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To study the diabetic mellitus (DM) patient's reaction to sepsis, we investigated the survival rate, the bacteremia, plasma endotoxin and plasma endothelin-1 levels in E. coli septic peritonitis rats with or without streptozotocin-induced DM. No significant difference could be detected between the DM and nondiabetic rats in the survival rate, the bacteremia level or the plasma endotoxin level. The DM rat manifested a significant increase compared to the nondiabetic rat in the plasma endothelin-1 level four hours after the outbreak of peritonitis. Endothelin-1 may thus play some role in the E. coli septic peritonitis rat with DM.

Esophageal cancer is one of the most difficult malignancies to cure. The prognosis remains unsatisfactory despite significant advances in surgical techniques and perioperative management. The optimal treatment strategy for localized esophageal cancer has not yet been established. Surgical resection remains the mainstay of treatment for esophageal cancer, and curative resection is the most important surgery. Extended esophagectomy with three-field lymphadenectomy provides the highest quality of tumor clearance and prolongation of patient survival. There has been intense effort in developing novel strategies to treat patients with resectable esophageal cancer. Various combined-modality approaches have been attempted to improve treatment outcomes. Definitive chemoradiotherapy has an impact on long-term survival in patients with resectable esophageal cancer. Accordingly, there are three main combined-modality approaches: esophagectomy with adjuvant chemotherapy or chemoradiotherapy; primary definitive chemoradiotherapy with or without salvage esophagectomy, and preoperative chemoradiotherapy followed by planned esophagectomy. Recently, owing to the remarkable advances in optical technology, minimally invasive esophagectomy using endoscopic instruments has been introduced into esophageal cancer surgery. This article reviews recent changes in the treatment of esophageal cancer surgery, and considers the role of esophagectomy.

Positron emission tomography (PET), a functional imaging modality, has provided the transition between the research environment and the clinical environment over the last 10 years. Its primary use is in the field of oncology, where it is being increasingly used in the management of several tumor types including esophageal cancer. 18F-Fluorodeoxyglucose PET (FDG-PET) scans may also be used to distinguish between benign and malignant tumors, to identify different stages of tumor spread, to assess for tumor recurrence, and monitor the response to therapy of malignant diseases. This review aims to outline the current and future roles of PET scanning in the field of esophageal cancer.

BACKGROUND: Obesity is reported to increase the risk of colorectal cancer. We investigated whether it was associated with mortality or morbidity after colorectal-cancer surgery. METHODS: 70 colorectal-cancer patients who underwent elective surgery were investigated in this study. The intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas were quantified by CT scan preoperatively. We investigated whether body mass index (BMI), IAF, or SCF were associated with postoperative mortality or morbidity. RESULTS: The mortality rate was 0%. 11 (16%) of 70 patients had medical complications (pneumonia, 9; arrhythmia, 2) and 16 (23%) had surgery-related complications (wound infection, 12; anastomotic leakage, 5) postoperatively. There was no significant difference in the postoperative medical or surgery-related morbidity rate between the IAF+ (males, ≥160 cm2; females, ≥120 cm2) and IAF– groups. The surgery-related morbidity rate was significantly higher in the SCF+ group (male, ≥180 cm2; female, ≥250 cm2) than in the SCF– group and multilogistic regression analysis confirmed that diabetes mellitus and SCF were significant for surgery-related morbidity. CONCLUSIONS: Subcutaneous fat accumulation is significantly associated with postoperative surgery-related morbidity after colorectal-cancer surgery.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis. We have investigated the relationship between TIMP-3 reduction and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 90 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Immunostaining of TIMP-3 was seen in the cytoplasm of cancer cells and normal oesophageal epithelial cells, particularly in cells located in shallow areas of the tumour. TIMP-3 preserved (+), moderate (+/-), and reduced (-) cases accounted for 30, 27, and 33 of the 90 patients, respectively (33, 30, 37%). Significant correlations were observed between TIMP-3 expression and depth of tumour invasion (P=0.001), number of lymph node metastases (P=0.003), infiltrative growth pattern (P=0.003), and disease stage (P=0.005). The survival rates of patients with TIMP-3 (-) cancer were significantly lower than those of patients with TIMP-3 (+) and TIMP-3 (+/-) cancer (P=0.0003). The mean 5-year survival rates of patients with TIMP-3 (+), (+/-), and (-) were 50, 58, and 21%, respectively. In conclusion, decreased expression of TIMP-3 protein correlates with invasive activity and metastasis. This makes the prognosis for patients with cancer that has lost TIMP-3 significantly less favourable than that for patients with cancer that has maintained TIMP-3.

Purpose: Transforming growth factor (TGF)-β regulates cell growth inhibition. When tumor cells lose their sensitivity to TGF-β growth inhibition, the excess TGF-β that results may act on tumor cells to facilitate tumor development. Previously, we have shown that an elevated systemic TGF-β1 level is not related to tumor progression in esophageal cancer (Y. Fukai et al., Int J Cancer 2003;104:161–6). We considered that systemic inflammation or chronic disease, in addition to the tumor, may influence the plasma TGF-β level. Therefore, we examined the hypothesis that the plasma TGF-β level measured from the azygos vein would independently predict tumor progression and prognosis in patients with esophageal cancer. Experimental Design: Fifty-seven plasma samples were obtained intraoperatively from the azygos vein in patients with esophageal cancer. ELISA was used to quantify the plasma TGF-β1 levels, which were correlated with pathological features and patient survival. Results: The mean plasma TGF-β1 level measured from the azygos vein of esophageal cancer patients was 5.09 ± 0.48 ng/ml (mean ± SE). The survival rates of patients with a high TGF-β1 level (defined as a level above the 4.6 ng/ml level of normal controls) in the azygos vein were significantly lower than those of patients with a low TGF-β1 level (P = 0.0317). Moreover, the TGF-β1 level in the azygos vein was an independent prognostic factor for overall survival (P = 0.0474). Conclusions: The level of plasma TGF-β1 measured from the azygos vein is an independent predictor in patients with esophageal cancer and may reflect tumor progression more specifically because the azygos vein is responsible for venous return from the esophagus.

