Effects of different combinations of mechanical loading intensity, duration, and frequency on the articular cartilage in mice.

BACKGROUND: Understanding how healthy articular cartilage responds to mechanical loading is critical. Moderate mechanical loading has positive effects on the cartilage, such as maintaining cartilage homeostasis. The degree of mechanical loading is determined by a combination of intensity, frequency, and duration; however, the best combination of these parameters for knee cartilage remains unclear. This study aimed to determine which combination of intensity, frequency, and duration provides the best mechanical loading on healthy knee articular cartilage in vitro and in vivo. METHODS AND RESULTS: In this study, 33 male mice were used. Chondrocytes isolated from mouse knee joints were subjected to different cyclic tensile strains (CTSs) and assessed by measuring the expression of cartilage matrix-related genes. Furthermore, the histological characteristics of mouse tibial cartilages were quantified using different treadmill exercises. Chondrocytes and mice were divided into the control group and eight intervention groups: high-intensity, high-frequency, and long-duration; high-intensity, high-frequency, and short-duration; high-intensity, low-frequency, and long-duration; high-intensity, low-frequency, and short-duration; low-intensity, high-frequency, and long-duration; low-intensity, high-frequency, and short-duration; low-intensity, low-frequency, and long-duration; low-intensity, low-frequency, and short-duration. In low-intensity CTSs, chondrocytes showed anabolic responses by altering the mRNA expression of COL2A1 in short durations and SOX9 in long durations. Furthermore, low-intensity, low-frequency, and long-duration treadmill exercises minimized chondrocyte hypertrophy and enhanced aggrecan synthesis in tibial cartilages. CONCLUSION: Low-intensity, low-frequency, and long-duration mechanical loading is the best combination for healthy knee cartilage to maintain homeostasis and activate anabolic responses. Our findings provide a significant scientific basis for exercise and lifestyle instructions.

Transcutaneous Carbon Dioxide Improves Contractures After Spinal Cord Injury in Rats.

BACKGROUND: Joint contractures are a major complication in patients with spinal cord injuries. Positioning, stretching, and physical therapy are advocated to prevent and treat contractures; however, many patients still develop them. Joint motion (exercise) is crucial to correct contractures. Transcutaneous carbon dioxide (CO2) therapy was developed recently, and its effect is similar to that of exercise. This therapy may be an alternative or complementary approach to exercise. QUESTION/PURPOSES: Using an established model of spinal cord injury in rats with knee flexion contractures, we sought to clarify whether transcutaneous CO2 altered (1) contracture, as measured by ROM; (2) muscular and articular factors contributing to the loss of ROM; (3) fibrosis and fibrosis-related gene expression in muscle; and (4) the morphology of and fibrosis-related protein expression in the joint capsule. METHODS: Thirty-six Wistar rats were divided into three equal groups: caged control, those untreated after spinal cord injury, and those treated with CO2 after spinal cord injury. The rats were treated with CO2 from either the first day (prevention) or 15th day (treatment) after spinal cord injury for 2 or 4 weeks. The hindlimbs of rats in the treated group were exposed to CO2 gas for 20 minutes once daily. Knee extension ROM was measured with a goniometer and was measured again after myotomy. We calculated the muscular and articular factors responsible for contractures by subtracting the post-myotomy ROM from that before myotomy. We also quantified histologic muscle fibrosis and evaluated fibrosis-related genes (collagen Type 1, α1 and transforming growth factor beta) in the biceps femoris muscle with real-time polymerase chain reaction. The synovial intima's length was measured, and the distribution of fibrosis-related proteins (Type I collagen and transforming growth factor beta) in the joint capsule was observed with immunohistochemistry. Knee flexion contractures developed in rats after spinal cord injuries at all timepoints. RESULTS: CO2 therapy improved limited-extension ROM in the prevention group at 2 weeks (22° ± 2°) and 4 weeks (29° ± 1°) and in the treatment group at 2 weeks (31° ± 1°) compared with untreated rats after spinal cord injuries (35° ± 2°, mean difference, 13°; 39° ± 1°, mean difference, 9°; and 38° ± 1°, mean difference, 7°, respectively) (95% CI, 10.50-14.86, 8.10-10.19, and 4.73-9.01, respectively; all p < 0.001). Muscular factors decreased in treated rats in the prevention group at 2 weeks (8° ± 2°) and 4 weeks (14°± 1°) and in the treatment group at 2 weeks (14 ± 1°) compared with untreated rats (15° ± 1°, 4.85-9.42; 16° ± 1°, 1.24-3.86; and 17° ± 2°, 1.16-5.34, respectively; all p < 0.05). The therapy improved articular factors in the prevention group at 2 weeks (4° ± 1°) and 4 weeks (6° ± 1°) and in the treatment group at 2 weeks (8° ± 1°) compared with untreated rats (10° ± 1°, 4.05-7.05; 12° ± 1°, 5.18-8.02; and 11° ± 2°, 1.73-5.50, respectively; all p < 0.05). CO2 therapy decreased muscle fibrosis in the prevention group at 2 weeks (p < 0.001). The expression of collagen Type 1, α1 mRNA in the biceps femoris decreased in treated rats in the prevention group at 2 and 4 weeks compared with untreated rat (p = 0.002 and p = 0.008, respectively), although there was little difference in the expression of transforming growth factor beta (p > 0.05). CO2 therapy did not improve shortening of the synovial intima at all timepoints (all p > 0.05). CO2 therapy decreased transforming growth factor beta immunolabeling in joint capsules in the rats in the prevention group at 2 weeks. The staining intensity and Type I collagen pattern showed no differences among all groups at all timepoints. CONCLUSION: CO2 therapy may be useful for preventing and treating contractures after spinal cord injuries. CO2 therapy particularly appears to be more effective as a prevention and treatment strategy in early-stage contractures before irreversible degeneration occurs, as shown in a rat model. CLINICAL RELEVANCE: Our findings support the idea that CO2 therapy may be able to improve the loss of ROM after spinal cord injury.

