Int Urol Nephrol DOI 10.1007/s11255-013-0619-4
UROLOGY - CASE REPORT
Caecum perforation after renal transplantation: a case report and review of literature David N. Gachoka • Shipeng Yu • Dinkar Kaw
Received: 24 October 2013 / Accepted: 25 November 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Gastrointestinal (GI) complication used to be the second most common complication in renal transplant patients after infection (Bardaxoglou et al. in Transpl Int 6(3):148–152, 1993). Review of transplant registry reveals that GI complication is no longer the second most common type of complication after renal transplant, but that it is still a common cause of significant amount of deaths in renal transplant recipients (De Bartolomeis et al. in Transpl Proc 37(6):2504–2506, 2005). In a study of 1,515 adults with severe GI complication after renal transplant, Sarkio et al. (Transpl Int 17(9):505–510, 2004) reported that gastroduodenal ulcers followed by colon perforation were the two biggest groups of GI complications during the first year after renal transplantation. Colonic perforation is estimated to occur in about 1 % of all cases of renal transplant patients, and it does predispose to potentially fatal complication. About 50 % of all colonic perforation is due to complication of acute inflammation of diverticular disease (Bardaxoglou et al. in Transpl Int 6(3):148–152, 1993; Guice et al. in Am J Surg 138(1):43–48, 1979; Koneru et al. in Arch Surg 125(5):610–613, 1990; Coccolini et al. in Transpl Proc 41(4):1189–1190, 2009). This is particularly so because these patients were previously exposed to uremia before transplantation which alters their protein metabolism hence
D. N. Gachoka S. Yu Department of Internal Medicine, University of Toledo Medical Center, 3000 Arlington Avenue, Toledo, OH 43614, USA e-mail: [email protected]
D. Kaw (&) Division of Nephrology, Department of Medicine, University of Toledo Medical Center, 3000 Arlington Avenue, Toledo, OH 43614, USA e-mail: [email protected]
interfering with tissue healing there after (Carson et al. in Ann Surg 188(1):109–113, 1978). GI complications including colon perforation after renal transplantation have effect on a patient’s long-term survival (Gil-Vernet et al. in Transpl Proc 39(7):2190–2193, 2007). Despite this, the role of renal transplantation medication compared to anatomic anomaly in GI complication has been equivocal. Keywords Colon perforation Diverticular disease Immunosuppression Corticosteroids
Case presentation A 57-year-old Hispanic female with a history of uncontrolled-type two diabetes mellitus and hypertension who presented to the outpatient clinic for a follow-up visit 3 days after being discharged following a living donor kidney transplant. During her recent transplant surgery, she had received induction immunosupressive therapy with campath (alemtuzumab) and solumedrol 500 mg intravenously. She was started on tacrolimus and mycophenolate for maintenance immunosuppressive therapy immediately after surgery. On post-operative day one and two, she received intravenous solumedrol 250 and 125 mg, respectively. On day three, she was transitioned to oral prednisone 60 mg, which was tapered off to 5 mg in 5 days. Her immediate post-operative course was complicated by anemia for which she received two units of packed red blood cells and moderate nausea that was treated with metoclopramide. On post-operation day number five, she was discharge to home in stable condition with a 3-day followup appointment to renal transplant clinic. On presenting to the clinic, she reported mild-to-moderate pain in the lower abdominal region as well as nausea
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Fig. 1 Patient’s CXR on discharge, 07-17-2012
for 1 day, which prompted the re-admission for further evaluation. She also reported good appetite and being able to pass flatus despite not having had any bowel movement during the same period. On examination, she was in moderate distress and her vital signs were as follows: blood pressure of 114/57 mmHg, pulse of 87 beats per minute without orthostatic changes, temperature of 98.7 °F, respiratory rate of 22 breaths per minute, and oxygen saturation of 92 % on room air. Abdominal examination showed increased distension compared to the day of discharge and a clean surgical incision in the right iliac fossa. She expressed mild tenderness on squeezing this area. On auscultation, she had moderately decreased bowel sounds in all four quadrants and also exhibited tympani to percussion on the right side of her abdomen. The rest of her examination was normal. Her laboratory test results on admission showed a white blood count of 25,000/mm3 with segmented polymorphic neutrophils of 95 % and bands 4 %; lymphocytes counts was 0 %, platelet count of 369,000/mm3, hemoglobin of 9.6 g/dL, hematocrit of 28.5 %, sodium of 124 meq/L, potassium of 4.2 meq/L, chloride of 91 meq/L, bicarbonate of 21 meq/L, BUN 47 of mg/dL, creatinine of 2.04 mg/dL, magnesium of 1.5 mg/dL, and phosphorous of 4 mg/dL. Her total bilirubin was 0.9 mg/dL, indirect bilirubin 0.7 mg/dL, uric acid 9.8 mg/dL, calcium 9.2 mg/dL, and glucose 130 mg/dL and tacrolimus level of 33.9 ng/mL. An abdominal series X-ray revealed significant interval increase in free air under the diaphragm when compared to previous study before the discharge which was concerning for possible GI perforation (Figs. 1, 2). CAT scan of the chest and abdomen revealed a large volume of free
