Extracorporeal membrane oxygenation for the anesthetic management of a patient with severe airway stenosis caused by thyroid carcinoma invasion.

The treatment of a thyroid carcinoma extending into the thoracic cavity with severe airway stenosis is difficult, since there is a risk of acute respiratory decompensation at every stage of anesthesia. Extracorporeal membrane oxygenation (ECMO) is a life support technique for maintaining both the cardiac and respiratory functions. It is used for the management of acute, severe, reversible respiratory or cardiac failure refractory to conventional management. We herein describe the use of ECMO for the anesthetic management of an elderly patient with severe airway stenosis caused by thyroid carcinoma invasion, which underwent total thyroidectomy with the resection of four tracheal rings and end-to-end anastomosis under a median sternotomy. Although the risks and benefits should be carefully weighed before a decision to use ECMO is made, the use of ECMO in the management of general anesthesia may be a rational and effective strategy for maintaining oxygenation.

Lipid starvation and hypoxia synergistically activate ICAM1 and multiple genes in an Sp1-dependent manner to promote the growth of ovarian cancer.

BACKGROUND: Elucidation of the molecular mechanisms by which cancer cells overcome hypoxia is potentially important for targeted therapy. Complexation of hypoxia-inducible factors (HIFs) with aryl hydrocarbon receptor nuclear translocators can enhance gene expression and initiate cellular responses to hypoxia. However, multiple molecular mechanisms may be required for cancer cells to adapt to diverse microenvironments. We previously demonstrated that a physical interaction between the ubiquitously expressed transcription factor Sp1 and HIF2 is a major cause of FVII gene activation in poor prognostic ovarian clear cell carcinoma (CCC) cells under hypoxia. Furthermore, it was found that FVII activation is synergistically enhanced when serum-starved cells are cultured under hypoxic conditions. In this study, we investigated whether HIFs and transcription factor Sp1 cooperate to activate multiple genes in CCC cells under conditions of serum starvation and hypoxia (SSH) and then contribute to malignant phenotypes. METHODS: To identify genes activated under hypoxic conditions in an Sp1-dependent manner, we first performed cDNA microarray analyses. We further investigated the molecular mechanisms of synergistic gene activations including the associated serum factors by various experiments such as real-time RT-PCR, western blotting and chromatin immunoprecipitation. The study was further extended to animal experiments to investigate how it contributes to CCC progression in vivo. RESULTS: ICAM1 is one such gene dramatically induced by SSH and is highly induced by SSH and its synergistic activation involves both the mTOR and autonomously activated TNFα-NFκB axes. We identified long chain fatty acids (LCFA) as a major class of lipids that is associated with albumin, a serum factor responsible for synergistic gene activation under SSH. Furthermore, we found that ICAM1 can be induced in vivo to promote tumor growth. CONCLUSION: Sp1 and HIFs collaborate to activate genes required for the adaptation of CCC cells to severe microenvironments, such as LCFA starvation and hypoxia. This study highlights the importance of transcriptional regulation under lipid starvation and hypoxia in the promotion of CCC tumor growth.

Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment.

Protein disulfide isomerase (PDI), an endoplasmic reticulum chaperone protein, catalyzes disulfide bond breakage, formation, and rearrangement. The effect of PDI inhibition on ovarian cancer progression is not yet clear, and there is a need for potent, selective, and safe small-molecule inhibitors of PDI. Here, we report a class of propynoic acid carbamoyl methyl amides (PACMAs) that are active against a panel of human ovarian cancer cell lines. Using fluorescent derivatives, 2D gel electrophoresis, and MS, we established that PACMA 31, one of the most active analogs, acts as an irreversible small-molecule inhibitor of PDI, forming a covalent bond with the active site cysteines of PDI. We also showed that PDI activity is essential for the survival and proliferation of human ovarian cancer cells. In vivo, PACMA 31 showed tumor targeting ability and significantly suppressed ovarian tumor growth without causing toxicity to normal tissues. These irreversible small-molecule PDI inhibitors represent an important approach for the development of targeted anticancer agents for ovarian cancer therapy, and they can also serve as useful probes for investigating the biology of PDI-implicated pathways.

Omentum-preserving gastrectomy for advanced gastric cancer: a propensity-matched retrospective cohort study.

