Margaret G. Keane

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)

Objectives Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Design Retrospective multinational study including SCN diagnosed between 1990 and 2014. Results 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCNs related mortality was 0.1% (n=1). Conclusions After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. Trial registration number IRB 00006477.

Systematic review of novel ablative methods in locally advanced pancreatic cancer.

Unresectable locally advanced pancreatic cancer with or without metastatic disease is associated with a very poor prognosis. Current standard therapy is limited to chemotherapy or chemoradiotherapy. Few regimens have been shown to have a substantial survival advantage and novel treatment strategies are urgently needed. Thermal and laser based ablative techniques are widely used in many solid organ malignancies. Initial studies in the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Modifications to the various applications, in particular combining the techniques with high quality imaging such as computed tomography and intraoperative or endoscopic ultrasound has enabled real time treatment monitoring and significant improvements in safety. We conducted a systematic review of the literature up to October 2013. Initial studies suggest that ablative therapies may confer an additional survival benefit over best supportive care but randomised studies are required to validate these findings.

A case-control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer

Objectives Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers (BTC) are often diagnosed late and at an advanced stage. Population-based screening programmes do not exist and diagnosis is primarily dependent on symptom recognition. Recently symptom-based cancer decision support tools (CDSTs) have been introduced into primary care practices throughout the UK to support general practitioners (GPs) in identifying patients with suspected PDAC. However, future refinement of these tools to improve their diagnostic accuracy is likely to be necessary. Setting The Health Improvement Network (THIN) is a primary care database, which includes more than 11 million electronic patient records, from 562 GP practices in the UK. Participants All patients with a diagnosis of PDAC or BTC between 2000 and 2010 were included in the study along with six matched controls; 2773 patients with PDAC, 848 patients with BTC and 15 395 controls. Primary and secondary outcome measures The primary aim of this study was to determine the early symptom profiles of PDAC and BTC. Secondary aims included comparing early symptom trends between BTC and PDAC, defining symptom onset in PDAC and evaluating trends in routine blood tests nearest to the time of diagnosis. Results In the year prior to diagnosis, patients with PDAC visited their GP on a median of 18 (IQR 11–27) occasions. PDAC was associated with 11 alarm symptoms and BTC with 8. Back pain (OR 1.33 (95% CI 1.18 to 1.49) p<0.001), lethargy (1.42 (95% CI 1.25 to 1.62) p<0.001) and new onset diabetes (OR 2.46 (95% CI 2.16 to 2.80)) were identified as unique features of PDAC. Conclusions PDAC and BTC are associated with numerous early alarm symptoms. CDSTs are therefore likely to be useful in identifying these tumours at an early stage. Inclusion of unique symptoms, symptoms with an early onset and routinely performed blood tests is likely to further improve the sensitivity of these tools.

Endoscopic drainage of walled-off pancreatic necrosis using a novel self-expanding metal stent.

BACKGROUND AND STUDY AIMS This report describes the use of a novel, fully covered, self-expanding metal stent (FCSEMS) for endoscopic ultrasound (EUS)-guided drainage of walled-off pancreatic necrosis (WON). PATIENTS AND METHODS Patients with WON, as defined by the revised Atlanta Criteria, were included in this open-lable, two-center, observational study. The WON was punctured using a cystotome, and the FCSEMS was inserted under fluoroscopic guidance. Necrosectomy procedures were performed as necessary. RESULTS A total of 19 patients were included. The median maximum collection size was 15 cm with a median of 50 % necrosis. A total of 14/19 patients underwent necrosectomy, requiring a median of 4 procedures. Resolution or reduction in the size of collection by at least 80 % was achieved in all patients. Percutaneous or surgical drainage was required in three patients. Five stents migrated or dislodged. One patient had abdominal pain post-procedure. Five patients died during follow-up (three from multi-organ failure, and two unrelated to pancreatitis). CONCLUSIONS Use of this stent is feasible and safe for drainage of WON. However, stent displacement rates were high, and improvements to the stent design are required before it can be advocated for routine use in WON.

Update on the Management of Cholangiocarcinoma

Cholangiocarcinoma (CC) is a rare cancer arising from the epithelium of the biliary tree, anywhere from the small peripheral hepatic ducts to the distal common bile duct. Classification systems for CC typically group tumours by anatomical location into intrahepatic, hilar or extrahepatic subtypes. Surgical resection or liver transplantation remains the only curative therapy for CC, but up to 80% of patients present with advanced, irresectable disease. Unresectable CC remains resistant to many chemotherapeutic agents, although gemcitabine, particularly in combination with other agents, has been shown to improve overall survival. Ongoing investigation of biological agents has also yielded some promising results. Several novel interventional and endoscopic techniques for the diagnosis and management of non-operable CC have been developed: initial results show improvements in symptoms and progression-free survival, but further randomised studies are required to establish their role in the management of CC.

Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint

Purpose Cdc7 is a serine/threonine kinase which is responsible for the ‘firing’ of replication origins leading to initiation of DNA replication. Inhibition or depletion of Cdc7 in normal cells triggers a DNA origin activation checkpoint causing a reversible G1 arrest. Here we investigate Cdc7 as a novel therapeutic target in pancreatic cancer. Experimental design Cdc7 target validation was performed by immunoexpression profiling in a cohort of 73 patients with pancreatic adenocarcinoma including 24 controls. Secondly Cdc7 kinase was targeted in Capan-1 and PANC-1 pancreatic cancer cell line models using either an siRNA against Cdc7 or alternatively a small molecule inhibitor (SMI) of Cdc7 (PHA-767491). Results Cdc7 was significantly overexpressed in pancreatic adenocarcinoma compared to benign pancreatic tissue (median LI 34.3% vs. 1.3%; P<0.0001). Cdc7 knockdown using siRNA in Capan-1 and PANC-1 cells resulted in marked apoptotic cell death when compared with control cells. A prominent sub-G1 peak was seen on flow cytometry (sub-G1 51% vs. 3% and 45% vs. 0.7% in Capan-1 and PANC-1 cells, respectively). Annexin V labelling confirmed apoptosis in 64% vs. 11% and 75% vs. 8%, respectively. Western blotting showed cleavage of PARP-1 and caspase-3 and presence of γH2A.X. TUNEL assay showed strong staining in treated cells. These results were mirrored following Cdc7 kinase inhibition with PHA-767491. Conclusions Our findings show that Cdc7 is a potent anti-cancer target in pancreatic adenocarcinoma and that Cdc7 immunoexpression levels might be used as a companion diagnostic to predict response to therapeutic siRNAs or SMIs directed against this kinase.

Novel endoscopic approaches in the diagnosis and management of biliary strictures

Indeterminate bilary strictures present the clinician with a wide differential diagnosis. Histological confirmation is usually required for treatment, but tissue acquisition remains challenging. Novel developments in endoscopic technology, such as single operator cholangioscopy and confocal endomicroscopy, have led to improvements in diagnostic accuracy in recent years. In patients with non-resectable malignant biliary obstruction, effective biliary decompression improves symptoms and enables patients to undergo palliative therapies. Improvements in endoscopic techniques, biliary stents and the development of local ablative techniques have led to further improvements in stent patency and survival in these patients. In this article, we review emerging diagnostic and therapeutic techniques for the endoscopic management of indeterminate biliary strictures.

Pneumomediastinum secondary to mephedrone inhalation

A 23-year-old man presented to the emergency department with severe, central, pleuritic chest pain. The pain was present on waking and exacerbated by movement. On examination, supraclavicular and anterior chest wall surgical emphysema was noted, otherwise examination and initial observations were normal. A chest x-ray and subsequent chest CT demonstrated a pneumomediastium with significant subcutaneous emphysema. There was no history of vomiting or chest trauma, but the patient had inhaled mephedrone, a synthetic stimulant drug, 36 h prior. Pneumomediastinum is an uncommon complication of inhalational drug use.

Risk of malignancy in resected pancreatic mucinous cystic neoplasms

Pancreatic mucinous cystic neoplasms (MCNs) are rare mucin‐producing cystic tumours defined by the presence of ovarian‐type stroma. MCNs have a malignant potential and thus surgery is frequently performed. The aim of this cohort study was to define better the criteria for surgical resection in patients with MCN.

Novel biomarkers and endoscopic techniques for diagnosing pancreaticobiliary malignancy

The UK incidence of pancreatic ductal adenocarcinoma is 9 per 100,000 population, and biliary tract cancer occurs at a rate of 1–2 per 100,000. The incidence of both cancers is increasing annually and these tumours continue to be diagnosed late and at an advanced stage, limiting options for curative treatment. Population-based screening programmes do not exist for these cancers, and diagnosis currently is dependent on symptom recognition, but often symptoms are not present until the disease is advanced. Recently, a number of promising blood and urine biomarkers have been described for pancreaticobiliary malignancy and are summarised in this review. Novel endoscopic techniques such as single-operator cholangioscopy and confocal endomicroscopy have been used in some centres to enhance standard endoscopic diagnostic techniques and are also evaluated in this review.