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Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 18  |  Issue : 4  |  Page : 249-254

Management of chronic pancreatitis


Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India

Date of Submission02-Nov-2021
Date of Acceptance20-Nov-2021
Date of Web Publication23-Dec-2021

Correspondence Address:
Manu Tandan
Details - MD, DM, Senior Consultant Gastroenterologist, Asian Institute of Gastroenterology, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/am.am_125_21

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  Abstract 


Chronic pancreatitis is a chronic inflammatory disorder in which irreversible changes result in fibrosis leading to endocrine and exocrine insufficiency. Pain is often the dominant symptom and as the disease is irreversible all therapy is directed at relieving pain. Lifestyle changes include the modification of diet as well as cessation of alcohol and smoking. A stepup approach in accordance with the WHO pain ladder is ideal for relief of pain. Exocrine deficiency is seen 6–15 years after the onset of chronic pancreatitis (CP) and clinically presents as steatorrhea, weight loss, and specific nutrient deficiency. Lipase is the rate-limiting enzyme and deficiency occurs when over 90% of the pancreatic tissue is lost. Pancreatic enzyme replacement therapy is the therapy of choice and coated microspheres are the mode of delivery for enzyme replacement. The enzyme preparations are best taken between meals and an acid suppressant such as proton pump inhibitor facilitates in better absorption and delivery as these enzymes act best in a high pH. The management of sequalae of CP such as PD strictures, common bile duct strictures, pancreatic leaks, and calculi is individualized, and endotherapy offers an excellent option in properly selected cases. Endoscopic retrograde cholangiopancreatoscopy (ERCP) and subsequent stenting of the pancreatic or biliary ducts is rewarding in strictures as well as in PD leaks. Large calculi are fragmented at ESWL before clearing the duct at ERCP. Endoscopic ultrasound is a rapidly evolving technology, now being increasingly used in the management of consequences of CP. Surgery is advised for patients not amenable or responding to endotherapy.

Keywords: Chronic pancreatitis, common bile duct, endoscopic retrograde cholangiopancreaticography, endoscopic ultrasound, pancreatic duct, pancreatic enzyme replacement therapy


How to cite this article:
Tandan M, Sayyed M. Management of chronic pancreatitis. Apollo Med 2021;18:249-54

How to cite this URL:
Tandan M, Sayyed M. Management of chronic pancreatitis. Apollo Med [serial online] 2021 [cited 2022 Nov 28];18:249-54. Available from: https://apollomedicine.org/text.asp?2021/18/4/249/333598




  Introduction Top


Chronic pancreatitis (CP) is a chronic inflammatory disorder of varied and multiple etiologies leading to irreversible fibrosis and damage to the pancreas. This process can result in loss of both exocrine and endocrine function and episodic or continuous pain. When considering the management of CP, one must look into the following:

  • Management of pain
  • Exocrine insufficiency
  • Endocrine insufficiency
  • Management of complications and sequelae of CP.


In this review, we will briefly discuss all of the above, except the management of diabetes secondary to CP.


  Management of Pain Top


Pain is the presenting symptom in over 75% of patients with CP and is present in 85%–97% of cases during the course of the disease.[1] Multiple mechanisms of pain causation have been considered to explain pancreatic pain in CP. These include ductal hypertension, ischemia, inflammation, neural entrapment, oxidative stress, nociception, and central neuroplasticity.

The clinical picture can be placed in any of the following three case scenarios:[2]

  1. Ductal hypertension with stone or stricture
  2. Post endoscopic or surgical ductal decompression
  3. Minimal duct disease.


