Management
of Surgical Gastrointestinal Complications in Renal Transplant Recipients Richard S. Faro, MD, Robert J.
Corry,
MD
\s=b\ Gastrointestinal (GI) complications developed in 19 (7.2%) of 265 patients after renal transplantation, and 3 (16%) patients died. Complications included colon perforations, colonic bleeding, small-bowel infarction, pancreatitis, subphrenic abscess, and upper GI tract bleeding. Ulcers located in the second portion of the duodenum developed in six patients; four of them required operation for massive hemorrhage, which occurred during or immediately after the administration of high-dose methylprednisolone for rejection. However, the association of methylprednisolone and colon perforation was not clear from this report. Early diagnosis and prompt operation for surgical-type GI complications in transplant recipients contribute to a low mortality.
(Arch Surg 114:310-312, 1979) after renal trans¬ have been associated with a relatively who received immunosuppres¬ in Probable factors associated with GI compli¬ sive therapy.1-7 cations are steroid hormones, other immunosuppressive agents, renal failure, and the existence of GI tract disease before organ transplantation. For example, uremia may be associated with abdominal pain, and GI ulcération may be associated with bleeding, pancreatitis, enterocolitis, and ileus."·8" Although it is not clear whether adrenal cortico¬ steroid hormones lead to a higher rate of mucosal ulcéra¬ tion,1" their role in the lowering of host defenses and in the impairing of healing is well understood. Once a major surgical condition of the abdomen occurs, such as a perfo¬ ration, the patient receiving immunosuppresive therapy cannot combat intraperitoneal sepsis as effectively as the patient with a normal immune system. The present study was done to evaluate our experience with surgical condi¬ tions involving the GI tract in the transplant recipient receiving immunosuppressive therapy, stressing factors in management that might lead to a lower mortality.
(GI) complications Gastroi n testi n al plantation high mortality patients
SUBJECTS AND TREATMENTS Between April 1973 and February 1978, a total of 265 patients underwent renal transplantation at the University of Iowa College for publication Oct 3, 1978. From the Transplantation Service, Department of Surgery, University of Iowa College of Medicine, Iowa City. Dr Faro is now with the Department of Surgery, Creighton University School of Medicine. Reprint requests to Department of Surgery, University Hospitals, Iowa City, IA 52242 (Dr Corry).
Accepted
of Medicine. The following surgical complications developed in 19 (7.2%) of the 265 patients: bleeding esophagitis, two patients; hemorrhagic gastritis, one patient; duodenal ulcer, eight patients (two cases involving the proximal duodenum and six cases involv¬ ing the distal duodenum or second-to-third portion); small-bowel infarction, one patient; colon perforation, three patients (one case involving splenic flexure and two cases involving perforation of the sigmoid colon); colonie bleeding, two patients (one case involv¬ ing cecal ulcération and one case undetermined); pancreatitis, one patient; and subphrenic abscess, one patient. Seventeen of the 19 patients received cadaver kidneys and two patients received living related-donor kidneys. All patients were given azathioprine, 7 to 10 mg/kg as a loading dose and 2 to 3 mg/kg as a daily maintenance dose. Prednisone was given daily in a dose of 1 to 1.5 mg/kg until rejection occurred. Rejection episodes were treated with 15 mg/kg of intravenous (IV) methylprednisolone sodium succinate daily for a maximum of eight days. After the adminis¬ tration of high-dose IV methylprednisolone therapy, the patient continued to receive the same dose of prednisone that he received before the rejection therapy was started. All recipients of renal transplants received antacids after the transplant procedure. Antacids were not increased during a rejection episode. Three weeks after the transplant procedure, patients had usually been treated for one rejection episode with high-dose IV methylprednisolone and they were given 35 to 45 mg of prednisone each day in four divided doses. Gradually, prednisone therapy was tapered to 20 mg by six months. Second- and third-rejection episodes were treated in the same way if a substantial return of renal function occurred after treatment for the previous rejection
episode.