BACKGROUND AND OBJECTIVES: We clarified the impact of omentectomy for advanced gastric cancer on patient survival from the surgical results of a high-volume center in Japan. METHODS: Patients who received curative gastrectomy were divided into two groups based on whether they underwent omentectomy. The propensity score-matching method was used to assemble a well-balanced cohort, and relapse-free survival and the pattern of recurrence were compared. RESULTS: For this study, 330 patients who fulfilled the inclusion criteria participated and were divided into two groups: group R, patients who received omentectomy, and group P, patients who received omentum-preserving gastrectomy. After performing score-matching, 196 patients were selected. The 3- and 5-year relapse-free survival rates were 72.9% (95% confidence interval, 64.1-81.7) and 66.2% (56.6-75.8%) in group R, and 76.7% (67.9-81.2) and 67.3% (55.1-79.5) in group P, which were not significantly different (P = 0.750). Regarding sites of relapses, no differences were observed between the groups (P = 0.863). CONCLUSIONS: In this series, omentum-preserving gastrectomy for advanced gastric cancer did not increase the peritoneal relapse rate or affect patient survival compared to conventional gastrectomy. The non-inferiority of the omission of omentectomy should be evaluated by a randomized controlled trial.

A randomized phase II trial of omentum-preserving gastrectomy for advanced gastric cancer.

This randomized Phase II trial is being conducted to evaluate the impact of omentectomy for advanced gastric cancer on patient survival. The primary endpoint is the 3-year relapse-free survival rate and the secondary endpoints are 5-year overall survival, intraoperative blood loss, length of the operation and postoperative morbidity (especially postoperative ileus). The planned sample size is 250 patients (125 for complete removal of the omentum and 125 for preservation of the omentum) to determine whether omentum-preserving gastrectomy may be a candidate procedure for a Phase III trial in a randomized Phase II setting.

Usefulness of multidisciplinary therapy combining neoadjuvant chemotherapy with S-1 plus cisplatin and postoperative sequential chemotherapy in patients with scirrhous gastric cancer.

BACKGROUND/AIMS: The outcomes of patients with scirrhous gastric cancer (SGC) remain poor. We retrospectively compared outcomes according to historically different treatments for SGC and studied the therapeutic usefulness of NAC with S-1 plus cisplatin followed by postoperative sequential chemotherapy. METHODOLOGY: We studied 93 patients with SGC. Between 1995 and 2000, 29 patients did not receive NAC and were instead given conventional anti-cancer drugs. Between 2000 and 2003, 20 patients received 4 weeks of NAC with low-dose cisplatin plus 5-fluorouracil (5-FU) followed by postoperative sequential treatment with new anticancer agents (neoadjuvant low-dose FP group). Between 2003 and 2006, 44 patients received 2 courses of NAC with S-1+cisplatin followed by postoperative sequential administration of new anticancer agents (neoadjuvant S-1+cisplatin group). Response rates and overall survival were compared among the treatment groups. RESULTS: The rates of response to NAC were 15% in the neoadjuvant low-dose FP group and 36% in the neoadjuvant S-1+cisplatin group. Overall survival was significantly longer in the neoadjuvant S-1+cisplatin group than the other groups. CONCLUSIONS: Our results suggest that multidisciplinary therapy combining NAC with S-1+cisplatin and postoperative sequential administration of new anticancer drugs is therapeutically useful in patients with SGC.

Combination effects of SC144 and cytotoxic anticancer agents.

Previously, we synthesized a series of hydrazide class of compounds and examined their cytotoxicity in a number of cancer cell lines. Among these analogues, SC144 exhibited potent cytotoxicity against a panel of drug-sensitive and drug-resistant cancer cell lines. To further explore its therapeutic potentials in the combination settings, we evaluated the synergy between SC144 and selected conventional chemotherapeutic agents in in-vitro cancer cell models. SC144 showed synergism with both 5-fluorouracil and oxaliplatin when cotreated in colorectal cancer HT29 cells. Pretreatment with SC144 in oxaliplatin-resistant HTOXAR3 cells was more effective than oxaliplatin pretreatment. In addition, the combination of SC144 and paclitaxel exhibited synergism in MDA-MB-435 cells with a schedule-dependent block in cell cycle. In an MDA-MB-435 mouse xenograft model, coadministration of SC144 and paclitaxel delayed tumor growth in an SC144 dose-dependent manner. Evaluation of the pharmacokinetics of SC144 revealed that intraperitoneal administration of SC144 showed a two-compartmental pharmacokinetics elimination profile that was not observed in the oral dosing. In summary, these studies further validate SC144 as a novel anticancer agent and provide insights for developing combination therapies for both drug-sensitive and drug-resistant cancers.

