Advanced Therapy in Gastroenterology and Liver Disease - part 10 doc

782 / Advanced Therapy in Gastroenterology and Liver Disease Since then there have been several studies that have repro- duced these results, although a convincing benefit in mortality has not been demonstrated (Imrie et al, 2002). Most recently there have been reports that NG feeding is well tol- e rated in these patients. Our practice is to begin enteral feeding in patients by an endoscopically or radiologically placed nasojejunal feeding tube after day 2 or 3 in patients with severe pancreatitis. Feeding is started at low rate of 20 cc/hr. Although this does not provide complete caloric requirements, small amounts of feeding are usually tolerated and may preserve the intestinal barrier. If nausea and vomiting are present, a NG tube can be placed and kept to drainage. A small group of patients (between 10 to 20%) will not tol- erate this method of feeding and require TPN. Triglyceride levels should be checked after the onset of feeding, especially in patients with known hypertriglyceridemia. Pharmacotherapy with Cytokines, Enzyme Inhibitors, and Anti-Inflammatory Agents Multiple cytokines and anti-inflammatory mediators have been implicated in the pathogenesis of acute pancreatitis. Thus, blockage by a single agent (eg, interleukin-10,lexipafant) has not been effective in the treatment of pancreatitis. Surgical Therapy and Management of Other Complications Surgical therapy is used to treat infected necrosis or complications. The following chapter is on surgical management of pancreatitis. Surgical management includes necrosectomy to remove necrotic tissue with intraoperative and postoperative lavage of debris and pancreatic fluids. Percutaneous catheter-directed debridement of infected necrosis has been described, but is best directed to patients who are hemodynamically and clinical stable. Further, a number of these patients will subsequently require surgery. It is not our practice to recommend percutaneous drainage, except in carefully selected patients with pancreatic abscesses. Endoscopic drainage with placement of trans- gastric and tranduodenal catheters and nasopancreatic tubes for irrigation has been described. The experience with this method is limited and it requires specific endoscopic experience, with experienced surgical backup. Acute fluid collections can be observed early in the course of acute pancreatitis and will usually resolve spontaneously; treatment is required only if they become symptomatic or infected. Pseudocysts are localized collections of necrotic debris and fluid within a wall of granulation tissue that persist for > 4 weeks. Regardless of its size, an asymptomatic pse udocyst does not require any therapy and may be observed indefinitely. If the cyst is symptomatic (pain, obstruction), it may be drained using a variety of methods inc luding endoscopic, percutaneous, and surgical. Cysts may be drained endoscopically either by cyst-gastrostomy o r cyst duodenostomy or by transampullary stent drainage. There is a separate chapter on endoscopic management of pancreatitis (see Chapter 138,“Pancreatitis: Endoscopic Therapy”). Percutaneous drainage is attempted if the loca- tion precludes endoscopic cystgastrotomy or when multiple noncommunicating cysts are observed. If the pseudocyst does not resolve with drainage, a proximal pancreatic duct stricture may be present and an ERCP should be performed. ERCP prior to cyst drainage should only be attempted if the pseudocyst can be immediately drained , because if there is contrast entry into the pseudocyst (as in communicating cysts) it increases the chance of infection in the event that drainage is not performed. Pseudocysts may become infected, rupture, or hemorrhage. Post-ERCP Pancreatitis Approximately 1 to 10% of ERCPs may be complicated by acute pancreatitis. This is usually mild, but severe pancreatitis and death may occur. Table 136-5 summarizes risk factors and preventive measures. The judicious use of non- imaging procedures (magnetic resonance cholangiopan- creatography and EUS) to circumvent diagnostic ERCP is important because preventative measures have limited success. Short duration (1 to 2 days) pancreatic duct stenting appears to be effective in high risk patients, including those undergoing pancreatic sphincterotomy, SO dysfunction, and pancreatic endotherapy. Prevention of Recurrence In patients with predicted biliary pancreatitis, if gallstones are not observed on an initial ultrasound, the procedure should be repeated after the pancreatitis has resolved. Patients with biliary pancreatitis have a significant risk of recurrence unless a cholecystectomy is performed. In patients with mild to moderate pancreatitis, this can be accomplished prior to discharge. Patients who refuse surgery or are very high operative risks benefit from endoscopic biliary sphincterotomy to prevent recurrence. Patients with alcohol use should be counseled about ces- sat ion. T he treatment of patients with p ancr eas div isum is controversial, but those with recurrent pancreatitis in whom no other etiology is identified may benefit from pancre- at ic sphincterotomy of the minor ampulla. H yperlipidemic patients should receive appropriate lipid lowering medica- t io ns and patients with acute recurrent pancreatitis may benefit from further endoscopic workup including ERCP, EUS, and SO manometry. Ampullary or pancreatic cancer may present in pancreatitis.Young patients or those with a famil y hist o r y should be offered genetic testing in the appro- p riate setting. 