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Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future.
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Carcinoma Pulmonar de Células não Pequenas , Imunoterapia Adotiva , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Animais , Imunoterapia Adotiva/métodos , Camundongos , Linhagem Celular Tumoral , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Cadeia Pesada da Proteína-1 Reguladora de Fusão/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Anticorpos Monoclonais/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , FemininoRESUMO
BACKGROUND: The Japanese National Clinical Database (NCD) is a large-scale, nationwide, web-based data entry system that covers the majority of surgical cases performed in Japan. An NCD specializing in urological surgery was launched based on the NCD system in 2018. METHODS: All urological surgeries performed at more than 1000 institutions were registered from 2018. We herein report the number of surgeries conducted as stipulated in the "Certified Urology Surgeon Training Curriculum" between April 2018 and December 2021. RESULTS: A total of 1 377 677 cases were registered from 1185 facilities nationwide under the initiative of the Japanese Urological Association. We examined the number of procedures performed every year for each of the 10 categories. CONCLUSIONS: The NCD system sustainably provides important information relating to the preoperative status, operational outcome, and best practice for urological surgery in Japan.
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BACKGROUND: The optimal subsequent treatment strategy for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiotherapy (CRT) and consolidative durvalumab therapy remains unknown. We aimed to determine the optimal subsequent treatment strategy for this clinical population. MATERIALS AND METHODS: We retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy. Patients who received tyrosine kinase inhibitors as subsequent therapy were excluded. RESULTS: Out of 122 patients who received subsequent chemotherapy, 55% underwent platinum-based, 25% non-platinum-based, and 20% immune checkpoint inhibitor (ICI)-containing therapies. In the platinum-based group, patients with a durvalumab-progression-free survival (Dur-PFS) ≥ 1 year had a significantly longer median subsequent therapy-PFS (SubTx-PFS) than those with Dur-PFS < 1 year (13.2 months vs. 4.7 months; hazard ratio, 0.45; 95% confidence interval, 0.21-0.97; P = .04). Furthermore, among patients receiving non-platinum-based chemotherapy, the median SubTx-PFS was longer in the combined with angiogenesis inhibitor group than in the without group, although the difference was not statistically significant. No significant difference of SubTx-PFS was observed between the reason for durvalumab discontinuation and the outcomes of ICI-containing therapy. CONCLUSION: In clinical practice, platinum-based chemotherapy rechallenge is frequently employed following progression subsequent to CRT and consolidative durvalumab therapy for LA-NSCLC. Optimal treatment strategies may consider Dur-PFS and angiogenesis inhibitor feasibility. Further research is warranted to identify clinical biomarkers that can help identify patients who would benefit from ICI rechallenge.
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A 74-year-old man visited the urology clinic with the chief complaint of urinary retention in December 2014. Serum level of initial prostate specific antigen (PSA) was 50 ng/ml and he was diagnosed with Gleason Score 4ï¼4 prostate adenocarcinoma with regional lymphadenopathy (cT3aN1M0). PSA level had declined after the treatment with combined androgen blockade. In November 2018, he was diagnosed with castration resistant prostate cancer (CRPC) as local progression was detected by computed tomography (CT) while PSA level did not increase. Since local symptoms worsened, resulting in repeated hematuria after the treatment with enzalutamide, palliative radiation therapy to the prostate (45 Gy) was performed. Five months later, follow-up CT showed multiple metastasis in bilateral lung and left testicle. Serum level of neuron-specific enolase (NSE) was 24.4 ng/ml without an elevated in serum PSA level. He received rebiopsy of the prostate, but no malignant findings were observed. Consequently, bilateral orchiectomy was performed for diagnosis of left testicular tumor. Pathological examination revealed metastasis of neuroendocrine prostate cancer (NEPC). Chemotherapy using cisplatin and irinotecan was administered after orchiectomy. Complete response of lung lesions was achieved and serum level of NSE decreased within normal range. No recurrence has been confirmed for 4 years after the completion of chemotherapy.
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Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Terapia Combinada , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Fatores de Tempo , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Orquiectomia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapiaRESUMO
Introduction: Urinary fistula is a rare complication following robot-assisted partial nephrectomy. For cases refractory to conservative treatment, only ureteral stent placement and percutaneous drainage are the established treatment alternatives. Case presentation: A 44-year-old man presented with urinary fistula 3 weeks after robot-assisted partial nephrectomy for right renal cell carcinoma. Follow-up observations were conducted for 2 weeks; however, no improvements were observed. Additionally, the patient did not improve following percutaneous drainage and ureteral stent insertion. Subsequently, the patient received percutaneous injections of fibrin glue, with the urinary fistula showing significant improvements on the following day. Conclusion: Our findings indicated that percutaneous fibrin glue injection can effectively treat refractory urinary fistula following partial nephrectomy.