Mechanical Stress by Spasticity Accelerates Fracture Healing After Spinal Cord Injury.

Accelerated fracture healing in patients with spinal cord injuries (SCI) is often encountered in clinical practice. However, there is no distinct evidence in the accelerated fracture healing, and the mechanisms of accelerated fracture healing in SCI are poorly understood. We aimed to determine whether SCI accelerated fracture healing in morphology and strength, to characterize the healing process with SCI, and to clarify the factors responsible for accelerated fracture healing. In total, 39 male Wistar rats were randomly divided into healthy control without intervention, SCI only, fracture with SCI, botulinum toxin (BTX) A-treated fracture with SCI, and propranolol-treated fracture with SCI groups. These rats were assessed with computed microtomography, histological, histomorphological, immunohistological, and biomechanical analyses. Both computed microtomography and histological analyses revealed the acceleration of a bony union in animals with SCI. The strength of the healed fractures after SCI recovered to the same level as that of intact bones after SCI, while the healed bones were weaker than the intact bones. Immunohistology revealed that SCI fracture healing was characterized by formation of callus with predominant intramembranous ossification and promoting endochondral ossification. The accelerated fracture healing after SCI was attenuated by BTX injection, but did not change by propranolol. We demonstrated that SCI accelerate fracture healing in both morphology and strength. The accelerated fracture healing with SCI may be due to predominant intramembranous ossification and promoting endochondral ossification. In addition, our results also suggest that muscle contraction by spasticity accelerates fracture healing after SCI.

Stretching After Heat But Not After Cold Decreases Contractures After Spinal Cord Injury in Rats.

