Chronic relapsing pancreatitis

Chronic

Relapsing

CHARLES MARKS,

M.D.,

From the Departments of Surgery, Marquette University Medical School, Milwaukee County General Hospital, Milwaukee, Wisconsin, and Veterans Administration Hospital, Wood, Wisconsin.

T

HE

RETROPERITONEAL

pancreas

the

makes

anatomic

assessing

plies deficiency

with

mellitus

calcification

radiologic

structural

disorder,

which

(Fig.

serum

it remains

the very

with

episodes

prominent

obstruction fibrosis,

difficult

ilarly,

preventing duct

frequently

of biliary

and

which

ciated

resulting

in a shrunken,

containing pancreatic

pancreatic

calculi,

or multiple

with intervening

dilated

areas filled with

creatic secretion.

(Fig.

often

theory

invoked

[I].

This

by

concept

Doubilet attributes

of

electrode

that [Z] on

stimulation

that stimulation

of the

of

the

body

causes

of the tail

to

the

left

lower

quadrant.

of the three areas re-

pain

extending

with radiation

across

to the back.

the

Clinical

study of these patients

indicates

extent

needs to be involved

the

of the pancreas

pathologic

abdominal

Mulholland

the

is of

It is noteworthy

stimulation

in a bandlike

epigastrium

of the reflux

and

alcoholism

and the pattern

pain, and stimulation

extending

sults

2.)

acceptance

feature

stimulation

Simultaneous

pan-

BILIARY PATHOLOGY

disease permits

does resec-

gives rise to pain in the left lower epigastrium

or

strictures

the presence

Neither

or gastric

In this large group of

indicate

mid-epigastric

and

to

to these

head gives rise to pain in the right

epigastrium,

deposits.

refractory

treatment.

pain utilizing

pancreatic

nodular

with chronic relapsthere is no evidence

of Bliss and his co-workers

hard,

long

is

or acalculous

of persistent

a prominent

of the pancreas

inspissated

biliary

functional

vagotomy,

a history

the studies

may

lithiasis,

else is the site of single

In one third of these patients

or

cholecystectomy

relief of the very severe pain asso-

degeneration,

is frequently

containing

anatomic

pain may vary in extent.

areas of calcareous duct

pancreatic

with this disorder.

always

hyperplasia, and cystic

to

the

totally

of surgical

tion provide

pan-

changes

patients,

ductal

Sim-

directed

and the pain attributable

remains

splanchnicectomy,

fibrosis,

tortuous,

disease

pancreatitis

pancreas

concept,

into

however,

parameters

demonstrate

organ

is present.

are rarely

parenchymal

The

cholecystitis

by

disordered

is

if cholelithiasis

ing pancreatitis,

PATHOLOGIC CHANGES

thereby

out

pancreatitis

chronically

this

or compression.

In two thirds of patients

pain

within the pancreas.

The

of

partial or complete

bile

also carried

associated

in architectural

of the

Sphincterotomy

PANCREATIC PAIN

pancrea-

of acute or subacute

of

a common

pancreatitis,

attacks

offshoot

In these situations,

chronic

have resulted

ducts.

calculi,

reflux

via

channel.

of the

in distention

choledochojejunostomy

to assess

relapsing

to spasticity

at this site caused by either spasm,

biliary

of acute

in

time repeated creatitis

logical

pancreatic

in serum amylase

although

pancreatic

a

in

pancreas

pain

resulting

readily overcoming

in

and the

the

and

thereby

calcareous

of

of Oddi,

becomes

im-

severe and agonizing chronic

1.) Elevations

lipase,

within

Wisconsin

of pancreatic

biliary

disturbance

Until

evidence

accompanies

titis.

Steatorrhea

indicates

efficiency.

provides objectively

basis.

attack

of pathologic

of its exocrine function

endocrine

change

difficulty

Milwaukee,

sphincter

the

inaccessible

provides

and extent

on a clinical

onset of diabetes its

and

the presence

processes

of

it relatively

sense

of

SITUATION

Pancreatitis

and

process back

that the whole

to produce pain

in

the

severe

so classically

asso-

ciated with pancreatitis.