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BACKGROUND: Sarcopenia is known to bring about adverse outcomes in elderly populations and dialysis patients. However, whether it is a risk factor in kidney transplant recipients (KTRs) has not yet been established. In the present study, the association of sarcopenia with mortality was investigated in KTRs. METHODS: We conducted a single-center prospective cohort study and recruited KTRs who were more than 1-year posttransplant from August 2017 to January 2018. The participants were followed for 5 years, and the Kaplan-Meier method and Cox proportional hazards model were used to assess patient survival. RESULTS: A total of 212 KTRs with a median age of 54 years and median transplant vintage of 79 months were enrolled in this study. Among them, 33 (16%) had sarcopenia according to the Asia Working Group for Sarcopenia 2019 at baseline. During the 5-year follow-up period, 20 (9.4%) died, 5 returned to dialysis after graft loss, and 4 were lost to follow-up. The 5-year overall survival rate was 90%. After 1:1 propensity score matching, a matched cohort with 60 KTRs was generated. The overall survival rate was significantly lower in the sarcopenia group compared to the non-sarcopenia group (p = 0.025, log-rank test). Furthermore, mortality risk was significantly higher in the sarcopenia group compared to the non-sarcopenia group (hazard ratio = 7.57, 95% confidence interval = 0.94-62). CONCLUSION: Sarcopenia was a predictor of mortality in KTRs. KTRs with suboptimal muscle status who were at risk for poor survival could have a clinical benefit by interventions for sarcopenia.
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BACKGROUND: In the use of therapeutic plasma exchange (TPE) as antibody removal therapy for ABO-incompatible (ABOi) kidney transplantation, it is technically possible to perform online hemodiafiltration (OHDF) and TPE simultaneously for patients who are receiving OHDF. In this study, we report tandem therapy of pre-dilution OHDF and centrifugal plasma exchange (cTPE), instead of membrane plasma exchange, which is the mainstay of TPE in Japan. METHODS: A total of 14 sessions of tandem cTPE and pre-dilution OHDF were performed as preoperative antibody removal therapy for 6 ABOi kidney transplant recipients. cTPE intra-circuit pressure, decreased antibody titer, and adverse events were evaluated. The study was carried out following the ethical standards of the Declaration of Helsinki and Istanbul. Donors were not prisoners or individuals who were coerced or paid. RESULTS: The tandem therapy was completed safely in 12 of the 14 sessions, with no problems such as pressure upper and lower limit alarms or circuit coagulation. In 2 sessions, the tandem therapy had to be interrupted due to coagulation on the dialysis circuit side. Antibody titers were reduced by a median of 3-fold for both IgG and IgM. There was no acute antibody-associated rejection. CONCLUSIONS: In preoperative apheresis therapy for ABOi kidney transplantation, tandem therapy of pre-dilution OHDF and cTPE may be a useful treatment option that can be performed safely and results in sufficient reduction of antibody levels.
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Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Hemodiafiltração , Transplante de Rim , Troca Plasmática , Humanos , Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Masculino , Pessoa de Meia-Idade , Adulto , FemininoRESUMO
Background and Objectives: Our aim was to clarify the oncological outcomes of the two different approaches to laparoscopic nephroureterectomies (LNUs) in Japan, and to examine whether there were any significant differences between the transperitoneal approach and the retroperitoneal approach. Materials and Methods: We retrospectively evaluated patients who underwent an LNU for upper tract urothelial carcinoma (UTUC) from January 2013 to December 2022. We identified 52 patients who underwent a transperitoneal LNU (tLNU) and 93 who underwent a retroperitoneal LNU (rLNU). We adopted age, smoking, and pT-stage matching, and 43 patients were classified in each group. We investigated the time from surgery to recurrence (RFS: recurrence-free survival), the time to death (OS: overall survival), and the time to non-urothelial-tract recurrence-free survival (NUTRFS). A Cox regression analysis was performed to evaluate the risk factors that influenced recurrence. Results: There were no significant differences in the RFS, OS, and NUTRFS between the two matched groups. In the multivariate Cox regression analysis, the pT stage (pT3≥ vs. pT2≤) had an HR = 2.09 and a p = 0.01, and was an independent prognostic risk factor regarding cancer recurrence. Conclusions: There were no significant differences in the oncological outcomes between the tLNU and rLNU groups. It is suggested that the transperitoneal approach should be selected for LNUs.
