Evaluation of the widths of the mucosal strips in pathological examination of specimens of endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer in Japan. Pathological evaluation of ESD specimens is considered essential to determine if additional gastrectomy is necessary. Usually, specimens resected by ESD are sliced into 2-3 mm wide sections, and each section is examined for depth of tumor and lymphovascular invasion. Nevertheless, in most cases of additional gastrectomy, lymph node metastasis is not present. Given that there are few-studies on how clinical-decisions based on the pathologic-evaluation-method, in particular the specimen cut-width, influence patient outcomes, we retrospectively evaluated whether reducing the number of cuts to one-half or one-third would result in underestimation of the real need for additional surgery. The effect of the actual cut-width on recommended treatment (referral to operation) and patient-outcomes was also assessed. METHODS: Pathological records of 498 lesions from 439 patients were reviewed and re-evaluated. All pathological descriptions are based on the gastric cancer classification system of the Japanese Gastric Cancer Association, 15th edition. RESULTS: In 5.8% and 8.5% of the total specimens, underdiagnosis of tumor-depth and lymphovascular invasion occurred when the number of sections was reduced to one-half and one-third, respectively. Significantly more submucosal invasions were found in the group in which the cut-with was between 3 and 4 mm than in the group in which the cut width was less than 3 mm. CONCLUSION: Evaluation of the appropriate cut-width is important and should be discussed from the standpoint of labor costs and lost opportunities to search for molecular markers in ESD materials.

[A Case of Robot-Assisted Conversion Surgery for Gastric Cancer with Peritoneal Dissemination That Responded to Intravenous and Intraperitoneal Paclitaxel Combined with S-1 Chemotherapy].

This case involved a 69-year-old female patient with peritoneal dissemination of an advanced gastric cancer. She underwent chemotherapy comprisingintravenous and intraperitoneal paclitaxel combined with S-1. After 20 courses, a staging laparoscopy was performed, and pathological analysis of the peritoneal dissemination and cytologic analysis of ascites fluid yielded negative results. A radical robot-assisted total gastrectomy was successfully performed. The pathological stage was determined to be ypT4aN2M0, ypStage ⅢB. We continued to administer the same chemotherapy regimen for 15 courses (total: 35 courses)after surgery. No recurrence has been detected during the 1-year period after surgery.

[A Case of Duodenal Gastrointestinal Stromal Tumor Resection with Preservation of the Pancreatic Head Following Chemotherapy with Imatinib].

A 60-year-old male was admitted to our hospital on account of a duodenal submucosal tumor on the opposite side of Vater's papilla identified on a screening gastroduodenoscopy. The tumor was diagnosed as a duodenal gastrointestinal stromal tumor(GIST)due to positive c-kit and DOG1tests. Gastroduodenography and enhanced computed tomography showed a 50mm tumor widely invadingthe descendingportion of the duodenum close to the papilla of Vater and indicated the need for extended resection includingpancreaticoduodenectomy to achieve curation. Preoperative chemotherapy was initiated with imatinib mesylate(imatinib)to preserve the pancreas. A 16 month course of imatinib shrunk the tumor up to 21mm and laparoscopic partial duodenectomy was performed as a curative resection. So far, no local tumor recurrence has been seen for 26 months after the surgery. Herein, we report this case with a review of the literature.

Aralin, a type II ribosome-inactivating protein from Aralia elata, exhibits selective anticancer activity through the processed form of a 110-kDa high-density lipoprotein-binding protein: a promising anticancer drug.

Aralin from Aralia elata is a newly identified type II ribosome- inactivating protein, which preferentially induces apoptosis in cancer cells. In this study, we identified that the aralin receptor is a 110-kDa high-density lipoprotein-binding protein (HDLBP), which functions as a HDL receptor. The sensitivities of tumor cell lines to aralin were dependent on the expression levels of the 110-kDa HDLBP and its forced expression in aralin-resistant Huh7 cells conferred aralin sensitivity. HDLBP-knockdown HeLa cells showed a significant aralin resistance in vitro and in vivo. Conversely, ectopic expression of the 150-kDa HDLBP resulted in increased aralin sensitivity in vivo, accompanying enhanced expression of the 110-kDa HDLBP. Thus, these results showed that the 110-kDa HDLBP in lipid rafts acted as an aralin receptor and that its expression levels determined aralin sensitivity, suggesting that aralin could be a promising anticancer drug for HDLBP-overexpressing tumors.

