Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study.

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Natural history of incidentally diagnosed prostate cancer after holmium laser enucleation of the prostate.

OBJECTIVES: There is no consensus on the management plan for incidental prostate cancer (IPCa) after holmium laser enucleation of the prostate (HoLEP). This study aims to investigate the natural course of this disease and suggest appropriate treatment in real clinical practice. METHODS: The medical records of a prospective cohort of patients with LUTS/BPH who underwent HoLEP between July 2008 and December 2020 at Seoul National University Hospital were retrospectively reviewed. Patients who underwent HoLEP for palliative purpose of prostate cancer control were excluded. The natural history of IPCa was assessed by the clinician in a descriptive manner for each treatment option. RESULTS: Among 2630 patients, 141 (5.4%) were diagnosed with IPCa after HoLEP. Pathologic T stage and magnetic resonance imaging results were highly associated with the physician's primary treatment decision-making for IPCa. Active surveillance (AS) was performed in 80% of patients, of whom 90% underwent follow-up without intervention, while the remaining 10% underwent deferred active treatment with a median follow-up of 46.3 months due to International Society of Urological Pathology grade group upgrading or increasing core involvement percentage. Meanwhile, 20% of patients underwent immediate active treatment. With a median follow-up period of 88.3 months after treatment, only one of 25 patients had biochemical recurrence. CONCLUSIONS: The incidence of IPCa after HoLEP was 5.4%, and among these, approximately 20% proceeded with immediate definitive therapy and an additional 6% ultimately received definitive therapy within a median of 4 years of AS but showed excellent oncological outcomes.

N,P-Doped Carbon Nanodots for Food-Matrix Decontamination, Anticancer Potential, and Cellular Bio-Imaging Applications.

We report a facile one-step thermal treatment method for the synthesis of biocompatible, fluorescent nitrogen-phosphorus-doped carbon nanodots (NPCDs) as multifunctional agents for the food matrix decontamination, cancer targeting, and cellular bio-imaging. NPCDs exhibit high toxicity towards L. monocytogenes, as illustrated by fluorescent live-dead cell counting, disruption of membrane permeability/potential, changes in the levels of cellular ions, genetic materials, and proteins, as well as intracellular production of reactive oxygen species. The tryptophan and protein peaks released in NPCDs treated cells contributed to indole ring breathing and correlated with induced cell death. NPCDs significantly inhibited bacterial biofilm formation on a solid substrate. NPCDs-coated low-density polyethylene (LDPE) film crosslinked with 1% aminopropyltriethoxy silane (APTES) via silane-hydroxyl linking as a food-grade wrap significantly reduced bacterial counts in a raw chicken food model. Furthermore, NPCDs induced apoptosis in HeLa cervical cancer cells, as confirmed by the distorted cell morphology, fluorescence microscopic analysis, presence of fragmented nuclei and the qPCR results of mRNA expression levels of apoptotic markers. Moreover, NPCDs were also applicable in utilized for the cellular bio-imaging of KM12-C colon cancer cells under confocal microscopy owing to their excellent luminescence properties. Overall, NPCDs represent a promising platform to reduce the environmental health risks associated with hazardous pathogens, anticancer targeting, and their application in cellular bio-imaging as multifunctional targets/nanocarriers.

Primary Tumor Characteristics Are Important Prognostic Factors for Sorafenib-Treated Patients with Metastatic Renal Cell Carcinoma: A Retrospective Multicenter Study.

We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients.

Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study.

OBJECTIVE: To evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal cell carcinoma (mRCC). METHODS: A total of 177 mRCC patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed. RESULTS: Among all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) ≥grade 3 AEs. During the treatment, one myocardial infarction was observed. The number of ≥grade 3 AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence interval [CI], 5.2-8.9), and 32.6 months (95% CI, 27.3-63.8) for the total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5-10.5), and not reached yet (95% CI, 1.0-31.1) for the first-line sorafenib group, respectively. CONCLUSIONS: Sorafenib produced tolerable safety, with a ≥grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients.

Adjuvant interleukin-2, interferon-alpha, and 5-fluorouracil immunochemotherapy after radical nephrectomy for locally advanced renal cell carcinoma.

