Friday, December 1, 2023
Klaus Mergener, MD, PhD, FACP, FACG, Private Practice, Digestive Health Specialists, Tacoma, Washington. Dr. Mergener is a Fellow of the American College of Physicians and the American College of Gastroenterology (ACG). He is a member of the American Society for Gastrointestinal Endoscopy (ASGE) and serves as the ASGE CPT representative to the American Medical Association. Dr. Mergener is also the ACG Governor for Washington State and serves on the National GI Carrier Advisory Committee.
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Klaus Mergener, MD, PhD, FACP, FACG, Private Practice, Digestive Health Specialists, Tacoma, Washington. Dr. Mergener is a Fellow of the American College of Physicians and the American College of Gastroenterology (ACG). He is a member of the American Society for Gastrointestinal Endoscopy (ASGE) and serves as the ASGE CPT representative to the American Medical Association. Dr. Mergener is also the ACG Governor for Washington State and serves on the National GI Carrier Advisory Committee.
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Pancreatic diseases were again a major focus of oral and poster presentations during this year's annual scientific meeting of the American College of Gastroenterology. This review discusses a subset of these presentations related to the diagnosis and management of acute pancreatitis, chronic pancreatitis, and pancreatic neoplasms. These topic forums were chosen specifically for their interest to practicing internists and gastroenterologists.
Acute pancreatitis is an inflammatory process that is manifest clinically by epigastric and back pain, nausea, and vomiting. In mild cases, these signs and symptoms gradually improve as the local inflammatory process resolves. In severe acute pancreatitis, systemic complications, including shock, renal failure, and adult respiratory distress syndrome, may supervene. The overall mortality of acute pancreatitis remains approximately 5% to 10%.
Gallstones and alcohol are the 2 most common causes of acute pancreatitis, accounting for more than 80% of cases. A large number of less common causes (including medications, trauma, neoplasms, anatomic variants, metabolic problems) may be identified in 10% of patients.
Endoscopic retrograde cholangiopancreatography (ERCP) carries a substantial risk of postprocedure pancreatitis (overall > 5% in prospective trials but as high as > 20% in subgroups of patients). A large number of studies have evaluated various medications administered before ERCP in an effort to minimize the risk of post-ERCP pancreatitis, but to date most have been found to be ineffective.
During this year's meeting, Schwartz and colleagues[1] presented the results of a prospective, randomized, placebo-controlled trial in 326 patients evaluating the effect of lidocaine sprayed on the ampulla of Vater. Unfortunately, this intervention was not found to result in a lower incidence of post-ERCP pancreatitis. In a relatively small trial of 62 patients, Ramdhaney and colleagues[2] found that volume expansion with 10% Dextran-40 at a dose of 3 mL/kg before ERCP led to a decrease in serum amylase but did not significantly alter the number of patients who developed post-ERCP pancreatitis.
Several poster presentations focused on rare causes of acute pancreatitis. Belitsis and colleagues[3] described a patient who was found to have the unusual combination of an intraductal papillary mucinous tumor and pancreas divisum. Duterte and associates[4] reminded us that anatomic abnormalities other than pancreas divisum, namely an annular pancreas, need to be included in the differential diagnosis of acute pancreatitis. Likewise, rare genetic syndromes, such as familial adenomatous polyposis, can be associated with acute pancreatitis due to ampullary obstruction from duodenal adenomas.[5] Chaudary and colleagues[6] saw 7 patients (of 1700) who may have developed acute pancreatitis as a result of interferon and ribavirin therapy for chronic hepatitis C. In addition, Khan and coworkers[7] performed a retrospective analysis of children undergoing stem cell transplantation and found that 8 cases of acute pancreatitis occurred in 445 transplants (1.8%). Seven of 8 patients recovered without long-term sequelae, and no death occurred in this series. Jayadevan and colleagues[8] described a patient with acute pancreatitis that was caused by a solid pseudopapillary tumor of the pancreas. This rare tumor accounts for approximately 1% to 2% of pancreatic exocrine tumors, occurs mostly in women, and is often slow growing and incidentally diagnosed.
