Cost-benefit analysis of the work-up for pancreatic cancer

Cost-Benefit Analysis of the Work-Up for Pancreatic Cancer

Carlos Alvarez, MI), Edward H. Livingston, MD, Stanley W. Ashley, MD, Michael Schwarz, MI), Howard m. Reber, MD, Los Angeles, California

We reviewed the records of 126 patients with pancreatic cancer to assess the value of diagnostic tests. The most commonly performed studies were computed tomography (CT) (97% of patients), endoscopic retrograde cholangiopancreatography (ERCIP) (44%), and fine-needle aspiration (FNA) (41%). Of 34 patients who were found to have a mass in the body or tail of the pancreas on CT, 13 underwent ERCP; the results found by ERCP did not affect the management of the patients, whereas the results of FNA in 12 patients eliminated the need for operation. Of 14 patients with suspected metastases as evidenced by CT, the results of 3 ERCPs had no impact, whereas 5 of 7 patients who had FNAs avoided operation. Of five patients with normal results on CT, three had an ERCP that identified tumor. Of 26 patients with atypical CTs, the results of 12 of 16 ERCPs and 3 of 5 FNAs confirmed cancer. In contrast, in 48 patients with a mass in the head of the pancreas and biliary dilatation, ERCP did not alter the patients' management; only 3 of 14 patients who had FNAs avoided operation. Thus, the results of ERCP rarely altered the management of the patient when the CT showed a mass but was useful when the scan was normal or atypical. FNA was helpful in patients with cancer in the body or tail of the pancreas or with suspected metastases and in confirming the diagnosis when the CT was ineonclusive.

From the Department of Surgery, UCLA School of Medicine, and the I)epartment of Surgery, Sepulveda Veterans Administration Medical Center, Los Angeles, California.

Requests for reprints should be addressed to Howard A. Reber, MD, Surgical Service (112), Sepulveda Veterans Administration Medi- cal Center, 16111 Plummet Street, Los Angeles, California 91343.

Presented at the 33rd Annual Meeting of the Society for Surgery of the Alimentary Tract, San Francisco, California, May 11-13, 1992.

p ancreatic cancer is the fourth leading cause of cancer deaths in the United States, with over 25,000 cases

diagnosed yearly [1,2]. Although surgical resection remains the only potentially curative therapy, in the majority of patients, the disease is so far advanced at the time of presentation that they are candidates for palliation only. The diagnostic evaluation of such patients has two gener- al goals. The first is to establish the diagnosis with some certainty prior to operation. The second is to accurately stage the tumor, which, from a practical standpoint, means determining whether it is resectable. A variety of noninvasive and invasive tests are available to diagnose pancreatic cancer, and, used in combination, they can accomplish these goals with considerable accuracy [3]. However, the cost and potential morbidity of such a work-up has not been carefully examined. With the current pressure to curtail medical costs and the impending rationing of health care dollars in the United States, these considerations have assumed increasing significance. This study was designed to test the hypothesis that, although many of these studies provide new information about the tumors, the results often have little impact on the subsequent management of the patient. To determine this, we reviewed the records of all patients with a diagnosis of pancreatic cancer treated over a 5-year period at the UCLA Medical Center, focusing on the value of the most commonly performed diagnostic tests.

PATIENTS AND METHODS The records of all patients diagnosed with pancreatic

cancer at the UCLA Medical Center from July 1986 to June 1991 were reviewed. Eleven patients with endocrine and cystic tumors of the pancreas were excluded. Only those patients whose diagnostic work-up was sufficiently detailed in the medical record and who had a confirmed tissue diagnosis of pancreatic adenocarclnoma were included.

The records, including letters of referral and outside hospital records when available, were analyzed for the number of diagnostic tests undertaken and whether, at the time, these tests were considered diagnostic, suspicious, or negative. All tests documented in the medical record and performed during the period when the patient was symptomatic were included. Diagnostic tests were evaluated for their impact on subsequent management, particularly with regard to decisions about definitive therapy and whether an operation was ultimately performed. Implicit in this analysis was the assumption that preoperative biliary decompression is of no value. This has only recently been established [4,5], and it was clear that this premise had not been completely accepted by all managing physicians, at least during the initial years of

THE AMERICAN JOURNAL OF SURGERY VOLUME 165 JANUARY 1993 53

ALVAREZET AL

T A B L E I Estimated Health Care Financing Administration

Reimbursement Rates for Diagnostic Tests in Patients With Pancreatic Cancer in Los Angeles County in 1992

Cost Test ($)