Survival rates of all cadaver transplants at our center were 61%, 56%, and 50% at one, two, and three years, respectively, whereas patient survival rates were 90%, 88%, and 83%, respectively.11 Transplant survival rates in patients with living related-donor kidneys were 76%, 76%, and 74% at one, two, and three years, respectively, and patient survival rates were 93% at all three years." These actuarial survival rates included poor-risk patients as well as patients with second and third transplants. Poor-risk patients were recipients older than 50 years of age or patients with juvenile-onset diabetes mellitus.
RESULTS Colon Perforation Two of the patients had sigmoid perforations within the first month after transplantation while they were being treated with high-dose methylprednisolone therapy for rejection episodes. Both of these patients had poor renal
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Calgary User on 05/26/2015
function at the time of perforation. One was treated with a transverse colostomy and suturing of the perforation, and the other was treated with a sigmoid resection, descending colostomy, and mucous fistula. In a third patient who had normal renal function, peritonitis developed after excision of an ileal loop. Exploration revealed a splenic flexure perforation at the site of an intraperitoneal abscess. A divided-limb transverse colostomy and drainage of the abscess were carried out. These three patients had extensive intraperitoneal irri¬ gations and underwent meticulous removal of fibrinous exúdate. All of them were operated on immediately after the diagnosis was made and they recovered uneventfully. Colonie
Bleeding
Bloody diarrhea developed in two patients. One patient, who received a cadaver transplant 90 days earlier, required operation for massive colonie bleeding. This patient was recovering from a transplant nephrectomy after two rejec¬ tion episodes, the second of which failed to respond to high-dose IV methylprednisolone therapy. At operation, the cecal wall appeared thickened and inflamed. A right hemicolectomy was performed and a very large cecal ulcer measuring approximately 7 x 8 cm was found. Microscopic examination of the ulcer disclosed cytomegalovirus inclu¬ sion bodies in the ulcer bed. After operation, the patient recovered uneventfully and returned to long-term hemodi¬ alysis therapy. In the second patient, who had normal renal function, bloody diarrhea developed one year after trans¬ plantation while the patient was receiving anticoagulant therapy for pulmonary embolism. Bleeding ceased sponta¬ neously in this patient after correction of the prothrombin time. Subsequent barium enema examination and colonos¬ copy revealed no abnormalities. Internal Hernia With Small-Bowel Infarction In a 23-year-old woman who had received peritoneal dialysis, small-bowel obstruction developed nine weeks after transplantation. This episode occurred after several days of high-dose IV methylprednisolone therapy for rejection. Abdominal roentgenograms disclosed multiple air-fluid levels, and a closed-loop small-bowel obstruction with infarction was noted at laparotomy. The patient recovered uneventfully after small-bowel resection, and she returned to long-term hemodialysis therapy. Within a few months, she received a second cadaver renal transplant
and has normal renal function IV2 years later. Pancreatitis
Pancreatitis developed in a 40-year-old man one year after transplantation. He had not been treated for rejec¬ tion since the first two weeks after transplantation, and he was receiving 15 mg of prednisone per day. Results of an ultrasound examination were normal and arteriography showed a distal pancreatic mass. Because of continued abdominal pain and a possible pancreatic pseudocyst, the
underwent exploratory laparotomy that disclosed edematous pancreatitis without a pseudocyst. Adhesions were lysed and the patient's pain resolved. He continued to have normal renal function and is being maintained on a regimen of 12.5 mg of prednisone 2% years after operation. Occasionally, he has had left upper quadrant and epigastric pain that has resolved on conservative management.
patient
Subphrenic
Abscess
Abdominal distention developed in a 58-year-old man 38 days after transplantation. Diagnostic paracentesis showed purulent fluid, and at operation a ruptured sub¬ phrenic abscess with extensive generalized peritonitis was noted. Thorough irrigation of the abdomen and drainage of the left renal fossa were carried out. The origin of the subphrenic abscess was the left renal fossa. He had had a bilateral nephrectomy a few weeks earlier, but there had been no fever or flank tenderness at the time of transplan¬ tation. His condition deteriorated and he died of general¬ ized sepsis on the 33rd postoperative day.
