Initial Clinical Experience of a Novel Shapeable Bolus for Radiotherapy in a Patient With a Facial Cutaneous Squamous Cell Carcinoma: A Case Report.

Radiation therapy with X-rays for skin cancer uses a bolus to increase the surface dose. Commercial gel sheet boluses adhere poorly to the patient's body because of surface irregularities. This causes an air gap and reduces the surface dose. We have developed a novel shapeable bolus (HM bolus; Hayakawa Rubber Co., Ltd., Hiroshima, Japan), and we describe the first clinical application of this bolus here. The case was an 82-year-old male with a facial cutaneous squamous cell carcinoma. The postoperative radiotherapy plan using the HM bolus provided a more uniform dose to the target compared with a plan without the HM bolus. The HM bolus adhered stably to the patient's skin, and there were no issues with its clinical use.

[Profile of Generic Drugs Associated with the Discontinuation of the Supply].

A consistent and uninterrupted supply of pharmaceuticals is essential for optimal pharmacotherapy. However, some cases of supply disruptions and recalls have been reported. In particular, the withdrawal of some drugs from the market was occurred in recent year. Nevertheless, the characteristics of these drugs were unknown. The aim of this study was to analyze the ratio of generic drugs and the profile of generic drugs that have been withdrawn from the market. Data were collected from a drug information database for the period between April 2017 and March 2022 and analyzed for characteristics, such as price, number of suppliers, and reasons for withdrawal. The results showed a 1.4-fold increase in the number of drugs discontinued in 2021 compared with that in 2017, with 78.6% of the drugs discontinued being generic drugs. The proportion of discontinued generic drugs costing less than 10 yen (29.2%) was higher than those remaining on the market (15.0%). Additionally, the proportion of withdrawn generic drugs sold by four or more suppliers (67.6%) was higher than those that remained in the market (38.4%). In most cases (78.8%), the reasons for the discontinuation of these generic drugs were not disclosed. This study showed that most drugs withdrawn in Japan during the study period were generic drugs, characterized by low prices or many suppliers. Our study contributes to the understanding of the instability in the pharmaceutical supply chain in Japan.

Evaluation of In-room Volumetric Imaging Doses for Image-guided Radiotherapy: A Multi-institutional Study.

Aims: We investigated imaging dose and noise under clinical scan conditions at multiple institutions using a simple and unified method, and demonstrated the need for diagnostic reference levels in image-guided radiotherapy (IGRT). Materials and Methods: Nine cone-beam and helical computed tomography (CT) scanners (Varian, Elekta, Accuray Inc., and BrainLAB) from seven institutions were investigated in this study. The weighted cone-beam dose index (CBDIw) was calculated for head and pelvic protocols using a 100 mm pencil chamber under the conditions used in actual clinical practice at each institution. Cone-beam CT image noise was evaluated using polymethylmethacrylate head and body phantoms with diameters of 16 and 32 cm, respectively. Results: For head and pelvic protocols, CBDIw values ranged from 0.94-6.59 and 1.47-20.9 mGy, respectively. Similarly, standard deviation (SD) values ranged from 9.3-34.0 and 26.9-97.4 HU, respectively. The SD values tended to increase with decreasing imaging dose (r = -0.33 and -0.61 for the head and pelvic protocols, respectively). Conclusions: Among the nine machines, the imaging dose for high imaging dose institutions was approximately 20 mGy to the pelvic phantom, and there was a 14-fold difference in dose compared with the other institutions. These results suggest the need to establish DRLs for IGRT to guide clinical decision-making.

Management of Cervical Internal Carotid Artery Stenosis or Occlusion in Tandem Lesion with Acute Ischemic Stroke: Which Is More Appropriate Percutaneous Transluminal Angioplasty or Stent?

OBJECTIVE: Carotid artery stenting (CAS) is the established treatment strategy of the cervical internal carotid artery (cICA) stenosis, but its use for acute tandem lesions remains controversial. We investigated the clinical and procedural outcomes of management of cICA lesions and evaluated the risk factors for complications. METHODS: Fifty patients who underwent acute mechanical thrombectomy for tandem lesion between January 2014 and June 2022 were included. Treatment of the cICA lesion was classified into the CAS group or the non-CAS group. The risk factors for postoperative ischemic events or symptomatic intracranial hemorrhage (sICH) were analyzed. RESULTS: The CAS group included 36 patients (72%) and the non-CAS group 14 (28%). Postoperative complications were observed in 9 patients (18%). Thromboembolic complications occurred in 4 patients (29%) of the non-CAS group but in 1 patient (3%) of the CAS group. Severe calcification of the cICA (P = 0.04), non-CAS (P = 0.018), and more than 60% residual stenosis (P = 0.016) were significant risk factors associated with thromboembolic complications. sICH occurred in 4 patients (11%) of the CAS group but in none of the non-CAS group. More than 80% stenosis improvement was significantly associated with sICH (P = 0.049). Twenty-nine patients (58%) had a good clinical outcome at 90 days after onset. CONCLUSIONS: Acute CAS is effective for the management for cICA tandem lesions during mechanical thrombectomy, but care not to overextend may be important to reduce the risk of sICH. Severe calcification of the cICA may increase the risk of postoperative thromboembolic complications using non-CAS treatment.

