Journal of Surgical Oncology 4 3 5 6 4 0 (1990)

Cystadenocarcinoma of the Pancreas: Neo-Adjuvant Therapy and CEA Monitoring

DENNIS WOOD, MD, ALLAN W. SILBERMAN, MD, LAURENCE HEIFETZ, MD,

LESLIE MEMSIC, MD AND M. MICHAEL SHABOT, MD

From the Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California

Cystadenocarcinoma of the pancreas is generally considered to be unre- sponsive to chemotherapy and radiation therapy. We present two cases of laparotomy-proven unresectable cystadenocarcinoma which responded to intravenous 5-fluorouracil (1,000 mg/m2/24 hr X 5 days X 2) and 4,000 rads of radiation therapy. Both patients had objective response with marked shrinkage of the tumor as determined by clinical examination and computed tomography. At reexploration both tumors had become com- pletely resectable with histologically clear margins and negative lymph nodes .Carcinoembryonic antigen (CEA) levels were elevated in both pa- tients at initial presentation (86 and 71 ngiml). The CEA levels declined to 19.9 and 66.0 ng/ml, respectively, after neo-adjuvant therapy, and both fell to normal levels after resection. Although surgical resection has been considered the only curative therapy for patients with pancreatic cystad- enocarcinoma, we suggest that preoperative irradiation and chemotherapy may reduce the size of seemingly unresectable tumors. We also recom- mend serial CEA determinations in patients with levels initially elevated as a marker of the response to neo-adjuvant and operative therapy.

KEY WORDS: pancreatic cancer, pre-operative chemotherapy, radiation

INTRODUCTION Cystadenocarcinoma of the pancreas is a rare malig-

nant neoplasm, often confused with pancreatic pseudocysts, and is difficult to distinguish either grossly or histologically from its benign counterpart, the cystad- enoma. Compared to the much more common and ag- gressive adenocarcinoma of the pancreas, cystadenocar- cinornas tend to be slow growing, locally recurrent, and late metastasizing despite the fact that these neoplasms often attain considerable size prior to their diagnosis. As a consequence of the natural history of these tumors, aggressive surgical therapy with en bloc resection of sur- rounding tissues has been advocated. For the same ra- tionale, i.e., slow growth and large size, chemotherapy and radiation therapy have generally not been utilized in the treatment of these tumors.

We present two patients with laparotomy proven un- resectable cystadenocarcinoma of the pancreas who re- sponded to neo-adjuvant therapy with combined radia-

tion and chemotherapy which allowed subsequent en bloc surgical resection. In addition, carcinoembryonic antigen (CEA) levels which were elevated in both pa- tients fell to normal following the neo-adjuvant and sur- gical therapy.

CASE REPORTS Patient A is a 50-year-old Korean male who presented

in September of 1986 with a large abdominal tumor. An abdominal computerized tomographic (CT) scan (Fig. 1) showed a 20 X 16 cm soft tissue mass which appeared to involve the left lobe of the liver, the small bowel mesentery, and the head of the pancreas. Para-aortic lymphadenopathy was also present.

Accepted for publication August 14, 1989. Address reprint requests to A. W. Silherman, M.D., Cedars-Sinai Comprehensive Cancer Center, 8700 Beverly Blvd., Los Angeles, CA 90048.

6 1990 Wiley-Liss, Inc.

Cystadenocarcinoma of the Pancreas 57

Fig. 1. involving the left lobe of liver and mesentery. Para-aortic lymphadenopathy (L) is present.

Patient A: Abdominal CT scan showing a large mass (M) displacing the head of the pancreas and

The patient underwent exploratory laparotomy which 140

opment of the porta hepatis. Multiple biopsies of the 120

however, was 92 ng/ml (normal < 2), suggesting ma- loo

lignancy. On the presumption of malignant cystadeno- :i carcinoma, the patient received 4,400 rads of external 7o beam radiation sandwiched between two courses of in- 4 60

confirmed the unresectability of this lesion due to envel- 130

tumor revealed only cystadenoma. The patient’s CEA, 110

fusional intravenous 5-fluorouracil (1,000 mg/m2/24 hr 50 X 5 days). 40

30 20

10 0

_ _ _ ̂ ____.....___

Within 2 months, the CEA had decreased to 19.9 ng/ ml (Fig. 2). On clinical examination the tumor was markedly decreased in size. In January 1987, the patient underwent re-exploration. The tumor had been rendered Baseline During After Fostop

5-FU/Rad Rx 5-FU/Rad Rx

CEA levels for patients A and B. resectable and was removed in continuity with the head of the pancreas, duodenum, gastric antrum, and right and transverse colon. A Roux-en-Y pancreaticojejunostomy ,

Fig. 2.

choledochojejunostomy, gastrojejunostomy, and ileoco- lostomy were performed.

Pathologic examination of the tumor revealed well- differentiated mucinous cystadenocarcinoma with all margins free of tumor. There was no evidence of lym- phatic or venous invasion.

Postoperatively, the patient’s CEA dropped to 2.9 ng/ ml. A CT scan 3 months postoperatively showed no ev- idence of recurrent or metastatic disease (Fig. 3 ) . Two years postoperatively the patient continues without evi- dence of disease with a CEA of 7.9.

Patient B is a 79-year-old Caucasian male in whom a

retroperitoneal mass was incidentally discovered during an angiographic procedure for peripheral vascular dis- ease. Four years previously he had undergone right upper lobectomy for alveolar cell carcinoma of the lung. An abdominal CT scan (Fig. 4) confirmed a large cystic mass adherent to the tail of the pancreas, posterior stom- ach, spleen, left adrenal gland, left kidney, and retro- peritoneum. CT-guided aspiration was nondiagnostic for carcinoma but yielded an amylase of 1,600 units (normal < 120 units).

