The safety and benefit of pancreatic juice cytology under ERCP in IPMN patients

BackgroundInternational consensus guidelines 2012 for intraductal papillary mucinous neoplasia (IPMN), defined two characteristics: high-risk stigmata (HRS) and worrisome features (WF). Patients with WF require detailed examination including cytology. However, routine endoscopic retrograde cholangiopancreatography (ERCP) for cytology is not recommended in the guidelines due to risk of post-ERCP pancreatitis (PEP). Our aim was to clarify what types of IPMN were susceptible for PEP and gain benefit of ERCP.Patients/methodsWe examined 138 consecutive IPMN patients who underwent ERCP in our hospital, retrospectively. Patients were classified into HRS, WF and the others (N) based on imaging findings before ERCP. We assessed pancreatic juice cytology, PEP frequency and rate of malignant IPMN at 12 months after ERCP.ResultsThe rates of cytological malignancy were 0% (N), 4.8% (WF) and 19.5% (HRS). The PEP frequency was 14.5%, and these risk factors were branch duct (BD)-IPMN, body/tail cysts and brush cytology by multivariate logistic analysis. The rates of malignant IPMN were 0% (N), 16.4% (WF) and 48.8% (HRS). Furthermore, we examined patients with WF in detail. The PEP frequency/rate of malignancy were 3.6%/23.1% in patients with main pancreatic duct (MPD) dilatation (5–9 mm), and the sensitivity of cytology was 33.3%. On the other hand, the PEP frequency/rate of malignancy were 17.2%/0% in patients with BD-IPMN fulfilling only cyst size over 30 mm.ConclusionsRoutine ERCP for IPMN, especially for BD-IPMN, is not recommended. ERCP may be beneficial for WF patients with MPD dilatation based on a balance between PEP risk and presence of malignancy.     

Risk Factors for the Development of High-risk Stigmata in Branch-duct Intraductal Papillary Mucinous Neoplasms

Objective Strict follow-up is recommended for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) to avoid missing the development of high-risk stigmata (HRS) at a premalignant stage. This study explored the risk factors associated with the development of HRS during follow-up. Methods We performed a retrospective analysis of 283 patients with BD-IPMN, treated at Okayama University Hospital in Japan between January 2009 and December 2016. Only patients with imaging studies indicative of classical features of BD-IPMN without HRS and followed for over one year were included in the study. We performed radiological follow-up every six months and collected patients'' demographic data, cyst characteristics, and clinical outcomes and used univariate logistic regression models to determine the odds of developing HRS. Results Ten patients (3.5%) developed HRS after a median surveillance period of 55.8 months. The main pancreatic duct (MPD) size (5-9 mm) and cyst growth rate (>2.5 mm/year) were both suggested to be possible risk factors for the development of HRS [odds ratio, 14.2; 95% confidence interval (CI), 3.1-65.2, p=0.0006, and odds ratio, 6.1; 95% CI 1.5-25.5, p=0.014]. Regarding the number of worrisome features (WFs), the rate of HRS development was 2.0% (4/199) in cases with no WF, 1.6% (1/62) in cases with single WF and 22.7% (5/22) in cases with multiple WFs, respectively. The rate of HRS development was significantly higher in cases with multiple WFs than in the other cases (p<0.0001). Conclusion MPD dilation, rapid cyst growth, and multiple WFs were significant risk factors for the development of HRS. In the presence of such features, it is necessary to closely follow the development of HRS and avoid missing the best opportunity to perform surgical intervention.     