Although the principal treatment goals in patients with acute pancreatitis remain supportive care and the early recognition and management of complications, the identification of patients who may benefit from ERCP is also important. As the result of several randomized controlled trials, it is commonly accepted that ERCP is indicated in the acute setting when severe pancreatitis is complicated by progressive jaundice or cholangitis.[9]
One of the highlights at this year's meeting was a debate between 2 experts in the field of pancreatic disease, Dr. Kozarek and Dr. Banks, who discussed advantages and disadvantages of performing ERCP to seal and stent a pancreatic duct disruption in patients with acute pancreatitis. According to Dr. Kozarek,[10] pancreatic ductal disruption or leak is a common event in severe pancreatitis (Figures 1 and 2), occurring in 37% of 144 patients admitted with severe pancreatitis at Virginia Mason Medical Center during a 5-year period.[11] Ductal disruption may lead to peripancreatic fluid collections, fistulae, pancreatic ascites, and necrosis and, if present, predicts a prolonged length of hospital stay. Dr. Kozarek argued that treatment of such leaks with a combination of endoscopic stenting of the pancreatic duct, percutaneous drains, and surgery as necessary is safe, will promote healing of the leak, and will improve patient outcome.
Figure 1. ERCP in a patient with severe acute pancreatitis showing a normal common bile duct and a pancreatic ductal disruption with contrast extravasation in the head of the gland.
Figure 2. Corresponding CT scan to Figure 1, showing a large acute fluid collection (*) due to pancreatic ductal disruption.
Dr. Banks[12] expressed that there is a lack of controlled data to support this approach, especially within the first few days of presentation, when a large number of these patients are acutely ill with organ failure and hemodynamic instability. He stressed that the primary treatment goal during this early period (which he arbitrarily defined as < 2 weeks from presentation) remains supportive care and that one of the most common mistakes made in the early management of acute pancreatitis is insufficient rehydration. However, Dr. Banks conceded that there is a subgroup of patients, specifically those with pancreatic ascites and peripancreatic fluid collections, who may benefit from an ERCP (in his opinion usually after the first 2 weeks), especially if they fail to improve.
Both experts stressed the importance of a multidisciplinary approach to this difficult patient population. Further studies are needed to better define the role of pancreatic duct stenting in severe acute pancreatitis.
No obvious etiology is identifiable by history, laboratory tests, and standard imaging studies in 10% to 20% of patients with acute pancreatitis. Consensus has not been achieved to date on the optimal approach to the diagnostic evaluation of these patients. Dr. Sherman and Dr. Steinberg discussed the issue of performing ERCP with sphincter of Oddi manometry (SOM) in this patient population in an effort to detect sphincter of Oddi dysfunction (SOD).
According to Dr. Sherman, SOD is the most common problem identified in patients undergoing evaluation for "idiopathic" pancreatitis at Indiana University. When SOM is performed in this patient population, approximately 35% will be found to have SOD. Dr. Sherman[13] stressed the importance of performing both biliary and pancreatic manometry and of performing both biliary and pancreatic sphincterotomy if manometry is found to be abnormal. In his experience, symptoms improved in 83% of patients who were found to have elevated sphincter of Oddi pressures vs only 33% of patients who had normal sphincter pressures. A detailed review of this complicated topic was recently published by Sherman and Lehman.[14]
Dr. Steinberg[15] emphasized several issues related to SOD: (1) normal values for sphincter pressures are poorly standardized; (2) the natural history of SOD, especially as it relates to idiopathic pancreatitis, is poorly understood; and (3) the complication rate of performing sphincterotomy in this patient population may be as high as 20% to 40%. In his opinion (and the opinion of this reviewer), there remains a lack of well-controlled clinical trials in this area, and questions such as who should undergo SOM, whether to study one or both papillary sphincters, and whether to perform single (biliary or pancreatic) sphincterotomy vs upfront dual sphincterotomies will require further investigation.
Although histologic changes in acute pancreatitis revert to normal after the acute attack resolves, chronic pancreatitis leads to progressive and irreversible structural changes in the pancreas and eventually results in a permanent impairment of exocrine and endocrine functions.
Alcohol abuse accounts for 70% to 80% of all cases of chronic pancreatitis; the remainder are idiopathic (10% to 20%) or due to diverse causes, such as hereditary pancreatitis, tropical pancreatitis, and metabolic or anatomic abnormalities. Sclerosing pancreatitis is a rare form of chronic pancreatitis that until recently has been described exclusively in the Asian literature. Characteristics of this entity include symptoms of chronic pancreatitis, diffuse enlargement of the pancreas with abnormal pancreatography, hypergammaglobulinemia, and a striking elevation in IgG subclass 4.