Noninvasive Abdominal ultrasound 166 Abdominal computed tomography 495

with/without contrast

Invasive Ultrasound-guided fine-needle aspi- 125

ration Esophagogastrod uodenoscopy 239 Percutaneous transhepatic cholan- 318

giography Diagnostic laparoscopy 371 Percutaneous transhepatic cholan- 431

giography with drainage catheter Computed tomography-guided fine- 456

needle aspiration Magnetic resonance imaging 623 Visceral angiography 627 Endoscopic retrograde cholangio- 660

pancreatography Endoscopic retrograde cholangio- 833

pancreatography with blliary stent

TABLE I l l Tests Performed in Patients Treated at the UCLA Medical

Center for the Diagnosis of Pancreatic Cancer, 1986 to 1991

No. of No. of % of Test Tests Patients Patients

Computed tomography 139 122 97 Ultrasound 70 65 52 Endoscooic retrograde cholangio- 62 55 44

pancreatography Fine-needle aseiration 58 49 39 Percutaneous transhepatic chol- 40 38 30

angiography Angiography 4 4 3 Laoaroscopy 3 3 2

TABLE IV Results with Computed Tomography

No. of Patients

Findings (%)

Head mass and biliary dilatation 48 (39) Body or tail mass 34 (28) Metastatic disease 14 (12) Normal or atypical* 26 (21)

*Included examinations reoorted as snowing a pancreatic neaG mass without biliary obstruction, btltary obstruction without a mass effect in tile Dancreas. ane the presence of biliary ano pancreatic ductal dilatation without a mass noted in the oancreas.

T A B L E I I

Patient Profile

Mean age (y, range) 64 (38-95) Males 75 Females 51 Duration of symptoms (wk) 12 Location of mass in pancreas

Head 87 (69%) Body 39 (3 t %)

Eventual management No operation 23 (18%) Operation 103 (82%) Resection 20 (16%) Palliative bypass 60 (48%) Exploration 23 (18%)

the review. Only complications that could be directly attributed to the various diagnostic tests were considered. Costs were calculated based on the Health Care Financ- ing Administration (HCFA)Medicare reimbursement rates in Southern California for 1992 [6] for each of the diagnostic tests (Table I) and did not include any addi- tional expenses based on complications or therapeutic delay; the actual cost was in many cases considerably greater.

RESULTS The records of 126 patients were available for review.

Patient characteristics are shown in Table IT. In 87 patients (69%), the tumors were located in the head of the pancreas, whereas 39 (31%) had disease of the body and/ or tail of the pancreas. At presentation, the mean duration of symptoms was 12 weeks. Sixty-three patients (50%) presented with pain, 54 (43%) with jaundice, and 9 with other symptoms, typically vomiting.

The majority (83%) of the diagnostic evaluations were directed by community physicians prior to referral to UCLA for definitive treatment. Patients underwent an average of 4.2 tests; these are listed in Table HI. Comput- ed tomography (CT) usually with and without contrast, ultrasonography (US), endoscopic retrograde cholangiopancreatography (ERCP), CT- or US-guided fine-needle aspiration (FNA), and percutaneous transhepatic cholangiography (PTC) were the most commonly performed studies. Although the performance of US was documented in 52% of patients, sufficiently detailed reports were rarely available. CT was dearly the preferred diagnostic study and was considered the minimum diagnostic evaluation in most patients. Upper gastrointestinal contrast studies were performed in 47 patients (37%), upper endoscopy (EGD) in 34 (27%), and magnetic resonance imaging in 5 (4%).

One hundred twenty-two patients underwent 139 CT scans (Table IV). The most common finding was a mass in the head of the pancreas in conjunction with common bile duct dilatation (39%). The next most common finding was a mass in the body or tail of the gland (28%).

54 THE AMERICAN JOURNAL OF SURGERY VOLUME 165 JANUARY 1993

DIAGNOSING PANCREATIC CANCER

Fourteen patients (12%) had evidence of metastatic disease, which was in the liver in 13. A total of 26 patients (21%) had normal (5 patients) or atypical findings (21 patients) (e.g., bile duct dilatation without a mass, a mass in the head without bile duct dilatation, or biliary and pancreatic ductal dilatation without a mass). Four patients did not undergo CT. Two of these four had tumors diagnosed incidentally at laparotomy, one patient who was too obese to enter the scanner had a tumor found by US, and one other patient with a tumor obstructing the duodenum was studied solely by EGD prior to surgery, Of 139 CT scans, 124 (89%) detected abnormalities consistent with a pancreatic tumor, and the results of 93 (67%) CT scans were thought to be diagnostic.

