION: A 56-year-old woman had initially presented with an ulcerating lesion of the right fifth toe. The histological and immunohistochemical analysis revealed features consistent with CIC-rearranged Ewing-like sarcoma, which was confirmed with genetic analysis. Despite aggressive local control and a multidrug chemotherapy regimen, the patient developed multifocal metastases involving the lungs, femur, and cerebrum. The cerebral lesions were managed with surgery and gamma knife radiosurgery, with mixed results. CONCLUSION: CIC-rearranged Ewing-like sarcomas have recently been recognized as a distinct disease entity with a highly aggressive course. Treatment paradigms have yet to be defined to properly manage such an aggressive pathological process.

8.
Hepatology ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925805

RESUMO

BACKGROUND & AIMS: Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) exceeds 20% and BTC is currently the leading cause of death in PSC patients. To open new avenues for management, we aimed to delineate novel and clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). APPROACH & RESULTS: We analysed formalin fixed, paraffin embedded tumor tissue from 186 PSC-BTC patients from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations and copy number variations, along with histomorphological and immunohistochemical characterization. Irrespective of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, e.g. TP53 (35.5%), KRAS (28.0%), CDKN2A (14.5%), and SMAD4 (11.3%), as well as potentially druggable mutations (e.g. HER2/ERBB2). We found a high frequency of non-typical/non-ductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%) CONCLUSION: Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC show a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC.

9.
Mayo Clin Proc ; 95(2): 306-318, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31685261

RESUMO

OBJECTIVE: To select optimal therapies based on the detection of actionable genomic alterations in tumor samples is a major challenge in precision medicine. METHODS: We describe an effective process (opened December 1, 2017) that combines comprehensive genomic and transcriptomic tumor profiling, custom algorithms and visualization software for data integration, and preclinical 3-dimensiona ex vivo models for drug screening to assess response to therapeutic agents targeting specific genomic alterations. The process was applied to a patient with widely metastatic, weakly hormone receptor positive, HER2 nonamplified, infiltrating lobular breast cancer refractory to standard therapy. RESULTS: Clinical testing of liver metastasis identified BRIP1, NF1, CDH1, RB1, and TP53 mutations pointing to potential therapies including PARP, MEK/RAF, and CDK inhibitors. The comprehensive genomic analysis identified 395 mutations and several structural rearrangements that resulted in loss of function of 36 genes. Meta-analysis revealed biallelic inactivation of TP53, CDH1, FOXA1, and NIN, whereas only one allele of NF1 and BRIP1 was mutated. A novel ERBB2 somatic mutation of undetermined significance (P702L), high expression of both mutated and wild-type ERBB2 transcripts, high expression of ERBB3, and a LITAF-BCAR4 fusion resulting in BCAR4 overexpression pointed toward ERBB-related therapies. Ex vivo analysis validated the ERBB-related therapies and invalidated therapies targeting mutations in BRIP1 and NF1. Systemic patient therapy with afatinib, a HER1/HER2/HER4 small molecule inhibitor, resulted in a near complete radiographic response by 3 months. CONCLUSION: Unlike clinical testing, the combination of tumor profiling, data integration, and functional validation accurately assessed driver alterations and predicted effective treatment.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Carcinoma Lobular/genética , Carcinoma Lobular/terapia , Genômica/métodos , Medicina de Precisão/métodos , Algoritmos , Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Análise Mutacional de DNA , Feminino , Genes Neoplásicos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica
11.
Cancer Med ; 9(3): 1152-1160, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31829518

