Assistant-Based Standardization of Prone Position Thoracoscopic Esophagectomy

Thoracoscopic esophagectomy in the prone position (TEPP) might enable solo-surgery in cases requiring resection of the esophagus and the surrounding lymph nodes due to the associated advantages of good exposure of the surgical field and ergonomic considerations for the surgeon. However, no one approach can be for all patients requiring extensive lymphadenectomy. We recently developed an assistant-based procedure to standardize exposure of the surgical field. Patients were divided into 1 of 2 groups:a pre-standardization group (n＝37) and a post-standardization group (n＝28). The thoracoscopic operative time was significantly shorter (p＝0.0037) in the post-standardization group (n＝28; 267±31min) than in the pre-standardization group (n＝37;301±53min). Further, learning curve analysis using the moving average method showed stabilization of the thoracoscopic operative time after the standardization. No significant differences were found in the number of mediastinal lymph nodes dissected or intraoperative blood loss between the 2 groups. There were also no significant differences in the complication rate. Assistant-based surgery and standardization of the procedure resulted in a well-exposed and safe surgical field. TEPP decreased the operative time, even in patients requiring extensive lymphadenectomy

Successfully Treated Pneumatosis Cystoides Intestinalis with Pneumoperitoneum Onset in a Patient Administered α-glucosidase Inhibitor

An 80-year-old woman, who had been administered α-glucosidase inhibitor for diabetes, was brought to the hospital with the sensation of abdominal fullness and pain. Abdominal computed tomography indicated pneumatosis cystoides intestinalis (PCI) in the small intestinal wall, with free air within the abdomen. A blood examination showed no increases in white blood cells or C-reactive protein level. The patientʼs condition improved with conservative therapy. PCI with pneumoperitoneum induced by α-glucosidase inhibitor is rare, with only 27 cases (excluding the present case) reported in Japan to date. In PCI with pneumoperitoneum, differentiation from gastrointestinal perforation is important and following the clinical symptoms over time is vital

Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer

Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy

Evaluation of Poly-MVA as a new radio-protectant against high LET particle irradiation

Poly-MVA, a commercially available health supplement containing α-lipoic acid palladium complex, was evaluated for its potential in protecting mice from radiation-induced death. Treatment of 8 Gy X-ray-irradiated mice with Poly-MVA before and after exposure increased the survival rate from 60% to 100% 30 days after irradiation. The best efficacy was based on adequate absorption of Poly-MVA by a healthy mouse intestine. A dose higher than 8 Gy X-rays or 5.5 Gy carbon ions induced serious intestinal injury, which caused malabsorption of Poly-MVA. Poly-MVA treatment alone was ineffective to rescue mice exposed to a dose higher than 5.5 Gy of carbon ion irradiation. However, the synergistic radio-protective effect of Poly-MVA and amifostine was excellent on 9 Gy X-ray-irradiated mice. Combined administration of Poly-MVA and amifostine is expected to be useful in treating high LET particle-induced injury.平成29 年度HIMAC 共同利用研究成果発表

Evaluation of Poly-MVA as a new radio-protectant against high LET particle irradiation

Ploy MVA was evaluated for its potential to protect mouse from radiation. Treatment of 8 Gy X-ray-irradiated mice with polyMVA increased survival rate to 100% 30 days after irradiation. The best effect was based on adequate absorption of ployMVA by a health mouse intestine. Doses higher than 8 Gy X-rays or 5.5 Gy carbon ions induce serious intestinal injury, which caused impedient absorption of ployMVA. We found simple ployMVA treatment was ineffective in protecting mice from carbon ion irradiation of doses higher than 5.5 Gy. However, the synergistic effect of ployMVA and Amifostine against irradiation deserves further exploration. In the FY 2018, we have plotted a credible survival fraction of the mice exposed to X-ray irradiation, which has laid the foundation for the heavy ion experiments.平成30年度放射線医学総合研究所重粒子線がん治療装置等共同利用研究報告