Acute pancreatitis-onset carcinoma in situ of the pancreas with focal fat replacement diagnosed using serial pancreatic-juice aspiration cytologic examination (SPACE)

A 59-year-old woman was admitted for acute pancreatitis. Abdominal computed tomography and magnetic resonance imaging revealed a swollen pancreatic parenchyma with dilatation of the main pancreatic duct (MPD) of the pancreas tail, which was separated from the normal pancreas body side by a locally atrophic part of the pancreas. Magnetic resonance cholangiopancreatography showed MPD stricture in the pancreas tail with dilatation of the upstream MPD. Endoscopic ultrasonography revealed that the MPD stricture of the pancreas tail was surrounded by a blurred and hypoechoic area. Endoscopic retrograde cholangiopancreatography was performed for serial pancreatic-juice aspiration cytologic examination (SPACE). The result indicated adenocarcinoma. Distal pancreatectomy was performed, and the histopathological examination showed high-grade PanIN (carcinoma in situ of the pancreatic duct) of the pancreas tail with atrophy and fibrosis of the pancreatic parenchyma, and local fat replacement adjacent to the lesion. The final histopathological diagnosis was carcinoma in situ of the pancreatic duct of the pancreas tail. Acute pancreatitis and local fatty change of the pancreatic parenchyma with MPD stricture are important clinical manifestations of pancreatic carcinoma in situ (PCIS) and performing SPACE in cases of MPD stricture without a recognizable mass is preferable for a diagnosis of PCIS.     

Endoluminal ultrasonography for pancreatic diseases.

Endoluminal ultrasonography was performed on 146 patients with pancreatobiliary diseases by using high-frequency, thin ultrasonic probes, and the usefulness of the new technique in diagnosis of pancreatic diseases was reported. The ultrasound probe could be inserted into the main pancreatic duct in 43 of 46 patients (93.5%), and images of the lesions could be obtained in 42 patients (91.3%). Endoluminal ultrasonography revealed a hypoechoic mass with clear margins and central echogenicity in patients with pancreatic carcinoma. Endoluminal ultrasonography showed normal pancreatic parenchyma as a fine reticular pattern and did not reveal the tumors surrounding the stenosis in patients with focal pancreatitis. Endoluminal ultrasonography in patients with intraductal papillary adenocarcinoma of the pancreas revealed cystic lesions with mural nodules more than 4 mm, mucus echoes, and solid tumors with mixed echo patterns. There were no severe complications, and acute pancreatitis occurred in none of 46 patients, but high-level serum amylase after examination occurred in 5 patients (10.9%). Endoluminal ultrasonography is useful for differential diagnosis in patients with small pancreatic tumors or cystic lesions, especially intraductal papillary tumors of the pancreas. Endoluminal ultrasonography is recommended as a precise examination for the diagnosis of cystic lesions of the pancreas or stenosis of the main pancreatic duct after ERCP and EUS.     

Current understanding of precursors to pancreatic cancer

Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors,i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian‐type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1 cm) IPMNs of the gastric type are not always morphologically distinguishable from low‐grade PanINs. Mucin expression profiles suggest intestinal‐type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB‐type IPMNs progress toward ductal adenocarcinoma. It is a well‐described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step‐wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas.     

Diagnostic usefulness of laparoscopic fine‐needle aspiration for intraductal papillary tumor of the pancreas

A 67‐year‐old man who was followed up for 20 years for a diagnosis of chronic pancreatitis developed a unilocular cystic lesion in the pancreatic body and a gallstone. The cystic lesion (3.0 cm in diameter) was considered to be a pseudocyst with suspicion of a mucinous cystic tumor. Laparoscopic ultrasonography and fine‐needle aspiration (FNA) were performed following laparoscopic cholecystectomy. Under laparoscopic observation, the pinhole puncture was immediately closed. Analysis of the fluid revealed clusters of epithelial cells with mild atypia, remarkably elevated tumor markers (carcinoembryonic antigen and CA19‐9) and a K‐ras oncogene mutation. Distal pancreatectomy was performed 3 months after laparoscopic FNA and the pancreatic mass was diagnosed as an intraductal papillary tumor. The patient’s postoperative course was uneventful and he continues to do well without signs of recurrence. Laparoscopic FNA appears useful and safe for the diagnosis of cystic masses in the pancreas.     

