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1.
Nat Genet ; 56(5): 809-818, 2024 May.
Article in English | MEDLINE | ID: mdl-38671320

ABSTRACT

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.


Subject(s)
Carcinoma, Renal Cell , Genetic Predisposition to Disease , Genome-Wide Association Study , Kidney Neoplasms , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Humans , Kidney Neoplasms/genetics , Carcinoma, Renal Cell/genetics , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Case-Control Studies , White People/genetics
2.
Int. braz. j. urol ; 49(5): 580-589, Sep.-Oct. 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1506417

ABSTRACT

ABSTRACT Objective: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). Materials and Methods: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. Results: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. Conclusion: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

3.
Int Braz J Urol ; 49(5): 580-589, 2023.
Article in English | MEDLINE | ID: mdl-37390124

ABSTRACT

OBJECTIVE: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). MATERIALS AND METHODS: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. RESULTS: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. CONCLUSION: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.


Subject(s)
Penile Neoplasms , Video-Assisted Surgery , Aged , Humans , Male , Middle Aged , Inguinal Canal/surgery , Inguinal Canal/pathology , Lymph Node Excision/methods , Lymph Nodes/pathology , Penile Neoplasms/surgery , Penile Neoplasms/pathology , Treatment Outcome , Video-Assisted Surgery/methods , Retrospective Studies
4.
Int. braz. j. urol ; 44(3): 483-490, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-954036

ABSTRACT

ABSTRACT Background and Purpose: Recent advances in cancer treatment have resulted in bet- ter prognosis with impact on patient's survival, allowing an increase in incidence of a second primary neoplasm. The development of minimally invasive surgery has provided similar outcomes in comparison to open surgery with potentially less mor- bidity. Consequently, this technique has been used as a safe option to simultaneously treat synchronous abdominal malignancies during a single operating room visit. The objective of this study is to describe the experience of two tertiary cancer hospitals in Brazil, in the minimally invasive treatment of synchronous abdominal neoplasms and to evaluate its feasibility and peri-operative results. Materials and Methods: We retrospectively reviewed the data from patients who were submitted to combined laparoscopic procedures performed in two tertiary hospitals in Brazil from May 2009 to February 2015. Results: A total of 12 patients (9 males and 3 females) with a mean age of 58.83 years (range: 33 to 76 years) underwent combined laparoscopic surgeries for the treatment of at least one urological disease. The total average duration of surgery was 339.8 minutes (range: 210 to 480 min). The average amount of intraoperative bleeding was 276.6mL (range: 70 to 550mL) and length of hospitalization was 5.08 days (range: 3 to 10 days). Two patients suffered minor complications regarding Clavien system during the immediate postoperative period. Conclusions: Combined laparoscopic surgery for the treatment of synchronous tumors is feasible, viable and safe. In our study, there was a low risk of postoperative morbidity.


Subject(s)
Humans , Male , Female , Adult , Aged , Carcinoma/surgery , Laparoscopy/methods , Abdominal Neoplasms/surgery , Neoplasms, Multiple Primary/surgery , Postoperative Complications , Prostatectomy/methods , Time Factors , Brazil , Reproducibility of Results , Retrospective Studies , Blood Loss, Surgical , Treatment Outcome , Operative Time , Tertiary Care Centers , Length of Stay , Middle Aged , Nephrectomy/methods
5.
Int Braz J Urol ; 44(3): 483-490, 2018.
Article in English | MEDLINE | ID: mdl-29219275

ABSTRACT

BACKGROUND AND PURPOSE: Recent advances in cancer treatment have resulted in better prognosis with impact on patient's survival, allowing an increase in incidence of a second primary neoplasm. The development of minimally invasive surgery has provided similar outcomes in comparison to open surgery with potentially less morbidity. Consequently, this technique has been used as a safe option to simultaneously treat synchronous abdominal malignancies during a single operating room visit. The objective of this study is to describe the experience of two tertiary cancer hospitals in Brazil, in the minimally invasive treatment of synchronous abdominal neoplasms and to evaluate its feasibility and peri-operative results. MATERIALS AND METHODS: We retrospectively reviewed the data from patients who were submitted to combined laparoscopic procedures performed in two tertiary hospitals in Brazil from May 2009 to February 2015. RESULTS: A total of 12 patients (9 males and 3 females) with a mean age of 58.83 years (range: 33 to 76 years) underwent combined laparoscopic surgeries for the treatment of at least one urological disease. The total average duration of surgery was 339.8 minutes (range: 210 to 480 min). The average amount of intraoperative bleeding was 276.6mL (range: 70 to 550mL) and length of hospitalization was 5.08 days (range: 3 to 10 days). Two patients suffered minor complications regarding Clavien system during the immediate postoperative period. CONCLUSIONS: Combined laparoscopic surgery for the treatment of synchronous tumors is feasible, viable and safe. In our study, there was a low risk of postoperative morbidity.


