Analyses of integrated EPID images for on-treatment quality assurance to account for interfractional variations in volumetric modulated arc therapy

Purpose: To investigate the effects of interfractional variation, such as anatomical changes and setup errors, on dose delivery during treatment for prostate cancer (PC) and head and neck cancer (HNC) by courses of volumetric modulated arc therapy (VMAT) aided by on‐treatment electronic portal imaging device (EPID) images. Methods: Seven patients with PC and 20 patients with HNC who had received VMAT participated in this study. After obtaining photon fluence at the position of the EPID for each treatment arc from on‐treatment integrated EPID images, we calculated the differences between the fluence for the first fraction and each subsequent fraction for each arc. The passing rates were investigated based on a tolerance level of 3% of the maximum fluence during the treatment courses and the correlations between the passing rates and anatomical changes. Results: In PC, the median and lowest passing rates were 99.8% and 95.2%, respectively. No correlations between passing rates and interfractional variation were found. In HNC, the median passing rate of all fractions was 93.0%, and the lowest passing rate was 79.6% during the 35th fraction. Spearman’s correlation coefficients between the passing rates and changes in weight or neck volume were − 0.77 and − 0.74, respectively. Conclusions: Analyses of the on‐treatment EPID images facilitates estimates of the interfractional anatomical variation in HNC patients during VMAT and thus improves assessments of the need for re‐planning or adaptive strategies and the timing thereof

Regulatory T Cells in Type 1 Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is a newly recognized pancreatic disorder. Recently, International Consensus Diagnostic Criteria for AIP (ICDC) was published. In this ICDC, AIP was classified into Type 1 and Type 2. Patients with Type 1 AIP have several immunologic and histologic abnormalities specific to the disease, including increased levels of serum IgG4 and storiform fibrosis with infiltration of lymphocytes and IgG4-positive plasmacytes in the involved organs. Among the involved organs showing extrapancreatic lesions, the bile duct is the most common, exhibiting sclerosing cholangitis (IgG4-SC). However, the role of IgG4 is unclear. Recently, it has been reported that regulatory T cells (Tregs) are involved in both the development of various autoimmune diseases and the shift of B cells toward IgG4, producing plasmacytes. Our study showed that Tregs were increased in the pancreas with Type 1 AIP and IgG4-SC compared with control. In the patients with Type 1 AIP and IgG4-SC, the numbers of infiltrated Tregs were significantly positively correlated with IgG4-positive plasma cells. In Type 1 AIP, inducible costimulatory molecule (ICOS)+ and IL-10+ Tregs significantly increased compared with control groups. Our data suggest that increased quantities of ICOS+ Tregs may influence IgG4 production via IL-10 in Type 1 AIP

Examination of MARCO activity on dendritic cell phenotype and function using a gene knockout mouse.

We have reported the upregulation of MARCO, a member of the class A scavenger receptor family, on the surface of murine and human dendritic cells (DCs) pulsed with tumor lysates. Exposure of murine tumor lysate-pulsed DCs to an anti-MARCO antibody led to loss of dendritic-like processes and enhanced migratory capacity. In this study, we have further examined the biological and therapeutic implications of MARCO expression by DCs. DCs generated from the bone marrow (bm) of MARCO knockout (MARCO⁻/⁻) mice were phenotypically similar to DCs generated from the bm of wild-type mice and produced normal levels of IL-12 and TNF-α when exposed to LPS. MARCO⁻/⁻ DCs demonstrated enhanced migratory capacity in response to CCL-21 in vitro. After subcutaneous injection into mice, MARCO⁻/⁻ TP-DCs migrated more efficiently to the draining lymph node leading to enhanced generation of tumor-specific IFN-γ producing T cells and improved tumor regression and survival in B16 melanoma-bearing mice. These results support targeting MARCO on the surface of DCs to improve trafficking and induction of anti-tumor immunity

Therapeutic strategy for acute appendicitis based on laparoscopic surgery

Abstract Purpose The treatment strategies for acute appendicitis differ depending on the facility, and various studies have investigated the usefulness of conservative treatment with antibiotics, laparoscopic surgery, and interval appendectomy (IA). However, although laparoscopic surgery is widely used, the clinical strategy for acute appendicitis, especially complicated cases, remains controversial. We assessed a laparoscopic surgery-based treatment strategy for all patients diagnosed with appendicitis, including those with complicated appendicitis (CA). Methods We retrospectively analysed patients with acute appendicitis treated in our institution between January 2013 and December 2021. Patients were classified into uncomplicated appendicitis (UA) and CA groups based on computed tomography (CT) findings on the first visit, and the treatment course was subsequently compared. Results Of 305 participants, 218 were diagnosed with UA and 87 with CA, with surgery performed in 159 cases. Laparoscopic surgery was attempted in 153 cases and had a completion rate of 94.8% (145/153). All open laparotomy transition cases (n = 8) were emergency CA surgery cases. No significant differences were found in the incidence of postoperative complications in successful emergency laparoscopic surgeries. In univariate and multivariate analyses for the conversion to open laparotomy in CA, only the number of days from onset to surgery ≥ 6 days was an independent risk factor (odds ratio: 11.80; P < 0.01). Conclusion Laparoscopic surgery is preferred in all appendicitis cases, including CA. Since laparoscopic surgery is difficult for CA when several days from the onset have passed, it is necessary that surgeons make an early decision on whether to operate