Transforming growth factor-beta (TGF-beta) regulates cell growth inhibition, and inactivation of the TGF-beta signaling pathway contributes to tumor development. In our previous study, altered expression of TGF-beta, TGF-beta-specific receptors and Smad4 was shown to correlate with tumor progression in esophageal squamous cell carcinoma (SCC). These components, however, were maintained normally in some patients with esophageal SCC. In our study, the mechanism by which aggressive esophageal SCC maintains these components was investigated, with particular emphasis on the participation of c-Ski and SnoN as transcriptional co-repressors in TGF-beta signaling. Immunohistochemistry for c-Ski and SnoN was carried out on surgical specimens obtained from 80 patients with esophageal SCC. The expression of c-Ski and SnoN was also studied in 6 established cell lines derived from esophageal SCC and compared to an immortalized human esophageal cell line by Western blotting. High levels of expression of c-Ski, detected immunohistologically, were found to correlate with depth of invasion (p = 0.0080) and pathologic stage (p = 0.0447). There was, however, no significant correlation between expression of SnoN and clinicopathologic characteristics. A significant correlation between c-Ski and TGF-beta expression was observed. Moreover, in patients with TGF-beta negative expression, the survival rates of patients with c-Ski positive expression were significantly lower than those of patients with c-Ski negative expression (p = 0.0486). c-Ski was expressed at a high level in 5 of 6 cell lines derived from esophageal SCC compared to immortalized esophageal keratinocytes. Furthermore, the cyclin-dependent kinase (CDK) inhibitor, p21 that was up-regulated by TGF-beta signaling was expressed at a low level in the 5 cell lines. The expression of c-Ski protein as a transcriptional co-repressor in TGF-beta signaling seems to be correlated with tumor progression of esophageal SCC.

Focal adhesion kinase (p125(FAK); 'FAK') is a tyrosine kinase that is localised to cellular focal adhesions and is associated with a number of other proteins, such as integrin adhesion receptors. We performed an immunohistochemical analysis of FAK protein expression to determine the relationship between FAK overexpression and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 91 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Seven human ESCC cell lines-TE-1, TE-2, TE-8, TE-13, TE-15, TT, and TTn-and one immortalized human keratinocyte cell line-HaCaT-were used in Western blot analysis. Immunostaining of FAK was seen in the cytoplasm of cancer cells, particularly in cells located in the invasive fronts of cancer nests. FAK overexpression was detected in 54 of the 91 patients (59.3%). Significant correlations were observed between FAK overexpression and cell differentiation (P=0.0057), depth of tumour invasion (P=0.0023), presence of regional lymph node metastasis (P=0.0097), number of lymph node metastases (P=0.0026), and disease stage (P=0.012). The survival rates of patients with FAK-overexpressing cancer were significantly lower than those of patients without FAK-overexpression cancer (P=0.006). The 5-year survival rate of patients without FAK overexpression was 69%, whereas that of patients with FAK overexpression was 38%. On Western blot analysis, FAK was expressed at a high level in TE-1, TE-8, TE-15, and TT cells, at a moderate level in TE-2 and TTn cells, and at a low level in TE13 and HaCaT cells. FAK phosphorylation at tyrosine 397 was demonstrated in proportion to the intensity of FAK in all cell lines except TE15 and HaCaT. In conclusion, FAK overexpression of ESCC was related to cell differentiation, tumour invasiveness, and lymph node metastasis. Consequently, patients with ESCC who had FAK overexpression had a poor prognosis.

Anastomotic insufficiency is considered to be one of the most serious complications associated with esophageal reconstruction. The purposes of this study were to identify (1) the relationship between anastomotic insufficiency and tissue blood flow (TBF) in the gastric tube in the perioperative period, and (2) the effects of intravenous prostaglandin E1 (PGE1) on TBF in the gastric tube. The study group consisted of 44 patients who were to undergo esophagectomy for esophageal cancer. Intraoperative and postoperative TBF on the serosal side of the gastric tube were measured by laser-Doppler tissue blood flowmetry. The TBF of the Leakage(+) group (n = 5) was poorer than that of the Leakage(?) group (n = 39) during the intraoperative and postoperative periods. There was a significant difference in TBF between the two groups at postoperative day (POD) 3. There was a tendency in the PGE1(+) group (n = 18) to exhibit richer blood flow through the anastomosis than the PGE1(?) group (n = 26), intraoperatively, but the difference was not significant. Two of five Leakage(+) cases were also in the PGE1(+) group. There was no relationship between intraoperative medication with PGE1 and incidence of leakage. The TBF of three-field lymph node dissection and reconstruction of the retrosternal route group (n = 21) was poorer than that of the two-field lymph-node dissection and reconstruction of the posterior mediastinal route group (n = 23). The TBF in the gastric tube after esophagectomy may be a predictor of anastomotic insufficiency. However, PGE1 treatment in the intraoperative period alone is not effective in preventing anastomotic insufficiency.

In esophageal squamous cell carcinoma (SCC), we used immunohistochemical analysis to further elucidate the correlation of p53 protein expression with clinicopathological factors, as well as with risk factors, such as tobacco smoking, alcohol consumption and a family history of cancer, using odds ratios (ORs). The expression of p53 protein was demonstrated in 55.1% of 89 esophageal SCC cases examined by immunohistochemistry. The expression of p53 protein did not correlate with gender, age, histological grading, lymph node metastasis, or TNM stage. The prevalence of p53 expression was significantly higher in patients with multiple primary esophageal cancers (P0.05). p53 expression did not correlate with prognosis in univariate survival analysis. The esophageal SCC in either smokers or alcohol users was 4.67-5.83 times more likely to express p53 protein, while the likelihood of p53 expression in patients who use both tobacco and alcohol was more than 14.0 times. However, a significant association was not found between p53 expression and a family history of cancer, this having an OR as low as 1.85. The expression of p53 protein did not correlate with clinicopathological factors and prognosis in univariate and multivariate survival analyses. In contrast, tobacco smoking and alcohol consumption were shown to be strongly associated with p53 mutations in esophageal carcinogenesis.

BACKGROUND KAI1/CD82, a tumor metastasis suppressor gene, is correlated inversely with the progression and invasion of several tumors. It also has been reported that the KAI1 gene is related to the tumor suppressor gene p53. This study was performed to clarify the correlation between KAI1/CD82 expression and clinicopathologic characteristics and p53 expression in patients with esophageal squamous cell carcinoma (ESCC). The authors also investigated mutation of the KAI1 gene coding region to determine whether this may reduce KAI1 expression in ESCC. METHODS Using immunohistochemistry with anti-KAI1 polyclonal antibody and monoclonal antibody against p53, KAI1/CD82 and p53 expression were detected in 55 patients with ESCC who had undergone surgery. The authors examined the KAI1 gene mutation in 22 patients with ESCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and DNA sequencing. RESULTS KAI1/CD82 expression was positive in 36 of 55 patients (65.5%). There was a significant inverse correlation between KAI1/CD82 expression and regional lymph node metastasis (P = 0.0045), distant metastasis (P = 0.0092), the number of lymph node metastases (P = 0.0019), and pathologic stage (P = 0.0046). The survival rates of KAI1/CD82 negative patients were poorer than those of positive patients (P = 0.024). The correlation between KAI1 positive and p53 positive tumors was not statistically significant. None of the 22 patients with ESCC showed mutation of the KAI1 gene by PCR-SSCP. In one patient, there was polymorphism in the SSCP assay and DNA sequencing. CONCLUSIONS The authors demonstrated immunohistochemically that the expression of KAI1 protein appeared to be correlated with lymph node metastasis. Mutation does not seem to be a mechanism for dysregulation of the KAI1 protein in ESCC. Cancer 2000;89:955–62. © 2000 American Cancer Society.

