The technology used to add information to a real visual field is defined as augmented reality technology. Augmented reality technology that can interactively manipulate displayed information is ...called mixed reality technology. HoloLens from Microsoft, which is a head-mounted mixed reality device released in 2016, can display a precise three-dimensional model stably on the real visual field as hologram. If it is possible to accurately superimpose the position/direction of the hologram in the surgical field, surgical navigation-like use can be expected. However, in HoloLens, there was no such function. The authors devised a method that can align the surgical field and holograms precisely within a short time using a simple manual operation. The mechanism is to match the three points on the hologram to the corresponding marking points of the body surface. By making it possible to arbitrarily select any of the three points as a pivot/axis of the rotational movement of the hologram, alignment by manual operation becomes very easy. The alignment between the surgical field and the hologram was good and thus contributed to intraoperative objective judgment. By using the method of this study, the clinical usefulness of the mixed reality device HoloLens will be expanded.
Photon radiation therapy is a major curative treatment for cancer. However, the lack of robust predictive biomarkers for radiosensitivity precludes personalized radiation therapy. Clonogenic assays ...are the gold standard method for measuring the radiosensitivity of cancer cells. Although a large number of publications describe the use of clonogenic assays to measure cancer cell radiosensitivity, the robustness of results from different studies is unclear. To address this, we conducted a comprehensive detailed literature search of 256 common cancer cell lines and identified the eight cell lines most-frequently examined for photon sensitivity using clonogenic assays. Survival endpoints and experimental parameters from all 620 relevant experiments were compiled and analyzed. We found that the coefficients of variation for SF
(surviving fraction after 2 Gy irradiation) and for D
(dose that yields a surviving fraction of 10%) were below 30% for all cell lines, indicating that SF
and D
have acceptable inter-assay precision. These data support further analysis of published data on clonogenic assays using SF
and D
as survival endpoints, which facilitates robust identification of biological profiles representative of cancer cell sensitivity to photons.
In the era of precision medicine, radiotherapy strategies should be determined based on genetic profiles that predict tumor radiosensitivity. Accordingly, pre-clinical research aimed at discovering ...clinically applicable genetic profiles is needed. However, how a given genetic profile affects cancer cell radiosensitivity is unclear. To address this issue, we performed a pilot in vitro study by utilizing
mutational status as a model for genetic profile. Clonogenic assays of
mutant (
= 6) and wild-type (
= 9) non-small cell lung carcinoma (NSCLC) cell lines were performed independently by two oncologists. Clonogenic survival parameters SF
, SF
, SF
, SF
, mean inactivation dose (MID), D
, D
, α, and β were obtained using the linear quadratic model. The differences in the clonogenic survival parameters between the
mutant and wild-type cell lines were assessed using the Mann-Whitney U test. As a result, for both datasets, the
values for SF
, SF
, D
, α, and α/β were below 0.05, and those for SF
were lowest. These data indicate that a genetic profile of NSCLC cell lines might be predictive for their radiation response; i.e.,
mutant cell lines might be more sensitive to low dose- and low fraction sized-irradiation.
Postaxial polydactyly is a common congenital foot anomaly. However, the severity of the anomaly varies from simple cases with only soft tissue duplication to complex cases with bone and joint ...disorders. In our clinical practice, we found a new morphological anomaly of postaxial polydactyly. We encountered several cases of postaxial polydactyly with bone fragments located between the fourth and fifth toes. The bone fragments were independent of the joint cavity. The mechanisms underlying its development remain unknown because it is a novel disorder. In the present study, we investigated the characteristics of the excess bone to formulate an embryological hypothesis.
We examined the frequency and trends in the occurrence of excess bone using data from photographs and radiographs of these cases. An example of a disorder similar to excess bone is mosaic-like alignment, as reported by Iba et al. We also compared the characteristics of the mosaic-like alignment with those of the excess bone. Based on these data and existing embryological knowledge, we hypothesized the origin of the excess bone.
