Relationship between Pancreatic Exocrine Function and Histological Changes in Chronic Pancreatitis

To confirm correlation between function and histology of the exocrine pancreas in chronic pancreatitis, we compared exocrine pancreatic function, as estimated by cholecystokinin secretin test (CST), with histological findings in 108 patients. Exocrine pancreatic insufficiency was graded from 0 to 4 according to the number of abnormal CST parameters. Histological findings also were graded from 0 to 4. Results of CST in 108 patients were normal (grade 0) in 52, equivocal (grade 1) in 23, and abnormal (grades 2-4) in 33. Normal histological findings (grade 0) were observed in 54 patients, equivocal (grade 1) in 15, and abnormal (grades 2-4) in 39. We confirmed that there was a significant correlation between histological grading and overall scoring (tau = 0.59, p less than 0.01) or individual parameters (tau = -0.36 for volume, -0.45 for amylase output, and -0.54 for maximal bicarbonate concentration (p less than 0.01) of CST. Sensitivity of CST was 67% in 39 patients with histologically confirmed chronic pancreatitis, specificity was 90% in 69 patients without chronic pancreatitis, based on histological evidence, and efficiency was 81%. In conclusion, we confirmed a highly significant correlation between direct function test (CST) and histology of the exocrine pancreas.     

Exocrine Pancreatic Function among Diabetic Patients in Thailand

Pancreozymin-secretin-stimulated secretion was measured for volume, bicarbonate concentration and total amylase output in 16 noninsulin-dependent patients and 23 age-, sex-, and weight-matched similar control subjects. Another group of 17 insulin-dependent patients was studied using secretin stimulation and the secretory response compared to a similar group of 37 control subjects. Pancreozymin-secretin-stimulated pancreatic function was normal in noninsulin-dependent patients. Abnormal values for at least one parameter of secretion were found in 82% of insulin-dependent patients. Amylase output was low in 35% and bicarbonate concentration was low in 30%. Hypersecretion occurred in 35%. One patient had abnormal values for all three parameters and three patients had two abnormal values. Hypersecretory response to secretin stimulation is considered to be an early finding of pancreatic exocrine dysfunction among insulin-dependent patients. Progressive secretory failure occurs as the pathological process increases, and a decrease in total amylase output becomes the most significant abnormality.     

Distinguishing Pancreatic Cancer from Autoimmune Pancreatitis

Both autoimmune pancreatitis (AIP) and pancreatic cancer frequently present with obstructive jaundice. However, AIP is a rare disease and its diagnosis carries vastly different therapeutic and prognostic implications compared with that of pancreatic cancer. The clinical challenge is to distinguish AIP from pancreatic cancer, because the price of misdiagnosis can be heavy. Recently, two strategies for differentiating AIP from pancreatic cancer were published, one from Japan and the other from the United States. The Japanese strategy relies on cross-sectional imaging, endoscopic retrograde pancreatogram, and serum IgG4. The American strategy uses imaging (CT scan), serology (serum IgG4), and evidence of other organ involvement (on CT scan) as the first tier of tests. If the differentiation cannot be made by these methods, a core biopsy of the pancreas, steroid trial, or surgical resection is recommended. The two strategies reflect differences in clinical practice and local preferences in the use of certain diagnostic tests. However, both strategies require thorough familiarity with the diseases and the tests being used.     

