Peripheral circulation evaluation with near-infrared spectroscopy in skeletal muscle during cardiopulmonary bypass.

BACKGROUND: We designed a non-invasive, observational, real-time study, using near-infrared spectroscopy (NIRS) to assess the in vivo effects of cardiopulmonary bypass (CPB) on patients' skeletal muscle as well as the effects of hemodilution and hypothermia on tissue oxygen delivery during CPB. METHODS: The study included 20 consecutive adult patients undergoing open-heart surgery with CPB. Evaluation parameters for peripheral circulation were measured using the NIRO-200NX and recorded every 30 seconds. To assess how hemodilution influences peripheral circulation parameters, we compared data between a group of patients with hematocrit (Hct) values >22% (high Hct group) and those with Hct values ⩽22% (low Hct group). RESULTS: Changes in the concentration of oxygenated hemoglobin (ΔO2Hb, µmol/L), which flows into the skeletal muscle, was an important factor for deciding the tissue oxygenation index (TOI%), showing the tissue oxygen saturation. The low Hct group showed a significant increase in the normalized tissue hemoglobin index (nTHI), showing the percentage change in the amount of initial hemoglobin and TOI compared to the high Hct group. Changes in the concentration of oxygenated hemoglobin (ΔO2Hb, µmol/L) and deoxygenated hemoglobin (ΔHHb, µmol/L) were significantly less in the low Hct group than in the high Hct group, thus, showing good peripheral circulation despite the low hematocrit levels. CONCLUSION: Our study indicated the presence of a compensatory mechanism in which increased blood flow of the microcirculation is in compensation for the lack of oxyhemoglobin delivery caused by hemodilution.

Minimally invasive video-assisted thoracoscopic lobectomy for better clinical outcomes in peripheral T1NO lung cancer.

It is an unresolved issue whether various thoracotomies affect clinical outcomes. In addition, a wide variety of technical approaches of video-assisted thoracic surgery depend on the facility. We reviewed 152 consecutive patients with clinical T1N0M0 lung cancer that underwent three types of lobectomy with systematic mediastinal lymphadenectomy in a single institute: 46 conventional thoracotomies (OPEN), 50 anterolateral small thoracotomies mainly using the thoracoscope as a light guide (ASSIST), and 56 minimum thoracotomies in which only a thoracoscope view was used (PURE). Total discharge from the chest drainage tube, length of hospital stay, and post-thoracotomy pain were significantly less in PURE than in OPEN and ASSIST. The results of mediastinal lymphadenectomy were equivalent. The 3-year survival rates were also similar among the three groups. We conclude that good clinical outcomes, especially reduced post-thoracotomy pain, seemed to correlate with the lesser degree of destruction of the chest wall with the identical quality as an acceptable cancer operation in PURE.

Effect of magnesium sulfate pretreatment and significance of matrix metalloproteinase-1 and interleukin-6 levels in coronary reperfusion therapy for patients with acute myocardial infarction.

Magnesium (Mg) inhibits the influx of calcium in vascular smooth muscle cells. The purposes of this study were to test the hypothesis that an intravenous administration of magnesium might effect the complement response and to determine the effects of a magnesium pretreatment of patients with acute myocardial infarction (AMI) on the incidence of reperfusion injuries. Thirty-eight AMI patients were treated with coronary reperfusion therapy within 6 hours of onset. They were randomly divided into two groups: group pretreated with intravenous magnesium sulfate (0.27 mmol/kg) (magnesium group, n = 19), and nonpretreated controls (placebo group). The reperfusion injuries observed within 1 hour after the coronary reperfusion included arrhythmias, aggravated chest pain, and ST segment elevation in 12-lead electrocardiograms. Coronary recanalization was performed in 36 patients. The incidence of reperfusion arrhythmia was significantly lower in the magnesium group than in the placebo group (17% vs 78%, p<0.001). At the postreperfusion stage, there was a tendency for the degree of ST segment reelevation in the magnesium group lower than in the placebo group (2.5 +/- 2.3 mm vs 4.7 +/- 3.8 mm, p = 0.07). No marked difference was observed in the incidence of chest pain aggravation between the two groups (67% vs 73%, ns). The peak serum levels of interleukin-6 (IL-6) were significantly lower in the magnesium group than those in the placebo group (38.9 +/- 25.0 vs 92.3 +/- 76.5 pg/mL, p = 0.016). The peak serum levels of matrix metalloproteinase-1 (MMP-1) were lower than those in the placebo group (16.2 +/- 4.8 vs 19.7 +/- 9.0 ng/mL, p = 0.09), but the difference was not significant. A positive correlation was observed between the peak MMP-1 values and the peak IL-6 values (r = 0.57, p = 0.001) in all patients. Increased serum ionized Mg2+ may inhibit arrhythmic recurrence and the production of IL-6 and MMP-1 after reperfusion and prevent the increase of myocardial lesions caused by calcium overload on myocytes. The increased IL-6 production may induce MMP-1, leading to tissue organ injury. Pretreatment with magnesium sulfate may protect the myocardium of AMI patients from reperfusion injuries.

