Serial immunological testing in patients with gastric cancer

Summary Standard immunological parameters measuring non-specific cellular immune reactivity were determined in 175 patients with different stages of gastric cancer prior to surgery and during follow-up. Several tests measuring monocyte activity were also employed. The total number of T cells and their subpopulations T_a and T_29° was unchanged except depression of T_29° in stage IV. The blastogenic response of lymphocytes to PHA as assessed by stimulation of protein synthesis was only depressed in stage IV. In contrast the PHA-induced lymphokine production was increased in all patients but the differences were significant for stage III and IV. Monocyte Fc receptor expression was increased in stages II-IV, while nitro blue tetrazolium reduction and antibody dependent cellular cytotoxicity of monocytes was elevated in stage IV. The number of extractable monocytes was not increased. Longitudinal studies suggested that most of the parameters normalized during follow-up. No major long-term impact of chemoimmunotherapy (5-FU+BCG) on the immune parameters was observed except a transient increase in PPD reactivity approximately 1 year after commencement of treatment. In patients with stage III gastric cancer the increased occurrence of suppressor cells (mostly monocytes) and elevated cytostatic activity of monocytes was associated with a longer survival while the increased lymphokine production and Fc receptor expression were seen in the group of patients succumbing earlier. We concluded that most of the changes in immune parameters were seen only in advanced disease and paradoxically disappeared in the course of disease. The determination of monocyte activity seems to be a sensitive indicator of immune system dearrangements in earlier stages of cancer and a useful prognostic factor in gastric cancer.     

Serial pulmonary function testing in patients with systemic lupus erythematosus

Previous studies have documented the pulmonary function abnormalities associated with systemic lupus erythematosus (SLE). There are very few data, however, regarding the progression of such changes. To study this question, we evaluated the pulmonary function of a group of 25 patients with SLE from two to seven years after a set of pulmonary function tests had been performed as part of their overall initial assessment. Reductions in diffusing capacity, FVC, and total lung capacity did not change significantly for the group over the period of our study. The mean FEF25-75%, which was initially low, and the mean FEV1/FVC ratio, which was initially normal, both decreased significantly. The observed abnormalities in airway function were not related to smoking history. Other aspects of lupus activity, as measured by serum creatinine levels and clinical activity, did not appear related to progression of lung disease.     

Serial lung function testing in patients treated with amiodarone: a prospective study

PURPOSE: Amiodarone has proven to be effective in many cases of cardiac arrhythmias, refractory ventricular tachycardia, and ventricular fibrillation. Pulmonary toxicity is a possible side effect of the drug, with a reported incidence of 2 to 15 percent per year. To determine the effect of amiodarone on lung function, we prospectively studied serial lung function tests in a cohort of 91 patients with refractory cardiac arrhythmias treated with this agent. PATIENTS AND METHODS: Spirometry and carbon monoxide diffusing capacity (DLCO) were measured at zero, three, six, 12, 18, and 24 months, with a mean follow-up of 351 days. RESULTS: For the whole population taking a mean dose of amiodarone of 367 mg daily (range: 136 to 512 mg), there was no accelerated rate of decline in spirometric indices or DLCO. Analysis of lung function changes by multivariate analysis demonstrated that an accelerated decline in DLCO values occurred in elderly patients (p less than 0.05) but not in patients with pre-existing lung disease or cigarette smokers. In four patients (4.5 percent), clinical evidence of amiodarone pulmonary toxicity developed that was associated with a fall in DLCO of greater than 20 percent. All four patients recovered after the drug was stopped. Another 15 patients, without clinical evidence of pulmonary toxicity, had a sustained decline in DLCO of greater than 20 percent. These 15 patients remained asymptomatic over the next 11 months without interruption of therapy. A greater than 20 percent fall in DLCO was a sensitive test for clinically evident amiodarone pulmonary toxicity, but had a positive predictive value of only 21 percent. CONCLUSION: An isolated fall in DLCO, in the absence of clinical evidence of toxicity, does not necessitate stopping amiodarone. An unchanged DLCO value appears to be a reliable negative predictor of pulmonary toxicity.     