Upper
GI Tract
Hemorrhage
Upper GI
bleeding occurred in ten patients. After trans¬ plantation, bleeding duodenal ulcers developed in eight patients, five of whom required emergency operations. Four of the patients who were operated on had ulcers located in the second portion of the duodenum in the periampullary region. There was no history of antecedent peptic ulcer disease in nine of the ten patients before transplantation. The one patient with duodenal ulcer disease before transplantation refused an elective opera¬ tion and required a subtotal gastrectomy for pain and intermittent bleeding. Massive bleeding occurred either during or after high-dose methylprednisolone therapy for rejection in seven patients. Two critically ill patients with distal duodenal ulcers underwent duodenotomy and suture ligation of the bleeding ulcers. One of these patients died of aspiration pneumonia four days after operation and the other is symptom-free. A subtotal gastrectomy was performed in three patients, two of whom had distal duodenal ulcers. In two of these patients, marginal ulcers later developed that required higher resections with bilat¬ eral truncal vagotomies. The remaining patients, including two with distal duodenal ulcers and three with duodenal bulb ulcers, responded to medical management. On the ninth day after transplantation, diffuse hemorrhagic gastritis developed in one patient who required transfu¬ sions. Esophagitis developed in the final two patients, with one patient bleeding massively from an esophageal ulcer. Both of them were transfused and have not required operations. In all patients, diagnoses were either made roentgenographically or endoscopically.
COMMENT
Gastrointestinal complications of a surgical nature after renal transplantation are more common in this than in the general population, and because of the lowered immunity
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Calgary User on 05/26/2015
in these
patients, higher morbidity rates and higher mortality expected. The incidence of GI complications after renal transplantation in this series was 7.2% (19/265), and the mortality was 16% (3/19). In a reported series of GI complications after renal transplantation, complication rates varied from 6% to 26.9%, and mortality varied from 35% to 46%. However, when comparing mortality among are
different
series, the incidence of a particular type of complication differs. Also, a major GI complication in a poor-risk patient is more likely to lead to mortality. Although 38 patients in our overall series were in the poor-risk category, only three poor-risk patients had surgi¬ cal GI complications, which undoubtedly resulted in a lower mortality. Furthermore, since more than half of our patients had upper GI bleeding that could be managed medically or surgically if necessary, a higher survival rate could be expected than if half of our patients with compli¬ cations had had peritonitis from a colon perforation. Nevertheless, it seemed rather obvious that prompt opera¬ tive intervention in both cases of massive bleeding and perforation led to a better survival than would be expected if operation had been delayed. Careful and frequent abdominal examinations of patients with fever and even mild abdominal complaints are important in making an early diagnosis of GI emergency. Spontaneous colon perforations have been attributed to steroid therapy,1 diverticulitis,1·41- ischemia,7 and operative trauma." It has been speculated that steroids and azathio¬ prine may cause lymphoid depletion in the colonie lymphoid patches, resulting in bacterial invasion and consequent perforation.1 When colon perforations occur, early operative treatment with extensive debridement of infected fibrinous exúdate and thorough irrigation is even more crucial in this group of patients who combat bacterial infections poorly. Immunosuppressive therapy should be
discontinued except for continuation of a mairtenance dose of prednisone. Discontinuation of immunosuppressive therapy is not usually necessary in patients without peri¬ tonitis since infection is not a major problem. A case of cecal ulcération with hemorrhage secondary to cytomegalovirus in an immunologically deficient patient was previously reported by Wolfe and Cherry.13 No other complications of cytomegalovirus disease were noted in the patient in our series except for the cecal ulcer. Patients with uremia have an increased secretion of acid as well as gastrin.14 The association of bleeding with rejection episodes and poor renal function in this series of patients was quite apparent. It is known that adrenal corticosteroid therapy is complicated by the appearance of peptic ulcer disease in those patients who have received a total dose of over 1,000 mg of prednisone.10 Ten of our patients had high-dose methylprednisolone therapy with total doses far exceeding the equivalent of 1,000 mg of
