RESUMO
Purpose: To evaluate the utility of model-based deep learning reconstruction in prostate diffusion-weighted imaging (DWI). Methods: This retrospective study evaluated two prostate diffusion-weighted imaging (DWI) methods: deep learning reconstruction (DL-DWI) and traditional parallel imaging (PI-DWI). We examined 32 patients with radiologically diagnosed and histologically confirmed prostate cancer (PCa) lesions ≥10â¯mm. Image quality was evaluated both qualitatively (for overall quality, prostate conspicuity, and lesion conspicuity) and quantitatively, using the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) for prostate tissue. Results: In the qualitative evaluation, DL-DWI scored significantly higher than PI-DWI for all three parameters (p<0.0001). In the quantitative analysis, DL-DWI showed significantly higher SNR and CNR values compared to PI-DWI (p<0.0001). Both the prostate tissue and the lesions exhibited significantly higher ADC values in DL-DWI compared to PI-DWI (p<0.0001, p=0.0014, respectively). Conclusion: Model-based DL reconstruction enhanced both qualitative and quantitative aspects of image quality in prostate DWI. However, this study did not include comparisons with other DL-based methods, which is a limitation that warrants future research.
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This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the various advantages of laparoscopic surgery including minimal invasiveness, this technique has been widely used. However, expert surgeons have insufficient time for providing training to beginners due to the shortage of surgeons and limited working hours. Skill transfer efficiency has to be improved for which there is an urgent need to develop objective surgical skill evaluation methods. Therefore, a simple motion capture-based surgical instrument motion measurement system that could be easily installed in an operating room for skill assessment during practical surgical training was developed. The tip positions and orientations of the instruments were calculated based on the marker positions attached to the root of the instrument. Because the patterns of these markers are individual, this system can track multiple instruments simultaneously and detect exchanges. However due to the many obstacles in the operating room, the measurement data included noise and outliers. In this study, the effect of this decrease in measurement accuracy on feature calculation was determined. Accuracy verification experiments were conducted during wet-lab training to demonstrate the capability of this system to measure the motion of surgical instruments with practical accuracy. A surgical training experiment on a cadaver was conducted, and the motions of six surgical instruments were measured in 36 cases of laparoscopic radical nephrectomy. Outlier removal and smoothing methods were also developed and applied to remove the noise and outliers in the obtained data. The questionnaire survey conducted during the experiment confirmed that the measurement system did not interfere with the surgical operation. Thus, the proposed system was capable of making reliable measurements with minimal impact on surgery. The system will facilitate surgical education by enabling the evaluation of skill transfer of surgical skills.
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Competência Clínica , Laparoscopia , Laparoscopia/educação , Humanos , Instrumentos Cirúrgicos , Movimento (Física) , Cadáver , Nefrectomia/educação , Nefrectomia/métodosRESUMO
OBJECTIVES: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) using oral 5-aminolevulinic acid hydrochloride reduced residual tumors in high-risk non-muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD-TURBT for intravesical recurrence after a second transurethral resection for high-risk NMIBC. METHODS: High-risk NMIBC patients initially treated with PDD-TURBT (PDD group) were prospectively registered between 2018 and 2020. High-risk patients with NMIBC who were initially treated with white-light TURBT (WL group) were retrospectively registered. Intravesical recurrence-free survival after the second transurethral resection was compared between the PDD and WL groups using propensity score matching analysis. RESULTS: In total, 177 patients were enrolled in the PDD group, and 306 patients were registered in the WL group. After propensity score matching (146 cases in each group), intravesical recurrence within 1 year was significantly less frequent in the PDD group than in the WL group (p = 0.004; hazard ratio [HR] 0.44, 95% confidence interval [CI]: 0.25-0.77). In subgroup analysis, PDD-TURBT showed a particularly high efficacy in reducing intravesical recurrence within 1 year, especially in cases of tumors measuring less than 3 cm (p = 0.003; HR 0.31, 95% CI: 0.14-0.67), absence of residual tumor at second transurethral resection (p = 0.020; HR 0.37, 95% CI: 0.16-0.86), and no postoperative intravesical Bacillus Calmette-Guérin therapy (p < 0.001; HR 0.27, 95% CI: 0.13-0.58). CONCLUSIONS: PDD-TURBT may reduce short-term intravesical recurrence in patients with high-risk NMIBC.
