Yusuke Tando

Evidence-based clinical practice guidelines for chronic pancreatitis 2015.

Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

Pancreatic Dysfunction and Treatment Options

Pancreatic steatorrhea and pancreatic diabetes are the dominant symptoms of patients in the decompensated stage of chronic pancreatitis (CP). In this stage, the nutritional state is greatly disturbed and hypoglycemia and labile infection are involved. Pancreatic enzyme replacement therapy is the principal treatment method for pancreatic steatorrhea. Before initiating this therapy, dietary fat intake must be determined and pancreatic lipase and bicarbonate secretion function must be evaluated. Upper small intestinal pH is regulated by gastric acid secretion, and abnormal gastric emptying changes lipolysis. In addition, precipitation of bile acids in the upper small intestine and ileal brakes due to undigested fats and carbohydrates must be considered. Porcine pancreatin, bacterial lipase, and acid-resistant fungal lipase are used as enzymes for replacement therapy. Conventional, entero-coating, and enteric-coated microsphere preparations of porcine pancreatin are available for treatment and are formulated to protect against gastric acids, to dissolve enzymes at optimum pH, and to be emptied simultaneously with food from the stomach. Gastric acid secretion suppressants, such as H2 blockers or a proton pump inhibitor, can also be used concomitantly with pancreatin preparations. In consideration of both strengths and weaknesses of these preparations, types and dosages of enzyme replacement therapy should be carefully prescribed, and fecal fats should be examined repeatedly by a simple and rapid method during treatment. Attention should also be paid to changes in body weight and nutritional indices (e.g., nutritional parameters, fat-soluble vitamins). The relationship between carbohydrate maldigestion/malabsorption in CP patients and treatment of pancreatic diabetes are topics for future research.

Serum fatty acid composition in normal Japanese and its relationship with dietary fish and vegetable oil contents and blood lipid levels

A survey was conducted on 110 normal Japanese adults (55 men and 55 women) to determine their caloric intake, dietary fat content and its origin (animal, plant, or marine). In addition, their blood lipid levels and fatty acid compositions were examined. Men in their 30s-50s consumed 2,600-2,800 calories and 60 g of fats, while women in the same age range consumed 2,000-2,200 calories and 52-58 g of fats. In both sexes, caloric, fat, and cholesterol intakes were lower for those in their 60s but protein and crude fiber consumption remained generally unchanged. When the dietary fats were classified according to origin, men and women in their 30s were found to consume less oil of marine origin. This appeared to be the result of a western style diet for Japanese adults in their 30s. Compared with men, women exhibited lower blood lipid levels. As age increased, the total cholesterol level of the blood rose in women. Thus the blood lipid level was generally equal in the two groups in their 60s. There was a positive correlation between the blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and dietary consumption of fish oil. The marine/plant lipid ratio was positively correlated with the blood EPA/arachidonic acid ratio. Therefore, it was believed that the origin of the dietary fats consumed is a factor in determining the blood fatty acid profile. The linoleic acid (18:2), arachidonic acid (20:4), and 18:2 + 20:4 contents were negatively correlated to the total cholesterol level in the blood but positively correlated to the HDL-cholesterol level. Polyunsaturated fatty acids (18:2 + 20:4 + 20:5 + 22:6) were negatively correlated with the blood triglyceride level. From the findings presented above, we concluded that dietary fats not derived from animal sources should be classified into fish and vegetable oils to evaluate their dietary significance. We also noted that Japanese in their 30s consume less fish oil, indicating the western trend in their dietary lipid consumption.

Near-infrared spectrometry analysis of fat, neutral sterols, bile acids, and short-chain fatty acids in the feces of patients with pancreatic maldigestion and malabsorption