RESUMO

OBJECTIVES: Previous studies noted discordance of programmed death-1 (PD-1) and one of its ligands (PD-L1) across patient-matched primary and metastatic clear cell renal cell carcinoma (ccRCC). There are inconsistencies if the primary or metastatic tumor has higher expression, and whether metastatic tumor expression is associated with patient outcome. Thus, we examined PD-1 and PD-L1 in patient-matched tumors using a large number of ccRCC patients with long follow-up. MATERIALS AND METHODS: We analyzed PD-1 and PD-L1 using immunohistochemistry in patient-matched primary and metastatic tumors from 110 ccRCC patients. Concordance was assessed among longitudinal metastatic tumors, as well as across patient-matched primary and metastatic tumors. Cox proportional hazards regression was used to evaluate the associations of metastatic tumor expression with cancer-specific survival. RESULTS: We observed inter-metastatic tumor heterogeneity of PD-1 in 25 (69%) of the 36 patients and of PD-L1 in seven (19%) patients. Concordance between patient-matched primary and metastatic tumors was 73% (Kappa = 0.16, 95% CI: -0.003-0.32). Similarly, concordance of PD-L1 between metastatic and patient-matched primary tumors was 78% (Kappa = 0.27, 95% CI: 0.09-0.46). Both markers demonstrated higher expression in primary vs metastatic tumors. Metastatic tumor expression of PD-1 was significantly associated with metastatic location (P < .0001) and ccRCC-specific survival (HR = 2.15, 95% CI: 1.06-4.36, P = .035). CONCLUSIONS: The expression of PD-1 and PD-L1 is discordant across patient-matched ccRCC tumors, with higher expression in primary tumors. Higher PD-1 expression was associated with metastatic location and lower cancer-specific survival. If validated, these results highlight the importance of evaluating these biomarkers in metastatic tissue specifically.

12.
J Urol ; 203(2): 275-282, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31393812

RESUMO

PURPOSE: Data supporting complete metastasectomy of metastatic renal cell carcinoma were derived primarily from the era of cytokine therapy. Whether complete metastasectomy remains beneficial in patients who receive more recently approved systemic therapies has not been well studied. The objective of this study was to examine survival outcomes among patients treated with complete metastasectomy in the era of targeted therapy and checkpoint blockade availability. MATERIALS AND METHODS: We queried our institutional nephrectomy registry and identified 586 patients who underwent partial or radical nephrectomy of unilateral, sporadic renal cell carcinoma with a first occurrence of metastasis between 2006 and 2017. Of these patients 158 were treated with complete metastasectomy. Associations of complete metastasectomy with cancer specific and overall survival were assessed using Cox proportional hazards models. RESULTS: Median followup after the diagnosis of metastasis was 3.9 years, during which 403 patients died, including 345 of renal cell carcinoma. Of the patients treated with complete metastasectomy 147 (93%) did not receive any systemic treatment of the index metastatic lesion(s). Two-year cancer specific survival was significantly greater in patients with vs without complete metastasectomy (84% vs 54%, p <0.001). After adjusting for age, gender, and the timing, number and location of metastases complete metastasectomy was associated with a significantly reduced likelihood of death from renal cell carcinoma (HR 0.47, 95% CI 0.34-0.65, p <0.001). CONCLUSIONS: Complete surgical resection of metastases of renal cell carcinoma was associated with improved cancer specific survival in the post-cytokine era. It may be considered in appropriate patients after a process of shared decision making.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Metastasectomia/métodos , Nefrectomia , Idoso , Carcinoma de Células Renais/mortalidade , Citocinas/uso terapêutico , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento
13.
Urol Oncol ; 38(2): 41.e19-41.e27, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761613

RESUMO

OBJECTIVES: Anxiety and depression have been associated with inferior overall survival for several malignancies, including metastatic renal cell carcinoma (RCC). However, there is minimal data evaluating this association for localized RCC. We evaluated the association of anxiety or depression with survival in patients with surgically treated localized clear cell RCC (ccRCC). PATIENTS AND METHODS: We reviewed our institutional nephrectomy registry of 1,990 adults who underwent radical or partial nephrectomy for unilateral, sporadic, nonmetastatic ccRCC between 1995 and 2011. Baseline anxiety and depression were identified using ICD-9 codes. Associations of anxiety or depression with 30-day complications and oncologic outcomes were evaluated using Cox proportional hazards models as well as adjustment for propensity score (PS) quintile and re-weighting by stabilized inverse probability weights. RESULTS: A total of 197 (10%) patients were identified with a diagnosis of anxiety or depression. Median follow-up among survivors was 10.0 (IQR 7.3-13.6) years, during which time 864 patients died, including 363 from RCC. After PS adjustment, clinical and pathologic features were well balanced between groups. Patients with anxiety or depression had increased overall 30-day complications compared to those without (17% vs. 11%, P = 0.011). No significant differences were noted in time to local ipsilateral recurrence (P = 0.54), distant metastases (P = 0.96), or death from RCC (P = 0.42) between patients with vs. without anxiety or depression, while patients with anxiety or depression trended toward worse overall survival (hazard ratio 1.29, 95%CI 0.98-1.69, P = 0.065). CONCLUSIONS: Neither anxiety nor depression were significantly associated with oncologic outcomes among patients who underwent surgery for localized ccRCC. The trend toward worse overall survival among patients with anxiety or depression warrants further investigation.

