Prophylactic Consecutive Administration of Haloperidol Can Reduce the Occurrence of Postoperative Delirium in Gastrointestinal Surgery

Postoperative delirium has in recent years been a common complication which can interfere with the recovery of patients after surgery. Unfortunately there is still no medical procedure available which can completely prevent the occurrence of postoperative delirium. Haloperidol is a psychopharmacological agent that has been used to treat the delirium and agitation, especially in geriatric patients. To assess the effectiveness and safety of the use of haloperidiol for the reduction of postoperative delirium, we performed a randomized, comparative clinical study in which 78 patients who underwent gastrointestinal surgery received either 5 mg of haloperidol intravenously postoperatively at 21:00 for 5 consecutive days, or normal saline with the same schedule. Postsurgical evaluation revealed the incidence of postoperative delirium to be only 10.5% (4 of 38 patients) in the group receiving haloperidol treatment, compared to 32.5% (13 of 40 patients) in the saline treatment group. No significant neuroleptic side effects were seen in any of the patients. These results suggest that daily postoperative administration of haloperidol can reduce the occurrence of postoperative delirium safely

Plasma Leptin Level, the Adipocyte-Specific Product of the Obese Gene, Is Associated with Tumor Progression and Is a Marker of the Nutritional Status of Patients with Gastric Cancer

Leptin, a product of the obese gene, is synthesized and released into the circulation in response to increased energy storage in adipose tissue. Leptin plays an important role in the regulation of body weight and energy balance. However, leptin levels in patients with malignant tumor have not been fully examined. The purpose of the present study is to clarify the clinical implications of leptin levels in the circulation in patients with gastric cancer. The subjects were 103 patients with gastric cancer at various stages. Levels of leptin in the plasma were determined with a commercially available human leptin-selective quantitative enzyme immunoassay kit. There were clear decreasing trends in leptin levels along with tumor progression in both males and females, and statistically significant differences were observed in males between stages II and IV, and in females between stages I and IV. Plasma leptin levels of females were consistently higher than those of males when we compared them with patients in the same stages. Moreover, statistically significant decreases in leptin levels were observed postoperatively. However, there were no statistically significant relationships between leptin levels and clinicopathological findings. There was a positive correlation between levels of plasma leptin and values of the body mass index. These findings may indicate that plasma leptin levels do not involve factors relevant to specific tumor growth but involve some tumor-related nutritional status due to tumor progression. We conclude that leptin levels are reflected during tumor-bearing status, and these are also useful markers for both indicating tumor progression and discovering the nutritional status of patients with gastric cancer

Immunohistochemical Detection of Occult Serosal Microinvasion in Primary Lesions of Gastric Cancer with Subserosal Invasion

In gastric cancer, the presence or absence of serosal invasion by cancer in the primary lesion is an important prognostic factor. Pathological findings are routinely determined by hematoxylin-eosin (H&E) staining, but it is well known that micrometastasis or microinvasion are easily overlooked by H&E staining. Cytokeratin (CK) proteins serve as reliable markers for cells from epithelial origins. The purpose of this study was to clarify the usefulness of CK immunohistochemical staining in the detection of serosal microinvasion in gastric cancer with subserosal invasion. We examined 50 primary lesions from 50 gastric cancer patients with subserosal invasion. Two consecutive sections were prepared for simultaneous staining with ordinary H&E and CK immunostaining with anticytokeratin antibody (CAM 5.2), respectively. Although there were no differences in the postoperative survival rates between patients with or without microinvasion, serosal microinvasion was 0detected in 8 (16%) of 50 patients by CK staining, including 1 patient whose invasion was detected by both H&E and CK stainings. CK immunostaining enabled us to make an accurate and detailed diagnosis which we believe to be useful for detecting serosal microinvasion in the primary lesion in gastric cancer with subserosal invasion

Cytokeratin-Positive Cells in Lymph Nodes in Which Metastases Are Undetectable by Conventional Histological Staining in Advanced Gastric Cancer

Detection of occult metastases in lymph nodes by immunostaining is becoming of increasing interest as a way to improve the accuracy of predicting the prognosis for patients with gastric cancer. Immunohistochemical detection of cytokeratin (CK) is recognized as the most sensitive method for identification of cancerous epithelial cells. In this study, lymph nodes were stained for CK in an effort to detect micrometastases and the clinical implications of the results were examined. We immunostained sections from a total of 1,198 lymph nodes from 25 totally gastrectomized patients with T3 or T4 gastric cancer who had been diagnosed as having no nodal involvement by conventional hematoxylin-eosin (HE) staining. Eighty (6.7%) of 1,198 lymph nodes from 15 (60%) of the 25 patients were immunostained with a CK-specific monoclonal antibody. CK-positive cells were more frequent in patients with macroscopic types of 3,4 and 5 gastric cancer. Patients with nodes that were both HE-negative and CK-negative had the best postoperative survival, followed by patients with HE-negative and CK-positive nodes and, finally, by patiof micrometastases in lymph nodes is a reliable indicator of the prognosis of patients with advanced gastric cancer

Expression of heavy subunit of gamma-glutamylcysteine synthetase (gamma-GCSh) in human colorectal carcinoma

Gamma-glutamylcysteine synthetase (gamma-GCS) is a heterodimer consisting of heavy (gamma-GCSh) and light (gamma-GCSl) subunits. gamma-GCS catalyzes the rate-limiting de novo biosynthesis of glutathione (GSH), an abundant physiological antioxidant that plays important roles for regulating oxidative stress. Expression of gamma-GCSh and gamma-GCSl are sensitive to oxidative stress. To investigate whether expression of gamma-GCS is correlated with tumor progression, we used immunohistochemical approaches to examine 16 human colorectal adenomas and resected 57 carcinomas from untreated patients. In adjacent normal colorectal epithelium, levels of gamma-GCSh expression were low. Strong cytoplasmic staining for gamma-GCSh was detected in 3 (18.8%) adenoma and 48 (84.2%) carcinomas. The frequency of gamma-GCSh expression in carcinoma was significantly higher than in adenoma (p<0.0001). We used RNase protation assay and Western blot to determine levels of gamma-GCSh mRNA and protein from 10 pairs of matched carcinomas with adjacent normal controls. Elevated expression of both gamma-GCSh mRNA and protein were found in 6 cases, suggesting that transcriptional and/or posttranscriptional regulation play an important role in the upregulation of gamma-GCS during colorectal carcinogenesis. We also examined the expression of another redox-regulated gene, multidrug resistance protein 1 (MRP1). Strong staining for MRP1 was detected in 1 (6.3%) adenoma and 40 (70.2%) carcinomas. The frequency of MRP1 expression in carcinoma was significantly higher than in adenoma ( p<0.0001). Nuclear p53 expression was detected in 30 (52.6%) of carcinomas. There is a significant correlation between gamma-GCSh and MRP1 expression (p=0.013) but not between gamma-GCSh and p53. Since gamma-GCS is a sensor of oxidative stress, these results are consistent with the notion that oxidative stress is associated with colorectal tumor progression