Laparoscopic resection of submucosal gastric tumors.

In order to elucidate the efficacy in gastric surgery, we evaluated seven resected cases of a submucosal gastric tumor in which laparoscopic techniques were used. The patients consisted of 1 man and 6 women. The tumors were located in the upper, middle, and lower third of the stomach in 4, 1, and 2 cases, respectively. Three tumors were located mainly on the anterior gastric wall, 2 were on the posterior wall, and 2 were on the lesser curvature. The resected tumor size averaged 3.2 x 2.6 cm. The tumors were classified as intraluminal type (4 cases) and the extraluminal type (3 cases) according to the classification of growth type. A histopathological examination identified 4 leiomyomas, 1 leiomyosarcoma, and 4 smooth muscle tumors of indeterminate malignant potential. After a tumor resection, no recurrence of the lesions occurred during the postoperative follow-up. An extraluminal growing tumor was easily resected by the laparoscopic method without any additional procedures, and this therefore seemed to be a good indication for the laparoscopic method. In contrast, an intraluminal tumor was found to be more difficult to resect using the laparoscopic method without a companion method, e.g., intraoperative endoscopy, because of the difficulties in the detection and resection of the tumor from the serosal side. A more efficient technique must therefore be developed for this type of tumor.

Finger bougie method compared with pyloroplasty in the gastric replacement of the esophagus.

To elucidate the necessity of pyloroplasty for the gastric tube through the posterior mediastinum in esophageal surgery, gastric emptying and duodenogastric reflux (DGR) were evaluated in 16 cases undergoing an anterior pylorectomy (group P) and in 16 cases treated by the finger bougie method (group F). First, the obstruction and reflux symptoms were examined based on a patient questionnaire using a brief scoring system. The median value of the symptom score showed the patients in P to have more symptoms than those in F; however, the difference was not significant (8.0 vs 6.0). Secondly, the swallowed Tc O4- (85MBq) was counted using a gamma camera at three sites on the sternal bone in the upright position based on a gastric transit scintigram. Both the descending time of the RI peak and the clearance rates were similar between the two groups. Thirdly, intragastric 24-h pH monitoring was carried out. Antimony pH sensors were anchored 5 and 15cm below the esophagogastrostomy. We could not find any difference between the two groups in both the %time pH > 4 and %time pH > 7. These findings thus revealed no big difference between groups P and F. The finger bougie method to drain the vagotomized posterior mediastinal stomach was found to achieve results similar to conventional pyloroplasty, while it was also simpler and safer.

Renormalization group for renormalization-group equations toward the universality classification of infinite-order phase transitions.

We derive a renormalization group to calculate the nontrivial critical exponent of the divergent correlation length, thereby providing a universality classification of essential singularities in infinite-order phase transitions. This method thus resolves the vanishing scaling matrix problem. The exponent is obtained from the maximal eigenvalue of a scaling matrix in this renormalization group, as in the case of ordinary second-order phase transitions. We exhibit several nontrivial universality classes in infinite-order transitions different from the well known Berezinskii-Kosterlitz-Thouless transition.