At laparotomy the mass extended superiorly to the left hemidiaphragm; inferiorly to the left kidney; and in-

58 Wood et al.

Fig. 3. metastatic disease.

Patient A: CT scan 3 months following surgery demonstrating no evidence of recurrent or

Fig. 4. pancreas, posterior stomach, spleen, left adrenal gland, left kidney, and posterior retroperitoneum.

Patient B: Abdominal CT scan demonstrating a large cystic mass (M) adherent to the tail of the

volved the pancreas, spleen, and aorta. The lesion was considered surgically unresectable. Frozen section of the mass was reported as a cyst wall with epithelial lining, consistent with cystadenoma. The patient underwent Roux-en-Y cystjejunostomy for presumed benign cystad-

enoma. Final pathologic sections revealed moderately well-differentiated cystadenocarcinoma.

Following recovery from the initial laparotomy, the patient received neo-adjuvant therapy with intravenous 5-fluorouracil(l000 mg/m2/24 x 5 days x 2) and 4,000

Cystadenocarcinoma of the Pancreas 59

Fig. 5 . demonstrating decrease in tumor mass (M).

Patient B: CT scan following two courses of 5-fluorouracil (5-FU) and 4,000 R of radiation

rads of external beam radiation. During therapy a pan- creatic cyst abscess developed which required CT-guided insertion of a drainage catheter. The CEA level dropped insignificantly (71.2 ng/ml pretreatment; 66 ng/ml post- treatment); however, follow-up CT scan (Fig. 5 ) re- vealed a dramatic decrease in tumor size.

The patient underwent exploratory laparotomy and en bloc resection of tumor, distal pancreas, spleen, left kid- ney, and left adrenal gland. Pathologic examination con- firmed moderately well differentiated cystadenocarci- noma which was now discrete from the pancreas, kidney, and spleen. There was an extensive amount of fibrosis and necrotic tumor. All surgical margins were free of tumor.

Postoperatively, the CEA dropped to 5.7 ng/ml, and 6 months later a CT scan (Fig. 6) demonstrated no recur- rent abdominal tumor.

DISCUSSION Cystadenocarcinoma of the pancreas is a rare neo-

plasm representing approximately 1 % of all malignant pancreatic tumors. Cystadenocarcinomas have a better prognosis than most other pancreatic malignancies; how- ever, this prognosis is contingent upon total excision of the tumor. Hodgkinson and associates from the Mayo Clinic reported a 68% five-year survival rate after cura- tive resection [l]. In contrast, if only a partial resection were performed, the five-year survival was 14%. Ac- cording to ReMine and associates from the Lahey Clinic,

the average survival of patients with surgically unresect- able disease is only three months [2].

In larger series, 33-67% of patients were considered unresectable at the time of surgery [1,3]. Since cystad- enocarcinoma of the pancreas has been considered unre- sponsive to chemotherapy and radiation therapy [4], this substantial group of surgically unresectable patients have had no therapeutic options and a poor prognosis.

We present two cases of laparotomy proven unresect- able cystadenocarcinoma of the pancreas, both of which responded dramatically to neo-adjuvant therapy with in- fusional 5-fluorouracil and radiation therapy. The de- crease in tumor size was confirmed by clinical examina- tion and/or CT scan. Both patients at re-exploration had a dramatic decrease in tumor size, such that resection was now possible with all margins and lymph nodes free of disease.

CEA levels were elevated in both patients at initial presentation (86 and 71 ng/ml). The CEA levels declined to 19.9 ng/ml and 66.0 ng/ml, respectively, after neo- adjuvant therapy, and both fell to normal values after resection. This elevation of the CEA level is in agree- ment with other anecdotal reports of elevated serum or cyst-fluid CEA levels with cystadenocarcinoma [5,6].

Resection is considered the only curative therapy for patients with pancreatic cystadenocarcinoma. We sug- gest that combined neo-adjuvant therapy with radiation and chemotherapy be considered prior to any attempt at surgical debulking , since the pre-operative therapy may

60 Wood et al.

Fig. 6. Patient B: CT scan 6 months after resection without evidence of recurrent or metastatic tumor.

reduce the size of the tumor, making it completely re- 2. sectable at a later operation. In addition, the concept of 3. debulking, although theoretically attractive, has never been shown to be efficacious in any solid tumor other than possibly ovarian carcinoma [7]. We also recom- 4.

mend serial CEA determinations in patients with levels initially elevated as a marker of the response to neo- 5 .

adjuvant and operative therapy. 6.

REFERENCES I . Hodgkinson DJ, ReMine WH, Weiland LH: A clinicopathologic

study of 21 cases of pancreatic cystadenocarcinoma. Ann Surg I88:679-684, 1978.

7.

ReMine SG, Frey D, Rossi RL, Munson L, Braasch JW: Cystic neoplasms of the pancreas. Arch Surg 122:443-446, 1987 Compagno J, Oertel JE: Mucinous cystic neoplasms of the pan- creas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). AJCP 69373-580, 1978. Kerlin DL, Frey CF, Bodai BI, Twomey PL, Ruebner B: Cystic neoplasms of the pancreas. Surg Gynecol Obstet 165:475-478, 1987. Ferrer JP, Hensley G, Kalser MH, Zeppa R: Cystadenocarcinoma and carcinoembryonic antigen (CEA). Cancer 42:632-634, 1978. Yu HC, Shetty J: Mucinous cystic neoplasm of the pancreas with high cdrcinoembryonic antigen. Arch Pathol Lab Med 109:375- 377, 1985. Silberman, AW. Surgical debulking of tumors. Surg Gynecol Ob- stet 155577-585, 1982.