Prostaglandins (PGs), which play a pivotal role in the cytokine network, have been implicated in the pathophysiology of circulatory shock, but the precise role of cyclooxygenase-2 (COX-2) in circulatory shock is still not known. This study investigated whether or not COX-2 affects liver and bowel injury during hemorrhagic shock (HS). Male Sprague-Dawley rats were subjected to decompensated HS followed by resuscitation. Besides the time course of tissue injury and mRNA expression of COX-2 in the liver and bowel during HS, we investigated the effect of N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS398), a specific inhibitor of COX-2, on injury to these organs. The liver injury, evaluated by plasma aminotransferase levels and histology, was evident at the end of the shock period (Shock-0h) and had significantly increased 1 h after the start of resuscitation (Shock-1h) (P < 0.01). The bowel injury, assessed by histological findings in the terminal ileum, was scarcely detectable at Shock-0h but became noticeable at Shock-1h (P < 0.01). COX-2 mRNA expression was up-regulated in the liver during HS whereas it did not change in the bowel. NS398 treatment significantly exacerbated both liver and bowel injury. These lines of evidence suggest that COX-2-derived PGs provide protection against HS-induced liver and bowel injury.

We have examined the expression of nitrotyrosine, a marker of peroxynitrite formation, in 55 esophageal cancers by immunohistochemistry. Nitrotyrosine was detected in 21 of 55 (38.2%) esophageal cancers. Comparison of nitrotyrosine expression and the pathological findings showed that there was a significant association between the expression of nitrotyrosine and each of the depth of tumor invasion (P

Background: It remains unproven whether nitric oxide (NO) exerts a toxic effect on hepatocytes directly or through the formation of a more toxic compound during hemorrhagic shock (HS). NO reacts at a very high rate constant with superoxide to give peroxynitrite, a potentially toxic molecule. In this study, we investigated whether or not peroxynitrite contributed to tissue injury in the liver during HS. Methods: Male Sprague-Dawley rats were subjected to decompensated HS followed by resuscitation. In addition to the time course of tissue injury and inducible NO synthase (iNOS) messenger RNA (mRNA) expression in the liver during HS, we investigated the effect of N6-(iminoethyl)- L -lysine( LNIL) (a specific inhibitor of iNOS) and also that of uric acid (a natural scavenger of peroxynitrite) on tissue injury and nitrotyrosine formation (a footprint of peroxynitrite) in the liver. Results: The liver injury, evaluated by plasma aminotransferase levels and histology, became evident at the end of the shock period and had significantly increased 1 hour after the start of resuscitation (Shock-1h). There was no iNOS mRNA expression in the liver at baseline, and it had clearly increased by Shock-1h. Treatment with LNIL or uric acid significantly attenuated the tissue injury with a prominent reduction in nitrotyrosine formation in the liver. Conclusions: These lines of evidence suggest that one of the mechanisms by which NO production causes liver injury during HS may be its reaction with superoxide to form peroxynitrite. (Surgery 2000;127:439-46.)

Hemorrhagic shock (HS) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils (PMN) and may progress to organ failure, inducing acute respiratory distress syndrome (ARDS). To examine the hypothesis that interleukin-6 (IL-6) contributes to PMN infiltration and lung damage in HS, we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of IL-6 and activation of Stat3. Using semiquantitative RT-PCR, we found a striking increase in IL-6 mRNA levels only in resuscitated HS, with peak levels observed 1 h after initiation of resuscitation. Increased IL-6 protein expression was localized to bronchial and alveolar cells. Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in Stat3 activation with kinetics similar to IL-6 mRNA. In situ DNA binding assay determined Stat3 activation predominantly within alveoli. Intratracheal instillation of IL-6 alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli, marked elevation of bronchoalveolar lavage cellularity, and increased wet-to-dry ratio. These findings indicate that IL-6 production and Stat3 activation occur early in HS and may contribute to PMN-mediated lung injury, including ARDS after HS.

症例は64歳,男性.1989年10月低血糖による異常行動を主訴として入院した.理学的所見では前胸部,後頭部に皮疹がみられ肝脾腫を認めた.画像診断では肝・脾内に腫瘤性病変は見られなかったが,腹腔鏡検査では肝表面に地図状の白斑が認められ,組織学的には門脈域を中心に肉芽腫様病変の形成を特徴とする,異型性を有する小型リンパ球浸潤からなる病変が多発し,免疫染色・電顕所見も併せてT細胞性リンパ腫と診断した.皮疹からの生検組織でも同様の所見がみられ,皮膚T細胞性リンパ腫(small cerebriform cell type)と診断した.血清学的に抗インスリン受容体抗体が陽性を示し,低血糖は,paraneoplastic syndromeと考えられた.本症例は1975年に紅皮症と診断されたが,当時の皮膚生検組織にもlymphoma cellが認められ,15年間subclinicalな状態で経過したものと考えられた.皮膚T細胞性リンパ腫に肝肉芽腫様病変を合併した例は稀であり,さらに肝浸潤により低血糖を招来した例は,本邦では文献的に検索し得た範囲内では第1例目と考えられた.

This paper describes a patient with malignant lymphoma of the small intestine who developed perforated peritonitis in a remission-stage four months after chemotherapy. A 65-year-old male was admitted to the hospital because of abdominal pain and distension. He had received chemotherapy for a malignant lymphoma of the small intestine four months previously and was in remission. Plain chest X-ray revealed free air in the bilateral subphrenic areas. Emergency laparotomy was performed following a diagnosis of perforated peritonitis. Perforation of the jejunum was recognized. Partial jejunal resection and drainage were performed. The resected specimens exhibited a simple ulcer and no lymphoma cells. With recent progression of chemotherapy therapeutic outcomes of malignant lymphomas become better. However, careful attention is still needed, because there are some cases causing perforation even in a remmssion stage after successful chemotherapy like this case.