prednisone. Four patients had ulcers of the second portion of the duodenum diagnosed at duodenotomy to control hemor¬ rhage. Two other patients had distal duodenal ulcers noted on upper GI series that healed after medical therapy. The following several factors were noted in all four patients
undergoing emergency operation for control of hemor¬ rhage: (1) Hemorrhage in all patients occurred two weeks to two months after transplantation, either immediately after or during high-dose IV methylprednisolone therapy. (2) There was no history of ulcer disease before transplan¬ tation. (3) All patients had massive rectal bleeding with minimal blood return from gastric lavage, which indicated
the distal location of the ulcer. If a precise location of the bleeding cannot be determined preoperatively, duodenoto; my extending into the second portion of the duodenum must be performed. Obviously, great care must be taken with closure of the duodenotomy in these patients, most of whom have been receiving high-dose methylprednisolone. The association of prednisone and methylprednisolone with duodenal ulcération in this series of patients seems clear. Although treatment of rejection episodes with highdose corticosteroid therapy is tantamount to a respectable graft success rate, these high doses should be discontinued when massive upper GI tract hemorrhage occurs. Even though the association of colon perforations and corticoste¬ roids is less clear,17' high-dose therapy should be stopped because of the sepsis that ensues. Although the signs of colon perforation in the patient receiving corticosteroid therapy may be subtle, early diagnosis and surgical treat¬ ment have proved to be the most important factors in lowering patient mortality in this series.
Nonproprietary
Name and Trademark of
Drug
Azathioprine—Imuran. References 1. Hadjiyannakes EJ, Evans DB, Smellie WAB, et al: Gastrointestinal complications after renal transplantation. Lancet 2:781-785, 1971. 2. Lewicki AM, Saite S, Merrill JP: Gastrointestinal bleeding in one renal transplant patient. Radiology 102:533-537, 1972. 3. Libertino JA, Zinman L, Dowd JB, et al: Gastrointestinal complications related to human renal homotransplantation. Surg Clin North Am 51:733\x=req-\
737, 1971.
4. Penn I, Brettschneider L, Simpson K, et al: Major colonic problems in human homotransplant recipients. Arch Surg 100:61-65, 1970. 5. Penn I, Durst, Machado M, et al: Acute pancreatitis and hyperamylasemia in renal homograft recipients. Arch Surg 105:167-172, 1972. 6. Penn I, Groth CG, Brettschneider L, et al: Surgical correctable intra-abdominal complications before and after renal homotransplantation. Ann Surg 168:865-870, 1968. 7. Powis SJA, Barnes AD, Davison-Edwards P, et al: Ileocolonic problems after cadaveric renal transplantation. Br Med J 1:99-101, 1972. 8. Seldin DW, Carter NW, Rector FC Jr: Consequences of Renal Failure and Their Management. Boston, Little Brown & Co, 1963, pp 173-175. 9. Starzl TE: Experience in Renal Transplantation. Philadelphia, WB Saunders Co, 1964, pp 111-125. 10. Conn MD, Blitzer BL: Nonassociation of adrenocorticosteroid therapy and peptic ulcer. N Engl J Med 294:473-479, 1976. 11. Corry RJ, Thompson JS, Freeman RM: Critical comparison of renal transplant survival between recipients of live related donor and cadaver organs. Surg Gynecol Obstet 146:519-523, 1978. 12. Ferri BT: Perforation and inflammation of diverticula of the colon secondary to long-term adrenocorticosteroid therapy for bronchial asthma and pulmonary emphysema. South Med J 54:355-359, 1961. 13. Wolfe BM, Cherry JD: Hemorrhage from cecal ulcers of cytomegalovirus infections. Ann Surg 177:490-494, 1973. 14. Durkin MG, Essig LJ, Nolph KD: Gastrin removal during peritoneal dialysis, abstracted. Clin Res 19:657, 1971. 15. Sterioff S, Orringer MB, Cameron JL: Colon perforation associated with steroid therapy. Surgery 75:56-58, 1974.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Calgary User on 05/26/2015
of Surgical Gastrointestinal Complications in Renal Transplant Recipients Richard S. Faro, MD, Robert J.
