The effectiveness of a virtual reality teaching module on advance care planning and advance decision for medical professionals.

BACKGROUND: The concepts of advance care planning (ACP) and advance decisions/directives (ADs) are widely recognized around the world. The Patient Right to Autonomy Act in Taiwan, the first of its kind in Asia, went into effect in 2019. However, a lack of knowledge and confidence regarding ACP and ADs is a barrier for medical professionals in discussing ACP and ADs with their patients. In addition, in Asian countries, physicians tend to make family-centered decisions, which influence how they can implement ADs. METHODS: Virtual reality (VR) is known for its immersive and interactive simulation experience and can upgrade medical education. We developed a VR teaching module to help medical professionals better understand ACP and ADs, with assessment tools integrated into the module. The participants were asked to answer seven knowledge items embedded in the module and fill out the surveys regarding attitudes toward ACP and ADs and confidence in implementing ADs before and after the module. They also reported behaviors related to ADs before and three months after the VR experience. RESULTS: From July 2020 to June 2022, 30 physicians and 59 nurses joined the study, and 78.7% of them had no prior experience in hospice care. After learning from the VR module, all 89 participants were able to answer all seven items correctly. The results showed a slightly more positive attitude toward ACP and ADs (scores: 32.29 ± 3.80 versus 33.06 ± 3.96, p < .05) and more confidence in implementing ADs (scores: 13.96 ± 2.68 versus 16.24 ± 2.67, p < .001) after the VR module. Changes in AD-related behaviors (scores: 11.23 ± 4.01 versus 13.87 ± 4.11, p < .001) were also noted three months after the VR experience. CONCLUSIONS: This study found that medical professionals may have better knowledge of ACP and ADs, slightly improved attitudes toward ACP and ADs, and greater confidence in implementing ADs after experiencing the VR module. Most importantly, the findings suggested that using a VR format may help motivate medical professionals to perform essential behaviors related to ADs, including introducing ADs to their patients and discussing ADs with their own family.

Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy.

This study investigated whether oncogenic and tumor-suppressive gene mutations are involved in the differential outcomes of patients with rectal carcinoma receiving neoadjuvant chemoradiotherapy (nCRT). Genomic DNA was obtained from formalin-fixed paraffin-embedded (FFPE) specimens of patients with rectal carcinoma who received a complete nCRT course. Gene mutation status was examined in specimens from patients before and after nCRT by using the AmpliSeq platform. Our data revealed that the nonsynonymous p53, APC, KRAS, CDKN2A, and EGFR mutations were observed in 93.1%, 65.5%, 48.6%, and 31% of the patients with rectal adenocarcinoma, respectively. BRAF, FBXW7, PTEN, and SMAD4 mutations were observed in 20.7% of patients with rectal carcinoma. The following 12 gene mutations were observed more frequently in the patients exhibiting a complete response than in those demonstrating a poor response before nCRT: ATM, BRAF, CDKN2A, EGFR, FLT3, GNA11, KDR, KIT, PIK3CA, PTEN, PTPN11, SMAD4, and TP53. In addition, APC, BRAF, FBXW7, KRAS, SMAD4, and TP53 mutations were retained after nCRT. Our results indicate a complex mutational profile in rectal carcinoma, suggesting the involvement of BRAF, SMAD4, and TP53 genetic variants in the outcomes of patients with nCRT.

Dynamic hybrid-phase computed tomography simulation in lung stereotactic body radiotherapy: A feasibility study.

