Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy.

BACKGROUND: The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS: Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS: In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS: Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.

Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Invasive intraductal oncocytic papillary neoplasms (IOPN) and adenocarcimoma arising from intraductal papillary mucinous neoplasms (A-IPMN) of the pancreas: comparative analysis of clinicopathological features, patterns of recurrence and survival: a multicentre study.

BACKGROUND: Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown. METHODS: Consecutive patients undergoing pancreatic resection (2010-2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN). RESULTS: 415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574). CONCLUSIONS: Invasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Fork-tip needle biopsy versus fine-needle aspiration in endoscopic ultrasound-guided sampling of solid pancreatic masses: a randomized crossover study.

BACKGROUND: A novel fork-tip fine-needle biopsy (FNB) needle has recently been introduced for endoscopic ultrasound (EUS)-guided sampling. The aim of this study was to compare the performance of fork-tip FNB histology and standard fine-needle aspiration (FNA) cytology in the diagnosis of solid pancreatic masses. METHODS: A randomized crossover study was performed in patients referred for EUS-guided sampling. Three passes were taken with each needle in a randomized order. Only samples reported as diagnostic of malignancy were considered positive. The primary end point was the sensitivity of diagnosis of malignancy. Secondary end points included the amount of sample obtained, ease of diagnosis, duration of tissue sampling, pathologist viewing time, and cost. RESULTS: 108 patients were recruited. Median age was 69 years (range 30 - 87) and 57 were male; 85.2 % had a final diagnosis of malignancy. There were statistically significant differences in sensitivity (82 % [95 % confidence interval (CI) 72 % to 89 %] vs. 71 % [95 %CI 60 % to 80 %]), accuracy (84 % [95 %CI 76 % to 91 %] vs. 75 % [95 %CI 66 % to 83 %]), proportion graded as a straightforward diagnosis (69 % [95 %CI 60 % to 78 %] vs. 51 % [95 %CI 41 % to 61 %]), and median pathology viewing time (188 vs. 332 seconds) (P < 0.001) between FNB and FNA needles, respectively. There was no significant difference in cost between an FNB or FNA strategy. CONCLUSION: The diagnostic performance of the fork-tip FNB needle was significantly better than that of FNA; it was associated with ease of diagnosis, shorter pathological viewing times, and was cost neutral.

Impact of metal and plastic stents on endoscopic ultrasound-guided aspiration cytology and core histology of head of pancreas masses.

BACKGROUND: Stents are frequently placed in patients with biliary obstruction due to a mass in the head of the pancreas. The impact of plastic or self-expandable metal stents (SEMSs) on endoscopic ultrasound (EUS)-guided tissue sampling is unclear. This study aimed to assess, using strict pathological criteria, whether stents impair fine-needle aspiration (FNA) or fine-needle biopsy (FNB). METHODS: All patients with a solid mass in the head of the pancreas who underwent EUS-guided tissue sampling between 2010 and 2016 at our unit were included. Factors with possible impact on diagnostic performance were analyzed using logistic regression. Analysis was performed using both strict (malignant only) and less strict (suspicious for malignancy) cutoffs. RESULTS: Of 631 individuals undergoing 698 procedures, 535 (84.8 %) had a final diagnosis of malignancy, 141 had SEMS, 149 had plastic stents, and 341 had no stent. Using strict criteria, SEMS were associated with an increased occurrence of incorrect diagnosis of EUS tissue sampling, with an odds ratio (OR) of 1.96 (95 % confidence interval [CI] 1.24 - 3.10). Increasing tumor size (OR 0.72, 95 %CI 0.59 - 0.87), increasing number of passes (OR 0.84, 95 %CI 0.72 - 0.99), and fork-tip biopsy needle (OR 0.52, 95 %CI 0.31 - 0.86) were independently associated with a decrease in incorrect diagnosis. Repeat tissue sampling was more common with SEMSs (10.2 %) than with plastic stents (2.9 %) or no stents (4.5 %) (P < 0.02). CONCLUSION: SEMS use had a negative impact on tissue diagnosis in pancreatic head masses, whereas use of a fork-tip biopsy needle and increasing number of passes were independently associated with improved accuracy.

