Endocrine Pancreatic Insufficiency Research Articles

Diagnostik und Therapie der chronischen Pankreatitis

Chronic pancreatitis is characterized by recurrent or persisting pain. As the exocrine pancreatic insufficiency occurs early in the progression of the disease, the endocrine function may persist intact. Imaging procedures and pancreatic function tests are used to make a diagnosis. Therapy consists of pain reduction, which might require endoscopic or surgical intervention. Treatment of exocrine and endocrine pancreatic insufficiency is based on diet and substitution of pancreatic enzymes, minerals and vitamins, as well as insulin.

Microsphere Bead Arrays and Sequence Validation of 5/7/9T Genotypes for Multiplex Screening of Cystic Fibrosis Polymorphisms

The development of simple and rapid methods for the detection of the common genetic mutations associated with cystic fibrosis (CF) requires access to positive-control samples including the 5/7/9T variants of intron 8. We used PCR and a simple multiplex bead-array assay to identify 5/7/9T control samples from 29 commercially available DNA samples. Unpurified PCR products were directly hybridized to color-coded beads containing allele-specific capture probes for 5/7/9T detection. The performance of the assay was investigated using reverse-complement oligonucleotides, individual PCR products, and multiplex PCR products for 5/7/9T detection within a complex CFTR screening assay. Samples were genotyped by grouping the relative signal intensities from each capture probe. Of 29 commercially available DNA samples analyzed, 2 5T/7T, 2 5T/9T, 9 7T/9T, 11 7T/7T, and 5 9T/9T genotypes were identified. The genotype within each sample group was confirmed by DNA sequencing. The assay was compatible with the analysis of 10 to 1000 ng of genomic DNA isolated from whole blood and allowed for the separate identification of primary CFTR mutations from reflex variants. The correct identification of positive controls demonstrated the utility of a simple bead-array assay and provided accessible samples for assay optimization and for routine quality control in the clinical laboratory.

Exocrine and endocrine pancreatic insufficiency after pancreatic surgery

The pancreas is the central organ for digestion and for control of glucose homeostasis. Indications for major pancreatic surgery are complications of chronic and acute pancreatitis and pancreatic malignancies. The postoperative pancreatic function is determined by type of resection, resection of adjacent organs, the underlying disease and preoperative pancreatic function. Standard treatment following major pancreatic surgery includes the administration of pancreatic enzyme preparations and inhibition of acid secretion by proton pump inhibitors. Postoperatively most patients also develop diabetes mellitus, which requires insulin substitution. Hypoglycemia is the most difficult clinical problem to handle following total pancreatectomy.

Exocrine and endocrine pancreatic insufficiency after pancreatic surgery

The pancreas is the central organ for digestion and for control of glucose homeostasis. Indications for major pancreatic surgery are complications of chronic and acute pancreatitis and pancreatic malignancies. The postoperative pancreatic function is determined by type of resection, resection of adjacent organs, the underlying disease and preoperative pancreatic function. Standard treatment following major pancreatic surgery includes the administration of pancreatic enzyme preparations and inhibition of acid secretion by proton pump inhibitors. Postoperatively most patients also develop diabetes mellitus, which requires insulin substitution. Hypoglycemia is the most difficult clinical problem to handle following total pancreatectomy.