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Ácido Aminolevulínico , Recidiva Local de Neoplasia , Neoplasias não Músculo Invasivas da Bexiga , Fármacos Fotossensibilizantes , Idoso , Feminino , Humanos , Masculino , Ácido Aminolevulínico/administração & dosagem , Cistectomia/métodos , Intervalo Livre de Doença , Invasividade Neoplásica , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/epidemiologia , Neoplasia Residual , Neoplasias não Músculo Invasivas da Bexiga/mortalidade , Neoplasias não Músculo Invasivas da Bexiga/patologia , Neoplasias não Músculo Invasivas da Bexiga/cirurgia , Fármacos Fotossensibilizantes/administração & dosagem , Pontuação de Propensão , Estudos Prospectivos , Estudos Retrospectivos , Ressecção Transuretral de BexigaRESUMO
OBJECTIVE: To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). METHODS: A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. RESULTS: The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.
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3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , 3-Iodobenzilguanidina/efeitos adversos , 3-Iodobenzilguanidina/uso terapêutico , Feocromocitoma/radioterapia , Estudos Retrospectivos , Masculino , Feminino , Paraganglioma/radioterapia , Pessoa de Meia-Idade , Adulto , Neoplasias das Glândulas Suprarrenais/radioterapia , Idoso , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To assess the effectiveness of pre- and postoperative supervised pelvic floor muscle training (PFMT) on the recovery of continence and pelvic floor muscle (PFM) function after robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: We carried out a single-blind randomised controlled trial involving 54 male patients scheduled to undergo RARP. The intervention group started supervised PFMT 2 months before RARP and continued for 12 months after surgery with a physiotherapist. The control group was given verbal instructions, a brochure about PFMT, and lifestyle advice. The primary outcome was 24-h pad weight (g) at 3 months after RARP. The secondary outcomes were continence status (assessed by pad use), PFM function, and the Expanded Prostate Cancer Index Composite (EPIC) score. RESULTS: Patients who participated in supervised PFMT showed significantly improved postoperative urinary incontinence (UI) compared with the control group (5.0 [0.0-908.0] g vs 21.0 [0.0-750.0] g; effect size: 0.34, P = 0.022) at 3 months after RARP based on 24-h pad weight. A significant improvement was seen in the intervention compared with the control group (65.2% continence [no pad use] vs 31.6% continence, respectively) at 12 months after surgery (effect size: 0.34, P = 0.030). Peak pressure during a maximum voluntary contraction was higher in the intervention group immediately after catheter removal and at 6 months, and a longer duration of sustained contraction was found in the intervention group compared with the control group. We were unable to demonstrate a difference between groups in EPIC scores. CONCLUSION: Supervised PFMT can improve postoperative UI and PFM function after RARP. Further studies are needed to confirm whether intra-anal pressure reflects PFM function and affects continence status in UI in men who have undergone RARP.
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Diafragma da Pelve , Prostatectomia , Neoplasias da Próstata , Incontinência Urinária , Humanos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Masculino , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , Incontinência Urinária/fisiopatologia , Pessoa de Meia-Idade , Diafragma da Pelve/fisiopatologia , Método Simples-Cego , Idoso , Neoplasias da Próstata/cirurgia , Terapia por Exercício/métodos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Cuidados Pós-Operatórios/métodos , Modalidades de FisioterapiaRESUMO
New technologies such as laparoscopic and robotic surgery are spreading, and there is a demand for physicians to keep up with novel methods. In contrast to the recent focus on healthcare professional burnout, the mental and physical costs during surgery are not well-understood. We aimed to quantify surgeons' workloads in daily urological surgical practice and clarify potential background factors associated with such workloads. Urologists in Hokkaido, Japan, were invited to this study. Between December 2020 and December 2021, participants repeatedly reported workloads, which were assessed using the National Aeronautics and Space Administration-Task Load Index (NASA-TLX), after each surgery in conjunction with participants' names, patients' backgrounds, their roles (independent operator, operator under supervision, instructor, and 1st or 2nd assistant), and surgical outcomes, via SurveyMonkey®. Because of the heterogeneity among individuals, a linear mixed-effects model was utilized to analyze factors associated with NASA-TLX, calculating the parameter estimates (PE) of regression coefficients for each factor and their 95% confidence interval (CI). Sixty-five urologists (5 women) joined the study, and 2169 data were collected within 7 days after surgeries. A linear mixed-effects model revealed that female surgeons (PE + 15.56, 95% CI 2.36-28.77), urgent/emergency surgery (PE + 6.65, 95% CI 4.59-8.70), intraoperative complications (PE + 9.26, 95% CI 6.76-11.76), and near-miss incidents (PE + 3.81, 95% CI 2.27-5.36) were associated with higher workloads. Regarding the surgeons' role, operator under supervision (PE + 12.46, 95% CI 9.86-15.06) showed the highest workloads. Surgeons' workloads decreased as the number of previous cases of the same procedure increased. Surgeons' workloads were associated with various factors. Given that the highest workloads were for operators under supervision, instructors should be aware of trainees' high workloads and devise appropriate instructional interventions.
