Abstract In this study, the effects on the maintenance of normal bloodstream by lipopolysaccharide (LPS) were investigated in the parallel‐group randomized double‐blind study using supplement containing Pantoea agglomerans LPS (201.5 μg/tablet as LPS). Screening was previously performed in the implementation of the study. Adult males and females with normal value to borderline (healthy subjects) in the hematologic parameters, for which reference values were given, were chosen in this study. The period of ingestion of the supplement was 3 months. As the result, a significant decrease in the rate of change (the ratio when the baseline was 1) of HbA1c, which is a glycative stress marker, was found in the group which ingested LPS supplement after 3 months. Also, a significant increase in the number of fingertip capillary vessels was found compared with the control group. From these results, the effects of the maintenance of bloodstream by ingestion of LPS were shown.

Lipopolysaccharide fromPantoea agglomerans (LPSp) facilitates Ca and P turnover in chicken calvaria and femurs. This study investigated osteoporosis prevention by the oral administration of LPSp in mice and in double-blind clinical tests. Using ovariectomized (OVX) osteoporosis mice model, we investigated the effects of LPSp on the bone density and Ca concentration after ingesting LPSp-containing water for 4 weeks. Oral administration of LPSp tended to suppress the decline in the bone density and the cortical bone thickness in the OVX mice. Moreover, the Ca concentrations were maintained in the OVX-LPSp mice. The effects of LPSp on bone turnover were tested in randomized and double-blind clinical test subjects, who were healthy women aged 40-79 years. The subjects ingested either soy milk without LPSp (control group) or with LPSp (LPSp group) for 3 months. The results showed that the LPSp group on premenopause maintained their bone density compared with the control group pre- and postmenopause. Moreover, these effects were maintained for 2 months postobservation. LPSp maintains bone volume and density in vivo. Thus, a combination of soy milk and LPSp may be useful for osteoporosis prevention.

At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of α-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. SI tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG ≥ 150 mg/dl, or LDL ≥ 120 mg/dl, or HDL < 40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases.

Background/Aims: The influence of high Body Mass Index (BMI) on long-term outcome is scarcely known in patients with colorectal carcinoma. Methodology: In the present study was analysed 356 consecutive patients with colorectal carcinoma, in order to address the impact of BMI on patients' characteristics, surgical procedures, and clinical outcomes following radical resection. Patients were divided into the following 3 categories according to BMI; high BMI group (BMI >= 24.0 kg/m(2)), middle BMI group (21.0 <= BMI < 24.0 kg/m2), and low BMI group (BMI < 21.0 kg/m(2)). Results: Low BMI was significantly correlated with advanced tumor stage compared with middle BMI group (p<0.05). The mean number of lymph node dissected per patients of the high BMI group was significantly lower than the middle BMI group (p<0.05). The 5-year disease-free survival rates of both high and low BMI groups were significantly lower than middle BMI group, respectively. Low and high BMI also became worse independent prognostic factors by multivariate analysis, respectively (p<0.01; low vs. middle, p<0.05; high vs. middle). Conclusions: Both high and low BMI became independent prognostic factors of disease recurrence in patients with colorectal carcinoma, as low BMI was correlated with tumor progression and high BMI influenced the number of lymph node dissected.

Aim: The response to fluoropyrimidine chemotherapeutic drugs is different in individual tumors. Predictive biomarkers of antitumor effects by these drugs are unknown. 5'-Deoxy-5-fluorouridine (5'-DFUR), a fluoropyrimidine chemotherapeutic drug, is converted to 5-fluorouracil (5-FU) by pyrimidine nucleoside phosphorylase (PyNPase). It is suggested that 5'-DFUR will efficiently exert antitumor effects via PyNPase in tumor tissues. The change of PyNPase activity in tumor tissues following 5'-DFUR administration may reflect antitumor effects, and may be useful for detecting predictive factors of antitumor effects. The aim of this study was to search for predictive factors of antitumor effects by analyzing the relationship between clinicopathological factors and the change of PyNPase activity in colorectal tumor tissues after preoperative 5'-DFUR administration. Patients and Methods: PyNPase activity in colorectal tissues from 45 patients with colorectal tumors was measured using an ELISA method. Results: The reduction rate of PyNPase activity in colorectal tumor tissues after preoperative 5'-DFUR administration was correlated with significant differences in lymphatic invasion, stage, and histologic classification. It is suggested that lymphatic invasion, stage (distant metastasis), and histologic classification may be predictive factors for evaluating antitumor effects and selecting 5-FU-based chemotherapeutic drugs for patients with colorectal tumors.

Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients.

