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Surgical Treatment of Pancreatic Cancer

Some 40% of pancreatic cancers are locally advanced at the time of diagnosis, often due to adherence to the portal or mestenteric vein. This is often regarded as a criterion of unresectability by many surgeons, who will then proceed with resection of an adherent vein only if the ‘point of no return’ has been passed, while other surgeons consider vascular resection a necessary adjunct to PD. Consequently, some authors report high rates of vessel resection in their surgical series.115–117

There are no randomised controlled trials

available comparing pancreatic resection with and without vascular resection; the literature consists of several case series reporting various pancreatic resections with varying rates of venous and/or arterial resection. Recently, a systematic review of the outcome of portal–mesenteric vein resection during pancreatectomy was published.116

The positive results with palliative gemcitabine for advanced pancreatic cancer made this a logical candidate for further studies.135 In 2007, the results of a randomised controlled trial of adjuvant gemcitabine versus surgery alone (the CONKO-1 trial) were published.136

In this review, 52 studies describing 6,333 pancreatic resections were analysed. In 1,646 patients (26%), a concomitant venous resection was performed. The analysis revealed that this is a time-consuming procedure with high intraoperative blood loss. The reported post-operative morbidity and mortality rates were 42 and 6%, respectively (in the studies providing such information). A positive resection margin (R+) was present in 40% of patients and lymph node positivity (N+) was 67% (range 42–97%). The calculated median survival was 13 months (from 31 studies including 917 patients). Thus, the review shows that venous involvement is associated with high rates of positive resection margins and lymph node metastases, and that the possibility of cure by surgery is improbable. The same should be true for arterial resection. However, from a palliative point of view, pancreatectomy plus venous resection and reconstruction can be performed as safely as conventional pancreatectomy and is associated with a better survival rate than other palliative measures.117

Taken together, a judicious use

of vascular resection seems appropriate. At the same time, one may state that pancreatic resections should be performed only in centres where there is at least competence for the resection and reconstruction of the portal–mesenteric veins.

Adjuvant Oncological Therapy

It is obvious that pancreatic carcinoma cannot generally be cured by surgery alone. Adjuvant therapy was developed on the basis of studies that indicated – contrary to common knowledge at the time – that 5-fluorouracil (5-FU) and radiation had a demonstrable effect in advanced pancreatic cancer.119–123

Although five-year survival rates may have improved, survival at five years does not equal cure. In reality, death continues beyond five years, and the absolute majority of resected patients will die from the disease.2,45,118

In the

mid-1980s, the Gastrointestinal Tumor Study Group (GITSG) published a small randomised controlled trial and a supportive non-randomised trial that showed a survival benefit for radiotherapy combined with 5-FU versus surgery alone.124,125

survivals of 17 months in the observation group, 12 months with chemoradiation, 22 months with chemotherapy alone and 20 months with both chemotherapy and chemoradiation. The corresponding five-year survival estimates were 11, 7, 29 and 13%, respectively. The study group concluded that adjuvant 5-FU had a positive effect on survival, while chemoradiotherapy seemed to have a negative effect.134

Post-operative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone: the median disease-free survival was 13 months versus seven months in the control group. At the 2008 American Society of Clinical Oncology (ASCO) annual meeting, it was further reported that post-operative gemcitabine prolonged medial overall survival from 20 to 23 months. The corresponding three- and five-year survival rates were, respectively, 36 and 21% with gemcitabine versus 20 and 9% in the observation group.137

In a Japanese study, adjuvant gemcitabine

resulted in a significantly longer disease-free survival than surgery alone: 11 versus five months. The corresponding median overall survivals were 22 and 18 months, respectively.138

Further weak support

By contrast, the randomised ESPAC-3 study failed to show a significant difference in survival between post-operative adjuvant 5-FU and gemcitabine; median survival was a reasonable 23 months in both groups, which compares well with earlier studies.140 Thus, although the most recent randomised controlled trials support the use of adjuvant chemotherapy, there is currently not enough evidence to favour gemcitabine over 5-FU in terms of long-term outcome. However, there are indications that the side effects are less severe if gemcitabine is used.140

was given by the Radiation Therapy Oncology Group (RTOG)-9704 trial, in which gemcitabine added before and after flurouracil-based chemoradiotherapy resulted in a slightly longer overall survival than the addition of 5-FU (21 versus 17 months, which was statistically non-significant).139

Some researchers propose that multidrug adjuvant treatment may be more efficient, a strategy that has also been tried in the past.52,126,131,141–145 A regimen of 5-FU, cisplatinum and interferon has shown promising results in phase II studies, but at the price of a high rate of toxicity.146,147 Although many US protocols have included fluorouracil-based chemoradiotherapy, its role in the adjuvant situation remains unsettled. European researchers argue that it is of no proven benefit regarding survival,133,134,140

while the RTOG-9707 study group claims that Although criticism was not lacking (few

patients, slow patient accrual, selection bias), these studies had great impact on the therapy tradition in the US, and several non-randomised treatment series were subsequently published.30,126–130 Europeans were more hesitant about adjuvant therapy, especially as two European randomised controlled trials failed to show a survival benefit.131,132

Pancreatic Cancer 1 (ESPAC-1) study.53,133,134

A turning point was the European Study Group for In a joint effort between 53

hospitals in 11 countries, 289 patients were randomised into a 2x2 factorial study, a further 68 patients were randomly assigned to chemoradiotherapy or no chemoradiotherapy and a further 188 were randomised to chemotherapy or no chemotherapy. Subgroup analyses (for which the study was underpowered) showed median

EUROPEAN ONCOLOGY & HAEMATOLOGY it decreases the risk of locoregional recurrence.139

A problematic feature of post-operative adjuvant therapy is that as many as 20–30% of resected patients never receive treatment because of slow recovery or other reasons.124,125,132,148,149


chemoradiotherapy has been proposed as a more logical way to deliver therapy. Although there may be several potential advantages, they are mostly of unproved clinical benefit.150

Available phase II data

indicate that pre-operative treatment is safe and does not increase peri-operative morbidity or mortality, and it has even been suggested that local post-radiation fibrosis may decrease the rate of pancreatojejunal leakage.151–153

In clinical series, neoadjuvant therapy and subsequent pancreatic resection have typically resulted in 39

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