A Lasser

BH Smith

BM Wolfe

D Sutherland

HS Cooper

I Penn

Lawrence J. Koep

LJ Perloff

MD Goodman

MK Misra

OI Sawyerr

P Eras

RJ Goodall

RL Simmons

RY Calne

TE Starzl

Thomas E. Starzl

Thomas G. Peters

WC Bernstein

English

PubMed

Crossref

Major colonic complications of hepatic transplantation

Koep, LJ

Peters, TG

Starzl, TE

Name not available

Major Colonic complications of hepatic transplantation

D-Scholarship@Pitt

•• j , ., ~1ajor Colonic COlnplications of Hepatic Transplantation* LAWRI::SCE J. KOH. M.D., THOMAS G. PETI::RS, M.D., THOMAS E. STARZL, M.D., PH.D. THE SI::RJES of orthotopic hepatic transplants at the Uni\'ersity of Colorado Medical Center now includes 157 patients. In this series there have been eight major colonic complications. providing an incidence of 5 per cent. Of this group of eight patients, only three survived, yielding a hospital mortality rate of 63 per cent for those patients in whom colonic complica-tions developed. Earlier reports from both this center and Cambridge-Kings College have identified the biliary tract as the most frequent source of complications in hepatic transplantation.2 . 14 As our experience in-creases, however, colonic complications are assuming a more identifiable position in the postoperative pe-riod. The colon's contribution to H'nal-transplant morbidity is now well established. The incidences of colonic complications associated with renal transplan-tation, 1-5 per cent, are similar to the incidence in our series of hepatic transplantations. I. 8.10.11 Case material is summarized in Table I. Report of Eight Cases Patient 1. A 2Y2-year-old girl underwent hepatic transplanta-tion for biliary atresia. Despite good hepatic function, a bile leak necessitated biliary revision at two weeks. This was accompanied by a brief period of rectal bleeding, which ceased spontaneously. On her sixty-fifth post-transplant day the patient underwent negative exploratory laparotomy because of suspicion that an abdominal abscess was present. Four days later, massive hematochezia recur-red. Laparotomy revealed bleeding from a cecal ulcer. necessitat-ing right hemicolectomy with i1eotransverse colostomy. Bleeding ceasd but pulmonary and hepatic failure rapidly developed. Dif-fuse cytomegalovirus inclusion disease of the lung. liver. and brain was found. Patient 2. A 16-year-old girl received an orthotopic hepatic transplant for chronic active hepatitis. Despite an initially benign course, rejection occurred on the forty-seventh post-transplant day, necessitating increased steroid administration. Five days later, hepatic function was again normal, but the following day free intraperitoneal air was seen on chest x-ray. Exploration of the ab-domen disclosed a freely perforated diverticulum of the right colon with diffuse peritonitis. Hemicolectomy with ileostomy and mucous • Received for publication December 15, 1978. Supported by research grants MRIS 8118-01 and 7227-01 from the Veterans Administration; by Grant Numbers AM·17260 and AM-07772 from the National Institutes of Health; and by Grant Numben RR-00051 and RR-00069 from the General Clinical RESEARCH Centers Program of the Division of Research Resources, National Institute of Health. Address reprint requests to Dr. Koep: Box C-305, Department of Surgery, University of Colorado Medical Center, 4200 East Ninth Avenue, Denver, Colorado 80262. ,. , ' . From the Department of Surgery. UllIverszty of Colorado Medical Cenl" Denver. Colorado, and ~ Denver Velerans Administration HOSPital. . Denver, Colorado fistula was performed. Pulmonary and renal failure ensued, and .the patie~ll died four days later of severe Pnfumocyslis carin" pneumoma. Patient 3. A R~-year-old boy with biliary atresia recei\ed an orthotopic hepatic transplant following a particularly difficult hepatect0Il!Y. Operative trauma to the right colon produced serosal tears, which were repaired. Six days later, laparotomy for intl'3-abdominal bleeding disclosed a free perforation at the previous colonic repair site. This perforation was closed and widely draine-d; however, three days later it again disrupted, necessitating right colonic resection, ileostomy, and mucous fistula. Initial recovef) was good, but biliary obstruction and later rejection intervened. Three weeks after colonic resection the patient died of pneumonia and hepatic failure. Patient 4. A 29-year-old man experienced severe enceph_ alopathy following a portacaval shunt, necessitating an orthotopic hepatic transplant. Two early episodes of