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1.
Invest New Drugs ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842657

ABSTRACT

This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.

2.
PLoS One ; 19(2): e0298573, 2024.
Article in English | MEDLINE | ID: mdl-38412181

ABSTRACT

OBJECTIVE: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of this study was to examine the effect of CPFE on lung cancer risk and lung cancer-related mortality in patients with rheumatoid arthritis (RA). METHODS: We conducted a multicenter retrospective cohort study of patients newly diagnosed with lung cancer at five community hospitals between June 2006 and December 2021. Patients were followed until lung cancer-related death, other-cause death, loss to follow-up, or the end of the study. We used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis. RESULTS: A total of 563 patients with biopsy-proven lung cancer were included (82 RA patients and 481 non-RA patients). The prevalence of CPFE was higher in RA patients than in non-RA patients (40.2% vs.10.0%) at lung cancer diagnosis. During follow-up, the crude incidence rate of lung cancer-related death was 0.29 and 0.10 per patient-year (PY) in RA and non-RA patients, and 0.32 and 0.07 per PY in patients with CPFE and patients without ILD or emphysema, respectively. The estimated death probability at 5 years differed between RA and non-RA patients (66% vs. 32%, p<0.001) and between patients with CPFE and patients without ILD or emphysema (71% vs. 24%, p<0.001). In addition to clinical cancer stage and no surgery within 1 month, RA and CPFE were identified as independent predictive factors for increased lung cancer-related mortality (RA: adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.65-4.76; CPFE: adjusted HR 2.01; 95% CI 1.24-3.23). CONCLUSIONS: RA patients with lung cancer had a higher prevalence of CPFE and increased cancer-related mortality compared with non-RA patients. Close monitoring and optimal treatment strategies tailored to RA patients with CPFE are important to improve the poor prognosis of lung cancer.


Subject(s)
Arthritis, Rheumatoid , Emphysema , Lung Diseases, Interstitial , Lung Neoplasms , Pulmonary Emphysema , Pulmonary Fibrosis , Humans , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/epidemiology , Pulmonary Fibrosis/diagnosis , Lung Neoplasms/complications , Lung Neoplasms/epidemiology , Retrospective Studies , Pulmonary Emphysema/complications , Pulmonary Emphysema/epidemiology , Pulmonary Emphysema/diagnosis , Lung Diseases, Interstitial/complications , Emphysema/complications , Emphysema/epidemiology , Arthritis, Rheumatoid/complications
3.
Eur Urol Oncol ; 7(3): 625-632, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38296736

ABSTRACT

BACKGROUND: Androgen deprivation therapy (ADT), administered alone, as combined androgen blockade (CAB) or as ADT plus androgen receptor signalling inhibitors (ARSIs) or ADT plus docetaxel, is the standard treatment for metastatic hormone-naïve prostate cancer (mHNPC) in Japanese real-world practice. OBJECTIVE: To investigate treatment patterns and clinical outcomes in LATITUDE criteria high-risk mHNPC. DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, multicentre, J-ROCK registry study enrolled patients initiating ADT in Japan after May 2019, and categorised them as cohort 1 (ADT or CAB) or cohort 2 (ADT plus ARSIs or docetaxel). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-specific antigen (PSA) response, progression-free survival (PFS), time to castrate-resistant prostate cancer (CRPC), overall survival (OS), and safety were evaluated. PFS, time to CRPC, and OS were estimated via the Kaplan-Meier method and between-cohort comparisons via multivariate Cox regression models. RESULTS AND LIMITATIONS: In total, 974 patients were included (cohort 1: 38.1%, cohort 2: 61.9%). CAB was preferred (67.4%) to ADT alone in cohort 1, and abiraterone acetate plus prednisolone was used most frequently in cohort 2 (59.4%). The proportion of patients with ≥50%/≥90% PSA decline or who achieved PSA ≤0.2/≤0.1 ng/ml tended to be higher in cohort 2. PFS (adjusted hazard ratio 0.42; 95% confidence interval [CI] 0.31-0.55), time to CRPC (0.28; 95% CI 0.23-0.36), and OS (0.54; 95% CI 0.35-0.82) were longer in cohort 2. In cohorts 1 and 2, adverse drug reactions of special interest (ADRSIs) occurred in 1.3% and 15.1%, and fatal adverse events occurred in 1.9% and 1.7%, respectively. Limitations included nonrandomised design, varying time since marketing authorisation for ARSIs, and limited safety assessments. CONCLUSIONS: ADT plus ARSIs or docetaxel was used more frequently to treat high-risk mHNPC than standard ADT/CAB and was associated with more favourable clinical outcomes. Although ADRSIs were reported more in cohort 2, the safety profile was considered tolerable. PATIENT SUMMARY: Although many treatment options are available for high-risk metastatic prostate cancer, there are limited reports on real-world clinical experience with different therapies outside of the clinical trial setting. In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone-naïve prostate cancer across Japan. We found that androgen deprivation therapy in combination with newer androgen receptor signalling inhibitors resulted in improved response compared with androgen deprivation therapy alone or in combination with a first-generation antiandrogen.