Systematic review and meta-analysis of observational studies on BD-IPMNS progression to malignancy

BackgroundThe vast majority of presumed branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are referred to a surveillance program due to the relatively low risk of malignancy. We aim to evaluate all available data from observational studies focused on the risks of BD-IPMN progression and malignancy to provide vital insights into its management in clinical practice.MethodsA comprehensive search was conducted at PubMed, Cochrane, Web of Science and Embase for observational studies published before January 1st, 2020. The progression of BD-IPMN was defined as the development of worrisome features (WFs) or high-risk stigmata (HRS) during surveillance. Overall malignancy was defined as all malignancies, such as malignant IPMN, concomitant pancreatic ductal adenocarcinoma (PDAC) and other malignancies, including BD-IPMN with high-grade sec. Baltimore consensus 2015 or BD-IPMN with high-grade dysplasia (carcinoma in situ) sec. WHO 2010. A meta-analysis was performed to investigate the presence of a mural nodule as a possible predictor of malignancy.ResultsTwenty-four studies were included, with a total of 8941 patients with a presumed BD-IPMN. The progression rate was 20.2%, and 11.8% underwent surgery, 29.5% of whom showed malignancy at the final pathology. Of those, 78% had malignant IPMNs, and 22% had concomitant pancreatic cancer. Overall, 0.5% had distant metastasis. The meta-analysis showed that the risk of malignancy in the presence of a mural nodule >5 mm had a RR of 5.457 (95% CI 1.404–21.353), while a nonenhancing mural nodule or an enhancing mural nodule < 5 mm had a RR of 5.286 (95% CI 1.805–15.481) of harboring malignancy.ConclusionMost presumed BD-IPMNs entering surveillance do not become malignant. Of those submitted to surgery, concomitant PDAC adds to the overall risk of detecting malignancy.     

New onset diabetes predicts progression of low risk pancreatic mucinous cysts

BackgroundPatients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts.MethodsWe evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method.ResultsThe 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5–57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%–20.2%), compared to only 0.8% (95%CI, 0.0%–2.3%) for patients without NODM. Among patients with the largest cysts (20–29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%–89.9%) compared to only 7.5% (95%CI, 1.6%–15.2%) for patients without NODM.ConclusionNew onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.     

Indication for resection and possibility of observation for intraductal papillary mucinous neoplasm with high-risk stigmata

Background/ObjectivesAccording to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs.MethodsWe enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN.ResultsFifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45).ConclusionsLarge nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.     

Minimal main pancreatic duct dilatation in small branch duct intraductal papillary mucinous neoplasms associated with high-grade dysplasia or invasive carcinoma

BackgroundThe aim of this study was to determine the incidence of high-grade dysplasia (HGD) or invasive carcinoma in patients with small branch duct intraductal papillary mucinous neoplasms (BD-IPMNs).Methods923 patients who underwent surgical resection for an IPMN were identified. Sendai-negative patients were identified as those without history of pancreatitis or jaundice, main pancreatic duct size (MPD) <5 mm, cyst size <3 cm, no mural nodules, negative cyst fluid cytology for adenocarcinoma, or serum carbohydrate antigen 19-9 (CA 19-9) <37 U/L.ResultsBD-IPMN was identified in 388 (46.4%) patients and 89 (22.9%) were categorized as Sendai-negative. Overall, 68 (17.5%) of BD-IPMN had HGD and 62 (16.0%) had an associated invasive-carcinoma. Among the 89 Sendai-negative patients, 12 (13.5%) had IPMNs with HGD and only one patient (1.1%) had invasive-carcinoma. Of note, older age (OR 1.13, 95% CI 1.03–1.23; P = 0.008) and minimal dilation of MPD (OR 11.3, 95% CI 2.40–53.65; P = 0.002) were associated with high-risk disease in Sendai-negative patients after multivariable risk adjustment.ConclusionThe risk of harboring a high-risk disease remains low in small BD-IPMNs. However, Sendai-negative patients who are older than 65 years old and those with minimal dilation of MPD (3–5 mm) are at greater risk of high-risk lesions and should be given consideration to be included as a “worrisome feature” in a future guidelines update.     