rejection abated in response to increased steroid administration. A month after transplantation, a wound infection ",as opened, exposing the transverse colon. Two months later a small erosion produced a colocutaneous fistula. Two initial repair attempts were un. successful but, a year after transplantation, a segmental colonic resection and primary anastomosis healed the fistula. The pa, tient remains well two years following transplantation. Patient 5, A P~-year-old boy underwent hepatic transplan' tation for biliary atresia. The hospital course was unremark. able, and the patient was discharged with normal hepatic function after 10 weeks. One and a half years after transplantation, he was admitted for vomiting and melena. An upper-gastrointn-tinal tract barium study demonstrated a duodenal ulcer, and gastroscopy revealed gastric distention with a tight pylorus that could not be passed. Despite appropriate antacid therapy, melena recurred and became massive two weeks later. Laparotomy ",as hindered by extensive abdominal adhesions, but nu ulcer was seen through a gastroduodenostomy. Further exploration revealed pneumatosis cystoides intestinalis confined to the colon. BecauK bleeding was massive, a colectomy with ileoproctostomy was performed. The colon, though completely covered with muco~ petechiae, had no ulcerations. Recovery was uneventful, and mild diarrhea resolved within a month. Six months later the patient dit'CI suddenly of varicella meningitis; there was no colonic abnor· mality at autopsy. Patient 6. A 15-year-old boy with alpha ,-antitrypsin deficiency had severe cirrhosis that necessitated orthotopic hepatic transplantation. His recovery was complicated by twO episodes of rejection. The first evidence of rejection was s~n a month after transplantation, and was readily reversed by In' creased steroid administration. The second episode of rejection developed a month later and was more resistant to steroids. AI this time, massive lower-gastrointestinal-tract bleeding suddenly occurred. Although hepatic function was impaired at this time. clotting was corrected with fresh plasma. Continued hemat<; chezia necessitated laparotomy, which revealed pneumatoSIS cystoides intestinalis and intraluminal blood confined to the (( al " ir d rt· f, d, p: C1 It e: II I ,. I 0 cI P P " h kl tr ti h ~ d b \. bi p I • 1I U n p ry, '1'1", tht ai, Ido tnd nil an uh sal ra· 'us 'd; ht , rv I d. ,Ia h· I lie in er ;t ~d n· lie iI' 1-,. t .n , ·t I-.d JI J is P d ~ ,I J i d TABLE I. eli/liral Summary Age (years) Patient 2VY Patient 2 16 Patient 3 5Y2 Patient 4 29 Patient 5 3VY Patient 6 15 Patient 7 44 Patient 8 22 Days after Transplant 69 52 6 94 512 56 65 19 Colonic Complication Hematochezia from cecal ulceration Right colonic perforation at probable diverticulum Right colonic perforation at traumatic repair site Transverse colocutaneous fistula ~assive hematochezia with pneumatosis cystoides intestinalis of colon ~assive hematochezia with pneumatosis cystoides intestinalis of colon Hematochezia with cecal ulceration Hematochezia with cecal ulcerations colon. C'olectomy with ileoproctostomy terminated the bleeding, although examination of the specimen revealed only petechiae, without mucosal ulcers. Following colectomy liver function initially deteriorated, then gradually improved until the patient's discharge from the hospital two months later. There has been no further bleeding, and bowel habits are normal two years following hepatic transplantation. Patient 7. A 44-year-old man with sclerosing cholangitis described an untreated episode of colitis many years previously. Prior to hepatic transplantation, barium-enema examination, colonoscopy, and biopsies revealed no abnormality. Following transplantation, at one and two months, the patient experienced episodes of rejection responding to increased steroid adminis· Iralion. During the second episode, sudden. massive, lower-gastrointestinal-tract bleeding occurred. Laparotomy revealed an otherwise normal colon distended with blood. Colectomy and ileosigmoidostomy controlled the bleeding, Examination of the specimen revealed cecal ulcers with cytomegalovirus changes. Hepatic function continued to deteriorate. and the patient died two weeks later. At autopsy both cytomegalovirus pneumonia and massive hepatic necrosis with cytomegalovirus were present. Patient 8. A 22-year-old woman who had chronic active ~e~atitis experienced several episodes of encephalopathy fol-Wing a distal splenorenal shunt. She then received a hepatic ':-ansplant, complicated by air embolism. Her post-transplanta-;:On course was further complicated by persisting hepatic failure. tpatorenal syndrome, and coma, Two months following trans-~antation she began to have melena following dialysis. Gastro-~ldenoscopy twice revealed only gastritis with slight erosions I ' WIthout bleeding. The serum urea nitrogen was kept below .",25 rng/dJ. A week later, massive lower-gastrointestinal· tract tedlllg occurred. and persisted despite correction of the de-prtss~d hepatic clotting factors. Mesenteric angiography was ~KEFndlagnosticK Laparotomy confirmed colonic bleeding and t~ghD hernicolectomy with ileotransverse colostomy terminated e bleeding. Examination of the specimen revealed Candida '''''ri'is with numerous ulcerations of the right colon. The ~:Dienl died a day .Iater. of pulmll~aKryI and hepatic faiIUl·e. topsy confirmed dlssenllnaled candIdiaSIS. Procedure Right hemicolectomy Wilh ileotransverse colostomy Right hemicolectomy with ileostomy and mucous fistula I) Closure colonic perforation 2) Right colectomy with ileo- and mucous fistula I) Closure colonic perforation 2) Limited colonic resection and anastomosis Colectomy with ileo-proctostomy Colectomy with ileoproctostomy I) Colectomy with ileo-sigmoidostomy 2) Ileostomy with mucous fistula Right hemicolectomy with _ ileotrans\,erse colostomy Discussion Results Died 3 days later Died 5 dan laler Died 17 days later Well after 2 years Died 6 months later Well after 2 years Died 6 weeks later Died 1 day later These patients sustaining colonic complications fol-lowing hepatic transplantation were condierably yoqnger than those reported to have had similar complications following renal transplantation. The age range of this group of eight patients was 2.5 to 44 years, w.th a mean of 17.1 years. This probably re-flects the younger age distribution of all the hepatic transplant recipients, mean 21 years. The 5: 3 male predominance of this group may have been influ-enced by transplant recipient selection in which males have enjoyed an 85: 72 advantage. These eight complications appear to fall into four general categories: trauma, diverticula, infections, and pneumatosis cystoides intestinalis of the colon. Those two patients who had colonic trauma sustained it either during transplantation (Patient 3) or later, as a result of an open wound (Patient 4). One colonic operative injury during hepatic transplantation had been reported earlier.9 This injury was repaired dur-ing transplantation and healed well; this patient is not included in this report. Diverticular perforation occurred only once, and then in the right colon (Patient 2). This differs from the more frequent left-colonic diverticulum perfora-tion observed in renal transplantation. Since many of our patients are severely constipated, stercoraceous erosion in the right colon may have been a contrib-uting factor. 1 220 KOE\'. ET AL. Infectious uln'ration of the right (!olon occurred in three patients. Patient I died with diffuse cyto-megalovirus infection and. though not originally identified in the resected colon. cytomegalo"irus was probably the cause of the cecal ulcers. In Patient 7 cytomegalovirus was identified in the colonic ulcers. Both patients had multiple-organ involvement with cytomegalovirus.3.6.12.16 The other infection, also producing cecal ulcers, was fungal. In addition to cecal ulcers, many other organs were involved by dis-seminated candidiasis. Nystatin is customarily given orally to prevent fungal overgrowth once bowel func-tion returns.· Unfortunately. a prolonged ileus pre-cluded this prophylaxis. Each of these patients was found to have right-colonic lesions that necessitated resection for massive hematochezia. No other enteric pathogen was identified, and no evidence of pseudo-membranous colitis was present. Pneumatosis cystoides intestinalis confined to the colon was found in Patients 5 and 6. Both patients were explored emergently for rectal bleeding, and the diag.lOsis was n9t suspected preoperatively. Colec-tomy with ileoproctostomy was performed in either. case, and petechiae were present in much of the colon '\ in both patients, though in neither were ulcers iden-tified. There was no clotting defect in either patient. Both patients had no identifiable pulmonary disease, neither patient was receiving respiratory assistance, and, following resection, there was no evidence of any gastrointestinal bleeding in either patient. Conserva-tive therapy has been effective when pneumatosis cys-toides intestinalis is identified roentgenographicallyK~D When sepsis or bleeding suggests further disruption of mucosal integrity, as occurred in these patients, resection is necessary. 