Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions.

Pancreatic cystic lesions (PCL) are increasingly diagnosed. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) cytology is often used for diagnostic confirmation but can be inconclusive. In this study, the role of molecular analyses in the pre-operative diagnostics of PCL is evaluated. Targeted Next Generation Sequencing (NGS) applied on cytology smears was retrospectively evaluated in a cohort of 37 resected PCL. Usefulness of NGS on fresh cyst fluids was tested in a prospective cohort of patients with newly diagnosed PCL (n = 71). In the retrospective cohort, cytology plus NGS displayed higher sensitivity (94.1% vs. 87.1%) and specificity (100% vs. 50%) than cytology alone for the detection of mucinous neoplasms. In the prospective cohort, sensitivity and specificity of conventional cytology alone were 54.2% and 100% for the detection of mucinous neoplasia and 50.0% and 100% for the detection of high-grade dysplasia, respectively. Adding NGS, all lesions which underwent histopathologic verification (12/71, 17%) could be classified without false positive or false negative results regarding the detection of mucinous neoplasm so far. NGS analysis of cfDNA in PCL fluids is feasible and can increase diagnostic accuracy in the detection of mucinous neoplasms compared to cytology alone. However, algorithms for the detection of high-risk lesions need further improvement.

Elevated hemoglobin A1c is associated with the presence of pancreatic cysts in a high-risk pancreatic surveillance program.

BACKGROUND: Emerging evidence demonstrates that surveillance of individuals at high-risk (HRIs) of developing pancreatic adenocarcinoma allows for identification and treatment of resectable tumors with improved survival. Population-based data suggest that hyperglycemia may be present up to three years before the development of pancreatic cancer. We investigated whether elevated hemoglobin A1c (HbA1c) is associated with the development of pancreatic cysts in a pancreatic surveillance program. METHODS: We performed a retrospective study of HRIs who underwent pancreatic surveillance at a single institution between May 2013 and March 2019, according to published criteria. We collected demographic information, clinical data including HbA1c, and imaging results. We compared data using univariable and multivariable analyses. Our primary outcome was the presence of pancreatic cysts on initial surveillance in patients with elevated HbA1c. RESULTS: Ninety-eight patients underwent surveillance imaging via EUS or MRCP and seventy-four patients met inclusion criteria. Thirty patients were found to have cysts on initial imaging. Older age (p < 0.01) and HbA1c in the prediabetic range or higher (p = 0.01) were associated with the presence of cysts or solid lesions on univariable analysis. After controlling for confounders, age (aOR 9.08, 95% CI 2.29-36.10), and HbA1c > 5.7% (aOR 5.82, 95% CI 1.50-22.54) remained associated with presence of cysts and solid lesions in HRIs. In patients with cysts or solid lesions there was a strong association between increased age and elevated HbA1c (p < 0.01). CONCLUSION: HRIs with elevated HbA1c were more likely to have pancreatic cysts compared to individuals with lower HbA1c on initial imaging in a pancreatic surveillance program. These findings may help tailor the surveillance protocols for those at increased risk of developing pancreatic adenocarcinoma.

Endoscopic Ultrasound-Guided Fine-Needle Aspiration Microhistology in Asymptomatic and Symptomatic Pancreatic Cystic Lesions.

OBJECTIVE: This study aimed to analyze the usefulness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) microhistology to detect malignancy in pancreatic cystic lesions (PCLs). METHODS: Patients with PCLs were identified and submitted to EUS-FNA from January 2010 to January 2017. The percentage of samples suitable for diagnostic classification by microhistology and the positive and negative likelihood ratios to detect malignancy in asymptomatic (APC) and symptomatic (SPC) PCLs were determined. RESULTS: Endoscopic ultrasound-guided fine-needle aspiration was performed in 510 patients. The resulting material was processed by microhistology and useful for diagnosis in 432 (84.2%). Clinical characteristics of APC (341) and SPC (169) revealed that APC patients were younger (P = 0.004) and had smaller PCLs (23 vs 35 mm; P < 0.001). In APC, we found more preneoplastic (38.7% vs 30.2%; P = 0.0016) and a lower number of malignant PCLs (8.2% vs 24.3%; P < 0.001). In APC and SPC, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of microhistology to detect malignancy were 71.4%, 99.7%, 95.2%, 97.5%, and 97.4% (k = 0.80) and 58.5%, 96.9%, 85.7%, 87.9%, and 87.6%, respectively. CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration was technically feasible. Microhistology was especially useful to detect neoplastic or malignant PCLs in APC patients.

