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1.
Cancer Diagn Progn ; 4(5): 638-645, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39238621

RESUMO

Background/Aim: Data on metastasis-directed radiotherapy (MDRT) are limited, particularly regarding its association with the prostate-specific antigen (PSA) doubling time (PSADT). The present study evaluated the oncological outcomes of MDRT on the basis of the PSADT in oligo-recurrent prostate cancer patients. Patients and Methods: We retrospectively reviewed clinical data of 35 MDRTs for 29 patients at the Kitasato University Hospital, targeting oligometastatic prostate cancer developed after radical treatment for non-metastatic prostate cancer. Thirty-five MDRTs were classified into the PSADT >3 months (n=25) or PSADT ≤3 months group (n=10). Statistical analyses were performed to compare associations between the two PSADT groups and oncological outcomes such as progression-free survival (PFS) and PSA response after MDRT. Results: There were no significant differences between the two groups in terms of the clinicopathological features. Kaplan-Meier analysis showed that PFS was significantly better in the PSADT >3 months group than in the PSADT ≤3 months group [median: 13.3 versus (vs.) 2.6 months, p=0.046]. Regarding castration sensitivity, the predictive role of PSADT >3 months was maintained in 21 patients who received MDRT without prior salvage hormone therapy (median PFS: 12.7 vs. 2.6 months, p=0.024). In the castration-resistant setting (n=14), the frequency of a decrease in serum PSA levels after MDRT by 90% was 54.5% (median PFS: 23.1 months). Conclusion: MDRT can provide benefit especially for patients with PSADT ≥3 months who had oligo-recurrence after the radical treatment for non-metastatic prostate cancer.

2.
Jpn J Clin Oncol ; 54(5): 569-576, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38305663

RESUMO

OBJECTIVE: comprehensive genomic profiling test has been covered by Japanese health insurance since June 2019. However, no real-world data on the test have been reported with a focus on Japanese patients with prostate cancer. METHODS: we retrospectively reviewed the data of 45 consecutive patients with metastatic castration-resistant prostate cancer, who underwent the comprehensive genomic profiling tests at Kitasato University Hospital between August 2019 and December 2022. Patients' characteristics, prevalence of gene alterations and therapeutic impact of genotype-matched therapy were assessed. RESULTS: genomic data were obtained using a tissue-based test (n = 32) and liquid-based test (n = 13). Actionable genomic alternations were identified in 51.1% of patients, and 22.2% were treated with genotype-matched therapy. The main reason for not receiving genotype-matched therapy was disease progression, accounting for 46.2% (6/13). Kaplan-Meier analysis showed significantly longer overall survival after the comprehensive genomic profiling tests in patients with genotype-matched therapy under public insurance (17.8%, n = 8) than those without it (median: not reached vs. 18.1 months; P = 0.003). Five (62.5%) out of the eight patients with genotype-matched therapy under public insurance had BRCA1 or 2 deleterious alteration. Multivariate analyses showed that BRCA deleterious alteration (17.8%, n = 8) was an independent risk factor for shorter time to castration-resistant prostate cancer (hazard ratio: 2.46, 95% confidence interval: 1.04-5.87; P = 0.041), and no patients with the alteration had ≤5 bone metastases. CONCLUSIONS: the results of this study showed the promising survival outcomes in patients with genotype-matched therapy under public insurance, even in the castration-resistant prostate cancer setting. Further detection of promising therapeutic target gene is expected to increase the number of patients who reach genotype-matched therapies.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Japão/epidemiologia , Idoso de 80 Anos ou mais , Testes Genéticos , Metástase Neoplásica , População do Leste Asiático
3.
Curr Oncol ; 30(5): 5062-5071, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37232841

RESUMO

The indications for stereotactic body radiotherapy (SBRT) for prostate cancer have increased. However, the relationships between adverse events and risk factors remain unclear. This study aimed to clarify associations between adverse events and dose index for prostate SBRT. Participants comprised 145 patients irradiated with 32-36 Gy in 4 fractions. Radiotherapy-related risk factors such as dose-volume histogram parameters and patient-related risk factors such as T stage and Gleason score were evaluated in a competing risk analysis. Median follow-up duration was 42.9 months. A total of 9.7% had acute Grade ≥ 2 GU toxicities and 4.8% had acute Grade ≥ 2 GI toxicities. A total of 11.1% had late Grade ≥ 2 GU toxicities and 7.6% had late Grade ≥ 2 GI toxicities. Two (1.4%) patients suffered from late Grade 3 GU toxicities. Similarly, two (1.4%) patients suffered from late Grade 3 GI toxicities. Acute GU and GI events correlated with prostate volume and dose to the hottest 10 cc volume (D10cc)/volumes receiving a minimum of 30 Gy (V30 Gy) of rectum, respectively. Late GI toxicity, frequency, and rectal hemorrhage correlated with rectal D0.1 cc/D1 cc, maximum dose to the bladder, and rectal D0.1 cc, respectively. Toxicities after prostate SBRT using 32-36 Gy/4 fractions were acceptable. Our analysis showed that acute toxicities correlated with volume receiving a medium dose level, and late toxicities correlated with highest point dose of organs at risk.


