Operative Drainage of the Pancreatic Duct Delays

Functional Impairment in Patientswith Chronic PancreatitisA Prospective Analysis

WILLIAM H. NEALON, M.D., COURTNEY M. TOWNSEND, JR., M.D., and JAMES C. THOMPSON, M.D.

In a prospective study, 85 patients with chronic pancreatitishave been subjected to evaluation by morphologic analysis (en-doscopic retrograde cholangiopancreatography), by exocrinefunction tests (bentiromide PABA and 72-hour fecal fat test-ing), and by endocrine funcfion tests (oral glucose tolerancetest and fat-stimulated release of pancreatic polypeptide). Allpatients were graded on a five-point system, with 1 point as-sessed for an abnormal result in each of the five tests per-formed. Zero score denoted mild disease; 1-2 points signaledmoderate disease; and 3-5 points indicated severe disease. In68 patients, both an initial and late (mean follow-up period of14 months) evaluation were performed. Forty-one patients un-derwent modified Puestow side-to-side Roux-en-Y pancreati-cojejunostomy. The Puestow procedure alone was performed in18 patients. Eight patients also had drainage of pseudocysts,seven also had a biliary bypass, and eight had pseudocystdrainage plus bypass, in addition to the Puestow. There wereno deaths. Of the 68 patients who were studied twice, 30 hadoperations and 38 did not. None of the patients with severedisease improved their grade during follow-up. Of 24 patientswho did not undergo operation, 17 (71%) who were gradedmild/moderate progressed to a severe grade at follow-up. Bycontrast, only three of the 19 patients operated on (16%) andwho were initially graded as mild/moderate progressed to se-vere disease at follow-up testing. More than 75% of all of thepatients had a history of weight loss. Twenty-six of 30 patientsoperated on (87%) (all of whom had lost weight before surgery)gained a mean 4.2 kg (range 1.4-2.7 kg) after surgery, com-pared with no significant weight change (range -3.6-2.7 kg)among patients not operated on. These findings support a pol-icy of early operation for chronic pancreatitis, perhaps even inthe absence of disabling abdominal pain.

Presented at the 108th Annual Meeting of the American SurgicalAssociation, San Francisco, California, May 2-4, 1988.

Supported by grants from the National Institutes of Health (5R37DK 15241-17, PO1 DK 35608, RCDA CA 00854, MOI RR00073)and by a grant from the American Cancer Society (PDT-220).

Reprint requests and correspondence: James C. Thompson, M.D.,Department of Surgery, the University ofTexas Medical Branch, Gal-veston, TX 77550.

Submitted for publication: May 5, 1988.

From the Department of Surgery, the University of TexasMedical Branch, Galveston, Texas

C HRONIC PANCREATITIS (CP) is associated withone or all ofa triad ofabdominal pain, exocrineinsufficiency and endocrine insufficiency. As

the disease progresses, the two functional deficits oftenproceed to steatorrhea and diabetes mellitus. By stan-dard teaching, the progression to end-stage levels offunctional impairment are not altered by operations.'Insulin therapy and exogenous pancreatic enzyme sup-plementation may partially control the functional defi-cits. Unrelenting abdominal pain, often causing narcotichabituation, has been a greater clinical challenge. Themajor, nearly singular, indication for operation in thetreatment of CP has been unrelenting abdominalpain.2-8

Operative procedures for CP are generally classified aseither resectional (partial or total pancreatectomy), ordecompressive, most commonly represented by theside-to-side longitudinal pancreaticojejunostomy (mod-ified Puestow procedure). Both types of operative pro-cedures are said to control pain successfully in 60-90%of patients.28 The impact of operation on pancreaticfunction has been evaluated only in passing,9'i2 and evi-dence for a favorable influence of operation on functionhas been demonstrated in only a small subset ofpatientsin one recent report.'3 No comparison of operative andnonoperative treatment of CP has been reported pre-viously.Uniform analysis of patients with CP has been elusive

because no accepted means to stratify patients on thebasis of severity of disease has been accepted. We haverecently developed a grading system based upon mor-phologic and functional measurements."'

