Tatsuji Homma

Long‐Term Follow‐Up of Patients with Sick Sinus Syndrome: A Comparison of Clinical Aspects Among Unpaced, Ventricular Inhibited Paced, and Physiologically Paced Groups

To analyze the prognosis of the sick sinus syndrome (SSS), we compared the clinical aspects among unpaced, ventricular paced, and physiologically paced patients who were followed over a long period. Unpaced intrinsic SSS was not always progressive and patients did not necessarily require permanent pacing. The incidence of concomitant AV conduction disturbance was 65.6% before pharmacologic autonomic block, (PAB), but this was significantly reduced to 31.7% after PAB. Follow‐up study of the physiologically paced groups revealed no development of either new or more than second degree AVB. The VVI group had significantly more complications (68%) than the physiologically paced groups, mainly chronic atrial fibrillation (36%) and thromboembolism (20%). In addition, cardiothoracic ratio (CTR) in the VVI group was significantly greater compared with that in the physiologic groups. Nine deaths occurred during the follow‐up period in the pacing groups, including six with VVI and three with physiologic pacing. In the VVI pacing group, heart failure and thromboembolism were most commonly the causes of death, while in the physiologic pacing groups, the causes of death were noncardiac. Although the survival rate in the ventricular paced group was not significantly different from that in the physiologic pacing groups, cardiac deaths were fewer in the latter group. Considering our clinical data, the decision to use ventricular pacing needs to be carefully weighed in patients with sick sinus syndrome, and physiologic pacing is more highly recommended. (PACE, Vol. 11. November 1988)

Effects of leukocyte and platelet depletion on ischemia--reperfusion injury to dog pancreas.

BACKGROUND/AIMS Ischemia-reperfusion injury has been studied in various organs. Effects of leukocyte and platelet depletion on ischemia-reperfusion injury were evaluated using the isolated, perfused dog pancreas in vivo. METHODS Pancreatic exocrine and endocrine functions were stimulated by an intra-arterial injection of cholecystokinin (10(-12) mol) and intravenous injection of glucose and arginine (1 g/kg body wt), respectively. The functions before and after 60 minutes of ischemia were evaluated in the no treatment and in the leukocyte and platelet depletion groups. RESULTS Cholecystokinin increased prostaglandin I2 and thromboxane A2 production and stimulated exocrine pancreatic secretion. Glucose and arginine stimulated insulin and glucagon release from the pancreas. Sixty minutes of ischemia followed by 60 minutes of reperfusion damaged the pancreatic acinar and ductular cells. Ischemia of 60 minutes followed by 90 minutes of reperfusion damaged beta cells. Removal of leukocytes (97.6%) and platelets (99.4%) by using a filter throughout the experiment prevented the ischemia-reperfusion injury, reduced plasma lipid peroxide and thromboxane A2, and increased prostaglandin I2 levels. CONCLUSIONS Leukocytes and platelets seem to damage the pancreas during ischemia-reperfusion by increasing the peroxidation of structurally important cell membrane lipids and reduced the thromboxane A2 prostaglandin I2 ratio, a predictor of cellular injury.

A Study of Chronic Pancreatitis by Serial Endoscopic Pancreatography

The pancreatic duct system was studied with repeated endoscopic retrograde pancreatography in 31 patients with chronic pancreatitis, 32 patients with suspected chronic pancreatitis, and 16 controls without pancreatic disease. In chronic alcoholic pancreatitis the pancreatograms showed marked changes during the initial examination with progression even after abstinence or reduction of drinking. In the alcoholics with suspected chronic pancreatitis, progressive lesions in branch ducts with almost intact main ducts were recognized. In contrast, no remarkable alterations on serial pancreatograms were observed in nonalcoholic cases with definite or suspected chronic pancreatitis. These results suggest that pancreatic duct lesions play an important role in the development and progression of chronic alcoholic pancreatitis in contrast to chronic nonalcoholic pancreatitis.

Elevated serum levels of Dupan-2 in pancreatic cancer patients negative for Lewis blood group phenotype.

