GENETIC DELETION OF DETOXIFIC ENZYME GSTM1 AND GSTTI AS A HOST SUSCEPTIBLE FACTOR FOR NASOPHARYNGEAL CARCINOMA

Objective: To study the gene polymorphisms of GSTT1 and GSTM1 in nasopharyngeal carcinoma (NPC) patients and controls in an incidental area to evaluate the relationship between specific genotype and genotype combinations of these polymorphisms with the risk of NPC. Methods: Cases and controls all came from the Southwestern Guangxi. DNAs were extracted from their WBC. PCR technique was used to calculate the deletion rate of the two detoxific enzyme genes. Results: In this high risk area of NPC, the residents had high level deletion rates of 47.4% (64/135) Ml and T1 40.7% (55/135). The deletion rates were even higher in NPC patients, 61.5% (56/91) for Ml and 59.3% (54/91) for T1 respectively. There were statistical significances compared with control,P<0.05 andP<0.01 for Ml and T1 respectively. The difference was more significant in terms of combined Ml and T1 deletion between patients and controlsx ²=12.533,P=0.002. Conclusion: The combined deletion of detoxific enzyme genes GSTM1 and GSTT1 may be an important genetic susceptible factor for NPC in Guangxi. Biography: DENG Zhuo-lin (1929-), male, professor of pathology, Guangxi Medical University, majors in tumor pathology. E-mail :zhuolin@hotmail.com     

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.     

Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.     

Loss of Fhit expression in head and neck squamous cell carcinoma and its potential clinical implication.

PURPOSE: Abnormalities of FHIT, a candidate tumor suppressor gene, have frequently been found in multiple malignancies, including head and neck squamous cell carcinoma (HNSCC). To define its role in HNSCC treated with surgery and postoperative radiotherapy (PORT), the Fhit protein expression status was investigated in 80 patients enrolled in a prospective Phase III clinical trial addressing the dose and fractionation regimen of PORT. EXPERIMENTAL DESIGN: Immunohistochemical staining of HNSCC tissue sections for Fhit expression was performed. The Fhit expression status was correlated with the clinicopathological characteristics and clinical course. The median follow-up duration was 4.9 years. RESULTS: Loss of Fhit expression was found in 52 of the 80 study patients (65%). There was not a significant association between Fhit expression and clinical characteristics. Patients whose tumor exhibited negative Fhit expression had a significantly worse 5-year overall survival duration [hazard ratio = 0.49; 95% confidence interval, 0.23-1.03; P = 0.05 (log-rank test)] than did those whose tumor exhibited positive Fhit expression. One third of the patients with a Fhit-negative tumor had distant metastasis during the follow-up period. Paradoxically, patients classified as high risk who had a Fhit-negative tumor experienced locoregional recurrence less often (18%) than did high-risk patients who had a Fhit-positive tumor (33%). CONCLUSIONS: Loss of Fhit expression is a poor prognostic indicator in patients with HNSCC. However, tumors lacking Fhit expression may be more sensitive to PORT and therefore more susceptible to locoregional control.     

Lanzoprazole promotes gastric carcinogenesis in rats with duodenogastric reflux

Background Duodenogastric reflux is known to cause an increased frequency of cancer in the glandular portion of the stomach in rats. Furthermore, it is debated whether inhibition of gastric acid secretion may promote gastric carcinogenesis. In the present study we examined the combined effect of gastroduodenal reflux and acid inhibition with respect to the development of gastric carcinoma in the rat.Methods Following the construction of a gastrojejunostomy in male Wistar rats, half of them were given the proton pump inhibitor lanzoprazole for 1 year. The rats were then killed and the pH in the stomach and gastrin in blood were measured. The stomach was examined macroscopically as well as histologically.Results Gastrin levels at autopsy were significantly increased in treated rats compared to the control group, confirming an effect of lanzoprazole on gastric acid secretion. Body weight was significantly reduced in the treated rats. Thirty of 79 rats developed gastric cancer, and they were all adenocarcinomas of the Lauren intestinal type. Gastric cancers occurred significantly more often in lanzoprazole-treated rats (50%) compared with controls (27%).Conclusion Lanzoprazole given orally enhances the carcinogenic effect of duodenogastric reflux in rats.     