In the present study, this grading system was used inorder to prospectively evaluate all patients who were

321

NEALON, TOWNSEND, AND THOMPSON

TABLE 1. Reasonsfor not Operating on 44 Patients who wereFollowed Without Operation and who Served as Control Subjects

Mild/Total Moderate Severe

(n = 44) (n = 26) (n = 18)

Nondisabling pain 18 10 8Small mainPancreatic duct 17 1 1 6Patient refusal 7 4 3Cirrhosis 2 1 1

admitted to our service with a diagnosis of CP. Afterinitial evaluation, a grade was assessed for each patient,who was then assigned to either supportive care or oper-

ation. Follow-up evaluation and revised grading was ob-

tained after a mean interval of 14 months. The impactof operative or nonoperative therapy on the progressionof endocrine and exocrine dysfunction was determined,and is presented here.

Methods

Patients with a diagnosis of CP at the University ofTexas Medical Branch in Galveston were referred to ourPancreas Clinic. Over the course of 42 months (Sep-tember 1984-March 1988), 92 patients with CP were

seen. Eighty-five of these patients agreed to participatein this study and were admitted to our Clinical ResearchCenter for testing. Virtually all patients with CP were

considered candidates for study, and exclusion fromstudy occurred only when patients chose not to partici-pate. Patients who had not yet had an ERCP were sentto our surgical endoscopy unit for that procedure.We used a protocol approved by the Investigation

Review Board of the University of Texas MedicalBranch. Signed, written informed consent was obtainedfrom all participants. All patients were asked aboutpresent or past ethanol abuse, abdominal pain (charac-ter and duration), weight loss, diarrhea, fatty stools, pre-vious operations, previous episodes of pancreatitis, dia-betes, and need for narcotics. In order to validate stud-ies, pancreatic enzyme supplements were stopped 5 daysbefore admission. ERCP was performed on those pa-

TABLE 2. Svstem for Grading Chronic Pancreatitis

; PP OGTT PABA t 72-hour FF ERCP

1 Point I Point I Point I Point 1 Point

0 Points = mild grade1-2 Points = moderate grade3-5 Points = severe gradeEach of five tests, fat-stimulated pancreatic polypeptide (PP), oral

glucose tolerance test (OGTT), bentiromide PABA, 72-hour fecal fat(72-h FF), and endoscopic retrograde cholangiopancreatography(ERCP) are performed. Abnormal results on each test is assessed onepoint.

tients who had not previously undergone the procedure.On separate days each patient underwent: 1) a fatty-meal (Lipomul,T Upjohn Company, Kalamazoo, MI)stimulated release of pancreatic polypeptide (PP), 2) anoral glucose tolerance test (OGTT) with simultaneousmeasurement of insulin (by radioimmunoassay) andglucose, 3) a bentiromide PABA test'5 combined withd-xylose, and 4) a 72-hour fecal fat measure (72-hourFF). Serum levels of amylase, lipase, bilirubin and alka-line phosphatase were obtained. No patients were stud-ied during a relapse or exacerbation of an acute inflam-matory episode. After a mean interval of 14 months,each patient underwent an initial evaluation (5 studies)and an identical follow-up examination.

Criteria for Operative or Nonoperative Therapy

An absolute requirement for operation was abdomi-nal pain. The pain was of sufficient severity to necessi-tate repeated hospitalizations, repeated visits to emer-gency rooms, and use of narcotics, often daily. The painwas sufficiently severe to induce weight loss and to re-strict the ability of the patient to maintain employmentor to conduct normal activities. Intermittent pain wasan indication for operation only when the frequencyand severity were increasing and disabling. All candi-dates for operation had advanced abnormalities onERCP with dilatation of the main pancreatic duct(MPD) greater than 8 mm. The reasons for not operat-ing on patients included: nondilated MPD, nondisa-bling pain, patient refusal, and associated cirrhosis(Table 1).The operative procedure employed in all patients was

a modified Puestow procedure-that is, a longitudinalside-to-side Roux-en-Y pancreaticojejunostomy, as de-scribed by Partington and Rochelle.'6 The anastomosisextended to the tail of the gland on the left and past thegenu of the MPD in the head of the gland. Any ductalstones were removed. The modified Peustow was com-bined with a choledochoenterostomy in patients whodemonstrated no evidence of cholangiography fromERCP ofa typical stricture ofthe distal (intrapancreatic)common bile duct, associated with sustained elevationofserum alkaline phosphatase to greater than 450 IU/dl.Pseudocyst drainage was used in all patients with asso-ciated pseudocysts.