Fig. 2 Patient’s CXR on admission, 07-20-2012
Fig. 3 Patient’s abdominal CAT, 07-20-2012
intraperitoneal air with extensive inflammatory changes along the ascending colon and the adjacent small bowel suggesting perforation (Fig. 3). It also revealed a normal appendix with the remaining colon-containing stool up to the hepatic flexure without evidence of obstruction. Ultrasound of the transplanted kidney was normal. The patient was taken for an emergent exploratory laparotomy. Prior to surgery, her hyponatremia was corrected with 3 % saline solution. She was started on zosyn and one dose of intravenous vancomycin. On laparatomy, perforation was localized at the cecum. A right hemicolectomy and ileostomy were done. Post-operatively, her immunosuppressive medications were restarted intravenously, and she
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was able to transfer back to the regular surgical ward 3 days later. Pathology results from the resected colon showed no malignancy or CMV inclusion bodies but areas of distended colon with diffuse acute serositis and purulent serosal exudates. Variable amount of acute inflammation as well as focal transmural necrosis consistent with perforation was also noted on some areas of the colon. The patient was discharged home 8 days after the operation. Repeat chest X-ray before discharged showed resolved pneumoperitoneum.
Discussion Two patterns of colonic perforation have been described in the past, acute, and chronic. Acute pattern present few days or weeks after transplantation, and it usually is from diverticulitis or cytomegalovirus enteritis. Our case patient had no diverticular disease on pre-operative colonoscopy. The chronic pattern occurs years later after graft implantation, and it is usually associated with malignancies. Many causes for acute GI complications after renal transplantation have been discussed in the literature. However, it still remains difficult to distinguish if these complications arise entirely from post-transplant immunosuppression or from other causes such as infection. Several authors have in the past explored the role of immunosuppressive therapy in colonic complications by proposing that the use of highdose steroid therapy as used during the induction phase during renal transplant can precipitate GI perforation. They attribute this to the steroids effects of thinning the intestinal lymphoid tissue, diminishing resistance to bacterial invasion, and decreasing fibroblastic reparative activity thereby slowing down the turnover of the intestinal mucosa cells [4, 6, 9]. In their chart review study of 1,401 renal transplant patients, 30 of whom did experience colonic perforation, Stelzner et al.  reported that the incidence and outcome of this complication was associated with the intensity of immunosuppressant. Patients who were exposed to mean daily dose of corticosteroids three times higher were more likely to have fatal outcome compared to those who did not. Of note is that the current post-transplant immunosuppressive regiment has undergone multiple changes. Corticosteroids are now being used at lower doses or are being used only during immediate post-operative period, though at much higher doses with fast taper to steroid free maintenance immunosuppression as was in our patient. It is possible that the short exposure to the high-dose corticosteroids during the patient’s immediate post-operative period could have contributed to her GI perforation possibly from one of the above mechanisms. The role of toxic tacrolimus level contributing to GI perforation is not clear. To date, GI perforation has not
been reported as an adverse effect of tacrolimus. It is possible that in this case, toxic tacrolimus level could have contributed to GI perforation by means of immune over suppression. Literature review, however, does not support this, but instead propose that this medication is likely to be associated with increased incidence of diarrhea  rather than constipation or obstruction. On readmission, our case patient tacrolimus level was 33.9 ng/mL, which is more than two times above the normal level. Despite this, she reported having constipation rather than diarrhea. Right-side colon perforation after renal transplantation is rare when compared to the left side. This is attributed to the preferred anatomic location of colonic diverticular [4, 5]. When present, right-side colon perforation is thought