Early and Long-Term Results of Surgery for Severe Necrotising Pancreatitis

Background: Necrotising pancreatitis is a challenging problem for the surgeon, as it is associated with considerable morbidity and mortality. The indications, timing of surgical intervention and type of procedure continue to be debated in an effort to improve the outcome of this devastating disease process. Methods: A retrospective analysis of early and long-term results in a series of 44 consecutive patients (34 men, 10 women, median age 46.5, range 13–74 years) who underwent necrosectomy for severe necrotising pancreatitis. In 16 patients necrosectomy and primary abdominal closure with drains was performed, 14 patients had planned staged necrosectomy and delayed abdominal closure with drains, and in 14 patients necrosectomy with open laparostomy was undertaken. Results: There were 8 deaths (18%) and 14 cases (32%) of significant hospital morbidity (fistula 10, pseudocyst 2, renal failure 2). Variables which correlated with mortality were: high APACHE II score, acute renal failure requiring dialysis, and requirement for surgical intervention at an early stage (within the first two weeks). A total of 28 late complications occurred in 21 of the surviving patients (endocrine pancreatic insufficiency 10, exocrine pancreatic insufficiency 2, pseudocyst 2, chronic renal failure 2, incisional hernia 10, recurrent pancreatitis 1, and chronic pain 1). Conclusions: Low mortality can be achieved in patients with severe necrotizing pancreatitis with aggressive surgical intervention and careful perioperative management. Long-term morbidity remains high, and emphasises the need for prolonged follow-up.

Pancreatic diseases.

Pancreatic diseases.

An evidence-based approach to the surgical management of resectable pancreatic adenocarcinoma.

Randomized prospective trials have addressed various treatment approaches to pancreatic adenocarcinoma in order to improve on the dismal prognosis associated with this disease. We conducted a comprehensive review of prospective randomized clinical trials and summarized the contemporary treatment of resectable pancreatic carcinoma. A literature search strategy identified prospective randomized clinical trials for pancreatic carcinoma using standard medical subject heading terms. The articles were critically reviewed and ranked according to a standardized three-tiered system (Ia, Ib, Ic) by a panel of experts. Surgical studies have demonstrated that morbidity and mortality are similar for pylorus-preserving and classic pancreaticoduodenectomy. Extended retroperitoneal lymphadenectomy can be performed with similar mortality but increased morbidity compared with standard pancreaticoduodenectomy but does not prolong survival. Pancreaticogastrostomy and pancreaticojejunostomy appear to be comparable techniques for pancreatic duct reconstruction. Pancreatic-enteric anastomosis is associated with lower rates of pancreatic fistula and endocrine insufficiency than duct occlusion without anastomosis. Intraperitoneal drainage after pancreatic resection is unwarranted and may contribute to intraabdominal complications. Routine use of prophylactic octreotide does not lower the rate of pancreatic fistula; it should be considered for reoperative pancreatic resection or for a soft gland. Early trials found that adjuvant chemoradiation therapy prolongs survival. But in more recent studies chemoradiation after resection has failed to show a survival advantage over surgery alone. Surgical resection remains the only potentially curative therapy for adenocarcinoma of the pancreas. There is no clear indication as to a single preferable resection approach.

Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis.

Chronic pancreatitis (CP) is a progressive inflammatory process resulting in exocrine and endocrine pancreatic insufficiency in advanced stages. Cysteine-rich secretory protein (CRISP-3) has been identified as a defense-associated molecule with predominant expression in the salivary gland, pancreas and prostate. In this study, we investigated CRISP-3 expression in normal pancreatic tissues, chronic pancreatitis tissues, pancreatic cancer tissues and pancreatic cancer cell lines, as well as in other gastrointestinal organs. 15 normal pancreatic tissues, 14 chronic pancreatitis tissues and 14 pancreatic cancer tissues as well as three pancreatic cancer cell lines were analyzed. Moreover, hepatocellular carcinoma and esophageal, stomach and colon cancers were also analyzed together with the corresponding normal controls. CRISP-3 was expressed at moderate to high levels in chronic pancreatitis tissues and at moderate levels in pancreatic cancer tissues but at low levels in normal pancreatic tissues, and was absent in three pancreatic cancer cell lines. CRISP-3 expression was below the level of detection in all cancerous gastrointestinal tissues and in all normal tissues except 2 of 16 colon tissue samples. CRISP-3 mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells and in small proliferating ductal cells in CP tissues and CP-like lesions in pancreatic cancer tissues. In contrast, CRISP-3 expression was weak to absent in the cytoplasm of cancer cells as well as in acinar cells and ductal cells in pancreatic cancer tissues and normal pancreatic tissues. These results reveal that the distribution of CRISP-3 in gastrointestinal tissues is predominantly in the pancreas. High levels of CRISP-3 in acinar cells dedifferentiating into small proliferating ductal cells in CP and CP-like lesions in pancreatic cancer suggests a role of this molecule in the pathophysiology of CP.

