Mucinous Cystic Lesions Research Articles

A new needle-based confocal laser endomicroscopy pattern of malignant pancreatic mucinous cystic lesions (with video).

Background and Objectives:The diagnosis of malignant pancreatic cystic lesions (PCLs) remains challenging. Needle-based confocal laser endomicroscopy (nCLE) is an emerging promising imaging technique capable of real-time in vivo microscopic imaging of the cyst wall. We aimed to develop and validate a new nCLE diagnostic criteria for malignant mucinous cystic lesions (MLs).Methods:Patients referred for EUS-FNA of indeterminate PCLs with at least one worrisome features according to Fukouka consensus were consecutively prospectively enrolled from July 2016 to July 2018. The final diagnosis was based on surgical histology, cytopathology, or committee consensus. Five investigators nonblindly reviewed nCLE features and identified potential diagnostic feature for malignant MLs, which was also reviewed in histology imaging accordingly. Furthermore, the nCLE diagnostic feature was evaluated with an independent nCLE dataset by two investigators in a double-blind manner.Results:A nCLE pattern of dark aggregates of neoplastic cells was identified as diagnostic for MLs, which was consistent with histological findings of irregular branching and budding in malignant MLs. An independent validation revealed that the accuracy, sensitivity, and specificity of this feature for the diagnosis of malignant MLs were 94%, 75%, and 100%, respectively.Conclusion:The new nCLE criterion is promising for diagnosis of malignant MLs which warrants further confirmation in large cohort.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytologic Evaluation of Intraductal Papillary Mucinous Neoplasm and Mucinous Cystic Neoplasms of Pancreas.

To evaluate the role of endoscopic ultrasound-guided fine needle aspiration cytology in identifying mucinous cystic lesions (MCLs) in histologically proven cases of intraductal papillary mucinous neoplasm (IPMN) or mucinous cystic neoplasm (MCN) and risk of malignancy associated with each cytologic category based on the Papanicolaou Society of Cytopathology (PSC) guidelines. All resected cases with histologic diagnosis of IPMN or MCN at our institution from January 1, 2004, to August 31, 2019, with associated cytology were included. Available cytology slides of nondiagnostic (ND), negative/benign (BN), and atypical cytology (AC) cases were reviewed and reclassified based on the PSC guidelines. A total of 120 cases were identified, including 57 IPMNs with low-grade or moderate dysplasia (LGD/MD) and high-grade dysplasia (HGD), 34 MCNs with LGD/MD or HGD, and 29 IPMNs with invasive malignancy. After cytology slide review and reclassification, we observed that ND and BN cases were paucicellular and lacked ancillary testing (carcinoembryonic antigen levels or KRAS mutation analysis). The risk-of-malignancy rates were 33% for ND, 11% for BN, 28.5% for AC, 17% for MCL, and 100% for suspicious/positive cytologic diagnosis. A multidisciplinary approach including combined use of cytology and ancillary testing is helpful in establishing a diagnosis of MCL and identifying associated malignancy.

Sa1411 DIAGNOSTIC ACCURACY OF INTRACYSTIC GLUCOSE VS. CEA FOR THE DIAGNOSIS OF MUCINOUS PANCREATIC CYSTIC LESIONS: A META-ANALYSIS

