Effect of anti-allergic agents on chemotaxis of neutrophils by stimulation of chemotactic factor released from hepatocytes exposed to ethanol

In an attempt to clarify a mechanism of neutrophil infiltration in the liver of alcoholics and possible therapeutic effect of antiallergic agents on accumulation of these cells in the liver, we investigated chemotaxis of neutrophils by stimulation of a chemotactic factor released from rat hepatocytes exposed to ethanol. When hepatocytes were incubated with more than 30 mM ethanol for 24 hr, chemotactic activity for both rat and human neutrophils was demonstrated in the conditioned medium. An enhanced chemotactic activity of the conditioned medium was reduced in the presence of antibody against KC/gro protein, one of the interleukin-8-related cytokines in rodents. Antiallergic agents such as azelastine or ketotifen at a concentration of >0.01 µM markedly reduced chemotaxis of neutrophils. Prednisolone at a concentration of >10 µM also reduced chemotaxis of neutrophils. These results suggest that neutrophil accumulation in the liver of human alcoholics could be induced by a chemotactic factor produced by the ethanol-treated hepatocytes and that antiallergic agents could be effective against the extent of alcoholic hepatitis by reducing chemotaxis of neutrophils.     

Cardiovascular response to exercise in pacemaker implanted patients with fixed heart rate

Cardiovascular response to supine exercise was studied in 11 patients with chronic ventricular pacing for complete atrioventricular block whose heart rate was fixed during exercise, and compared with 11 age- and sex-matched normal subjects. Oxygen uptake increased linearly with increasing work rate, and attained maximum values of 15.7 +/- 0.7 and 29.5 +/- 1.1 ml/min.kg, respectively. In both groups, cardiac output increased in association with oxygen uptake, although the maximum value in the patients was less than one half that in the controls (6.8 +/- 0.5 and 15.1 +/- 0.3 l/min). Stroke volume, however, could change in patients, as in the controls under similarly increased afterloads (maximum values were 96 +/- 7 and 93 +/- 3 ml/beat, respectively). During exercise, the systolic arterial pressure elevated to a similar extent in both groups (221 +/- 14 and 235 +/- 12 mmHg, respectively). The increase in stroke volume in the patients was achieved by complete systolic emptying and the Frank-Starling mechanism. It is considered that in patients with ventricular pacing, exercise can produce an increase in stroke volume when myocardial function is not impaired.     

Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To analyze hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) using the tumor-node-metastasis(TNM) staging system.METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009.We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system(7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center.Portal vein invasion(vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein,vp2 as an invasion or tumor thrombus in the second branch of the portal vein,vp3 as an invasion or tumor thrombus in the first branch of the portal vein,and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.RESULTS: The cumulative 5-year overall survival(5yr OS) and 5-year disease-free survival(5yr DFS) rates of the 372 patients were 58.3% and 31.3%,respectively.The 5yr DFS and 5yr OS of vp3-4 patients(n = 10) were 20.0%,and 30.0%,respectively,which was comparable with the corresponding survival rates of vp1-2 patients(P = 0.466 and 0.586,respectively).In the subgroup analysis of patients with macroscopic PVTT(vp2-4),the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not(P = 0.747).There was a significant difference in the DFS between patients with stage Ⅰ HCC and those with stage Ⅱ HCC(5yr DFS 39.2% vs 23.1%,P 0.001); however,theDFS for stage Ⅱ was similar to that for stage Ⅲ(5yrD FS 23.1% vs 13.8%,P = 0.330).In the subgroup analysis of stage Ⅱ-Ⅲ HCC(n = 148),only alpha-fetoprotein(AFP) 100 mg/dL was independently associated with DFS.CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2.AFP stratified the stage Ⅱ-Ⅲ HCC patients according to prognosis.     