To determine the risk of death at an early stage of fulminant viral hepatitis, we created severity indexes drawn from clinical data on the day of development of encephalopathy in 128 patients with fulminant hepatitis B and 103 with fulminant hepatitis non-A, non-B. In fulminant hepatitis B, the risk score was 2.75×BL+2.75×BR+2.7×AG+2.3×WB+1.67×CD+1.56×AL−0.098×PR−0.88, where BL is 1 if total bilirubin is higher than 20 mg/dl, BR is 1 if the ratio of total to direct bilirubin exceeds 2.2, AG is 1 if age is above 40 yr, WB is 1 if white blood cell count is less than 4,000 cells/mm3 or more than 18,000 cells/mm3, CD is 1 if a hazardous disease coexists and AL is 1 if ALT is less than 100 times the upper limit of normal (otherwise all are 0), and PR is prothrombin time (percentage of normal value). Using a cutoff score of 0, we found the positive predictive value, negative predictive value and predictive accuracy to be 0.90, 0.86 and 0.89, respectively. Sensitivity and specificity were 0.94 and 0.77, respectively. In fulminant non-A, non-B hepatitis, the risk score was 2.66×BR+2.25×BL+2.24×DI+2.05×AL ± 1.38×AG+0.00021×WB−6.33. BR is 1 if the ratio of total to direct bilirubin is more than 1.5, BL is 1 if total bilirubin is higher than 15 mg/dl, DI is 1 if the duration of illness before encephalopathy is less than 4 days or more than 12 days, AL is 1 if the ALT level exceeds 40 times the upper limit of normal and AG is 1 if age exceeds 50; otherwise all variables are 0. WB is WBC count per cubic millimeter. Positive predictive value, negative predictive value and predictive accuracy were 0.92, 0.80 and 0.89, respectively. Sensitivity and specificity were 0.95 and 0.70, respectively. These prediction equations were validated prospectively on a population of testing samples comprising 52 patients with fulminant hepatitis B and 47 with fulminant non-A, non-B hepatitis. Positive predictive values were 0.92 and 0.92, negative predictive values were 0.71 and 0.78 and predictive accuracies were 0.87 and 0.89 for patients with fulminant hepatitis B and fulminant non-A, non-B hepatitis, respectively. They may be used for selecting candidates for liver transplantation and for evaluating efficacy of a new therapy. (HEPATOLOGY 1994;19:1065–1071.)

The incidence of HCV positivity and its relation to surgical and disease history was studied in elderly Japanese. The subjects included 230 individuals (97 men and 133 women) aged 60 to 102 years (mean: 79.2 years), and anti-HCV positivity was found in 42 cases (18.3%). More than 10% of the subjects in each age decade were anti-HCV positive, with the highest rate seen in the 60–69-year-old group (31.0%). No age-related differences in anti-HCV titer were observed. Twenty-eight of 32 subjects examined were HCV-RNA positive and analysis of HCV-RNA status revealed that most anti-HCV-positive subjects had a persistent HCV infection. About 60% of the anti-HCV-positive subjects had undergone surgery, supporting the conclusion that horizontal transmission via surgery or blood transfusion was an important route of HCV transmission. Liver dysfunction was noted in 33.3% of the anti-HCV-positive subjects, always in association with the presence of HCV RNA. Liver cirrhosis was diagnosed for two subjects, but no liver cancers were detected. One of two autopsied cases, a 91-year-old female who had undergone surgery 20 years before, showed characteristic features of chronic persistent hepatitis in spite of normal liver function tests before death. Our findings suggest that not only long-term monitoring for liver cirrhosis and liver cancer but also attention to the infection risk of transmission to others is needed in the care of elderly anti-HCV-positive individuals.

In order to study the mortality rate and bacteremia, plasma endotoxin, and plasma endothelin-1 levels in antibiotic therapy for E. coli peritonitis, blood samples were obtained from rats given intraperitoneal injections of latamoxef or placebo. Intraperitoneal injections of latamoxef improved the prognosis of peritonitis rats. Two h after treatment, bacteremia levels were noticeably higher in rats treated with placebo than in rats treated with latamoxef, but the latamoxef-treated group manifested a significant elevation of plasma endotoxin and endothelin-1 levels compared to the placebo-treated group. The results of this study demonstrate that treating E. coli septic peritonitis with selected antibiotics induces increased plasma endotoxin levels, which are associated with elevation of plasma endothelin-1 levels.

症例は50歳,女性.1987年11月クモ膜下出血にて左右中大脳動脈瘤クリッピング術を施行し,赤血球濃厚液5単位の輸血を受けた.輸血1ヵ月後に肝機能障害が出現.輸血後肝と診断し,安静・輸液などの治療により肝機能は一時改善したが,発症2ヵ月後に再び悪化し,意識障害はなかったが,PT 43.2%と重症化した.G-I療法,FFPなどの投与により肝機能は軽快した.経過中に抗ミトコンドリア抗体(AMA)が高力価陽性を示したが,肝炎の改善とともに力価は陰性化した.しかし発症約3年後,肝機能が正常にもかかわらず,AMAは再び,一過性に陽性となったが,現在はまた陰性が持続している.回復期に施行した腹腔鏡では肝両葉に大きな結節性病変を認め,馬鈴薯肝と診断した.組織学的には再生結節の所見であり,原発性胆汁性肝硬変(PBC)の所見はみられなかった.本例はAMAの産生機序,生理的意義を考える上で興味深いと思われた.

Cell cycle regulators, such as cyclinD1 and p53, play major roles in the tumor response to radiation and chemotherapy in esophageal squamous cell carcinoma (SCC). Pin1-mediated prolyl-isomerization potentiates cell cycle progression and cell proliferation, including the regulation of cyclinD1 and p53. Herein, we investigated the effect of Pin1 in association with cyclinD1 and p53 on the sensitivity of esophageal SCC to chemoradiotherapy (CRT). The expression levels of Pin1, cyclinD1 and p53 were examined immunohistochemically in endoscopic biopsy specimens from 68 advanced esophageal SCC patients before CRT to determine whether their expression levels predicted the clinical effectiveness of CRT in individual cancers. Forty-six of the 68 patients (67.6%) had an effective response to CRT, whereas 22 patients (32.4%) had an ineffective response. There was no significant correlation between clinical responses and expression levels of cyclinD1 or p53. However, the clinical response of the high Pin1 expression group was significantly higher than that of the low expression group (P=0.0200). Moreover, our data indicate that the combined immunohistochemical evaluation of Pin1, cyclinD1 and p53 expression in pretreatment biopsy samples is a useful indicator of sensitivity to CRT in advanced esophageal SCC. Thus, Pin1 may influence cyclinD1 and p53 functions and predict CRT sensitivity.

