Vasomotion in human arteries and their regulations based on ion channel regulations: 10 years study.

Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.

Discordance in HER2 status between primary gastric adenocarcinoma tumors and cells from the corresponding malignant effusions.

BACKGROUND: Metastasis of gastric cancer commonly manifests as a malignant effusion, which presents an alternative cell source for human epidermal growth factor receptor 2 (HER2) status identification. This study aimed to compare HER2 status in primary gastric adenocarcinoma tumors and corresponding cell blocks prepared from malignant effusions (CB-MEs). METHODS: HER2 status was retrospectively evaluated by immunohistochemistry (IHC) in primary gastric adenocarcinomas and paired pathologically confirmed CB-MEs of 45 patients. Silver in situ hybridization (SISH) was also performed in cases with IHC 2+ for primary gastric adenocarcinomas and above IHC 1+ for CB-MEs. RESULTS: HER2 positivity was observed in 4.4% (2/45) of primary gastric adenocarcinomas and 6.7% (3/45) of CB-MEs. The HER2 concordance rate between primary gastric adenocarcinomas and CB-MEs was 88.9% (40/45) (κ = - 0.056). All five patients with HER2 positivity in the primary tumor or a CB-ME had a negative result in the corresponding paired sample. Of the 15 patients with two or more serially sampled CB-MEs, HER2 expression determined by IHC differed between each CB-ME in six (40%) patients, and all three patients with HER2 positivity in CB-MEs exhibited HER2 positivity in one of the serially sampled CB-MEs. CONCLUSIONS: The HER2 positivity rate was very low in gastric cancer patients with malignant effusions. Our results suggest that HER2 positivity was discordant between the primary gastric adenocarcinoma and corresponding CB-MEs and among serially sampled CB-MEs. The possibility of detecting HER2 positivity can be improved if the primary gastric adenocarcinoma tumor as well as all the available CB-MEs from each patient are analyzed.

H2 Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO).

This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K(+) channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, N(G)-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.

Dietary aflatoxin B1 intake, genetic polymorphisms of CYP1A2, CYP2E1, EPHX1, GSTM1, and GSTT1, and gastric cancer risk in Korean.

PURPOSE: We investigated the effects of aflatoxin B1 (AFB1) intake, genetic polymorphisms of AFB1 metabolic enzymes, and interactions between the polymorphisms and intake of AFB1 with regard to the risk of gastric cancer in Korean. METHODS: The participants in the study included 477 gastric cancer patients and 477 age- and sex-matched control subjects. Direct interviews and a structured questionnaire were used to determine the level of exposure to AFB1, and the GoldenGate assay and multiplex polymerase chain reaction were used for genotypic analyses of the cytochrome P450 1A2 (CYP1A2), cytochrome P450 1E1, epoxide hydrolase 1, and glutathione S-transferase genes. RESULTS: The probable daily intake of AFB1 was significantly higher among gastric cancer patients than among control subjects (cases vs. controls: 1.91 ± 0.87 vs. 1.65 ± 0.72 ng/kg bw/day, p < 0.0001), and increased AFB1 intake was significantly associated with an elevated risk of gastric cancer (odds ratio 1.94; 95 % confidence interval 1.43-2.63). However, genetic polymorphisms of AFB1 metabolic enzymes were not associated with gastric cancer, with the exception of CYP1A2. Moreover, there was no interaction between AFB1 intake and the genotypes of metabolic enzymes that affect gastric cancer risk. CONCLUSIONS: Our results suggest that dietary AFB1 exposure might be associated with a risk of gastric cancer. However, the effect of AFB1 on gastric carcinogenesis may not be modulated by genetic polymorphisms of AFB1 metabolic enzymes.

Mechanism of Relaxation Via TASK-2 Channels in Uterine Circular Muscle of Mouse.

Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K(+) channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K(+) conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.

Delayed duodenal stump fistula after laparoscopic distal gastrectomy with Billroth-II reconstruction for early gastric cancer: A case report.