Laparoscopic transhiatal approach for resection of an adenocarcinoma in long-segment Barrett's esophagus

Barrett's esophagus(BE) is a precursor of esophageal adenocarcinoma and is associated with gastroesophageal reflux disease, which is often preceded by a hiatal hernia. We describe a case of esophageal adenocarcinoma arising in long-segment BE(LSBE) associated with a hiatal hernia that was successfully treated with a laparoscopic transhiatal approach(LTHA) without thoracotomy. The patient was a 42-year-old male who had previously undergone laryngectomy and tracheal separation to avoid repeated aspiration pneumonitis. An ulcerative lesion was found in a hiatal hernia by endoscopy and superficial esophageal cancer was also detected in the lower thoracic esophagus. The histopathological diagnosis of biopsy samples from both lesions was adenocarcinoma. There were difficulties with the thoracic approach because the patient had severe kyphosis and muscular contractures from cerebral palsy. Therefore, we performed subtotal esophagectomy by LTHA without thoracotomy. Using hand-assisted laparoscopic surgery, the esophageal hiatus was divided and carbon dioxide was introduced into the mediastinum. A hernial sac was identified on the cranial side of the right crus of the diaphragm and carefully separated from the surrounding tissues. Abruption of the thoracic esophagus was performed up to the level of thearch of the azygos vein via LTHA. A cervical incision was made in the left side of the permanent tracheal stoma, the cervical esophagus was divided, and gastric tube reconstruction was performed via a posterior mediastinal route. The operative time was 175 min, and there was 61 m L of intra-operative bleeding. A histopathological examination revealed superficial adenocarcinoma in LSBE. Our surgical procedure provided a good surgical view and can be safely applied to patients with a hiatal hernia and kyphosis.     

Clinical characteristics of hepatoduodenal lymph node metastasis in gastric cancer

AIM: To assess the clinical features of hepatoduodenal lymph node(HDLN) metastasis and to clarify the optimal indication of HDLN dissection.METHODS: We investigated a total of 276 patients who underwent gastrectomy with extended lymphadenectomy,including HDLN dissection,for gastric cancer between 1999 and 2012. Of these,26 patients(9.4%) had HDLN metastasis. First,we investigated the clinicopathological characteristics,their perioperative clinical outcomes,such as postoperative complications,and prognostic outcomes between patients with and without HDLN metastasis. Second,we detected the prognostic factors,particularly in patients with HDLN metastasis. Third,we assessed the therapeutic value of HDLN dissection to determine its optimal indication.RESULTS: The five-year overall survival rate of the patients with HDLN metastasis was 29%. Univariate and multivariate logistic regression analyses revealed that the tumour location(the middle or lower stomach [P = 0.005,OR = 5.88(95%CI: 1.61-38.1)] and p T category [T3 or T4,P = 0.017,OR = 4.45(95%CI: 1.28-21.3)] were independent risk factors for HDLNmetastasis. Cox proportional hazard analysis identified p N3 as an independent poor prognostic factor in the patients with HDLN metastasis [P = 0.021,HR = 5.17(95%CI: 1.8-292)]. For patients who underwent radical HDLN dissection,HDLN metastasis was a prognostic indicator in p N3 gastric cancer(P 0.0001),but not p N1-2(P = 0.602). Furthermore,the index of therapeutic value of HDLN dissection for gastric cancer in the middle or lower stomach and the upper stomach was 3.4 and 0.0,respectively.CONCLUSION: We suggest that HDLN dissection should be indicated for p N1 or p N2 gastric cancers located at the middle or lower stomach.     

