Carcinoma of the Ampulla of Vater Whipple Operation and Ten-Year Arrest in Three Cases

SEVENTEEN years have elapsed since Whipple, Parsons and Mullins6 presented. their original radical procedure of two-stage pancreatoduodenectomy in the sugical treatment of carcinoma of the ampulla of Vater. Until then the accepted operation for malignant lesions of the ampulla and the papilla of Vater was transduodenal excision of the tumor, and complete surgical eradication of the lesion was rarely accomplished. In the intervening years many modifications in the surgical technique of pancreatoduodenectomy have been reported, but the procedure in general has become known throughout the surgical world as the Whipple operation. Also, as the technique of the procedure has become standardized, surgeons have adapted the operation to malignant lesions of the head of the pancreas, the com-

For their value as factors in the evaluation of pancreatoduodenectomy for carcinoma of the ampulla of Vater, the late results in three cases in which the Whipple operation was performed for this lesion are presented. At the time of the report, the time that had elapsed since operation was 12 years in one case, 11 in another and 10 in the third. After this article was written, one patient died of carcinoma of the body of the pancreas, but whether the lesion was a recurrence, a metastatic growth, or a second primary lesion could not be determined. There was no evidence of recurrence or metastasis in two of the patients. This report is based upon observation in recent surgical care of two of the patients and upon direct information of the other patient. SEVENTEEN years have elapsed since Whipple, Parsons and Mullins6 presented. their original radical procedure of two-stage pancreatoduodenectomy in the sugical treatment of carcinoma of the ampulla of Vater. Until then the accepted operation for malignant lesions of the ampulla and the papilla of Vater was transduodenal excision of the tumor, and complete surgical eradication of the lesion was rarely accomplished. In the intervening years many modifications in the surgical technique of pancreatoduodenectomy have been reported, but the procedure in general has become known throughout the surgical world as the Whipple operation. Also, as the technique of the procedure has become standardized, surgeons have adapted the operation to malignant lesions of the head of the pancreas, the common duct, the stomach and duodenum and other lesions in the area, some of which are benign in character. 2 4, 5 It would seem that the technique of the procedure has become more standardized than have the indications for the operation, and it is only through adequate follow-up in individual cases that the operation can eventually be evaluated in its application to a specific disease. The purpose of this paper is to report the late result in three patients upon whom Whipple operations were performed, by the late Dr. Verne C. Hunt, for carcinoma of the ampulla of Vater. One of the operations was done 12 From the Surgical Service, St. Vincent's Hospital, Los Angeles.
Presented before the Section on General Surgery at the 80th Annual Session of the California Medical Association, Los Angeles, May 13 to 16, 1951. years, one 11 years, and one more than 10 years ago.
Dr. Hunt and the author, during their association, operated upon five patients who had carcinoma of the ampulla of Vater. The surgical procedures consisted of transduodenal cautery excision of the ampulla of Vater, with reimplantation of the common duct and the duct of Wirsung into the duodenum in two cases, and one-stage Whipple procedure in three cases. In 1941 Hunt4 reported the results of the two transduodenal cautery excision procedures and two of the Whipple procedures. At that time the results were as follows: Of the two patients upon whom transduodenal excision of the ampulla had been done, one died 25 months after the operation of extensive metastases to the mediastinum. The other was alive, but with metastases, 34 months after the operation. (This patient died four years after the operation of generalized abdominal metastases.) Both the patients in whom the Whipple procedure was carried out were alive and well at the time of Dr. Hunt's report. Subsequently Dr. Hunt and the author employed the Whipple procedure in another case which was not reported. Two of the three patients recently were again under the author's surgical care, and direct information concerning the other is available to him.

CASE REPORTS
The cases are numbered 3, 4 and 5 in order that cases 3 and 4 may be numbered as they were in Dr. Hunt's original report. CASE 3 (Abstracted from Dr. Hunt's report): A woman 60 years of age, first observed March 13, 1940, had progressive, painless jaundice of four months' duration, with loss of 50 pounds in body weight. There was no history suggestive of biliary colic at any time. The patient was emaciated and there was intense jaundice. Areas of excoriation and multiple pustules over the entire body were noted. The liver was enlarged to the level of the umbilicus and the distended gallbladder was palpable. There was complete uterine prolapsus and edema of the lower extremities to the knees. The diagnosis was carcinoma of the head of the pancreas or common duct. At operation the gallbladder was observed to be distended and the common duct was dilated. When the common duct was explored a tumor 2 cm. in diameter was palpated in the ampulla. The duodenum was incised and the tumor was visualized.
