An experimental study in etiologic effect of pancreas divisum on chronic pancreatitis and its pathogenesis

ＩＮＴＲＯＤＵＣＴＩＯＮＴｈｅｐａｔｉｅｎｔｓｗｉｔｈｐａｎｃｒｅａｓｄｉｖｉｓｕｍ（ＰＤ）ｗｅｒｅｃｏｎｓｉｄｅｒｅｄｔｏｈａｖｅａｈｉｇｈｅｒｒｉｓｋｆｏｒｃｈｒｏｎｉｃｒｅｃｕｒｅｎｔｐａｎｃｒｅａｔｉｔｉｓ．Ｂｕｔｔｈｅｅｔｉｏｌｏｇｙａｎｄ...     

State-art: diagnosis and management in pancreas divisum

Pancreas divisum (PD), the most common congenital variant of pancreatic duct anatomy, occurs when the ductal systems of the ventral and dorsal pancreatic ducts fail to fuse during the second month of gestation. With non-union of the ducts, the major portion of the pancreatic exocrine secretion enters the duodenum by way of the dorsal duct and minor papilla. It has been generally accepted that a relative obstruction to pancreatic exocrine secretory flow through the minor duct and minor papilla could result in pancreatitis in small numbers of patients with PD. The debate whether PD causes pancreatitis continues, although most authorities agree that PD is a definite cause in a subgroup of patients. Most patients with PD and well-documented acute recurrent pancreatitis have responded favorably to surgical sphincteroplasty of the minor papilla. Endoscopic retrograde cholangiopancreatography (ERCP) is the most common procedure for diagnosis PD in patients who have pancreatobiliary symptoms. MRCP is being increasingly used to establish the diagnosis and secretin stimulation can improve ductal images greatly. Endoscopic management of symptomatic patients with PD is evolving. Only a limited number of series are available, using endoscopic pancreatic stent placement, minor papilla endoscopic papillotomy, or both to decompress the dorsal duct in an effort to restore pancreatic exocrine secretory flow. Even with relatively small numbers of patients and a near absence of controlled, randomized trials, it appears that the patients most likely to benefit, as with surgery, are those with well-documented ARP rather than pain alone or chronic pancreatitis. Overall we recommend that pancreatic stenting and pancreatic sphincterotomy should be done only in large centers with experience in therapeutic ERCP. Further randomized trials would be of interest.     

Minor papilla cannulation and dorsal ductography in pancreas divisum

Until recently, pancreas divisum represented a major technical barrier to a complete evaluation of pancreatic ductal anatomy. Technical refinements have now made it possible to achieve minor papilla cannulation and dorsal ductography in more than 90% of attempts. In 120 consecutive dorsal ductograms, structural pathology was demonstrated in 36 subjects (30%): chronic pancreatitis in 23, pancreatic stones in 10, pseudocyst(s) in 4, ductal "cut-off" in 7, pancreatic cancer in 3, and partial agenesis in 1 (some patients had more than one finding). For patients in whom alcohol abuse was excluded, ductal pathology was present in 25%. Abnormal ventral ductograms were present in only 8% of cases, demonstrating that dorsal ductography has an appreciable additional diagnostic yield. When the clinical situation indicates the need for pancreatography, minor papilla cannulation should be performed if major papilla cannulation fails or reveals only the ventral pancreatogram of pancreas divisum.     

Annular pancreas: a clinical, endoscopic, and immunohistochemical study.

A patient with annular pancreas presenting with severe upper abdominal pain is discussed. Endoscopic retrograde cholangiopancreatography (ERCP) was diagnostic, with successful injection of major and minor papillae showing pancreas divisum, an annular duct emptying at the major papilla and changes of severe chronic pancreatitis in all duct systems. Pylorus preserving pancreatoduodenectomy gave complete pain relief. The annulus was shown immunohistochemically to be entirely of ventral gland origin. Chronic pancreatitis was histologically less severe in the dorsal gland. Antegrade dye injection with x-ray showed dorsal to ventral connection in the resected specimen.     

Long-term results of endoscopic management of pancreas divisum with recurrent acute pancreatitis