Corry,
MD
\s=b\ Gastrointestinal (GI) complications developed in 19 (7.2%) of 265 patients after renal transplantation, and 3 (16%) patients died. Complications included colon perforations, colonic bleeding, small-bowel infarction, pancreatitis, subphrenic abscess, and upper GI tract bleeding. Ulcers located in the second portion of the duodenum developed in six patients; four of them required operation for massive hemorrhage, which occurred during or immediately after the administration of high-dose methylprednisolone for rejection. However, the association of methylprednisolone and colon perforation was not clear from this report. Early diagnosis and prompt operation for surgical-type GI complications in transplant recipients contribute to a low mortality.
(Arch Surg 114:310-312, 1979) after renal trans¬ have been associated with a relatively who received immunosuppres¬ in Probable factors associated with GI compli¬ sive therapy.1-7 cations are steroid hormones, other immunosuppressive agents, renal failure, and the existence of GI tract disease before organ transplantation. For example, uremia may be associated with abdominal pain, and GI ulcération may be associated with bleeding, pancreatitis, enterocolitis, and ileus."·8" Although it is not clear whether adrenal cortico¬ steroid hormones lead to a higher rate of mucosal ulcéra¬ tion,1" their role in the lowering of host defenses and in the impairing of healing is well understood. Once a major surgical condition of the abdomen occurs, such as a perfo¬ ration, the patient receiving immunosuppresive therapy cannot combat intraperitoneal sepsis as effectively as the patient with a normal immune system. The present study was done to evaluate our experience with surgical condi¬ tions involving the GI tract in the transplant recipient receiving immunosuppressive therapy, stressing factors in management that might lead to a lower mortality.
(GI) complications Gastroi n testi n al plantation high mortality patients
SUBJECTS AND TREATMENTS Between April 1973 and February 1978, a total of 265 patients underwent renal transplantation at the University of Iowa College for publication Oct 3, 1978. From the Transplantation Service, Department of Surgery, University of Iowa College of Medicine, Iowa City. Dr Faro is now with the Department of Surgery, Creighton University School of Medicine. Reprint requests to Department of Surgery, University Hospitals, Iowa City, IA 52242 (Dr Corry).
Accepted
of Medicine. The following surgical complications developed in 19 (7.2%) of the 265 patients: bleeding esophagitis, two patients; hemorrhagic gastritis, one patient; duodenal ulcer, eight patients (two cases involving the proximal duodenum and six cases involv¬ ing the distal duodenum or second-to-third portion); small-bowel infarction, one patient; colon perforation, three patients (one case involving splenic flexure and two cases involving perforation of the sigmoid colon); colonie bleeding, two patients (one case involv¬ ing cecal ulcération and one case undetermined); pancreatitis, one patient; and subphrenic abscess, one patient. Seventeen of the 19 patients received cadaver kidneys and two patients received living related-donor kidneys. All patients were given azathioprine, 7 to 10 mg/kg as a loading dose and 2 to 3 mg/kg as a daily maintenance dose. Prednisone was given daily in a dose of 1 to 1.5 mg/kg until rejection occurred. Rejection episodes were treated with 15 mg/kg of intravenous (IV) methylprednisolone sodium succinate daily for a maximum of eight days. After the adminis¬ tration of high-dose IV methylprednisolone therapy, the patient continued to receive the same dose of prednisone that he received before the rejection therapy was started. All recipients of renal transplants received antacids after the transplant procedure. Antacids were not increased during a rejection episode. Three weeks after the transplant procedure, patients had usually been treated for one rejection episode with high-dose IV methylprednisolone and they were given 35 to 45 mg of prednisone each day in four divided doses. Gradually, prednisone therapy was tapered to 20 mg by six months. Second- and third-rejection episodes were treated in the same way if a substantial return of renal function occurred after treatment for the previous rejection
episode.
