Article

Re-resection for Isolated Local Recurrence of Pancreatic Cancer is Feasible, Safe, and Associated with Encouraging Survival

Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Annals of Surgical Oncology (Impact Factor: 3.93). 12/2012; 20(3). DOI: 10.1245/s10434-012-2762-z
Source: PubMed

ABSTRACT

Background
Local recurrence of pancreatic cancer occurs in 80 % of patients within 2 years after potentially curative resections. Around 30 % of patients have isolated local recurrence (ILR) without evidence of metastases. In spite of localized disease these patients usually only receive palliative chemotherapy and have a short survival.
Purpose
To evaluate the outcome of surgery as part of a multimodal treatment for ILR of pancreatic cancer.
Methods
All consecutive operations performed for suspected ILR in our institution between October 2001 and October 2009 were identified from a prospective database. Perioperative outcome, survival, and prognostic parameters were assessed.
Results
Of 97 patients with histologically proven recurrence, 57 (59 %) had ILR. In 40 (41 %) patients surgical exploration revealed metastases distant to the local recurrence. Resection was performed in 41 (72 %) patients with ILR, while 16 (28 %) ILR were locally unresectable. Morbidity and mortality were 25 and 1.8 % after resections and 10 and 0 % after explorations, respectively. Median postoperative survival was 16.4 months in ILR versus 9.4 months in metastatic disease (p < 0.0001). In ILR median survival was significantly longer after resection (26.0 months) compared with exploration without resection (10.8 months, p = 0.0104). R0 resection was achieved in 18 patients and resulted in 30.5 months median survival. Presence of metastases, incomplete resection, and high preoperative CA 19-9 serum values were associated with lesser survival.
Conclusions
Resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with favorable survival outcome. This concept warrants further evaluation in other institutions and in randomized controlled trials.

