Pancreatic duct pressure (PDP) dynamics comprise an intricately modulated system that helps maintain homeostasis of pancreatic function. It is affected by various factors, including the rate of pancreatic fluid secretion, patency of the ductal system, sphincter of Oddi function, and pancreatic fluid characteristics. Disease states such as acute and chronic pancreatitis can alter the normal PDP dynamics. Ductal hypertension or increased PDP is suspected to be involved in the pathogenesis of pancreatic pain, endocrine and exocrine pancreatic insufficiency, and recurrent pancreatitis. This review provides a comprehensive appraisal of the available literature on PDP, including the methods used in the measurement and clinical implications of elevated PDP.

Sphincter of Oddi dyskinesia is a functional disorder of the papillary region which can lead to clinical symptoms due to functional obstruction of biliary and pancreatic outflow. Based on the severity of the clinical symptoms the disorder can be graded into three types (biliary and pancreatic types I-III). The manometric diagnosis of this disorder using sphincter of Oddi manometry is hampered by the relatively high risk of pancreatitis after endoscopic retrograde cholangiopancreatography. Although papillary manometry is often carried out in North America, in Europe this is the exception rather than the rule. Manometrically, sphincter of Oddi dyskinesia is characterized by an increased pressure in the biliary and/or the pancreatic sphincter segments and can be treated by endoscopic papillotomy. This overview counterbalances the arguments for primary invasive diagnostics and a pragmatic clinical approach, i.e. papillotomy should be directly carried out when a sphincter of Oddi dyskinesia is clinically suspected. For patients with biliary or pancreatic type I, endoscopic papillotomy is the treatment of choice. In biliary type II sphincter of Oddi manometry could be helpful for clinical decision-making; however, the exact risk-benefit ratio is still difficult to assess. In type III patient selection and the low predictive value of manometry for treatment success questions the clinical usefulness of sphincter of Oddi manometry.

Sphincter of Oddi dysfunction (SOD) is a term used to describe a group of heterogenous pain syndromes caused by abnormalities in sphincter contractility. Biliary and pancreatic SOD are each sub-classified as type I, II or III, according to the Milwaukee classification. SOD appears to carry an increased risk of acute pancreatitis as well as rates of post ERCP pancreatitis of over 30%. Various mechanisms have been postulated but the exact role of SOD in the pathophysiology of acute pancreatitis is unknown. There is also an association between SOD and chronic pancreatitis but it is still unclear if this is a cause or effect relationship. Management of SOD is aimed at sphincter ablation, usually by endoscopic sphincterotomy (ES). Patients with type I SOD will benefit from ES in 55%-95% of cases. Sphincter of Oddi manometry is not necessary before ES in type I SOD. For patients with types II and III the benefit of ES is lower. These patients should be more thoroughly evaluated before performing ES. Some researchers have found that manometry and ablation of both the biliary and pancreatic sphincters is required to adequately assess and treat SOD. In pancreatic SOD up to 88% of patients will benefit from sphincterotomy. Therefore, there have been calls from some quarters for the current classification system to be scrapped in favour of an overall system encompassing both biliary and pancreatic types. Future work should be aimed at understanding the mechanisms underlying the relationship between SOD and pancreatitis and identifying patient factors that will help predict benefit from endoscopic therapy.

Chronic, debilitating abdominal pain is arguably the most important component of chronic pancreatitis, leading to significant morbidity and disability. Attempting to treat this pain, which is too often unsuccessful, is a frustrating experience for physician and patient. Multiple studies to improve understanding of the pathophysiology that causes pain in some patients but not in others have been performed since the most recent reviews on this topic. In addition, new treatment modalities have been developed and evaluated in this population. This review discusses new advances in neuroscience and the study of visceral pain mechanisms, as well as genetic factors that may play a role. Updates of established therapies, as well as new techniques used in addressing pain from chronic pancreatitis, are reviewed. Lastly, outcome measures, which have been highly variable in this field over the years, are addressed.

The pathogenesis of pain in chronic pancreatitis remains an enigma. The cause of pain is almost certainly multifactorial and may vary at different stages of the disease process. These factors may include the release of excessive oxygen-derived free radicals, tissue hypoxia and acidosis, inflammatory infiltration with influx of pain transmittent substances into damaged nerve ends, and the development of pancreatic ductal and tissue fluid hypertension due to morphological changes of the pancreas. Investigations into the causes of pain have been limited by changes in the dynamics with the progression of the disease process, limitations in studying functional and morphological changes of the pancreas in the clinical setting, and the psychosomatic profile of patients. Many of these patients are addicted to alcohol, and suffer from personality disorders. The difficulty in quantifying pain, which is at best subjective, further compounds the issue, especially when assessing the efficacy of treatment.

