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Surgical treatment of obstructive pancreatitis
Surgical treatment of obstructive pancreatitis Thomas J. Howard, MD, Cindy L. Maiden, MD, Howard G. Smith, MD, Eric A. Wiebke, MD, Stuart Sherman, MD, Glen A. Lehman, MD, and James A. Madura, MD, Indianapolis, Ind.
Background. Unlike chronic calcific pancreatitis, obstructive pancreatitis occurs as a consequence of an obstruction or stricture in the main pancreatic duct. The purpose of this paper is to identify the best method of surgical treatment for patients with obstructive pancreatitis. Methods. Retrospective analysis of 224 patients surgically treated for chronic pancreatitis during a 7-year period (1988 through 1994) identified 23 patients with obstructive pancreatitis. Patients were classified by surgical treatment into pancreaticoduodenectomy (five patients), side-to-side pancreaticojejunostomy (nine patients), or distal pancreatectomy (nine patients) groups and analyzed. Results. Despite similar demographics, patients treated with distal pancreatectomy had significantly better outcomes (seven of nine) than those treated with either pancreaticoduodenectomy (zero of four) or side-to-side pancreaticojejunostomy (two of eight) at a mean follow-up of 26 months (chi-squared, p = O.009). Multivariate analysis revealed stricture location, cause ofpancreatitis, maximal duct dilatation, exocrine insufficiency, or continued alcohol intake had no influence on surgical outcome in this series (p = O.698, logistic regression analysis). Conclusions. At 2 years of foUow-up, distal pancreatectomy provided superior relieffrom pain and recurrent pancreatitis compared with pancreaticoduodenectomy or side-to-side pancreaticojejunostomy. Obstructive pancreatitis is best treated by distal rather than proximal pancreatic resection or drainage. (SuRcERY 1995;118:727-35.) From the Surgical Service, Roudebush Veterans Administration Medical Center, and the Departments of Surgery and Gastroenterology, Indiana University School of Medicine, Indianapolis, Ind.
for intractable pain a n d r e c u r r e n t episodes o f pancreatic inflamm a t i o n in chronic pancreatitis remains an inexact science. 1 Chronic calcific pancreatitis is r e g a r d e d to have two anatomic variants, a large duct form (larger than 7 m m diameter) a n d a small d u c t form (smaller than 5 m m diameter).2 Duct drainage by longitudinal side-to-side pancreaticojejunostomy is the best initial surgical t r e a t m e n t for patients with the large duct varia n t ) In contrast, some form of p r o x i m a l resection, eit h e r a p a n c r e a t i c o d u o d e n e c t o m y o r duodenal-preserving pancreatic h e a d resection, is the best surgical treatm e n t option for patients with the small duct variant. 4-7 T h e r e remains, however, a small subset of patients with chronic pancreatitis in w h o m a b n o r m a l p r o t e i n precipitates a n d glandular calcification are n o t the p r e d o m i n a n t pathologic feature. Obstructive pancreatitis occurs CHOOSING THE OPTIMAL SURGICAL t r e a t m e n t
Supported by Indiana Universitybiomedical research grant 22-881-38. Presented at the Fifty-secondAnnual Meeting of the Central Surgical Association,Cleveland, Ohio, March 9-11, 1995. Reprint requests: Thomas J. Howard, MD, Emerson Hall #523, 545 Barnhill Dr., Indianapolis, IN 46202.
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as a result of a narrowing of the m a i n pancreatic duct, which results in localized, segmental pancreatic inflamm a t i o n distal to this obstruction. 8 T h e p u r p o s e o f this p a p e r is to identify the best m e t h o d of surgical treatm e n t for this subset of patients with chronic pancreatitis.
METHODS During a 7-year p e r i o d from 1988 t h r o u g h 1994 all patients with chronic pancreatitis requiring surgical t r e a t m e n t at I n d i a n a University Hospital were reviewed. O f 224 patients requiring surgical treatment, 23 patients satisfied o u r strict anatomic a n d rnorphologic criteria for obstructive pancreatitis. For inclusion into this study, patients were selected on the basis o f (1) absence o f malignant disease, (2) a history of r e c u r r e n t pancreatitis o r severe a b d o m i n a l pain, (3) no glandular calcification, a n d (4) evidence o n endoscopic r e t r o g r a d e chol a n g i o p a n c r e a t o g r a m (ERCP) o f isolated major pancreatic duct stricture or cutoffwith m o r p h o l o g i c evidence of pancreatitis distal to the stricture. Proximal in this rep o r t is defined as toward the h e a d of the pancreas, a n d distal is defined as toward the tail o f the pancreas. All ERCPs were reviewed to identify b o t h the location SURGERY
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Fig. 1. ERCP shows smooth tapered stricture in proximal body of pancreas (arrow).
Fig. 2. Abdominal CAT scan shows transition (arrow) between normal pancreatic parenchyma and pancreatic inflammatory changes in body of pancreas. of main pancreatic duct stricture or obstruction a n d to measure the maximal dilatation o f the m a i n pancreatic duct. A pancreatic duct stricture was defined as a localized narrowing of the pancreatic duct measuring less than 5 m m in l e n g t h 9 Strictures were localized to the
head, neck, or proximal body of the pancreas. Ductal dilatation was m e a s u r e d at the p o i n t of maximal dilatation distal to the stricture on x-ray films by calipers, a n d the m e a n of two readings was taken for final analysis (Fig. 1). The magnification factor was a c c o u n t e d for by
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T a b l e I. Patient characteristics a n d cause of pancreatitis in 23 patients with obstructive pancreatitis Side-to-side pancreaticojejunostomy (N = 9)
Pancreaticoduodenectomy (N = 5)
Age (yr) Gender In] (% male) Cause [n (%)] Alcohol Post-ERCP Postoperative Indeterminate Gallstones Hyperlipidemia
Distal pancreatectomy (N = 9)
49 _+ 12 3 (60)
44 +- 14 4 (44)
41 _+ 13 6 (67)
3 (60) 0 0 0 1 (20) 1 (20)
2 (22) 2 (22) 22 (22) 3 (34) 0 0
2 1 2 2 1 1
(22) (11) (22) (22) (11) (11)
Total (N = 23)
45 +_ 13 13 (57) 7 (30) 3(13) 4 (17) 5 (22) 2 (9) 2 (9)
T a b l e II. Pain duration, p r i o r hospitalizations, ductal dilatation, a n d preoperative e n d o c r i n e a n d exocrine insufficiency in patients treated by W h i p p l e p a n c r e a t i c o d u o d e n e c t o m y , side-to-side pancreaticojejunostomy, o r distal pancreatectomy Pancreaticoduodenectomy (N=5)
Duration of pain [n (%)] <1 yr 1 to5yr >5 yr Mean number of prior hospitalizations Mean maximum ductal dilatation distal to stricture (ram) Preoperative exocrine insufficiency* [n (%)] Preoperative diabetes mellitus]-
Side-to-side pancreaticojejunostomy (N=9)
Distal pancreatectomy (N=9)
0 4 (80) 1 (20) 8_+3 5.32 + 1.42
2 (22) 5 (56) 2 (22) 7_+2 7.36 _+ 1.81
4 (44) 3 (33) 2 (23) 5_+1 4.34 _+0.89
1 (20) 1 (20)
1 (11) 2 (22)
2 (22) 3 (33)
*Symptomatic steatorrhea that responds to exogenous pancreatic enzyme replacement. j-Elevated blood glucose level requiring exogenous insulin for control.
measuring the width of the e n d o s c o p e in the duoden u m a n d making the adjustments as previously described. 1~ Morphologic evidence o f pancreafitis was identified by characteristic findings on c o m p u t e d tom o g r a p h i c scan o r ERCP (Fig. 2). 9, 11 Five patients were surgically treated with pancreaticoduodenectomy, nine with side-to-side pancreaficojej u n o s t o m y with or without duodenal-sparing pancreatectomy, a n d nine with distal p a n c r e a t e c t o m y (50% to 60%). A positive o u t c o m e after surgical t r e a t m e n t was strictly defined as no r e c u r r e n t episodes of pancreatitis or a b d o m i n a l pain. In addition, patients classified as having a positive o u t c o m e were taking no narcotic analgesics for r e c u r r e n t a b d o m i n a l symptoms. A negative outcome was defined as r e c u r r e n t a b d o m i n a l pain similar to that e x p e r i e n c e d before operation, r e c u r r e n t hospitalizations for pain or pancreatifis, or the n e e d for c o n t i n u e d narcotic medication. Follow-up information was u p d a t e d to S e p t e m b e r 1994, a n d a 100% follow-up was achieved by direct patient interview d u r i n g a r e t u r n
clinic visit or t e l e p h o n e conversation by one o f the authors (C.L.M.) who was uninvolved in the operations. Mortality was defined as in-hospital mortality and n o t 30-day mortality after surgical treatment. Exocrine insufficiency was defined as symptomatic steatorrhea that r e s p o n d e d to exogenous pancreatic enzyme supplementafion. Diabetes mellitus was defined as elevated b l o o d glucose levels requiring exogenous insulin for control. Patients who d i e d were included in all b u t the analysis o f o u t c o m e data. Statistical analysis was p e r f o r m e d by using analysis of variance with Bonferroni's post-test for interval variables or the chi-squared test for categorical variables. Multivariate analysis by logistic regression with the SAS statistical p r o g r a m (SAS Institute Inc., Cary, N.C.) was used to evaluate the influence of stricture site, cause of pancreafifis, ductal dilatation, exocrine insufficiency, a n d c o n t i n u e d alcohol use on the o u t c o m e o f surgical treatment. Values are expressed as m e a n - SEM. A p value < 0.05 was taken to be significant.