Mediastinal hematoma as an unusual intrathoracic manifestation of Boerhaave Syndrome: A case report.

INTRODUCTION: Boerhaave Syndrome (BS) is rare but life-threatening condition caused by a sudden increase in the intraluminal pressure due to vomiting. We present a case of BS manifesting as a posterior mediastinal hematoma, indicative of a potentially fatal condition. PRESENTATION OF CASE: A 51-year-old man presented with acute chest pain after vomiting. Enhanced Computed Tomography revealed mediastinal fluid with a left pleural effusion, leading to a diagnosis of BS. Emergency surgery revealed a posterior mediastinal hematoma with active bleeding due to a torn proper esophageal artery. Hemostasis and a wall repair were performed, and the patient was discharged uneventfully. DISCUSSION: This case highlights two important aspects. Firstly, a spontaneous esophageal perforation can manifest as a mediastinal hematoma due to the subpleural arterial injury, delaying bacterial spillage. While preoperative thoracentesis may not always diagnose BS accurately, bloody thoracic drainage can serve as an alternative diagnostic sign. Secondly, the mediastinal hematoma itself poses a serious risk, as it can lead to a catastrophic outcome even before bacterial contamination occurs, emphasizing the necessity of a timely surgical intervention in BS cases. CONCLUSION: BS can manifest as a mediastinal hematoma, and the absence of gastrointestinal content in the thoracic drainage does not rule out the possibility of BS. Prompt surgical intervention remains essential, as a mediastinal hematoma alone can result in a catastrophic outcome. This case highlights the significance of a comprehensive diagnostic assessment for BS.

Texture of cooked rice prepared from aged rice and its improvement by reducing agents.

The textures of cooked rice prepared from aged rice grains and their improvement by reducing agents were investigated. For aged rice that was stored for 5 months without air by the operation of a vacuum packing machine, the stickiness/hardness ratio of cooked rice was as low as that of aged rice stored in air. The results of electrophoresis showed that oxidation of proteins in the former was advanced to the same degree as in the latter. The stickiness/hardness ratios of the aged rice were increased by the addition of sodium sulfite, cysteine, and dithiothreitol to the cooking water. Sodium sulfite, cysteine, and dithiothreitol cleave disulfide bonds to sulfhydryl groups. Therefore, cleaving disulfide bonds to sulfhydryl groups improved the texture. The addition of them to the cooking water also increased the extractable solids at the time of heating. Hence cleaving disulfide bonds to sulfhydryl groups must increase extractable solids. Consequently, the gelatinized paste layer thickened and the thick paste layer softened the cooked rice.

Multiple Gastric Gastrointestinal Stromal Tumors in a Patient with Neurofibromatosis Type 1.

Gastrointestinal stromal tumors (GISTs) are relatively common in neurofibromatosis type 1 (NF 1) patients. Approximately 90% of GISTs associated with NF 1 are located in the small intestine, while sporadic GISTs are most commonly located in the stomach. Here we report an extremely rare case of an NF 1 patient with multiple gastric GITs (90 or more) but without multiple small intestinal tumors. A 63-year-old female patient who had a history of NF 1 underwent surgery for a gastric neuroendocrine tumor and gastric submucosal tumor (SMT). During the operation, multiple small nodules were identified on the serosal surface of the upper stomach. SMT and multiple nodules on the serosal surface were diagnosed as GISTs consisting of spindle cells positive for KIT, CD34, and DOG-1. Both GIST and the normal gastric mucosa showed no mutations not only in the c-kit gene (exons 8, 9, 11, 13, and 17) but also in the PDGFRA gene (exons 12, 14, and 18). This patient is being followed up without the administration of a tyrosine kinase inhibitor.

Aralin, a new cytotoxic protein from Aralia elata, inducing apoptosis in human cancer cells.

In this study, we purified a novel cytotoxic protein, aralin, from the shoots of Aralia elata. Aralin is composed of two subunits, A and B chains whose molecular weights are 29,100 and 32,200, respectively. In the assay using a normal human lung fibroblast cells (WI-38) and its SV40-transformed cells (VA-13), aralin demonstrated selective cytotoxicity against the virus-transformed cell line; the IC50 values of WI-38 and VA-13 were 10 and 0.8 ng/ml, respectively. Aralin showed positive response to DNA fragmentation in human lymphocyte HL-60 cells, and caspase specific inhibitors suppressed aralin-induced DNA fragmentation. These results indicate that the cytotoxicity of aralin is brought about primarily through the induction of apoptosis. Aralin also exhibited potent cytotoxic activity against various types of human cancer cell lines; cervical carcinoma cells (HeLa) proved the most sensitive, with an IC50 value of 0.08 ng/ml.