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Carcinoma de Células de Transição , Laparoscopia , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Nefroureterectomia , Carcinoma de Células de Transição/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias Ureterais/patologia , Neoplasias Ureterais/cirurgia , Nefrectomia , Recidiva Local de Neoplasia/cirurgiaRESUMO
BACKGROUND: Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has been reported to be effective in treating conservative renal failure and renal anemia in patients undergoing dialysis. However, its effects on post-transplant anemia have not yet been reported. This study aimed to determine whether daprodustat may be a useful treatment for post-transplant anemia. MATERIALS: Excluding 5 cases in which the drug was discontinued due to side effects, 21 post-transplant patients treated with daprodustat for ≥12 months and available for follow-up were analyzed. Changes in hemoglobin levels, iron metabolism, estimated glomerular filtration rate, and low-density lipoprotein levels were evaluated over 1 year. RESULTS: The average hemoglobin level was 10.1 g/dL before treatment, and after 1, 2, 3, 6, 9, and 12 months, these had increased significantly to 10.9, 11.2, 11.9, 12.3, 12.3, and 12.6, respectively. Ferritin levels were significantly lower throughout the 12-month study period. Transferrin saturation was significantly lower than before treatment during the first 6 months, with no significant differences after that. The participants' estimated glomerular filtration rate and low-density lipoprotein cholesterol levels did not change significantly throughout the treatment. CONCLUSION: Daprodustat significantly increased hemoglobin levels was easily dose-adjusted and was relatively safe for continuous use over 1 year. It was also effective in patients who had responded inadequately to erythropoiesis-stimulating agents. Therefore, we conclude that daprodustat may be a useful treatment for post-transplant anemia.
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Anemia , Glicina , Glicina/análogos & derivados , Hemoglobinas , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Anemia/tratamento farmacológico , Anemia/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Glicina/uso terapêutico , Hemoglobinas/metabolismo , Hemoglobinas/análise , Taxa de Filtração Glomerular , Adulto , Barbitúricos/uso terapêutico , Idoso , Transplantados , Resultado do TratamentoRESUMO
BACKGROUNDS: There are advantages and disadvantages with closure of an arteriovenous fistula (AVF) after kidney transplantation, but some cases require closure. The general procedure for closure is angioplasty with exposure of the anastomotic site, but this is often time-consuming and complicated. We have developed a simpler, less invasive, and shorter procedure for AVF closure, in which the anastomotic site itself is not peeled off and the outflow vein close to this site is ligated using 1-0 silk. In this study, we examined the utility of this procedure. METHODS: A retrospective case series study was conducted by review of electronic medical records of patients and surgeries. All patients (n = 52) who underwent AVF closure after kidney transplantation at our hospital between January 2008 and April 2021 were reviewed. Perioperative and long-term postoperative results were examined. This study was carried out following the ethical standards of the Declaration of Helsinki and Istanbul. Donors were not from prisoners, or from those individuals who are coerced of paid. RESULTS: Simple ligation was performed for 46 patients (88.5%). The median time after renal transplantation was 40 (24.5-66.5) months. Median operative time and blood loss were 20 (12.2-30) minutes and 10 (5-15) mL, respectively. Two patients (4.3%) developed the aneurysm after the AVF closure using the simple ligation. CONCLUSION: The simple ligation technique had a relatively shorter operative time and only 2 cases had aneurysm formation. These results suggest that this technique is an option for closure of an AVF after kidney transplantation.
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Derivação Arteriovenosa Cirúrgica , Transplante de Rim , Humanos , Estudos Retrospectivos , Ligadura , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Derivação Arteriovenosa Cirúrgica/métodos , Idoso , Fístula Arteriovenosa/cirurgia , Fístula Arteriovenosa/etiologia , Resultado do Tratamento , Duração da CirurgiaRESUMO
Thirteen years after kidney donation, a 70-year-old man was referred to a nephrologist because of proteinuria. The serum creatinine, albumin, and urinary protein levels were 2.39 mg/dL, 3.0 g/dL, and 6.72 g/gCr, respectively. A kidney biopsy revealed thickening of the glomerular basement membrane with sub-epithelial deposits, suggesting membranous nephropathy. Considering the apparent interstitial fibrosis and diffuse glomerulosclerosis, supportive treatment was chosen. However, 11 months after the kidney biopsy, hemodialysis was required. The present case constitutes an important teaching point, as glomerular disease can occur in living donors and require careful and long-term medical checkup examinations.