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HEAD
t
BODY
IECK k . . -,,
~ j ~z. ~ S-C~'O Yr~l ~I. /
O- ipp e pancreaticoduodenectomy X-Pancreaticojejunostomy
1-Distalpancreatectomy
Fig. 3, Anatomic location of pancreatic duct strictures in 23 patients with chronic obstructive pancreatitis.
RESULTS Of the 23 patients studied, 13 were male a n d 10 were female. Age range of the study g r o u p was b r o a d (19 to 64 years) with an average age of 45.2 -+ 13 years across the entire study group. The cause o f pancreatitis was d e t e r m i n e d to be alcoholic in seven patients, postoperative or post-ERCP in seven patients, idiopathic in five patients, gallstone in two patients, a n d hyperlipidemia in two patients. No differences were n o t e d between treatment groups in any of these variables (Table I). All b u t one patient p r e s e n t e d with initial complaints of a b d o m i n a l pain, a n d 77% h a d accompanying radiation to the back. Duration of pain before t r e a t m e n t was divided into less than 1 year (26%), 1 to 5 years (52%), a n d greater than 5 years (22%) (Table II). A t r e n d was n o t e d for patients in the distal p a n c r e a t e c t o m y a n d side-to-side pancreaticojejunostomy groups to have a shorter duration of pain before surgical intervention, b u t this did n o t reach statistical significance (p = 0.235). The incidence of preoperative diabetes in the groups was 20% to 33% with no statistical difference f o u n d between groups. In addition, the rate o f preoperative exocrine insufficiency was similar between groups (11% to 22%). T h e location of pancreatic duct strictures for each g r o u p is shown in Fig. 3. Average ductal dilatation as calculated from ERCP was d e t e r m i n e d to be 5 . 3 2 - 1.42 m m for the p a n c r e a t i c o d u o d e n e c t o m y group, 7.36 _+ 1.81 m m for the side-to-side pancreaticojejunostomy group, a n d 4.34 _+ 0.89 m m for the distal resection group. Before o p e r a t i o n 36% of the patients h a d pseudocysts a n d 11 patients (48%) h a d b e e n treated with either biliary or pancreatic duct stents. Perioperative complications of w o u n d infection, intraabdominal abscess, pancreatic fistula, a n d early re-
operation rates are given in Table III. These rates were similar between groups a n d n o t different from o t h e r published surgical series. 24' 6, 7 Postoperative deaths occurred in two patients. O n e death occurred in a patient who u n d e r w e n t a p a n c r e a t i c o d u o d e n e c t o m y a n d exper i e n c e d a fatal ventricular tachyarrythmia on postoperative day 4. T h e second death occurred 58 days after a side-to-side pancreaticojejunostomy while the patient was still in hospital on the medical service for an exacerbation of chronic obstructive p u l m o n a r y disease. This death was presumably d u e to an acute myocardial infarction. No perioperative deaths o c c u r r e d in the distal pancreatic resection group, a n d no late deaths were f o u n d in our study group. Postoperative follow-up in patients who u n d e r w e n t p a n c r e a f i c o d u o d e n e c t o m y averaged 45 + 26 months, side-to-side pancreaticojejunostomy averaged 26-+ 17 months, a n d distal p a n c r e a t e c t o m y averaged 29 _+ 20 m o n t h s (Table 1V). Recurrence of p a n c r e a t i t i s - a b d o m inal pain, if present, occurred on average 3.8 _+ 3 m o n t h s after pancreaficoduodenectomy, 5.5 - 3 m o n t h s after side-to-side pancreaticojejunostomy, a n d 25 - 12 months after distal pancreatectomy. All patients with symptom recurrence in the p a n c r e a t i c o d u o d e n e c tomy a n d side-to-side pancreaficojejunostomy groups occurred within 8 months of operation. N o n e of the four patients in the p a n c r e a f i c o d u o d e n e c t o m y g r o u p h a d a positive outcome, only two of eight patients in the side-to-side pancreaticojejunostomy g r o u p h a d a positive outcome, whereas seven o f nine patients in the distal p a n c r e a t e c t o m y g r o u p h a d a positive outcome. (chisquared, 9.360 with 2 degrees of freedom, p = 0.009). W h e n these data were analyzed by multivariate analysis with logistic regression, surgical t r e a t m e n t outcomes were u n r e l a t e d to the pancreatic duct stricture location,
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Table III. Postoperative morbidity a n d mortality rates
Pancreaticoduodenectomy (N=5) Morbidity [n (%)] Intraabdominal fluid collection Pancreatic fistula Wound infection Need for reoperation Clostridium difficile colitis Cerebrovascular accident Line infection Small bowel fistula Mortality [n (%)]
Side-to-side pancreaticojejunostomy (N=9)
0 1 (20) 0 0 1 (20) 1 (20) 0 0 1 (20)
1 (11) 0 3 (33) 1 (11) 0 0 1 (11) 1 (11) 1 (11)
Distal pancreatectomy (N= 9) 0 0 0 0 1 (11) 0 1 (11) 0 0
T a b l e IV. Results o f operative m a n a g e m e n t in 21 surviving patients with obstructive pancreatitis*
Pancreaticoduodenectomy (N=4)
Side-to-side pancreaticojejunostomy (N=8)
Distal pancreatectomy (N=9)
45+-26
26-+17
29-+20
0 4 (100)
2 (25) 6 (75)
7 (78) t 2 (22)t
3 (75) 1 (25) (n = 3) 0 0 0
4 (50) 4 (50) (n = 2) 2 (100) 2 (25) 1 (13)
1 (11) 8 (89) (n = 2) 0 2 (22) 2 (22)
Follow-up (mo) Outcomes [n (%)] Good Poor Continued narcotic use Yes No Continued ethanol use [n (%)] Postoperative exocrine insufficiency [n (%) ] Postoperative new onset diabetes mellitus [n (%)] *Two patients who died are excluded from follow-up studies. j-Chi-squared, 9.360 with 2 degrees of freedom, p = 0.009.
cause of pancreatitis, maximal d u c t dilatation, developm e n t of exocrine insufficiency, or postoperative ethanol intake (p = 0.689). In seven patients whose cause o f chronic pancreatitis was alcohol use, only two h a d positive outcomes. O f the five patients with p o o r outcomes, three abstained from alcohol use after operation. T h e two patients with p o o r outcomes who d i d n o t abstain from alcohol use after o p e r a t i o n were b o t h in the sideto-side pancreaticojejunostomy group. Pain r e c u r r e d in one o f these patients before resumption of alcohol consumption. DISCUSSION Chronic calcific pancreatitis, generally related to alcohol intake, is the most c o m m o n form of chronic pancreatitis in western industrialized n a t i o n s ) 2 As a result of the routine availability a n d increasing use o f ERCP a n d c o m p u t e d t o m o g r a p h i c scanning, patients with chronic calcific pancreatitis have b e e n divided into two distinct subgroupings on the basis of anatomy, those with a large pancreatic d u c t (larger than 7 m m diame-
ter) a n d those with a small pancreatic duct (smaller than 5 m m ) ) ' 2 F o r patients with the large duct variant, a side-to-side pancreaticojejunostomy is associated with long-lasting pain relief in 60% to 80% of patients with minimal perioperative morbidity a n d mortality. 3 Because pancreatic d u c t a n d tissue pressures have b e e n shown to be elevated in patients with the dilated duct variant of chronic pancreatitis, ductal drainage to alleviate this glandular hypertension is intuitively a p p e a b ing. 13 Patients with the small duct variant of chronic pancreatitis obtain pain relief in 60% to 80% of cases when treated by either p a n c r e a t i c o d u o d e n e c t o m y or duodenal-sparing h e a d o f the pancreas resection. 57 Proximal pancreatic h e a d resection in this group removes a large p o r t i o n of their disease process, which is characteristically localized to the pancreatic h e a d a n d uncinate process. 5-7 In addition, proximal resection removes n e u r o p a t h i c n e u r o n s in and a r o u n d the h e a d o f the gland that may contribute to their pain syndrome. 14 Despite these n o t e d anatomic differences between large a n d small duct variants of chronic calcific pancreatitis,
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both variants have identical histologic and pathologic features. In contrast, obstructive pancreatitis has distinct histologic features and pathogenesis from chronic calcific pancreatitis/5 Whereas chronic calcific pancreatitis is characterized by irregularly distributed fibrosis, intraductal protein plugging, and calcified pancreatic duct stones, obstructive pancreatitis has uniform fibrosis, no intraductal protein plugging, and a conspicuous lack of calcified pancreatic duct stones. 16Furthermore, whereas sporadic lobular obstruction by abnormal protein precipitates and diffuse pancreaticolithiasis is the presumed pathogenesis of chronic calcific pancreatitis, pancreatic duct narrowing with distal obstruction and inflammation is the presumed pathogenesis of obstructive pancreatitis. 