Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 34
Filter
1.
Int J Urol ; 30(12): 1087-1095, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37622340

ABSTRACT

Partial nephrectomy (PN) is the standard treatment for T1 renal cell carcinoma. PN is affected more by surgical variations and requires greater surgical experience than radical nephrectomy. Patient-specific simulations and navigation systems may help to reduce the surgical experience required for PN. Recent advances in three-dimensional (3D) virtual reality (VR) imaging and 3D printing technology have allowed accurate patient-specific simulations and navigation systems. We reviewed previous studies about patient-specific simulations and navigation systems for PN. Recently, image reconstruction technology has developed, and commercial software that converts two-dimensional images into 3D images has become available. Many urologists are now able to view 3DVR images when preparing for PN. Surgical simulations based on 3DVR images can change surgical plans and improve surgical outcomes, and are useful during patient consultations. Patient-specific simulators that are capable of simulating surgical procedures, the gold-standard form of patient-specific simulations, have also been reported. Besides VR, 3D printing is also useful for understanding patient-specific information. Some studies have reported simulation and navigation systems for PN based on solid 3D models. Patient-specific simulations are a form of preoperative preparation, whereas patient-specific navigation is used intraoperatively. Navigation-assisted PN procedures using 3DVR images have become increasingly common, especially in robotic surgery. Some studies found that these systems produced improvements in surgical outcomes. Once its accuracy has been confirmed, it is hoped that this technology will spread further and become more generalized.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Robotic Surgical Procedures , Surgery, Computer-Assisted , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Nephrectomy/methods , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Robotic Surgical Procedures/methods , Surgery, Computer-Assisted/methods , Imaging, Three-Dimensional/methods
2.
EBioMedicine ; 92: 104596, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37182269

ABSTRACT

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. FINDINGS: RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. INTERPRETATION: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. FUNDING: This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research.


Subject(s)
Birt-Hogg-Dube Syndrome , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Birt-Hogg-Dube Syndrome/genetics , Birt-Hogg-Dube Syndrome/complications , Carcinogenesis , RNA , Forkhead Transcription Factors
3.
Urology ; 173: 127-133, 2023 03.
Article in English | MEDLINE | ID: mdl-36403677

ABSTRACT

OBJECTIVE: To improve the management of cirrhotic patients diagnosed with new renal masses, we used a nationally representative cohort to assess the perioperative outcomes of nephrectomy in the setting of liver disease. The incidences of liver disease and renal masses are both rising in the US. Delaying liver transplantation to address other health concerns may have life changing consequences in these patients, thus these results help to guide treatment decisions at this critical junction in care. METHODS: A retrospective study of the 2016-2019 Nationwide Readmissions Database was performed in adults undergoing nephrectomy for non-emergent indications. Outcomes were compared between 3 cohorts: no chronic liver disease (no CLD), chronic liver disease (CLD), and decompensated cirrhosis (DC). Mixed regression models were used to evaluate the association between CLD and DC with outcomes of interest including morbidity, mortality, readmission rates, non-home discharges, length of stay, and costs. RESULTS: A total of 183,362 patients were evaluated. The mortality rate in the DC cohort (7%) was higher than with CLD (0.4%) and no CLD (0.3%), (P <.001). DC was associated with higher mortality (OR 8.29, 95% CI 4.07 - 16.88), postoperative bleeding requiring transfusion (OR 5.55, 95% CI 3.72 - 8.26), non-home discharge (OR 5.12, 95% CI 3.16 - 8.30) and readmission (OR 1.79, 95% CI 1.09 - 2.94) compared to no CLD. The DC cohort had the greatest length of stay and costs. CONCLUSION: Patients undergoing nephrectomy with DC have increased morbidity, mortality, readmission rates, non-home discharges, LOS and costs. Alternative management strategies may be considered in these patients.


