Since preoperative radiation therapy combined with chemotherapy(CTRT) was first performed in 1986 for patients with pancreatic adenocarcinoma, there have been several reported experiences with varying drugs and radiotherapy regimens. We describe those experiences and contrast them to a series of patients treated at our institution with resectional surgery before CTRT. Finally, the current role of preoperative CTRT in the therapy of pancreatic adenocarcinoma is proposed.

Two groups of patients with adenocarcinoma of the pancreas treated with either preoperative chemoradiation (preop CTRT) or postoperative chemoradiation (postop CTRT) were retrospectively analyzed for various treatment-related parameters. Between November 1986 and October 1996, a total of 70 patients with pancreatic adenocarcinoma were enrolled into preop CTRT protocols at our institution. Twenty-five patients with adenocarcinoma of the head of the pancreas underwent pancreaticoduodenectomy with curative intent. After the closure of the preop CTRT protocols, we had the opportunity to perform 23 pancreatic resections without preop CTRT. After surgery, these patients were advised to undergo CTRT. These two groups of patients were therefore selected consecutively, dependent only on the time of referral and no other bias. These two cohorts of patients are compared for various intraoperative parameters, length of hospital stay, pathologic findings, time to recurrence, and survival. Mean age was 65 and 66 years in the preop and postop CTRT groups, respectively. Sex distribution was almost equal. Treatment breaks resulting in greater than 1 week delay in the radiotherapy occurred in 2 (8%) of 25 patients in the preop CTRT group (myelotoxicity in 1 case and biliary sepsis in 1 case), whereas no treatment breaks >1 week occurred in those receiving postop CTRT. Eleven patients in preop CTRT had grade 3 or 4 toxicity, whereas none was noted in those with postop CTRT. There was one postoperative death in the preop CTRT group and none in the postop CTRT group. Mean time to the start of CTRT was 45 days (range, 20-66 days) after pancreaticoduodenectomy. Delay of >60 days to the onset of CTRT occurred in 2 (22%) patients and was attributable to patient delays in time to recover from surgery or patient noncompliance. Furthermore, 5 of 23 patients (22%) in the postop CTRT group did not receive treatment for various reasons. Average estimated operative blood loss was 1933 mL (median 1550) and 1060 mL (median 1000) for preop and postop CTRT groups, respectively. Mean length of operation was 488 minutes (median 480) and 486 minutes (median 480). Median length of postoperative stay was 22 and 20 days (ranges, 9-144 and 10-38). Pathological findings in the resected specimens showed significantly fewer involved nodes in the preop CTRT group (28 vs 87%; P = 0.0006), whereas similar numbers of nodes/patient were counted in each group (14 vs 22, P = 0.11). More negative resection margins were observed in the preop CTRT group (28 vs 56%; P = not significant). A significantly greater amount of fibrosis replacing the tumor was observed in the preop CTRT group (70 vs 40%; P = 0.0001). There were no significant survival differences observed (median 20 months vs 25 months; P = 0.48), in follow-up that ranged from 4 to 76 months (median 44 months for surviving patients) for the preop group and 4 to 40 months (median 16 months for surviving patients) for those with postop CTRT. Local failure either alone or as a component of distant failure occurred in 16 per cent (4 of 25 patients) with preop CTRT and 16.6 per cent (3 of 18) with postop CTRT. Analysis of differences between those treated with preoperative and postoperative CTRT demonstrates similarity in toxicity and effects. However, 22 per cent of patients intended for postoperative therapy did not receive treatment.

Much has been written about preoperative strategies in the treatment of pancreatic adenocarcinoma, yet there has been very little comment concerning other periampullary malignancies. This review discusses current issues relevant to the further development of preoperative adjuvant treatment of pancreatic adenocarcinoma. A small series of patients with ampullary adenocarcinomas treated with preoperative adjuvant chemoradiotherapy is also described.

The modern era has witnessed both the triumphs of the first resectional procedures for pancreatic cancer and the failures of most of these operations to cure [1–4]. Similarly, it has seen optimistic first reports and less sanguine follow-ups of various adjunctive radiation therapy and chemotherapy regimens [5–11]. This chapter will briefly review these landmarks and will then cover modern management for the patient with carcinoma of the exocrine pancreas.

A 9-year experience with fine-needle aspiration (FNA) in patients with resectable pancreatic adenocarcinoma was reviewed to determine whether this procedure is associated with positive peritoneal cytology, peritoneal recurrences, or decreased survival in patients who had pancreatic resection with curative intent. Forty-one patients underwent pancreatic resection for primary pancreatic adenocarcinoma from July 1987 to February 1996. Nine patients had open biopsies prior to definitive resection and were excluded from this study. Of the remaining 32 patients, 21 (66%) had preoperative computed tomography-guided or fluoroscopically guided FNA biopsy of the pancreas for diagnosis. FNA confirmed the diagnosis of adenocarcinoma in 17 of 21 patients (80%). Fifteen of 21 FNA biopsies were performed in patients who went on to receive neoadjuvant chemoradiation. Twenty-eight of 32 patients (87%) had peritoneal washings at the time of laparotomy. Five patients had suspicious or positive washings (18%), and 23 patients had negative washings (82%). Three of 18 patients (16.7%) who had both FNA and peritoneal washings and 2 of 10 patients (20%) who had no FNA but had peritoneal washings had positive or suspicious peritoneal cytology. Eight of 32 patients ultimately failed in the peritoneum. Six of 21 patients (28%) who had prior FNA and 2 of 11 (18%) who had no prior FNA failed in the peritoneum. Although the number of patients is small, none of these differences proved to be statistically significant. No difference in median survival was observed between the FNA and no FNA groups. We conclude that FNA is a safe and useful tool to confirm the diagnosis of pancreatic cancer when patients are to be treated with neoadjuvant chemoradiation.

The treatment of patients with pancreatic cancer requires the expertise of medical oncologists, radiation oncologists, radiologists, and surgical oncologists. The surgeon's role in the management of patients with pancreatic cancer extends beyond the performance of surgical resection and bypass procedures to include diagnosis, staging (including determination of resectability), and therapy (both curative and palliative). If a lesion is deemed resectable, the surgeon's goal is to achieve clear pathologic margins in order to optimize the patient's chances for cure. The surgeon also plays a key role in the palliation of disease in patients with unresectable lesions. Biliary and duodenal bypass, endoscopic stenting, laparoscopy, and celiac ganglion injection may be needed to maximize a patient's remaining quality of life. In addition, the surgical oncologist should be involved in clinical trials testing neoadjuvant or adjuvant chemoradiotherapies that may lead to the development of more effective therapies for pancreatic cancer.