BACKGROUND: Contractures are a prevalent and potentially severe complication in patients with neurologic disorders. Although heat, cold, and stretching are commonly used for treatment of contractures and/or spasticity (the cause of many contractures), the sequential effects of these modalities remain unclear. QUESTIONS/PURPOSES: Using an established rat model with spinal cord injury with knee flexion contracture, we sought to determine what combination of heat or cold before stretching is the most effective for treatment of contractures derived from spastic paralyses and investigated which treatment leads to the best (1) improvement in the loss of ROM; (2) restoration of deterioration in the muscular and articular factors responsible for contractures; and (3) amelioration of histopathologic features such as muscular fibrosis in biceps femoris and shortening of the joint capsule. METHODS: Forty-two adolescent male Wistar rats were used. After spasticity developed at 2 weeks postinjury, each animal with spinal cord injury underwent the treatment protocol daily for 1 week. Knee extension ROM was measured with a goniometer by two examiners blinded to each other's scores. The muscular and articular factors contributing to contractures were calculated by measuring ROM before and after the myotomies. We quantitatively measured the muscular fibrosis and the synovial intima length, and observed the distribution of collagen of skeletal muscle. The results were confirmed by a blinded observer. RESULTS: The ROM of heat alone (34° ± 1°) and cold alone (34° ± 2°) rats were not different with the numbers available from that of rats with spinal cord injury (35° ± 2°) (p = 0.92 and 0.89, respectively). Stretching after heat (24° ± 1°) was more effective than stretching alone (27° ± 3°) at increasing ROM (p < 0.001). Contrastingly, there was no difference between stretching after cold (25° ± 1°) and stretching alone (p = 0.352). Stretching after heat was the most effective for percentage improvement of muscular (29%) and articular (50%) factors of contractures. Although quantification of muscular fibrosis in the rats with spinal cord injury (11% ± 1%) was higher than that of controls (9% ± 0.4%) (p = 0.01), no difference was found between spinal cord injury and each treatment protocol. The total synovial intima length of rats with spinal cord injury (5.9 ± 0.2 mm) became shorter than those of the controls (7.6 ± 0.2 mm) (p < 0.001), and those of stretching alone (6.9 ± 0.4 mm), stretching after heat (7.1 ± 0.3 mm), and stretching after cold (6.7 ± 0.4 mm) increased compared with rats with spinal cord injury (p = 0.01, p = 0.001, and p = 0.04, respectively). The staining intensity and pattern of collagen showed no difference among the treatment protocols. CONCLUSIONS: This animal study implies that heat or cold alone is ineffective, and that stretching is helpful for the correction of contractures after spinal cord injury. In addition, we provide evidence that heat is more beneficial than cold to increase the effectiveness of stretching. CLINICAL RELEVANCE: Our findings tend to support the idea that stretching after heat can improve the loss of ROM and histopathologic features of joint tissues. However, further studies are warranted to determine if our findings are clinically applicable.

Effects of hydrogen-rich water and ascorbic acid treatment on spontaneously hypertensive rats.

Hydrogen-rich water (HW) has been suggested to possess antioxidant properties of value in treatments of lifestyle diseases and for prevention of latent pathologies. To date, the potential benefits of HW against the deleterious effects of excessive salt intake and hypertension have not been investigated. Here, we first examined the effects of HW or HW supplemented with 0.1% ascorbic acid (HWA) on spontaneously hypertensive rats (SHR) that had been fed a normal diet. In comparison to control rats given distilled water (DW), we found that HW did not significantly influence systolic blood pressure (SBP) or diastolic blood pressure (DBP) in SHR; however, the increase in SBP and DBP were inhibited in the HWA group. Next, four groups of SHR were given DW, 0.1% ascorbic acid-added DW (DWA), HW, or HWA in combination with a 4% NaCl-added diet. SHR fed the 4% NaCl-added diet showed increased hypertension; HWA treatment resulted in a significant reduction in blood pressure. The HWA group tended to have lower plasma angiotensin II levels than the DW group. In addition, urinary volumes and urinary sodium levels were significantly lower in the HWA group than the DW group. Urinary isoprostane, an oxidative stress marker, was also significantly lower in the HWA group, suggesting that the inhibitory effect of HWA on blood pressure elevation was caused by a reduction in oxidative stress. These findings suggest a synergistic interaction between HW and ascorbic acid, and also suggest that HWA ingestion has potential for prevention of hypertension.

Effects of cyclic tensile strain and microgravity on the distribution of actin fiber and Fat1 cadherin in murine articular chondrocytes.

Chondrocytes as mechano-sensitive cells can sense and respond to mechanical stress throughout life. In chondrocytes, changes of structure and morphology in the cytoskeleton have been potentially involved in various mechano-transductions such as stretch-activated ion channels, integrins, and intracellular organelles. However, the mechanism of cytoskeleton rearrangement in response to mechanical loading and unloading remains unclear. In this study, we exposed chondrocytes to a physiological range of cyclic tensile strain as mechanical loading or to simulated microgravity by 3D-clinostat that produces an unloading environment. Based on microarray profiling, we focused on Fat1 that implicated in the formation and rearrangement of actin fibers. Next, we examined the relationship between the distribution of Fat1 proteins and actin fibers after cyclic tensile strain and microgravity. As a result, Fat1 proteins did not colocalize with actin stress fibers after cyclic tensile strain, but accumulated near the cell membrane and colocalized with cortical actin fibers after microgravity. Our findings indicate that Fat1 may mediate the rearrangement of cortical actin fibers induced by mechanical unloading.

Suppressive ability of defatted rice bran against lipid oxidation in cookies containing iron.

