Label‐free multiphoton excitation imaging as a promising diagnostic tool for breast cancer

Histopathological diagnosis is the ultimate method of attaining the final diagnosis; however, the observation range is limited to the two‐dimensional plane, and it requires thin slicing of the tissue, which limits diagnostic information. To seek solutions for these problems, we proposed a novel imaging‐based histopathological examination. We used the multiphoton excitation microscopy (MPM) technique to establish a method for visualizing unfixed/unstained human breast tissues. Under near‐infrared ray excitation, fresh human breast tissues emitted fluorescent signals with three major peaks, which enabled visualizing the breast tissue morphology without any fixation or dye staining. Our study using human breast tissue samples from 32 patients indicated that experienced pathologists can estimate normal or cancerous lesions using only these MPM images with a kappa coefficient of 1.0. Moreover, we developed an image classification algorithm with artificial intelligence that enabled us to automatically define cancer cells in small areas with a high sensitivity of ≥0.942. Taken together, label‐free MPM imaging is a promising method for the real‐time automatic diagnosis of breast cancer.     

Regional differences of fMR signal changes induced by hyperventilation: comparison between SE-EPI and GE-EPI at 3-T.

PURPOSE: To evaluate whether reproducible signal change of brain tissues by hyperventilation (HV) can be seen on spin-echo (SE)-echo planar imaging (EPI) at 3-T and to examine the sensitivity of SE-EPI for measuring vascular reactivity in regions of the brain, such as the hippocampal formation, that are difficult to visualize with gradient-echo (GE)-EPI due to susceptibility artifacts. MATERIALS AND METHODS: Six healthy human subjects performed a voluntary HV task. The task design was as follows: two minutes normal breathing (rest) followed by two minutes HV, giving a basic four-minute block that was repeated three times for a total scan time of 12 minutes for one run. Each subject performed the run both for SE-EPI and GE-EPI. Statistical analysis was performed to detect the area with significant cerebrovascular reactivity. The percentage signal change was also obtained for each cerebral region. RESULTS: Both GE-EPI and SE-EPI showed globally significant signal decreases in the cerebral cortex. In GE-EPI, the frontal cortex showed a larger signal decrease than the other gray matter tissues (P < 0.05). In SE-EPI, the differences among gray matter tissues except for the hippocampal formation were not significant. The hippocampal formation showed the largest signal change (P < 0.05) in SE-EPI, but no significant signal change was observed in GE-EPI due to the presence of susceptibility artifacts. CONCLUSION: HV using SE-EPI at 3-T provides robust and reproducible signal decreases and may make the evaluation of the vascular reactivity in hippocampal formation feasible.     

Clinical evaluation of double stenting for duodenal and biliary obstructions caused by pancreatic head carcinoma using covered self‐expandable metallic stents

Five patients with non‐resectable pancreatic head carcinoma complicated by duodenal and biliary obstructions were successfully treated by double stenting with covered self‐expandable metallic stents (EMS). Diamond (Boston Scientific, Natick City, MA, USA) stents covered with a polyurethane membrane were used to treat biliary obstructions, whereas covered Ultraflex (Boston Scientific) stents for esophageal stenting were used to treat duodenal obstructions. That is, Diamond stents were initially placed in the biliary tract percutaneously in one patient and endoscopically in the remaining four patients. Subsequently, covered Ultraflex stents were placed in the duodenum. Double stenting with EMS was successfully performed in all five patients without inducing early technical complications. All patients were able to take a liquid diet orally at a mean 1.6 days after the double stenting procedure and were able to eat solid foods thereafter. Sludge‐induced biliary obstructions were detected in two patients 3 and 6 months after the placement of EMS. However, recurrent biliary obstruction was not noted in the remaining three patients. The EMS left in the duodenum were not obstructed during the observation period. The survival period of the patients ranged from 86 to 363 days (mean 172 days). There have not been any reports evaluating the usefulness of double stenting using covered EMS for duodenal and biliary obstructions. Because favorable results were obtained by double stenting in our patients, stenting for duodenal and biliary obstructions caused by non‐resectable pancreatic head carcinoma may become a useful treatment modality substituting for bypass surgery.     

Clinical outcomes of definitive radiotherapy for patients with cT1aN0M0 esophageal cancer unsuitable for endoscopic resection and surgery