Survival rates of all cadaver transplants at our center were 61%, 56%, and 50% at one, two, and three years, respectively, whereas patient survival rates were 90%, 88%, and 83%, respectively.11 Transplant survival rates in patients with living related-donor kidneys were 76%, 76%, and 74% at one, two, and three years, respectively, and patient survival rates were 93% at all three years." These actuarial survival rates included poor-risk patients as well as patients with second and third transplants. Poor-risk patients were recipients older than 50 years of age or patients with juvenile-onset diabetes mellitus.
RESULTS Colon Perforation Two of the patients had sigmoid perforations within the first month after transplantation while they were being treated with high-dose methylprednisolone therapy for rejection episodes. Both of these patients had poor renal
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Calgary User on 05/26/2015
function at the time of perforation. One was treated with a transverse colostomy and suturing of the perforation, and the other was treated with a sigmoid resection, descending colostomy, and mucous fistula. In a third patient who had normal renal function, peritonitis developed after excision of an ileal loop. Exploration revealed a splenic flexure perforation at the site of an intraperitoneal abscess. A divided-limb transverse colostomy and drainage of the abscess were carried out. These three patients had extensive intraperitoneal irri¬ gations and underwent meticulous removal of fibrinous exúdate. All of them were operated on immediately after the diagnosis was made and they recovered uneventfully. Colonie
Bleeding
Bloody diarrhea developed in two patients. One patient, who received a cadaver transplant 90 days earlier, required operation for massive colonie bleeding. This patient was recovering from a transplant nephrectomy after two rejec¬ tion episodes, the second of which failed to respond to high-dose IV methylprednisolone therapy. At operation, the cecal wall appeared thickened and inflamed. A right hemicolectomy was performed and a very large cecal ulcer measuring approximately 7 x 8 cm was found. Microscopic examination of the ulcer disclosed cytomegalovirus inclu¬ sion bodies in the ulcer bed. After operation, the patient recovered uneventfully and returned to long-term hemodi¬ alysis therapy. In the second patient, who had normal renal function, bloody diarrhea developed one year after trans¬ plantation while the patient was receiving anticoagulant therapy for pulmonary embolism. Bleeding ceased sponta¬ neously in this patient after correction of the prothrombin time. Subsequent barium enema examination and colonos¬ copy revealed no abnormalities. Internal Hernia With Small-Bowel Infarction In a 23-year-old woman who had received peritoneal dialysis, small-bowel obstruction developed nine weeks after transplantation. This episode occurred after several days of high-dose IV methylprednisolone therapy for rejection. Abdominal roentgenograms disclosed multiple air-fluid levels, and a closed-loop small-bowel obstruction with infarction was noted at laparotomy. The patient recovered uneventfully after small-bowel resection, and she returned to long-term hemodialysis therapy. Within a few months, she received a second cadaver renal transplant
and has normal renal function IV2 years later. Pancreatitis
Pancreatitis developed in a 40-year-old man one year after transplantation. He had not been treated for rejec¬ tion since the first two weeks after transplantation, and he was receiving 15 mg of prednisone per day. Results of an ultrasound examination were normal and arteriography showed a distal pancreatic mass. Because of continued abdominal pain and a possible pancreatic pseudocyst, the
underwent exploratory laparotomy that disclosed edematous pancreatitis without a pseudocyst. Adhesions were lysed and the patient's pain resolved. He continued to have normal renal function and is being maintained on a regimen of 12.5 mg of prednisone 2% years after operation. Occasionally, he has had left upper quadrant and epigastric pain that has resolved on conservative management.
patient
Subphrenic
Abscess
Abdominal distention developed in a 58-year-old man 38 days after transplantation. Diagnostic paracentesis showed purulent fluid, and at operation a ruptured sub¬ phrenic abscess with extensive generalized peritonitis was noted. Thorough irrigation of the abdomen and drainage of the left renal fossa were carried out. The origin of the subphrenic abscess was the left renal fossa. He had had a bilateral nephrectomy a few weeks earlier, but there had been no fever or flank tenderness at the time of transplan¬ tation. His condition deteriorated and he died of general¬ ized sepsis on the 33rd postoperative day.