The differential diagnosis between mucinous(M) and non-mucinous (NM) pancreatic cystic lesions (PCLs) is often difficult and both false positive and negative results can lead to clinically relevant overtreatment and undertreatment. Dosage of intracystic Carcinoembryonic antigen (CEA) with a cut-off>192 ng/ml suggests the diagnosis of M-PCL, but its sensitivity is limited. Recently, it has been reported that low levels of intracystic glucose diagnose M-PCLs with high accuracy, but data are limited and heterogeneous. We aimed to perform a meta-analysis to gather data on sensitivity, specificity and accuracy of intracystic glucose as compared with CEA for the diagnosis of M-PCLs. A computerized bibliographic search was performed on Pubmed. Pooled effects were calculated using a random-effects model and expressed in terms of pooled sensitivity and specificity and OR (95% CI) for accuracy for the diagnosis of M-PCLs. Heterogeneity was evaluated by I2 and publication bias by Begg-Mazumdar test and funnel plot visual inspection. Overall, 4 cohort studies were included (3 conducted in the US, 1 in Portugal), for a total of 319 patients (207 M, 112 NM). The cut-off employed for glucose were 50 in 3 studies and 66 mg/dl in one, while all studies employed the CEA cut-off of 192 ng/ml. The employed gold-standard for diagnosis in the 4 studies was a composite of surgical pathology and cytology. Dosage of glucose showed a higher pooled sensitivity and lower heterogeneity (92%; I2= 0%) compared to CEA (69.4%; I2=64%), while specificity was higher for CEA (75.6% glucose vs 92% CEA) with lower heterogeneity (I2=89% glucose vs 69% CEA). Dosage of glucose was very close to be significantly superior in terms of pooled accuracy (OR 1.96; 95% CI 0.97-3.94; p=0.057; I2=53%). There was no publication bias at Begg-Mazumdar test and funnel plot. Our meta-analysis suggests that intracystic dosage of glucose is more sensitive, but CEA more specific for the diagnosis of mucinous PCLs, with an overall better accuracy of glucose. Given the heterogeneity of the results and the relative low number of investigated patients considering the high prevalence of PCLs, more studies are needed to define if combined use of both markers with different cut-offs is needed to increase accuracy significantly.

MRI of mucinous pancreatic cystic lesions: a new updated morphological approach for the differential diagnosis.

Pancreatic cystic lesions (PCLs) have been increasingly identified over the past 2decades due to the widespread use of high-resolution non-invasive abdominal imaging. They cover a vast spectrum, from benign to malignant and invasive lesions, thus they constitute a significant clinical entity. Among PCLs, mucin-producing lesions are those at risk of progression to malignancy. They include mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN). The diagnosis and management of these cystic lesions are a dilemma since there is a significant overlap in the morphology of benign and premalignant lesions. At the moment, there is no single test that will allow a correct diagnosis in all cases. Magnetic resonance (MR) and endoscopic ultrasound (EUS) morphology, with cyst fluid analysis and cytohistology done with EUS-guided procedure are the best techniques that can narrow the differential diagnosis and identify potentially malignant lesions requiring resection from those requiring follow-up only. The purpose of this paper is to present an updated review of MR imaging findings of mucinous PCLs and to provide a new morphological approach that can serve as a practical guide for the diagnosis of these lesions, allowing a more confident characterization and avoiding relevant misdiagnosis. Furthermore, we provide some information about EUS and cystic fluid analysis and cytohistology, since they are diagnostic modalities that radiologists and surgeons should be familiar with.

Loss of microRNA-21 leads to profound stromal remodeling and short survival in K-Ras-driven mouse models of pancreatic cancer.

The microenvironment of pancreatic cancer adenocarcinoma (PDAC) is highly desmoplastic with distinct tumor-restraining and tumor-promoting fibroblast subpopulations. Re-education rather than indiscriminate elimination of these fibroblasts has emerged as a new strategy for combination therapy. Here, we studied the effects of global loss of profibrotic noncoding regulatory microRNA-21 (miR-21) in K-Ras-driven p53-deleted genetically engineered mouse models of PDAC. Strikingly, loss of miR-21 accelerated tumor initiation via mucinous cystic neoplastic lesions and progression to locally advanced invasive carcinoma from which animals precipitously succumbed at an early age. The absence of tumor-restraining myofibroblasts and a massive infiltrate of immune cells were salient phenotypic features of global miR-21 loss. Stromal miR-21 activity was required for induction of tumor-restraining myofibroblasts in in vivo isograft transplantation experiments. Low miR-21 expression negatively correlated with a fibroblast gene expression signature and positively with an immune cell gene expression signature in The Cancer Genome Atlas PDAC data set (n = 156) mirroring findings in the mouse models. Our results exposed an overall tumor-suppressive function of miR-21 in in vivo PDAC models. These results have important clinical implications for anti-miR-21-based inhibitory therapeutic approaches under consideration for PDAC and other cancer types. Mechanistic dissection of the cell-intrinsic role of miR-21 in cancer-associated fibroblasts and other cell types will be needed to inform best strategies for pharmacological modulation of miR-21 activity to remodel the tumor microenvironment and enhance treatment response in PDAC.