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    • "To date, concepts with pure palliative aim can be separated from semi-curative treatment for oligometastasized lesions due to the biological differences of the underlying disease. Local intensified treatment options of isolated local recurrences consist of either radical surgical approaches or neoadjuvant chemoradiation in case of unresectability [3-5]. In cases of peritoneal metastasis which frequently occur or in cases of distant metastasis predominantly to the liver and lungs, systemic therapy with, for example, FOLFIRINOX or gemcitabine (GEM) or other novel approaches including molecular targeted treatments, is the palliative treatment of choice with impact on overall survival (OS) compared to observation alone [6]. "
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    ABSTRACT: Background Pancreatic cancer (PAC) patients experience a high rate of locoregional recurrences and distant metastasis finally leading to their demise even after curatively-intended multidisciplinary treatment approaches including surgery, chemotherapy and radiotherapy. However, clinical reports on bone and brain metastases in PAC patients are extremely rare and thus timing and dose description are not well defined. Our work therefore summarizes a mono-institutional experience on the use of radiotherapy (RT) for PAC patients with metastatic disease with the aim of identifying overall survival and treatment response in this rarely reported patient group. Method Forty-four PAC patients with 66 metastatic lesions were treated with palliative radiotherapy (RT). Thirty-three patients (48 lesions), 7 patients (11 lesions) and 5 patients (7 lesions) with bone, liver and brain metastases analyzed respectively were analyzed; one patient had both bone and cerebral metastases and was treated for the lesions, thus including him in both subgroups. Indications for RT were pain, neurological impairment, risk of pathological fracture or imminent danger for development of any of these conditions in case of tumor progression. Median age was 64 years (range 38 to 78 years) and there were 27 male (61%) and 17 (39%) female patients. Analyses of overall survival (OS) and local control were performed. OS was calculated from the first day of RT. Results Median overall survival (mOS) of all patients after start of RT was 4.2 months. Survival rates after 1, 3 and 6 months were 79.3%, 55.3% and 30.3% respectively. Patients presenting with bone metastasis had a mOS of 3.1 months and after 1, 3 and 6 months, survival rates were 75.3%, 46.5% and 19.9% respectively. Symptomatic response to therapy was recorded in 85% of all evaluated patients with bone metastasis. Patients undergoing radiosurgery because of liver metastasis were locally controlled in all but one patient after a median follow-up of 8.3 months. Conclusion Overall survival of all patients with metastatic disease was considerably worse. A major goal for the future must be the selection of an appropriate RT treatment in terms of duration and technique for these PAC patients.
    Full-text · Article · May 2014 · European journal of medical research
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    • "An unusual aggressiveness and early metastatic locoregional, as well as distant, spread of pancreatic cancer cells is the basis of the urgent need for new therapeutic options for this cancer, as its incidence is still nearly equal to its mortality, in Western countries (Siegel et al., 2012). The failure of clinical treatment in patients with PDAC is often attributed to the early metastatic growth, a high level of drug resistance to standard therapy options and high rates of local recurrence (Strobel et al., 2013). However, inadequate diagnostic tools as well as the limited therapeutic options for PDAC, also known as pancreatic cancer, also account for its ranking as the fourth leading cause of cancer-related death worldwide (Siegel et al., 2012). "
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    ABSTRACT: In recent years, it has become clear that the current standard therapeutic options for pancreatic cancer are not adequate and still do not meet the criteria to cure patients suffering from this lethal disease. Although research over the past decade has shown very interesting and promising new therapeutic options for these patients, only minor clinical success was achieved. Therefore, there is still an urgent need for new approaches that deal with early detection and new therapeutic options in pancreatic cancer. To provide optimal care for patients with pancreatic cancer, we need to understand better its complex molecular biology and thus to identify new target molecules that promote the proliferation and resistance to chemotherapy of pancreatic cancer cells. In spite of significant progress in curing cancers with chemotherapy, pancreatic cancer remains one of the most resistant solid tumour cancers and many studies suggest that drug-resistant cancer cells are the most aggressive with the highest relapse and metastatic rates. In this context, activated Notch signalling is strongly linked with chemoresistance and therefore reflects a rational new target to circumvent resistance to chemotherapy in pancreatic cancer. Here, we have focused our discussion on the latest research, current therapy options and recently identified target molecules such as Notch-2 and the heparin-binding growth factor midkine, which exhibit a wide range of cancer-relevant functions and therefore provide attractive new therapeutic target molecules, in terms of pancreatic cancer and other cancers also. LINKED ARTICLES This article is part of a themed section on Midkine. To view the other articles in this section visit
    Full-text · Article · Feb 2014 · British Journal of Pharmacology
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    • "An unusual aggressiveness and early metastatic locoregional as well as distant spread of pancreatic cancer cells still reflects the urgent necessity of new therapeutic options for this deadly disease since its incidence still nearly equals mortality in western countries (Siegel et al., 2012). The clinical treatment failure of patients is often attributed to the early metastatic growth, an unmet high drug-resistance to standard therapy options and high rates of local recurrence (Strobel et al., 2013). However, insufficient diagnostic tools as well as therapeutic options for PDAC, also known as pancreatic cancer, still substantiate its ranking as the 4 th leading cause of cancer related death worldwide (Siegel et al., 2012). "
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    ABSTRACT: Unlabelled: In recent years, it has become clear that the current standard therapeutic options for pancreatic cancer are not adequate and still do not meet the criteria to cure patients suffering from this lethal disease. Although research over the past decade has shown very interesting and promising new therapeutic options for these patients, only minor clinical success was achieved. Therefore, there is still an urgent need for new approaches that deal with early detection and new therapeutic options in pancreatic cancer. To provide optimal care for patients with pancreatic cancer, we need to understand better its complex molecular biology and thus to identify new target molecules that promote the proliferation and resistance to chemotherapy of pancreatic cancer cells. In spite of significant progress in curing cancers with chemotherapy, pancreatic cancer remains one of the most resistant solid tumour cancers and many studies suggest that drug-resistant cancer cells are the most aggressive with the highest relapse and metastatic rates. In this context, activated Notch signalling is strongly linked with chemoresistance and therefore reflects a rational new target to circumvent resistance to chemotherapy in pancreatic cancer. Here, we have focused our discussion on the latest research, current therapy options and recently identified target molecules such as Notch-2 and the heparin-binding growth factor midkine, which exhibit a wide range of cancer-relevant functions and therefore provide attractive new therapeutic target molecules, in terms of pancreatic cancer and other cancers also. Linked articles: This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4.
    Full-text · Article · Sep 2013 · British Journal of Pharmacology
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