CA19-9, a serum marker for pancreatic cancer, gives false-negative results in patients who are negative for the Lewis blood group phenotype. To determine whether other markers may compensate for this drawback, serum levels of CA50, Span-1, sialyl SSEA-1 and Dupan-2 were assayed and compared with those of CA19-9 in 207 normal subjects and in 200 patients with pancreatic carcinoma whose Lewis blood group phenotypes were confirmed. In normal subjects with the Lewis negative phenotype, the serum levels of CA50 and Span-1, as well as CA19-9, were significantly low, whereas those of sialyl SSEA-1 were independent of the Lewis blood group phenotype. Serum levels of Dupan-2 were significantly higher in normal subjects with the Le (a-b-) phenotype as compared with those with Le(a-b+). The sensitivity for pancreatic carcinoma was 81% for CA19-9, 84% for CA50, 82% for Span-1, 51% for sialyl SSEA-1 and 63% for Dupan-2. Among the 39 CA19-9 negative patients, 13 were determined as being Lewis negative by the serum dot-ELISA technique. Although the positive rates were essentially comparable when each marker was combined with CA19-9, a highly elevated serum level of Dupan-2, which strongly suggested the presence of malignancy, was most frequently encountered in 39 patients who were not diagnosed by CA19-9 assay, especially those with Lewis negative blood groups. With regard to the three other markers, we found few patients with a highly elevated serum level in either the Lewis-negative or -positive groups. We conclude that Dupan-2 tended to be elevated in patients with pancreatic cancer who were negative for the Lewis blood group phenotype.

CA19-9 as a screening and diagnostic tool in symptomatic patients: the Japanese experience.

Although the prognosis for pancreatic cancer is generally poor, the Japanese Pancreatic Cancer Register reported in 1992 that the survival rate for resected pancreatic cancer was much higher than that for more conservative treatment. T1 and T2 pancreatic tumors are much more frequently resectable than are T3 and T4 tumors, and the 5-year survival rate for unresected T2, T3, and T4 cases is 0%. These findings emphasize the importance of early diagnosis of resectable pancreatic cancer. CA19-9 has shown satisfactory sensitivity in detecting advanced pancreatic cancer; we sought to determine the effectiveness of CA19-9 as part of a screening program for early cancer. Using elastase 1, CA19-9, and ultrasonography, we developed and tested a program of mass screening on persons presenting with and without abdominal complaints.

Comparative study of CA242 and CA19-9 for the diagnosis of pancreatic cancer.

A comparative study of a new tumour marker, CA242, and CA19-9 was conducted with special reference to their diagnostic usefulness in pancreatic cancer. CA242 showed sensitivity similar to that of CA19-9 for overall cases and early cases (stage I tumour) of pancreatic cancer. For other malignancies, the positive rates of CA242 were lower than those of CA19-9 except for colorectal cancer. An important characteristics of CA242 was that it was only slightly and infrequently elevated in the sera of patients with benign diseases such as chronic pancreatitis, chronic hepatitis and liver cirrhosis. This characteristic was more apparent in the patients with benign obstructive jaundice, indicating that the serum level of this marker was scarcely affected by cholestasis. Using cut-off levels corresponding to a 90% specificity, the clinical results obtained with CA242 in the diagnosis of pancreatic cancer were similar to those obtained with CA19-9, except that CA19-9 was falsely negative in some patients with early-stage pancreatic cancer. These findings suggest the usefulness of this marker for screening pancreatic cancer in patients on their first hospital visit. However, CA242 was found to be influenced by the Lewis blood group system. This unfavourable result is attributed to the C241 catcher antibody of this assay system, which has almost the same epitope specificity as the C50 and the NS19-9 monoclonal antibodies. In conclusion, CA242 is superior to CA19-9 in diagnosing pancreatic cancer by virtue of its higher specificity.

