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Peristomal varices after proctocolectomy in patients with primary sclerosing cholangitis
GASTROENTEROLOGY1986;90:316-22
Peristomal Vgrices After Proctocolectomy in Patients With Primary Sclerosing Cholangitis RUSSELL H. WIESNER, NICHOLAS F. LARUSSO, ROGER R. DOZOIS, and SANDRA J. BEAVER Division of Gastroenterology and Internal Medicine and the Section of Gastroenterology General Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
Primary sclerosing cholangitis is a chronic cholestatic liver disease that is commonly qssociated with chronic ulcerative colitis. We observed the development of varices in the abdominal wall surrounding the ileostomy stomq of patients with primary sclerosing cholangitis who underwent proctocolectomy and ileostomy for chronic ulcerative colitis. In 10 of 19 patients, the development of peristomal varices was documented 12-133 mo after operation. Risk factors for the development of peristomal varices included splenomegaly, esophageal varices, advanced histologic stage at liver biopsy, low serum albumin, thrombocytopenia, and an increased prothrombin time. Recurrent bleeding from peristomal varices was a major problem; 7 of 10 patients required repeated blood transfusions. The only therapy of long-term benefit was surgical decompression of the portal venous system in 1 patient and liver transplantation in a second patient. In contrast, there was no perirectal bleeding in 4 patients with primary sclerosing cholangitis who underwent proctocolectomy with an ileoanal anastomosis. Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease of unknown etiology that may lead to cirrhosis, portal hypertension, and premature death secondary to liver failure (1,~). Primary sclerosing cholangitis is associated with chronic ulcerative colitis (CLJC) in 70% of our patients (2).Although CUC has not been demonReceived December 27, 1984. Accepted August 19, 1985. Address requests for reprints to: Russell H. Wiesner, M.D., Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55905. This work was supported by the Mayo Foundation, by a grant-in-aid from Merck Sharp, and Dohme Research Laboratories, and by a National Institutes of Health grant (RR-585). The authors thank Dawn C. Warien and Nancy L. Evans for typing the manuscript. 0 1986 by the American Gastroenterological Association 0016-5085/86/$3.50
and
strated to play an etiologic role in PSC, patients with PSC and CUC may undergo proctocolectomy prophylactically because of an increased risk sf developing colon cancer, or therapeutically because of severe bowel symptoms. In such patients, a conventional (i.e., Brooke) or continent (i.e., Kock pouch) ileostomy is frequently the surgical procedure performed. The development of varices in the abdominal wall surrounding the stoma of patients with chronic liver disease who have undergone proctocolectomy and ileostomy has been described (3-6).Edwards (7) demonstrated that potential portosystemic venous channels exist or may develop between the parietal surfaces of the abdominal viscera and the posterior abdominal wall. Thus, in patients with portal hypertension who undergo abdominal operation (i.e., total proctocolectomy and ileostomy), portosystemic shunts may develop within adhesions of the abdominal wall at the site of the ileostomy stoma because of the direct contact of the mesenteric circulation with the circulation of the posterior abdominal wall. This can lead to bleeding from erosions of dilated submucosal veins. Although peristomal varices have been considered an unusual occurrence, the frequency of peristomal variceal formation, the incidence of bleeding, the effect of therapy, and the risk factors predisposing to peristomal variceal formation have not been previously described. Because PSC is the most common liver disease associated with CUC (8),this study determined the frequency with which peristomal varices develop in a large homogeneous group of patients with PSC and CUC who underwent total proctocolectomy and the formation of an abdominal ileal stoma. In addition, we compared clinical, biochemical, and hepatic histologic features of Abbreviations used in this paper: CUC, chronic colitis; PSC, primary sclerosing cholangitis.
ulcerative
February 1986
patients with PSC in whom peristomal varices developed with those of patients with PSC who did not develop peristomal varices after proctocolectomy. Finally, we evaluated therapeutic modalities for peristomal variceal bleeding. Our results demonstrated that formation of peristoma1 varices with bleeding occurred frequently in PSC patients with advanced hepatic histologic stage disease after total proctocolectomy and abdominal ileal stoma formation. Further, the data suggested that portal hypertension, decreased hepatic synthetic function, and hypersplenism are features of patients with PSC who are likely to develop this serious complication. Once peristomal varices form, bleeding becomes a major problem, and frequently blood transfusions are required. Treatment options include local pressure, surgical decompression of the portal venous system, and liver transplantation. Alternative surgical procedures, not requiring abdominal ileostomy, such as proctocolectomy with ileoanal anastomosis, appear to be associated with a lower risk of local variceal formation and may be the treatment of choice for patients with PSC and CUC who must undergo proctocolectomy.
