Prognostic significance of low HER2 expression in gastric cancer: a retrospective, single-center analysis.

INTRODUCTION: Mutated human epidermal growth factor receptor 2 (HER2) is an oncogene with critical pathogenic roles in breast cancer. HER2-low-positive breast cancer is a recently described subtype. We aimed to explore the clinical and molecular characteristics of gastric cancer with low HER2 expression, drawing on recent developments in breast cancer subtypes. MATERIALS AND METHODS: This retrospective study involved 129 patients with HER2-non-amplified gastric cancer treated in Iwate prefectural Iwai Hospital from 2013 to 2019. Tumors were classified as HER2-null or low-positive based on immunohistochemistry score 0 or 1 + or 2 + with HER2 negativity in situ hybridization, respectively. Statistical analyses, including Kaplan-Meier analyses and Cox proportional hazards model were conducted. RESULTS: Low HER2 expression was present in 26% (33/129) of the patients. Clinicopathological characteristics were not significantly different between the HER2-low and null groups. Kaplan-Meier analysis of overall survival was significantly longer in the HER2-low group than in the HER2-null group (P = 0.01). In multivariate Cox regression analysis, HER2-null status was associated with worse survival (hazard ratio 3.01; 95% confidence interval 1.18-7.65; and P = 0.02). CONCLUSION: This study highlights the prognostic importance of low HER2 expression in gastric cancer, similar to that observed in HER2-low-positive breast cancer, and suggests reclassification of gastric cancer to improve personalized treatment. Future studies should elucidate the molecular underpinnings of low HER2 expression in gastric cancer to guide novel therapeutic strategies and improve outcomes.

Synaptic pruning through glial synapse engulfment upon motor learning.

Synaptic pruning is a fundamental process of neuronal circuit refinement in learning and memory. Accumulating evidence suggests that glia participates in sculpting the neuronal circuits through synapse engulfment. However, whether glial involvement in synaptic pruning has a role in memory formation remains elusive. Using newly developed phagocytosis reporter mice and three-dimensional ultrastructural characterization, we found that synaptic engulfment by cerebellar Bergmann glia (BG) frequently occurred upon cerebellum-dependent motor learning in mice. We observed increases in pre- and postsynaptic nibbling by BG along with a reduction in spine volume after learning. Pharmacological blockade of engulfment with Annexin V inhibited both the spine volume reduction and overnight improvement of motor adaptation. These results indicate that BG contribute to the refinement of the mature cerebellar cortical circuit through synaptic engulfment during motor learning.

Iodine dose optimization in portal venous phase virtual monochromatic images of the abdomen: Prospective study on rapid kVp switching dual energy CT.

PURPOSE: To investigate iodine dose concentration required for adequate hepatic parenchymal enhancement on fast-kilovoltage-switching dual-energy computed tomography (DECT) of the abdomen based on patient body weight. MATERIALS AND METHODS: The protocol of this prospective study was approved by the local Institutional Review Board and written informed consent for study participation was obtained from all patients. The study cohort of 204 consecutive patients who underwent whole body single-source DECT to screen for tumor metastases and/or recurrence after surgical resection of malignant tumors were randomly assigned to one of three protocols according to the iodine dose (400, 500, and 600 mgI/kg). For each case, two radiologists quantitatively and qualitatively reviewed three energy levels (65, 70, and 75 kilo electron volt [keV]) of the portal venous phase virtual monochromatic images (VMIs). CT numbers of the liver and the qualitative hepatic parenchymal enhancement were compared among the VMIs with the three protocols and three energy levels. RESULTS: Hepatic enhancement (ΔHU > 50HU) was achieved at 65 keV with 400, 500, and 600 mgI/kg, at 70 keV with 500 and 600 mgI/kg, and at 75 keV with 600 mgI/kg. The hepatic parenchymal enhancement was graded as sufficient hepatic enhancement in 97%, 100%, and 99% at 65 keV with 400, 500, and 600 mgI/kg, 88% and 97% at 70 keV with 500 and 600 mgI/kg, and 84% at 75 keV with 600 mgI/kg, respectively. CONCLUSION: The iodine dose can be reduced to 400 mgI/kg at 65 keV or 500 mgI/kg at 70 keV in DECT without compromising hepatic parenchymal enhancement.

Intensity-modulated radiation therapy for elderly patients (aged ≥75 years) with localized prostate cancer: Comparison with younger patients (aged <75 years).

The aim of the present study was to evaluate the efficacy and safety of intensity-modulated radiation therapy (IMRT) for elderly patients with prostate cancer (age ≥75 years) compared with younger patients (<75 years). The numbers of patients enrolled into the elderly and younger groups were 238 and 853, respectively. More than half of the patients in the elderly group were high-risk, and the total risk of the elderly group was higher than that of younger group. The median follow-up periods for the elderly and younger groups were 42 (range, 2-108) and 49 (range, 2-120) months, respectively. All patients were treated with IMRT at a dose of 74-78 Gy with or without androgen-deprivation therapy. The biochemical failure-free rates (BFFRs) at 3-year follow-up for the elderly and younger groups were 93.3 and 95.7%, respectively; there was no significant difference between the 2 groups in regard to the BFFR. The clinical failure-free rates (CFFR) at 3-year follow-up for the elderly and younger groups was 95.8 and 98.5%, respectively; the 2 groups did not differ significantly in regard to the CFFR. The cumulative incidence rates of gastrointestinal toxicity (grade ≥2) and genitourinary toxicity (grade ≥2) at 3-year follow-up were 10.5 and 1.3%, respectively; there was no significant difference between the elderly and younger groups. It was concluded that in prostate cancer patients aged 75 years or older, IMRT has a treatment effect equivalent to that in patients <75 years old; adverse events are also comparable.