Grading System

One morphologic (ERCP), two exocrine (bentiromideand 72-h FF) and two endocrine (OGTT and fat-stimu-lated PP) tests were used in producing a grading systemranging from 0 to 5 points, as adapted from our previousreport.'4 The point system has been modified to include

322 Ann. Surg. * September 1988

PUESTOW CHRONIC PANCREATITIS

the endocrine measures of PP and OGTT (Table 2).ERCP tests with advanced changes according to theCambridge grade"7 were assessed a grade of 1. In patientsin whom a pancreatogram could not be obtained byERCP (either because of duct obstruction or technicalfailure), an intraoperative pancreatogram was obtained.Each abnormal function test was assessed 1 point. Anypatient with a score of0 was graded as having mild CP,1-2 points as having moderate CP, and 3-5 points as

severe-grade CP (Table 2).The NBT-PABA (Chymex,R Adria Laboratories,

Dublin, OH) test, commonly referred to as the bentiro-mide test, and a simultaneous d-xylose test were per-

formed as previously described.'4After an overnight fast, release ofPP was induced by a

fatty meal (Lipomul), consisting of 71% fat by weight,long-chain triglycerides, at a dose of 1.5 ml/kg body-weight. Serial blood samples were obtained for laterassay of PP. Release was measured by standard radioim-munoassay methods used in our laboratory.'8A standard oral glucose tolerance test with simulta-

neous measure of circulating insulin-like immunoreac-tivity (ILI) and a 72-hour FF test were performed as

previously described.'4Since September 1984, 85 patients with chronic pan-

creatitis have been studied at least once. Ofthis number,68 patients have been studied twice, once at initial eval-uation and again after a mean 14-month interval. Threepatients have been lost to follow-up, and 14 were studiedinitially and have not yet reached the appropriate fol-low-up period. There were 33 women and 52 men with a

mean age of 44 years (range 19-68 yrs). Ethanol-in-duced pancreatic inflammation was the etiologic factorin 79 patients (93%); one man had CP which was pre-

sumed related to a previous exposure to toxic amountsof an insecticide; and five patients had idiopathic pan-

creatitis.

Operation

Forty-one patients had operations after initial evalua-tion. Two patients who were studied had previously un-

dergone main pancreatic duct (MPD) decompression(Puestow procedure), both with advanced disease; thesepatients have been excluded from this analysis. Thirty ofthe 41 patients who underwent operations were evalu-ated initially and during follow-up (mean 14.8 months).Thirty-eight of 44 patients who did not undergo surgeryhave had initial and follow-up testing. We have com-

pared early and late functional tests in the 30 patientswho were operated on and the 38 who were not.The chosen operative procedures are listed in Table 3.

Each operation included the modified Puestow proce-dure.16

TABLE 3. List ofOperative Procedures Used in this Study

Patients

Puestow alone 18 (44%)Puestow + pseudocyst 8 (20%)Puestow + biliary bypass 7 (17%)Puestow + pseudocyst + biliary bypass 8 (20%)

All 41 operated patients underwent the modified Puestow longitu-dinal side-to-side Roux-en-Y pancreaticojejonostomy, alone or com-bined with other procedures (below).

Results

Of 41 operations, no deaths have occurred. Three pa-tients had wound infections, and all three underwentbiliary-enteric anastomosis. No pseudocysts have re-curred in the postoperative period during which we havefollowed the patients.

Grade Changes Among Patients of the Two StudyGroups

Our two study groups (patients who were operated onand those who were not) were not randomized. Initialevaluation was completed on 85 patients. Of the 41 pa-tients operated on, 25 have been rated as having mild/moderate CP and 16 as having severe-grade CP.Twenty-six patients who did not undergo surgery wererated as having mild/moderate CP, and 18 were rated ashaving severe CP. Of 51 patients initially graded as hav-ing mild/moderate CP, 25 were operated on and 26 werenot. Nineteen of the 25 patients with mild/moderate CPwho were operated on were studied during follow-up.After operation, 16 of these 19 patients (84%) initiallygraded as having mild/moderate CP were assessed thatsame grade during follow-up (Table 4). Three patientsoperated on progressed to severe-grade. Twenty-four ofthe 26 patients not operated on and who were initiallygraded as having mild/moderate CP have had follow-uptesting, and only seven of those 24 patients (29%) wereassessed that same grade during follow-up; 17 patientsprogressed to severe-grade (Table 4). The difference insustained pancreatic function between the group ofmild/moderate patients operated on (16 of 19, or 84%)and the group not operated on (7 of 24, or 29%) was

