Tropical calcific pancreatitis and fibrocalculus pancreatic diabetes in Bangladesh

The relationship between tropical calcific pancreatitis (TCP) and fibrocalculus pancreatic diabetes (FCPD) is still unclear. The clinical, biochemical and radiological data of age-matched TCP and FCPD subjects have been briefly discussed in the present review. Fibrocalculus pancreatic diabetes patients present with a significantly lower BMI compared with TCP patients. Analysis of the family history reveals that some kind of environmental factors seem to play a predominant role in the development of diabetes in FCPD patients, although these factors remain to be identified. Both TCP and FCPD patients predominantly come from a rural background. Fasting and 2 h blood glucose values as well as fructosamine levels in FCPD patients are approximately four-times higher than those of TCP patients. Measurements of early renal haemodynamic and microvascular changes (glomerular filtration rate, kidney size, microalbuminuria and microtransferrinuria) indicate an early renal involvement in FCPD patients. Tropical calcific pancreatitis subjects have approximately twice as high fasting C-peptide values compared with FCPD patients. Findings of single stranded DNA measurements suggest the involvement of oxidative damage in FCPD patients. Ketosis resistance is the most conspicuous clinical feature in the FCPD group and this relative absence of ketosis is probably due to a defect in the ketone body synthesis pathway and/or in the regulation of counterbalancing hormones. Endoscopic retrograde pancreatography findings of TCP and FCPD patients suggest that FCPD should not be considered only as a form of secondary diabetes consequent to generalized pancreatic damage in TCP.     

Sonographically-guided extracorporeal shockwave lithotripsy for pancreatic stones in patients with chronic pancreatitis

Over a 2 year period, 10 patients with pancreatic stones due to alcohol induced chronic pancreatitis (proven by endoscopic retrograde pancreatography) underwent extracorporeal shockwave lithotripsy. Prior to shockwave therapy, all patients underwent endoscopic sphincterotomy. Targeting of shockwave lithotripsy was exclusively performed under sonographic control. All patients were treated with a second generation electrohydraulic spark gap lithotriptor and fragmentation of concrements could be achieved in all cases. Complete duct clearance was confirmed in seven patients by endoscopic retrograde pancreatography in one session, with endoscopic fragment extraction by basket and/or balloon catheter. In three patients, balloon dilation of concomitant strictures located in the head of the pancreas was performed prior to fragment extraction. All stone-free patients showed no further symptoms over the follow-up period of 12 months. Three patients in whom complete extraction of fragments was not successful experienced minor symptoms over the 12 month follow-up period.     

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis

Summary Conclusion Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled, that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes). Background We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis. Methods Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied. Results The urinary CPR excetion in controls was 94.9±20.5 μg/d. The urinary CPR excretion in calcific pancreatitis was 12.8±7.4 μg/d and it resembled that in IDDM (9.4±5.8 μg/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5±30.1 μg/d, being similar to that in NIDDM (49.3±21.0 μg/d). The plasma glucagon level in calcific pancreatitis was 64.1±15.9 ρg/mL, which was significantly lower than the values in IDDM (111.2±50.2 ρg/mL) and NIDDM (96.7±21.9 ρg/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4±29.6 ρg/mL) were significantly lower than that in controls (12.9±21.6 ρg/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.     

Pancreatic stenting for the preservation of pancreatic function in chronic pancreatitis with stricture

Background: Although many reports have documented pain relief achieved by pancreatic stenting, the effect of stenting on pancreatic function is less clear. In addition, the effects of stent caliber and patency have not been considered in most previous studies. Pain and pancreatic function after stenting of the main pancreatic duct (MPD) were examined. Methods: Records of 24 patients with chronic pancreatitis who had an MPD stricture treated with a 10‐Fr stent from June 1996 to June 2002 were reviewed. The average age was 57.0 ± 1 years, and the male : female ratio was 7 : 1. Eleven patients had diabetes mellitus. Stent patency, pancreatic pain and pancreatic endocrine and exocrine function were examined before stenting and 6 months after stenting. Stenting was continued for 1 year or more, with repeated stent exchange every 3 months. Results: The stent became occluded in 29% of cases, migration occurred in 15% of cases, and the 50% patency time was 125 days. Pancreatic pain was relieved by stenting in all cases. The diameter of the MPD, the Bentiromide test value, weight and body mass index were improved. Conclusion: Stenting relieves blockage of the main pancreatic duct and provides both pain relief and preservation of residual pancreatic function.     