The endoscopic evaluation of gastritis,gastric remnant residue,and the incidence of secondary cancer after pylorus-preserving and transverse gastrectomies

Background Pylorus-preserving gastrectomy (PPG) and transverse gastrectomy (TrG) have been accepted as function-preserving procedures for node-negative early gastric cancer. It is believed that a better quality of life is guaranteed after PPG or TrG compared to that after distal subtotal gastrectomy (DSG) with Billroth type-I reconstruction. However, objective evaluations of the gastric remnant following gastrectomy have not been widely reported, and the real advantages and disadvantages of PPG or TrG over DSG remain unclear. Moreover, the risk of secondary cancer after PPG or TrG is uncertain.Methods Between 1991 and 2000, 834 DSGs were carried out in our institute for preoperatively diagnosed patients with early gastric cancer. The degree of residual gastritis and the amount of diet residue in the gastric remnant were evaluated by annual gastrointestinal endoscopic investigations prospectively for 72 patients after PPG, 95 patients after TrG, and 60 patients after DSG. These analyses were performed using the RGB classification (residue, gastritis, bile). The incidence of disease greater than or equal to grade 2 was calculated, and the time trends of the incidence for each procedure were also studied for 3 years after gastrectomy. In addition, secondary cancer cases in the gastric remnant mucosa were checked for each procedure during this period, and the incidence of secondary cancer after each operation was calculated.Results The incidence of gastritis, of grade 2 or more, found in the gastric remnant was significantly lower after PPG (1.4%) and TrG (2.1%) than after DSG (43.3%). However, the incidence of moderate or greater residue in the gastric remnant, grade 2 or more, was significantly higher after PPG (45.8%) and TrG (40.0%) than after DSG (11.7%). The analysis of time trends of gastritis and diet residue reflected the significant advantage or disadvantage for each procedure 1 year after surgery. The analysis also included these factors without consideration of elapsed time following surgery. Two patients after PPG (2.8%) and three patients after TrG (3.2%) developed secondary cancer in the gastric remnant. No DSG-treated patient showed new cancer genesis in the remaining stomach.Conclusion PPG and TrG have the advantage over DSG in preventing postoperative gastritis in the gastric remnant. On the other hand, moderate or greater diet residue in the gastric remnant is more common after PPG or TrG than after DSG. For the risk of carcinogenesis in the remnant gastric mucosa, we could not conclude that there was any apparent difference between these range-limited gastrectomies and conventional DSG. Further study is necessary to determine the significant advantages and disadvantages of using PPG or TrG.     

Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer

Background Despite curative resection, 50%–90% of gastric cancer patients die of disease relapse. Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities, more recent studies have not been able to define the standard treatment for advanced gastric cancer. The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG (bacille Calmette-Guérin) and FAM (5-fluorouracil, adriamycin, mitomycin C) chemotherapy on the survival of patients with locally advanced resectable gastric cancer.Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were randomly assigned to three treatment groups: BCG + FAM (immunochemotherapy), FAM (chemotherapy), and control (surgery only). Treatment was continued for 2 years or until death. Further postsurgical follow up was carried on for up to 10 years.Results Overall 10-year survival was 47.1% for the immunochemotherapy group (P < 0.037 vs FAM and P < 0.0006 vs control), 30% for the chemotherapy group (vs control, NS), and 15.2% for the control group. In patients with pT2/T3 primary tumors, 10-year survival was 55.3% for BCG + FAM vs 28.2% for FAM (P < 0.01) and 14.6% for the control group (P < 0.00018). BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer. Immunochemotherapy was well tolerated.Conclusion This study, based on a limited number of patients, indicates that adjuvant immunochemotherapy (BCG + FAM) may prolong the survival of gastric cancer patients after curative gastrectomy; in particular, in patients with pT2/T3 tumors and intestinal-type primary tumors. There was no survival benefit from FAM adjuvant chemotherapy.     

Prostatosis treated with acupuncture and herbal medicine

According to differentiation of symptoms and signs, prostatosis was divided into pattern of dampness and heat in the lower energizer, pattern of qi stagnation and blood stasis, pattern of deficiency and cold in the lower abdomen, and pattern of qi deficiency and kidney deficiency. Prostatosis were treated mainly by acupuncture, plus moxibustion and Chinese medicine, and the effect was good. Author: Zhao Chang-quan (1949-), male, junior consultant doctor Translator: Huang Guo-qi     

Acupuncture treatment of 32 cases of lumbar intervertebral disc protrusion

Yaoyangguan (GV 3), Shiqizhui (Ex-B 8) and Yanglingquan (GB 34) were selected as main points and a three-part needle insertion technique was used to treat 32 cases of lumbar intervertebral disc protrusion. The curative rate was 96.9%. Deep puncture is the key to the treatment. Author: Chen Feng(1962-), male, junior consultant doctor Translator: Wang Si-you