8 Despite these differences, most surgical series have centered their investigations around the more c o m m o n group of patients with chronic calcific pancreatitisY 7 Unfortunately, on the basis of these observatious the subset of patients with obstructive pancreatitis may not benefit from the current surgical treatment regimens advocated for patients with chronic calcific pancreatitis. To our knowledge no study has been undertaken to assess the optimal surgical treatment of patients with obstructive pancreatitis. If one can extrapolate from the known pathologic findings of obstructive pancreatitis coupled with the currently available evidence for the cause of pain in patients with chronic pancreatitis, it seems reasonable to assume that removal of the most diseased portion of the gland and contiguous resection of inflammatory neuropathic neurons by distal pancreatectomy would be the treatment of choice in patients with obstructive pancreatitis. In our study we found this to be the case. In a select group of patients with anatomic evidence of isolated ductal obstruction and morphologic evidence of pancreatitis who have no evidence of glandular calcification, resection of the diseased distal portion of the pancreas provided significantly better relief from pain and recurrent episodes of pancreatitis than provided by either duct drainage or proximal resection. Furthermore, these findings held true irrespective of the location of the pancreatic duct stricture, cause of pancreatitis, degree of duct dilatation, incidence of postoperative exocrine insufficiency, or the continued use of alcohol. The use of a 50% t o 60% distal pancreatectomy to treat patients with obstructive pancreatitis in this series did not result in a higher morbidity or mortality rate, and the incidence of postoperative endocrine and exocrine insufficiency was similar between groups and comparable to other surgical series. 2, 4, 6, 7,17 The diagnosis of obstructive pancreatitis in this series is made on the basis of anatomic and morphologic criteria rather than histopathologic tissue examination; thus we cannot state unequivocally that patients in the
Surgery October 1995 pancreaticoduodenectomy or side-to-side pancreaticojejunostomy groups had histopathologic evidence of obstructive pancreatitis distal to their pancreatic duct stricture. In six of nine patients in the distal pancreatectomy group whose histology slides were reviewed, n o n e had protein plugging or microcalcification, consistent with the diagnosis of obstructive pancreatitis. O n the basis of these findings we assume our anatomic and morphologic criteria to be accurate in identifying patients with an obstructive pattern of pancreafifis. Perhaps our criteria simply identified a subgrouping of patients with chronic pancreafitis whose disease is localized to the body and tail of the gland as described by Sawyer and Frey. 17 Irrespective of the true nature of this localized segmental pancreafifis, on the basis of our data and that of Sawyer and Frey it is best treated by distal pancreatic resection. Unlike the tendency for increased involvement in the head and uncinate process in chronic calcific pancreafifis, the inflammatory process in obstructive pancreafitis is localized in the body and tail of the gland. Therefore, although head resection in chronic calcific pancreatifis removes the most diseased portion of the gland, it leaves behind the most diseased portion in obstructive pancreatitis. W h e n side-to-side pancreaticojejunostomyis used to provide duct drainage both through and distal to the area of stricture, we found only 25% of patients had a good outcome. To explain these observations we postulate that despite adequate decompression of the pancreatic duct obstruction, sufficient irreversible neuronal and glandular destruction has occurred as to warrant this procedure unreliable for pain relief. This theory is supported by the fact that two patients in the pancreaticojejunostomy group who had p o o r outcomes have been subsequently treated with distal pancreatectomy; both have had good initial results at 3 and 4 mos of follow-up, respectively. One might argue that the ductal dilatation in our study was not sufficient to allow for the optimal use of pancreaticojejunostomy. Although the average duct diameter of this group was at the lower end of the spectrum of patients shown to benefit from side-to-side pancreaficojejunostomy, recent reports have emphasized success even in marginally dilated ducts. 18 Furthermore, six of eight patients in this group had postoperative ERCP confirming a patent pancreaticojejunostomy. Ductal dilatation per se does not seem to play a role in determining the efficacy of surgical intervention in our study. In fact, patients with the smallest average duct size before surgical intervention (distal pancreatectomy group) had the best postoperative outcomes when compared with the other two study groups. This finding is counter to that reported in chronic calcific pancreatitis where increasing ductal dilatation was found to be a strong indicator of a positive o u t c o m e )
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Pain d u r a t i o n b e f o r e surgical i n t e r v e n t i o n was lowest in patients w h o u n d e r w e n t distal p a n c r e a t e c t o m y . This m a y reflect a selection bias in that the technically easier surgical p r o c e d u r e s with a lower m o r b i d i t y a n d mortality (side-to-side p a n c r e a t i c o j e j u n o s t o m y a n d distal pancreatectomy) w e r e o f f e r e d earlier t h a n pancreatic o d u o d e n e c t o m y to patients with c h r o n i c pancreatitis. W h e t h e r the d u r a t i o n o f p a i n b e f o r e surgical t r e a t m e n t inversely correlates with operative o u t c o m e was n o t specifically studied, a l t h o u g h studies involving c h r o n i c calcific pancreatitis suggest j u s t t h e opposite. 19 O t h e r s have n o t e d that p a n c r e a t i c g l a n d u l a r calcification is a late m a n i f e s t a t i o n o f c h r o n i c alcoholic pancreatitis a n d may n o t b e t h e best i n d i c a t o r o f this particular disease process. 19 C a t e g o r i z i n g patients as h a v i n g obstructive pancreatitis o n the basis o f t h e lack o f gland u l a r calcifications is o p e n to criticism a n d m a y n o t b e specific. In fact, o n e p a t i e n t in the distal p a n c r e a t e c t o m y g r o u p whose p a i n r e c u r r e d has h a d p a n c r e a t i c calcifications after t r e a t m e n t by distal p a n c r e a t e c t o m y . This p a t i e n t was k e p t in the study g r o u p b e c a u s e h e was initially classified as h a v i n g i d i o p a t h i c pancreatitis with n o e v i d e n c e o f g l a n d u l a r calcification. W h e t h e r this patient was primarily misclassified o r c h r o n i c calcific pancreatitis has d e v e l o p e d since is u n k n o w n . T h e s e c o n d p a t i e n t in the distal p a n c r e a t e c t o m y g r o u p w h o h a d a negative o u t c o m e h a d h y p e r l i p i d e m i a . R e c u r r e n t relapses o f p a i n a n d pancreatitis in this p a t i e n t w e r e d u e to c o n t i n u e d g l a n d u l a r insult resulting f r o m docum e n t e d p o o r c o n t r o l o f h e r elevated lipid levels r a t h e r t h a n failure to select t h e p r o p e r surgical t r e a t m e n t . Ind e e d , this p a t i e n t w e n t a l m o s t 3 years f r o m the t i m e o f h e r distal p a n c r e a t e c t o m y until she h a d a n o t h e r episode o f pancreatitis. T h e e x a c t m e c h a n i s m for isolated ductal o b s t r u c t i o n r e m a i n s u n c l e a r in m a n y o f the patients i n c l u d e d in this study. A l t h o u g h obstructive pancreatitis is classically d e s c r i b e d in the setting o f a ductal malignancy, we have f o u n d a significant p o r t i o n o f patients e x p e r i e n c e b e n i g n p a n c r e a t i c d u c t strictures after an e p i s o d e o f severe acute pancreatitis f r o m m a n y diff e r e n t causes. 15,16 It is for these reasons that we believe strongly that selection for surgical p r o c e d u r e s s h o u l d n o t be b a s e d o n p r e s u m e d cause o f pancreatitis b u t r a t h e r a n a t o m i c a n d m o r p h o l o g i c e v i d e n c e o f an obstructive pattern. It is increasingly e v i d e n t that p a n c r e a t i c s u r g e o n s m u s t have a n u m b e r o f d i f f e r e n t o p e r a t i o n s within t h e i r a r m a m e n t a r i u m to a d e q u a t e l y treat the d i f f e r e n t m o r p h o l o g i c manifestations o f c h r o n i c pancreatitis. 5, 6 T h e overall success o f any o p e r a t i o n in m a n a g i n g p a i n a n d r e c u r r e n t pancreatitis m a y be less a result o f the o p e r a t i o n t h a n the e r r o n e o u s a p p l i c a t i o n o f a p a r t i c u l a r p r o c e d u r e to an i n c o m p a t i b l e a n a t o m i c a n d m o r p h o logic p r o b l e m . 6 W i t h t h e o b s e r v a t i o n that c h r o n i c obstructive pancreatitis is a distinct disease entity f r o m
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o t h e r f o r m s o f c h r o n i c pancreatitis, we have d e t e r m i n e d that the surgical a p p r o a c h to these patients also deserves special consideration. R a t h e r t h a n basing operative strategy o n the diagnosis o f c h r o n i c pancreatitis, anat o m i c i n f o r m a t i o n o n the m a i n p a n c r e a t i c d u c t a n d m o r p h o l o g i c i n f o r m a t i o n o n the g l a n d s h o u l d b e o b t a i n e d to p r o p e r l y identify patients with obstructive pancreatitis. T h e best surgical t r e a t m e n t o f this well-def i n e d g r o u p is distal r a t h e r t h a n p r o x i m a l r e s e c t i o n o r drainage.
