matter of debate. Surgeons who do not perform a prophylactic bypass feel that it needlessly increases

the postoperative length of stay and can be associated with delayed gastric emptying and increased

morbidity and mortality. However, data from a prospective, randomized trial of prophylactic

gastrojejunostomy in patients with unresectable cancer do not support this view.52 In this study, 44

patients were randomized to a gastrojejunostomy, and 43 did not undergo gastric bypass. No mortality

occurred in either group. No difference was observed in either the complication rate or the

postoperative length of stay (Table 55-16). However, late duodenal obstruction developed in 19% of the

patients who did not undergo bypass. A recent multicenter prospective randomized controlled trial has

confirmed these results.53 Therefore, we believe that a prophylactic gastrojejunostomy should be

performed in patients undergoing surgical palliation for unresectable pancreatic carcinoma.

Pain

Tumor-associated pain can be incapacitating in patients with unresectable pancreatic cancer. The

postulated causes of tumor-associated pain are many and include tumor infiltration into the celiac

plexus, increased parenchymal pressure caused by pancreatic duct obstruction, pancreatic inflammation,

gallbladder distention resulting from biliary obstruction, and gastroduodenal obstruction. The

management of pain in patients dying of carcinoma of the pancreas is one of the most important aspects

of their care. The appropriate use of oral agents can be successful in most patients. Patients with

significant pain should receive their medication on a regular schedule and not on an “as-needed” basis.

The use of long-acting morphine derivative compounds appears to be best suited for such treatment.

Percutaneous neurolytic block of the celiac axis, performed under either fluoroscopic or CT guidance, is

also successful in the majority of patients at eliminating pain. Patients with unresectable cancer at the

time of surgical exploration should receive a chemical splanchnicectomy, with 20 mL of 50% alcohol

injected on either side of the aorta at the level of the celiac axis.54

MANAGEMENT

Table 55-16 Prospective Randomized Trial of Prophylactic Gastrojejunostomy in

Patients with Unresectable Periampullary Cancer

SUMMARY

8 The decision to perform nonoperative versus surgical palliation for pancreatic cancer is influenced by

a number of factors, including the patient’s symptoms, overall health status, predicted procedure-related

morbidity and mortality, and projected survival. Surgical palliation can be completed with acceptable

perioperative morbidity and mortality and postoperative length of stay. The avoidance of late

complications of recurrent jaundice, duodenal obstruction, and disabling pain would strengthen the

argument in favor of surgical palliation in those patients expected to survive 6 months or more.

Nonoperative methods of palliation should be considered for patients in whom preoperative staging

suggests distant metastatic disease or a locally unresectable tumor, patients who are not candidates for

operative intervention, and those not expected to survive more than 3 months.

Radiation and Chemotherapy for Unresectable Pancreatic Carcinoma

Specific antitumor therapies in patients with advanced pancreatic carcinoma have been studied for

years, with limited success. Trials evaluating the use of chemotherapy and radiation therapy both alone

and in combination have shown a marginal improvement in survival, often with relatively high toxicity

rates and some negative impact on quality of life. Recently gemcitabine, a deoxycytidine analog capable

of inhibiting DNA replication and repair, has become increasingly popular. When gemcitabine was

compared with bolus 5-FU in a randomized phase III trial, it was shown to confer a significant survival

benefit in advanced pancreatic cancer, increasing median survival from 4.4 to 5.7 months and increasing

1-year survival from 2% to 18%, respectively.55 A key end-point in this study was “clinical benefit

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response,” based on reducing pain, improving performance status, and inducing weight gain, which was

attained in 24% of patients receiving gemcitabine compared with 5% for those receiving 5-FU. In

patients with metastatic pancreatic cancer that had progressed with 5-FU and then been treated with

gemcitabine, the median survival (in 63 of 74 patients enrolled) was 3.9 months.56 Seventeen patients

(27%) attained a clinical benefit response with a median duration of 14 weeks. Gemcitabine is generally

well tolerated with a low incidence of significant toxicity and therefore seems to be a reasonable choice

for palliative therapy.

Long before gemcitabine was established as an option for adjuvant therapy, it was approved in the

metastatic setting based on clinical benefit in patients who had symptomatic advanced disease.55 Over

the last two decades, several combinations of gemcitabine based chemotherapy have failed to improve

outcome in patients with metastatic disease. Recently, both FOLFIRINOX (5-FU, leucovorin, irinotecan,

and oxaliplatin) and nab-paclitaxel/gemcitabine were proven superior to gemcitabine alone in patients

with metastatic pancreatic cancer leading to improvement in response rate (RR), progression-free

survival (PFS) and OS.57,58 Objective response rates have improved by nearly fivefold with these newer

systemic regimens.

In addition to gemcitabine, other agents are currently being studied for a role in the palliation of

patients with pancreatic adenocarcinoma. Examples of such agents are paclitaxel (Taxol), matrix

metalloproteinase inhibitors (e.g., marimastat and perillyl alcohol), and inhibitors of angiogenesis, such

as TNP-470. The results of such studies are eagerly awaited.

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