Synchronized Collapse and Formation of Long-Period Stacking and Chemical Orders in Mg85Zn6Y9\mathrm{Mg_{85}Zn_6Y_9}

Long period stacking ordered (LPSO) structures that are synchronized with the chemical order in Mg–TM (transition metal)–RE (rare earth) systems have received special attention as a new type of strengthening phase for Mg alloys. For example, the rapidly solidified powder metallurgy alloy $Mg_{97}Zn_{1}Y_{2}$ with an LPSO phase has a yield strength exceeding 600 MPa [1], while the cast $Mg_{97}Zn_{1}Y_{2}$ alloy with an LPSO phase produced using a hot extrusion process has a yield strength exceeding 350 MPa, which is sufficient for use in many components for airplanes and automobiles [2].The crystalline structures of the LPSO phases in Mg–TM–RE systems have been reported by many researchers [3], [4], [5] and [6], and four types of LPSO phases (10H, 14H, 18R, and 24R) have been reported. The hexagonal ABAB… stacking sequence is changed due to the incorporation of TM and RE concentrate layers. As a result, long period stacking orders are formed along the c axis. Accordingly, rhombohedral (R) and hexagonal (H) Bravais lattices occur, depending on the stacking period of the hcp stacking layer [6].Furthermore, based on scanning transmission and transmission electron microscopy (STEM and TEM, respectively) observations for Mg-Al-Gd alloy, the existence of in-plane ordering has been proposed by Yokobayashi et al. [7]. They found that $L1_{2}-type$ ordered clusters were regularly aligned in the segregated layer. Recently, Egusa et al. revised the crystalline structure models for the 18R- and 14H-type LPSOs of Mg–Zn–Y taking into consideration the in-plane order resulting from the alignment of the $L1_{2}-type$ cluster in the Zn–Y segregated layers [8]. Yamasaki et al. also proposed a 10H-type LPSO crystalline structure in a Mg–Zn–Y alloy [9]. Schematic diagrams of the stacking and in-plane ordering of the 18R-type LPSOs are shown in Fig. 1

D03\mathrm{D0_{3}}+hcp mixed phase with nanostructures in Mg85Zn6Y9\mathrm{Mg_{85}Zn_{6}Y_{9}} alloy obtained by high-pressure and high-temperature treatments

High pressure and high temperature state of long period stacking order structure (LPSO) synchronized with chemical concentration in Mg$_{85}$Zn$_{6}$Y$_{9}$ alloy have been investigated. A stripe-patterned nanostructure consisting of D0$_{3}$ and hcp phases is formed in Mg$_{85}$Zn$_{6}$Y$_{9}$ alloy by high pressure and high temperature treatments. The nanostripe patterns are created by the phase separation of LPSO synchronized with chemical concentration. A pressure–temperature phase diagram is given in this research. LPSO is stable below 673 K, the D0$_{3}$+hcp mixed phase dominant above 973 K under the pressure up to 20 GPa. Phase separation under high pressure is useful for the fabrication of nanostructured metallic materials

for patients with advanced biliary tract cancer

Background: The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and only a few standard treatments are available for this condition. We performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with three peptides derived from cancer-testis antigens. Methods: This study was conducted as a phase I trial. Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. Three HLA-A*2402 restricted epitope peptides-cell division cycle associated 1 (CDCA1), cadherin 3 (CDH3) and kinesin family member 20A (KIF20A)-were administered subcutaneously, and the adverse events and immune response were assessed. The clinical effects observed were the tumor response, progression-free survival (PFS) and overall survival (OS). Results: The three-peptide vaccination was well-tolerated up to a dose of 3 mg per peptide (9 mg total). No grade 3 or 4 adverse events were observed after vaccination. Peptide-specific T cell immune responses were observed in all patients and stable disease was observed in 5 of 9 patients. The median PFS and OS were 3.4 and 9.7 months. The Grade 2 injection site reaction and continuous vaccination after PD judgment appeared to be prognostic of OS. Conclusions: Multiple-peptide vaccination was well tolerated and induced peptide-specific T-cell responses