to result from such causes as ischemic and nonischemic colitis, right-side fecal impaction, nonspecific ulcers, or nonobstructive colonic dilatation (NOCD). Ogilve first advanced the concept of nonobstructive colonic dilatation in 1948. The theory proposes that as the colon dilatates, there is inhibition of the sympathetic stimuli that leads to the arrest of the colon’s normal spike and motor activity. This dilatation is thought to follow the law of Laplace, which relates wall tension to the increasing radius of a hollow viscus. In the distended colon, the cecum has the largest diameter exposing it to the highest wall tension and subjecting it to distension-induced ischemia. The overall effect may present on pathology specimens as mucosal hemorrhage, necrosis, ulceration, or sub mucosal vein thrombosis all of which may suggest the effect of dilatation to colonic perforation . This may explain the necrosis identified in our patients pathology specimen. The role of CMV infection causing GI perforation is another possibility that we explored in this case. We, however, did not find any serological or pathological evidence to support this cause. Moreover, CMV reactivation and disease are most likely to occur in CMV seronegative recipients of an organ from a seropositive donor, and it usually occurs between 2 weeks and 4 months post-transplant. Our case patient and donor both were CMV seropositive, and she was also taking CMV prophylaxis (valganciclovir), which makes it even more impossible for CMV infection to be the cause of her acute GI complication. To summarize, GI perforation after renal transplant is relatively infrequent, but it is associated with the worst outcome. In our literature review, it was apparent that rightside colon perforation is rare and from obscure causes despite predisposing to the same serious consequences associated with any other site of GI perforation. Common identifiable causes of GI perforation are numerous with the most obvious ones being acute inflammation of diverticular disease; CMVassociated perforation as well as overt infection including clostridium difficile-associated colitis. Some of the obscure
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causes are thought to results from NOCD, immunosupression medication side effects, or electrolytes imbalance experienced after renal transplantation. In our index case, the cause of cecum perforation is not clear. We can only hypothesize that any of the above causes could have caused this complication despite contrary evidence during the investigative work up. The perforation could also be possibly from a currently not well-defined mechanism. Since GI perforation in renal transplant patients can lead serious adverse outcome despite mild-to-moderate symptoms manifestation, there is urgent need for proper diagnosis and subsequent intervention. A high index of suspicion for GI perforation in patients presenting with GI symptoms should be exercised and an emergent laparatomy offered since it has been shown to lower the risk of fatal complications [6, 8].
9. Conflict of interest All authors in this manuscript have no conflict of interest. 10.
References 11. 1. Bardaxoglou E, Maddern G, Ruso L, Siriser F, Campion JP, Le Pogamp P et al (1993) Gastrointestinal surgical emergencies following kidney transplantation. Transpl Int 6(3):148–152 2. De Bartolomeis C, Collini A, Barni R, Ruggieri G, Bernini M, Carmellini M (2005) Cytomegalovirus infection with multiple
colonic perforations in a renal transplant recipient. Transpl Proc 37(6):2504–2506 Sarkio S, Halme L, Kyllonen L, Salmela K (2004) Severe gastrointestinal complications after 1,515 adult kidney transplantations. Transpl Int 17(9):505–510 Guice K, Rattazzi LC, Marchioro TL (1979) Colon perforation in renal transplant patients. Am J Surg 138(1):43–48 Koneru B, Selby R, O’Hair DP, Tzakis AG, Hakala TR, Starzl TE (1990) Nonobstructing colonic dilatation and colon perforations following renal transplantation. Arch Surg 125(5):610–613 Coccolini F, Catena F, Di Saverio S, Ansaloni L, Faenza A, Pinna AD (2009) Colonic perforation after renal transplantation: risk factor analysis. Transpl Proc 41(4):1189–1190 Carson SD, Krom RA, Uchida K, Yokota K, West JC, Weil R 3rd (1978) Colon perforation after kidney transplantation. Ann Surg 188(1):109–113 Gil-Vernet S, Amado A, Ortega F, Alarcon A, Bernal G, Capdevila L et al (2007) Gastrointestinal complications in renal transplant recipients: MITOS study. Transpl Proc 39(7): 2190–2193 Rigotti P, Van Buren CT, Payne WD, Peters C, Kahan BD (1986) Gastrointestinal perforations in renal transplant recipients immunosuppressed with cyclosporin. World J Surg 10(1): 137–141 Stelzner M, Vlahakos DV, Milford EL, Tilney NL (1997) Colonic perforations after renal transplantation. J Am Coll Surg 184(1): 63–69 Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B et al (1997) Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 64(3):436–443