Kenji Kudoh

Correlation between bile acid malabsorption and pancreatic exocrine dysfunction in patients with chronic pancreatitis.

Fecal bile acid and fecal fat were determined in 18 normal subjects and 22 patients with chronic pancreatitis, and the relation of fecal bile acid excretion to exocrine pancreatic dysfunction was studied. In chronic pancreatitis fecal bile acid was approximately three times that of control subjects, and large amounts of primary bile acid were detected. A significant correlation between fecal bile acid excretion and bicarbonate secreted from the pancreas was found. This evidence of bile acid malabsorption was not observed until bicarbonate output was ∼0.05 mEq/h/kg. A slight correlation between fecal bile acid and absorption rates of fat was demonstrated. These results suggest that bile acid malabsorption observed in chronic pancreatitis is related to an impairment of pancreatic bicarbonate secretion.

Dietary analysis of Japanese patients with chronic pancreatitis in stable conditions

In order to examine the malnutritional condition of outpatients with pancreatitis, a dietary investigation was conducted in Japanese patients with chronic pancreatitis (n=38) and healthy subjects (n=35) of the same age for 3–7 consecutive days, and the characteristics of their food intake were examined. The patients with pancreatitis took in less calories, fat, carbohydrate, and protein than the healthy subjects, by 900 kcal, 20g, 150g, and 20 g, respectively. On the other hand, the fat energy ratio in the patients was 20%, similar to that in the healthy subjects. Also, when the fat intake was classified according to origin, i.e., animal, marine, or plant, the proportions for animal (g) and plant (g) were low, while marine fat accounted for a significantly higher percentage than in the healthy subjects. The intake of cholesterol and Ca in the patients was significantly smaller than that in the healthy subjects, but no significant difference was observed in the intake per body weight of proteins and Ca. It seems, possible that the low calorie, low protein, low fat, and low carbohydrate intake may be factors in the malnutritional condition of the patients with chronic pancreatitis. Analysis of covariance and principal component analysis showed that the body weight of the patients was closely correlated with decreases of caloric intake and intake of carbohydrate. The above results revealed that low body weight in patients with chronic pancreatitis was closely related to the decrease of calorie and carbohydrate intake, in addition to maldigestion and malabosorption of nutrients.

Changes in plasma fatty acid profile in Japanese patients with chronic pancreatitis.

The serum zinc, prealbumin, retinol-binding protein and carotene concentrations and the plasma fatty acid composition were determined to assess the nutritional condition of 24 patients with chronic pancreatitis compared with that of 20 healthy controls. The daily food intake and faecal fat excretion of the two groups were also measured. In the chronic pancreatitis group, the calorie and fat intakes were significantly lower than those of the controls. Serum levels of zinc, prealbumin and carotene were also significantly lower than those of the controls. Percentages of plasma linoleic and arachidonic acids were low, while percentages of palmitoleic acid, eicosapentaenoic acid and docosahexaenoic acid were high. Fish oil intake correlated negatively with plasma linoleic acid concentration (P < 0.05). The above results indicate that the relatively high intake of fish oil and the relatively low intake of dietary fat in Japanese patients with chronic pancreatitis with a mild degree of steatorrhoea results in an abnormally low plasma level of linoleic acid.

Faecal lipid excretion levels in normal Japanese females on an unrestricted diet and a fat-restricted diet measured by simultaneous analysis of faecal lipids

Faecal lipid excretion was determined in 16 females on an unrestricted diet and on a fat-restricted diet using a chromatographic method for the simultaneous analysis of faecal lipids. The fat-restricted diet reduced the total quantity of faeces and the amounts of fatty acids, neutral sterols and bile acids excreted were almost halved compared with when on an unrestricted diet. This indicates that dietary fat, fibre and cholesterol affect the amount of faecal bile acid, neutral sterol and fatty acid excretion. The amount of cholesterol/animal sterols excreted and the percentage of primary bile acids were, however, similar for both the fat-restricted and unrestricted diets.

