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Ulcerogenic tumor of the duodenum
Ulcerogenic Tumor of the Duodenum William E. Evans, MD, Columbus, Ohio Raymond G. Armstrong, MD, Lackland, Texas William Schulte, MD, Milwaukee, Wisconsin John C. Garancis, MD, Milwaukee, Wisconsin
Fulminating ulcer disease associated with pancreatic islet cell tumors has been reported frequently [1,21. Occurrence of the Zollinger-Ellison syndrome in association with duodenal tumors has been less often encountered [3-51. Experience with three such cases is reviewed. Case Reports Case I. The patient (MC), a forty-three year old black woman, developed typical ulcer symptoms and in February 1963 an ulcer of the greater curvature of the stomach was roentgenographically demonstrated. She was admitted to the Milwaukee County General Hospital in March 1963 because of severe epigastric pain and vomiting. X-ray studies showed the ulcer to have healed on antacid therapy, but a pyloric channel ulcer was identified on follow-up films three weeks later. A twelve hour overnight collection of gastric secretion showed a volume of 410 mm with 115 mEq/L of free acid. There was no augmentation of acid output after histamine stimulation. Symptoms recurred four weeks later, and a gastric ulcer was again identified. Exploration was carried out, and a gastric and duodenal ulcer was identified. Numerous peripancreatic nodes were obtained, but tumor could not be identified by frozen section examination. A 1 cm mass was found in the tail of the pancreas and resected, but no tumor was identified. Since the diagnosis of islet cell tumor could not be verified microscopically, the operative treatment was confined to selective vagotomy and hemigastrectomy. Permanent sections showed a 3 by 8 mm submucosal tumor from the resected cuff of duodenum interpreted to be a “carcinoid tumor.” Several small lymph nodes showed metastatic tumor of the same configuration.
From the Medical College of Wisconsin, Milwaukee, Wisconsin. Reprint requests should be addressed to Dr Evans, Department gery, The Ohio State University Hospital, 410 West 10th Avenue, bus, Ohio 43210.
598
of SurColum-
The patient was lost to follow-up study. Three years later, in June 1966, she was admitted to a hospital in St. Paul, Minnesota complaining of abdominal pain. Stoma1 ulceration was identified on gastrointestinal contrast series, and transthoracic vagotomy was performed. In April 1967, stoma1 ulceration recurred. In September 1967, perforation of the stoma1 ulcer occurred, and the patient underwent total gastrectomy. No tumor was identified at the time of surgery. The patient was last seen in March 1968, and was doing well, five years after the original demonstration of metastatic tumor.
Comment: Because of inability to establish a tissue diagnosis at the time of initial operation in 1963, vagotomy and hemigastrectomy were carried out. The significance of the “carcinoid tumor” identified on permanent sections was not appreciated and fulminant ulcer diathesis continued until total gastrectomy was finally performed in 1967. When last evaluated in March 1968, the patient was doing well approximately five years after the duodenal tumor and lymphatic metastases were identified.
Figure 1. Tumor in duodenal wall. Hematoxylin eosin stain; original magnification X 10.
and
The American Journal of Surgery
Ulcerogenic
Case II. The patient (JC), a forty year old black man, underwent emergency plication of a perforated duodenal ulcer at the Milwaukee County General Hospital in March 1962. Prior to discharge, twelve hour gastric analysis was carried out, revealing 460 mm of gastric drainage with 89 mEq/L of free acid. He returned in July 1962 with epigastric pain. An active ulcer was demonstrated by barium contrast studies. Findings on gastric analysis were essentially unchanged. Persistent epigastric pain led to the patient’s readmission in September 1963, and selective vagotomy and hemigastrectomy were carried out. The patient was not seen again until January 1965, when iron deficiency anemia, weakness, and abdominal pain led to re-evaluation. The upper gastrointestinal series showed marked mucosal edema and irregularity of the proximal small bowel immediately distal to the stomach and a moderately dilated jejunum consistent with excessive acid production. Antacid therapy was reinstituted, resulting in control of the symptoms and demonstration of ulcer healing. The patient was readmitted in March 1966 with active massive gastrointestinal hemorrhage. Blood was replaced, and the hemorrhage spontaneously stopped. Twelve hour gastric analysis showed 700 mm of gastric drainage with 20 mEq/L of free acid. The Hollander test indicated intact vagal trunk. Barium studies demonstrated ulceration of the lesser curvature, for which truncal vagotomy and re-resection were carried out. Pain recurred in August 1965. The patient required readmission in May 1966 because of severe anemia. Barium studies showed confined perforation of the lesser curvature ulcer. Overnight gastric analysis contained 700 mm of gastric juice with 54 mEq/L of free acid. Finally in August 1966, total gastrectomy was performed. At operation multiple ulcers were seen to occupy nearly the entire gastric remnant. No tumor was identified. The patient died in March 1968 of chronic pancreatitis presumed to be the result of chronic alcoholism. At autopsy a submucosal duodenal islet cell tumor was identified along with involved regional nodes containing metastases. The pancreas was free from tumor. Figure 1 shows the submucosal tumor found in the first portion of the duodenum; Figure 2 is a high powered view showing invasion of Brunner’s gland; and Figure 3 is a higher powered view demonstrating regular nuclei arrangement of the cells in sheets mimicking carcinoid tumor. Histologic interpretation was islet cell adenocarcinoma of the duodenum.