A277 DISCREPANCIES IN EUS-FNA CYTOPATHOLOGY AND SURGICAL SPECIMEN PATHOLOGY FOR HIGH RISK PANCREATIC MUCINOUS CYSTIC LESIONS: A CASE SERIES

Abstract Background Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the primary method of sampling pancreatic cystic lesions with reported specificity near 100% for diagnosing malignancy. Discrepant positive malignant cytopathology with final surgical pathology of pancreatic cystic lesions has not previously been described. Aims To present a case series and review the literature regarding the implications of positive malignant cytology with discrepant surgical pathology for high risk pancreatic mucinous cystic lesions. Methods Patient demographics, clinical history, procedure details, pathology evaluations and follow-up were collected. A thorough literature review was performed. Results Three patients with high-risk pancreatic cystic lesions on cross-sectional imaging underwent EUS-FNA evaluation. None of these patients had a history of pancreatitis. Cytology was reported as positive for adenocarcinoma in all patients by separate gastrointestinal cytopathologists. All patients underwent surgical resection. The pathology for all resected specimens were reported as intraductal papillary mucinous neoplasm. The resected cysts for two patients demonstrated foci of high-grade dysplasia and the third noted low grade dysplasia. All surgical pathology underwent consensus review by three separate gastrointestinal pathologists. None of the patients were treated with adjuvant chemotherapy. All patients have been followed post-operatively with surveillance magnetic resonance imaging with no evidence of recurrence to date (median follow-up time 239 days, range 133 – 447 days). Conclusions This phenomenon sheds light on the potential for variable interpretations of EUS-FNA cytopathology and surgical resection pathology for high risk pancreatic cystic neoplasms. EUS-FNA may identify foci of adenocarcinoma that is not seen on surgical pathology specimens. Further research is required to examine the long-term outcomes of these patients. Funding Agencies None

Pancreatic mucinous cystic neoplasms: a clinicopathological study of 11 cases and detailed review of literature

BackgroundMucinous cystic neoplasms (MCNs) of pancreas are relatively rare, occur almost exclusively in middle-aged females, and are overwhelmingly located in the body and tail of the pancreas, histologically show an ovarian type stroma. MCNs are premalignant, low aggressive tumors. Here we describe the clinicopathologic and radiologic features and follow up of cases diagnosed in our practice. We also present a detailed review of recent literature.Materials and methodsBased on strict criteria, 11 cases diagnosed between 2002 and 2016 were included in the study.ResultsAll cases were reviewed histologically. Mean and median age was 46.7 and 46 years respectively. All patients were females and 9 out of 11 cases were located in the body and/or tail of the pancreas. Mean tumor size was 8 cm. Grossly, cysts were uni or multilocular and ranged from a few millimeters to several centimeters in diameter. Microscopically, all cases showed characteristic tall columnar, mucin producing epithelium and ovarian type stroma. Atypia was mild in 8 cases and severe in 3 cases. The latter 3 cases were classified as non-invasive MCNs with high grade dysplasia (2 cases) and MCN with an associated invasive carcinoma (1 case). On immunohistochemistry, all cases showed epithelial positivity for cytokeratin AE1/AE3 and stromal positivity for vimentin and smooth muscle actin. Follow up was available in 7 cases. All patients were alive and well with no recurrence.ConclusionsOur cases show features similar to those described in other published studies although cases in our series tended to be larger in number. Since these tumors are relatively rare, premalignant and have strict diagnostic criteria, they must always be considered in the differential diagnosis of pancreatic mucinous cystic lesions. Larger studies incorporating greater number of patients and more detailed follow up will help in increasing our understanding of MCNs.

Diagnostic yield of endoscopic ultrasound with fine-needle aspiration in pancreatic cystic lesions

Abstract Introduction Despite advances in imaging techniques, in many cases they are insufficient to establish the diagnosis of pancreatic cystic lesions (PCL). There are few publications in our setting that evaluate the combination of several methods obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to evaluate the overall utility of EUS-FNA in the diagnosis of PCL. Material and methods Retrospective study based on a database updated prospectively of a cohort of patients referred for EUS-FNA due to PCL detected in an imaging test. The sensitivity, specificity and diagnostic yield of carcinoembryonic antigen (CEA), cytology and viscosity were studied to detect mucinous lesions. Results From November 2013 to April 2018, 122 EUS were performed for PCL. EUS-FNA was performed in 94/122 (77%) and 21/122 (17.2%) patients were operated on. We included 33/122 patients who had diagnostic confirmation by histology, imaging (serous cyst with typical pattern) or clinical evolution. The study of the ROC curve determined the cutoff point ≥419 ng/ml to differentiate mucinous/non-mucinous cystic lesions. The diagnostic yield of CEA was 87.5% (21/24), cytology 81.8% (27/33) and viscosity 84.4% (27/32). The three parameters in combination obtained the best result (30/33, 90.9%). Conclusion The combination of CEA analysis, cytology and viscosity of pancreatic fluid obtained by EUS-FNA increases the performance in the diagnosis of mucinous pancreatic cystic lesions, with it being greater than 90%.