TABLE 4. The Change in Severity Gradefrom Initial Evaluationto Follow-upfor Mild/Moderate Stage in Operated

and Nonoperated Patients

Mild/Moderate (n = 43)

Initial Progressed toEvaluation Follow-up Severe

Operated 19/19 (100%) 16/19 (84%) 3/19 (16%)Nonoperated 24/24 (100%) 7/24 (29%)* 17/24 (71%)*

* p <0.05

VOl. 208.- NO. 3 323

324 NEALON, TOWNSEND, AND THOMPSON

TABLE 5. Ethanol Use in Patients with Mild/Moderate Grade atInitial Testing and in Follow-up

Not OperatedOn Operated On Total

(n = 22) (n = 19) (n = 41)

Continued ETOH atInitial-Testing 10 (45%) 11 (58%) 21 (51%)

Continued ETOH atFollow-up 9 (41%) 12 (63%) 21 (51%)

significant by X2 analysis. Mean follow-up for the groupoperated on was 14.8 months (10-15 month range); forthe group not operated on, it was 14.1 (9-15 monthrange).Ofthe 34 patients with severe disease at initial testing,

16 have been operated on; 1 of these have had follow-up testing. Fourteen of 18 patients not operated on andwho had severe disease were tested both initially andduring follow-up. No patient, whether operated on ornot, with a severe grade showed any improvement. Thesevere functional deficit appears to be fixed.

Comparison ofthe Two Study Groups

Continued ethanol use was monitored by interviewonly, and those data are reliable only in the sense ofhaving been obtained from each patient in a uniformfashion. The distnrbution of patients according to eth-

TABLE 6. Comparison ofClinical Features at the Time ofInitialAssessment for all Operated and Nonoperated Patients

Not Operated OperatedOn On Total

(n = 44) (n = 41) (n = 85)

Disabling abdominalpain 28 (64%) 41 (100%) 69 (81%)

Weight loss 32 (73%) 34 (83%) 66 (78%)Steatorrhea 10 (23%) 11 (27%) 21 (25%)Insulin-dependent

diabetes mellitus 9 (20%) 8 (19%) 17 (20%)

TABLE 7. Body Weight in Chronic Pancreatitis Patients as aFunction of Weight Loss Before Initial Evaluation, Percentage

ofPatients with Weight Gain in Follow-up, and MeanNumbers ofKilograms Gained or Lost.

Operated On Not Operated On

History of weightloss 23 of 30 (77%) 31/38 (82%)

Gained weight atfollow-up 26 of 30 (87%) 5/38 (13%)*

Mean weightgain at follow-up (range) 4.2 kg (1.4-12.7) 0.495 kg (-3.6-2.7)*

Ann. Surg. * September 1988

anol use is nearly the same for all patients and for thesubset of patients classified as having mild/moderate CP(Table 5).Serum amylase was elevated in 37 of 85 patients

(44%) and lipase in 51 of 85 patients (60%); the eleva-tions were distributed proportionately between the pa-tients who were operated on and those who were not.Elevation of alkaline phosphatase occurred in 29% ofpatients, primarily in patients operated on who had dis-tal common bile duct stenosis. Calcification of the pan-creas was seen in 32 of41 (78%) of patients operated onand in 29 of 44 (66%) patients not operated on, and wasuniformly distributed between those with mild/moder-ate and severe CP.

Disabling abdominal pain was present in all patientswho were operated on, but in only 64% (28 of 44) ofpatients not operated on (Table 6). After operation, re-lief of pain was achieved in 38 of 41 patients (93%).Longer follow-up is required for establishing accurateinformation regarding pain relief. No patient not oper-ated on experienced spontaneous relief of pain.Weight loss (more than 4.5 kg over 6 months) was

distributed similarly between the two groups 77% ofthose operated on and 82% of those not operated on.Weight gain after operation was observed in 87% of pa-tients. The mean weight gain among the 26 patients whodid gain was 4.2 kg (range 1.4-12.7 kg) (Table 7). The 24postoperative ERCPs documented patency of the pan-creaticojejunal anastomosis in each.