Procedure. One stage Whipple operation: Resection of the duodenum and the head of the pancreas; ligation and division of the common duct; division and ligation of the duct of Wirsung; cholecystogastrostomy, posterior gastroenterostomy and choledochostomy.
The pathologic diagnosis was adenocarcinoma, Grade II, of the ampulla of Vater, with invasion of the pancreas. was inserted into the sinus and continuous suction was maintained. After 27 days the sinus was packed with gauze, drainage ceased and the sinus healed in a few days. The patient was dismissed from the hospital 48 days after the operation. Follow-up: After the death of Dr. Hunt in 1943, the patient had no medical care throughout the remainder of the war years. When examined in July, 1947, the patient weighed 175 pounds and the chief complaints were related to obesity and uterine prolapsus. Appetite and bowel habits were normal. There was no evidence of recurrence or metastases.
Observed again in July, 1950, the patient, then 71 years of age, had difficulty in voiding because of prolapsus, and there was intermittent bleeding from the uterus. There were no digestive complaints and no evidence of recurrence or metastases. The weight was still 175 pounds.
Vaginal hysterectomy was carried out. The postoperative course was very satisfactory and the patient was dismissed from the hospital on the eighth postoperative day. When last observed she was entirely well. f f t CASE 4 (Abstracted from Dr. Hunt's report): A woman 43 years' of age was admitted to hospital January 29, 1941, because of anorexia, nausea and pain radiating into the back for three months; jaundice for one month, and a loss of thirteen pounds in body weight.
Neither the liver nor the gallbladder was palpable. Secondary anemia was noted in laboratory studies, and calcification of the gallbladder was observed roentgenographically.
The preoperative diagnosis was calculous disease of the gallbladder and of the common duct. At operation, the gallbladder was observed to be thick-walled and it was con- tracted on a single large stone. The common duct was greatly dilated.
Operation included cholecystectomy, exploratory choledochotomy, and T-tube drainage of the common duct.
When the T-tube was clamped, profuse bile drainage developed. In a cholangiogram, complete block of the common duct was observed. In exploratory duodenotomy' six weeks later an ampullary tumor which seemed to involve the posterior wall of the duodenum and the head of the pancreas was observed. Total duodenectomy and cautery excision of part of the head of the pancreas, pancreato-jejunostomy, choledochojejunostomy and posterior gastroenterostomy were carried out. (The open end of the jejunum was drawn up and sutured over the severed head of the pancreas.) The pathologic diagnosis was adenocarcinoma of the papilla of Vater, Grade III, with involvement of the duodenum and extension to the head of the pancreas and adjacent lymph nodes. (Figure 2.) The postoperative course was entirely satisfactory. There was drainage of bile but not of pancreatic secretion. The patient was dismissed from the hospital on the 24th day.
Follow-up: The patient remained well unt'il June, 1949, when acute obstruction of the small intestine developed. At operation' the obstruction was observed to be caused by primary carcinoma of the ileum, and resection with end-toend anastomosis was done. Thereafter the patient had vague distress in the right upper quadrant of the abdomen, but at the time of this report there was no evidence of recurrence or metastasis of either of the primary tumors.
(After this article was submitted for publication, the patient in Case 4 was operated upon elsewhere for recurrent obstruction of the small bowel. At operation a mass, CARCINOMA OF THE AMPULLA OF VATER described as the size of a large lemon, was observed in the body of the pancreas. A specimen of the mass was excised and the pathologic report was mucoid adenocarcinoma. The pathologist made the following comment: "While the tumor is not histologically identical with the structures of the previous known primaries in the ampulla and in the jejunum, it is compatible with recurrence or metastasis of these tumors. Likewise, it may represent a separate primary carcinoma of the pancreas, since primary carcinoma of the pancreas may produce this morphology." As the patient was not in satisfactory condition for pancreatectomy, the incision was closed. When reoperation was carried out several months later, the tumor was deemed inoperable. It had grown considerably in size and had encircled the aorta and the portal vein. The patient died August 1,1951. It was never possible to determine whether this tumor was a recurrence or a metastasis of the original tumor or whether it was another primary carcinoma of the body of the pancreas.) t f f CASE 5 (not previously reported): A man 55 years of age was observed July 29, 1941, because of jaundice following cholecystectomy and common duct drainage which had been done elsewhere in September, 1940. The patient had returned to the surgeon in November, 1940, because of chills, fever and jaundice. The common duct then was explored. No stones were found and an anastomosis was made between the common duct and the pylorus. A biliary fistula developed, and material drained from it intermittently. The jaundice cleared for about three months, but with the intermittent cessation of drainage from the fistula, the jaundice deepened progressively, chills and fever occurred and the body weight decreased 35 pounds.