Materials and Methods For 4 yr, we have been conducting a prospective, randomized medical treatment trial in patients with PSC. To date, 70 patients have been diagnosed as having PSC and have been entered into this study. These patients serve as the study population for this report. Primary sclerosing cholangitis was defined as a cholestatic liver disease of >6-mo duration that was associated with a serum alkaline phosphatase level greater than two times the upper limit of normal, and with radiologic demonstration of diffuse narrowing, irregularity, dilatation, and/or tortuosity of the extrahepatic bile ducts, with or without involvement of the intrahepatic bile ducts. Liver biopsy findings compatible with the diagnosis of PSC were also required. Exclusion criteria included bile duct operation or documented choledocholithiasis before the diagnosis of PSC, congenital biliary tract anomalies, and clinical or radiologic abnormalities suggestive of cholangiocarcinoma. All patients were followed up at the Mayo Clinic at 6-mo intervals. Correspondence was maintained with the patient’s local physician at monthly intervals by our nurse coordinator. With this approach, we were able to accurately document the frequency and the severity of peristomal variceal bleeding and blood transfusion requirements. Hepatic histologic staging of PSC was performed according to the criteria of Ludwig et al. (9). All PSC patients with abdominal ileostomies underwent a careful examination of the external stoma1 area for the presence of venous engorgement. Those patients with PSC who noted bleeding from the peristomal area also underwent endoscopic evaluation of the internal stoma to determine if peristomal varices were present. In 6 patients with
PERISTOMAL VARICES AFTER PROCTOCOLECTOMY
31;
PSC who had peristomal
varices on physical or endoscopic examination, or both, mesenteric angiograms were obtained that confirmed venous dilatation and collateral vessels in the peristomal area in all cases. However. mesenteric angiograms were not used to routinely screen all patients with PSC who had had abdominal ileostomies. A single patient with PSC, who had noted bleeding from an abdominal ileostomy, did not have evidence oi peristomal varices on physical and on endoscopic: examination of the stoma, but did have erosions within thr: stoma. Further evaluation of this patient by mesenteric: of peristomal angiography confirmed the absence varices. Peristomal varices were defined as dilated veins surrounding the abdominal ileal stoma that appeared as protruding blue ridges (Figure 1A). We were only able to demonstrate internal varices endoscopically in 2 of the 10 patients who had external evidence of peristomal varices. Clinical, biochemical, and histologic features of PSC patients at the time of diagnosis of peristomal varices were compared with those of PSC patients with abdominal ileostomies who had not developed peristomal varices at their most recent evaluation. At each evaluation, all patients underwent a barium swallow study or upper endoscopy, or both, to determine if esophageal varices were present. Four patients with PSC who underwent proctocolectomy for CUC had an ileoanal pull-through procedure and were also evaluated as part of this study. For purposes of this study, a major peristomal bleed WRS
defined as bleeding that prompted medical attention and required therapeutic intervention such as the local use of Gelfoam, pressure dressings, a blood transfusion. or an? combination thereof. Because most patients experieuced daily oozing at the stoma1 site, such episodes were not considered a major bleed. Statistical analysis was performed with the Student’s t-test and the X2-test. A probability ~I.05 was considered significant.
unpaired value of
Results Of the 70 patients colonoscopic associated
appearance
with PSC, 49 (70%) had the and biopsy evidence of
CUC. Of these 49 patients with PSC associated with CUC, 23 [47%) underwent total proctocolectomy. The indications for proctocolectomy were severity of bowel symptoms related to CUC in 20 patients, cancer prophylaxis in 2 patients with moderate dysplasia on rectal biopsy, and progression of liver disease in 1 patient. Of these 23 patients 17 had
with PSC who underwent proctocolectomy, a Brooke ileostomy, 2 had a Kock pouch
procedure, and 4 had an endorectal ileoanal anastomosis. Of the 19 patients with PSC who underwent proctocolectomy and abdominal ileostomy formation, peristomal varices became evident on physical examination (Figure 1A) in 10 patients (53%); in 6 of the 10, varices were confirmed by angiography (Figure 2).
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WIESNER ET AL.
Figu Ire
1.
A. Peri sitomal varices surrounding patient after portacaval shunt.
GASTROENTEROLOGY Vol. 90. No. 2
abdominal
ileostoma in a patient with PSC. B. Resolution
Of the 10 patients in whom peristomal varices developed, 6 were women and their mean age was 46.3 yr (Table 1). The mean duration of PSC to onset of peristomal varices was 55 mo (range O-180 mo), and the mean duration from proctocolectomy to onset of peristomal varices was 50 mo (range 12-133 mo). The diagnosis of PSC was made after proctocolectomy in 4 of 10 patients in whom peristomal varices developed. All patients with peristomal varices had splenomegaly, and 7 of 10 had hepato-
of peristomz 11\ rarices i ni he
megaly at the time peristomal varices were first diagnosed (Table 2). Esophageal varices were diagnosed in 7 of 10 patients, 2 of whom had endoscopic documentation of esophageal variceal bleeding. All patients with peristomal varices had advanced histologic (stage III-IV) disease on liver biopsy, and 3 of 10 had ascites on physical examination or by ultrasonographic examination at the time peristomal varices were first diagnosed. Laboratory evaluation (Table 3) revealed that 8 of 10 patients had an
February 1986
PERISTOMAL VARICES AFTER PROCTOCOLECTOMY
319
Table 1. Clinical Characteristics of Patients With Primary Sclerosing Cholangitis Who Underwent Proctocolectomy Ulcerative Colitis
for Chronic Proctocolectomy and ileoanal anastomosis (n = 4)
Proctocolectomy and abdominal ileostomy
Age cur) Sex (M/F) Duration of PSC to PSV or at most recent follow-up Imo) Duration of CLJC to proctocolectomy (mo) Duration of CUC to diagnosis of PSC (mo) Duration of proctocolectomy to formation of PSV or at most recent follow-up (mo) Figure 2. Subtraction films of venous phase of a superior mesenteric angiogram. Arrowheads mark the course of the tortuous superior mesenteric vein that drains the stoma1 varices.
increased serum bilirubin level, a decreased serum albumin level, and a decreased platelet count. An increased prothrombin time was found in 6 of 10 patients with PSC at the time peristomal varices were diagnosed. Mean follow-up from the time of diagnosis of peristomal varices was 31 mo (range 19-49 mo). All patients with peristomal varices acknowledged that they had regular oozing from their peristomal site at the time of intubation of the Kock pouch or at the time of changing ileostomy appliances. In addition, all patients had major bleeding episodes as defined above. Episodes of major bleeding occurred a mean of 12 times per year (range 4-40). Transfusions were required in 7 of 10 patients; of those 7 who required transfusions, a mean of 7.5 U (range Z-13 U) of blood were transfused per year. Treatment regimens for abdominal peristomal varices included oral propranolol (Inderal, Ayerst Laboratories, New York, N.Y.), local Gelfoam (The Upjohn Co., Kalamazoo, Mich.), and pressure dressings. In 6 patients, oral propranolol therapy was initiated and the dose was titrated to decrease the resting pulse by 20%. In those patients treated with propranolol, there was no apparent decrease in frequency or amount of peristomal bleeding. In two instances, a decompressive surgical shunt
PSV (n = 10)
No PSV (n = 9)
46.3 ? 4.3 416 55.0 f 18.9
40.7 + 3.6 712 57.7 2 16.6
42.2 2 7.1 212 41.3 r 19.1
163.2 + 23.1
104.7 + 29.7
113.9 2 57.0
177.8 ? 36.0
130.0 ? 36.6
142.1 t 49.1
50.4 -+ 11.8
93.6 ? 15.7
45.3 ? 12.5
CUC, chronic ulcerative colitis; PSC, primary sclerosing cholangitis; PSV, peristomal varices. Values are given as mean 2 SE. No significant differences were found between patients with PSC with PSV and those without PSV.
