ASP7266, a Novel Antibody against Human Thymic Stromal Lymphopoietin Receptor for the Treatment of Allergic Diseases.

Thymic stromal lymphopoietin (TSLP), positioned at the top of the inflammatory cascade, is a key regulator that enhances allergic inflammatory responses by activating T helper type 2 cells, Group 2 innate lymphoid cells (ILC2), and myeloid dendritic cells (mDCs) via the TSLP receptor (TSLPR). We evaluated the inhibitory effects of ASP7266, a novel recombinant fully human IgG1 monoclonal antibody against TSLPR, on TSLP signaling and inflammation. The inhibitory effects of ASP7266 and the control antibody tezepelumab on TSLP and TSLPR interactions were investigated using a proliferation assay with TSLP stimulation and a chemokine production assay. The pharmacological effects of ASP7266 were investigated by examining differentiation of naive CD4+ T cells, ILC2 cytokine production, and ascaris extract-induced skin allergic reaction in cynomolgus monkeys. ASP7266 potently inhibited TSLP-induced cell proliferation and C-C motif chemokine ligand 17 production. Furthermore, ASP7266 inhibited TSLP-stimulated mDC-mediated naive CD4+ T-cell differentiation and interleukin 5 production by lineage-negative peripheral blood mononuclear cells, which can be considered ILC2 in vitro. In sensitized monkeys, ASP7266 completely suppressed ascaris extract-induced allergic skin reactions. Based on these results, ASP7266, a novel human therapeutic antibody against TSLPR, is a potential therapy for patients with allergic diseases. SIGNIFICANCE STATEMENT: TSLP, positioned at the top of the inflammatory cascade, plays a key role in various allergic diseases, including asthma, chronic rhinosinusitis with nasal polyposis, and atopic dermatitis. Here we show that the anti-TSLPR antibody ASP7266 exhibited excellent pharmacological activity in preclinical studies. Therefore, ASP7266 has the potential to be a promising treatment option for patients with allergic disorders.

Utility of Ultrasonography of the Median Nerve With a High-Frequency Probe for the Diagnosis of Dialysis-Related Carpal Tunnel Syndrome.

This cross-sectional study aimed to determine the utility of ultrasonography with improved resolution using a high-frequency probe for dialysis-related carpal tunnel syndrome (CTS). This study targeted 125 hemodialysis patients at our hospital. A 12 MHz probe was placed on the carpal tunnel area to identify the median nerve. The compression rate of the nerve was calculated by measuring the smallest diameter of the compressed nerve and largest diameter of the unaffected part. To quantify CTS symptoms, we determined the presence of Tinel's sign, measured pinch strength, and used questionnaires to assess numbness and pain. The association of these clinical data with the compression rate was examined. Mean compression rate was 12.1 ± 1.1%. The compression rate cutoff value for those positive with Tinel's sign was 25%, (sensitivity and specificity were 0.80 and 0.91, respectively), and that for those with a history of CTS surgery was 25% (sensitivity and specificity were 0.67 and 0.89, respectively). Multiple regression analysis identified duration of dialysis, ß2-microglobulin(ß2-Mg) concentration, positivity for Tinel's sign, history of CTS surgery, and pinch strength as independent compression rate determinants. Notably, compression rates were significantly higher in patients with a ≥4-year duration of dialysis and a ß2-Mg level of 20 mg/L or more. The compression rate of the median nerve measured by an improved ultrasound device significantly correlated with clinical symptoms, medical history, and serological features associated with dialysis-related CTS. Because ultrasonography is non-invasive, the examination might be a simple method especially for early diagnosis of dialysis-related CTS.

[A Case Treated with Selective Embolization for Hemorrhage during Tonsillectomy].

Though tonsillectomy is one of the most common surgical procedures in otorhinolaryngology generally for benign diseases and mainly for young people, uncontrollable perioperative bleeding associated with tonsillectomy is a rare but potentially life-threatening event. We report herein on a case of a 19-year-old female with uncontrollable hemorrhage during a tonsillectomy, which was controlled through selective embolization. To the best of our knowledge, this is the first report on endovascular treatment in the management of tonsillectomy-associated intraoperative uncontrollable hemorrhage rather than postoperative bleeding. Selective embolization for perioperative bleeding during a tonsillectomy is considered as an efficient and important therapeutic option in the definitive treatment of this life-threatening occurrence. We also reviewed patients who underwent tonsillectomy in our hospital in the past five years. The ratio of postoperative hemorrhage was 11.8%. All patients with post-tonsillectomy hemorrhage were classified as grade 1 bleeding (spontaneous cessation).

Cervical pregnancy: a report of four cases.

