Chronic pancreatitis

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Chronic pancreatitis
Other namesPancreatitis – chronic – discharge [1]
Chronische Pankreatitis mit Verkalkungen - CT axial.jpg
Axial CT showing multiple calcifications in the pancreas in a patient with chronic pancreatitis
Specialty Gastroenterology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Nausea and vomiting [1] [2]
Complications Exocrine pancreatic insufficiency, Endocrine pancreatic insufficiency (Type 3c diabetes), pancreatic pseudocyst, [3] pancreatic cancer, [3] vitamin deficiency (fat-soluble vitamins) [3]
CausesAlcohol(ism), Immune disorder [4]
Diagnostic method Serum trypsinogen, Fecal fat test [1]
TreatmentPain medicines, avoiding alcohol(and smoking), among other possible management efforts [1]
Frequency50 per 100,000 persons (prevalence)

Chronic pancreatitis is a long-standing inflammation of the pancreas that alters the organ's normal structure and functions. [1] It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption. It is a disease process characterized by irreversible damage to the pancreas as distinct from reversible changes in acute pancreatitis. [5] [6] Tobacco smoke and alcohol misuse are two of the most frequently implicated causes, and the two risk factors are thought to have a synergistic effect with regards to the development of chronic pancreatitis. [3] Chronic pancreatitis is a risk factor for the development of pancreatic cancer. [3]

Contents

Signs and symptoms

There have been three pain symptom profiles described in those with chronic pancreatitis. Type A involves intermittent, severe symptom flare-ups with or without objective pancreatitis separated by pain-free periods. The type A symptom profile is usually more common early in the course of chronic pancreatitis. [3] Type B chronic pancreatitis involves chronic pain accompanied by intermittent severe attacks. [3] And, the type C symptom profile of chronic pancreatitis involves chronic, long-term, severe pain without interspersed acute flare-ups or symptom exacerbations. [3]

Causes

Among the causes of chronic pancreatitis are the following: [4]

Chronic alcohol misuse and smoking are well-established risk factors for the development of chronic pancreatitis, and the two are thought to have a synergistic effect with regard to disease development. [3] [9] Alcohol use is present in 42–77% of those who have chronic pancreatitis, and tobacco use is present in greater than 60% of those with chronic pancreatitis. [3] Genetic mutations are thought to be responsible for 10% of cases. This includes mutations of the cystic fibrosis transmembrane conductance regulator (CFTR), serine protease inhibitor Kazal-type 1 (SPINK1), and the chymotrypsin C (CTRC) proteins. [3] 28% of cases of chronic pancreatitis are idiopathic (of an unknown cause). [3] In a small group of patients, chronic pancreatitis has been shown to be hereditary. Hereditary pancreatitis, which causes 1% of chronic pancreatitis, involves a mutation of the Trypsin 1 gene that is inherited in an autosomal dominant fashion. [3] Almost all patients with cystic fibrosis have established chronic pancreatitis, usually from birth. Cystic fibrosis gene mutations have also been identified in patients with chronic pancreatitis but in whom there were no other manifestations of cystic fibrosis. Obstruction of the pancreatic duct because of either a benign or malignant process may result in chronic pancreatitis. [10]

Pathophysiology

PRSS1 Protein PRSS1 PDB 1trn.png
PRSS1

The mechanism of chronic pancreatitis viewed from a genetic standpoint indicates early onset of severe epigastric pain beginning in childhood. It is an autosomal dominant disease; chronic pancreatitis disease is identified in the cationic trypsinogen gene PRSS1, and mutation, R122H. R122H is the most common mutation for hereditary chronic pancreatitis with replacement of arginine with histidine at amino acid position 122 of the trypsinogen protein. There are, of course, other mechanisms – alcohol, malnutrition, smoking – each exhibiting its own effect on the pancreas. [5]

Diagnosis

The diagnosis of chronic pancreatitis is made based on the history and characteristics of symptoms combined with findings on radiologic imaging. [3] Serum amylase and lipase may be moderately elevated in cases of chronic pancreatitis.