was performed. One patient underwent a mesocaval shunt that effectively controlled bleeding. Within 2 mo after the shunt procedure, there was almost complete disappearance on physical examination of peristomal varices (Figure 1B).This patient did not experience further episodes of bleeding from the peristomal site. The second patient underwent a proximal side-to-side splenorenal shunt which thrombosed in the first postoperative week. This
Table
2. Physical and Radiologic Findings of Patients With Primary Sclerosing Cholangitis Who Underwent Proctocolectomy for Chronic Ulcerative Colitis Proctocolectomy and abdominal ileostomy NO
Peristomal varices (n = 10) Splenomegaly Esophageal varices Hepatomegaly Ascites
10 7 7 3
peristomal varices (n = 9)
Proctocolectomy and ileoanal anastomosis (n = 4) 2 1 2 1
0” Oh 2 0
Patients with peristomal varices vs. patients varices: a p < 0.001; b p < 0.01.
without
peristomal
320
Table
WIESNER ET AL.
GASTROENTEROLOGY Vol. 90, No. 2
3. Biochemical and Hepatic Histologic Features of Patients With Primary Sclerosing Cholangitis Who Underwent Proctocolectomy for Chronic Ulcerative Colitis Proctocolectomy and abdominal ileostomy No
Peristomal varices (n = 10) Albumin (gidl) (normal, >3.1) Prothrombin time (s) (normal, C11.3) Platelet (X 103/mm3) (normal, 150 X lOa
2.8 2 0.2"
peristomal varices (n = 9) 3.5 t 10.1
11.6 k 0.3b 10.7 2 0.2 117 t 20"
22Ok
37
Proctocolectomy and ileoanal anastomosis (n = 4) 3.3 2 0.3 11.0 + 0.2 204 L 45
to 350 X 103)
Total bilirubin (mgidl) (normal, C1.1) No. of patients in histologic stage III-IV
5.0 t 1.6
10
2.4 2 1.3 6
5.0 ? 3.1
developed peristomal varices; however, these differences did not reach statistical significance. Four patients who underwent proctocolectomy and ileoanal anastomosis were followed up for a mean of 45 mo (range 12-73 mo). During this follow-up period, none of the patients experienced perianal bleeding. All 4 patients who underwent the ileoanal pull-through procedure had advanced hepatic histologic (stage III-IV) disease; 2 of the 4 patients had splenomegaly on physical examination, and 1 had documented esophageal varices on barium swallow study. These clinical findings are similar to those of patients with PSC who underwent proctocolectomy and developed peristomal varices; however, statistical analysis was not performed because of the small number of patients in the ileoanal pull-through group.
4
Values are mean ‘- SE. Patients with peristomal varices vs. patients without peristomal varices: a p < 0.005; b p < 0.02.
patient continues to experience significant peristoma1 variceal bleeding. One patient underwent liver transplantation because of liver failure and complications of portal hypertension, which included recurrent bleeding from peristomal varices. This patient had complete regression of the peristomal varices on physical examination within 2 wk of liver grafting. In the patients with PSC who underwent proctocolectomy but did not form peristomal varices, age, sex, indication for proctocolectomy, and duration of CUC were similar to those of patients who did form peristomal varices (Table 2). Mean duration of follow-up of patients with PSC who did not develop peristomal varices was 94 mo (range 30-228 mo). Portal hypertension, as manifested by the finding of splenomegaly on physical examination or the presence of esophageal varices on barium swallow study or esophagoscopy, was found significantly more often in the patients who developed peristomal varices (Table 2). The physical finding of hepatomegaly and ascites occurred more often in the patients with PSC who had peristomal varices; however, this was not statistically significant. Biochemical evaluation revealed that mean levels of serum albumin and mean platelet counts were significantly lower and the mean prothrombin time was significantly higher in the patients with PSC who developed peristomal varices [Table 3). The mean level of serum bilirubin tended to be higher and the presence of advanced hepatic histologic (stage III-IV] disease was more common in the patients with PSC who
Discussion Our study indicates that peristomal variceal formation occurs frequently in patients with PSC associated with CUC who undergo total proctocolectomy and ileostomy. Because angiography was not used to screen all patients with PSC and abdominal ileostomas, a true incidence of this complication cannot be given. However, we demonstrated that 10 of 19 (53%) patients with PSC who underwent proctocolectomy and abdominal ileostoma formation developed peristomal varices. We also demonstrated that [a) portal hypertension, defined as the presence of splenomegaly or the demonstration of esophageal varices, or both, (b) hypersplenism, manifested by a diminished platelet count, and (c) diminished hepatic synthetic function, as manifested by a decrease in serum albumin or an increased prothrombin time, or both, are all associated with a high risk of developing peristomal varices. Once peristomal varices formed, all 10 patients had major bleeding from the peristomal site, and 7 of the 10 patients required blood transfusions. In general, most major bleeding episodes could easily be controlled with local measures such as lying down, pressure dressings, or the local use of Gelfoam without the need for blood transfusions. In the follow-up period, however, seven major bleeding episodes occurred in 4 patients who required hospitalization and immediate blood transfusion. There were no deaths attributed to peristomal variceal bleeding in our group of patients with PSC. Propranolol therapy was given to 6 of the 10 patients with peristomal varices to decrease portal venous pressure. This therapy did not appear to decrease the frequency or the amount of peristomal bleeding, however. In 2 patients who had repeated major bleeding from the stoma1 site and required multiple transfusions, a
February 1986
