Adjacent Duodenum Research Articles

A Pilot Study of Percutaneous Cholecystoenteric Anastomosis: A New Option for High-Risk Patients with Symptomatic Gallstones

PurposeTo evaluate the safety and effectiveness of percutaneous cholecystoenteric anastomosis (PCEA) creation in patients with indwelling cholecystostomy tubes who are high-risk surgical candidates. Materials and MethodsFourteen (male, 10; female, 4) patients with a mean age of 79 years (range, 53–92 years) with previously inserted cholecystostomy tubes underwent PCEA with the adjacent duodenum using a lumen-apposing metal stent (LAMS) between January 2015 and October 2022. Intraprocedural adverse events and postprocedural safety and effectiveness outcomes were evaluated. Nine procedures were performed under sedation and 5 under general anesthesia. ResultsTechnical success was achieved in 100% of the patients. In 12 patients (86%), the existing cholecystostomy tube was removed after the insertion of the LAMS. Three patients (21%) had a pre-existing cholecystoduodenal fistula, in which the stent was placed, and 11 (79%) underwent creation of a de novo anastomosis. The mean procedure time was 1.5 hours (range, 1–2 hours). The mean length of stay after the procedure was 2.4 days (range, 1–10 days). There were no intraprocedural adverse events. One patient with severe pre-existing cardiac comorbidities died during his postprocedural stay despite a technically successful procedure. One patient had delayed closure of the long-standing cholecystocutaneous tract. ConclusionsEarly clinical experience with PCEA using an LAMS suggests that it is a safe and effective option for the creation of internal gallbladder drainage in patients who are not candidates for surgical cholecystectomy.

Zinc Phosphide Intoxication in Three Horses: A Case Repor

Three adult crossbred Thoroughbred horses died in June 2018 at a ranch near Hamedan, Iran. Rigor mortis was evident with no signs of post-mortem bloating in the carcasses. The neck muscles appeared excessively cyanotic in necropsy. In addition, widespread petechiae were observed on the inner surface of the thoracic intercostal muscles. Dropsy was visible in the inner surface of the abdominal wall and peritoneum. The stomach content was watery and dark gray. Furthermore, gastric mucosa was also gray. The livers had a dark appearance and the adjacent duodenum was gaseous and blackened. The kidneys showed autolysis with areas of medullary hyperemia. In addition to decomposition, a specific odor similar to the garlic aroma or natural gas could be smelled from the carcasses. Tissues and contents of various organs, as well as food and water samples, were collected for diagnostic tests. Preliminary toxicological studies showed detectable amounts of phosphide in the samples collected from gastric contents of the animals, and complementary tests confirmed the presence of zinc phosphide in the concentrate feed.

Gallbladder-duodenal fistula detected by ultrasound - a case report.

Gallbladder-duodenal (cholecystoduodenal) fistula is an uncommon bilioenteric fistula between the gallbladder and the duodenum. It usually occurs following a chronic case of cholecystitis upon which the gallbladder adheres to the adjacent duodenum, and a stone penetrates through the wall. The case presented herein is that of a gallbladder-duodenal fistula detected primarily with the use of ultrasound imaging, and subsequently confirmed by computed tomography. The patient is a 54-year-old woman who was admitted with upper abdominal pain. The fistula was caused by chronic cholecystitis, however no gallstones were present in the duodenum. Surgical management was undertaken for the patient, and the recovery was uneventful.

901 INTRAPERITONEAL EUS-GUIDED RESCUE OF A GASTROJEJUNAL ANASTOMOSIS

A 74-year-old man with history of diabetes mellitus, hypertension and advanced pancreatic adenocarcinoma s/p covered metal biliary stent placement one year prior presented with nausea, vomiting and progressive intolerance to oral intake over a one-week period. CT of the abdomen demonstrated invasion of the tumor into the adjacent duodenum causing a gastric outlet obstruction (GOO). Surgical consultation felt risk of perioperative morbidity and mortality was prohibitively elevated and gastroenterology was consulted.