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Cirurgiões , Carga de Trabalho , Humanos , Feminino , Masculino , Estudos Prospectivos , Adulto , Pessoa de Meia-Idade , Japão , Procedimentos Cirúrgicos Urológicos , Inquéritos e Questionários , LaparoscopiaRESUMO
We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p < 0.01).
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Carcinoma de Células de Transição , Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Estudos Prospectivos , Estudos Transversais , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , Biomarcadores , Invasividade Neoplásica , Receptores Acoplados a Proteínas GRESUMO
OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.
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Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Masculino , Feminino , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/mortalidade , Japão/epidemiologiaRESUMO
OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.
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Carcinoma de Células de Transição , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/mortalidade , Progressão da Doença , Inibidores de Checkpoint Imunológico/uso terapêutico , Japão/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/mortalidade , Estudos de CoortesRESUMO
OBJECTIVE: According to the rapid progress in surgical techniques, a growing number of procedures should be learned during postgraduate training periods. This study aimed to clarify the current situation regarding urological surgical training and identify the perception gap between trainees' competency and the competency expected by instructors in Japan. METHODS: Regarding the 40 urological surgical procedures selected via the Delphi method, we collected data on previous caseloads, current subjective autonomy, and confidence for future skill acquisition from trainees (<15 post-graduate years [PGY]), and the competencies when trainees became attending doctors expected by instructors (>15 PGY), according to a 5-point Likert scale. In total, 174 urologists in Hokkaido Prefecture, Japan were enrolled in this study. RESULTS: The response rate was 96% (165/174). In a large proportion of the procedures, caseloads grew with accumulation of years of clinical practice. However, trainees had limited caseloads of robotic and reconstructive surgeries even after 15 PGY. Trainees showed low subjective competencies at present and low confidence for future skill acquisition in several procedures, such as open cystectomy, ureteroureterostomy, and ureterocystostomy, while instructors expected trainees to be able to perform these procedures independently when they became attending doctors. CONCLUSION: Trainees showed low subjective competencies and low confidence for future skill acquisition in several open and reconstructive procedures, while instructors considered that these procedures should be independently performable by attending doctors. We believe that knowledge of these perception gaps is helpful to develop a practical training program.
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Competência Clínica , Procedimentos Cirúrgicos Urológicos , Urologia , Humanos , Japão , Urologia/educação , Procedimentos Cirúrgicos Urológicos/educação , Procedimentos Cirúrgicos Urológicos/normas , Masculino , Feminino , Inquéritos e Questionários/estatística & dados numéricos , Avaliação das Necessidades , Educação de Pós-Graduação em Medicina , Adulto , Urologistas/educação , Urologistas/estatística & dados numéricos , Urologistas/normas , Técnica Delphi , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Several guidelines recommended that second transurethral resection should be performed in patients with diagnosis of high-risk non-muscle-invasive bladder cancer. However, therapeutic benefits of second transurethral resection before bacillus Calmette-Guérin intravesical instillation were conflicting amongst previous studies. We investigated the prognostic impact of second transurethral resection before bacillus Calmette-Guérin instillation in high-risk non-muscle-invasive bladder cancer patients. METHODS: This retrospective study included 3104 non-muscle-invasive bladder cancer patients who received bacillus Calmette-Guérin instillations between 2000 and 2019 at 31 collaborative institutions. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors of intravesical recurrence, disease progression, cancer-specific mortality and overall mortality. RESULTS: In the entire population, patients undergoing second transurethral resection (33%, 1026/3104) had a lower risk of intravesical recurrence on univariate analysis (hazard ratio 0.85, 95% confidence interval 0.73-0.98, P = 0.027), although it did not remain significant on multivariate analysis (hazard ratio 0.90, 95% confidence interval 0.76-1.07, P = 0.24). Subgroup analysis revealed that, in pT1 patients (n = 1487), second transurethral resection was significantly correlated with a lower risk of intravesical recurrence on multivariate analysis (hazard ratio 0.80, 95% confidence interval 0.64-1.00, P = 0.048), but lower risks of disease progression (hazard ratio 0.75, 95% confidence interval 0.56-1.00, P = 0.049), cancer-specific mortality (hazard ratio 0.54, 95% confidence interval 0.35-0.85, P = 0.007) and overall mortality (hazard ratio 0.73, 95% confidence interval 0.55-0.97, P = 0.027) on univariate analysis. CONCLUSIONS: Second transurethral resection confers accurate pathological staging and could be used to safely select good candidates for intravesical bacillus Calmette-Guérin instillation. We further confirm that second transurethral resection could confer an oncological benefit in pT1 bladder cancer patients treated by bacillus Calmette-Guérin instillation, and so strongly recommend second transurethral resection in this patient population.