784 CHAPTER 137 CHRONIC PANCREATITIS:SURGICAL CONSIDERATIONS OSCAR JOE HINES,MD,AND HOWARD A. REBER,MD depression that often accompanies the chronic pain state. Nutrition may be impaired because oral intake is limited by the pain that it produces. The patient may be addicted to narcotics. Type of Surgical Procedure The type of operation depends on the anatomy of the pancreatic ductal system, and whether or not the pancreas is diffusely involved with the disease or it involves one part of the gland more than the others. Thus, patients with a dilated pancreatic duct (> 7 mm in the body of the gland) are candidates for a drainage operation that decompresses the duct. Those with a duct that is of normal caliber will probably require resection of a part of the pancreas, usually the head of the gland. Morbidity Patients who undergo a pancreatic resection may develop exocrine insufficiency and/or diabetes if enough pancreas is removed. Whereas this may be an acceptable price to pay for pain relief in some patients, others might be unable to manage the dietary and insulin requirements that would ensue (eg, patients who are addicted to narcotics and/or alcohol). So a resection operation might be contraindicated in them. However, even in patients with narcotic and/or alcohol addiction and a dilated duct, a duct decompression operation may be appropriate, because it almost never produces exocrine or endocrine insufficiency. Preoperative psychiatric examination may help the surgeon to decide about whether or not operation should be considered. Preoperative Imaging All patients require preoperative imaging studies to help with decisions about the kind of operation that may be indicated. The goals of imaging are (1) to assess the diameter of the d uct, (2) to determine the presence of any associated disease (eg, cysts, bile duct obstruction), and (3) to search for an unsuspected pancreatic malignancy. All patients should und ergo a high resolution computed tomography (CT) scan with fine cuts through the pancreas during the arterial phase of the study. Endoscopic ultrasound (EUS) w ith fine needle aspiration (FNA) of any suspicious area Chronic pancreatitis is characterized by chronic inflammation with fibrosis and obliteration of both the endocrine and exocrine components of the gland. These changes are irreversible, progressive, and may culminate in clinically significant pancreatic insufficiency and diabetes. Although chronic alcoholism is the usual etiology, some patients develop the disease because of chronic ductal obstruction, some because of genetic predisposition, and a substantial number for reasons as yet unknown. Regardless of the cause, the most common symptom of the disease is chronic abdominal pain, and pain relief is the most frequent reason for surgical intervention. Other reasons include various intra-abdominal complications of pancreatitis (eg, bile duct or duodenal obstruction, pseudocyst), and the concern that pancreatic cancer may be present. We will describe the surgical considerations related to each. Chronic Abdominal Pain The etiology of the pain is multifactorial and, in general, is not well understood. Factors include continued alcohol consumption that results in local release of oxygen-derived free radicals, diminished pancreatic blood flow and tissue acidosis, perineural sheath destruction with exposure to various nociceptive agents, and elevated pancreatic ductal and parenchymal pressures. The initial therapy for pain in all of these patients should be nonoperative and includes recommendations for the cessation of alcohol intake, and the administration of oral analgesic agents. Referral for consideration of surgery requires (1) an assessment of the significance of the pain for the individual patient, which is highly subjective, (2) a determination of the type of surgical procedure that might be appropriate, and (3) an evaluation of the ability of the patient to deal with any long term morbidity that an operation might produce. PAIN ASSESSMENT In general, operation may be indicated in patients whose pain int erferes with the quality of their lives. For exam- ple, the attacks of pain may require frequent hospitalizations that interfere with school or employment. The patient ma y be unable to function productively because of the Chronic Pancreatitis: Surgical Considerations / 785 may be indicated if the results of the CT scan raise a question about malignancy. There is a separate chapter on EUS and FNA (see Chapter 5,“Endoscopic Ultrasonography and Fine-Needle Aspiration”). O perations to relieve pain in these patients either (1) drain a dilated pancreatic ductal system or (2) resect dis- eased pancreatic tissue if the duct is not enlarged. The main pancreatic duct normally measures 4 to 5 mm in the head, 3 to 4 mm in the body, and 2 to 3 mm in the tail of the pancreas. The duct is considered dilated when it is at least 7 mm in diameter in the body of the gland. Ductal Drainage Operation In patients with a dilated pancreatic duct, a ductal drainage operation (longitudinal pancreaticojejunostomy, Puestow procedure) is likely to be effective. The operation involves wide exposure of the anterior surface of the pancreas, and incision of the anterior wall of the duct throughout the length of the gland. Pancreatic duct stones are removed and a Roux-en-Y jejunal limb is constructed and sewn along the length of the duct, so that pancreatic secretions empty directly into the bowel. The operative results for longitudinal pancreaticojejunostomy are summarized in Table 137-1. The morbidity and mortality ( < 2%) rates are minimal and there is almost no risk of diabetes because little if any pancreatic tissue is resected. Pain is