Groove Pancreatitis - Cause of Recurrent Pancreatitis

Abstract Background. Groove pancreatitis or paraduodenal pancreatitis represents a rare type of pancreatitis, and can be classified into cystic dystrophy of the duodenal wall in heterotopic pancreas, paraduodenal cyst or myoadenomatosis. Case presentation. We present a case of a 58 year old man, drinker and smoker who was admitted in the Department of Gastroenterology for abdominal pain, weight loss and nausea. From his history we have noticed frequent presentations of recurrent acute pancreatitis in the last two years. Laboratory tests have revealed cholestasis, high value of lipase and high value of amylase, with normal value of CA 19.9. The magnetic resonance from the last two years showed the same appearances: a large and edematous head of pancreas, a thickening of the wall of adjacent duodenum and an inhomogeneous area with cystic transformation in the head of the pancreas. We performed endoscopic ultrasound with fine needle aspiration. The histopathological result showed only inflammatory cells. We have established the diagnosis of groove pancreatitis. Conclusion. Groove pancreatitis represents a rare condition, with an incidence of 0.4%-14% on biopsies. Endoscopic ultrasound is the best method for diagnosis, it could evaluate also the duodenal wall.

What Is the Role of Upper Endoscopy in Patients With Gastric Pneumatosis?

Gastric pneumatosis is a rare finding. It can be seen with both gastric emphysema and emphysematous gastritis. Both may have similar presentations and differentiating between the two conditions is difficult radiographically. However, making the distinction between them is crucial; as GE has a benign clinical course while EG is more maleficent, and carries significant mortality. Early endoscopy may help differentiate between the two processes. We present a series of two immunocompromised patients that presented with radiographic findings consistent with gastric pneumatosis. A 52 y.o male with history of HIV, diabetes, and dialysis dependent end-stage renal disease presented with a 3-day history of epigastric fullness, vomiting, and chills. He was febrile at 101.6F and his abdominal exam revealed mild distension, active bowel sounds with no appreciable tenderness. CT abdomen revealed a distended stomach with air within the gastric wall as well as the presence of portal venous gas. Endoscopy was performed on the 2nd day of hospitalization and showed erythematous gastric mucosa in the body and antrum. He improved with conservative measures including antibiotics and was eventually discharged. The second case was a 58 y.o female with history of stage 4 squamous cell lung carcinoma with bony metastases, ESRD on dialysis, systolic heart failure, and diabetes who presented with left hip pain and found to have left proximal femur erosion with effusion and was admitted for hemiarthroplasty. On POD #1 she became unstable and was transferred to the MICU. A CT abdomen revealed portal venous gas with pneumatosis of the stomach and adjacent duodenum. Endoscopy performed the same night revealed a diffusely ulcerated, edematous hemorrhagic gastric mucosa sparing the pre-pyloric region. The patient was a poor surgical candidate and was subsequently managed medically. Despite resuscitative efforts the patient experienced cardiac arrest and expired. Treatment for GE is supportive as this condition tends to be self limiting. Management of EG is more active including correction of acid-base and electrolyte abnormalities, fluid resuscitation and IV antibiotics. Gastrectomy may be necessary in EG if medical management fails. As both conditions can present similarly differentiating between the two is pivotal. We found early endoscopy helped guide our management. We recommend consideration of endoscopy as part of the evaluation of patients presenting with gastric pneumatosis.2622_A Figure 1. Coronal CT image showing portal venous gas with pneumatosis of the stomach and the adjacent duodenum2622_B Figure 2. Transverse CT image showing portal venous gas with pneumatosis of the stomach and the adjacent duodenum