Assuntos
Neoplasias da Próstata , Radiocirurgia , Masculino , Humanos , Próstata , Radiocirurgia/efeitos adversos , Pelve , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Reto
4.
BMC Cancer ; 23(1): 214, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882764

RESUMO

BACKGROUND: Despite the widespread availability of medication choices for metastatic castration-resistant prostate cancer (mCRPC), biomarkers to predict the efficacy of each mCRPC treatment have not yet been established. This study developed a prognostic nomogram and a calculator to predict the prognosis of patients with mCRPC who received abiraterone acetate (ABI) and/or enzalutamide (ENZ). METHODS: In total, 568 patients with mCRPC who underwent ABI and/or ENZ between 2012 and 2017 were enrolled. A prognostic nomogram based on the risk factors was developed using the Cox proportional hazards regression model and clinically important factors. The discriminatory ability of the nomogram was assessed according to the concordance index (C-index). A 5-fold cross-validation was repeated 2000 times to estimate the C-index, and the means of the estimated C-index for the training and validation sets were determined. A calculator based on this nomogram was then developed. RESULTS: The median overall survival (OS) was 24.7 months. Multivariate analysis showed that the time to CRPC, pre-chemotherapy, baseline prostate-specific antigen, baseline alkaline phosphatase, and baseline lactate dehydrogenase levels were independent risk factors for OS (hazard ratio [HR]: 0.521, 1.681, 1.439, 1.827, and 12.123, p = 0.001, 0.001, < 0.001, 0.019, and < 0.001, respectively). The C-index was 0.72 in the training cohort and 0.71 in the validation cohort. CONCLUSIONS: We developed a nomogram and calculator to predict OS in Japanese patients with mCRPC who received ABI and/or ENZ. Reproducible prognostic prediction calculators for mCRPC will facilitate greater accessibility for clinical use.


Assuntos
Nomogramas , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Acetato de Abiraterona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Benzamidas
5.
J Pain Palliat Care Pharmacother ; 37(1): 72-77, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36378038

RESUMO

(Case 1) A 45-year-old male was diagnosed with prostate cancer. Treatment was administered using bicalutamide and leuprorelin acetate, while a transdermal fentanyl (TDF) was applied for pain relief. However, TDF continued to peel off owing to excessive sweating, even when reinforced by a protective layer. As such, TDF was discontinued and pain control was initiated using other medicines. Sweating occurred irregularly because of hot flashes, approximately four to five times per day. (Case 2) A 37-year-old male was diagnosed with a malignant thymoma and sacral metastasis. For analgesic control, etodolac tablets, carbamazepine tablets, and TDF were administered. Subsequently, the dose of the TDF was gradually increased, but the analgesic effect was low; thus, fentanyl blood concentration was measured. The measurements showed that even higher TDF doses did not increase fentanyl blood levels. During this period, full body sweating began to occur to a large extent due to unknown causes, and it was thought that the absorption of fentanyl decreased. When using a TDF, it is necessary to monitor patients for any sweating during treatment, while also considering changes in medication in some cases. This should promote the maintenance and improvement of the quality of life of the affected patients.


Assuntos
Fentanila , Neoplasias , Masculino , Humanos , Pessoa de Meia-Idade , Adulto , Analgésicos Opioides , Dor/tratamento farmacológico , Sudorese , Qualidade de Vida , Neoplasias/complicações , Administração Cutânea , Adesivo Transdérmico
6.
Sci Rep ; 12(1): 11023, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35773371