Sphincter of Oddi dyskinesia (SOD) is a functional disorder of the papilla region that can lead to clinical symptoms and functional obstruction of biliary and pancreatic outflow. Based on the severity of the clinical symptoms, the disorder is classified as one of three types (biliary or pancreatic type I-III). Diagnosis of SOD is hampered by the relative risk of endoscopic sphincter manometry to cause pancreatitis. Manometrically, SOD is characterized by increased pressure in the biliary or pancreatic sphincter segment and can be treated with endoscopic papillotomy. This review is an attempt to balance the arguments for invasive diagnosis with a pragmatic clinical approach in which papillotomy is performed if clinical suspicion and patient presentation support a dysfunction of the papilla. For patients with biliary or pancreatic type I, endoscopic papillotomy is the treatment of choice. In biliary type II, SO manometry may be helpful for clinical decision making; however, the ratio of risks to benefits is difficult to assess based on the present data. In type III SOD, patient selection and the low predictive value of manometry for treatment success raise questions about the clinical usefulness of SO manometry.

The treatment of pancreatic duct strictures is based on an accurate assessment of the etiology of the disease, and then the degree of symptomatology. Our outline for therapy is as follows: Exclude a diagnosis of malignancy by using radiologic, endoscopic, histologic, and molecular biologic modalities. Once a benign stricture has been demonstrated, we favor a trial of endoscopic dilation and stent placement For the unresectable pancreatic neoplasm, in which an obstructive etiology for pain is suspected, a trial of endoscopic dilation and stent placement also should be considered. In benign pancreatic duct strictures complicated by biliary obstruction, and where the most durable treatment modality is sought, surgical intervention merits earlier consideration. Pancreatic duct stent placement should seldom be considered definitive therapy, and the risk of stent-induced duct injury must be weighed against potential therapeutic benefit.

Technical improvement in endoscopic and manometric technique has allowed direct manometry of the human sphincter of Oddi (SO). The aim of the present review is to describe the present status of physiologic and clinical knowledge of the SO, with emphasis on contributions from Danish Gastroenterology.

The SO is a zone with an elevated basal pressure with superimposed phasic contractions. It acts mainly as a resistor in the regulation of bile flow. Neurohormonal regulation influences the motility pattern. The contractions are under the control of slow waves. Clinical subgroups show abnormalcy in SO manometric pattern especially in patients with biliary or pancreatic pain without demonstrable organic substrate. Evidence suggests that endoscopic sphincterotomy may be of benefit in these patients.

In this study, we investigated the relationship between pain and pancreatic pressure in patients with chronic pancreatitis (CP). We studied 12 patients with CP undergoing surgery and five controls with cancer of the pancreatic tail. CP was staged on the basis of morphological (ERP) and functional (serum-pancreolauryl test) criteria. Patients kept daily records of the intensity of pain on a linear analog scale. Intraoperatively, pressure within the pancreas was assessed by the introduction of a fine needle into the pancreatic parenchyma connected to a pressure transducer. In controls, pressure was determined in macroscopically normal tissue in the head of the pancreas. Pancreatic pressure was significantly higher in CP than in controls (29.9 +/- 3.1 vs 7.2 +/- 1.1 mmHg, p < 0.001). No relationship was found between the pain score and the pancreatic pressure. Pressure was positively correlated with ductal changes (r = 0.831; p < 0.001), but not with exocrine function of the pancreas. Postoperatively, pancreatic pressure fell by 15.3% in four patients with CP in whom pressure assessment was repeated after surgical decompression. We conclude that pancreatic parenchyma pressure is not closely related to pain in CP.

Sphincter of Oddi activity and the common bile duct (CBD) and pancreatic duct (PD) pressures were measured by means of endoscopic manometry in 15 patients (11 men and 4 women aged 18-77 (median, 40) years) with various degrees of chronic pancreatitis. Eleven of the 15 patients studied had an abnormal manometric pattern: elevated base-line pressures were seen in 8 patients, elevated duct pressures in 6 patients, abnormal peristalsis in 6 patients, and discoordination in 4 patients. There was no relation between the severity of chronic pancreatitis as shown by endoscopic retrograde pancreatography and the pancreatic function test and the manometric findings. However, a positive correlation between the sphincter of Oddi base-line pressure and the pancreatic duct pressure was found. It is concluded that manometric abnormalities are common findings in patients with chronic pancreatitis. Whether this is primary or secondary to the inflammatory process is still uncertain.

Pathophysiology of the sphincter of Oddi--or sphincter of Oddi dysfunction--manifests as either a biliary-type pain syndrome or recurrent pancreatitis. Imaging studies are unreliable, and direct endoscopic manometry is used to diagnose this entity. Milwaukee biliary classification, in addition to manometry, helps guide therapy. Endoscopic sphincterotomy in selected patients achieves permanent relief of symptoms. Endoscopic therapy for recurrent pancreatitis is still experimental.

