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BACKGROUND: Radical cystectomy in women generally includes the removal of the uterus, ovaries, and anterior vaginal wall, but the criteria for reproductive organ sparing are not clear. METHODS: A total of 2674 patients with bladder cancer were retrospectively reviewed, having undergone cystectomy at this nationwide multicenter from January 2013 to December 2019. We evaluated the incidence of malignancy in reproductive organs in a cohort of 417 women and analyzed the clinicopathological features of reproductive organ involvement. Recurrence-free survival and overall survival were reported using Kaplan-Meier survival curves. RESULTS: Median follow-up was 36.9 months. Of the 417 patients with urothelial carcinoma of the bladder, 325 underwent hysterectomy, and 92 had a spared uterus and anterior wall of the vagina. Twenty-nine (8.9%) patients exhibited reproductive organ involvement; this consisted of 22 (6.8%) uteri, 16 (4.9%) vaginas, and two (0.6%) ovaries. Incidental primary reproductive malignancies were found in only two (0.6%) patients. Recurrence-free survival and overall survival were significantly shorter in patients with reproductive organ involvement than in those without. Patients with reproductive organ involvement were more likely to have tumors with ≥ cT3 or sub-localization at the posterior/trigone/bladder neck. CONCLUSIONS: The risk of reproductive organ involvement cannot be ignored in women undergoing radical cystectomy for urothelial carcinoma of the bladder, therefore, the eligibility criteria for reproductive organ preservation should be considered carefully.
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Interferometers, which are built using spatially propagating light or matter waves, are commonly used to measure physical quantities. These measurements are made possible by exploiting the interference between waves traveling along different paths. This study introduces a novel approach to sensing of the Aharonov-Bohm phase, an ion matter-wave interferometer operating within a two-dimensional rotational trajectory in a trap potential. The ion orbitals in the nearly circular potential change rotation direction with time. This reversal of rotation direction results in a corresponding change in the interference phase. Our study is the first attempt to utilize propagating matter waves of an ion in constructing a two-dimensional interferometer for the measurement of physical quantities. Given that the scale factor of the interferometer to the cyclotron motion and the rotation of the system is common, the sensitivity to the Aharonov-Bohm phase in this study corresponds to a rotation sensitivity of approximately 300 rad/s. Besides advancing interferometry, our work also lays the foundation for future research into the use of ion matter waves in gyroscopic applications.
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OBJECTIVES: This study aims to develop a prognostic model that estimates the post-operative risk of cancer-specific mortality in patients with bladder cancer who underwent radical cystectomy (RC). METHODS: We analyzed the data from patients with bladder cancer who had undergone radical cystectomy without receiving adjuvant chemotherapy across 36 institutions in the Japan Urological Oncology Group. The data were randomly split into training (N = 1348) and validation sets (N = 674) in a 2:1 ratio. Twenty-five variables were analyzed, and a multivariable Cox regression model predicting cancer-specific mortality was developed and validated. Prognostic scores were categorized into good and poor prognostic groups based on the upper tertile. The performance of the model was compared against the CheckMate 274 risk classification as a reference, which is used for determining the indication of adjuvant nivolumab therapy. RESULTS: The final model incorporated eight variables. In the validation set, it outperformed the CheckMate 274 risk classification with superior time-dependent area under the curves (5-year: 0.81 vs. 0.67) and was well-calibrated. Furthermore, our model reclassified 27.8% of patients categorized as high-risk by the CheckMate 274 risk classification into the good prognosis group. CONCLUSIONS: We developed and validated a prognostic model for patients with bladder cancer who underwent RC. This model will be beneficial in identifying patients with poor prognosis and those who are potential candidates for clinical trials of adjuvant therapy.