systemic shunt procedure was performed to diminish peristomal variceal bleeding. One patient underwent a mesocaval shunt, which completely eliminated bleeding and led to regression of the abdominal peristomal varices. In a second patient, a proximal side-to-side splenorenal shunt was attempted; however, this shunt thrombosed in the early postoperative period and peristomal variceal bleeding persisted. A single patient with severe peristomal variceal bleeding underwent successful liver transplantation, which led to rapid regression of peristomal varices on physical examination and prevented further bleeding from the peristomal site. Thus, the formation of peristomal varices in patients with PSC who have undergone proctocolectomy and abdominal ileostomy for associated CUC is a common, serious problem without satisfactory therapy. Cognizance of this problem should influence decisions regarding proctocolectomy and the type of surgical anastomosis to be performed. It seems reasonable to consider proctocolectomy in the patient with PSC who shows toxic manifestations of CUC [i.e., fever, anemia, and weakness] that are unresponsive to medical therapy. Further, total proctocolectomy is indicated for the presence of a colonic malignancy or for the presence of premalignant changes, such as moderate to severe colonic dysplasia that complicates CUC. For the patients with PSC in whom proctocolectomy is indicated, particularly when there is clinical evidence of portal hypertension, our results suggest that an ileoanal pull-through procedure may be the treatment of choice. This approach eliminates the possibility of formation of peristomal varices. Although the possibility of developing varices at the site of the ileoanal anastomosis does exist, we have not observed this problem in the 4 patients with PSC who underwent proctocolectomy and ileoanal pull-through procedures and who were followed for up to 73 mo. Should an ileoanal anastomosis not be a therapeutic option because of the patient’s age or anatomic considerations, an ileorectostomy is probably preferable to a Brooke ileostomy or a Kock pouch procedure. Although both conventional and continent ileostomies were associated with peristomal variceal formation and bleeding in our series, the z patients who had a Kock pouch procedure developed severe peristomal bleeding that required surgical intervention. Because of the trauma associated with the intubation of the stoma of the Kock pouch and the frequent need for surgical revision of the Kock pouch, it seems prudent to avoid this surgical procedure in patients with PSC who have had a total proctocolectomy. Our data further support the conclusion that
PERISTOMAL
VARICES AFTER PROCTOCOLECTOMY
321
proctocolectomy should probably be avoided in a patient with PSC and long-standing, quiescent CUC without dysplastic changes. This is particularly important in the patient with PSC who has clinical evidence of portal hypertension, hypersplenism, or advanced histologic stage of the disease on liver biopsy. In this group of patients, regular colonoscopic surveillance for dysplastic changes seems a preferable alternative, given the frequency and severity of the problems associated with peristomal varices suggested by our results. The potential for peristoma1 variceal formation and bleeding quantified in this study suggests that a proctocolectomy specifically to influence the course of PSC should be avoided because there are presently no data to suggest a beneficial effect of proctocolectomy on the natural history of PSC. In those unfortunate patients who develop peristoma1 varices associated with major bleeding episodes, a conservative therapeutic approach seems best. Local treatment with pressure dressings and Gelfoam generally will temporarily control bleeding. Should bleeding become a major problem that requires multiple transfusions, however, surgical intervention with a decompressive shunt procedure should be considered. With the advent of liver transplantation as a viable therapeutic option for patients with PSC and liver failure, any decision regarding shunt operation should include the consideration that patients who have a portacaval shunt have an increased operative mortality associated (10). Thus, in the patient with liver transplantation who has PSC and portal hypertension associated with severe peristomal variceal bleeding, consideration should be given to liver transplantation as a definitive procedure. If such a patient is not considered a liver transplant candidate, a portacaval shunt is a reasonable option for treatment of severe, recurrent, peristomal variceal bleeding. In summary, this study showed that recurrent bleeding from peristomal varices is a common problem in patients with PSC and portal hypertension who have undergone total proctocolectomy and abdominal ileostomy. The results suggested that, in is patients with PSC in whom proctocolectamy clearly indicated because of complications associated with severe CUC, an ileoanal pull-through procedure is probably the surgical treatment of choice. Patients with severe peristomal variceal bleeding should be treated in a conservative fashion, if possible, with pressure dressings, local use of Gelfoam, and blood transfusions. If the patient is a liver transplant candidate, portacaval shunt surgery should be avoided.
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ki3fereixis 1. Wiesner
2. 3.
4.
5.
RH, LaRusso NF. Clinicopathologic features of the syndrome of primary sclerosing cholangiiis. Gastroenterology 1980;79:20@-6. LaRusso NF, Wiesner RH, Ludwig J, MacCarty RL. Primary sclerosing cholangitis. N Engl J Med 1984;310:899-903. Ricci RL, Lee KR, Greenberger NJ. Chronic gastrointestinal bleeding from ileal varices after total proctocolectomy for ulcerative colitis: correction by mesocaval shunt. Gastroenterology 1980;78:1053-8. Adson MA, Fulton RE. The ileal stoma and portal hypertension: an uncommon site of variceal bleeding. Arch Surg 1977; 112:501-3. Cameron AD, Fone DJ. Portal hypertension and bleeding ileal
6. 7. 8.
9.
10.
varices after colectomy and ileostomy for chronic ulcerative colitis. Gut 1970;11:755-9. Eade MN, Williams JA, Cooke WT. Bleeding from an ileostomy caput medusae. Lancet 1969;ii:1166-8. Edwards EA. Functional anatomy of the porta-systemic communications Arch Intern Med 1951;88:137-54. Schrumpf E, Fausa 0, Kolmannskog F, Elqjo K;Ritland S, Gjone E. Sclerosing cholangitis in ulcerative colitis: a follow-up study. Stand J Gastroenterol 1982;17:33-9. Ludwig J, Barham SS, LaRusso NF, Elveback LR, Wiesner RH, McCall JT. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis or chronic ulcerative colitis. Hepatology 1981;1:632-40. Starzl TE, Iwatsuki S, Van Thiel DH, et al. Evolution of liver transplantation. Hepatology 1982;2:614-36.