relieved in 85% of patients for the first several years. Most patients gain weight because they no longer experience pain with eating, although the degree of mal- a bsorption does not change. The major drawback of this operation is that within 5 years, pain recurs in as many as 40 to 50% of patients. In a small number, this may be due to stricturing of the anastomosis, but in most, it is probably associated with disease progression or the development of a complication. Recurrence of pain may also herald the appearance of pancreatic cancer. Pancreatic Resection Patients with a normal diameter or narrowed duct may be candidates for pancreatic resection. This is especially true when the pancreatic head is enlarged and contains multiple cysts and calcifications. Pancreaticoduodenectomy (Whipple resection) or pylorus-preserving pancreaticoduodenectomy are performed most commonly, and we pre- fer the latter. Pylorus preservation is felt by many to allow for better postoperative nutrition and weight gain, but little objective data support this. The operative mortality rate is < 3% and permanent pain relief is to be expected in 85 to 90%. These operations are more likely to produce endocrine (22%) and exocrine (55%) insufficiency, which is their major drawback. Of course, some patients develop these problems anyhow as the disease progresses. In an effort to design an operation that would provide permanent pain relief and avoid the exocrine and endocrine insufficiency of a major resection, surgeons have designed several new procedures that combine limited resection of the head of the pancreas with a pancreaticojejunostomy. The so-called Beger or Frey operations remove most o f the head of the pancreas except for a shell of pancreatic tissue posteriorly. The cavity thus created is drained into a Roux-en-Y limb of jejunum; gastroduodenal continuity is not disturbed. This operation can be performed whether or not the pancreatic duct is dilated. If it is, the TABLE 137-1. Results of Longitudinal Pancreaticojejunostomy for Chronic Pancreatitis Number Mortality Mean Pain Author Year of Patients (%) follow-up (mo) Relief (%) Leger 1973 45 4.5 63 Prinz 1978 42 5 108 76 Prinz 1981 43 4.5 95 65 Sarles 1982 69 4.2 60 85 Warshaw 1984 33 3 43 88 Bradley 1986 48 0 69 66 Nealon 1988 41 0 14.8 93 T ABLE 137-2. Results of Resection for Chronic Pancreatitis Number Operative Pain New New Type of of Mortality Relief Onset DM Endocrine Study Y ear Resection Patients (%) (%) (%) Insufficiency (%) Heise 2001 PPW 41 4.8 54 19 67 Drainage 59 – 59 16 54 DP 26 – 89 21 50 Jimenez 2000 PPW 39 1.4 60 10 63 SW 33 – 70 12 77 Martin 1996 PPW 45 2.2 92 46 77 Beger 1999 DPPHR 504 0.8 91 21 – Frey 1994 LRLPJ 50 0 87 11 11 DM = diabetes mellitus; DP = distal pancreatectomy; DPPHR = duodenum-preserving pancreatic head resection; LRLPJ = local pancreatic head resection with longitudinal pancreaticojejunostomy; PPW = pylorus-preserving Whipple; SW = standard Whipple. 786 / Advanced Therapy in Gastroenterology and Liver Disease pancreaticojejunostomy is extended over the body of the pancreas to incorporate the dilated duct in that area. Early results suggest that pain relief is excellent in 85 to 90% of patients, that the relief persists beyond several years, and t hat exocrine or endocrine insufficiency are not precipi- tated by the surgery. In those patients whose bile duct has also been obstructed by the fibrotic pancreas, this “coring” of pancreatic tissue from the head of the gland may decom- press that duct as well. This operation is contraindicated if there is a concern about the presence of a malignant neo- plasm in the head of the pancreas; a pancreaticoduodenectomy should be performed in these cases. Uncommonly, chronic pancreatitis is localized predominantly in the body or tail of the pancreas. In these cases, a distal pancreatectomy (with or without splenec- tomy) may be effective. The surgeon should investigate the possibility that an occult malignancy may have produced a more proximal duct obstruction, and that a neoplastic duct stricture is the reason for such localized pancreatitis. Otherwise in patients with predominantly distal disease, distal pancreatectomy is safe and pain relief can be expected in as many as 90% of patients after 4 years. For the usual patient who has diffuse disease involving the entire pancreas, distal pancreatectomy is ineffective, however. Because it results in a brittle diabetes which is often difficult to con- trol, and because lesser procedures are likely to be effective, total pancreatectomy for chronic pancreatitis is almost never done today. Complications of Chronic Pancreatitis Pseudocyst A pancreatic pseudocyst is a collection of fluid usually in the v icinit y of the pancreas, which develops in association with a leak of pancreatic juice from the inflamed parenchyma or from a disrupted duct. The wall of the pseudocyst is comprised of fibrous nonepithelialized tissue. Occasionally a pseudocyst may present at great dis- tance from the pancreas (eg, thorax, groin), when the fluid dissects through tissue planes. The majority of acute pseudocysts that appear during an episode of acute pancreatic inflammation resolve without intervention. However, most pseudocysts that develop on a background of chronic pancreatitis are unlikely to resolve spontaneously, and they may need treatment. Asymptomatic pseudocysts up to 5 to 6 cm in diameter may be safely observed, and are usually followed with either serial ultrasound o r CT examinations. Larger cysts or pseudocysts of any size that are symptomatic require intervention. Symptoms are most often from gastrointestinal (GI) o bstruction