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Extranodal extension in metastatic lymph nodes (LNs) is a poor prognostic factor in bladder cancer (BC). Furthermore, cancer invasion levels in sentinel LNs are associated with prognosis in melanoma. The present study aimed to evaluate the LN invasion level, defined as the extent of cancer invasion in anatomical and immunological LN substructures, and compare it with the pathological node (pN) stage of the tumor-node-metastasis staging system in BC. A total of 98 patients with BC who underwent radical cystectomy and pelvic lymphadenectomy were retrospectively assessed. The LN invasion level was classified as follows: Level 0, no cancer cell within the resected LNs; Level 1, cancer cells confined to intracapsular lymph vessels and subcapsular or transverse sinuses; Level 2, cancer cells infiltrating the cortex, paracortex or medulla; and Level 3, cancer cells infiltrating or beyond the LN capsule. The proportion of patients with Levels 0, 1, 2 and 3 was 70.4% (69/98), 8.2% (8/98), 14.3% (14/98) and 7.1% (7/98), respectively. Kaplan-Meier survival curves of recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) with LN invasion levels better stratified outcome patient when using Levels 1-3 compared with pN1-3. In addition, LN invasion levels better predicted RFS, CSS and OS, in comparison with the pN stage (c-index of 0.672 vs. 0.646, 0.688 vs. 0.665, and 0.702 vs. 0.661, respectively). Finally, multivariate analysis revealed that the predictive accuracy of the model integrating pathological tumor (pT) stage and LN invasion levels in RFS, CSS and OS was greater than that of the conventional model that included pT and pN stage (c-index of 0.723 vs. 0.703, 0.710 vs. 0.694, and 0.725 vs. 0.692, respectively). In conclusion, the model with LN invasion levels accurately predicted the prognosis of patients with BC after radical cystectomy and pelvic lymphadenectomy.
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BACKGROUND: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. METHODS: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. CONCLUSIONS: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.
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Escisión del Ganglio Linfático , Metástasis Linfática , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Antígeno Prostático Específico/sangre , Anciano , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/terapia , Pronóstico , Ganglios Linfáticos/patología , Estudios Retrospectivos , Periodo Posoperatorio , Terapia Recuperativa , Antagonistas de Andrógenos/uso terapéuticoRESUMEN
Purpose: Colistin is classified by the World Health Organization (WHO) as a critically important and last-resort antibiotic for the treatment of infections caused by carbapenem-resistant bacteria. However, colistin resistance mediated by chromosomal mutations or plasmid-linked mobilized colistin resistance (mcr) genes has emerged. Methods: Thirteen mcr-positive Aeromonas species isolated from water samples collected in Eastern Ghana were analyzed using whole-genome sequencing (WGS). Antimicrobial susceptibility was tested using the broth microdilution method. Resistome analysis was performed in silico using a web-based platform. Results: The minimum inhibitory concentration (MIC) of colistin for all except three isolates was >4 µg/mL. Nine new sequence types were identified and whole-genome analysis revealed that the isolates harbored genes (mcr-3-related genes) that code for Lipid A phosphoethanolamine transferases on their chromosomes. BLAST analysis indicated that the amino acid sequences of the mcr-3-related genes detected varied from those previously reported and shared 79.04-99.86% nucleotide sequence identity with publicly available mcr-3 variants and mcr-3-related phosphoethanolamine transferases. Analysis of the genetic context of mcr-3-related genes revealed that the genetic environment surrounding mcr-3-related genes was diverse among the different species of Aeromonas but conserved among isolates of the same species. Mcr-3-related-gene-IS-mcr-3-related-gene segment was identified in three Aeromonas caviae strains. Conclusion: The presence of mcr-3-related genes close to insertion elements is important for continuous monitoring to better understand how to control the mobilization and dissemination of antibiotic resistance genes.
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BACKGROUND: Clostridioides difficile infection is associated with antibiotic use and manifests as diarrhea; however, emerging cases of fulminant diarrhea caused by binary toxin-producing C. difficile unrelated to prior antibiotic exposure have been reported. Although fulminant colitis caused by C. difficile has been documented, instances of intussusception remain scarce. Here, we present a case of adult intussusception with severe hypokalemia and pneumonia resulting from a community-acquired C. difficile infection in Japan. CASE PRESENTATION: An 82-year-old male presented with dizziness, progressive weakness, and diarrhea. Initial vital signs indicated severe respiratory and circulatory distress, and laboratory findings revealed hypokalemia, pneumonia, and septic shock. Imaging confirmed intussusception of the ascending colon. Although colonoscopy suggested a potential tumor, no malignancy was found. The C. difficile rapid test result was positive, indicating community-acquired C. difficile infection. Treatment with vancomycin was initiated; however, intussusception relapsed. Surgical intervention was successful and led to clinical improvement. The patient's complex pathophysiology involved community-acquired C. difficile-induced severe diarrhea, hypokalemia, hypermetabolic alkalosis, and subsequent intussusception. Although adult intussusception is uncommon, this case was uniquely linked to binary toxin-producing C. difficile. The identified strain, SUH1, belonged to a novel sequence type (ST1105) and clade 3, suggesting a highly virulent clone. Resistome analysis aligned with phenotypic susceptibility to metronidazole and vancomycin, confirming their treatment efficacy. CONCLUSION: This case report highlights a binary toxin-producing C. difficile that caused intussusception. The consideration of community-acquired C. difficile in the differential diagnosis of severe enteritis is necessary, even in Japan.