Atherosclerotic carotid plaque characteristics vary with time from ischemic event: A multicenter, prospective magnetic resonance vessel wall imaging registry study.

Recent studies report that the rate of recurrent stroke is highest in the stages immediately following cerebral infarction and decreases over time in patients with atherosclerotic carotid stenosis. The purpose of this study was to identify temporal differences in early stage carotid plaque components from acute cerebrovascular ischemic events using carotid MRI. Carotid plaque images were obtained on 3 T MRI from 128 patients enrolled in MR-CAS. Among the 128 subjects, 53 were symptomatic and 75 asymptomatic. The symptomatic patients were classified into three groups based on interval from onset of symptoms to the date of the carotid MRI (Group <14 days; 15-30 days; and > 30 days). The volume of each plaque component was identified and quantified from MR images. The presence of juxtaluminal loose matrix/inflammation (LM/I) was identified as a possible indicator of inflammation on the luminal side. Plaque components were compared between groups using the Wilcoxon rank-sum or the Chi-square test. Patient characteristics and carotid plaque morphology were similar among all four groups. The median volume of LM/I in Group >30 days was significantly lower than in other groups (0 mm3 vs 12.3 mm3 and 18.1 mm3; p = 0.003). In addition, the prevalence of juxtaluminal LM/I decreased over time (ptrend = 0.002). There were no statistically significant differences in other plaque components between the symptomatic groups. The volume of LM/I was significantly smaller in Group >30 days and prevalence of juxtaluminal LM/I in the atherosclerotic carotid plaque was high in the early stages after events. This suggests that carotid plaques undergo rapid evolution after an acute cerebrovascular ischemic event.

A novel real-time shapeable soft rubber bolus for clinical use in electron radiotherapy.

We have developed soft rubber (SR) bolus that can be shaped in real-time by heating flexibly and repeatedly. This study investigated whether the SR bolus could be used as an ideal bolus, such as not changing of the beam characteristics and homogeneity through the bolus and high plasticity to adhere a patient in addition to real-time shapeable and reusability, in electron radiotherapy. Percentage depth doses (PDDs) and lateral dose profiles (LDPs) were obtained for 4, 6, and 9 MeV electron beams and were compared between the SR and conventional gel boluses. For the LDP at depth of 90% dose, the penumbra as lateral distance between the 80% and 20% isodose lines (P80-20) and the width of 90% dose level (r90) were compared. To evaluate adhesion, the air gap volume between the boluses and nose of a head phantom was evaluated on CT image. The dose profiles along the center axis for the 6 MeV electron beam with SR, gel, and virtual boluses (thickness = 5 mm) on the head phantom were also calculated for the irradiation of 200 monitor unit with a treatment planning system and the depth of the maximum dose (dmax) and maximum dose (Dmax) were compared. The PDDs,P80-20, andr90between the SR and gel boluses corresponded well (within 2%, 0.4 mm, and 0.7 mm, respectively). The air gap volumes of the SR and gel boluses were 3.14 and 50.35 cm3, respectively. Thedmaxwith SR, gel and virtual boluses were 8.0, 6.0, and 7.0 mm (no bolus: 12.0 mm), and theDmaxvalues were 186.4, 170.6, and 186.8 cGy, respectively. The SR bolus had the equivalent electron beam characteristics and homogeneity to the gel bolus and achieved excellent adhesion to a body surface, which can be used in electron radiotherapy as an ideal bolus.

[Standardization of Hypnotic Agents for Prevention of Falls: A Pharmacoeconomic Study].