The purpose of the present study was to assess the contribution of simultaneous functional/anatomical imaging using integrated 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), compared with PET alone for the evaluation of initial lymph node staging in esophageal cancer. We studied 167 consecutive patients with thoracic esophageal squamous cell carcinoma (SCC) who had radical esophagectomy performed between January 1999 and April 2007. For individual nodal group evaluation, PET/CT showed 46.0% sensitivity (p

Background Carcinoid tumors rarely arise in the extrahepatic bile duct and can be difficult to distinguish from carcinoma. There are no reports of clear cell carcinoid (CCC) tumors in the distal bile duct (DBD) to the best of our knowledge. Herein, we report a CCC tumor in the DBD and review the literature concerning extrahepatic bile duct carcinoid tumors. Case presentation A 73-old man presented with fever and occult obstructive jaundice. Ultrasonography, computed tomography (CT) and magnetic resonance cholangiopancreaticography (MRCP) demonstrated a nodular tumor projection in the DBD without regional lymph node swelling. Under suspicion of carcinoma, we resected the head of the pancreas along with 2nd portion duodenectomy and a lymph node dissection. The surgical specimen showed a golden yellow polypoid tumor in the DBD (0.8 × 0.6 × 0.5 cm in size). The lesion was composed of clear polygonal cells arranged in nests and a trabecular pattern. The tumor invaded through the wall into the fibromuscular layer. Immunohistochemical stains showed that neoplastic cells were positive for neuron-specific enolase (NSE), chromogranin A, synaptophysin, and pancreatic polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and somatostatin. The postoperative course was uneventful and he is living well without relapse 12 months after surgery. Conclusion Given the preoperative difficulty in differentiating carcinoid from carcinoma, the pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors located within the intra-pancreatic bile duct.

Neuroleptic malignant syndrome (NMS), a potentially hazardous side effect of antipsychotic agents, usually develops within 10 days after receiving these agents. We describe a 65-year-old male who developed NMS after taking neuroleptics for alcohol dependence syndrome for several years. He was successfully treated by stopping these agents but three months later, an advanced sigmoid colon cancer was detected. He underwent surgery and the clinical course was uneventful. The present case is rare in that he developed NMS after long-term neuroleptic therapy and concurrent alimentary tract malignancy can be a risk factor for the development of NMS.

Esophageal carcinoma is one of the most lethal tumors, and identification of prognostic factors for patients with this disease is important. Propyl isomerase Pin1 is overexpressed in some human cancers and thought to be an important regulator of cyclinD1. However, the relationships between Pin1 expression and clinicopathologic features in patients with esophageal squamous cell carcinoma (SCC) have not been explored. Here, we investigated the role of Pin1 in association with cyclinD1 in esophageal SCC progression and its clinicopathological significance. The expressions of Pin1 and cyclinD1 were examined immunohistochemically in surgical specimens from 119 esophageal SCC patients. The expression levels of Pin1 and cyclinD1 in 6 esophageal SCC-derived cell lines were compared with those in an immortalized human esophageal cell line by western blotting. Pin1 overexpression was correlated with lymph node metastasis (P=0.0384), and its expression was related to cyclinD1 expression. Pin1 expression was correlated with poor prognosis in esophageal SCC patients (P=0.0044), and found to be an independent prognostic factor (P=0.0277). Pin1 was overexpressed in 5 of 6 esophageal SCC-derived cell lines compared with immortalized esophageal keratinocytes. Moreover, the Pin1 level was correlated with the cyclinD1 level in 4 of the 6 cell lines. In conclusion, Pin1 expression is correlated with cyclinD1 expression and may be a useful prognostic factor for esophageal SCC.

Background Perioperative steroid therapy is often used in oesophageal cancer surgery and we evaluate the effect of this therapy on the secretory leukocyte protease inhibitor levels in the lungs (a major antiprotease in the conducting airways) and postoperative course in oesophageal cancer patients. Methods Twenty-one patients operated on for oesophageal cancer in 2003–2004 were treated with perioperative steroid therapy (250 mg of methylprednisolone intravenously 1 h before the operation). Fifteen consecutive patients operated on in 2002 served as a control group. Secretory leukocyte protease inhibitor in bronchoalveolar lavage fluid and the postoperative course in the two groups were compared. Results The mortality rate was 0% and there was no significant difference in the morbidity rate between the two groups. Days of intubation and systemic inflammatory response syndrome were significantly shorter for the steroid group. The bronchoalveolar lavage fluid secretory leukocyte protease inhibitor level was significantly higher in the steroid group than in the control group on postoperative days 2 and 3. The secretory leukocyte protease inhibitor level on postoperative day 3 was remarkably lower for the patients intubated for ≥5 days and for those with pulmonary complications. Conclusion Perioperative steroid therapy increased the bronchoalveolar lavage fluid secretory leukocyte protease inhibitor level and reduced the days of intubation and systemic inflammatory response syndrome in patients with oesophagectomy.

Background Although several studies have indicated that Helicobacter pylori eradication develops reflux oesophagitis, others reported that its eradication had a beneficial effect on reflux symptoms. The results are still controversial. Objective To study whether H. pylori eradication increases the occurrence rate of reflux oesophagitis in patients with peptic ulcers. Method One hundred and two consecutive patients who had peptic ulcers and were H. pylori-positive by C-urea breath testing were followed prospectively. They all received 1-week triple therapy and underwent endoscopy at 1-year intervals or when relapse of the peptic ulcer or occurrence of reflux oesophagitis was suspected. Results Reflux oesophagitis developed in 32 (31.4%) out of 102 patients and they were of grade A (27 patients) and grade B (five patients) by the Los Angeles classification System. H. pylori infection was cured in 77 (75.5%) out of 102 patients. There was no significant difference in age (53.4+/-1.2 vs. 53.9+/-1.4 years, P = 0.43), gender (male/female, 29/3 vs. 53/17, P = 0.14), ulcer location (gastric/duodenal/both, 15/12/5 vs. 35/26/9, P = 0.97), H. pylori status (persistent/cured, 9/23 vs. 16/54, P = 0.57) or length of follow-up time (355+/-32 vs. 348+/-23 days, P = 0.30) between the 32 patients with reflux oesophagitis and the other 70 patients. Only the presence of hiatal hernia before therapy was significant for the prevalence of reflux oesophagitis by the log-rank test (P = 0.002), and the Cox proportional hazard models confirmed these findings (odds ratio, 3.46; 95% confidence interval, 1.64-7.30; P = 0.0012). Conclusions The eradication of H. pylori did not increase the prevalence of reflux oesophagitis, and only the presence of hiatal hernia before therapy was significantly related to the development of reflux oesophagitis.

