Previous studies of molecular prognostic markers following resection for exocrine pancreatic cancer have produced conflicting results. Our aim was to undertake a comprehensive analysis of potentially useful molecular markers in a large, multicentre patient population and to compare these markers with standard pathological prognostic variables. Formalin‐fixed, paraffin‐embedded specimens of pancreatic ductal adenocarcinoma were analysed from 157 patients [100 men and 57 women with a median (range) age of 60 (33–77) years] who had undergone pancreatectomy. Immunohistochemistry was used to detect expression of p16INK4, p53, p21WAF1, cyclin D1, erbB‐2 and erbB‐3. Mutations in codons 12 and 13 of the K‐ras oncogene were detected by SSCP and sequencing following DNA extraction and amplification by PCR. The median (range) survival post‐resection was 12.5 (3–83) months. Abnormalities of p16INK4, p53, p21WAF1, cyclin D1, erbB‐2 and erbB‐3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no significant correlation between expression of any of these markers and patient survival. K‐ras mutations were found in 73 (75%) of 97 cases with amplifiable DNA. The presence of K‐ras mutation alone did not correlate with survival, but there were significant differences in survival according to the type of K‐ras mutation (p = 0.0007). Reduced survival was found in patients with GaT, cGT and GcT K‐ras mutations compared to GtT, aGT and GaC mutations. In conclusion, survival was associated with type of K‐ras mutation but not expression of p16INK4, p53, p21WAF1, cyclin D1, erbB‐2 and erbB‐3. Int. J. Cancer 89:469–474, 2000. © 2000 Wiley‐Liss, Inc.

Pancreatic cancer has a very poor prognosis and is a common cause of cancer death in the Western world. Certain genetic alterations may be important in the prognosis of pancreatic cancer. Activation mutations in the K- ras oncogene occur in around 90% of pancreatic cancers, and the overexpression of growth factors epidermal growth factor (EGF), transforming growth factor (TGF)alpha, TGFbetas 1-3, acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and growth factor receptors c-erbB-2 and -3 and TGFRbetas 1-3 is common. High mutation levels of cell cycle control genes such as p53, p16, p21, SMAD4, and cyclin D1 are found, and there is abnormal expression of apoptotic genes, such as bcl-2, bcl-XL, and bax. The expression of several of these growth factors and their receptors has been found to be associated with poorly differentiated tumors of an advanced stage and decreased survival. However, the inactivation and loss of expression of p16, p53, and p21, and the expression of several apoptotic genes, such as bax and bcl-2, have not been found to be of any prognostic significance. The expression of wild type p53, however, may predict responsiveness to chemotherapy. TGFbeta1 expression has been shown to be associated with longer survival in patients with pancreatic cancer. Two studies (including our own) have found bcl-XL expression to be significantly associated with poor survival. These and newer molecular markers may prove to be important in the choice of future therapies for pancreatic cancer.

Pancreatic cancer remains one of the leading causes of cancer related death worldwide with an overall fiveyear survival of less than 5%. Potentially curative surgery, which alone can improve 5-year survival to 10%, is an option for only 10%-20% of patients at presentation owing to local invasion of the tumour or metastatic disease. Adjuvant chemotherapy has been shown to improve 5-year survival to 20%-25% but conflicting evidence remains with regards to chemoradiation. In this article we review the current evidence available from published randomised trials and discuss ongoing phase Ⅲ trials in relation to adjuvant therapy in pancreatic cancer.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Pancreatic cancer; Adjuvant; Gemcitabine; Chemotherapy; Chemoradiotherapy; Phase Ⅲ Core tip: This paper discusses every major trial undertaken in the field of adjuvant therapy in pancreatic cancer. The evolution of chemotherapeutic regimes over the past 25 years and the controversy surrounding chemoradiation are analysed, in addition to looking at the phase Ⅲ trials currently in progress.

Background/Aims: The matrix metalloproteinases are a family of proteolytic enzymes which normally have an important physiological role in tissue remodelling and wound healing, but more recently have been implicated in the proteolytic events which occur during tumour invasion. Methods: The expanding family of matrix metalloproteinases and the specific tissue inhibitors of the matrix metalloproteinases are reviewed including their classification, structure, function, regulation of activity, and tissue expression with particular reference to pancreatic cancer. The effect of synthetic matrix metalloproteinases inhibitors in preclinical studies is reviewed together with the results of ongoing clinical trials in pancreatic cancer. Results: Pancreatic cancer is associated with the overexpression of several matrix metalloproteinases with a reduced expression of their specific inhibitors. Orally bioavailable matrix metalloproteinase inhibitors have successfully completed phase I/II clinical trials with promising results. Multicentre randomised controlled phase IIb/III clinical trials aren currently under way in pancreatic cancer. Conclusions: Matrix metalloproteinase inhibition may represent a novel approach to the management of pancreatic cancer not only in advanced disease, but in the adjuvant treatment setting following tumour resection either alone or in combination with existing chemotherapeutic agents.

Background This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection. Results This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery before and 4371 (59.1 per cent) during the pandemic. Overall, 4.3 per cent (187 of 4371) developed postoperative SARS-CoV-2 in the pandemic cohort. The pulmonary complication rate was similar (7.1 per cent (216 of 3031) versus 6.3 per cent (274 of 4371); P = 0.158) but the mortality rate was significantly higher (0.7 per cent (20 of 3031) versus 2.0 per cent (87 of 4371); P < 0.001) among patients who had surgery during the pandemic. The adjusted odds of death were higher during than before the pandemic (odds ratio (OR) 2.72, 95 per cent c.i. 1.58 to 4.67; P < 0.001). In mediation analysis, 54.8 per cent of excess postoperative deaths during the pandemic were estimated to be attributable to SARS-CoV-2 (OR 1.73, 1.40 to 2.13; P < 0.001). Conclusion Although providers may have selected patients with a lower risk profile for surgery during the pandemic, this did not mitigate the likelihood of death through SARS-CoV-2 infection. Care providers must act urgently to protect surgical patients from SARS-CoV-2 infection.