Upper
GI Tract
Hemorrhage
Upper GI
bleeding occurred in ten patients. After trans¬ plantation, bleeding duodenal ulcers developed in eight patients, five of whom required emergency operations. Four of the patients who were operated on had ulcers located in the second portion of the duodenum in the periampullary region. There was no history of antecedent peptic ulcer disease in nine of the ten patients before transplantation. The one patient with duodenal ulcer disease before transplantation refused an elective opera¬ tion and required a subtotal gastrectomy for pain and intermittent bleeding. Massive bleeding occurred either during or after high-dose methylprednisolone therapy for rejection in seven patients. Two critically ill patients with distal duodenal ulcers underwent duodenotomy and suture ligation of the bleeding ulcers. One of these patients died of aspiration pneumonia four days after operation and the other is symptom-free. A subtotal gastrectomy was performed in three patients, two of whom had distal duodenal ulcers. In two of these patients, marginal ulcers later developed that required higher resections with bilat¬ eral truncal vagotomies. The remaining patients, including two with distal duodenal ulcers and three with duodenal bulb ulcers, responded to medical management. On the ninth day after transplantation, diffuse hemorrhagic gastritis developed in one patient who required transfu¬ sions. Esophagitis developed in the final two patients, with one patient bleeding massively from an esophageal ulcer. Both of them were transfused and have not required operations. In all patients, diagnoses were either made roentgenographically or endoscopically.
COMMENT
Gastrointestinal complications of a surgical nature after renal transplantation are more common in this than in the general population, and because of the lowered immunity
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Calgary User on 05/26/2015
in these
patients, higher morbidity rates and higher mortality expected. The incidence of GI complications after renal transplantation in this series was 7.2% (19/265), and the mortality was 16% (3/19). In a reported series of GI complications after renal transplantation, complication rates varied from 6% to 26.9%, and mortality varied from 35% to 46%. However, when comparing mortality among are
different
series, the incidence of a particular type of complication differs. Also, a major GI complication in a poor-risk patient is more likely to lead to mortality. Although 38 patients in our overall series were in the poor-risk category, only three poor-risk patients had surgi¬ cal GI complications, which undoubtedly resulted in a lower mortality. Furthermore, since more than half of our patients had upper GI bleeding that could be managed medically or surgically if necessary, a higher survival rate could be expected than if half of our patients with compli¬ cations had had peritonitis from a colon perforation. Nevertheless, it seemed rather obvious that prompt opera¬ tive intervention in both cases of massive bleeding and perforation led to a better survival than would be expected if operation had been delayed. Careful and frequent abdominal examinations of patients with fever and even mild abdominal complaints are important in making an early diagnosis of GI emergency. Spontaneous colon perforations have been attributed to steroid therapy,1 diverticulitis,1·41- ischemia,7 and operative trauma." It has been speculated that steroids and azathio¬ prine may cause lymphoid depletion in the colonie lymphoid patches, resulting in bacterial invasion and consequent perforation.1 When colon perforations occur, early operative treatment with extensive debridement of infected fibrinous exúdate and thorough irrigation is even more crucial in this group of patients who combat bacterial infections poorly. Immunosuppressive therapy should be
discontinued except for continuation of a mairtenance dose of prednisone. Discontinuation of immunosuppressive therapy is not usually necessary in patients without peri¬ tonitis since infection is not a major problem. A case of cecal ulcération with hemorrhage secondary to cytomegalovirus in an immunologically deficient patient was previously reported by Wolfe and Cherry.13 No other complications of cytomegalovirus disease were noted in the patient in our series except for the cecal ulcer. Patients with uremia have an increased secretion of acid as well as gastrin.14 The association of bleeding with rejection episodes and poor renal function in this series of patients was quite apparent. It is known that adrenal corticosteroid therapy is complicated by the appearance of peptic ulcer disease in those patients who have received a total dose of over 1,000 mg of prednisone.10 Ten of our patients had high-dose methylprednisolone therapy with total doses far exceeding the equivalent of 1,000 mg of
