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Introduction: Oligometastatic prostate cancer can be well-controlled through combined local and metastasis-directed therapies. However, the effects of cytoreductive radical prostatectomy and metastasectomy remain unclear. Case presentation: A 52-year-old man presented with prostate cancer and isolated bone metastasis to the thoracic spine. Six months after neoadjuvant hormonal therapy, the patient underwent cytoreductive radical prostatectomy and total en bloc spondylectomy. The postoperative course was uneventful. Hormonal therapy was terminated 5 years after surgery, and no biochemical or radiological progression was observed at 7 years postoperatively. Conclusion: Although careful patient selection is necessary, cytoreductive radical prostatectomy and metastasectomy are effective treatments for well-selected patients with oligometastatic prostate cancer.
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Introduction: In addition to reduced nectin-4 expression, the upregulation of ATP-binding cassette transporters has been suggested as a potential mechanism of resistance to enfortumab vedotin. Case presentation: A 76-year-old man previously treated with platinum-containing chemotherapy and pembrolizumab for metastatic bladder cancer was administered enfortumab vedotin because of disease progression. Subsequently, metastasectomy was performed for oligometastatic lesions (in the lung and adrenal gland) that exhibited growth during enfortumab vedotin therapy. Immunostaining analysis revealed decreased nectin-4 expression and elevated MDR1, MRP1, and BCRP expression in the metastatic lesions. Conclusion: Decreased nectin-4 expression and increased ATP-binding cassette transporter expression are potential factors in the development of enfortumab vedotin resistance in urothelial carcinoma. Immunohistochemical evaluation of these proteins may aid in predicting treatment efficacy.
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INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC); however, validating body composition-related biomarkers for their efficacy remains incomplete. We evaluated the association between body composition-related markers and the prognosis of patients with mRCC who received ICI-based first-line therapies. PATIENTS AND METHODS: We retrospectively investigated 60 patients with mRCC who underwent ICI-based therapy as their first-line treatment between 2019 and 2023. Body composition variables, including skeletal muscle, subcutaneous fat, and visceral fat indices, were calculated using baseline computed tomography scans. Sarcopenia was defined according to sex-specific cut-off values of the skeletal mass index. The associations between body composition indices and objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Patients with sarcopenia had lower ORR and DCR than those without sarcopenia (33.3% vs. 61.1%, p = 0.0436 and 52.4% vs. 94.4%, p = 0.0024, respectively). Patients with sarcopenia had a significantly shorter median PFS (14 months vs. not reached, p = 0.0020) and OS (21 months vs. not reached, p = 0.0023) than patients without sarcopenia did. Sarcopenia was a significant predictor of PFS (hazard ratio [HR], 4.31; 95% confidence interval [CI], 1.65-14.8; p = 0.0018) and OS (HR, 5.44; 95% CI, 1.83-23.4; p = 0.0013) along with poor IMDC risk. No association was found between the subcutaneous, visceral, and total fat indices and the therapeutic effect of ICI-based therapy. CONCLUSIONS: Sarcopenia was associated with a lower response and shorter survival rates in patients with mRCC who received first-line ICI-based therapy.
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Introduction: Although undifferentiated pleomorphic sarcomas are aggressive, a subset of these tumors are immunogenic and may respond to immunotherapy. Case presentation: A 69-year-old man developed bilateral adrenal tumors and underwent bilateral adrenalectomy. Pathological examination revealed undifferentiated pleomorphic sarcoma harboring tertiary lymphoid structures and infiltration of CD8+ T cells. Genome profiling revealed PD-L1 amplification, microsatellite instability, and a high tumor mutation burden. He developed local recurrence and multiple peritoneal dissemination 2 months after surgery; adriamycin chemotherapy was ineffective for these lesions. Sustained complete remission of all lesions was achieved by administering pembrolizumab. Conclusion: Immunohistochemical analysis focusing on tertiary lymphoid structures and genome profiling to evaluate microsatellite instability and tumor mutation burden are essential for precision medicine and informed clinical decision-making when treating advanced undifferentiated pleomorphic sarcoma.