The strategy for pain management is lifestyle changes and pharmacotherapy. Lifestyle changes include avoidance of alcohol and smoking, small frequent feeds, antioxidant rich foods such as nuts and fruits as well as folate rich diet, especially in alcohol-induced CP.[3] The WHO pain ladder is the ideal strategy for the management of pain, beginning with the mildest analgesic and gradually stepping up if the need arises.[4] In our country, opioid agonist such as tramadol is preferred to pethidine. Physicians should guard against the possibility of addiction. Antioxidants especially Methionine-containing drugs have been shown to benefit a section of patients. These counter the oxidative stresses at the acinar level in patients with CP.[5],[6] Pregabagalin alone or in combination with methionine have shown pain relief in patients.[7],[8] Tricyclic antidepressants as well as SSRIs have been shown to be useful in cases where neurosensitivity as well an element of anxiety and depression are associated.[9]


  Pancreatic Exocrine Insufficiency (PEI) Top


Pancreatic exocrine insufficiency (PEI) is known to occur when there is a deficiency of the digestive enzymes, lipase, proteasesor amylase leading to malabsorption of the ingested nutrients with resultant consequences. Lipase is the rate-limiting enzyme as far as PEI is concerned for many reasons. Lipase is the earliest enzyme lost in CP. There is no non pancreatic source of Lipase unlike amylase and proteases which are produced by salivary glands and intestinal brush border, respectively. Lipase is degraded fastest in the small intestinal lumen as compared to the other two enzymes and the bicarbonate in the duodenum deactivates this enzyme further.[10] Patients with alcoholic CP develop PEI in 50%–62% of patients over 6 years, while those with idiopathic CP develop the same in the second or third decade after the onset of disease.[11],[12] In mild CP, steatorrheas is seen in 10% of patients, whereas in severe CP, this incidence rises to 34%.[13] Clinical steatorrhea is less common in our population probably because of lower fat consumption. Weight loss as well as subtle signs of fat soluble vitamin deficiency should alert the physician to a subclinical PEI. This can be confirmed by a fecal elastase test.

PERT is the standard of care to treat PEI. The enzyme preparations available in our country are mostly enteric-coated microspheres which are acid resistant and pH sensitive. The coating dissolves in the duodenum and ideally need a pH of around 6 for their action. These pancreatic enzymes are derived from porcine pancreas. The dosing of PERT for PEI in CP depends on body weight, severity of CP, and composition of food. The dosing schedule should therefore be individualized and flexible. As a general guideline, 25000–40000 units of lipase are needed with every meal and 10–25000 of lipase units with a snack. These are ideally consumed before the start or midway during a meal.[14],[15] A proton-pump inhibitor is added to raise the pH to 6 which, as mentioned earlier, is ideal for the release and activity of these enzymes.[16] Noncompliance for any reason is the most common cause of failure of therapy. Other common factors being the failure of the microspheres to reach or release in the duodenum as well as the concomitant use of calcium or magnesium-containing antacids.

The role of pancreatic enzymes in the pain management is controversial. It is thought that proteases in the enzyme preparation will act in the duodenum by suppressing cholecystokinin and reduce pancreatic stimulation. However, a Cochrane review of over 360 patients revealed no significant pain relief with the available enzymes.[17] Another meta-analysis of nine studies was evaluated for pain relief. Only four of these studies revealed benefit and these enzyme preparations were non coated.[18] Hence, the role of enzymes in the management of pain in CP is debatable. High protease content and noncoated spheres which release in the duodenum may help to relieve pain.


  Management of Complications and Sequalae of Chronic Pancreatitis Top


In this section, we will deal with the endoscopic management of complications and sequalae of CP. The role of surgery and its comparable benefits for and against role of endoscopy is beyond the scope of this article. Endoscopic retrograde cholangiopancreatoscopy (ERCP) is the instrument of choice in these procedures. Endoscopic ultrasound (EUS) is a rapidly evolving technology and is now increasing used in therapy in CP. We have published our earlier experience as a review.[19] In this review, the endoscopic management of benign common bile duct (CBD) stricture secondary to CP, pancreatic strictures, pancreatic calculi, and pancreatic ductal leaks (PDL) will be discussed. The evolving role of EUS in CP will be also discussed.