The lymphatic channels of the esophagus run vertically along the axis of the esophagus and some of them drain into the cervical lymph glands upwards and into the abdominal glands downwards, and the pattern of lymph node metastasis of esophageal carcinoma is widespread. In various classifications of pattern of lymphatic spread, four classifications were proposed; location, number, ratio, and size. No definite survival advantage of aggressive lymph node dissection during esophagectomy has been proved compared with less dissection. Stage migration, micrometastasis, and sentinel lymph node concept all make it possible to individualize surgical management of esophageal carcinoma as a part of various multimodal treatments. Early diagnosis, standardization of surgery including routine lymph node dissection, and perioperative management of patients have all led to better survival rates of esophageal carcinoma.

A 73-year-old man, who underwent a potentially curative resection of cancer of the descending colon 13 years before, was found to have a well-defined hepatic tumor on ultrasonography. A lateral segmentectomy was performed for a solitary hepatic tumor. Histopathological examination of the tumor indicated well differentiated adenocarcinoma compatible with the metastasis from the previous descending colon cancer. There have been no signs of recurrence for 5 years after the hepatic resection. This case suggests that distant metastasis from colorectal could be found several years after operation like in this case, and consequently long-term and strict follow-up is required after curative resection of the primary lesion.

BACKGROUND:Some of the mortalities caused by infectious diseases and/or distant metastases following surgery are thought to be due to immunological suppression. For this reason, techniques that reduce immunological suppression following surgery may reduce mortalities and/or incidences of micrometastases in distant organs.MATERIALS AND METHODS:Mice were anesthetized and their peritoneal cavities were opened for 30 min. Immunological suppression was estimated by the presence of tumor necrosis factor-a (TNF) after injection with OK-432 (dead bacterial bodies). The mice were administered with either Staphylococcus aureus or cancer cells of Meth A fibrosarcoma. Survival times and lung metastastic foci were then observed at 3 weeks. Results were compared for mice with or without treatment by OK432 or TNF prior to surgery.RESULTS:While significant suppression of TNF production was observed after laparotomy, administration of a macrophage-activating agent (TNF or OK-432) 3 h prior to laparotomy prevented immune suppression after the laparotomy. Laparotomy increased mortalities from bacterial infections and promoted the number of lung metastases. By contrast, administration of TNF or OK-432 3 h prior to the laparotomy decreased mortalities and metastases after the laparotomy.CONCLUSION:These results suggest that appropriate activation of macrophages prior to surgery is a method to reduce some of the detrimental effects caused by surgical operations.

悪性線維性組織球腫 (MFH) は, 軟部組織悪性腫瘍の中では頻度が高い腫瘍であるが, 後腹膜に発生するものは比較的稀である. 症例は77歳, 女性. 主訴は直腸脱. 受診時, 10cm長の直腸脱を認めた. また左側腹部に弾性硬な30cm大の巨大な腹部腫瘤を認め, 精査の結果, 後腹膜腫瘍の診断にて手術を施行した. 腫瘍は, 左側後腹膜に腎と接するように存在し, 上縁は膵下縁, 下縁は総腸骨動静脈, 内側は大動脈および下大静脈に接していたが腫瘍を周囲後腹膜より剥離しGerota筋膜を腫瘍に付ける層で剥離を行い, 左腎の合併切除は行わなかった. 腫瘍径は30×15×9.5cm, 重量2,300g, 割面は肉眼的にゼラチン様の部分と白色の硬い多結節状の部分が存在し組織学的に前者はmyxofibrosarcoma様であること, また後者はstoriform patternを示したことより本症例はMFHと診断された.

