補体制御因子sMAPとH因子を融合した新規抗補体薬sMAP-FHの開発

博士（医学）福島県立医科大

Successful Endoscopic Closure Using Polyglycolic Acid Sheets with Fibrin Glue for Nonhealing Duodenal Ulcer with Perforation after Proton Beam Therapy of Liver Tumor

We describe the first case of a nonhealing duodenal ulcer with perforation after proton beam therapy (PBT) of a liver tumor that was successfully treated endoscopically using polyglycolic acid (PGA) sheets with fibrin glue. A 69-year-old man received PBT for a liver tumor. Esophagogastroduodenoscopy (EGD) 3 months after PBT revealed a duodenal ulcer. A proton pump inhibitor was administered for 7 weeks, and the ulcer healed. Six months after the EGD, recurrence of the duodenal ulcer with perforation occurred. An emergency open surgery with placement of the omental patch was performed. However, 5 days after the surgery, because the EGD revealed a perforation site in the duodenal ulcer that was not closed, the conservative treatment was continued. Twenty-eight days after the surgery, EGD revealed that the perforation size had increased. Therefore, we conducted endoscopic closure therapy using PGA sheets with fibrin glue. Eleven days after the closure procedure, the EGD showed that the perforation site was filled with granulation tissue and was closed. Forty-nine days after the procedure, EGD revealed that the ulcer had healed. This endoscopic closure treatment was effective for a nonhealing duodenal ulcer with perforation after PBT of a liver tumor

Drug treatment for chemotherapy-induced peripheral neuropathy in patients with pancreatic cancer

Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the prognosis of unresectable PC is poor, it has been dramatically improved by new chemotherapy treatments, such as the combination of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel. However, as oxaliplatin and paclitaxel are common neurotoxic drugs, chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe adverse effect of both treatments. As there are no agents recommended in the ASCO guidelines, we review the methods used to treat CIPN caused by PC treatment. The efficacy of duloxetine was observed in a large randomized controlled trial (RCT). In addition, pregabalin was more effective than duloxetine for CIPN in two RCTs. Although duloxetine and pregabalin can be effective for CIPN, they have several side effects. Therefore, the choice between the two drugs should be determined according to effect and tolerability. Mirogabalin is also used in patients with PC and there is hope it will yield positive outcomes when treating CIPN in the future

Prevention of Stricture after Endoscopic Submucosal Dissection for Superficial Esophageal Cancer: A Review of the Literature

Endoscopic resection has been the standard treatment for intramucosal esophageal cancers (ECs) because of the low risk of lymph node metastases in the lesions. In recent years, endoscopic submucosal dissection (ESD), which can resect large ECs, has been performed. However, the risk of esophageal stricture after ESD is high when the mucosal defect caused by the treatment exceeds 3/4 of the circumference of the lumen. Despite the subsequent high risk of luminal stricture, ESD has been performed even in cases of circumferential EC. In such cases, it is necessary to take measures to prevent stricture. Therefore, in this review, we aimed to clarify the current status of stricture prevention methods after esophageal ESD based on previous literature. Although various prophylactic methods have been reported to have stricture-preventing effects, steroid injection therapy and oral steroid administration are mainstream. However, in cases of circumferential EC, both steroid injection therapy and oral steroid administration cannot effectively prevent luminal stricture. To solve this issue, clinical applications, such as tissue shielding methods with polyglycolic acid sheet, autologous oral mucosal epithelial sheet transplantation, and stent placement, have been developed. However, effective prophylaxis of post-ESD mucosal defects of the esophagus is still unclear. Therefore, further studies in this research field are needed

Efficacy and Safety of Peroral Endoscopic Myotomy for Esophageal Achalasia and Achalasia-Related Diseases in Patients Aged 75 Years and Over

Peroral endoscopic myotomy (POEM) has become a popular treatment for esophageal achalasia and other esophageal motility disorders. However, its efficacy and safety in elderly patients are unclear. To clarify that, we reviewed the medical records of patients who underwent POEM in our hospital. A total of 11 patients who underwent POEM for esophageal achalasia (n = 10) and jackhammer esophagus (n = 1) were included. Procedural success, defined as the completion of an esophageal and gastric myotomy, was 100%. Clinical success, defined as an Eckardt score of 3 or less, without the use of additional treatments at 2 months, was 100%. The median Eckardt score significantly decreased after the POEM (baseline vs. 2 months after POEM; 7 (2–8) vs. 0 (0–1), p < 0.01). In the second and third years, the cumulative treatment effect maintenance rate was 88.9%. All patients taking antithrombotic agents had safe operations with the temporary discontinuation of these agents. There were four adverse events (two pneumoperitoneum, one mucosal injury, and one pneumonia), all of which improved with fasting or antibiotics. In conclusion, POEM is an effective and safe treatment for esophageal achalasia and achalasia-related diseases in patients aged 75 years and over