Butter Blood

Acute pancreatitis induced by hypertriglyceridemia is a rare but well-established complication, though the exact pathogenesis remains unclear. Estimated rates account for 1-4% of acute pancreatitis cases with noticeable rising risk as serum levels increase (triglycerides > 1000 carry 5% risk; triglycerides > 2000 carry 10-20% risk). Occurrence is more commonly associated in those with acquired disorders (such as diabetes mellitus, hypothyroidism, obesity, pregnancy, medication-induced, nephrotic syndrome) than in those with inborn errors of lipoprotein metabolism (such as familial combined hyperlipidemia, familial hypertriglyceridemia). Therapeutic measures in such patients include standard pancreatitis management, along with lipidlowering oral agents, low-molecular weight heparin, and insulin in those who are diabetic. In situations where these measures fail to improve patient clinic course, plasma exchange is used to expedite removal of triglycerides (TG). Here, we present a case of a noncompliant, insulin-dependent diabetic patient found to have hypertriglyceridemia-induced pancreatitis. Case: A 40-year-old African American male with poorly-controlled, insulin-dependent diabetes presented to our facility with complaints of abdominal pain accompanied with nausea and vomiting. Laboratory examination was consistent with severe pancreatitis and mild ketoacidosis (Table 1). Abdominal CT scan confirmed the clinical diagnosis of severe pancreatitis of the pancreatic head and uncinate process with inflammation of the adjacent duodenum (Image 1-2). The appearance of latescent serum accompanied with lipemic serum pointed toward a diagnosis of pancreatitis secondary to hypertriglyceridemia.Figure 1Figure 2Figure 3As our patient did not carry a familial history of genetic abnormalities of lipoprotein metabolism, we attributed the hypertriglyceridemia secondary to his poorly-controlled diabetes and diabetic ketoacidosis. The patient was treated with gemfibrozil, atorvastatin, IV fluids, bowel rest, and insulin infusion. Improvement of his triglyceride level coincided with improvement in blood sugars and abdominal pain. Plasmapharesis was not undertaken in this patient given improvement with conventional therapies.

Management of splenic and pancreatic trauma

The spleen and pancreas are at risk for injury during abdominal trauma. The spleen is more commonly injured because of its fragile structure and its position immediately beneath the ribs. Injury to the more deeply placed pancreas is classically characterized by discordance between the severity of pancreatic injury and its initial clinical expression. For the patient who presents with hemorrhagic shock and ultrasound evidence of major hemoperitoneum, urgent "damage control" laparotomy is essential; if splenic injury is the cause, prompt "hemostatic" splenectomy should be performed. Direct pancreatic injury is rarely the cause of major hemorrhage unless a major neighboring vessel is injured, but if there is destruction of the pancreatic head, a two-stage pancreatoduodenectomy (PD) may be indicated. At open laparotomy when the patient's hemodynamic status can be stabilized, it may be possible to control splenic bleeding without splenectomy; it is always essential to search for injury to the pancreatic duct and/or the adjacent duodenum. Pancreatic contusion without ductal rupture is usually treated by drain placement adjacent to the injury; ductal injuries of the pancreatic body or tail are treated by resection (distal pancreatectomy with or without splenectomy), with generally benign consequences. For injuries of the pancreatic head with pancreatic duct disruption, wide drainage is usually performed because emergency PD is a complex gesture prone to poor results. Postoperatively, the placement of a ductal stent by endoscopic retrograde catheterization may be decided, while management of an isolated pancreatic fistula is often straightforward. Non-operative management is the rule for the trauma victim who is hemodynamically stable. In addition to the clinical examination and conventional laboratory tests, investigations should include an abdominothoracic CT scan with contrast injection, allowing identification of all traumatized organs and assessment of the severity of injury. In this context, non-operative management (NOM) has gradually become the standard as long as the patient remains hemodynamically stable and there is no suspicion of injury to hollow viscera, with the patient being carefully monitored on a surgical service. The development of arteriography with splenic artery embolization has increased the rate of splenic salvage; this can be performed electively based on specific indications (blush on CT, pseudoaneurysm, arteriovenous fistula), and may also be considered for severe splenic injury, abundant hemoperitoneum, or severe polytrauma. For pancreatic injury, in addition to CT scan, magnetic resonance pancreatography (MRCP) or even endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to identify a ductal rupture. If the pancreatic duct is intact, laboratory and CT imaging surveillance is performed just as for splenic injury. In case of pancreatic ductal injury, ERCP stenting can be considered. However, if this is unsuccessful, the therapeutic decision can be difficult: while NOM can still be successful, complications may arise that are difficult to treat while distal pancreatectomy, although initially more agressive may avoid these complications if performed early.