Tumor of Duodenum
Figure 2. Tumor in duodenal wall invading Brunner’s glands. Hematoxylin and eosin stain; original magnification X 30.
several hours’ duration. Intermittent epigastric pain, which usually was relieved by antacids, had been present for eight months. There had been no gastrointestinal bleeding. Epigastric pain resolved on antacid therapy within twelve hours of admission. Roentgenograms of the upper gastrointestinal tract did not demonstrate ulceration. The twelve hour overnight gastric analysis showed 3,100 mm of gastric juice with 310 mEq/L of free acid. The patient became asymptomatic during this period of hospitalization and was discharged. During the next six months severe pain occurred frequently and diarrhea consisting of three to four loose watery stools per day developed. The patient was readmitted in June 1967, and exploration carried out. There was no evidence of active ulcer. No tumor could be identified in the pancreas; however, biopsy specimens taken from peripancreatic lymph nodes showed metastatic tumors interpreted to be of islet cell origin. Total gastrectomy was performed. Prior to closure of the duodenal stump, a 1 cm
Comment: This patient presented relentless fulminating ulcer diathesis, for which multiple surgical procedures were required. At autopsy an 8 mm submucosal tumor was identified in the duodenum just distal to the line of previous resection. Despite numerous abdominal explorations the tumor was not identified, resulting in delay in proper definitive therapy. Case III. The patient (FY), a fifty year old white man, was admitted to Wilford Hall USAF Hospital in January 1967 for evaluation of severe epigastric pain of
Volume 124, November 1972
Figure 3. Regular nuclei with arrangement of cells in acini and sheets that mimic carcinoid morphologically. Hematoxylin and eosin stain; original magnification X 44.
597
Evans et al
Figure 4. Submucosal ner’s gland.
tumor is seen adjacent
to Brun-
submucosal nodule was identified in the first portion of the duodenum just distal to the line of resection. The nodule was removed with a cuff of the duodenal wall, and the duodenal stump was closed. Reconstruction was carried out by loop esophagojejunostomy and distal jejunojejunostomy. The excised portion of the duodenal wall demonstrated a submucosal tumor lying adjacent to Brunner’s glands. (Figure 4.) Higher power views were interpreted as showing carcinoid tumor of the duodenum. (Figure 5.) The Armed Forces Institute of Pathology reported the lesion to be a carcinoid-islet cell tumor of the duodenum. Comment: Four and a half years after total gastrectomy the patient is doing well. Persistent episodes of abdominal pain associated with extremely high gastric acid values led to exploration. A decision for total gastrectomy was based upon identification of metastatic islet cell tumor found in peripancreatic lymph node. Identification of the primary lesion resulted from careful palpation of the intraluminal duodenal stump. Despite the peripancreatic lymph node metastasis, the patient is doing well four and a half years after total gastrectomy.
specimen, although this was not identified at operation. Significance of this lesion was not appreciated. Only in case III was the tumor identified during surgery. This experience, as well as that of others, suggests that failure to obtain a positive tumor diagnosis during exploration of patients expected to have the Zollinger-Ellison syndrome should prompt careful evaluation of the duodenum. In these three cases, lymph node metastasis was present. Oberhelman previously reported that only five of eleven patients in his series with duodenal tumors associated with the Zollinger-Ellison syndrome had metastasis and that local excision of the duodenal lesion might be sufficient for control of ulcer diathesis [3]. The presence of lymph node metastasis indicated the need for total gastrectomy as the preferred primary treatment in the patients in this report. Failure to initially carry out total gastrectomy in two of these patients was followed by continued fulminating ulcer disease. In addition, primary tumor excision had been carried out in case I at the initial operation, but subsequently total gastrectomy was eventually required. In cases II and III the original histologic diagnosis of the tumor was carcinoid tumor of the .duodenum. The similarity of the histologic pattern under light microscopy between carcinoid and islet cell tumors of the duodenum has been described in detail by Weichert, Reed, and Creech [5]. This similarity may also occur when lesions arise from the pancreas. Schulte et al report that one third of the pancreatic non-beta cell non-insulin-secreting islet cell tumors exhibited areas that could be confused with carcinoid tumors [6]. These authors indicate that the final diagnosis must be based on the clinical history and course coupled with histologic appearance, the differential criteria being based upon behavior of the tumor [5,6].