BACKGROUND:The depth of tumor penetration is a crucial factor in determining the prognosis of patients with esophageal carcinoma. Patients with superficial esophageal carcinoma (SEC) have a far more favorable clinical course compared with those with advanced cancers. The outcome for patients with mucosal cancer is excellent with a 5-year survival rate exceeding 80%. On the other hand, submucosal cancer often metastasizes to regional and/or distant lymph nodes or other organs, and the prognosis of these patients are far from satisfactory.METHODS:Among 334 patients with esophageal cancer who underwent surgery between December 1980 and December 2006, 100 patients (30%) had SEC confined to the epithelium, lamina propria mucosa, or submucosa. Patient and tumor characteristics of those 100 patients were studied.RESULTS:The prevalence of SEC has increased from 13% (8 of 61) in the initial 5-year period (1985-1989) to 44% (41 of 93) in the recent 7-year period (2000-2006). Subjective symptoms were present in 7 (14%) of 51 mucosal cancers and in 13 (27%) of 49 submucosal cancers. The remaining 80 patients (80%) had no subjective symptoms. Ninety-one patients (91%) were diagnosed to have the lesions by endoscopy at the time of screening for gastric problems, and only nine were detected by gastrointestinal series. Four of 51 patients with mucosal cancer had venous or lymph vessel invasion, and among those, only one (2%) had a solitary perigastric lymph node metastasis. In 49 patients with submucosal cancer, 35 (71%) had lymph vessel invasion, 28 (57%) had venous invasion, and 16 (33%) had lymph node metastases. In particular, 15 of 35 patients with positive lymph vessel invasion had lymph node metastasis, whereas only 1 of 14 with negative lymph vessel invasion had lymph node metastasis (P < .05). Among 17 patients with nodal involvement, 4 patients with upper thoracic SEC had upper mediastinum and/or cervical nodal metastases, 11 patients with middle thoracic SEC had widespread upper and lower mediastinal and abdominal metastases, and 2 patients with lower thoracic SEC had lower and abdominal lymph node metastases. Seventy-nine patients were alive without recurrence at last follow-up. Five of 49 patients with submucosal cancer died of recurrent disease, and 4 of these developed regional nodal recurrence around the bilateral laryngeal recurrent nerves. Forty-two patients (42%) developed double cancers during the follow-up period, and 5 died of a second cancer. The 3- and 5-year survival rates of all 100 patients were 85% and 73%, and those disease-specific survival rates were 96% and 93%, respectively. The 3- and 5-year survival rates for patients with mucosal cancer were 89% and 83%, and those for submucosal cancer were 80%, and 64%, respectively.CONCLUSIONS:Esophagectomy with extensive lymphadenectomy should be carried out particularly for upper thoracic submucosal cancer, whereas esophagectomy with moderate lymphadenectomy may be preferred for mucosal cancer. Patients with SEC should be examined for another primary cancer preoperatively and periodically during follow-up.

Objective Tyrosine kinases and its receptors play important roles in growth, migration, and invasion of malignant cells. Among those, there are only few reports examining the expression pattern of Eph/ephrin signalling system in oesophageal carcinoma. The prognostic importance of ephrin-B2 ligand (EFNB2) and its receptor EphB4, and its correlation with clinicopathologic characteristics are yet to be delineated in patients with oesophageal carcinoma. Materials and methods EFNB2 gene and EphB4 receptor gene were examined of mRNA specimens in 61 patients with oesophageal squamous cell carcinoma using reverse-transcriptase polymerase chain reaction. EFNB2 protein was selectively examined using an immunohistochemical analysis. Results EFNB2 mRNA expression was detected in 38 (62.3%) and EphB4 expression was found in 44 (72.1%) out of 61 cancer tissues analysed. There was a statistically significant correlation between EFNB2 expression and number of lymph node metastasis (P < 0.05), and a trend toward statistical significance for correlation between EFNB2 expression and American Joint Committee on Cancer Classification Stage (P < 0.1), indicating that EFNB2 expression was up-regulated by advancement of the disease process. EFNB2 protein was strongly expressed in tumour with high mRNA EFNB2 expression and was weakly expressed in tumour with low mRNA expression in some representative tumours. The 5-year overall survival rate (23%) of patients with positive EFNB2 gene expression was significantly worse than 55% of negative expression (P < 0.05). The results of multivariate analysis of prognosticators for survival showed that positive EFNB2 gene expression (P < 0.01) and number of lymph node metastasis (P < 0.05) were identified as significant factors indicative of a poorer survival. Conclusions EFNB2 gene expression may be a biological marker and a useful prognostic indicator in patients with oesophageal squamous cell carcinoma.

