Diagnostic impact of monitoring transcranial motor-evoked potentials to prevent ischemic complications during endovascular treatment for intracranial aneurysms

Neurosurgical Review - The present study aimed to determine the incidence of intraprocedural motor-evoked potential (MEP) changes and to correlate them with intraprocedural ischemic complications...     

Axillary management based on American college of surgeons oncology group Z0011 criteria makes it possible to omit intraoperative diagnosis of sentinel lymph nodes in early breast cancer patients

The ACOSOG Z0011 trial has resulted in the omission of axillary lymph node dissection (ALND) in early breast cancer patients with one or two metastatic sentinel lymph nodes (SLNs). There has been increasing interest in the necessity of intraoperative assessment of SLNs in patients treated based on the Z0011 criteria. We evaluated the utility of intraoperative assessment in these eligible patients. A total of 1396 patients were treated following the Z0011 criteria from April 2012 to December 2019. We examined the proportion and clinicopathological features of patients who underwent ALND due to three or more metastatic SLNs and the sensitivity of intraoperative assessment. Only 16 (1.1%) patients had three or more metastatic SLNs diagnosed by intraoperative assessment, and they immediately underwent ALND. Of the clinicopathological factors, high clinical tumor stage (p = 0.002) and high Ki-67 labeling index value (p = 0.056) were more likely to be associated with the presence of three or more metastatic SLNs. The major independent risk factor for three or more metastatic SLNs was high clinical tumor stage (OR 3.94 [95% CI 1.42–11.0]; p = 0.009). Intraoperative assessment had low sensitivity (70.5%) and a high false-negative rate (29.5%) in detecting SLN metastases. The main finding of our study was the small proportion of patients who required ALND due to three or more metastatic SLNs according to the Z0011 criteria. The Z0011 strategy enables intraoperative assessment of SLNs to be omitted in early breast cancer patients.     

The effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy: A longitudinal analysis (FRARP-QL Study)

ObjectivesWe aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP).Materials and MethodsWe longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP.ResultsThe median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening.ConclusionsFrailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.     

Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.     

Results of definitive radiotherapy with concurrent chemotherapy for maxillary sinus carcinomas with neck lymph node metastasis

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan–Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.     

A surveillance study of patterns of reirradiation practice using external beam radiotherapy in Japan

The aim of this study was to survey the present status and patterns of reirradiation (Re-RT) practice using external beam radiotherapy in Japan. We distributed an e-mail questionnaire to the Japanese Society for Radiation Oncology partner institutions, which consisted of part 1 (number of Re-RT cases in 2008–2012 and 2013–2018) and part 2 (indications and treatment planning for Re-RT and eight case scenarios). Of the 85 institutions that replied to part 1, 75 (88%) performed Re-RTs. However, 59 of these 75 institutions (79%) reported difficulty in obtaining Re-RT case information from their databases. The responses from 37 institutions included the number of Re-RT cases, which totaled 508 in the period from 2009 to 2013 (institution median 3; 0–235), and an increase to 762 cases in the period from 2014 to 2018 (12.5; 0–295). A total of 47 physicians responded to part 2 of the survey. Important indications for Re-RT that were considered were age, performance status, life expectancy, absence of distant metastases and time interval since previous radiotherapy. In addition to clinical decision-making factors, previous total radiation dose, volume of irradiated tissue and the biologically equivalent dose were considered during Re-RT planning. From the eight site-specific scenarios presented to the respondents, >60% of radiation oncologists agreed to perform Re-RT. Re-RT cases have increased in number, and interest in Re-RT among radiation oncologists has increased recently due to advances in technology. However, several problems exist that emphasize the need for consensus building and the establishment of guidelines for practice and prospective evaluation.     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

Cdc7 kinase is required for postnatal brain development

The evolutionally conserved Cdc7 kinase plays crucial roles in initiation of DNA replication as well as in other chromosomal events. To examine the roles of Cdc7 in brain development, we have generated mice carrying Cdc7 knockout in neural stem cells by using Nestin-Cre. The Cdc7^Fl/Fl Nestin^Cre mice were born, but exhibited severe growth retardation and impaired postnatal brain development. These mice exhibited motor dysfunction within 9 days after birth and did not survive for more than 19 days. The cerebral cortical layer formation was impaired, although the cortical cell numbers were not altered in the mutant. In the cerebellum undergoing hypoplasia, granule cells (CGC) decreased in number in Cdc7^{Fl/F l}Nestin^Cre mice compared to the control at E15-18, suggesting that Cdc7 is required for DNA replication and cell proliferation of CGC at mid embryonic stage (before embryonic day 15). On the other hand, the Purkinje cell numbers were not altered but its layer formation was impaired in the mutant. These results indicate differential roles of Cdc7 in DNA replication/cell proliferation in brain. Furthermore, the defects of layer formation suggest a possibility that Cdc7 may play an additional role in cell migration during neural development.