recurrent 340

American Jouvnal of Surgevy

Chronic PANCREATIC

Relapsing

Pancreatitis

3-l 1

SURGERY

Increasing understanding of the importance of intrapancreatic ductal disorganization and obstruction has led to an attempt to decompress the pancreatic ductal system by transduodenal exploration of the pancreatic duct, with elimination of the obstructing mechanism by incision, dilatation, or very infrequently by removal of a single obstructing calculus. In these cases, operative pancreatography is useful in delineating multiple ductal strictures. Caudal pancreaticojejunostomy as described by Duval [A’] provides a suitable method of decompression of the pancreatic duct by amputating the tail of the pancreas in continuity with the spleen and establishing a distal pancreaticojejunostomy utilizing a Roux-en-Y loop; thereby, reflux of intestinal contents into the pancreatic duct is prevented 2nd retrograde drainage of the obstructed duct is concurrently established. (Fig. 3.) To provide drainage of more of the pancreatic duct, Doubilet [4] described the procedure of “split” pancreaticojejunostomy. This technic was introduced for patients with severe pain due to chronic relapsing pancreatitis in whom operative pancreatography demonstrated obstruction of the pancreatic duct. The operation has the merit of being technically simple and does conserve all pancreatic tissue. Transection of the body of the pancreas is followed by clearing out the duct and inserting a small French catheter into each opened end of the pancreatic duct. A defunctionalized Roux-en-Y loop is

FIG. 1. Chrottic relapsing pnncrcatitis with calcification in the hcati of the pancreas as well as a witleniqi: of tile duodenal loop and pyloric obstruction is tliscloic(l by barium study.

brought up between the sectioned ends of the pancreas and after closing the jejunal opening, two lateral pancreaticojejunal anastomoses are created to provide decompression of both ends of the pancreatic duct over the catheter 1%.hich is brought out through an anterior jejunal opening to the exterior. Increasing experience with the pathologic in chronic relapsing pancreatitis changes demonstrated the frequent presence of long or multiple strictures of the pancreatic duct. When such a state of affairs exists, none of the foregoing procedures can be expected to help, thus, total decompression of the duct with conservation of pancreatic parenchyma can only

3

2 IQc. 2. Specimen tion of duct. FIG. 3. Specimen

of pancreas

after subtotal

pancreatectomy

of spleen and tail of pancreas

jrjunostomy. L’ol. 113. March 1967

in patient

demonstrates with relapsing

areas of cystic degeneration pancreatitis

and oblitera-

who had distal pancrcatico-

Marks be established by longitudinal pancreaticojejunostomy [5]. Two main technical procedures can be utilized, each one making use of a defunctionalized Roux-en-Y loop after dividing the jejunum some 14 inches below the ligament of Treitz. 1. Ductal-jejunul anastomosis: The anterior surface of the pancreas is incised in its full extent up to the superior mesenteric vessels, thereby opening all pockets of retained pancreatic secretion and all calcareous debris, and intraductal calculi are removed. The defunctionalized limb of jejunum can be sutured to the longitudinally opened duct by side to side anastomosis. 2. Pancreatic implantation: The presence of a long pancreas firmly apposed to the spleen requires splenectomy and mobilization of the pancreas from the left as far as the superior mesenteric vessels. The tail of the pancreas is amputated at splenectomy and the dilated pancreatic duct found. A probe is passed into the duct, and the anterior wall of the pancreas and duct is incised, all structures being incised and the duct cleared so as to open up all pockets. After obtaining adequate drainage, the tail and body of the pancreas can be implanted into the open end of the defunctionalized jejunal limb. lnterrupted silk sutures are used to approximate the serosa of the jejunum to the surface of the pancreas beyond all incised areas, thereby providing optimal pancreatic drainage into the small intestine. Pancreatic Resection. The unrelenting nature of chronic relapsing pancreatitis is not infrequently refractory to the aforementioned tissue-conserving procedures with persistence of severe pain while diabetes mellitus and steatorrhea continue unabated. The role of pancreaticoduodenectomy and total pancreatectomy has received emphasis in the work of Whipple [6’,7], Priestley, Comfort, and Radcliff et al. [8], Waugh et al. [9], Longmire, Jordan, and Briggs [IO], and Zollinger, Keith, and Ellison [II 1. Distal pancreatectomy is, of course, indicated in the infrequent situation in which the pathologic process is localized to this portion of the pancreas. In our experience it has been a sequel only to blunt abdominal trauma with distal pancreatic injury. Distal pancreatectomy and splenectomy may be a preliminary to caudal pancreaticojejunostomy, as previously indicated.