急性脑梗死患者胰腺内外分泌功能变化及其临床意义研究

目的探讨急性脑梗死患者胰腺内外分泌功能变化及其临床意义。方法选择2010年1月—2015年1月在上海市第十人民医院就诊的急性脑梗死患者93例作为脑梗死组,根据梗死面积分为大面积22例、中面积31例、小面积40例,根据神经功能缺损程度分为轻度32例、中度50例、重度11例;另选择同期在上海市第十人民医院体检健康者30例作为对照组。比较不同梗死面积、神经功能缺损程度脑梗死患者治疗前空腹血糖(FPG)、空腹胰岛素(FINS)、稳态模型的胰岛素抵抗指数(HOMA-IR)、C肽及粪弹性蛋白酶-1(FE-1),比较脑梗死组治疗前后及对照组FPG、FINS、HOMA-IR、C肽及FE-1。结果大面积和中面积脑梗死患者FPG、FINS、HOMA-IR高于小面积脑梗死患者,C肽及FE-1低于小面积脑梗死患者(P0.05);大面积脑梗死患者FPG、FINS、HOMA-IR高于中面积脑梗死患者,C肽及FE-1低于中面积脑梗死患者(P0.05)。重度和中度脑梗死患者FPG、FINS、HOMA-IR高于轻度患者,C肽及FE-1低于轻度患者(P0.05);重度脑梗死患者FPG、FINS、HOMA-IR高于中度患者,C肽及FE-1低于中度患者(P0.05)。脑梗死组患者治疗前FPG、FINS和HOMA-IR高于对照组,C肽和FE-1低于对照组(P0.05);脑梗死组患者治疗后FPG、FINS、HOMA-IR、C肽及FE-1与对照组比较,差异无统计学意义(P0.05);脑梗死组患者治疗后FPG、FINS、HOMA-IR低于治疗前,C肽及FE-1高于治疗前(P0.05)。结论急性脑梗死患者存在胰腺内外分泌功能紊乱,且与梗死面积及神经功能缺损程度有关,纠正胰腺内外分泌功能紊乱有助于促进急性脑梗死患者的康复。     

Short and Long-Term Outcomes of Diabetes Mellitus in Patients with Autoimmune Pancreatitis after Steroid Therapy

Background/Aims

Autoimmune pancreatitis (AIP) is frequently associated with diabetes mellitus (DM). This study evaluated the effect of steroid therapy on the course of DM in AIP.

Methods

Glucose tolerance was examined in 69 patients with AIP. DM onset was classified as either a simultaneous onset with AIP or an exacerbation of pre-existing DM. Based on the changes in the HbA1c levels and insulin dose, the responses of DM to steroids were classified as improved, no change, or worsened.

Results

Thirty (46%) patients were diagnosed as having DM (simultaneous onset, n=17; pre-existing, n=13). Three months after starting the steroid treatment, the DM improved in 13 (54%) of 24 DM patients. The DM improved in 55%, had no change in 36%, and worsened in 9% of the 11 simultaneous onset DM patients, and it improved in 54%, had no change in 31%, and worsened in 15% of the 13 pre-existing DM patients. At approximately 3 years after starting the steroid treatment, the DM improved in 10 (63%) of 16 patients. The pancreatic exocrine function improved in parallel with the changes in the DM in seven patients.

Conclusions

Because approximately 60% of DM associated with AIP is responsive to steroids in the short- and long-terms, marked DM associated with AIP appears to be an indication for steroid therapy.     

Pathological Pancreatic Exocrine Function and Duct Morphology in Patients with Cholelithiasis

Most authors claim alcohol consumption to be the only relevant reason for chronic pancreatitis. However, gallstones might cause this disease, as they do cause acute pancreatitis. In this study 91 gallstone patients and 94 age-matched controls were investigated concerning exocrine pancreatic function (fecal elastase-1 concentrations). Furthermore x-rays of 100 consecutive ERCP patients were evaluated for differences concerning pancreatic duct changes between patients with and without evidence of cholelithiasis. Pathological elastase 1 levels were more frequent in gallstone patients (30,8%) as compared to age-matched controls (19%). Symptoms such as upper abdominal pain, bloating, and fat intolerance were reported more often in gallstone patients. In ERCP of gallstone patients (N = 60), 77% were found to have chronic pancreatitis according to the Cambridge classification, while in nongallstone-patients (N = 32) 47% had chronic pancreatitis. In conclusion, according to these data a pathophysiological connection between gallstones and chronic pancreatitis appears to be probable.     

Exocrine Pancreatic Function in Hepatic Cirrhosis

Exocrine pancreatic function was assessed by the standard test meal method of Lundh in a control group, and 13 patients with nonalcoholic, postnecrotic cirrhosis of the liver. In six of these patients, splenorenal shunts were performed and exocrine pancreatic function was assessed before and three months after operation. In three of the six, the secretin-pancreozymin stimulation test was also performed.
An increased volume but normal trypsin output was observed in the un-operated cirrhotic patients. An increase both in volume and in trypsin was found in the cirrhotic patients after shunting using the test meal stimulation. There was no appreciable difference, however, when tested with secretin and pancreozymin.
Hypersecretion in cirrhotics, with or without shunts, is probably due to a by-pass of the hepatic degradation of normal pancreatic secretogogues produced by the intestine.     