Subject(s)
Androgen Antagonists , Prostatic Neoplasms , Male , Humans , Aged , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/mortality , Treatment Outcome , Androgen Antagonists/therapeutic use , Middle Aged , Time Factors , Longitudinal Studies , Neoplasm Metastasis , Aged, 80 and over , Japan
4.
Sci Rep ; 13(1): 21548, 2023 12 06.
Article in English | MEDLINE | ID: mdl-38057434

ABSTRACT

The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno's concordance index was 0.661 (95% confidence interval [CI] 0.629-0.696) in the training set and 0.640 (95% CI 0.566-0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians' prognosis-based decision-making.


Subject(s)
Biliary Tract Neoplasms , Nomograms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gemcitabine , Deoxycytidine , Prognosis , Cisplatin/therapeutic use , Biliary Tract Neoplasms/pathology
5.
Clin Cancer Res ; 29(23): 4760-4769, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37796614

ABSTRACT

PURPOSE: This study aimed to investigate the safety and efficacy of lenvatinib in real-world settings, including patients excluded from the REFLECT trial, a phase III trial that compared lenvatinib with sorafenib. PATIENTS AND METHODS: This multicenter, nonrandomized, open-label prospective study was conducted at 10 medical facilities in Japan (jRCTs031190017). Eligible patients had advanced hepatocellular carcinoma (HCC) and were suitable for lenvatinib therapy. The study included patients with high tumor burden (with >50% intrahepatic tumor volume, main portal vein invasion, or bile duct invasion), Child-Pugh B status, and receiving lenvatinib as second-line therapy following atezolizumab plus bevacizumab. RESULTS: From December 2019 to September 2021, 59 patients were analyzed (47 and 12 patients with Child-Pugh A and B, respectively). In patients with Child-Pugh A, the frequency of aspartate aminotransferase elevation was high (72.7%) in the high-burden group. No other significant ad verse events (AE) were observed even in second-line treatment. However, patients with Child-Pugh B had high incidence of grade ≥3 AE (100.0%) and high discontinuation rates caused by AE (33.3%) compared with patients with Child-Pugh A (80.9% and 17.0%, respectively). Median progression-free survival was 6.4 and 2.5 months and median overall survival was 19.7 and 4.1 months in Child-Pugh A and B, respectively. Lenvatinib plasma concentration was higher in patients with Child-Pugh B on days 8 and 15 and correlated with dose modifications and lower relative dose intensity. CONCLUSIONS: Lenvatinib is safe and effective for advanced HCC in patients with Child-Pugh A, even with high tumor burden. However, it carries a higher risk of AE and may not provide adequate efficacy for patients with Child-Pugh B status.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Prospective Studies , Tumor Burden , Liver Neoplasms/pathology , Antineoplastic Agents/adverse effects , Niacinamide/adverse effects , Treatment Outcome
6.
Cancer Sci ; 114(3): 1165-1179, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36382538