REFERENCES
1. Ihse I, Borch K, LarssonJ. Chronic pancreatitis: results of operations for relief of pain. World J Surg 1990;14:53~. 2. MarkowitzJS, Rattner DW, Warshaw AL. Failure of symptomatic relief after pancreaticojejunal decompression for chronic pancreatitis: strategies for salvage. Arch Surg 1994;129:374~0. 3. Pfinz RA, Greenlee HB. Pancreatic duct drainage in chronic pancreatitis. Hepatogastroenterology 1990;37:295-300. 4. Taylor RH, Bagley RH, BraaschJW, Warren KW. Ductal drainage or resection for chronic pancreatitis. AmJ Surg 1981;144:28-33. 5. Howard J, Zhang Z. Pancreaticoduodenectomy (Whipple resection) in the treatment of chronic pancreatitis. WorldJ Surg 1990; 14:7%82. 6. Frey C, Amikura K. Local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy in the management of patients with chronic pancreatitis. Ann Surg 1994; 220:492-507. 7. Beger H, Bfichler M, Oettinger W, Roscher R. Duodenum-preserving resection of the head of the pancreas in severe chronic pancreatitis. Ann Surg 1989;209:273-8. 8. Suda K, Mogaki M, Oyama T, Matsnmoto Y. Histopathologic and immunohistochemical studies on alcoholic pancreatitis and chronic obstructive pancreatitis: special emphasis on ductal obstruction and genesis of pancreatitis. Am J Gastroenterology 1990;85:271-6. 9. Axon ATR, Classen M, Cotton PB, Cremer M, Freeny PC, Lees WR. Pancreatography in chronic pancreatitis: international definitions. Gut 1984;25:1107-12. 10. Misra SP, Gldati P, Thorat VI~ VijJC, Anand BS. Pancreaticobilim-y ductal union in biliary diseases: an endoscopic retrograde cholangiopancreatographic study. Gastroenterology 989;96:90712. 11. Foley WD, Stewart ET, Lawson I, et al. Computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatiography in the diagnosis of pancreatic disease: a comparative study. Gastrointest Radiol 1980;5:29-35. 12. K16ppel G, Maillet B. Pathology of acute and chronic pancreatitis. Pancreas 1993;8:659-70. 13. Bradley EL III. Pancreatic duct pressure in chronic pancreatifis. AmJ Surg 1982;144:313-6. 14. Bochman DE, Bfichler M, Malfertheiner P, Beger HG. Analysis of nerves in chronic pancreatitis. Gastroenterology 1988;94:145969. 15. SahelJ, Sarles H. Chronic calcifying pancreatifis and obstructive pancreatitis: two entities. In: Gyr KE, Singer MV, Sarles H, eds. Pancreatitis: concepts and classification. Amsterdam: Elsevier, 1984:47-9. 16. De Angelis C, Valente G, Spaccaprietra M, et al. Histological study of alcoholic, nonalcoholic, and obstructive chronic pancreatitis. Pancreas 1992;7:193-6. 17. Sawyer R, Frey CF. Is there still a role for distal pancreatectomy in surgery for chronic pancreatitis? AmJ Stirg 1994;168:6-9.
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18.Delcore R, Rodriguez FJ, Thomas JH, Forster J, Hermreck AS. The role of pancreaficojejunostomy in patients without dilated pancreatic ducts. AmJ Surg 1994;168:598-602. 19. Girdwood AH, Marks IN, Barnman PC, Konler RE, Cohen M. Does progressive pancreatic insufficiency limit pain in calcific pancreatitis with duct stricture or continued alcohol insult?J Clin Gastroenterol 1981;3:241-5.
DISCUSSION Dr. Richard A. Prinz (Chicago, Ill.). In most patients with chronic pancreatitis the head of the gland is considered to be the main source of difficulty and the driving force for pain. Modifications in operations used to relieve pain in chronic pancreatitis have t e n d e d to focus on better ways of dealing with the head. In Europe the Beger procedure or duodenalpreserving resection of the head and in this country the Frey procedure that removes part of the head to enhance pancreatic duct drainage are clear-cut examples of this trend emphasizing the h e a d of the gland. You point out that distal pancreatectomy is still an effective procedure for relieving pain in select patients with chronic pancreatitis. You claim that it is useful for treating a so-called obstructive type of disease. I am not sure that is a widely accepted or clinically useful classification of chronic pancreatitis. It is not clear to me how to identify or differentiate patients who have this so-called obstructive form of the disease before operation. About one half of the patients I treat whose chronic pancreatitis is caused by excess alcohol intake do not have calcifications. So the absence of calcifications is not specific e n o u g h to identify this group of patients. I would like you to describe howyou recognize patients with this type of chronic pancreatitis. I would like you to c o m m e n t on the cause and mechanism of this problem. You state that 50% of your patients had stents placed endoscopically in the pancreatic duct. Were the pancreatic duct strictures present before the stents were placed? Or did the stent placement play a role in the cause of these strictures? Is this a h o m o g e n e o u s group of patients or are you actually comparing apples to oranges in this review? It would be very helpful to know the frequency and severity of pain and the quantity of narcotic use in these patients before their treatment. This would give a better handle o n whether you are evaluating similar patients and place your results in better perspective. The location of the strictures are certainly not similar in the patients in this series. This brings up the question of how the original choice of operation was made. The described locations would indicate that at least three of the five strictures in patients undergoing Whipple resection were left in, or potentially left in, by removing the head of the pancreas and duodenum. Distal pancreatectomy is a reasonable operation for disease localized to the tail of the gland. In patients who do benefit from distal pancreatectomy the stricture should be removed along with the damaged parenchyma of the tail of the gland for us to see that this would result in patient benefit. My final question would be about your approach to those patients who have u n d e r g o n e pancreaticoduodenectomy a n d still have continued pain. Have you performed any completion
Surgery October 1995 pancreatectomies to try to relieve this pain? We have done this in a small n u m b e r of patients a n d have even combined it with autotransplantation of the tail to the thigh a n d really have not met with success in obtaining pain relief in that type of patient. Dr. T h o m a s E. Stellato (Cleveland, Ohio). You have some intriguing conclusions. Is there any role any more for the lateral pancreaticojejunostomy in light of the data? Are there any situations where you would still perform that operation? Dr. Henry Buehwald (Minneapolis, Minn.). I have followed up several patients with hyperlipidemic pancreatitis. I have always b e e n impressed that they have a diffuse inflammatory process and that they did not have any particular areas of ductal stenosis unless there was another process concurrently present, such as alcoholism. Your series included two patients with hyperlipidemic pancreatitis. I would be interested to know whether they h a d any improvement by any of the procedures that you performed. Dr. Roger G. Keith (Saskatoon, Saskatchewan, Canada). I think you have underemphasized the significance of your study. You have quite clearly d o c u m e n t e d that a proximal resection for distal obstructive disease that leaves the disease in situ is ineffective in reversing chronic obstructive pancreatitis. A n o t h e r factor that has b e e n an area of some controversy concerns the performance of a longitudinal pancreaticojejunostomy when the pancreatic duct is minimally dilated at 7 mm, which may be ineffective in reversing chronic obstructive pancreatitis. Focal strictures of the pancreatic duct with significant disease distal to that lesion seen in neoplastic lesions have b e e n excluded from this report. From your original database how many cases of pancreatic duct carcinoma were excluded? Dr. Howard (closing). Dr. Prinz asked howwe differentiate patients before operation. Most patients come to us now with a fairly rigid workup, including ERCPs, computed tomographic scans, plus or minus magnetic resonance imaging scans. You can pretty well define b o t h the ductal and the morphologic abnormalities in patients with chronic pancreatitis. There is a subset of patients who have large duct disease, as we discussed. There is a subset with small duct disease who have a pancreatic mass in tile head that we think may be the cause of their recurrent bouts of pain a n d pancreatitis. Those are clearly m u c h different than the patients that we are talking about today, which are a selected group of patients who have a pancreatic duct abnormality and focal pancreatitis upstream from that duct stricture. The key question is whether the duct stricture causes the distal pancreatitis. We c a n ' t answer that; I'm not sure anyone can. We think the cause of these problems to be a severe b o u t of pancreatitis with fat necrosis and glandular necrosis with an area of necrosis in the ductal system. W h e n this heals, it heals by scarring and fibrosis, which leads to a pancreatic duct stricture. Comparing apples a n d oranges may be an issue in any retrospective review. Clearly, we could have b e e n more diligent in recording our patients' preoperative narcotic a n d pain use before operation. But I have always found it difficult in a retrospective setting to get adequate documentation of the number ofoxycodones (Tyloxes) or hydrocodones (Vicodins) that a patient takes a n d what that n u m b e r truly means several m o n t h s after having an intervention.
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Did the patients undergoing Whipple resection have strictures in the neck a n d body a n d were their strictures adequately removed? All these operations were performed by experienced pancreatic surgeons, a n d all of the strictures were removed. So why did these patients have continued pain? Our theory on this is that, as Beget et al. 7 have pointed out, there are neuropathic neurons in areas of chronic pancreatic inflammation that may be left b e h i n d even after taking out the stricture when you resect the head of the gland. It makes m u c h more sense, if this is in fact the case, to take out the tail of the gland which contains those neuropathic neurons, a n d therefore provide pain relief. Our approach to p a t i e n t s who have h a d a pancreaticoduodenectomy with continued pain is to restudy t h e m with ERCP to see whether they have a stricture at their pancreaticojejunostomy, which we f o u n d in several patients in our series to be the cause of their recurrent abdominal pain. We have had recurrent pain in patients who have h a d longitudinal side-to-side pancreaticojejunostomies in this group. I have reoperated on them a n d resected the tail of the gland, leaving the head of the gland drained by a proximal small pancreaticojejunostomy. As I mentioned, this is fairly early in our series, but at 3 a n d
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4 m o n t h s of follow-up these patients have had relief of their pain, are tolerating a regular diet, and are off all narcotic medication. However, I must emphasize these are clearly very preliminary data. Dr. Stellato asked about the role of lateral pancreaticojejunostomy. Surgeons are using it more a n d more often to treat small duct disease a n d reportedly have had good outcomes with minimal exocrine a n d endocrine insufficiency. We have not been satisfied with that, a n d we think there are some people with pancreatic disease who require excisional therapy and that includes distal pancreatectomy. Dr. Buchwald points out hyperlipidemia does affect the whole gland. What I think we are seeing in our two patients with hyperlipidemic pancreatitis is that during their bouts of recurrent pancreatitis they had glandular or ductal necrosis that has resulted in a pancreatic duct stricture. In patients who have hyperlipidemic pancreatitis, if they continue to have abdominal pain a n d inability to eat, they should be studied with ERCP looking for the presence of ductal strictures or stenosis. Dr. Keith b r o u g h t up the issue about neoplasms in our database. I d o n ' t know the answer to that question off the top of my head, a n d I will have to defer to our paper.
