Prevalence and clinical evolution of isolated ventral pancreatitis in alcoholic chronic pancreatitis

BACKGROUND: The role of pancreas divisum in chronic pancreatitis is controversial. Ductal changes limited to the pancreatic ventral duct (isolated ventral pancreatitis) have only been described as isolated case reports. METHODS: In a cohort of 542 patients with chronic pancreatitis we determined the frequency of ventral chronic pancreatitis among patients with pancreas divisum and analyzed the clinical presentation of 10 patients with isolated ventral alcohol-induced pancreatitis compared with 10 patients with isolated dorsal alcohol-induced pancreatitis and 30 patients with chronic pancreatitis and without pancreas divisum. Magnetic resonance pancreatography under secretin stimulation was used to evaluate the status of the dorsal pancreatic duct in some patients during follow-up. RESULTS: We identified 62 (11.4%) patients with pancreas divisum and 16 (2.9%) patients with incomplete pancreas divisum. The ventral duct was affected by chronic pancreatitis in 74% of these patients. Isolated ventral or dorsal duct alterations were identified in 14% and 26%, respectively, of patients with pancreas divisum. Patients with isolated ventral pancreatitis had pain symptoms similar to those of the two other groups but had no endocrine or exocrine insufficiency on initial presentation. After a mean follow-up of 44 months, 83% of patients studied with isolated ventral pancreatitis developed alterations of the dorsal ductal part of the gland. CONCLUSION: We conclude that isolated ventral alcohol-induced pancreatitis is one of the first manifestations of generalized pancreatic disease where the anatomic factor of pancreas divisum plays only a marginal role.     

Pancreas divisum does not modify the natural course of chronic pancreatitis

Background Pancreas divisum is the most common congenital variant of the pancreas; however, its clinical significance remains controversial. The purpose of our study was to determine the role of pancreas divisum in the development of chronic pancreatitis. Methods We compared the clinical presentation, morphological findings, and course of disease of 30 patients with chronic pancreatitis associated with pancreas divisum (there was coexisting chronic alcohol abuse in 18 cases) to those of 57 patients with chronic pancreatitis and no evidence of pancreas divisum (15 with nonalcoholic pancreatitis and 42 with alcoholic pancreatitis). Results Sex distribution, age at onset of disease, clinical presentation, course of disease, and frequency of complications were not affected by the presence of pancreas divisum. Although the etiology of pancreatitis in patients with pancreas divisum may be attributed to impaired drainage of the majority of the gland through the minor papilla, we observed a relatively low frequency of isolated dorsal duct involvement in our patients irrespective of alcohol use (25% and 28% in patients with and without a history of alcohol abuse, respectively). However, involvement of the ventral duct was commonly observed (75% and 72%, respectively). Conclusions The presence of pancreas divisum in our study did not modify the natural course of chronic nonalcoholic or alcoholic pancreatitis. Pancreas divisum is not likely to play a dominant role in the etiopathogenesis of chronic pancreatitis.     

Pancreas divisum is a probable cause of acute pancreatitis: a report of 137 cases

The incidence of pancreas divisum (PD) was evaluated in a retrospective series of 1,825 successful consecutive ERCPs. One hundred thirty-seven pancreas divisums (7.5%) were found in 80 males and 57 females at a mean age of 49.2 years. The ventral ducts were visualized in 82.5% and the dorsal ducts in 74.1% of attempted cannulations of the minor papilla. Pancreas divisum was significantly more frequent in patients presenting with acute idiopathic pancreatitis (50.0%) or acute biliary pancreatitis (23.7%) than in controls or in the general population. This difference was not found in acute pancreatitis due to other etiologies. Acute pancreatitis associated with PD is generally recurrent, is not severe, but may be complicated by necrotic pseudocysts. The frequency of PD was also significantly increased in patients with gallbladder stones but not with common bile duct stones. In other pathological groups--chronic pancreatitis and pancreatic cancer--the frequency of pancreas divisum was not statistically different from that observed in controls and/or in the general population. We conclude that on a statistical basis, PD is a probable cause of acute pancreatitis, especially in its idiopathic recurrent variety, and that its frequency is increased in patients with gallbladder stones.     