Review of the diagnosis and management of intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasms are common lesions with the potential of harbouring/developing a pancreatic cancer. An accurate evaluation of intraductal papillary mucinous neoplasms with high-resolution imaging techniques and endoscopic ultrasound is mandatory in order to identify patients worthy either of surgical treatment or surveillance. In this review, the diagnosis and management of patients with intraductal papillary mucinous neoplasms are discussed with a specific focus on current guidelines. Areas of uncertainty are also discussed, as there are controversies related to the optimal indications for surgery, surveillance protocols and surveillance discontinuation.

Multivariate analysis of the factors affecting the prognosis of walled-off pancreatic necrosis after endoscopic ultrasound-guided drainage.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided drainage has become the treatment of choice for walled-off pancreatic necrosis (WOPN). However, no consensus exists on the most significant patient- and procedure-related factors that affect prognosis. The aim of the study is to investigate the correlation between patient- and procedure-related factors and post-procedure complications after EUS-guided drainage. METHODS: A retrospective analysis of the clinical characteristics of patients with WOPN who underwent EUS-guided drainage at our endoscopy center between November 2011 and August 2017 was performed. Chi-square analysis and binary logistic regression statistical methods were used to analyze the correlation between influencing factors and prognosis. RESULTS: A total of 85 patients (male/female, 50/35) with WOPN were included in the study. The average age was 44.95 years. The cyst diameter was 10.58 ± 4.78 cm. Multivariate analysis showed that WOPN with higher solid content (> 30%) increased the probability of endoscopic necrosectomy (OR 6.798; 95% CI 1.423, 32.470; p = 0.016). The use of a metal stent increased the probability of endoscopic necrosectomy (OR 3.503; 95% CI 1.251, 9.810; p = 0.017) and the length of hospitalization (OR 3.315; 95% CI 1.192, 9.215; p = 0.022). Female patients had a higher probability of requiring endoscopic necrosectomy (OR 2.683; 95% CI 1.027, 7.007; p = 0.044) and prolonged hospitalization (OR 2.675; 95% CI 1.065, 6.721; p = 0.036). CONCLUSION: The solid content of WOPN, type of stent, and sex of patients were associated with increased probability of endoscopic necrosectomy.

Progression of pancreatic cystic lesions without any risk features is associated with initial cyst size and obesity.

BACKGROUND AND AIM: The clinical significance of incidental pancreatic cystic lesions (PCLs) remains unclear in those that are not accompanied by worrisome features or high-risk stigmata. We aimed to investigate the natural course of PCLs without any risk features and examine the clinical factors associated with their progression. METHODS: We conducted a retrospective cohort study of 427 patients with PCLs, which were incidentally detected by computed tomography between January 2003 and December 2012. Progression of PCLs without any risk features and the clinical factors associated with their progression were investigated. The length of time to significant growth was also evaluated. RESULTS: Ninety-four (22.0%) of the 427 patients had asymptomatic PCLs that showed significant growth after a median surveillance period of 5.3 years; approximately 27.7% of the patients showed significant size changes in the first 5 years, while the remaining 72.3% showed significant changes after 5 years. The cumulative rate of patients with significant growth was associated with initial cyst size and high body mass index. In the growth group, additional treatments were required for 12 patients, one of whom developed malignancy. Four patients in the stable group underwent additional treatment and showed no malignant change. CONCLUSIONS: One-fifth of the asymptomatic PCLs significantly increased in size after a long-term follow-up period, which was associated with initial cyst size and obesity. The size of PCLs mostly increased after 5 years; although the malignancy risk of PCLs was low, it was still a concern.

Etiologic Distribution of Pancreatic Cystic Lesions Identified on Computed Tomography/Magnetic Resonance Imaging.

OBJECTIVES: This study aimed to determine the distribution of etiology of pancreatic cysts using established criteria/markers from cyst fluid analysis and cytology that have been reported to have high specificity in published literature. METHODS: A retrospective study of pancreatic cysts using an endoscopic database from March 2002 and May 2013 was conducted. Pancreatic cysts <10 mm and cysts with a history of pancreatic cancer were excluded. RESULTS: In our cohort of 758 patients with pancreatic cyst(s), the cyst etiology was as follows: mucinous cyst/side-branch intraductal papillary mucinous neoplasms (SB-IPMNs)/mucinous cystic neoplasms (MCN; 48.2%), pseudocyst (27.6%), serous cystadenoma (11%), simple cysts (6.4%), mucinous cystadenocarcinoma (5.1%), and other (1%). Approximately 41% (n = 310) of the cysts were ≥3 cm in size and included the following: pseudocyst (39.7%), mucinous cysts/SB-IPMN/MCN (28.1%), serous cystadenoma (16.7%), mucinous cyst adenocarcinoma (9.7%), and simple cyst (4.8%). In 118 patients with a known history of acute pancreatitis, the cyst diagnoses included pseudocyst (68.7%), mucinous cyst/SB-IPMN/MCN (18.6%), benign/simple cyst (7.6%), and mucinous cystadenocarcinoma (2.5%). CONCLUSIONS: In patients with cystic pancreatic lesion noted on cross-sectional imaging, approximately half of the patients have lesions without malignancy or malignant potential and therefore not requiring surveillance. Endoscopic ultrasound/endoscopic ultrasound-guided fine-needle aspiration evaluation of the pancreatic cysts can help optimize their further management.