En bloc Pancreaticodudenectomy with Colectomy for Locally Advanced Right Sided Colon Cancer

A 57 year old male presented to our outpatient clinic with history of on and off melena, weight loss and decreasing appetite for 10 months duration and a noticeable mass on the right upper quadrant. Abdominal examination revealed an intra-abdominal lump in right upper quadrant which was subsequently evaluated by colonoscopy, which revealed an ulcero-proliferative growth in the hepatic flexure and the biopsy from it confirmed well-differentiated adenocarcinoma. Contrast enhanced computed tomography demonstrated hepatic flexure mass with possible invasion into adjacent duodenum without features of advanced disease. After completion of necessary preoperative assessment and investigations, patient was explored with curative intent and underwent extended right hemicolectomy with en bloc pancreaticodudenectomy. Patient was discharged on 10th postoperative day and at 14 months follows up; he was doing well without any evidence of recurrence.

A Rare Presentation of an Aortoenteric Fistula After Aortic Aneurysm Repair

Aortoenteric fistula is a well described complication of endovascular repair of abdominal aortic aneurysms (AAA). Aortoenteric fistula formation is rare but potentially life-threatening and has been reported in 0.6%-2% of cases. Multiple causes of aortoenteric fistulas have been described including endograft infection, kinking of endograft within the aorta, or simple erosion of the foreign material. Although acute gastrointestinal bleeding is the most common presentation, chronic gastrointestinal bleeding and asymptomatic presentation have been described. Given its close proximity to the descending aorta, the third portion of the duodenum is the most common location for aortoenteric fistulas. We report an unusual case of an asymptomatic aortoenteric fistula to the duodenal bulb. An 80 year old female with history of chronic obstructive pulmonary disease, hypertension and peripheral vascular disease initially presented with intermittent abdominal pain and hematemesis. CT scan showed an infrarenal 6.5 cm AAA compressing the adjacent duodenum with evidence of air within the thrombus suggesting presence of an aortoenteric fistula to third portion of the duodenum. Patient underwent emergent placement of aortouniiliac endograft stent for repair of AAA by interventional radiology. She was maintained on total parenteral nutrition post procedure. Two months after AAA repair, an upper endoscopy was performed prior to the initiation of oral feeding and showed a 3 cm ulcer with graft material in the duodenal bulb. Patient was asymptomatic at this time with no evidence of gastrointestinal bleeding. There was no evidence of graft infection or migration. Although an unusual location, we believe the patient had developed a second aortoenteric fistula to the duodenal bulb. In recent years, endovascular aneurysm repair is the procedure of choice for repair of infrarenal aortic aneurysms. There have been multiple rare complications associated with this procedure, aortoenteric fistulas being one of the most described. Most patients present with acute gastrointestinal bleeding with fistulas affecting the third portion of the duodenum necessitating endovascular or surgical repair. There are no reported cases of asymptomatic fistulization to the duodenal bulb. Gastroenterologists should be aware of this unusual presentation.Figure 1

Use of a duodenal serosal patch in the repair of a colon rupture in a female Solomon Island eclectus parrot

