Charted-particle therapy (CPT) benefits cancer patients by localizing doses in the tumor volume while minimizing the doses delivered to normal tissue through its unique physical and biological characteristics. The world’s first CPT applied on humans was proton beam therapy (PBT), which was performed in the mid-1950s. Among heavy ions, carbon ions showed the most favorable biological characteristics for the treatment of cancer patients. Carbon ions show coincidence between the Bragg peak and maximum value of relative biological effectiveness. In addition, they show low oxygen enhancement ratios. Therefore, carbon-ion radiotherapy (CIRT) has become mainstream in the treatment of cancer patients using heavy ions. CIRT was first performed in 1977 at the Lawrence Berkeley Laboratory. The CPT technology has advanced in the intervening decades, enabling the use of rotating gantry, beam delivery with fast pencil-beam scanning, image-guided particle therapy, and intensity-modulated particle therapy. As a result, as of 2019, a total of 222,425 and 34,138 patients with cancer had been treated globally with PBT and CIRT, respectively. For more effective and efficient CPT, many groups are currently conducting further studies worldwide. This review summarizes recent technological advances that facilitate clinical use of CPT.

Charted-particle therapy (CPT) benefits cancer patients by localizing doses in the tumor volume while minimizing the doses delivered to normal tissue through its unique physical and biological characteristics. The world’s first CPT applied on humans was proton beam therapy (PBT), which was performed in the mid-1950s. Among heavy ions, carbon ions showed the most favorable biological characteristics for the treatment of cancer patients. Carbon ions show coincidence between the Bragg peak and maximum value of relative biological effectiveness. In addition, they show low oxygen enhancement ratios. Therefore, carbon-ion radiotherapy (CIRT) has become mainstream in the treatment of cancer patients using heavy ions. CIRT was first performed in 1977 at the Lawrence Berkeley Laboratory. The CPT technology has advanced in the intervening decades, enabling the use of rotating gantry, beam delivery with fast pencil-beam scanning, image-guided particle therapy, and intensity-modulated particle therapy. As a result, as of 2019, a total of 222,425 and 34,138 patients with cancer had been treated globally with PBT and CIRT, respectively. For more effective and efficient CPT, many groups are currently conducting further studies worldwide. This review summarizes recent technological advances that facilitate clinical use of CPT.

We investigated the use of Polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) composites with applied mechanical stimulation as scaffold for bone tissue engineering. PCL-based three-dimensional (3D) structures were fabricated in a solvent-free process using a 3D-printing technique. The mass fraction of β-TCP was varied in the range 0–30%, and the structure and compressive modulus of the specimens was characterized. The shape and interconnectivity of the pores was found to be satisfactory, and the compressive modulus of the specimens was comparable with that of human trabecular bone. Human mesenchymal stem cells were seeded on the composites, and various biological evaluations were performed over 9 days. With a mass fraction of β-TCP of 30%, differentiation began earlier; however, the cell proliferation rate was lower. Through the use of mechanical stimulation, however, the proliferation rate recovered, and was comparable with that of the other groups. This stimulation effect was also observed in ECM generation and other biological assays. With mechanical stimulation, expression of osteogenic markers was lower on samples with a β-TCP content of 10 wt% than without β-TCP; however, with mechanical stimulation, the sample with a β-TCP content of 30 wt% exhibited significantly greater expression of those markers than the other samples. We found that mechanical stimulation and the addition of β-TCP interacted closely, and that a mass fraction of β-TCP of 30% was particularly useful as a bone tissue scaffold when accompanied by mechanical stimulation.
Biological Assay ; Bone and Bones ; Cell Proliferation ; Humans ; Mesenchymal Stromal Cells

PURPOSE: This study aimed to investigate the incidence and risk factors of early postoperative small bowel obstruction (EPSBO) after laparotomy for trauma patients. METHODS: From 2009 to 2016, consecutive patients who had undergone laparotomy for trauma were retrospectively evaluated. EPSBO was defined as the presence of signs and symptoms of obstruction between postoperative days 7 and 30, or obstruction occurring anytime within 30 days and lasting more 7 days. RESULTS: Among 297 patients who met the inclusion criteria, 72 (24.2%) developed EPSBO. The length of hospital stay was significantly longer in patients with EPSBO than in those without EPSBO (median [interquartile range], 34 [21–48] days 24 [14–38] days, P < 0.001). Multivariate logistic analysis identified male sex (adjusted odds ratio [AOR], 3.026; P = 0.008), intraoperative crystalloid (AOR, 1.130; P = 0.031), and Abbreviated Injury Scale (AIS) score for mesenteric injury (AOR, 1.397; P < 0.001) as independent risk factors for EPSBO. The incidence of adhesive small bowel adhesion after 30 days postoperatively did not significantly differ between the 2 groups (with EPSBO, 5.6% without EPSBO, 5.3%; P = 0.571). Most of the patients with EPSBO were recovered by conservative treatment (95.8%). CONCLUSION: After laparotomy for trauma patients, the incidence of EPSBO was 24.2% in our study. EPSBO was associated with a longer hospital stay. Male sex, use of intraoperative crystalloid, and AIS score for mesenteric injury were significant independent risk factors for EPSBO. Patients with these risk factors should be followed-up more carefully.
Abbreviated Injury Scale ; Abdominal Injuries ; Adhesives ; Humans ; Ileus ; Incidence ; Laparotomy ; Length of Stay ; Male ; Odds Ratio ; Retrospective Studies ; Risk Factors