Management of Pain in Chronic Pancreatitis

Management of Pain in Chronic Pancreatitis

A Prospective Evaluation of Pancreatic Exocrine Function in Patients with Acute Pancreatitis: Correlation with Extent of Necrosis and Pancreatic Endocrine Insufficiency

Aims: The aim of this prospective study was to assess pancreatic exocrine function in patients recovering from a first attack of acute pancreatitis, and to evaluate its relationship to severity of attack, extent of pancreatic necrosis and severity of pancreatic endocrine insufficiency. Methods: Between December 2000 and November 2001, 23 patients were prospectively evaluated. Pancreatic exocrine function was measured by the faecal elastase-1 test and insufficiency was classified as moderately impaired or severely impaired. Pancreatic necrosis was determined by contrast-enhanced CT scan, and its extent was categorised according to Balthazar’s classification. The severity of pancreatic endocrine insufficiency was categorised according to insulin dependence. Attacks were classified as mild (n = 16) or severe (n = 7) according to the Atlanta criteria. Results: Pancreatic exocrine insufficiency was significantly more frequent in patients recovering from severe attacks than mild (n = 6, 86% vs. n = 2, 13%; p = 0.002), and in those who developed pancreatic necrosis or pseudocyst than those who did not (6 of 7 patients vs. 2 of 16 patients, and 5 of 5 patients vs. 3 of 18 patients respectively; p = 0.002). The development of exocrine insufficiency correlated strongly with the extent of pancreatic necrosis (r = –0.754, p < 0.001), and the severity of pancreatic endocrine insufficiency (n = 4, r = –0.453, p = 0.03). Conclusion: Pancreatic exocrine insufficiency is a common occurrence in patients recovering from severe acute pancreatitis, and its severity correlates with the extent of pancreatic necrosis and the severity of concomitant pancreatic endocrine insufficiency.

Pancreatic disease in the elderly

Pancreatic diseases occur in patients of every age. Older individuals suffer more often from gallstone related acute pancreatitis, ischaemic and idiopathic acute pancreatitis, whereas alcohol-induced acute pancreatitis occurs only in a minority of cases. Similarly, alcohol-related chronic pancreatitis in elderly people is rare and late-onset idiopathic chronic pancreatitis is the most common form of the disease. This form of chronic pancreatitis is characterized by faster progression to endocrine and exocrine pancreatic insufficiency and less severe pain compared to the clinical picture found in younger patients.Ductal pancreatic adenocarcinomas, which are responsible for more than 90% of exocrine pancreatic tumours, are typically a disease of the elderly patient. Today pancreatic resection still offers the only hope for cure and also can be performed safely in elderly patients. Age, by itself, is not a reason for withholding surgical intervention from an individual patient. Today, denial of pancreatic resection is much more likely to be based on severe co-morbidity.

Upper GI 06

Aims: To assess pancreatic exocrine function in patients recovering from first attack of acute pancreatitis, and to evaluate its relationship to severity of attack and the development of local pancreatic complications and endocrine pancreatic insufficiency. Methods: Between December 2000 and November 2001, 23 patients were prospectively evaluated. Pancreatic exocrine function was measured by the faecal elastase-1 test. Attacks were classified as mild (n = 16) or severe (n = 7) according to the Atlanta criteria. Results: Pancreatic exocrine insufficiency was significantly more frequent in patients recovering from severe attacks than mild (n = 6, 86 per cent versus n = 2, 13 per cent; P = 0.002), and in those who developed pancreatic necrosis or pseudocyst than those who did not [6 of 7 patients versus 2 of 16 patients, and 5 of 5 patients versus 3 of 18 patients, respectively; P = 0.002]. The development of exocrine insufficiency correlated strongly (P < 0.001) with the presence of pancreatic necrosis and pseudocyst formation, but not with pancreatic endocrine insufficiency (n = 4, P = 0.07). ‘Severe’ exocrine insufficiency (n = 7) occurred in all six patients with pancreatic necrosis involving more than one-third of the gland. Exocrine insufficiency persisted during follow-up (median 3 months) in patients with severe disease. Conclusions: Pancreatic exocrine insufficiency is a common occurrence in patients recovering from severe acute pancreatitis, and its severity relates to the extent of pancreatic necrosis. A follow-up study is required to evaluate the long-term potential for recovery, and the duration of therapy with pancreatic enzyme supplementation.