when the cyst distorts or compresses the stomach, duodenum, or bile duct, or produces abdominal pain. Serious complications also can occur, although they are unc ommon ( < 5% o f cases). These include hemorrhage into the cyst, perforation of the cyst, or cyst infection. Hemorrhage is usually caused by erosion of the splenic or gastroduodenal artery or other major vessel within the wall of the cyst, and the bleeding is often confined to the cyst l umen. The diagnosis should be suspected if there are clinical signs of hypovolemia and a falling hematocrit. There may be abdominal pain, and a mass may be palpable. An abdominal CT scan shows the cyst with the contained blood clot. Angiography confirms the diagnosis, and the radiologist should attempt to embolize the bleeding vessel. If not, emergency surgery with ligation of the vessel or excision of the cyst is required. Perforation of a pseudocyst is a surgical emergency that is characterized by the sud- den onset of intense abdominal pain with peritonitis. Patients require urgent surgery with irrigation of the peri- toneal cavity and usually external cyst drainage. Infection of a pseudocyst should be suspected if signs of sepsis develop. Diagnosis by CT scan and treatment by percutaneous cyst aspiration and drainage are usually effective. In the absence of a life threatening complication, elec- tive surgery of pseudocysts is usually delayed until the cyst has developed a mature wall that will hold sutures at the time of repair. For those cysts that develop following an episode of acute pancreatitis, this requires 4 to 6 weeks. In most cases the patient can eat and be discharged from the hospital during the interval. Pseudocysts that resolve spontaneously usually will do so during this time. If no episode of clinically significant acute pancreatitis preceded the development of the cyst, as is often the case in patients with chronic pancreatitis, usually no waiting period is necessary. Pseudocysts may be treated surgically, or by endoscopic or radiologic drainage . Endoscopic methods require the placement of a plastic stent through the stomach or duodenal wall into the adjacent cyst. The stent is eventually removed, and in about 80% of cases, the cyst is perma- nently eradicated. These endoscopic techniques require expertise, which still is not widely available. They are discussed in the next chapter (see Chapter 138,“Pancreatitis: Endoscopic Therapy”). Radiologic approaches usually con- sist of percutaneous external drainage of the cyst with even- tual removal of the drainage catheter many weeks later. Many of these pseudocysts recur. Surgical treatment usually consists of drainage of the cyst internally to either the stomach (cystgastrostomy) or to a Roux-en-Y limb of jejunum (cystjejunostomy). Both are safe and effective, with recurrence rates < 10%. If the pseudocyst is in the tail of the pancreas, a distal pancreatectomy with excision of the cyst may be best. Pancreatic Fistula In the setting of chronic pancreatitis, a pancreatic fistula is usually the result of a ductal disruption from an episode of a cute pancreatitis. The diagnosis is made by finding a high amylase level (usually many thousands of U/L) in the fistula effluent. Some fistulas will close spontaneously, provided t hat ductal continuity can be re-established as healing occurs, infection is eradicated, and nutrition is adequate. However, the frequent presence of duct obstruction in chronic pancreatitis may make it less likely that the fistula will close. Parenteral nutrition is usually not required and most patients are able to eat a regular diet. There is no evidence that oral intake delays resolution of fistula. The use of somatostatin does not appear to hasten fistula closure, although if it is a high output fistula (ie, > 200 mL/d), the secretory inhibitor may simplify management of the patient. Fistulas that persist for as long as 1 year, or those whose anatomic characteristics preclude spontaneous closure (eg, duct obstruction between fistula and duodenal lumen, duct discontinuity), will require operative repair. This is best done by creating an anasta- mosis between the pancreatic duct at the point of the leak and a Roux-en-Y limb of jejunum. The success rate of operative repair is > 90%. Biliary Stricture or Obstruction Jaundice may occur in up to one-third of patients with chronic calcific pancreatitis at some point during the disease, usually when there is pancreatic swelling at the time of an episode of acute pancreatitis. This often resolves as the acute inflammation subsides, but as many as 10% of patients are left with obstruction of the common duct. This is due to fibrosis of the head of the pancreas resulting in constriction of the duct as it passes through this portion of the gland. The stricture usually appears as a long, symmetrical narrowing when it is visualized by magnetic resonance cholangiopan- creatography or endoscopic retrograde cholangiography. The proximal duct and gallbladder may be distended, but o bstruction of the duct is almost never complete, which dif- ferentiates it from a malignant obstruction. A simple biliary bypass using a Roux-en-Y choledochojejunostomy effectively treats such a biliary stricture. Endoscopic procedures are discussed in the next chapter. Intestin al Compression or Obstruction A mino r it y of patients will present with obstruction of the second or third portion of the duodenum. Upper endoscopy and CT scan should be p e r f ormed to rule out the presence of a neoplastic process. Then a loop gastrojejunostomy can be done to bypass the obstruction. O bstruction of the colon (usually the transverse