Resection of pancreatic cystic neoplasms in recurrent acute pancreatitis prevents recurrent pancreatitis but does not identify more malignancies

BACKGROUNDRecurrent acute pancreatitis (RAP) may be a presenting feature of and an indication for resection of pancreatic cysts, including intra-ductal papillary mucinous neoplasm (IPMN). Few data are available regarding the prevalence of malignancy and post-operative RAP in this population.AIMTo study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy.METHODSThis retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016. The prevalence of preoperative high-risk cyst features, and of neoplasia was compared between patients with and without RAP. To identify the cause of pancreatitis, all the patients had a detailed history of alcohol, smoking, medications obtained, and had cross-sectional imaging (contrast-enhanced computed tomography/magnetic resonance imaging) and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis. The incidence of RAP post-resection was the primary outcome.RESULTSIPMN accounted for 101 cases (58.7%) {[branch duct (BD) 59 (34.3%), main duct (MD) 42] (24.4%)}. Twenty-nine (16.9%) presented with RAP (mean 2.2 episodes): 15 had BD-IPMN, 8 MD-IPMN, 5 mucinous cystic neoplasm and 1 serous cystic neoplasm. Malignancy was similar among those with vs without RAP for all patients [6/29 (20.7%) vs 24/143 (16.8%)] and IPMN patients [6/23 (26.1%) vs 23/78 (29.5%)], although tended to be higher with RAP in BD-IPMN, [5/15 (33.3%) vs 3/44 (6.8%), P = 0.04]. At mean follow-up of 7.2 years, 1 (3.4%) RAP patient had post-resection RAP. The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02 (P < 0.0001). CONCLUSIONMalignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP. In addition, specific cyst charac-teristics were not clearly associated with RAP. The incidence of RAP was markedly decreased in almost all patients following cyst resection.     

SPINK1 mutations and risk of pancreatic cancer in a Chinese cohort

ObjectiveThe relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP).MethodsThis is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients’ demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status.ResultsPC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14–1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04–0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered.ConclusionsCP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.     

Comorbidities Drive the Majority of Overall Mortality in Low-Risk Mucinous Pancreatic Cysts Under Surveillance

Background & AimsThe Charlson Comorbidity Index (CACI) has been suggested as a tool to determine comorbidity burden and guide management for patients with mucinous pancreatic cysts (Intrapapillary Mucinous Neoplasms and Mucinous Cystic Neoplasms), but has not been studied well among “low-risk” mucinous pancreatic cysts i.e. without worrisome features (WF) and high-risk stigmata (HRS). This study sought to determine the comorbidity burden among surveillance population of low-risk pancreatic cysts and provide their follow-up mortality outcomes.MethodsA single center study retrospectively reviewed a prospective pancreatic cyst database and included individuals with low-risk cysts undergoing serial imaging during 2016. Electronic medical records were reviewed to determine their baseline age-adjusted CACI (age-CACI). After 4 years, their progression to WF, disease specific (pancreatic malignancy-related, DSM), extra-pancreatic (EPM), and overall mortalities (OM) were determined using Kaplan-Meir Survival Analysis.Results502 individuals underwent prospective surveillance. The study included 440 individuals with low-risk suspected or presumed mucinous cysts and excluded 50 and 12 individuals with WF and HRS respectively. Over a median follow-up of 56 months, 12 WF progressions, 2 DSMs, 42 EPMs, and 44 OMs were observed. Baseline age-CACI had good predictive capacity for 4-year EPM (Area-Under Curve: 0.87; p< .0001). The median age-CACI of 4 enabled cohort stratification into Low (age-CACI <4) and High CACI (age-CACI ≥4) groups. A significantly higher OM (p< .001) was observed among the High CACI group as compared to the Low CACI group.ConclusionThrough real-time application of CACI to patient outcomes, our analysis supports incorporation of this comorbidity assessment tool in making shared surveillance decisions among low-risk pancreatic cyst population.     

International Consensus Guidelines parameters for the prediction of malignancy in intraductal papillary mucinous neoplasm are not properly weighted and are not cumulative

Background

The International Consensus Guidelines (ICG) stratify risk for malignancy in patients with intraductal papillary mucinous neoplasm (IPMN) into three progressive categories according to whether patients show ‘no criteria’, ‘worrisome features’ (WFs) or ‘high-risk stigmata’ (HRS).

Objectives

This study was conducted to test the hypothesis that type (clinical versus radiological) and quantity of ICG WFs and HRS carry unequal weight and are not cumulative in the prediction of risk for malignancy or invasiveness in IPMN.