Symptoms of diarrhea, with oily, bulky, and foul-smelling stools indicated steatorrhea or fat malabsorption due to exocrine pancreatic insufficiency. Exocrine pancreatic insufficiency can be confirmed by also checking a fecal elastase level, with low levels specifying exocrine pancreatic insufficiency. [3] A quantitative fecal fat test can also be done to quantify the fat levels in the stool and confirm the presence of exocrine pancreatic insufficiency. [3]

When chronic pancreatitis is caused by genetic factors, elevations in ESR, IgG4, rheumatoid factor, ANA and anti-smooth muscle antibody may be detected. [11]

Computed tomography, magnetic resonance cholangiopancreatography (MRCP), and endoscopic ultrasound (EUS) all have similar sensitivity and specificity for diagnosing chronic pancreatitis. [3] MRCP is particularly utilized for its sensitivity in imaging the pancreatic ducts and bile ducts for associated changes such as stones or strictures. [3] [12] A biopsy of the pancreas is not required for the diagnosis. [3] On imaging, pancreatic and bile duct dilatation, atrophy of the pancreas, multiple calcifications of the pancreas, and enlargement of pancreatic glands can be found. [12]

On MRI scan, there is a low T1 signal due to inflammation, fibrosis, focal lesions, and calcifications. In those who are given a contrast agent, there would be a higher T1 signal with late gadolinium enhancement due to compression from the fibrotic areas. The overall thickness of the pancreas will be reduced. [12]

Treatment

The different treatment options for the management of chronic pancreatitis are medical measures, therapeutic endoscopy, and surgery. [13] Treatment is directed, when possible, to the underlying cause, and to relieve pain and malabsorption. Insulin dependent diabetes mellitus may occur and need long-term insulin therapy. [14] The abdominal pain can be very severe and require high doses of analgesics, sometimes including opiates. Medications such as pregabalin, gabapentin, tricyclic antidepressants and serotonin–norepinephrine reuptake inhibitors (SNRIs) are commonly used to treat pain in chronic pancreatitis. [3] Alcohol cessation is important to manage pain and slow the calcific process, possibly reducing the future risk of flare-ups. [13] Antioxidants may help, but it is unclear if the benefits are meaningful. [15]

Endoscopic treatments, including removal of stones in the pancreatic duct, and dilation of strictures may be done. [3] Extracorporeal shockwave lithotripsy can also be done, in which external acoustic waves are administered to break the stones. This may be combined with endoscopic retrograde cholangiopancreatography to collect larger stones. [3]

Behavioral treatments such as cognitive behavioral therapy including resilience training, stress management, chronic pain rehabilitation programs and addiction treatment may also be used as adjunct treatments. [3]

Pancreatic enzymes

Pancreatic enzyme replacement is often effective in treating the malabsorption and steatorrhea associated with chronic pancreatitis. Treatment of CP consists of the administration of a solution of pancreatic enzymes with meals. Some patients do have pain reduction with enzyme replacement, and since they are relatively safe, giving enzyme replacement to a chronic pancreatitis patient is an acceptable step in treatment for most patients. Treatment may be more likely to be successful in those without the involvement of large ducts and those with idiopathic pancreatitis. [16]

Surgery

Surgery to treat chronic pancreatitis tends to be divided into two areas – resectional and drainage procedures. Among the reasons to opt for surgery is if there is a pseudocyst, fistula, ascites, or a fixed obstruction. [4] The Puestow procedure (anastomosis of the pancreatic duct to the jejunum to allow drainage of the obstructed duct), pancreaticoduodenectomy (partial pancreatic resection), or total pancreatectomy with or without autologous islet cell transplantation (removal of the whole pancreas, which is usually reserved for cases refractory to other surgical and medical interventions) may be used for treatment of chronic pancreatitis. [17] [3]

Epidemiology

The annual incidence of chronic pancreatitis is 5 to 12 per 100,000 persons. [18] The prevalence of chronic pancreatitis in the U.S. is 90-100 per 100,000 adults. [19] [20] Chronic pancreatitis affects people in countries around the world. [20]

See also

Related Research Articles

<span class="mw-page-title-main">Pancreas</span> Organ of the digestive system and endocrine system of vertebrates

The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e., it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins and fats in food entering the duodenum from the stomach.

<span class="mw-page-title-main">Pancreatitis</span> Inflammation of the pancreas

Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancreatitis.