or splenic flexure) can also occur from chronic pancreatitis. If this is due to an episode of acute inflammation, the obstruction will likely resolve. If it persists, then a colonoscopy should be performed to rule out malignancy. Persistence of the o bstruction requires a resection of the involved segment o f c olo n and an e nd-t o-e nd anastomosis. Pancreatic Malignancy P atients with long standing chronic pancreatitis are at a 10% lifetime risk for the development of pancreatic ade- nocarcinoma. During examination for surgery in a patient with chronic pancreatitis, imaging studies may show focal changes in the pancreas that suggest malignancy, or other aspects of the clinical presentation (eg, rising or markedly elevated CA19-9, change in character of pain, accelerated weight loss) may have raised the clin- ician’s index of suspicion about the possibility that cancer is present. If there is concern about malignancy, we recommend EUS examination, which is currently the most sensitive diagnostic study to identify small cancers, and also can be used to obtain tissue from the lesion that could confirm the diagnosis. EUS and FNA are discussed in Chapter 5 (“Endoscopic Ultrasonography and Fine-Needle Aspiration”). However, whether or not the diagnosis is confirmed pre- operatively, patients in whom the surgeon suspects the coexistence of pancreatic cancer with underlying chronic pancreatitis require pancreatic resection. This means a pancreaticoduodenectomy for head and uncinate lesions and a distal pancreatectomy for body and tail lesions. Even if cancer is not found when the resected specimen is examined by the pathologist, this approach represents the cur- rent standard of care in such circumstances. This is because resection operations are safe, they are one of the standard operations normally done for chronic pancreatitis without coexisting cancer, and pancreatic cancer is uniformly fatal when it is not surgically resected. Conclusion T he s urgical considerations for patients with chronic pancreatitis include procedures to address chronic pain, various complications of the disease, and pancreatic cancer. The decision to operate in any single patient with pain from the disease is complex, and should be based on a variety of factors that include the psychosocial makeup of the patient as well as pancreatic anatomy. If surgery is indicated, the type of operation hinges on the appearance of the pancreatic ducts (Figure 137-1). In patients with a dilated duct, a drainage procedure is often the best option because this offers good pain relief and the least long term morbidity. If the ducts are not enlarged, failed prior ductal drainage, or there is concern about the presence of cancer, then resection should be performed. Newer operations that r esect most of the head of the pancreas but still preserve GI continuity (Beger et al, 1999; Frey and Amikura, 1994) may provide the best long term pain relief with the least lo ng term morbidity. Patients with chronic pancreatitis can develop pseudocysts, pancreatic fistulas, and biliary or intestinal obstruction. The pancreatic surgeon must b e prepared to deal with all of these issues. Chronic Pancreatitis: Surgical Considerations / 787 790 / Advanced Therapy in Gastroenterology and Liver Disease FIGURE 138-1. (A) T echnique of pancreatic sphincterotomy using a pull type sphincterotome. ( Left top) Biliary sphincterotomy is performed using a standard pull type sphincterotome. ( Right top) Pancreatic spincterotomy performed with a pull type sphincterotome cutting in the 1 o’clock direction. ( Left bottom) Completed biliary and pancreatic sphincterotomy. A guidewire is in the pancreatic duct. (Right bottom) A 6 F pancreatic stent is placed following performance of the pancreatic sphincterotomy. (B) Traction sphincterotome positioned in minor papilla. Note the extent of the minor papilla mound ( arrows). Duodenal juice at the minor papilla orifice is aspirated away before cutting to prevent heat dissipation to juice and boiling the adjacent tissues during the sphincterotomy. (C) Wire is bowed taught and cut is performed rapidly with minimal coagulation utilizing the ERBE generator. The optimal cut length in this setting is unknown. The 5 mm length minor papilla sphincterotomy is complete without white tissue coag- ulum. (D) White pancreatic stone removed through patent sphincterotomy orifice with balloon catheter. C D BA Pancreatitis: Endoscopic Therapy / 791 ventral pancreatogram, a major papilla pancreatic sphincterotomy is usually performed to facilitate access to the duct prior to attempts at stricture dilation and stent placement. There are two methods to cut the major pancreatic s phincter. A standard pull-type sphincterotome (with or without a guide wire) is inserted into the pancreatic duct and oriented along the axis of the pancreatic duct (usually in the 12 to 1 o’clock position). Although the landmarks to determine the length of incision are imprecise, author- ities recommend a cutting length of 5 to 10 mm. The cutting wire of the sphincterotome should not extend more than 6 to 7 mm up the duct when applying electrocautery, so as to prevent deep ductal injury.Alternatively,a needle- knife can be used to perform the sphincterotomy over a previously placed pancreatic stent. Performing a biliary sphincterotomy first can expose the pancreaticobiliary sep- tum and allow the length of the cut to be gauged more accurately. Cannulation of the ventral pancreatic duct may be unsuccessful in patients with recurrent, idiopathic pancreatitis and should heighten the suspicion that pancreas divisum may be present. If the pancreatogram