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Clostridioides difficile , Infecciones por Clostridium , Infecciones Comunitarias Adquiridas , Hipopotasemia , Intususcepción , Humanos , Masculino , Anciano de 80 o más Años , Clostridioides difficile/aislamiento & purificación , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/complicaciones , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/microbiología , Hipopotasemia/etiología , Intususcepción/microbiología , Intususcepción/etiología , Neumonía/microbiología , Neumonía/complicaciones , Japón , Antibacterianos/uso terapéutico , Diarrea/microbiología , Diarrea/etiologíaRESUMEN
BACKGROUND: It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. METHODS: We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. RESULTS: This study included 67 patients treated with salvage radiotherapy with a median age of 67 years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3 years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6 months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6 months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. CONCLUSIONS: In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6 months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.
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Recurrencia Local de Neoplasia , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata , Terapia Recuperativa , Humanos , Masculino , Terapia Recuperativa/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/sangre , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Antígeno Prostático Específico/sangre , Clasificación del Tumor , Supervivencia sin Enfermedad , Márgenes de EscisiónRESUMEN
OBJECTIVES: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). METHODS: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves for non-urinary tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Interaction terms within IPTW-adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien-Dindo grade 3 or higher) was analyzed. RESULTS: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107-month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: -6.8 to 7.3]; CSS, 1.2 [-4.9 to 7.3]; OS, 0 [-6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). CONCLUSIONS: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR-associated factors, and (2) PU was associated with unfavorable perioperative outcomes.
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Cistectomía , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/efectos adversos , Cistectomía/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/mortalidad , Masculino , Estudios Retrospectivos , Femenino , Anciano , Persona de Mediana Edad , Japón/epidemiología , Resultado del Tratamiento , Uretra/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Estimación de Kaplan-Meier , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/epidemiología , Anciano de 80 o más Años , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.
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Fibras de la Dieta , Suplementos Dietéticos , Microbioma Gastrointestinal , Inulina , Ratones Endogámicos C57BL , Psyllium , Neoplasias de la Vejiga Urinaria , Animales , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Inulina/administración & dosificación , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/patología , Humanos , Femenino , Traumatismos por Radiación/prevención & control , Intestinos/microbiología , Intestinos/efectos de la radiación , Linfocitos T CD8-positivosRESUMEN
Utility of a recently developed long-read pipeline, Emu, was assessed using an expectation-maximization algorithm for accurate read classification. We compared it to conventional short- and long-read pipelines, using well-characterized mock bacterial samples. Our findings highlight the necessity of appropriate data-processing for taxonomic descriptions, expanding our understanding of the precise microbiome.
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Bacterias , Secuenciación de Nucleótidos de Alto Rendimiento , Microbiota , ARN Ribosómico 16S , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Microbiota/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Algoritmos , Nanoporos , ADN Bacteriano/genéticaRESUMEN
OBJECTIVES: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD). METHODS: Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance-free survival (CRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS. CONCLUSIONS: Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2-mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer.
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Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Estadificación de Neoplasias , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/mortalidad , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Metástasis Linfática/patología , Japón , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Micrometástasis de Neoplasia/patología , Pronóstico , Pueblos del Este de AsiaRESUMEN
BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.
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Ganglios Linfáticos , Metástasis Linfática , Recurrencia Local de Neoplasia , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/sangre , Prostatectomía/métodos , Antígeno Prostático Específico/sangre , Persona de Mediana Edad , Tasa de Supervivencia , Estudios de Seguimiento , Pronóstico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/sangre , Anciano , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Escisión del Ganglio Linfático , Estudios Retrospectivos , Estadificación de Neoplasias , Clasificación del Tumor , Márgenes de EscisiónRESUMEN
BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.
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Anticuerpos Monoclonales , Enfermedades del Sistema Nervioso Periférico , Humanos , Masculino , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anciano de 80 o más Años , Conducción Nerviosa/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/tratamiento farmacológico , Supervivencia sin Progresión , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patologíaRESUMEN
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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Cistectomía , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/métodos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/mortalidad , Masculino , Femenino , Pronóstico , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/mortalidad , Japón/epidemiologíaRESUMEN
In cases of rectal invasion by locally invasive prostate cancer (LAPC) leading to severe pain or bleeding, total pelvic exenteration (TPE) is necessary. Here, we present two cases of successful minimally invasive TPE: one performed laparoscopically for local recurrence with rectal bleeding after laparoscopic radical prostatectomy, and another done robotically for LAPC (clinical T4N1M0) accompanied by rectal bleeding. Medical treatments were ineffective in the latter case, and the tumor occupied a significant portion of the pelvis. We adopted a simultaneous transperineal approach and performed intracorporeal ileal conduit formation. Our cases highlight the challenging nature of minimally invasive TPE for symptomatic LAPC. Despite its complexity, these techniques prove viable and valuable in managing LAPC-related symptoms, emphasizing their practical utility in clinical settings.
