Jeffrey B. Matthews, MD FACS, discusses his topic of Surgery for Chronic Pancreatitis
[MUSIC PLAYING] My name is Dr. Jeff Mathews, I'm the Chairman of the Department of Surgery and Surgeon in Chief at the University of Chicago Medicine. Today's topic is surgery for chronic pancreatitis. Chronic pancreatitis represents a spectrum of inflammatory diseases of the pancreas and its attendant complications. Chronic pancreatitis is characterized by irreversible morphologic changes in the gland, permanent loss of function, and typically patients present with a pattern of recurrent attacks, or persistent pain with progressive functional loss. We've made many new insights into the pathogenesis of chronic pancreatitis, beyond the historical focus on alcohol consumption. In fact the disease, for so long, had been stigmatized as a condition only affecting alcoholics that it really blocked progress in the field and to lead to an unfair treatment of patients seeking care. Alcohol is definitely a risk factor for many patients but, in fact, most alcoholics are unaffected by chronic pancreatitis. Increasingly we're recognizing that hereditary and genetic factors are involved in the pathogenesis of this disease. And, in fact, there is a considerable spectrum of disease as it progresses from acute pancreatitis to recurrent acute pancreatitis to chronic pancreatitis. Increasingly we're recognizing that this condition also affects pediatric populations, where it has previously been under diagnosed and under recognized. Genetic factors in pancreatitis have become the subject of considerable interest over the last 10 to 15 years. And there are number of gene defects have been identified that predispose to pancreatitis. These include gene defects that originate in the function of the acinar cells, the enzyme secreting cells, and include the gene, PRSS1, which is mutated in many cases of hereditary pancreatitis. PRSS1 one is a gene that encodes for cationic trypsinogen, which is a pancreatic digestive enzyme. There are also gene defects that affect the function of duct cells, the cells in the pancreas that are responsible for so secreting pancreatic juice and for diluting and flushing the pancreatic enzymes on their way to the digestive tract. And these include defects in the gene responsible for cystic fibrosis, the cystic fibrosis transmembrane conductance regulator, CFTR. These gene factors in pancreatitis show variable patterns of inheritance both autosomal dominant and autosomal recessive types of patterns of inheritance are described. And a number of modifier genes including the gene SPINK1 has been shown to be involved. These genetic variations interplay with a number of environmental factors which include alcohol consumption and increasingly recognize the problem of tobacco smoking. So there is a spectrum of gene environment interactions that are responsible for producing acute pancreatitis and recurrent pain-- chronic pancreatitis as shown on this slide here. Classic alcohol related chronic pancreatitis may be favored on the left by minor variations in genes, such as SPINK1, whereas on the right hand side of this slide, we can see a predominance of genetic influence of the PRSS1 gene mutation in hereditary causes of pancreatitis. But what are patients affected by? Patients Are affected by their symptoms, particularly the symptoms of incapacitating pain. They also suffer from exocrine insufficiency associated with fibrosis and atrophy of the exocrine portion of the pancreas and the attendant weight loss and malnutrition that follows. Additionally patients over time frequently develop type C three diabetes which is due to the destruction of the pancreas by the inflammatory and fibrotic process. Patients also develop symptoms because of complications of chronic pancreatitis, which include biliary or duodenal obstruction as well as pseudocyst formation and the development of cancer. But the major indication for surgical therapy is pain. We have a number of approaches to affect the pain of chronic pancreatitis and none of them are entirely satisfactory. There are non-operative approaches that include pharmacotherapy, including pancreatic enzyme therapy, pain medications including narcotics and non-narcotic GABA agents. Neural ablation therapies such as celiac plexus block or thoracoscopic splanchnicectomy have been applied. As well as endoscopic therapies such as main pancreatic duct stenting, and stone removal. But these are often ineffective and consideration for surgery is often driven by this predominant symptom of pain. Now the choice of operation. The type of operation that we would recommend for a patient with chronic pancreatitis reflects the assumptions that we're making about why the patient is having pain. Patient typically is thought to have pain when there is obstruction of the main pancreatic duct due to stones or strictures. Inflammation, pseudocyst formation can also be sources of pancreatic pain. And in properly selected surgical patients pain relief can be achieved in about 80 to 85% of cases. But it's important to recognize that we don't always relieve pain with any of