Background. Unlike chronic calcific pancreatitis, obstructive pancreatitis occurs as a consequence of an obstruction or stricture in the main pancreatic duct. The purpose of this paper is to identify the best method of surgical treatment for patients with obstructive pancreatitis. Methods. Retrospective analysis of 224 patients surgically treated for chronic pancreatitis during a 7-year period (1988 through 1994) identified 23 patients with obstructive pancreatitis. Patients were classified by surgical treatment into pancreaticoduodenectomy (five patients), side-to-side pancreaticojejunostomy (nine patients), or distal pancreatectomy (nine patients) groups and analyzed. Results. Despite similar demographics, patients treated with distal pancreatectomy had significantly better outcomes (seven of nine) than those treated with either pancreaticoduodenectomy (zero of four) or side-to-side pancreaticojejunostomy (two of eight) at a mean follow-up of 26 months (chi-squared, p = O.009). Multivariate analysis revealed stricture location, cause ofpancreatitis, maximal duct dilatation, exocrine insufficiency, or continued alcohol intake had no influence on surgical outcome in this series (p = O.698, logistic regression analysis). Conclusions. At 2 years of foUow-up, distal pancreatectomy provided superior relieffrom pain and recurrent pancreatitis compared with pancreaticoduodenectomy or side-to-side pancreaticojejunostomy. Obstructive pancreatitis is best treated by distal rather than proximal pancreatic resection or drainage. (SuRcERY 1995;118:727-35.) From the Surgical Service, Roudebush Veterans Administration Medical Center, and the Departments of Surgery and Gastroenterology, Indiana University School of Medicine, Indianapolis, Ind.
for intractable pain a n d r e c u r r e n t episodes o f pancreatic inflamm a t i o n in chronic pancreatitis remains an inexact science. 1 Chronic calcific pancreatitis is r e g a r d e d to have two anatomic variants, a large duct form (larger than 7 m m diameter) a n d a small d u c t form (smaller than 5 m m diameter).2 Duct drainage by longitudinal side-to-side pancreaticojejunostomy is the best initial surgical t r e a t m e n t for patients with the large duct varia n t ) In contrast, some form of p r o x i m a l resection, eit h e r a p a n c r e a t i c o d u o d e n e c t o m y o r duodenal-preserving pancreatic h e a d resection, is the best surgical treatm e n t option for patients with the small duct variant. 4-7 T h e r e remains, however, a small subset of patients with chronic pancreatitis in w h o m a b n o r m a l p r o t e i n precipitates a n d glandular calcification are n o t the p r e d o m i n a n t pathologic feature. Obstructive pancreatitis occurs CHOOSING THE OPTIMAL SURGICAL t r e a t m e n t
Supported by Indiana Universitybiomedical research grant 22-881-38. Presented at the Fifty-secondAnnual Meeting of the Central Surgical Association,Cleveland, Ohio, March 9-11, 1995. Reprint requests: Thomas J. Howard, MD, Emerson Hall #523, 545 Barnhill Dr., Indianapolis, IN 46202.
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as a result of a narrowing of the m a i n pancreatic duct, which results in localized, segmental pancreatic inflamm a t i o n distal to this obstruction. 8 T h e p u r p o s e o f this p a p e r is to identify the best m e t h o d of surgical treatm e n t for this subset of patients with chronic pancreatitis.
METHODS During a 7-year p e r i o d from 1988 t h r o u g h 1994 all patients with chronic pancreatitis requiring surgical t r e a t m e n t at I n d i a n a University Hospital were reviewed. O f 224 patients requiring surgical treatment, 23 patients satisfied o u r strict anatomic a n d rnorphologic criteria for obstructive pancreatitis. For inclusion into this study, patients were selected on the basis o f (1) absence o f malignant disease, (2) a history of r e c u r r e n t pancreatitis o r severe a b d o m i n a l pain, (3) no glandular calcification, a n d (4) evidence o n endoscopic r e t r o g r a d e chol a n g i o p a n c r e a t o g r a m (ERCP) o f isolated major pancreatic duct stricture or cutoffwith m o r p h o l o g i c evidence of pancreatitis distal to the stricture. Proximal in this rep o r t is defined as toward the h e a d of the pancreas, a n d distal is defined as toward the tail o f the pancreas. All ERCPs were reviewed to identify b o t h the location SURGERY
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Fig. 1. ERCP shows smooth tapered stricture in proximal body of pancreas (arrow).
Fig. 2. Abdominal CAT scan shows transition (arrow) between normal pancreatic parenchyma and pancreatic inflammatory changes in body of pancreas. of main pancreatic duct stricture or obstruction a n d to measure the maximal dilatation o f the m a i n pancreatic duct. A pancreatic duct stricture was defined as a localized narrowing of the pancreatic duct measuring less than 5 m m in l e n g t h 9 Strictures were localized to the
head, neck, or proximal body of the pancreas. Ductal dilatation was m e a s u r e d at the p o i n t of maximal dilatation distal to the stricture on x-ray films by calipers, a n d the m e a n of two readings was taken for final analysis (Fig. 1). The magnification factor was a c c o u n t e d for by
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T a b l e I. Patient characteristics a n d cause of pancreatitis in 23 patients with obstructive pancreatitis Side-to-side pancreaticojejunostomy (N = 9)
Pancreaticoduodenectomy (N = 5)
Age (yr) Gender In] (% male) Cause [n (%)] Alcohol Post-ERCP Postoperative Indeterminate Gallstones Hyperlipidemia
Distal pancreatectomy (N = 9)
49 _+ 12 3 (60)
44 +- 14 4 (44)
41 _+ 13 6 (67)
3 (60) 0 0 0 1 (20) 1 (20)
2 (22) 2 (22) 22 (22) 3 (34) 0 0
2 1 2 2 1 1
(22) (11) (22) (22) (11) (11)
Total (N = 23)
45 +_ 13 13 (57) 7 (30) 3(13) 4 (17) 5 (22) 2 (9) 2 (9)
T a b l e II. Pain duration, p r i o r hospitalizations, ductal dilatation, a n d preoperative e n d o c r i n e a n d exocrine insufficiency in patients treated by W h i p p l e p a n c r e a t i c o d u o d e n e c t o m y , side-to-side pancreaticojejunostomy, o r distal pancreatectomy Pancreaticoduodenectomy (N=5)
Duration of pain [n (%)] <1 yr 1 to5yr >5 yr Mean number of prior hospitalizations Mean maximum ductal dilatation distal to stricture (ram) Preoperative exocrine insufficiency* [n (%)] Preoperative diabetes mellitus]-
Side-to-side pancreaticojejunostomy (N=9)
Distal pancreatectomy (N=9)
0 4 (80) 1 (20) 8_+3 5.32 + 1.42
2 (22) 5 (56) 2 (22) 7_+2 7.36 _+ 1.81
4 (44) 3 (33) 2 (23) 5_+1 4.34 _+0.89
1 (20) 1 (20)
1 (11) 2 (22)
2 (22) 3 (33)
*Symptomatic steatorrhea that responds to exogenous pancreatic enzyme replacement. j-Elevated blood glucose level requiring exogenous insulin for control.
measuring the width of the e n d o s c o p e in the duoden u m a n d making the adjustments as previously described. 1~ Morphologic evidence o f pancreafitis was identified by characteristic findings on c o m p u t e d tom o g r a p h i c scan o r ERCP (Fig. 2). 9, 11 Five patients were surgically treated with pancreaticoduodenectomy, nine with side-to-side pancreaficojej u n o s t o m y with or without duodenal-sparing pancreatectomy, a n d nine with distal p a n c r e a t e c t o m y (50% to 60%). A positive o u t c o m e after surgical t r e a t m e n t was strictly defined as no r e c u r r e n t episodes of pancreatitis or a b d o m i n a l pain. In addition, patients classified as having a positive o u t c o m e were taking no narcotic analgesics for r e c u r r e n t a b d o m i n a l symptoms. A negative outcome was defined as r e c u r r e n t a b d o m i n a l pain similar to that e x p e r i e n c e d before operation, r e c u r r e n t hospitalizations for pain or pancreatifis, or the n e e d for c o n t i n u e d narcotic medication. Follow-up information was u p d a t e d to S e p t e m b e r 1994, a n d a 100% follow-up was achieved by direct patient interview d u r i n g a r e t u r n
clinic visit or t e l e p h o n e conversation by one o f the authors (C.L.M.) who was uninvolved in the operations. Mortality was defined as in-hospital mortality and n o t 30-day mortality after surgical treatment. Exocrine insufficiency was defined as symptomatic steatorrhea that r e s p o n d e d to exogenous pancreatic enzyme supplementafion. Diabetes mellitus was defined as elevated b l o o d glucose levels requiring exogenous insulin for control. Patients who d i e d were included in all b u t the analysis o f o u t c o m e data. Statistical analysis was p e r f o r m e d by using analysis of variance with Bonferroni's post-test for interval variables or the chi-squared test for categorical variables. Multivariate analysis by logistic regression with the SAS statistical p r o g r a m (SAS Institute Inc., Cary, N.C.) was used to evaluate the influence of stricture site, cause of pancreafifis, ductal dilatation, exocrine insufficiency, a n d c o n t i n u e d alcohol use on the o u t c o m e o f surgical treatment. Values are expressed as m e a n - SEM. A p value < 0.05 was taken to be significant.