Epitope analysis of SPan-1 and DUPAN-2 using synthesized glycoconjugates sialyllact-N-fucopentaose II and sialyllact-N-tetraose

Epitope analysis of Span-1 and DUPAN-2 was compared with that of CA19-9 using the synthesized glycoconjugate sialyllacto-N-fucopentaose II (SLF11, sialyl-Lewisc) and its precursor, sialyllact-N-tetraose (LSTa, sialyl-Lewis”), conjugated to human serum albumin. The CA19-9 and DUPAN-2 assay systems specifically recognized SLF II and LSTa, respectively. The Span-1 assay system recognized both SLF IIIand LSTa, although the reactivity with the former was far stronger than that with the latter. These results were, in general, compatible with those obtained from assaying these markers in the sera of two pancreatic cancer patients with definite Lewis-negative phenotype and in the sera of 39 CA19-9-negative pancreatic cancer patients. In conclusion, DUPAN-2 is the precursor of CA19-9 and is accumulated in the sera of pancreatic cancer patients with Lewis-negative phenotype and Span-1 has an advantage over CA19-9 in the diagnosis of patients with Lewis-negative phenotype, although both markers have almost the same sensitivity for this malignancy.

The study of the mass screening of persons without symptoms and of the screening of outpatients with gastrointestinal complaints or icterus for pancreatic cancer in japan, using ca19-9 and elastase-1 or ultrasonography

SummaryTo investigate the possibility of detecting carcinomas of the pancreas at an early stage by mass screening of persons without symptoms or by screening the outpatients with gastrointestinal complaints or jaundice, we performed a multicentral study of the mass screening of 10,162 persons at five local areas and of the outpatient screening of 4506 at 17 hospitals for pancreatic cancer in Japan for two years from 1984 to 1985, using serum CA19-9 and elastase-1 determinations or ultrasonography.Mass screening of 10,162 persons over 40 years old found only four (0.04%) cases of pancreatic cancer, including one case that was curatively treated. According to the screening of 4506 outpatients with gastrointestinal complaints or icterus, 85 (1.9%) patients were found to have pancreatic cancer. Of these 85 patients, 28 could undergo curative treatment. In addition to them, 73 (1.6%) patients with other digestive organ cancer were found. Our results suggest that the mass screening of persons without symptoms is not worthwhile in the early detection of pancreatic cancer, but outpatient screening is useful for detecting curative cancers of the pancreas.

The Role of Oxygen Free Radicals in Experimental Acute Pancreatitis in the Rat

SummaryIn order to elucidate the role of oxygen-derived free radicals in acute pancreatitis, scavengers and an inhibitor of production of these free radicals were administered to rats with experimentally-induced acute pancreatitis. Acute reflux pancreatitis was produced by the occlusion of the common bile duct (OCD). Catalase and superoxide dismutase (SOD) were used as scavengers, and allopurinol was used as an inhibitor of production of free radicals. Six h after surgery, serum amylase, lipase, and thiobarbituric acid (TBA) reactant levels were elevated significantly, and histological changes in the pancreas, consisting of edema, inflammatory cell infiltration, and necrosis, partially around the intralobular and interlobular ducts, developed in the control rats receiving no agent. However, serum lipase and amylase levels in the rats given each agent were significantly lower (p<0.05) than in the controls. The histological changes in the pancreas were less marked in agent-treated rats than in untreated rats. These results suggest that oxygen-derived free radicals participate in the development of acute pancreatitis.

Criteria for Pancreatic Disease Diagnosis in Japan : Diagnostic Criteria for Chronic Pancreatitis

Chronic pancreatitis was not a clinical entity until around 1960 in Japanese gastroenterology. The diagnosis of chronic pancreatitis had been vague and difficult to ascertain. The diagnostic criteria for chronic pancreatitis were first proposed in 1971, and they were subsequently revised in 1983. Patient numbers of chronic pancreatitis were summed by national surveys under each of the common diagnostic criteria. Total patient number and incidence rate of chronic pancreatitis are recognized as increasing throughout Japan, based on results of two national surveys of chronic pancreatitis. The diagnostic criteria for chronic pancreatitis in Japan were again revised in 1995, because the 1983 criteria were too complicated, and there had been more recent progress in clinical investigations of the pancreas. The essential revised points of the Diagnostic Criteria, 1995, are introduced in this review along with some discussion.