Cookies containing iron, defatted rice bran, and several oils were prepared, and their oxidative stability evaluated. Oxidation was suppressed by the defatted rice bran, but a limit to the suppressive effect was observed. The maximum peroxide values obtained with defatted rice bran were low, and similar, regardless of the degree of unsaturation of the oils. A chemical analysis suggested that proteins and polyphenols in the defatted rice bran contributed to the suppressive effect. Cookies without the defatted rice bran showed decreasing maximum peroxide value as the relative humidity increased. No such dependence was observed for the cookies containing defatted rice bran. The water sorption isotherm of defatted rice bran indicated that the weak dependence was due to low water sorption.

Synthesis of acyl arbutin by an immobilized lipase and its suppressive ability against lipid oxidation in a bulk system and O/W emulsion.

Acyl arbutin was synthesized through the condensation of arbutin with a saturated fatty acid (C6-18) by the immobilized lipase in a batch reaction. The conversion at 10 and 20 g/l-solvent of immobilized lipase reached 45% over 2 d, but the initial reaction rate per amount of immobilized lipase decreased at 20 g/l-solvent. The radical scavenging activity of acyl arbutin in an ethanol solution was independent of the acyl chain length, although the rate constant, k, estimated for the oxidation of methyl linoleate in a bulk system with acyl arbutin by using the Weibull equation, decreased as the acyl chain length increased. This indicates the antioxidative ability of acyl arbutin with a long acyl chain to be due to its lipophilicity. Furthermore, it is suggested that dodecanoyl arbutin mainly acted on the interface between the oil and water phases in an O/W emulsion, and effectively suppressed the oxidation induced at the interface.

Fatty Acid Composition and Applications of Eriobotrya japonica Seed Oil.

The loquat (Eriobotrya japonica) is commonly found in Japan. Its fruits are consumed raw or used in processed foods, and its leaves are used as a traditional medicine and in the manufacturing of cosmetics. Additionally, its seeds have several industrial applications. Therefore, this study aimed to estimate the fatty acid composition of loquat seed oil, and to evaluate its potential application as a deodorant. Palmitic acid, linoleic acid, behenic acid, and lignoceric acid were found to be the primary fatty acids present in the seeds, among which linoleic acid was involved in the deodorization of allyl methyl sulfide. Based on these results, loquat seed oil has potential for use in deodorant production.

Predictive factors for anastomotic leakage in the neck after retrosternal reconstruction for esophageal cancer.

BACKGROUND/AIMS: Anastomotic leakage after transthoracic esophagectomy for esophageal cancer can induce life-threatening morbidity. This study investigated the predictive factors for anastomotic leakage in the neck after retrosternal reconstruction. METHODOLOGY: A total of 129 esophageal carcinoma patients undergoing transthoracic esophagectomy and esophagogastric anastomosis in the neck via a retrosternal approach were enrolled between April 1985 and March 2002. Predictive factors for anastomotic leakage were statistically evaluated. In a preliminary study using 18 cases, thoracic inlet space (TIS) was recommended to be extended more than 700 mm2. RESULTS: Partial resection of the bony structures was performed in 32 patients. The method of anastomosis and partial resection of bony structures according to the TIS independently influenced the likelihood of anastomotic leakage, with hand-sewn anastomosis and an absence of partial resection increasing its occurrence. CONCLUSIONS: Stapled anastomosis following the partial resection of the sternum and the left clavicle is recommended to avoid anastomotic leakage. These findings should be clarified by a randomized controlled study in a high-volume hospital.

[Chemical constituents of Myristica fragrans Houttuyn seed and their physiological activities].

The antioxidative activity of phenylpropanoid compound extracts from nutmeg (Myristica fragragrans Houttuyn) seed was determined. The antioxidant activity was evaluated using the 1,1-diphenyl-2-picrylhydrazyl radical-scavenging method, superoxide disumutase assay, ferric thiocyanate assay, and radical-scavenging effect assay with electron-spin resonance. High antioxidant activity was found in monoterpenoid extracts including terpinene-4-ol (3), alpha-terpineol (4), and 4-allyl-2,6-dimethoxyphenol (12). Compound, 12 expressed particularly high antioxidant activity.

Antioxidant effects and antimicrobial activites of phytoncide.

Physiological activities of four types of phytoncide solutions (A, AB, CY and D-types), prepared from various plants widely distributed in nature, were examined. We assayed these phytoncide solutions, testing for active oxygen inhibition, DPPH radical scavenging effects, nitrogen monoxide inhibition, and lipid peroxide inhibition. The AB- and D-types of phytoncide solutions especially showed comparably potent antioxidant effects. Antibacterial and antifungal assays were conducted using the AB- and D-types, with results showing significant inhibitory activities with these solutions.