Comments
That gastric hypersecretion and fulminating peptic ulcer disease can occur with duodenal tumors of “islet cell-carcinoid” type has been previously reported 13-51. Three additional cases are presented. Problems of diagnosis parallel those of other reports. Grossly these small lesions may be overlooked if careful intraluminal palpation of the duodenum is not carried out. In case II identification of the primary tumor escaped detection until autopsy despite several extensive explorations. In case I identification of the duodenal tumor resulted from histologic identification of a nodule identified in the surgical
598
Figure 5.
Higher power view showing trabeculae pattern.
The American Journal of Surgery
Ulcerogenic
References
Summary Three patients with “islet cell-carcinoid” tumors of the duodenum are reviewed. In each .of these cases the presence of lymph node metastasis eventually prompted total gastrectomy as the course of treatment. The patient in case I is now clinically free of tumor five years after operation. In case II the patient’s death occurred two years after surgery, and although tumor was found at operation, it was not related to his death. In case III the patient is alive and well five years after his surgical procedures.
Volume
124, November
Tumor of Duodenum
1972
1. Ellison EH, Wilson SD: The Zollinger-Ellison syndrome: reappraisal and evaluation of 260 registered cases. Ann Surg 160: 512, 1964. 2. Zollinger. RM, Ellison EH: Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg 142: 709, 1955. 3. Oberhelman HA Jr: Excisional therapy for ulcerogenic tumors of the duodenum. Arch Surg 104: 447,1962. 4. McCorriston JR: Heterotopic pancreatic tissue in wall of duodenum associated with bleeding duodenal ulcer. Canad J Surgl: 153,1958. 5. Weichert R, Reed R, Creech 0: Carcinoid-islet cell tumors of the duodenum. Ann Surg 165: 660,1967. 6. Schulte W: Personal communication.
599
Fulminating ulcer disease associated with pancreatic islet cell tumors has been reported frequently [1,21. Occurrence of the Zollinger-Ellison syndrome in association with duodenal tumors has been less often encountered [3-51. Experience with three such cases is reviewed. Case Reports Case I. The patient (MC), a forty-three year old black woman, developed typical ulcer symptoms and in February 1963 an ulcer of the greater curvature of the stomach was roentgenographically demonstrated. She was admitted to the Milwaukee County General Hospital in March 1963 because of severe epigastric pain and vomiting. X-ray studies showed the ulcer to have healed on antacid therapy, but a pyloric channel ulcer was identified on follow-up films three weeks later. A twelve hour overnight collection of gastric secretion showed a volume of 410 mm with 115 mEq/L of free acid. There was no augmentation of acid output after histamine stimulation. Symptoms recurred four weeks later, and a gastric ulcer was again identified. Exploration was carried out, and a gastric and duodenal ulcer was identified. Numerous peripancreatic nodes were obtained, but tumor could not be identified by frozen section examination. A 1 cm mass was found in the tail of the pancreas and resected, but no tumor was identified. Since the diagnosis of islet cell tumor could not be verified microscopically, the operative treatment was confined to selective vagotomy and hemigastrectomy. Permanent sections showed a 3 by 8 mm submucosal tumor from the resected cuff of duodenum interpreted to be a “carcinoid tumor.” Several small lymph nodes showed metastatic tumor of the same configuration.
From the Medical College of Wisconsin, Milwaukee, Wisconsin. Reprint requests should be addressed to Dr Evans, Department gery, The Ohio State University Hospital, 410 West 10th Avenue, bus, Ohio 43210.
598
of SurColum-
The patient was lost to follow-up study. Three years later, in June 1966, she was admitted to a hospital in St. Paul, Minnesota complaining of abdominal pain. Stoma1 ulceration was identified on gastrointestinal contrast series, and transthoracic vagotomy was performed. In April 1967, stoma1 ulceration recurred. In September 1967, perforation of the stoma1 ulcer occurred, and the patient underwent total gastrectomy. No tumor was identified at the time of surgery. The patient was last seen in March 1968, and was doing well, five years after the original demonstration of metastatic tumor.