B cell function in patients with chronic pancreatitis and its relation to exocrine pancreatic function

Summary Exocrine pancreatic function was evaluated by a Lundh meal test and a secretin-cholecystokinin test in 16 patients with chronic pancreatitis. B cell function was assessed by measuring the concentration of C-peptide after stimulation with oral glucose and intravenous glucagon. The C-peptide response to intravenous glucagon and oral glucose was closely correlated (r = 0.88,p < 0.01). Plasma C-peptide after glucagon was significantly correlated to the post-prandial concentration of lipase (r = 0.72,p < 0.001), amylase (r=0.64,p < 0.05) and to amylase output (r = 0.64,p < 0.05). Eight out of nine patients treated with insulin had residual B cell function, but it diminished significantly with increasing duration of diabetes. We conclude that B cell function is correlated to pancreatic enzyme secretion and that patients with insulin-treated diabetes secondary to chronic pancreatitis have a residual insulin secretion similar to that of patients with Type 1 (insulin-dependent) diabetes.     

Gallbladder dynamics in chronic pancreatitis

Gallbladder dynamics, cholecystokinin (CCK), and pancreatic polypeptide (PP) release were studied in 14 patients with chronic pancreatitis (CP) (2 females, 12 males; age range 24–56 years) and 12 control subjects (4 females, 8 males, 21–50 years). On day 1, gallbladder contractility was investigated after ceruletide intravenous infusion (2.5 ng/kg/min for 10 min). On day 2, a mixed standard test meal (1450 kJ) was administered orally. Gallbladder volume was assessed at three time intervals before (–30, –15, 0 min) and at 5, 10, 20, 30, 40, 50, 60, 80, 100 and 120 min after stimulation by means of ultrasonography. CCK and PP plasma levels were determined at each time interval.Exocrine pancreatic function was assessed using the pancreolauryl serum test (PLT). Six patients with CP had severe exocrine pancreatic insufficiency (EPI) (PLT<1.8 g/ml) with steatorrhea, eight patients had mild-moderate EPI. Fasting gallbladder volume was increased in CP (32.3±3.1 cm³) as compared to controls (20.5±1.2 cm³) (P<0.01). Peak gallbladder contraction (percent of initial volume) in CP ranged from 5 to 55% (controls: 8–46%) following ceruletide and from 17 to 86% (controls: 27–80%) following the test meal (NS). There was no correlation between the degree of EPI according to PLT and peak gallbladder contraction. Gallbladder emptying in CP patients was not different from controls, although the postprandial CCK response was significantly impaired (P<0.01). Postprandial PP response in CP was correlated with the PLT result (r=0.78;P<0.01) but not with gallbladder emptying or refilling time. We conclude that gallbladder emptying and refilling following the oral administration of a test meal or the stimulation with a pharmacological dose of ceruletide is normal in patients with chronic pancreatitis. Postprandial gallbladder emptying is not influenced by the degree of exocrine pancreatic insufficiency.     

Development of carcinoma in chronic calcific pancreatitis

Development of carcinomas of the pancreas over an underlying chronic pancreatitis is a rare event. Diminution of pancreatic calcification, following the development of carcinoma, has been previously reported only once. We report another such case.     

Long term follow up of patients with chronic pancreatitis and pancreatic stones treated with extracorporeal shock wave lithotripsy

BACKGROUND: There have been conflicting reports as to whether pancreatic ductal drainage achieved by endoscopy and lithotripsy improves the clinical outcome of patients with chronic pancreatitis. AIMS: To determine the clinical outcome in patients with chronic pancreatitis who received extracorporeal shock wave lithotripsy (ESWL), and were followed up for two to eight years. METHODS: Eighty patients with severe chronic pancreatitis and endoscopically unretrievable obstructive stones underwent ESWL with a piezoelectric lithotripter between 1989 and 1996. Clinical status, relief of symptoms, further endoscopic or surgical interventions, and mortality were defined. RESULTS: Forty three (54%) patients were treated successfully with ESWL. The only feature associated with treatment success was the presence of a single stone rather than multiple stones. Successfully treated patients tended to experience less pain, although this did not reach statistical significance. A slight increase in weight was noted in our patients; however, there was no notable improvement in anomalous stools and diabetes mellitus. Five patients died due to extrapancreatic reasons. No pancreatic carcinomas developed. CONCLUSIONS: ESWL associated with endoscopic drainage is a safe technique that is particularly successful in patients with a single stone. However, pancreatic drainage by endoscopy and ESWL has almost no effect on pain in chronic pancreatitis. Furthermore, endoscopic management and ESWL does not prevent or postpone the development of glandular insufficiency.     