Steatorrhea and a previous diagnosis of insulin-de-pendent diabetes mellitus was comparably distributedbetween the two groups and was limited almost exclu-sively to patients classified as severe. A subset ofpatientswith diabetes mellitus in the mild/moderate group wasidentified and has been studied.'9 An abnormal OGTTwas a more common finding, ofcourse, than was insulindependence, and was also proportionately distributed,in 32 of 44 patients not operated on (73%) and 29 of41patients operated on (71%).

Release ofPP

Enhanced release of PP after fat ingestion was notedin 22 of 51 patients who were graded as having mild/moderate CP. No patients graded as having severe CPhad enhanced PP, and all other mild/moderate patientsreleased PP in a manner indistinguishable from normalvolunteers. Depressed PP release was seen in 26 of 34initially severe patients. None of the patients with mild/moderate CP had low PP.

Discussion

Loss of pancreatic function appears to be progressivein patients who are in the early stages of CP. We have

Vol. 208 * No. 3 PUESTOW CHRONII

shown that operative decompression in patients withmild/moderate CP arrests, but does not reverse this pro-

gressive loss of function. The modified Puestow proce-

dure'6 has been used to relieve the chronic abdominalpain associated with CP. Previous studies report success-

ful relief of pain in 60-90% of patients.28Chronic pancreatitis has been difficult to evaluate in a

systematic fashion. Until recently, no stratification ofpatients with CP on the basis of severity of dysfunctionhas been available. We have developed a method forgrading CP according to its severity,'4 and in the present

study, have applied this method to a group of CP pa-

tients who were treated either by operation or by medi-cal management (Table 2).Ammann and colleagues' evaluated 245 patients with

CP over a 20-year period and found that pain was gradu-ally and spontaneously relieved as the disease pro-

gressed. In their experience, operation appeared to havelittle effect on this outcome. Because relief ofpain is theprimary indication for operating upon patients with CP,this study raised serious questions about the appropri-ateness of operation for CP. Efforts to define a func-tional benefit from operation for CP have not clarifiedthe dilemma over appropriate operative indica-tions.3'5'9"0 In the studies cited, functional status was notimproved after operation, and no controls (those notoperated on) were studied. Spontaneous improvementof pancreatic function in isolated cases has been re-

ported and is unexplained.'2"13Our present finding that operation failed to improve

pancreatic function is consistent with previous re-

ports.3'5'9-" Our most important finding is that the rateof progressive functional impairment is significantly de-layed by operation (Table 4). This finding suggests thatany patient with CP with a dilated main pancreatic ductshould be considered for operation. Of particular inter-est as operative candidates are CP patients with intactpancreatic function, since function deteriorates withtime. Weight loss in CP patients is a recognized sideeffect of chronic pain, malabsorption and chronic dis-ease.3'4 We have found a significant weight gain in thoseof our patients operated on, probably as a result of abo-lition of postprandial pain. Postoperative weight gain inthe patients with mild/moderate CP suggests that pan-creatic malabsorption is not the primary source of theirweight loss. This operative benefit supports a liberal pol-icy of pancreatic duct decompression.Our patients were not randomly assigned to opera-

tion. Patients with small, nondilated MPD were notconsidered candidates for modified Puestow procedure.An additional 18 patients had large MPD, although theirabdominal pain was not disabling. On the basis of ourfindings, this group would be more readily advised tohave an operation. Seven additional patients refusedoperation and two patients had cirrhosis (Table 1).The two most commonly recognized bad prognostic

C PANCREATITIS 325

signs of CP have traditionally been continued ethanolabuse and glandular calcification. Continued ethanolabuse has been implicated as a factor contributing toaccelerated functional impairment.20 In our patientswith mild/moderate CP, 58% of those operated on and45% of those not operated on had a history of alcoholabuse before initial evaluation. Sixty-three percent ofthose operated on and 41% of those not operated onwere still drinking at follow-up. The alcohol ingestionvaried widely in specific amount and in length of timebut exceeded 5 years in all patients and was character-ized as excessive. Continued ethanol abuse alone doesnot explain the progressive functional deficits we haveobserved in the patients not operated on, since opera-tion halted deterioration.Every CP patient who is a candidate for operation

should be evaluated for evidence of biliary stenosiscaused by entrapment of the distal common bile duct inthe fibrosed pancreatic head.7'2'23 Fifteen of the 41 pa-tients operated on (35%) had common bile duct stenosis,associated with alkaline phosphatase elevation; this fre-quency is within those previously reported.23-25 Theoverall incidence among patients operated on and notoperated on was 18%.