When examined, the patient was deeply jaundiced and the body weight was 140 pounds, but the general condition was fair despite the long illness, probably because of the intermittent drainage of bile. There was a sinus, which was not draining, in the right upper quadrant of the abdomen. The liver was palpable 4 cm. below the costal margin.
The -preoperative diagnosis was stricture of the common duct, and at operation stricture of the distal half of the common duct was observed, with dilation of the common duct and of the hepatic ducts above the stricture. The common duct was reconstructed over a rubber tube.
Recovery was satisfactory. There was no external biliary drainage. The patient was dismissed from the hospital on the 19th postoperative day.
On November 3, 1941, chills, fever and progressive jaundice developed. In an x-ray film of the abdomen, it was noted that the tube, which had been placed in the common duct, had passed. Jaundice seemed to fluctuate somewhat in intensity, but the chills and fever continued. The patient was operated upon again and the common duct was re-explored, exploratory duodenotomy was carried out and a tumor of the ampulla was observed. Duodenectomy, cautery resection of the head of the pancreas, pancreatojejunostomy, choledochojejunostomy over a rubber tube splint and posterior gastroenterostomy were done. (The open end of the jejunum was sutured over the severed end of the pancreas.) The pathologic diagnosis was papillary adenocarcinoma, Grade I, of the major duodenal papilla. (Figure 3.) Postoperative drainage of fluid which had the characteristics of pancreatic secretion developed. This was managed by suction and as much as 2,000 cc. of fluid was withdrawn in 24 hours. However, the amount had decreased considerably at the end of two weeks and drainage ceased entirely in four weeks. The patient was dismissed from the hospital on the 18th postoperative day.
The patient remained well until he was hospitalized May 25, 1942, for meningitis. There was a heavy growth of pneumococci, type 29 (Newfeld) on cultures of spinal fluid.
Sulfadiazine and sodium sulfadiazine were given and the  December, 1945, and then because of intermittent attacks of chills and fever, pain in the right upper quadrant of the abdomen, and jaundice. There were no palpable abdominal masses and in an x-ray film of the abdomen the rubber tube, which had been placed in the common duct, was observed to be still present. It was advised that the tube be removed surgically because of the probability that jaundice and cholangitis were caused by obstruction of the tube by bile sediment and stony material. Operation was refused and the patient was not observed again until September 6, 1950. In recent months jaundice had been constant, chills and fever frequent and pain and ache in the right upper quadrant of the abdomen increasingly severe. Body weight had decreased 45 pounds and the patient was emaciated and completely incapacitated.
The jaundice was of bronzing type. The liver was hard and tender and could be outlined well below the costal margin. There were no abdominal masses or nodules and no ascites. There was pronounced secondary anemia. The urine contained 2-plus albumin, and bile. In other laboratory data there was evidence of extensive liver damage. The rubber tube was roentgenographically observed to be still present in the right upper abdomen, and there were four shadows of what appeared to be calculi arranged transversely to the left of the tube at the level of the second lumbar vertebra. (Figure 4.) The preoperative diagnosis was: (1) obstructive jaundice caused by obstruction of the rubber tube by bile sediment and stony material, (2) extensive liver damage and (3) pancreatic calculi.
At operation, dense adhesions involving the colon, the liver, the closed end of the stomach and the old choledocho- jejunostomy were observed. The liver was enlarged and firm and had the appearance typical of biliary cirrhosis. When the jejunum was exposed the common duct was observed to be dilated and the rubber tube was readily palpable because it was encased in a hard mass of stony material fully four cm. in diameter within the scarred common duct. The distal end of the rubber tube was buried in jejunal mucosa with a minute biliary fistula evidenced by a trickle of bile along the side of the tube. The tube was entirely filled with stony material. The stones in the pancreatic duct were palpable. In exploration of the abdomen, no evidence of tumor was noted.