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Vacina BCG/uso terapêutico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Administração Intravesical , Progressão da Doença , Recidiva Local de Neoplasia/patologia , Invasividade Neoplásica/patologia , Adjuvantes Imunológicos/uso terapêuticoRESUMO
RATIONALE: The increasing use of immune checkpoint inhibitors (ICIs) for treating malignant tumors result in the concomitant rise of immune-related adverse events (irAEs). This case report may provide useful insight to understanding the etiology of ICI-induced hypophysitis, a severe irAE leading to potentially fatal secondary adrenal insufficiency. PATIENT CONCERNS: An 81-year-old Japanese man was hospitalized for diabetic ketoacidosis following 4 courses of ICI combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma. DIAGNOSIS: Insulin secretion was depleted, leading to diagnosis of fulminant type 1 diabetes. Adrenocorticotropic hormone (ACTH) and cortisol levels were very high (60.8 pmol/L and 1575 nmol/L, respectively) upon admission. ACTH and cortisol returned to normal ranges on the 2nd day. On the 8th day, an ACTH loading test showed intact cortisol response (peak value 519 nmol/L). However, on the 14th day, there was a sharp decrease in ACTH and cortisol levels (10.5 pmol/L and 47 nmol/L, respectively) accompanied by fatigue and a drop in blood pressure to 97/63 mm Hg. As secondary adrenal insufficiency was suspected, hydrocortisone replacement was initiated. An ACTH loading test on the 17th day revealed low cortisol peak (peak value 232 nmol/L), indicating sudden disruption of adrenal function. Magnetic resonance imaging showed no abnormal findings and there was no other pituitary hormone deficiency. These findings, along with the patient clinical course, suggest that secondary adrenal insufficiency was caused by acute ACTH producing cell destruction as an irAE associated with ICI therapy. INTERVENTIONS: The patient hyperglycemia and ketoacidosis were treated using extracellular fluid and insulin therapy. After development of adrenal insufficiency, hydrocortisone 20 mg was started, and the patient symptoms improved. OUTCOMES: He was continued on insulin therapy, hydrocortisone, and reinitiated nivolumab. LESSONS: This case provides a detailed course of the fulminant onset of ACTH deficiency during ICI administration, emphasizing the importance of close monitoring.
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Insuficiência Adrenal , Carcinoma de Células Renais , Cetoacidose Diabética , Inibidores de Checkpoint Imunológico , Insulinas , Neoplasias Renais , Idoso de 80 Anos ou mais , Humanos , Masculino , Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico , Carcinoma de Células Renais/patologia , Cetoacidose Diabética/induzido quimicamente , Hidrocortisona/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Insulinas/uso terapêutico , Ipilimumab/efeitos adversos , Neoplasias Renais/patologia , Nivolumabe/efeitos adversosRESUMO
A 23-year-old male was aware of pain around his left hip joint and visited a nearby orthopedic clinic. Swelling of the right testis was pointed out, and a testicular tumor was suspected. He was referred to the urology department of a local hospital. Blood analysis showed an increase of α-fetoprotein (AFP) (3,620 ng/ml). Computed tomographic (CT) -scan revealed a left iliac bone metastasis and morbid fracture. Right radical inguinal orchiectomy was performed. The pathological examination revealed mixed germ cell tumor (embryonic carcinoma and immature teratoma: 70%, seminoma: 30%). The diagnosis was non-seminomatous germ cell tumor, stage IIIc, and poor risk on the International Germ Cell Consensus Classification. After one cycle of a bleomycin, etoposide and cisplatinum (BEP) regimen, he was referred to our hospital. After a total of 4 cycles of BEP, AFP was normalized. Denosumab was also administered monthly. The CT-scan showed a reduction of bone metastasis and recovery of ossification. Bone biopsy did not show viable tumor cells. Because extirpation of the remaining mass would require resection of the left part of the pelvic bone with significant functional loss of the left limb, we performed close follow-up after an additional 2 courses of the etoposide and cisplatin regimen. The patient is currently alive without recurrence at 45 months after the last systemic chemotherapy.
