Published papers

Purpose: Rectal complications in radiotherapy for cervical cancer can highly affect quality of life and correlate with rectal dose. Vaginal gauze packing (VP) and rectal retraction (RR) are widely used for rectal dose reduction in high-dose-rate brachytherapy. We aimed to perform a dosimetric comparison of these two methods for three-dimensional image-guided adaptive brachytherapy. Material and methods: We retrospectively examined 50 patients with cervical cancer treated with definitive radiotherapy, including intra-cavitary brachytherapy, performed with VP and RR. We extracted two fractions for each patient: one fraction with VP and the next fraction with RR, and then compared dose-volume parameters. In total, 50 fractions each were analyzed in VP and RR groups. Dose to 90% (D90) of high-risk clinical target volume (HR-CTV), and minimum dose to most exposed 2.0 cm3 of other organs at risk (D2cm3) for the rectum and bladder were determined from planning computed tomography. Results: There were no significant differences between VP and RR in D90 of HR-CTV (mean: 7.479 Gy and 7.652 Gy, respectively, p = 0.172). The D2cm3 values for the rectum (mean: 4.234 Gy vs. 4.627 Gy, p = 0.008) and bladder (mean: 5.959 Gy vs. 6.690 Gy, p < 0.001) were significantly lower with VP compared with RR. Conclusions: VP reduced the dose to the rectum and bladder when compared with RR without impairing the dose to CTV.

Colorectal large villous adenomas are sometimes associated with McKittrick–Wheelock syndrome, a condition characterized by severe diarrhea leading to dehydration, electrolyte depletion, and acute renal failure, which can be life-threatening in some cases. The efficacy of radiotherapy for colorectal villous adenoma has rarely been reported. We present a rare case of McKittrick–Wheelock syndrome in an older man caused by a large colorectal villous adenoma. This case is notable because palliative external beam radiotherapy of 30 Gy in 10 fractions not only reduced the tumor size but also resulted in significant symptom relief. This report demonstrates the efficacy of palliative radiotherapy for severe colorectal villous adenomas as a valid treatment option, particularly in older patients with complications.

The aim of this study was to identify 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) parameters that could predict the prognosis of patients with esophageal cancer before and after undergoing chemoradiation therapy. We retrospectively reconstructed images under the same conditions for patients who underwent pre- and post-treatment 18F-FDG-PET for chemoradiation therapy for esophageal cancer. Correlations between 2-year survival rates and pretreatment values, differences between pre- and post-treatment quotients, and their ratios were examined for various standardized uptake values (SUV), metabolic tumor volumes (MTV), and each SUVmean (Mean SUV)*MTV (Vol.mean). We enrolled 29 patients who underwent pre-and post-treatment 18F-FDG-PET. The median overall survival was 21.4 months (range, 3.6–100.9 months). Pre-treatment MTV had the most favorable hazard ratio (HR) for survival. However, the MTV product (Vol.meanQ), SUV corrected for basal metabolic rate using Mifflin-St Jeor estimation (BMR.ms), Vol.mean (SUVmeanQ) using the qPET method, SUVmean, and HR using Vol.meanQ corrected for body weight were nearly equivalent. No significant results were obtained for the pre- and post-treatment quotients. The pre- and post-treatment Vol.meanQ is a useful prognostic parameter that considers the effect of age-related loss of lean body mass. The use of parameters, including metabolism, will facilitate more appropriate use of 18F-FDG-PET before and after chemoradiation therapy.

Osteoclast differentiation is a dynamic differentiation process, which is accompanied by dramatic changes in metabolic status as well as in gene expression. Recent findings have revealed an essential connection between metabolic reprogramming and dynamic gene expression changes during osteoclast differentiation. However, the upstream regulatory mechanisms that drive these metabolic changes in osteoclastogenesis remain to be elucidated. Here, we demonstrate that induced deletion of a tumor suppressor gene, Folliculin (Flcn), in mouse osteoclast precursors causes severe osteoporosis in 3 weeks through excess osteoclastogenesis. Flcn-deficient osteoclast precursors reveal cell autonomous accelerated osteoclastogenesis with increased sensitivity to receptor activator of NF-κB ligand (RANKL). We demonstrate that Flcn regulates oxidative phosphorylation and purine metabolism through suppression of nuclear localization of the transcription factor Tfe3, thereby inhibiting expression of its target gene Pgc1. Metabolome studies revealed that Flcn-deficient osteoclast precursors exhibit significant augmentation of oxidative phosphorylation and nucleotide production, resulting in an enhanced purinergic signaling loop that is composed of controlled ATP release and autocrine/paracrine purinergic receptor stimulation. Inhibition of this purinergic signaling loop efficiently blocks accelerated osteoclastogenesis in Flcn-deficient osteoclast precursors. Here, we demonstrate an essential and novel role of the Flcn-Tfe3-Pgc1 axis in osteoclastogenesis through the metabolic reprogramming of oxidative phosphorylation and purine metabolism. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).