Of 117 patients with a suspicious or diagnostic CT, 49 (42%) underwent ERCP. Forty-six (94%) had ERCP after a CT was done, 37 (76%) of which were performed after a diagnostic CT. Twenty-one (43%) ERCPs were done after an inconclusive or negative CT was obtained. The initial CT evaluation followed an ERCP in seven cases and was diagnostic in six of the seven, including the one tumor missed by ERCP. The results of CT were diagnostic or suspicious in 67% of cases in which the ERCP was negative. In the two patients in whom both tests were considered negative, distant metastases were found at the time of exploration.

Fifty-nine of the patients who had a CT scan did not undergo ERCP. However, 12 (17%) patients in this group underwent PTC. Fifty percent of these were diagnostic, and all demonstrated distal common bile duct obstruction. The remainder were performed for therapeutic drainage. Thus, 47 (37%) of the 126 patients were diagnosed without the use of cholangiography. CT was diagnostic in 46 (98%) of these patients. The one patient with a negative CT scan who did not undergo cholangiography was found at exploration to have a mass in the head of the pancreas with mesenteric vessel invasion and required palliative bypass.

Fifty-five patients (44%) underwent 62 ERCP examinations. Forty were performed for a tumor of the head of the pancreas, and 16 were undertaken for lesions of the body of the pancreas. Thirty-two (52%) were considered diagnostic, 16 (26%) were consistent with an obstructing tumor, and 7 (11%) were negative, for an overall sensitiv- ity of 87%. Only one failed attempt was reported, due to an inability to cannulate the ampulla. Four (57%) of the ERCPs with negative results were obtained when CT or US examination showed a lesion of the body of the pancreas. Thirty-eight (68%) of the ERCPs were performed after a diagnostic CT scan was done, and 9 were obtained after a CT scan that was found to be either negative or suspicious only. The ERCP was negative in two of these nine cases. There were three patients who underwent resection in this group; all had their tumors detected by both techniques.

Fifty-three patients with lesions in the head of the pancreas presented with jaundice. An ERCP was performed in 27 of these patients and was diagnostic in 24 (89%). Ten of these patients underwent resection. The

results of the CT scan were diagnostic in eight of nine patients in whom it was performed and suspicious in the other. All four patients from this group who had an ERCP also had a diagnostic CT, whereas the results of only three ERCPs were diagnostic.

Tissue diagnosis using FNA was attempted preoperatively in 59 patients. Forty-nine (83%) of these were done percutaneously, with either CT (41 patients) or US (8 patients) guidance. Four aspirations were performed en- doscopically with masses partially or completely obstructing the duodenum; one was performed in a patient who also underwent percutaneous aspiration. Seven patients had biopsy testing performed at a previous explora- tory laparotomy prior to referral to UCLA for definitive treatment. In total, the results were positive in 45 (76%0) of the patients and nondiagnostic in 14.

Thirty-nine aspirations were done in 34 patients with pancreatic head lesions. The results of 24 (62%) were diagnostic. In eight (33%) of these cases, the need for an operation was obviated. Three of these patients were el- derly (older than 80 years of age), and two had liver metastases. Three patients who were candidates for resection underwent percutaneous biliary drainage as definitive therapy; the basis for these decisions was not obvious from the medical records. A total of 67% of all patients with a positive tissue diagnosis and 76% of those undergoing attempted biopsy eventually underwent an operation.

Twenty-five patients with lesions of the body or tail of the pancreas underwent 28 percutaneous aspirations; 21 (75%) of these were positive. Thirteen of these patients did not undergo operation after a positive diagnosis, and 3 underwent palliative bypass. The five patients who underwent explorative surgery despite a positive biopsy were all found to have inoperable disease, and no other procedure was done. Patients with lesions of the pancreas body and no preoperative tissue diagnosis, including four who had unsuccessful attempts to obtain tissue, underwent diagnostic laparotomy without palliation in nine cases and palliative bypass in six. Two patients underwent resection, one with a negative aspiration and the other without any attempt at a tissue diagnosis.

Five patients (7%) had documented complications of ERCP. These included two episodes of acute pancreatitis, two episodes of cholangitis (one complicated by hepatic abscess), and one case of respiratory arrest due to over- sedation. Nine (29%) patients undergoing PTC had complications from the procedure. These included four with major hemorrhage, two with contrast-related renal failure, and one each with cholangitis, bile peritonitis, and persistent pain at the insertion site. There were no complications related to percutaneous aspiration or endoscopic biopsy. Likewise, there was no clear association between diagnostic tests and postoperative complications.