Abstract A48: Genetic ablation of microRNA-21 profoundly remodels stroma and shortens survival of K-Ras-driven pancreatic cancer mouse models

Abstract The tumor microenvironment of pancreatic cancer adenocarcinoma (PDAC) is highly desmoplastic with distinct tumor-restraining and tumor-promoting fibroblast subpopulations. Re-education rather than indiscriminate elimination of these fibroblasts has emerged as a new strategy for combination therapy. Here, we studied global loss of profibrotic noncoding regulatory microRNA-21 (miR-21) in K-Ras-driven genetically engineered mouse models of PDAC. We generated mouse strains carrying wild-type or knockout alleles of Mir-21 in a well-characterized K-Ras-driven, p53-deleted PDAC model (LSL-KrasG12D; p53lox/+;Pdx1-Cre, KPC). Even though miR-21 expression was upregulated in cancer cells and cancer-associated fibroblasts in KPC tumors, global loss of miR-21 activity did not inhibit tumor growth. Strikingly, loss of miR-21 accelerated tumor initiation via mucinous cystic neoplastic lesions and progression to locally advanced invasive carcinoma from which animals precipitously succumbed at an early age. We uncovered a cell-autonomous requirement of miR-21 activity for induction of tumor-restraining myofibroblasts, whose absence led to a profound remodeling of the stroma and massive infiltrate of tumor-permissive immune cells. Low miR-21 expression negatively correlated with a fibroblast gene expression signature and positively with an immune cell gene expression signature in TCGA PDAC data set (n = 156) mirroring findings in genetic models. In vitro and in vivo isograft experiments showed that miR-21 activity was dispensable for cancer cell growth but required for complete execution of TGF-b-mediated programs. Our results suggest that modulation of miR-21 activity may provide a novel therapeutic opportunity to affect the composition of fibroblast subpopulations and enhance current chemotherapy and/or immunotherapy treatments. Citation Format: Josh Schipper, Ian Beddows, Matti Kiupel, Jose Conejo-Garcia, Lorenzo Sempere. Genetic ablation of microRNA-21 profoundly remodels stroma and shortens survival of K-Ras-driven pancreatic cancer mouse models [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A48.