Minimal duct disease

CP can present with pain and minimal ductal changes in the absence of any obstruction.[20],[21] If these patients fail to respond to lifestyle changes and pharmacotherapy as described earlier, endoscopic pancreatic sphincterotomy can be performed for pain relief. Studies have shown relief between 64% and 98% of patients in patients of CP with minimal duct disease.[22],[23] Restenosis has been reported in 14% cases on long-term follow-up.[24] A long sphincterotomy can reduce the incidence of stenosis. In patients with pancreas divisum and minimal duct disease, relief has been reported in a significant number of patients following minor papilla sphincterotomy.[25]

An additional biliary sphincterotomy is only indicated in the following circumstances: (1) Cholangitis, (2) CBD dilated >12 mm, (3) serum alkaline phosphatase >2 times upper limit of normal, and (4) sometimes to gain access to main pancreatic duct (MPD) in case of difficult cannulation.[26]

Benign common bile duct stricture

CP is one of the most common causes of benign CBD stricture in our country. The incidence varies between 3% and 46%.[27] These can be temporary due to inflammation or irreversible following fibrosis in the head of pancreas. Most of these remain asymptomatic. Biliary stenting is the therapy of choice for symptomatic patients or those with abnormal liver function tests.[28] Single plastic stent (SPS) use has shown uniformly poor results with a success rate of around 25%.[29] The single most important factor for poor response is the presence of calcification in the head of pancreas.[30] Multiple plastic stents (MPS) or a fully covered self-expanding metal stent (FCSEMS) are the standard of care in such patients. A study revealed the success rate of using MPS as 92% as compared to 24% with a single stent.[31] Others have shown a success of 60% with MPS[32] as compared to 31% with SPS.[33] A initial pilot multicenter study of FCSEMS for benign CBD strictures due to CP showed a response rate of 80.5% following dwell time of around 11 months with migration rates of around 19%.[34] A systematic review of 25 studies and over 900 patients showed a success rate of 77% with FCSEMS as compared to 33% with MPS at a follow-up of 12 months.[35] Long-term follow-up of 5 years in patients was treated with FCSEMS revealed that 60% were symptom free.[36] FCSEMS is now used routinely in patients with CBD stricture who have severe disease, tight strictures or extensive calcification in head.


  Strictures of Main Pancreatic Duct Top


MPD strictures are a sequalae of CP and are more common in the alcoholic etiology group of patients. They can coexist with calculi. In our experience of over a thousand patients with calculi, the incidence of strictures was 18%.[37] Malignancy should always be excluded before endotherapy. Ideally, only single strictures in head, genu, or proximal body are suited for stenting [Figure 1]. Patients with multiple strictures all along the MPD (chain of lake appearance) should ideally be sent for surgery. Studies using SPS have revealed success rate of 70%–94% on follow-up ranging from 14 to 69 months.[38] A high recurrence rate of 38% has been reported on follow.[39] The concept of MPS for MPD strictures was pioneered by Costa Magna who placed MPS after dilatation. In his study, an average of three stents between 8.5 and 11.5 French diameter was used. Stricture resolution was seen in 95%, pain relief in 84% on a follow-up of over 3 years.[40] FCSEMS has been tried in resistant strictures. They have the limitation of early migration and causation of de novo strictures at the site of the inner flange. Antimigratory stents such as the “bumpy stent” have been utilized to minimize migration.[41] However, validation for regular usage of FCSEMS is still awaited. The European Society of Gastrointestinal Endoscopy (ESGE) clinical guidelines specifically mention that FCSEMS should only be placed in the setting of clinical trials.[28]
Figure 1: Pancreatogram showing dilated pancreatic duct in the body and tail with stricture in head. Subsequent image depicting pancreatic stent placement

Click here to view



  Pancreatic Calculi Top


Pancreatic calculi are the consequence of CP and are seen in 50% of cases.[42] The calculi seen in the idiopathic nonalcoholic variety of CP, common in India, are dense and large.[43],[44],[45] These calculi are adherent to the mucosa of MPD and difficult to extract endoscopically.[43] Small calculi can be extracted by the standard procedure of pancreatic sphincterotomy and balloon sweep.[43] The use of mechanical lithotripter and Dormia baskets is technically challenging because of thin diameter and tortuosity of MPD. Pancreatoscopy and laser lithotripsy are ideally reserved for patients who do not respond to an adequately performed Extra Corporeal Shockwave lithotripsy (ESWL)[43] [Figure 2]. ESGE guidelines of 2012 and 2018 clearly state that for calculi larger than 5 mm in the MPD should be first subjected to ESWL followed by ERCP.[28],[46]
Figure 2: Fluoroscopy image showing radio-opaque calculi in the pancreatic head region. Subsequent ESWL and pancreatogram revealed well-pulverized pancreatic duct calculi