Peristomal Vgrices After Proctocolectomy in Patients With Primary Sclerosing Cholangitis RUSSELL H. WIESNER, NICHOLAS F. LARUSSO, ROGER R. DOZOIS, and SANDRA J. BEAVER Division of Gastroenterology and Internal Medicine and the Section of Gastroenterology General Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
Primary sclerosing cholangitis is a chronic cholestatic liver disease that is commonly qssociated with chronic ulcerative colitis. We observed the development of varices in the abdominal wall surrounding the ileostomy stomq of patients with primary sclerosing cholangitis who underwent proctocolectomy and ileostomy for chronic ulcerative colitis. In 10 of 19 patients, the development of peristomal varices was documented 12-133 mo after operation. Risk factors for the development of peristomal varices included splenomegaly, esophageal varices, advanced histologic stage at liver biopsy, low serum albumin, thrombocytopenia, and an increased prothrombin time. Recurrent bleeding from peristomal varices was a major problem; 7 of 10 patients required repeated blood transfusions. The only therapy of long-term benefit was surgical decompression of the portal venous system in 1 patient and liver transplantation in a second patient. In contrast, there was no perirectal bleeding in 4 patients with primary sclerosing cholangitis who underwent proctocolectomy with an ileoanal anastomosis. Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease of unknown etiology that may lead to cirrhosis, portal hypertension, and premature death secondary to liver failure (1,~). Primary sclerosing cholangitis is associated with chronic ulcerative colitis (CLJC) in 70% of our patients (2).Although CUC has not been demonReceived December 27, 1984. Accepted August 19, 1985. Address requests for reprints to: Russell H. Wiesner, M.D., Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55905. This work was supported by the Mayo Foundation, by a grant-in-aid from Merck Sharp, and Dohme Research Laboratories, and by a National Institutes of Health grant (RR-585). The authors thank Dawn C. Warien and Nancy L. Evans for typing the manuscript. 0 1986 by the American Gastroenterological Association 0016-5085/86/$3.50
and
strated to play an etiologic role in PSC, patients with PSC and CUC may undergo proctocolectomy prophylactically because of an increased risk sf developing colon cancer, or therapeutically because of severe bowel symptoms. In such patients, a conventional (i.e., Brooke) or continent (i.e., Kock pouch) ileostomy is frequently the surgical procedure performed. The development of varices in the abdominal wall surrounding the stoma of patients with chronic liver disease who have undergone proctocolectomy and ileostomy has been described (3-6).Edwards (7) demonstrated that potential portosystemic venous channels exist or may develop between the parietal surfaces of the abdominal viscera and the posterior abdominal wall. Thus, in patients with portal hypertension who undergo abdominal operation (i.e., total proctocolectomy and ileostomy), portosystemic shunts may develop within adhesions of the abdominal wall at the site of the ileostomy stoma because of the direct contact of the mesenteric circulation with the circulation of the posterior abdominal wall. This can lead to bleeding from erosions of dilated submucosal veins. Although peristomal varices have been considered an unusual occurrence, the frequency of peristomal variceal formation, the incidence of bleeding, the effect of therapy, and the risk factors predisposing to peristomal variceal formation have not been previously described. Because PSC is the most common liver disease associated with CUC (8),this study determined the frequency with which peristomal varices develop in a large homogeneous group of patients with PSC and CUC who underwent total proctocolectomy and the formation of an abdominal ileal stoma. In addition, we compared clinical, biochemical, and hepatic histologic features of Abbreviations used in this paper: CUC, chronic colitis; PSC, primary sclerosing cholangitis.
ulcerative
February 1986
patients with PSC in whom peristomal varices developed with those of patients with PSC who did not develop peristomal varices after proctocolectomy. Finally, we evaluated therapeutic modalities for peristomal variceal bleeding. Our results demonstrated that formation of peristoma1 varices with bleeding occurred frequently in PSC patients with advanced hepatic histologic stage disease after total proctocolectomy and abdominal ileal stoma formation. Further, the data suggested that portal hypertension, decreased hepatic synthetic function, and hypersplenism are features of patients with PSC who are likely to develop this serious complication. Once peristomal varices form, bleeding becomes a major problem, and frequently blood transfusions are required. Treatment options include local pressure, surgical decompression of the portal venous system, and liver transplantation. Alternative surgical procedures, not requiring abdominal ileostomy, such as proctocolectomy with ileoanal anastomosis, appear to be associated with a lower risk of local variceal formation and may be the treatment of choice for patients with PSC and CUC who must undergo proctocolectomy.