The surgical treatment of these patients is summarized in Table II. A total of 20 patients (15%) were found at operation to have resectable tumors, which included 18 in the head of the gland and 2 in the body and tail of the pancreas. One patient had a recurrence within 3 months


ALVAREZ ET AL

of the operation, which is consistent with the concept that body and tail lesions are usually advanced at the time of diagnosis. The other was a localized tumor of the tail. Two younger patients (ages 38 and 49 years) who underwent resection were found incidentally to have pancreatic head tumors at exploration. Both operations were carried out to relieve jaundice and suspected choledocholithiasis after inconclusive US examinations. The other 17 patients had CT scans that documented or suggested tumors in every case. ERCPs were performed in seven of these patients, all with diagnostic CT scans. The result of one scan was normal, and the remainder were positive. Six (30%) of 20 resections performed in this group had a preoperative tissue diagnosis.

COMMENTS In recent years, enormous strides have been made in

pancreatic imaging, and a variety of tests are now available for the evaluation of the patient with suspected pancreatic carcinoma [7,8]. It has been well documented that these studies can, with a good degree of accuracy, establish the diagnosis and determine resectability. For example, Warshaw and associates [3] reported that, using a combination of CT, angiography, and laparoscopy, they could preoperatively identify unresectable cancer in 95% of patients. Based on such results, a variety of complex algorithms for the evaluation of these patients have been developed and applied [8,9]. Moreover, it is our impression that many physicians are reluctant to refer their patients for surgery without an extensive battery of tests designed to determine resectability. Although some patients clearly benefit from such scrutiny, the impact of such a work-up on survival has been negligible [10,11]. The effect on subsequent management of the patient and the cost of such a work-up, both in dollars and morbidity, have never been adequately assessed.

Three recent developments in the treatment of pancreatic malignancy have had important implications regarding the choice of an appropriate diagnostic strategy. Foremost has been the demonstration that pancreaticoduodenectomy can be performed with an operative mortality of less than 5% [12-14]. The result has been a slightly more optimistic attitude toward surgery for pancreatic cancer. It has also reduced the motivation for extensive diagnostic efforts designed to find a reason to avoid resection. The second development has been the demonstration that preoperative biliary decompression is of no benefit and may actually increase the morbidity of subsequent operation by colonizing the biliary tree [4,5]. This has considerably weakened the argument in favor of preoperative biliary visualization with PTC or ERCP. On the other hand, the development of increasingly effective means of nonoperative palliation, primarily through endoscopic stenting [15,16], has prompted a renewed inter- est in methods that can determine resectability without exploration. Based on these new considerations, we sought to determine whether a more cost-effective algorithm for the evaluation of these patients could be developed.

Such an analysis, which is focused on the impact of the diagnostic studies on management, is limited, to a certain extent, by its retrospective design. For that reason, we were unable to evaluate those patients in whom pancreatic cancer was part of the differential diagnosis but who were subsequently found to have another disease (e.g., chronic pancreatitis) that explained their symptoms. In addition, because we evaluated the tests in terms of their effects on the decisions for or against operation, we may have overlooked some of their intangible benefits. For example, it is impossible to gauge what impact these studies may have had on the surgeon's ability to counsel the patient preoperatively regarding outcome. Likewise, by providing more information about the characteristics and exact location of the tumors or by establishing the tissue diagnosis preoperatively, these tests may have simplified the operation itself. Nevertheless, our intent in this review was primarily to draw attention to the fact that many of these patients are being studi~ in greater detail than necessary.

Our analysis suggests that several assumptions have had a major impact on the management of pancreatic cancer at our institutionl In particular, US, which has been advocated by many researchers as the initial study in patients with suspected pancreatic cancer [8,17], was performed in only 52% of our patient population. Al- though we continue to believe that US should be done early when biliary stone disease is suggested by the patient's history or when it is unclear whether jaundice is obstructive in etiology, CT was clearly the noninvasive diagnostic study of choice. Indeed, in about half of the patients, US was never done and in no instance was a patient operated on for suspected pancreatic cancer without a CT scan. Likewise, although 30% of all of our patients had a PTC, the number declined as surgeons realized that biliary decompression was not helpful. In the last year of the study, only three were performed. Finally, it was our impression that most of our surgeons and referring physicians still believe that surgical bypass is preferable to stenting in patients with unresectable disease. Presumably this is because of the frequency with which the stents become obstructed and need to be replaced [15] and because 20% to 30% of patients can be expected to develop gastric outlet obstruction during the course of their illness [17]. Thus, it would appear that the diagnostic work-up was aimed primarily at establishing a diagnosis, rather than at staging the disease. As a result, exceedingly few patients underwent angiography or laparoscopy in an attempt to identify unresectable disease prior to operation. For these reasons, we chose to limit our analysis to the value of ERCP and FNA in patients who had already undergone a CT scan.

