Yo Kawarada

Pigment epithelium-derived factor gene therapy inhibits human pancreatic cancer in mice.

Purpose: Pigment epithelium–derived factor (PEDF), which has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, is also expressed in the pancreas. Previously, we have screened the expression of PEDF by immunohistochemical analysis and showed that low expression of PEDF is associated with increased risk of hepatic metastasis and short survival. The purpose of this study was to investigate whether PEDF gene is a potent tumor suppressor and a potential candidate for cancer gene therapy. Experimental Design: We investigated both in vitro and in vivo growth characteristics of human pancreatic adenocarcinoma cell lines that were stably transfected to overexpress human PEDF and therapeutic effects of lentivirus-based vectors expressing PEDF on tumor growth in murine s.c. tumor model. Results: We discovered that cells secreted PEDF protein in the media and this exhibited strong inhibitory effects on proliferation and migration of human umbilical vein endothelial cells. The size of PEDF-overexpressing pancreatic adenocarcinoma tumors was significantly smaller than that of control tumors in s.c. tumor models. Moreover, the growth of PEDF-overexpressing pancreatic adenocarcinoma cells was significantly suppressed in comparison with control cells in peritoneal metastasis models. In gene transfer models, intratumoral injection of a lentivirus vector encoding PEDF (LV-PEDF) caused significant inhibition of tumor growth. The antitumor effect observed after treatment with LV-PEDF was associated with decreased microvessel density in tumors. Conclusion: Our data suggest that PEDF may exert a biological effect on tumor angiogenesis and PEDF gene therapy may provide a new approach for treatment of pancreatic adenocarcinoma.

CT evaluation of paraaortic lymph node metastasis in patients with biliary cancer

BackgroundThe extent of paraaortic lymph node (PAN) metastasis parellels that of distant metastases in patients with biliary carcinoma. Accurate preoperative assessment of PAN metastasis has a crucial impact on surgical indications. In this retrospective study, we evaluated whether computed tomography (CT) scans were useful for diagnosing PAN metastases and excluding patients with PAN metastases from an indication for surgery.MethodsBetween March 1999 and November 2003, 57 patients with biliary carcinoma underwent radical lymphadenectomy or surgical biopsy of PANs. Nine of these patients were diagnosed as having PAN metastasis microscopically. All patients had undergone abdominal CT scans before surgery. To diagnose PAN metastases, we used the following diagnostic criteria. (1) Size; when lymph nodes were greater than 12 mm, 10 mm, 8 mm, or 6 mm in longo or short-axis diameter, the nodes were considered metastatic. (2) Shape and size; when the axial ratio of a lymph node was greater than 0.5, 0.7, 1.0, and the maximum diameter of the long or short axis was greater than 12 mm, 10 mm, 8 mm, or 6 mm, the node was considered metastatic. (3) Internal structure; if the internal structure of a PAN was heterogeneous, the node was considered metastatic. A positive predictive value was calculated for each included criterion when patients numbered ten or more.ResultsPositive predictive values using the above criteria ranged from 13% to 36%. Only one patient had PANs with heterogeneous internal structures.ConclusionsWe were unable to determine surgical indications based on the morphological criteria revealed by a CT scan.

Lazaroid reduces production of IL-8 and IL-1 receptor antagonist in ischemic spinal cord injury