Subject(s)
Abdominal Neoplasms/surgery , Carcinoma/surgery , Laparoscopy/methods , Neoplasms, Multiple Primary/surgery , Adult , Aged , Blood Loss, Surgical , Brazil , Female , Humans , Length of Stay , Male , Middle Aged , Nephrectomy/methods , Operative Time , Postoperative Complications , Prostatectomy/methods , Reproducibility of Results , Retrospective Studies , Tertiary Care Centers , Time Factors , Treatment Outcome
6.
BJU Int ; 110(11 Pt B): E653-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22892057

ABSTRACT

UNLABELLED: What's known on the subject? and What does the study add? In spite of its low specificity, PSA is the most widely used screening test for prostate cancer (PCa), and is considered the main cause of the stage migration recently observed. The ratio of free to total PSA (%fPSA) has been shown to increase PSA accuracy in cancer detection; however, few screening studies have systematically evaluated its role in cancer detection rates in men with PSA levels <4.0 ng/mL and normal DRE. The present study supports a possible role of %fPSA as an adjunct to screening in men with total PSA 2.5-4.0 ng/mL and normal DRE, with a marked increase in cancer detection rates in a large Brazilian PCa screening study. We believe that %fPSA maybe a useful refinement to biopsy indications in men with low PSA levels. OBJECTIVE: • To evaluate the role of the free to total prostate-specific antigen ratio (%fPSA) in identifying prostate cancer (PCa) in men with a prostate-specific antigen (PSA) level of 2.5-3.9 ng/mL and a normal digital rectal examination (DRE). PATIENTS AND METHODS: • A prospective PCa screening study was conducted, which included 17571 men aged ≥ 45 years, across six Brazilian states, where men were recalled for further evaluation in the case of either a suspicious DRE and/or PSA ≥ 4.0 ng/mL, or PSA 2.5-3.9 ng/mL and %fPSA ≤ 15. • We evaluated the impact of a %fPSA ≤ 15 on cancer detection rates and the clinical and pathological stage of tumours in men with a normal DRE and PSA 2.5-3.9 ng/mL. RESULTS: • When suspicious DRE and/or PSA ≥ 4.0 ng/mL were considered as criteria to prompt further evaluation, the cancer detection rate was 3.1%. When %fPSA ≤ 15 in men with total PSA levels of 2.5-3.9 ng/mL were considered as criteria, the PCa detection rate increased to 3.7%. Considering %fPSA ≤ 15 in men with PSA 2.5-3.9 ng/mL and normal DRE, the positive predictive value of biopsy was 31.1%. • Clinical stage was more favourable among men with PSA 2.5-3.9 ng/mL, normal DRE, and %fPSA ≤ 15 compared with men with normal DRE and PSA ≥ 4.0 ng/mL (P= 0.02). • Among those who underwent radical prostatectomy, pathological stage and the proportion of insignificant tumours were similar between men with PSA 2.5-3.9 ng/mL, normal DRE findings and %fPSA ≤ 15, and men with PSA ≥ 4.0 ng/mL. CONCLUSIONS: • The use of %fPSA ≤ 15 as a biopsy indication in men with normal DRE and PSA 2.5-4.0 ng/mL in a PCa screening programme, increased cancer detection rates. Tumours in this subset of patients had similar pathological characteristics. • Using %fPSA ≤ 15 to indicate biopsy in men with PSA 2.5-3.9 ng/mL is a useful adjunct to PCa screening.


Subject(s)
Early Detection of Cancer/statistics & numerical data , Mass Screening/methods , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/diagnosis , Brazil/epidemiology , Follow-Up Studies , Humans , Incidence , Male , Prospective Studies , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology
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