Click here to view


Proper selection of cases is a must for success at ESWL. ESWL is ideal for large calculi in head and proximal body with pain as the dominant symptom. Patients with multiple or extensive calculi in the head body and tail should be subjected to surgery.[37] Success rates have been high and in our experience of 5124 cases who underwent ESWL complete stone clearance was seen in 72.6%, partial in 17.3% while it was unsuccessful in the rest.[47] Long-term pain relief on a 8-year follow-up was seen in 60% of patients.[48] Patients had reduction in pain score, number of hospitalizations, and analgesic use resulting in improved quality of life.[47] In our experience, ESWL is an effective and safe procedure with very few complications. In properly selected patients, it should be offered as the first line of treatment for large pancreatic calculi.

Pancreatic ductal leaks

PDL are defined as extravasation of contrast material from the pancreatic ductal system during ERCP.[49] This generally follows a blow out of MPD or side branches secondary to a proximal obstruction by stricture or stones. PDL is also seen following acute necrotizing pancreatitis or blunt trauma to the abdomen. The resultant fluid can lead to internal or external fistulae, pseudocyst, ascites, or pleural effusion [Figure 3]. Endoscopic therapy consists of performing a pancreatic sphincterotomy and placing a stent. This helps to convert a high pressure system into a low pressure one and divert the fluid across the stent into the duodenum.[50] Resolution of leak was seen in 92% of patients when stents bridged the disruption, 50% when stent was placed proximal to the disruption and 44% when a short transpapillary stent was placed.[49]
Figure 3: Magnetic resonance imaging showing gross pericardial effusion and subsequent magnetic resonance cholangiopancreatography image showing pancreatic ductal leak from tail region tracking upwards into pericardium in patient suffering from acute on chronic pancreatitis

Click here to view



  Role of Endoscopic Ultrasound in Chronic Pancreatitis Top


EUS is a rapidly evolving technology and is now used both in the diagnosis and management of CP. EUS is the best modality for the diagnosis of early CP as it visualizes both ductal and parenchymal changes. It has a sensitivity of 100% for early CP.[51],[52] Its therapeutic role is discussed below. A detailed review of drainage of pancreatic fluid collections (PFCs) is beyond the scope of this article.

Pancreatic fluid collections

EUS offers many distinct advantages over conventional ERCP in the management of PFC. Around 44%–53% of PFC are away from duodenal of gastric wall and these can be drained EUS guided.[53] Vascular structures can be identified at EUS and avoided during drainage. EUS can help place a stent in the dependent position of the PFC as well as dynamically follow its collapse. A comparative study of EUS and surgical cystogastrostomy revealed that EUS was better regarding cost, hospital stay, and physical and mental health.[54]

Endoscopic ultrasound guided drainage of main pancreatic duct

In 10%–15% of cases cannulation of MPD is not feasible. EUS-guided drainage either through the stomach or duodenum is the alternative. The duodenal position is preferred as the EUS scope is more stable. A guidewire is passed, and stents are placed by the rendezvous technique. Success rates vary between 77% and 92% in expert hands.[55],[56] The procedure is ideally performed at centers with expertise.

Endoscopic ultrasound guided celiac block

Patients who have pain as there dominant symptom and have not responded to the earlier mentioned methods can undergo EUS-guided celiac nerve or plexus block. A combination of triamcilone and bupivacaine is injected under guidance. Pain relief is seen in 55%–60% of patients and can last for few months.[57],[58],[59] Postural hypertension and diarrhea are the possible side effects.[51],[58],[59]


  Conclusion Top


CP is a complex, multifactorial irreversible disease with multifaceted presentation and complications. A team of physicians, gastroenterologists, interventional radiologists, and surgeons are required for its management. Each patient is individualized to identify the best modality of treatment to which he is suited. The patient should always be informed that all therapy is palliative as there is no cure for CP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  In this article
Abstract
Introduction
Management of Pain
Pancreatic Exocr...
Management of Co...
Strictures of Ma...
Pancreatic Calculi
Role of Endoscop...
Conclusion
References
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