Comparison of the diagnostic performance of 2 core biopsy needles for EUS-guided tissue acquisition from solid pancreatic lesions.

BACKGROUND AND AIMS: A new core biopsy needle with a novel tip, opposing bevel, and sheath design has recently been introduced for EUS-guided fine-needle biopsy (FNB). The diagnostic utility of this needle for differentiating solid pancreatic masses is currently unknown. The aim of this study was to compare the diagnostic performance and yield for tissue acquisition from solid pancreatic lesions of the opposing bevel needle with those of a reverse bevel EUS-FNB needle. METHODS: Consecutive patients with solid pancreatic masses undergoing EUS-FNB using the opposing bevel (n = 101) and the reverse bevel (n = 100) core biopsy needles were included in the study. Final diagnosis was based on positive histology or at least 12 months of follow-up in cases with a negative biopsy. The primary outcome was the diagnostic performance of the 2 needles for malignant pancreatic masses. A secondary outcome was the diagnostic yield. RESULTS: Compared with the reverse bevel needle, using strict criteria the opposing bevel needle provided significantly higher sensitivity (71.1% vs 90.1%; P = .0006) and overall accuracy (74% vs 92%; I = 0.0006) for discriminating malignant from benign solid pancreatic masses. The proportion of samples classified as adequate for histologic analysis was 87% for the reverse bevel needle versus 99% for the opposing bevel needle (p = 0.002) Multivariate analysis controlling the needle gauge and site did not show any significant difference in accuracy and sensitivity between the 2 groups. There were no adverse events in either group. CONCLUSIONS: In this first, large, single-center preliminary cohort study, an EUS core biopsy needle with a novel tip, opposing bevel, and sheath design afforded substantially superior tissue yield and diagnostic performance compared with a reverse-bevel needle. If replicated by randomized controlled trials, our findings suggest that similarly designed needles could become the standard of care for EUS-guided tissue acquisition from solid pancreatic masses.

Sulfatase-2: a prognostic biomarker and candidate therapeutic target in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer death in the UK. Its poor prognosis is attributed to late detection and limited therapeutic options. Expression of SULF2, an endosulfatase that modulates heparan sulfate proteoglycan 6-O-sulfation and is reportedly tumourigenic in different types of cancer, was investigated. METHODS: SULF2 expression was determined immunohistochemically in archival surgical resection tissue sections from 93 patients with a confirmed histological diagnosis of PDAC between 2002 and 2008 followed for a median of 9 years. Relationships with clinico-pathological parameters and patient survival were explored. RESULTS: The majority of PDACs showed positive SULF2 staining in tumour cells and intratumoural or tumour-adjacent stroma. Greater than 25% SULF2-positive tumour cells was present in 60% of cancers and correlated with tumour stage (P=0.002) and perineural invasion (P=0.024). SULF2 intensity was scored moderate or strong in 81% of cancers and positively correlated with vascular invasion (P=0.015). High SULF2 expression, defined as >50% SULF2-positive tumour cells and strong SULF2 staining, was associated with shorter time to radiological progression (P=0.018, HR 1.98, CI 1.13-3.47). Similarly, by multivariate analysis, high SULF2 expression was independently associated with poorer survival (P=0.004, HR 2.10, CI 1.26-3.54), with a median survival of 11 months vs 21 months for lower PDAC SULF2. CONCLUSIONS: Elevated SULF2 in PDAC was associated with advanced tumour stage, vascular invasion, shorter interval to radiological progression and shorter overall survival. SULF2 may have roles as a prognostic biomarker and as a therapeutic target for patients with PDAC.

Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasm and derivation of a prognostic model: An international multicenter study (ADENO-IPMN study).

BACKGROUND: Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival. METHODS: Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed. RESULTS: In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00). CONCLUSION: A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.

Impact of prior biliary stenting on diagnostic performance of endoscopic ultrasound for mesenteric vascular staging in patients with head of pancreas and periampullary malignancy.