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Myelolipoma is a benign tumor composed of mature adipose tissue and normal hematopoietic components. It usually occurs in the adrenal glands but rarely in the extra-adrenal region. However, it is difficult to differentiate extra-adrenal myelolipoma from well-differentiated liposarcoma on the basis of the radiological findings. We report the case of a 66-year-old male with perirenal and extra-adrenal myelolipoma who underwent radical tumor resection with nephrectomy after a preoperative diagnosis of liposarcoma. Intraoperative assessment by the surgeon and intraoperative pathological evaluation are important considering the divergent prognoses of myelolipoma and liposarcoma.
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A 42-year-oldman visited our hospital because of gradually worsening penile swelling over 3 weeks. A hard mass on the glans was palpated; however, we were unable to observe it due to severe phimosis. Magnetic resonance imaging of the pelvis revealed enlargement of glans and swelling of bilateral inguinal lymph nodes as both showed a low signal intensity on T2-weightedimaging, a high signal intensity on diffusion-weighted imaging, and a low signal intensity on the apparent diffusion coefficient map. Fluorine- 18-deoxyglucose (FDG) positron emission tomography showed FDG uptake at the external iliac, common iliac, obturator, and cervical lymph nodes besides the glans and inguinal lymph nodes. Although his serum squamous cell carcinoma antigen level was within the normal range, his soluble interleukin-2 receptor concentration was elevated to 2,290 U/ml. Therefore, we diagnosed these lesions as penile cancer with multiple lymph node metastases, with a possible differential diagnosis of malignant lymphoma. We planned a penile needle biopsy; however, the rapid plasma reagin test and treponema pallidum hemagglutination test, which were performed during the preoperative examination, were positive and led to a diagnosis of secondary syphilis. The patient was treated with oral amoxicillin at 1,500 mg/day for 8 weeks. The penile and lymph node swelling subsided after starting medication.
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Fluorodesoxiglucosa F18 , Neoplasias del Pene , Masculino , Humanos , Metástasis Linfática/patología , Neoplasias del Pene/patología , Ganglios LinfáticosRESUMEN
The heat shock response (HSR) is a cellular mechanism for counteracting acute proteotoxic stress. In eukaryotes, transcriptional activation of the HSR is regulated by heat shock factor 1 (HSF1). Activation of HSF1 induces the expression of heat shock proteins (HSPs) that function as molecular chaperones to fold and maintain the three-dimensional structure of misfolded proteins. The regulation of the degree and duration of the HSR is controlled by multiple biochemical mechanisms that include posttranslational modification of HSF1 and numerous protein-protein interactions. In this chapter, we describe a method to evaluate the activation and deactivation of the HSR at the transcriptional level using a short half-life luciferase reporter assay. This assay can be used to further characterize the HSR or as a screen for small molecule inducers, amplifiers, or repressors.
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Proteínas de Choque Térmico , Factores de Transcripción , Factores de Transcripción del Choque Térmico/genética , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Respuesta al Choque Térmico/genética , Luciferasas/genética , Luciferasas/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismoRESUMEN
Background: It is common to repeat prostate-specific antigen (PSA) measurements for men with PSA elevation before prostate biopsy. In this scenario, they may have considerable psychological distress in fear of the presence of cancer until retests. We assessed possible clinical factors causing transient PSA rise and explored the parameters predictive of subsequent PSA change. Methods: As interfering conditions, the history of ejaculation, bicycling, and any types of infections were assessed using the questionnaire. The pattern of PSA change was compared in association with the various clinical factors. Predictive significance of PSA kinetics such as coefficient of variation (CV) and PSA velocity (PSAV) for PSA values at retest was evaluated. Results: The rate of reversion to the normal range was 38.3% at retest. The rate of 12.8% of men showed a large increase by ≥20%, whereas 38.2% of men showed a large decline by ≥20% from the baseline. Men with younger age (≤60 years), small prostate (<20 cc), and prior history of ejaculation or infections showed significantly larger PSA decrease than their counterparts. Those with large CV or PSAV before the baseline more frequently showed PSA decrease below the age-specific cutoff or decline by ≥10% from the baseline at retest. These parameters associated with PSA kinetics had independent predictive values for relevant PSA change at retest. Conclusions: Ejaculation and any types of infections should be avoided before PSA tests. Men with large PSA fluctuation before the baseline are likely to show a significant PSA decrease at retest. This predictive information may help both physicians to determine whether to proceed to an immediate biopsy and patients to reduce their psychological burden.