To assess the feasibility of dynamic hybrid-phase computed tomography (CTDHP) simulation when patients undergo lung stereotactic body radiation therapy (SBRT). Eighteen non-small-cell lung-cancer patients were immobilised in a stereotactic body frame with abdominal compression. All underwent dynamic hybrid-phase CT scans that were compared with cone-beam CT (CBCT). We also determined the internal target volume (ITV) and evaluated the following four metrics: the "AND" function in the Boolean module of Eclipse, volume overlap (VO), Dice similarity coefficient (DSC), and dose-volume histogram. The average ITV values of 4DCTDHP and 3D-CBCT were respectively 12.82±10.42 and 14.6±12.18 cm3 (n=72, p<0.001), and the average ITV value of AND was 11.7±10.1 cm3. The average planning target volume (PTV) of 4DCTDHP and 3D-CBCT was 25.63±18.04 and 28.00±19.82 cm3 (n=72, p<0.001). The median AND difference between ITV and PTV was significant (p<0.01) and had a significantly linear distribution (R2=0.991 for ITV, R2=0.972 for PTV). The average VO of PTV was greater than that of ITV (0.81±0.096; 0.78±0.11). We also observed that the average DSC in PTV (0.83±0.066) was greater than that in ITV (0.81±0.084). The average results indicated that 97.9%±3.44 of ITVCBCT was covered by 95% of the prescribed dose. The average minimum, maximum and mean percentage doses of ITVCBCT were 87.9%±9.46, 107.3%±1.57, and 101.3%±1.12, respectively. This paper has demonstrated that dynamic hybrid-phase CT simulation for patients undergoing lung SBRT and also published evaluation metrics in scientific analysis. Our approach also has the advantage of adequate margin and fewer phases in CT simulation.

Evaluating the benefit of adjuvant radiotherapy after extensive lymph node dissection for gastric cancer: a single-institute retrospective study.

OBJECTIVE: This study aimed to evaluate whether adjuvant radiotherapy (RT) can improve the treatment outcome of patients with locally advanced gastric cancer who underwent extensive lymph node dissection (ELND). MATERIALS AND METHODS: This retrospective study included patients with gastric cancer pathological stages IIA-IIIC at Taipei Tzu Chi Hospital between 2008 and 2015. Patients (a) aged >80 years, (b) with distant metastasis at diagnosis, (c) with coexisting malignancies, (d) who did not complete the prescribed RT course, and (e) who died 1 month after surgery were excluded. Among 420 patients diagnosed with gastric cancer, 98 were included. RESULTS: The median follow-up was 24.5 months. Of 39 patients who underwent adjuvant RT, 38 also received adjuvant chemotherapy (CT). Of 59 patients who did not receive adjuvant RT, only 34 received adjuvant CT. ELND was performed in 67.3% of the patients. The 5-year overall survival (OS) rate was 40%. In the univariate analyses, adjuvant CT regimen, 5-fluorouracil + leucovorin, was associated with worst outcome, while TS-1 was associated with better survival outcome (P = 0.018). The number of involved lymph nodes was strongly related to the OS and disease-free survival (DFS) (P < 0.001). We tried using different numbers of involved lymph nodes as a cutoff point and found that adjuvant RT significantly improved both OS and DFS in patients whose involved lymph nodes were ≥4 (OS, P = 0.017; DFS, P = 0.015). In multivariate analyses, better DFS was associated with negative surgical margin (P = 0.04), earlier disease stage (P = 0.001), adjuvant radiotherapy (P = 0.045), and adjuvant CT regimen TS-1 (P = 0.001). CONCLUSION: Adjuvant RT could improve DFS of patients with locally advanced gastric cancer with or without ELND. When the number of involved lymph nodes is ≥4, adjuvant RT is strongly suggested.

Use of electronic portal images to evaluate setup error and intra-fraction motion during free-breathing breast IMRT treatment.