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New approaches involving immune checkpoint inhibitors and antibody-drug conjugates prolong overall survival in patients with metastatic urothelial carcinoma. However, the access to such systemic therapy in clinical practice is suboptimal, and whether these agents improve overall survival in patients with metastatic urothelial carcinoma over time remains unclear. Hence, we investigated the overall survival trend from the initiation of first-line therapy with these agents to identify changes due to the medication and time of treatment initiation. We retrospectively evaluated 195 patients from a single center. They were treated with chemotherapy, pembrolizumab, or avelumab or enfortumab vedotin. The treatment was categorized into chemotherapy, pembrolizumab or avelumab/enfortumab vedotin period. The new agents prolonged overall survival from the start of first-line therapy. Furthermore, sequential treatment with these agents in real-world clinical practice has been reported to prolong overall survival. These study results will have major implications when a new first-line therapy is approved in the future.
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Antineoplásicos Imunológicos , Carcinoma de Células de Transição , Imunoconjugados , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Estudos Retrospectivos , Antineoplásicos Imunológicos/uso terapêutico , Imunoconjugados/uso terapêuticoRESUMO
OBJECTIVE: Adjuvant nivolumab prolonged disease-free survival compared with placebo in patients at high risk of recurrence following radical cystectomy or radical nephroureterectomy in the CheckMate 274 trial. However, the ideal eligibility criteria for adjuvant therapy in real-world clinical practice remain controversial. METHODS: We retrospectively analyzed clinical data of 409 patients who underwent radical cystectomy (n = 252) or radical nephroureterectomy (n = 157) and validated the risk of recurrence based on the classification used in the CheckMate 274 trial. We also investigated the impact of perioperative chemotherapy, lymph node dissection and pathological factors on prognosis. RESULTS: The median follow-up time was 37.5 and 32.1 months in bladder cancer and upper tract urothelial carcinoma, respectively. Among the high-risk patients based on CheckMate 274 trial, disease-free survival was considerably shorter for bladder cancer and upper tract urothelial carcinoma patients than for low-risk patients (hazard ratios: 4.132 and 7.101, respectively). The prevalence of adjuvant chemotherapy in high-risk patients was low (24 and 38% for bladder cancer and upper tract urothelial carcinoma, respectively). The extent of lymph node dissection in bladder cancer and presence of lymph node dissection in upper tract urothelial carcinoma did not affect prognosis. Cox proportional multivariate analysis revealed CheckMate 274-high-risk as a poor prognostic factor in bladder cancer and upper tract urothelial carcinoma. CONCLUSIONS: This study validated the risk classification for recurrence following radical cystectomy and radical nephroureterectomy using the CheckMate 274 criteria in real-world practice. Further research would help assess the degree of benefit obtained from adjuvant nivolumab.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/patologia , Cistectomia , Nefroureterectomia , Nivolumabe , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Ensaios Clínicos como AssuntoRESUMO
Arsenic is a known human urinary bladder carcinogen. While arsenic is known to cause aberrant DNA methylation, the mechanism of arsenic-triggered bladder carcinogenesis is not fully understood. The goal of this study was to identify aberrant DNA methylation in rat bladder urothelial carcinoma (UC) induced by dimethylarsinic acid (DMAV), a major organic metabolite of arsenic. We performed genome-wide DNA methylation and microarray gene expression analyses of DMAV-induced rat UCs and the urothelium of rats treated for 4 weeks with DMAV. We identified 40 genes that were both hypermethylated and downregulated in DMAV-induced rat UCs. Notably, four genes (CPXM1, OPCML, TBX20, and KCND3) also showed reduced expression in the bladder urothelium after 4 weeks of exposure to DMAV. We also found that CPXM1 is aberrantly methylated and downregulated in human bladder cancers and human bladder cancer cells. Genes with aberrant DNA methylation and downregulated expression in DMAV-exposed bladder urothelium and in DMAV-induced UCs in rats, suggest that these alterations occurred in the early stages of arsenic-induced bladder carcinogenesis. Further study to evaluate the functions of these genes will advance our understanding of the role of aberrant DNA methylation in arsenic bladder carcinogenesis, and will also facilitate the identification of new therapeutic targets for arsenic-related bladder cancers.