ABSTRACT

Acinar cell carcinoma (ACC) of the pancreas is a malignant tumor of the exocrine cell lineage with a poor prognosis. Due to its rare incidence and technical difficulties, few authentic human cell lines are currently available, hampering detailed investigations of ACC. Therefore, we applied the organoid culture technique to various types of specimens, such as bile, biopsy, and resected tumor, obtained from a single ACC patient. Despite the initial propagation, none of these organoids achieved long-term proliferation or tolerated cryopreservation, confirming the challenging nature of establishing ACC cell lines. Nevertheless, the biopsy-derived early passage organoid developed subcutaneous tumors in immunodeficient mice. The xenograft tumor histologically resembled the original tumor and gave rise to infinitely propagating organoids with solid features and high levels of trypsin secretion. Moreover, the organoid stained positive for carboxylic ester hydrolase, a specific ACC marker, but negative for the duct cell marker CD133 and the endocrine lineage marker synaptophysin. Hence, we concluded the derivation of a novel ACC cell line of the pure exocrine lineage, designated HS-1. Genomic analysis revealed extensive copy number alterations and mutations in EP400 in the original tumor, which were enriched in primary organoids. HS-1 displayed homozygous deletion of CDKN2A, which might underlie xenograft formation from organoids. Although resistant to standard cytotoxic agents, the cell line was highly sensitive to the proteasome inhibitor bortezomib, as revealed by an in vitro drug screen and in vivo validation. In summary, we document a novel ACC cell line, which could be useful for ACC studies in the future.


Subject(s)
Carcinoma, Acinar Cell , Pancreatic Neoplasms , Humans , Mice , Animals , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/metabolism , Carcinoma, Acinar Cell/pathology , Homozygote , Sequence Deletion , Pancreatic Neoplasms/pathology , Organoids/metabolism , Cell Line , Pancreatic Neoplasms
7.
Intern Med ; 62(12): 1801-1806, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-36351574

ABSTRACT

A 77-year-old man was referred to our hospital for abnormal thoracic radiographs. Computed tomography (CT) revealed a 20-mm subpleural ground-glass opacity in the right S6 area. A CT-guided biopsy revealed lung adenocarcinoma. Fluorodeoxyglucose-positron emission tomography revealed multiple abnormal bone accumulations, and a subsequent biopsy of a left iliac bone lesion revealed chronic lymphocytic leukemia. A right lower lung lobectomy was performed for the lung adenocarcinoma (cT1bN0M0, stage IA2). An aggressive biopsy of the bone lesion confirmed a rare case of double primary malignancies, which determined the patient's treatment and outcomes.


Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Leukemia, Lymphocytic, Chronic, B-Cell , Lung Neoplasms , Male , Humans , Aged , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/diagnostic imaging , Adenocarcinoma of Lung/diagnostic imaging , Tomography, X-Ray Computed
8.
Mod Rheumatol ; 33(4): 723-731, 2023 Jul 04.
Article in English | MEDLINE | ID: mdl-35920411

ABSTRACT

OBJECTIVES: The aim is to evaluate outcomes and risk factors for death in patients with rheumatoid arthritis (RA) who developed Pneumocystis pneumonia (PCP). METHODS: We included RA patients who were diagnosed with PCP at seven participating community hospitals between July 2005 and October 2020. Clinical features were compared between survivors and non-survivors. Disease-modifying antirheumatic drugs (DMARDs) before PCP onset and after PCP recovery were also examined. RESULTS: Seventy RA patients developed PCP, and among them, 60 (85.7%) received methotrexate (MTX) monotherapy (40%) or MTX combination therapy with other DMARDs (45.7%). PCP was more likely to occur after 12 months of MTX monotherapy and within 3 months of MTX combination therapy. Thirteen patients (18.6%) died despite PCP treatment. Multivariable logistic regression analysis revealed that coexisting RA-associated interstitial lung disease (odds ratio, 6.18; 95% confidence interval, 1.17-32.63) and delayed PCP treatment with anti-Pneumocystis drugs (odds ratio, 15.29; 95% confidence interval, 1.50-156.15) are significant risk factors for PCP mortality in RA patients. Most survivors successfully resumed DMARD therapy without PCP prophylaxis; one recurrent PCP case was observed during follow-up (median, 4.1 years). CONCLUSIONS: To avoid a treatment delay, RA patients should be followed up for signs and symptoms of PCP development, especially those with RA-associated interstitial lung disease.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Lung Diseases, Interstitial , Pneumonia, Pneumocystis , Humans , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/drug therapy , Retrospective Studies , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Methotrexate , Antirheumatic Agents/adverse effects , Risk Factors , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/drug therapy
9.
Int J Urol ; 29(9): 1061-1070, 2022 09.
Article in English | MEDLINE | ID: mdl-36018236