Duodenal stump fistula (DSF) is one of the most serious complications of gastrectomy. The mean time to diagnosis of DSF is approximately 9 days after operation. Our report describes an extremely rare case of delayed DSF 144 days after a laparoscopic distal gastrectomy. A 58-year-old man with drug-induced liver cirrhosis (Child-Pugh class A) underwent laparoscopic distal gastrectomy with Billroth-II reconstruction for early gastric cancer. On postoperative day 1, he underwent reoperation because of intra-abdominal bleeding. Ongoing bleeding was observed in the stapler line of the duodenal stump and was controlled using metallic surgical clips. The patient was discharged on postoperative day 14, without complications. After 144 days following the first operation, he visited the emergency room with right flank pain and high fever. Computed tomography revealed free air and abscess near the duodenal stump site. Emergency laparotomy, abscess unlooping, and drain insertion were performed. After surgery, bile was drained by intra-abdominal drainage, and fistulography showed a duodenal fistula. The patient was discharged 55 days after his third surgery. This is an extremely rare case of DSF, which may be caused by the metallic surgical clips used for hemostasis of the duodenal stump stapler line. We believe that the use of metallic surgical clips for hemostasis of the duodenal stump after Billroth-II reconstruction should be avoided.

Clinical significance of the number of retrieved lymph nodes in early gastric cancer with submucosal invasion.

The prognosis of early gastric cancer (EGC) with submucosal invasion is favorable; however, several cases of recurrence have been reported even after curative gastrectomy. This study aimed to investigate risk factors and evaluate the clinical significance of the number of retrieved lymph nodes (LNs) in EGC with submucosal invasion. We retrospectively analyzed the data of 443 patients with gastric cancer with submucosal invasion after curative gastrectomy for recurrent risk factors. Recurrence was observed in 22 of the 443 gastric cancer patients with submucosal invasion. In the univariate analysis, the risk factors for recurrence were the number of retrieved LNs ≤ 25 and node metastasis. In the multivariate analysis, retrieved LNs ≤ 25 (hazard ratio [HR] = 5.754, P-value = .001) and node metastasis (HR = 3.031, P-value = .029) were independent risk factors for recurrence after curative gastrectomy. Body mass index was related to retrieved LNs ≤ 25 in univariate and multivariate analyses (HR = .510, P = .002). The number of retrieved LNs and node metastases were independent risk factors for EGC with submucosal invasion. For EGC with submucosal invasion, retrieved LNs > 25 are necessary for appropriate diagnosis and treatment.

Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients.

This study compared the tumor immune microenvironments (TIMEs) of primary gastric cancer (PGC) and paired metastatic gastric cancer (MGC). CD4+ and CD8+ T-cell density and PD-L1 expression were evaluated by multiplex immunohistochemistry, DNA mismatch repair (MMR) by immunohistochemistry, and immune-related genes by RNA sequencing. Twenty-three patients who underwent surgical treatment for PGC and MGC were enrolled in this study. CD8+ T-cell, PD-L1+ cell, and PD-L1+CK+ cell densities were significantly lower in MGC than PGC. PD-L1 positivity using a combined positive score (≥ 1%) and deficient MMR were observed in 52.2% and 8.7% of PGC samples, respectively, whereas both occurred in only 4.3% of MGC samples. The most frequent TIME types were inflamed (34.8%) and adaptive immune resistance (34.8%) in PGC, and immune desert (65.2%) and immunological ignorance (73.9%) in MGC. In transcriptome analysis, the expression of the T-cell inflamed gene set and co-stimulatory gene module was down-regulated in MGC compared to PGC. The total CD8+ T-cell density was an independent prognostic marker in both PGC and MGC (univariate P = 0.002, multivariate P = 0.006). Our result suggest that the TIME of metastatic tumors was less immunologically active compared to that of primary tumors in gastric cancer patients.

Physiological function and molecular composition of ATP-sensitive K+ channels in human gastric smooth muscle.

Gastric motility is controlled by slow waves. In general, the activation of the ATP-sensitive K+ (KATP) channels in the smooth muscle opposes the membrane excitability and produces relaxation. Since metabolic inhibition and/or diabetes mellitus are accompanied by dysfunctions of gastric smooth muscle, we examined the possible roles of KATP channels in human gastric motility. We used human gastric corpus and antrum smooth muscle preparations and recorded the mechanical activities with a conventional contractile measuring system. We also identified the subunits of the KATP channels using Western blot. Pinacidil (10 µM), a KATP channel opener, suppressed contractions to 30% (basal tone to -0.2 g) of the control. The inhibitory effect of pinacidil on contraction was reversed to 59% of the control by glibenclamide (20 µM), a KATP channel blocker. The relaxation by pinacidil was not affected by a pretreatment with L-arginine methyl ester, tetraethylammonium, or 4-aminopyridine. Pinacidil also inhibited the acetylcholine (ACh)-induced tonic and phasic contractions in a glibenclamide-sensitive manner (42% and 6% of the control, respectively). Other KATP channel openers such as diazoxide, cromakalim and nicorandil also inhibited the spontaneous and ACh-induced contractions. Calcitonin gene-related peptide (CGRP), a gastric neuropeptide, induced muscle relaxation by the activation of KATP channels in human gastric smooth muscle. Finally, we have found with Western blot studies, that human gastric smooth muscle expressed KATP channels which were composed of Kir 6.2 and SUR2B subunits.