BACKGROUND: The long-term efficacy of endoscopic treatment in pancreas divisum is controversial. This study evaluated the long-term results of dorsal duct stent insertion and endoscopic sphincterotomy of the minor papilla in patients presenting with recurrent acute pancreatitis or chronic pain. METHODS: Pancreas divisum was diagnosed in 175 patients between 1980 and 1998. Twenty-four patients seen with recurrent acute pancreatitis without underlying chronic calcifying pancreatitis or significant alcohol consumption were included in this study with a follow-up of at least 24 months. Eight were treated by sphincterotomy of the minor papilla alone, and 16 underwent dorsal duct stent insertion for a median duration of 8 months. RESULTS: The median duration of follow-up after endoscopic management was 39 months (range 24-105; interquartile range 40.5). All patients had recurrent acute pancreatitis before endoscopic treatment during a median period of 5 years. At the end of the follow-up there were only 2 recurrences of acute pancreatitis (p < 0.01). The number of patients with chronic pain before endoscopic treatment and at the end of follow-up decreased from 20 of 24 (83%) to 7 of 24 (29%) without reaching statistical significance. The 25% recurrence rate was estimated at 50 months by Kaplan-Meier analysis. Nine patients presented with a dilated dorsal duct before endoscopic treatment. After stent insertion, dorsal duct dilatation appeared in all 16 patients who underwent stent placement, and pancreatic duct stenosis developed in 3. Four patients (19%) required further treatment for pain recurrence or acute pancreatitis, with surgical procedures being performed in 2 cases. Complications occurred in 9 of 24 patients (38%), mainly acute pancreatitis or stenosis of the minor papilla. All complications except one were managed conservatively. Complications seemed to be less frequent after minor papilla sphincterotomy than after pancreatic stent insertion (25% vs. 44%). CONCLUSION: In patients with pancreas divisum, both dorsal duct stent insertion and minor papilla sphincterotomy decrease the rate of recurrent acute pancreatitis, whereas relief of chronic pain was less obvious.     

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.     

10955例经内镜逆行胰胆管造影术患者临床总结分析

目的探讨经内镜逆行胰胆管造影术（ERCP）对胆胰疾病的诊疗价值。方法回顾性分析1995年1月至2013年7月间完成ERCP诊治的患者10955例,其中男6186例,女4769例,平均年龄（65．57±14．44）岁。总结并分析ERCP诊治病种、发病年龄、年度数量、麻醉方式及插管成功率等指标。结果10955例患者中,诊断性ERCP167例,治疗性ERCP10788例。2002年至2012年ERCP手术例数年平均增长率是19．58％。首次ERCP胆管插管成功率是97．23％,总ERCP胆管插管成功率是99．59％。常见的ERCP诊治疾病包括肝外胆管结石（40．85％）、肝门部胆管癌（10．53％）、化脓性胆管炎（10．44％）、胰头癌（10．04％）、慢性胰腺炎（8．24％）、肝外胆管癌（7．68％）、壶腹周围癌（6．96％）、胆源性胰腺炎（3．94％）、良性乳头狭窄（3．88％）、乳头癌（3．50％）。肝外胆管结石、化脓性胆管炎、良性乳头狭窄高发年龄是40～50岁,慢性胰腺炎高发年龄是50—60岁,胆源性胰腺炎、肝门部胆管癌、肝外胆管癌、胰头癌、壶腹周围癌、乳头癌的高发年龄是70—80岁。2011年至2013年中,98．74％患者行全凭静脉麻醉ERCP。结论ERCP已经成为胆胰疾病诊治的重要手段,适合于肝外胆管结石、化脓性胆管炎、恶性胆管梗阻等疾病,尤其是高龄患者的诊治。全凭静脉麻醉ERCP是安全、有效的。     

Incidence and risk factors for post-ERCP pancreatitis in pancreas divisum patients without chronic pancreatitis

Abstract

Aims: The studies on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in pancreas divisum (PD) patients without chronic pancreatitis (CP) are rare. In this study, we aimed to evaluate the incidence of PEP in PD patients without CP and the risk and protective factors for PEP.

Methods: Consecutive patients with symptomatic PD that underwent ERCP from January 2005 to December 2017 were retrospectively analyzed. The patients were divided into PD without CP group and CP group. The basic information and medical records of patients were collected. The risk and protective factors for PEP in PD patients without CP were analyzed by univariate logistic analysis.

Results: A total of 89 ERCP procedures were performed in 51 PD patients without CP, and 249 procedures in 136 patients with CP. The incidence of PEP was significantly higher in PD patients without CP than those with CP (15.7% vs. 5.6%, p?=?.005). Female gender were independent risk factors for PEP, while dorsal duct stent placement was a protective factor.

Conclusion: CP may be a protective factor against PEP in PD patients. Female was a risk factor for PEP in PD patients and dorsal duct stent placement was a preventive factor that reduced the incidence of PEP in PD patients without CP.     

Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases

The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangio- pancreatography （ERCP） or endoscopic ultrasound （EUS）, or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute pancreatitis, recurrent idiopathic pancreatitis, and in the prevention of post-ERCP pancreatitis. These stents are currently routinely placed to reduce intraductal hypertension, bypass obstructing stones, restore lumen patency in cases with dominant, symptomatic strictures, seal main pancreatic duct disruption, drain pseudocysts or fluid collections, treat symptomatic major or minor papilla sphincter stenosis, and prevent procedure-induced acute pancreatitis. The present review aims at updating and discussing techniques, indications, and results of endoscopic pancreatic duct stent placement in acute and chronic inflammatory diseases of the pancreas.     

