CHAPTER 111: Islet Cell Transplantation

INTRODUCTION

• Chronic pancreatitis is a continuous inflammatory disease, characterized by irreversible morphologic changes that typically cause pain and permanent loss of function

• Incidence of chronic pancreatitis is 1.6–23 per 100,000 of the population—National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

• Continuum of disease

Acute pancreatitis → recurrent pancreatitis → chronic pancreatitis

• Risk factors of chronic pancreatitis (TIGARO—based on the first letters of each risk factor)

  • Toxic-metabolic (alcohol, tobacco, medications)

  • Idiopathic

  • Genetic (mutations of the CFTR, SPINK1, PRSS genes)

  • Autoimmune

  • Recurrent

  • Obstructive (pancreas divisum, sphincter of Oddi dysfunction)

• Symptoms chronic pancreatitis

  • Fatigue

  • Steatorrhea

  • Vitamin deficiencies

  • Diabetes mellitus

  • Increased risk of pancreatic cancer

• Pain is the only sensation that can be elicited from the pancreas

  • Abdominal pain of severe intensity

  • Often radiates to the back and left shoulder

  • Produces strong autonomic responses

  • Alcohol or food consumption aggravates the symptoms

  • Ductal hypertension—Interstitial hypertension

  • Scarring of pancreatic nerves

  • Neuronal damage by bioactive substances released from inflammatory cells and activated pancreatic enzymes

• Pancreatitis-induced pain is intractable and difficult to manage clinically. Initial intervention is conservative:

  • Nonopioid analgesics (acetaminophen, nonsteroidal antiinflammatory drugs)

  • Opioid analgesics (morphine, meperidine)

  • Nonnarcotic pain modulators (gabapentin, etc.)

  • Enzyme replacement therapy

  • Celiac nerve block

  • Pancreatic denervation

  • Endoscopic retrograde sphincterotomy

• 30–50% of patients require surgery due to:

  • Intractable pain not controlled by conservative intervention

  • Biliary obstruction

  • Gastrointestinal obstruction

  • Pseudocysts

  • Pancreatic fistula or ascites

  • Hemorrhage

  • Differentiation from carcinoma

• Up to 50% of patients require surgery: Denervation or resection

  • Puestow

  • Kausch (1909)–Whipple (1935)

  • Beger

  • Frey

  • Berne

  • Izbicki

• In patients in whom surgical intervention has failed, pancreatectomy can relieve pain; however, it is a drastic measure that leads to the development of “brittle diabetes”

• Auto islet transplantation (AIT) following total pancreatectomy relieves severe abdominal pain associated with chronic pancreatitis and preserves endocrine function

AUTO ISLET TRANSPLANTATION (AIT) (FIGURE 111-1)

• Procedure (islet isolation)

• After removal of the organ, it is immediately submerged in University of Wisconsin (UW) organ preservation solution during initial resection of fat and fibrotic tissue and transport to clean room isolation facility

• The volume and weight of the pancreas are recorded

• The organ ducts are cannulated for perfusion of the enzyme (Figures 111-2 to 111-5)

  • Although introduction of the enzyme through the ducts is preferred, depending on the degree of fibrosis, intraparenchymal injection of the enzyme may be necessary for complete perfusion of the organ

• To maximize the surface area of the tissue exposed to enzymatic action during digestion, the pancreas is cut into smaller pieces

• The pancreas and enzyme mixture is loaded into the digestion chamber, containing several Teflon balls (Figures 111-6)

  • Teflon balls provide mechanical forces during the digestion to facilitate the release of the islets and exocrine from the connective tissue

• Once the chamber is attached to the shaker arm and connected to automatic isolation system, the digestion can proceed

• Through precise control of the temperature of the system, the degree of digestion can ...