Serial electrophysiological testing of antiarrhythmic drug efficacy in patients with recurrent ventricular tachycardia

The purpose of the present study was to determine the predictivevalue of serial electrophysiological testing during antiarrhythmictherapy in patients with recurrent ventricular tachycardia and/orventricular fibrillation in regard to symptomatic status andoutcome. Eleven patients (ten male, one female, mean age 54 ±10 years, mean ± S.D.J with recurrent ventricular tachycardiawere studied. Mean ejection fraction was 34 ± 12%. Mostpatients suffered from coronary artery disease. The median durationof recurrent ventricular tachycardia before the study was 12weeks (minimum one week, maximum 16 years). In seven patientsbetween one and 61 cardioversions had been performed beforethe study to terminate ventricular tachycardia. Ventricular tachycardia could be initiated by programmed rightventricular stimulation in all patients. After control recordingshad been obtained, the stimulation tests were repeated duringantiarrhythmic therapy until an effective regimen was found.The following drugs were used in this sequence: disopyramide,mexiletine, propafenone, aprindine plus beta-adrenergic blockingdrugs and digitalis. In three patients, there was no change in the inducibility ofventricular tachycardia during therapy whereas in eight patients,ventricular tachycardia was more difficult to induce or no longerinducible. Patients were followed at regular intervals (meanfollow-up time 41 ± 22 weeks). In those three patientsin whom ventricular tachycardia was still inducible, two suddendeaths occurred; one patient was referred to surgery becauseof persistent spontaneous and inducible attacks of ventriculartachycardia despite antiarrhythmic therapy. No cardiac deathoccurred in the eight patients in whom ventricular tachycardiawas more difficult to induce or no longer inducible. All patientswere asymptomatic, and had no recurrence of their ventriculartachycardia in their Hotter ECGs. Thus far, serial electrophysiological testing has been usefulin predicting antiarrhythmic drug efficacy in patients withrecurrent ventricular tachycardia. It may help to prevent suddendeath in these highly endangered patients.     

Serial exercise testing in patients with effort angina: variable tolerance, fixed threshold

To investigate the frequency and mechanism of variable threshold angina, seven treadmill exercise tests were performed in each of 28 patients with stable effort angina and exercise-induced ST segment depression. Each patient had tests at 8 AM on 4 days within a 2 week period and on 1 of these days had three additional tests at 9 AM, 11 AM and 4 PM. Time to 1 mm ST depression increased from 277 +/- 172 seconds on day 1 to 319 +/- 186 seconds on day 2, 352 +/- 213 seconds on day 3 and 356 +/- 207 seconds on day 4 (p less than 0.05). Rate-pressure product at 1 mm ST depression remained constant. Similarly, time to 1 mm ST depression increased from 333 +/- 197 seconds at 8 AM to 371 +/- 201 seconds at 9 AM and to 401 +/- 207 seconds at 11 AM and decreased to 371 +/- 189 seconds at 4 PM (p less than 0.01). Again, rate-pressure product at 1 mm ST depression remained constant. The standard deviation for time to 1 mm ST depression, calculated as a percent of the mean for each patient's seven tests and then averaged for the entire group, was 22 +/- 11%. The standard deviation for rate-pressure product at 1 mm ST depression, calculated in the same way, was significantly less at 8.4 +/- 2.8% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serial exercise testing in pulmonary embolism

A patient underwent exercise testing during evaluation for unexplained dyspnea. Evidence of ventilation-perfusion mismatch was noted and subsequent testing revealed multiple pulmonary emboli. Ventilation perfusion parameters by serial exercise testing progressively improved during the course of the patient's illness but did not totally normalize. A discussion of the utility of exercise testing in the evaluation of the patient with unexplained dyspnea is provided and the potential value of serial exercise testing in the management of patients with pulmonary emboli is discussed.     