RESUMO

We compared clinical outcomes associated with seed brachytherapy (SEED-BT) alone and SEED-BT plus external-beam radiotherapy (EBRT) for intermediate-risk prostate cancer using propensity score-matched analysis. From 2006 to 2011, 993 patients diagnosed with intermediate-risk were treated with either SEED-BT alone (n = 775) or SEED-BT plus EBRT (n = 158) at 3 tertiary hospitals. In the propensity score-matched analysis (102 pairs), median follow-up was 95 months (range 18-153 months). The 8-year biochemical recurrence-free rate (bRFR) was significantly better with SEED-BT alone than with combined radiotherapy (93.3% vs. 88.4%; HR 0.396; 95% CI 0.158-0.991). Grade 2 or greater late genitourinary toxicities were significantly fewer with SEED-BT alone than with combined radiotherapy (21.0% vs. 33.2%; HR 0.521; 95% CI 0.308-0.881). Similarly, grade 2 or greater late gastrointestinal toxicities were significantly fewer with SEED-BT alone (0% vs. 12.2%; HR 0.125; 95% CI 0.040-0.390). For the unfavorable intermediate-risk subgroups, SEED-BT alone yielded a significantly better bRFR than the combined radiotherapy (HR 0.325; 95% CI 0.115-0.915). SEED-BT alone might be a better disease-management plan than SEED-BT plus EBRT for intermediate-risk prostate cancer regardless of favorable and unfavorable characteristics.


Assuntos
Braquiterapia , Gastroenteropatias , Neoplasias da Próstata , Braquiterapia/efeitos adversos , Gastroenteropatias/etiologia , Humanos , Masculino , Pontuação de Propensão , Neoplasias da Próstata/tratamento farmacológico , Dosagem Radioterapêutica , Estudos Retrospectivos
7.
Int J Urol ; 29(10): 1147-1154, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35613936

RESUMO

OBJECTIVE: This study aimed to assess survival outcomes in older patients with de novo metastatic prostate cancer who initially received androgen deprivation therapy. METHODS: The retrospective multicenter study included 2784 men with metastatic prostate cancer who were treated with androgen deprivation therapy between 2008 and 2017. Patients were classified into <75, 75-79, and ≥80 age groups. Propensity score matching was conducted to assess the cancer-specific survival of the groups. The 5-year net overall survival of each group was derived to evaluate relative survival compared with the general population using the Pohar-Perme estimator and the 2019 Japan Life Table. RESULTS: During the follow-up (median, 34 months), 1014 patients died, of which 807 died from metastatic prostate cancer progression. Compared with the <75 group, the cancer-specific survival of the 75-79 group was similar (hazard ratio 1.07; 95% confidence interval 0.84-1.37; P = 0.580), whereas that of the ≥80 group was significantly worse (hazard ratio 1.41; 95% confidence interval 1.10-1.80; P = 0.006). The 5-year net overall survival of the <75, 75-79, and ≥80 age groups were 0.678, 0761, and 0.718, respectively. The 5-year net overall survival of patients aged ≥80 years with low- and high-volume disease were 0.893 and 0.586, respectively, which was comparable with those in patients aged <75 years (0.872 and 0.586, respectively). CONCLUSIONS: Older metastatic prostate cancer patients aged ≥80 years had poorer cancer-specific survival compared with younger patients. Conversely, 5-year net overall survival in older patients aged ≥80 years was comparable with that in younger patients aged <75 years.


Assuntos
Neoplasias da Próstata , Idoso , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias da Próstata/patologia , Estudos Retrospectivos
8.
Angew Chem Int Ed Engl ; 61(25): e202201965, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35390216

RESUMO

We report on the fluorescence properties of a new class of emissive and stable π-radicals that contain a boron atom at a position distant from the radical center. A fully planarized derivative exhibited an intense red fluorescence with high fluorescence quantum yields (ΦF >0.67) even in polar solvents. To elucidate the origin of this phenomenon, we synthesized another boron-stabilized radical that contains a bulky aryl group on the boron atom. A comparison of these derivatives, as well as with conventional donor-π-acceptor (D-π-A)-type emissive π-radicals, unveiled several characteristic features in their photophysical properties. A theoretical analysis revealed that the SOMO-LUMO electronic transition generates an emissive D1 state. Unlike conventional D-π-A-type π-radicals, this state does not undergo significant structural relaxation. The boron-stabilized π-radicals demonstrated promising potential for organic light-emitting diodes as an emitting material.

