Comparison of two intraductal brush cytology devices for suspected malignant biliary strictures: randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with biliary brush cytology is commonly used to diagnose malignant pancreatobiliary strictures. This trial compared the sensitivity of two intraductal brush cytology devices. METHODS: A randomized controlled trial in which consecutive patients with suspected malignant, extrahepatic biliary strictures were randomized (1:1) to a dense or conventional brush cytology device. Primary endpoint was sensitivity. Interim analysis was conducted after 50% of the patients completed follow-up. Results were interpreted by a data safety monitoring board. RESULTS: Between June 2016 and June 2021, 64 patients were randomized to the dense (27 patients, 42%) or conventional brush (37 patients, 58%). Malignancy was diagnosed in 60 patients (94%) and benign disease in 4 patients (6%). Diagnoses were confirmed by histopathology in 34 patients (53%), cytopathology in 24 patients (38%), and clinical or radiological follow up in 6 patients (9%). Sensitivity of the dense brush was 50%, compared to 44% for the conventional brush (p = 0·785). DISCUSSION: The results of this randomized controlled trial showed that the sensitivity of a dense brush is not superior to a conventional brush for diagnosing malignant extrahepatic pancreatobiliary strictures. This trial was prematurely ended for reasons of futility. TRIAL REGISTRATION: Netherlands Trial Register number; NTR5458.

Diagnostic accuracy of the AGA, IAP, and European guidelines for detecting advanced neoplasia in intraductal papillary mucinous neoplasm/neoplasia.

BACKGROUND: Follow-up in patients with intraductal papillary mucinous neoplasm (IPMN) aims to detect advanced neoplasia (high-grade dysplasia/cancer) in an early stage. The 2015 American Gastroenterological Association (AGA), 2017 International Association of Pancreatology (IAP), and the 2018 European Study Group on Cystic tumours of the Pancreas (European) guidelines differ in their recommendations on indications for surgery. However, it remains unclear which guideline is most accurate in predicting advanced neoplasia in IPMN. METHODS: Patients who underwent surgery were extracted from a prospective database (January 2006-January 2021). In patients with IPMN, final pathology was compared with the indication for surgery according to the guidelines. ROC-curves were calculated to determine the diagnostic accuracy for each guideline. RESULTS: Overall, 247 patients underwent surgery for cystic lesions. In 145 patients with IPMN, 52 had advanced neoplasia, of which the AGA guideline would have advised surgery in 14 (27%), the IAP and European guideline in 49 (94%) and 50 (96%). In 93 patients without advanced neoplasia, the AGA, IAP, and European guidelines would incorrectly have advised surgery in 8 (8.6%), 77 (83%) and 71 (76%). CONCLUSION: The European and IAP guidelines are clearly superior in detecting advanced neoplasia in IPMN as compared to the AGA, albeit at the cost of a higher rate of unnecessary surgery. To harmonize care and to avoid confusion caused by conflicting statements, a global evidence-based guideline for PCN in collaboration with the various guidelines groups is required once the current guidelines require an update.

Validation of combined carcinoembryonic antigen and glucose testing in pancreatic cyst fluid to differentiate mucinous from non-mucinous cysts.

BACKGROUND: More accurate diagnosis of mucinous cysts will reduce the risk of unnecessary pancreatic surgery. Carcinoembryonic antigen (CEA) and glucose in pancreatic cyst fluid (PCF) can differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCN). The current study assessed the value of combined CEA and glucose testing in PCF. METHODS: Cross-sectional validation study including prospectively collected PCF from patients undergoing endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and pancreatic surgery. We performed laboratory measurements for CEA and glucose and measured glucose levels by a hand glucometer. Primary outcome was diagnostic accuracy evaluated by receiver operator curves (ROC), sensitivity, specificity, positive, and negative predictive value (PPV, NPV). RESULTS: Overall, PCF was collected from 63 patients, including 33 (52%) with mucinous and 30 (48%) with non-mucinous PCN. Histopathology (n = 36; 57%), cytopathology (n = 2; 3%), or clinical and/or radiological diagnosis (n = 25; 40%) was used as reference standard. Combined CEA (cut-off ≥ 192 ng/ml) and laboratory glucose testing (cut-off ≤ 50 mg/dL) reached 92% specificity and 48% sensitivity, whereas either positive CEA (cut-off ≥ 20 ng/ml) or glucose testing (cut-off ≤ 50 mg/dL) showed 97% sensitivity and 50% specificity. Sensitivity and specificity were 80% and 68% for CEA ≥ 20 ng/mL versus 50% and 93% for CEA ≥ 192 ng/mL (the conventional cut-off level). Laboratory and glucometer glucose both reached 100% sensitivity and 60% and 45% specificity, respectively. None of the biomarkers and cut-offs reached a PPV exceeding 90%, whereas both glucose measurements had a NPV of 100% (i.e., high glucose excludes a mucinous cyst). CONCLUSION: Combined CEA and glucose testing in PCF reached high specificity and sensitivity for differentiating mucinous from non-mucinous PCN. Glucose testing, whether alone or combined with the new CEA cut-off (≥ 20 ng/mL), reached > 95% sensitivity for mucinous cysts, whereas only glucose reached a NPV > 95%.