OBJECTIVE: The diagnostic performance of endoscopic ultrasound (EUS) for stratification of head of pancreas and periampullary tumours into resectable, borderline resectable and locally advanced tumours is unclear as is the effect of endobiliary stents. The primary aim of the study was to assess the diagnostic performance of EUS for resectability according to stent status. DESIGN: A retrospective study was performed. All patients presenting with a solid head of pancreas mass who underwent EUS and surgery with curative intent during an 8-year period were included. Factors with possible impact on diagnostic performance of EUS were analysed using logistic regression. RESULTS: Ninety patients met inclusion criteria and formed the study group. A total of 49 (54%) patients had an indwelling biliary stent at the time of EUS, of which 36 were plastic and 13 were self-expanding metal stents (SEMS). Twenty patients underwent venous resection and reconstruction (VRR). Staging was successfully performed in 100% unstented cases, 97% plastic stent and 54% SEMS, p<0.0001. In successfully staged patients, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for classification of resectability were 70%, 70%, 70%, 42% and 88%. For vascular involvement (VI), sensitivity, specificity, accuracy, PPV and NPV were 80%, 68%, 69%, 26% and 96%. Increasing tumour size OR 0.53 (95% CI, 0.30 to 0.95) was associated with a decrease in accuracy of VI classification. CONCLUSIONS: EUS has modest diagnostic performance for stratification of staging. Staging was less likely to be completed when a SEMS was in situ. Staging EUS should ideally be performed before endoscopic retrograde cholangiopancreatography and biliary drainage.

COVID-19 and liver cancer: lost patients and larger tumours.

BACKGROUND: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. OBJECTIVE: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. DESIGN: We prospectively audited our service for the first year of the pandemic (March 2020-February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019-February 2020). RESULTS: We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. CONCLUSION: The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.

Morphological and p40 immunohistochemical analysis of squamous differentiation in endoscopic ultrasound guided fine needle biopsies of pancreatic ductal adenocarcinoma.

The basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and upregulation in TP63ΔN (p40) network. Adenosquamous histology can be observed. This study assessed immunohistochemical p40 expression in fine needle biopsy (FNB) samples with PDAC and association with cytomorphological features of squamous differentiation and clinical data. 106 EUS FNBs with PDAC were assessed for eight cytomorphological features of squamous differentiation. P40 H-score (intensity 0-3 × percentage positive nuclei) was analysed for association with morphological features, patient age, gender, operability, chemotherapy and survival. P40 H-score in 14 paired FNBs and resections was compared. P40 h-score was 1-3 in 31%, 4-30 in 16% and > 30 in 13% of FNBs. It was significantly associated with intercellular bridges, elongated cell shape, sharp cell borders, angular nuclei with homogenous chromatin (p < 0.001) and dense cytoplasm (p = 0.002). Keratinisation was not seen. Inoperable patients (n = 81) had a shorter median survival for h-score > 30 (n = 9, 1.8 months) than for h-score ≤ 30 (n = 66, 6.7 months) not quite reaching statistical significance (p = 0.08). P40 was significantly associated with squamous morphology in FNBs with PDAC. P40 H-score > 30 showed a trend towards shorter survival in inoperable patients. Squamous differentiation may be a treatment target in PDAC.

A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?

Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409; TM6SF2 rs58542926). Here, we have considered single-nucleotide polymorphisms (SNPs) in candidate immunoregulatory genes (MICA rs2596542; CD44 rs187115; PDCD1 rs7421861 and rs10204525), in 594 patients with NAFLD and 391 with NAFLD-HCC, from three European centres. Associations between age, body mass index, diabetes, cirrhosis and SNPs with HCC development were explored. PNPLA3 and TM6SF2 SNPs were associated with both progression to cirrhosis and NAFLD-HCC development, while PDCD1 SNPs were specifically associated with NAFLD-HCC risk, regardless of cirrhosis. PDCD1 rs7421861 was independently associated with NAFLD-HCC development, while PDCD1 rs10204525 acquired significance after adjusting for other risks, being most notable in the smaller numbers of women with NAFLD-HCC. The study highlights the potential impact of inter individual variation in immune tolerance induction in patients with NAFLD, both in the presence and absence of cirrhosis.