Comment: Because of inability to establish a tissue diagnosis at the time of initial operation in 1963, vagotomy and hemigastrectomy were carried out. The significance of the “carcinoid tumor” identified on permanent sections was not appreciated and fulminant ulcer diathesis continued until total gastrectomy was finally performed in 1967. When last evaluated in March 1968, the patient was doing well approximately five years after the duodenal tumor and lymphatic metastases were identified.
Figure 1. Tumor in duodenal wall. Hematoxylin eosin stain; original magnification X 10.
and
The American Journal of Surgery
Ulcerogenic
Case II. The patient (JC), a forty year old black man, underwent emergency plication of a perforated duodenal ulcer at the Milwaukee County General Hospital in March 1962. Prior to discharge, twelve hour gastric analysis was carried out, revealing 460 mm of gastric drainage with 89 mEq/L of free acid. He returned in July 1962 with epigastric pain. An active ulcer was demonstrated by barium contrast studies. Findings on gastric analysis were essentially unchanged. Persistent epigastric pain led to the patient’s readmission in September 1963, and selective vagotomy and hemigastrectomy were carried out. The patient was not seen again until January 1965, when iron deficiency anemia, weakness, and abdominal pain led to re-evaluation. The upper gastrointestinal series showed marked mucosal edema and irregularity of the proximal small bowel immediately distal to the stomach and a moderately dilated jejunum consistent with excessive acid production. Antacid therapy was reinstituted, resulting in control of the symptoms and demonstration of ulcer healing. The patient was readmitted in March 1966 with active massive gastrointestinal hemorrhage. Blood was replaced, and the hemorrhage spontaneously stopped. Twelve hour gastric analysis showed 700 mm of gastric drainage with 20 mEq/L of free acid. The Hollander test indicated intact vagal trunk. Barium studies demonstrated ulceration of the lesser curvature, for which truncal vagotomy and re-resection were carried out. Pain recurred in August 1965. The patient required readmission in May 1966 because of severe anemia. Barium studies showed confined perforation of the lesser curvature ulcer. Overnight gastric analysis contained 700 mm of gastric juice with 54 mEq/L of free acid. Finally in August 1966, total gastrectomy was performed. At operation multiple ulcers were seen to occupy nearly the entire gastric remnant. No tumor was identified. The patient died in March 1968 of chronic pancreatitis presumed to be the result of chronic alcoholism. At autopsy a submucosal duodenal islet cell tumor was identified along with involved regional nodes containing metastases. The pancreas was free from tumor. Figure 1 shows the submucosal tumor found in the first portion of the duodenum; Figure 2 is a high powered view showing invasion of Brunner’s gland; and Figure 3 is a higher powered view demonstrating regular nuclei arrangement of the cells in sheets mimicking carcinoid tumor. Histologic interpretation was islet cell adenocarcinoma of the duodenum.
Tumor of Duodenum
Figure 2. Tumor in duodenal wall invading Brunner’s glands. Hematoxylin and eosin stain; original magnification X 30.
several hours’ duration. Intermittent epigastric pain, which usually was relieved by antacids, had been present for eight months. There had been no gastrointestinal bleeding. Epigastric pain resolved on antacid therapy within twelve hours of admission. Roentgenograms of the upper gastrointestinal tract did not demonstrate ulceration. The twelve hour overnight gastric analysis showed 3,100 mm of gastric juice with 310 mEq/L of free acid. The patient became asymptomatic during this period of hospitalization and was discharged. During the next six months severe pain occurred frequently and diarrhea consisting of three to four loose watery stools per day developed. The patient was readmitted in June 1967, and exploration carried out. There was no evidence of active ulcer. No tumor could be identified in the pancreas; however, biopsy specimens taken from peripancreatic lymph nodes showed metastatic tumors interpreted to be of islet cell origin. Total gastrectomy was performed. Prior to closure of the duodenal stump, a 1 cm
Comment: This patient presented relentless fulminating ulcer diathesis, for which multiple surgical procedures were required. At autopsy an 8 mm submucosal tumor was identified in the duodenum just distal to the line of previous resection. Despite numerous abdominal explorations the tumor was not identified, resulting in delay in proper definitive therapy. Case III. The patient (FY), a fifty year old white man, was admitted to Wilford Hall USAF Hospital in January 1967 for evaluation of severe epigastric pain of
Volume 124, November 1972
Figure 3. Regular nuclei with arrangement of cells in acini and sheets that mimic carcinoid morphologically. Hematoxylin and eosin stain; original magnification X 44.