Abstract I19: Early detection of pancreatic cancer: Challenges and opportunities

Abstract Research in early detection of pancreatic cancer is considered one of the highest priority areas by the National Cancer Institute (NCI) in its updated Roadmap for Progress in Pancreatic Ductal Adenocarcinoma (2019). However, current United States Screening and Prevention Task Force (USPSTF) guidelines recommend against screening for pancreatic cancer in the general population, due to the lack of credentialed biomarkers and the considerable potential for overdiagnosis. On the contrary, individuals at high-risk for pancreatic cancer represent an opportunity for cancer interception, including the conduct of imaging and biomarker validation studies in prospective cohorts. High-risk cohorts ripe for surveillance include individuals harboring germline deleterious mutations, those with pancreatic mucinous cystic lesions, and patients with new onset diabetes. Approximately 10% of pancreatic cancer patients carry germline mutations in genes such as BRCA1/2, ATM, PALB2, CDKN2A, and mismatch repair genes, amongst others. In the past year, the National Comprehensive Cancer Network (NCCN) guideline for germline testing has evolved towards a recommendation of “universal testing” in all index cases, which has been facilitated through the availability of relatively cheap CLIA multi-gene panels. “Cascade testing” of unaffected family members can identify asymptomatic individuals who might benefit from surveillance. Notably, the risk of harboring or developing pancreatic cancer varies widely between carrier mutations, and the guidelines for screening modality and interval are still evolving. A second high-risk group includes individuals with mucinous pancreatic cysts. It is important to reiterate that the overwhelming majority of patients with mucinous cysts will not progress to cancer, and routinely used clinical and imaging criteria can lead to overtreatment in a significant minority of patients. Thus, algorithms that improve the management of cystic lesions using the confluence of clinical, radiological, biochemical and molecular parameters are under active development. Pancreatic cancer is a “diabetogenic” neoplasm, with over three quarters of patients developing some measure of paraneoplastic aberration in glucose homeostasis. While 25-40% of pancreatic cancer patients present with frank new onset or worsening diabetes (classified as Type 3c diabetes) less than 1% of patients with new onset diabetes harbor an asymptomatic cancer. Thus, while adult new onset diabetes represents a high-risk population, significant enrichment of this population is needed in order to enable a clinically feasible early detection program. Algorithms such as “Enriching New Onset Diabetes for Pancreatic Cancer” (ENDPAC) that leverage structured data within electronic medical records (EMR) will enable the selection of individuals with the highest probability of subclinical disease. Following the discussion on high risk cohorts, we will pivot to some of the current challenges underlying biomarker development in the context of early detection, and why CA19-9 remains the only FDA approved biomarker for this disease despite 1000s of publications on this subject. Finally, we will briefly allude to how imaging modalities might be utilized in the context of localizing subclinical disease, including recent data on extra-pancreatic alterations induced by systemic metabolic alterations by the developing neoplasm that can be detected using standard of care imaging assays. Early detection of pancreatic cancer continues to be a challenging conundrum, but sustained investment and team science efforts facilitated by the National Cancer Institute and foundations, including the Lustgarten Foundation, Pancreatic Cancer Action Network and Cancer Research UK, are making tangible advances within this space. Citation Format: Anirban Maitra. Early detection of pancreatic cancer: Challenges and opportunities [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I19.

Rendimiento diagnóstico de la punción mediante ultrasonografía endoscópica de las lesiones quísticas del páncreas

IntroductionDespite advances in imaging techniques, in many cases they are insufficient to establish the diagnosis of pancreatic cystic lesions (PCL). There are few publications in our setting that evaluate the combination of several methods obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to evaluate the overall utility of EUS-FNA in the diagnosis of PCL. Material and methodsRetrospective study based on a database updated prospectively of a cohort of patients referred for EUS-FNA due to PCL detected in an imaging test. The sensitivity, specificity and diagnostic yield of carcinoembryonic antigen (CEA), cytology and viscosity were studied to detect mucinous lesions. ResultsFrom November 2013 to April 2018, 122 EUS were performed for PCL. EUS-FNA was performed in 94/122 (77%) and 21/122 (17.2%) patients were operated on. We included 33/122 patients who had diagnostic confirmation by histology, imaging (serous cyst with typical pattern) or clinical evolution. The study of the ROC curve determined the cutoff point ≥419 ng/ml to differentiate mucinous/non-mucinous cystic lesions. The diagnostic yield of CEA was 87.5% (21/24), cytology 81.8% (27/33) and viscosity 84.4% (27/32). The three parameters in combination obtained the best result (30/33, 90.9%). ConclusionThe combination of CEA analysis, cytology and viscosity of pancreatic fluid obtained by EUS-FNA increases the performance in the diagnosis of mucinous pancreatic cystic lesions, with it being greater than 90%.

69 NanoPac-2017-01 Mid-Study Report: Safety, Tolerability, and Preliminary Efficacy of Intracystic Submicron Particle Paclitaxel (SPP) for the Treatment of Mucinous Cysts