9.
Radiat Oncol ; 17(1): 71, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410307

RESUMO

BACKGROUND: We compared the oncological outcomes of patients who received seed brachytherapy (SEED-BT) with those who received radical prostatectomy (RP) for intermediate-risk prostate cancer. METHODS: Candidates were patients treated with either SEED-BT (n = 933) or RP (n = 334). One-to-one propensity score matching was performed to adjust the patients' backgrounds. We compared the biochemical recurrence (BCR)-free rate using the Phoenix definition (prostate-specific antigen [PSA] nadir plus 2 ng/mL) for SEED-BT and the surgical definition (PSA cut-off value of 0.2 ng/mL) for RP. We also directly compared the BCR-free rates using the same PSA cut-off value of 0.2 ng/mL for both SEED-BT and RP. RESULTS: In the propensity score-matched analysis with 214 pairs, the median follow-up treatment was 96 months (range 1-158 months). Fifty-three patients (24.7%) were treated with combined SEED-BT and external-beam radiotherapy. Forty-three patients (20.0%) received salvage radiotherapy after RP. Comparing the BCR-free rate using the above definitions for SEED-BT and RP showed that SEED-BT yielded a significantly better 8-year BCR-free rate than did RP (87.4% vs. 74.3%, hazard ratio [HR] 0.420, 95% confidence interval [CI] 0.273-0.647). Comparing the 8-year BCR-free rate using the surgical definition for both treatments showed no significant difference between the two treatments (76.7% vs. 74.3%, HR 0.913, 95% CI 0.621-1.341). SEED-BT had a significantly better 8-year salvage hormonal therapy-free rate than did RP (92.0% vs. 85.6%, HR 0.528, 95% CI 0.296-0.942, P = 0.030). The 8-year metastasis-free survival rates (98.5% vs. 99.0%, HR 1.382, 95% CI 0.313-6.083, P = 0.668) and overall survival rates (91.9% vs. 94.6%, HR 1.353, 95% CI 0.690-2.650) did not significantly differ between the treatments. CONCLUSIONS: The BCR-free rates did not significantly differ between patients treated with SEED-BT and those treated with RP for intermediate-risk prostate cancer even when they were directly compared using the surgical definition for BCR. SEED-BT and RP can be adequately compared for oncological outcomes.


Assuntos
Braquiterapia , Neoplasias da Próstata , Braquiterapia/efeitos adversos , Humanos , Masculino , Recidiva Local de Neoplasia/cirurgia , Antígeno Prostático Específico , Prostatectomia/efeitos adversos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Terapia de Salvação
10.
Int J Urol ; 29(5): 398-405, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35080069

RESUMO

OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Estudos Retrospectivos , Carga Tumoral
11.
Diagn Cytopathol ; 50(3): 123-132, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34981669

RESUMO

BACKGROUND: Bile cytology is useful in diagnosing biliary tract lesions, albeit often challenging due to equivocal findings. To achieve better diagnoses for clinical decisions, we conducted cytomorphological and immunocytochemical studies of bile cytology cases. MATERIALS AND METHODS: We re-evaluated 40 bile cytology cases with initial equivocal diagnoses, taken from the cytology records of Jichi Medical University Hospital, including 1778 bile cytology specimens. First, we assessed the cases by the diagnostic bile cytology criteria of the Japanese Society of Clinical Cytology. Second, we searched for useful immunocytochemical markers by extensive immunohistochemical analyses using tissue microarray for 10 antibodies: S100P, IMP3, GLUT1, p53, S100A4, Mapsin, MUC17, CD10, MDM2, and SMAD4. Microarrays were from 257 extrahepatic bile duct carcinoma cases. To elucidate the utility of immunocytochemistry, we applied selected markers to immunocytochemical evaluation of the equivocal cases after cell transfer. RESULTS: The criteria indicated a sensitivity 60%, specificity 87%, and accuracy 70%. Irregularly overlapping (88%), arranged (96%), and shaped (76%) nuclei were more common in malignant cases, while enlarged nuclei were more frequent in benign cases (67% vs. 28%). We applied S100P and IMP3, which showed higher accuracy (88% and 77%) in tissue microarray, to immunocytochemistry. The sensitivity of S100P and IMP3 were 69% and 70%, respectively. The specificity of S100P and IMP3 were 50% and 100%, respectively. CONCLUSION: The criteria showed a certain effectiveness even in challenging cases, and some pitfalls associated with reactive changes of benign cells. Although comprehensive diagnosis including cytomorphology seems preferable, S100P and IMP3 are promising immunocytochemical markers.