SummaryConclusion. Near-infrared spectrometry is a new, rapid, and accurate method for measuring fecal fat that does not require a great deal of chemical knowledge and that can be used by anyone. This method is considered indispensable for the diagnosis of pancreatic steatorrhea and treatment follow-up.Methods. Fecal fats (GLC method, van de Kamer method), neutral sterols (GLC method), bile acids (GLC method) and short-chain fatty acids (HPLC method) were assayed by the respective conventional methods in 120 subjects, including patients with pancreatic dysfunction, and the results were compared with the those obtained by near-infrared spectrometry. The correlations between fecal fat excretion measured by the GLC method (x) and van de Kamer method (x) and by near-infrared spectrometry (y) were expressed by y=1.10 x-0.16 (r=0.949, P<0.01) and y=0.750x+1.654 (r=0.930, p<0.01), respectively.Results. The sensitivity and specificity of near-infrared spectrometry for fecal fats were 94.9 and 98.2%, respectively, when compared with the GLC method, and 87.5 and 90.0%, respectively, when compared with the van de Kamer method. In contrast, near-infrared spectrometry was not nearly as accurate as the conventional methods for determining neutral sterols, bile acids, and short-chain fatty acids.

Effect of omeprazole on changes in gastric and upper small intestine pH levels in patients with chronic pancreatitis

Gastric and upper small intestine pH levels were measured continuously over 24 hours in patients with chronic pancreatitis, and values obtained before and after the administration of omeprazole were compared. Additionally, omeprazole was administered for 2 weeks and the fecal excretion of fat was compared before and after drug therapy. Postprandial gastric pH levels, initially 2.9 to 3.2, increased by 1.6 to 2.1 after treatment. Postprandial upper small intestine pH levels, initially 5.1 to 5.5, increased by 0.7 to 1.0. The lowest pH value of the upper small intestine was 2.2 to 2.4 postprandially; this was increased by > 1.0 after omeprazole, and the amplitude of pH variation was reduced. The cumulative proportions of intraintestinal pH strata of < or = 3, < or = 4, or < or = 5, and higher, initially being 16.4% to 17.1%, 27.4% to 31.7%, and 52.6% to 57.8%, respectively, were remarkably improved after drug treatment. Gastric pH and upper small intestine pH levels showed a positive correlation; an increase in gastric pH levels by 2 corresponded to an increase in small intestine pH levels by 1. After omeprazole administration, mean fecal excretion of fat was decreased to 4.1 +/- 2.6 g/d (range, 1.1 to 9.8 g/d) from 6.5 +/- 3.9 g/d (range, 1.6 to 13.5 g/d). Decreases in excretion of fat averaged 3.4 g/d (range, 2.2 to 4.5 g/d) in patients with steatorrhea. It was concluded that steatorrhea due to chronic pancreatitis can be improved to some extent by improving upper small intestine pH levels following the elevation of gastric pH levels after administration of omeprazole.

Bile acid malabsorption as a cause of hypocholesterolemia seen in patients with chronic pancreatitis

SummaryA determination of caloric consumption based on a dietary survey table, fat and cholesterol intake, and analyses of fecal fatty acids and neutral sterols, and bile acid analysis (gas chromatographic method) were conducted on 33 subjects (including 17 patients with chronic pancreatitis and 16 normal controls). The factors related to hypocholesterolemia in chronic pancreatitis (CP) patients were investigated and the following conclusions were obtained: (1) The total caloric intake and fat consumption by the CP patients were significantly lower with the exception of cholesterol consumption. (2) Significant increases were noted in fecals fat, neutral sterols, and bile acid excretion by the CP patients. (3) A significant positive correlation was noted between the total cholesterol and body mass index (BMI), reaffirming that the cholesterol level can be used as an indicator of nutritional status. (4) A significant negative correlation was noted between the serum total cholesterol and fecal bile acid excretion. These findings indicate that CP patients suffer from neutral sterol malabsorption, in addition to dietary fat maldigestion and bile acid malabsorption. Furthermore, bile acid malabsorption is cited as a factor in the development of hypocholesterolemia in CP patients.