Materials and Methods For 4 yr, we have been conducting a prospective, randomized medical treatment trial in patients with PSC. To date, 70 patients have been diagnosed as having PSC and have been entered into this study. These patients serve as the study population for this report. Primary sclerosing cholangitis was defined as a cholestatic liver disease of >6-mo duration that was associated with a serum alkaline phosphatase level greater than two times the upper limit of normal, and with radiologic demonstration of diffuse narrowing, irregularity, dilatation, and/or tortuosity of the extrahepatic bile ducts, with or without involvement of the intrahepatic bile ducts. Liver biopsy findings compatible with the diagnosis of PSC were also required. Exclusion criteria included bile duct operation or documented choledocholithiasis before the diagnosis of PSC, congenital biliary tract anomalies, and clinical or radiologic abnormalities suggestive of cholangiocarcinoma. All patients were followed up at the Mayo Clinic at 6-mo intervals. Correspondence was maintained with the patient’s local physician at monthly intervals by our nurse coordinator. With this approach, we were able to accurately document the frequency and the severity of peristomal variceal bleeding and blood transfusion requirements. Hepatic histologic staging of PSC was performed according to the criteria of Ludwig et al. (9). All PSC patients with abdominal ileostomies underwent a careful examination of the external stoma1 area for the presence of venous engorgement. Those patients with PSC who noted bleeding from the peristomal area also underwent endoscopic evaluation of the internal stoma to determine if peristomal varices were present. In 6 patients with
PERISTOMAL VARICES AFTER PROCTOCOLECTOMY
31;
PSC who had peristomal
varices on physical or endoscopic examination, or both, mesenteric angiograms were obtained that confirmed venous dilatation and collateral vessels in the peristomal area in all cases. However. mesenteric angiograms were not used to routinely screen all patients with PSC who had had abdominal ileostomies. A single patient with PSC, who had noted bleeding from an abdominal ileostomy, did not have evidence oi peristomal varices on physical and on endoscopic: examination of the stoma, but did have erosions within thr: stoma. Further evaluation of this patient by mesenteric: of peristomal angiography confirmed the absence varices. Peristomal varices were defined as dilated veins surrounding the abdominal ileal stoma that appeared as protruding blue ridges (Figure 1A). We were only able to demonstrate internal varices endoscopically in 2 of the 10 patients who had external evidence of peristomal varices. Clinical, biochemical, and histologic features of PSC patients at the time of diagnosis of peristomal varices were compared with those of PSC patients with abdominal ileostomies who had not developed peristomal varices at their most recent evaluation. At each evaluation, all patients underwent a barium swallow study or upper endoscopy, or both, to determine if esophageal varices were present. Four patients with PSC who underwent proctocolectomy for CUC had an ileoanal pull-through procedure and were also evaluated as part of this study. For purposes of this study, a major peristomal bleed WRS
defined as bleeding that prompted medical attention and required therapeutic intervention such as the local use of Gelfoam, pressure dressings, a blood transfusion. or an? combination thereof. Because most patients experieuced daily oozing at the stoma1 site, such episodes were not considered a major bleed. Statistical analysis was performed with the Student’s t-test and the X2-test. A probability ~I.05 was considered significant.
unpaired value of
Results Of the 70 patients colonoscopic associated
appearance
with PSC, 49 (70%) had the and biopsy evidence of
CUC. Of these 49 patients with PSC associated with CUC, 23 [47%) underwent total proctocolectomy. The indications for proctocolectomy were severity of bowel symptoms related to CUC in 20 patients, cancer prophylaxis in 2 patients with moderate dysplasia on rectal biopsy, and progression of liver disease in 1 patient. Of these 23 patients 17 had
with PSC who underwent proctocolectomy, a Brooke ileostomy, 2 had a Kock pouch
procedure, and 4 had an endorectal ileoanal anastomosis. Of the 19 patients with PSC who underwent proctocolectomy and abdominal ileostomy formation, peristomal varices became evident on physical examination (Figure 1A) in 10 patients (53%); in 6 of the 10, varices were confirmed by angiography (Figure 2).
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WIESNER ET AL.
Figu Ire
1.
A. Peri sitomal varices surrounding patient after portacaval shunt.
GASTROENTEROLOGY Vol. 90. No. 2
abdominal
ileostoma in a patient with PSC. B. Resolution
Of the 10 patients in whom peristomal varices developed, 6 were women and their mean age was 46.3 yr (Table 1). The mean duration of PSC to onset of peristomal varices was 55 mo (range O-180 mo), and the mean duration from proctocolectomy to onset of peristomal varices was 50 mo (range 12-133 mo). The diagnosis of PSC was made after proctocolectomy in 4 of 10 patients in whom peristomal varices developed. All patients with peristomal varices had splenomegaly, and 7 of 10 had hepato-
of peristomz 11\ rarices i ni he
megaly at the time peristomal varices were first diagnosed (Table 2). Esophageal varices were diagnosed in 7 of 10 patients, 2 of whom had endoscopic documentation of esophageal variceal bleeding. All patients with peristomal varices had advanced histologic (stage III-IV) disease on liver biopsy, and 3 of 10 had ascites on physical examination or by ultrasonographic examination at the time peristomal varices were first diagnosed. Laboratory evaluation (Table 3) revealed that 8 of 10 patients had an
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PERISTOMAL VARICES AFTER PROCTOCOLECTOMY
319
Table 1. Clinical Characteristics of Patients With Primary Sclerosing Cholangitis Who Underwent Proctocolectomy Ulcerative Colitis
for Chronic Proctocolectomy and ileoanal anastomosis (n = 4)
Proctocolectomy and abdominal ileostomy
Age cur) Sex (M/F) Duration of PSC to PSV or at most recent follow-up Imo) Duration of CLJC to proctocolectomy (mo) Duration of CUC to diagnosis of PSC (mo) Duration of proctocolectomy to formation of PSV or at most recent follow-up (mo) Figure 2. Subtraction films of venous phase of a superior mesenteric angiogram. Arrowheads mark the course of the tortuous superior mesenteric vein that drains the stoma1 varices.
increased serum bilirubin level, a decreased serum albumin level, and a decreased platelet count. An increased prothrombin time was found in 6 of 10 patients with PSC at the time peristomal varices were diagnosed. Mean follow-up from the time of diagnosis of peristomal varices was 31 mo (range 19-49 mo). All patients with peristomal varices acknowledged that they had regular oozing from their peristomal site at the time of intubation of the Kock pouch or at the time of changing ileostomy appliances. In addition, all patients had major bleeding episodes as defined above. Episodes of major bleeding occurred a mean of 12 times per year (range 4-40). Transfusions were required in 7 of 10 patients; of those 7 who required transfusions, a mean of 7.5 U (range Z-13 U) of blood were transfused per year. Treatment regimens for abdominal peristomal varices included oral propranolol (Inderal, Ayerst Laboratories, New York, N.Y.), local Gelfoam (The Upjohn Co., Kalamazoo, Mich.), and pressure dressings. In 6 patients, oral propranolol therapy was initiated and the dose was titrated to decrease the resting pulse by 20%. In those patients treated with propranolol, there was no apparent decrease in frequency or amount of peristomal bleeding. In two instances, a decompressive surgical shunt
PSV (n = 10)
No PSV (n = 9)
46.3 ? 4.3 416 55.0 f 18.9
40.7 + 3.6 712 57.7 2 16.6
42.2 2 7.1 212 41.3 r 19.1
163.2 + 23.1
104.7 + 29.7
113.9 2 57.0
177.8 ? 36.0
130.0 ? 36.6
142.1 t 49.1
50.4 -+ 11.8
93.6 ? 15.7
45.3 ? 12.5
CUC, chronic ulcerative colitis; PSC, primary sclerosing cholangitis; PSV, peristomal varices. Values are given as mean 2 SE. No significant differences were found between patients with PSC with PSV and those without PSV.