Overexpression of the fibroblast growth factor receptor-1 gene correlates with liver metastasis in colorectal cancer.

Expression of the fibroblast growth factor (FGF)-1, FGF-2, fibroblast growth factor receptor (FGFR)-1, and FGFR-2 genes has been reported in various cancers and is associated with poor outcomes in patients with solid tumors. This study examined the relations between the relative expression of the FGF genes and clinicopathological factors, especially invasion and metastasis, in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal carcinoma. The relative expression levels of FGF-1, FGF-2, FGFR-1, and FGFR-2 mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time, reverse-transcription polymerase chain reaction. The relative expression level of the FGFR-2 gene was higher in normal adjacent mucosa than in cancer, whereas the relative expression levels of the FGF-1, FGF-2, and FGFR-1 genes were similar. FGFR-1 gene expression levels were higher in the presence than in the absence of liver metastasis. An analysis of the relation between clinicopathological features and gene expression showed that overexpression of FGFR-1 correlated with liver metastasis. Our results suggested that overexpression of the FGFR-1 gene might lead to liver metastasis in colorectal cancer. Overexpression of the FGFR-1 gene may thus be a useful predictor of liver metastasis in patients with colorectal cancer.

Clinicopathological significance of the gene expression of matrix metalloproteinase-7, insulin-like growth factor-1, insulin-like growth factor-2 and insulin-like growth factor-1 receptor in patients with colorectal cancer: insulin-like growth factor-1 receptor gene expression is a useful predictor of liver metastasis from colorectal cancer.

Matrix metalloproteinase-7 (MMP-7), secreted by cancer cells, has been implicated classically in the basement membrane destruction associated with tumor cell invasion and metastasis. Epidemiological studies have established a correlation between high levels of circulating insulin-like growth factor-1 (IGF-1) and the relative risk of colorectal cancer, which is known to produce MMP-7. We examined the clinicopathological significance of the relative expression of MMP-7, IGF-1, IGF-2 and IGF-1 receptor genes in patients with colorectal cancer, especially with regard to metastasis. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 205 patients with untreated colorectal carcinoma. MMP-7, IGF-1, IGF-2, IGF-1R and beta-actin mRNA in cancer tissue and adjacent normal mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. MMP-7 and IGF-1R gene expression levels were higher in cancer tissue than in adjacent normal mucosa. In contrast, IGF-1 gene expression was lower in cancer tissue than in adjacent normal mucosa. As for the relationship of gene expression to clinicopathological factors, IGF-1R expression correlated with venous invasion and liver metastasis. IGF-1R gene expression is thus considered a useful predictor of liver metastasis from colorectal cancer.

Reduced expression of the claudin-7 gene correlates with venous invasion and liver metastasis in colorectal cancer.

Claudins, members of a large family of adherent junction proteins, regulate the integrity and function of tight junctions and influence tumorigenesis. Studies have suggested that altered levels of different claudins are related to carcinoma-cell invasion and disease progression. This study examined the relationship between the relative expression of claudin genes and clinicopathological factors, especially invasion and metastasis, in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa from 205 patients with untreated colorectal carcinoma. The relative expression levels of claudin-1, -3, -4 and -7 mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time, reverse-transcription polymerase chain reaction. The relative expression levels of the claudin-1, -3 and -4 genes were higher in cancer than in normal adjacent mucosa, whereas the relative expression of the claudin-7 gene was similar. An analysis of the relationship between the clinicopathological features and gene expression showed that reduced expression of claudin-7 correlated with venous invasion and liver metastasis. There was also a correlation between claudin-3 and -4 gene expression. Our results suggested that a reduced expression of the claudin-7 gene might lead to venous invasion and liver metastasis in colorectal cancer. Reduced expression of the claudin-7 gene may thus be a useful predictor of liver metastasis in patients with colorectal cancer.

Clinicopathological significance of the gene expression of matrix metalloproteinases and reversion-inducing cysteine-rich protein with Kazal motifs in patients with colorectal cancer: MMP-2 gene expression is a useful predictor of liver metastasis from colorectal cancer.

Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and membrane-type matrix metalloproteinase 1 (MT1-MMP) are involved in colorectal cancer invasion and metastasis. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) inhibits MMP-2, MMP-9 and MT1-MMP. We examined the clinicopathological significance of the relative expression of these genes in patients with colorectal cancer, especially with regard to metastasis. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 205 patients with untreated colorectal carcinoma. MMP-2, MMP-9, MT1-MMP, RECK and beta-actin mRNA of cancer tissue and adjacent normal mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. MT1-MMP gene expression was higher in cancer tissue than in adjacent normal mucosa. In contrast, MMP-2, MMP-9 and RECK gene expression levels were lower in cancer tissue than in adjacent normal mucosa. As for the relationship between the gene expression and clinicopathological factors, MMP-2 expression correlated with the depth of invasion, venous invasion and liver metastasis; MMP-9 and RECK expression correlated with venous invasion. There were positive correlations among the gene expression levels of MMP-2, MMP-9 and RECK. MMP-2 gene expression was considered a useful predictor of liver metastasis from colorectal cancer.

Evaluation of calorie intake according to age and sex in patients undergoing surgery for gastric cancer.

BACKGROUND/AIMS: We studied food intake in 107 patients undergoing gastric surgery, with emphasis on postoperative quality of life (QOL). The time course of food intake after surgery, sex- and age-related differences in food intake, and the relation of food intake to surgical procedure were evaluated retrospectively. METHODOLOGY: The following variables were studied: 1) the time required for stabilization of food intake, assessed on the basis of the time course of food intake after operation; 2) the relations of sex and age to postoperative food intake, assessed by comparing food intake according to sex and age; and 3) postoperative food intake according to surgical procedure, evaluated by calculating the ratio of postoperative food intake to the food intake of healthy individuals matched for sex and age. RESULTS: At 6, 12, and 24 months after operation, there was no difference in food intake among the three operative procedures; food intake was stable from 6 months onward. When food intake was analyzed according to age, similar trends were seen in men and women, and there were no significant differences in food intake among patients in their 40s, 50s, or 60s. Food intake was significantly lower in patients in their 70s than in patients in the other age groups. Food intake even in women with significantly decreased food intake or in patients 70 years or older was not necessarily low as compared with food intake levels in healthy individuals. CONCLUSIONS: Food intake is substantially affected by the period of time after surgery, as well as by sex, and age at the time of surgery.

Modified POSSUM to predict postoperative morbidity following gastrectomy.

BACKGROUND/AIMS: In order to predict morbidity after gastrectomy for gastric cancer in aged patients, the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) scoring system was applied. METHODOLOGY: A total of 123 patients who had gastrectomies for gastric cancer at the age of 75 or above, between 1994 and 2002, were enrolled in this study. Postoperative morbidities and mortalities were analyzed and POSSUM scores were calculated. RESULTS: The predicted mortality and morbidity rates according to the POSSUM scores in this series were 47.9% and 14.1% respectively. The observed morbidity and mortality rates were 39.8% and 1.6% respectively. Using these results, we created a modified POSSUM equation to predict the morbidity in this population, expressed as ln[R/(1-R)] = -2.59 + (0.087 x PS) + (0.013 x OS), where PS: Physiological Severity, OS: Operative Severity, R=predicted morbidity rate. We applied this equation prospectively to 26 patients who underwent gastrectomies in 2003. The figures for predicted morbidity and observed morbidity were 37.3% and 38.5% respectively, indicating that our modified equation predicted morbidity more accurately than the POSSUM. CONCLUSIONS: The POSSUM over-predicted the morbidity of patients who underwent gastrectomy. However, after creating a modified equation using data from retrospective analysis, a modified POSSUM was found to predict the prospective morbidity rate accurately.

Lateral lymph node dissection for lower rectal cancer.

BACKGROUND/AIMS: This study was conducted to evaluate the effects of lateral lymph node dissection (LLD) on overall survival, disease-free survival, and local recurrence for the patients with lower rectal cancer. METHODOLOGY: From 1990 through 2000, 169 consecutive patients with T2 (TNM classification) or more advanced, extended lower rectal cancer (located below the peritoneal reflection) underwent curative resection at Kanagawa Cancer Center were reviewed. One hundred and forty-three patients who underwent LLD and the 26 patients who did not were entered in this study. RESULTS: Cox's multivariate regression analysis showed T stage (TMN classification), N stage (TNM classification), and LLD were found to be significantly related to the rates of both cumulative survival and disease-free survival. That mean LLD was identified as a significant prognostic factor. But disease-free survival did not differ significantly between the patients who underwent LLD and those who did not undergo LLD in stage I, II, or III disease (p = 0.3681, p = 0.1815, and p = 0.0896, respectively). The local recurrence rate was similar in patients who received LLD (17.5 percent) and in those who did not receive LLD (23.1 percent; p = 0.498). But 7 patients with lateral lymph node metastasis (33.3 percent) remained disease free. And these patients had local lateral lymph node metastasis and benefited from LLD. CONCLUSIONS: LLD can substantially improve outcomes in selected patients at high risk for lateral lymph node metastasis. A randomized controlled clinical study is necessary to clarify the role of LLD in the treatment of rectal cancer.