Subject(s)
Liver Diseases , Liver Transplantation , Adult , Humans , Liver Transplantation/adverse effects , Retrospective Studies , Liver Diseases/complications , Liver Diseases/epidemiology , Patient Discharge , Nephrectomy/adverse effects , Risk Factors , Length of Stay , Patient Readmission , Postoperative Complications/etiology
4.
Cancer Med ; 12(5): 6437-6444, 2023 03.
Article in English | MEDLINE | ID: mdl-36397716

ABSTRACT

BACKGROUND: Risk stratification of kidney cancer patients after nephrectomy may tailor surveillance intensity and selection for adjuvant therapy. Transcriptomic approaches are effective in predicting recurrence, but whether they add value to clinicopathologic models remains unclear. METHODS: Data from patients with clear cell renal cell carcinoma (ccRCC) was downloaded from The Cancer Genome Atlas. Clinicopathologic variables were used to calculate SSIGN (stage, size, grade, and necrosis) scores. The 16 gene recurrence score (RS) signature was generated using RNA-seq data. Transcriptomic risk groups were calculated using the original thresholds. SSIGN groups were divided into low, intermediate, and high risk. Disease-free status was the primary endpoint assessed. RESULTS: SSIGN and RS were calculated for 428 patients with non-metastatic ccRCC. SSIGN low-, intermediate-, and high-risk groups demonstrated 2.7%, 15.2%, and 27.5%, 3-year recurrence risk, respectively. On multivariable analysis, the RS was associated with disease-free status (sub-distribution hazard ratio (sHR) 1.43 per 25 RS [95% CI (1.00-1.43)], p = 0.05). By risk groups, RS further risk stratified the SSIGN intermediate-risk group (sHR 2.22 [95% CI 1.10-4.50], p = 0.03). SSIGN intermediate-risk patients with low and high RS had a 3-year recurrence rate of 8.0% and 25.2%, respectively. Within this risk group, the area under the curve (AUC) at 3 years was 0.69 for SSIGN, 0.74 for RS, and 0.78 for their combination. CONCLUSIONS: Transcriptomic recurrence scores improve risk prediction even when controlling for clinicopathologic factors. Utility may be best suited for intermediate-risk patients who have heterogeneous outcomes and further refinement for clinical utility is warranted.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Transcriptome , Neoplasm Staging , Kidney Neoplasms/genetics , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Risk Factors , Nephrectomy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Prognosis
5.
Molecules ; 27(23)2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36500549

ABSTRACT

The majority of clear cell renal cell carcinomas (ccRCCs) are characterized by mutations in the Von Hippel−Lindau (VHL) tumor suppressor gene, which leads to the stabilization and accumulation of the HIF2α transcription factor that upregulates key oncogenic pathways that promote glucose metabolism, cell cycle progression, angiogenesis, and cell migration. Although FDA-approved HIF2α inhibitors for treating VHL disease-related ccRCC are available, these therapies are associated with significant toxicities such as anemia and hypoxia. To improve ccRCC-specific drug delivery, peptide amphiphile micelles (PAMs) were synthesized incorporating peptides targeted to the CD70 marker expressed by ccRCs and anti-HIF2α siRNA, and the ability of HIF2α-CD27 PAMs to modulate HIF2α and its downstream targets was evaluated in human ccRCC patient-derived cells. Cell cultures were derived from eight human ccRCC tumors and the baseline mRNA expression of HIF2A and CD70, as well as the HIF2α target genes SLC2A1, CCND1, VEGFA, CXCR4, and CXCL12 were first determined. As expected, each gene was overexpressed by at least 63% of all samples compared to normal kidney proximal tubule cells. Upon incubation with HIF2α-CD27 PAMs, a 50% increase in ccRCC-binding was observed upon incorporation of a CD70-targeting peptide into the PAMs, and gel shift assays demonstrated the rapid release of siRNA (>80% in 1 h) under intracellular glutathione concentrations, which contributed to ~70% gene knockdown of HIF2α and its downstream genes. Further studies demonstrated that knockdown of the HIF2α target genes SLC2A1, CCND1, VEGFA, CXCR4, and CXCL12 led to inhibition of their oncogenic functions of glucose transport, cell proliferation, angiogenic factor release, and cell migration by 50−80%. Herein, the development of a nanotherapeutic strategy for ccRCC-specific siRNA delivery and its potential to interfere with key oncogenic pathways is presented.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , RNA, Small Interfering/genetics , Micelles , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , CD27 Ligand/genetics , CD27 Ligand/metabolism
6.
J Kidney Cancer VHL ; 9(3): 41-46, 2022.
Article in English | MEDLINE | ID: mdl-36310638