13 The etiology of the perforations resulting from trauma or diverticula is apparent. The etiology of those episodes of massive gastrointestinal bleeding re-sulting from either cecal ulcers or diffuse petechiae is less obvious. All patients were immunosuppressed, and four had recently had steroid administration in-creased because of transplant rejection (Patients 2, 4, 6 and 7). Hepatic function was severely depressed in three patients (Patients 6, 7 and 8). Patients 7 and 8 probably had sepsis. All patients. however, bled in the presence of completely normal dotting. Diagnostic maneuvers were restricted by the pre-cipitous nature of the complications, particularly bleeding. In only two patients (Patients 6 and 8) were dotting defects found, and both defects were cor-rected well before operation. Occult bleeding is quite common during periods of impaired clotting sec-ondary to hepatic dysfunction. Sigmoidoscopy was always performed and, despite profuse bleeding, permitted inspeni()n of mucosa below the peritoneal reflection. Gastroduodenoscop), was performed in the last four patients; the one error in diagnosis oe.· cllrred becausl' the pediatric gastroscope could nOt negotiate the tight pylorus in Patient 5. Angi<>graphy was attempted in Patient 8 only. The results Were nondiagnostic and the delay nearly fatal. Angiog_ raphy remains a desirable diagnostic tool if the delay can be tolerated. Nonoperative management consists of correction of clotting defects and administration of vasopressin although the route remains controversial.;5 lperativ~ management has consisted of resecting and ex-teriorizing perforations. Bleeding has been managed by resection and primary anastomosis. Patient 7 had a re-exploration for sepsis and, although the ileosig_ moidostomy appeared intact, it was converted to an ileostomy and mucous fistula. References I. Bernstein WC, Nivatvongs S, Tallent MB: Colonic and rectal complications of kidney transplantation in man. Dis Colon Rectum 16: 255. 1973 2. Caine RY, Williams R: Orthotopic liver transplantation: qh~ first 60 patients. Br Med J I: 471, 1977 3. Cooper HS, Raffensperger EC,Jonas L. et al: Cytomegalovirus inclusions in patients with ulcerative colitis and toxic dilation requiring colonic resection. Gastroenterology 72: l25S 1977 ' 4. Eras P, Goldstein MJ. Sherlock P: Candida infection of th~ gastrointestinal tract. Medicine 51: 367.1972 5;- Goodall RJ: Pneumatosis coli: Report of two cases. Dis Colon Rectum 21: 61,1978 6. Goodman MD, Porter DD: Cytomegalovirus vasculitis with fatal colonic hemorrhage. Arch Pathol 96: 281, 1973 7. Lasser A, Conte M. Soli tare GB: Stercoraceous perforation of the cecum: Report of two cases. Dis Colon Rectum 18: 410. 1975 8. Misra MK, Pinkus GS, Birtch AG. et al: Major colonic diseases complicating renal transplantation. Surgery 73: 942, 1975 9. Penn I, Brenschneider L, Simpson K, et al: Major colonic problems in human homotransplant recipients. Arch Surg 100: 61, 1970 10. Perloff LJ. Chon H, Petrella EJ, et al: Acute colitis in the renal allograft recipient. Ann Surg 183: 77. 1976 11. Sawyerr 01, Garvin PJ. Codd JE, et al: Colorectal complica-tions of renal allograft transplantation. Arch Surg 113.: 84. 1978 12. Simmons RL, ~fatas AJ. Ranazzi LC, et al: Clinical characteris-tics of the lethal cytomegalovirus infection following renal transplantation. Surgery 82: 537, 1977 13. Smith BH, Welter LH: Pneumatosis intestinalis. Am J Clin Pathol 48: 455. 1967 14. Starzl TE, Putnam CW, Hansbrough JF, et al: Biliary compli-cations after liver transplantation: With special reference lO the biliary cast syndrome and techniques of secondary duct repair. Surgery 81: 212,1977 15. Sutherland D. Frech RS, Weil R. et al: The bleeding cecal ulcer: Pathogenesis. angiographic diagnosis. and nonopen-tive control. Surgery 71: 290, 1972 16. Wolfe BM, Cherry JD: Hemorrhage from cecal ulcers of cytomegalovirus infection: Report of a case. Ann Surg 177:490.1973 I . l· I I I I I LYM asSOCI" mecha ing fn the ble The within mary:' nosis f patter: colore progn paire( hema~ tients inerea res pOl come. who T maste highe count· prima progn relate treat)] Th preor patieJ • Re· t De. lity of 4102 .. t Ba Add OIl. M 

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Major colonic complications of hepatic transplantation

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