The results can be most simply summarized in terms of the impact of ERCP and FNA in each of the four groups delineated by CT scan (Table IV). In patients with a mass in the body and tail of the pancreas on CT, 13 ERCPs were performed, 11 of which were abnormal and 2 normal. None of these ERCPs seemed to have any effect on subsequent management. In contrast, FNA was



performed in 18 patients, of which 17 were positive. Tis- sue diagnosis avoided operation in 12 of these patients whose tumors appeared unresectable on CT or who were too debilitated to undergo operation. Lesions of the body and tail of the pancreas were far advanced at the time of diagnosis [17], which is consistent with most series that have studied these tumors. Because of the location of these tumors, palliative biliary or gastric bypass is usually unnecessary, and FNA, by establishing the diagnosis nonoperatively, is of considerable value.

In the patients with evidence of metastatic disease, only three ERCPs were undertaken, and none had any impact on management. However, in this group in which survival is often too short for surgical bypass to provide meaningful palliation, we believe that endoscopic stenting is indicated. Nevertheless, it was not employed in this series. Stenting may also be of value in patients with obvious metastases and no pancreatic mass on CT. Of seven FNAs of metastases, six were positive; tissue diagnosis avoided operation in five.

The findings in the normal or atypical CT group were quite different. Of the five patients with normal CT scans, all had ERCPs, and the result of three (60%) ERCPs were positive, suggesting the need for operation. There were no FNAs. Likewise, in the 21 patients with atypical findings, ERCP strengthened the diagnosis of carcinoma in 75% of the 16 patients in whom it was performed. FNA was also useful, confirming the diagnosis of tumor in three of five patients. Thus, ERCP was of considerable value in patients with both normal and atypical findings, and FNA was helpful in the patients with atypical results.

The group of patients with a mass in the head of the pancreas and bile duct dilatation accounted for the great- est number of tests. Of 20 ERCPs that were performed, 16 were positive. Stents were placed in five patients; since all patients eventually underwent operation, the place- ment of these stents was probably unnecessary. The pri- mary argument for ERCP in this setting is to rule out an obstructing bile duct stone or chronic pancreatitis as the etiology of the mass and duct obstruction; however, we believe that the majority of these patients can be identified by their atypical history, the results of US (which was done as part of the work-up for jaundice in most of these patients) or CT, or from the findings at operation. In this setting, given the current results of pancreaticoduodenectomy, resection may not be inappropriate management for the few patients in whom cancer cannot be ruled out. Likewise, in this group, of 14 FNAs that were performed, 11 were positive. The results of these FNAs altered management in three high-risk patients in whom the findings of the tissue diagnosis avoided subsequent operation. Positive biopsy findings may have simplified management by eliminating the need to obtain a tissue diagnosis at the time of operation. There were, in fact, only a few patients in whom a preoperative tissue diagnosis was confirmed at operation. Nevertheless, most expe- rienced pancreatic surgeons are willing to proceed with resection without histologic proof of malignancy when

SUSPECTED PANCREATIC CANCER

1

MASS IN HEAD BODY/TAIL METASTASES NON- W/ CBD DILATATION MASS DIAGNOSTIC

1 1 1 1

Figure 1. Proposed algorithm for the cost-effective diagnostic evaluation of patients with suspected I~ancreatic cancer. CT = computed tomography; CBD = common bile duct; FNA = fine- needle aspiration; ERCP -- endoscopic retrograde cholangiopancreatography.

the clinical findings are consistent with the diagnosis. The strength of this argument is clearly related to the beliefs of the individual surgeon. With regard to morbidity, all the ERCP complications occurred in this group and, in at least two cases, considerably complicated the operative management. Although FNA proved highly accurate and was not associated with apparent morbidity, there remains the risk of seeding tumor along the needle tract [18]. We concluded that, in most patients with a mass in the head of the pancreas and bile duct obstruction, it is reasonable to proceed directly from CT to operation. Neither ERCP nor FNA significantly altered the management in most patients.