ABSTRACT

Belzutifan was recently approved for the management of Von Hippel-Lindau disease (VHL). Given the morbidity of recurrent treatment, systemic therapy to reduce or eliminate the need for surgery has been long-awaited. Herein, we sought to gain insight about future utilization by surveying VHL kidney cancer experts in the United States. A survey developed by members of the VHL Alliance (VHLA) Clinical Advisory Council was distributed to kidney cancer providers at VHLA and National Comprehensive Cancer Network (NCCN) centers. Surveys were administered on a secure web-based platform. A total of 60 respondents from 29 institutions participated. Urologists (50%) and medical oncologists (43%) represented the majority of participants. The majority (98%) of respondents anticipated that belzutifan's approval would significantly change the current treatment landscape. Most reported that therapy should be continuous (76%). There was a difference in willingness to prescribe belzutifan by specialty (38% of urologists vs 91% of medical oncologists (P = 0.02)). In individuals with renal tumors <3 cm, 36% would still recommend surveillance, while 36% would initiate belzutifan to prevent growth. In those with multifocal renal lesions and growth of a solitary tumor on belzutifan, 50% would proceed with only treatment of that site. In conclusion, VHL kidney cancer specialists anticipate a paradigm shift with the approval of belzutifan. Provider roles may change with movement away from surgical management. Opinions on treatment indications, such as when to initiate therapy and how to best salvage, vary widely and therefore collaborative efforts among experts may assist in the development of new clinical guidelines.

7.
Oncotarget ; 13: 1054-1067, 2022.
Article in English | MEDLINE | ID: mdl-36128328

ABSTRACT

Loss-of-function mutations in genes encoding the Krebs cycle enzymes Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) induce accumulation of fumarate and succinate, respectively and predispose patients to hereditary cancer syndromes including the development of aggressive renal cell carcinoma (RCC). Fumarate and succinate competitively inhibit αKG-dependent dioxygenases, including Lysine-specific demethylase 4A/B (KDM4A/B), leading to suppression of the homologous recombination (HR) DNA repair pathway. In this study, we have developed new syngeneic Fh1- and Sdhb-deficient murine models of RCC, which demonstrate the expected accumulation of fumarate and succinate, alterations in the transcriptomic and methylation profile, and an increase in unresolved DNA double-strand breaks (DSBs). The efficacy of poly ADP-ribose polymerase inhibitors (PARPis) and temozolomide (TMZ), alone and in combination, was evaluated both in vitro and in vivo. Combination treatment with PARPi and TMZ results in marked in vitro cytotoxicity in Fh1- and Sdhb-deficient cells. In vivo, treatment with standard dosing of the PARP inhibitor BGB-290 and low-dose TMZ significantly inhibits tumor growth without a significant increase in toxicity. These findings provide the basis for a novel therapeutic strategy exploiting HR deficiency in FH and SDH-deficient RCC with combined PARP inhibition and low-dose alkylating chemotherapy.


Subject(s)
Carcinoma, Renal Cell , Dioxygenases , Kidney Neoplasms , Adenosine Diphosphate Ribose , Animals , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Citric Acid Cycle , DNA , Fumarate Hydratase/genetics , Fumarates , Humans , Jumonji Domain-Containing Histone Demethylases , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Lysine , Mice , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Succinate Dehydrogenase/genetics , Succinates , Temozolomide/pharmacology
8.
iScience ; 25(6): 104463, 2022 Jun 17.
Article in English | MEDLINE | ID: mdl-35874919

ABSTRACT

Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment.