Methods

A retrospective review of a prospectively maintained database of patients who underwent surgical resection for IPMN at a single, university-based medical centre during 1992–2012 was performed. Differences that achieved a P-value of <0.05 were considered significant.

Results

Of 362 patients, 340 were eligible for entry into the study and were categorized as demonstrating no criteria (n = 70), WFs (n = 185) or HRS (n = 85). Patients in the WFs group had higher rates of malignant and invasive IPMN than those in the no-criteria group [26.5% versus 4.3% (P < 0.0001) and 15.7% versus 4.3% (P = 0.02), respectively]. Patients in the HRS group had higher rates of malignant and invasive IPMN than those in the WFs group [56.5% versus 26.5% (P = 0.0001) and 42.4% versus 15.7% (P = 0.0001), respectively]. When radiological parameters only were considered for WFs versus HRS, no difference was found in rates of malignant or invasive IPMN. By contrast, when clinical parameters only were considered, patients in the HRS group had higher rates of malignant or invasive IPMN [66.7% versus 8.1% (P = 0.04) and 66.7% versus 2.7% (P = 0.01), respectively]. There was no stepwise increase in rates of malignant or invasive IPMN with the number of WFs. However, patients with only one WF had a lower risk for malignancy than patients with two or more WFs.

Conclusions

The type and quantity of ICG WFs and HRS carry unequal weight and are not cumulative in the prediction of risk for malignancy or invasiveness in IPMN.     

Concordance of EUS and MRI/MRCP findings among high-risk individuals undergoing pancreatic cancer screening

Background/Objectives: Surveillance with endoscopic ultrasonography (EUS) and MRI/magnetic retrograde cholangiopancreatography (MRCP) is recommended for individuals at high risk for pancreatic cancer. We sought to characterize the findings of these surveillance exams and define the level of concordance between these two modalities.Methods173 asymptomatic high-risk individuals (HRIs) meeting criteria for pancreatic cancer surveillance underwent EUS, MRI/MRCP, or both between 2008 and 2021. Clinical records were reviewed in all cases.ResultsHRIs underwent an average of 3.6 ± 3.2 surveillance exams over a period of 3.3 ± 3.5 years. Abnormalities including intraductal papillary mucinous neoplasms (IPMNs), solid lesions, and parenchymal irregularities were identified in 50.9% (n = 88). Four of these abnormalities (2.3%) had worrisome features, defined by cyst size, thickened/enhancing cyst walls, rapid growth rate, or change in main pancreatic duct diameter. All four worrisome lesions were seen on both MRI/MRCP and EUS. No pancreatic cancers were detected. Baseline EUS and MRI/MRCP exams were compared in 106 patients for concordance, and most (n = 66, 62.3%) were concordant. High levels of concordance were specifically observed for a dilated main pancreatic duct (p < 0.01) and cystic lesions >5 mm (p = 0.01). Among discordant cases, most (30/40; 75%) involved abnormal tissue heterogeneity seen primarily on EUS. None of these discordant lesions ultimately developed worrisome features.ConclusionsWorrisome pancreatic lesions were uncommon in our high-risk pancreatic cancer population and were detected by both EUS and MRI/MRCP. There was mild discordance with respect to less worrisome findings, but these discrepancies were not associated with any adverse clinical outcomes.     

Importance of each high-risk stigmata and worrisome features as a predictor of high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas

BackgroundHigh-risk stigmata (HRS) and ‘worrisome features’ (WFs) are defined as predictive factors for malignancies of intraductal papillary mucinous neoplasms (IPMNs). We performed this study to determine the importance and odds ratio (OR) of each HRS and WFs as predictors for high-grade dysplasia (HGD).MethodsWe analyzed 295 patients who underwent pancreatectomy for branch duct and mixed-type IPMN, and evaluated the association between HRS and WFs (as defined by the ‘2017 Fukuoka Consensus Guidelines’) and HGD.ResultsThe proportions of patients with low-grade dysplasia (LGD), HGD, and invasive carcinoma were 47%, 28%, and 25%, respectively. Multivariate analysis comparing patients with LGD and HGD using all HRS and WFs revealed that an enhancing mural nodule ≥5 mm (OR: 4.1), pancreatitis (OR: 2.2), and thickened/enhancing cyst walls (OR: 2.2) were independent predictive factors for HGD. Based on the OR (the former factor is two points and the latter two factors are each one point), the incidence of HGD in patients with none (n = 43), one (n = 82), two (n = 25), three (n = 52), and four (n = 19) of these predictive factors were 9%, 26%, 52%, 62%, and 63%, respectively. Assuming a score of one or higher as a surgical indication, the sensitivity, specificity, positive predict value, and negative predict value of HGD were 95, 38, 44, and 91%.ConclusionsOur derived scoring system using more important factors in HRS and WFs may be useful for predicting HGD and determining surgical indications of IPMN.     