14.
Am J Surg Pathol ; 44(5): 673-680, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31876580

RESUMO

Intraductal carcinoma of the prostate (IDC-P) has been recently recognized by the World Health Organization classification of prostatic tumors as a distinct entity, most often occurring concurrently with invasive prostatic adenocarcinoma (PCa). Whether documented admixed with PCa or in its rare pure form, numerous studies associate this entity with clinical aggressiveness. Despite increasing clinical experience and requirement of IDC-P documentation in protocols for synoptic reporting, the specifics of its potential contribution to assessment of grade group (GG) and cancer quantitation of PCa in both needle biopsies (NBx) and radical prostatectomy (RP) specimens remain unclear. Moreover, there are no standard guidelines for incorporating basal cell marker immunohistochemistry (IHC) in the diagnosis of IDC-P, either alone or as part of a cocktail with AMACR/racemase. An online survey containing 26 questions regarding diagnosis, reporting practices, and IHC resource utilization, focusing on IDC-P, was undertaken by 42 genitourinary subspecialists from 9 countries. The degree of agreement or disagreement regarding approaches to individual questions was classified as significant majority (>75%), majority (51% to 75%), minority (26% to 50%) and significant minority (≤25%). IDC-P with or without invasive cancer is considered a contraindication for active surveillance by the significant majority (95%) of respondents, although a majority (66%) also agreed that the clinical significance/behavior of IDC-P on NBx or RP with PCa required further study. The majority do not upgrade PCa based on comedonecrosis seen only in the intraductal component in NBx (62%) or RP (69%) specimens. Similarly, recognizable IDC-P with GG1 PCa was not a factor in upgrading in NBx (78%) or RP (71%) specimens. The majority (60%) of respondents include readily recognizable IDC-P in assessment of linear extent of PCa at NBx. A significant majority (78%) would use IHC to confirm or exclude intraductal carcinoma if other biopsies showed no PCa, while 60% would use it to confirm IDC-P with invasive PCa in NBx if it would change the overall GG assignment. Nearly half (48%, a minority) would use IHC to confirm IDC-P for accurate Gleason pattern 4 quantitation. A majority (57%) report the percentage of IDC-P when present, in RP specimens. When obvious Gleason pattern 4 or 5 PCa is present in RP or NBx, IHC is rarely to almost never used to confirm the presence of IDC-P by the significant majority (88% and 90%, respectively). Most genitourinary pathologists consider IDC-P to be an adverse prognostic feature independent of the PCa grade, although recommendations for standardization are needed to guide reporting of IDC-P vis a vis tumor quantitation and final GG assessment. The use of IHC varies widely and is performed for a multitude of indications, although it is used most frequently in scenarios where confirmation of IDC-P would impact the GG assigned. Further study and best practices recommendations are needed to provide guidance with regards to the most appropriate indications for IHC use in scenarios regarding IDC-P.

15.
Hum Pathol ; 91: 114-122, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31299266

RESUMO

Mutations of the succinate dehydrogenase (SDHX) enzyme subunits commonly lead to a loss of function of the holoenzyme complex, and germline SDHX mutations lead to a genetic predisposition to SDH-deficient neoplasms, including renal cell carcinomas (RCC). Similarly, loss-of-function alterations of fumarate hydratase (FH) leads to a genetic predisposition to hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated RCC. Loss of FH leads to an accumulation of fumarate and aberrantly high levels of S-(2-succino)-cysteine (2SC). Subtype-specific consecutively diagnosed renal cell neoplasms were selected for the study and cases were not otherwise selected based on clinicopathologic features. Tissue microarrays were constructed from 1009 renal cell neoplasms (papillary: 400, clear cell: 203, chromophobe: 87, oncocytomas [original diagnosis]: 273, unclassified: 46) and these cases were immunostained for SDHA/SDHB to screen for SDH loss. A smaller subset (n = 730; oncocytomas, papillary and unclassified RCCs) were screened for FH-deficiency using immunohistochemistry for FH/2SC. Loss of SDHA/SDHB was seen in three of 273 tumors originally diagnosed as oncocytomas (1.1%). Diffuse nuclear and cytoplasmic 2SC staining, with retained FH expression was seen in one case (suggestive of dysfunctional FH protein), while absent FH was seen in 3 cases (2/400 papillary RCCs, 0.5% and 2/46 unclassified RCCs, 4.35%). No aberrant FH/2SC expression was noted in 273 cases originally diagnosed as oncocytomas. SDH-deficient RCCs were identified only in the cases originally diagnosed as oncocytomas (1.1%), while FH-deficient RCCs were identified in the papillary (0.5%) and unclassified RCC cohorts (4.35%). These results can help guide immunohistochemistry-based screening strategies for these tumors.