An improved technique for accessory papilla cannulation in pancreas divisum

Cannulation of the accessory papilla with dorsal pancreas ductography was accomplished in 13 of 15 consecutive cases of pancreas divisum. When routine cannulation of the main pancreatic papilla fails to produce a pancreatogram or yields only a ventral pancreas, the use of intravenous secretin and a 23-gauge needle catheter is recommended to facilitate accessory duct cannulation.     

Laparoscopic Pancreatic Biopsy in Autoimmune Pancreatitis—Report of TWO Cases

Two cases of autoimmune pancreatitis that were diagnosed by laparoscopic pancreatic biopsy are reported. Patient 1 was a 71–year-old woman with obstructive jaundice and dry eyes. Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis of the distal common bile duct and proximal main pancreatic duct. Only the head of the pancreas was enlarged. The patient had associated Sjogren's syndrome and sclerosing cholangitis. Patient 2 was a 65–year-old man with obstructive jaundice that occurred after laparoscopic cholecystectomy. ERCP revealed a diffusely irregular and narrowed pancreatic duct and stenosis of the distal common bile duct. The whole pancreas was enlarged. Both patients underwent laparoscopic pancreatic biopsy to rule out pancreatic cancer. The definitive diagnosis in each case was autoimmune pancreatitis. The postoperative course in both cases was uneventful. Both patients recovered quickly with steroid therapy undertaken soon after the biopsy. In summary, a laparoscopic approach for the pancreatic biopsy in autoimmune pancreatitis appears to be feasible and useful in determining the therapeutic strategy. (Dig Endosc 1999; 11: 250–254)     

A Histopathological Study on Ventral and Dorsal Pancreas Tissues in Patients with Pancreas Divisum

Abstract: Five cases of pancreas divisum, clinically diagnosed by endoscopic retrograde choledochopancreatography (ERCP), were studied histopathologically. They consisted of four biopsied cases and one patient who underwent pancreatoduodenectomy under the diagnosis of a suspected pancreatic carcinoma. Fibrosis was found in three out of the five cases, two cases with fibrosis in the dorsal pancreas and one in the ventral pancreas. In the two dorsal fibrosis pancreas cases, fibrosis was distributed in the intra- and interlobular areas and was accompanied by atrophy or disappearance of the acinar cells. These findings were compatible with chronic obstructive pancreatitis, distal to a stricture of the pancreatic duct. In the one ventral fibrosis pancreas case, i. e., the pancreatoduodenectomized case, fibrosis was distributed mainly in the interlobular area associated with hemosiderin deposition. Hemosiderin deposition was also observed in inflammatory foci at the posterior aspect of the ventral pancreas. Hence, such interlobular fibrosis developed in relation to the inflammatory foci, and was not caused by pancreas divisum. Therefore, in pancreas divisum, abnormal findings were observed in the dorsal pancreas tissue, and they were compatible with chronic obstructive pancreatitis. (Dig Endosc 1994; 6 : 74–79)     

Involvement of pancreatic and bile ducts in autoimmune pancreatitis

AIM:To examine the involvement of the pancreatic andbile ducts in patients with autoimmune pancreatitis.METHODS:Clinical and cholangiopancreatographic find-ings of 28 patients with autoimmune pancreatitis wereevaluated.For the purposes of this study,the pancreaticduct system was divided into three portions:the ventralpancreatic duct;the head portion of the dorsal pancre-atic duct;and the body and tail of the dorsal pancreaticduct.RESULTS:Both the ventral and dorsal pancreatic ductswere involved in 24 patients,while in 4 patients only thedorsal pancreatic duct was involved.Marked stricture ofthe bile duct was detected in 20 patients and their initialsymptom was obstructive jaundice.Six patients showedmoderate stenosis to 30%-40% of the normal diameter,and the other two patients showed no stenosis of thebile duct.Although marked stricture of the bile duct wasdetected in 83%(20/24)of patients who showed nar-rowing of both the ventral and dorsal pancreatic ducts,itwas not observed in the 4 patients who showed involve-ment of the dorsal pancreatic duct alone(P=0.0034).     

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.     

