Objective
Identifying the predictive factors for tumor recurrence after partial nephrectomy (PN) is useful to determine patients who require careful observation after surgery. Therefore, we ...investigated recurrence after partial nephrectomy (PN) in patients with clinical T1 renal cell carcinoma (RCC) and analyzed predictive factors for recurrence-free survival (RFS).
Methods
This study included 1227 patients who underwent PN for clinical T1 RCC and retrospectively investigated patients’ characteristics and tumor factors that are associated with tumor recurrence.
Results
The median patient age was 59 years, and the median tumor size was 30 mm. Although 970 (74%) and 319 (26%) patients had clinical T1a and T1b RCCs, respectively, 20 patients (1.6%) were upstaged to pathological T3a. A positive surgical margin was found in 19 (1.5%) patients. The distribution of surgical approaches was open surgery in 428 (35%) patients and minimally invasive surgery in 799 (65%) patients. With a median follow-up of 35 months (Interquartile range 19–55 months), 39 (3.2%) patients, including ten with local recurrence, five with recurrence in the ipsilateral kidney, and 28 with other organs or lymph-nude, developed recurrence. The 3-year RFS was 99%, and the median recurrence time from PN was 19 months (interquartile range: 11–37 months). Multivariate analysis identified high grade tumor and upstaging to pT3a as significant predictors for worse RFS.
Conclusion
Patients with high grade tumors and tumors upstaged to pT3 had a high risk of worse RFS, which suggested that careful monitoring is required for such patients after PN, even if a good prognosis is achieved in patients with clinical T1 RCC.
Abstract
Botulinum toxin-A (BTX) administration into muscle is an established treatment for conditions with excessive muscle contraction. However, botulinum therapy has short-term effectiveness, and ...high-dose injection of BTX could induce neutralizing antibodies against BTX. Therefore, prolonging its effects could be beneficial in a clinical situation. Insulin-like growth factor-1 receptor (IGF1R) and its ligands, insulin-like growth factor (IGF) -I and II, regulate the physiological and pathological processes of the nervous system. It has been suggested that IGF1R is involved in the process after BTX administration, but the specific regeneration mechanism remains unclear. Therefore, this study aimed to determine how inhibition of IGF1R signaling pathway affects BTX-induced muscle paralysis. The results showed that anti-IGF1R antibody administration inhibited the recovery from BTX-induced neurogenic paralysis, and the synaptic components at the neuromuscular junction (NMJ), mainly post-synaptic components, were significantly affected by the antibody. In addition, the wet weight or frequency distribution of the cross-sectional area of the muscle fibers was regulated by IGF1R, and sequential antibody administration following BTX treatment increased the number of Pax7
+
-satellite cells in the gastrocnemius (GC) muscle, independent of NMJ recovery. Moreover, BTX treatment upregulated mammalian target of rapamycin (mTOR)/S6 kinase signaling pathway,
HDAC4
,
Myog
,
Fbxo32/MAFbx/Atrogin-1
pathway, and transcription of synaptic components, but not autophagy. Finally, IGF1R inhibition affected only mTOR/S6 kinase translational signaling in the GC muscle. In conclusion, the IGF1R signaling pathway is critical for NMJ regeneration via specific translational signals. IGF1R inhibition could be highly beneficial in clinical practice by decreasing the number of injections and total dose of BTX due to the prolonged duration of the effect.
New pathological subtypes of renal cell carcinoma (RCC) were designated in the 2016 World Health Organization (WHO) classification corresponding to the features commonly seen in patients with ...end‐stage renal disease (ESRD). To determine the clinicopathological findings of new subtypes, we reanalyzed all sections from 315 kidneys in 291 ESRD patients bearing RCC tumors surgically resected in three Japanese institutes by the central pathologist. Clear cell RCC was diagnosed in 144 kidneys (45.7%), acquired cystic disease (ACD)‐associated RCC in 100 (31.7%), papillary RCC in 41 (13.0%), and other minor subtypes in 30 (9.52%). Multivariate analysis showed that longer duration of dialysis, young age, and male sex were independent prognostic clinical factors for the occurrence of ACD‐associated RCC. ACD‐associated RCC included more WHO/International Society of Urologic Pathology (ISUP) grade 3/4 cases compared to other RCCs. In contrast, other unfavorable findings were less frequent in ACD‐associated RCC, including the presence of a sarcomatoid component, lymphovascular invasion, and necrosis. In conclusion, ACD‐associated RCC is a common histology in Japanese patients with ESRD. In addition, ACD‐associated RCC showed more cases with a higher WHO/ISUP grade, but fewer cases with other unfavorable pathological features, suggesting a favorable prognosis of ACD‐associated RCC.
Combined immunotherapy of nivolumab plus ipilimumab for intermediate- and poor-risk metastatic clear cell renal cell carcinoma showed prolonged progression-free survival and high objective response ...rate in a randomized phase III clinical trial. However, the efficacy of this treatment for papillary renal cell carcinoma remains unclear. In the present study, we analysed the efficacy of nivolumab plus ipilimumab therapy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma.
This is a retrospective study of 30 patients with metastatic renal cell carcinoma who received nivolumab and ipilimumab as first-line therapy between December 2015 and May 2020. The objective response rate, progression-free survival and toxicity were compared between the two groups (clear cell renal cell carcinoma and papillary renal cell carcinoma).