13C-urea breath test in patients having undergone total gastrectomy.

BACKGROUND/AIMS: In this study, we performed 13C-urea breath test in patients who had undergone total gastrectomy and investigated the content of (13)CO2 in the CO2 gas expired after direct influx of 13C-urea into the small intestine. METHODOLOGY: 13C-Urea breath test was performed in 31 patients who had undergone total gastrectomy at this department for the treatment of stomach cancer and consented to participate in this study. The test was performed in two ways, i.e. with and without mouth washing (gargling) on taking 13C-urea. RESULTS: Among 41 measurements, the delta13C was less than 2.5% per hundred in 9 measurements (22.2%) and less than 2.0% per hundred in 6 measurements (14.6%). The delta13C exceeded 50% per hundred, in 4 subjects (9.8%). There were no differences between the methods with and without gargling. CONCLUSIONS: The results of this study suggested the possibility that 13C-urea is decomposed even in the jejunum or the lower part of intestine resulting in absorption of H(13)CO3 and another possibility that 13C-urea is directly absorbed from the intestine and decomposed in the blood.

Bone disorder and vitamin D after gastric cancer surgery.

BACKGROUND/AIMS: The present study was conducted to investigate the relationship between bone metabolic disorder after gastrectomy for gastric cancer and vitamin D metabolites or the hormones involved in calcium metabolism. METHODOLOGY: Twenty-one patients who had undergone gastrectomy for gastric cancer and had been followed for less than 10 years were assessed for bone disorder by microdensitometry. The levels of 1,25-dihydroxy vitamin D (1,25(OH)2VD), 25-hydroxy vitamin D (25(OH)VD), 24,25-dihydroxy vitamin D (24,25(OH)2VD), N-PTH, calcitonin, estradiol, osteocalcin, and ALP were measured and assessed for correlations with clinicopathological factors, including the operative procedure and the number of years since surgery. RESULTS: Bone disorder was found in 9 out of 21 patients (42.9%). The prevalence was significantly higher in patients who had undergone surgery more than 2 years before assessment, so there was a relationship between the period after surgery and bone disorder. Among the vitamin D metabolites, the level of 1,25(OH)2VD was normal in all patients, whereas 25(OH)VD was reduced in 6 out of 21 patients (28.6%) and 24,25(OH)2VD was reduced in 17 patients (81.0%). The 1,25(OH)2VD was significantly higher in the patients with Grade I to III bone disorder compared to the patients with normal bones or early bone disease. The 1,25(OH)2VD/25(OH)VD ratio was significantly higher in the patients without passage of food through the duodenum due to the reconstructive method, while the 25(OH)VD/24,25(OH)2VD ratio was significantly higher in the patients with remaining of duodenal food passage. PTH was decreased in about 50% of the patients, while calcitonin was normal in all patients. Estradiol was decreased in one female patient, while it was elevated in 10 of the 17 men (58.8%). The osteocalcin level was high in all patients irrespective of the period after surgery. CONCLUSIONS: After gastrectomy, the incidence of bone metabolic disorder increases with time. Changes of vitamin D metabolites, particularly 25(OH)VD and 24,25(OH)2VD, seem to be closely associated with post-gastrectomy bone disease.

Laparoscopy-assisted distal gastrectomy with 3-cm laparotomy, left hepatic lobe compression technique, and selection of automatic anastomosis device.

In this study, we performed laparoscopy-assisted distal gastrectomy (LADG) and lymph node dissection with an incision of 3 cm aiming at radical cure and low invasiveness. We introduce and discuss this technique of minilaparotomy and recommend a device for anastomosis. In LADG, a skin incision of 5cm or greater is made in order to pull out the stomach in other institutes. Whether function is distinctly better after laparoscopy-assisted surgery than after abdominal section has not been elucidated so far, so we should seek an aesthetic advantage. We have used a 3-cm abdominal wound to date. If the wound is smaller than this, the body of the SDH25 cannot be inserted, and currently a wound less than 3cm may thus not be possible. The shaft of the SDH is straight, making it easy to confirm the direction even through a laparoscope. The shaft of the anvil head of the PPCEEA is too long, so that when it is connected with the body through the 3-cm incision, it is necessary to draw it through the remnant stomach to a great extent.