Can pancreatic steatorrhea be diagnosed without chemical analysis

SummaryConclusionVisual observation of feces, considering fecal output, is considered to be an excellent method of detection of steatorrhea when judged by experienced doctors.MethodsFeces from 192 patients with untreated chronic pancreatitis or under pancreatic enzyme therapy were investigated. Feces were collected for three consecutive days and homogenized with water. Fecal samples were freeze-dried and analyzed for fatty acids by gas chromatography (GLC). The quantity of fat was calculated from the amount of fatty acid to obtain daily fecal fat excretion. Comparison of GLC method with van de Kamer method gave a significant (p<0.01) positive correlation with correlation coefficient of 0.916 (n=38). Steatorrhea was defined as fecal fat excretion exceeding 5 g/d. Mild steatorrhea was defined as 5–10 g/d, and severe steatorrhea as more than 10 g/d.ResultsThree visual identification items were used to consider fecal output exceeding 200 g/d: fecal fat concentration exceeding 4%, appearance, and odor. The results were compared with the results from GLC method. Detection of steatorrhea by means of visual properties was the most accurate, and correlation coefficient was 0.843 (p<0.01) by Spearman’s rank correlation test. This detection method was also significantly effective for differentiation of normal stool from mild and severe steatorrhea. The sensitivity and specificity were 89.3 and 91.1%, respectively, indicating a favorable result.

A Brief Outline of the History of the Pancreatic Anatomy

In the middle of the 18th century, Kouan Kuriyama, a Japanese physician of the Choshu Domain, depicted the anatomy of the human pancreas in a report to his master, Toyo Yamawaki. This report is the first anatomical description of the pancreas in Japan. In the Mediterranean area, the pancreas was apparently first described about 2,000 years before his observation. Although there are quite a few reviews on the history of this complex organ, our brief essay offers a historical outline of the pancreas.

Study on Pancreatic Insufficiency (Chronic Pancreatitis) and Steatorrhea in Japanese Patients with Low Fat Intake

The incidence of steatorrhea is said to be lower and its grade milder in Japanese because their fat intake is lower than that of Europeans and Americans. Failure to take this into account creates difficulties when attempting to compare data on pancreatic exocrine insufficiency in different countries. The authors examined the incidence and grade of steatorrhea in Japanese chronic pancreatitis (CP) patients whose daily fat intake was <40 g (25 patients) or ≥40 g (35 patients). In addition, 23 CP patients with steatorrhea and daily fecal fat excretion ≥5 g were given a pancreatic enzyme preparation at a dose 3–8 times higher than the usual dose to investigate its effect on fecal fat excretion. Among CP patients whose fat intake was <40 g, the incidence of fecal fat excretion <5 g was 56% and that of fecal fat excretion ≥10 g (severe steatorrhea) was 8%. In CP patients whose fat intake was ≥40 g, the incidences were 27.9 and 34.9%, respecetively; a significant increase in the number of affected patients was noted when fat intake was ≥40 g. The fat absorption rate was 76.2% among patients whose fat intake was <40 g and 77.8% among patients whose fat intake was ≥40 g, revealing no significant difference between the two groups. The proportion of CP patients whose fat absorption rate ≦80% was 32% at a fat intake <40 g and 39% at a fat intake ≥40 g, revealing no significant difference between the two groups.

Gastric emptying in patients with autoimmune pancreatitis.

Objectives: Autoimmune pancreatitis (AIP) and its extrapancreatic lesions seem to be clinical manifestations of organs involved in IgG4-related systemic disease. To clarify whether the stomach is a target organ, gastric function was evaluated in patients with AIP. Methods: In 6 patients with AIP, gastric emptying was assessed by Carbon 13 (13C) acetate breath test before and after steroid therapy. Based on 4-hour breath samples, the half 13CO2 excretion time (T1/2) and the time of maximal excretion (Tmax) were calculated as gastric emptying parameters. Data of 20 healthy volunteers were used as controls. The number of IgG4-positive plasma cells in gastrofiberscopic biopsy specimens was counted before and after steroid therapy. Results: Both T1/2 and Tmax in patients with AIP decreased significantly after steroid therapy (T1/2: 1.89 ± 0.21 hours vs 1.69 ± 0.15 hours, P = 0.046; and Tmax: 1.1 ± 0.2 hours vs 0.96 ± 0.2 hours, P = 0.027), and became similar to those of the controls (T1/2: 1.69 ± 0.32 hours and Tmax: 0.98 ± 0.2 hour). The number of IgG4-positive plasma cells infiltrating the gastric mucosa decreased after steroid therapy. Conclusions: Gastric emptying was impaired in patients with AIP and improved to the reference range after steroid therapy. The stomach may be a target organ of IgG4-related systemic disease.