Insulin-glucose hemostasis is commonly disturbed inCP. The prevalence of insulin-dependent diabetes mel-litus (20%) in this group, is consistent with most re-ports,2-8 and was about equal in patients operated onand those not operated on. An abnormal OGTT was farmore common, of course, than insulin-dependent dia-betes mellitus, but again, it was uniformly distributedamong patients operated on (71%) and those not oper-ated on (73%).

Release of PP after fat is depressed after experimen-tally induced pancreatic fibrosis in the dog26 and in pa-tients with CP.27 Pancreatic exocrine deficits have beenshown to correlate directly with the failure of PP to riseafter a meal stimulation in humans.27 Recently, we havefound that release of PP is a more reliable indicator ofadvanced CP than is glucose-stimulated release of in-sulin.19The indication for operation in CP is unrelenting

pain. The fact that spontaneous relief of pain might beanticipated had raised doubts concerning the appropri-ateness of operation.' Some sentiment has favored theuse of operation only in the late stages of CP. Our find-ings support an alternative policy of early operation inCP patients with less severe pain, in whom a good func-tional state may be preserved. The additional benefit ofarresting weight loss and inducing weight gain, which wehave demonstrated in 87% of operated patients, furthersupports liberalizing the indications for operation in CP.

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and outcome of chronic pancreatitis. Gastroenterology 1984;86:820-828.

326 NEALON, TOWNSEND, AND THOMPSON Ann. Surg. -September1988

2. Traverso LW, Tompkins RK, Urrea PT, Longmire WP, Jr. Surgi-cal treatment ofchronic pancreatitis. Twenty-two years' experi-ence. Ann Surg 1979; 190:312-319.

3. Sato T, Miyashita E, Yamauchi H, Matsuno S. The role ofsurgicaltreatment for chronic pancreatitis. Ann Surg 1986; 203:266-271.

4. White TT, Slavotinek AH. Results ofsurgical treatment ofchronicpancreatitis. Report of 142 cases. Ann Surg 1979; 189:217-224.

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6. Prinz RA, Kaufman BH, Folk FA, Greenlee HB. Pancreaticojeju-nostomy for chronic pancreatitis. Two- to 21 -year follow-up.Arch Surg 1978; 113:520-525.

7. Warshaw AL. Conservation of pancreatic tissue by combined gas-tric, biliary, and pancreatic duct drainage for pain from chronicpancreatitis. Am J Surg 1985; 149:563-569.

8. Taylor RH, Bagley FH, Braasch JW, Warren KW. Ductal drain-age or resection for chronic pancreatitis. Am J Surg 1981;141:28-33.

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10. Bradley EL III, Nasrallah SM. Fat absorption after longitudinalpancreaticojejunostomy. Surgery 1984; 95:640-643.

11. Bradley EL III. Long-term results of pancreatojejunostomy in pa-tients with chronic pancreatitis. Am J Surg 1987; 153:207-213.

12. Begley CG, Roberts-Thomson IC. Spontaneous improvement inpancreatic function in chronic pancreatitis. Dig Dis Sci 1985;30:1117-1120.

13. Garcia-Puges AM, Navarro S, Ros E, et al. Reversibility of exo-crine pancreatic failure in chronic pancreatitis. Gastroenterol-ogy 1986; 91:17-24.

14. Nealon WH, Beauchamp RD, Townsend CM, Jr, et al. Diagnosticrole of gastrointestinal hormones in patients with chronic pan-creatitis. Ann Surg 1986; 204:430-437.

15. Gyr K, Stalder GA, Schiffmann I, et al. Oral administration of achymotrypsin-labile peptide: a new test of exocrine pancreaticfunction in man (PFT). Gut 1976; 17:27-32.