Pancreatitis associated with congenital abnormalities of the pancreaticobiliary system

BACKGROUND/AIMS: The relationship between pancreas divisum and pancreatitis remains controversial. The aim of this study was to examine the frequency and features of pancreatitis associated with congenital abnormalities of the pancreaticobiliary system, and the role that these malformations have in the occurrence of pancreatitis. METHODOLOGY: We retrospectively examined endoscopic retrograde cholangiopancreatograms of 6850 patients including 186 patients who were diagnosed clinically as having acute pancreatitis and 211 who were diagnosed as having chronic pancreatitis. RESULTS: A total of 175 patients were diagnosed as having congenital abnormalities of pancreaticobiliary system. Acute and chronic pancreatitis was associated respectively with 3.0% and 5.0% of patients with pancreaticobiliary maljunction (n=100), 17.1% and 28.6% of those with pancreas divisum (n=35), 6.6% and 20.0% of those with partial pancreas divisum (n=30), and 16.7% and 33.3% of those with choledochocele (n=6). These anomalies were present in 6.5% and 10.9% of patients with acute and chronic pancreatitis, respectively. Isolated chronic dorsal pancreatitis was detected in 8 patients with pancreas divisum. In chronic pancreatitis associated with pancreaticobiliary maljunction, pancreatic stones or protein plugs were situated only in the dilated common channel or main pancreatic duct of the head. CONCLUSIONS: Congenital abnormalities of the pancreaticobiliary system constitute one etiology of pancreatitis.     

Pancreas divisum: congenital anatomic variant or anomaly? Contribution of endoscopic retrograde dorsal pancreatography

The relationship between pancreas divisum and pancreatic disease has been studied in a series of 304 patients. This congenital anatomic variant, consisting of a separate pancreatic ductal system, was diagnosed by endoscopic pancreatography and dorsal duct opacification was achieved in 97 of these patients. This anatomic variation was observed with the same frequency in cases of pancreatitis (acute and chronic) (6.9%) and in the series of patients investigated by endoscopic pancreatography taken as a whole (5.7%). Moreover, incidences of pancreatic disease in patients with and without pancreas divisum were not statistically different when compared. These results show that pancreas divisum should not be regarded as an etiologic factor in pancreatitis but should be considered as a coincidental anatomic variant encountered in nearly 10% of the population. The results obtained herein do not support the hypothesis that stenosis of the accessory papilla occurs frequently in cases of pancreas divisum. We conclude that no further therapy should be systematically proposed for patients with pancreas divisum and pancreatitis.     

Isolated ventral pancreatitis in an alcoholic with pancreas divisum

An alcoholic with no history of clinical pancreatitis was found to have pancreas divisum and marked changes of chronic pancreatitis isolated to the ventral pancreas. Pancreas divisum has been suggested to cause recurrent pancreatitis in some patients. Gross and histologic changes of pancreatitis in only the dorsal pancreas of surgically resected specimens from patients with pancreas divisum is thought to support the concept that obstruction at the minor papilla produces dorsal pancreatitis. Alternative explanations for the occurrence of segmental pancreatitis and the possible synergistic role of ethanol and bile are reviewed.     

Isolated ventral pancreatitis in a patient with pancreas divisum

A previously healthy 22-yr-old woman was found to have chronic pancreatitis restricted to the ventral pancreas in association with pancreas divisum. When conservative treatment failed, sphincteroplasty of both papillae was performed with good results. This well-documented case represents a clear exception to the commonly held concept that obstruction of the dorsal duct is the essential pathogenic factor in the development of pancreatitis associated with pancreas divisum. The importance of visualizing both the dorsal and ventral pancreatic ducts to direct therapy for patients with idiopathic pancreatitis is discussed. Theories of the pathogenesis of concomitant pancreatitis and pancreas divisum are reviewed.     

Pancreatic duct dilatation after secretin stimulation in patients with pancreas divisum

Pancreas divisum is the most common anatomical variant of pancreatic ductal anatomy. It has been suggested that obstruction at the accessory papilla in subjects with pancreas divisum can be assessed by measurement of ductal diameter by ultrasonic examination after a maximal secretory stimulus with i.v. secretin. We have prospectively assessed this test in 44 individuals; nine healthy controls, nine patients with abdominal pain and normal pancreatic anatomy, 17 patients with pancreas divisum and abdominal pain but no other evidence of pancreatitis, and nine patients with pancreas divisum and either chronic or recurrent acute pancreatitis. We have found no correlation between ductal anatomy and response to i.v. secretin. Secretin provocation tests do not indicate which patients have accessory papillary stenosis and do not add support to the hypothesis of obstruction leading to pancreatitis in patients with pancreas divisum.     