In this study, we examined the morphine-induced modulation of the nociceptive spinal dorsal horn neuronal activities before and after formalin-induced inflammatory pain. Intradermal injection of formalin induced time-dependent changes in the spontaneous activity of nociceptive dorsal horn neurons. In naive cats before the injection of formalin, iontophoretically applied morphine attenuated the naturally and electrically evoked neuronal responses of dorsal horn neurons. However, neuronal responses after the formalin-induced inflammation were significantly increased by morphine. Bicuculline, GABAA antagonist, increased the naturally and electrically evoked neuronal responses of dorsal horn neurons. This increase in neuronal responses due to bicuculline after the formalin-induced inflammation was larger than that in the naive state, suggesting that basal GABAA tone increased after the formalin injection. Muscimol, GABAA agonist, reduced the neuronal responses before the treatment with formalin, but not after formalin treatment, again indicating an increase in the GABAergic basal tone after the formalin injection which saturated the neuronal responses to GABA agonist. Morphine-induced increase in the spinal nociceptive responses after formalin treatment was inhibited by co-application of muscimol. These data suggest that formalin-induced inflammation increases GABAA basal tone and the inhibition of this augmented GABAA basal tone by morphine results in a paradoxical morphine- induced increase in the spinal nociceptive neuronal responses after the formalin-induced inflammation.
Animals ; Bicuculline ; Cats ; Formaldehyde ; GABA Agonists ; Inflammation ; Injections, Intradermal ; Morphine ; Muscimol ; Neurons ; Nociceptors ; Posterior Horn Cells* ; Spinal Cord

The frontal sinus is one of the four paranasal sinuses in humans, and knowledge of its anatomy is important when performing surgery involving the frontal bone or sinus. Although many studies have measured the frontal sinus using radiography and computed tomography (CT), few studies have evaluated by using three-dimensional (3D) analysis. The purpose of this study was to analyze the frontal sinus using 3D reconstruction analysis and determine the differences in linear and volumetric measurements between sexes, sides, and ages. The sample comprised 281 facial CT scans: 173 and 108 from males and females, respectively. The width, height, and length of each frontal sinus and total volume were all larger in males than in females. Almost all linear and volumetric measurements were larger in young adults than in older for both sexes, but not all of the differences were statistically significant. Linear and volumetric measurements were larger for males than females regardless of age group. There were no statistically significant differences between the right and left sides except the width in males. The size of the frontal sinus was strongly influenced by sex and age. The measurements reported here might be useful for improving surgical procedures involving the frontal sinus.

Frankfort horizontal line, the line passing through the orbitale and porion, is one of the most widely used intracranial landmarks in cephalometric analysis. This study investigated the use of the orbito-occipital line extending from the orbitale to the external occipital protuberance as a novel horizontal line of the skull for substituting the Frankfort horizontal line. We evaluated the reproducibility of the new landmark and measured the angle between the orbito-occipital line and the Frankfort line. This study was conducted on 170 facial computed tomography (CT) scans of living adults from the Department of Plastic Surgery. After three-dimensionally reconstructed images were obtained from facial CT, the porion, orbitale, and external occipital protuberance were indicated by two observers twice. The angles between the orbito-meatal line (inferior orbital rim to porion; the Frankfort line) and the orbito-occipital line (inferior orbital rim to external occipital protuberance) were measured. There was no significant intraobserver or interobserver bias. The overall angle between the Frankfort line and orbito-occipital line was –0.5°±2.2° (mean±standard deviation). There was no statistically significant difference among side and sex. This study demonstrated good reproducibility of a new landmark—the external occipital protuberance—tested to replace the porion. The orbito-occipital line is a reliable, reproducible, and easily identifiable line, and has potential as a novel standard horizontal line to replace or at least supplement the Frankfort line in anthropological studies and certain clinical applications.

Objectives: . Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. Methods: . We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. Results: . Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. Conclusion . Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the “2019 Seoul Consensus on Esophageal Achalasia Guidelines”) were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.

The authors report below a clinical study of 23 patients bearing 31 primary central nervous system lymphomas diagnosed between January 1985 and December 1994. The cohort included 13 men and 10 women whose mean age was 46 years, ranging from 28 to 61 years. No patient had antecedent of human immunodeficiency virus positivity but one had a past history of rheumatoid arthritis. The duration of symptom was less than 8 weeks in 52% of the patients. Symptom groups included increased intracranial pressure(78%), focal neurological decificit(52%), neuropsychiatric symptoms(43%), and seizures(13%). The histopathologcal diagnosies were done in 19 cases(10 cases by resective surgery, 9 cases by open or stereotactic biopsy). The others were diagnosed by the typical clinical course such as rapid disappearance of lesions after steroid therapy, and/or radiological findings. Histological subtypes(National Cancer Institute Working Formulation) was confirmed in 8 patients including 3 cases of diffuse larger cell type. Phenotype was determined in 7 patients: 4 were B-cell type and 3 were T-cell type. One patient committed suicide during the radiation therapy and was therefore excluded from the survival analysis. All but two patients received radiation therapy. Five patients received chemotherapy. The over-all Kaplan-Meier survival rate was 46% at 2 years and 15.5% at 5 years. On univariate analysis, statistically significant prognostic factor associated with survival was not found but the higher Karnofsky score and single lesion were found to be favorable to the long-term survival. In the statistical analysis of the patients who received radiation therapy, surgical resection did not significantly influence the survival.
Arthritis, Rheumatoid ; B-Lymphocytes ; Brain Neoplasms ; Central Nervous System* ; Cohort Studies ; Drug Therapy ; Female ; HIV ; Humans ; Lymphoma ; Male ; Phenotype ; Suicide ; Survival Rate ; T-Lymphocytes