prednisone. Four patients had ulcers of the second portion of the duodenum diagnosed at duodenotomy to control hemor¬ rhage. Two other patients had distal duodenal ulcers noted on upper GI series that healed after medical therapy. The following several factors were noted in all four patients
undergoing emergency operation for control of hemor¬ rhage: (1) Hemorrhage in all patients occurred two weeks to two months after transplantation, either immediately after or during high-dose IV methylprednisolone therapy. (2) There was no history of ulcer disease before transplan¬ tation. (3) All patients had massive rectal bleeding with minimal blood return from gastric lavage, which indicated
the distal location of the ulcer. If a precise location of the bleeding cannot be determined preoperatively, duodenoto; my extending into the second portion of the duodenum must be performed. Obviously, great care must be taken with closure of the duodenotomy in these patients, most of whom have been receiving high-dose methylprednisolone. The association of prednisone and methylprednisolone with duodenal ulcération in this series of patients seems clear. Although treatment of rejection episodes with highdose corticosteroid therapy is tantamount to a respectable graft success rate, these high doses should be discontinued when massive upper GI tract hemorrhage occurs. Even though the association of colon perforations and corticoste¬ roids is less clear,17' high-dose therapy should be stopped because of the sepsis that ensues. Although the signs of colon perforation in the patient receiving corticosteroid therapy may be subtle, early diagnosis and surgical treat¬ ment have proved to be the most important factors in lowering patient mortality in this series.
Nonproprietary
Name and Trademark of
Drug
Azathioprine—Imuran. References 1. Hadjiyannakes EJ, Evans DB, Smellie WAB, et al: Gastrointestinal complications after renal transplantation. Lancet 2:781-785, 1971. 2. Lewicki AM, Saite S, Merrill JP: Gastrointestinal bleeding in one renal transplant patient. Radiology 102:533-537, 1972. 3. Libertino JA, Zinman L, Dowd JB, et al: Gastrointestinal complications related to human renal homotransplantation. Surg Clin North Am 51:733\x=req-\
737, 1971.
4. Penn I, Brettschneider L, Simpson K, et al: Major colonic problems in human homotransplant recipients. Arch Surg 100:61-65, 1970. 5. Penn I, Durst, Machado M, et al: Acute pancreatitis and hyperamylasemia in renal homograft recipients. Arch Surg 105:167-172, 1972. 6. Penn I, Groth CG, Brettschneider L, et al: Surgical correctable intra-abdominal complications before and after renal homotransplantation. Ann Surg 168:865-870, 1968. 7. Powis SJA, Barnes AD, Davison-Edwards P, et al: Ileocolonic problems after cadaveric renal transplantation. Br Med J 1:99-101, 1972. 8. Seldin DW, Carter NW, Rector FC Jr: Consequences of Renal Failure and Their Management. Boston, Little Brown & Co, 1963, pp 173-175. 9. Starzl TE: Experience in Renal Transplantation. Philadelphia, WB Saunders Co, 1964, pp 111-125. 10. Conn MD, Blitzer BL: Nonassociation of adrenocorticosteroid therapy and peptic ulcer. N Engl J Med 294:473-479, 1976. 11. Corry RJ, Thompson JS, Freeman RM: Critical comparison of renal transplant survival between recipients of live related donor and cadaver organs. Surg Gynecol Obstet 146:519-523, 1978. 12. Ferri BT: Perforation and inflammation of diverticula of the colon secondary to long-term adrenocorticosteroid therapy for bronchial asthma and pulmonary emphysema. South Med J 54:355-359, 1961. 13. Wolfe BM, Cherry JD: Hemorrhage from cecal ulcers of cytomegalovirus infections. Ann Surg 177:490-494, 1973. 14. Durkin MG, Essig LJ, Nolph KD: Gastrin removal during peritoneal dialysis, abstracted. Clin Res 19:657, 1971. 15. Sterioff S, Orringer MB, Cameron JL: Colon perforation associated with steroid therapy. Surgery 75:56-58, 1974.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Calgary User on 05/26/2015