Case Description-A 444-g (0.98-lb) 4-year-old sexually intact female Solomon Island eclectus parrot (Eclectus roratus solomonensis) was referred and evaluated for a suspected colonic obstruction. Clinical Findings-The parrot had a 3-day history of not passing feces and lack of appetite following treatment of dystocia that included percutaneous collapse of the egg and manual removal of egg fragments via the cloaca. During this procedure, a tear in the cloacal mucosa developed. The tear was repaired via a midline cloacotomy. Although clinically stable at the time of referral, the parrot became lethargic and bradycardic and had delayed crop emptying. Treatment and Outcome-A midline celiotomy and cloacotomy were performed to relieve the colonic obstruction, during which the severely distended colon ruptured. The colonic defects were closed in a simple interrupted pattern, and a serosal patch was applied by use of the adjacent duodenum. The bird recovered uneventfully from anesthesia and was passing voluminous feces with mildly increased effort within 1 hour after surgery. At 3 weeks after surgery, the parrot was passing feces with no increase in effort and had a normal appetite. Clinical Relevance-Application of a duodenal serosal patch for repair of a colon rupture was successful in this parrot. Gastrointestinal obstruction is rare in birds, but should be considered in birds that have regurgitation, decreased fecal production, and gastrointestinal dilation. Because birds lack an omentum, serosal patching with adjacent duodenum should be considered as a viable option in avian surgery.

Sonographic Findings in Groove Pancreatitis

Groove pancreatitis is a rare form of chronic pancreatitis involving the anatomic plane between the pancreatic head and duodenum. The radiographic diagnosis remains challenging, and most patients undergo exploratory laparotomy on suspicion of a periampullary malignancy. The appearance of groove pancreatitis on transabdominal and intraoperative sonography has rarely been reported in the literature. The sonographic findings in our 2 patients included a hypoechoic thin area between the pancreatic head and duodenum, a hyperechoic and thickened wall of the adjacent duodenum, and a heterogeneous or hyperechoic dorsocranial part of the pancreatic head.

Nododuodenal Fistula Caused by Tuberculosis

A 39-year-old woman presented to our hospital with upper abdominal pain. She had been taking anti-tuberculosis medications for 3 months because of pulmonary tuberculosis. Esophagogastroduodenoscopy showed a creamy discharge from an opening in the duodenal bulb (Fig. 1), and abdominal computed tomography with coronal reformatting showed that the lymph nodes had eroded the adjacent duodenum, resulting in a small oval collection of gas (Fig. 2). The continuous use of anti-tuberculosis medication resulted in complete healing of the duodenal fistula. Tuberculous lesions of the duodenal bulb may primarily affect the duodenum or produce compression because of the enlarged lymph nodes. The common complications of duodenal tuberculosis are fistulous communications with adjacent structures, perforation, and obstruction. Our case was a rare but interesting case that showed a creamy discharge from a nododuodenal fistula resulting from tuberculosis. Figure 1 Esophagogastroduodenoscopy identified creamy discharges from an opening in the duodenal bulb. Figure 2 Abdominal computed tomogaraphy with coronal reformatting shows that the lymph nodes eroded the adjacent duodenum, resulting in a small oval gas collection in the suprapancreatic lymph nodes with foci of low attenuation (arrow).

Cholecystitis of a duplicated gallbladder complicated by a cholecystoenteric fistula

Gallbladder duplications are uncommon anatomic variants that are sometimes mistaken for other entities on imaging. We present a surgically confirmed case of cholecystitis in a ductular-type duplicated gallbladder complicated by the formation of an inflammatory fistula to the adjacent duodenum. Both US and magnetic resonance cholangiopancreatography were performed preoperatively, in addition to intraoperative cholangiography, which confirmed the presence of a duplicated gallbladder.