ABSTRACT

OBJECTIVE: The prognosis of high-risk metastatic hormone-naïve prostate cancer is poor, and real-world evidence of therapeutic options and sequences is lacking. The J-ROCK study aimed to evaluate the outcomes in a real-world setting in Japan. METHODS: Patients with high-risk metastatic hormone-naïve prostate cancer diagnosed after May 2019 were eligible. Based on their treatment within 3 months after diagnosis, patients were allocated to either cohort 1 (androgen deprivation therapy alone or combined androgen blockade with bicalutamide) or cohort 2 (androgen deprivation therapy with abiraterone acetate+prednisolone, docetaxel, enzalutamide, or apalutamide). RESULTS: In this first interim analysis (cut-off January 2021), 410 patients were enrolled, including 163 patients in cohort 1 and 247 in cohort 2. The median follow-up period was 7.6 (range 0.1-20.5) months. A higher proportion of patients in cohort 2 (42.5%) achieved nadir prostate-specific antigen levels ≤0.2 ng/ml within a year, compared with cohort 1 (22.1%). Prostate-specific antigen-progression-free survival was also more favorable in cohort 2 (adjusted hazard ratio 0.629 [95% confidence interval 0.345-1.147]). CONCLUSIONS: The higher proportion of cohort 2 suggest a paradigm shift has occurred in the real-world treatment of high-risk metastatic hormone-naïve prostate cancer in Japan. Some factors including prostate-specific antigen may affect treatment selection but need further observation. Most patients in cohort 2 received abiraterone acetate+prednisolone. The proportion of patients in cohort 1 receiving combined androgen blockade was lower than previously reported in Japan. This analysis suggest that more intensive therapy tends to prolong prostate-specific antigen-progression-free survival in patients with high-risk metastatic hormone-naïve prostate cancer.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Prostatic Neoplasms , Abiraterone Acetate/therapeutic use , Androgen Antagonists , Androgens/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Japan/epidemiology , Male , Prednisolone/adverse effects , Prostate-Specific Antigen , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Registries , Treatment Outcome
10.
Nihon Hinyokika Gakkai Zasshi ; 113(2): 68-72, 2022.
Article in Japanese | MEDLINE | ID: mdl-37081655

ABSTRACT

A 75-year-old woman was admitted to our hospital with suspected gastrointestinal perforation and underwent emergency surgery. Bladder perforation was revealed during the surgery, and she was referred to our department. We detected a tumor on the apex of the bladder and performed partial resection of the bladder. Based on histopathological examination, a diagnosis of urachal cancer was established. Gemcitabine and cisplatin (GC) therapy was administered as an adjuvant therapy because of the high risk of peritoneal dissemination. She had the purulent spondylitis and gluteus medius abscess at the first course of GC therapy. We stopped GC therapy within the first course due to the adverse events and decreased performance status. Computed tomography revealed tumor recurrence in the pelvis three months after discontinuation of GC therapy. As the companion diagnostics revealed MSI-High, we administrated pembrolizumab. She was taking prednisolone 5 mg for SLE, but stable disease was observed after 5 courses of pembrolizumab. However, pembrolizumab was discontinued for eight months due to the stent graft insertion for the common iliac artery aneurysm. She had progressive disease after eight months interval of treatment. We restarted pembrolizumab but she was hospitalized for tumor fever after a total of eight courses. The patient died a month later. This seems to be the first case wherein pembrolizumab was administered for urachal cancer with MSI-High.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Microsatellite Instability , Female , Humans , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/pathology , Cisplatin
11.
Chron Respir Dis ; 18: 14799731211012965, 2021.
Article in English | MEDLINE | ID: mdl-33906454