INTRODUCTION: Pancreatic Mucinous cystic lesions (MCL) have significant potential for malignant transformation; delivery of SPP as a direct intratumoral injection confirmed SPP present at the delivery site for at least 100 days in a prior study; intracystic therapy with SPP may prevent progression to cancer without corresponding systemic toxicities. METHODS: Aim: To determine safety and preliminary efficacy of SPP for treatment of MCLs using endoscopic ultrasound Fine Needle Injection (EUS-FNI). Materials and Methods: Subjects with confirmed MCL, based on elevated intracystic CEA and cytology, receive intracystic SPP via EUS FNI at volumes equal to the aspirated cyst fluid volume in sequential cohorts at 6, 10, and 15 mg/mL in a standard “3+3” dose-escalation protocol. The highest dose with acceptable safety and tolerability profile, as determined by a DSMB, will proceed into the second phase of the study; 9 additional subjects will receive two injections of SPP (same dose) 12 weeks apart. Subjects are followed for 6 months for clinical endpoints including: safety and tolerability evaluations, physical examination findings and vital signs; pharmacokinetic analysis of systemic paclitaxel drug levels; and cyst volume response as reported by imaging at 3 and 6 months. RESULTS: Nine subjects have been enrolled to date; 5 have completed the study (1 injection). EUS, imaging, CEA and amylase concentration were consistent with branched duct IPMN cyst (BD-IPMN) or MCNs (Table 1). To date, no dose limiting toxicities, serious adverse events related to treatment, or clinically significant blood work (chemistry; hematology; coagulation) or urinalysis have been reported. Adverse events potentially related to SPP include mild, transient abdominal pain/discomfort in 4 subjects and nausea in 2 subjects. Systemic paclitaxel concentration did not exceed 1 ng/mL, and was undetectable at 2 weeks supporting retention of SPP at delivery site. Cyst volumes in 3 of 5 completed subjects reduced by month 6, 2 remained stable (Table 2). CONCLUSION: Intracystic SPP appears safe and tolerable when administered at 6, 10, and 15 mg/mL in a volume equal to that of aspirated cyst fluid. Minimal systemic study drug exposure is experienced. No patients developed pancreatitis. Intracystic SPP appears to prevent continued growth of the cysts and may reduce total cyst volume. Subject enrollment to the second phase (2 injections 12 weeks apart) is underway at 15 mg/mL.

Rapid on-site glucometry of cystic fluid is a feasible and accurate method for the diagnosis of mucinous cystic pancreatic lesions

Combined portal vein (PV) resection is performed for pancreatic head cancer to achieve clear resection margins. This can be complicated by the formation of varices due to sinistral portal hypertension after pancreaticoduodenectomy (PD) with combined PV resection. However, clinical strategies to prevent varices formation due to sinistral portal hypertension remain controversial. Moreover, the critical vein among splenic vein (SPV), inferior mesenteric vein, left gastric vein, or middle colonic vein requiring preservation to prevent the development of varices remains unclear.We retrospectively analyzed patients with pancreatic cancer who underwent PD with combined PV resection over 18 years at our institution. Varices were evaluated using enhanced computed tomography (CT) and endoscopy. Preoperative types of porto-mesenterico-splenic confluence, venous drainage, and venous resection types were determined by operative records and CT findings.Of the 108 subjects, the incidence of postoperative varices was observed in 24.1% of cases over 5.6 months. These varices were classified into five types based on location, as pancreaticojejunostomy anastomotic (11.5%), gastrojejunostomy anastomotic (11.5%), esophageal (11.5%), splenic hilar-gastric (23.1%), and right colonic (65.4%) varices. No case of variceal bleeding occurred. Multivariate analysis showed SPV ligation as the greatest risk factor of varices (P < 0.001), with a higher incidence of left-sided varices in patients with all the SPV venous drainage sacrificed (60%) than in the others (16.7%). Therefore, sacrificing all the SPV venous drainage was the only independent risk factor of varices (P = 0.049).Preservation of SPV venous drainage should be considered during SPV ligation to prevent post-PD varices.

Cell block processing is optimal for assessing endoscopic ultrasound fine needle aspiration specimens of pancreatic mucinous cysts

AimsThe cell block technique for assessing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) specimens from pancreatic mucinous cystic lesions (MCLs) was systematically evaluated for the first time, including comparisons with three...

Interobserver agreement among expert pathologists on through-the-needle microforceps biopsy samples for evaluation of pancreatic cystic lesions