We investigated whether Helicobacter pylori (HP) eradication increases the incidence of reflux esophagitis (RE) in patients with peptic ulcers. From 2001-2005 consecutive out patients with peptic ulcers and HP received eradication and were followed endoscopically. HP was cured in 119 and RE developed in 33 of the 153 patients. RE developed in 24 of the 119 HP-eradicated patients and 9 of the 34 HP-persistent patients. The estimated RE occurrence rate within 1 year was higher in the HP-eradicated patients than in the HP-persistent patients, but it was reversed at 2 years by the Kaplan-Meier analysis. In 76 patients follow up foror = 18 months, hiatal hernia, duodenal ulcer, and eradication failure were significantly associated with the increased RE rate by univariate and multivariate analysis. The follow-up period after HP eradication affected the RE occurrence rate, and eradication failure significantly increased the RE development in patients followed up foror = 18 months.

Background Receptor-binding cancer antigen expressed on SiSO cells (RCAS1) has been reported to act as a ligand for a receptor present on normal peripheral lymphocytes and to induce apoptotic cell death. We aimed to elucidate the significance of RCAS1 expression in human esophageal squamous cell carcinomas (ESCC). Methods RCAS1 expression was examined immunohistochemically in surgically resected esophageal carcinoma tissues from 114 patients. We also examined the relationships between RCAS1 expressions, the tumor Ki-67 indices (a marker of proliferation), and the number of CD8+ tumor-infiltrating lymphocytes (TILs). Results RCAS1 immunoreactivity was detected in the membranes and cytoplasm of the tumor cells. Of the 114 esophageal carcinomas, 39 (34.2%) were strongly positive for RCAS1 immunostaining on the membranes of the cancer cells, 41 (36.0%) were weakly positive, and 34 (29.8%) were negative. A comparison of RCAS1 expression and clinicopathological characteristics in all 114 patients revealed significant associations between RCAS1 expression and lymph node status (P

BACKGROUND The purpose of the current study was to assess whether [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) provides incremental value (e.g., additional information on lymph node involvement or the presence of distant metastases) compared with computed tomography (CT) in patients with esophageal carcinoma. METHODS The authors examined 149 consecutive patients with thoracic esophageal carcinoma. Eighty-one patients underwent radical esophagectomy without pretreatment, 17 received chemoradiotherapy followed by surgery, 3 underwent endoscopic mucosal resection, and the remaining 48 patients received definitive radiotherapy and chemotherapy. The diagnostic accuracy of FDG-PET and CT was evaluated at the time of diagnosis. RESULTS The primary tumor was visualized using FDG-PET in 119 (80%) of 149 patients. Regarding lymph node metastases, FDG-PET had 32% sensitivity, 99% specificity, and 93% accuracy for individual lymph node group evaluation and 55% sensitivity, 90% specificity, and 72% accuracy for lymph node staging evaluation. PET exhibited incremental value over CT with regard to lymph node status in 14 of 98 patients who received surgery: 6 patients with negative CT findings were eventually shown to have lymph node metastases (i.e., they had positive PET findings and a positive reference standard [RS]); 6 patients with positive CT findings were shown not to have lymph node metastases (i.e., they had negative PET findings and a negative RS); and 2 patients were shown to have cervical lymph node metastases in addition to mediastinal or abdominal lymph node metastases. Among the remaining patients, PET showed incremental value over CT with regard to distant organ metastases in six patients. The overall incremental value of PET compared with CT with regard to staging accuracy was 14% (20 of 149 patients). CONCLUSIONS FDG-PET provided incremental value over CT in the initial staging of esophageal carcinoma. At present, combined PET-CT may be the most effective method available for the preoperative staging of esophageal tumors. Cancer 2005. © 2004 American Cancer Society.

Background and aims. We often come across patients with complicated appendicitis (perforation, abscess formation, or peritonitis) and it is essential to get accurate and detailed information on these patients preoperatively. In this study, we investigated whether or not preoperative computed tomography is useful for identifying these patients. Patients and methods. Plain and intravenously-contrasted helical computed tomography was obtained preoperatively in 94 (75%) of 125 patients who underwent appendectomy. Twenty-eight (30%) of the 94 patients had complicated appendicitis (Compli(+) group). We compared clinical factors and computed tomography findings of the Compli(+) group with those of 66 other patients (Compli(−) group). Results. There was no significant difference between the Compli(+) and Compli(−) groups in gender, white blood cell count, the present rate of an enlarged appendix, or appendicolith. Fat stranding and free fluid on computed tomography were significantly associated with complicated appendicitis by both univariate and multilogistic regression analysis. Fourteen (70%) of the 20 patients with fat stranding and free fluid on computed tomography had complicated appendicitis and only 1 (4%) of the 28 Compli(+) patients had neither fat stranding nor free fluid on computed tomography. Conclusion. Our study has indicated that fat stranding and free fluid on computed tomography are significant for complicated appendicitis and helical computed tomography is a powerful tool for identifying patients with complicated appendicitis preoperatively.

Background We investigated whether secretory leukocyte protease inhibitor (SLPI) is associated with pulmonary complications after esophagectomy. Methods We measured serial changes in the SLPI concentration in the bronchoalveolar lavage fluid (BALF) of 34 patients who underwent and examined the relationship between SLPI and postoperative morbidity. Results Fifteen (44%) of 34 patients (high group) had a BALF SLPI concentration >90,000 pg/mL at the end of the surgery (postoperative day [POD] 0). There was no significant difference between the high group and other 19 patients (low group) with respect to age, sex, preoperative comorbid conditions, tumor stage, surgical technique, operating time, or blood loss volume. Days of intubation and pulmonary complication rate were significantly increased in the high group compared with the low group. Logistic regression analysis revealed that the BALF SLPI level on POD 0 was significant for pulmonary complications. Conclusions Our results indicate that assaying SLPI levels in BALF can be useful for the prediction of pulmonary complications after esophagectomy.

Objectives: Despite recent advances in diagnosis and treatment of esophageal carcinoma, the future risk of hematogenous recurrence is still unpredictable. To identify risk factors of hematogenous recurrence in esophageal carcinoma, we used pathological and immunohistochemical analysis to examine relationships among clinical outcomes, clinicopathological features, and E-cadherin expression.Methods: Subjects were 102 patients with thoracic esophageal cancer who had undergone curative esophagectomy without preoperative treatment. We used univariate and multivariate logistic regression analyses to examine the relationship among clinical outcomes, clinicopathological features, and E-cadherin expression.Results: There was no significant relationship between E-cadherin expression and clinicopathological features at operation. However, the survival rates of patients with E-cadherin-negative tumors were significantly lower than those of patients with E-cadherin-weak and E-cadherin-positive tumors (P