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Previous studies indicated the occurrence of compartment syndrome after testicular detorsion. In such cases, testicular blood flow may improve with tunica albuginea incision. A 14-year-old man presented with right-sided testicular torsion. No improvement in testicular appearance after detorsion led to a tunica albuginea incision for immediate recovery of testicular blood flow. The affected testis, covered with a tunica vaginalis patch, exhibited no atrophy at the 6-month follow-up. Magnetic resonance imaging revealed that the affected testis had blood flow comparable to that on the unaffected side. This technique is useful for avoiding orchiectomy in testes with poor blood flow after detorsion.
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BACKGROUND: Adrenocortical carcinoma is an aggressive tumor which often recurs despite apparent complete resection. This study assessed the long-term outcomes for patients with recurrent adrenocortical carcinoma after multimodal salvage therapy with chemotherapy, chemoradiotherapy and surgery. METHODS: We retrospectively reviewed medical records of patients who had a pathological diagnosis of adrenocortical carcinoma between 1996 and 2017. Kaplan-Meier curves were used to assess progression-free and cancer-specific survivals among all patients and cancer-specific survival among patients with tumor recurrence. Log-rank test was used to compare patient survivals by modality of salvage therapy (chemotherapy, chemoradiotherapy and chemotherapy/chemoradiotherapy plus surgery). RESULTS: Of 20 patients who underwent initial surgery, recurrence occurred in 14 (70%) with a median interval of 7.5 (range 1.0-12.6) months. Salvage therapy provided was chemotherapy only (n = 7), chemoradiotherapy (n = 2) and chemotherapy/chemoradiotherapy plus surgery (n = 5). Of the five patients who received salvage surgery, three underwent repeated resections. The potential benefit of multimodal salvage therapy was suggested in five patients (4 with chemotherapy/chemoradiotherapy plus surgery and 1 with chemoradiotherapy) who achieved durable disease control (cancer-specific survival from initial recurrence, 22-258 months). With a median follow-up of 25 months from recurrence, the 5-year cancer-specific survival rate was 58%. cancer-specific survival after recurrence was prolonged in patients with ≤ stage 3 disease, positive response to chemotherapy/chemoradiotherapy and salvage surgery. CONCLUSIONS: Long-term disease control and survival could be achieved in highly selected patients with recurrent adrenocortical carcinoma using a multidisciplinary approach. Patients who had relatively limited recurrent sites and responded well to chemotherapy/chemoradiotherapy may be considered for salvage surgery on a case-by-case basis.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Carcinoma Corticosuprarrenal/terapia , Terapia Recuperativa , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Quimioradioterapia , Neoplasias de la Corteza Suprarrenal/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: The human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2; also known as B7 homolog 7 [B7-H7]) regulates immune responses. However, its immunoregulatory role in upper tract urothelial carcinoma (UTUC) remains unclear. METHODS: We evaluated the immunohistochemical expression of HHLA2 and fibroblast activation protein (FAP), which is a marker of cancer-associated fibroblasts, in UTUC tissues from 85 patients who underwent nephroureterectomy. The associations between the expressions of HHLA2 and FAP and clinicopathological characteristics were investigated. RESULTS: The increased expression of HHLA2 in tumor cells (t-HHLA2) was associated with a low histological grade, a negative lymphovascular invasion (LVI), and a low neutrophil-to-lymphocyte ratio, whereas an increased expression of HHLA2 in stromal cells (s-HHLA2) was associated with a high histological grade. No correlation was observed between the expression of t-HHLA2 and s-HHLA2. FAP was expressed only in the stromal cells (s-FAP). Positive s-FAP expression was significantly associated with increased s-HHLA2 expression, higher histological grade, higher pathological T stage, and positive LVI. Higher t-HHLA2 was associated with longer cancer-specific and progression-free survival. In contrast, positive s-FAP was associated with short progression-free survival. CONCLUSION: These findings suggest that the progression of UTUC may involve increased co-expression of HHLA2 and FAP in the tumor stroma.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/patología , Pronóstico , Nefroureterectomía , Fibroblastos/metabolismo , InmunoglobulinasAsunto(s)