ABSTRACT

The detection of exercise-induced hypoxemia is important for evaluating disease status in patients with chronic respiratory diseases. The 6-min walk test (6MWT) is useful for detecting exercise-induced hypoxemia. This pilot study aimed to validate the breath-holding test (BHT) as a screening for exercise-induced hypoxemia and compare its utility with that of the 6MWT in patients with chronic respiratory diseases. Fifty-nine patients with chronic respiratory diseases underwent BHTs lasting 10, 15, and 20 s. Percutaneous oxygen saturation (SpO2), pulse rate, and severity of dyspnoea were measured. The participants also underwent a 6MWT, a pulmonary function test, and analysis of arterial blood gas at rest. Multivariate linear regression analysis was performed to identify significant predictors of desaturation in the 6MWT. The minimum SpO2 during the BHT (all durations) and 6MWT were significantly correlated. Receiver operating characteristic analysis revealed the optimal cut-off for predicting SpO2 < 90% during the 6MWT as a minimum SpO2 ≤ 94% during the 15-s BHT. Perceived dyspnoea and maximum pulse rate were significantly lower during the 15-s BHT than during the 6MWT. In the multivariate linear regression analysis, the minimum SpO2 during the 15-s BHT (ß, 0.565, p < 0.001) and %DLco (ß, 0.255, p < 0.028) were independent predictors of desaturation in the 6MWT. The minimum SpO2 during the 15-s BHT may be a useful measure for screening for exercise-induced hypoxemia in patients with chronic respiratory diseases. The BHT is easier to perform, more readily available, and better tolerated than the 6MWT.


Subject(s)
Exercise Test , Pulmonary Disease, Chronic Obstructive , Dyspnea/diagnosis , Dyspnea/etiology , Humans , Hypoxia/diagnosis , Hypoxia/etiology , Oxygen , Pilot Projects , Walk Test
12.
Jpn J Radiol ; 39(5): 494-502, 2021 May.
Article in English | MEDLINE | ID: mdl-33387186

ABSTRACT

PURPOSE: To evaluate the safety and effectiveness of whole-liver transcatheter arterial chemoinfusion and bland embolization (TACBE) with fine-powder cisplatin and trisacryl gelatin microspheres for the treating unresectable multinodular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The medical records of all patients who underwent TACBE sessions were retrospectively reviewed. 15 patients (11 men, 4 women; mean age, 72.5 years) and 22 procedures (BCLC B;17 C;5) were included in the analysis. The cisplatin resulting solution and microspheres were infused through a microcatheter placed nonselectively. Overall survival (OS) was defined as the time from commencement of initial TACBE until any cause of death. Toxicity was assessed by the CTCAE version 5.0, and the tumor response was evaluated by the mRECIST. Liver function was assessed by the albumin-bilirubin (ALBI) score. RESULTS: The 1-year OS rate was 64.6% (95% CI 0.438-0.955). Severe adverse effects were not observed except for grade 3 increase in the ALT, ALT, vasovagal episode. The objective response and disease control rare were 54.5% and 68.2%, respectively. The ALBI scores from pre-treatment to the follow-up ranged from - 2.39 to - 2.26 (p = 0.38). CONCLUSION: Whole-liver TABCE with fine-powder cisplatin and trisacryl gelatin microspheres was well tolerated and effective in patients with multinodular HCC.