Cheema and colleagues[16] reviewed the charts of 202 adults who underwent pancreatectomies during a 4-year period. The study authors found that 3 of these 202 patients met most criteria for the diagnosis of sclerosing pancreatitis and could have been candidates for a trial of steroids before pancreatectomy. Our group from Virginia Mason Medical Center presented the first report of endoscopic ultrasonography (EUS) findings in a patient with sclerosing pancreatitis.[17] Characteristic features that distinguish this entity from classic alcoholic chronic pancreatitis include a markedly edematous, hypoechoic pancreatic gland in the absence of pancreatic duct or side branch dilatation and a dramatic reduction in the size of the gland after steroid therapy.
Pain is the predominant symptom of chronic pancreatitis, with exocrine and endocrine insufficiency occurring in 15% to 20% of patients. On imaging studies, diffuse calcification deposition is pathognomonic of chronic pancreatitis (Figure 3), and in the setting of a typical history, no further test is needed to confirm the diagnosis. Fuhrman and Kasmin[18] presented an interesting case of a patient with pancreas divisum and focal pancreatitis who developed calcifications only in the ventral portion of the pancreas.
Figure 3. Transabdominal ultrasound revealing diffuse calcifications in a patient with alcoholic pancreatitis.
The treatment of chronic pancreatitis focuses on pain control, the relief of pancreatic duct obstruction, and the detection and management of complications. Narcotic agents are often necessary to control the pain of chronic pancreatitis. Endoscopic therapy can achieve stricture dilatation and pancreatic stone removal in the majority of patients with improvement of pain in roughly two thirds of cases followed up for 1-3 years (Figures 4 and 5).
Figure 4. ERCP revealing a massively dilated pancreatic duct in a patient with alcoholic pancreatitis. Multiple pancreatic stones are seen within the duct (arrows).
Figure 5. Endoscopic image of a pancreatic stone after removal with a balloon catheter.
Celiac plexus blockade has been studied extensively but in its commonly used form appears to be less effective in chronic pancreatitis compared with pancreatic cancer. Mahajan and coworkers[19] added epinephrine to the traditional celiac plexus block medications (bupivacaine and triamcinolone) in 11 patients who previously had not responded to the traditional block. Although there was a trend toward improvement of pain, this did not reach statistical significance, and larger prospective trials are needed to determine whether this modification is helpful in clinical practice.
The principal complications of pancreatitis are pseudocyst formation and common bile duct obstruction. Less common complications include pancreatic fistulae with ascites or pleural effusion,[20] splenic vein thrombosis, and pseudoaneurysm formation.[21,22]
The Indiana University group reviewed their experience with endoscopic therapy for biliary strictures in chronic pancreatitis[23] in an effort to determine patient characteristics that may predict stricture resolution and the success rate of this intervention. A query of their database revealed 72 patients who during the last 8 years underwent repetitive stenting; 22 patients (31%) had resolution of the bile duct stricture after a mean duration of stenting of 17.5 months. Stricture resolution was more likely to occur in nonalcoholic patients without pancreatic calcifications. This report underscores earlier studies that documented a relatively poor long-term outcome for endoscopic stenting of biliary strictures in chronic pancreatitis.
Inserting larger self-expandable metal stents (SEMS) (Figure 6) into benign biliary strictures is associated with long-term complications, such as stent occlusion and migration. Transient stenting with SEMS prostheses is usually not feasible because these stents cannot be removed after deployment. Ginsberg and colleagues[24] examined a new bioabsorbable self-expanding biliary endoprosthesis in a porcine model. The new stent is composed of biocompatible polylactide filaments and impregnated with barium sulfate for radiopacity. The investigators found that these stents were effectively deployed endoscopically with good radiographic visualization. However, the bioabsorption rate could not be determined in this 12-month study because all stents remained present at the end of the study period. The search for a biodegradable product therefore continues.
Figure 6. Endoscopic and fluoroscopic images of a self-expandable metal stent inserted in a patient with malignant bile duct stricture. Placement of these stents in benign strictures, such as those due to chronic pancreatitis, should be avoided.
Pancreatic pseudocysts are walled-off collections of pancreatic secretions and may form as a result of acute or chronic pancreatitis (Figure 7). A study by Cai and coworkers[25] documented, as one may expect, that pseudocyst formation in acute pancreatitis is unlikely to occur in patients with a low Glasgow severity score. Baradarian and colleagues[26] performed a meta-analysis of studies describing the outcome of patients with pseudocysts complicating acute pancreatitis. The study authors found that patients with large (> 6 cm) pseudocysts had a 15% chance of developing complications, whereas patients with smaller pseudocysts rarely had complications.