Our conclusions are summarized in a simple algorithm (Figure 1). In patients with a mass in the head of the pancreas and bile duct dilatation, neither ERCP nor FNA is necessary if the patient is to undergo operation. When a mass in the body or tail of the pancreas or metastases are evident on CT, the results of FNA may eliminate the need for operation in selected patients. When the CT findings are normal or atypical, ERCP and/or FNA may be obtained to confirm the diagnosis. These recommendations are not new. Indeed, the Policy and Procedure Manual of the American Society for Gas- trointestinal Endoscopy (ASGE) states: " . . . Diagnostic ERCP is generally not indicated as further evaluation of pancreatic malignancy which has been demonstrated by US or CT unless management will be altered" [19]. However, as our data suggest, these guidelines are often not followed.

Using the Southern California Medicare reimbursement rates (Table I) [3], we calculated the potential cost savings if such an approach had been applied. An average cost per patient was calculated based on the studies that were actually performed and on those that would have been performed according to our recommendations. In many hospitals in the United States, including our own, actual costs are generally double that approved by the HCFA. In this series, this algorithm would have reduced the cost per patient from $1,395 to $910, a savings of $485. If these conservative cost estimates were extrapo- lated to the 28,500 new cases of pancreatic cancer diag-


ALVAREZ ET AL

nosed in this country each year, it would have meant a reduction from $39.7 million to $33.4 million, a savings of $6.3 million.

REFERENCES 1. Boring CC, Squires TS, Tong T. Cancer statistics, 1992. CA 1992; 42: 19-38. 2. Fontham C, Correa P, Cohn I. Epidemiology of cancer of the pancreas. In: Howard JM, Jordan GL, Reber HA, editors. Surgical diseases of the pancreas. Philadelphia: Lea & Febiger, 1987: 613-26. 3. Warshaw AL, Gu GY, Wittenberg J, Waxman AC. Preopera- tive staging and assessment of resectability of pancreatic cancer. Arch Surg 1990; 125: 230-3. 4. McPherson GAD, Benjamin IS, Hedgson HJF. Preoperative percutaneous transhepatic biliary drainage: the results of a con- trolled trial. Br J Surg 1984; 71: 371-5. 5. Hatfield ARW, Terblanche J, Fataar S. Preoperative external biliary drainage in obstructive jaundice. Lancet 1982; 2: 896-9. 6. Part 405. Federal health insurance for the aged and disabled. Federal Register 1991; 56: 59621-819. 7. Warshaw AL, Fernandez-del Castillo C. Pancreatic cancer. N Engl J Med 1992; 326: 455-65. 8. Niederau C, Grendell JH. Diagnosis of pancreatic cancer: imaging techniques and tumor markers. Pancreas 1992; 7: 66-86. 9. Warshaw AL, Swanson RS. Pancreatic cancer in 1988: possibili- ties and probabilities. Ann Surg 1988; 208: 541-53. 10. Kairaluoma MI, MyUyla V, Partio E, et al. impact of new imaging techniques on survival in cancer of the head of the pancreas and periampullary region. Acta Chir Seand 1985; 151: 69-72. 11. Savarino V, Mansi C, Bistolfi L, Zentilin P, CeUe G. Failure of new diagnostic aids in improving detection of pancreatic cancer at a resectable stage. Dig Dis Sci 1983; 28: 1078-82. 12. Grace PA. Pitt HA. Tompkins RK. Decreased morbidity and mortality after pancreaticoduodenectomy. Am J Surg 1986; 151: 141-9. 13. Crist DW, Sitzmann JV, Cameron JL. Improved hospital morbidity, mortality, and survival after the Whipple procedure. Ann Surg 1987; 206: 358-65. 14. Trede M, Schwall G, Saeger H. Survival after pancreaticoduodenectomy. Ann Surg 1990; 211: 447-58. 15. Cotton PB. Nonsurgieal palliation of jaundice in pancreatic cancer. Surg Clin North Am 1989; 69: 613-27. 16. Speer AG, Cotton PB, Russell RCG, et al. Randomized trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet 1987; 2: 57-62. 17. Way LW. Diagnosis of pancreatic and other periampullary cancers. In: Howard JM, Jordan GL, Reber HA, editors. Surgical diseases of the pancreas. Philadelphia: Lea & Febiger, 1987: 641-53. 18. Bergenfeldt M, Eckberg O, Aspelin P, Genell S. Needle-tract seeding after percutaneous fine-needle biopsy of pancreatic carcinoma. A report of two cases. Acta Chir Seand 1988; 154: 77-9. 19. American Society for Gastrointestinal Endoscopy. Policy and procedure manual for gastrointestinal endoscopy: guidelines for training and practice, 1990.