Pancreaticoduodenectomy was demonstrated to be a feasible operation for cancer by Whipple in 1935 [6], first as a two stage and later as a one stage procedure. In 1946 he reported on the use of this procedure in several cases of pancreatic fibrosis with calcareous deposition [7]. In 1953 Cattell and Warren [12] recommended this procedure as the operation of choice for chronic relapsing pancreatitis, but very little enthusiasm has been engendered for this approach. In 1944 Priestley, Comfort, and Radcliff [8] published a report on total pancreatectomy for hyperinsulinism due to a benign pancreatic insulinoma; two years later Waugh et al. [9] described successful total pancreatectomy in four patients with chronic relapsing pancreatitis. Longmire, Rhoads and their co-workers [10,13] have also employed this procedure as have Schulte and Ellison [14] ; however, it must be stressed that this is a formidable operation for a benign disease. The recommendation of Child and Fry [15] that 95 per cent pancreatic resection, leaving a portion of the head within the duodenal concavity, reduces the magnitude of the operation without loss of efficacy in curing the severe intractable pain of chronic relapsing pancreatitis is worthy of consideration and in this series this procedure was carried out in one patient with success after the previous failure of more conincluding cholecystecservative operations, tomy, choledochostomy, sphincterotomy, and caudal pancreaticojejunostomy. CASE

REPORT

The patient (N. R. C.) was a forty-four year old white man. In the previous eighteen years he had had several attacks of acute pancreatitis associated with hyperamylasemia and spontaneous resolution, with the development of persistent severe abdominal pain which radiated through to the back and which had been refractory to many surgical procedures. 4t the age of eighteen years, cholecystectomy had been performed, with no evidence of gallstones. Seven years later he was admitted to a hospital because of acute intestinal obstruction for which laparotomy and adhesiolysis were carried out. During this time he had consumed a considerable amount of alcohol but in later years had ceased drinking entirely. Diabetes mellitus developed, with fasting blood sugar being 147 mg. per cent. He began to have mild steatorrhea, the stool samples demonstrating many fat globules and defective absorption of radioAmerican

Journal

of Surgery

Chronic Relapsing Pancreatitis

iodinated triolein. Flat plates of the abdomen over the years gradually demonstrated a widening of the duodenal loop; subsequently, calcification became evident in the region of the pancreas. Nine years ago, he returned to the hospital because of constant pain and a weight loss of 50 pounds. At this time laparotomy was performed and a cystic duct remnant measuring 2 inches long was removed; operative cholangiography demonstrated a normal common duct. Sphincterotomy was performed via a transduodenal approach. In the ensuing seven years he was frequently readmitted to the hospital with attacks of pancreatitis. Therefore, six months ago he again underwent laparotomy at which time distal pancreatectomy and splenectomy were performed in addition to pancrcaticojejunostomy utilizing a defunctionalized Koux-en-U loop. This section of pancreas revealed extensive fibrosis and replacement of most of the acini with fibrous tissue. Four months later he was readmitted to the hospital having lost an additional 40 pounds in weight and complaining elf severe epigastric pain radiating to the back and requiring heavy narcosis. Significant laboratory data were serum amylase between 50 and 75 Somogyi units, urine amylase 9(i units, alkaline phosphatase :;i.1King-Armstrong units, and bromsulfalein 6.9. ,Subsequently, repeated studies of alkaline phosphatase demonstrated levels of 11.5 and 9.7 King-Armstrong units. In \-iew of persistent severe pain associated with known chronic relapsing pancreatitis, 95 per cent subtotal pancreatectomy was elected. Exploration was performed through a long transverse epigastric incision, and tedious dissection was necessary to divide the massive dense adhesions consequent to the many previous laparotomies. After the stomach and transverse colon were identified, the gastrocolic omentum was divided and the lesser sac entered. The area of the previous pancreaticojejunostomy was 1’01.113.

March

1967

343

gradually mobilized (Fig. 4A), the area of jejunum transected, and the open end closed in two layers utilizing chromic catgut with mucosal closure and interrupted No. 3-O silk for seromuscular reinforcement. The splenic artery was identified, mobilized, and ligated. The pancreas was mobilized from the posterior abdominal wall and gradually dissected off the splenic vein until the contluence of the splenic and superior mesenteric and portal veins was reached. The second part of the duodenum was mobilized utilizing the Kocher maneuver, and a decision had to be reached whether to be satisiied with 93 per cent pancreatectomy or to perform total pancreatectomy and duodenectomy. In view of the fibrous involvement of the portal vein, it was decided to leave the small portion of gland nestling within the concavity of the duodenum. The pancreas was thus transected at this site and the specimen removed for study. (Fig. *R.) Interrupted silk sutures were used to appose the peri pancreatic capsular tissue in this area and the abdomen was closed with drainage. Because of the great difficulty in dealing with the intraperitoneal adhesions and the slow but steady ooze resulting from prolonged and tedious dissection, 12,500 cc. of blood were replaced to compensate the estimated blood loss of 13,.X)0 cc. In addition, 2 units of fresh frozen plasma and 2 units of regular plasma as well as 2,800 cc. of a 5 per cent dextrose and saline solution were administered in the course of the four hour operation. Immediately after completion of the procedure, the patient’s blood sugar was 2X mg. per cent, and examination of the urine disclosed the presence of a 4+ glycosuria. Nine hours later serum amylase was 102 units and blood sugar had dropped to 168 mg. per cent with no perceptible glycosuria. Penicillin were administered intraveand Chloromycetin@ nously and the patient pursued a benign course.