Effects of dietary factors and the NAT2 acetylator status on gastric cancer in Koreans.

Environmental dietary carcinogens and genetic polymorphisms in metabolic enzymes have been reported to be the risk factors for gastric cancer. This study was undertaken to investigate the effects of the diet, the N-acetyltransferase (NAT) 2 acetylation status and their interaction on gastric cancer risk. The study population consisted of 471 gastric cancer patients and 471 age- and sex-matched control subjects. NAT2 genotypes were identified using single-nucleotide primer extension reaction methods. Thirty-one alleles related to 12 polymorphism sites were assayed in this study. Significantly increased odds ratios were observed in former smokers (OR = 2.39, 95% CI = 1.57-3.62), heavy drinkers (OR = 1.28, 95% CI = 1.06-1.55) and individuals who eat well-done meat (OR = 1.24, 95% CI = 1.09-1.41). The odds ratios (95% CI) for high intake of kimchi, stews and soybean paste were 3.27 (2.44-4.37), 1.96 (1.50-2.58) and 1.63 (1.24-2.14), respectively. The NAT2 genotype alone was not associated with gastric cancer risk. A significant gene-environment interaction was observed between environmental carcinogens and NAT2 genotypes. The odds ratios for kimchi, stews and soybean paste were higher in slow/intermediate acetylators than in rapid acetylators. The odds ratios for slow/intermediate acetylators were 2.28 (95% CI: 1.29-4.04) for light smokers and 3.42 (95% CI: 2.06-5.68) for well-done meat intake. The NAT2 acetylator genotype may be an important modifier of the effects of environmental factors on gastric cancer risk.

Endoluminal closure of an unrecognized penetrating stab wound of the duodenum with endoscopic band ligation: A case report.

BACKGROUND: A penetrating injury of a hollow viscus is an obvious indication for an exploratory laparotomy, but is not typically an indication for endoscopic treatment. CASE SUMMARY: A 27-year-old man visited the emergency department with a self-inflicted abdominal stab wound. Injuries to the colon and ileum were detected, but an injury to the second portion of the duodenum was missed. On the day following admission to our institution, the patient became hemodynamically unstable with massive hematochezia, although there was no evidence of bleeding in the Levin tube or Jackson-Pratt drain. We thus performed an upper gastrointestinal endoscopy and discovered a missed duodenal injury that was actively bleeding. An endoscopic band ligation was performed for hemostasis and closure of the perforation. The patient was subsequently discharged without any complications. CONCLUSION: A penetrating injury of the duodenum can be overlooked, so careful abdominal exploration is very important. If a missed duodenal injury is suspected, a cautious endoscopic approach may be helpful.

Optimal extent of lymph node dissection for T1 gastric cancer, with special reference to the distribution of micrometastasis, and accuracy of preoperative diagnosis for wall invasion.

BACKGROUND/AIMS: Preoperative diagnosis for wall invasion and lymph node metastasis is sometimes difficult in T1 gastric cancer. Optimum dissection extent of lymph nodes for T1 gastric cancer was studied from the aspect of subclassification of wall invasion and lymph node metastasis including micrometastasis. METHODOLOGY: 184 patients with cT1 or pT1 gastric cancer were studied. The grade of clinical wall invasion (cT) and clinical lymph node status (cN) were diagnosed by endoscopy and computed tomography or intraoperative findings. Lymph node metastasis (pN) was studied by hematoxylin and eosin staining and immunohistochemistry (IHC). RESULTS: In 79 cM tumors, 60 (75.9%) were diagnosed as pM. In 88 cSM tumors, 42 (47.7%) were diagnosed as pSM. In 94 pM gastric cancers, micrometastases were found in two patients (2.1%) and in N1 stations. Two (1.9%) of 70 pSM cancers had micrometastasis in No. 7, 8a and 12a stations. Lymph node metastasis (pN) correlated significantly with the depth of tumor invasion, lymphatic invasion and venous invasion. Regarding the pN2 stations, one (1.1%) of 94 pM tumors had lymph node metastasis in No.7 station, and 9 (12.9%) of 70 pSM tumors had nodal involvement in No.7, 8a, 11p, 12a and 14v stations. All eight pN+/cM tumors were diagnosed as nN0 and four (1.4%) of 23 pN+/cSM tumors were correctly diagnosed as pN+. In contrast, 8 (9.9%) of 81 cN0/cM tumors and 19 (24.1%) of 79 cN0/cSM tumors had histological lymph node metastasis (pN+). CONCLUSIONS: Accuracy of the clinical diagnosis of lymph node metastasis is very low. Accordingly, prophylactic lymph node dissection is recommended even for cT1 and cN0 tumors. For cN0/cM cancer, D1+No.7 is recommended. D1+No.7, 8a, 9, 11p is recommended for cSM cancer, located in U or M region and additional dissection of No. 14v is recommended for cSM cancer located in L region.