Helicobacter pylori in Autoimmune Pancreatitis and Pancreatic Carcinoma

Background:Helicobacter pylori has been suggested to be involved in pancreatic diseases, namely autoimmune pancreatitis and pancreatic carcinoma. We investigated the presence of conserved sequences of Helicobacter in pancreatic tissue and pancreatic juice from patients with chronic nonautoimmune and autoimmune pancreatitis as well as pancreatic ductal adenocarcinoma (PDAC). Methods: 35 pancreatic juices collected during routine endoscopic retrograde cholangiopancreatography and 30 pancreatic tissues were studied. Nested PCR was used to detect H. pylori in the isolated DNA samples. In order to exclude a methodological bias, the samples were analyzed blindly in 2 different laboratories using either conventional or LightCycler PCR for H. pylori urease A and 16S ribosomal DNA. Results: In the pancreas of 11 patients with autoimmune pancreatitis, no H. pylori DNA could be detected. Further, in none of the other tissue samples of chronic pancreatitis or PDAC could we detect any Helicobacter sequences. Out of the pancreatic juice samples, none demonstrated either of the 2 Helicobacter gene sequences investigated. Conclusion: Despite good scientific reasoning for an involvement of Helicobacter in pancreatic diseases, a direct infection of the microbial agent seems unlikely. Rather, the pathomechanism must involve molecular mimicry in autoimmune pancreatitis, or the transformation of nitric food constituents to nitrosamines in pancreatic cancer.     

Short-Term and Long-Term Pancreatic Exocrine and Endocrine Functions After Pancreatectomy

Exocrine and endocrine functions of the pancreaswere assessed in 44 Japanese patients who underwentpancreatic head resection. Functions were analyzedcomparing levels before surgery, at a short-termfollow-up (<2 months), and at a long-term follow-up(12-31 months). The N-benzoyl-L-tyrosyl-p-aminobenzoicacid (BT-PABA) excretion test, fasting blood sugar (FBS)level, and oral glucose tolerance test (OGTT) were used to determine pancreatic function. Thepatients were divided into three groups according to thesize of the main pancreatic duct: group 1, 15 patientswith a normal sized duct (3 mm); group 2, 20 with a moderately dilated duct (>3 mm,<10 mm); and group 3, 9 with a markedly dilated duct(10 mm). The mean BT-PABA value (6-hr urinary PABArecovery rate) in group 1 showed no change during the postoperative period. In contrast, theBT-PABA values in groups 2 and 3 had dropped by theshort-term follow-up and returned to the preoperativelevel by the long-term examination. FBS and 120-min OGTT levels were not different between the threegroups preoperatively. Although these values showed nochange in all the three groups at the short-termmeasurements, the FBS in group 3 and 120-min levels in all the three groups had increased at thelong-term. These findings suggest that exocrinepancreatic function shows a short-term deterioration inpatients with a dilated pancreatic duct but recovers to the preoperative level over the long term afterpancreatic head resection. Endocrine insufficiency,however, may occur at a long-term point after surgeryirrespective of the preoperative pancreatic ductal dilatation.     

Plasma Calprotectin Levels in Patients Suffering from Acute Pancreatitis

Calprotectin (Cal) concentration is elevated in acute inflammatory reactions and its increase in the plasma suggests a diagnostic potential for Cal assay. This study aimed (a) to evaluate the Cal plasma levels in patients suffering from acute pancreatitis (AP) and (b) to assess whether early assay of Cal plasma levels can be helpful in assessment of the severity of AP. Forty-six consecutive patients, median age 45 years, suffering from a first attack of AP were recruited at two medical centers. Data collected on admission included age, sex, delay between pain onset and admission, and Glasgow score. A severe outcome was defined according to the Atlanta criteria. AP was defined as edematous or necrotic according to the CT findings. Plasma Cal and serum C reactive protein (CRP) were assayed in all patients within the first 24 hr after hospitalization. Sixty subjects suffering from blood hypertension were recruited as controls. Plasma Cal was measured by a commercial ELISA system. In all AP patients and in none of the controls, plasma Cal concentration was higher than the normal limit. Cal values in AP patients were significantly higher than in controls (P < 0.0001). There was not a statistically significant difference in Cal values between patients with severe and patients with mild AP. Plasma Cal values did not differ in necrotizing and edematous AP. During the follow-up plasma Cal was reassayed in six of the patients with abdominal fluid collection and the values were higher in the two patients with infected necrosis. We conclude that plasma Cal is elevated in patients with AP but it is not a useful marker for early prediction of pancreatitis severity. Further studies could evaluate its usefulness in pancreatic infected necrosis.     