these therapies in chronic pancreatitis. Pain is a complicated and poorly understood process and this slide here highlights some of the complexities involved in the pathogenesis of pain for patients suffering from chronic pancreatitis. On the lower left hand corner, we can see that many patients are affected by problems related to the so-called plumbing of the pancreas duct obstruction leading to duct hypertension, a duct obstruction from stones or stricturing from fibrosis. Patients can also develop pain due to inflammation and calcifications in pseudocyst formation in the head of the pancreas and this is often something that can be addressed surgically. But many patients on the right hand side of the slide will also have problems related to the perception of pain. And there are problems that develop with the central perception, central sensitization to pain, impaired inhibitory pain modulation pathways, and so forth. And these are poorly understood and a target of substantial research. Now as I mentioned the choice of operation depends upon the anatomic target. Some patients will have dilation of the main pancreatic duct, due to stone or stricture formation. And these will be patients that can benefit from surgical decompression of the main pancreatic duct. Other patients will have head predominant disease. It's been stated that the head is the quote unquote motor of pain in some patients with chronic pancreatitis. And in these patients resection is recommended. So large duct disease is shown here. Patient with main pancreatic duct that is dilated as shown on the right on an ERCP. Or on the left on a CAT scan when a pancreatic duct approaches seven millimeters or greater it becomes a target for surgical decompression. The surgical approach that we take is a lateral pancreaticojejunostomy. The name of the procedure is often called a Puestow procedure and it involves a Roux-en-Y configuration of the intestine and intestinal conduit that is laid over the main pancreatic duct. The main pancreatic duct is unroofed in both the direction of the tail of the gland as well as through the head of the gland and intraductal stones and strictures are treated and the duct is essentially decompressed laterally. A variation of the Puestow procedure known as the Fry procedure adds a limited coring out of the pancreatic head to remove calcifications and impacted stones but essentially accomplishes surgical decompression as well. The surgical approach to duct decompression is often better than endoscopic approaches to decompression for patients with large duct disease. There have been now several prospective randomized trials that have compared surgical decompression to endoscopic decompression. An example of this is the study from the Dutch showing in a randomized prospective study over a two-year follow-up and now subsequently they've published five-year follow-up, comparing endoscopic intervention to surgical therapy. Endoscopic success was achieved only in about 50% of patients. Whereas a surgical therapy was successfully completed all patients. And as shown on the right, the pain scores that the patients experience were considerably lower after surgical drainage and remained that way over the two, and then subsequently five years, of follow up. So surgery is often a better choice for patients with large duct disease. What about patients with head predominant disease? That should be treated by surgical resection. When a patient such as the one shown here on the CAT scan show diffuse enlarging of the pancreatic head due to parenchymal or ductile calcifications, due to cavitation formation pseudocyst formation within the gland, or inflammatory changes around the pancreas. There may even be raised a question of the development of neoplasia. In these situations resection of the pancreatic head is recommended. Now that can be accomplished by a number of different methods. Traditionally it's been performed by the Whipple procedure-- pancreaticoduodenectomy. More recently surgeons in Europe as well as in the United States, including at University of Chicago Medicine, we perform a more limited pancreatic head resection, and I'll show you the difference. This is the classic Whipple procedure shown here on the left you can see that the pancreaticoduodenectomy, Whipple procedure, consists of removal of the pancreatic head, the duodenum, them as well as the gallbladder and distal bile duct. On the right the reconstruction is shown in the patients will have three anastomoses as part of their surgical reconstruction, a pancreaticojejunostomy, a hepaticojejunostomy to reestablish bile flow, and a duodeno or gastrojejunostomy to reestablish GI tract continuity. This is a tried and true approach to patients with chronic pancreatitis with head predominant disease and it's highly effective. The alternative is a procedure known as a duodenum preserving pancreatic head resection. There are several variations on this, which carry various eponyms. The first one described is the procedure introduced by Dr. Hans Beger, called the Beger procedure, and it involves a resection of the pancreatic head, similar to