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HEAD
t
BODY
IECK k . . -,,
~ j ~z. ~ S-C~'O Yr~l ~I. /
O- ipp e pancreaticoduodenectomy X-Pancreaticojejunostomy
1-Distalpancreatectomy
Fig. 3, Anatomic location of pancreatic duct strictures in 23 patients with chronic obstructive pancreatitis.
RESULTS Of the 23 patients studied, 13 were male a n d 10 were female. Age range of the study g r o u p was b r o a d (19 to 64 years) with an average age of 45.2 -+ 13 years across the entire study group. The cause o f pancreatitis was d e t e r m i n e d to be alcoholic in seven patients, postoperative or post-ERCP in seven patients, idiopathic in five patients, gallstone in two patients, a n d hyperlipidemia in two patients. No differences were n o t e d between treatment groups in any of these variables (Table I). All b u t one patient p r e s e n t e d with initial complaints of a b d o m i n a l pain, a n d 77% h a d accompanying radiation to the back. Duration of pain before t r e a t m e n t was divided into less than 1 year (26%), 1 to 5 years (52%), a n d greater than 5 years (22%) (Table II). A t r e n d was n o t e d for patients in the distal p a n c r e a t e c t o m y a n d side-to-side pancreaticojejunostomy groups to have a shorter duration of pain before surgical intervention, b u t this did n o t reach statistical significance (p = 0.235). The incidence of preoperative diabetes in the groups was 20% to 33% with no statistical difference f o u n d between groups. In addition, the rate o f preoperative exocrine insufficiency was similar between groups (11% to 22%). T h e location of pancreatic duct strictures for each g r o u p is shown in Fig. 3. Average ductal dilatation as calculated from ERCP was d e t e r m i n e d to be 5 . 3 2 - 1.42 m m for the p a n c r e a t i c o d u o d e n e c t o m y group, 7.36 _+ 1.81 m m for the side-to-side pancreaticojejunostomy group, a n d 4.34 _+ 0.89 m m for the distal resection group. Before o p e r a t i o n 36% of the patients h a d pseudocysts a n d 11 patients (48%) h a d b e e n treated with either biliary or pancreatic duct stents. Perioperative complications of w o u n d infection, intraabdominal abscess, pancreatic fistula, a n d early re-
operation rates are given in Table III. These rates were similar between groups a n d n o t different from o t h e r published surgical series. 24' 6, 7 Postoperative deaths occurred in two patients. O n e death occurred in a patient who u n d e r w e n t a p a n c r e a t i c o d u o d e n e c t o m y a n d exper i e n c e d a fatal ventricular tachyarrythmia on postoperative day 4. T h e second death occurred 58 days after a side-to-side pancreaticojejunostomy while the patient was still in hospital on the medical service for an exacerbation of chronic obstructive p u l m o n a r y disease. This death was presumably d u e to an acute myocardial infarction. No perioperative deaths o c c u r r e d in the distal pancreatic resection group, a n d no late deaths were f o u n d in our study group. Postoperative follow-up in patients who u n d e r w e n t p a n c r e a f i c o d u o d e n e c t o m y averaged 45 + 26 months, side-to-side pancreaticojejunostomy averaged 26-+ 17 months, a n d distal p a n c r e a t e c t o m y averaged 29 _+ 20 m o n t h s (Table 1V). Recurrence of p a n c r e a t i t i s - a b d o m inal pain, if present, occurred on average 3.8 _+ 3 m o n t h s after pancreaficoduodenectomy, 5.5 - 3 m o n t h s after side-to-side pancreaticojejunostomy, a n d 25 - 12 months after distal pancreatectomy. All patients with symptom recurrence in the p a n c r e a t i c o d u o d e n e c tomy a n d side-to-side pancreaficojejunostomy groups occurred within 8 months of operation. N o n e of the four patients in the p a n c r e a f i c o d u o d e n e c t o m y g r o u p h a d a positive outcome, only two of eight patients in the side-to-side pancreaticojejunostomy g r o u p h a d a positive outcome, whereas seven o f nine patients in the distal p a n c r e a t e c t o m y g r o u p h a d a positive outcome. (chisquared, 9.360 with 2 degrees of freedom, p = 0.009). W h e n these data were analyzed by multivariate analysis with logistic regression, surgical t r e a t m e n t outcomes were u n r e l a t e d to the pancreatic duct stricture location,
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Table III. Postoperative morbidity a n d mortality rates
Pancreaticoduodenectomy (N=5) Morbidity [n (%)] Intraabdominal fluid collection Pancreatic fistula Wound infection Need for reoperation Clostridium difficile colitis Cerebrovascular accident Line infection Small bowel fistula Mortality [n (%)]
Side-to-side pancreaticojejunostomy (N=9)
0 1 (20) 0 0 1 (20) 1 (20) 0 0 1 (20)
1 (11) 0 3 (33) 1 (11) 0 0 1 (11) 1 (11) 1 (11)
Distal pancreatectomy (N= 9) 0 0 0 0 1 (11) 0 1 (11) 0 0
T a b l e IV. Results o f operative m a n a g e m e n t in 21 surviving patients with obstructive pancreatitis*
Pancreaticoduodenectomy (N=4)
Side-to-side pancreaticojejunostomy (N=8)
Distal pancreatectomy (N=9)
45+-26
26-+17
29-+20
0 4 (100)
2 (25) 6 (75)
7 (78) t 2 (22)t
3 (75) 1 (25) (n = 3) 0 0 0
4 (50) 4 (50) (n = 2) 2 (100) 2 (25) 1 (13)
1 (11) 8 (89) (n = 2) 0 2 (22) 2 (22)
Follow-up (mo) Outcomes [n (%)] Good Poor Continued narcotic use Yes No Continued ethanol use [n (%)] Postoperative exocrine insufficiency [n (%) ] Postoperative new onset diabetes mellitus [n (%)] *Two patients who died are excluded from follow-up studies. j-Chi-squared, 9.360 with 2 degrees of freedom, p = 0.009.
cause of pancreatitis, maximal d u c t dilatation, developm e n t of exocrine insufficiency, or postoperative ethanol intake (p = 0.689). In seven patients whose cause o f chronic pancreatitis was alcohol use, only two h a d positive outcomes. O f the five patients with p o o r outcomes, three abstained from alcohol use after operation. T h e two patients with p o o r outcomes who d i d n o t abstain from alcohol use after o p e r a t i o n were b o t h in the sideto-side pancreaticojejunostomy group. Pain r e c u r r e d in one o f these patients before resumption of alcohol consumption. DISCUSSION Chronic calcific pancreatitis, generally related to alcohol intake, is the most c o m m o n form of chronic pancreatitis in western industrialized n a t i o n s ) 2 As a result of the routine availability a n d increasing use o f ERCP a n d c o m p u t e d t o m o g r a p h i c scanning, patients with chronic calcific pancreatitis have b e e n divided into two distinct subgroupings on the basis of anatomy, those with a large pancreatic d u c t (larger than 7 m m diame-
ter) a n d those with a small pancreatic duct (smaller than 5 m m ) ) ' 2 F o r patients with the large duct variant, a side-to-side pancreaticojejunostomy is associated with long-lasting pain relief in 60% to 80% of patients with minimal perioperative morbidity a n d mortality. 3 Because pancreatic d u c t a n d tissue pressures have b e e n shown to be elevated in patients with the dilated duct variant of chronic pancreatitis, ductal drainage to alleviate this glandular hypertension is intuitively a p p e a b ing. 13 Patients with the small duct variant of chronic pancreatitis obtain pain relief in 60% to 80% of cases when treated by either p a n c r e a t i c o d u o d e n e c t o m y or duodenal-sparing h e a d o f the pancreas resection. 57 Proximal pancreatic h e a d resection in this group removes a large p o r t i o n of their disease process, which is characteristically localized to the pancreatic h e a d a n d uncinate process. 5-7 In addition, proximal resection removes n e u r o p a t h i c n e u r o n s in and a r o u n d the h e a d o f the gland that may contribute to their pain syndrome. 14 Despite these n o t e d anatomic differences between large a n d small duct variants of chronic calcific pancreatitis,
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both variants have identical histologic and pathologic features. In contrast, obstructive pancreatitis has distinct histologic features and pathogenesis from chronic calcific pancreatitis/5 Whereas chronic calcific pancreatitis is characterized by irregularly distributed fibrosis, intraductal protein plugging, and calcified pancreatic duct stones, obstructive pancreatitis has uniform fibrosis, no intraductal protein plugging, and a conspicuous lack of calcified pancreatic duct stones. 16Furthermore, whereas sporadic lobular obstruction by abnormal protein precipitates and diffuse pancreaticolithiasis is the presumed pathogenesis of chronic calcific pancreatitis, pancreatic duct narrowing with distal obstruction and inflammation is the presumed pathogenesis of obstructive pancreatitis. 