Risk of pancreatitis with mutation of the cystic fibrosis gene

BACKGROUND: Between 5% and 15% of patients with recurrent pancreatitis have no identified etiology after routine investigation and advanced endoscopic evaluation. OBJECTIVE: To determine whether mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is a risk factor for idiopathic pancreatitis. METHODS: We compared the frequency of CFTR mutations as measured by DNA probe analysis in a case group of persons with idiopathic pancreatitis and a control group without pancreatitis, all of whom underwent endoscopic retrograde cholangiopancreatography. A separate analysis compared the prevalence of CFTR mutations between the case group and controls with pancreatitis of known etiology. A subgroup comparison was made between cases of pancreas divisum with pancreatitis and controls with pancreas divisum and no pancreatitis. RESULTS: CFTR mutations were present in 19 (19%) of 96 cases and 7 (3.5%) of 198 controls without pancreatitis (odds ratio, OR = 6.7; 95% CI, 2.8-16.3; p < 0.00001). Compared to the controls with a known cause of pancreatitis (N = 78), cases had a higher prevalence of CFTR mutations (19% vs 2.6%, OR = 9.4; CI, 2.1-41.7; p= 0.0005). Among subjects with pancreas divisum, CFTR mutations were present in 8 (22%) of 37 cases compared to 0 (0%) of 20 controls (OR = 11.8; CI, 8.9-14.7; p= 0.02). CONCLUSION: The risk of idiopathic pancreatitis is greater among persons with CFTR mutations as compared to persons without CFTR mutations. Among persons with pancreas divisum, CFTR mutations appear to increase the risk for pancreatitis.     

Management of pancreas divisum

Pancreas divisum is the most common congenital anomaly of the pancreas. Abnormal hedgehog protein signaling appears related to the formation of several pancreatic malformations, including annular pancreas, pancreatic-biliary malunion, pancreatic rests, and pancreas divisum. Pancreas divisum by itself should not necessarily require intervention. A careful evaluation should be performed to exclude other causes of symptoms. If the patient is asymptomatic, no further evaluation is necessary. However, a significant percentage of patients with pancreas divisum and acute recurrent pancreatitis benefit from intervention. Surgical sphincteroplasty and endoscopic interventions appear similar in outcome. Thus, endoscopic intervention with prophylactic temporary stenting is advised as initial therapy. Surgery should be reserved for patients with chronic pancreatitis.     

Pancreatic tumor associated with pancreas divisum

BACKGROUND: Although there has been considerable controversy regarding pancreas divisum and pancreatitis, little discussion of this has taken place. The purpose of the present paper was to investigate the relationship between these two conditions. METHODS: A retrospective investigation was undertaken of pancreatic tumors associated with pancreas divisum, in 650 cases of pancreatic carcinoma, 80 cases of intraductal papillary mucinous tumor of the pancreas and 32 cases of pancreas divisum. RESULTS: Of these 32 cases, four (12.5%) were associated with pancreatic tumor: pancreatic carcinoma (n = 3) and intraductal papillary mucinous tumor (n = 1). All tumors developed from the dorsal pancreas of pancreas divisum. Periductal and interlobular fibrosis detected in the non-carcinomatous pancreas of the margin of distal pancreatectomy implied that chronic dorsal pancreatitis associated with pancreas divisum preceded carcinoma. CONCLUSIONS: Pancreatic tumors were detected in 12.5% of cases of pancreas divisum. In pancreas divisum, longstanding pancreatic duct obstruction caused by relative stenosis of the minor duodenal papilla might be a factor promoting oncogenesis.     

Dynamic CT scanning of pancreatic duct after secretin provocation in pancreas divisum

Variations in pancreatic duct diameter at CT scanning and serum pancreatic amylase response following secretin administration were studied in 29 patients with pancreas divisum and unexplained upper abdominal pain. Eleven healthy individuals were used as controls. At endoscopie retrograde pancreatography (ERP) six patients had signs of marked and six moderate pancreatitis, whereas there were no pancreatitis changes in 17 of the patients. At CT scanning patients with marked pancreatitis (ERP) had significantly increased pancreatic duct diameter as compared to patients without signs of pancreatitis. The duct was visualized in 52% of all patients before and 71% after secretin stimulation the corresponding figures for healthy controls, being 18% both before and after secretin. In patients without signs of pancreatitis, it was demonstrated in 5/17 (29%) before and 11/17 (65%) after secretin, whereas it was seen in 10/12 (83%) pancreatitis patients both before and after the hormonal provocation. In five of the nonpancreatitis patients in whom the duct was measurable before and at all study intervals (10, 20, and 50 min) after secretin, there was a significant duct dilation response both at 10 min and when comparing the maximal duct diameter after secretin to the initial values. In contrast secretin did not affect the duct caliber in pancreatitis patients. Serum pancreatic amylase increased significantly after secretin administration to healthy controls and nonpancreatitis patients but was uninfluenced in the marked and moderate pancreatitis groups, respectively. However, when all pancreatitis patients were grouped together, the amylase levels were significantly elevated by secretin. In conclusion, secretin provocation caused duct dilation at CT scanning in pancreas divisum patients without signs of pancreatitis at ERP. In this group secretin also increased the number of patients with visualized pancreatic duct. However, in pancreas divisum patients with pancreatitis and in healthy controls no such findings were observed. Secretin stimulation increased samylase in a nonspecific way. If secretin at CT scanning causes dilation of the pancreatic duct compared to its initial measurable width or visualization of an initially not demonstrable duct in patients with unexplained upper abdominal pain, the presence of pancreas divisum without morphologically manifest pancreatitis should be considered.     