16.
Urology ; 133: 145-150, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31356826

RESUMO

OBJECTIVE: To report on the long-term oncologic outcomes of 3 subtypes of low grade cystic renal epithelial neoplasms-multilocular cystic neoplasm of low malignant potential (MCLMP), cystic clear cell RCC (ccRCC), and cystic clear cell papillary RCC (ccpRCC), following 2016 reorganization by the World Health Organization. MATERIALS AND METHODS: A total of 3865 patients underwent radical or partial nephrectomy for unilateral, sporadic ccRCC between 1970 and 2010, of which 145 had previously been classified as cystic ccRCC. One genitourinary pathologist, blinded to outcome, rereviewed and reclassified the specimens by 2016 WHO criteria. Oncologic outcomes were estimated using the Kaplan-Meier method. RESULTS: Of 145 specimens, 18 (12%) were classified as MCLMP, 95 (66%) cystic ccRCC, and 32 (22%) cystic ccpRCC. Those with MCLMP were more likely female (61% vs 29% vs 31%, P = .03) with larger tumors (median 4.6 cm vs 3.0 cm vs 2.3 cm, P = .02) compared to those with cystic ccRCC and cystic ccpRCC, respectively. Only 2% of cystic ccRCC had tumor necrosis or grade 3 nucleoli present. Median follow-up for survivors was 10.3 years (interquartile range 7.4-14.9). Overall, 1 MCLMP, 5 cystic ccRCC, and 4 ccpRCC recurred during follow-up. Ten- and 20-year cancer-specific survival was 100% across all subtypes. CONCLUSION: In a large cohort of patients previously classified as cystic ccRCC with pathologic rereview and long-term follow-up, we noted that MCLMP is the least common subtype of low grade cystic renal epithelial neoplasms. Regardless, all subtypes are associated with an excellent long-term prognosis following surgical resection.


Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Nefrectomia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Nefrectomia/métodos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
17.
Eur Urol Oncol ; 2(4): 390-396, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31277775

RESUMO

BACKGROUND: Delaying radical cystectomy (RC) after a diagnosis of muscle-invasive bladder cancer (MIBC) has been associated with adverse survival. However, data are lacking regarding the impact of RC delay in patients receiving neoadjuvant chemotherapy (NAC). OBJECTIVES: To assess whether the time from last cycle of NAC to RC (time to cystectomy, TTC) is associated with survival among MIBC patients. DESIGN, SETTING, AND PARTICIPANTS: The study cohort comprised 226 patients treated with NAC and RC between 1999 and 2015 for cT2-T4N0M0 bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics were used to test the association between TTC and clinicopathologic variables. Overall mortality (OM) and cancer-specific mortality (CSM) were analyzed via Kaplan-Meier estimation according to TTC. We assessed factors associated with OM and CSM using multivariable Cox regression analyses. RESULTS AND LIMITATIONS: The median TTC was 7.57wk (interquartile range 5.2-10.8). Patients with a Charlson comorbidity index (CCI) ≥1 had a longer TTC than those with a score of <1 (p=0.027). The group with TTC >10wk had significantly lower OM-free (p=0.003) and CSM-free rates (p<0.001) than the group with TTC ≤10wk. TTC was independently associated with higher risk of OM (p=0.027) and CSM (p=0.004) after accounting for age, gender, pathologic extravesical disease, and nodal status. CONCLUSIONS: TTC of >10wk after NAC was associated with adverse survival among patients with MIBC. Patients with a higher CCI were more likely to have prolonged TTC. PATIENT SUMMARY: The impact of delaying radical cystectomy in patients who have received neoadjuvant chemotherapy (NAC) is unknown. In this study we assessed whether prolonged time to cystectomy (TTC) after NAC affects survival outcomes in patients with muscle-invasive bladder cancer. We found that TTC of >10wk was associated with adverse overall survival and cancer-specific survival, and attempts should be made to shorten TTC after preoperative chemotherapy.