Objective The worldwide incidence of superficial esophageal cancer (SEC) is increasing. The aim of this study is to review the systematic surgical outcomes of esophagectomy for SEC. Data sources Only manuscripts written in English and written between 1980 and 2003 were selected from MEDLINE. The keywords consisting of superficial esophageal cancer, early esophageal cancer, and early stage or superficial stage or stage I in esophageal cancer were searched. Study selection There were no exclusion criteria for published information relevant to the topics. The most representative articles were selected when there were several articles from the same institution. Case reports were excluded. Data extractions Thirty-two manuscripts were finally collected from MEDLINE and eight articles were also added from reference lists of the pertinent literatures. In evaluating the statistical analysis of the complications of the reported literature, collective method was used. Data synthesis The collected information was organized. Conclusions The conclusions drawn from those articles showed that the overall prevalence of SEC accounted around 10% and increased to 25% in the 2000s. The overall incidence of lymph node metastasis of SEC was about 25% and its incidences in mucosal and submucosal cancer were 5 and 35%, respectively. The percentage of the cases of squamous cell carcinoma (SCC) vs adenocarcinoma (AC) widely varied depending on the geographic locations reported; most SCC cases were from the Asian countries and most AC cases were from the European countries. Clinical significance of multimodal treatment for SEC has dramatically developed in the recent era and could provide various potential therapeutic options for SEC. These concepts make it possible to individualize surgical management of SEC as part of various multimodal treatments . The operative approaches for SEC varied from minimally invasive thoracoscopic esophagectomy, limited transabdominal distal esophagectomy, conventional transthoracic esophagectomy, transhiatal esophagectomy without thoracotomy, en bloc esophagectomy, and to extended esophagectomy with a complete three-field lymph node dissection. A 5-year overall survival rate of SEC after esophagectomy was good (46 to 83%) to excellent (71 and 100%) for mucosal SEC, but far from satisfactory (33 and 78%) for submucosal SEC. Early diagnosis, development of multimodal treatment, standardization of the surgical procedure including routine lymph node dissection, and improved perioperative management of patients have led to a better survival for patients with SEC.

Objective: The worldwide incidence of superficial esophageal cancer (SEC) is increasing. The aim of this study is to review the system- atic surgical outcomes of esophagec- tomy for SEC. Data sources: Only manuscripts written in English and written between 1980 and 2003 were selected from MEDLINE. The key- words consisting of superficial esophageal cancer, early esophageal cancer, and early stage or superficial stage or stage I in esophageal cancer were searched. Study selection: There were no exclusion criteria for published information relevant to the topics. The most representative arti- cles were selected when there were several articles from the same insti- tution. Case reports were excluded. Data extractions: Thirty-two manu- scripts were finally collected from MEDLINE and eight articles were also added from reference lists of the pertinent literatures. In evaluating the statistical analysis of the complica- tions of the reported literature, col- lective method was used. Data synthesis: The collected information was organized. Conclusions: The conclusions drawn from those articles showed that the overall prevalence of SEC accounted around 10% and increased to 25% in the 2000s. The overall incidence of lymph node me- tastasis of SEC was about 25% and its incidences in mucosal and submu- cosal cancer were 5 and 35%, respectively. The percentage of the cases of squamous cell carcinoma (SCC) vs adenocarcinoma (AC)

The aim of this study is to clarify the clinicopathological features of patients having non-metastatic lymph nodes in the previously operated neck for oromaxillary squamous cell carcinoma (OSCC). The clinicopathological factors of 9 such patients were comparatively analyzed with those of 78 other patients who underwent neck dissection (ND). The following observations were elicited from the data: (1) These 9 patients were alive and without OSCC for periods ranging from 1 year to 15 years and 9 months since their initial cancer treatments. (2) The interval between ND and clinical and/or imaging recognition of newly developed lymph nodes with suspicion of recurrence was significantly longer in these 9 patients. (3) The initially removed lymph nodes tended to be in a less advanced stage of disease. (4) Retrospectively, discrimination of non-metastatic lymph nodes from metastatic nodes was difficult in only one patient. (5) Each of the extirpated lymph nodes from 7 of the 9 patients showed a varying grade of reactive lymphadenitis on histopathology. In conclusion, the occurrence of benign hyperplastic lymph nodes in the previously operated neck region suggested favorable prognosis, though the immunological mechanism is not understood.

OBJECTIVE:Opinions are conflicting about 3-field lymph node dissection (3FLND) during esophagectomy for esophageal cancer. In the current study, we sought to determine the prevalence of cervical and upper thoracic lymph node metastasis in patients with squamous cell carcinoma of the thoracic esophagus and to determine the impact of 3FLND on mortality, morbidity, survival, and recurrence rate.MATERIALS AND METHODS:Among 287 patients with squamous cell carcinoma of the thoracic esophagus seen between November 1985 and December 2001, 141 (49%) underwent extended esophagectomy with 3FLND (cervical, mediastinal, and abdominal lymph node dissection). Patients were observed and clinicopathologic information collected prospectively on all patients until death or August 2002. The median follow-up was 41 months, ranging from 10 to 173 months.RESULTS:Hospital mortality and morbidity rates were 6.4% and 80%, respectively. Thirty-four of 70 node-positive patients had cervicothoracic nodal involvement. Sixteen patients (11%) had nodal involvement confined only to the cervicothoracic nodes, and no patients with lower thoracic esophageal carcinoma showed cervicothoracic involvement alone. The frequency of cervical nodal disease was correlated with nodal status within the mediastinum (P <0.01). The 1-, 3-, and 5-year overall survival rates for all 141 patients were 76%, 58%, and 48%, respectively. Among significant variables verified by univariate analysis, independent prognostic factors for overall survival determined by multivariate analysis were number of lymph node metastasis (P <0.01), amount of blood transfusion (P <0.05), length of operation (P <0.05), and presence of pulmonary complications (P <0.05).CONCLUSIONS:Extended esophagectomy with 3FLND can be performed with an acceptable mortality. Metastases frequently involved the upper thoracic and cervical lesions, and cervical nodal disease was correlated with thoracic nodal status. 3FLND proved to be an important staging system in 11% of patients. An excellent overall survival suggests a superiority of 3FLND when performed at experienced centers.