The recent development of microforceps for EUS through-the-needle biopsy (TTNB) sampling of the wall of pancreatic cystic lesions (PCLs) allows the collection of histologic specimens never handled and evaluated before by pathologists. We aimed to estimate the interobserver agreement among pathologists in evaluating such samples. TTNB specimen slides from 40 PCLs with worrisome features were retrieved and independently evaluated for specimen adequacy, presence of lining epithelium, grade of epithelial dysplasia, presence of ovarian type stroma, and specific diagnosis by 6 expert pathologists from 6 different tertiary care centers. The Gwet's AC1 was used to assess interobserver agreement. An almost perfect agreement was observed for specimen adequacy (AC1, .82; 95% confidence interval [CI], .79-.98), presence of lesional epithelium (AC1, .90; 95% CI, .86-.92), epithelial dysplasia (AC1, .97; 95% CI, .95-.99), and ovarian-like stroma (AC1, .90; 95% CI, .86-.93). When considering all diagnoses separately, a moderate to substantial agreement was observed (AC1, .62; 95% CI, .57-.67), similarly to mucinous cysts versus serous adenoma versus other diagnoses (AC1, .65; 95% CI, .59-.70) and for mucinous cysts versus all other diagnoses (AC1,.74; 95% CI, .68-.84). The agreement for diagnosis of mucinous cystic neoplasm versus intraductal mucinous papillary neoplasm was almost perfect (AC1, .88; 95% CI, .81-.95). Interobserver agreement between expert pathologists in the evaluation of TTNB samples from PCLs with worrisome features was close to perfection for all evaluated parameters, except definitive diagnosis. When mucinous cystic lesions were compared versus all other diagnoses, the agreement became substantial, thus indicating that TTNB specimens can provide important information for PCL management decisions.

Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions

Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P= .0397) were significantly associated with high-risk PCLs. We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.

Laparoscopic resection of the uncinate process of the pancreas due to a branch-type IPMN

Background: A 68-years-old man was diagnosed of a symptomatic 36 mm branch-type IPMN covering all the uncinate process of the pancreas. He previously presented two episodes of acute mild pancreatitis. On MRI was observed a small duct communicating the IPMN with the main pancreatic duct. Endoscopic ultrasound confirmed a mucinous cystic lesion in the uncinate process with an amylase level of 85.854 U/L and CEA 243 ng/ml. Methods: A laparoscopic formal resection of the uncinate process of the pancreas was proposed. The patient was placed in supine with the legs spread open. The gastro-colic ligament was opened and the head of the pancreas exposed. The uncinate process of the pancreas was gently dissected from the right mesocolon, third portion of the duodenum and superior mesenteric vein. Pancreatic branches of the inferior anterior pancreatico-duodenal artery were divided. The communication duct of the IPMN with the main pancreatic duct was dissected and sutured after completing the uncinectomy. A drain was left in place. Results: Total operative time was 430 min. Blood lost was uncountable. On postoperative course presented a grade B (antibiotic therapy) postoperative pancreatic fistula. Lenght of stay was 8 days. Definitive diagnosis confirmed a IPMN with low-grade dysplasia (no dysplasia in the communicating duct). Conclusion: Laparoscopic uncinectomy is a challenging operation, but an excellent alternative to pancreatico-duodenectomy in selected cases of premalignant lesions.

Systematic review of the utility of 18-FDG PET in the preoperative evaluation of IPMNs and cystic lesions of the pancreas

The aim of this systematic review is to assess the role of 18-fluorodeoxyglucose positron emission tomography in the preoperative evaluation of intraductal papillary mucinous neoplasms and cystic lesions of the pancreas. A computerized PubMed search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies evaluating positron emission tomography in the preoperative evaluation of pancreatic cystic lesions. A total of 14 studies evaluated the role of 18-fluorodeoxyglucose positron emission tomography/positron emission tomography-computed tomography, 9 of which evaluated only intraductal papillary mucinous neoplasms and 5 evaluated all pancreatic cystic lesions, including intraductal papillary mucinous neoplasms. Pooled analysis was carried out for studies evaluating intraductal papillary mucinous neoplasms only and studies evaluating all cystic lesions. Imaging with 18-fluorodeoxyblucose positron emission tomography had a positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of 90%, 91%, 85%, 95%, and 91% in identifying malignancy (defined as either invasive and/or high-grade dysplasia) in intraductal papillary mucinous neoplasms and a positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of 85%, 81%, 79%, 86%, and 88% in identifying malignancy in other cystic lesions. Pooled analysis reported the positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of Sendai consensus guidelines (SCG) criteria as 69%, 69%, 68%, 55%, and 58%. The Fukuoka consensus guidelines (FCG) only had sensitivity, specificity, and accuracy reported as 61%, 52%, and 52%, respectively. The 18-fluorodeoxyblucose positron emission tomography had a high degree of accuracy of detecting malignancy in intraductal papillary mucinous neoplasm and cystic lesion of the pancreas. Comparison of the utility of positron emission tomography with the Fukuoka consensus guidelines and the Sendai consensus guidelines suggest that positron emission tomography is superior to present guidelines in detecting malignant intraductal papillary mucinous neoplasm and cystic lesion of the pancreas. Further studies in larger patient cohorts may be required to corroborate these findings and to determine the place of positron emission tomography in the management of intraductal papillary mucinous neoplasm and cystic lesions of the pancreas.