Clinicopathological features of skip metastasis in colorectal cancer.

BACKGROUND/AIMS: Japanese general rules for the staging of colorectal cancer conventionally classify lymph node metastasis into three groups according to location with respect to the primary tumor. Skip metastasis, in which distant nodes are positive but regional nodes are negative, is often encountered but poorly understood. We studied the clinicopathological features of skip metastasis in colorectal cancer. METHODOLOGY: The location of positive nodes was classified in 323 patients with Dukes' stage C colorectal cancer. Skip n2 lymph node metastasis was defined as positive N2 metastasis without negative N1 or N3 metastasis. Clinicopathological findings and survival were compared between the patients with skip n2 metastasis (skip n2 group) and those with n1 (n1 group) or n2 metastasis (n2 group). RESULTS: There were 211 patients in the n1 group, 91 in the n2 group, and 21 in the skip n2 group. Pathological examination showed that the skip n2 group had fewer positive nodes than the n1 and n2 groups, but was positioned between these groups with respect to the degree of lymphatic invasion. Cumulative survival was significantly poorer in the n2 group than in the skip n2 group (p = 0.039 by log-rank test). Survival was similar in the skip n2 group and n1 group. There was also no difference in survival between patients in the skip n2 group and patients with one, two, or three N1 metastases. CONCLUSIONS: Lymph nodes with skip n2 metastasis are most likely sentinel nodes of the primary tumor in patients with colorectal cancer. The prognosis of patients with skip n2 metastasis is therefore better than that of patients with n2 metastasis and similar to that of patients with n1 metastasis.

The validity of sentinel lymph node biopsy using dye technique alone in patients with gastric cancer.

BACKGROUND/AIMS: We investigated whether sentinel lymph node biopsy using dye technique alone is useful or not in decision-making for less invasive surgery in patients with gastric cancer. METHODOLOGY: The subjects were 43 patients who had undergone laparotomy for gastric cancer and consented to undergo sentinel lymph node biopsy using patent blue dye. The patients enrolled were 26 males and 17 females, with a mean age of 62.5 years. The tumor sites were upper third of the stomach in 14, middle third in 16, and lower third in 13 patients. The depth of invasion was mucosa in eight, submucosa in 19, muscularis propria in five, subserosa in five, and serosa in six patients. Total gastrectomy was performed in 12, subtotal gastrectomy in 28, and proximal gastrectomy in three patients. RESULTS: The mean number of sentinel lymph node biopsies per surgery was 3.5 +/- 4.1. We were able to perform blue node biopsy in 40 out of 43 patients, but could not find any blue nodes in three patients. Among the 40 patients in whom blue nodes were identified, 29 patients with no metastasis in blue nodes had no evidence of lymph node metastasis (NO). The depth of invasion was not deeper than subserosa in all these patients. Metastasis was observed in one out of the three patients in whom no blue nodes were found. CONCLUSIONS: When the depth of invasion was not deeper than the subserosa and blue nodes were identified, no metastases in either non-blue nodes or blue nodes could be found in the absence of metastatic blue nodes. Therefore, if the depth of invasion is not deeper than the subserosa in gastric cancer, metastatic search in blue nodes seems sufficient and less invasive surgery can be performed safely. Even when the invasion depth is not deeper than the submucosa, the tumor could be metastatic to Group 2 lymph nodes in patients in whom blue node biopsy revealed metastases. When metastasis is found in lymph nodes by intraoperative frozen section diagnosis, less invasive surgery for gastric cancer is not indicated.

Water-generated negative air ions activate NK cell and inhibit carcinogenesis in mice.

Negative ions are considered to have potential health benefits, but few studies have examined their effects in vivo. We studied water-generated negative ions (WNI) with respect to physical properties as well as immunologic activation and anti-tumor activity (inhibition of carcinogenesis and tumor growth) in mice. Electrically, generated negative ions (ENI) served as control. Water-generated negative ions had a long life, significantly enhanced the cytotoxic activity of natural killer cells, and significantly decreased the incidence of cancer and inhibited tumor growth. Anti-tumor effects were attributed to enhancement of natural killer cell activity. The mechanisms and applications of negative ions warrant further investigation.