Assuntos
Neoplasias dos Ductos Biliares , Bile , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Proteínas de Ligação a RNA/análise
12.
Transl Androl Urol ; 11(12): 1771-1785, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36632151

RESUMO

A multidisciplinary approach is necessary to manage advanced prostate cancer. The Advanced Prostate Cancer Consensus Conference (APCCC) in 2019 provided a practical guide to help clinicians consider therapeutic options in controversial areas, but healthcare systems vary across the world. At the 109th annual meeting of the Japanese Urological Association in December 2021, Japanese urologists voted on the questions in the APCCC 2019 guidelines regarding prostate-specific membrane antigen-positron emission tomography (PSMA-PET), management of oligometastatic prostate cancer, management of nonmetastatic castration-resistant prostate cancer (CRPC), management of a primary tumor in metastatic settings, systemic treatment of newly diagnosed metastatic castration-sensitive prostate cancer (CSPC), management of metastatic CRPC (mCRPC), and tumor genomic testing. We summarize the "real-world" status of the management of advanced prostate cancer in Japan. Several differences were noted in the management of advanced prostate cancer between Japanese urologists and the APCCC 2019 guidelines. Many Japanese urologists chose conventional imaging modalities for detecting metastasis instead of PSMA-PET. More Japanese urologists prefer androgen-deprivation therapy (ADT) alone in the management of low-volume metastatic CSPC than the APCCC panelists do, In the management of M0 CRPC, darolutamide and enzalutamide were chosen more by Japanese urologists than by the voters at the APCCC 2019. Bicalutamide remains one of the options for the management of mCRPC in Japan. More Japanese urologists do not recommend microsatellite instability (MSI) and BRCA1/2 tests than the voters at the APCCC 2019. Clinical evidence in Japan should be collected to address these discrepancies.

13.
CEN Case Rep ; 11(2): 237-241, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34762263

RESUMO

Herein we report the case of a 37-year-old woman with recurrence of lupus nephritis (LN) in a renal allograft during pregnancy. She had developed end-stage renal disease due to LN and was put on hemodialysis at the age of 26 years. She underwent kidney transplantation at the age 28 years. Maintenance immunosuppressants included methylprednisolone, tacrolimus, and mycophenolate mofetil, which were changed to azathioprine when she desired pregnancy. The renal allograft function remained stable and seemingly disease-free until proteinuria and functional decline occurred during the pregnancy (age: 34 years). The baby was delivered by performing a cesarean section at 33 weeks of gestation. Renal allograft biopsy revealed crescent formation. Light microscopy revealed tuft necrosis and endocapillary proliferation. Immunofluorescence microscopy revealed the deposition of immunoglobulin G and C1q. A recurrence of LN (ISN/RPS class IV-G [A/C]) was diagnosed, and the patient was treated with pulse steroid therapy and azathioprine was replaced with mycophenolate mofetil. This treatment improved acute or active lesions of LN and temporarily benefited the renal allograft function. Unfortunately, there were irreversible chronic changes and a gradual decline in the renal allograft function.


Assuntos
Transplante de Rim , Nefrite Lúpica , Adulto , Aloenxertos/patologia , Azatioprina/uso terapêutico , Cesárea , Feminino , Humanos , Transplante de Rim/efeitos adversos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/patologia , Masculino , Ácido Micofenólico/uso terapêutico , Gravidez
14.
Asian J Urol ; 8(3): 280-288, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34401335

RESUMO

OBJECTIVE: Cytopathic effects and local immune response were analyzed histologically in prostatic cancer (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). METHODS: Four high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, n=3) or without neoadjuvant therapy (NT, n=4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values. RESULTS: ssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of single-stranded DNA (ssDNA) LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ=0.656, p<0.0001) as well as CD4+ T cells and CD20+ B cells (ρ=0.644, p<0.0001) in PCa with GT. CONCLUSIONS: Enhanced cytopathic effect and local immune response might be indicated in PCa patients with HSV-tk/GCV gene therapy.

15.
Urol Case Rep ; 38: 101712, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34123730

RESUMO

Poly (ADP-ribose) polymerase inhibitors exhibit strong activity for treating the DNA damage repair defect in patients with prostate carcinoma (PCa). Although conventional DNA-damaging agents can theoretically lead to synthetic antitumoral effects, no report has clearly mentioned the clinical use of cisplatin for treating PCa patients with the breast cancer gene (BRCA)2 mutation. We administered 80 mg/m2 cisplatin triweekly to a patient with metastatic castration-resistant PCa (mCRPC) with the BRCA2 mutation, and after ten cycles, the prostate-specific antigen was dramatically decreased. We suggest that BRCA2 mutations may indicate the use of cisplatin for treating patients with mCRPC.