Pancreatitis and pancreatic cancer: A case of the chicken or the egg.

Acute pancreatitis (AP), chronic pancreatitis (CP) and pancreatic cancer are three distinct pancreatic diseases with different prognoses and treatment options. However, it may be difficult to differentiate between benign and malignant disease. AP may be a first symptom of pancreatic cancer, particularly in patients between the ages of 56 and 75 with presumed idiopathic AP who had a concomitant diagnosis of new-onset diabetes mellitus or patients who present with CP at diagnosis of AP. In these patients, additional imaging is warranted, preferably by endoscopic ultrasonography. CP may lead to pancreatic cancer through oncogenic mutations, mostly in patients with hereditary CP, and in patients in whom risk factors for pancreatic cancer (e.g., nicotine and alcohol abuse) are also present. Patients with PRSS1-mediated CP and patients with a history of autosomal dominant hereditary CP without known genetic mutations may be considered for surveillance for pancreatic cancer. Pancreatic inflammation may mimic pancreatic cancer by appearing as a focal mass-forming lesion on imaging. Differentiation between the above mentioned benign and malignant disease may be facilitated by specific features like the duct-penetrating sign and the duct-to-parenchyma ratio. Research efforts are aimed towards developing a superior discriminant between pancreatitis and pancreatic cancer in the form of imaging modalities or biomarkers. This may aid clinicians in timely diagnosing pancreatic cancer in a potentially curable stage.

Outcomes After Conservative, Endoscopic, and Surgical Treatment of Groove Pancreatitis: A Systematic Review.

BACKGROUND: Groove pancreatitis (GP) is a focal form of chronic pancreatitis affecting the paraduodenal groove area, for which consensus on diagnosis and management is lacking. GOALS: We performed a systematic review of the literature to determine patient characteristics and imaging features of GP and to evaluate clinical outcomes after treatment. RESULTS: Eight studies were included reporting on 335 GP patients with a median age of 47 years (range, 34 to 64 y), with 90% male, 87% smokers, and 87% alcohol consumption, and 47 months (range, 15 to 122 mo) of follow-up. Most patients presented with abdominal pain (91%) and/or weight loss (78%). Imaging frequently showed cystic lesions (91%) and duodenal stenosis (60%).Final treatment was conservative (eg, pain medication) in 29% of patients. Endoscopic treatment (eg, pseudocyst drainage) was applied in 19% of patients-34% of these patients were subsequently referred for surgery. Overall, 59% of patients were treated surgically (eg, pancreatoduodenectomy). Complete symptom relief was observed in 50% of patients who were treated conservatively, 57% who underwent endoscopic treatment, and 79% who underwent surgery. CONCLUSIONS: GP is associated with male gender, smoking, and alcohol consumption. The vast majority of patients presents with abdominal pain and with cystic lesions on imaging. Although surgical treatment seems to be the most effective, both conservative and endoscopic treatment are successful in about half of patients. A stepwise treatment algorithm starting with the least invasive treatment options seems advisable.

Comparing 3 guidelines on the management of surgically removed pancreatic cysts with regard to pathological outcome.