胰腺导管腺癌、慢性胰腺炎及正常胰腺组织中胰腺上皮内瘤变的比较研究

目的探讨胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中各级别PanIN的发生率以及与临床病理学参数间的关系。方法回顾性研究长海医院2001年1月-2003年12月间外科切除和同期尸检获得的250例胰腺标本中PanIN的发生情况,并联系临床病理指标进行相关分析。结果250例胰腺标本中,有156例存在PanIN病变,发生率62.4％。其中,胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中PanIN的发生率分别为75.6％、46.0％和30.0％,胰腺导管腺癌PanIN发生率明显高于慢性胰腺炎及正常胰腺组织(P<0.01);慢性胰腺炎中高级别PanIN发生率明显高于正常胰腺组织(P<0.05)。PanIN-3仅在胰腺导管腺癌和慢性胰腺炎中见到。胰腺导管腺癌中,有烟酒嗜好和(或)糖尿病者高级别PanIN的发生率53.7％,明显高于对照组29.4％(P<0.01)。PanIN的发生率以61-70岁年龄组为最高。结论胰腺导管腺癌、慢性胰腺炎和正常胰腺组织中PanIN的发生率逐渐增加,程度逐渐加重,支持胰腺癌发生的分子模型。     

Spleen-preserving distal pancreatectomy with preservation of the splenic artery and vein for intraductal papillary-mucinous tumor (IPMT): three interesting cases

Preservation of the spleen at distal pancreatectomy has recently attracted considerable attention. Since our first trial and success with spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for tumors of the pancreas and chronic pancreatitis, this procedure has been performed more frequently. Three patients with intraductal papillary-mucinous tumor underwent spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein. In this procedure, the splenic vein is identified behind the pancreas and the connective tissue membrane is cut longitudinally above the splenic vein. An important point is to remove the splenic vein from the pancreas from the body of the pancreas toward the spleen. In one patient with intraductal papillary-mucinous tumor in the body of the pancreas who had undergone distal gastrectomy for duodenal ulcer 32 years previously, residual proximal gastrectomy could be avoided with this procedure. In this case, the histological diagnosis was a pseudocyst, and epithelial dysplasia was found in other pancreatic ductuli. In another case, epithelia were borderline between hyperplasia and adenoma. In both of these cases, the histological diagnosis was different from the preoperative diagnosis. Even with advances in imaging techniques, diagnosis of a cystic lesion of the pancreas is still very difficult. Ordinary distal pancreatectomy with splenectomy would have been oversurgery in these two cases, which could be avoided using our procedure. Severe complications were not found in any of the three cases and the postoperative course was uneventful. The patients have been followed as outpatients without any recurrence. Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein is easy and safe, and should be performed for some patients with intraductal papillary mucinous tumor of the pancreas.     

Does acute alcoholic pancreatitis precede the chronic form or is the opposite true? A histological study

OBJECTIVES: Whether acute alcoholic pancreatitis occurs in a normal pancreas or in a pancreas that has already been altered by chronic pancreatitis is unclear. Our objective is to clarify the relation between acute and chronic alcoholic pancreatitis by histologic study of the pancreas in a group of patients having a first attack of acute alcoholic pancreatitis. METHODS: From January 1989 to December 1999, 138 patients with acute pancreatitis, of whom 28 had alcoholic pancreatitis, were seen by us; in 21 of the latter 28 patients, it was the first attack. Of these 21, 6 underwent surgery for acute necrotic pancreatitis. In all 6 patients, adequate pancreatic biopsies were obtained during surgery. Tissue samples were prepared for histologic examination according to standard procedures. RESULTS: In all 6 patients, both acute necrotic and chronic lesions were found. The chronic lesions had characteristics of chronic calcifying pancreatitis and consisted of perilobular and intralobular fibrosis. loss of exocrine parenchyma, dilated interlobular ducts, and protein plugs within dilated ducts. CONCLUSIONS: This study suggests that acute alcoholic pancreatitis develops in a pancreas already affected by chronic pancreatitis. The hypothesis that in alcoholics chronic pancreatitis derives from acute pancreatitis is not supported by the present data.     