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Neoplasias Ósseas , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Adulto Jovem , Adulto , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Etoposídeo/uso terapêutico , alfa-Fetoproteínas/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Bleomicina/uso terapêutico , Orquiectomia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológicoRESUMO
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that produce catecholamines. [131I] MIBG-avid unresectable or metastatic PPGLs are treated with [131I] MIBG therapy. A high metabolic tumour volume (MTV) and total lesion glycolysis (TLG) can be poor prognostic factors. Therefore, we evaluated the metabolic responses to [131I] MIBG therapy with respect to other clinical factors.A retrospective study was performed on a series of 20 patients who underwent FDG-PET before and after [131I] MIBG therapy. We administered a single dose comprising 5.5 GBq of [131I] MIBG. Semi-quantitative parameters (SUVmax, MTV, and TLG) were calculated using the liver SUV (mean + 3SD) as a threshold on Metavol software. The semi-quantitative FDG-PET parameters for determining response were complete response , partial remission, stable disease, and progressive disease (PD). We divided our study participants into the PD and non-PD groups and compared the overall survival between the two groups. Subsequently, we evaluated the relationships between metabolic response and age, sex, tumour type, metastatic site, chemotherapy or external radiation history, and 24-hour urine catecholamine levels by univariate logistic regression analyses. Both MTV-based and TLG-based criteria for PD vs. non-PD were significant prognostic factors (p = 0.014). However, treatment response as evaluated based on the SUVmax was not a significant predictor. Higher urinary dopamine levels were associated with poor metabolic response as assessed by MTV and TLG. The other clinical parameters were non-significant. Poor metabolic response (measured with MTV and TLG) to [131I] MIBG therapy in unresectable or metastatic PPGLs was related to shorter OS. The poor metabolic response can be predicted using the urinary dopamine level.
RESUMO
OBJECTIVE: To determine the impact of postoperative complications on long-term survival outcomes in patients with bladder cancer undergoing radical cystectomy. METHODS: This retrospective multi-institutional study included 766 bladder cancer patients who underwent radical cystectomy between 2011 and 2017. Patient characteristics, perioperative outcomes, all complications within 90 days after surgery and survival outcomes were collected. Each complication was graded based on the Clavien-Dindo system, and grouped using a standardized grouping method. The Comprehensive Complication Index, which incorporates all complications into a single formula weighted by their severity, was utilized. Overall survival and recurrence-free survival (local, distant or urothelial recurrences) were stratified by Comprehensive Complication Index (high: ≥26.2; low: <26.2). A multivariate model was utilized to identify independent prognostic factors. RESULTS: The incidence of any and major complications (≥Clavien-Dindo grade III) was 70 and 24%, respectively. In terms of Comprehensive Complication Index, 34% (261/766) of the patients had ≥26.2. Patients with Comprehensive Complication Index ≥ 26.2 had shorter overall survival (4-year, 59.5 vs. 69.8%, respectively, log-rank test, P = 0.0037) and recurrence free survival (51.9 vs. 60.1%, respectively, P = 0.0234), than those with Comprehensive Complication Index < 26.2. The Cox multivariate model identified the age, performance status, pT-stage, pN-stage and higher CCI (overall survival: HR = 1.35, P = 0.0174, recurrence-free survival: HR = 1.26, P = 0.0443) as independent predictors of both overall survivial and recurrence-free survival. CONCLUSIONS: Postoperative complications assessed by Comprehensive Complication Index had adverse effects on long-term survival outcomes. Physicians should be aware that major postoperative complications can adversely affect long-term disease control.
