Effectiveness of steroid therapy for pancreatic cysts complicating autoimmune pancreatitis and management strategy for cyst-related complications.

Objectives: Autoimmune pancreatitis (AIP) sometimes becomes complicated with pancreatic cysts, although their detailed characteristics and management strategy have not been fully determined. We aimed to clarify the efficiency of steroid therapy and the risk factors for cyst formation and cyst-related complications. Methods: One hundred sixty-three AIP patients were retrospectively analyzed for relevant factors of cyst formation. We compared subjects with and without steroids to evaluate drug effectiveness on cyst size change and investigated the factors associated with cyst-related complications. Results: Thirty-two patients (19.6%) had complicating pancreatic cyst formation, and 40 cystic lesions of ≥10 mm in size were detected. Multivariate analysis revealed a drinking habit, abdominal/back pain, and elevated serum amylase to be significantly associated with cyst formation. Steroid-treated cysts became significantly reduced in size in the short-term and disappeared significantly more frequently within 1-year as compared with non-treated ones, which was confirmed by multivariate analysis. Six of 40 cysts exhibited cyst-related complications significantly associated with multilocular morphology and larger size. Conclusions: Steroid therapy is an effective choice for cysts developing in AIP to promote the release of pancreatic juice stasis. Larger lesions with multilocular morphology should be monitored closely for cyst-related complications and be considered strong candidates for steroid therapy.

EUS-Guided Pancreatic Cyst Ablation: a Clinical and Technical Review.

PURPOSE OF REVIEW: Pancreatic cystic lesions represent a growing public health dilemma, particularly as our population ages and cross-sectional imaging becomes more sensitive. Mucinous cysts carry a clinically significant risk of developing pancreatic cancer, which carries an extremely poor prognosis. Determining which cysts will develop cancer may be challenging, and surgical resection of the pancreas carries significant morbidity. The goal of this paper is to review the rationale for cyst ablation and discuss prior and current research on cyst ablation techniques and efficacy. Indications, contraindications, and factors related to optimal patient selection are outlined. RECENT FINDINGS: Endoscopic ultrasound-guided chemoablation of pancreatic cysts has been performed in neoplastic cysts, with varying levels of efficacy. Safety concerns arose due to the risk of pancreatitis in alcohol-based treatments; however, the most recent data using a non-alcohol chemoablation cocktail suggests that ablation is effective without the need for alcohol, resulting in a significantly more favorable adverse event profile. Endoscopic ultrasound-guided chemoablation of neoplastic pancreatic cysts is a promising, minimally invasive approach for treatment of cysts, with recent significant advances in safety and efficacy, suggesting that it should play a role in the treatment algorithm.

Steroid Therapy and Steroid Response in Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP), a unique subtype of pancreatitis, is often accompanied by systemic inflammatory disorders. AIP is classified into two distinct subtypes on the basis of the histological subtype: immunoglobulin G4 (IgG4)-related lymphoplasmacytic sclerosing pancreatitis (type 1) and idiopathic duct-centric pancreatitis (type 2). Type 1 AIP is often accompanied by systemic lesions, biliary strictures, hepatic inflammatory pseudotumors, interstitial pneumonia and nephritis, dacryoadenitis, and sialadenitis. Type 2 AIP is associated with inflammatory bowel diseases in approximately 30% of cases. Standard therapy for AIP is oral corticosteroid administration. Steroid treatment is generally indicated for symptomatic cases and is exceptionally applied for cases with diagnostic difficulty (diagnostic steroid trial) after a negative workup for malignancy. More than 90% of patients respond to steroid treatment within 1 month, and most within 2 weeks. The steroid response can be confirmed on clinical images (computed tomography, ultrasonography, endoscopic ultrasonography, magnetic resonance imaging, and 18F-fluorodeoxyglucose-positron emission tomography). Hence, the steroid response is included as an optional diagnostic item of AIP. Steroid treatment results in normalization of serological markers, including IgG4. Short- and long-term corticosteroid treatment may induce adverse events, including chronic glycometabolism, obesity, an immunocompromised status against infection, cataracts, glaucoma, osteoporosis, and myopathy. AIP is common in old age and is often associated with diabetes mellitus (33-78%). Thus, there is an argument for corticosteroid therapy in diabetes patients with no symptoms. With low-dose steroid treatment or treatment withdrawal, there is a high incidence of AIP recurrence (24-52%). Therefore, there is a need for long-term steroid maintenance therapy and/or steroid-sparing agents (immunomodulators and rituximab). Corticosteroids play a critical role in the diagnosis and treatment of AIP.