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.

[Cystic lesions of the pancreas : Differential diagnostics and treatment]. / Zystische Raumforderungen des Pankreas : Differenzialdiagnostik und Therapie.

Cystic space-occupying lesions of the pancreas represent incidental findings in most cases. As there is a potential risk of malignant transformation further evaluation of the lesions as well as a follow-up of these patients is usually recommended. Before this work-up is initiated the clinical situation of the patient as a whole and comorbidities, age and personal preferences have to be taken into account. So far there are no biomarkers that reliably predict the risk of malignant transformation. Imaging by magnetic resonance tomography (MRI) in combination with magnetic resonance cholangiopancreatography (MRCP) is more accurate than computed tomography to identify worrisome features. During follow-up, endoscopic ultrasound (EUS) can be used as complementary method to MRI/MRCP. Using contrast enhancement or endoscopic fine needle aspiration (EUS-FNA) may influence the therapeutic strategy in some patients. Whereas for some cystic pancreatic lesions consensus has been reached, varying recommendations exist for intraductal papillary mucinous neoplasms (IPMN). There is consensus that in main-duct as well as in mixed-type IPMN surgery is recommended. The management of branch-duct type IPMN, however, remains controversial. A multidisciplinary expert panel including gastroenterologists, visceral surgeons, radiologists and pathologists is essential to discuss all cases of patients with cystic pancreatic lesions and to guarantee an optimal, patient-centered treatment recommendation.

A Rare Case of Pancreatic Endometrial Cyst and Review of the Literature.

Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are extremely rare lesions that are difficult to diagnose before surgery. We report the case of a 26-year-old patient with a recent episode of left abdominal pain who presented with a large cyst in the pancreatic body. Laboratory results showed white blood cell and C-reactive protein elevation, whereas the patient's tumor marker levels were within the normal range. Distal pancreatectomy with splenectomy was performed. The final histopathological examination confirmed the presence of endometriotic cysts within the pancreas. Only 13 cases of endometriotic cysts of the pancreas have been previously reported. The preoperative diagnosis is challenging, and most patients undergo pancreatic resection because of suspected neoplasms. This case report reviews previous studies and discusses the clinicopathological features, pathogenesis, and appropriate treatment for pancreatic endometrial cysts.

Pancreatic cystosis in patients with cystic fibrosis: A qualitative systematic review.

BACKGROUND: Patients with cystic fibrosis (CF) and a CFTR gene mutation may present with a variety of pancreatic disorders. The presence of multiple macrocysts (>1 cm) replacing the entire pancreatic parenchyma is termed pancreatic cystosis. Lack of clear data makes clinical decision making challenging and controversial. The aim of this review is to perform a qualitative systematic analysis of the literature with intention to evaluate management plans. METHODS: Electronic databases MEDLINE, Embase, and Scopus were searched for relevant studies, and 19 studies describing patients with pancreatic cystosis were included and analyzed for clinical features and therapy offered. RESULTS: The data of 24 patients were collected from included studies. Eight cases (33%) had a documented CFTR gene mutation and 10 (42%) were symptomatic at presentation. Imaging modalities included ultrasound in 18 (75%), CT in 12 (50%), and MRI in 8 (33%) cases. An average size of the largest cyst was 5.4 cm. 6 (25%) patients were offered therapy that described surgical (3), endoscopic (1), or medical therapy (2). Surgeries offered included total pancreatectomy, partial pancreatic resection of uncertain extent, and complex cyst resection. Endoscopic treatment was cystogastrostomy. Novel medical treatment was utilized with Doxepin, Propantheline, and Clonidine, resulting in reduction in cyst size and overall clinical improvement. CONCLUSION: Patients with pancreatic cystosis should not be denied treatment when necessary. This literature review is the most comprehensive thus far of cystic fibrosis and pancreatic cystosis, and it did not provide identification of a definitive treatment plan or demonstrate contraindication to specific therapies.

The Role of Endoscopic Ultrasound-guided Drainage for Autoimmune Pancreatitis-associated Pancreatic Cysts: A Report of Five Cases and a Literature Review.