Neoplasias Óseas , Neoplasias de la Próstata , Masculino , Humanos , Imagen por Resonancia Magnética/métodos , Proyectos Piloto , Médula Ósea/patología , Imagen de Cuerpo Entero/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Programas Informáticos , Neoplasias Óseas/secundarioRESUMEN
Introduction: We report a rare case of abdominal wall abscess caused by ileal diverticulitis that developed along the midline below the umbilicus and resembled a urachal carcinoma. Case presentation: A 76-year-old woman with diabetes presented with abdominal enlargement below the umbilicus. Computed tomography revealed a well-enhanced mass, which was visualized on magnetic resonance imaging as a continuous mass connected to the restiform structure, extending from the umbilicus to the bladder. As the mass showed high uptake on 18F-fluorodeoxyglucose positron emission tomography, urachal carcinoma was suspected, and surgery was subsequently performed. As the tumor adhered to the ileum, partial resection of the small intestine was required. The pathological diagnosis was abdominal wall abscess associated with ileal pseudodiverticulitis. Conclusion: Although abdominal wall abscess caused by ileal diverticulitis is rare, it should be considered as a differential diagnosis of urachal carcinoma.
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BACKGROUND: The neuroendocrine (NE) pathway cannot be ignored as a mechanism for castration-resistant prostate cancer (CRPC) progression. The neuromediator, gastrin-releasing peptide (GRP) may be involved in the aberrant activation of the normal androgen receptor (AR) and increased AR variants. This study focused on plasma levels of progastrin-releasing peptide (ProGRP) and examined the treatment outcomes with androgen receptor axis-targeted (ARAT) agents. METHODS: One hundred patients with metastatic CRPC were enrolled. Enzalutamide (ENZ) or abiraterone acetate/prednisone (AA/P) were administered to 50 patients each in a nonrandomized manner as a first-line or later choice. Plasma ProGRP levels were determined using a chemiluminescent enzyme immunoassay, and data were collected prospectively. The study endpoints were prostate-specific antigen (PSA) response and survival estimates. RESULTS: In the ENZ series, ProGRP levels correlated with the maximum PSA change from baseline (high ProGRP: -34.5% vs. low ProGRP: -85.7% p = .033). PSA progression-free survival (PFS), radiographic/symptomatic (r/s) PFS, and overall survival (OS) in patients with high ProGRP were significantly worse than those in patients with low ProGRP (median PSA-PFS: 3.3 vs. 10.0 months, p = .001, r/s PFS: 5.0 vs. 15.0 months, p < 0.001, and OS 17.5 vs. 49.0 months, p < .001, respectively). In addition, ProGRP showed an independent predictive value for all survival estimates in multivariate analyses. In the AA/P series, ProGRP levels did not correlate with the PSA change or predict PSA-PFS and r/s PFS, but they maintained a significant difference in OS (19.0 vs. 48.0 months, p = .003). CONCLUSIONS: Plasma ProGRP provides a consistent predictive value for OS in metastatic CRPC patients who underwent therapy with ARAT agents. Meanwhile, ProGRP showed different predictive profiles for PSA- and r/s PFS between ENZ and AA/P. These findings clinically suggest a mechanism for CRPC progression involving the NE pathway via the GRP. The underlying mechanism of different predictive profiles by the ARAT agent should be explored in future research.
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Antineoplásicos , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Receptores Androgénicos/metabolismo , Receptores Androgénicos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Antígeno Prostático Específico , Antineoplásicos/uso terapéutico , Acetato de Abiraterona/uso terapéutico , Péptidos/uso terapéuticoRESUMEN
A mycotic aneurysm after intravesical instillation of bacillus Calmette-Guérin (BCG) for early-stage bladder cancer is a rare, but life-threatening, complication. In the present report, we have described the case of a patient who had undergone endovascular aneurysm repair for a rapidly growing saccular abdominal aortic aneurysm after BCG therapy. Three months after endovascular aneurysm repair, the patient had developed an abscess that required open surgery. Cultures from a blood sample and the abscess revealed Mycobacterium bovis BCG. A mycotic aneurysm due to BCG therapy should be suspected in patients with a history of BCG treatment. Such patients should immediately start antitubercular therapy.