Alcool et pancréas

The mechanism of the pancreatic toxicity of alcohol is not completely elucidated. Many cofactors may contribute to the pancreatic toxicity of alcohol: diet, genetic factors. Chronic pancreatitis occurs after a long lasting and heavy alcoholism. During the first years, acute manifestations occur and, then endocrine and exocrine pancreatic insufficiency.

Surgical management of recurrent pancreatitis in children with pancreas divisum.

To analyze an institutional experience with pancreatitis in childhood to clarify the frequency of pancreas divisum in that patient population, the characteristics of pancreatitis in children with pancreas divisum, and the role of surgical management in their treatment. The role of pancreas divisum in causing acute and relapsing pancreatitis and chronic, recurring abdominal pain is controversial. Although the anatomical abnormality is present from birth, most investigators have reported cases with onset of symptoms in adulthood. The reported pediatric experience with this disorder is small, and the natural history of pancreatitis in children with pancreas divisum has not been well elucidated. A retrospective chart review of all children 18 years of age and younger with a discharge diagnosis of pancreatitis identified 135 patients treated in the authors' institution from 1978 to 1998. Ten patients were found to have anatomical variants of pancreas divisum associated with recurrent or chronic pancreatitis. The medical records of these patients were reviewed for data on the presentation, diagnostic findings, imaging studies, treatment, surgical findings, and pathologic findings in these children. Chart review and telephone calls were used to assess the current state of health in nine patients available for follow-up. Pancreas divisum was identified in 7.4% of all children with pancreatitis and 19.2% of children with relapsing or chronic pancreatitis. Patients had early onset of recurrent episodic epigastric pain and vomiting, at a mean age of 6 years. Three patients had a positive family history of pancreatitis and one was proven by DNA analysis to have hereditary pancreatitis. Pancreatitis was documented by elevated amylase or lipase levels, and endoscopic retrograde cholangiopancreatography was the method of diagnosis of pancreas divisum in all patients. Eight patients had complete pancreas divisum and two had incomplete variants. Eight patients underwent surgery to improve ductal drainage. Seven underwent transduodenal sphincteroplasty of the accessory papilla, along with sphincteroplasty of the major papilla in two (plus septoplasty in one). Three patients underwent longitudinal pancreaticojejunostomy, as a primary procedure in one patient with midductal stenosis and in two because of recurring pancreatitis after sphincteroplasty. The surgical findings and histologic examination of five patients undergoing distal pancreatectomy revealed striking changes of advanced chronic pancreatitis. Patients responding to sphincteroplasty alone showed less severe histologic changes. Overall, three of seven patients had excellent results, three were improved, and one had continued disabling attacks of pancreatitis. The mean duration of follow-up was 7.3 years, and there were no deaths. No patients had endocrine or exocrine pancreatic insufficiency, and none required chronic analgesics. Pancreas divisum is an important cause of recurrent pancreatitis in childhood and should be sought aggressively in children with more than one episode of pancreatitis or pancreatitis with a history of chronic recurrent abdominal pain. Surgical intervention is directed toward relief of ductal obstruction and may involve accessory duct sphincteroplasty alone or in combination with major sphincteroplasty and septoplasty. Patients with more distal ductal obstruction or ductal ectasia may benefit from pancreaticojejunostomy.

Quality of life and outcomes after pancreaticoduodenectomy.