Poor prognosis in esophageal cancer patients with postoperative complications.

We investigated the relationship between postoperative complications and prognosis in esophageal cancer patients. Two hundred five patients with esophageal cancer were divided into three case groups. Group A (n = 100) consisted of cases without postoperative complications. Groups B (n = 58) and C (n = 47) consisted of cases with minor and major postoperative complications. The 5-year survival rates were 41.8%, 21.3%, and 20.2% in groups A, B, and C, respectively. There was a significant difference in the prognosis between groups A and B, and also between groups A and C. Any patients who died within 5 years without a relapse their cases were excluded from the study; the 5-year survival rates were 46.7%, 32.3%, and 22.5% in groups A, B, and C, respectively, with a significant difference between groups A and B. There were no significant differences between the three groups regarding the patient characteristics. These results therefore indicate that postoperative complications might contribute to a poor prognosis in cancer patients.

Clinical evaluation of adjuvant chemoradiotherapy with CDDP, 5-FU, and VP-16 for advanced esophageal cancer.

OBJECTIVES: The aim of this study was to evaluate the efficacy of adjuvant chemoradiotherapy following surgery in patients with advanced esophageal cancer. SUBJECTS AND METHODS: We followed the cases of 57 such patients treated at our hospital, involving 19 who received adjuvant chemoradiotherapy (CR group), 19 who received radiotherapy alone (R group), and 19 who did received neither (N group). In the CR group, chemotherapy, consisting of cis-diaminodichloroplatinum (CDDP), 5-fluorouracil (5-FU), and etoposide (VP-16), was combined with radiotherapy was administered from 4 weeks after surgery. Concurrent radiotherapy was started at 3 weeks after esophagectomy. CDDP at 50 mg/m2 was administered on days 1 and 7.5-FU at 500 mg/m2 and VP-16 at 60 mg/m2 were administered on days 3, 4, and 5. Thirteen patients (68.4%) were treated with more than 2 cycles of chemotherapy combined with radiation. RESULTS: Side-effects of severe anorexia (grade 3) and leukocytopenia (< 1900/microliter) were observed in 47% and 39% of the patients, respectively. However no treatment-related death was observed. The 5-year-survival rate was 25.2%, 18.9%, and 15.8%, in the CR group, R group, and N group, respectively. The recurrence rate was 66.7% in the CR group, which was higher than in the matched control groups (46.2% in the N group and 54.5% in the R group), but with no a significant difference. CONCLUSION: These results suggested that adjuvant chemoradiotherapy did not contribute to improvement in prognosis for these patients with advanced esophageal cancer.

Profound duodenogastric reflux causes pancreatic growth in rats.

Although duodenogastric reflux is a physiological event, excessive reflux may be a pathogenetic factor in several diseases of the foregut, including cancer. Long term profound duodenogastric reflux produces pancreatic and gastric tumours in rats. The trophic effect of surgically induced duodenogastric reflux on the pancreas was investigated and the mechanisms involved were examined. Rats with profound reflux from a split gastroenterostomy were compared with sham operated and unoperated controls after two and six weeks. In the six week experiment, one reflux and one sham group were given the cholecystokinin (CCK) receptor antagonist devazepide (25 nmol/kg/h). Duodenogastric reflux caused a significant increase in pancreatic weight, DNA, and plasma CCK and gastrin concentrations at both two and six weeks. Devazepide substantially reduced the pancreatic weight increase after six weeks but did not abolish it completely. CCK and gastrin were not affected by devazepide. These results suggest that CCK is largely responsible for the pancreatic growth induced by reflux but another factor may also be involved. The trophic effect of duodenogastric reflux may contribute to the increased incidence of pancreatic cancer reported after gastric surgery.

The inhibitory effect caused by suramin on the paracrine growth of human cancer cells and fibroblasts.