Excess bone and mosaic-like alignments showed different characteristics. Therefore, both were considered completely different disorders. We hypothesized that excess bone was caused by damage to the interdigital ectoderm immediately before interdigital programmed cell death.
We encountered a new form of postaxial polydactyly. This can be a factor influencing the treatment strategy because it can affect alignment and stability.
In cancer therapy today, carbon ion radiotherapy is used mainly as monotherapy, whereas cisplatin is used concomitantly with X-ray radiotherapy. The effectiveness of concomitant carbon ions and ...cisplatin is unclear. To obtain the information on the mechanisms potentially shared between carbon ions or X-rays and cisplatin, we assessed the correlation of sensitivity to the single treatments. In 20 human cancer cell lines, sensitivity to X-rays strongly correlated with sensitivity to cisplatin, indicating the presence of potentially shared target mechanisms. Interestingly, the correlation of sensitivity to carbon ions and cisplatin was much weaker than that of sensitivity to X-rays and cisplatin, indicating the presence of potentially different target mechanisms between carbon ions and cisplatin. Assessment of clonogenic cell death by 4',6-diamidino-2-phenylindole dihydrochloride staining showed that mitotic catastrophe was more efficiently induced by carbon ions than by the same physical dose of X-rays, while apoptosis and senescence were not. These data indicate that the correlation of sensitivity to carbon ions and cisplatin is weaker than that of sensitivity to X-rays and cisplatin, which are helpful as biological basis to understand the potentially shared mechanism among these treatments. Further investigation is mandatory to elucidate the clinical efficacy of carbon ions and cisplatin combination.
Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood ...lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy specimens were obtained from seven prospectively recruited patients with cervical cancer, before treatment and after receiving radiotherapy at a dose of 10 Gy (in five fractions). The samples were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, and 200 nuclei per sample were randomly identified and assessed for the presence of MN or apoptosis, based on nuclear morphology. The median number of MN-harboring nuclei was significantly greater in samples from patients treated with radiotherapy than in pre-treatment samples (151 (range, 16–327) versus 28 (range, 0–61); p = 0.015). No significant differences in the number of apoptotic nuclei were observed between pre-treatment and 10 Gy samples (5 (range, 0–30) versus 12 (range, 2–30); p = 0.30). This is the first report to demonstrate MN induction by radiotherapy in solid tumors. The results provide clinical evidence of the activation of antitumor immune responses by radiotherapy.
•Integration of published radiosensitivity (RS) data is important but labor-intensive.•We developed deep learning-aided programs to extract RS data from the literature.•Programs #1–3 screen papers ...containing RS data obtained by clonogenic assays (CAs).•Program #4 extracts CA-derived SF2 data from semi-logarithmic survival curves.•Programs #1–4 in combination help scientists mine CA-derived RS data from papers.
Integrated analysis of existing radiosensitivity data obtained by the gold-standard clonogenic assay has the potential to improve our understanding of cancer cell radioresistance. However, extraction of radiosensitivity data from the literature is highly labor-intensive. To aid in this task, using deep convolutional neural networks (CNNs) and other computer technologies, we developed an analysis pipeline that extracts radiosensitivity data derived from clonogenic assays from the literature.
Three classifiers (C1–3) were developed to identify publications containing radiosensitivity data derived from clonogenic assays. C1 uses Faster Regions CNN with Inception Resnet v2 (fRCNN-IRv2), VGG-16, and Optical Character Recognition (OCR) to identify publications that contain semi-logarithmic graphs showing radiosensitivity data derived from clonogenic assays. C2 uses fRCNN-IRv2 and OCR to identify publications that contain bar graphs showing radiosensitivity data derived from clonogenic assays. C3 is a program that identifies publications containing keywords related to radiosensitivity data derived from clonogenic assays. A program (iSF2) was developed using Mask RCNN and OCR to extract surviving fraction after 2-Gy irradiation (SF2) as assessed by clonogenic assays, presented in semi-logarithmic graphs. The efficacy of C1–3 and iSF2 was tested using seven datasets (1805 and 222 publications in total, respectively).