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Neoplasias da Bexiga Urinária , Humanos , Cistectomia/efeitos adversos , Cistectomia/métodos , Incidência , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Sobreviventes de CâncerRESUMO
Introduction: Surgeons' mental workload during endoscopic sinus surgery (ESS) has not been fully evaluated. The assessment was challenging due to the great diversity of each patient's anatomy and the consequence variety of surgical difficulties. In this study, we examined the mental workload of surgeons with various surgical skill levels during ESS under the standardized condition provided by novel-designed 3D sinus models. Materials and methods: Forty-seven participants performed a high-fidelity ESS simulation with 3D-printed sinus models. Surgeons' mental workload was assessed with the national aeronautics and space administration-task load index (NASA-TLX). Associations between the total and subscales score of NASA-TLX and surgical skill index, including the board certification status, the number of experienced ESS cases, and the objective structured assessment of technical skills (OSATS), were analyzed. In addition, 10 registrars repeated the simulation surgery, and their NASA-TLX score was compared before and after the repetitive training. Results: The total NASA-TLX score was significantly associated with OSATS score (p = 0.0001). Primary component analysis classified the surgeons' mental burden into three different categories: (1) the skill-level-dependent factors (temporal demand, effort, and performance), (2) the skill-level-independent factors (mental and physical demand), and (3) frustration. After the repetitive training, the skill-level-dependent factors were alleviated (temporal demand; z = -2.3664, p = 0.0091, effort; z = -2.1704, p = 0.0346, and performance; z = -2.5992, p = 0.0017), the independent factors were increased (mental demand; z = -2.5992, p = 0.0023 and physical demand; z = -2.2509, p = 0.0213), and frustration did not change (p = 0.3625). Conclusion: Some of the mental workload during ESS is associated with surgical skill level and alleviated with repetitive training. However, other aspects remain a burden or could worsen even when surgeons have gained surgical experience. Routine assessment of registrars' mental burdens would be necessary during surgical training to sustain their mental health.
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Upper urinary tract urothelial carcinoma (UTUC) after intravesical bacillus Calmette-Guerin (BCG) therapy is rare, and its incidence, clinical impact, and risk factors are not fully understood. To elucidate the clinical implications of UTUC after intravesical BCG therapy, this retrospective cohort study used data collected between January 2000 and December 2019. A total of 3226 patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) and treated with intravesical BCG therapy were enrolled (JUOG-UC 1901). UTUC impact was evaluated by comparing intravesical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) rates. The predictors of UTUC after BCG treatment were assessed. Of these patients, 2873 with a medical history that checked UTUC were analyzed. UTUC was detected in 175 patients (6.1%) during the follow-up period. Patients with UTUC had worse survival rates than those without UTUC. Multivariate analyses revealed that tumor multiplicity (odds ratio [OR], 1.681; 95% confidence interval [CI], 1.005-2.812; p = 0.048), Connaught strain (OR, 2.211; 95% CI, 1.380-3.543; p = 0.001), and intravesical recurrence (OR, 5.097; 95% CI, 3.225-8.056; p < 0.001) were associated with UTUC after BCG therapy. In conclusion, patients with subsequent UTUC had worse RFS, CSS, and OS than those without UTUC. Multiple bladder tumors, treatment for Connaught strain, and intravesical recurrence after BCG therapy may be predictive factors for subsequent UTUC diagnosis.
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We investigated the ability of echo-planar imaging with L1-regularized iterative sensitivity encoding-based diffusion-weighted imaging (DWI) to improve the image quality and reduce the scanning time in prostate magnetic resonance imaging. We retrospectively analyzed 109 cases of prostate magnetic resonance imaging. We compared variables in the quantitative and qualitative assessments among 3 imaging groups: conventional parallel imaging-based DWI (PI-DWI) with an acquisition time of 3 minutes 15 seconds; echo-planar imaging with L1-regularized iterative sensitivity encoding-based DWI (L1-DWI) with a normal acquisition time (L1-DWINEX12) of 3 minutes 15 seconds; and L1-DWI with a half acquisition time (L1-DWINEX6) of 1 minute 45 seconds. As a quantitative assessment, the signal-to-noise ratio (SNR) of DWI (SNR-DWI), the contrast-to-noise ratio (CNR) of DWI (CNR-DWI), and the CNR of apparent diffusion coefficient were measured. As a qualitative assessment, the image quality and visual detectability of prostate carcinoma were evaluated. In the quantitative analysis, L1-DWINEX12 showed significantly higher SNR-DWI than PI-DWI (P = .0058) and L1-DWINEX6 (P < .0001). In the qualitative analysis, the image quality score for L1-DWINEX12 was significantly higher than those of PI-DWI and L1-DWINEX6. A non-inferiority assessment demonstrated that L1-DWINEX6 was non-inferior to PI-DWI in terms of both quantitative CNR-DWI and qualitative grading of image quality with a <20% inferior margin. L1-DWI successfully demonstrated a reduced scanning time while maintaining good image quality.