Background The objective of this study was to investigate the effects of OPC-6535 on Propionibacterium acnes –primed and lipopolysaccharide-induced liver injury in the rat. Methods P. acnes was administered intravenously to the rat at 16 mg/kg 7 days before the experiments. In liver perfusion experiments, lipopolysaccharide was mixed in perfusion buffer at 2.5 μg/mL. The chemiluminescence method and histochemical reduction of nitro blue tetrazolium were used for detecting superoxide. Release of cytokines into the perfusate was examined. In in vivo experiments, lipopolysaccharide was administered intravenously to the rat at 200 μg/kg. Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cytokines were determined in the plasma, and myeloperoxidase activity was measured in the liver tissue. OPC-6535 was given intravenously at 1 mg/kg 30 minutes before lipopolysaccharide challenge, and was then, in perfusion experiments, added to the buffer at 10 μmol/L. Results In perfusion experiments, P. acnes and lipopolysaccharide caused dramatic production of superoxide, tumor necrosis factor-α (TNF-α) and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1). Superoxide was mainly from hepatic macrophages. Treatment with OPC-6535 suppressed superoxide and TNF-α but did not affect GRO/CINC-1. In in vivo experiments, P. acnes and lipopolysaccharide increased the level of TNF-α, GRO/CINC-1, AST and ALT in the plasma, and myeloperoxidase activity in the liver. OPC-6535 reduced TNF-α, AST, and ALT, but did not affect GRO/CINC-1 or myeloperoxidase. Conclusion Attenuation of liver injury by OPC-6535 is believed to be due to its inhibitory effects on superoxide and TNF-α production by hepatic macrophages in P. acnes – and lipopolysaccharide-treated rats.

Background Our aim was to determine whether minichromosome maintenance protein (MCM) 2 expression is useful in predicting tumor proliferation rates and outcome after therapy in patients undergoing surgery for esophageal squamous cell carcinoma (SCC). In addition, we evaluated whether the expression of this proliferation marker was correlated with that of another marker, Ki-67, in esophageal SCC. Methods We examined immunohistochemical expression of MCM2 and Ki-67 in surgically resected tissues from 93 patients with esophageal SCC. Results The mean nuclear labeling index of MCM2 was markedly higher in SCC than in normal epithelia (P

BACKGROUND The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium-99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging. METHODS The authors observed 25 patients with thoracic esophageal carcinomas who underwent radical esophagectomy. The day before surgery, technetium-99m colloidal rhenium sulfide was injected into the submucosa at four sites around the primary tumor. Lymphoscintigraphy was performed. Esophagectomy and regional lymph node dissection were performed 17 hours after the technetium-99m injection. After surgery, the resected lymph nodes were evaluated by CK staining. RESULTS Lymphoscintigraphy detected sentinel lymph nodes in 92% of the patients (23 of 25 patients). The accuracy of sentinel lymph node was 91.3% (21 of 23 patients), the sensitivity was 86.7% (13 of 15 patients), and the false-negative rate was 8.7% (2 of 23 patients). A comparison of the number of sentinel lymph nodes and clinicopathologic factors showed that there was a significant association between the number of sentinel lymph nodes and lymph node status (P < 0.01), pathologic stage (P < 0.05), and the number of metastatic lymph nodes (P < 0.05). Occult metastasis was detected by CK staining in 14 (56%) of the 25 patients and in 23 (1.7%) of 1406 lymph nodes. Because the 2 false-negative (sentinel lymph node–negative and nonsentinel lymph node–positive) patients who had occult metastases in the sentinel lymph nodes, the accuracy of sentinel lymph node evaluation using CK staining was 100% (23 of 23). CONCLUSIONS Lymphatic mapping with technetium-99m colloidal rhenium sulfide was used to identify the lymphatic basin and was feasible in patients with esophageal SCC. An analysis of sentinel lymph nodes using CK immunohistochemistry increased the accuracy of sentinel lymph node. Cancer 2003;98:932–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11559

Background. Intensive care unit (ICU) psychosis is still a relatively frequent complication after esophageal surgery. We investigated the correlation between ICU psychosis and serum melatonin concentration during the period after esophagectomy. Methods. The study group comprised 41 patients who underwent esophagectomy for treatment of esophageal cancer between 1999 and 2001. The cohort included 36 men and 5 women, aged 36 to 78 years. After surgery, blood samples were collected 4 times a day for 4 days. Serum levels of melatonin were determined with a melatonin radioimmunoassay kit. The regularity of the melatonin circadian rhythm pattern, as defined by the frequency of occurrence of the peak level of melatonin secretion, was determined (the pattern was described as irregular at less than 3 times in the measurement period). Results. Of the 41 patients who met the inclusion criteria, 11 (26.8%) had ICU psychosis develop. These patients were older than those patients in whom ICU psychosis did not develop (P =.01). No significant differences were seen in the duration of surgery, volume of blood loss, term in the ICU, term of intubation, tumor location, disturbances of organ function, and postoperative complications between patients in whom ICU psychosis developed, and those patients in whom it did not. Patients with ICU psychosis tended to have abnormally low serum levels of melatonin. Of the 41 patients studied, 9 (22%) had an irregular pattern of melatonin circadian rhythm. A significant correlation was seen between ICU psychosis and an irregular melatonin circadian rhythm (P =.0001). Conclusion. Irregular patterns of melatonin circadian rhythm may be associated with ICU psychosis. Supplementation with melatonin, or acceleration of melatonin secretion, may protect patients from development of ICU psychosis and may promote recovery to a normal mental state. (Surgery 2003;133:662-8.)

Tonsillar tuberculosis is one of the uncommon forms of extrapulmonary tuberculosis. We report a case of tonsillar tuberculosis associated with pulmonary and laryngeal foci. A 23-year-old female was admitted for evaluation of hoarseness and difficulty in swallowing. Bilateral palatine tonsils were enlarged, and a tonsillectomy was performed. Since a histological study revealed tonsillar tuberculosis, antituberculous agents were administered. After the treatment the pulmonary lesions detected with chest computed tomography were improved, and her symptoms were relieved. The possibility of tonsillar tuberculosis should be considered when unexplained enlarged tonsil is observed in patients with pulmonary tuberculosis.