No negative feedback regulation between plasma CCK levels and luminal tryptic activities in patients with pancreatic insufficiency

SummaryThe study was conducted on five healthy subjects and six patients with calcifying pancreatitis (CP) and steatorrhea. Following overnight fasting, one tube each was placed in the stomach and the upper part of the small intestine, respectively. Through the gastric tube, a test meal that included 30 g of fat (total calories, 625 kcal, 500 mL) was infused over a span of 30 min. Every 30 min (up to 150 min), fluid samples in the upper small intestine were collected and chilled, and the amylase, trypsin, and lipase levels were determined. In addition, in the case of the CP patients, a high-potency pancreatin preparation was infused into the stomach together with the test meal. In order to determine the plasma CCK level, blood sample were collected before test meal infusion and at 10, 20, 30, 45, 60, 90, 120, and 150 min subsequent to infusion. The plasma CCK was extracted using a Sep-Pak C-18 cartridge and analyzed with radioimmunoassay using an OAL-656 antibody. The result was converted to the CCK-8 level and expressed in pg/mL. The enzyme activities in the upper small intestine of the CP patients after test meal administration amounted to 22.8 (amylase), 10.8 (trypsin), and 16.9% (lipase) compared with the corresponding figures for the normal subjects. Following administration of a high-potency pancreatin in patients with CP, enzyme activities in the upper small intestine increased to 132.2 (amylase), 38.7 (trypsin), and 45.3% (lipase) compared with levels in the normal subjects. However, the healthy subjects and the CP patients, both with and without treatment with supplementary exogenous enzymes, all exhibited similar profiles in the plasma CCK response to stimuli. Based on these findings, we concluded that a negative feedback mechanism does not exist between the tryptic activity of the upper small intestine and the CCK secretory response in patients with chronic pancreatitis.

Effects of FL-386 on Faecal Lipid Excretion in Humans

A newly synthesized inhibitor of pancreatic lipase and micelle formation, FL-386, was administered at a dose of 400 mg (in the diet, for seven consecutive days) to nine healthy adult volunteers, and changes in faecal mass, frequency of defaecation, and properties of the stools were observed. High performance liquid chromatography and gas-liquid chromatography were used to analyse the faeces for short-chain carboxylic acids, neutral sterols, bile acids, fats and hydroxyfatty acids. FL-386 had little effect on the amounts and composition of short-chain carboxylic acids, neutral sterols, and bile acids excreted, nor did it produce changes in the composition of fatty acids, or the percentages of hydroxyfatty acids in the stool. However, in those patients treated with FL-386, the faecal mass was increased, and stools were softer and contained increased amounts of fatty acids. The compound did not produce particularly fatty stools. It was concluded that FL-386 induces slight disturbance in the digestion and absorption of dietary lipids.

Effects of Pancreatic Digestive Enzymes, Sodium Bicarbonate, and a Proton Pump Inhibitor on Steatorrhoea Caused by Pancreatic Diseases

Forty-five patients with pancreatic steatorrhoea (27 with calcified pancreatitis, 13 with non-calcified pancreatitis, two with pancreaticoduodenectomy, one with total pancreatectomy, and two with pancreatic cancer) were divided into four groups and given the following medication for 2 to 4 weeks: 4 to 6 g/day of sodium bicarbonate (group I); 9 g/day of high-lipase pancreatin (lipase, 56 600 U/g, Fédération Internationale Pharmaceutique (FIP); group II); 12 to 24 tablets or 9.0 g of commercial pancreatic enzyme preparations (group III); or 50 mg of omeprazole (group IV). Faecal fat excretion was evaluated before and after drug administration. Faecal fat excretion was reduced by 2.9 g (range, 1.7 to 5.0 g) in group I; 8.8 g (range, 2.9 to 39.9 g) in group II; 10.8 g (range, 2.3 to 21.8 g) in group III; and 4.3 g (range, 3.6 to 5.6 g) in group IV. The pancreatic digestive enzyme preparation was more effective than sodium bicarbonate and agents that raise the pH of the upper small intestine (such as proton-pump inhibitors) in reducing faecal fat excretion. The results indicate that all of the preparations used are effective against mild pancreatic steatorrhoea. If the condition is more advanced, however, a massive dosage of pancreatic digestive enzyme and possibly the combined use of an agent to raise the pH of the upper small intestine are likely to be effective.