19.
Eur Urol ; 76(2): 244-251, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31060824

RESUMO

BACKGROUND: Long-term data comparing partial nephrectomy (PN) and thermal ablation are lacking. OBJECTIVE: To update our experience with PN, percutaneous radiofrequency ablation (RFA), and percutaneous cryoablation for cT1 renal masses. DESIGN, SETTING, AND PARTICIPANTS: A total of 1798 patients with primary cT1N0M0 renal masses treated between 2000 and 2011 at Mayo Clinic were identified. INTERVENTION: Percutaneous ablation versus PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Local recurrence, metastases, and death from renal cell carcinoma (RCC) were compared with propensity-score-adjusted Cox models. RESULTS AND LIMITATIONS: Among 1422 cT1a patients, 1055, 180, and 187 underwent PN, RFA, and cryoablation with median clinical follow-up of 9.4, 7.5, and 6.3yr, respectively. Comparisons of RFA with PN resulted in hazard ratios (HRs) of 1.49 (95% confidence interval [CI] 0.55-4.04, p=0.4), 1.46 (95% CI 0.41-5.19, p=0.6), and 1.99 (95% CI 0.29-13.56, p=0.5) for local recurrence, metastases, and death from RCC. Comparisons of cryoablation to PN resulted in HRs of 1.88 (95% CI 0.76-4.66, p=0.18), 0.23 (95% CI 0.03-1.72, p=0.15), and 0.29 (95% CI 0.01-6.11, p=0.4) for these same outcomes. Five-year CSS was 99%, 96%, and 100% for PN, RFA, and cryoablation, respectively. Among 376 cT1b patients, 324 and 52 underwent PN and cryoablation with median clinical follow-up of 8.7 and 6.0yr, respectively. Comparisons of cryoablation with PN resulted in HRs of 1.22 (95% CI 0.33-4.48, p=0.8), 0.95 (95% CI 0.21-4.38, p>0.9), and 1.94 (95% CI 0.42-8.96, p=0.4) for local recurrence, metastases, and death from RCC, respectively. Five-year CSS was 98% and 91% for PN and cryoablation, respectively. Limitations include retrospective review and selection bias. CONCLUSIONS: With mature follow-up at a single institution, percutaneous ablation appears to have acceptable results for cT1 renal tumors and is appropriate for patients with a contraindication for surgery. For cT1a patients, clinically relevant differences between PN and ablation are unlikely, and treatment choice should involve shared decision making. For cT1b patients, death from RCC was more common with cryoablation, and large differences in this outcome cannot be ruled out. Further research is needed to confirm the oncologic effectiveness of cryoablation in the cT1b setting. PATIENT SUMMARY: With appropriate patient triage, partial nephrectomy and percutaneous ablation can be used to treat cT1 renal masses, although additional follow-up and further study are still needed.

20.
Clin Genitourin Cancer ; 17(3): 216-222.e5, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060857

RESUMO

INTRODUCTION: The objective of the study was to determine whether sarcopenia is associated with pathologic and survival outcomes for patients with muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). PATIENTS AND METHODS: We identified MIBC patients treated with cisplatin-based NAC in our cystectomy registry from 2000 to 2016. Pre- and post-NAC computed tomography images were analyzed with BodyCompSlicer, a validated body composition assessment tool. Sarcopenia was defined as a skeletal muscle index (SMI) below sex-specific international consensus values. Associations of clinical features with pathologic downstaging ( .05). Meanwhile, only post-NAC sarcopenia (hazard ratio, 1.90; 95% confidence interval, 1.02-3.56; P = .04) was independently associated with an increased risk of CSM. CONCLUSION: Sarcopenia after NAC and before RC appeared to be prognostic. Although skeletal muscle mass declined significantly during NAC, neither the degree of muscle loss nor pretreatment SMI were significantly associated with downstaging after NAC and RC. These data do not support the use of sarcopenia as a risk stratification tool for selection of patients for or monitoring response to NAC.


Assuntos
Cisplatino/efeitos adversos , Sarcopenia/epidemiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Quimioterapia Adjuvante/efeitos adversos , Cisplatino/uso terapêutico , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sarcopenia/induzido quimicamente , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico por imagem
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