from the major papilla is successful, a fine branching of the ventral duct typical of pancreas divisum must be ascertained. In patients over the age of 40 years with pancreatic duct cut- off in the head of the pancreas, the endoscopist must be wary of underlying pancreatic malignancy causing an abrupt cut-off of the ventral pancreatic duct masquerad- ing as pancreas divisum. If the ventral pancreatogram is typical of pancreas divisum, the minor papilla is sought. Approaches to the minor papilla for cannulation begin with an endoscopic still photo of the minor papilla orifice to refer to during attempted minor papilla cannulation (Lehman and Sherman, 1995). The use of intravenous secretin (Secreflo, Repligen Inc.) 16 µg to induce pancreatic ductal secretion may aid in identifying the minor papilla orifice and successful cannulation. We have reported our experience with spraying the minor papilla with meth- ylene blue prior to secretin administration to more accurately locate the minor papilla and improve success of minor papilla cannulation (Park et al, 2003). For cannulation, we commonly use the highly tapered 3-4-5 F catheter loaded with the 0.018 inch roadrunner guide wire (Wilson- Cook, Winston-Salem, NC). Once the dorsal duct is accessed and the anatomy is defined, minor papilla therapy is considered. We reserve minor papilla therapy for patients who have experienced at least two bouts of documented pancreatitis or for patients with chronic pancreatitis with strictures, duct disruptions or stones in the d orsal duct. In patients with pancreas divisum, a minor papilla sphincterotomy is usually necessary. The minor papilla sphincterotomy may be performed with a needle- knif e sphincterotome over a 3 or 4 F pancreatic stent or with a standard pull-type sphincterotome. The technique is similar to that of major papilla pancreatic sphincterotomy, except that the direction of the incision is usually in the 10 to 12 o’clock position and the length of the sphincterotomy is limited to 4 to 8 mm. Chronic Pancreatitis Endoscopic therapy is now being applied in the setting of chronic pancreatitis for patients presenting with pain and/or clinical episodes of acute pancreatitis. One of the aims of endoscopic therapy is to alleviate the obstruction to exocrine juice flow. Outflow obstruction may be caused by ductal strictures (biliary or pancreatic), pancreatic stones, pseudocysts, and minor or major papilla stenosis. Although the endoscopic approach has never been directly compared with surgery, endoscopic drainage is appealing in that it may offer an alternative to surgical drainage procedures, with generally less morbidity and mortality. Furthermore, endoscopic procedures do not preclude sub- sequent surgery, should it be necessary. Moreover, the out- come from reducing the intraductal pressure by endoscopic methods may be a predictor for the success of surgical drainage. Benign strictures of the main pancreatic duct may be a consequence of generalized or focal inflammation or necrosis around the main pancreatic duct. Given the puta- tive role of ductal hypertension in the genesis of symptoms (at least in a subpopulation of patients), the utility of pancreatic duct stents for treatment of dominant pancreatic duct strictures is being evaluated. Underlying malignancy must be considered and excluded by tissue sampling at ERCP or by endoscopic ultrasonography with fine-needle aspiration of the strictured segment. Most pancreatic stents are simply standard polyethylene biliary stents with extra sid e holes at ap proximately 1 cm intervals to permit better side branch juice flow. Stents made of other materials have received limited evaluation. The technique for placing a stent in the pancreatic duct is similar to that used for insert- ing a biliary stent. In most patients, a pancreatic sphincterotomy (with or without a biliary sphincterotomy) via the major or minor papilla is performed to facilitate placement of accessories and stents. A guide wire must be maneuvered upstream to the narrowing. Hydrophilic flex- ible tip wires are especially helpful for bypassing strictures. Torqueable wires are occasionally necessary to achieve this goal. High-grade strictures require dilatation prior to inser- tion of the endoprosthesis. This may be performed with hydrostatic balloon dilating catheters or graduated dilating cathe ters. Extremely tight strictures may permit passage of only a small caliber guide wire. Such wires may be left in situ overnight and usually permit dilator passage the ne xt day. Alternatively, 3 F angioplasty balloons or the Soehendra stent retriever may be helpful to effectively dilate the stricture. Although one preliminary report suggested that l uminal patency of the duct persisted at a mean time 792 / Advanced Therapy in Gastroenterology and Liver Disease of 5 months following balloon dilation alone, most author- ities have observed recurrence of strictures after onetime dilation and therefore advocate stenting. As a rule, the diameter of the stent should not exceed the size of the downstream duct. Therefore, 5, 7, or 8.5 F stents are commonly used in smaller ducts, whereas 10 to 11.5 F stents or dual side-by-side 5 to 7 F stents may be inserted in patients w ith severe chronic pancreatitis and a dilatated main pancreatic duct. The tip of the stent in the pancreas must extend upstream to the narrowed segment and into a st raight portion of the pancreatic duct to avoid stent tip erosion through the duct wall. For diagnostic trials of pancreatic stenting in patients with nearly daily pain, most st ents are left in place for 3 to 4 weeks. The appropriate duration