8 Despite these differences, most surgical series have centered their investigations around the more c o m m o n group of patients with chronic calcific pancreatitisY 7 Unfortunately, on the basis of these observatious the subset of patients with obstructive pancreatitis may not benefit from the current surgical treatment regimens advocated for patients with chronic calcific pancreatitis. To our knowledge no study has been undertaken to assess the optimal surgical treatment of patients with obstructive pancreatitis. If one can extrapolate from the known pathologic findings of obstructive pancreatitis coupled with the currently available evidence for the cause of pain in patients with chronic pancreatitis, it seems reasonable to assume that removal of the most diseased portion of the gland and contiguous resection of inflammatory neuropathic neurons by distal pancreatectomy would be the treatment of choice in patients with obstructive pancreatitis. In our study we found this to be the case. In a select group of patients with anatomic evidence of isolated ductal obstruction and morphologic evidence of pancreatitis who have no evidence of glandular calcification, resection of the diseased distal portion of the pancreas provided significantly better relief from pain and recurrent episodes of pancreatitis than provided by either duct drainage or proximal resection. Furthermore, these findings held true irrespective of the location of the pancreatic duct stricture, cause of pancreatitis, degree of duct dilatation, incidence of postoperative exocrine insufficiency, or the continued use of alcohol. The use of a 50% t o 60% distal pancreatectomy to treat patients with obstructive pancreatitis in this series did not result in a higher morbidity or mortality rate, and the incidence of postoperative endocrine and exocrine insufficiency was similar between groups and comparable to other surgical series. 2, 4, 6, 7,17 The diagnosis of obstructive pancreatitis in this series is made on the basis of anatomic and morphologic criteria rather than histopathologic tissue examination; thus we cannot state unequivocally that patients in the
Surgery October 1995 pancreaticoduodenectomy or side-to-side pancreaticojejunostomy groups had histopathologic evidence of obstructive pancreatitis distal to their pancreatic duct stricture. In six of nine patients in the distal pancreatectomy group whose histology slides were reviewed, n o n e had protein plugging or microcalcification, consistent with the diagnosis of obstructive pancreatitis. O n the basis of these findings we assume our anatomic and morphologic criteria to be accurate in identifying patients with an obstructive pattern of pancreafifis. Perhaps our criteria simply identified a subgrouping of patients with chronic pancreafitis whose disease is localized to the body and tail of the gland as described by Sawyer and Frey. 17 Irrespective of the true nature of this localized segmental pancreafifis, on the basis of our data and that of Sawyer and Frey it is best treated by distal pancreatic resection. Unlike the tendency for increased involvement in the head and uncinate process in chronic calcific pancreafifis, the inflammatory process in obstructive pancreafitis is localized in the body and tail of the gland. Therefore, although head resection in chronic calcific pancreatifis removes the most diseased portion of the gland, it leaves behind the most diseased portion in obstructive pancreatitis. W h e n side-to-side pancreaticojejunostomyis used to provide duct drainage both through and distal to the area of stricture, we found only 25% of patients had a good outcome. To explain these observations we postulate that despite adequate decompression of the pancreatic duct obstruction, sufficient irreversible neuronal and glandular destruction has occurred as to warrant this procedure unreliable for pain relief. This theory is supported by the fact that two patients in the pancreaticojejunostomy group who had p o o r outcomes have been subsequently treated with distal pancreatectomy; both have had good initial results at 3 and 4 mos of follow-up, respectively. One might argue that the ductal dilatation in our study was not sufficient to allow for the optimal use of pancreaticojejunostomy. Although the average duct diameter of this group was at the lower end of the spectrum of patients shown to benefit from side-to-side pancreaficojejunostomy, recent reports have emphasized success even in marginally dilated ducts. 18 Furthermore, six of eight patients in this group had postoperative ERCP confirming a patent pancreaticojejunostomy. Ductal dilatation per se does not seem to play a role in determining the efficacy of surgical intervention in our study. In fact, patients with the smallest average duct size before surgical intervention (distal pancreatectomy group) had the best postoperative outcomes when compared with the other two study groups. This finding is counter to that reported in chronic calcific pancreatitis where increasing ductal dilatation was found to be a strong indicator of a positive o u t c o m e )
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Pain d u r a t i o n b e f o r e surgical i n t e r v e n t i o n was lowest in patients w h o u n d e r w e n t distal p a n c r e a t e c t o m y . This m a y reflect a selection bias in that the technically easier surgical p r o c e d u r e s with a lower m o r b i d i t y a n d mortality (side-to-side p a n c r e a t i c o j e j u n o s t o m y a n d distal pancreatectomy) w e r e o f f e r e d earlier t h a n pancreatic o d u o d e n e c t o m y to patients with c h r o n i c pancreatitis. W h e t h e r the d u r a t i o n o f p a i n b e f o r e surgical t r e a t m e n t inversely correlates with operative o u t c o m e was n o t specifically studied, a l t h o u g h studies involving c h r o n i c calcific pancreatitis suggest j u s t t h e opposite. 19 O t h e r s have n o t e d that p a n c r e a t i c g l a n d u l a r calcification is a late m a n i f e s t a t i o n o f c h r o n i c alcoholic pancreatitis a n d may n o t b e t h e best i n d i c a t o r o f this particular disease process. 19 C a t e g o r i z i n g patients as h a v i n g obstructive pancreatitis o n the basis o f t h e lack o f gland u l a r calcifications is o p e n to criticism a n d m a y n o t b e specific. In fact, o n e p a t i e n t in the distal p a n c r e a t e c t o m y g r o u p whose p a i n r e c u r r e d has h a d p a n c r e a t i c calcifications after t r e a t m e n t by distal p a n c r e a t e c t o m y . This p a t i e n t was k e p t in the study g r o u p b e c a u s e h e was initially classified as h a v i n g i d i o p a t h i c pancreatitis with n o e v i d e n c e o f g l a n d u l a r calcification. W h e t h e r this patient was primarily misclassified o r c h r o n i c calcific pancreatitis has d e v e l o p e d since is u n k n o w n . T h e s e c o n d p a t i e n t in the distal p a n c r e a t e c t o m y g r o u p w h o h a d a negative o u t c o m e h a d h y p e r l i p i d e m i a . R e c u r r e n t relapses o f p a i n a n d pancreatitis in this p a t i e n t w e r e d u e to c o n t i n u e d g l a n d u l a r insult resulting f r o m docum e n t e d p o o r c o n t r o l o f h e r elevated lipid levels r a t h e r t h a n failure to select t h e p r o p e r surgical t r e a t m e n t . Ind e e d , this p a t i e n t w e n t a l m o s t 3 years f r o m the t i m e o f h e r distal p a n c r e a t e c t o m y until she h a d a n o t h e r episode o f pancreatitis. T h e e x a c t m e c h a n i s m for isolated ductal o b s t r u c t i o n r e m a i n s u n c l e a r in m a n y o f the patients i n c l u d e d in this study. A l t h o u g h obstructive pancreatitis is classically d e s c r i b e d in the setting o f a ductal malignancy, we have f o u n d a significant p o r t i o n o f patients e x p e r i e n c e b e n i g n p a n c r e a t i c d u c t strictures after an e p i s o d e o f severe acute pancreatitis f r o m m a n y diff e r e n t causes. 15,16 It is for these reasons that we believe strongly that selection for surgical p r o c e d u r e s s h o u l d n o t be b a s e d o n p r e s u m e d cause o f pancreatitis b u t r a t h e r a n a t o m i c a n d m o r p h o l o g i c e v i d e n c e o f an obstructive pattern. It is increasingly e v i d e n t that p a n c r e a t i c s u r g e o n s m u s t have a n u m b e r o f d i f f e r e n t o p e r a t i o n s within t h e i r a r m a m e n t a r i u m to a d e q u a t e l y treat the d i f f e r e n t m o r p h o l o g i c manifestations o f c h r o n i c pancreatitis. 5, 6 T h e overall success o f any o p e r a t i o n in m a n a g i n g p a i n a n d r e c u r r e n t pancreatitis m a y be less a result o f the o p e r a t i o n t h a n the e r r o n e o u s a p p l i c a t i o n o f a p a r t i c u l a r p r o c e d u r e to an i n c o m p a t i b l e a n a t o m i c a n d m o r p h o logic p r o b l e m . 6 W i t h t h e o b s e r v a t i o n that c h r o n i c obstructive pancreatitis is a distinct disease entity f r o m
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o t h e r f o r m s o f c h r o n i c pancreatitis, we have d e t e r m i n e d that the surgical a p p r o a c h to these patients also deserves special consideration. R a t h e r t h a n basing operative strategy o n the diagnosis o f c h r o n i c pancreatitis, anat o m i c i n f o r m a t i o n o n the m a i n p a n c r e a t i c d u c t a n d m o r p h o l o g i c i n f o r m a t i o n o n the g l a n d s h o u l d b e o b t a i n e d to p r o p e r l y identify patients with obstructive pancreatitis. T h e best surgical t r e a t m e n t o f this well-def i n e d g r o u p is distal r a t h e r t h a n p r o x i m a l r e s e c t i o n o r drainage.