Marks being discharged from the hospital on the twentyfourth postoperative day. Follow-up study of this patient over the ensuing six months has indicated a most favorable result with complete absence of pain. In the first three weeks after operation, there was a remarkable improvement in his diabetic state, with a drop in the fasting blood sugar from a preoperative mean level of 236 mg. per cent to normal. Subsequent elevation in blood sugar levels has led to its stabilization at IGOmg. per cent, this being readily controlled with 15 units of NPH insulin. Triolein absorption studies have revealed no change in the amount of fecal fat loss, and with improvement in appetite he has gained X pounds in weight. CLINICAL

MATERIAL

Thirty-seven patients with chronic relapsing pancreatitis have been studied in the surgical services at the Milwaukee County General Hospital and Veterans Administration Hospital. Surgery was indicated in twenty-five patients who underwent a total of forty-seven surgical procedures in an attempt to lessen the severe and intractable pain. These procedures included the following: cholecystectomy, thirteen; choledochostomy, six; sphincterotomy, six ; pancreatic cyst drainage, eight; pancreatic abscess drainage, one; transductal removal of pancreatic calculus, one; gastric resection, two; vagotomy and gastrojejunostomy, one; distal pancreatectomy with pancreaticojejunostomy, six ; longitudinal pancreatic0 jejunostomy, one ; subtotal pancreatectomy, one; total pancreatectomy, one. These operations were performed for biliary disease (cholecystitis, cholelithiasis, choledocholithiasis, or cholesterosis of the gallbladder), eight (32 per cent); traumatic pancreatitis with pseudocyst, two (8 per cent) ; alcoholism, fifteen (60 per cent). It is evident that in 60 per cent of the group of patients who presented for surgical therapy, chronic relapsing pancreatitis was attributable to long-sustained chronic alcoholism ; 8 per cent of this group (two patients) presented with a pseudocyst after traumatic pancreatitis and 32 per cent had associated biliary disease confirmed surgically or pathologically after study of the removed gallbladder. MORTALITY

Three patients in this series died as a result of the disease or its surgical treatment. Two of the three patients died within two weeks of the surgical procedures, providing an operative mortality of 4.5 per cent but a case mortality of

8 per cent. One of these patients died after drainage of a traumatic pancreatic pseudocyst consequent to a crush injury of the abdomen. The second death occurred in a patient with chronic relapsing pancreatitis attributable to sustained alcoholism. Distal pancreatectomy and splenectomy with a Roux-en-Y pancreaticojejunostomy were performed, but death occurred ten days later subsequent to the development of a subphrenic abscess and peritonitis. The third death occurred in a patient with chronic relapsing pancreatitis attributable to alcoholism. Cholecystectomy had been performed in 1955 and gastrectomy and caudal pancreatectomy with pancreaticojejunostomy in 1956. Eight years later he was admitted to the hospital with gram-negative septicemia to which he succumbed. This terminal episode complicated choledocholithiasis with acute suppurative cholangitis and the development of microabscesses of the liver. This case attests to the problems that may be associated with the development or persistence of biliary disease and its sequelae. POSTOPERATIVE

PROGRESS

Inherent in the fact that forty-seven operative procedures were necessary in these twentyfive patients is the inference that biliary surgery in patients without biliary tract disease is unlikely to cause any lessening of the pain of relapsing pancreatitis. An understanding of the pathologic changes in the pancreas emphasizes the improbability of relief resulting from indirect operations. Drainage of pancreatic cysts is certainly associated with success in alleviating symptoms as well as in preventing fatal rupture of an enlarging cyst with its persistent hyperamylasemia. In two patients, pancreatic cystectomy with external drainage was performed; in one of these patients, persistence of a pancreatic fistula occurred, resolving slowly with spontaneous closure. In the remaining five patients, internal drainage was achieved by cystogastrostomy in one and cystojejunostomy in four. Their postoperative course was uneventful with complete relief of symptoms. ACUTE