Subject(s)
Acrylic Resins/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Cisplatin/therapeutic use , Gelatin/therapeutic use , Liver Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Powders , Retrospective Studies , Survival Rate , Treatment Outcome
13.
Int J Urol ; 28(3): 273-279, 2021 03.
Article in English | MEDLINE | ID: mdl-33258172

ABSTRACT

OBJECTIVES: To investigate whether the result of the 1-mg dexamethasone suppression test can predict the improvement of comorbidities after adrenalectomy in patients with subclinical Cushing syndrome. METHODS: This retrospective study included 117 subclinical Cushing syndrome patients who underwent adrenalectomy. The numbers of prescribed drugs for metabolic comorbidities and the clinical variables at diagnosis were compared with those at the follow up. Patients were classified into subgroups according to the result of the 1-mg dexamethasone suppression test. RESULTS: Significant improvements in blood pressure, serum cholesterol and body mass index were observed. Furthermore, a significant improvement in glycated hemoglobin was observed in patients with diabetes mellitus. These improvements led to a discontinuation or reduction of prescribed drugs after surgery. In addition, the greatest reduction of prescribed drugs was observed in patients whose serum cortisol levels were between 1.8 and 3.0 µg/dL after the 1-mg dexamethasone suppression test. CONCLUSIONS: The result of the 1-mg dexamethasone suppression test can be a useful factor predicting the improvement of comorbidities after adrenalectomy. Current data might give us a new insight into the decision-making for the treatment of subclinical Cushing syndrome.


Subject(s)
Adrenalectomy , Cushing Syndrome , Cushing Syndrome/diagnosis , Cushing Syndrome/surgery , Dexamethasone , Humans , Japan/epidemiology , Retrospective Studies
14.
PLoS One ; 15(12): e0243110, 2020.
Article in English | MEDLINE | ID: mdl-33264361

ABSTRACT

OBJECTIVE: The aim of this study was to compare long-term mortality following diagnosis of pulmonary nontuberculous mycobacterial (NTM) disease between patients with and without rheumatoid arthritis (RA) and to evaluate predictive factors for death outcomes. METHODS: We reviewed the electronic medical records of all patients who were newly diagnosed with pulmonary NTM disease at participating institutions between August 2009 and December 2018. Patients were followed until death, loss to follow-up, or the end of the study. Taking into consideration the presence of competing risks, we used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis. RESULTS: A total of 225 patients (34 RA patients and 191 non-RA controls) were followed, with a mean time of 47.5 months. Death occurred in 35.3% of RA patients and 25.7% of non-RA patients. An exacerbation of pulmonary NTM disease represented the major cause of death. The estimated cumulative incidence of all-cause death at 5 years was 24% for RA patients and 23% for non-RA patients. For NTM-related death, the 5-year cumulative incidence rate was estimated to be 11% for RA patients and 18% for non-RA patients. Gray's test revealed that long-term mortality estimates were not significantly different between patient groups. Fine-Gray regression analysis showed that the predictive factors for NTM-related death were advanced age (adjusted hazards ratio 7.28 [95% confidence interval 2.91-18.20] for ≥80 years and 3.68 [1.46-9.26] for 70-80 years vs. <70 years), male sex (2.40 [1.29-4.45]), Mycobacterium abscessus complex (4.30 [1.46-12.69] vs. M. avium), and cavitary disease (4.08 [1.70-9.80]). CONCLUSIONS: RA patients with pulmonary NTM disease were not at greater risk of long-term mortality compared with non-RA patients. Rather, advanced age, male sex, causative NTM species, and cavitary NTM disease should be considered when predicting the outcomes of RA patients with pulmonary NTM disease.


Subject(s)
Arthritis, Rheumatoid/epidemiology , Mycobacterium Infections, Nontuberculous/mortality , Aged , Aged, 80 and over , Arthritis, Rheumatoid/mortality , Female , Humans , Male , Regression Analysis , Retrospective Studies , Survival Analysis
15.
Int J Urol ; 27(11): 1024-1030, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32875619