Exocrine Pancreatic Function in Chronic Liver Diseases

To confirm the respective influence of chronic alcoholism and liver disease on exocrine pancreatic function in cholecystokinin secretin (CS), tests were performed on patients with chronic liver cirrhosis (LC) and non-cirrhotic (nLC) disease of alcoholic (A) and nonalcoholic (nA) etiology. Results were compared in four subgroups (ALC, N = 26; AnLC, N = 45; nALC, N = 18; and nAnLC, N = 43). Volume of duodenal juice and bicarbonate output (BO) were increased and maximal bicarbonate concentration was decreased in ALC, compared with those in normal controls. Comparison of LC and nLC indicated that the volume, BO, and amylase output (AO) were greater in LC than in nLC of alcoholic etiology, but not in those of nonalcoholic etiology. The initial disappearance rate (KICG) of indocyanine green (ICG) excretion correlated with a parameter of CS test in alcoholic liver disease (vs. volume: r = -0.51, p less than 0.01 vs BO: r = -0.40, p less than 0.01), but not in nonalcoholic liver disease. Concurrent chronic pancreatitis with pain and definite exocrine insufficiency was observed in only one ALC patient and in four AnLC patients, but in none of the nonalcoholics. In alcoholic liver disease, exocrine pancreatic secretion tends to increase with severity of liver damage, but concurrence of definite chronic pancreatitis is not correlated with the severity.     

Increased Postprandial Response of Glucagon-Like Peptide-2 in Patients with Chronic Pancreatitis and Pancreatic Exocrine Insufficiency

Background/Aims: Glucagon-like peptide-2 (GLP-2) is a nutrient-released gastrointestinal (GI) hormone that acts as an intestinal growth factor, and exogenous GLP-2 has been shown to increase superior mesenteric artery (SMA) blood flow. We aimed to investigate how assimilation of nutrients affects postprandial GLP-2 responses and to correlate these with postprandial SMA blood flow. Methods: Responses of the GI hormone glucose-dependent insulinotropic polypeptide (GIP) and GLP-2 were measured following an 80-min liquid meal test in 8 patients (6 males) with chronic pancreatitis (CP) and pancreatic exocrine insufficiency (PEI) and 8 healthy control subjects (5 males). Postprandial GI hormone responses were correlated with change in SMA flow as assessed by the resistance index. Results: Patients with CP and PEI exhibited the greatest postprandial GLP-2 responses (1,870 8 249 vs. 1,199 ± 108 pM·80 min, p = 0.027). No difference was observed with regard to GIP. GLP-2, but not GIP, responses correlated significantly with postprandial SMA flow. Conclusion: These results suggest that delayed assimilation of nutrients in patients with CP and PEI increases the secretion of GLP-2 - possibly due to delivery of a larger nutrient load to the distal part of the small intestine, where GLP-2 secreting L-cells are abundant - and that this hypersecretion of GLP-2 is associated with a higher SMA flow.     

急性胰腺炎后胰腺功能和形态变化的研究现状

急性胰腺炎作为临床上常见的疾病,关于其治愈或好转后胰腺功能和形态改变的研究较少。目前认为急性胰腺炎发病后只要去除诱发病因以及相关并发症,胰腺功能和形态就可恢复,但这一观点仍存争议。本文就急性胰腺炎后胰腺功能和形态的变化作一综述。     

Pancreatic Secretory Proteins in Sera from Rats before and after Induction of Experimental Pancreatitis