Long-term survival after gastrectomy and metastasectomy for gastric cancer with synchronous bone metastasis.

Bone metastasis is a rare event in patients with gastric cancer, but pathologic fracture, paralysis, pain and hematological disorders associated with the bone metastasis may influence the quality of life. We report herein the case of a 53-year-old man who presented with primary remnant gastric cancer with bone metastasis. The patient requested further investigations after detection of a metastatic lesion in the 2nd lumbar vertebra during evaluation for back pain that had persisted for 3 mo. No other metastatic lesions were detected. He underwent total gastrectomy and palliative metastasectomy to aid in reduction of symptoms, and he received combination chemotherapy with tegafur (S-1) and cisplatin. The patient survived for about 60 mo after surgery. Currently, there is no treatment guideline for gastric cancer with bone metastasis, and we believe that gastrectomy plus metastasectomy may be an effective therapeutic option for improving quality of life and survival in patients with resectable primary gastric cancer and bone metastasis.

Long-term Survival after Repeated Local Therapy and Salvage Chemotherapy for Recurrent Metastases from Gastric Cancer: a Case Report and Literature Review.

We report a rare case of long-term survival in a patient who received local therapy and salvage chemotherapy for recurrent metastases, along with a literature review. A 65-year-old male patient underwent subtotal gastrectomy for advanced gastric adenocarcinoma. Six months after gastrectomy, 2 metastatic intra-abdominal lymph node enlargements were detected, which were treated with radiotherapy. At 55 months after gastrectomy, an abdominal wall mass was detected, which was treated by surgical resection. The patient received 5-fluorouracil/leucovorin/irinotecan chemotherapy for 27 months before and after radiotherapy and docetaxel chemotherapy for 6 months after surgical resection of the abdominal wall metastasis. At the last visit, 7.8 years since the initial resection of the primary gastric cancer and 6.2 years since detection of the first metastases, the patient was disease-free and required no further chemotherapy. This case suggests that repeated local therapy offers potential for long-term survival in a carefully selected subset of patients with recurrent metastases.

Dietary vitamin D intake and vitamin D related genetic polymorphisms are not associated with gastric cancer in a hospital-based case-control study in Korea.

There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations, but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway. The effects of vitamin D intake, vitamin D related genetic polymorphisms, and their association with the incidence of gastric cancer were investigated in a hospital case-control study, including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex. Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects. No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls, nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses. Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels, but not with the active form of the vitamin, 1,25-dihydroxyvitamin D. There were no statistically significant interactions between vitamin D intake, and VDR or TXNIP polymorphisms. This study suggests that dietary vitamin D intake is not associated with gastric cancer risk, and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis.

Clinical features of gastric emptying after distal gastrectomy.

PURPOSE: Gastric emptying may influence the quality of life of patients who undergo distal gastrectomy. Little is known, however, about gastric emptying after distal gastrectomy. The aim of our study was to investigate gastric emptying patterns after distal gastrectomy. METHODS: This gastric-emptying study investigated patients who underwent distal gastrectomy in the 6 months or more before May 2008 to July 2013 at Chungbuk National University Hospital with a study sample of 205 patients. We analyzed patterns of gastric emptying. RESULTS: Delayed gastric emptying was found in 109 of the 205 patients (53.2%). Food stasis was more frequent in a group with delayed gastric emptying. In multivariate analysis, risk factors for gastroparesis were laparoscopic operation (hazard ratio [HR], 2.731; P = 0.008) and duration of less than 24 months after distal gastrectomy (HR, 2.795; P = 0.001). Delayed gastric emptying tended to decrease with duration of the postoperative period. CONCLUSION: Delayed gastric emptying is common in distal gastrectomy, and is related to laparoscopic operation and duration of the postoperative period. Food stasis was more frequent in a group with delayed gastric emptying.

Comparison of outcomes of surgeon-performed intraoperative ultrasonography-guided wire localization and preoperative wire localization in nonpalpable breast cancer patients undergoing breast-conserving surgery: A retrospective cohort study.