To reduce the number of falls caused by hypnotic agents, the standardization of insomnia treatment was carried out at Yamaguchi University Hospital from April 2019. There were concerns that medical costs would increase due to the selected medicines-suvorexant and eszopiclone-being more expensive than conventional benzodiazepines. In this study, the standardization of insomnia treatment was evaluated by pharmacoeconomics. The costs of the hypnotic agents was considered, as was the cost of examination/treatment following falls. Effectiveness was evaluated as the incidence of falls within 24 hours of taking hypnotic agents. This analysis took the public healthcare payer's perspective. Propensity score matching based on patient background, showed that, per hospitalization the medicine costs of the recommended group increased by 1,020 yen, however, the examination/treatment costs following falls decreased by 487 yen when compared with the non-recommended group. Overall, the recommended group incurred costs of 533 yen more per hospitalization for patients prescribed hypnotic agents compared to the non-recommended group, but the incidence of falls for the recommended group was significantly lower than that in the non-recommended group (1.9% vs. 6.3%; p<0.01). These results suggest that in order to prevent the incidence of falls by 1 case, it is necessary to increase costs by 12,086 yen which is the subthreshold cost for switching to the recommended medicine as standardization. The selection of recommended medicines may be a cost-effectiveness option compared with non-recommended medicines.

Dosimetric evaluation of skin collimation with tungsten rubber for electron radiotherapy: A Monte Carlo study.

PURPOSE: Skin collimation provides a sharp penumbra for electron beams, while the effect of bremsstrahlung from shielding materials is a concern. This phantom study was conducted to evaluate the safety and efficacy of a real-time variable shape rubber containing-tungsten (STR) that can be placed on a patient's skin. METHODS: Electron beam profiles were acquired with the STR placed on a water-equivalent phantom and low melting-point alloy (LMA) placed at the applicator according to commonly used procedures (field sizes: 20- and 40-mm diameters). Depth and lateral dose profiles for 6- and 12-MeV electron beams were obtained by Monte Carlo (MC) simulations and were benchmarked against film measurements. The width of the off-axis distance between 80% and 20% doses (P80-20 ) and the maximum dose were obtained from the lateral dose profiles. Bremsstrahlung emission was analyzed by MC simulations at the depth of maximum dose (R100 ). RESULTS: The depth dose profiles calculated by the MC simulations were consistently within 2% of the measurements. The P80-20 at R100 for 20- and 40-mm diameters were 4.0 mm vs. 7.6 mm (STR vs. LMA) and 4.5 mm vs. 9.2 mm, respectively, for the 6-MeV electron beam with 7.0-mm-thick STR, and 2.7 mm vs. 5.6 mm and 4.5 mm vs. 7.1 mm, respectively, for the 12-MeV electron beam with 12.0-mm-thick STR. A hotspot was not observed on the lateral dose profiles obtained with the STR at R100 . The bremsstrahlung emission under the region shielded by the STR was comparable to that obtained with the LMA, even though the STR was placed on the surface of the phantom. CONCLUSIONS: Skin collimator with STR provided superior dosimetric characteristics and comparable bremsstrahlung emission to LMA collimator at the applicator. STR could be a new tool for the safe and efficient delivery of electron radiotherapy.

Deconstructive Endovascular Treatment of Ruptured Serpentine Basilar Artery Aneurysm by Mid-Basilar Occlusion.

BACKGROUND: No clear treatment course for cerebral aneurysms in the main trunk of the basilar artery (BA) has been established thus far. CASE DESCRIPTION: A 69-year-old man with a history of hypertension presented to the emergency department with a sudden headache followed by decreased consciousness. Head computed tomography revealed a subarachnoid hemorrhage from the front of the brain stem to the basal cistern, and a lump-like dilation localized in the main trunk of the BA in the front of the midbrain. A rotated 360° large cerebral serpentine aneurysm was observed from the upper BA to the proximal part of the superior cerebellar artery. Endovascular treatment was performed under general anesthesia. To avoid a perforator infarction, short-segment parent artery embolization was performed only at the rupture point and the proximal part of the aneurysm. A magnetic resonance imaging scan 1 day after surgery revealed only microinfarction in the pons just below the embolus. The patient developed mild left hemiparesis postoperatively but soon improved and was discharged from the hospital. CONCLUSIONS: Parent vessel sacrifice carries a risk of perforator injury due to extension of thrombosis from the blind pouch into eloquent perforator vessels. Minimizing this risk requires careful evaluation of anatomy and strategic occlusion, which preserves runoff into relatively large vessels, such as the superior cerebellar artery, the anterior inferior cerebellar artery, or the penetrating branch from the blind pouch, as much as possible.

[Dosimetric Characteristics of a Real Time Shapeable Tungsten Containing Rubber with Electron Beams].