of pancreatic stent placement and the interval from the placement to change of the pancreatic stent is not known. The following two options are available: (1) the stent can be left in place until symptoms or complications occur and (2) the stent can be left in place for a predetermined interval (eg, 3 months). If the patient fails to improve, the stent should be removed, because ductal h ypertension is unlikely to be the cause of pain. If the patient has benefited from stenting, one can remove the stent and observe the patient clinically, continue stenting f or a more prolonged period, or perform a surgical drainage procedure. The majority of patients with a stricture have associated calcifie d pancreatic duct stones. For optimal results, the FIGURE 138-2. A 57-year-old male with history of alcohol-induced chronic pancreatitis with recurrent monthly attacks of pain requiring multiple hospitalizations. Pancreatogram via major papilla reveals tight stricture of downstream pancreatic duct with multiple filling defects in the dilated upstream pancreatic duct (A). A hydrophilic 0.025 inch guide wire is used for engagement of the stricture and access to the dilated duct (B). A 4 mm diameter hydrostatic balloon catheter is used for stricture dilatation after a 5-7-10 F dilation catheter was not successfully passed through the stricture (C). One 7 F by 8 cm long with a three-quarter external pigtail and single internal flap was placed into the pancreatic duct. This stent was removed 1 month later and the patient has been without pain 1 year later (D). A C B D Pancreatitis: Endoscopic Therapy / 793 therapy must address both the stones and stricture. In the larg est m ulticenter trial, Rosch and colleagues (2002) reported on the long-term follow up of over 1000 patients with chronic pancreatitis undergoing initial endoscopic therapy during the period 1989 to 1995. One thousand two hundred and eleven patients from eight centers in Europe with pain and obstructive chronic pancreatitis underwent endoscopic therapy, including endoscopic pancreatic sphincterotomy, pancreatic stricture dilation, pancreatic stone fragmentation by extracorporeal shock wave lithotripsy and pancreatic stone removal, pancreatic stent placement, or a combination of these methods. One thousand eighteen patients (84%) were observed for symptomatic improvement and need for pancreatic surgery over a mean of 4.9 years (range 2 to 12 years). Success of endo- sc opic therapy was defined as a significant reduction or elimination of pain and reduction in pain medication. Partial success was defined as reduction in pain, though fur ther interventions were necessary for pain relief. Failure of endoscopic therapy was defined as the need for pancreatic decompressive surgery or patients that were lost t o follow-up. Over long-term follow-up, 69% of patients were successfully treated with endoscopic therapy and 15% e xp erienced a partial success. Twenty percent of patients required surgery, with a 55% significant reduction in pain. Five percent of patients were lost to follow-up. The group of patients that had the highest frequency of completed treatment were patients with stones alone (76%) as compared to patients with strictures alone (57%) and patients with strictures and stones (57%) ( p < .001). Interestingly, the percentage of patients with no or minimal residual pain at follow-up was similar in all groups (strictures alone 84%, stones alone 84%, and strictures plus stones 87%) (p = .677). The authors of this report concluded that endoscopic therapy for chronic pancreatitis in experienced centers is effective in the majority of patients and the beneficial response to successful endoscopic therapy in chronic pan- cr eatitis is durable and long term. Endoscopic methods alone will likely fail in the presence of large or impacted stones and stones proximal to a st ricture. Extracorporeal shock wave lithotripsy can be used to fragment stones and facilitate their removal. Thus, this procedure is complementary to endoscopic techniques and imp roves the success of nonsurgical ductal decompression. FIGURE 138-3. A 40-year-old female with alcohol-induced chronic pancreatitis complicated by pancreatic main duct stones. Pancreatogram revealing dilatated pancreatic duct with 5 mm diameter filling defect consistent with a pancreatic stone (A). After pancreatic sphincterotomy, a non- wire guided stone extraction basket was used. The basket is opened fully in the dilatated pancreatic duct and the stone is engaged (B). Basket is slowly closed on the stone (C). Stone is extracted and follow-up pancreatogram with a balloon catheter reveals no residual filling defects. No further stenting was performed (D). DC BA 794 / Advanced Therapy in Gastroenterology and Liver Disease In a recent retrospective review of the efficacy of ESWL as an adjunct to endoscopic therapy, Kozarek and colleagues (2002) examined 40 patients who underwent a total of 46 ESWL sessio ns (average 1.15 sessions per patient). Eighty percent (80%) of patients did not require surgery and had significant pain relief, reduced number of hospitalizations, and r educed narcotic use as compared to the pre-ESWL period over a mean 2.4 years follow-up. Only randomized controlled studies comparing surgical, medical, and endoscopic techniques will allow us to determine the true long-term efficacy of pancreatic d uct stenting for stricture therapy. There remain many unanswered questions: Which patients are the best candidates? Is proximal pancreatic ductal dilatation a pre- r equisite? Does the response to stenting depend on the etiology of the chronic pancreatitis? Finally, as