Before delivering of intensity-modulated radiotherapy, kilo-voltage image-guidance radiotherapy is widely used in setup error correction and monitoring intra-fraction motion effectively. Accordingly, this study proposes and tests an image integration technique for observing intra-fraction motion during beam delivery, with the wider objective of reducing both image-guidance time and the dose delivered to normal breast tissue. The study sample comprised 33 female patients with breast cancer, and 241 sets of portal images acquired using a VARIAN aSi-1000 electronic portal imaging device. Motion amplitudes and vectors were collected and calculated separately by two senior therapists. The setup error in 3 axes was computed for every fraction, with average shifting for lateral, longitudinal and vertical direction was -0.3-mm ± 0.5, -0.1-mm ± 0.5 and -0.6-mm ± 1.6, with the average vector of setup error being 2.9-mm ± 1.4. The average intra-fraction motion for vertical direction was (A: -0.1-mm ± 1.0; B: -0.0 ± 1.1), for longitudinal was (A: -0.4-mm ± 1.7; B: 2.0 ± 1.1), and for lateral direction was (A: 0.3-mm ± 1.3; B: 0.2 ± 1.8). The average intra-fraction vector was 2.9-mm ± 1.3 for therapist A, and 3.4-mm ± 1.8 for therapist B. Offline Review commercial software was utilized for setup error and motion analysis, and data analysis and reliability testing were conducted with statistical package of the social sciences. Pearson correlations between the two therapists was moderate (0.59, p << 0.01), and the Cohen's kappa value for inter rater agreement between different evaluators was fair in the anterior-posterior direction (0.25, p << 0.01), with slight agreement in other two directions and vectors. The study presented efficient and dose reduction method to evaluate setup error and intra-fraction motion during breast intensity-modulated radiotherapy treatment.

Is quality of registry treatment data related to registrar experience and workload? A study of Taiwan cancer registry data.

BACKGROUND: Although cancer treatment information has been collected through the Cancer Registry system in Taiwan for more than 10 years, the accuracy of such data has never been evaluated. This study examined the accuracy rate between registrar experience and on-site chart review for the first course of cancer treatment. METHODS: In this retrospective chart review study, 392 randomly selected medical records from 14 hospitals were re-abstracted by experienced abstractors. The kappa coefficients of accuracy for the abstracting data were calculated against the gold standard. Correlations between registrar background and workload were then identified through regression analysis. RESULTS: Regarding surgery type, low accuracy rates were noted for gastric cancer (84.0%), oral cavity cancer (84.6%), and bladder cancer (88.9%). For chemotherapy, low accuracy rates were observed for hematopoietic diseases (81.3%) and esophageal cancer (88.0%). For radiotherapy, low accuracy rates were noted for esophageal cancer (80.0%), cervical cancer (81.8%), and lymphoma (85.7%). When stratifying by surgery type after adjustment for hospital caseload, a high accuracy rate was found for cancer registrars who had progressed from basic to advanced licenses within 5 years of graduating. CONCLUSION: The accuracy rate for the first course of cancer treatment was affected by the cancer type and the experience of cancer registrars, but it was not affected by the workload of cancer registrars. We recommend that cancer registrars with basic licenses upgrade to advanced licenses as soon as possible. Medical record collaboration should establish documentation for checklist of radiotherapy and surgical operation records.

Haptoglobin is a serological biomarker for adenocarcinoma lung cancer by using the ProteomeLab PF2D combined with mass spectrometry.

Identification of serological biomarker is urgently needed for cancer screening, monitoring cancer progression, treatment response, and surveillance for recurrence in lung cancer. Therefore, we try to find new serological biomarker that has more specificity and sensitivity for lung cancer diagnostics. In this study, the 2-D liquid phase fractionation system (PF2D) and mass spectrometry approach has been used for comparison the serum profiles between lung cancer patients and healthy individuals. Eight proteins were identified form PF2D and subsequently by mass spectrometry. Among these proteins, haptoglobin (HP) and apolipoprotein AI (APOA1) were chosen and validated with turbidimetric assay. We found that HP levels were significantly higher and APOA1 levels were significantly lower in lung cancer patients. However, after the participants were stratified by gender, the expression trends of HP and APOA1 in lung cancer patients existed only in men, which is gender specific phenomenon. HP, APOA1 and carcinoembryonic antigen (CEA), used for distinguishing lung adenocarcinoma, had a sensitivity of 64%, 64% and 79%, respectively. Area under the ROC curve (AUC) of HP, APOA1 and CEA were 0.768, 0.761 and 0.884, respectively. When restricted to male subjects, HP, APOA1 and CEA showed sensitivity of 89%, 73% and 100%, respectively. AUC of HP, APOA1 and CEA were 0.929, 0.840 and 0.877, respectively. Therefore, our results showed that combined with PF2D system and mass spectrometry, this is a promising novel approach to identify new serological biomarkers for lung cancer research. In addition, HP may be a potential serological biomarker for lung adenocarcinoma diagnostics, especially in male subjects.

Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem.

Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)-based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups-1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and < 1cm. Comparison was then made among the following 3 types of LINAC-based radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2cm(3) to 21.9cm(3). Regarding the dose homogeneity index (HIICRU) and conformity index (CIICRU) were without significant difference between techniques statistically. However, the average CIICRU = 1.09 ± 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 ± 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V4Gy of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V2Gy of normal brain, VMAT plans had attained 6.4 ± 5%; this was significantly better (p < 0.05) than either DCA or IMRS plans, at 9.2 ± 7% and 8.2 ± 6%, respectively. Owing to the multiple arc or beam planning designs of IMRS and VMAT, both of these techniques required higher MU delivery than DCA, with the averages being twice as high (p < 0.05). If linear accelerator is only 1 modality can to establish for SRS treatment. Based on statistical evidence retrospectively, we recommend VMAT as the optimal technique for delivering treatment to tumors adjacent to brainstem.

Amine-surface-modified superparamagnetic iron oxide nanoparticles interfere with differentiation of human mesenchymal stem cells.

Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used for stem cell labeling and tracking. Surface modification has been known to improve biocompatibility, biodistribution, and labeling efficiency of SPIO nanoparticles. However, the effects of amine (NH 3+)-surface-modified SPIO nanoparticles on proliferation and differentiation of human mesenchymal stem cells (hMSCs) remain unclear. The purpose of this study is to investigate how amine-surface-modified SPIO nanoparticles affected hMSCs. In this study, intracellular uptake and the contiguous presence of amine-surface-modified SPIO nanoparticles in hMSCs were demonstrated by Prussian blue staining, transmission electron microscopy and magnetic resonance imaging. Moreover, accelerated cell proliferation was found to be associated with cellular internalization of amine-surface-modified SPIO nanoparticles. The osteogenic and chondrogenic differentiation potentials of hMSCs were impaired after treating with SPIO, while adipogenic potential was relatively unaffected. Altered cytokine production profile in hMSCs caused by amine-surface-modified SPIO nanoparticles may account for the increased proliferation and impaired differentiation potentials; concentrations of the growth factors in the SPIO-labeled condition medium including amphiregulin, glial cell-derived neurotrophic factor, heparin-binding EGF-like growth factor and vascular endothelial growth factor, as well as soluble form of macrophage colony-stimulating factor receptor and SCF receptor, were higher than in the unlabeled-condition medium. In summary, although amine-surface-modified SPIO labeling is effective for cell tracking, properties of hMSCs may alter as a consequence and this needs to be taken into account when evaluating therapeutic efficacies of SPIO-labeled stem cells in vivo.

Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells.

BACKGROUND: Spinocerebellar ataxia (SCA) refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs) of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs) possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs) can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model. METHOD: Transgenic mice bearing poly-glutamine mutation in ataxin-2 gene (C57BL/6J SCA2 transgenic mice) were serially transplanted with hMSCs intravenously or intracranially before and after the onset of motor function loss. Motor function of mice was evaluated by an accelerating protocol of rotarod test every 8 weeks. Immunohistochemical stain of whole brain sections was adopted to demonstrate the neuroprotective effect of hMSC transplantation on cerebellar PCs and engraftment of hMSCs into mice brain. RESULTS: Intravenous transplantation of hMSCs effectively improved rotarod performance of SCA2 transgenic mice and delayed the onset of motor function deterioration; while intracranial transplantation failed to achieve such neuroprotective effect. Immunohistochemistry revealed that intravenous transplantation was more effective in the preservation of the survival of cerebellar PCs and engraftment of hMSCs than intracranial injection, which was compatible to rotarod performance of transplanted mice. CONCLUSION: Intravenous transplantation of hMSCs can indeed delay the onset as well as improve the motor function of SCA2 transgenic mice. The results of this preclinical study strongly support further exploration of the feasibility to transplant hMSCs for SCA patients.