Jejunotomy, removal of the rubber tube, choledocholithotomy, pancreolithotomy and T-tube drainage of the common duct through jejunostomy were carried out. The jejunum was incised longitudinally distal to the choledochojejunostomy, the rubber tube was exposed at the end and extracted from the common duct and, by means of scoops, 15 grams of stony material was removed from the duct.
Irrigation of the duct was productive of more material which was not weighed. A sinus tract into the head of the pancreas was probed and dilated and the four stones were removed from the duct. (Figure 5.) T-tube drainage of the common duct was established by inserting the tube into the jejunum and passing the proximal end of the T well into the common duct. The jejunum was sutured about the long arm of the T, and the tube was brought out through a stab incision.
Postoperatively there was scant flow of watery green bile with offensive odor, and the jaundice increased for the first week. It appeared that the liver was damaged beyond ade- quate function. However, at the end of the first week the daily output of bile began to increase and the jaundice became static. The patient was dismissed from the hospital to a rest home on the eleventh postoperative day. Jaundice fluctuated and recovery was very slow. Irrigation of the T-tube was productive of gravel from time to time, and the character of the bile remained watery and at times purulent. At the end of two months the jaundice had cleared and the patient had gained ten pounds. Eight months after the operation, recovery still was not complete. There was a gain of 25 pounds in body weight, there was no jaundice, chills or fever, the T-tube was clamped most of the time but irrigation of the tube from time to time still was productive of some bile gravel, and the patient occasionally had colic. DISCUSSION The original slides of the tumors in the cases reported were reviewed with Dr. James E. Kahler, pathologist, St. Vincent's Hospital, Los Angeles, and with Dr. John W. Budd, pathologist, Los Angeles Tumor Institute, and they concurred in the original diagnoses. While tumors of this type have been called carcinoma of the ampulla, it has been pointed out by others and it is evident from study of the lesions in Cases 3 and 4 that it is often impossible to determine the origin. The tumors in Cases 3 and 4 were almost identical in that they involved the papilla, the ampulla, the common and pancreatic ducts and the wall of the duodenum and invaded the head of the pancreas. Despite the tendency to local invasion, the curability of these lesions, in contrast to that of carcinoma of the head of the pancreas, by the operation of pancreatoduodenectomy is by now well recognized. This contrast is explained by the essential differences in the pathologic nature of the two lesions. Carcinoma of the papilla usually is less malignant, tends to produce the outstanding symptom of obstructive jaundice earlier, and to metastasize later than does carcinoma of the head of the pancreas. Miller and co-workers5 observed that the perineural lymphatics of the duodenum, pancreas and common duct were involved by malignant cells in 66.6 per cent of the 27 cases in which radical operation was done for carcinoma of the head of the pancreas and malignant cells were found in the transected end of the common duct in four of the cases. These phenomena were not observed in relation to lesions of the papilla.
With regard to Case 3 it is noteworthy that although the pancreatic duct was ligated, the patient had no digestive or metabolic disturbance. In the immediate postoperative period, drainage of pancreatic secretion and bile developed and suction was applied to the sinus until the 27th postoperative day when the external sinus was packed and the drainage ceased. In order to explain the excellent gastrointestinal function, one might postulate that when the external sinus was packed an internal sinus formed between the pancreas and a defect in the end of the jejunum.
There seems to be no doubt that the tumor causing the intestinal obstruction in Case 4 was a primary lesion of the small bowel. This is consistent with the now not uncommon observation of multiple primary cancers in a person who probably will die eventually of one of them or of another malignant lesion.
The retention of the rubber tube within the common duct in Case 5 was not intended. Normally such tubes pass in a matter of weeks, but no doubt the dense scarring of the duct produced by the three previous operations caused retention in this instance. It is remarkable that the patient lived despite five years of intermittent obstructive jaundice and the associated cholangitis and liver damage. From the postoperative course it was evident that not only was the connnon duct filled with bile sediment, but that the hepatic ducts and no doubt many of the interlobar ducts contained the same material due to the prolonged obstruction. It is impossible to say how completely the biliary tract will return to normal function or how long it will take to do so. 1930 Wilshire Boulevard.