Pancreatic cystic tumors: an update

Abstract Pancreatic cystic tumors (PCTs) comprise a heterogeneous group of entities, accounting for 2% to 10% of pancreatic lesions. The most common types are intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasm (MCN), and serous cystic neoplasm (SCN), which account for approximately 90% of PCTs. This review discusses updates in pathologic features, malignant transformation, biologic behavior, and molecular evolution of PCTs. IPMN includes main duct and branch duct types. These can also be classified into 4 histologic subtypes based on cell lineages of differentiation, and may be associated with different tumorigenic pathways and clinicopathologic characteristics. The gastric type is the most common and is rarely associated with carcinomas, whereas the pancreatobiliary type is significantly more associated with invasive carcinoma. MCN is a mucinous cystic lesion with the presence of ovarian-type pericystic stroma. Prognosis of the resected non-invasive MCN is excellent, but the long-term survival of MCNs with invasive carcinoma may be poor. SCN includes microcystic adenoma, macrocystic adenoma, and solid variant serous adenoma. Serous cystadenocarcinoma is defined by the presence of distant metastases, which is rare in literature. Intraductal tubulopapillary neoplasm is characterized by uniformly high-grade dysplasia and ductal differentiation without overt production of mucin, with high risk for developing invasion. Acinar cell cystadenoma is a rare benign lesion with acinar differentiation. In addition, some pancreatic neuroendocrine tumors may assume a cystic configuration, sometimes referred to as cystic pancreatic endocrine neoplasm tumor, with a lower pathologic stage. Solid pseudopapillary tumor is composed of poorly cohesive monomorphic epithelial cells forming solid and pseudopapillary structures, with excellent prognosis.

Long-Term Outcome of Mucinous Pancreatic Cystic Lesions in Cancer Survivors or Patients With Extra-Pancreatic Malignancy

Introduction: During surveillance or staging, cancer survivors or patients with extra-pancreatic malignancy may be found to have pancreatic cysts (PCs). Clinical guidelines support decisions based on cyst features without consideration of patient characteristics, including extra-pancreatic cancer-related factors. We evaluated long-term outcomes to assess the behavior of pancreatic cysts in patients with historical or concomitant malignancies. Methods: We retrospectively identified cancer survivors or patients with an extra-pancreatic malignancy who underwent EUS-FNA for suspected PCs from 1/1/2007 to 12/31/2012 and had follow-up details up to 9/1/2017. Comorbidities were classified by Charlson Comorbidity Index (CMI). Cyst high risk features were classified using the 2017 Fukuoka consensus guidelines. Descriptive statistics were used to summarize patient and procedure characteristics and non-parametric tests were used to calculate differences between medians. Results: A total of 113 patients were identified. Median age was 69 (IQR 61-75). Median CMI was 4 (IQR 3-5). By cancer history, 53 (46.9%) were cancer survivors. Most common pre-existing malignancy was breast cancer (N=21, 18.6%). Ten (8.9%) patients had a family history of pancreatic cancer. Cytology identified a mucinous lesion in 73 (64.6%). The median size of mucinous PCs was 21 mm (IQR 14-26) compared to 20 mm (IQR 14.75-25) in other PCs. (p=0.93) Mucinous PCLs were low risk in 55/73 (75.3%) patients and 18/73 (24.7%) had at least one high risk feature on EUS-FNA. In patients with mucinous lesions (n=73), the median follow up after diagnosis was 5 (IQR 4-7) years and 17 (23.3%) patients died of non-pancreatic related causes. Stable lesions were identified in 65 (89%). Six (8.2%) patients were found to have a lesion that increased in size. Ten (13.7%) patients underwent pancreatic resection. On pathology, 7 patients had IPMN with low grade dysplasia, 2 patients high grade dysplasia and one patient had a serous cystadenoma. Conclusion: Over a median follow up of 5 years, two patients (1.8%) were found to have high grade dysplasia and had surgical resection. Patients with extra-pancreatic malignancies are likely at the same risk for malignant degeneration relative to the general population and patients with low risk mucinous lesions could be safely followed. In high-risk patients, comorbidities should be factored in with cyst features for surgical decision-making.