BACKGROUND 21-aminosteroids (lazaroids) have demonstrated the protective effect against cerebral ischemic injury through the inhibition of lipid peroxidation. We examined whether lazaroids affected the production of proinflammatory and antiinflammatory cytokines in ischemic spinal cord injury model. MATERIALS Anesthetized New Zealand white rabbits underwent a 20-minute infrarenal aortic cross-clamping (AXC) with pretreatment of either an intravenous 3 mg/kg lazaroid U74389G (group L; n = 10) or the same volume saline (group P; n = 10). Sham operation group (group S; n = 6) underwent only exposure of the aorta. Plasma concentrations of interleukin (IL)-8, -1beta, -1 receptor antagonist (IL-1ra) and tumor necrosis factor (TNF)-alpha were measured at four time points. Functional assessment with Tarlov score at 24 and 48 hours after pretreatment, pathologic assessment of the spinal cord, and measurements of cytokine levels in the spinal cord were performed. RESULTS The maximum elevation of plasma IL-8 and -1ra levels occurred at 1 hour after declamping in four measurement points. Plasma IL-8 and -1ra levels in group L were significantly lower than those in group P (*p < 0.05). Plasma TNFalpha peaked at 5 minutes after declamping, but decreased afterwards. Plasma TNFalpha levels were not different among three groups. Spinal IL-8 levels in group L (0.98 +/- 0.34 ng/g tissue) were lower than those in group P (7.26 +/- 2.26 ng/g tissue)(*p < 0.05). Spinal IL-1ra and TNFalpha were not significantly different. Tarlov score and pathologic assessment were better in group L. CONCLUSIONS Lazaroid U-74389G reduced the production of systemic IL-8 and -1ra and spinal IL-8 when AXC caused spinal cord injury. These results indicate that lazaroids may attenuate ischemic endothelial cell injury or activation of leukocytes.

A new marking technique for peripheral lung nodules avoiding pleural puncture: the intrathoracic stamping method

While performing thoracoscopic wedge resection of the lung, the location of the lesion is generally identified by visual inspection or palpation. When difficulty in identification of the lesion by thoracoscopy is anticipated, preoperative marking is performed. However, complications and technical difficulties plague current marking techniques. To overcome this problem, we designed a new, safe and easy marking technique that avoids pleural puncture, called the intrathoracic stamping method.

Esophageal delta-shaped anastomosis: a new method of stapled anastomosis for the cervical esophagus and digestive tract.

We describe a new technique of anastomosis between the esophagus and digestive tract, developed as an extension of a functional end-to-end anastomosis, and named the “esophageal delta-shaped anastomosis.” We also report its short-term clinical results. We used this anastomotic technique in nine patients undergoing surgery for thoracic esophageal carcinoma. The reconstruction route was posterior mediastinal (n = 5), antethoracic (n = 3), or retrosternal (n = 1), and the organs for esophageal replacement were the gastric tube (n = 7) or the colon (n = 2). When using the gastric tube, a linear stapler is inserted into two intestinal windows; one created at the stump of the esophagus and the other created in the posterior wall near the greater curvature of the gastric tube. The stapler is fired, ensuring that the staple line does not sharply cross the staple line of the lesser curvature of the gastric tube. Two linear staplers are then used to close the window transversally to form a delta shape. There were no complications related to the anastomosis. The esophageal delta-shaped anastomosis is a simple and safe method for esophagogastrostomy or esophagoenterostomy, which uses a combination of introverted and extroverted stapling, resulting in a larger lumen not limited by the lumen of the esophagus or the organs used for esophageal replacement.

Immunoglobulin G4‐related disease presenting as a pulmonary nodule with an irregular margin

We report a case of immunoglobulin G4 (IgG4)‐related lung disease presenting as a solitary pulmonary nodule with an irregular margin on computed tomography. The nodule showed a high standardized uptake value on positron emission tomography. A malignant pulmonary tumour could not be excluded. Middle lobectomy was performed. Histological analysis revealed marked lymphoplasmacytic infiltration and storiform fibrosis. Immunostaining indicated the presence of IgG4‐positive plasma cells. A definitive diagnosis of IgG4‐related disease was confirmed.