9.
Int J Comput Assist Radiol Surg ; 17(6): 1029-1037, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35426565

ABSTRACT

PURPOSE: To ensure that the use of surgical training tools results in improvement of surgical skills, it is necessary to be able to measure and assess surgeons' skills. We established the Short-Time Power of Difference (STPOD) method as an evaluation tool for evaluating targeting technique. The STPOD method evaluates the distance from the actual movement of the forceps to the shortest linear path between two points in a short time period. We examined the effectiveness of the STPOD method as a new forceps kinematic analysis. METHODS: Six residents were categorized as novices and six urologists as experts. All participants performed box trainer training and LapPASS® Simulator training. During the procedure, objective scores (time, distance, and STPOD) were recorded. STPOD (Power) evaluated motion smoothness and STPOD (Stop) evaluated the stop time of the forceps. RESULTS: STPOD (Stop) on the right side of the experts was significantly lower than that of the novices in the box trainer. Furthermore, there were significant differences in the distances of left side and STPOD (Power) between the experts and the novices in the simulator. In the correlation of parameters between the box trainer and the simulator, time showed the strongest correlation, STPOD (Power) and distance showed a mild correlation. CONCLUSION: We showed the construct validity of STPOD (Power) and STPOD (Stop) using both the box trainer and the simulator. This method is a good evaluation tool for assessing a physician's skill; however, there are much more complex motions that are performed in actual surgery. Future studies are needed to focus on evaluation in an environment closer to actual surgery and comparing with other existing methods.


Subject(s)
Laparoscopy , Surgeons , Clinical Competence , Humans , Laparoscopy/education
10.
Asian J Endosc Surg ; 15(2): 313-319, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34698452

ABSTRACT

INTRODUCTION: To determine whether training laparoscopic nephrectomy (LN) with a virtual reality (VR) simulator improves the performance of porcine LN. METHODS: Twelve urological residents were assigned to two groups: a training and a non-training group. All participants performed baseline assessments of LN skills and time on the LapPASS® simulator. The training group received preoperative LapPASS® training. Both groups then performed LN using a porcine model. The operations were videotaped and evaluated using the Global Operative Assessment of Laparoscopic Skills (GOALS) system. After porcine LN, the training group performed a final LN with the LapPASS® simulator. RESULTS: There was no significant difference in the operation time required for porcine LN. There were no significant differences in the total A (autonomy), B (bimanual dexterity), D (depth perception), or T (tissue handling) GOALS scores. However, the total E (efficiency) score in the training group was higher than that in the non-training group (P = .030). The final LN score with LapPASS® was significantly higher than the baseline (P = .004). CONCLUSIONS: The results of this study demonstrated that VR LN training improved performance in an actual operation. VR-based procedural simulation could become a vital part of the laparoscopic training program for residents.


Subject(s)
Internship and Residency , Laparoscopy , Virtual Reality , Animals , Clinical Competence , Computer Simulation , Humans , Laparoscopy/education , Swine , User-Computer Interface
11.
Hinyokika Kiyo ; 67(5): 205-209, 2021 May.
Article in Japanese | MEDLINE | ID: mdl-34126664

ABSTRACT

Lymphoepithelioma-like carcinoma (LELC) of the ureter is very rare and only 14 previous cases have been reported. Here, we report a case of LELC of the ureter. A 76-year-old woman was admitted to our hospital complaining of gross hematuria. Left ureteral cancer was suspected by the imaging examination, and laparoscopic left total nephroureterectomy was performed. Histopathological examination showed pure type of LELC in the ureter. She is alive without disease recurrence at fifteen months after surgery.


Subject(s)
Carcinoma, Squamous Cell , Ureter , Ureteral Neoplasms , Aged , Female , Humans , Neoplasm Recurrence, Local , Nephroureterectomy , Ureter/diagnostic imaging , Ureter/surgery , Ureteral Neoplasms/diagnostic imaging , Ureteral Neoplasms/surgery
12.
Asian J Endosc Surg ; 14(3): 504-510, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33258261

ABSTRACT

INTRODUCTION: In laparoscopic surgery, surgical instruments are inserted from a trocar to the target organ in a blind fashion, which carries a risk of organ injury. To clarify the risks associated with surgical instrument insertion, we measured grip strength and pushing/pressing force during surgical instrument insertion in laparoscopic surgery. METHODS: Using forceps with sensors inside a trocar, 10 urologists performed a laparoscopic procedure in pigs, in which they were asked to touch the abdominal wall. The surgeons closed their eyes during the procedure and stopped moving the forceps when they felt them come into contact with the abdominal wall. They were ordered to grip the forceps strongly or softly and to move them rapidly or slowly during the procedure. Grip strength and the pushing/pressing force when the forceps hit the abdominal wall were measured and analyzed. RESULTS: The mean pushing/pressing force when the surgeons gripped the forceps strongly and moved them rapidly (strong/rapid), strongly/slowly, softly/rapidly, and softly/slowly were 2.8, 2.0, 1.7, and 1.1 N, respectively. The pushing/pressing force was significantly greater when the surgeons gripped the forceps strongly, regardless of the forceps speed (P < .001). The pushing/pressing force was significantly greater when the surgeons moved the forceps rapidly, regardless of grip strength (P < .001). CONCLUSIONS: When surgeons insert laparoscopic instruments through trocars, the instruments should be gripped softly and moved slowly to avoid organ injuries.


