Survival, Complications and Patient Reported Outcomes after Pancreatic Surgery.

BACKGROUND: Long-term effects of complications in pancreatic surgery have not been systematically evaluated. The objectives were to assess potential effects of complications on survival and patient reported outcomes (PROs) as well as feasibility of PRO questionnaires in patients with periampullary and pancreatic tumors. METHODS: From October 2008 to December 2011, 208 patients undergoing pancreatic surgery were included in a prospective observational study. ESAS, EORTC QLQ-C30 and QLQ-PAN26 questionnaires were completed at inclusion, then every third month. Complications were recorded according to the Clavien-Dindo (CD) classification and Comprehensive Complication Index (CCI). RESULTS: 148 complications were registered in 100 patients (48%), 36 patients (17%) had CD IIIa or above. 125 patients (60%) completed baseline questionnaires, 80 (39%) responded after three and 54 (28%) after six months. Complications were associated with reduced long-term survival in patients with pancreatic ductal adenocarcinoma (PDAC) (p = 0.049) and other malignant diseases. No significant relationship was found between complications and PROs, except for anxiety, which was significantly increased in patients with complications. CONCLUSION: Postoperative complications led to increased anxiety at 3 months after surgery and were associated with reduced long-term survival in patients with malignancy. A short, patient derived, disease specific questionnaire is required in the clinical research context.

Role of surgery in pancreatic cancer.

Treatment of pancreatic cancer is multimodal and surgery is an essential part, mandatory for curative potential. Also chemotherapy is essential, and serious postoperative complications or rapid disease progression may preclude completion of multimodal treatment. The sequence of treatment interventions has therefore become an important concern, and numerous ongoing randomized controlled trials compare clinical outcome after upfront surgery and neoadjuvant treatment with subsequent resection. In previous years, borderline resectable and locally advanced pancreatic cancer was most often considered unresectable. More effective chemotherapy together with the latest improvements in surgical expertise has resulted in extended operations, pushing the borders of resectability. Multivisceral resections with or without resection of major mesenteric vessels are now performed in numerous patients, resulting in better outcome, recorded as overall survival and/or patient reported outcome. But postoperative morbidity increases concurrently, and clinical benefit must be carefully evaluated against risk of potential harm, associated with new comprehensive multimodal treatment sequences. Even though cost/utility analyses are deficient, extended surgery has resulted in significantly longer and better life for many patients with no other treatment alternative. Improved selection of patients to surgery and/or chemotherapy will in the near future be possible, based on better tumor biology insight. Clinically available biomarkers enabling personalized treatment are forthcoming, but these options are still limited. The importance of surgical resection for each patient's prognosis is presently increasing, justifying sustained expansion of the surgical treatment modality.

Updated therapeutic outcome for patients with periampullary and pancreatic cancer related to recent translational research.

Chemotherapy with improved effect in patients with metastatic pancreatic cancer has recently been established, launching a new era for patients with this very aggressive disease. FOLFIRINOX and gemcitabine plus nab-paclitaxel are different regimens, both capable of stabilizing the disease, thus increasing the number of patients who can reach second line and even third line of treatment. Concurrently, new windows of opportunity open for nutritional support and other therapeutic interventions, improving quality of life. Also pancreatic surgery has changed significantly during the latest years. Extended operations, including vascular/multivisceral resections are frequently performed in specialized centers, pushing borders of resectability. Potentially curative treatment including neoadjuvant and adjuvant chemotherapy is offered new patient groups. Translational research is the basis for the essential understanding of the ongoing development. Even thou biomarkers for clinical management of patients with periampullary tumors have almost been lacking, biomarker driven trials are now in progress. New insight is constantly made available for clinicians; one recent example is selection of patients for gemcitabine treatment based on the expression level of the human equilibrium nucleoside transporter 1. An example of new diagnostic tools is identification of early pancreatic cancer patients by a three-biomarker panel in urine: The proteins lymphatic vessel endothelial hyaluronan receptor 1, regenerating gene 1 alpha and translation elongation factor 1 alpha. Requirement of treatment guideline revisions is intensifying, as combined chemotherapy regimens result in unexpected advantages. The European Study Group for Pancreatic Cancer 4 trial outcome is an illustration: Addition of capecitabine in the adjuvant setting improved overall survival more than expected from the effect in advanced disease. Rapid implementation of new treatment options is mandatory when progress finally extends to patients with this serious disease.

Pancreatic cancer-improved care achievable.

Pancreatic adenocarcinoma is one of the most aggressive cancers, and the decline in mortality observed in most other cancer diseases, has so far not taken place in pancreatic cancer. Complete tumor resection is a requirement for potential cure, and the reorganization of care in the direction of high patient-volume centers, offering multimodal treatment, has improved survival and Quality of Life. Also the rates and severity grade of complications are improving in high-volume pancreatic centers. One of the major problems worldwide is underutilization of surgery in resectable pancreatic cancer. Suboptimal investigation, follow up and oncological treatment outside specialized centers are additional key problems. New chemotherapeutic regimens like FOLFIRINOX have improved survival in patients with metastatic disease, and different adjuvant treatment options result in well documented survival benefit. Neoadjuvant treatment is highly relevant, but needs further evaluation. Also adjuvant immunotherapy, in the form of vaccination with synthetic K-Ras-peptides, has been shown to produce long term immunological memory in cytotoxic T-cells in long term survivors. Improvement in clinical outcome is already achievable and further progress is expected in the near future for patients treated with curative as well as palliative intention.