Resection of mediastinal goiter extending to the carina with use of artificial pneumothorax, two-lung ventilation, and thoracoscopy, with the patient in a prone position

A 67-year-old woman was presented with a mediastinal tumor extending from the left lobe of the thyroid and passing through the posterior trachea, causing displacement of the esophagus to the left side of the patient and then descending into the right side of the mediastinum to below the carina. Surgery was performed under two-lung ventilation with the patient in a prone position; general anesthesia was performed with a single-lumen tube combined with artificial pneumothorax. In thoracoscopic surgery, we were able to confirm and preserve anatomical structures. After detachment of the tumor at the level of the left and right subclavian arteries, the patient was placed supine, a cervical incision was added, and the tumor was extracted. The tumor was diagnosed as a nonmalignant mediastinal goiter (MG). No such surgical report was found in the literature, and one would be useful for this new approach to MG removal.

Atypical presentation of a cushion sign-positive stomach gastrointestinal stromal tumor with cystic formation: A case report

Gastrointestinal stromal tumors (GIST) typically appear as solid masses, and cystic formation is uncommon. Most stomach GISTs with cystic formation progress outside the gastric wall and are frequently misdiagnosed as epigastric cystic tumors derived from pancreas or liver. An asymptomatic 72-year-old male underwent esophagogastroduodenoscopy, which revealed a submucosal tumor (SMT), approximately 50 mm in diameter, at the anterior wall of the gastric angle. The SMT was very soft with positive cushion sign. Endoscopic ultrasonography and contrast-enhanced computed tomography revealed that the SMT was a cystic tumor with solid component. Laparoscopic and endoscopic cooperative surgery were performed to remove the tumor. Histopathological analysis revealed that the tumor was a GIST with cystic formation. To the best of our knowledge, this the first documented case of a cushion sign-positive stomach GIST with cystic formation, which had mainly developed inside the stomach. This case suggests that we should keep in mind the possibility of cystic formation of GIST when the tumor has a solid component, even if it appears as a cushion sign-positive SMT.

Development of a novel training system for laparoscopic inguinal hernia repair

Abstract Background: Laparoscopic inguinal hernia repair is considered technically difficult. Although a simulation-based curriculum has been developed to help trainees, access to simulation training outside North America is limited. This study aimed to develop an educational system for the transabdominal preperitoneal (TAPP) approach based on the TAPP checklist, an assessment tool we had developed and validated earlier. Material and methods: Consensus within the TAPP education working group consisting of local TAPP experts, hernia experts and a surgical educator to develop educational tools and the educational system based on the TAPP checklist. The system was piloted in several institutes, and participants were surveyed on its efficacy. Results: We systematically developed an educational video and training manual explaining each item of the TAPP checklist and conveying basic knowledge of the procedure. We integrated the training tool with evaluation and feedback to develop an educational system. In a pilot study, seven trainees at five hospitals were trained using this system and found it very useful for mastering the TAPP procedure. Conclusions: We have developed a training system for TAPP procedure and successfully implemented it in several hospitals. Further research will focus on the educational value of this tool.

A Late-onset Spinal Epidural Abscess after Neoadjuvant Chemotherapy and Esophagectomy

患者:67歳,男性 主訴:突然の下半身脱力 既往歴:特記すべきことなし. 家族歴:特記すべきことなし. 生活歴:喫煙 10本/日を 45年間. 現病歴:検診にて食道癌と診断され,精査加療目的に当院紹介受診となった.上部消化管内視鏡検査に て切歯より約 40 cmの胸部下部食道に Type 2病変を認め,T2N2M0,Stage IIIの診断で術前化学療法とし て 5-fluorouracil(以下,5-FUと略記)/cisplatin(以下,CDDPと略記)併用療法を計 2コース施行した. 化学療法レジメンは,5-FU 800 mg/m2(day 1~5,24時間),CDDP 80 mg/m2(day 1,2時間)の点滴静注 とし,4週間を 1コースとした.Common Terminology Criteria for Adverse Events v4.0(CTCAEv4.0)に基づ いて Grade 1の口内炎を認めたが,その他明らかな有害事象なく経過した.その結果,RECISTによる効果 判定で partial responseとなり腫瘍とリンパ節の縮小が得られたため,胸腔鏡下食道亜全摘術,3領域郭清,