Endoscopic botulinum toxin injection into the minor papilla for treatment of idiopathic recurrent pancreatitis in patients with pancreas divisum.

BACKGROUND: In some patients with pancreas divisum, obstruction to the flow of pancreatic juice into the duodenum is the presumptive cause of acute recurrent pancreatitis. However, identification of those patients who may benefit from minor papilla sphincterotomy or stent placement is difficult. METHODS: Five patients with acute recurrent pancreatitis and pancreas divisum were therefore treated by endoscopic injection of 50 units of botulinum toxin into the minor papilla in an outpatient setting. RESULTS: Botulinum toxin injection was successfully performed on six occasions in 5 patients and no adverse effects were noted. Two patients relapsed after 9 and 10 months, respectively, but had definite relief of symptoms after needle-knife sphincterotomy. One patient relapsed 7 months after botulinum toxin injection but became symptom free again after a second botulinum toxin injection. Another patient is still in clinical remission 4 months after botulinum toxin administration, and 1 patient did not respond to either botulinum toxin administration or to sphincterotomy and stent placement. CONCLUSIONS: Endoscopic injection of botulinum toxin into the minor papilla in patients with pancreas divisum and acute recurrent pancreatitis is a safe procedure that is easy to perform and provides short-term relief in some patients. Response to botulinum toxin injection may predict whether patients with pancreas divisum and acute recurrent pancreatitis will benefit from other forms of endoscopic therapy.     

Ultrasound secretin test in patients with pancreas divisum--an aid in the diagnosis of papillary or dorsal duct stenosis?

BACKGROUND: Pancreas divisum is a common anatomical variant of pancreatic ductal anatomy. Obstruction of the accessory papilla could cause pain and pancreatitis. It has been suggested that accessory papillary sphincter obstruction can be assessed by sonographic measurement of pancreatic duct diameter after secretin stimulation. METHODS: We now compared our results of sonographic pancreatic duct diameter measurements before and during 10 min after intravenous injection of 1 CU secretin per kg body weight in 32 patients with confirmed pancreas divisum and 20 healthy volunteers. RESULTS: The healthy controls showed a short-lasting duct caliber enlargement by about 93% of the basal diameter within 5 min after secretin injection. 25 pancreas divisum patients without pancreatic disease had a secretin-induced duct dilatation by about only 58%. In four patients with pancreas divisum and chronic pancreatitis no or just a slight duct dilatation was observed after stimulation. Two patients with dorsal duct stenosis as well as one patient with accessory papilla stenosis, however, showed a marked and prolonged secretin-induced duct enlargement by about 155% of the basal duct diameter. CONCLUSION: In this investigation pancreatic duct response to secretin stimulation in pancreas divisum patients without pancreatic disease was less marked than in normal individuals. Thus, a particularly distinct and long-lasting duct dilatation could support the suspicion of accessory papilla or pancreatic duct stenosis.     

Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis

BACKGROUND: The mechanism by which pancreas divisum may lead to recurrent episodes of acute pancreatitis in a subset of individuals is unknown. Abnormalities of the cystic fibrosis gene product (CFTR) have been implicated in the genesis of idiopathic chronic pancreatitis. The aim of this study was to determine if CFTR function is abnormal in patients with pancreas divisum and recurrent acute pancreatitis (PD/RAP). METHODS: A total of 69 healthy control subjects, 12 patients with PD/RAP, 16 obligate heterozygotes with a single CFTR mutation, and 95 patients with cystic fibrosis were enrolled. CFTR function was analyzed by nasal transepithelial potential difference testing in vivo. The outcomes of the PD/RAP patients following endoscopic and surgical treatments were concomitantly analyzed. FINDINGS: Direct measurement of CFTR function in nasal epithelium in response to isoproterenol demonstrated that the values for PD/RAP were intermediate between those observed for healthy controls and cystic fibrosis patients. The median value was 13 mV for PD/RAP subjects, which was statistically different from healthy controls (22 mV, p= 0.001) and cystic fibrosis pancreatic sufficient (-1 mV, p < 0.0001) and pancreatic insufficient (-3 mV, p < 0.0001) patients. INTERPRETATIONS: These results suggest a link between CFTR dysfunction and recurrent acute pancreatitis in patients with pancreas divisum and may explain why a subset of patients with pancreas divisum develops recurrent acute pancreatitis.     