OBJECTIVES: To investigate the efficacy of interleukin-2 (IL-2), interferon-alpha, and 5-fluorouracil combination immunochemotherapy as adjuvant therapy after radical nephrectomy for nonmetastatic pathologic Stage T3 renal cell carcinoma. METHODS: Thirty patients who underwent radical nephrectomy for pT3N0M0 renal cell carcinoma at our department from June 1999 to December 2003 were studied retrospectively. Of the 30 patients, 9 (adjuvant group) also received adjuvant interleukin-2, interferon-alpha, and 5-fluorouracil immunochemotherapy after surgery; the other 21 (nonadjuvant group) did not. A comparative analysis of the two groups was performed with respect to disease-free and overall survival. Side effects from immunochemotherapy were also assessed. RESULTS: The adjuvant therapy and nonadjuvant therapy groups were not significantly different with respect to age, sex, Eastern Cooperative Oncology Group performance status, pathologic subtype, pathologic stage, tumor size, and Fuhrman's grade. The two groups demonstrated a significant difference in the time to progression (log-rank test, P = 0.011). Although 3 patients had died at a mean follow-up of 23.8 months (range 7.5 to 35) in the nonadjuvant group, apparent differences between the two groups in overall survival were not statistically significant (log-rank test, P = 0.2487). Combination immunochemotherapy was mostly well tolerated, and all side effects were limited to World Health Organization grades 1 and 2. CONCLUSIONS: Despite the ongoing controversy surrounding its effectiveness in the treatment of metastatic renal cell carcinoma, the results of our preliminary study suggest that interleukin-2, interferon-alpha, 5-fluorouracil combination immunochemotherapy may be effective as adjuvant therapy after complete resection of pT3N0M0 renal cell carcinoma.

Early removal of nasogastric tube after cystectomy with urinary diversion: does postoperative ileus risk increase?

OBJECTIVES: To examine the risk factors of postoperative ileus and investigate whether the duration of postoperative nasogastric tube (NGT) use affects the rate of postoperative ileus in patients undergoing radical cystectomy with urinary diversion. METHODS: A total of 101 patients underwent radical cystectomy with urinary diversion from 1999 to 2003. We examined the demographic and perioperative variables of the patients who did and did not develop postoperative ileus. We divided the patients into two groups--those who had the NGT removed within 24 hours and those who had the NGT removed at first flatus. We compared the two groups for the incidence of ileus and clinical variables. RESULTS: Postoperative ileus was observed in 23 patients (23%). The demographic data of both groups were not different in terms of age or American Society of Anesthesiologists score. Also, the operative time, estimated blood loss, type of diversion, and postoperative complication rate were not significantly different between the two groups (P >0.05). However, the risk of postoperative ileus was significantly greater in those who took polyethylene glycol for bowel preparation than in those who took sodium phosphate (40% versus 18%, respectively, P = 0.02). No significant difference in the prevalence of ileus was found between the patients whose NGT was removed within 1 day and those in whom it was removed after 2 days (25% versus 22%, respectively, P >0.05). CONCLUSIONS: The results of our study suggest that the use of sodium phosphate for bowel preparation may reduce the incidence of postoperative ileus and that early NGT removal after cystectomy is not correlated with ileus.

Biodistribution and excretion of radioactivity after the administration of 166Ho-chitosan complex (DW-166HC) into the prostate of rat.

PURPOSE: The objective of this study was to determine the fate of the 166Ho-chitosan complex (DW-166HC) in rats by examining its absorption, distribution and excretion after administration into the prostate. METHODS: About 100 microCi of DW-166HC [containing 0.1875 mg of Ho(NO3)3.5H2O and 0.25 mg of chitosan] was administered intraprostatically. The level of radioactivity in blood, urinary and faecal excretion, and radioactivity distribution were examined. To determine the effect of chitosan in DW-166HC, 166Ho nitrate alone [0.1875 mg of Ho(NO3)3.5H2O] was administered into the prostate of male rats, and radioactivity distribution was examined using whole-body autoradiography. RESULTS: After administration of DW-166HC into the prostate, cumulative urinary and faecal excretion over the period 0-72 h was 0.35% and 0.11%, respectively. The radioactivity at the administration site was extremely high at all time points up to 144 h (>98% of injected dose). The small amount of radioactivity which did transfer from the administration site distributed mainly to the liver, spleen, kidney cortex and bone. Compared with the DW-166HC group, the group that received 166Ho nitrate alone displayed three- to fourfold higher levels of radioactivity in the main tissues, including liver, spleen, kidney cortex and bone, at 24 h after administration (P < 0.05). CONCLUSION: The results of this study show clearly that most of the administered DW-166HC remained at the administration site. It is concluded that the chitosan complex may be used to retain 166Ho within a limited area in cancer of the prostate.