PURPOSE: This study investigated the dosimetric characteristics of electron beams shaped with a real-time shapeable tungsten-containing rubber (STR) collimator. METHODS: Circular irradiation fields of 40 mm diameter were shaped using STR or low melting-point alloy (LMA) placed on the electron applicator. The STR heated with approximately 70-degree warm water was molded into the template bottom of the applicator. Percent depth doses (PDDs) and lateral dose profiles of 6 and 12 MeV electron beams were measured and compared between STR and LMA. For the PDDs, the depths of maximum dose (dmax), 90% dose (d90), and 80% dose (d80) were evaluated. For the lateral dose profiles, penumbra as the width of the off-axis distance from 80% to 20% doses and treatment diameter covering over 90% dose were evaluated at the surface, dmax, d90, and d80. The transmission of the STR was also investigated at thicknesses fit to electron applicator for 6 and 12 MeV electron beams. RESULTS: The STR was softened with 70-degree warm water. Therefore, it was easy to mold it and attach the applicator. The PDDs and penumbras at the surface, dmax, d90, and d80 for the STR were almost equal to those for the LMA with 6 and 12 MeV electron beams. The treatment diameters covering over 90% dose for the irradiation fields with 40 mm diameter at dmax (LMA vs. STR) were 20.9 vs. 21.1 mm and 19.2 vs. 18.4 mm for 6 and 12 MeV electron beams, respectively. The transmission of the STR was almost same as that of LMA. CONCLUSIONS: The dosimetric characteristics of the STR on the electron applicator were almost same as those of the LMA. The heated STR was shaped easily, flexibly, and immediately. The STR can be used as a substitute for LMA in electron radiotherapy.

Estimation of radiation shielding ability in electron therapy and brachytherapy with real time variable shape tungsten rubber.

PURPOSE: To clarify the physical characteristics of a newly developed real time variable shape rubber containing tungsten (STR) with changes in heat and estimate its shielding abilities against electron beams and γ-rays from 192Ir. METHODS: Dynamic mechanical analysis for the STR (density = 7.3 g/cm3) was conducted at a frequency of 1.0 Hz in the temperature range of -60 °C to 60 °C. We evaluated tanδ, defined as the ratio (E″/E') between the storage modulus (E') and loss modulus (E″). The transmission rates were measured against 6- and 12-MeV electron beams and the percentage depth dose and lateral dose profile were compared with low-melting alloy (LMA). For the shielding rate of 192Ir against γ-rays, measurement data and Monte Carlo simulation data were obtained with STR thickness ranging from 1.0 mm to 16.0 mm. RESULTS: At 36 °C, the tanδ value was 0.520, while at 60 °C, this value was 1.016. For 6- and 12-MeV electron beams, the transmission rates decreased with increasing STR thickness and reached plateaus at approximately 1.0% and 4.0% with STR thickness of >7.0 and >12.0 mm, respectively. The dose distributions were almost equal to those for LMA. Against γ-rays, the thickness of STR that obtained a 50% attenuation rate for 192Ir was 5.804 mm. The Monte Carlo calculation results were 2.6% higher on average than the measurement results. CONCLUSION: The STR can be changed shape in real time at 60 °C and maintains its shape at body temperatures. It has adequate shielding abilities against megavoltage electron beams and γ-rays from 192Ir.

Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report.

Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT)/calcium folinate (leucovorin, LV) was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX) were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy.

Catalyst self-adaptation in conjugate addition to nitroalkenes and nitroacrylates: instant chirality control in diphenylmethane-based phosphoramidite ligands.

The tropos diphenylmethane-based phosphoramidite ligand (A) provides high catalytic activity and enantioselectivity in the Cu catalysis of conjugate addition to nitroalkenes and nitroacrylate, by virtue of instant chirality control in A.

Achiral benzophenone ligand-rhodium complex with chiral diamine activator for high enantiocontrol in asymmetric transfer hydrogenation.

The chirality of an achiral benzophenone-based rhodium complex can be controlled by chiral diamines to afford significantly high enantioselectivity in the catalytic asymmetric transfer hydrogenation of ketones (up to 99% ee, 99% yield).

"Achiral" benzophenone ligand for highly enantioselective Ru catalysts in ketone hydrogenation.

[reaction: see text] The chirality of an "achiral" benzophenone-based complex can be controlled. The benzophenone-based complex thus controlled affords high enantioselectivity in the catalytic asymmetric ketone hydrogenation (up to 99% ee, >99% yield).

Highly enantioselective spiro cyclization of 1,6-enynes catalyzed by cationic skewphos rhodium(I) complex.

A cationic rhodium(I) complex having a skewphos ligand is shown to be a highly enantioselective catalyst for asymmetric carbocyclization of 1,6-enynes with tri-substituted olefins to control quaternary stereogenic centers of spiro-rings.