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This study aimed to analyze male renal transplant recipients' experience with their partners' pregnancy and childbirth and to investigate their methods of nursing their condition. We performed semistructured interviews and collected data from 6 Japanese males who underwent a kidney transplant after their partner had given birth. The data were analyzed using the Qualitative Synthesis Method (KJ Method). The mean age of the participants at data collection was 40.3 ± 4.7 years, whereas it was 34.7 ± 5.8 years when the transplant was performed. The Qualitative Synthesis Method revealed 7 symbols related to the pregnancy and childbirth experience of the partners of male kidney transplant recipients. Males who received a kidney transplant struggled with severe renal disease before the transplant. They also experienced indecisiveness about whether they should go through with the transplant. However, their lives changed because of the transplant and having children. This situation resulted in a sense of responsibility and a reason to live robustly for the male kidney transplant recipients. Nevertheless, they faced distress as kidney transplant patients. Their wives supported them through this experience. They communicated to their children what they learned from the experience while effectively dealing with their condition. The improvement in their sexual function resulting from the transplant influenced their determination to get married. It is necessary to offer information about the recovery of fertility and the possibility of having a child when choosing renal replacement therapy, give explanations based on evidence, and construct a counseling system.
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Transplante de Rim , Gravidez , Feminino , Criança , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Transplante de Rim/psicologia , Cônjuges , Transplantados/psicologia , FertilidadeRESUMO
Infusion-related reactions (IRRs) are the major side effects of rituximab administration. Although several studies have reported predictive markers for IRRs in patients with malignancies, there are no such reports for patients without malignancies. Accordingly, we aimed to clarify the predictive markers for rituximab-induced IRRs in renal transplant recipients. This retrospective study included 116 inpatients aged ≥18 years who received an initial dose of 150 mg/m2 of rituximab for desensitization before renal transplantation with loxoprofen and diphenhydramine before rituximab infusion between June 2007 and February 2022. Overall, 45 patients were evaluated and 71 patients were excluded in this study. IRRs were observed in 12 (26.7%) patients. The proportion of men in the IRRs group was significantly higher than that in the non-IRRs group (p = 0.023). Additionally, body weight, body surface area (BSA), and body mass index (BMI) were significantly higher in the IRRs group than in the non-IRRs group (body weight, p = 0.0058; BSA, p = 0.0051; BMI, p = 0.017). Their cutoff values for predicting rituximab-induced IRRs, based on the receiver-operating characteristic curve, were 74.850 kg, 1.910 m2 and 24.164 kg/m2, respectively. In conclusion, the male sex, high actual body weight, BSA, and BMI may be new predictive markers for rituximab-induced IRRs in renal transplant recipients. Therefore, clinicians should carefully monitor patients who receive rituximab before renal transplantation and present with the predictive markers.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Transplante de Rim , Humanos , Masculino , Adolescente , Adulto , Rituximab/efeitos adversos , Estudos Retrospectivos , Peso Corporal , Fatores de RiscoRESUMO
Treatment options for urothelial carcinoma were limited until the emergence of immune checkpoint inhibitors, and even now, the prognosis of metastatic disease is poor compared with the other two major genitourinary cancers, renal cell carcinoma and prostate cancer. Despite the increasing use of immune checkpoint inhibitors in the sequential treatment of urothelial carcinoma, conflicting results from similar randomized clinical trials call into question the efficacy of this treatment. In addition, physicians must be aware of the clinical characteristics of immune checkpoint inhibitors, including immune-related adverse events, pseudo- and hyperprogression. This review summarizes the conflicting results of recent clinical trials and provides insights into the role of immune checkpoint inhibitors in the treatment of urothelial carcinoma.
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Carcinoma de Células Renais , Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Masculino , Humanos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologiaRESUMO
The patient, a 54-year-old woman, underwent a living donor kidney transplant at Osaka City University Hospital 7 years before the bariatric surgery. Her comorbidities were diabetes, sleep apnea, and severe obesity (weight 103 kg, body mass index [BMI] 36 kg/m2), and her diabetes was poorly controlled with an HbA1c of 8.5%. On admission, she weighed 99 kg, BMI was 34 kg/m2, Serum creatinine (S-Cre) was 1.54 mg/dL, and HbA1c was 7.1%. A laparoscopic sleeve gastrectomy was performed, and her weight decreased without complications during the perioperative period. She was discharged on postoperative day 28. Two months after surgery, her weight was 87 kg, BMI 30 kg/m2, S-Cre 1.34 mg/dL, HbA1c 6.7 %, renal function improved, urine protein decreased, and insulin dosage decreased dramatically. We report this valuable case because there are no reports of bariatric surgery in Japanese renal transplant recipients.