BACKGROUND: Colorectal cancer patients with lymph node metastasis constitute a heterogeneous population with variable prognoses. In this study, my colleagues and I propose a simpler lymph node (LN) staging system for colorectal cancer.STUDY DESIGN: Four-hundred and twenty-three consecutive colorectal cancer patients were studied. Of these, 36 were excluded because another carcinoma was present. The remaining 387 patients entered the TNM staging analysis. In the survival analysis, 76 patients with distant metastasis were excluded and the remaining 311 patients (LN- = 204 and LN+ = 107) were studied. The diameter of the largest metastatic LN (MLN) was measured on histopathological slides. After examination of various cutpoints and survival outcomes, patients with MLNs were classified into n1 (less than or equal to 9 mm) and n2 (greater than or equal to 10 mm) groups, according to size of MLNs (n-stage).RESULTS: Using disease-free survival (DFS) and overall survival (OS) as outcomes, patients were separated into significant prognostic groups by MLN size (univariate, p < 0.0001) (5-year Survival, DFS: n0 = 91.5%, n1 = 62.2%, and n2 = 34.4%; OS: n0 = 85.1%, n1 = 63.5%, and n2 = 42.5%) and International Union Against Cancer/American Joint Commute on Cancer (UICC/AJCC) (N-stage) (univariate, p < 0.0001) (5-year survival, DFS: NO = 91.5%, NI = 60.5%, and N2 = 36.8%; OS: NO = 85.1%, N1 = 65.3%, and N2 = 38.0%). But in patients with fewer than 15 LNs examined (n = 31), only the new nodal stage stratified patients into significant groups (OS: p = 0.003 and DFS: p = 0.001). Only the UICC/AJCC N-stage subcategories were further split into significant prognostic groups by MLN size (UICC/AJCC NI: DFS, p = 0.048 and OS, p = 0.11; N2: DFS, p = 0.04 and OS, p = 0.04). n-stage was an independent important factor both in the DFS and OS in multivariable analysis.CONCLUSIONS: MLN size is a strong prognostic variable in colorectal carcinoma. This new metric may help clinicians treating colorectal cancer patients, but additional studies are required before clinical application. (C) 2005 by the American College of Surgeons.

Risk analysis of pulmonary complications after extended esophagectomy with three‐field lymph node dissection (3FLND) has been little reported in the literature.

Purpose: Angiogenesis plays an important role in a multitude of biological processes including those of tumorigenesis and cancer progression. Hypoxia is the prime driving factor for tumor angiogenesis and the family of hypoxia-inducible factors (HIFs) plays a pivotal role in this process. The role of HIF in tumor angiogenesis has been underscored in different carcinomas but yet to be reported for colorectal carcinomas. Experimental Design: In this study, we examined HIF [HIF-1α (HIF1) and HIF-2α (HIF2)] expression in 87 curatively resected colorectal carcinoma samples, and the results were correlated with clinicopathological factors, microvessel density, cyclooxygenase 2 expression, and patient prognosis. Results: HIF1 (44.8%) was more frequently expressed than HIF2 (29.9%). Most of the clinicopathological factors representing the tumor aggressiveness were significantly correlated with overexpression of HIF2 but not with HIF1 expression. HIF2 expression had direct correlation with microvessel density and cyclooxygenase 2 expression. and, in contrast, HIF1 expression had a weak but significant inverse correlation in T1 and T2 tumors only. HIF2 expression alone and the combined expression of HIF1 and HIF2 had significant impact on patient survival. In the multivariate analysis, however, only the combined expression of HIF1 and HIF2 remained independently significant. Conclusions: Taken together, our results suggest that HIF2 expression may play an important role in angiogenesis and that the combined expression of HIF1 and HIF2 may play an important role in tumor progression and prognosis of colorectal carcinomas. Therefore, HIF expression could be a useful target for therapeutic intervention.