noted, how FIGURE 138-4. A 41-year-old woman with a history of abdominal pain, pancreatitis and pancreatic calcification on computed tomography scan. Abdominal radiograph reveals solitary radio-opaque stone in head/body region (A). Pancreatogram reveals an 8 mm obstructing stone in body of pancreas pancreatic duct (B). A 0.018 inch diameter guide wire was advanced beyond the stone. Further contrast filling of duct demonstrating upstream dilatation. Stone extraction with basket was unsuccessful (C). Extracorporeal shock wave lithotripsy performed with excellent fragmentation of stone. Pancreatogram 1 week post-ESWL. Mild duct irregularity in body of pancreas duct with minimal upstream dilatation. All stone fragments were removed and no pancreatic stent was placed. (Patient reported a history of abdominal injury in an auto accident over 10 years before the onset of symptoms) (D). A DC B [...]... radiation therapy Following combined modality chemoradiotherapy, chemotherapy alone was administered (5-FU 200 mg/m2/d as a continuous infusion) in two 6-week courses during weeks 9 to 14 and 17 to 22 There were significant grade 3 and 4 gastrointestinal (GI) toxicities, including vomiting, mucositis, diarrhea, and GI bleeding in the IFN-based chemotherapy, requiring hospitalization in 43% of patients However,... of inactivating the CCK-releasing peptide that exists in the proximal small bowel and is largely responsible for stimulating CCK release In these patients, it can be demonstrated that there are high levels of CCK in the blood This 800 / Advanced Therapy in Gastroenterology and Liver Disease is a proximal small intestine phenomenon and the pancreatic proteases must be delivered to the upper small intestine... Inc, WinstonSalem, NC) may be performed prior to needle-knife puncture into the pseudocyst The needle-knife puncture is performed perpendicular to the lumen with short bursts of cautery and a forceful entry into the pseudocyst cavity This perpendicular approach will minimize tracking into the gut wall and reduce bleeding A guide wire is placed into the pseudocyst and coiled in the cavity to maintain... deficiencies particularly on bone mineral accretion, neurological function, and membrane integrity Patients with PI are routinely supplemented with fat-soluble vitamins at between one and two times the normal Much work on essential fatty acid levels (linoleic acid [18:2n-6] and alpha-linolenic acid [18:3n-3], and the longer products, arachidonic acid [20:4n-6] and eicosapentanoic acid [20:5n-3] and docosahexanoic... pancreatic ducts and the parenchyma We are continuing to evaluate EUS and secretin against each other in patients with suspected small duct disease who present with chronic abdominal pain and negative radiographic testing A preliminary report from our laboratory indicates that EUS was only 57% as sensitive and 64% as specific as a secretin test in patients with unexplained abdominal pain who ultimately... The pain of chronic pancreatitis often does not follow a classical pattern, such as that seen in acute pancreatitis where the pain is mid-epigastric and radiates to the back Indeed, chronic pancreatitis pain may mimic other causes of abdominal pain and may be quite nonspecific in its clinical presentation The pain can be constant or intermittent and there may be frequent pain-free intervals Eating may... R9 7-0 4 This phase III trial randomized 518 resected PC patients to 5-FU continuous infusion (250 mg/m2/d for 3 weeks), followed by 5-FU continuous infusion (250 mg/m2/d) during radiation therapy (50.4 Gy in 1.8 Gy/fractions), followed by 2 cycles 5-FU continuous The challenges in managing patients with pancreatic cancer (PC) are underscored by the seemingly immutable survival data, including a 5-year... question being asked was whether Gemcitabine before and after 5-FU based chemoradiotherapy would be more efficacious than continuous infusion 5-FU before and after the same 5-FU based chemoradiotherapy In 1997, when this study was designed, there was inadequate knowledge regarding how to safely administer Gemcitabine concurrently with irradiation to allow for concurrent Gemcitabine and radiotherapy This... approximately 40-fold by having two CFTR mutations, 20-fold by having a SPINK1 mutation, and 900fold by having both two CFTR mutations and a SPINK1 mutation (Grendell, 2003).* Diagnosis The diagnosis of chronic pancreatitis is rather easy in patients with big duct disease and quite challenging in patients with small duct disease Table 13 9-2 lists diagnostic tests that are carried out worldwide in the examination... have been documented in SDS patients Patients should have their bone mineral density monitored Serial radiographic determinations in patients with skeletal deformities or examinations of sites of bony pain (eg, spinal radiographs for vertebral compression fractures) should be performed 810 / Advanced Therapy in Gastroenterology and Liver Disease Orthopedic interventions may be needed With exocrine pancreatic . nonspecific in its clinical presentation. The pain can be constant or intermittent and there may be frequent pain-free intervals. Eating may exacerbate the pain, leading to fear of eating and w eight. the pain of chronic pancreatitis could not be distinguished in any accurate manner 800 / Advanced Therapy in Gastroenterology and Liver Disease is a proximal small intestine phenomenon and the. 782 / Advanced Therapy in Gastroenterology and Liver Disease Since then there have been several studies that have repro- duced these results, although a convincing benefit in mortality has

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