Association of palliative care management and survival after chemotherapy discontinuation in patients with advanced pancreatic adenocarcinoma: A retrospective single-centre observational study

BackgroundPalliative care (PC) is integrated into standard oncology care. However, its clinical impact at the end of life remains unclear in pancreatic adenocarcinoma (PA). We aimed to describe the end-of-life care pathway and to assess whether PC referral influences survival after chemotherapy discontinuation (CD) among advanced PA patients.MethodsThis retrospective single-centre observational study was conducted among deceased patients with advanced PA who had received chemotherapy between January 1, 2016, and December 31, 2021. Baseline characteristics, the timing of PC referral and events after CD were collected. The primary outcome was time from CD to death.ResultsAmong the 148 included patients, 53.4% (n = 79) received PC, mostly late after the CD (n = 133, 89.9%), 16.9% (n = 25) received chemotherapy in the last 14 days of life and 75.6% died at the hospital. None received PC in the 8 weeks following the diagnosis. PC referral significantly increased PC department admissions (p < 0.001) and decreased medical unit admissions (p < 0.001). The median survival after the CD was 35 days (IQR: 19–64.5). PC referral was associated with increased survival after CD (HR: 0.65 [0.47–0.90], p = 0.010, Cox) and after adjusting (HR: 0.65 [0.42–0.99], p = 0.045, Cox).ConclusionThe study suggests that PC may be associated with longer survival after CD in advanced PA patients. However, PC is underused, and patients are referred late in their care pathway.     

Differentiation between pancreatic metastases from renal cell carcinoma and pancreatic neuroendocrine neoplasm using endoscopic ultrasound

ObjectivesPancreatic metastases from renal cell carcinoma (PRCC) often appear many years after treatment of the primary tumor, and differentiation from pancreatic neuroendocrine neoplasm (PanNEN) can be challenging due to their hypervascularity. Here, we investigated the utility of endoscopic ultrasound (EUS) for differentiation of these conditions.MethodsA retrospective analysis was performed in 17 and 79 consecutive patients with pathologically proven PRCC and non-functional PanNEN who were examined by EUS. In cases examined by EUS elastography or contrast-enhanced harmonic EUS (CH-EUS), the lesions were classified as stiff or soft, or into three vascular patterns as hypoechoic, isoechoic, and hyperechoic. CH-EUS images at 20 s, 40 s, 60 s, 3 min and 5 min were used for evaluation. EUS images were independently reviewed by two readers who were blinded to all clinical information.ResultsThe patients with PRCC were significantly older than those with PanNEN (median, 71 (range, 45–81) vs. 58 (22–76), P = 0.001) and more often had multiple tumors (6/17 (35%) vs. 7/79 (9%), P = 0.010). In EUS findings, PRCC lesions significantly more frequently had a marginal hypoechoic zone (MHZ) (11/17 (65%) vs. 27/79 (34%), P = 0.028), being classified as soft (12/13 (92%) vs. 26/58 (45%), P = 0.002), and showed sustained hyperechoic vascular patterns at 5 min (7/8 (88%) vs. 4/59 (7%), P < 0.001) compared to PanNEN lesions.ConclusionsThe presence of a MHZ, a soft lesion, and a sustained hyperechoic vascular pattern in EUS may be useful for differentiating PRCC from PanNEN.     