BackgroundStudies on the clinical outcomes of radiotherapy for clinical (c)T1aN0M0 (UICC-TNM Classification, Eighth Edition) esophageal cancer (EC) are limited. Therefore, this retrospective study aimed to clarify the clinical outcomes of definitive radiotherapy (RT) or chemoradiotherapy (CRT) for cT1aN0M0 EC unsuitable for endoscopic resection and surgery.MethodsPatients with cT1aN0M0 esophageal squamous cell carcinoma who underwent definitive RT or CRT between January 2009 and December 2020 were retrospectively reviewed. The initial response, toxicities, survival rates, recurrence patterns, and salvage treatments of the patients were evaluated. Initial response was measured using the Response Evaluation Criteria in Solid Tumors guideline. Toxicity was assessed and documented following the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Survival rates from the date of initiation of treatment were measured using the Kaplan–Meier method.ResultsTwenty patients treated with definitive RT or CRT were included in the study. The median follow-up duration was 55 months (range, 13–131 months). All patients achieved complete response to the initial treatment. Grade 3 acute toxicities observed esophagitis (10%), pneumonitis (5%), and leukopenia (5%). Late toxicities higher than grade 3 were not observed. The 1-, 3-, and 5-year overall and disease-specific survival rates were 100% and 100%, 83% and 100%, and 67% and 100%, respectively. No treatment-related deaths occurred. Among the 20 patients, 6 showed local recurrence and 2 showed metachronous recurrence. Seven patients underwent salvage endoscopic submucosal dissection (ESD), and one underwent argon plasma coagulation treatment. After the endoscopic treatment, no recurrences were observed.ConclusionsDefinitive RT or CRT was considered an alternative initial treatment for patients with cT1aN0M0 EC who were unsuitable for endoscopic resection and surgery.     

Correlation between the length of the pyloric cuff and postoperative evaluation after pylorus-preserving gastrectomy

Background  

Recent years have seen the preserved pyloric cuff being lengthened in pylorus-preserving gastrectomy for early gastric cancer. We performed clinical assessment of the symptoms after pylorus-preserving gastrectomy in patients treated at the National Cancer Center Hospital in Japan during the past 9 years.     

Psychiatric Symptoms and Subthalamic Nucleus Stimulation in Parkinson's Disease. A Retrospective Study in Our Japanese Patients

Objectives. With respect to postoperative activities of daily living (ADL), we retrospectively investigated associated psychiatric symptoms that influenced beneficial effects of subthalamic nucleus (STN) stimulation in our Japanese patients with Parkinson disease (PD). Materials and Methods. Twenty‐five patients underwent bilateral STN stimulation. Pre‐ and 3 months after the surgery, their parkinsonian symptoms were evaluated with Unified Parkinson Disease Rating Scale (UPDRS) and Schwab‐England (S‐E) ADL scale. Stepwise multiple analysis was performed to determine the factors affecting postoperative ADL. Results. Eleven out of 25 patients manifested drug‐induced psychosis preoperatively, although their mean dosage of levodopa was small (366.4 ± 152.7 mg). Disease duration positively affected the severity of the patients’ psychiatric symptoms. Postoperative S‐E score showed a significant improvement compared to the pretreatment baseline in both of “on” and “off” medication states, as all their cardinal motor symptoms were significantly ameliorated. Preoperative scores for thought disorder and axial disability negatively impact on the postoperative S‐E score in “on” state (p < 0.01). Preoperative score for intellectual impairment was only a significant predictor of worse postoperative ADL in “off” state. Conclusions. The markedly lower dose of levodopa may suggest ethnic characteristics of our Japanese patients with respect to tolerance for antiparkinsonian medications. Preoperative manifestation of drug‐induced psychosis and cognitive dysfunction were the major factor that strikingly suppressed daily activities after STN stimulation.     

Subcellular relationships between cholinergic terminals and estrogen receptor-alpha in the dorsal hippocampus

Cholinergic septohippocampal neurons are affected by circulating estrogens. Previously, we found that extranuclear estrogen receptor-alpha (ERalpha) immunoreactivity in presynaptic profiles had an overlapping distribution with cholinergic afferents in the rat hippocampal formation. To determine the subcellular relationships between cholinergic presynaptic profiles and ERalpha, hippocampal sections were dually immunolabeled for vesicular acetylcholine transporter (VAChT) and ERalpha and examined by electron microscopy. Within the hippocampal formation, immunoreactivities for VAChT and ERalpha both were presynaptic, although their subcellular targeting was distinct. VAChT immunoreactivity was found exclusively within presynaptic profiles and was associated with small synaptic vesicles, which usually filled axon terminals. VAChT-labeled presynaptic profiles were most concentrated in stratum oriens of the hippocampal CA1 region and dentate inner molecular layer and hilus. In contrast, ERalpha immunoreactivity was found in clusters affiliated either with select vesicles or with the plasmalemma within preterminal axons and axon terminals. ERalpha-immunoreactive (IR) presynaptic profiles were more evenly distributed between hippocampal lamina than VAChT-IR profiles. Quantitative ultrastructural analysis revealed that VAChT-IR presynaptic profiles contained ERalpha immunoreactivity (ranging from 3% to 17%, depending on the lamina). Additionally, VAChT-IR presynaptic profiles apposed ERalpha-IR dendritic spines, presynaptic profiles, and glial profiles; many of the latter two types of profiles abutted unlabeled dendritic spines that received asymmetric (excitatory-type) synapses from unlabeled terminals. The presence of ERalpha immunoreactivity in cholinergic terminals suggests that estrogen could rapidly and directly affect the local release and/or uptake of acetylcholine. The affiliation of cholinergic terminals with excitatory terminals near ERalpha-labeled dendritic spines or glial profiles suggests that alterations in acetylcholine release could indirectly affect estrogen-modulated structural plasticity.