DISCUSSION Charles Frey: You have shown that there is a redun-

dancy in the tests used to make the diagnosis of pancreatic cancer and that the use of your algorithm would result in a cost savings. You've deafly demonstrated that endoscopic retrograde cholangiopancreatography (ERCP) is overused. Importantly, you've defined the circumstances

in which ERCP is useful, that is, when the computed tomographic (CT) scan is normal or equivocal.

There is a need for caution before this algorithm is adopted as a standard for reimbursement. This study involves patients with proven cancer of the pancreas. It does not include patients in whom the diagnosis was un- certain, e.g., those with either chronic pancreatitis or cancer of the pancreas. There is no analysis in the study of those tests most useful in distinguishing chronic pancreatitis from cancer of the pancreas.

Your study includes few patients who have undergone angiography nor does it addresss the usefulness of angiography, either in defining the resectability of pancreatic cancer or in contributing to the safety of operations such as pancreaticoduodenectomy.

Why did so few patients undergo ultrasonography (US) in this study? In our experience, almost 100% of patients have had US prior to their presentation to us.

Stanley W. Ashley: We would have liked to review the results of diagnostic studies in the group of patients who are suspected to have a pancreatic cancer but ultimately prove to have some other process, but we found it almost impossible to identify that group retrospectively. Although we cannot draw any conclusions about the work-up that is most appropriate for such patients, it is our belief that, using our algorithm, exceedingly few patients with benign disease, either because of atypical history, the results of US, or the findings at operation, would reach the stage at which resection is seriously considered. For those few patients who do, we believe that it is appropriate to proceed with the resection. Using this approach, such a procedure might be performed in some patients with chronic pancreatitis.

With regard to the role of angiography, we do not have any data on which to base our conclusions because it has been performed in this setting only rarely at UCLA. However, our belief is that, although complete venous occlusion is clearly indicative of vascular invasion, com- pression is difficult to interpret. Since most of these patients undergo laparotomy for surgical bypass even if their disease is unresectable, we believe that vascular invasion can be assessed at that time. As far as the vascular anatomy is concerned, most arterial anomalies, such as a replaced right hepatic artery, can be identified at the time of operation. There are concerns about the celiac axis occlusion being unmasked by ligating the gastroduo- denal artery, but I think that risk is more theoretical than real.

With regard to US, we have no objection to its use as an initial study in the determination of surgical jaundice and in evaluating cholelithiasis. We're assessing those patients about whom we have become truly suspicious of the presence of pancreatic cancer.

Andrew L. Warshaw (Boston, MA): I don't disagree with any of your conclusions, based on the parameters that you studied. However, this is a study of diagnosis, not of staging, and, as you noted in your data, only 3% or 4% of your patients had angiography or laparoscopy. CT scanning was done in every patient to identify a mass. No attempt was made using CT to determine the resectabili-



ty of the tumors by evaluating encasement of the portal vein or superior mesenteric vessels (other than looking for liver metastases).

I believe that the principal aim of preoperative staging is to identify those patients who will not benefit from an operation and in whom the major cost saving will not be the thousands of dollars you saved by not doing angiography and laparoscopy, but the saving of both many thousands of dollars by not operating at all and the human cost of undergoing an operation. Therefore, I suggest that there are still two cost analyses yet to be done: those of the patient benefits and those of the dollar benefits.

I have three questions. Assuming 90% of unresectable tumors can be identified preoperatively with another thousand dollars worth of investment in the performance of angiography or perhaps laparoscopy, what percentage of your patients who underwent operation could have been managed without an operation, perhaps instead with biliary stenting or with no operation at all, and what would be the relative dollar savings in that circumstance?

Second, as more patients with pancreatic cancer are undergoing extensive preoperative treatment, such as radiotherapy, would it beho0v~ us to know which patients are suitable for such treatment before undertaking radiotherapy or surgery?

Third, what advice do you have for the surgeons who don't perform many Whipple operations and who cannot achieve the 5% or less mortality rate that is achieved at UCLA, Johns Hopkins, the Lahey Clinic, the Mayo Clin- ic, and at other major centers? Should some of those patients be evaluated more extensively at the local level before a decision is made about the most appropriate operation and where it should be done?

Stanley W. Ashley: Regarding the cost savings that might have been possible by avoiding operation we continue to believe that, except in patients with obviously metastatic disease, exploration and, if the patient's tumor is deemed unresectable, surgical bypass is the best option, not only because of the stent plugging but also because of the more than 20% incidence of gastric outlet obstruction in these patients.

With regard to radiotherapy, I'm not aware of any data that support the use of preoperative radiotherapy, which we do not perform. If there were convincing data in that respect, we would need to revise our algorithm.