Pancreatic carcinoma accompanied by pseudocyst: Report of two cases

Two cases of pancreatic cancer accompanied by pseudocyst are reported. Case 1 was a 60-year-old man who was admitted to our hospital complaining of left lower abdominal discomfort. A cystic lesion, about 3 cm in diameter, was found in the pancreatic tail by ultrasonography (US) and computed tomography (CT). No signs of chronic pancreatitis were found. At operation, an elastic, hard, white tumor, about 1 cm in diameter, was felt adjacent to the cystic lesion on the duodenal side. Histologically, this tumor was a duct cell carcinoma with an adjacent pseudocyst upstream of the pancreas. Case 2 was a 57-year-old man who complained of back pain and loss of body weight. US and CT examination revealed a cystic lesion, 11×7 cm in size, in the tail of the pancreas. Histological examination of the resected speciment revealed both a duct cell carcinoma, 3 cm in size, in the body of the pancreas and a pseudocyst, 9 cm in size. Pseudocysts accompanying carcinoma are thought to develop from obstruction of the pancreatic duct by the carcinoma, followed by intraductal high pressure and disruption of ductules upstream of the pancreas. Thus, we should pay careful attention to pseudocyst of the pancreas, especially when signs of diffuse chronic inflammation cannot be found, to help identify duct cell carcinoma in the early stage. Further detailed examinations of the cyst fluid or pancreatic juice, such as cytology, tumor marker determinations, or establishment of K-ras codon 12 mutation, are needed.     

An apparent idiopathic case of relapsing acute pancreatitis

We describe a case of relapsing acute pancreatitis apparently idiopathic in a 55-year-old man. The patient did not smoke and was a modest and irregular drinker of wine. Endoscopic retrograde cholangiopancreatography showed an initial dilatation of secondary ducts like a chronic pancreatitis of class I of Cremer. Ultrasound and computed tomography resulted negative for pancreatic lesions. In the follow-up however, magnetic resonance cholangiopancreatography detected the presence of an intraductal mucin-hypersecreting neoplasm, a duct-ectatic mucinous cystic tumor of the pancreas, in the uncinate process. This is a benign lesion clearly recognized nowadays by magnetic resonance cholangiopancreatography, because this radiological technique shows the grape-like clusters of cystic lesions in secondary ducts communicating with the main duct on the same plane. The radiological picture above excludes a malignant lesion and a biopsy specimen is not required. Furthermore, an intraductal mucin-hypersecreting neoplasm of the pancreas does not require an immediate surgical resection because of its slow evolution and can be followed-up. Conversely cystoadenocarcinoma spreads in peripheral ducts and does not communicate with the Wirsung duct. It requires both surgical resection and a biopsy specimen for histological diagnosis. In the last episode of acute pancreatitis, a sphincterotomy was performed at endoscopic retrograde cholangiopancreatography and our patient had no more pain for one year.     

Intraductal papillary-mucinous tumors of the pancreas: Clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic

BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreatic ducts is increasingly recognized. This study investigated if clinical, imaging, or, histological features predicated outcome, formulated a treatment algorithm, and clarified relationships among IPMT, mucinous cystic neoplasms of the pancreas (MCN), and chronic pancreatitis. METHODS: The medical records, radiographs, and pathological specimens of 15 patients with IPMT (dilated main pancreatic duct or branch ducts with mucin overproduction) who were evaluated between October 1983 and January 1994 were reviewed. RESULTS: One patient had hepatic metastases. Fourteen underwent an operation (6 distal pancreatectomy, 4 total pancreatectomy, and 4 pancreaticoduodenectomy); all had dysplastic intraductal epithelium and chronic pancreatitis, whereas 3 had invasive adenocarcinoma. After a median of 25 months, 10 patients were alive; 3 of 4 with malignant and 2 of 11 with benign IPMT died (P < 0.05). Patients with or without carcinoma had similar clinical and radiographic features. A clinical diagnosis of chronic pancreatitis had been made in 9 patients with benign IMPT and in none with malignant IPMT (P < 0.05). CONCLUSIONS: IPMT is a dysplastic and likely precancerous lesion that is frequently diagnosed as chronic pancreatitis and is separate from MCN. Because it is not possible to distinguish noninvasive from invasive IPMT preoperatively, complete surgical excision of the dysplastic process is our treatment of choice whenever appropriate. (Gastroenterology 1996 Jun;110(6):1909-18)     

Chronic pancreatitis: controversies in etiology, diagnosis and treatment.