Subject(s)
Abdominal Injuries/prevention & control , Abdominal Wall , Laparoscopy , Surgical Instruments , Abdominal Injuries/etiology , Abdominal Wall/surgery , Accelerometry/instrumentation , Animals , Biomechanical Phenomena , Hand Strength , Humans , Laparoscopy/adverse effects , Laparoscopy/instrumentation , Models, Animal , Pressure , Stress, Mechanical , Surgical Instruments/adverse effects , Swine , Urologists
14.
Cancer Chemother Pharmacol ; 86(1): 75-85, 2020 07.
Article in English | MEDLINE | ID: mdl-32537714

ABSTRACT

PURPOSE: Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab. METHODS: After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined. RESULTS: The median follow-up was 8.3 months (range 0.2-29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p < 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased (< 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| > 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline. CONCLUSION: Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , C-Reactive Protein/analysis , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Nivolumab/therapeutic use , Adult , Aged , Aged, 80 and over , Biomarkers, Pharmacological/blood , Biomarkers, Tumor/blood , Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Female , Humans , Inflammation/metabolism , Kidney Neoplasms/blood , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , ROC Curve , Treatment Outcome
16.
PLoS One ; 15(1): e0226581, 2020.
Article in English | MEDLINE | ID: mdl-31895931

ABSTRACT

BACKGROUND: Sarcopenia is defined as a low skeletal muscle volume. Recent studies have reported that sarcopenia is associated with a poor prognosis in various cancers. The purpose of this study is to evaluate the correlation between the psoas muscle volume and recurrence-free survival in patients with localized clear cell renal cell carcinoma (ccRCC). METHODS: A total of 316 male patients with localized ccRCC who underwent radical nephrectomy at Yokohama City University Hospital (Yokohama, JAPAN) and Kanagawa Cancer Center (Yokohama, JAPAN) between 2002 and 2018 were enrolled in this study. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area on the contralateral side of the tumor on axial CT, which was calculated at the level of L4 (mm2) divided by the square of the body height (m2). We divided patients into two groups based on the median PMI (409.64mm2/m2). RESULTS: The lower PMI group showed poorer recurrence-free survival (RFS) than the higher PMI group (p = 0.030). Regarding 5-year RFS, a lower PMI was a significant predictor of recurrence (p = 0.022, hazard ratio (HR): 2.306) and a multivariate analysis revealed that a lower PMI (4 cm (p = 0.044, HR: 2.341), and pathological stage >2 (p<0.001, HR: 3.660) were independent risk factors for poor RFS. CONCLUSIONS: The presence of sarcopenia (lower PMI) was found to be associated with poor RFS in male ccRCC patients. The PMI might serve as a measure of patient frailty and might be useful for prognostic risk stratification in ccRCC.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Neoplasm Recurrence, Local/epidemiology , Nephrectomy/adverse effects , Psoas Muscles/pathology , Sarcopenia/epidemiology , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/pathology , Follow-Up Studies , Humans , Incidence , Japan/epidemiology , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/etiology , Prognosis , Retrospective Studies , Risk Factors , Sarcopenia/diagnosis , Sarcopenia/etiology , Survival Rate , Young Adult
17.
Urol Int ; 102(1): 37-42, 2019.
Article in English | MEDLINE | ID: mdl-30326476

