placement of clips for postoperative radiation therapy. If, as in most cases, the tumor cannot be

resected, a tissue biopsy should be performed, in addition to a chemical splanchnicectomy with alcohol

for pain management. In some cases, a prophylactic gastrojejunostomy may be indicated because of the

potential for obstruction by tumor at the ligament of Treitz.

Postoperative Results

4 During the 1960s and 1970s, many centers reported operative mortality following PD in the range of

20% to 40%, with postoperative morbidity rates as high as 40% to 60%. During the last three decades, a

dramatic decline in operative morbidity and mortality following PD has been reported at a number of

centers, with operative mortality rates in the range of 2% to 3%.33–35 The reasons behind this decline

appear to be the following: (a) fewer, more experienced surgeons are performing the operation on a

more frequent basis, (b) preoperative and postoperative care has improved, (c) anesthetic management

has improved, and (d) large numbers of patients are being treated at high-volume centers.36

Although the operative mortality rates for pancreatic cancer have been reduced significantly, the

complication rates approach 40% (Table 55-13). Pancreatic fistula remains the most frequent serious

complication following PD, with an incidence ranging from 5% to 15%. In the past, the development of

pancreatic fistula after PD was associated with mortality rates of 10% to 40%. Although the incidence of

pancreatic fistula following PD remains stable, the overall associated mortality rate has diminished

owing to improved management. Important supportive measures include careful maintenance of fluid

and electrolyte balance, parenteral nutrition, and controlling the pancreatic leak with percutaneous or

intraoperative drainage.

Table 55-12 Results for Minimally Invasive Pancreatoduodenectomy

COMPLICATIONS

Table 55-13 Complications After Pancreaticoduodenectomy

Long-Term Survival

5 Historically, 5-year survival rates for patients undergoing resection for adenocarcinoma of the head of

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the pancreas were reported to be in the range of 5%. However, recent studies have suggested an

improved survival for patients following PD. In 2006, Winter et al.37 reported on 1,175 patients who

underwent operative resection for pancreatic adenocarcinoma. The actuarial 5-year survival for these

patients was 18%, with a median survival of 18 months (Fig. 55.8). In this study, factors found to be

important predictors of survival included tumor diameter (<3 cm), negative resection margin status,

well/moderate tumor differentiation, and postoperative chemoradiation treatment. Patients who

underwent resection with negative margins had a median survival of 20 months and a 5-year survival of

21%, whereas those with positive margins fared significantly worse, with a median survival of 14

months and a 5-year survival of 12%. The outcome was particularly favorable in the subgroup of

patients with small tumors (<3 cm) who underwent margin-negative, node-negative resections; the

median survival was 44 months and the 5-year survival was 43%.

ADJUVANT AND NEOADJUVANT THERAPY

6 At present, the general consensus of most surgeons treating patients with pancreatic carcinoma is that

any future improvement in survival for this disease will involve improvements in systemic therapy.

Despite advances in surgery and perioperative care that have resulted in markedly reduced

postoperative mortality after pancreatoduodenectomy, the median survival for pancreatic cancer

patients has changed minimally over the past two decades. Even with optimal surgical management, 5-

year survival averages 15% to 20% for resectable disease and 3% for all stages combined.

Approximately 85% of patients with resected pancreatic cancer will ultimately recur and die of their

disease. These outcomes suggest that in most cases pancreatic cancer is a systemic disease at the time of

diagnosis, making surgical resection alone inadequate therapy. The results of the most important

randomized prospective trials of adjuvant therapy for pancreatic cancer are summarized in Table 55.14.

In 1985, the Gastrointestinal Tumor Study Group reported encouraging results from a prospective,

randomized trial to evaluate the efficacy of adjuvant radiation and chemotherapy following curative

resection for adenocarcinoma of the head of the pancreas.38 Forty-three patients were randomized to

either adjuvant therapy with radiation and 5-fluorouracil (5-FU) or no adjuvant therapy. The median

survival for the 21 patients who received adjuvant therapy was 20 months, and three (14%) survived 5

years or longer. For the 22 patients who received no adjuvant therapy, the median survival was 11

months, and only 1 patient (4.5%) survived 5 years.

The randomized trial conducted by the European Organization for Research and Treatment of Cancer

(EORTC),39 sought to recapitulate the results of the GITSG study in 114 patients with pancreatic head

lesions (observation, n = 54 and adjuvant treatment, n = 60). However, chemotherapy (5-FU) given

during radiation was given as a continuous infusion (rather than via bolus) during each radiation

sequence, depending on toxicity, for up to 5 days. No chemotherapy was given postchemoradiation.

Fifty-six percent of patients received the intended chemotherapy dose during radiation. Patients in the

chemoradiation arm had a median survival of 17.1 months versus 12.6 months in the observation arm (p

= 0.099); 2- and 5-year overall survivals were 37% and 20%, respectively, for the experimental arm

and 23% and 10%, respectively, for the control arm.

The ESPAC-1 trial published in 2004 analyzed 289 patients recruited from 53 hospitals in a 2 × 2

factorial design.40 The four study groups included (1) surgery only (n = 69); (2) chemotherapy only (n

= 73) consisting of 5-FU, 425 mg/m2, and leucovorin, 20 mg/m2, given daily for 5 days every 4 weeks

for six cycles of treatment; (3) radiation therapy and 5-FU given (n = 75) according to the original

GITSG method; and (4) both treatments (n = 73, chemoradiation followed by chemotherapy). The

major study conclusions were that the 5-year overall survival comparisons between patients who

received chemotherapy versus those that did not (21% vs. 8%, p = 0.009) and those that received

radiation therapy versus those that did not (10% vs. 20%, p = 0.05). The authors concluded that

adjuvant chemotherapy had a beneficial effect in resected pancreatic cancer, whereas chemoradiation

had a deleterious effect. A quality-of-life questionnaire showed no difference between those that

received chemotherapy and those that did not, and those that received chemoradiation and those that

did not. Thus, the survival benefit of adjuvant chemoradiation for pancreatic cancer patients remains

unclear, and the optimal regimen has yet to be determined.

The RTOG 9704 trial, presented in abstract form in 2006,41 contained 442 eligible patients who

received adjuvant chemoradiation (5,040 cGy) given as continuous fractions with radiosensitizing doses

of 5-FU. The comparisons were with the addition of either three cycles of 5-FU (one prechemoradiation,

two postchemoradiation for 12 weeks) versus four cycles of gemcitabine (one prechemoradiation, three

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