16. Partington PF, Rochelle RE. Modified Puestow procedure forretro-grade drainage of the pancreatic duct. Ann Surg 1960;152:1037-1043.

17. Axon ATR, Classen M, Cotton PB, et al. Pancreatography inchronic pancreatitis: international definitions. Gut 1984;25:1107-1112.

18. Lonovics J, Guzman S, Devitt PG, et al. Action of pancreaticpolypeptide on exocrine pancreas and on release of cholecysto-kinin and secretin. Endocrinology 1981; 108:1925-1930.

19. Nealon WH, Townsend CM, Jr, Thompson JC. The time courseof beta cell dysfunction in chronic ethanol-induced pancreati-tis: a prospective analysis. Surgery (In Press)

20. Ammann RW, Buehler H, Muench R, et al. Differences in thenatural history of idiopathic (nonalcoholic) and alcoholicchronic pancreatitis. A comparative long-term study of 287patients. Pancreas 1987; 2:368-377.

21. Warshaw AL, Schapiro RH, Ferrucci JT, Jr, Galdabini JJ. Persis-tent obstructive jaundice, cholangitis, and biliary cirrhosis dueto common bile duct stenosis in chronic pancreatitis. Gastroen-terology 1976; 70:562-567.

22. Stabile BE, Calabria R, Wilson SE, Passaro E, Jr. Stricture of thecommon bile duct from chronic pancreatitis. Surg GynecolObstet 1987; 165:121-126.

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DISCUSSION

DR. CHARLES F. FREY (Sacramento, California): Dr. Nealon and hiscolleagues have observed the natural rate of impairment of pancreaticexocrine and endocrine function in chronic pancreatitis to be signifi-cantly delayed by pancreaticojejunostomy as compared with a nonop-erated group. This observation, if confirmed, is of fundamental im-portance, and could alter our operative indications in patients withchronic pancreatitis.

Pain or complications of chronic pancreatitis have been the chiefindications for operative intervention, not prevention of exocrine andendocrine function deterioration.

This paper challenges a long-held assumption and provides a ratio-nale for early operative intervention in patients with chronic pancreati-tis who have dilated pancreatic duct, even when pain is not severe, topreserve exocrine and endocrine function.There are many questions I would like clarified about the data on

which the authors' conclusions were based.Were these two groups of patients comparable? We know they were

not comparable with regard to pain, and if I understand correctly,about halfthe patients, 17 (in the nonoperative group) had small mainpancreatic ducts. These are patients who would not be expected tobenefit from longitudinal pancreaticojejunostomy and may have adifferent rate ofdeterioration ofendocrine and exocrine function thanpatients with large ducts.How did the authors' observations fit with the reports which esti-

mate that after longitudinal pancreaticojejunostomy, 10-20% of pa-tients will over time develop progressively more severe exocrine orendocrine insufficiency.

Were the authors confident they did not measure exocrine and en-docrine function too soon after an exacerbation ofchronic pancreatitisin the nonoperated group? The pancreatic literature is replete withevidence that about one third of patients after an exacerbation ofpancreatitis will show evidence of severe impairment of exocrine andendocrine function as long as 45 days after an acute attack.Could the authors tell us how they interpreted the ERCP data re-

garding the diseased major pancreatic duct in the operated group ofpatients where contrast spills into the Roux-en-Y limb after injectionon ERCP? Also, could the authors tell us why they chose oral glucosetolerance test rather than a glucagon C peptide test favored by manyendocrinologists?Did the authors have any data as to whether exocrine and endocrine

function stabilized after other operations on the pancreas such as pan-creaticoduodenectomy or some of the newer duodenal preserving pro-cedures?

Finally, the authors are to be complimented on the thoroughnesswith which they studied this large group of patients and for the hardwork it must have entailed as well as their development of a gradingsystem by which we can quantify changes in pancreatic structure andfunction. The authors also deserve our congratulations for presenting apaper so well done, so well presented, and of such fundamental im-portance.

DR. ANDREW L. WARSHAW (Boston, Massachusetts): I join Dr. Freyin congratulating the authors on presenting an extremely importantpaper. I have some reservations about their conclusions, but they raisethree important challenges to concepts that are widely held by gastro-enterologists in particular.