Various conservative treatments for cervical pregnancy have been reported. However, unlike tubal ectopic pregnancy, the treatment of cervical pregnancy has not been well established. For patients who desire fertility preservation, treatment with methotrexate chemotherapy carries a high success rate for preservation of the uterus. When methotrexate is injected i.v. or i.m., expulsion of pregnant tissue occasionally takes up to 1 month. In this report, we present four cases of cervical pregnancy which were successfully managed by methotrexate injection into the bilateral uterine arteries. In cases presenting with massive bleeding, embolization of the bilateral uterine arteries was performed. Cervical pregnancy was aborted within 8 days safely, and fertility could be preserved without harmful side-effects.

[A case of urachal abscess accompanied by a stone].

A 64-year-old woman presented to our hospital with the chief complaints of abdominal pain and appetite loss, and she was admitted to the internal medicine department. Kidney, ureter and bladder X-ray revealed intrapelvic calcification near the bladder, and so, the patient consulted our department. Computed tomography and magnetic resonance imaging revealed an urachal abscess accompanied by a stone. Open surgery was performed under general anesthesia. The mass adhered tightly to the intestine and bladder. The urachal abscess ruptured during the operation, and pus leaked into the intraabdominal cavity. Partial cystectomy was performed to remove the mass completely. The stone existed in the urachal abscess, and its constituents were CaOxa (51%) and CaP (49%). The pathological diagnosis was urachal abscess without malignancy.

Case of three delayed complications of radiotherapy: bilateral vocal cord immobility, esophageal obstruction and ruptured pseudoaneurysm of carotid artery.

We report the first case of three delayed complications following irradiation for laryngeal carcinoma: bilateral vocal cord immobility, obstruction of esophagus and spontaneously ruptured pseudoaneurysm of common carotid artery. Medial fixation of bilateral vocal cords and stenosis of cervical esophagus were noted at 28 years after radiotherapy. Spontaneous rupture of a pseudoaneurysm bulging into the hypopharynx and obstruction of the esophagus occurred at 35 years after irradiation. The life-threatening hemorrhage was successfully treated by microcoil embolization of the common carotid artery. The relationship between these complications and irradiation is also discussed.

Spontaneous hemothorax in neurofibromatosis treated with percutaneous embolization.

We evaluated the effectiveness of transcatheter arterial coil embolization therapy for the treatment of spontaneous hemothorax followed by aneurysm rupture in neurofibromatosis patients. Three patients were treated for massive hemothorax caused by arterial lesions associated with neurofibromatosis. Bleeding episodes were secondary to ascending cervical artery aneurysm and dissection of vertebral artery in 1 patient, and intercostal artery aneurysm with or without arteriovenous fistula in 2 patients. Patients were treated by transarterial coil embolization combined with chest drainage. In 1 patient, the ruptured ascending cervical artery aneurysm was well embolized but, shortly after the embolization, fatal hemorrhage induced by dissection of the vertebral artery occurred and the patient died. In the other 2 patients, the ruptured intercostal artery aneurysm was well embolized and they were successfully treated and discharged. Transcatheter arterial coil embolization therapy is an effective method for the treatment of spontaneous hemothorax followed by aneurysm rupture in neurofibromatosis patients.

Development of a semi-automated superimposing image verification system using a template matching algorithm in radiotherapy.

To analyze shifts in the isocenter of images, we developed a semi-automated superimposing image-verification system that is capable of automatically quantifying shifts in the isocenter through image analysis with a personal computer (PC). The accuracy and usefulness of this software were examined through a comparison of nine portal images with a simulation image and by comparing nine portal images with a DRR image, using a human pelvic phantom. The difference between the known magnitude of shift and the magnitude of shift detected with this method was analyzed as detection error. When the portal images were compared with the simulation image, the 95% confidence interval (95% CI) of detection errors (mean+/-SD) was 0.57+/-0.36 mm (95% CI: 0.49-0.65 mm). When the portal images were compared with the DRR image, the respective figures were 0.68+/-0.38 mm (95% CI: 0.59-0.77 mm). No significant difference was noted between these two categories of comparison (N.S). The absolute detection error (mean+/-SD) in all directions was 0.34+/-0.34 mm for the comparison of portal images with the simulation image and 0.41+/-0.36 mm for the comparison of portal images with the DRR image. This system seems to be appropriate for verification of the treatment field by improving the accuracy of radiotherapy as a method of computer-assisted landmark recognition during image comparison.

Dynamic CT of acute cholangitis: early inhomogeneous enhancement of the liver.

