Chronic Pancreatitis

The following sections are included:

• Foreword

• Preface

• Contributors

• Contents

The exocrine pancreas consists of ductules and ducts that conduct the secretion product of acinar cells to the duodenum. The ducts and aggregates of acinar cells branch and rejoin, producing a complicated arrangement. With the development of chronic pancreatitis, the acinar cells lose their zymogen granules and become shorter, causing the lumen to enlarge. The result is that the acini take on the appearance of ductules. Together with the ductules that are retained, they form tubular complexes. This regressive process frequently is erroneously described as ductular proliferation. Inflammatory cells that attack during chronic pancreatitis can damage pancreatic nerves, possibly leading to pain. Inflammatory cells also accumulate along pancreatic ducts, where epithelium is lost, altering an important barrier.

The following sections are included:

• Introduction

• Etiology

• Pathogenesis

• References

Changes in gene expression are required for most of the functions supported by pancreatic cells including secretion, proliferation, differentiation, and apoptosis. In recent years, transcription factor proteins which regulate gene expression by modulating mRNA synthesis have emerged as key molecular mediators of these functions in non-pancreatic cells. Overwhelming evidence also points to the importance of transcription factors in defining the developmental plan of many organisms. Furthermore, alterations in these molecules are responsible for several human diseases. Therefore, several laboratories, including ours, have initiated significant efforts to identify and characterize the function of transcription factors in exocrine pancreatic cell populations. In this article, we provide an up-dated overview of the current knowledge in this expanding field of pancreatic cell research.

Growth factors and related molecules are critical for the proper development of the pancreas, and for its maintenance in a normal morphological and functional state. Many different growth factors are involved in the regulation of proliferation and differentiation. The morphological and functional changes that occur with chronic pancreatitis are accompanied by changes in some of the growth factors. In addition to the growth factors that may be produced by components of the pancreas, additional ones may come from the inflammatory cells that invade during pancreatitis. This chapter is concerned with the cell signaling that is important in normal and pathological conditions of the pancreas. Although knowledge about the relationship between chronic pancreatitis and growth factors remains incomplete, several studies have revealed changes that occur with chronic pancreatitis. The relationship of specific growth factors to pancreatic parameters, as determined by in vitro studies and study of pathological tissue, is discussed.

Hereditary pancreatitis is a rare form of pancreatitis inherited as an autosomal dominant disorder with penetrance of about 80%. It accounts for about one or two percent of all cases of pancreatitis. The symptoms, signs, and course resemble other commoner types of pancreatitis, but the age of onset is usually before age 21 and the disease occurs in multiple family members in several generations. The recently identified defective gene is located on chromosome 7q35 and the phenotype is associated with an Arg-His substitution at residue 117 of the cationic trypsinogen gene. Patients with the hereditary form of pancreatitis have a high risk of pancreatic cancer several decades after the onset of symptoms.

The following sections are included:

• Etiology and clinical course

• Characteristics of alcoholic and idiopathic chronic pancreatitis
  • Gender distribution
  • Pain
  • Calcification
  • Exocrine and endocrine insufficiency
  • Complications, surgery, death

• Implications
  • Clinical features and courses of chronic pancreatitis
  • Hypothetical pathogenesis

• Acknowledgments

• References

Chronic pancreatitis is a multifactorial disease with different clinical presentations. A primary and a secondary obstructive form may be distinguished. The risk factors for primary chronic pancreatitis are genetic abnormalities, alcohol and smoking. Environmental agents also play a role as co-factors in secondary obstructive pancreatitis. The relationships between carcinoma and chronic pancreatitis need to be better clarified, but in clinical practice we have to consider the possibility that ductal adenocarcinoma may develop in the course of chronic pancreatitis.

The following sections are included:

• Pancreatic Ischemia

• Alterations in Pancreatic Nerves

• Conclusions

• References

The purposes of this communication are to discuss problems with current treatment of human exocrine insufficiency, the surgical preparation of exocrine insufficient dogs, how to maintain these dogs and to review our published data demonstrating use of this model to study novel treatments of exocrine insufficiency. Dogs with exocrine insufficiency due to ligation of pancreatic ducts excrete approximately 33% more fat compared to normal dogs (coefficient of fat absorption 63 vs 96%). Initially, dogs lose 7% of their preoperative body-weight. However, thereafter, weight stabilizes by feeding the dogs 2 cans of dog food in the morning and 1 can in the afternoon (580 kcal per can) and mixing 10 grams of porcine pancreatic powder with the dog food in the morning and 7 grams with the food in the afternoon. When the pancreatic insufficient dogs were not treated with enzymes, fat absorption was best with diets containing a relatively equal distribution of nutrients. However, correction of steatorrhea with powder bacterial lipase directly correlated (r=0.99; p<0.008) with greater proportions of fat calories in diets. Thus, dogs with exocrine insufficiency can be used to investigate treatment pancreatic steatorrhea and these types of studies may uncover novel and better treatments. For example, ingesting bacterial lipase (120 mg) with high fat meals might abolish human pancreatic steatorrhea. In addition dogs can be used to study pathophysiology of exocrine insufficiency, which is important because advances in the treatment may depend upon correcting abnormalities associated with treatment failure.