Antihypertensive Effect of γ-Aminobutyric Acid-Enriched Brown Rice on Spontaneously Hypertensive Rats.

'Haiibuki' is a giant embryo rice cultivar that contains abundant γ-aminobutyric acid (GABA) compared with conventional rice cultivars. Here, we performed a functional evaluation of 'GABA-enriched brown rice' (GEBR) prepared by modifying the 'Haiibuki' cultivar to contain more GABA. Study 1: Spontaneously hypertensive rats were divided into three groups [control (cornstarch), normal brown rice, and GEBR] and fed an orally administered diet for 4 wk. A significant blood pressure elevation-inhibitory effect was observed in the GEBR group as compared with the other groups. Study 2: Rats were divided into two groups and fed ad libitum for 12 wk. The two groups were control (commercial feed with 5% cornstarch) and GEBR (commercial feed with 5% GEBR). Body weight, blood pressure, food consumption, and water intake were measured during the study period, and blood chemistry was analyzed after the study. Plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and urinary isoprostane were measured 12 and 10 wk after the start of the study, respectively. A significant blood pressure elevation-inhibitory effect was observed in the GEBR group. The 8-OHdG and isoprostane levels were significantly lower in the GEBR group than in the control group, demonstrating an oxidative stress-reducing effect. Therefore, GEBR exhibited a blood pressure elevation-inhibitory effect under the conditions of this study. The antioxidative action may occur secondarily to the antihypertensive action of GABA, suggesting that the long-term ad libitum ingestion of GEBR prevents hypertension. A reduction in oxidative stress could reduce the chances of complications in cardiovascular diseases.

Impact of splenectomy in patients with gastric adenocarcinoma of the cardia.

Previous reports have suggested that splenectomy treatment of gastric carcinoma of the cardia results in poor patient outcome, but the reason for this is unclear. This study aimed to clarify the impact of splenectomy for gastric carcinoma patients. A total of 118 patients with gastric carcinoma of the cardia were enrolled in this study. The characteristics of patients with lymph node metastasis at the splenic hilum were determined, and the effects of lymph node dissection or splenectomy on postoperative morbidity, mortality, and pattern of recurrence were evaluated. Advanced tumors were common in patients with lymph node metastasis at the splenic hilum, Siewert type III, greater curvature sites, larger and deeper tumors, multiple metastatic lymph nodes, and high incidences of para-aortic lymph node metastasis frequently observed. The effectiveness of lymph node dissection of the splenic hilum was low and equal to that of dissection of the para-aortic lymph nodes. Postoperative morbidity, as represented by pancreatic fistula, was high following splenectomy or pancreaticosplenectomy, but patient mortality did not occur. Hematogenous metastasis was common, as well as peritoneal metastasis after curative gastrectomy. Splenectomy should be limited in those patients with gastric cardia tumors invading the spleen or with metastatic bulky lymph nodes extending to the spleen.

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.

Appropriate routes of reconstruction following transthoracic esophagectomy.

BACKGROUND/AIMS: The effectiveness of reconstructive methods after esophagectomy remains controversial. METHODOLOGY: A total of 211 patients who underwent transthoracic esophagectomy and esophagogastric anastomosis using the gastric conduit were enrolled in this study. A retromediastinal approach was used in 79 patients and a retrosternal approach in 132. The surgical outcomes were compared between the two groups. RESULTS: In the retrosternal group, anastomotic leakage (26.5%), stenosis of the anastomosis (13.6%), and respiratory complications (18.2%) were frequently observed. Five patients died of aspiration pneumonia probably due to stenosis of the anastomotic site in the retrosternal group. In the retromediastinal group, two patients died from bleeding of a peptic ulcer in the gastric conduit. Partial resection of the manubrium significantly reduced the incidence of leakage in the retrosternal group (4/29 vs. 31/68, p=0.0305). Retrosternal approach and stage were independent prognostic factors for overall survival whereas only stage was an independent prognostic factor for disease-specific survival. CONCLUSIONS: Retrosternal reconstruction is suggested as the unwillingly adopted method of choice after palliative esophagectomy (R2) for the following radiotherapy. Partial resection of the bony structures can be used to prevent postoperative morbidity in this operative procedure. Retromediastinal reconstruction is the possible method of choice in patients receiving curative esophagectomy.