was performed. One patient underwent a mesocaval shunt that effectively controlled bleeding. Within 2 mo after the shunt procedure, there was almost complete disappearance on physical examination of peristomal varices (Figure 1B).This patient did not experience further episodes of bleeding from the peristomal site. The second patient underwent a proximal side-to-side splenorenal shunt which thrombosed in the first postoperative week. This
Table
2. Physical and Radiologic Findings of Patients With Primary Sclerosing Cholangitis Who Underwent Proctocolectomy for Chronic Ulcerative Colitis Proctocolectomy and abdominal ileostomy NO
Peristomal varices (n = 10) Splenomegaly Esophageal varices Hepatomegaly Ascites
10 7 7 3
peristomal varices (n = 9)
Proctocolectomy and ileoanal anastomosis (n = 4) 2 1 2 1
0” Oh 2 0
Patients with peristomal varices vs. patients varices: a p < 0.001; b p < 0.01.
without
peristomal
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Table
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GASTROENTEROLOGY Vol. 90, No. 2
3. Biochemical and Hepatic Histologic Features of Patients With Primary Sclerosing Cholangitis Who Underwent Proctocolectomy for Chronic Ulcerative Colitis Proctocolectomy and abdominal ileostomy No
Peristomal varices (n = 10) Albumin (gidl) (normal, >3.1) Prothrombin time (s) (normal, C11.3) Platelet (X 103/mm3) (normal, 150 X lOa
2.8 2 0.2"
peristomal varices (n = 9) 3.5 t 10.1
11.6 k 0.3b 10.7 2 0.2 117 t 20"
22Ok
37
Proctocolectomy and ileoanal anastomosis (n = 4) 3.3 2 0.3 11.0 + 0.2 204 L 45
to 350 X 103)
Total bilirubin (mgidl) (normal, C1.1) No. of patients in histologic stage III-IV
5.0 t 1.6
10
2.4 2 1.3 6
5.0 ? 3.1
developed peristomal varices; however, these differences did not reach statistical significance. Four patients who underwent proctocolectomy and ileoanal anastomosis were followed up for a mean of 45 mo (range 12-73 mo). During this follow-up period, none of the patients experienced perianal bleeding. All 4 patients who underwent the ileoanal pull-through procedure had advanced hepatic histologic (stage III-IV) disease; 2 of the 4 patients had splenomegaly on physical examination, and 1 had documented esophageal varices on barium swallow study. These clinical findings are similar to those of patients with PSC who underwent proctocolectomy and developed peristomal varices; however, statistical analysis was not performed because of the small number of patients in the ileoanal pull-through group.
4
Values are mean ‘- SE. Patients with peristomal varices vs. patients without peristomal varices: a p < 0.005; b p < 0.02.
patient continues to experience significant peristoma1 variceal bleeding. One patient underwent liver transplantation because of liver failure and complications of portal hypertension, which included recurrent bleeding from peristomal varices. This patient had complete regression of the peristomal varices on physical examination within 2 wk of liver grafting. In the patients with PSC who underwent proctocolectomy but did not form peristomal varices, age, sex, indication for proctocolectomy, and duration of CUC were similar to those of patients who did form peristomal varices (Table 2). Mean duration of follow-up of patients with PSC who did not develop peristomal varices was 94 mo (range 30-228 mo). Portal hypertension, as manifested by the finding of splenomegaly on physical examination or the presence of esophageal varices on barium swallow study or esophagoscopy, was found significantly more often in the patients who developed peristomal varices (Table 2). The physical finding of hepatomegaly and ascites occurred more often in the patients with PSC who had peristomal varices; however, this was not statistically significant. Biochemical evaluation revealed that mean levels of serum albumin and mean platelet counts were significantly lower and the mean prothrombin time was significantly higher in the patients with PSC who developed peristomal varices [Table 3). The mean level of serum bilirubin tended to be higher and the presence of advanced hepatic histologic (stage III-IV] disease was more common in the patients with PSC who
Discussion Our study indicates that peristomal variceal formation occurs frequently in patients with PSC associated with CUC who undergo total proctocolectomy and ileostomy. Because angiography was not used to screen all patients with PSC and abdominal ileostomas, a true incidence of this complication cannot be given. However, we demonstrated that 10 of 19 (53%) patients with PSC who underwent proctocolectomy and abdominal ileostoma formation developed peristomal varices. We also demonstrated that [a) portal hypertension, defined as the presence of splenomegaly or the demonstration of esophageal varices, or both, (b) hypersplenism, manifested by a diminished platelet count, and (c) diminished hepatic synthetic function, as manifested by a decrease in serum albumin or an increased prothrombin time, or both, are all associated with a high risk of developing peristomal varices. Once peristomal varices formed, all 10 patients had major bleeding from the peristomal site, and 7 of the 10 patients required blood transfusions. In general, most major bleeding episodes could easily be controlled with local measures such as lying down, pressure dressings, or the local use of Gelfoam without the need for blood transfusions. In the follow-up period, however, seven major bleeding episodes occurred in 4 patients who required hospitalization and immediate blood transfusion. There were no deaths attributed to peristomal variceal bleeding in our group of patients with PSC. Propranolol therapy was given to 6 of the 10 patients with peristomal varices to decrease portal venous pressure. This therapy did not appear to decrease the frequency or the amount of peristomal bleeding, however. In 2 patients who had repeated major bleeding from the stoma1 site and required multiple transfusions, a
February 1986