a Whipple procedure but without the duodenectomy and a more simpler Roux-en-Y reconstruction. It's illustrated here. Now there have been several prospective randomized controlled trials that have attempted to compare the outcome of a Whipple procedure versus the duodenum-sparing alternative for pancreatic head resection. And there doesn't seem to be any major difference in terms of pain relief at least as looked at out to 24 months. The Whipple procedure may be associated with a higher risk of post operative diabetes and a lower quality of life in terms of quality of appetite, digestion, eating, so forth. But this is inconsistent from study to study and by and large, we generally see that these approaches are equivalent. Now some patients have more complex situations who are not amenable to simple duct decompression or to resection of an inflammatory mass. And we see many of these patients at the University of Chicago. For example the patient with small duct chronic pancreatitis, where there's no inflammatory mass to resect and there is no duct to decompress. Also patients who have had a previous operation for chronic pancreatitis, but who still have pain. Or who had an operation for chronic pancreatitis, did fine for a while and now have pain again. Such as shown on the lower right hand image which is of the patient that has had a prior Whipple procedure and a prior Puestow procedure, but still has pain. We call these patients sometimes patients who've had Wuestow procedures, when they've had a Whipple and a Puestow procedure. What are we going to do for that patient? And finally what will we do for the patient who has a genetic syndrome such as a hereditary pancreatitis associated with gene defects in the PRSS1 gene that places the entire gland at risk for recurring pancreatitis and that carries a higher risk of the development of pancreatic cancer. What do we do for these patients? Can we simply take out the entire pancreas? Is total pancreatectomy an option for these patients. Well historically this has been used for patients as a last resort and while it is effective in relieving pain and some of these patients, the long term morbidity, in terms of malabsorption and weight loss due to exocrine insufficiency, is a problem. But more importantly post operatively, with removal of the entire pancreas, patients have tended to be very brittle, difficult to control, diabetics. And this has been a problem that has made most surgeons shy away from doing total pancreatectomy for patients with chronic pancreatitis. However over the last 15 years or so we have introduced methods where patients can undergo total pancreatectomy and have their islets harvested, and preserved, and auto-transplanted back into their liver. And this procedure islet auto-transplantation mitigates or eliminates post-operative diabetes after total pancreatectomy. It's performed only in a handful of experienced centers worldwide. University Chicago is a leader in both pancreatic islet allo-transplantation and pancreatic islet auto-transplantation. And we have great experience in this condition here. And what's involved in the pancreatic islet auto transplantation procedure is the pancreas is removed. The pancreas is then subject to enzymatic digestion and a centrifugation purification process that shakes out the islet cells which are retrieved and then processed to be infused back into the portal vein where they take up shop in the patient's liver and can function to regulate blood glucose in an effective way. Pancreatectomy with islet auto transplantation can be effective for these desperate patients with chronic pancreatitis that have no other surgical alternative. In our experience, about 70% of these patients can come off of narcotics and can be made pain free. 40% percent of the patients undergoing this procedure are insulin independent, and the remainder have relatively easy to control diabetes on low doses of insulin. Now patient selection for total pancreatectomy with islet auto transplantation is absolutely critical. We reserve this approach for patients who are truly incapacitated by their symptoms, who have no conventional alternative, for patients who have hereditary syndromes, who have cancer risk, for patients who have failed prior surgery, increasingly for pediatric patients who have a strong family history and cancer risk. And we have a number of exclusion criteria such as pre-existent diabetes and liver disease. But this can be highly effective for the correct patient. So let me summarize and say that chronic pancreatitis often has an underlying genetic predisposition. We're learning more and more about what predisposes to pancreatitis. This is not just a disease of people who abuse alcohol. We have an incomplete but improving understanding of the mechanisms of pain in this disease surgical therapy should be targeted towards the presumed source of pain and emerging therapies including total pancreatectomy with islet auto transplantation can be performed in specialized centers, in selected patients. And this is something that we are championing here at the University of Chicago Medicine.