The prognostic role of fatigue,depression and anxiety on postoperative outcomes after pancreatectomy for pancreatic cancer. A prospective observational study (FAT-PRO study)

ObjectivesThis study aims to assess the prevalence of preoperative fatigue, depression and anxiety among patients undergoing pancreatic surgery for pancreatic cancer (PC), and possible relationship with postoperative outcomes.MethodsProspective data from 162 consecutive patients undergoing pancreatectomy for PC at a third-level referral centers for pancreatic surgery were collected. All patients preoperatively completed four questionnaires assessing depression (PHQ-9), anxiety (STAI-Y2), chronic illness fatigue (FACIT-F) and cancer therapy fatigue (FACT-G).ResultsForty patients (25%) where in the first quartile for chronic illness (FACIT-F ≤34) and/or cancer therapy (FACT-G ≤78) fatigue, 26 patients (16%) met the criteria for major depression (PHQ-9 ≥10) and 34 patients (21%) had anxiety symptoms (STAI-Y2 ≥40). Cancer therapy fatigue was significantly associated with higher rates of morbidity (70% vs 49%), major morbidity (Clavien-Dindo ≥3) (28% vs 11%), post-pancreatectomy hemorrhage (18% vs 4%), pulmonary complications (20% vs 9%) and mortality (8% vs null) (all P ≤ 0.01). Major depression was associated with higher rates of post-pancreatectomy hemorrhage and readmission (23% vs 5%). Multivariable logistic regression analysis of preoperative factors confirmed diabetes (OR 2.71, 95%CI 1.01–7.20; P = 0.04), ASA score ≥3 (OR 4.12, 95%CI 1.52–11.21; P < 0.01) and cancer therapy fatigue (OR 2.95, 95%CI 1.01–8.74; P = 0.04) to be independent predictors of major morbidity.ConclusionsHigher levels of fatigue (in particular cancer therapy fatigue) strongly correlates with worse postoperative outcomes.     

Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature

BackgroundThe current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.MethodsA systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.ResultsMCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93–95%). They are usually found incidentally at the age of 40–60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0–34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.ConclusionsCompared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.     

Incidence of Synchronous and Metachronous Pancreatic Carcinoma in 168 Patients with Branch Duct Intraductal Papillary Mucinous Neoplasm

Background/Aims: Although branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMN) are being diagnosed with increasing frequency, the incidence of concomitant pancreatic carcinoma (PC) is not well known. We investigated the incidence and clinical features of synchronous and metachronous PC in patients with BD-IPMN. Methods: We studied 168 BD-IPMN patients diagnosed by various imaging modalities, including endoscopic retrograde pancreatography, between 1990 and 2008. We reviewed the medical records and clinical features in both patients developing and not developing PC. The diagnosis of PC was histologically verified in all patients. Results: PC was observed in 9 (5.4%) of 168 patients. Five were synchronously detected at the time of BD-IPMN diagnosis, whereas four were metachronously identified during the follow-up period. All PCs occurred in regions separate from the BD-IPMN lesion. All PCs represented histologically invasive ductal adenocarcinomas, whereas the BD-IPMN lesion was diagnosed as adenoma. Patients developing PC were significantly older than patients not developing PC (p = 0.017). The diameters of the BD-IPMN lesions and main pancreatic ducts were significantly smaller in patients developing PC than patients not developing PC (p = 0.013 and p<0.001, respectively). Conclusions: It was not infrequent for PC to occur in the pancreas with BD-IPMN. Particular attention should therefore be paid to the development of PC, even in low-risk BD-IPMN, as well as to changes in BD-IPMN.     