Usefulness of Endoscopic Ultrasound with the Jelly-Filling Method for Esophageal Varices

Although the importance of endoscopic ultrasound (EUS) for esophageal varices (EVs) has been demonstrated, it is difficult to obtain sufficient EUS images with the water-filling method because of poor water stagnation in the esophagus. In this study on EVs, we aimed to evaluate the usefulness of the jelly-filling method for EUS. Consecutive patients who underwent EUS for EVs were included. The quality of EUS images, the diagnostic ability of the presence of blood vessels inside and outside the esophageal wall, and the procedure time were compared between the jelly-filling and water-filling methods. Thirty cases were analyzed (jelly-filling method in 13 and water-filling method in 17). The EUS image quality score was significantly higher in the jelly-filling method (jelly vs. water; three points vs. two points, p < 0.001). Additionally, EUS image quality scores in both nonexperts and experts were significantly higher in the jelly-filling method. The diagnostic ability of the presence of perforation veins was significantly higher in the jelly-filling method (jelly vs. water; 100% vs. 52.9%, p = 0.004). However, the procedure time was significantly longer in the jelly-filling method (p = 0.024). In conclusion, EUS using the jelly-filling method for EVs provided sufficient image quality

Usefulness of a Fork-Tip Needle in Endoscopic Ultrasound-Guided Fine-Needle Biopsy for Gastric Subepithelial Lesions

The sample adequacy and diagnostic accuracy of an endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) for gastric subepithelial lesions (SELs) have been reported to be imperfect. To resolve these issues, a fork-tip needle as an EUS-guided fine-needle biopsy (FNB) needle has been developed. This study was conducted to evaluate the usefulness of a fork-tip needle in an EUS-FNB for gastric SELs. Seventy-nine patients who received an EUS-FNA or FNB using a fork-tip needle for gastric SELs were included in the study. The sample adequacy and diagnostic accuracy were compared between the EUS-FNB with the fork-tip needle group (fork-tip group, n = 13) and the EUS-FNA with FNA needle group (FNA group, n = 66). In addition, a multivariate analysis of the factors influencing diagnostic accuracy was conducted. Regarding sample adequacy, there was no significant difference between the groups (100% vs. 90.9%, respectively; p = 0.582). The diagnostic accuracy of the fork-tip group was numerically higher than that of the FNA group (92.3% vs. 81.8%, respectively; p = 0.682). In a multivariate analysis, the diagnostic accuracy was related to the tumor size and location of the SEL but not to the needle type. In conclusion, this study does not show statistical superiority, but suggests the useful potential of a fork-tip needle

Association between Submucosal Fibrosis and Endoscopic Submucosal Dissection of Recurrent Esophageal Squamous Cell Cancers after Chemoradiotherapy

Endoscopic resection is a treatment of choice for a metachronous early-stage esophageal squamous cell carcinoma (ESCC) appearing after a radical cure of esophageal cancer by chemoradiotherapy (CRT). However, non-curative resection, and procedural complications including perforation due to radiation-induced submucosal fibrosis, are a concern. This study aimed to evaluate the association between submucosal fibrosis and the usefulness and safety of endoscopic submucosal dissection (ESD) in ESCC after CRT. This study retrospectively analyzed 13 lesions in 11 patients in our institute. Submucosal fibrosis under the lesion (F score) was classified into three levels (F0: none or mild, F1: moderate, and F2: severe) based on endoscopic and histopathologic findings. All lesions were F1 or greater (F1: 8 lesions and F2: 5 lesions). En bloc and R0 resection rates were both 100%. The procedural speed was slower in F2 than in F1 (F1 vs. F2; 15.1 mm2/min vs. 7.1 mm2/min, p = 0.019), without procedure-related adverse events. At a median follow-up of 42 months (range: 14–117 months) after ESD, 7 of 11 (63.6%) patients were alive without recurrence, and without ESCC-related death. ESCC after CRT reliably and safely resected en bloc by ESD but was more difficult in lesions with strong submucosal fibrosis