PANCREATITIS

Acute exacerbation

of chronic pancreatitis American Journal of Surgery

Chronic

Relapsing

has occurred in two patients. In one of these an episode of acute pancreatitis developed two years after cholecystectomy and sphincterotomy in an alcoholic patient whose biliary tract had been free of disease at surgery. The acute attack resolved with conservative management and the patient is being observed, having no strong indication at present for more radical surgery. The second patient, also an alcoholic, had undergone cholecystectomy, choledochostomy, and sphincterotomy for chronic pancreatitis associated with cholelithiasis in 1958. The following year caudal pancreatectomy with pancreaticojejunostomy was performed with good effect, leading to total relief from pain. One year later the patient was readmitted to the hospital because of obstructive jaundice due to common duct stones and cholangitis; at this time choledochostomy was performed with removal of common duct stones. This patient remained well for three more years at which time he was readmitted to the hospital with an attack of acute pancreatitis and responded to conservative management. This patient’s progress is at present being observed.

Pancreatitis

of more conservative operations had been ineffective and whose subsequent metabolic management retnained simple and uncomplicated. REFERENCES I.

2.

3.

4.

5.

6.

7.

8.

RESULTS

Follow-up study of the twenty-two surviving patients who had previously undergone surgery indicates that apart from the setbacks suffered by the three patients described, the severe pain of chronic pancreatitis had been lessened by definitive operations on the pancreas in those patients in whom no biliary disease was present. In those patients in whom concomitant biliary disease had been present, attention to this underlying cause resulted in some alleviation of the patient’s symptoms. SUMMARY

AND CONCLUSIONS

The intractable abdominal pain attributable to chronic relapsing pancreatitis can be lessened by well selected operative procedures. Although procedures directed to the biliary tract frequently decrease the pancreatic pain associated with biliary tract disease, procedures directed to the pancreas itself are necessary in the absence of biliary tract abnormality. The curative scope of partial pancreatectomy is expressed in terms of a patient in whom a series

Vol. 113. March

1967

345

9.

10.

11.

12.

13.

14.

15.

DOUBILF,.~,H. and MULHOLLAND, J. H. Eight year study of pancreatitis and sphincterotomy. J.ilX.A., 160: 521, 1956. BLISS, W. R., BURCH, B., MARTIN, M. M., and ZOLLINGER, R. M. Localization of referred pancreatic pain induced by electric stimulation. Gastuoenterology, 16: 317, 1950. DUVAL, M. D. Caudal pancreatico-jejunostomy for chronic relapsing pancreatitis. Ann. Surg., 140: 775, 1954. DOUBILET, H. “Split” pancreatico-jejunostomy for obstruction of the pancreatic duct. In: Current Surgical Management, Philadelphia, 1965. W. B. Saunders Co. PUESTOW, C. B. and GILLESBY, W. J, Retrograde drainage of the pancreas for chronic relapsing pancreatitis. Arch. Surg., 76: 898, 1958. WHIPPLE, A. 0. Surgical treatment of carcinoma of the ampullary and head of the pancreas. .4m. J. Surg., 40: 260, 1938. WHIPPLE, A. 0. Radical surgery for certain cases of pancreatic fibrosis associated with calcareous deposits. Ann. Surg., 124: 991, 1946. PRIESTLY, J. R. M., COMPORT, W., and RADCLIFF, J. Total pancreatectomy for hyperinsulinism due to islet cell adenoma. Survival and cure at 16 months after operation. Presentation of metabolic studies. Ann. Surg., 119: 211, 1944. WAUGH, J. M., DIXON, C. F., CLAGETT, 0. T., BOLLMAN, J. L., SPRAGUE, R. G., and COMFORT, B. W. Total pancreatectomy: a symposium presenting 4 successful cases and a report on metabolic observation. Proc. Staff Meet. Mayo Cl&., 21: 25, 1946. LONGMIRE,W. P., JORDAN, P. H., and BRIGGS, J. D. Experience with resection of the pancreas in the treatment of chronic relapsing pancreatitis. Ann. Surg., 144: 681, 1956. ZOLLINGER,R. M., KEITH, L. M., JR., and ELLISON, E. H. Pancreatitis. New England J. Med., 261: 497, 1954. CATTELL, R. B. and WARREN, K. W. Surgery of the Pancreas. Philadelphia, 1953. W. B. Saunders co. RHOADS, J. E., ZINTEL, H. A., and HELING, J., JR. Results of operations of the Whipple type in pancreatus-duodenal carcinoma. Ann. Surg., 146: 661, 1957. SCHULTE, W. J. and ELLISON, E. H. Total pancreatectomy for chronic calcific pancreatitis. In: Current Surgical Management. Philadelphia, 1965. W. B. Saunders Co. CHILD, C. G., III and FRY, W. J. 95% Distal pancreatectomy for chronic pancreatitis. Ann. Surg., 165: 543, 1965.