Extrahepatic Portal Vein Aneurysm—Report of Six Patients and Review of the Literature

Extrahepatic portal vein aneurysm is a rare condition. We report six patients with extrahepatic portal vein aneurysm, four of whom were surgically treated. In addition, a review of the literature was performed to examine natural history, management, and outcomes regarding portal vein aneurysm. Patients seen at our institution with extrahepatic portal vein aneurysm greater than 1.9 cm in diameter were reviewed (1998 to 2006). There were five females and one male; median age was 66.5 (30–77). Computed tomography (CT) scan was utilized for diagnosis in all cases. The median diameter of the aneurysm was 4.7 cm (2.7–6.0). Indications for surgery included gallstone pancreatitis, mass effect on the adjacent duodenum, a peripancreatic mass, and liver cirrhosis. Three patients underwent aneurysm resection, and one patient had an orthotropic liver transplant. Two patients were managed with observation. The median follow-up from first presentation and surgery was 50 months (9–181) and 5 months (2–73), respectively. At last follow-up, five patients were alive with radiologically proven portal vein patency. One patient died 2 months after liver transplantation. There was no case of aneurysmal rupture. One patient had intramural thrombus at presentation that resolved with conservative treatment. This report suggests that symptomatic aneurysms can be safely resected with excellent patency.

Unique distribution of interstitial cells of Cajal in the feline pylorus

The feline gastrointestinal (GI) tract is an important model for GI physiology but no immunohistochemical assessment of interstitial cells of Cajal (ICC) has been performed because of the lack of suitable antibodies. The aim of the present study was to investigate the various types of ICC and associated nerve structures in the pyloric sphincter region, by using immunohistochemistry and electron microscopy to complement functional studies. In the sphincter, ICC associated with Auerbach's plexus (ICC-AP) were markedly decreased within a region of 6-8 mm in length, thereby forming an interruption in this network of ICC-AP, which is otherwise continuous from corpus to distal ileum. In contrast, intramuscular ICC (ICC-IM) were abundant within the pylorus, especially at the inner edge of the circular muscle adjacent to the submucosa. Similar distribution patterns of nerves positive for vesicular acetylcholine transporter (VAChT), nitric oxide synthase (NOS) and substance P (SP) were encountered. Quantification showed a significantly higher number of ICC-IM and the various types of nerves in the pylorus compared with the circular muscle layers in the adjacent antrum and duodenum. Electron-microscopic studies demonstrated that ICC-IM were closely associated with enteric nerves through synapse-like junctions and with smooth muscle cells through gap junctions. Thus, for the first time, immunohistochemical studies have been successful in documenting the unique distribution of ICC in the feline pylorus. A lack of ICC-AP guarantees the distinct properties of antral and duodenal pacemaker activities. ICC-IM are associated with enteric nerves, which are concentrated in the inner portion of the circular muscle layer, being part of a unique innervation pattern of the sphincter.

Migratory Gallstone Causing Duodenal Obstruction

An 81-year-old man presented with abdominal pain and repeated bilious vomiting for 1 day. He had cholelithiasis for 5 years, documented by CT (A). This was confirmed on the lowest slice of a thoracic CT performed 6 months earlier for an unrelated pulmonary condition (B). Note the migration of the gallstone from the fundus of the gallbladder to the infundibulum. After admission, a CT demonstrated a fluid-filled gallbladder with a small amount of air and the absence of cholelithiasis (C). The duodenum was totally obstructed at the fourth portion by a calcified mass (D). At operation, a single gallstone measuring 5 5 3 cm (E) was present just distal to the ligament of Treitz. It was maneuvered distally, and removed by a proximal enterotomy. Based on the recent experience of others, no attempt was made to remove the gallbladder or close the cholecystoduodenal fistula. Recovery was uneventful. Cholecystoduodenal fistula commonly develops from the pressure and irritation of a large gallstone eroding through the adherent walls of the gallbladder and the adjacent duodenum, allowing the gallstone to enter the gastrointestinal tract and obstruct it. These images, obtained over a 5-year period, document the migration of the gallstone from the fundus of the gallbladder to the infundibulum and, ultimately, into the lumen of the duodenum, documenting the progression of disease. The most common site of intestinal obstruction is at the distal ileum where the lumen normally narrows, but it can occur anywhere along the gastrointestinal tract. Because of the size of this gallstone and the natural angulation caused by the attachment of the ligament of Treitz, a high obstruction resulted and accounted for the frequent bilious emesis seen in this patient.