The growth interactions between human cancer cells and primary cultured human fibroblasts, and the effects of suramin on them, were investigated using a double-chamber technique combined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Human fibroblasts obtained from various organs resected surgically were cultured in a monolayer and used after the third or fourth passage. In the double-chamber assay, the growth of cancer cells in the top chamber was significantly stimulated by some types of fibroblasts in the bottom chamber in a fibroblast density-dependent manner. Interestingly, the growth of cancer cells was stimulated at 140%-147% by fibroblasts obtained from an organ where cancer cells had developed, the MCF-7 versus mammary fibroblasts, and in LS-180 versus colonic fibroblasts, but not by their fibroblast-conditioned medium. Suramin completely inhibited the growth-enhancing interaction between MCF-7 and mammary fibroblasts, and between SH-101 and lung fibroblasts at a clinical concentration of from 50 micrograms/ml to 300 micrograms/ml. It also reduced the growth of LS-180 co-cultured with colon-fibroblasts, but the inhibitory effect was incomplete. These results suggest that mutual growth reliance exists between human cancer cells and primary cultured fibroblasts by diffusible factors secreted by both cells, and that these enhancing effects are related in part to the growth and metastasis of cancer cells in vivo. Suramin was found to have an inhibitory effect on their interaction at a clinically achievable concentration in vitro.

Investigation of suitability of devascularized upper half of the whole stomach as replacement for the esophagus.

One hundred and fifteen patients with esophageal cancer underwent esophageal replacement with the stomach. The patients were divided into group A (52 patients, stomach tube, ante- or retro-sternal route) and group B (54 patients, devascularized upper half of the whole stomach, posterior mediastinal route). The post-operative complications, post operative symptoms and nutritional status were investigated in both groups. Lung complications tended to occur more frequently in group A (28.8% versus 22.2%), showing no significant difference. The incidence of other complications did not show a remarkable difference between either group except for leakage at the site of anastomosis. Major leakage occurred in 11.5% and 5.6%, and minor leakage in 30.8% and 18.5%, respectively. Postprandial fullness, nausea, heart burn and diarrhea were found to be somewhat higher in Group B. Change of oral intake, body weight and other indices of nutritional status were investigated and compared with pre- operative data. The amount of oral intake and levels of serum albumin was higher in group B than in group A between one and 12 months. These results demonstrate the superiority of the devascularized upper half of the whole stomach as an esophageal substitute.

Clinical significance of the expression of epidermal growth factor and its receptor in esophageal cancer.

The epidermal growth factor receptor (EGFR) level in 56 esophageal cancer tissues was measured by 125I-EGF binding assay to elucidate its role in tumor progression. The survival rate of patients with high EGFR level (more than 50 fmol/mg protein) was significantly lower than that of patients with low EGFR level (less than 50 fmol/mg protein, P less than 0.01), although a correlation between EGFR level and the pathologic findings was not observed. The expression of EGF was examined immunohistochemically using anti-EGF monoclonal antibody in 100 esophageal cancer tissues; EGF-positive tumor cells were detected in 92.0%. The immunoreactivity of EGF was classified arbitrarily into four grades according to the number of stained tumor cells. The expression of EGF significantly correlated with the differentiation of esophageal squamous cell carcinoma (P less than 0.01, by chi-square test). The survival rate of patients with high EGF immunoreactivity (Grade 2 or 3) was much lower than in those with lower grade (0 or 1) tumors, (P less than 0.01). Patients with both high EGFR level and EGF immunoreactivity had a much worse prognosis than if both were low. Furthermore, the mitotic index was higher in groups with both high EGFR and EGF than if both were low (16.39 +/- 5.35 versus 6.90 +/- 3.31). These results suggest that EGF and EGFR in the autocrine system may play an important role in tumor progression in esophageal cancer and their expression could be of prognostic significance.

A novel in vitro chemosensitivity test using materials collected by endoscopic biopsy.

The usefulness of chemosensitivity testing of cells collected by endoscopic biopsy using the adenosine triphosphate assay (ATP assay) was investigated for esophageal tumors. Correlation between this chemosensitivity test and other chemosensitivity tests was more than 80% in most combinations. The predictive rate of clinical sensitivity was 77.8% and of clinical resistance was 68.8%. The predictive accuracy was 72.0%. These results will extend the indication and usefulness of chemosensitivity testing in inoperable and preoperable cases.