Inhibitory profile of nonapeptide derived from porcine troponin C against angiotensin I-converting enzyme.

A novel angiotensin I-converting enzyme (ACE) inhibitory peptide (RMLGQTPTK; 9mer) from porcine skeletal troponin C was investigated for its inhibitory profile. This peptide was noncompetitive and as hydrophobic as the known ACE inhibitory peptides. Aminopeptidase M quickly hydrolyzed 9mer, resulting in production of MLGQTPTK and LGQTPTK with inhibitory activities similar to those of 9mer. The main hydrolysis product of 9mer with carboxypeptidase A and B was RMLGQTPT showing very weak activity. Most products derived from 9mer hydrolysis by ACE, aminopeptidase, or carboxypeptidase showed weak but definite ACE inhibitory activities. Thus, 9mer was estimated to be a wholly efficient inhibitor with these fragment peptides.

Novel angiotensin I-converting enzyme inhibitory peptides derived from soya milk.

Inhibitors of angiotensin I-converting enzyme (ACE) are useful in treating hypertension, and many have been derived from food products, including soybeans. Using the industrial protease PROTIN SD-NY10, we developed a processed soya milk (PSM) with enhanced ACE inhibitory activity. The ACE inhibitory activity of PSM (IC(50)=0.26 µg/ml) was greater than that of regular soya milk (IC(50)=8.75 µg/ml). Eight novel ACE inhibitory peptides were purified from PSM by reversed-phase chromatography: FFYY (IC(50),1.9 µM), WHP (4.8 µM), FVP (10.1 µM), LHPGDAQR (10.3 µM), IAV (27.0 µM), VNP (32.5 µM), LEPP (100.1 µM), and WNPR (880.0 µM). The IC(50) values of these peptides are comparable to those reported for other ACE inhibitory peptides derived from wheat, chicken, bonito, wine, etc. Due to the relatively low IC(50) values of several peptides identified in this study, they may serve as ideal base components of food supplements for patients with hypertension.

Production of aralin, a selective cytotoxic lectin against human transformed cells, in callus culture of Aralia elata.

Recently we found that aralin, a novel lectin, from Aralia elata selectively induces apoptosis in human virus-transformed and cancer cells compared with normal cells. To overcome the reduction of aralin biosynthesis according to the development of leaves, we established callus tissues from the young shoots. The N-terminal amino acid sequence and immunochemical analyses revealed that ca-aralin, an aralin synthesized in the callus, was structurally identical with aralin except for the glycosylation of the B chain. The selective cytotoxic index (ratio of IC50 value against human lung normal cells versus virus-transformed cells) of ca-aralin was 2-fold higher than that of aralin. Thus, these results suggest that ca-aralin is more useful than aralin as an anticancer agent.

An apoptotic inducer, aralin, is a novel type II ribosome-inactivating protein from Aralia elata.

We recently found that aralin, a novel cytotoxic protein consisting of two subunits, from Aralia elata selectively induces apoptosis in transformed cells as compared to normal cells. Here we report that aralin is a lectin specific for galactose (Gal) and its derivatives, and possesses RNA N-glycosidase activity as a new type II ribosome-inactivating protein (RIP). The RNA N-glycosidase activity of aralin was detected in cell-free and whole cell systems by the generation of an R-fragment from 28S rRNA. Coinciding with appearance of the R-fragment in aralin-treated cells, significant inhibition of protein synthesis was observed prior to the onset of apoptosis. Aralin-evoked cell death was efficiently repressed by the addition of Gal and its derivatives. Interestingly, melibiose preferentially protected normal cells from apoptosis as compared with transformed cells. Using rhodamine-coupled aralin, the aralin receptor could be clearly detected around the cell surface of transformed cells, but to a lesser extent on normal cells. Receptor binding was suppressed by Gal. These results indicate that aralin is incorporated into cells via its Gal-containing cell surface receptor and induces apoptosis through its RIP activity. Moreover, the expression level and/or structural changes of the aralin receptor may affect the sensitivity toward aralin.