16.
Cancer Sci ; 112(9): 3616-3626, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34145921

RESUMO

The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Modelos Estatísticos , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Hemoglobinas/análise , Humanos , Japão/epidemiologia , Masculino , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Medição de Risco
17.
Clin J Gastroenterol ; 14(2): 531-537, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33646513

RESUMO

Sessile serrated adenomas/polyps (SSA/Ps), recently called sessile serrated lesions, have a neoplastic pathway in the large intestine and are treated as lesions with malignant potential. There are a few reports of traditional serrated adenomas in the duodenum but no reports of duodenal SSA/Ps. A 66-year-old man underwent screening upper gastrointestinal endoscopy and was found to have a white elevated lesion in the second portion of the duodenum. Magnifying blue laser imaging showed various sized villous-like structures with dilated crypt openings in the white surface mucosa, similar to a SSA/P. Based on these images, a duodenal adenoma was suspected at the time of endoscopic resection. Pathological findings of the resected specimen showed a saw-tooth structure corresponding to basal crypt dilatation and branching with mucus and positive immunostaining for MUC6 and MUC2, similar to a colonic SSA/P. MUC5AC did not stain the glandular crypt cells. KRAS mutation was detected. Immunohistochemical expression of Annexin A10 was clearly identified in the lesion. Although not all of molecular biological features were satisfied, these findings were similar to a colonic SSA/P which has malignant potential. This is the first report of a duodenal SSA/P which should be considered when evaluating elevated duodenal lesions.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adenoma/cirurgia , Idoso , Colo/patologia , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Duodeno , Humanos , Masculino
18.
BJUI Compass ; 2(2): 105-114, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35474890

RESUMO

Objectives: To evaluate the prognosis of newly diagnosed patients with metastatic hormone-naïve prostate cancer (mHNPC) and develop a novel prognostic model based on ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) risk classifications. Patients and methods: We retrospectively analyzed the data of 578 newly diagnosed mHNPC patients initially treated with androgen deprivation therapy. We evaluated three clinical factors, namely, CHAARTED risk classifications (high-volume disease [HVD] vs low-volume disease [LVD]), Gleason scores (GS, 9-10 vs ≤8), and hemoglobin (Hb, ≤13.0 g/dL vs >13.0 g/dL), for their prognostic potential in predicting time to castration-resistant prostate cancer (TTC) and overall survival (OS) of mHNPC patients by multivariate analysis. Moreover, we developed a novel prognostic model that consisted of significant prognostic factors. Results: Of the entire cohort, the median TTC and OS values were 18.3 and 67.5 months, respectively. HVD, GS 9-10, and Hb ≤13.0 g/dL were independent poor prognostic factors for both TTC and OS. We developed a novel prognostic model which could stratify mHNPC patients into four risk groups according to the numbers of poor prognostic factors: group 1, LVD with low-risk (LVD patients without GS 9-10 and Hb ≤13.0 g/dL); group 2, LVD with high-risk (LVD patients with GS 9-10, Hb ≤13.0 g/dL, or both); group 3, HVD with low-risk (HVD patients without GS 9-10 with or without Hb ≤13.0 g/dL); and group 4, HVD with high-risk (HVD patients with GS 9-10 with or without Hb ≤13.0 g/dL). The median TTC and OS of groups 1, 2, 3, and 4 were 124.8, 36.4, 17.9, and 11.2 months, and 117.2, 94.2, 67.9, and 46.2 months, respectively. A significant difference in TCC and OS was found between all groups. Conclusion: We developed a prognostic model for mHNPC patients that consisted of CHAARTED risk classifications, GS, and Hb. Our prognostic model could significantly stratify the prognosis of patients with LVD and HVD into two groups each. This model might be a good reference for shared decision making between patients and physicians on the initial treatment for mHNPC.

19.
Int J Clin Oncol ; 26(3): 578-590, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33226524

RESUMO

BACKGROUND: Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS. RESULTS: In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11-0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%. CONCLUSIONS: Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations.


Assuntos
Antagonistas de Androgênios , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Método Duplo-Cego , Humanos , Japão , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Pirazóis
20.
Cancer Sci ; 112(4): 1524-1533, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33159829

RESUMO

Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens.


Assuntos
Hormônios/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Idoso , Antagonistas de Androgênios/uso terapêutico , Biópsia/métodos , Humanos , Japão , Masculino , Estadiamento de Neoplasias/métodos , Prognóstico , Intervalo Livre de Progressão , Neoplasias da Próstata/tratamento farmacológico , Estudos Retrospectivos
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