Evaluation of bedding and nesting materials for laboratory mice by preference tests.

Bedding and nesting materials can improve the health and environmental welfare of laboratory mice. This study was carried out to examine which items are actually preferred by mice. Two series of studies were performed on four types of floor-covering materials (Wood-shavings (Clean-chip), Cloth (Agrebe), Recycled-paper (Paper-clean), Paper (Care-feeaz), and on four types of nesting materials (Recycled-paper (Shepherd-shack), Cloth (Agrebe), Wood (Wood-cylinder), and Polycarbonate (Mouse-igloo). Preference of bedding materials was judged by the time length of staying in a cage. The results indicate that mice stayed in the cloth material (Agrebe) longer than in other bedding materials (light 51.1 +/- 5.3%, dark 51.5 +/- 2.6%). In the second experiment, the duration of stay in Agrebe was significantly longer than that in the other nesting materials in the light phase (70.9 +/- 2.4%). In the dark phase, staying time both in Agrebe and Shepherd-shack were significantly longer. These data suggest that cloth bedding and nesting is recommended for the environmental enrichment of laboratory mice.

Surgical outcomes in patients with T4 gastric carcinoma.

BACKGROUND: There is controversy about the best therapeutic surgical approach for treatment of patients with T4 gastric cancer. STUDY DESIGN: We used univariate and multivariate analyses to review the surgical outcomes and prognostic factors of 117 patients who underwent surgery for T4 gastric carcinoma. RESULTS: Curative resection was performed in 38 (32.4%) patients, with the pancreas being the most frequently resected organ. The 5-year survival rate was 16.0% and the median survival time (MST) was 11 months for all 117 registered patients. The 5-year survival rates and MSTs in patients after curative and noncurative resection were 32.2% versus 9.5% and 20 months versus 8 months, respectively. These values differed considerably between the two groups (p < 0.0001). Curability was an independent prognostic factor among all registered patients, including those who underwent noncurative resection. A relatively small tumor diameter (< 100 mm) and few lymph node metastases (six or fewer metastatic lymph nodes) were independent prognostic factors when curative resection could be performed. Postoperative morbidity and mortality were acceptable after curative combined resection. CONCLUSIONS: We recommend the use of aggressive combined resection of adjacent organs, with extended lymph node dissection, for patients with T4 gastric carcinoma in whom curative resection can be used; that is, those with few metastatic lymph nodes (six or less) and a relatively small tumor diameter (100 mm). But noncurative resection should be avoided in patients with T4 gastric cancer.

Predictive factors for pancreatic fistula after pancreaticosplenectomy for advanced gastric cancer in the upper third of the stomach.

This study aimed to retrospectively investigate the predictive factors for pancreatic fistula following pancreaticosplenectomy. Pancreatic fistula is a major lethal complication of pancreaticosplenectomy. However, predictive factors for this condition have not yet been established. Between April 1992 and March 2000, 147 patients with advanced gastric cancer that was located predominantly in the upper third of the stomach were enrolled in this study. Predictive factors for pancreatic fistula were investigated using univariate and multivariate analyses. Pancreatic fistula, as defined according to our criteria, was observed in 73 (49.7%) patients. In the univariate analysis, age, body mass index, serum zinc level, hyperlipidemia, and comorbid disease all significantly affected the incidence of pancreatic fistula. In the multivariate analysis, body mass index, hyperlipidemia, and comorbid disease independently predicted the occurrence of pancreatic fistula. By contrast, the experience of the operating surgeon had no significant effect on the frequency of this condition. Our results suggest that pancreaticosplenectomy, the surgical merit of which is not apparent, should be avoided whenever possible. If this operative procedure must be used (e.g., in patients with extensive tumor presence), careful manipulation and appropriate drainage are essential, particularly in cases showing predictive factors of pancreatic fistula.

Comparison of results of surgery in the upper third and more distal stomach.

The results of surgery for gastric cancer in the upper third of the stomach and the more distal region were compared to explain the comparatively poor outcomes in the former. Characteristics and therapeutic results of 1245 patients who underwent curative gastrectomy (244 with tumors in the upper third of the stomach and 1001 with more distal cancers) were compared. Survival was significantly lower in patients with cancer of the upper third of the stomach than in patients with more distal cancers. There was a significant difference between the two groups in the survival of patients with advanced gastric cancer, particularly in those with pN1. Among patients with tumors deeper than T2 and pN1, survival was significantly reduced in those aged