To assess the quality of life (QOL) and functional outcome of patients after pancreaticoduodenectomy. Pancreaticoduodenectomy is gaining acceptance and is being performed in increasing numbers for various malignant and benign diseases of the pancreas and periampullary region. There is a general impression that pancreaticoduodenectomy can severely impair QOL and alter normal activities. Only a few small studies have evaluated QOL after pancreaticoduodenectomy. A standard QOL questionnaire was sent to 323 patients surviving pancreaticoduodenectomy who had undergone surgery at The Johns Hopkins Hospital between 1981 and 1997. Thirty items on a visual analog scale were categorized into three domains: physical (15 items), psychological (10 items), and social (5 items). Scores are reported as a percentile, with 100% being the highest possible score. The same QOL questionnaire was also sent to laparoscopic cholecystectomy patients and healthy controls. A separate component of the questionnaire asked about functional outcomes and disabilities. Overall QOL scores for the 192 responding pancreaticoduodenectomy patients in the three domains (physical, psychological, social) were 78%, 79%, and 81%, respectively. These QOL scores were comparable to those of the 37 laparoscopic cholecystectomy patients and the 31 healthy controls. The pancreaticoduodenectomy patients were subgrouped into chronic pancreatitis, other benign disease, pancreatic adenocarcinoma, and other cancers. Patients who underwent resection for chronic pancreatitis and pancreatic adenocarcinoma had significantly lower QOL scores in the physical and psychological domains compared with the laparoscopic cholecystectomy patients and the healthy controls. Common problems after pancreaticoduodenectomy were weight loss, abdominal pain, fatigue, foul stools, and diabetes. This is the largest single-institution experience assessing QOL after pancreaticoduodenectomy. These data demonstrate that as a group, patients who survive pancreaticoduodenectomy have near-normal QOL scores. Many patients report weight loss and symptoms consistent with pancreatic exocrine and endocrine insufficiency. Most patients have QOL scores comparable to those of control patients and can function independently in daily activities.

Early and long-term results after necrosectomy for necrotizing pancreatitis

Abstract Background Necrotizing pancreatitis is a difficult clinical problem associated with significant mortality and morbidity rates. Indications for surgical intervention, and the timing and type of intervention, remain controversial issues. A 10-year experience in the management of this condition in a tertiary referral centre is reviewed; treatment policies and early and long-term results are reported. Methods Between 1987 and 1997, 39 consecutive patients (32 men, seven women), with a mean age of 47 (range 13–74) years, underwent necrosectomy for severe necrotizing pancreatitis. Diagnosis was confirmed by contrast-enhanced computed tomography. Twenty-nine patients were referred from other hospitals in Northern Ireland. The aetiology included gallstones (15), alcohol (ten), idiopathic (seven), surgery (two), endoscopic retrograde cholangiopancreatography (two), blunt trauma (one), hyperlipidaemia (one) and pancreas divisum (one). Mean Acute Physiology And Chronic Health Evaluation (APACHE) II score on admission or arrival was 2 (range 5–21). Indications for surgical intervention were clinical deterioration with development of multiple organ failure, despite maximal medical support in the intensive care unit (ICU), or positive fine-needle aspiration for micro-organisms or radiographic evidence of infected necrosis (i.e. presence of gas within peripancreatic collection). The mean interval from onset to intervention was 23 (range 9–47) days. In 13 patients a conventional approach (necrosectomy with primary closure over drains) was used, 14 patients underwent planned staged necrosectomy with delayed closure over drains and in 12 patients necrosectomy with open laparostomy was undertaken. Results There were five deaths and 14 patients experienced significant hospital morbidity (fistula, ten; pseudocyst, two; renal failure, two). Variables which correlated with mortality rate were higher APACHE II score, acute renal failure requiring dialysis and early intervention. There was no difference in either mortality or morbidity rate between infected and sterile necrosis, or between the three surgical techniques. Long-term morbidity occurred in 20 surviving patients (incisional hernia, ten; endocrine pancreatic insufficiency, nine; exocrine pancreatic insufficiency, two; pseudocyst, two; chronic renal failure, two; recurrent pancreatitis, one; and chronic pain, one). Conclusion A low mortality rate can be achieved in patients with severe necrotizing pancreatitis with aggressive surgical intervention. Early maximal medical treatment and ICU support is essential before intervention, which should preferably be avoided early in the course of the disease and should be based on well defined criteria. The long-term morbidity rate remains high, although not always severe. This emphasizes the need for close follow-up.