This study aimed to determine the efficacy of intraoperative ultrasonography-guided wire localization guided breast-conserving surgery (BCS) for nonpalpable breast cancer and compare it to conventional preoperative wire localization (PWL) guided surgery.We retrospectively analyzed the medical charts of 214 consecutive nonpalpable breast cancer patients who underwent BCS using intraoperative ultrasonography-guided wire localization by a surgeon (IUWLS) and PWL, between April 2013 and March 2017. Positive surgical margins, reexcision rates, and resection volumes were investigated.Of the total cohort, 124 patients underwent BCS with IUWLS and 90 patients with PWL. The following did not differ between the IUWLS and PWL groups: positive margin status, re-excision rate, conversion rate, permanent positive margin status, reoperation rate, median optimal resection volume (ORV), median total resection volume (TRV), and median closest tumor-free margin. Rather, median (range) widest tumor-free margin was significantly smaller in the IUWLS group (9 mm [5-12]) than in the PWL group (14 mm [9-20]; P = .003]). Median (range) calculated resection ratio (CRR) was significantly lower in the IUWLS group (1.67 [0.87-9.38]) than in the PWL group (4.83 [1.63-21.04]; P = .02).In nonpalpable breast cancer patients undergoing BCS, IUWLS showed positive resection margins and reexcision rates equivalent to those of the conventional PWL method. Additionally, excision volume and widest tumor-free margin were smaller with IUWLS, confirming that healthy breast tissue is less likely to be resected with this method. Our results suggest that IUWLS offers an excellent alternative to PWL, while avoiding PWL-induced patient discomfort.

Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40.

Lymphatic invasion is known as an independent predictor of lymph node metastasis in gastric cancer. However, the diagnosis of lymphatic invasion is sometimes difficult by hematoxylin-eosin (H&E) staining. Immunostaining using D2-40 was performed to study the distribution of lymphatic vessel and lymphatic invasion in a series of 78 primary gastric cancers. D2-40 showed specific staining for the lymphatic vessels, but not for blood vessels. The lymphatic invasion was most frequently found in the upper half of submucosal layer. Positive rate of lymphatic invasion by H&E staining was 27% (21/78), and that by D2-40 was 44% (34/78). Lymphatic invasion on H&E staining was diagnosed as false negative in 17 (21.8%) of 78 primary gastric cancers and false positive in 4 (5.1%) of 78 primary gastric cancers. Sensitivity for lymph node metastasis by the lymphatic invasion diagnosed by D2-40 was significantly higher (89%, 24/27) than by H&E staining (41%, 11/27). These results suggest that the diagnosis of lymphatic invasion by D2-40 is more sensitive than H&E staining. Sensitivity for the prediction of lymph node metastasis from the lymphatic invasion status in primary tumor by D2-40 was significantly higher than by H&E staining. Based on our results, we recommend the use of D2-40 immunoreactions for the routine evaluation of lymphatic invasion in gastric cancer.

OS 02-06 PHYSIOLOGICAL REGULATION OF VASOMOTION BY INTRACELLULAR ATP-MEDIATED SYSTEM IN HUMAN ARTERY.

OBJECTIVE: Spontaneous oscillation of tone of blood vessel called vasomotion cause vessel to flow blood which is an oscillation of flow into an organ. Microcirculation is sensitive to hypoxic condition and metabolism but mechanism of vasomotion is still poorly understood. DESIGN AND METHOD: Purpose: We studied involvement of metabolism-mediated regulation by intracellular ATP level of vasomotion in human gastric artery. METHODS: Conventional contractile measuring system and Western blot were used. RESULTS: Circular muscle of human gastric artery produced sustained tonic contraction of 1.0 ±â€Š0.19 g by 50 mM high K (n = 36). Pinacidil (10 µM), which is known to activatorof ATP-sensitive K (KATP) channel inhibited vasomotion completely in a reversible manner. Inhibition of vasomotion by activators of KATP channel recovered by glibenclamide. Diazoxide (300 µM), cromakalim (10 µM) nicorandil (10 µM) which is known to activate KATP channel also completely blocked vasomotion in a glibenclamide sensitive manner. Inhibitory effect of these openers of KATP channel on serotonin and norepinephrine-induced contraction were also recoded in a glibenclmide-sensitive manner. In human artery, glucose-free condition which is elated metabolic changes inhibited vasomotion and it was recovered by glibenclamide. Finally, molecular subtypes of KATP channel was defined by Western blot in human artery. CONCLUSIONS: Vasomotion of human gastroepiploic artery was inhibited by activation of specific subtypes of KATP channel and alteration of metabolism.