The following sections are included:

• Normal human pancreatic secretion
  • Interdigestive secretion
  • Postprandial pancreatic secretion

• Pancreatic secretion in chronic pancreatitis
  • Development of exocrine insufficiency
  • Importance of steatorrhea
  • Regulation of pancreatic and other gastrointestinal functions by maldigestion

• Consequences for therapy of exocrine pancreatic insufficiency

• Acknowledgments

• References

The following sections are included:

• Interdigestive gastrointestinal motility in chronic pancreatitis

• Interdigestive pancreatic secretion and its coordination with the interdigestive gastrointestinal motility

• Postprandial gastrointestinal motility in chronic pancreatitis

• References

Chronic pancreatitis may be diagnosed by clinical presentation and non invasive imaging tests (plain Xrays, US, Ct-scan). Sometimes invasive imaging (ERCP, EUS)or pancreatic function tests are needed. Pancreatic function tests are usually needed when mild or moderate pancreatic insufficiency is present. In fact when severe pancreatic insufficiency is present non invasive imaging are diagnostic. In patients in which mild - moderate pancreatic insufficiency is suspected the “gold standard” for diagnosis are direct invasive pancreatic function tests. These tests require oroduodenal intubation to collect samples for measuring enzymes and/or bicarbonate after exogenous stimuli (secretin, CCK or cerulein, or both) are given. A few false negatives are reported in calcific pancreatitis and a few false positives are reported in mucosal bowel disease. In the rare patients in which a severe pancreatic insufficiency is suspected and non invasive imaging test are not diagnostic several non invasive (“tubeless”) pancreatic function tests may be useful. Many papers have been published on these “tubeless” tests and the most popular are: Faecal chymotrypsin, NBT-PABA test, Pancreolauryl test, Trypsin-like Immunoreactivity test, Dual-labeled Schilling test. Several comparative studies have been carried-out but there is no agreement in which is the best one. Two other tests have been recently proposed. The Amino Acid Consumption Test and Secretin induced plasma bicarbonato decrease: the first has been demonstrated inaccurate, the second has to be confirmed in other studies.

The following sections are included:

• Interpretation of pancreatic ductal changes in chronic pancreatitis

• Diagnostic accuracy and limitations of the ERCP in the diagnosis of chronic pancreatitis

• Clinical relevance and indications of ERCP for chronic pancreatitis

• References

Endoscopic ultrasonography is a new diagnostic technique used for imaging the gastrointestinal tract. Comparated to conventional transabdominal ultrasonography, EUS provides superior resolution for certain target organs and structures, and the procedure is not compromised by intervening gases within the gastrointestinal tract. Until 4-5 years ago EUS was less accurate than ERCP and too much expensive for being used in diagnosis of CP, but recent reports seem to open new prospective for EUS in diagnosis of CP. EUS may accurately diagnose advanced CP by the demonstration of dilatation of main pancreatic ducts, presence of stones or small cysts, parenchimal echogenicity. On the other hand diagnosis of advanced CP may be easily and cheaper done with abdominal US and/or CT scan. A few recent preliminary reports suggest a role for EUS in diagnosing early CP. Prospective larger studies are necessary to confirm there results before to submit to EUS all patients with a clinical suspicion of chronic pancreatitis and negative uninvasive imaging of pancreas. EUS cannot differentiate pancreatic cancer from pseudotumor in CP and in these patients endosonography guided biopsy can help in final diagnosis. Finally EUS may help interventional endoscopic treatment of complications of CP.

The following sections are included:

• INTRODUCTION

• ULTRASOUND IN THE DIAGNOSIS OF CHRONIC PANCREATITIS
  • Alteration of pancreatic size and morphology
  • Alteration of US structure
  • Calcifications
  • Dilatation of the main pancreatic duct
  • Biliary tree dilatation
  • Pancreatitis complications
  • Pseudocysts
  • Portal Hypertension

• COMPUTED TOMOGRAPHY IN THE DIAGNOSIS OF CHRONIC PANCREATITIS
  • Technique
  • Structure, size and shape of normal pancreas
  • CT criteria for the assessment of chronic pancreatitis
  • Vascular complications
  • Limitations of CT

• MAGNETIC RESONANCE IMAGING OF CHRONIC PANCREATITIS
  • Technique
  • Respiratory motion
  • Optimization of contrast resolution
  • Contrast material
  • Complementary techniques
  • Signal characteristics of CP

• BIBLIOGRAPHY

The purpose of this paper is to discuss the controversies in the treatment of painful chronic pancreatitis. Specifically, the natural history, pathophysiology, and medical and endoscopic treatments. Pain is the major cause of morbidity in patients with chronic pancreatitis. The natural history of pain is becoming better understood, but the cause of pain is uncertain. However, major hypotheses to explain pain under study are perineural inflammation and pancreatic hypertension. Strategies to treat pain are based on these hypotheses and include reducing pancreatic secretion by diet, medications and reducing pancreatic intraductal pressure with endoscopic therapies.

The following sections are included:

• NEEDLE ASPIRATION

• EXERNAL DRAINAGE
  • Follow-up
  • Complications
  • Results
  • Conclusions

• CYSTOGASTROSTOMY

• PERCUTANEOUS TREATMENT OF PSEUDOANEURYSMS COMPLICATING PANCREATITIS

• BIBLIOGRAPHY

The following sections are included:

• Introduction

• Resection or Drainage?

• Results

• References