The pathogenesis of idiopathic chronic pancreatitis remains poorly understood despite the high expectations for ascribing the pancreatic damage in affected patients to genetic defects. Mutations in the cationic trypsinogen gene, pancreatic secretory trypsin inhibitor, and the cystic fibrosis conductance regulator gene do not account for the chronic pancreatitis noted in most patients with idiopathic chronic pancreatitis. Small duct chronic pancreatitis can be best diagnosed with a hormone stimulation test. Endoscopic ultrasonography can detect abnormalities in both the parenchyma and ducts of the pancreas. The true value of endoscopic ultrasonography in diagnosing small duct chronic pancreatitis remains to be fully defined and is under active investigation. It is not clear whether endoscopic ultrasonography is more sensitive for early structural changes in patients with small duct disease or is over diagnosing chronic pancreatitis. Pancreatic enzyme supplementation with non-enteric formulation along with acid suppression (H2 blockers or proton pump inhibitors) is an effective therapy for pain in patients with small duct chronic pancreatitis. The role of endoscopic ultrasonography-guided celiac plexus block should be limited to treating those patients with chronic pancreatitis whose pain has not responded to other modalities. Total pancreatectomy followed by autologous islet cell autotransplantation appears to be potential therapeutic approach but for now should be considered experimental.     

Rare case of adult pancreatic hemangioma and review of the literature

Pancreatic hemangiomas are a rare type of cystic tumor, with very few cases reported in the literature. Herein, we present the case of a 28-year-old woman who was admitted to our hospital for abdominal pain. A physical examination failed to reveal any abnormalities that could explain her symptoms. A contrast-enhanced computed tomography showed a multilocular cyst with moderately enhanced septa and fluid-fluid levels in the body and tail of the pancreas. A serous cystadenoma or pseudocyst of the pancreas was initially suspected, and the patient underwent a subtotal pancreatectomy and splenectomy. The pathologic diagnosis was a pancreatic hemangioma. This is the second case of pancreatic hemangioma with fluid-fluid levels reported in the literature. Upon imaging, the presentation of this tumor can resemble serous or mucinous cystadenomas, pseudocysts of the pancreas, and side-branch type intraductal papillary mucinous neoplasms. This report reviews the clinical symptoms, radiologic features, pathologic characteristics, differential diagnoses, and treatment of this rare lesion type.     

Mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm: A case report

Mass forming chronic pancreatitis is very rare. Diagnosis could be done by the pathologic findings of focal inflammatory fibrosis without evidence of tumor in pancreas. A 34-year-old man presented with right upper abdominal pain for a few weeks and slightly elevated bilirubin level on clinical findings. Radiological findings of multidetector-row computed tomography, magnetic resonance(MR) imaging with MR cholangiopancreatography and endoscopic ultrasonography revealed focal branch pancreatic duct dilatation with surrounding delayed enhancing solid component at uncinate process and head of pancreas, suggesting branch duct type intraductal papillary mucinous neoplasm. Surgery was done and pathology revealed the focal chronic inflammation, fibrosis, and branch duct dilatation. Herein, I would like to report the first case report of mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm.     

Evidence of pancreatic neuropathy and neuropathic pain in hereditary chronic pancreatitis

Increased neural density and neural hypertrophy are characteristic features of pancreatic neuropathy in chronic pancreatitis. Here, we present the extraordinary case of prominent pancreatic neuropathy in a 21-year-old female patient with hereditary chronic pancreatitis and intractable pain who underwent total pancreatectomy. The histopathological analysis demonstrated remnant pancreatic tissue which was only composed of prominent intrapancreatic nerves and fibrosis, without any visible remaining functional pancreatic parenchyma. These histological alterations, including nerve hypertrophy and increased neural density, are known for different aetiologies of chronic pancreatitis, e.g. alcoholic, idiopathic and tropic pancreatitis. However, this is the first report of a patient with hereditary chronic pancreatitis demonstrating the characteristic features of pancreatic neuropathy and neuropathic pain.     

Serous cystadenoma of the pancreas communicating with a pancreatic duct

Summary Conclusion To differentiate serous cystadenoma from other cystic lesions communicating with the pancreatic duct, careful radiological examination is necessary. Background Communication between the cystic cavity and the pancreatic duct in an ordinary serous cystadenoma is uncommon, although it is not uncommon in other cystic lesions, such as pseudocyst, mucinous cystadenoma/adenocarcinoma, and intraductal papillary tumor. Methods A serous cystadenoma of the pancreas communicating with main pancreatic duct in a 76-yr-old male is reported. Results The communication was preoperatively demonstrated by endoscopic retrograde cholangiopancreatography and confirmed by histopathological examination of the resected specimen.     