BACKGROUND AND AIMS: Currently, 3 guidelines are available for the management of pancreatic cysts. These guidelines vary in their indication for resection of high-risk cysts. We retrospectively compared the final pathologic outcome of surgically removed pancreatic cysts with the indications for resection according to 3 different guidelines. METHODS: Patients who underwent pancreatic resection were extracted from our prospective pancreatic cyst database (2006-present). The final histopathologic diagnosis was compared with the initial indication for surgery stated by the guidelines of the International Association of Pancreatology (IAP), European Study Group on Cystic tumors of the Pancreas and American Gastroenterological Association (AGA). We considered surgery in retrospect justified for malignancy, high-grade dysplasia, solid pseudopapillary neoplasms, neuroendocrine tumors or symptom improvement. Furthermore, we evaluated the patients with suspected intraductal papillary mucinous neoplasm (IPMN) separately. RESULTS: Overall, 115 patients underwent pancreatic resection. The preoperative diagnosis was correct in 83 of 115 patients (72%) and differentiation between benign and premalignant in 99 of 115 patients (86%). In retrospect, surgery was justified according to the aforementioned criteria in 52 of 115 patients (45%). For patients with suspected IPMN (n = 75) resection was justified in 36 of 67 (54%), 36 of 68 (53%), and 32 of 54 (59%) of patients who would have had surgery based on the IAP, European, or AGA guidelines, respectively. The AGA guideline would have avoided resection in 21 of 75 (28%) patients, versus 8 of 75 (11%) and 7 of 75 (9%) when the IAP or European guideline would have been applied strictly. Nevertheless, 4 of 33 patients (12%) with high-grade dysplasia or malignancy would have been missed with the AGA guidelines, compared with none with the IAP or European guidelines. CONCLUSION: Although fewer patients undergo unnecessary surgery based on the AGA guidelines, the risk of missing malignancy or high-grade dysplasia with this guideline seems considerably high.

Long-term follow-up of neoplastic pancreatic cysts without high-risk stigmata: how often do we change treatment strategy because of malignant transformation?

UNLABELLED: * OBJECTIVE: Patients with potentially premalignant neoplastic pancreatic cysts without high-risk stigmata usually enter a surveillance program. Data on outcomes of such surveillance programs are scarce. We aimed to evaluate the resection rate and malignancy rate during follow-up. MATERIAL AND METHODS: From our prospective database (2006-2015) of patients with pancreatic cysts, we analyzed patients with pancreatic cysts without high-risk stigmata with at least six months follow-up. RESULTS: In total, 146 patients were followed for a median of 29 months (IQR 13.5-50 months). In 124 patients (84.9%), no changes in clinical or imaging characteristics occurred during follow-up. Thirteen patients (8.9%) developed an indication for surgery after a median follow-up of 25 months (IQR 12-42 months). Two patients did not undergo surgery because of comorbidity, 11 patients (7.5%) underwent resection. Indications for surgery were symptoms (n = 2), development of a pancreatic mass (n = 1), a new nodule (n = 2), thickened cyst wall (n = 1), pancreatic duct dilation (n = 3), and/or suspicion of mucinous cystic neoplasm (MCN) (n = 3). Postoperative histology showed one pancreatic malignancy not originating from the cyst, three mixed type-intraductal papillary mucinous neoplasm (IPMN), one side branch-IPMN, two MCN, one neuroendocrine tumor, one serous cystadenoma, one inflammatory cyst, and one lymphangioma. The highest grade of cyst dysplasia was borderline dysplasia. CONCLUSIONS: Most neoplastic pancreatic cysts without high-risk stigmata at initial presentation show no substantial change during 1-4-year follow-up. Only 7.5% of patients underwent surgery and less than 1% of patients developed pancreatic malignancy. This indicates that additional markers are needed to tailor treatment of pancreatic cysts.

Clinical outcomes and prevalence of cancer in patients with possible groove pancreatitis.

BACKGROUND AND AIM: Data on non-surgical treatment of groove pancreatitis (GP) and the risk of cancer are lacking. We aimed to determine the prevalence and predictors of cancer in patients in whom the diagnosis GP was considered, and to evaluate symptom improvement after treatment. STUDY: Patients referred with possible GP (2001-2014) were retrospectively included. An experienced radiologist reassessed imaging. GP patients received questionnaires evaluating their symptoms. RESULTS: From the 38 possible GP patients, 10 had cancer (26%) and 28 GP (74%). Compared with cancer patients, GP patients more frequently had cysts (2/10 vs. 18/28, P = 0.03), less often jaundice (6/10 vs 3/27, P < 0.01), an abrupt caliber change of the CBD (5/10 vs. 2/28, P < 0.01) or suspicious cytology (5/9 vs 2/20, P = 0.02). Of the 28 GP patients, 14 patients were treated conservatively of whom 12 reported symptom improvement after a median follow-up of 45 months (range 7-127 months). All 6 patients treated endoscopically and 7/8 patients treated surgically reported symptom improvement. Surgery, performed because of treatment failure (3/8) or inability to exclude malignancy (5/8), caused mortality in 1/8 patients. CONCLUSIONS: Suspicion of pancreatic cancer should be high in patients presenting with possible GP. Conservative, endoscopic and surgical treatment can all lead to symptom improvement, suggesting a 'step-up approach' to GP once cancer is excluded.