<span class="mw-page-title-main">Pancreatic cancer</span> Type of endocrine gland cancer

Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of pancreatic cancer are known.

<span class="mw-page-title-main">Malabsorption</span> Abnormality in absorption of food nutrients across the gastrointestinal tract

Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.

Steatorrhea is the presence of excess fat in feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the fecal fat level.

<span class="mw-page-title-main">Acute pancreatitis</span> Medical condition

Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes, in order of frequency, include: a gallstone impacted in the common bile duct beyond the point where the pancreatic duct joins it; heavy alcohol use; systemic disease; trauma; and, in children, mumps. Acute pancreatitis may be a single event; it may be recurrent; or it may progress to chronic pancreatitis and/or pancreatic failure.

<span class="mw-page-title-main">Gastrointestinal disease</span> Illnesses of the digestive system

Gastrointestinal diseases refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum; and the accessory organs of digestion, the liver, gallbladder, and pancreas.

Trypsinogen is the precursor form of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by enteropeptidase, which is found in the intestinal mucosa. Once activated, the trypsin can cleave more trypsinogen into trypsin, a process called autoactivation. Trypsin cleaves the peptide bond on the carboxyl side of basic amino acids such as arginine and lysine.

<span class="mw-page-title-main">Pancreatic enzymes (medication)</span> Amylase, lipase, and protease mixture

Pancreatic enzymes, also known as pancreases or pancrelipase and pancreatin, are commercial mixtures of amylase, lipase, protease and lactase. They are used to treat malabsorption syndrome due to certain pancreatic problems. These pancreatic problems may be due to cystic fibrosis, surgical removal of the pancreas, long term pancreatitis, pancreatic cancer, or MODY 5, among others. The preparation is taken by mouth.

<span class="mw-page-title-main">Pancreatectomy</span> Surgical removal of the pancreas

In medicine, a pancreatectomy is the surgical removal of all or part of the pancreas. Several types of pancreatectomy exist, including pancreaticoduodenectomy, distal pancreatectomy, segmental pancreatectomy, and total pancreatectomy. In total pancreatectomy, the gallbladder, distal stomach, a portion of the small intestine, associated lymph nodes and in certain cases the spleen are removed in addition to the entire pancreas. In recent years, the TP-IAT has also gained respectable traction within the medical community. These procedures are used in the management of several conditions involving the pancreas, such as benign pancreatic tumors, pancreatic cancer, and pancreatitis.

<span class="mw-page-title-main">Pancreas divisum</span> Congenital disorder of digestive system

Pancreas divisum is a congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts. Most individuals with pancreas divisum remain without symptoms or complications. A minority of people with pancreatic divisum may develop episodes of abdominal pain, nausea or vomiting due to acute or chronic pancreatitis. The presence of pancreas divisum is usually identified with cross sectional diagnostic imaging, such as endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP). In some cases, it may be detected intraoperatively. If no symptoms or complications are present, then treatment is not necessary. However, if there is recurrent pancreatitis, then a sphincterotomy of the minor papilla may be indicated.

<span class="mw-page-title-main">Exocrine pancreatic insufficiency</span> Inability to properly digest food due to a lack of digestive enzymes from the pancreas

Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas. EPI can occur in humans and is prevalent in many conditions such as cystic fibrosis, Shwachman–Diamond syndrome, different types of pancreatitis, multiple types of diabetes mellitus, advanced renal disease, older adults, celiac disease, IBS-D, IBD, HIV, alcohol-related liver disease, Sjogren syndrome, tobacco use, and use of somatostatin analogues.

Pancreatic diseases are diseases that affect the pancreas, an organ in most vertebrates and in humans and other mammals located in the abdomen. The pancreas plays a role in the digestive and endocrine system, producing enzymes which aid the digestion process and the hormone insulin, which regulates blood sugar levels. The most common pancreatic disease is pancreatitis, an inflammation of the pancreas which could come in acute or chronic form. Other pancreatic diseases include diabetes mellitus, exocrine pancreatic insufficiency, cystic fibrosis, pseudocysts, cysts, congenital malformations, tumors including pancreatic cancer, and hemosuccus pancreaticus.