BACKGROUND The role and potential value of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. The authors retrospectively assessed the performance of 18-F-fluorodeoxyglucose (FDG)-PET in the assessment of esophageal squamous cell carcinoma (SCC). METHODS The results using PET were compared with those using computed tomography (CT), and these were correlated with the pathologic findings. The authors studied 32 patients with thoracic esophageal SCC who had undergone radical esophagectomy. RESULTS Uptake of FDG in the primary tumor was found in 25 of the 32 (78.1%) cases. Comparison of the FDG uptake and the clinicopathologic findings showed that there was a significant association between the FDG uptake and each of the depth of tumor invasion (P 3) was significantly lower than that in cases with low FDG uptake (SUV, < 3; P < 0.05). In the evaluation of lymph node staging by the detection of lymph node metastasis, FDG-PET showed 77.8% sensitivity, 92.9% specificity, and 84.4% accuracy, and CT scanning showed 61.1% sensitivity, 71.4% specificity, and 65.6% accuracy. Positron emission tomography scanning showed a high degree of accuracy in the neck, upper thoracic, and abdominal regions. However, in the mid- and lower thoracic regions, the sensitivity was very low. The smallest lymph node metastasis that was detected by FDG-PET imaging was 6 mm. The average size of lymph node metastasis that was undetected by FDG-PET scanning was 7.3 mm (range, 1–17 mm). CONCLUSIONS In conclusion, FDG-PET may be used as a noninvasive diagnostic technique in assessing the aggressiveness of the tumor and the prognosis in patients with esophageal SCC. During the preoperative diagnostic procedures, the sensitivity, specificity, and accuracy of lymph node staging is higher with FDG-PET than with CT imaging. In view of the high specificity of FDG-PET, it also gives useful information to guide the choice of treatment of esophageal carcinoma. Cancer 2002;94:921–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10330

Esophageal cancer is a relatively common neoplasm throughout the world but is found at high frequency in many developing nations [1]. The number of superficial esophageal carcinomas identified has increased rapidly in recent years owing to advances in diagnostic methods, particularly endoscopy [2,3]. Small areas unstained with Lugol’s iodine are often observed in the mucosa surrounding esophageal squamous cell carcinoma (SCC). In patients in whom this type of esophageal SCC has been resected and where the esophageal mucosa shows multiple small areas that do not stain with Lugol’s iodine, there is often multicentric cancer of the esophagus [4].

Polymorphonuclear leukocytes (PMN) and inducible nitric oxide synthase (iNOS) appear to play important roles in the liver and in lung injury induced by hemorrhagic shock. Their precise roles in hemorrhagic shock-induced acute gastric mucosal lesions (AGML), however, are still poorly understood. In this study, we investigated the effect of neutropenia on hemorrhagic shock-induced AGML. We also examined the roles of iNOS in PMN infiltration into the mucosa and AGML during hemorrhagic shock by using L-N6-(1-iminoethyl)-lysine, a potent inhibitor of iNOS, and by reverse transcriptase polymerase chain reaction. Remarkable gastric mucosal damage occurs after hemorrhagic shock. PMN depletion caused by Vinblastine pretreatment significantly attenuates this AGML. Although low-dose L-N6-(1-iminoethyl)-lysine (50 microg/kg, iNOS inhibition) has no effect on AGML, high-dose L-N6-(1-iminoethyl)-lysine (250 microg/kg, iNOS + endothelial NOS inhibition) significantly exacerbates AGML without increasing PMN infiltration into the mucosa. The mRNA expression of iNOS in the stomach during hemorrhagic shock cannot be detected by reverse transcriptase polymerase chain reaction. We conclude that PMN play a pivotal role in hemorrhagic shock-induced AGML, iNOS does not regulate PMN infiltration into the mucosa, and endothelial NOS provides important protection against AGML during hemorrhagic shock.

In surgery for colorectal cancer, a tendency of immune suppression was noted as seen in surgery for other types of gastro-intestinal cancer. This tendency was also found in the biological response, and it was related to the operative procedures and insults for rectal cancer. The degree of immunosuppression was milder in patients who underwent procedures that preserve the natural sphincter than in those who underwent colostomy. It is important for surgeons to avoid postoperative immunosuppression in order to prevent recurrence and improve prognosis. Given similar degrees of operative insult and stage of cancer, an operative procedure which causes as little immunosuppression as possible should be selected.

In this study we investigated the effect of combined administration of UFT and Krestin (PSK) on the growth of intraperitoneal metastasis and temporal changes in the immune-endocrine system under this immunochemotherapy. At 7 days, Plasma ACTH levels of the PSK group were significantly lower than that of the control group (p

The ultrastructural localization of IgA, IgA1, and IgA2 deposited on liver tissues from 13 patients with alcoholic liver disease and 9 patients with nonalcoholic liver diseases was investigated by the immunoperoxidase method. A continuous pattern of IgA deposition along the perisinusoidal area was observed not only in the alcoholic patients but also in the non-alcoholic patients. Ultrastructurally, IgA deposits were seen on the plasma membranes of Kupffer cells, endothelial cells, and hepatocytes and in the endocytotic vesicles and phagosomes of Kupffer cells and endothelial cells. In the alcoholic group, deposits of IgA on collagen fibers were observed at sites where pericellular fibrosis developed but, on the other hand, IgA deposits were diminished or absent on the plasma membranes of hepatocytes. IgA1 showed the same deposit pattern as IgA. IgA2 was observed on and in Kupffer cells and endothelial cells but was not detected on the plasma membranes of hepatocytes. From these studies, the authors conclude that IgA deposition in the liver is not specific for alcoholic liver disease but may reflect the reduced metabolism of damaged liver. An additional finding was that, of the IgA subclasses, only IgA1 combined with the plasma membranes of hepatocytes.

Eight hundred thirty-five patients with acute appendicitis operated on at Tone Central Hospital during the eight-year period from January 1977 to February 1985 were reviewed. The clinico-pathological types of acute appendicitis were1 appendicitis without peritonitis1) catarrhalis2) phlegmonas3) gangrenous2 appendicitis with peritonitisIn children (under 16 years old), the white blood cell count usually increased remarkably in those with gangrenous appendicitis or appendicitis with peritonitis. On the other hand, in older people (65 or more), the white blood cell count didn't usually increase and physical signs weren't usually remarkable, even in patients with gangrenous appendicitis or appendicitis with peritonitis.

The effects of ursodeoxycholate administration on the biliary excretion of the antibiotics cefotiam and sulbenicillin were studied in five patients with stable hepatic function receiving percutaneous transhepatic biliary drainage for obstructive jaundice. Cefotiam (I g) and sulbenicillin (2 g) were administered intravenously before and after ursodeoxycholate administration, and the maximum concentrations of the antibiotics in the bile and total amounts excreted in the bile during the 4 h after administration were determined. After ursodeoxycholate administration, both the maximum concentration of cefotiam in the bile and the amount excreted increased significantly. Ursodeoxycholate also increased the peak concentration and total excretion of sulbenicillin. For both cefotiam and sulbenicillin, the amount of antibiotic excreted in the bile during the 4 h after administration showed a significant correlation with the amount of bile acids excreted in the bile. This strongly suggests a common mechanism for the biliary excretion of these antibiotics and bile acids. Ursodeoxycholate administration is a benign way to increase both the concentration and the total amount of antibiotic excreted in the bile. Therefore, it may be useful in the treatment of serious biliary tract infections, especially in patients receiving biliary drainage.