Radiological appearance of pancreatic calculi in tropical versus alcoholic chronic pancreatitis

Tropical and alcoholic forms of chronic pancreatitis differ in their clinical, aetiological and epidemiological features. We compared the radiological appearances of pancreatic calculi seen on plain roentgenogram of the abdomen of 89 patients with tropical calcific pancreatitis (TCP) and 32 patients with alcoholic calcific pancreatitis (ACP) seen in Madras, Southern India. While TCP was characterized by the frequent occurrence of large, discrete, dense calculi, patients with ACP had typically small, speckled calculi with irregular, hazy margins. The calculi in TCP resembled those described for hereditary pancreatitis. This is the first report comparing the radiological appearances of TCP and ACP patients seen at the same centre.     

Regional gastrointestinal transit times in patients with chronic pancreatitis

The mechanisms behind disrupted gastrointestinal (GI) motor function in patients with chronic pancreatitis (CP) have not been fully elucidated. We compared regional transit times in patients with CP to those in healthy controls, and investigated whether they were associated with diabetes mellitus, exocrine dysfunction, opioid treatment or quality of life. Twenty-eight patients with CP and 28 age- and gender-matched healthy controls were included. Regional GI transit times were determined using the 3D-Transit system, which consists of an ingestible electromagnetic capsule and a detector worn in an abdominal belt for 5 days. Exocrine function was assessed using the fecal elastase-1 test, and quality of life was assessed using the European Organization for Research and Treatment of Cancer questionnaire. Transit times were analyzed for associations with diabetes mellitus, exocrine pancreatic insufficiency (EPI), opioid treatment and quality of life. Compared with healthy controls, patients with CP had prolonged transit times in the small intestine (6.6 ± 1.8 vs 4.8 ± 2.2 hours, P = .006), colon (40 ± 23 vs 28 ± 26 hours, P = .02), and total GI tract (52 ± 26 vs 36 ± 26 hours, P = .02). There was no difference in gastric emptying time (4.8 ± 5.2 vs 3.1 ± 1.3 hours, P = .9). No associations between transit times and diabetes, EPI, or opioid consumption were found (all P > .05). Quality of life and associated functional and symptom subscales were not associated with transit times, except for diarrhea (P = .03). Patients with CP have prolonged small intestinal and colonic transit times. However, these alterations do not seem to be mediated by diabetes, EPI, or opioid consumption.     

内镜下诊治伴发胰管结石慢性胰腺炎的价值

目的探讨ERCP在胰管结石诊断和治疗中的临床价值及其安全性评估。方法分析2008年2月～2008年10月期间共20例接受ERCP诊断和治疗的伴发胰腺结石慢性胰腺炎患者的临床资料。结果20例病例中,16例（80％）胰管结石位于胰头处,3例（15％）位于胰头及胰体处,1例（5％）累及全程胰管。14例（70％）患者一次性取石完全,5例患者术后接受体外震波碎石（ESWL）,1例患者未能完成取石,建议其外科手术治疗．18例表现为腹痛的病例,在接受内镜下治疗结石后,腹痛症状均消失,在接受治疗后2～10d内出院,平均（5．3±2．43）d。术后2例（10％）出现一过性的血淀粉酶升高。结论对于伴有胰管结石的慢性胰腺炎病例而青,内镜下取石是安全有效的方法,同时应川支架及鼻胰管引流,不仅对胰管结石的治疗有效,而且充分的胰液引流对于缓解腹痛症状、减少术后的胰腺炎、高淀粉酶m症的发乍有着重要的作用。     

Analysis of risk factors for pancreatic duct stones formation in patients with alcoholic chronic pancreatitis

