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IntroductionGastric cancer poses a major therapeutic challenge. Improved visualization of tumor margins at the time of gastrectomy with fluorescent tumor-specific antibodies could improve outcomes. The present report demonstrates the potential of targeting gastric cancer with a humanized anti-carcinoembryonic antigen (CEA) antibody in orthotopic mouse models.MethodsMKN45 cells were injected subcutaneously into nude mice to establish xenograft models. Tumor fragments collected from subcutaneous models were then implanted into the greater curvature of the stomach to establish orthotopic models. For tumor labeling, a humanized anti-CEA antibody (M5A) and IgG as a control, were conjugated with the near-infrared dye IRDye800CW. Time (24-72 h) and dose (50-100 μg) response curves were performed in subcutaneous models. Orthotopic models received 50 μg of M5A-IR800 or 50 μg IgG-IR800 as a control and were imaged after 72 h. Fluorescence imaging was performed on the mice using the LI-COR Pearl Imaging System.ResultsIn subcutaneous models, tumor to background ratios (TBRs) reached 8.85 at 72 h. Median TBRs of orthotopic model primary tumors were 6.25 (interquartile range [IQR] 6.03-7.12) for M5A-IR800 compared to 0.42 (IQR 0.38-0.54) for control. Abdominal wall metastasis median TBRs were 13.52 (IQR 12.79-13.76) for M5A-IR800 and 3.19 (IQR 2.65-3.73) for the control. Immunohistochemistry confirmed CEA expression within tumors.ConclusionsHumanized anti-CEA antibodies conjugated to near-infrared dyes provide specific labeling of gastric cancers in mouse models. Orthotopic models demonstrated bright and specific labeling with TBRs greater than ten times that of control. This tumor-specific fluorescent antibody is a promising potential clinical tool for improving visualization of gastric cancer margins at time of surgical resection.

PURPOSE: Cervical cancer is a recalcitrant disease. To help overcome this problem, we previously established a patient-derived orthotopic xenograft (PDOX) model of cervical cancer. In the previous study, we found the tumor to be resistant to nab-paclitaxal (nab-PTX). We also previously developed the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R). The aim of the present study was to investigate the efficacy of S. typhimurium A1-R to overcome nab-PTX resistance in the cervical cancer PDOX model. METHODS: Cervical-cancer tumor fragments were implanted orthotopically into the neck of the uterus of nude mice. The cervical-cancer PDOX models were randomized into the following four groups after the tumor volume reached 60 mm3: G1: untreated group; G2: nab-PTX (i.v., 10 mg/kg, biweekly, 3 weeks); G3: Salmonella typhimurium A1-R (i.v., 5 × 107 CFU/body, weekly, 3 weeks); G4: nab-PTX combined with Salmonella typhimurium A1-R (nab-PTX, 10 mg/kg, i.v., biweekly, 3 weeks; S. typhimurium A1-R, 5 × 107 CFU/body, i.v., weekly, 3 weeks). Each group comprised eight mice. All mice were sacrificed on day 22. Tumor volume was measured on day 0 and day 22. Body weight was measured twice a week. RESULTS: Nab-PTX and Salmonella typhimurium A1-R did not show significant efficacy as monotherapy compared to the control group (P = 0.564 and P = 0.120, respectively). In contrast, nab-PTX combined with Salmonella typhimurium A1-R significantly suppressed tumor growth compared to the untreated control group and nab-PTX group (P

Objectives: This study investigated the incidence of lymph node metastasis and long‐term outcomes in patients with T1 colorectal cancer where endoscopic submucosal dissection (ESD) resulted in noncurative treatment. It is focused on those with deep submucosal invasion, a factor considered a weak predictor of lymph node metastasis in the absence of other risk factors. Methods: This nationwide, multicenter, prospective study conducted a post‐hoc analysis of 141 patients with T1 colorectal cancer ≥20 mm where ESD of the lesion resulted in noncurative outcomes, characterized by poor differentiation, deep submucosal invasion (≥1000 μm), lymphovascular invasion, high‐grade tumor budding, or positive vertical margins. Clinicopathologic features and patient prognoses focusing on lesion sites and additional surgery requirements were evaluated. Lymph node metastasis incidence in the low‐risk T1 group, identified by deep submucosal invasion as the sole high‐risk histological feature, was assessed. Results: Lymph node metastasis occurred in 14% of patients undergoing additional surgery post‐noncurative endoscopic submucosal dissection for T1 colorectal cancer. In the low‐risk T1 group, in the absence of other risk factors, the frequency was 9.7%. The lymph node metastasis rates in patients with T1 colon and rectal cancers did not differ significantly (14% vs. 16%). Distant recurrence was observed in one patient (2.3%) in the ESD only group and in one (1.0%) in the additional surgery group, both of whom had had rectal cancer removed. Conclusion: The risk of lymph node metastasis or distant occurrence was not negligible, even in the low‐risk T1 group. The findings suggest the need for considering additional surgery, particularly for rectal lesions (Clinical Trial Registration: UMIN000010136). [ABSTRACT FROM AUTHOR]