Antipituitary antibodies in patients with the primary empty sella syndrome

The frequency of detection of serum antibodies against pituitary cells was determined in 32 patients with the primary empty sella syndrome. Antibodies reacting with corticotropin-secreting mouse AtT20 and PRL-secreting rat GH3 cells were found in 24 (75%) and 15 (47%), respectively, of the 32 patients; 14 patients (44%) had antibodies reacting with both cell lines. In patients with pituitary adenomas, the prevalence of antipituitary antibodies was significantly lower than in those with the empty sella syndrome; 1 of 9 acromegalic patients had antibodies reacting with GH3 cells, and 2 of 9 prolactinoma patients and 1 of 7 patients with nonfunctioning adenomas had antibodies reacting with both AtT20 and GH3 cells. Among 6 patients with idiopathic diabetes insipidus, 1 patient had antibodies reacting with AtT20 and GH3 cells, and 2 patients had antibodies reacting with either AtT20 or GH3 cells. None of 5 patients with established autoimmune diseases (3 with systemic lupus erythematosus and 2 with autoimmune adrenal failure) had antipituitary antibodies in their serum. These results suggest that pituitary antibodies may be related to the development of pituitary atrophy and the primary empty sella syndrome, and that the test may be clinically useful as a screening test for the empty sella syndrome.     

Alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 19-9-producing gallbladder cancer

We report a rare case of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9-producing gallbladder cancer with high levels of CA125 and protein induced by vitamin K absence or antagonist II (PIVKA II). A 63-year-old man was diagnosed with gallbladder cancer with metastases to the liver, based on ultrasonography and computed tomography of the abdomen showing multiple tumorous lesions in the liver and a thickened gallbladder wall. Laboratory data showed high levels of tumor markers: 4647.4 ng/ml AFP, 9987.1 ng/ml CEA, 11704.0 U/ml CA19-9, 847.6 U/ml CA125, and 0.2 AU/ml PIVKA II. AFP in the present case showed an increase in Concanavalin A-nonbinding fraction and an increase inLens culinaris lectin-binding fraction by affinity column chromatography. The patient died of hepatic failure. Autopsy revealed gallbladder cancer consisting of papillary adenocarcinoma and moderately differentiated tubular adenocarcinoma. By immunohistochemical staining, AFP was detected in the papillary adenocarcinoma portion of the primary focus and metastatic tumor cells in the liver, but was not detected in noncancerous liver tissue. CEA and CA19-9 were detected mainly in the tubular adenocarcinoma portion.     

Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment in normal range weight and moderately obese type 2 diabetic patients

OBJECTIVE: To investigate whether the quantitative insulin sensitivity check index (QUICKI) and the reciprocal index of homeostasis model assessment (1/HOMA-IR) derived from fasting plasma glucose and insulin level are excellent surrogate indices of insulin resistance in both normal range-weight and moderately obese type 2 diabetic and healthy subjects. RESEARCH DESIGN AND METHODS: The association between QUICKI or 1/HOMA-IR and insulin resistance index assessed by euglycemic-hyperinsulinemic clamp (clamp-IR) was investigated in 121 type 2 diabetic and 29 healthy subjects recruited from among 120 (age 55 +/- 11, 48 +/- 15, and 52 +/- 15 years [means +/- SD], respectively). Type 2 diabetic subjects were divided into groups of 76 normal range-weight and 45 moderately obese subjects (BMI 21.4 +/- 2.3 vs. 27.2 +/- 2.2 kg/m(2), P < 0.0001). RESULTS: QUICKI and 1/HOMA-IR were significantly lower in the moderately obese group than in the normal range-weight type 2 diabetic and healthy groups (n = 120) (QUICKI, 0.338 +/- 0.030, 0.371 +/- 0.037, and 0.389 +/- 0.041, respectively, P < 0.0001; 1/HOMA-IR, 0.50 +/- 0.33, 0.92 +/- 0.55, and 1.24 +/- 0.82, P < 0.0001). QUICKI was strongly correlated with clamp-IR in normal range-weight, moderately obese type 2 diabetic, and healthy subjects (r = 0.641, 0.570, and 0.502, respectively; all subjects, r = 0.608, P < 0.01) and 1/HOMA-IR exhibited correlations comparable to those of QUICKI with clamp-IR (r = 0.637, 0.530, and 0.461, respectively; all subjects, r = 0.589, P < 0.001). In multiple regression models including QUICKI or 1/HOMA-IR as an independent variable, the estimation formula accounted for 55% of the variability of clamp-IR for the group of all type 2 diabetic subjects (R(2) = 0.547 and 0.551, respectively, P 相似文献