Pancreatic cystic lesions with atypical steroid response should be carefully managed in cases of autoimmune pancreatitis.

BACKGROUND AND AIM: Pancreatic cysts have been reported in cases with autoimmune pancreatitis (AIP) and are often treated by corticosteroid; however, their response to steroid has not been determined fully. We aimed to see the incidence and steroid response of pancreatic cysts and the features of cysts without proper response in cases with AIP. METHODS: Fifty-eight AIP cases were analyzed for the incidence and associated factors of pancreatic cystic lesions (≥ 10 mm). Of these, 47 cases, determined for steroid response, were retrospectively investigated for the factors associated with cyst change by corticosteroid therapy. RESULTS: At initial diagnosis, 17 pancreatic cystic lesions were recognized in 13 cases (22.4%) of AIP, with an average size of 30 mm (range: 11-130 mm), associated with higher incidence of elevated serum amylase (38.5% vs 11.1%, P = 0.02). Of these 13 cases, nine cases with 10 cystic lesions underwent steroid therapy in our hospital. All of seven unilocular cysts were dramatically shrunken or vanished in a few months; meanwhile, three cases with multilocular cysts showed scarcely any steroid response (P = 0.008). Of these three cases, two cases were revealed to accompany pancreatic ductal carcinoma, in contrast to null of seven unilocular cysts (P = 0.07). CONCLUSIONS: Pancreatic cystic lesions are sometimes recognized in cases with AIP, and most unilocular cysts can be minimized by corticosteroids. However, clinicians must be alert for atypical pancreatic cysts, such as multilocular cysts or cysts without obvious steroid response.

Steroid therapy has an acceptable role as the initial treatment in autoimmune pancreatitis patients with pancreatic cyst formation: Based on a Japanese nationwide study.

BACKGROUND: We attempted to determine the indications and limitations of steroid therapy as the first-line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF). METHODS: This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF. RESULTS: Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86% (86/100) of patients who had received steroid treatment, but only 33.3% (5/15) of patients who had not received steroids. Relapse after the remission (n = 86) occurred in 7.6% (6/86) of patients who had received steroid therapy, but 40% (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait and watch approach without steroid treatment (odds ratio = 0.126, P < .001) as a significant and independent negative predictor of remission of ACF. As for predictors of relapse, the presence of varix (odds ratio = 5.83, P = .036) was identified as an independent risk factor. CONCLUSION: Steroid therapy plays an important role as first-line therapy in AIP patients with pancreatic cyst formation, however, varix formation, besides the diameter of the cyst(s), is a risk factor for refractoriness to steroid therapy.

Endoscopic ultrasonography-guided ethanol lavage with paclitaxel injection treats patients with pancreatic cysts.