Significance of freshly cultured fibroblasts from different tissues in promoting cancer cell growth.

The interactions between human cancer cells and primary cultured human fibroblasts without cell-to-cell contact were investigated using double soft-agar culture. Human fibroblasts obtained from different organs were cultured in monolayers and used after the 3rd or 4th passage. In double soft-agar culture, colony formations of cancer cells in the overlayer were stimulated or inhibited by the presence of various kinds of fibroblast in the underlayer. The growth of all cancer cells tested was always stimulated by the presence of fibroblasts obtained from an organ in which cancer cells had already developed, and inhibited by those from skin. However, fibroblast-conditioned media failed to affect cancer cell growth, either in MTT assay or in soft-agar culture. These results suggest that mutual growth reliance exists between human cancer cells and primary cultured fibroblasts by diffusible factors secreted by both cells (paracrine growth) and that mutual growth enhancement occurs between cancer cells and fibroblasts derived from tissues in which cancer cells had originated.

A new experimental trial using repeated heating every 24 hours for local hyperthermic therapy with bleomycin in vivo.

This report presents the effect of repeated heating every 24 hrs using bleomycin (BLM) which, although seemingly contrary to the usual agreement that hyperthermia should be carried out with a long interval due to thermotolerance, holds many possibilities. FM3A cells on the foot pad of C3H mouse were immersed in a heated water bath at 43 and 44 degrees C for 30 min. The effect of repeated heating was appreciated by an improved growth curve and 50 day survival compared to mice which received heating twice with a 96-hr interval. Repeated heating every 24 hrs 5 times with BLM suppressed tumor growth significantly as compared to heating twice with a 96-hr interval without BLM. The longest survival time was obtained by the repeated heating with BLM among all protocols. There is therefore a good possibility that more effective results could be obtained clinically by repeated heating over a short period.

[Evaluation of increasing digital blood flow during early period of air-cooled cold test].

The present study was performed to elucidate peripheral hemodynamic changes, especially, digital blood flow, caused by an air-cooled cold test. Experiments were carried out by placing the subject's left hand in a box that was kept at a temperature of about 18 degrees C by air-cooling. At the same time, the digital blood flow, digital blood pressure, compliances of the peripheral resistance and capacitance vessels were measured. These parameters were measured on the left forefinger of the cooled side, and also on the opposite side according to Kato's method at 3 points, 1) at normal condition (before cooling stated). 2) 30 seconds after the cooling began and 3) 10 minutes after the cooling began. The following results were obtained; 1) The systemic blood pressure, digital blood pressure and heart rate showed no statistically significant differences in measurements taken at the above three stages. 2) The mean value of the digital blood flow was found to have increased after 30 seconds, and to have decreased after 10 minutes of cooling. Statistically, significant differences were noted at the above three stages. 3) The mean value of the peripheral vascular resistance was found to have increased after 30 seconds, and to have decreased after 10 minutes. 4) Compliances of the peripheral resistance vessel and capacitance vessel showed no significant changes on either side except between normal condition and after 10 minutes of cooling.

Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer.

Relationship between epidermal growth factor receptor (EGFR) status and various prognostic factors was investigated in 91 human breast cancer tissues. Epidermal growth factor receptor was measured by biochemical competitive binding assay using iodine 125 epidermal growth factor (125I)-EGF. The EGFR status was not correlated with axillary lymph node involvement, tumor size, stage, and histologic type, but significantly correlated with histologic grading (P less than 0.05) and lymphatic invasion (P less than 0.01). Between EGFR and estrogen receptor (ER) status, a clear inverse relationship was observed (P less than 0.01). The Ki-67-positive stained cell rate, which reveals the proportion of cycling cells, was significantly higher in EGFR-positive tumor tissues than in EGFR-negative cases. Furthermore, preliminary postoperative survey demonstrated a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors. These data suggest that EGFR status may be important for the prediction of biologically high malignant potential.