In a phase I study endoscopic removal of pancreatic duct stones and protein plugs was attempted in five patients suffering from chronic pancreatitis with severe chronic pain. The pancreatic duct contents could be extracted after successful sphincterotomy in three patients. Clearance of the pancreatic duct was followed by complete or partial relief of pain. The follow-up period was 17-48 months. Endoscopic extraction is, however, not without complications; it is technically difficult, and many attempts may be required. The combination of endoscopic therapy and extracorporeal shock-wave lithotripsy may be a better alternative.

The aim of the present study was to evaluate the needle method for pancreatic tissue fluid pressure measurements. Clinical evaluation was performed in 24 patients with chronic pancreatitis, comparing repeated pressure measurements via sonographically guided fine-needle puncture and intraoperative pressure measurements by direct puncture of pancreatic tissue and duct. In patients with chronic pancreatitis we found small week-to-week variations in sonographically guided percutaneous pressure measurements and good agreement between preoperative percutaneous pressure measurements and intraoperative pressure measurements via direct puncture. Furthermore, no significant difference was seen between pancreatic duct and tissue fluid pressure. The technical evaluation was performed by repeated pressure measurements in human pancreatic autopsy specimens and living rats in a pressure chamber at various external pressure levels. The basic calibration of the method evaluated by means of this pressure chamber study showed sufficient precision and accuracy of the needle technique for clinical and investigative purposes. In conclusion, our results suggest that pancreatic tissue fluid pressure can be reliably assessed by the needle technique.

Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results were compared with preoperative endoscopic retrograde cholangiopancreatography (ERCP) morphology. The preoperatively elevated pressure decreased in all patients but one, to normal or slightly elevated values. The median pressure decrease was 50% (range, 0-90%; p = 0.01). The drainage anastomosis (a pancreaticogastrostomy) was made in the body of the pancreas, but the pressure decrease in this region was not significantly different from that in the head and tail. The pressure decrease was independent of findings during ERCP (stone, total duct obstruction, or major ductal stenosis). In conclusion, the results showed a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings.

The relation between pancreatic tissue fluid pressure and pain, morphology, and function was studied in a cross-sectional investigation. Pressure measurements were performed by percutaneous fine-needle puncture. Thirty-nine patients with chronic pancreatitis were included, 25 with pain and 14 without pain. The pressure was higher in patients with pain than in patients without pain (p = 0.000001), and this was significantly related to a pain score from a visual analogue scale (p less than 0.001). Patients with pancreatic pseudocysts had both higher pressure and higher pain score than patients without (p = 0.004 and p = 0.0003, respectively). The pressure was significantly related (inversely) to pancreatic duct diameter only in the group of 19 patients with earlier pancreatic surgery (R = -0.57, p = 0.02). The pressure was not related to functional factors or the presence of pancreatic calcifications. In conclusion, pancreatic tissue fluid pressure is a valuable indicator of pain in chronic pancreatitis.

The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation. The predrainage pressures were higher in the tail of the pancreas (29 mm Hg; range, 16-37 mm Hg) than in the head (18 mm Hg; range, 2-30 mm Hg; p = 0.02). The regional pressure differences were significantly greater in four patients who had previously undergone pancreatic surgery than in the 12 patients without previous surgery. A stone, total obstruction, or major stenosis in the pancreatic duct at ERP was related to a downstream pressure gradient significantly higher than found in a non-obstructed pancreatic main duct, but the relation was not uniform. Generally, there was no significant relation between pancreatic duct diameter and pressure, but in each individual patient, the regional pressure tended to be highest in the region with the largest duct diameter. In conclusion, the study shows considerable regional pressure differences in chronic pancreatitis and indicates that the intraoperative pressure measurements give important information supplementary to ERP about the pathologic process in patients with chronic pancreatitis.

In this study both pancreatic and bile duct sphincter pressures were measured on the same occasion by means of endoscopic manometry in 42 patients with long-standing upper abdominal pain. Nine (53%) of the 17 patients with abnormal sphincter function had a marked difference between the pancreatic duct sphincter pressure (PSOP) and the bile duct sphincter pressure (BSOP): 6 patients with a clinical diagnosis of biliary dyskinesia showed elevated BSOPs, whereas the PSOPs were normal. The reverse, an abnormal PSOP but normal or only a slightly elevated BSOP, was registered in the three patients with chronic pancreatitis. These findings indicate that a motor abnormality may be restricted to only one of the sphincters. Thus, when the sphincter of Oddi is investigated only from the pancreatic duct, manometry may either fail to show an abnormal BSOP in some patients with biliary dyskinesia, or it may falsely suggest this diagnosis in patients with unrecognized pancreatitis.