Objective Autoimmune pancreatitis (AIP) has been recognized as a benign disease, which that shows a prompt response to corticosteroid treatment (CST). It was previously believed to not be associated with cyst formation; however, a few cases of AIP-associated pancreatic cyst (PC) have been reported. Some cases were reported to have been effectively treated by CST, while others were refractory to CST. Many of the patients received interventional treatment. Until now, there has been no consensus on the therapeutic strategies for AIP-associated PC. The aim of the present study is to describe a therapeutic strategy for this condition. Methods We conducted a retrospective study of 5 cases of AIP-associated PC that were treated by endoscopic ultrasonography-guided pancreatic fluid collection drainage (ESPD) or CST at Tokyo Medical University Hospital between March 2012 and October 2016, analyzed the therapeutic outcomes, and performed a literature review. Results The initial treatments included CST (n=2) and ESPD (n=3). All of the PCs disappeared after treatment In 1 of the patients who received CST case and 3 of the patients who received ESPD; however, the PC did not disappear in one of the patients who received CST (corticosteroid maintenance therapy), even after the dose of corticosteroids was increased; ESPD was eventually performed and the PC disappeared. There were no procedure-related complaints. Conclusion We propose that CST be administered as the first-line treatment for AIP-associated PC, particularly in cases of PC without a history of CST. However, ESPD can be applied to treat cases of corticosteroid refractory PC.

Hypernatremia and acute pancreatitis in chronic kidney disease: back to the salt mines. Questions.

BACKGROUND: Acute pancreatitis can be a life-threatening complication in patients with chronic kidney disease (CKD), especially in kidney transplant recipients. CASE DIAGNOSIS/TREATMENT: The patient was 7 years old when he received renal transplantation for CKD secondary to posterior urethral valves. Two years later, he presented with severe necrotizing pancreatitis (Ranson's score 5, Balthazar's score 8). Viral and genetic testing came back negative; pancreatitis was attributed to the patient's treatments (prednisone, trimethoprim-sulfamethoxazole, and everolimus). Twenty days later, necrotized pancreatic cysts had formed. Two drains were surgically inserted into the abdomen, and continuous cyst lavage was started with normal saline solution. Two days later, blood tests revealed severe hypernatremia and hypokalemia. We suspected unwanted peritoneal dialysis had occurred because of the high sodium chloride content and the absence of potassium in the normal saline solution being used for cyst lavage. We switched to a peritoneal dialysis solution for the lavage, leading to complete correction of hydroelectrolytic disorders. CONCLUSION: Acute pancreatitis is a frequent and potentially severe complication in CKD patients. It should be suspected in the presence of nonspecific symptoms, such as abdominal pain or vomiting. Rigorous monitoring of electrolytes is also mandatory for managing CKD patients with acute pancreatitis.

Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study.

OBJECTIVE: To analyse the prevalence, incidence and clinical relevance of pancreatic cysts detected as incidental finding in a population-based longitudinal study. DESIGN: A total of 1077 participants (521 men, mean age 55.8±12.8 years) of 2333 participants from the population-based Study of Health in Pomerania (SHIP) underwent magnetic resonance cholangiopancreaticography (MRCP) at baseline (2008-2012). MRCP was analysed for pancreatic cysts with a diameter ≥2 mm. 676/1077 subjects received a 5-year follow-up (2014-2016). The prevalence and incidence of pancreatic cysts (weighted for study participation) were assessed in association to age, gender and suspected epidemiological risk factors. Mortality follow-up was performed in 2015 for all SHIP participants (mean follow-up period 5.9 years, range 3.2-7.5 years). RESULTS: At baseline pancreatic cysts had a weighted prevalence of 49.1%, with an average number of 3.9 (95% CI 3.2 to 4.5) cysts per subject in the subgroup harbouring cysts. Cyst size ranged from 2 to 29 mm. Prevalence (p<0.001), number (p=0.001) and maximum size (p<0.001) increased significantly with age. The 5-year follow-up revealed a weighted incidence of 12.9% newly detected pancreatic cysts. 57.1% of the subjects initially harbouring pancreatic cysts showed an increase in number and/or maximum cyst size. Of all subjects undergoing MRCP, no participant died of pancreatic diseases within mortality follow-up. CONCLUSION: The prevalence of pancreatic cysts in the general population is unexpectedly high, and their number and size increase with age. Overall, no pancreatic cancer was observed in this collective during a 5-year follow-up. Nevertheless, prospective follow-up imaging showed minimal progress in more than 50%. Only about 6% of cysts and 2.5% of the study group initially presented with cysts of more than 1 cm and thus might be clinically meaningful.