ABSTRACT

OBJECTIVES: To evaluate the relationship between residual urine volume, pyuria and bladder carcinoma recurrence. METHODS: The clinical data of 305 patients who had post-void residual urine volume measured and preoperative pyuria were retrospectively collected. The patients were classified into three risk groups based on the presence of residual urine and pyuria: good (negative residual urine and pyuria), intermediate (positive residual urine or pyuria) and poor (positive residual urine and pyuria). Predictive factors for intravesical recurrence-free survival were statistically analyzed using Cox proportional hazard models and Kaplan-Meier methods. The propensity score matching method was used to adjust the patients' backgrounds. RESULTS: The median follow-up period for all patients was 44 months. The presence of residual urine (P = 0.0164) and pyuria (P = 0.0233) were two independent prognostic factors for recurrence. After patients were classified into risk groups, the poor-risk group showed significantly shorter recurrence-free survival compared with that of the good- (P = 0.0002) and intermediate-risk groups (P = 0.0090). Even after matching, the presence of residual urine was related to short recurrence-free survival in male patients (P = 0.0012). When stratified by European Organization for Research and Treatment of Cancer risk groups, the presence of pyuria was related to short recurrence-free survival, especially for intermediate-risk patients without bacillus Calmette-Guérin treatment. CONCLUSIONS: Post-void residual urine and preoperative pyuria are two risks for recurrence-free survival in non-muscle-invasive bladder cancer.


Subject(s)
Carcinoma , Pyuria , Urinary Bladder Neoplasms , Administration, Intravesical , BCG Vaccine/therapeutic use , Humans , Male , Neoplasm Recurrence, Local/epidemiology , Pyuria/epidemiology , Pyuria/etiology , Retrospective Studies , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery
16.
IJU Case Rep ; 3(2): 33-35, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32743464

ABSTRACT

INTRODUCTION: When ileal conduit construction is performed for urinary tract drainage during radical cystectomy, the conduit is usually constructed in the right lower abdomen. However, no reports have described ileal conduit construction in the left lower abdomen when it cannot be performed on the right side. In addition, some ingenuity is necessary for construction on the left. CASE PRESENTATION: A 75-year-old woman visited our hospital with chief complaint of gross hematuria. Computed tomography and cystoscopy showed a huge bladder tumor, and blood analysis showed anemia. The patient was treated by radical cystectomy with ileal conduit construction. An ileal conduit was constructed in the left lower abdomen; it was impossible to construct in the right lower abdomen because of the abdominal wall scar hernia due to the past open surgery. CONCLUSION: We herein reported a patient who underwent ileal conduit for urinary diversion on the left side of low abdominal wall.

17.
Hinyokika Kiyo ; 66(5): 157-160, 2020 May.
Article in Japanese | MEDLINE | ID: mdl-32483952

ABSTRACT

Metastases to the subcutaneous scrotum are extremely rare. Here, we report a 78-year-old man who presented with pain to the scrotum and inguinal area. Two years ago, he underwent total gastrectomy for gastric cancer. The pain was attributed to increased scrotal wall thickness. Incisional biopsy of the thickened scrotal wall revealed diffused infiltration of the subcutaneous tissue by islands of scirrhous type malignant cells. Moreover, immunohistochemical studies showed that the tumor cells were positive for CK7, CK20, and CDX-2. These features suggested a metastatic adenocarcinoma of upper gastrointestinal origin. Although there were no visceral metastases, the tumor cells were too widely spread to be dissected curatively. Palliative chemotherapy with tegafur, gimeracil, and oteracil (S-1) was restarted, and local pain was subsequently ameliorated. Since scrotal metastasis is unlikely to occur it is difficult to diagnose. Therefore, in patients with groin discomfort or swelling and a history of gastric cancer, metastatic adenocarcinoma should be included in the differential diagnosis for early detection of a tumor.