<span class="mw-page-title-main">Hereditary pancreatitis</span> Medical condition

Hereditary pancreatitis (HP) is an inflammation of the pancreas due to genetic causes. It was first described in 1952 by Comfort and Steinberg but it was not until 1996 that Whitcomb et al isolated the first responsible mutation in the trypsinogen gene (PRSS1) on the long arm of chromosome seven (7q35).

<span class="mw-page-title-main">Autoimmune pancreatitis</span> Type of chronic pancreatitis

Autoimmune Pancreatitis (AIP) is an increasingly recognized type of chronic pancreatitis that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone. Although autoimmune pancreatitis is quite rare, it constitutes an important clinical problem for both patients and their clinicians: the disease commonly presents itself as a tumorous mass which is diagnostically indistinguishable from pancreatic cancer, a disease that is much more common in addition to being very dangerous. Hence, some patients undergo pancreatic surgery, which is associated to substantial mortality and morbidity, out of the fear by patients and clinicians to undertreat a malignancy. However, surgery is not a good treatment for this condition as AIP responds well to immunosuppressive treatment. There are two categories of AIP: Type 1 and Type 2, each with distinct clinical profiles.

<span class="mw-page-title-main">Pancreatitis (veterinary)</span> Medical condition

Pancreatitis is a common condition in cats and dogs. Pancreatitis is inflammation of the pancreas that can occur in two very different forms. Acute pancreatitis is sudden, while chronic pancreatitis is characterized by recurring or persistent form of pancreatic inflammation. Cases of both can be considered mild or severe. It is currently undecided whether chronic pancreatitis is a distinct disease or a form of acute pancreatitis. Other forms such as auto-immune and hereditary pancreatitis are presumed to occur but there existence has not been proven.

<span class="mw-page-title-main">Ductal cells</span>

Ductal cells refer to the epithelial cell lining of the pancreatic duct that deliver enzymes from the acinar cells to the duodenum. They have the essential function of producing bicarbonate-rich (HCO3-) secretion to neutralize stomach acidity. The hormone secretin stimulates ductal cells and is responsible for maintaining the duodenal pH and preventing duodenal injury from acidic chyme. Ductal cells mix their production with acinar cells to make up the pancreatic juice.

Cystic fibrosis–related diabetes (CFRD) is diabetes specifically caused by cystic fibrosis, a genetic condition. Cystic fibrosis related diabetes mellitus (CFRD) develops with age, and the median age at diagnosis is 21 years. It is an example of type 3c diabetes – diabetes that is caused by damage to the pancreas from another disease or condition.

Type 3c diabetes is diabetes that comes secondary to pancreatic diseases, involving the exocrine and digestive functions of the pancreas. It also occurs following surgical removal of the pancreas.

<span class="mw-page-title-main">Dorsal pancreatic agenesis</span> Medical condition

Dorsal pancreatic agenesis is a congenital anomaly characterised by the absence of the duct of Santorini, tail and body of the pancreas. It is regarded as asymptomatic and the most common clinical manifestation is non-specific abdominal pain. While the cause is unclear, its mechanism is thought to be impaired dorsal buds or mutation of genes that regulate organogenesis during embryogenesis.