OBJECTIVE: Our objective was to describe the dynamic CT findings of acute cholangitis, especially early inhomogeneous enhancement of hepatic parenchyma. MATERIALS AND METHODS: Inhomogeneous enhancement of hepatic parenchyma was retrospectively evaluated on dynamic CT in 406 consecutive patients without irregular fatty liver or multiple hepatic tumors. Dynamic CT scans were obtained 30 sec (early phase) and 90 sec (late phase) after starting the contrast material injection. Thirteen patients were diagnosed as having acute cholangitis (cholangitis group), and the remaining 393 patients were classified as the control group. The frequency of inhomogeneous enhancement was compared between these two groups. In nine of the 13 patients in the cholangitis group, we also evaluated changes in inhomogeneous enhancement on follow-up dynamic CT scans obtained after the patients had undergone treatment for acute cholangitis. RESULTS: In the cholangitis group, 11 (85%) of 13 patients showed nodular, patchy, wedge-shaped, or geographic inhomogeneous enhancement throughout the liver in the early phase on dynamic CT. In the control group, 19 (5%) of 393 patients also showed inhomogeneous enhancement in the early phase on dynamic CT. The frequency of inhomogeneous enhancement was significantly higher in the cholangitis group than in the control group (p < 0.001). Follow-up dynamic CT performed after treatment for acute cholangitis showed decreased inhomogeneous enhancement or no inhomogeneous enhancement in seven (78%) of nine patients in the cholangitis group. CONCLUSION: Inhomogeneous enhancement in the early phase on dynamic CT is frequently seen in patients with acute cholangitis; this finding usually disappears after treatment.

Use of three-dimensional computed tomographic angiography of pulmonary vessels for lung resections.

BACKGROUND: Identification and appropriate treatment of the pulmonary artery (PA) is a key to successful anatomic resection of the lung. Preoperative identification of branching pattern of the PA seems to make pulmonary resection easier and safer especially when there is severe adhesion or incomplete fissure between the lobes. With the development of the multidetector row spiral computed tomography (MDCT), three-dimensional (3D) CT angiography can be obtained easily and can provide very useful information about various organs. We studied the usefulness of 3D-CT pulmonary angiography (3D-CTPA) in evaluating the PA branching pattern before anatomic pulmonary resection. METHODS: Fourteen patients with primary lung cancer undergoing anatomic pulmonary resections were the subjects of this study. The 3D-CTPA images were obtained using MDCT. The obtained images of the PA branching pattern were compared with intraoperative findings in each case at the time of thoracotomy. RESULTS: MDCT scanning required approximately 15 seconds per patient during a single respiratory pause and the 3D images were processed within 10 minutes after scannning. According to intraoperative findings, 98% (84 of 86) of PA branches were revealed to be successfully identified on preoperative 3D-CTPA. Two missed branches on 3D-CTPA were small vessels, which were less than 1.5 mm in actual diameter. Pulmonary vessels were clearly identified even when contrast medium was not administered intravenously. CONCLUSIONS: Obtaining 3D-CTPA using MDCT is noninvasive yet it provides precise preoperative information regarding pulmonary vessels. This technique is a far less invasive and an easier investigation than conventional pulmonary angiography. The 3D-CTPA navigation may have the potential to increase the safety of surgical procedure and to reduce surgical morbidity in anatomic lung resection.

Results of wedge resection for focal bronchioloalveolar carcinoma showing pure ground-glass attenuation on computed tomography.

BACKGROUND: Focal bronchioloalveolar carcinoma (BAC) showing pure ground-glass attenuation (GGA) on thin-section computed tomography (CT), which is considered to be an early-stage adenocarcinoma, has been diagnosed with increasing frequency due to the development and spread of the helical CT scanner. We discussed the appropriateness of limited resection for this type of lesion. METHODS: Between July 1996 and June 2001, 17 patients with localized BAC showing "pure GGA" (GGA without central scar formation) on thin-section CT underwent limited pulmonary resections. The mean patient age was 57.2 +/- 10.5 years old. Among these patients, four tumors were detected in a CT mass-screening program and the others were incidentally detected on CT during follow-up for other diseases. Fourteen patients underwent thoracoscopic wedge resection, and 3 underwent segmentectomy because of tumor location. RESULTS: The mean tumor diameter was 7.9 +/- 1.9 mm. On pathological examination, all tumors showed a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion. The median follow-up time was 32.0 months, with no cancer death or relapse to date. CONCLUSIONS: Focal BAC showing pure GGA on thin-section CT is peripheral in situ adenocarcinoma. Wedge resection by VATS is considered to be an appropriate treatment for this type of lung cancer. It can be a minimally invasive complete resection for this type of early cancer, and offer the best chance for long-term survival and good quality of life.