Morphological Study of Pancreas Divisum in Niigata Using ERCP

Abstract: The morphological characteristics and incidence of pancreas divisum (PD) in Niigata were investigated by studying 16,646 cases diagnosed by ERCP. These cases had been patients in 16 hospitals located in Niigata prefecture. PD was found in 114 (63 cases confirmed, 51 cases unconfirmed) of these 16,646 cases (0.68%). An unconfirmed case was defined as being a patient in whom only the short ventral pancreatic duct was visible through the main papilla, and the confirmed cases were classified into the 3 types according to the ductal systems of the dorsal and ventral pancreas. The classification of these 3 types was as follows. Type 1: Nonfusion between the ventral (VPD) and dorsal pancreatic ducts (DPD), which was visualized through the main papilla (MP) and the accessory papilla (AP), separately. Type 2: Only DPD was visualized through the AP. In spite of the cannulation of the MP, the VPD was not demonstrated. Type 3: Miscellaneous cases. The frequency of Type 1, Type 2, and Type 3 was 58.7% (37 cases), 28.6% (18 cases), and 12.7% (8 cases), respectively. Type 3 consisted of two subtypes. One (7 cases) was regarded as being when the patient had a very fine communicating branch between VPD and DPD, whether an obvious communicating branch could be detected or not by ERCP. The other subtype (only one case) showed very strange findings in which through the AP a short pancreatic duct distributed to the head of the pancreas and to the uncinate process was visualized and in which through the MP a long pancreatic duct to the tail was demonstrated, separately.     

Use of methylene blue to identify the minor papilla or its orifice in patients with pancreas divisum

BACKGROUND: In some patients with pancreas divisum, minor papilla cannulation is difficult because of uncertain identification of the papilla or its orifice, even after pancreatic secretory stimulation with secretin or cholecystokinin agonist. METHODS: Two techniques with methylene blue were used to identify the minor papilla and its orifice more clearly in a series of patients: spraying methylene blue over duodenal mucosa in the region suspected to contain the minor papilla with/without secretin or cholecystokinin agonist administration, and injection of contrast medium containing methylene blue into the ventral pancreatic duct by means of the major papilla in cases of incomplete pancreas divisum. Results were reviewed retrospectively. RESULTS: From January 2001 to May 2002, minor papilla cannulation with conventional methods initially failed in 38 of 305 patients with pancreas divisum because of an inconspicuous minor papilla orifice. Methylene blue was used to identity the minor papilla orifice in 14 of 38 patients (spraying, 13; injection, 1). Minor papilla cannulation was successful in 12 of 14 (86%) patients (spraying 11, injection 1). Mild pancreatitis developed in 1 patient. CONCLUSIONS: Methylene blue spraying or injection appears to be a helpful technique for identification of the inconspicuous minor papilla orifice in patients with pancreas divisum.     

ENDOSCOPIC APPROACH TO THE MINOR DUODENAL PAPILLA: SPECIAL EMPHASIS ON ENDOSCOPIC MANAGEMENT ON PANCREAS DIVISUM

Diagnostic and therapeutic approach to the minor duodenal papilla including standardized technique was reviewed. In cases in which a pancreatogram is not achieved or those in which only a small portion of the ductal anatomy is visualized via the major duodenal papilla, cannulation of the minor papilla provides a second route of access to the ductal system. Successful minor papilla cannulation requires meticulous attention to technique. As the orifice of the minor papilla is usually of pinpoint size, needle‐tipped catheters are useful. As minor papilla cannulation in pancreas divisum carries the risk of severe pancreatitis, the procedure should be performed with more caution. In some patients with pancreas divisum, an increased resistance to flow across the small orifice results in dorsal pancreatic duct hypertension and clinical symptoms including acute recurrent pancreatitis, chronic pancreatitis, and pancreatic‐type pain. Pancreas divisum patients with acute recurrent pancreatitis are the best candidates for endoscopic management for dorsal‐duct decompression including endoscopic minor papilla sphincterotomy and stenting.     

Endoscopic minor papilla interventions in patients without pancreas divisum

BACKGROUND: Endoscopic treatment through the minor papilla is well known in patients with pancreas divisum. However, there are few data concerning endoscopic minor papilla interventions in patients without pancreas divisum when access to the main pancreatic duct via the major papilla is technically difficult. METHODS: Records for 213 patients without pancreas divisum who, from April 2001 to June 2003, underwent ERCP for various pancreatic diseases were retrospectively reviewed. Patients were included if they had endoscopic interventions via the minor papilla because access through the major papilla was not possible. OBSERVATIONS: Minor papilla papillotomy or fistulotomy with endoscopic interventions was successful in 10 (91%) of 11 patients. Of these 10 patients, 9 had chronic pancreatitis and one had pancreatic ductal leak from previous pancreatic surgery. The reasons for the inability to access the main pancreatic duct to the tail of the gland via the major papilla included a distorted course of the main pancreatic duct (n=5), impacted stone (n=5), and stricture (n=8). In 8 patients, there were two causes. No complication related to the minor papilla interventions was observed in any patient. CONCLUSIONS: Endoscopic minor papilla interventions are technically feasible in patients with pancreatic diseases but not pancreas divisum when access to the main pancreatic duct via the major papilla is not possible.     

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.