References

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  2. 1 2 3 4 "What is chronic pancreatitis?". The University of Chicago Medicine. Archived from the original on 2017-05-09. Retrieved 2017-02-07. diabetes; upper abdominal pain that is frequently chronic and debilitating. Pain is the most common symptom of chronic pancreatitis. The pain may increase after drinking or eating and lessens when fasting or sitting and leaning forward. However, some people with chronic pancreatitis report little to no pain; from google (chronic pancreatitis smelly poop) result 1
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Vege SS, Chari ST (March 2022). "Chronic Pancreatitis". The New England Journal of Medicine. 386 (9): 869–878. doi:10.1056/NEJMcp1809396. PMID   35235728. S2CID   247221549.
  4. 1 2 3 Chronic Pancreatitis at eMedicine
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  6. ↑ Oiseth S, Jones L, Maza E, eds. (11 November 2020). "Chronic Pancreatitis". The Lecturio Medical Concept Library. Archived from the original on 9 July 2021. Retrieved 9 July 2021.
  7. ↑ "Type 3C diabetes (secondary diabetes) Pancreatic Cancer Symptoms". Pancreatic Cancer Action. Archived from the original on 2023-10-28. Retrieved 2023-10-28.
  8. ↑ Ramai D, Facciorusso A, Maida M, Capurso G, Chandan S, Spadaccini M, et al. (August 2023). "Prevalence of Osteopathy in Chronic Pancreatitis: A Systematic Review and Meta-Analysis". Clinical and Translational Gastroenterology. 14 (8): e00623. doi:10.14309/ctg.0000000000000623. PMC   10461948 . PMID   37477620.
  9. ↑ Ye X, Lu G, Huai J, Ding J (2015-04-16). "Impact of smoking on the risk of pancreatitis: a systematic review and meta-analysis". PLOS ONE. 10 (4): e0124075. Bibcode:2015PLoSO..1024075Y. doi: 10.1371/journal.pone.0124075 . PMC   4399880 . PMID   25879541.
  10. ↑ "Chronic pancreatitis – Causes". NHS Choices. National Health Service UK. Archived from the original on 2015-12-08. Retrieved 2015-11-29.
  11. ↑ Tolba R, Shroll J, Kanu A, Rizk MK (2015). "The Epidemiology of Chronic Abdominal Pain". Chronic Abdominal Pain. pp. 13–24. doi:10.1007/978-1-4939-1992-5_2. ISBN   978-1-4939-1991-8.
  12. 1 2 3 Kamat R, Gupta P, Rana S (April 2019). "Imaging in chronic pancreatitis: State of the art review". The Indian Journal of Radiology & Imaging. 29 (2): 201–210. doi: 10.4103/ijri.IJRI_484_18 . PMC   6639861 . PMID   31367093.
  13. 1 2 "American Gastroenterological Association Medical Position Statement: treatment of pain in chronic pancreatitis". Gastroenterology. 115 (3): 763–764. September 1998. doi:10.1016/s0016-5085(98)70156-8. PMID   9721174.
  14. ↑ Ewald N, Hardt PD (November 2013). "Diagnosis and treatment of diabetes mellitus in chronic pancreatitis". World Journal of Gastroenterology. 19 (42): 7276–7281. doi: 10.3748/wjg.v19.i42.7276 . PMC   3831209 . PMID   24259958.
  15. ↑ Ahmed Ali U, Jens S, Busch OR, Keus F, van Goor H, Gooszen HG, et al. (August 2014). "Antioxidants for pain in chronic pancreatitis". The Cochrane Database of Systematic Reviews. 2014 (8): CD008945. doi:10.1002/14651858.CD008945.pub2. PMC   10114264 . PMID   25144441.
  16. ↑ Sikkens EC, Cahen DL, Kuipers EJ, Bruno MJ (June 2010). "Pancreatic enzyme replacement therapy in chronic pancreatitis". Best Practice & Research. Clinical Gastroenterology. 24 (3): 337–347. doi:10.1016/j.bpg.2010.03.006. PMID   20510833.
  17. ↑ Nikolaidis P, Meranda J, Miller FH, Summers AL, Gabriel H, Talamonti M, et al. (2015). "Pancreatic Trauma and Surgery". Textbook of Gastrointestinal Radiology, 2-Volume Set. Elsevier. pp. 1856–1871. doi:10.1016/b978-1-4557-5117-4.00099-4. ISBN   978-1-4557-5117-4.
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  19. ↑ Sellers ZM, MacIsaac D, Yu H, Dehghan M, Zhang KY, Bensen R, et al. (August 2018). "Nationwide Trends in Acute and Chronic Pancreatitis Among Privately Insured Children and Non-Elderly Adults in the United States, 2007-2014". Gastroenterology. 155 (2): 469–478.e1. doi:10.1053/j.gastro.2018.04.013. PMC   6067969 . PMID   29660323.
  20. 1 2 Machicado JD, Dudekula A, Tang G, Xu H, Wu BU, Forsmark CE, et al. (September 2019). "Period prevalence of chronic pancreatitis diagnosis from 2001-2013 in the commercially insured population of the United States". Pancreatology. 19 (6): 813–818. doi:10.1016/j.pan.2019.07.003. PMC   6756969 . PMID   31350077.

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