ABSTRACT

INTRODUCTION: Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression affects carcinogenesis in various cancers and has been associated with determining the overall survival among men with metastatic hormone-naïve prostate cancer (mHNPC). In this study, we analyzed the value of LMWPTP for prediction of time to castration-resistant prostate cancer (CRPC) for men with mHNPC. MATERIALS AND METHODS: We retrospectively enrolled 45 men with mHNPC who were diagnosed from 2003 to 2009. All patients had received androgen deprivation therapy as first-line treatment. Prostate cancer tissues (pre-treatment needle biopsies) were immunohistochemically stained for LMW-PTP. Multivariate analyses (Cox proportional hazard model) were used to correlate baseline clinical factors of age, prostate-specific antigen (PSA), Gleason scores, T stage, N stage, extent of disease on bone scan (EOD), LMW-PTP expression and time to CRPC. Continuous variables were classified as dichotomous. RESULTS: Median age and PSA were 70.0 years and 87.8 ng/mL respectively. Median time to CRPC was 40.2 months. Median time to CRPC was significantly shorter in the high LMW-PTP group (14.8 months) than that in the low LMW-PTP group (86.3 months, p < 0.01). In multivariate analysis, age ≥70 years and high LMW-PTP expression were significant predictors of time to CRPC.


Subject(s)
Prostatic Neoplasms, Castration-Resistant/enzymology , Protein Tyrosine Phosphatases/metabolism , Proto-Oncogene Proteins/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Disease Progression , Humans , Immunohistochemistry , Male , Middle Aged , Molecular Weight , Multivariate Analysis , Neoplasm Metastasis , Neoplasm Staging , Proportional Hazards Models , Retrospective Studies , Time Factors
18.
BMC Urol ; 18(1): 97, 2018 Nov 06.
Article in English | MEDLINE | ID: mdl-30400941

ABSTRACT

BACKGROUND: Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. METHODS: We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. RESULTS: There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001). CONCLUSIONS: PD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.


Subject(s)
B7-H1 Antigen/biosynthesis , Biomarkers, Tumor/biosynthesis , Disease Progression , Gene Expression Regulation, Neoplastic , Programmed Cell Death 1 Receptor/biosynthesis , Urinary Bladder Neoplasms/metabolism , Aged , Aged, 80 and over , B7-H1 Antigen/genetics , Biomarkers, Tumor/genetics , Cell Line, Tumor , Female , Humans , Male , Middle Aged , Neoplasm Grading/trends , Programmed Cell Death 1 Receptor/genetics , Retrospective Studies , Urinary Bladder Neoplasms/genetics
19.
Mol Clin Oncol ; 9(3): 302-304, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30112175

ABSTRACT

Oxidative stress is a primary cause of vascular endothelial damage. In the prostate, ischemia increases the levels of reactive oxygen species, growth factors and cytokines, and induces the development of angiogenesis, which results in cancer progression. The expression levels of an oxidative stress marker, 8-hydroxyguanosine (8-OHdG), were compared between prostate cancer and non-neoplastic prostate tissues. A prostate tissue microarray composed of 10 cases of prostatic adenocarcinoma and 70 cases of benign prostatic hyperplasia was immunohistochemically stained for 8-OHdG. All cases expressed 8-OHdG. The levels of 8-OHdG expression in prostatic cancer (30.0% moderate and 70.0% strong) were significantly higher than those in benign prostatic hyperplasia (71.4% moderate and 28.6% strong; (p<0.01). Notably, 8-OHdG is expressed more highly in prostate cancer tissues in comparison to benign prostate tissues.

20.
Case Rep Oncol Med ; 2018: 7135180, 2018.
Article in English | MEDLINE | ID: mdl-29977636

ABSTRACT

INTRODUCTION: Horseshoe kidney is one of the most common congenital renal fusion anomalies. Due to its poor mobility and abnormal vasculature form, surgeons should pay close attention to all anatomical variations. CASE PRESENTATION: An 83-year-old woman was referred to our hospital because of left renal tumor in a horseshoe kidney incidentally found by her previous hospital. We performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell renal cell carcinoma. G2 INFα V-pT1a with a negative surgical margin. No evidence of recurrence has been noted, and the renal function is well preserved at 28 months after surgery. CONCLUSION: When performing laparoscopic partial nephrectomy for renal carcinoma, especially a horseshoe kidney, preoperative imaging is crucial for identifying the location of the renal vessels.

SELECTION OF CITATIONS
SEARCH DETAIL
...