BACKGROUND & AIMS: Endoscopic ultrasonography (EUS)-guided interventions have been used to treat patients with cystic lesions of the pancreas (CLPs). We used EUS to guide injection and lavage of ethanol, followed by injection of paclitaxel, into cysts, and investigated treatment response and predictors. METHODS: Fifty-two patients were enrolled in the study using the following inclusion criteria: unilocular or oligolocular cysts, indeterminate cystic lesions that required EUS fine-needle aspiration, and cystic lesions that grew during the observation period. Forty-seven patients were followed up for more than 12 months and their outcomes were analyzed. RESULTS: The mean diameter of the CLPs was 31.8 mm (range, 17-68 mm) and the estimated volume was 14.09 mL (range, 1.16-68.74 mL). Twenty CLPs were oligolocular. The mean level of carcinoembryonic antigen was 463 ng/mL (range, 1-8190 ng/mL). The median follow-up period was 21.7 months. A complete response was observed in 29 patients, a partial response in 6 patients, and persistent cysts in 12 patients. Four of 12 patients with persistent cysts underwent surgery. The histopathologic degree of epithelial ablation varied from 0% to 100%. Based on univariate analysis, EUS diameter and original volume predicted cyst resolution; in multivariate analysis, only original volume predicted resolution. Mild pancreatitis and splenic vein obliteration each occurred in 1 patient. CONCLUSIONS: EUS-guided injection and lavage of ethanol, followed by injection of paclitaxel, appears to be a safe method for treating pancreatic cysts; 62% of patients had complete resolution. Small cyst volume predicted complete resolution.

Association between lymphoepithelial cysts of the pancreas and HIV infection.

BACKGROUND & AIMS: To report the association of lymphoepithelial cysts (LEC) of the pancreas with Human Immunodeficiency Virus (HIV) infection. An association between LEC and HIV infection is already established in the parotid gland (PG). METHODS: Report of the first two cases of LEC of the pancreas associated with HIV infection and comparison of the clinical and histopathological aspects of LECs of the pancreas and of the PG. RESULTS: LECs of the pancreas were discovered by CT imaging in 2 patients with a history of HIV infection. Notably, LEC completely resolved in one patient after initiation of antiretroviral therapy. CONCLUSION: This is the first report of an association of LEC of the pancreas and HIV infection. In the presence of LEC of the pancreas, we propose a systematic screening for HIV infection and associated lesions in the PG. Antiretroviral therapy should be initiated in untreated patients. Surgery should be reserved for symptomatic patients in whom medical therapy has failed.

Large lymphoepithelial cyst of pancreas: a rare entity managed using lumen-apposing metal stent-case report and review of the literature.

Lymphoepithelial cysts (LECs) are extremely rare nonmalignant cysts of the pancreas. Asymptomatic LECs are managed conservatively, but symptomatic LECS have traditionally been managed with surgical resection. We report the first case of symptomatic infected LEC of the pancreas successfully managed with EUS guided endoscopic drainage with lumen-apposing metal stent. We also review the relevant literature and discuss the diagnosis and management of this rare cyst of the pancreas.

Cyclooxygenase-2 and Cytosolic Phospholipase A2 Are Overexpressed in Mucinous Pancreatic Cysts.

OBJECTIVES: Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer chemoprevention strategy for these lesions. We evaluated the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in the epithelium of pancreatic cysts and correlated enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) concentration. METHODS: Pathology of 80 resected pancreatic cysts was reviewed. Expression of COX-2, cPLA2, and AKT was quantified by tissue immunohistochemistry immunoreactivity scores (IRSs). IRS values were compared between cyst types and (in 30 cases) with matched cyst fluid PGE2 concentrations. RESULTS: The mean IRS was higher in the epithelium of mucinous vs nonmucinous cysts for COX-2 (6.1 ± 4.7 vs 3.2 ± 2.8, P = 0.01) and cPLA2 (6.9 ± 3.0 vs 2.9 ± 2.9, P < 0.001). Cyst epithelial COX-2 expression was higher in mucinous cysts with low-grade dysplasia vs those with high-grade dysplasia or invasive carcinoma (IRS 8.0 ± 3.9 vs 1.5 ± 2.9, P < 0.001), whereas the opposite was found for cPLA2 (6.2 ± 3.0 vs 8.6 ± 2.3, P = 0.005). Cyst fluid PGE2 concentrations did not correlate with either the IRS or a history of low- to moderate-dose ASA use. CONCLUSIONS: COX-2 and cPLA2 are overexpressed in the epithelium of mucinous pancreatic cysts. COX-2 and/or cPLA2 inhibition might prevent the emergence or progression of mucinous pancreatic cysts, but higher doses of ASA or nonsteroidal anti-inflammatory drugs may be necessary to substantially inhibit cyst epithelial COX-2 activity.