In response to your third question, obviously there are surgeons in the community that can perform resections with acceptable results. I think that if the expertise is not available locally, the patient should be transferred to a center with the necessary experience very early in the evaluation.

Arthur Sieular (New York, NY): My questions are related to fine-needle aspiration (FNA). Dr. Warshaw showed, in the postgraduate course of pancreatic disease, that if there is contamination of the peritoneum by FNA, that cells could be found in the effluent. Would that occurrence compromise the benefits of a positive diagnosis in a patient who Would undergo bypass and then develop disseminated malignancy?

The second question pertains to lesions in the body of

the pancreas. If the biopsy findings are negative, would that influence your decision to operate since the prognosis is poor?

Stanley W. Ashley: With regard to lesions of the body and tail of the pancreas that are obviously unresectable, we would recommend performing several biopsies and, if these are not successful, proceeding with exploration. In this study, two patients with tumors of the body and tail of the pancreas underwent explorative surgery.

The risk of contamination remains theoretical. With this algorithm, very few patients who had a positive aspiration would subsequently undergo explorative surgery, and this outweighs the risk.

Edward L. Bradley (Atlanta, GA): I agree with your algorithm. In Atlanta, we manage patients similarly.

If a FNA biopsy was positive for a lesion in the body of the pancreas, do you consider that to be a surgically incurable lesion? Under what conditions would you pro- pose to a patient with a positive FNA biopsy in the body of the pancreas that he or she undergo resection?

I'm concerned that studies of this nature, because they are economically driven, can be misinterpreted to be stan- dards of care. Can you address this issue?

Stanley W. Ashley: In patients with lesions in the body of the pancreas that do not appear to extend outside the pancreas on CT scan, exploration with the potential for resection is reasonable. This may be the group in whom it would be appropriate to perform laparoscopy to detect metastatic disease, particularly since we're not concerned about palliative bypass.

Lawrence W. Way (San Francisco, CA): Ten years ago, it was common for such patients to routinely undergo US, CT, transhepatic and retrograde cholangiography, and angiography. It is important to analyze the utility of these expensive tests in order to define the most efficient work-up. I support your response to Dr. Frey's question about US. There is a good argument that US is superflu- ous if the clinical findings strongly suggest neoplastic obstruction of the bile duct, since a CT scan is required and will provide the same information.

When I read your manuscript, I was reminded of a similar proposal by Alan Johnson (Br J Surg 1983; 70: 587) several years ago that should be acknowledged. Johnson and his coworkers proposed proceeding to surgery after no other test than US. The principal difference is that you have determined that CT instead of US is the pivotal test.

One concern about the present study is whether the utility of diagnostic tests can be assessed by this kind of retrospective analysis. The only patients included were those who proved to have pancreatic cancer. The diagnosis was known. In reality, however, the tests were not obtained just to prove or exclude pancreatic cancer. They were obtained to diagnose patients with jaundice and abdominal pain who had a variety of illnesses. Thus, the contribution of the tests in excluding pancreatic cancer and indicating an alternative diagnosis has been ignored. A prospective study would be helpful.

Another concern about this study is the use of unde- fined terms that are critical to using the algorithm. For


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example, a patient "suspected of having pancreatic cancer" is not defined. The difference betWeen "atypical findings on CT" and a "mass in the head of the pancreas" is not clarified. To use the proposed algorithm, the practi- tioner must know what these phrases mean.

Finally, algorithms for diagnosis depend critically on the treatment philosophy, and, as treatment changes, the diagnostic work-up may have to be updated. In fact, your algorithm may already be out of date if you think, as many do, that laparoscopy has a useful role in management.

Despite these questions, I basically agree with your scheme and the recommendation to make diagnoses as efficiently as possible, eliminating redundant tests and those that do not otherwise affect subsequent management.

Stanley W. Ashley. Our argument is philosophic. There are some aspects of this problem that could not be

addressed in a retrospective review. But our message is that, given the current emphasis on cost containment, too many studies are being performed in the preoperative evaluation of these patients.

W. P. Reed (Springfield, MA): The techniques of laparoscopic biliary and gastric bypass have now both been described. In the future, it is likely that many patients requiring palliative procedures for pancreatic cancer will be able to have them done laparoscopically. If that is the case, won't it be more important to do a complete preoperative assessment, including angiography, to be certain that patients are not incorrectly as- signed to palliative treatment on the basis of incomplete staging information.

Stanley W. Ashley: It might. I have not seen any reports that laparoscopic bypass is at a stage where it can be widely applied, but it may very well develop to that point.


Documents

Cost-benefit analysis of the work-up for pancreatic cancer