Paula Ghaneh

European evidence-based guidelines on pancreatic cystic neoplasms

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

Adjuvant and additive therapy for cancer of the pancreas

ZusammenfassungIn letzter Zeit konnte ein Fortschritt bei der Therapie von Pankreaskarzinomen verzeichnet werden.Aus spezialisierten Pankreas-Zentren wurden zunehmende Resektionsraten bei gleichzeitig verringerter postoperativer Mortalität berichtet.Aufgrund der äußerst aggressiven Tumorbiologie eines Pankreaskarzinoms besteht eine große Herausforderung bei der Identifizierung von effektiven onkologischen Therapiekonzepten beim fortgeschrittenen Pankreaskarzinom und bei der Entwicklung von resektionsbegleitenden Maßnahmen.Da es an großen randomisierten, kontrollierten Studien mangelt, stehen additive Therapiekonzepte nach Resektion eines Pankreaskarzinoms auf einer unzureichend wissenschaftlich fundamentierten Basis.Die ESPAC-1-Studie, die annähernd 600 Patienten rekrutierte,hat alle anderen Studien übertroffen, die adjuvante Therapie nbeim Pankreaskarzinom untersucht haben. Aufgrund dieser Studie konnte geschlussfolgert werden, dass die zurzeit am meisten Erfolg versprechende adjuvante Chemotherapie mit 5-Fluorouracil (FU) und Folinsäure (FA) zumindest im Vergleich mit multimodalen Behandlungsregimen ein gleich gutes oder sogar besseres Ergebnis erzielen kann. Dieses Regime könnte durch die Verwendung von Gemcitabine abgelöst werden, das in der ESPAC-3-Studie, die 990 Patienten aus verschiedenen europäischen Ländern (inklusive Deutschland),Kanada und Australien einschließt, evaluiert wird. Die Teilnahme an der ESPAC-III-Studie nimmt daher eine Schlüsselrolle für die Weiterentwicklung des klinischen Managements von Pankreaskarzinomen ein.AbstractRecent advances have been made in the treatment of pancreas cancer.Specialized pancreas centres have reported an increasing rate of resections with reduced postoperative mortality. On account of the highly aggressive nature of pancreas cancer, there is a great challenge in identifying effective therapy concepts for advanced stages of the cancer as well as for the development of resection-associated measures. As large-scale, randomised, controlled studies are lacking, the additive therapy concepts after resection do not have a sufficiently scientific basis.The ESPAC-1 study, which included 600 patients, surpassed all previous studies on adjuvant therapy for pancreas cancer.This study has shown,for example, that the most promising adjuvant chemotherapy with 5-fluorouracil and folic acid leads to an equal if not better result than the multimodal regimen.This regimen can be superseded with the use of Gemcitabine, which will be evaluated in the ESPAC-3 study that includes 990 patients from various European countries including Germany, as well as from Canada and Australia. Participation in the large, phase-3 study therefore plays a key role in the continued development of the management of pancreas cancer.

Progress by Collaboration: ESPAC Studies

Pancreatic cancer is amongst the top ten fatal cancers of the Western world, accounting for 57 000 deaths per year in Europe and 29 000 deaths per year in the United States.1 It is particularly difficult to treat because of its inaccessible location, late presentation, and frequently aggressive tumour biology. Five-year survival in the 10–15% of affected patients who undergo potentially curative surgery is limited to 17–24%,2,3 whilst overall 5-year survival in all patients is less than 0.5%.4 Although significant improvements in surgical outcome have been obtained with increasing specialisation and case-load,3,5 and further benefits may be anticipated with earlier investigation and referral of high risk groups, 6 the role of adjuvant and neo-adjuvant treatment accompanying surgery remains uncertain.7-10 Interestingly, chemotherapy is the principal modality in the treatment of advanced pancreatic cancer.11

OC-057 10 Years on from the improving outcomes guidance—development of a tertiary pancreatic cancer unit

Introduction In 2001 the National Institute for Clinical Excellence (NICE) published guidance on best practice for cancer services entitled Improving Outcomes Guidance (IOG). These guidelines specified centralisation, increased patient volume (>200 referrals/year), improved resection rates (>10%–15%) and reduced post-operative mortality rates (<5%). We looked at the development of a regional tertiary pancreatic centre over the 10 years following this, and how practice has changed over this time. Methods A prospectively maintained database of all referrals with suspected pancreatic cancer to the Supra-Regional Pancreas Centre in Liverpool was interrogated to assess changes in practice and outcome from 2001 to 2010 inclusive. Data were analysed with χ2 for trend for categorical data and log rank for survival data. Results 2076 patients with malignancy were referred, rising from 73 in 2001 to 364 in 2010. 511 resections for malignancy were performed (25%), ranging between 21% (42/182) in 2005 and 36% (33/87) in 2003 per year, with no trend over time. 710 patients underwent planned operation for malignancy over the 10-year period ranging from 41 procedures in 2001 and peaking at 97 in 2008, with 94 procedures in 2009 and 88 cases in 2010. The percentage of planned resections that had a successful resection increased from 51% (21/41) in 2001 to 90% (79/88) by 2010 (p<0.001). The mortality from resection was 9/567 (2%) and overall was 5% (37/710) including palliative procedures. The 1 year survival rates of patients who underwent a successful resection improved from 65% (13/20) in 2001 to 76% (69/91) by 2009 (p=0.02). There has been a rise in the number of intraductal papillary mucinous neoplasm (IPMN) resected with none in 2001 increasing to 12 resections during 2009, 10 in 2010 and 212 patients currently undergoing surveillance for IPMN. The number of staging laparoscopies has remained fairly constant at around 27 per year, despite the increase in referrals, which reflects more stringent criteria in selecting these patients for laparoscopy. Conclusion Over the last 10 years we have seen centralisation of services, which was completed in 2007. This has led to an increase in volume of cancer referrals in line with IOG guidance. Although resection rates have stayed constant, this reflects the increasing number of patients referred with irresectable disease for other treatments, including chemotherapy and novel cancer trials. There has been an improvement in case selection as demonstrated by a reduction in the percentage of bypass procedures, reflecting better pre-operative staging of patients. This has also lead to an improved 1-year survival in those patients who had a successful resection. Competing interests None declared.

European Adjuvant Trials

The results of large European randomized studies have been invaluable in determining a safe and standardized treatment protocol for patients with pancreatic cancer. It is clear that standard doses of postoperative adjuvant chemoradiotherapy have no survival advantage and may even be disadvantageous. Adjuvant chemotherapy, on the other hand, looks to be much more promising and warrants detailed evaluation. Further effective therapies can now be assessed within large cooperative organizations to improve the outlook, survival, expectancy, and quality of life for these patients. In this respect, ESPAC has been a major advance in clinical scientific investigation.

Metalloproteinases and Stromal Biology in Cancer

The normal extracellular matrix (ECM) comprises the basement membrane and interstitial stroma and functions as a supportive framework for parenchymal cells and a physical barrier which regulates the entry of cells into the tissue (35). The integrity of the ECM is carefully controlled but may be disrupted during tissue remodelling or various pathological situations including healing, inflammation and neoplastic disease (54,91,127). In several cancers including carcinoma of the breast and rectum, loss of basement membrane integrity is associated with an increased risk of metastases and a poorer prognosis (13,31). Pancreatic cancer is characterised by a strong desmoplastic reaction with proliferation of interstitial connective tissue (50) in particular type I collagen and fibronectin (63). In addition, however, loss of type IV collagen, the principal constituent of the basement membrane, is frequently observed indicating that proteolytic degradation may be an important feature of the invasive phenotype of pancreatic cancer (51,117).