Endoscopic Treatment in Pancreas Divisum

Objectives: We have reviewed the results of endo-scopic stunting with and without sphincterotnmy at the minor papilla in 34 patients with pancreas divisum and pain or pancreatitis. Methods: Symptoms before and after the procedure were scored and compared, as was the patient's estimate of the overall effectiveness of the treatment. Results: A statistically significant improvement in pain score was found in patients with acute recurrent pancreatitis and in patients with chronic pancreatitis, but not in a small group of patients suffering pain without pancreatitis. The overall effectiveness was found to be 78%, 60%, and 40%, respectively, for these three groups. Complications of treatment were common, but usually mild. There were no evident differences in outcomes between patients who did or did not undergo sphinctcrotomy of the minor papilla. Conclusions: This study confirms that there is a subgroup of patients with symptomatic pancreas divisum who improve with en-doscopic treatment. Correctly identifying these individuals remains a challenge.     

胰腺分裂内镜治疗价值

目的探讨内镜下治疗胰腺分裂的疗效和安全性。方法收集2006年6月至2013年6月在南京大学医学院附属鼓楼医院消化科就诊的8例胰腺分裂患者的临床资料,对术中及术后情况进行回顾性分析。结果8例胰腺分裂患者共行经内镜逆行胰胆管造影术28例次,均置入胰管支架,其中7例同时行副乳头括约肌切开术,6例行内镜下扩张术,1例行胰管取石术。术后出现1例次轻度胰腺炎。随访2～47个月,1例死于胰腺癌,3例已拔出支架,3例定期复查,1例失访。患者术后慢性胰腺炎急性发作频率及腹痛程度均较术前明显降低。结论内镜下治疗胰腺分裂安全有效,可减少胰腺炎发作频率,减轻术后腹痛程度,术后并发症发生率低。     

Fusion and duplication variants of pancreatic duct system

Summary The aim of this study was to assess the incidence of fusion and duplication variants of the pancreatic duct system and their clinical significance. A total of 650 endoscopic retrograde cholangiopancreatography were reviewed; 485 cases with satisfactory imaging of the pancreatic ducts were included in the study. Anatomic variants were observed in 48 patients (9.9%), fusion variants were 54.1% of the cases (22 pancreas divisum and 4 functional divisum), and duplication variants were 45.8% (13 bifurcations of the main pancreatic duct, 4 loop, 2N-shape, 3 ring). Clinical indications to endoscopic cholangiopancreatography were idiopathic acute pancreatitis (33.3%), suspected chronic pancreatitis (18.7%), unexplained abdominal pain (14.5%), suspected pancreatic mass (10.4%), chronic hyperamylasemia (6.2%), and acute biliary pancreatitis (16.6%). Except for acute biliary pancreatitis (significantly more frequent in duplication variants), no statistical difference was observed between the groups with anatomical variants concerning clinical features.     

Recurrent pancreatitis in a patient with autosomal-dominant polycystic kidney disease.

Autosomal-dominant polycystic kidney disease is an inherited disorder characterized by multiple cysts in kidneys and other organs. A 63-year-old man was evaluated for the etiology of recurrent pancreatitis and chronic renal failure. Multiple cysts of kidneys, liver, and pancreas and pancreas divisum was diagnosed. Pancreatitis should be included in the differential diagnosis of abdominal pain in patients with ADPKD. Pancreas divisum may be a predisposing factor for acute pancreatitis in these patients.     

Clinical experience in 82 patients with pancreas divisum: preliminary results of manometry and endoscopic therapy

Although it is clear that the majority of patients with pancreas divisum have no clinical disease, there is a subset of patients who have either unexplained abdominal pain or recurrent pancreatitis. Endoscopic therapy of the minor papilla may alter the clinical course of those patients with pancreas divisum and recurrent pancreatitis. Manometric study of the minor papilla is feasible and reveals a sphincter mechanism similar to the major papilla. Clinical response to endoscopic therapy may aid in selecting patients who might benefit from surgical sphincteroplasty. Refinement of manometric study of the minor papilla offers a potential method of detecting functional obstruction of dorsal duct drainage.