Out of 30 patients, 7 and 23 were diagnosed with papillary renal cell carcinoma and clear cell renal cell carcinoma, respectively. With a median follow-up of 7.2 months, the median progression-free survival was significantly shorter in papillary renal cell carcinoma than in clear cell renal cell carcinoma (2.4 vs. 28.1 months, P = 0.014). Of the seven patients with papillary renal cell carcinoma, one had partial response, one had stable disease and five had progressive disease, resulting in an objective response rate of 14.2%, which was lower compared to that of clear cell renal cell carcinoma (14.2 vs. 52.1%, P = 0.06). Discontinuation due to toxicity was not observed with papillary renal cell carcinoma, meanwhile 60.8% of patient with clear cell renal cell carcinoma discontinued treatment due to toxicity.
Nivolumab plus ipilimumab had modest efficacy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Nivolumab plus ipilimumab remains an option for a limited number of patients with intermediate- or poor-risk papillary renal cell carcinoma.
End‐stage renal disease (ESRD) patients on dialysis therapy have a higher incidence of renal cell carcinomas (RCCs), which consist of 2 major histopathological types: clear‐cell RCCs (ESRD‐ccRCCs) ...and acquired cystic disease (ACD)‐associated RCCs. However, their genetic and epigenetic alterations are still poorly understood. Here, we investigated somatic mutations, copy number alterations (CNAs), and DNA methylation profiles in 9 ESRD‐ccRCCs and 7 ACD‐associated RCCs to identify their molecular alterations and cellular origins. Targeted sequencing of 409 cancer‐related genes, including VHL, PBRM1, SETD2, BAP1, KDM5C, MET, KMT2C (MLL3), and TP53, showed ESRD‐ccRCCs harbored frequent VHL mutations, while ACD‐associated RCCs did not. CNA analysis showed that ESRD‐ccRCCs had a frequent loss of chromosome 3p while ACD‐associated RCCs had a gain of chromosome 16. Beadarray methylation analysis showed that ESRD‐ccRCCs had methylation profiles similar to those of sporadic ccRCCs, while ACD‐associated RCCs had profiles similar to those of papillary RCCs. Expression analysis of genes whose expression levels are characteristic to individual segments of a nephron showed that ESRD‐ccRCCs and ACD‐associated RCCs had high expression of proximal tubule cell marker genes, while chromophobe RCCs had high expression of distal tubule cell/collecting duct cell marker genes. In conclusion, ESRD‐ccRCCs and ACD‐associated RCCs had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively, and these 2 histopathological types of RCCs were indicated to have originated from proximal tubule cells of the nephron.
We revealed that 2 major histopathological types of renal cell carcinomas (RCCs) that arise in end‐stage renal disease (ESRD), namely clear‐cell RCCs (ESRD‐ccRCCs) and acquired cystic disease (ACD)‐associated RCCs, had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively. This finding indicates that these 2 histopathological types of RCCs arising in ESRD originated from proximal tubule cells of a nephron.
This study evaluated the bonding performance of coronal dentin disks, designed for biological restoration, and CAD/CAM resin composite disks when bonded to flat dentin surfaces using dual-cure resin ...cements, with and without a resin-coating (RC) technique. Three distinct groups were established within the non-RC group, each using one of the two types of resin cements in a self-adhesive mode: one-step self-etch adhesive (1-SEA) without light-cure, 1-SEA with light-cure, and a separate group using an alternate cement. Within the RC group, a subgroup was established for each cement. The microtensile bond strength (μTBS) of the disk-dentin beam was tested after 0 and 10,000 thermocycles in a 5°C/55°C. No significant μTBS difference was observed among the non-RC groups. However, when using RC, the μTBSs of coronal dentin disks significantly exceeded those of CAD/CAM resin composite disks. Thermocycle aging did not affect μTBS in any of the bonding methods, except in self-adhesive mode.
Background
With new options in adjuvant settings, clinical biomarkers to predict recurrence after radical surgery for high-risk renal cell carcinoma (hrRCC) are in need but are scarcely investigated. ...We aimed to verify the predictive value of perioperative C-reactive protein (CRP) kinetics on hrRCC recurrence.
Methods
We retrospectively evaluated 154 patients who underwent radical surgery for hrRCC (≥ pT3 and/or N1-2 and M0) at two institutions. Patients were classified into Normal (< 0.5) and High (≥ 0.5) according to their preoperative serum CRP (mg/dL). The High group were further classified into Normalized (< 0.5 at post) or Non-normalized (≥ 0.5 at post), and recurrence-free survival (RFS) was compared between groups. Factors for RFS were further analysed, and Harrell’s concordance index (C-index) for the accuracy of predicting RFS was compared with and without the addition of CRP-related variables to pre-existing models.
Results
The RFS was significantly shorter in the High (
n
= 72, 46.8%) compared to the Normal (
n
= 82, 53.2%) group (9.7 vs. 66.7 months,
p
< 0.001). Within the High group, Non-normalized (
n
= 27, 17.5%) patients showed a significantly shorter RFS compared to the Normalized (
n
= 45, 29.2%) group (6.2 vs. 20.3,
p
= 0.009). In the multivariable stepwise analysis, CRP kinetics (hazard ratio 2.15,
p
= 0.029) effectively predicted RFS while baseline CRP fell short of significance. Higher C-index improvement was observed with CRP non-normalization than the baseline value when added to factors in the Karakiewicz and University of California Los Angeles Integrated Staging System models.
Conclusions
CRP kinetics effectively predicted RCC recurrence after surgery and may aid in decision-making for adjuvant systemic therapy.
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