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Exenteración Pélvica , Neoplasias de la Próstata , Neoplasias del Recto , Masculino , Humanos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Exenteración Pélvica/métodos , Recto/cirugía , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Prostatectomía , Recurrencia Local de Neoplasia/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). METHODS: This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50 ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. RESULTS: The median preoperative and postoperative eGFR were 61.1 and 46.4 ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3-4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. CONCLUSION: Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment.
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Carcinoma de Células Transicionales , Hidronefrosis , Laparoscopía , Insuficiencia Renal , Humanos , Nefroureterectomía , Nefrectomía , Carcinoma de Células Transicionales/cirugía , Hidronefrosis/complicaciones , Tasa de Filtración Glomerular , Riñón/cirugía , Laparoscopía/efectos adversos , Estudios RetrospectivosRESUMEN
Congenital hypogonadotropic hypogonadism (CHH) is a genetically and clinically diverse disorder encompassing Kallmann syndrome (KS) and normosmic CHH (nCHH). Although mutations in numerous genes account for nearly 50% of CHH cases, a significant portion remains genetically uncharacterized. While most mutations follow the traditional Mendelian inheritance patterns, evidence suggests oligogenic interactions between CHH genes, acting as modifier genes to explain variable expressivity and incomplete penetrance associated with certain mutations.In this study, the proband presented with nCHH, while his son exhibited KS. We employed whole-exome sequencing (WES) to investigate the genetic differences between the two, and Sanger sequencing was used to validate the results obtained from WES.Genetic analysis revealed that both the proband and his son harboured a mutation in FGFR1 gene. Notably, an additional rare mutation in PROKR2 gene was exclusively identified in the son, which suggests the cause of the phenotypic difference between KS and nCHH.
Asunto(s)
Hipogonadismo , Síndrome de Kallmann , Humanos , Síndrome de Kallmann/genética , Mutación Missense , Hipogonadismo/genética , Mutación , Familia , Receptores de Péptidos/genética , Receptores Acoplados a Proteínas G/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
IMPORTANCE: Clostridium perfringens causes gas gangrene and food poisoning in humans, and monitoring this bacterium is important for public health. Although whole-genome sequencing is useful to comprehensively understand the virulence, resistome, and global genetic relatedness of bacteria, limited genomic data from environmental sources and developing countries hamper our understanding of the richness of the intrinsic genomic diversity of this pathogen. Here, we successfully accumulated the genetic data on C. perfringens strains isolated from hospital effluent and provided the first evidence that predicted pathogenic C. perfringens may be disseminated in the clinical environment in Ghana. Our findings suggest the importance of risk assessment in the environment as well as the clinical setting to mitigate the potential outbreak of C. perfringens food poisoning in Ghana.
Asunto(s)
Infecciones por Clostridium , Enfermedades Transmitidas por los Alimentos , Humanos , Clostridium perfringens , Aguas Residuales , Ghana , Enfermedades Transmitidas por los Alimentos/microbiología , Infecciones por Clostridium/microbiologíaRESUMEN
Coronavirus disease (COVID-19) has caused extensive mortality globally; therefore, biomarkers predicting the severity and prognosis of COVID-19 are essential. This study aimed to evaluate the application of presepsin (P-SEP) and thrombomodulin (TM), which are biomarkers of sepsis and endothelial dysfunction, respectively, in the prognosis of COVID-19. Serum P-SEP and TM levels from COVID-19 patients (n = 183) were measured. Disease severity was classified as mild, moderate I, moderate II, or severe based on hemoglobin oxygen saturation and the history of intensive care unit transfer or use of ventilation at admission. Patients in the severe group were further divided into survivors and non-survivors. P-SEP and TM levels were significantly higher in the severe group than those in the mild group, even after adjusting for creatinine values. In addition, TM levels were significantly higher in non-survivors than in survivors. Changes in the P-SEP levels at two time points with an interval of 4.1 ± 2.2 days were significantly different between the survivors and non-survivors. In conclusion, TM and continuous P-SEP measurements may be useful for predicting mortality in patients with COVID-19. Moreover, our data indicate that P-SEP and TM values after creatinine adjustment could be independent predictive markers, apart from renal function.