systemic shunt procedure was performed to diminish peristomal variceal bleeding. One patient underwent a mesocaval shunt, which completely eliminated bleeding and led to regression of the abdominal peristomal varices. In a second patient, a proximal side-to-side splenorenal shunt was attempted; however, this shunt thrombosed in the early postoperative period and peristomal variceal bleeding persisted. A single patient with severe peristomal variceal bleeding underwent successful liver transplantation, which led to rapid regression of peristomal varices on physical examination and prevented further bleeding from the peristomal site. Thus, the formation of peristomal varices in patients with PSC who have undergone proctocolectomy and abdominal ileostomy for associated CUC is a common, serious problem without satisfactory therapy. Cognizance of this problem should influence decisions regarding proctocolectomy and the type of surgical anastomosis to be performed. It seems reasonable to consider proctocolectomy in the patient with PSC who shows toxic manifestations of CUC [i.e., fever, anemia, and weakness] that are unresponsive to medical therapy. Further, total proctocolectomy is indicated for the presence of a colonic malignancy or for the presence of premalignant changes, such as moderate to severe colonic dysplasia that complicates CUC. For the patients with PSC in whom proctocolectomy is indicated, particularly when there is clinical evidence of portal hypertension, our results suggest that an ileoanal pull-through procedure may be the treatment of choice. This approach eliminates the possibility of formation of peristomal varices. Although the possibility of developing varices at the site of the ileoanal anastomosis does exist, we have not observed this problem in the 4 patients with PSC who underwent proctocolectomy and ileoanal pull-through procedures and who were followed for up to 73 mo. Should an ileoanal anastomosis not be a therapeutic option because of the patient’s age or anatomic considerations, an ileorectostomy is probably preferable to a Brooke ileostomy or a Kock pouch procedure. Although both conventional and continent ileostomies were associated with peristomal variceal formation and bleeding in our series, the z patients who had a Kock pouch procedure developed severe peristomal bleeding that required surgical intervention. Because of the trauma associated with the intubation of the stoma of the Kock pouch and the frequent need for surgical revision of the Kock pouch, it seems prudent to avoid this surgical procedure in patients with PSC who have had a total proctocolectomy. Our data further support the conclusion that
PERISTOMAL
VARICES AFTER PROCTOCOLECTOMY
321
proctocolectomy should probably be avoided in a patient with PSC and long-standing, quiescent CUC without dysplastic changes. This is particularly important in the patient with PSC who has clinical evidence of portal hypertension, hypersplenism, or advanced histologic stage of the disease on liver biopsy. In this group of patients, regular colonoscopic surveillance for dysplastic changes seems a preferable alternative, given the frequency and severity of the problems associated with peristomal varices suggested by our results. The potential for peristoma1 variceal formation and bleeding quantified in this study suggests that a proctocolectomy specifically to influence the course of PSC should be avoided because there are presently no data to suggest a beneficial effect of proctocolectomy on the natural history of PSC. In those unfortunate patients who develop peristoma1 varices associated with major bleeding episodes, a conservative therapeutic approach seems best. Local treatment with pressure dressings and Gelfoam generally will temporarily control bleeding. Should bleeding become a major problem that requires multiple transfusions, however, surgical intervention with a decompressive shunt procedure should be considered. With the advent of liver transplantation as a viable therapeutic option for patients with PSC and liver failure, any decision regarding shunt operation should include the consideration that patients who have a portacaval shunt have an increased operative mortality associated (10). Thus, in the patient with liver transplantation who has PSC and portal hypertension associated with severe peristomal variceal bleeding, consideration should be given to liver transplantation as a definitive procedure. If such a patient is not considered a liver transplant candidate, a portacaval shunt is a reasonable option for treatment of severe, recurrent, peristomal variceal bleeding. In summary, this study showed that recurrent bleeding from peristomal varices is a common problem in patients with PSC and portal hypertension who have undergone total proctocolectomy and abdominal ileostomy. The results suggested that, in is patients with PSC in whom proctocolectamy clearly indicated because of complications associated with severe CUC, an ileoanal pull-through procedure is probably the surgical treatment of choice. Patients with severe peristomal variceal bleeding should be treated in a conservative fashion, if possible, with pressure dressings, local use of Gelfoam, and blood transfusions. If the patient is a liver transplant candidate, portacaval shunt surgery should be avoided.
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ki3fereixis 1. Wiesner
2. 3.
4.
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RH, LaRusso NF. Clinicopathologic features of the syndrome of primary sclerosing cholangiiis. Gastroenterology 1980;79:20@-6. LaRusso NF, Wiesner RH, Ludwig J, MacCarty RL. Primary sclerosing cholangitis. N Engl J Med 1984;310:899-903. Ricci RL, Lee KR, Greenberger NJ. Chronic gastrointestinal bleeding from ileal varices after total proctocolectomy for ulcerative colitis: correction by mesocaval shunt. Gastroenterology 1980;78:1053-8. Adson MA, Fulton RE. The ileal stoma and portal hypertension: an uncommon site of variceal bleeding. Arch Surg 1977; 112:501-3. Cameron AD, Fone DJ. Portal hypertension and bleeding ileal
6. 7. 8.
9.
10.
varices after colectomy and ileostomy for chronic ulcerative colitis. Gut 1970;11:755-9. Eade MN, Williams JA, Cooke WT. Bleeding from an ileostomy caput medusae. Lancet 1969;ii:1166-8. Edwards EA. Functional anatomy of the porta-systemic communications Arch Intern Med 1951;88:137-54. Schrumpf E, Fausa 0, Kolmannskog F, Elqjo K;Ritland S, Gjone E. Sclerosing cholangitis in ulcerative colitis: a follow-up study. Stand J Gastroenterol 1982;17:33-9. Ludwig J, Barham SS, LaRusso NF, Elveback LR, Wiesner RH, McCall JT. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis or chronic ulcerative colitis. Hepatology 1981;1:632-40. Starzl TE, Iwatsuki S, Van Thiel DH, et al. Evolution of liver transplantation. Hepatology 1982;2:614-36.