Advanced endoscopic ultrasound management techniques for preneoplastic pancreatic cystic lesions.

Pancreatic cystic lesions can be benign, premalignant or malignant. The recent increase in detection and tremendous clinical variability of pancreatic cysts has presented a significant therapeutic challenge to physicians. Mucinous cystic neoplasms are of particular interest given their known malignant potential. This review article provides a brief but comprehensive review of premalignant pancreatic cystic lesions with advanced endoscopic ultrasound (EUS) management approaches. A comprehensive literature search was performed using PubMed, Cochrane, OVID and EMBASE databases. Preneoplastic pancreatic cystic lesions include mucinous cystadenoma and intraductal papillary mucinous neoplasm. The 2012 International Sendai Guidelines guide physicians in their management of pancreatic cystic lesions. Some of the advanced EUS management techniques include ethanol ablation, chemotherapeutic (paclitaxel) ablation, radiofrequency ablation and cryotherapy. In future, EUS-guided injections of drug-eluting beads and neodymium:yttrium aluminum agent laser ablation is predicted to be an integral part of EUS-guided management techniques. In summary, International Sendai Consensus Guidelines should be used to make a decision regarding management of pancreatic cystic lesions. Advanced EUS techniques are proving extremely beneficial in management, especially in those patients who are at high surgical risk.

Corticosteroid-responsive pancreatic cyst found in autoimmune pancreatitis.

There have been only a few reports of autoimmune pancreatitis complicated with pancreatic cyst and such cysts are rare, probably due to the absence of severe tissue necrosis and/or lack of stasis of the pancreatic juice in this condition. However, during a follow-up of 48 patients with this disease, we found 3 patients with pancreatic cysts, and this enabled us to evaluate their clinicopathological findings. Between September 1994 and July 2003, we treated and followed 48 patients with autoimmune pancreatitis, and found 3 patients with pancreatic cyst formation that was responsive to corticosteroid therapy. All of the patients with cysts had high serum IgG4 concentrations. After corticosteroid therapy, rapid resolution of the pancreatic cysts was observed. Immunostaining with goat polyclonal antibody for each IgG subclass showed severe infiltration of IgG4-positive plasma cells in the cyst wall in one patient. The high serum IgG4 concentration and favorable response to corticosteroid therapy suggests that a highly active state of the inflammatory process is closely associated with cyst formation, and that a corticosteroid-responsive pancreatic cyst is a characteristic feature of autoimmune pancreatitis.

Somatostatin analogue in treatment of coexisting glucagonoma and pancreatic pseudocyst: dissociation of responses.

After an acute episode of pancreatitis, a 63-year-old man was found to have a pancreatic glucagonoma. The tumor was resected without evidence of metastases. Three years later he had symptoms of uncontrolled diabetes, no skin lesions, and diarrhea and was found to have a pancreatic pseudocyst and multiple hepatic metastases. Glucagon concentrations were raised but were suppressible by glucose and somatostatin and responded to arginine stimulation. He was treated for 6 months with octreotide (Sandostatin), which reduced his symptoms; the pseudocyst resolved, but liver metastases continued to grow. Although spontaneous resolution of the pseudocyst is possible, this case appears to illustrate differences in sensitivity of endocrine and exocrine tissues to suppression by Sandostatin.

[Lanreotide acetate may cure cystic dystrophy in heterotopic pancreas of the duodenal wall]. / Le lanréotide peut traiter une dystrophie kystique de la paroi duodénale développée sur pancréas aberrant.

Cystic dystrophy in heterotopic pancreas of the duodenal wall is a rare but benign disease, associated in most of the cases with chronic pancreatitis. Treatment of this disease is controversial. We report here the use of a long-acting somatostatin synthetic stable analogue in the treatment of a cystic dystrophy in heterotopic pancreas of the duodenal wall: a 45-year-old man, hard drinker, was treated successfully during three months with lanreotide acetate; disappearance of cysts was confirmed by a computed tomography two months after the end of treatment.