597
Evans et al
Figure 4. Submucosal ner’s gland.
tumor is seen adjacent
to Brun-
submucosal nodule was identified in the first portion of the duodenum just distal to the line of resection. The nodule was removed with a cuff of the duodenal wall, and the duodenal stump was closed. Reconstruction was carried out by loop esophagojejunostomy and distal jejunojejunostomy. The excised portion of the duodenal wall demonstrated a submucosal tumor lying adjacent to Brunner’s glands. (Figure 4.) Higher power views were interpreted as showing carcinoid tumor of the duodenum. (Figure 5.) The Armed Forces Institute of Pathology reported the lesion to be a carcinoid-islet cell tumor of the duodenum. Comment: Four and a half years after total gastrectomy the patient is doing well. Persistent episodes of abdominal pain associated with extremely high gastric acid values led to exploration. A decision for total gastrectomy was based upon identification of metastatic islet cell tumor found in peripancreatic lymph node. Identification of the primary lesion resulted from careful palpation of the intraluminal duodenal stump. Despite the peripancreatic lymph node metastasis, the patient is doing well four and a half years after total gastrectomy.
specimen, although this was not identified at operation. Significance of this lesion was not appreciated. Only in case III was the tumor identified during surgery. This experience, as well as that of others, suggests that failure to obtain a positive tumor diagnosis during exploration of patients expected to have the Zollinger-Ellison syndrome should prompt careful evaluation of the duodenum. In these three cases, lymph node metastasis was present. Oberhelman previously reported that only five of eleven patients in his series with duodenal tumors associated with the Zollinger-Ellison syndrome had metastasis and that local excision of the duodenal lesion might be sufficient for control of ulcer diathesis [3]. The presence of lymph node metastasis indicated the need for total gastrectomy as the preferred primary treatment in the patients in this report. Failure to initially carry out total gastrectomy in two of these patients was followed by continued fulminating ulcer disease. In addition, primary tumor excision had been carried out in case I at the initial operation, but subsequently total gastrectomy was eventually required. In cases II and III the original histologic diagnosis of the tumor was carcinoid tumor of the .duodenum. The similarity of the histologic pattern under light microscopy between carcinoid and islet cell tumors of the duodenum has been described in detail by Weichert, Reed, and Creech [5]. This similarity may also occur when lesions arise from the pancreas. Schulte et al report that one third of the pancreatic non-beta cell non-insulin-secreting islet cell tumors exhibited areas that could be confused with carcinoid tumors [6]. These authors indicate that the final diagnosis must be based on the clinical history and course coupled with histologic appearance, the differential criteria being based upon behavior of the tumor [5,6].
Comments
That gastric hypersecretion and fulminating peptic ulcer disease can occur with duodenal tumors of “islet cell-carcinoid” type has been previously reported 13-51. Three additional cases are presented. Problems of diagnosis parallel those of other reports. Grossly these small lesions may be overlooked if careful intraluminal palpation of the duodenum is not carried out. In case II identification of the primary tumor escaped detection until autopsy despite several extensive explorations. In case I identification of the duodenal tumor resulted from histologic identification of a nodule identified in the surgical
598
Figure 5.
Higher power view showing trabeculae pattern.
The American Journal of Surgery
Ulcerogenic
References
Summary Three patients with “islet cell-carcinoid” tumors of the duodenum are reviewed. In each .of these cases the presence of lymph node metastasis eventually prompted total gastrectomy as the course of treatment. The patient in case I is now clinically free of tumor five years after operation. In case II the patient’s death occurred two years after surgery, and although tumor was found at operation, it was not related to his death. In case III the patient is alive and well five years after his surgical procedures.
Volume
124, November
Tumor of Duodenum
1972
1. Ellison EH, Wilson SD: The Zollinger-Ellison syndrome: reappraisal and evaluation of 260 registered cases. Ann Surg 160: 512, 1964. 2. Zollinger. RM, Ellison EH: Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg 142: 709, 1955. 3. Oberhelman HA Jr: Excisional therapy for ulcerogenic tumors of the duodenum. Arch Surg 104: 447,1962. 4. McCorriston JR: Heterotopic pancreatic tissue in wall of duodenum associated with bleeding duodenal ulcer. Canad J Surgl: 153,1958. 5. Weichert R, Reed R, Creech 0: Carcinoid-islet cell tumors of the duodenum. Ann Surg 165: 660,1967. 6. Schulte W: Personal communication.
599