Background Few prospective investigations have compared direct and indirect techniques through comprehensive and detailed clinical evaluations, considering the impact of all factors. Objectives This study aimed to compare and evaluate direct and indirect bonding methods at a single institution and to clarify the selection criteria for the bonding method. Materials and methods This single-centre, quasi-randomized controlled clinical trial included 153 patients who required fixed orthodontic treatment. They were randomly divided into indirect and direct binding groups by the project lead (K.K.), who was blinded to all clinical data, and performed the allocation using medical record numbers. The chair time for bracket bonding, discomfort during bracket bonding, oral hygiene after bonding, number of bracket failures, number of intentional bracket reattachments, post-treatment occlusal index, and total treatment time were assessed. Outcomes were compared using a two-sample t -test or Mann–Whitney U test (P  < .05). Results Fifty-eight patients were included in the indirect bonding group (20 male, 38 female; mean age: 20.63 ± 5.69 years) and 66 (14 male, 52 female; mean age: 23.17 ± 8.83 years) in the direct bonding group. Compared to the direct bonding group, the indirect bonding group had shorter chair time (P  < .001), a shorter total treatment period (P  < .01), and a better final occlusal relationship (P  < .001). The number of bracket detachments was higher (P  < .001) in the indirect bonding group, but the number of intentional reattachments was lower (P  < .001). Conclusion Indirect bonding may improve the efficiency of orthodontic treatment. Harms No harm was observed during the study. Trial registration number This trial was approved by the Ethics Review Committee of Okayama University (approval number: d10001), UMIN registration number 000022182. [ABSTRACT FROM AUTHOR]

Objective: Placental abruption is associated with adverse perinatal outcomes including intrauterine fetal demise, which subsequently results in stillbirth. However, few studies have demonstrated the preventability of stillbirth due to placental abruption. Therefore, we evaluated the possibility of preventing stillbirth caused by placental abruption by reviewing all stillbirths in our region. Methods: This study reviewed all stillbirths after 22 weeks of gestation in Shiga Prefecture, Japan from 2010 to 2019, excluding lethal disorders. We evaluated 350 stillbirth cases, with and without placental abruption. Results: There were 32 stillbirths with PA and 318 without placental abruption. The probability of preventing stillbirth was significantly higher in patients with placental abruption than in those without (30% vs. 8%, p < 0.001). We also determined the recommendations for preventing stillbirths with placental abruption. Conclusion: Some stillbirths caused by placental abruption can be prevented. We recommend improvements to perinatal maternal-fetal care and perinatal emergency transport systems. [ABSTRACT FROM AUTHOR]

Aims: Ulcerative colitis‐associated neoplasia (UCAN) is characterised by multifocal tumourigenesis. A wide range of metachronous lesions have been reported to occur after endoscopic treatment of UCAN, which suggests the development of sporadic tumours in lesions treated as UCAN. Therefore, we aimed to evaluate differences of immunohistochemistry (IHC) in features and clinicopathological characteristics of intramucosal lesions in patients with ulcerative colitis (UC). Methods and results: We examined 35 intramucosal lesions resected for carcinoma or dysplasia by total colectomy from patients with UC and 71 sporadic adenomas (SAs) endoscopically resected from patients without UC. UC lesions were divided into the conventional UCAN group, defined as p53 mutant pattern and normal expression of β‐catenin, and the non‐conventional UCAN group, defined as the rest. Ki‐67 distribution, α‐methylacyl‐CoA racemase (AMACR) expression and mucin phenotypes were compared using IHC, and clinicopathological characteristics were investigated. Conventional and non‐conventional UCAN lesions were located in the left colon and rectum. Relative to the SA lesions, UCAN lesions occurred in much younger patients and exhibited more frequent basal distribution of Ki‐67 in tumour crypts. Conventional UCAN lesions tended to be non‐polyploid and exhibited a higher frequency of normal AMACR expression than SA lesions. UC lesions were heterogeneous—only two of the eight patients with multiple lesions had lesions (both non‐conventional UCAN lesions) exhibiting concordant IHC staining features. Conclusions: The basal pattern of Ki‐67 distribution, normal expression of AMACR and a non‐intestinal mucin phenotype were determined as characteristic features suggestive of UCAN. Non‐polypoid growth was another a key feature of UCAN. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly lethal disease in part due to incomplete tumor resection. Targeting by tumor-specific antibodies conjugated with a fluorescent label can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we describe a patient-derived orthotopic xenograft model of pancreatic cancer that recapitulated the disease on a gross and microscopic level, along with physiologic clinical manifestations. We additionally show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively highlight the pancreatic cancer and its metastases in this model with a tumor-to-background ratio of 3.5 (SEM 0.9). The present results demonstrate the clinical potential of this labeling technique for fluorescence-guided surgery of pancreatic cancer.

BackgroundPleomorphic liposarcoma (PLPS) is a rare, heterogeneous and an aggressive variant of liposarcoma. Therefore, individualized therapy is urgently needed. Our recent reports suggest that trabectedin (TRAB) is effective against several patient-derived orthotopic xenograft (PDOX) mouse models. Here, we compared the efficacy of first-line therapy, doxorubicin (DOX), and TRAB in a platelet-derived growth factor receptor-α (PDGFRA)-amplified PLPS.MethodsWe used a fresh sample of PLPS tumor derived from a 68-year-old male patient diagnosed with a recurrent PLPS. Subcutaneous implantation of tumor tissue was performed in a nude mouse. After three weeks of implantation, tumor tissues were isolated and cut into small pieces. To match the patient a PDGFRA-amplified PLPS PDOX was created in the biceps femoris of nude mice. Mice were randomized into three groups: Group 1 (G1), control (untreated); Group 2 (G2), DOX-treated; Group 3 (G3), TRAB-treated. Measurement was done twice a week for tumor width, length, and mouse body weight.ResultsThe PLPS PDOX showed resistance towards DOX. However, TRAB could arrest the PLPS (p