Gastric Cancer

Opinion statement  

Serial complement measurements in patients with leukaemia

Summary. Haemolytic activity of the classical and alternative pathways and the levels of C4, C3 and factor B were serially measured in 153 serum samples of 41 patients with different types of leukaemia (9 AML, 14 ALL, 10 CML and 8 CLL). In parallel, the concentration of circulating immune complexes (CIC) was estimated using two methods, the complement consumption assay and the Clqsolubility test. Different complement profiles were found in different types of leukaemia. In AML, each complement parameter tested was elevated as compared to the control values (sera of healthy blood donors). Similar results were observed in ALL, although the differences were less marked. In CML, dissociation of the classical and alternative pathway activities was found: activities of the classical pathway and C4 were significantly elevated, whereas activity of the alternative pathway as well as C3 and factor B concentration did not differ significantly from the control values. In CLL, normal or slightly depressed complement levels were found. The concentration of circulating immune complexes measured by both methods was significantly increased as compared to control values. No significant positive or negative correlations were found between the complement levels and the immune complex concentrations determined in the same sera. An association between the clinical course of acute leukaemia and the complement levels was observed: significantly elevated complement titres were found in the blastic stage of the disease, whereas in remission normal values were recorded. The results of complement measurements performed in serum samples obtained before and after combination chemotherapy were compared on 32 occasions. In parallel to a significant decrease in the absolute number of blast cells in the peripheral blood, a normalization of the increased complement levels was observed after treatment.     

Serial testing of anti-arrhythmia preparations using the intracardiac electrophysiological study of patients with reciprocal paroxysmal tachycardias

Diagnostic investigation of 36 patients with reciprocal paroxysmal tachycardias, using intracardiac electrophysiologic tests, revealed supraventricular paroxysmal tachycardia in 29 patients, and ventricular paroxysmal tachycardia in 7. Serial trials of antiarrhythmic drugs in acute experiments with simultaneous electrophysiologic studies made possible efficient medication in 80% of the patients. A high correlation was demonstrated between the results of acute antiarrhythmic drug tests and subsequent long-term treatment. Ritmilen proved particularly effective in patients with paroxysmal tachycardias in the presence of the ventricular pre-excitation syndrome, while cordarone and etmozin were most effective antiarrhythmic drugs for reciprocal ventricular tachycardias. No preferential antiarrhythmic agent could be established for patients with reciprocal paroxysmal tachycardias due to double atrioventricular conduction.     

Gastric Cancer Chemoprevention

In 1996, approximately one million new cases of gastric cancer were found. It is the second most common cancer in the world, and seventy five percent of the new cases are found in Asia. It is therefore an important issue in Asian countries. Like most malignancies, the etiology of gastric cancer is still unclear. It is generally agreed that the pathogenesis is multifactorial, which may include dietary factors, environmental factors, bacterial and viral infections. The role of Helicobacter pylori infection in gastric carcinogenesis is certainly very important.     

Lack of Association of Helicobacter pylori Seroprevalence and Gastric Cancer in a Population with Low Gastric Cancer Incidence

Background: Previous studies have suggested that infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. Methods: We examined the sera of 111 Caucasian patients with histologically confirmed gastric cancer (36 with cancer of the cardia, 70 with cancer of the body or antrum, and 5 with stump carcinomas after Billroth-II procedures) and 111 age-matched controls with colorectal carcinomas for the presence of H. pylori IgG antibodies by enzyme-linked immunoassay. Results: The overall prevalence of H. pylori infection was 58.6% (65 of 111) in gastric cancer patients as compared with 50.5% (56 of 111) in matched control subjects (odds ratio, 1.39; 95% confidence interval, 0.82 to 2.36). Carcinomas of the cardia were not linked to H. pylori infection (odds ratio, 1.25; 95% confidence interval, 0.49 to 3.18), nor were carcinomas of the body and antrum (odds ratio, 1.26; 95% confidence interval, 0.65 to 2.46), nor diffuse or intestinal-type carcinomas (odds ratios, 1.79 and 1.0; 95% confidence intervals, 0.69 to 4.67 and 0.34 to 2.91, respectively). Age, sex, and height of the IgG immune response did not affect risk. Conclusions: In contrast to previous results, these data do not provide evidence that the contribution of H. pylori infection to the carcinogenesis of gastric cancer is of major significance in a population with low gastric cancer rates and with high socioeconomic status.     