BackgroundAlcoholic chronic pancreatitis (ACP) is the dominant cause of chronic pancreatitis (CP). As a main complication of CP, the formation of pancreatic duct stones (PDS) compromises pancreatic function and symptomatic patients are often subjected to aggressive treatments. The present study aimed to identify PDS risk factors in patients with ACP.MethodsA retrospective analysis of 93 ACP patients was performed; patients were divided into two groups: ACP with PDS (n = 48) and ACP without PDS (n = 45). Fourteen potential factors were analyzed by univariate and multivariate analyses to identify independent risk factors of PDS formation in ACP patients. A comparison of demographic and clinical characteristics between ACP patients with PDS and non-ACP patients with PDS (n = 43) was also carried out.ResultsACP accounted for 47.7% (93/195) of CP in this cohort. Among ACP patients, the morbidity of PDS was 51.6% (48/93). Significant risk factors of PDS formation for ACP patients included duration of drinking ≥24.7 years (OR, 9.036; 95% CI, 2.737–29.837; p < 0.001); daily alcohol consumption ≥147.0 g (OR, 3.147; 95% CI, 1.040–9.522; p = 0.042); and MPD narrowing (OR, 7.245; 95% CI, 2.205–23.811; p = 0.001). Shorter periods between diagnosis and PDS formation (PDP) were observed in ACP patients than non-ACP patients.ConclusionsAlcohol consumption accelerates the progression of PDS formation in patients with CP.     

Progression of pancreatic morphology in chronic pancreatitis is not associated with changes in quality of life and pain

Abstract

Objectives

In patients with chronic pancreatitis (CP), the aim was to explore the association between pancreatic morphological progression over four years and corresponding changes in disease characteristics, including quality of life (QOL), pain, and exocrine pancreatic function.     

Endotherapy for pain in chronic pancreatitis

Pain is the most distressing symptom of chronic pancreatitis. Although the pathogenesis of pain is still poorly understood, an increase in intraductal pressure may be the dominant factor. The management of pain can involve medical, endoscopic, neurolytic, and surgical therapies. Endotherapy includes pancreatic sphincterotomy, extraction of stones, placement of stent, and dilatation of strictures, sometimes preceded or followed by extracorporeal shock‐wave lithotripsy. Several studies have now shown that endotherapy provides partial or complete relief of pancreatic pain in a majority of patients with an acceptable frequency of early and late complications. Endotherapy should now graduate from an experimental form of treatment to a realistic treatment option in patients with chronic or relapsing pain, particularly in the setting of calcific chronic pancreatitis.     

Is increased pancreatic pressure related to pain in chronic pancreatitis?

In this study, we investigated the relationship between pain and pancreatic pressure in patients with chronic pancreatitis (CP). We studied 12 patients with CP undergoing surgery and five controls with cancer of the pancreatic tail. CP was staged on the basis of morphological (ERP) and functional (serum-pancreolauryl test) criteria. Patients kept daily records of the intensity of pain on a linear analog scale. Intraoperatively, pressure within the pancreas was assessed by the introduction of a fine needle into the pancreatic parenchyma connected to a pressure transducer. In controls, pressure was determined in macroscopically normal tissue in the head of the pancreas. Pancreatic pressure was significantly higher in CP than in controls (29.9 ± 3.1 vs 7.2 ± 1.1 mmHg, p < 0.001). No relationship was found between the pain score and the pancreatic pressure. Pressure was positively correlated with ductal changes (r = 0.831;p<0.001), but not with exocrine function of the pancreas. Postoperatively, pancreatic pressure fell by 15.3% in four patients with CP in whom pressure assessment was repeated after surgical decompression. We conclude that pancreatic parenchy pressure is not closely related to pain in CP.     

Clinical assessment of pancreatic diabetes caused by chronic pancreatitis

Despite the high prevalence of diabetes mellitus in patients with chronic pancreatitis, few studies of pancreatic diabetes have been reported. We investigated 154 patients with chronic pancreatitis, of whom 50% were diabetics, with special reference to the features and clinical course of pancreatic diabetes. We arrived to clarify the features of pancreatic diabetes by comparing pancreatic exocrine function in 112 patients with primary diabetes with findings in a separate group of 80 patients with chronic pancreatitis. Pancreatic diabetes is proposed as a type of diabetes in which exocrine pancreatic function is markedly decreased. Progressive and fatal angiopathies were found in patients with pancreatic diabetes after a long duration of diabetes. The present investigation suggests that treatment of malnutrition is necessary in patients with pancreatic diabetes and that control of blood glucose is often difficult in these patients because of the high incidence of insulin-induced hypoglycemic episodes. (Received Feb. 6, 1997; accepted July 25, 1997)     

Dissolution of pancreatic stones by oral trimethadione in a dog experimental model