Chronic pancreatitis: functional testing.

This article reviews the evolution of functional testing of the pancreas in Japan for the diagnosis and treatment of chronic pancreatitis (CP), contrasting the pre- with the postsecretin test (S test) era. In the pre-S test era, the diagnosis was based on symptoms, clinical findings, fasting serum diastase levels, and the vagostigmin- and ether-stimulation test unless morphologic evidence was available. The S test and CCK-pancreozymin (PZ) test (PS test) were introduced into Japan around 1963 and have been used as the gold standard of the exocrine pancreatic-function test. Through a series of attempts at standardization in 1971, 1985, and 1987, the method was standardized to collect duodenal juice for 60 min through a double- or triple-lumen tube after a bolus or during a continuous i.v. injection of secretin (100 U). The S test, however, is an invasive and cumbersome procedure. As a result, N-benzoyl-L-tyrosal-p-aminobenzoic acid (BT-PABA) testing and fecal chymotrypsin testing were introduced into Japan in the middle and late 1970s, respectively. Although simple and noninvasive, these two methods were found have lower sensitivity and specificity than the conventional S test. These two methods, therefore, are presently used more often for monitoring the course of disease and therapeutic effects. Additionally, the glucose tolerance test can be performed to detect endocrine pancreatic insufficiency.

Linkage Studies in a Large Kindred with Hereditary Pancreatitis Confirms Mapping of the Gene to a 16-cM Region on 7q

We report localization of the gene for autosomal dominant hereditary pancreatitis (HP) to a small region of the long arm of chromosome 7 in a large four-generation kindred. Affected family members may first become symptomatic in childhood or even infancy with progression to pancreatic calcification, pseudocyst formation, endocrine and exocrine insufficiency, and even pancreatic cancer in some cases. However, obligate gene carriers may remain virtually symptom free throughout life. HP is the most common cause of childhood pancreatitis in the United States. Gene mapping with microsatellite markers demonstrates that HP is tightly linked to the marker D7S684 (Zmax= 7.0, θ = 0.0). Three obligate recombinants place the HP locus within a 16-cM interval between markers D7S495 and D7S688. This confirms the localization of HP to 7q reported in a separate French kindred (2).

CHRONIC FIBROSING PANCREATITIS IN CHILDHOOD: Report of a Case and Literature Review

Chronic fibrosing pancreatitis in childhood is an uncommon condition of unknown etiology with a variety of clinical presentations, histopathologic features, and outcomes. The diagnosis is one of exclusion (of hereditary or secondary pancreatitis), which should include histological assessment. The histological features of this condition have been described, to our knowledge, in nine published cases. We report a case in a 13-year-old male, who presented, with obstructive jaundice and subsequently had evidence of endocrine and exocrine pancreatic insufficiency, despite a surgical decompression of the pancreatic-biliary duct system.

Chronic Fibrosing Pancreatitis in Childhood: Report of a Case and Literature Review

Chronic fibrosing pancreatitis in childhood is an uncommon condition of unknown etiology with a variety of clinical presentations, histopathologic features, and outcomes. The diagnosis is one of exclusion (of hereditary or secondary pancreatitis), which should include histological assessment. The histological features of this condition have been described, to our knowledge, in nine published cases. We report a case in a 13-year-old male, who presented with obstructive jaundice and subsequently had evidence of endocrine and exocrine pancreatic insufficiency, despite a surgical decompression of the pancreatic-biliary duct system.