Early Gastric Cancer in Japan

In Japan the mortality rate of gastric cancer is very high, 57.3 per cent in males. Because of such a high mortality our clinicians and investigators have been making efforts to detect the early gastric cancer cases. We experienced a remarkable increase in diagnosed cases in these years, which was attributed to the spread of endoscopic and cytologic diagnosis.

The roentgenologic signs of early gastric cancer are so minute in many instances that they can only be detected by a careful and skillful roentgenologic examination team.

The double contrast method employs the proper ratio of barium to air and changes the position of the patient in order to obtain the best view of the mucous fold.

Surgical intervention in the detected early gastric cancer cases in Japan has been greatly improved, as indicated in Table VI. We have in fact achieved the excellent five-year survival rate of 98 per cent.     

A Small Gastric Cancer in Association with Menetrier Disease

Abstract: We studied a 57-year-old man who was diagnosed as having giant rugae at a mass-screening for gastric cancer. He was examined endoscopically for check-up purposes. In addition to giant rugal folds which occurred throughout the entire fundus and body of the stomach, a type IIc lesion was noted in the posterior lower wall of the gastric body. A biopsy revealed signet ring cell carcinoma. A total gastrectomy was performed. A resected specimen was serially sectioned and underwent histopathological examination; hypertrophy and cystic elongation of the gastric glands indicative of so-called giant hypertrophic gastritis was seen. The histological type of the type IIc lesion was undifferentiated adenocarcinoma with the signet ring cells being confined to the mucosal layer. This patient had a rare case of Menetrier's disease complicated by intramucosal carcinoma.     

Circulating Ghrelin in Patients with Gastric or Colorectal Cancer

The purpose of this study was to investigate the pathophysiologic change of ghrelin in gastric and colorectal cancer patients, especially in those with cachexia. Fifty-eight gastric cancer patients, 20 colorectal cancer patients, and 24 healthy control individuals were included in this study. Thirty-one patients were defined as cachectic, based on the percentage of weight loss versus the previous normal weight. The remaining 47 patients were defined as noncachectic. Peripheral hormones, including ghrelin, insulin, leptin, growth hormone, glucagon, and cortisol, and body composition parameters were measured. Plasma ghrelin levels did not increase significantly in cachectic gastric (p=0.352) or colorectal (p=0.871) cancer patients as compared with controls and were not correlated with nutrition status and other hormones. The location of gastric cancer (proximal vs. distal) had no influence on ghrelin levels (p=0.966). These findings suggest that gastric and colorectal cancers may have their special effects on the production of ghrelin. Gastric or colorectal cancer cachexia may be partly due to the lack of increase in ghrelin, which makes exogenous ghrelin therapy feasible in this setting.     

Serum Interleukin-33 Levels in Patients with Gastric Cancer

Background  

Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines, and it is closely related to IL-18, one of the best characterized members of the IL-1 family. It’s been demonstrated that elevated levels of IL-18 are involved in a wide variety of tumors, especially in gastric cancer.     

Endoscopic Therapy in Patients with Inoperahle Early Gastric Cancer

The efficacy and safety of endoscopic therapy was investigated prospectively in 42 patients with 44 early gastric cancers who were not candidates for surgery. Thirty-five of the 44 lesions (80%) were treated by endoscopic therapy alone. Adequate tumor resection was possible in lesions less than 2 cm in diameter, in those of the protruding, flat, and erosive types, and in those located in the antrum. None of the 35 patients who were judged completely cured by the initial therapy developed recurrence or lymph node metastases in the follow-up period (range, 3-114 months; mean, 37 months). Therefore, endoscopic therapy appears effective in the treatment of patients with early gastric cancer when the risks of surgery are too high.