This study has traced the behavior of rat anionic trypsin-like immunoreactivity and pancreatic secretory trypsin inhibitor (PSTI) immunoreactivity in the serum of rats undergoing bile-pancreatic duct infusions of buffered solutions with and without the addition of the bile salt taurocholate. Enzymatic analysis of α-amylase was also done. A mild pancreatic inflammation followed infusion of buffer alone, as determined by gross inspection of the pancreas and the behavior of serum levels of the above proteins. Animals infused with buffer and 4% taurocholate had major inflammatory changes, including gross hemorrhage into the gland, and marked elevations in serum levels of the three proteins studied. Graphic analysis of the serum levels revealed distinct sharp rises in the serum levels of all three proteins in the taurocholate group. In the buffered saline group only an initial sharp rise was present, followed by a prolonged decrease back towards base-line values. The immunoreactive trypsin in the taurocholate group was present in three fractions with different molecular weights: trypsin in complex with protease inhibitors, trypsinogen, and degradation products. PSTI immunoreactivity showed the molecular size of free inhibitor and that of degradation products. The presence of trypsin in complex with protease inhibitors indicates the formation of active trypsin during acute pancreatitis, which is further supported by the presence of degradation products of trypsin and PSTI.     

Change of Both Endocrine and Exocrine Insufficiencies After Acute Pancreatitis in Non-Diabetic Patients: A Nationwide Population-Based Study

Acute pancreatitis (AP) is the most common pancreatic disease and consists of an acute inflammation of the pancreas. AP can contribute to endocrine and exocrine insufficiencies in survivors as a result of the key role of the pancreas in both glucose metabolism and nutritional digestion. The aim of this population-based study was to determine the endocrine or exocrine insufficiencies in patients after initial AP with biliary or alcohol-associated causes.We conducted a nationwide cohort study using data from Taiwan''s National Health Insurance Research Database collected between 2001 and 2010. A total of 12,284 patients with AP were identified.Alcohol-associated AP (odds ratio, 1.894; 95% CI, 1.520–2.268; P < 0.001) and ≥2 admissions for AP (odds ratio, 1.937; 95% CI, 1.483–2.391; P < 0.001) were significantly associated with newly diagnosed diabetes mellitus after AP. Further, only alcohol-associated AP (odds ratio, 1.215; 95% CI, 1.133–1.297; P < 0.001) was significantly associated with pancreatic exocrine insufficiency after AP. Additionally, alcohol-associated AP (odds ratio, 1.804; 95% CI, 1.345–2.263; P < 0.001) and ≥2 readmissions for AP (odds ratio, 3.190; 95% CI, 2.317–4.063; P < 0.001) were significantly associated with both exocrine and endocrine insufficiencies after AP.Our data showed that alcohol-associated AP, rather than a biliary cause, contributed to a higher extent to exocrine or endocrine insufficiencies. Furthermore, recurrent AP also led to endocrine insufficiency.     

13C-Labeled Trioctanoin Breath Test for Exocrine Pancreatic Function Test in Patients after Pancreatoduodenectomy

To assess exocrine pancreatic function in patients before and after pancreatoduodenectomy (PD), we used the breath test, with nonradioactive ¹³C-labeled trioctanoin, in 14 patients before pancreatic resection because of localized pancreatic mass (preop-PD group), and in 13 patients who had undergone pancreatoduodenectomy more than 5 yr before (post-PD group). The results were compared with those of the secretin test, N-benzolyl-L-tyrosyl-p-amino benzoic acid (BT-PABA) test, and fecal chymotrypsin. Means ± SD and frequencies of low values of the recovery of the breath test were 42.0 ± 3.4%, 0/5 in the control; 24.2 ± 10.5%, 14/14 in the preop-PD group; and 18.6 ± 8.0, 13/13 in the post-PD group. The overall sensitivities in the preop- and post-PD groups were 100% for the recovery and 93% for the maximal mass ratio of the breath test, 89% for the secretin test, 67% for the BT-PABA test, and 64% for fecal chymotrypsin. The recovery of the breath test correlated significantly with the duodenal outputs of lipase, amylase, and chymotrypsin, and was not affected in patients with obstructive jaundice or with low D-xylose absorption. The breath test is as sensitive as the secretin test, more reliable than the conventional tubeless tests, and is available to follow up the exocrine pancreatic function before and after pancreatoduodenectomy.