Experiments were conducted to develop a dissolution therapy for human pancreatic calculi in a dog experimental model of pancreatic calculi surgically prepared. On plain x-ray films of the abdomen, pancreatic calculi appeared in 19 of 39 dogs within 12 mo after operation. The antiepileptic agent trimethadione was given orally to 13 dogs at a dose of 1.0-1.5 g daily. Pancreatic calculi disappeared in 13 of 15 observations. The scanning electron microscopy, the elemental analysis, and the powder x-ray diffractometry of pancreatic calculi in this model revealed that the calculi closely resembled human pancreatic calculi, consisting mainly of a calcite of calcium carbonate. There was no histologic finding suggesting drug toxicity in the liver, the kidney, and the blood. Pancreatic calculi in 6 control dogs without the treatment neither disappeared nor diminished spontaneously. The oral treatment with trimethadione may have potential for dissolving human pancreatic calculi.     

Pancreatic exocrine function during acute exacerbation in WBN/Kob rats with spontaneous chronic pancreatitis

Summary Conclusion Pancreatic exocrine hypofunction is markedly deteriorated during acute exacerbation in a rat model with chronic pancreatitis. Background Little is known about pancreatic exocrine function during acute exacerbation in patients with chronic pancreatitis. We investigated changes in pancreatic exocrine function after inducing acute pancreatitis in an animal model of spontaneous chronic pancreatitis. Methods WBN/Kob rats with chronic pancreatitis sequentially underwent pancreatic exocrine function test 1–6 d after surgical preparation with external pancreatic fistula. We induced acute pancreatitis in another WBN/Kob rats by iv administration of cerulein at a rate of 10 μg/kg/h for 4 h 4 after surgical preparation. Pancreatic exocrine function test was undertaken in a conscious state 1 d before and after cerulein administration. Results In WBN/Kob rats not given cerulein, pancreatic exocrine function remained almost constant, at 3–6 d after surgery. Marked hyperamylasemia developed immediately after cerulein administration. After its administration, the pancreas microscopcially showed prominent intersitial edema and intracellular vacuolization of acinar cells in addition to the finding of pre-existing chronic pancreatitis. Basal and chole-cystokinin-stimulated flow rate, bicarbonate output, and protein output, which were substantially impaired 1 d before cerulein administration, were further reduced 1 d after its administration.     

Insulin secretion and pancreatic exocrine function in patients with chronic pancreatitis

Summary The relationship between insulin responses to oral glucose and pancreatic exocrine function were examined in 15 patients with chronic pancreatitis. Good correlations were found between the insulin responses and exocrine pancreatic function measured as the concentrations of pancreatic enzymes in duodenal juice after intravenous cholecystokinin-pancreazymin (CCK-PZ). There appears to be a roughly parallel loss of endocrine and exocrine function in the course of chronic pancreatitis.     

Secretory immunoglobulin A in pancreatic juice and pancreatic tissue of patients with chronic pancreatitis

Background—The predominace of secretory IgA(S-IgA) in intestinal secretions compared with blood is wellestablished, but concentrations of this protein in pancreatic juice andits origin, especially in chronic pancreatitis, are unknown.
Aims—To investigate the role of S-IgA in chronic pancreatitis.
Patients—Twenty one patients with chronicpancreatitis (group I), three patients with proven malignancies (groupII), and 12 patients without pancreatic disease (group III).
Methods—Pure human pancreatic juice was collectedendoscopically in four fractions after consecutive stimulation withsecretin and cholecystokinin (CCK). Samples were analysed for S-IgA,protein, trypsinogen, and proteolytic activity.
Results—The S-IgA level was significant increasedin fraction 1 of pancreatic juice of group I (1210 (1411) ng/ml)compared with controls (33 (70) ng/ml). Protein concentrations andtrypsinogen content were lower in group I than in the other groups.Proteolytic activity could be observed in 53% of all 133 pancreaticjuice samples, but in 87% of fraction 1. In pancreatic tissue of three patients with chronic pancreatitis both IgA and secretory component were detected by immunohistology. Expression of the secretory componentby human pancreatic epithelial cells was increased in patients withchronic pancreatitis compared with normal controls. The concentrationof S-IgA in pancreatic juice did not correlate with the serum S-IgAlevel. In contrast, serum levels of S-IgA were decreased in patientswith chronic pancreatitis.
Conclusion—There are high levels of S-IgA inhuman pancreatic juice following chronic inflammation and a protectiverole is suggested for this immunoglobulin.

Keywords:chronic pancreatitis; pancreatic juice; proteaseactivity; protease inhibitors; secretory IgA; immunohistochemistry