Adrenal pseudocyst mimicking cystic neoplasm of pancreatic tail

Cystic neoplasms of the pancreatic tail are usually picked up as incidental findings during imaging studies. We report an unusual case of adrenal pseudocyst mimicking cystic tumor of pancreatic tail who presented with abdominal pain and weight loss. Ultrasonography and CT of the abdomen revealed a cystic mass in relation to the pancreatic tail. On exploration, a cystic mass was present in the tail of the pancreas, for which distal pancreatectomy was performed. The histopathology report surprisingly revealed an adrenal pseudocyst without a cellular lining. The normal adrenal gland was compressed in the wall. This case highlights that this rare possibility should be considered in the differential diagnosis of cystic lesions of the pancreatic tail.     

A case of intraductal papillary mucinous tumour following recurrent attacks of pancreatitis lasting 26 years.

We report an interesting case of a patient with neither family nor personal history for pancreatic diseases that was admitted to our department in 1982, at the age of 25 years. At that time, medical history, absence of alcohol abuse, and radiological imaging suggested a diagnosis of idiopathic chronic pancreatitis. The patient underwent a left-pancreatectomy, with histological confirmation of chronic pancreatitis. He was asymptomatic until 1988, when episodes of pain arose, requiring a pancreatico-jejunostomy. No further problems ensued until 2004 when radiological investigation following pain-related symptoms revealed enormous dilation of the pancreatic duct. A pylorus-preserving pancreaticoduodenectomy resulting in total pancreatectomy was performed. Histological examination revealed an intraductal papillary mucinous non-invasive carcinoma. Review of the previously resected specimen revealed former misdiagnosis. This tumour usually affects an elderly population and nowadays is recognised as a possible cause of chronic obstructive pancreatitis. This report represents a slippery case of misdiagnosis and demonstrates that follow-up is always mandatory following a diagnosis of idiopathic chronic pancreatitis.     

Cyclooxygenase-2 expression associated with severity of PanIN lesions: a possible link between chronic pancreatitis and pancreatic cancer.

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key modulatory molecule in inflammation and neoplasia. Increasing evidence suggests a role for COX-2 in pancreatic cancer (PAC). However, expression of COX-2 in pancreatic intraepithelial neoplasia (PanIN), the precursor lesion of PAC which is often present in chronic pancreatitis (CP), has received little attention. METHOD: COX-2 immunostaining was performed on sections of PAC (n = 26), CP (n = 34), PanIN (n = 68) and normal pancreas (n = 11). Sections were also stained for macrophages (CD68), activated pancreatic stellate cells (alphaSMA), and collagen (Sirius Red) as markers of fibrosis.Semiquantitative scoring was based on the extent and intensity of immunostaining. RESULTS: COX-2 expression was increased in PAC compared to normal (p = 0.02) with 89% of cases exceeding COX-2 immunostaining in normal ducts. In PanIN lesions, COX-2 expression increased with escalating severity of the PanIN change (p < or = 0.01). COX-2 expression was increased in PanIN-2/3 compared to normal pancreas and CP (p < or = 0.001). In ducts of CP, COX-2 expression did not differ from that in normal tissue. There was no association between COX-2 expression and clinicopathological variables. CONCLUSION: The high level of COX-2 expression in PanIN lesions suggests that this enzyme could be a therapeutic target at a non-invasive stage of pancreatic carcinogenesis and feasible for chemoprevention in CP.     

Panniculitis and arthritis as the presenting manifestation of chronic pancreatitis

Although rare, panniculitis and polyarthritis can be the presenting manifestations of pancreatitis. Early recognition of this triad is critical because of the high mortality rate from pancreatic disease when the diagnosis is delayed. We report a patient with chronic alcohol intake whose sole presentation was severe polyarthritis and skin lesions secondary to chronic pancreatitis associated with extra pancreatic pseudocyst. Both arthritis and skin lesions disappeared after partial pancreatectomy and pancreatic stent insertion for a pancreatic duct stricture.     

Obstructing Pseudocyst of the Duct of Santorini in Pancreas Divisum

Pancreas divisum is a pancreatic duct anomaly that occurs due to failure of fusion of the dorsal and ventral ducts. While recognition of this anomaly is increasing due to more aggressive endoscopic retrograde cholangiopancreatography, its significance remains unclear. A patient with chronic pancreatitis and a history of alcohol abuse was noted to have pancreas divisum. At surgical exploration, intraoperative pancreatography revealed an obstructing pseudocyst of the duct of Santorini. Extended sphincteroplasty and cystduodenostomy as well as Roux-en-Y pancreatojejunostomy were necessary to insure adequate accessory duct drainage. Surgical therapy of pancreas divisum in chronic pancreatitis should be designed to correct existing pancreatic duct obstruction.