Subject(s)
Genital Neoplasms, Male/surgery , Stomach Neoplasms/surgery , Aged , Gastrectomy , Humans , Male , Scrotum , Subcutaneous Tissue
18.
Prostate ; 80(11): 850-858, 2020 08.
Article in English | MEDLINE | ID: mdl-32501559

ABSTRACT

BACKGROUND: Oligometastatic cancer has been suggested as an intermediate state between localized disease and wide-ranging metastases. The clinical significance of local treatment in oligometastatic prostate cancer (PCa) has been a recent topic of interest. However, standard definitions of oligometastasis are lacking. Here we studied risk factors among Japanese de novo oligometastatic patients with PCa. METHODS: We retrospectively assessed clinical data from 264 patients, including locally advanced (T3 or T4N0M0) cancer, lymph-node-positive cancer (Tany N1M0), and cancer with ≤10 bone metastases. All patients received androgen deprivation therapy only. The number of bone metastases and clinical factors were evaluated in association with overall survival (OS) and progression-free survival (PFS). The Mann-Whitney U test, Cox proportional hazard models, and Kaplan-Meier methods were used as statistical analyses. RESULTS: Median age, PSA at baseline and OS were 74 years, 55.2 ng/mL, and 129.0 months, respectively. The cutoff for the number of bone metastases having the greatest impact on OS was ≥3 (hazard ratio [HR]: 2.67; P = .0001). In multivariate analysis, non-regional lymph node (LN) metastases (HR: 2.15; P = .0222), ISUP grade group (GG) 5 (HR: 2.04; P = .0186) and ≥3 bone metastases (HR: 1.82; P = .0390) were independent predictors of OS. In risk classification based on these factors, OS and PFS were significantly classifiable into poor (2-3 factors), intermediate (1 factor), and good (no factors) risk groups (P < .0001). CONCLUSION: Not only the number of bone metastases, but also non-regional LN metastases predict OS in patients with de novo oligometastatic PCa.


Subject(s)
Bone Neoplasms/mortality , Bone Neoplasms/secondary , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Androgen Antagonists/therapeutic use , Humans , Japan/epidemiology , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prognosis , Progression-Free Survival , Randomized Controlled Trials as Topic , Retrospective Studies , Survival Rate
19.
Prostate ; 80(7): 559-569, 2020 05.
Article in English | MEDLINE | ID: mdl-32134137

ABSTRACT

BACKGROUND: The inflammatory process has been reported to be involved in the formation and progression of various types of cancer. Recently, a peripheral inflammatory index, combining the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and the lactate dehydrogenase (LDH) level, was proposed as a useful prognostic marker in advanced nonsmall cell lung cancer. The prognostic value of inflammatory markers in prostate cancer has not been established. We aimed to validate the prognostic significance of this peripheral inflammatory index in metastatic castration-resistant prostate cancer (mCRPC). METHODS: Clinical data of 196 mCRPC patients were retrospectively collected from multiple institutions. Clinical factors and inflammatory markers at the development of CRPC, including white blood cell count, absolute neutrophil count, dNLR, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, C-reactive protein (CRP), and LDH levels, were evaluated. The patients were classified into three groups based on the inflammatory index: Good (low dNLR and LDH), Intermediate (high dNLR or LDH), and Poor (high dNLR and LDH). Overall survival (OS) and cancer-specific survival after CRPC were analyzed using Cox proportional hazard models and Kaplan-Meier methods. RESULTS: The median age and baseline prostate-specific antigen level were 75 years and 397.15 ng/mL, respectively. On multivariate analysis, dNLR (≥1.51; hazard ratio [HR] = 1.624; P = .0173), LDH (≥upper limit of normal; HR = 2.065; P = .0004), alkaline phosphatase (≥310 U/L; HR = 2.546; P < .0001), and positive N stage (HR = 1.621; P = .048) were associated with poor OS after CRPC, whereas other inflammatory markers including the NLR were not. The Good inflammatory index group showed significantly longer OS after CRPC compared to the Intermediate and Poor groups, with median survivals of 46.2, 28.9, and 16.6 months, respectively. CONCLUSIONS: The novel inflammatory index combining dNLR and LDH was a useful prognostic parameter in patients with mCRPC. Our analysis suggested that dNLR emerged as a more valuable prognostic marker than NLR.


Subject(s)
Inflammation/pathology , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , Humans , Inflammation/blood , L-Lactate Dehydrogenase/blood , Lymphocytes/pathology , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Neutrophils/pathology , Prognosis , Prostatic Neoplasms, Castration-Resistant/blood , Retrospective Studies
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