Role of adipocytokines and its correlation with endocrine pancreatic function in patients with pancreatic cancer

IntroductionSome authors suggest that adipocytokines contribute to the induction of pancreatic carcinogenesis as well as the development of endocrine insufficiency.AimsWe evaluate the circulating concentrations of leptin, resistin and visfatin in patients with newly diagnosed pancreatic cancer (PC) and relationship between serum adipocytokines level and clinicopathological features of PC. Moreover the usefulness of those adipocytokines as possible biomarkers of endocrine pancreatic function in PC has been assessed.MethodsThe pilot study group consisted of 45 individuals (mean age 65.6 ± 11.5 years, BMI 21.8 ± 3.4 kg/m²) with newly diagnosed PC (within last 1–3 months) and 13 healthy individuals with age, gender and BMI matched to the study group. Among PC patients 18 (40%) had recently diagnosed diabetes. Fasting plasma leptin, resistin, visfatin concentrations were determined with ELISA (R&D Systems, Phoenix Pharmaceuticals) and insulin by RIA (DakoCytomation).ResultsPatients with PC as compared to controls had significantly lower plasma leptin (40.6 ± 21.3 vs 63.2 ± 16.3 pg/mL; p < 0,0008). In contrast PC patients showed more than six fold higher level of resistin (126.2 ± 143.2 vs 18.9 ± 7.2 ng/mL; p < 0.009) than controls. The median plasma visfatin was 2.8 ± 1.8 ng/mL, which was not significantly different from the controls (3.8 ± 1.1 ng/mL). When PC patients with and without diabetes were considered separately, plasma leptin concentrations among nondiabetic patients were slightly, but not significantly higher (44.6 ± 21.0) as compared to diabetics (34.5 ± 20.7). Moreover there was no difference between visfatin and resistin level in PC, among patients with and without diabetes. No significant differences between serum level of leptin, visfatin and resistin and age, gender, BMI, smoking status, tumor localization, distant metastases and pain has been found.ConclusionThe results of this study confirm previous findings that patients with newly diagnosed pancreatic cancer are characterized with lower level of leptin. This pilot study showed significantly higher resistin concentrations in patients with PC in comparison to healthy controls, which may be helpful in PC early diagnosis. Changes in leptin and resistin level in PC are not likely related to endocrine disorders.     

Portal blood – A new source of dendritic cells for pancreatic cancer vaccine

IntroductionCohort study evaluated dendritic cells (DCs) subsets in portal and peripheral blood of patients with pancreatic cancer (PC) and chronic pancreatitis (CHP).Material and methodsMyeloid type 1 (mDCs1) and 2 (mDCs2), plasmocytoid (pDCs) and SLAN + DCs were assessed in PC (n = 20) and CHP (n = 6) patients.ResultsPercentage of mDCs1 was significantly lower in PC patients when compared to CHP (0.48 ± 0.26 vs 0.76 ± 0.3; p = 0.038) only in portal, but not peripheral blood.DiscussionFurther studies to assess the functional properties of portal blood DCs and their applicability in anticancer vaccination are needed.     

Comparison of five-phase computed tomography images of type 1 autoimmune pancreatitis and pancreatic cancer: Emphasis on cases with atypical images

Background/objectivesInternational consensus diagnostic criteria (ICDC) include characteristic images of autoimmune pancreatitis (AIP); however, reports on atypical cases are increasing. The aims of this study were to compare CT findings between AIP and pancreatic cancer (PC), and to analyze type 1 AIPs showing atypical images.MethodsFive-phase CT images were compared between 80 type 1-AIP lesions and 80 size- and location-matched PCs in the case-control study. Atypical AIPs were diagnosed based on the four ICDC items.ResultsICDC items were recognized in most AIP lesions; pancreatic enlargement (87.7%), narrowing of the main pancreatic duct (98.8%), delayed enhancement (100%), and no marked upstream-duct dilation (97.5%). CT values of AIPs increased rapidly until the pancreatic phase and decreased afterward, while those of PCs gradually increased until the delayed phase (P < 0.0001). Atypical images were recognized in 14.8% of AIPs, commonly without pancreatic enlargement (18.5 mm) and sometimes mimicking intraductal neoplasms. The CT values and their ratios were different between atypical AIPs and size-matched PCs most significantly in the pancreatic phase, but similar in the delayed phase.ConclusionsOrdinary type 1 AIPs can be diagnosed with the ICDC, but atypical AIPs represented a small fraction. “Delayed enhancement” is characteristic to ordinary AIPs, however, “pancreatic-phase enhancement” is more diagnostic for atypical AIPs.