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Imagem Ecoplanar , Próstata , Masculino , Humanos , Imagem Ecoplanar/métodos , Próstata/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética/métodos , Razão Sinal-Ruído , Reprodutibilidade dos TestesRESUMO
Bladder cancer is a major and fatal urological disease. Cisplatin is a key drug for the treatment of bladder cancer, especially in muscle-invasive cases. In most cases of bladder cancer, cisplatin is effective; however, resistance to cisplatin has a significant negative impact on prognosis. Thus, a treatment strategy for cisplatin-resistant bladder cancer is essential to improve the prognosis. In this study, we established a cisplatin-resistant (CR) bladder cancer cell line using an urothelial carcinoma cell lines (UM-UC-3 and J82). We screened for potential targets in CR cells and found that claspin (CLSPN) was overexpressed. CLSPN mRNA knockdown revealed that CLSPN had a role in cisplatin resistance in CR cells. In our previous study, we identified human leukocyte antigen (HLA)-A*02:01-restricted CLSPN peptide by HLA ligandome analysis. Thus, we generated a CLSPN peptide-specific cytotoxic T lymphocyte clone that recognized CR cells at a higher level than wild-type UM-UC-3 cells. These findings indicate that CLSPN is a driver of cisplatin resistance and CLSPN peptide-specific immunotherapy may be effective for cisplatin-resistant cases.
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Proteínas Adaptadoras de Transdução de Sinal , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Bexiga Urinária , Humanos , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/terapia , Cisplatino/uso terapêutico , Imunoterapia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Regulação para Cima , Linfócitos T Citotóxicos/citologia , Células-Tronco Neoplásicas/efeitos dos fármacosRESUMO
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors arising from the neural crest cells that form the sympathetic and parasympathetic nervous systems. Radiotherapy with [131I]metaiodobenzylguanidine (MIBG) is recommended for unresectable PPGLs. We investigated the usefulness of the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) for predicting the prognosis of patients with unresectable PPGL(s) before receiving [131I]MIBG therapy. PATIENTS AND METHODS: We retrospectively analyzed the cases of 25 patients with unresectable PPGLs treated with [131I]MIBG at our hospital between 2001 and 2020. The MTV and TLG were measured in reference to liver accumulation. We divided the patients into two groups based on median values for the maximum standardized uptake value (SUVmax), MTV, and TLG, and evaluated between-group differences using log-rank tests. Cox proportional hazards models were used to determine whether there were significant differences in prognosis with respect to tumor type (pheochromocytoma vs. paraganglioma), site of metastasis, age, past treatment (chemotherapy, external radiation or [131I]MIBG treatment before the current [131I]MIBG treatment), urinary catecholamine, SUVmax, MTV, and TLG. RESULTS: The median follow-up time was 42 months (range 2-136 months). The median overall survival was 63 months. The overall survival (OS) was significantly shorter in the high-MTV group (log-rank test, p = 0.049) and the high-TLG group (p = 0.049), with no significant difference between the high- and low-SUVmax groups (p = 0.19). Likewise, there was no significant difference in prognosis according to pheochromocytoma or paraganglioma, metastasis location, age, or prior chemotherapy. A history of external radiation before [131I]MIBG treatment was associated with a significantly worse prognosis (hazard ration [HR] = 7.95, p = 0.0018). Urinary adrenaline and noradrenaline were not significant prognostic factors (p = 0.70, p = 0.25, respectively), but urinary dopamine did predict a worse outcome (p = 0.022). There was no increased risk of death for higher SUVmax or TLG (p = 0.63 and 0.057, respectively), but higher MTV did predict a worse outcome (HR = 7.27, p = 0.029). CONCLUSION: High MTV and high TLG were significantly associated with a poor prognosis after [131I]MIBG therapy for PPGLs. Other treatment strategies for such patients may need to be explored.