Pancreatic intraepithelial neoplasia-can we detect early pancreatic cancer?

Haugk B(2010) Histopathology 57, 503-514Pancreatic intraepithelial neoplasia - can we detect early pancreatic cancer? Pancreatic cancer is one of the most lethal cancers, with an incidence equalling mortality. Pancreatic cancer is a heterogeneous group in which pancreatic ductal adenocarcinoma (PDAC) is the most common. It is now established that PDAC develops through stepwise progression from precursor lesions. Detection and treatment of these precursor lesions would allow curative treatment. Three precursor lesions for PDAC have been identified. Two of these - mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) - are rare, radiologically detectable, cystic precursor lesions which can be cured if treated at the preinvasive stage. The third and most common precursor lesion has recently been defined as pancreatic intraepithelial neoplasia (PanIN). PanINs are microscopic lesions with no clinical correlate. They display a spectrum of cyto-architectural changes (PanIN-1, PanIN-2 and PanIN-3) mirrored in an increasing accumulation of molecular genetic changes, with PanIN-3 sharing many of the alterations with PDAC. Great advances in the understanding of pancreatic carcinogenesis have opened avenues for diagnosis and chemoprevention. However, access to the pancreas is limited, molecular tests are at the early stages and too little is known about the natural history of early PanINs to justify resection. Currently, screening focuses upon high-risk individuals only.

Mǔllerian cyst of the mesentery: A case report of an unusual location.

Mǔllerian cysts or paramesonephric cysts arise from the fused embryonic ducts, which typically regress in the uterus. These cysts are usually located paravertebrally. We present an unusual case of a Mǔllerian cyst developing within the mesentery of the ileocecum that was successfully resected. The patient presented to our surgical unit with abdominal pain and swelling. She underwent all the necessary tests to rule out other pathologies before she underwent right hemicolectomy. The patient was discharged without complications. Histopathology confirmed the presence of female reproductive tract epithelium, which was conclusive of a Mǔllerian cyst or paramesonephric cyst. Mǔllerian cysts are rarely malignant, and they are usually treated surgically. The incidence of Mǔllerian cysts is one in 105,000, with almost equal sex distribution. Their unusual intraperitoneal location further demonstrates their uncommon presentation.

Utility of endoscopic ultrasound-guided fine-needle biopsy in the diagnosis of type 1 autoimmune pancreatitis.

Background and study aims Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) performs poorly in the histological diagnosis of type 1 autoimmune pancreatitis (AIP). The aim of this study was to assess the performance of fine-needle biopsy (FNB) comparing reverse bevel (RB) and fork-tip (FT) needles. Patients and methods A retrospective study of prospectively maintained databases was performed. Patients with a final diagnosis of type 1 AIP who underwent EUS-FNB during diagnostic workup were included. Pathology reports were reviewed and classified as per international consensus diagnostic criteria (ICDC). The Primary outcome was EUS-FNB sensitivity in diagnosing type 1 AIP. Results Between March 2011 and December 2018, 24 patients with a final diagnosis of type 1 AIP underwent FNB. Six patients underwent biopsy with the RB needle and 18 with the FT needle. Mean age (±â€ŠSD) 62.2 (±â€Š11.4), 17 (70.8 %) male. No RB samples were diagnostic compared to 14 (78 %) FT; P  = 0.001; of which 13 (72 %) were level 1. In eight (44 %) of FT cases a diagnosis was not possible without histology. Initial biopsy was diagnostic in five (62.5 %) of these cases. Including repeat biopsy, seven (87 %) had a diagnosis made by FT needle. Obliterative phlebitis (44 %) was the least frequently identified pathological feature and immunoglobulin (IgG)4 + plasma cells > 10 per high power field (78 %) the most common. Conclusion The FT needle demonstrated good performance for diagnosing type 1 AIP. The results support the preferential use of this core biopsy needle for EUS pancreatic tissue sampling.