REFERENCES
1. Ihse I, Borch K, LarssonJ. Chronic pancreatitis: results of operations for relief of pain. World J Surg 1990;14:53~. 2. MarkowitzJS, Rattner DW, Warshaw AL. Failure of symptomatic relief after pancreaticojejunal decompression for chronic pancreatitis: strategies for salvage. Arch Surg 1994;129:374~0. 3. Pfinz RA, Greenlee HB. Pancreatic duct drainage in chronic pancreatitis. Hepatogastroenterology 1990;37:295-300. 4. Taylor RH, Bagley RH, BraaschJW, Warren KW. Ductal drainage or resection for chronic pancreatitis. AmJ Surg 1981;144:28-33. 5. Howard J, Zhang Z. Pancreaticoduodenectomy (Whipple resection) in the treatment of chronic pancreatitis. WorldJ Surg 1990; 14:7%82. 6. Frey C, Amikura K. Local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy in the management of patients with chronic pancreatitis. Ann Surg 1994; 220:492-507. 7. Beger H, Bfichler M, Oettinger W, Roscher R. Duodenum-preserving resection of the head of the pancreas in severe chronic pancreatitis. Ann Surg 1989;209:273-8. 8. Suda K, Mogaki M, Oyama T, Matsnmoto Y. Histopathologic and immunohistochemical studies on alcoholic pancreatitis and chronic obstructive pancreatitis: special emphasis on ductal obstruction and genesis of pancreatitis. Am J Gastroenterology 1990;85:271-6. 9. Axon ATR, Classen M, Cotton PB, Cremer M, Freeny PC, Lees WR. Pancreatography in chronic pancreatitis: international definitions. Gut 1984;25:1107-12. 10. Misra SP, Gldati P, Thorat VI~ VijJC, Anand BS. Pancreaticobilim-y ductal union in biliary diseases: an endoscopic retrograde cholangiopancreatographic study. Gastroenterology 989;96:90712. 11. Foley WD, Stewart ET, Lawson I, et al. Computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatiography in the diagnosis of pancreatic disease: a comparative study. Gastrointest Radiol 1980;5:29-35. 12. K16ppel G, Maillet B. Pathology of acute and chronic pancreatitis. Pancreas 1993;8:659-70. 13. Bradley EL III. Pancreatic duct pressure in chronic pancreatifis. AmJ Surg 1982;144:313-6. 14. Bochman DE, Bfichler M, Malfertheiner P, Beger HG. Analysis of nerves in chronic pancreatitis. Gastroenterology 1988;94:145969. 15. SahelJ, Sarles H. Chronic calcifying pancreatifis and obstructive pancreatitis: two entities. In: Gyr KE, Singer MV, Sarles H, eds. Pancreatitis: concepts and classification. Amsterdam: Elsevier, 1984:47-9. 16. De Angelis C, Valente G, Spaccaprietra M, et al. Histological study of alcoholic, nonalcoholic, and obstructive chronic pancreatitis. Pancreas 1992;7:193-6. 17. Sawyer R, Frey CF. Is there still a role for distal pancreatectomy in surgery for chronic pancreatitis? AmJ Stirg 1994;168:6-9.
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18.Delcore R, Rodriguez FJ, Thomas JH, Forster J, Hermreck AS. The role of pancreaficojejunostomy in patients without dilated pancreatic ducts. AmJ Surg 1994;168:598-602. 19. Girdwood AH, Marks IN, Barnman PC, Konler RE, Cohen M. Does progressive pancreatic insufficiency limit pain in calcific pancreatitis with duct stricture or continued alcohol insult?J Clin Gastroenterol 1981;3:241-5.
DISCUSSION Dr. Richard A. Prinz (Chicago, Ill.). In most patients with chronic pancreatitis the head of the gland is considered to be the main source of difficulty and the driving force for pain. Modifications in operations used to relieve pain in chronic pancreatitis have t e n d e d to focus on better ways of dealing with the head. In Europe the Beger procedure or duodenalpreserving resection of the head and in this country the Frey procedure that removes part of the head to enhance pancreatic duct drainage are clear-cut examples of this trend emphasizing the h e a d of the gland. You point out that distal pancreatectomy is still an effective procedure for relieving pain in select patients with chronic pancreatitis. You claim that it is useful for treating a so-called obstructive type of disease. I am not sure that is a widely accepted or clinically useful classification of chronic pancreatitis. It is not clear to me how to identify or differentiate patients who have this so-called obstructive form of the disease before operation. About one half of the patients I treat whose chronic pancreatitis is caused by excess alcohol intake do not have calcifications. So the absence of calcifications is not specific e n o u g h to identify this group of patients. I would like you to describe howyou recognize patients with this type of chronic pancreatitis. I would like you to c o m m e n t on the cause and mechanism of this problem. You state that 50% of your patients had stents placed endoscopically in the pancreatic duct. Were the pancreatic duct strictures present before the stents were placed? Or did the stent placement play a role in the cause of these strictures? Is this a h o m o g e n e o u s group of patients or are you actually comparing apples to oranges in this review? It would be very helpful to know the frequency and severity of pain and the quantity of narcotic use in these patients before their treatment. This would give a better handle o n whether you are evaluating similar patients and place your results in better perspective. The location of the strictures are certainly not similar in the patients in this series. This brings up the question of how the original choice of operation was made. The described locations would indicate that at least three of the five strictures in patients undergoing Whipple resection were left in, or potentially left in, by removing the head of the pancreas and duodenum. Distal pancreatectomy is a reasonable operation for disease localized to the tail of the gland. In patients who do benefit from distal pancreatectomy the stricture should be removed along with the damaged parenchyma of the tail of the gland for us to see that this would result in patient benefit. My final question would be about your approach to those patients who have u n d e r g o n e pancreaticoduodenectomy a n d still have continued pain. Have you performed any completion
Surgery October 1995 pancreatectomies to try to relieve this pain? We have done this in a small n u m b e r of patients a n d have even combined it with autotransplantation of the tail to the thigh a n d really have not met with success in obtaining pain relief in that type of patient. Dr. T h o m a s E. Stellato (Cleveland, Ohio). You have some intriguing conclusions. Is there any role any more for the lateral pancreaticojejunostomy in light of the data? Are there any situations where you would still perform that operation? Dr. Henry Buehwald (Minneapolis, Minn.). I have followed up several patients with hyperlipidemic pancreatitis. I have always b e e n impressed that they have a diffuse inflammatory process and that they did not have any particular areas of ductal stenosis unless there was another process concurrently present, such as alcoholism. Your series included two patients with hyperlipidemic pancreatitis. I would be interested to know whether they h a d any improvement by any of the procedures that you performed. Dr. Roger G. Keith (Saskatoon, Saskatchewan, Canada). I think you have underemphasized the significance of your study. You have quite clearly d o c u m e n t e d that a proximal resection for distal obstructive disease that leaves the disease in situ is ineffective in reversing chronic obstructive pancreatitis. A n o t h e r factor that has b e e n an area of some controversy concerns the performance of a longitudinal pancreaticojejunostomy when the pancreatic duct is minimally dilated at 7 mm, which may be ineffective in reversing chronic obstructive pancreatitis. Focal strictures of the pancreatic duct with significant disease distal to that lesion seen in neoplastic lesions have b e e n excluded from this report. From your original database how many cases of pancreatic duct carcinoma were excluded? Dr. Howard (closing). Dr. Prinz asked howwe differentiate patients before operation. Most patients come to us now with a fairly rigid workup, including ERCPs, computed tomographic scans, plus or minus magnetic resonance imaging scans. You can pretty well define b o t h the ductal and the morphologic abnormalities in patients with chronic pancreatitis. There is a subset of patients who have large duct disease, as we discussed. There is a subset with small duct disease who have a pancreatic mass in tile head that we think may be the cause of their recurrent bouts of pain a n d pancreatitis. Those are clearly m u c h different than the patients that we are talking about today, which are a selected group of patients who have a pancreatic duct abnormality and focal pancreatitis upstream from that duct stricture. The key question is whether the duct stricture causes the distal pancreatitis. We c a n ' t answer that; I'm not sure anyone can. We think the cause of these problems to be a severe b o u t of pancreatitis with fat necrosis and glandular necrosis with an area of necrosis in the ductal system. W h e n this heals, it heals by scarring and fibrosis, which leads to a pancreatic duct stricture. Comparing apples a n d oranges may be an issue in any retrospective review. Clearly, we could have b e e n more diligent in recording our patients' preoperative narcotic a n d pain use before operation. But I have always found it difficult in a retrospective setting to get adequate documentation of the number ofoxycodones (Tyloxes) or hydrocodones (Vicodins) that a patient takes a n d what that n u m b e r truly means several m o n t h s after having an intervention.
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Did the patients undergoing Whipple resection have strictures in the neck a n d body a n d were their strictures adequately removed? All these operations were performed by experienced pancreatic surgeons, a n d all of the strictures were removed. So why did these patients have continued pain? Our theory on this is that, as Beget et al. 7 have pointed out, there are neuropathic neurons in areas of chronic pancreatic inflammation that may be left b e h i n d even after taking out the stricture when you resect the head of the gland. It makes m u c h more sense, if this is in fact the case, to take out the tail of the gland which contains those neuropathic neurons, a n d therefore provide pain relief. Our approach to p a t i e n t s who have h a d a pancreaticoduodenectomy with continued pain is to restudy t h e m with ERCP to see whether they have a stricture at their pancreaticojejunostomy, which we f o u n d in several patients in our series to be the cause of their recurrent abdominal pain. We have had recurrent pain in patients who have h a d longitudinal side-to-side pancreaticojejunostomies in this group. I have reoperated on them a n d resected the tail of the gland, leaving the head of the gland drained by a proximal small pancreaticojejunostomy. As I mentioned, this is fairly early in our series, but at 3 a n d
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4 m o n t h s of follow-up these patients have had relief of their pain, are tolerating a regular diet, and are off all narcotic medication. However, I must emphasize these are clearly very preliminary data. Dr. Stellato asked about the role of lateral pancreaticojejunostomy. Surgeons are using it more a n d more often to treat small duct disease a n d reportedly have had good outcomes with minimal exocrine a n d endocrine insufficiency. We have not been satisfied with that, a n d we think there are some people with pancreatic disease who require excisional therapy and that includes distal pancreatectomy. Dr. Buchwald points out hyperlipidemia does affect the whole gland. What I think we are seeing in our two patients with hyperlipidemic pancreatitis is that during their bouts of recurrent pancreatitis they had glandular or ductal necrosis that has resulted in a pancreatic duct stricture. In patients who have hyperlipidemic pancreatitis, if they continue to have abdominal pain a n d inability to eat, they should be studied with ERCP looking for the presence of ductal strictures or stenosis. Dr. Keith b r o u g h t up the issue about neoplasms in our database. I d o n ' t know the answer to that question off the top of my head, a n d I will have to defer to our paper.