C1–3 yielded sensitivity of 91.2% ± 3.4% and specificity of 90.7% ± 3.6%. iSF2 returned SF2 values that were within 2.9% ± 2.6% of the SF2 values determined by radiation oncologists.
Our analysis pipeline is potentially useful to acquire radiosensitivity data derived from clonogenic assays from the literature.
Carbon-ion radiotherapy (CIRT) holds promise to treat inoperable locally-advanced non-small cell lung carcinoma (NSCLC), a disease poorly controlled by standard chemoradiotherapy using X-rays. Since ...CIRT is an extremely limited medical resource, selection of NSCLC patients likely to benefit from it is important; however, biological predictors of response to CIRT are ill-defined. The present study investigated the association between the mutational status of EGFR and KRAS, driver genes frequently mutated in NSCLC, and the relative biological effectiveness (RBE) of carbon-ion beams over X-rays. The assessment of 15 NSCLC lines of different EGFR/KRAS mutational status and that of isogenic NSCLC lines expressing wild-type or mutant EGFR revealed that EGFR-mutant NSCLC cells, but not KRAS-mutant cells, show low RBE. This was attributable to (i) the high X-ray sensitivity of EGFR-mutant cells, since EGFR mutation is associated with a defect in non-homologous end joining, a major pathway for DNA double-strand break (DSB) repair, and (ii) the strong cell-killing effect of carbon-ion beams due to poor repair of carbon-ion beam-induced DSBs regardless of EGFR mutation status. These data highlight the potential of EGFR mutation status as a predictor of response to CIRT, i.e., CIRT may show a high therapeutic index in EGFR mutation-negative NSCLC.
Satoyoshi syndrome is a rare multisystemic disorder of unknown etiology characterized by progressive muscle spasms, alopecia and diarrhea. Multiple protruding lesions with cystic glands, namely ...gastroenterocolitis cystica polyposa, manifest in the gastrointestinal tract. Since the first report of these lesions in 1977, which was unique to Satoyoshi syndrome, few studies have focused on their role, and the associated clinicopathological features are not well understood. Here, we report a 64‐year‐old Japanese woman with Satoyoshi syndrome who presented with multiple polypoid lesions in the stomach, duodenum, jejunum, ileum and colon. Histologically, the polypoid lesions in the intestine comprised multiple heterotopic submucosal glands containing cystically dilated glands and smooth muscle fibers in the lamina propria mucosa and/or submucosa. Additionally, we observed stromal changes, such as fibrosis, discontinuous and thinning muscularis mucosae, and diffuse neural fiber proliferation in the entire intestinal tract. Furthermore, multiple foci of adenocarcinomas were identified within several heterotopic submucosal glands. We hypothesized that multiple heterotopic submucosal glands in the present case corresponded to previously reported gastroenterocolitis cystica polyposa, suggesting that these lesions are essential in the histopathology and are a unique manifestation of Satoyoshi syndrome.
Introduction
We present a case of mucinous adenocarcinoma of the prostate with testicular and lung metastases following robot‐assisted radical prostatectomy, androgen deprivation therapy, and ...radiotherapy.
Case presentation
A 73‐year‐old man with a prostate‐specific antigen level of 4.3 ng/mL was diagnosed with prostate cancer. Following the robot‐assisted radical prostatectomy, the pathological diagnosis was mucinous adenocarcinoma of the prostate (pT3bpN0, Gleason score of 4 + 4). Salvage hormonal therapy and irradiation were performed after the prostatectomy. Enlargement of the left testis was noted, and 28 months after prostatectomy, computed tomography detected a left testicular tumor and nodular lesions in the bilateral lungs. The histopathological diagnosis of left high orchiectomy was metastasis of a mucinous adenocarcinoma of the prostate. Chemotherapy with docetaxel followed by cabazitaxel was initiated.
Conclusion
Mucinous prostate adenocarcinoma with distal metastases following prostatectomy has been managed for longer than 3 years with multiple treatments.
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