Bacteriological implications in the pathogenesis of secondary aortoenteric fistulas.

Abstract The role of bacterial infection in the pathogenesis of aorto-enteric fistula was examined by a collective review of the clinical features and bacteriology in 213 patients. The most common presentation, gastrointestinal bleeding, occurred in 49 per cent of patients, although 32 per cent had systemic or local signs of infection as a presenting symptom. Results of intraoperative cultures were available in 115 patients, 33 of whom had two or more isolates. The predominant organisms were Escherichia coli, Staphylococcus aureus, group D Streptococcus and Bacteroides spp. The Gram-positive aerobic cocci predominated in fistulas developing within the first postoperative year which is compatible with a primary infection due to intraoperative contamination with skin flora. The Enterobacteriaceae and anaerobes showed no predilection for early or late occurring fistulas, suggesting that infection in these patients may be secondary to mechanical erosion of the graft through the adjacent duodenum. In either event, the likelihood that the aorto-enteric fistula is complicated by prosthetic infection should be seriously considered by the surgeon in planning the operative procedure.

Pancreatic and Peripancreatic Diseases Mimicking Primary Pancreatic Neoplasia

A variety of anatomic variants and pathologic conditions in and around the pancreas may simulate primary pancreatic neoplasia at routine abdominal cross-sectional imaging. An ambiguous lesion whose appearance suggests a pancreatic origin requires a broad differential diagnosis that can subsequently be narrowed on the basis of both clinical history and features at optimal computed tomography (CT) and magnetic resonance (MR) imaging. Pancreas-specific multidetector CT and MR imaging techniques with thin collimation, multiplanar and multiphasic scans, and newly introduced curved planar reformation may help avoid potential diagnostic pitfalls. These techniques can help identify and characterize a mass in multiple viewing planes, thereby helping distinguish a true pancreatic neoplasm from peripancreatic adenopathy or from a tumor of the adjacent duodenum or small bowel. They can also help determine the cause of a tumor. It is important that the radiologist be familiar with the wide spectrum of anatomic variants and disease entities that can mimic primary pancreatic neoplasia in order to initiate the appropriate lesion-specific work-up and treatment and avoid unnecessary tests or procedures, including surgery.

Age- and Disease-Related Methylation of Multiple Genes in Nonneoplastic Duodenum and in Duodenal Juice

Methylation of CpG islands contributes to gene silencing during cancer development, and although some methylation alterations are promising diagnostic markers of cancer, some CpG islands are also methylated in normal tissues. We have previously observed that some normally unmethylated CpG islands that undergo methylation in pancreatic cancers are normally methylated in the adjacent duodenum. Because duodenal methylation patterns are an important consideration when sampling pancreatic tissues for pancreatic cancer methylation alterations, we determined the DNA methylation patterns of 24 genes in the normal duodenum of patients with pancreatic disease and related these patterns to demographic factors. The nonneoplastic duodenal mucosa of 158 patients with pancreatic carcinoma and 41 patients with chronic pancreatitis was analyzed using methylation-specific PCR and combined bisulfite restriction analysis. Secretin-stimulated pancreatic/duodenal juice from 15 individuals undergoing endoscopic investigation for upper gastrointestinal disease was also analyzed. Low-level methylation was detectable by methylation-specific PCR in the nonneoplastic duodenum of many patients with pancreatic cancer and chronic pancreatitis as well as in the pancreaticoduodenal secretions of patients without pancreaticobiliary disease. For many genes, the prevalence of methylation increased with age and was more prevalent in patients with pancreatic cancer than in age-matched patients with chronic pancreatitis. Our results indicate that strategies to detect pancreatic cancer using aberrantly methylated genes should rely on analysis of pure pancreatic juice rather than on pancreatic juice collected within the duodenal lumen. Patients who develop pancreatic cancer may have a greater propensity to methylate CpG islands than age-matched controls.