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BACKGROUND: Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity. We screened diagnostic biomarkers for KGIs following kidney transplantation using extracellular vesicles (EVs; exosomes and microvesicles) from the urine samples of patients. METHODS: One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study; urine samples were obtained prior to protocol/episode biopsies. EVs were isolated from urine samples, and EV RNA markers were assayed using quantitative reverse transcription polymerase chain reaction. Diagnostic performance of EV RNA markers and diagnostic formulas comprising these markers were evaluated by comparison with the corresponding pathological diagnoses. RESULTS: EV CXCL9, CXCL10, and UMOD were elevated in T-cell-mediated rejection samples compared with other KGI samples, while SPNS2 was elevated in chronic antibody-mediated rejection (cABMR) samples. A diagnostic formula developed through Sparse Logistic Regression analysis using EV RNA markers allowed us to accurately (with an area under the receiver operator characteristic curve [AUC] of 0.875) distinguish cABMR from other KGI samples. EV B4GALT1 and SPNS2 were also elevated in cABMR, and a diagnostic formula using these markers was able to distinguish between cABMR and chronic calcineurin toxicity accurately (AUC 0.886). In interstitial fibrosis and tubular atrophy (IFTA) urine samples and those with high Banff chronicity score sums (BChS), POTEM levels may reflect disease severity, and diagnostic formulas using POTEM detected IFTA (AUC 0.830) and high BChS (AUC 0.850). CONCLUSIONS: KGIs could be diagnosed with urinary EV mRNA analysis with relatively high accuracy.
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Exossomos , Nefropatias , Transplante de Rim , Humanos , Anticorpos , Biomarcadores/urina , Rejeição de Enxerto/genética , Rim/patologia , Nefropatias/patologia , Transplante de Rim/efeitos adversos , RNA , JapãoRESUMO
PURPOSE: The aging of the kidney transplant population is accelerating, and measures against geriatric syndromes including frailty and sarcopenia, which elevate the risk of needing long-term care and even death, are being considered important. Recently, both the frailty and sarcopenia criteria for Asians were revised based on various research reports and clinical experiences. The purpose of this study is twofold: firstly, to investigate the prevalence of frailty based on the revised Japanese version of the Cardiovascular Health Study (J-CHS) criteria and the Kihon Checklist (KCL) and that of sarcopenia based on the Asian Working Group for Sarcopenia (AWGS) 2019 as well as the relationship between frailty and sarcopenia, and secondly, to determine the concurrent validity of the KCL with the revised J-CHScriteria in older kidney transplant recipients. METHODS: This study was a single-center cross-sectional investigation carried out on older kidney transplant recipients who visited our hospital from August 2017 to February 2019. The diagnosis of frailty was assessed using the revised J-CHS criteria and the KCL. The diagnosis of sarcopenia was made by low skeletal muscle mass and either low physical performance or low muscle strength based on the AWGS 2019. To examine the relationship between frailty and sarcopenia, categorical variables were compared using chi-squared test and continuous variables Mann-Whitney U test. Spearman's correlation analysis was used to investigate the correlation between the KCL score and the revised J-CHS score. The concurrent validity of the KCL for estimating frailty based on the revised J-CHS criteria was evaluated using the receiver operating characteristics (ROC) curve analysis. RESULTS: A total of 100 older kidney transplant recipients were enrolled in this study. The median age was 67, 63 (63%) were males, and the median time after transplant was 95 months. The prevalence of frailty based on the revised J-CHS criteria and the KCL, and sarcopenia based on the AWGS 2019 was 15%, and 19%, and 16% respectively. Sarcopenia was significantly associated with frailty based on the KCL (p = 0.016), while not with frailty based on the revised J-CHS criteria (p = 0.11). The KCL score significantly correlated with the revised J-CHS score (p < 0.001). The area under the ROC curve was 0.91. CONCLUSION: Frailty and sarcopenia are interrelated complex geriatric syndromes that are risk factors for adverse health outcomes. In older kidney transplant recipients, frailty and sarcopenia were highly prevalent and frequently co-existed. Furthermore, the KCL was verified as a useful tool for frailty screening in these patient. Easy identification of patients with frailty, which is reversible, can help clinicians institute appropriate corrective measures for kidney transplant recipients to improve transplant outcomes.