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Application of immune checkpoint inhibitors (ICIs) in elderly patients remains challenging due to the scarcity of safety and efficacy data. An 84 year-old female with a right renal cell carcinoma invading the vena cava received two cycles of avelumab plus axitinib. As the thrombus showed a marked reduction, right nephrectomy and vena cava thrombectomy were performed. Pathological examination revealed intra-tumor infiltration of CD8+ T cells suggesting the efficacy of immunotherapy. Although immune function deteriorates with age (immunosenescence), our findings suggest that older patients may not necessarily be excluded from ICI therapy.
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INTRODUCTION AND IMPORTANCE: A two-step process involving ureteral stenting and surgical repair is generally recommended to manage a delayed diagnosis of postoperative ureteral injury; however, retrograde stenting is often difficult. CASE PRESENTATION: A 35-year-old female-to-male transgender person who underwent laparoscopic gender-affirming total hysterectomy with bilateral salpingo-oophorectomy developed right ureteral injury at 2 months postoperatively. Initially, the stenting guidewire could not pass through the stenotic tract and was diverted into the abdominal cavity. Using a 0.014-in. microguidewire and a 2-Fr microcatheter, both of which are designed for angiography, the ureteral stent was ultimately placed. The patient underwent surgical repair using the Boari flap technique. The double J catheter was removed at 1 month postoperatively, and postoperative retrograde pyelography revealed no urinary leakage or ureteral stricture. CLINICAL DISCUSSION: Immediate primary repair is desirable for intraoperative ureteral injuries. However, up to 70 % of ureteral injuries are diagnosed during the postoperative period. For a delayed diagnosis of ureteral injury, urinary diversion with ureteral stent, nephrostomy, or both, followed by delayed repair, is recommended to avoid the inflammatory phase. In this patient, ureteral stenting was difficult on the first attempt. Thin microguidewires designed for angiography could be useful in such difficult situation. CONCLUSION: A ureteral injury at the mid-ureter diagnosed at 2 months postoperatively was successfully managed using a two-step process involving ureteral stenting and surgical repair. A microguidewire and a microcatheter are useful for successful stenting in patients with late-diagnosed, severe ureteral strictures.
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Retrieving intravesical foreign bodies warrants open cystotomy; therefore, preoperative evaluation of the material, size, shape, and location is essential for surgical planning. A 79-year-old man presented with dysuria and admitted inserting a jump rope into his urethra. Reconstructed three-dimensional computed tomography showed an entangled jump rope; therefore an endoscopic surgery was deemed unsuitable. Instead, the rope was removed through a small open cystotomy. He had no complications. Intravesical foreign bodies are not rare, and they should be considered as a differential diagnosis in patients with lower urinary tract symptoms. Three-dimensional reconstruction computed tomography contributes to surgical planning.
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Introduction: We report two cases of renal cell carcinoma with brain metastases that showed remarkable responses to cabozantinib. Case presentation: (Case 1) A 70-year-old man with cT3aN0M0 clear cell renal cell carcinoma underwent radical nephrectomy and developed multiple brain metastases 2 months postoperatively. The brain lesions regressed after stereotactic radiotherapy followed by ipilimumab plus nivolumab therapy, but a new brain metastasis that caused hemiplegia developed after 6 months and showed no response to stereotactic radiotherapy. However, complete remission was achieved, and hemiplegia ceased within 2 weeks of cabozantinib therapy. (Case 2) A 63-year-old man with cT3aN0M1 clear cell renal cell carcinoma and brain metastases underwent upfront cytoreductive nephrectomy. The brain lesions progressed rapidly 1 month postoperatively. The lesions disappeared 2 weeks after cabozantinib plus nivolumab therapy. Conclusion: Cabozantinib, alone or in combination with immune checkpoint inhibitors, may be a viable option for clear cell renal cell carcinoma with brain metastases.