Figure 7. CT scan showing a large pancreatic pseudocyst in a patient with a history of acute gallstone pancreatitis.
The management of large symptomatic pseudocysts may involve percutaneous, endoscopic, or surgical drainage procedures. Percutaneous and endoscopic drainage is most commonly performed via an indwelling catheter or stent that is left in place for several weeks, since earlier reports have shown a high recurrence rate after simple needle aspiration of pseudocysts. Kessler and colleagues[27] suggested that EUS-guided fine-needle aspiration (EUS-FNA) may be adequate. However, they based this statement on 4 patients in whom relatively small pseudocysts were drained, and their data can therefore not be generalized.
Pancreatic cancer remains the fourth leading cause of cancer-related death in the United States and is second only to colorectal cancer as a cause of gastrointestinal cancer-related death. Only 15% to 20% of patients with pancreatic cancer are candidates for surgical resection, and even those with potentially resectable disease have a poor prognosis, with 5-year survival rates following pancreaticoduodenectomy of only 25% to 30%. A variety of diagnostic studies are available for the diagnosis and staging of pancreatic cancer. Early detection, however, remains one of the main challenges in our effort to reduce the mortality of this deadly disease.
When a pancreatic mass is found on imaging studies (Figure 8), causes other than adenocarcinomas, such as a cystic pancreatic tumor or a neuroendocrine tumor, need to be considered. Several presentations during this year's meeting highlighted other rare tumors that may sometimes mimic a pancreatic adenocarcinoma, including pancreatic acinar cell carcinoma, hepatoid carcinoma, duodenal sarcoma, and lymphoproliferative infiltration of the pancreas.[28-31]
Figure 8. CT scan showing a large mass in the pancreatic body (*).EUS-FNA confirmed adenocarcinoma.
Bounds and colleagues[32] explored the interpretation of cytology results from EUS-FNA biopsy specimens obtained to evaluate pancreatic masses (Figure 9).
Figure 9. EUS-FNA of a mass lesion. The needle can be clearly identified as a straight white line (arrow) and traced into the hypoechoic mass.
The previously reported sensitivity, specificity, and accuracy rate for this diagnostic modality vary widely, and the study authors hypothesized in the study that this may in part be due to the categorization of "suspicious" and "atypical" cytology. They prospectively recorded cytology results for 112 patients who underwent EUS-FNA for pancreatic mass lesions and calculated the sensitivity, specificity, and accuracy for malignancy in 3 different ways: (1) suspicious and atypical cytologies were included as diagnostic (liberal interpretation); (2) suspicious cytology was included in the diagnostic group and atypical cytology in the nondiagnostic group (moderate): and (3) both suspicious and atypical cytologies were included in the nondiagnostic group (conservative). The investigators found that the sensitivity improved from 51% (conservative interpretation) to 81% (liberal interpretation), whereas the specificity decreased from 91% to 70%, accordingly. They concluded that the discrepancy in the reported sensitivity, specificity, and accuracy rates may be partially explained by the inconsistent and nonstandardized categorization of cytology findings.
Eloubeidi and colleagues[33] prospectively evaluated the accuracy and complication rate of EUS-FNA in patients with suspected pancreatic cancer. One hundred fifty-eight EUS-FNAs were performed during a 22-month period. The study authors found a sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNA in solid pancreatic masses of 96.7%, 100%, 100%, and 89.7%, respectively. They concluded that this technique is highly accurate in diagnosing suspected pancreatic cancer and should be considered the modality of choice, especially when other modalities have failed to provide a definitive diagnosis. Complications in this study appeared similar to those of standard upper endoscopy, although 1 patient developed mild acute pancreatitis that resolved with observation.
In a report not strictly related to pancreatic malignancies, Mullick and colleagues[34] evaluated the utility of telomerase expression testing to differentiate cholangiocarcinoma from benign biliary epithelium. The same group had previously presented preliminary results using this test to distinguish pancreatic cancer from benign pancreatic tissue. Similar to their previous results, positive telomerase expression was extremely accurate and differentiated malignant from benign bile duct epithelium in all 27 patients tested. This finding is the first description of telomerase immunostaining and merits further evaluation as a method to screen and diagnose cholangiocarcinoma in biliary strictures and pancreatic malignancies.
A number of enlightening presentations regarding the etiology, diagnosis, and management of pancreatic disease were focused on during this year's meeting proceedings. The preceding discussion highlights the current state of the field, providing relevant context for future paths of investigation.
