Re-resection for Isolated Local Recurrence of Pancreatic Cancer is Feasible, Safe, and Associated with Encouraging Survival.
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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- "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). "
Article: Pancreatic Cancer[Show abstract] [Hide abstract]
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 visitBritish Journal of Pharmacology 02/2014; · 4.99 Impact Factor
- "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). "
Article: Pancreatic Cancer.[Show abstract] [Hide abstract]
ABSTRACT: In recent years, it becomes evident that current standard therapeutic options for pancreatic cancer are not sufficient enough and still do not meet the criteria to cure more efficiently patients that suffer from this deadly disease. Although the research of the latest decade showed very interesting and promising new therapeutic options for these patients, only minor success was clinically displayed, unfortunately. Therefore, pancreatic cancer is highly linked with the urgent necessity of new approaches that deal with early detection and new therapy options. In fact, to provide optimal care for pancreatic cancer patients, continuous investigations are crucial and will help to better understand its complex molecular biology, which in turn, is accompanied by the identification of new target molecules that may promote the progression and therapy resistance of pancreatic cancer cells. Despite significant effort directed at curing cancers with chemotherapy, pancreatic cancer is one of the most resistant cancer among solid tumors and many studies suggest that drug-resistant cancer cells are the most aggressive ones with highest relapse and metastatic rates. In line with this, it was recently shown that activated notch signaling is strongly linked with chemoresistance and therefore reflects a rationale new target to circumvent chemotherapy-resistance in pancreatic cancer. In summary, we focus our discussion in this review on latest research breakthroughs, current therapy options and recently identified target molecules such as Notch-2 and the heparin-binding growth-factor Midkine, that promote a plethora of cancer-relevant features and implicates therefore attractive new therapeutical target molecules in other cancers as well.British Journal of Pharmacology 09/2013; 171. DOI:10.1111/bph.12401 · 4.99 Impact Factor
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ABSTRACT: Background In the present retrospective analysis we analysed the therapeutic outcome of a set of patients, who were treated with chemoradiation (CRT) for recurrent pancreatic cancer (RPC) in a single institution. Patients and Methods Forty-one patients had a history of primary resection for pancreatic cancer. In case of an unresectable recurrency patients were treated with CRT at our institution between 2002 and 2010 with a median dose of 48.4 Gy (range 39.6–54 Gy). Concurrent chemotherapy regimes included Gemcitabine (GEM) in 37/41 patients (90%) and Fluorouracil (FU) or Capecitabine (CAP) in 4/41 patients (10%). Patients were re-evaluated after CRT with computed tomography and/or explorative laparotomy. During re-resection or laparotomy 15 patients received an additional intraoperative radiotherapy (IORT) with a median dose of 15 Gy (range 12–15 Gy). Median age was 65 years (range 39–76 years) and there were 26 male and 15 female patients. Results The median overall survival (mOS), local control (LC) and progression-free survival (PFS) were 16.1, 13.8 and 6.9 months respectively for all patients after the first day of CRT. Re-resection was possible in five patients (12%) and a complete remission (CR) as defined by tumor-free biopsy was seen in 6 patients (15%). When re-resection could be achieved after CRT mOS was improved to 28.3 months (n = 5 patients, 95%-CI 10.2 – 46.3 months). Patients receiving IORT had a significantly improved mOS compared to no IORT (p = 0.034). Fifteen patients (37%) experienced a local tumour progression and main site of distant metastasis was the liver (11 patients, 27%).Overall treatment-related toxicity was mild, grade III hematologic toxicity was observed in 11 patients (27%). Conclusion In summary we observed a good therapeutic response with mild to moderate toxicity levels for CRT in RPC. Overall survival and PFS were clearly improved in case of induction of a complete remission (tumor-free biopsies) or after achieving a re-resection, thus providing a curative intended therapy even in case of disease recurrence.Radiation Oncology 01/2013; 8(1):27. DOI:10.1186/1748-717X-8-27 · 2.36 Impact Factor