Abu-Elmagd, K

Casavilla, A

Demetris, AJ

Fung, JJ

Kocoshis, S

Ohya, T

Reyes, J

Starzl, TE

Todo, S

Tzakis, AG

Van Thiel, DH

Yunis, E

English

PubMed

D-Scholarship@Pitt

\ I ----------Clinical Intestinal Transplantation: Focus on Complications A.G. Tzakis. S. Todo, J. Reyes, K. Abu-Elmagd, A. Casavilla, T. Ohya, J.J. Fung, E. Yunis, AJ. Demetris, S. Kocoshis, D.H. Van Thiel, and T.E. Starzl NINE intestinal transplants (three adults. six childrenl have been performed at the University of Pittsburgh since the advent of FK 506. Eight patients had a combined liver-intestinal transplant. one had a solitary intestinal graft. Four of these were performed 3 to 5 weeks before this report. the other five are presented with 5- to 16-month follow-ups. The clinical profiles of the patients at transplantation are presented in Table I. Eight patients are alive with the original grafts including the pattent with the solitary mtestinal graft. One patient died. The methods and techniques have been previously reported. 1-4 Briefly. the solitary intestinal transplant was arterialized from the infrarenal aorta and drained into the recipient superior mesenteric vein. In the case of the liver-intestinal combination. seven were placed piggybackS onto the re-cipient inferior vena cava (lYC) and. in one case. the retrohepatlc IYC was replaced by the respective donor cava. Arterialization was from the infrarenal aorta with the use of fresh vascular grafts. A portacaval shunt provided permanent drainage of the recipient portal vein (PV) in two cases. In the remaining cases. the PY of the recipient was drained into the PY of the donor. A temporary portacaval shunt during the pro-From the Departments of Surgery, Pathology and Pediatrics. University Health Center of Pittsburgh, University of Pittsburgh, and the Veterans Administration Medical Center. Pittsburgh, Pennsylvania. Supported by Researcn Grants from the Veterans Administra-tion and Project Grant No. OK 29961 from the National Institutes of Health. Bethesda. Maryland. Address reprint requests to Thomas E. Starzi. MD. PhD. De-partment of Surgery. 3601 Fifth Avenue. Universrty of Pittsburgh, Pittsburgh, PA 15213. ,© 1992 by Appleton & Lange 0041-13451921$3.001 +0 Table 1. Patient CharactMstlc and Outcome HQIIIiIaI Stav TnI/IICIIII--', (w) Age C ... oIShort Cytaaac CurNrI trnmuno- ~t Pad .. Sex (y) Gut Syndrome Grill CIllUIII8ICtI s\IIIIlIWIIICIII' ICU Wild CUItWITPN (d) M 31.1 Gun shot Small bowei Negative FK 506. steroids. 2 40 Partial 36 498 injury of azaII1IOpriI18 SMA 2 F 2.3 NeaoIiZIlg Small bowel- Negative FK506 0.7 29 NoneSwk 418 enteroIiIis livw 3 F 26.7 ThI'Oll'lbcllia Small bowel- Negative FK 506. steroid8. 0.6 21 None 407 livw azaIhiopIi 18 4 M 4.3 GIIIIIOIdlisia Small bowei- NegIIive FK508 0.4 >38 Partial 6 298 liver 5 M 2.B Inteltinal Small bowel- Doubdul posdive FK 506. steroids 12.4* >12 Partial 171 a .... liver 6 F 0.8 Intelllnel Small bowel- NegIIive FK506 3.1' 22* a1NIia liver 7 F 1.1 VoIwIua Small bowel- NegIIive FK 1508. IIeroida 0.4 >4.8 Partial 35 liver 8 F 1.7 VoIwkIa Small bowel- NegIIive FK 1508 3 >1.7 Partial 33 livw 9 M 22.4 Mea YlII1ide Small bowel- Strongly positive FK 506. steroids. 2 >1.5 Partial 24 accidInt livw azaIhicIprine (injury of SMA right neptno. tomy) 'Pa1IInr 1 ,....,... a 7", CCIIne 01 OKT3. and patiIIe 1. 5. and II __ .-aid ~ tFoIIoiIMIo to SeoIImDIr 15.1991. *R ............ ~ 01 ~ Ieltclll!llftlJn. §Pllllnt CIIed oIlIDII*e acaa QVHD. 1238 qr~ Proceedings, Vol 24. No 3 (June), 1992: pp 1238-1240 , l ~ ; . f t 1 ~ f • 1 ? f I ! + I , INTESTINAL Tx COMPLICATIONS 1239 Table 2. CliniClli CoUrM No. 01 ReteaJOI1 EpisoOIs SmIIII Patient T echniceI CoIT\llliCallOnS BOMi Uver 8aCWIII 1 None 6 0 2 None 3 3 3 PSeudoaneurysm of the 2 0 femoral artlllY'-"'fe-qulred femoral artery graft 4 Spinal cord injury after 6 3 spinal tap 5 ParalysIS of the nght 4 hemJdiaphragm 6 Anastomotic bowel leak 0 0 1 7 None 0 0 0 8 HemophIlic requIred SO 0 0 a reconstrucuon 9 None cedure was used in three cases. because test clamping caused unacceptable congestion. Intestinal continuity was established at the time of the surgery In all cases but one who had a double enterostomy. Both ends of the intestinal graft were exteriorized in the first five cases and closed 8 to 16 weeks later. In the latter four cases in the series. only the distal end was exterior-ized. Immunosuppression was with FK 506 and prednisone supplementation." Azathioprine was given when sufficient FK 506 could not be administered mainly because of renal impainnent. Patient characteristics at transplantation and outcome are shown in Table I. Three patients are living at home. two of them are totally independent of any fonn of intravenous tIV) therapy. The difficulties encountered during the postoperative course are summarized in Table 2. REJECTION This complication presented with fever. malaise. dysmo-tility (ileus or diarrhea) of the graft. and malabsorption. All patients with longer follow-up (cases I to 5) developed at least one biopsy-confinned episode of rejection of their intestinal graft. Seventeen such episodes were diagnosed in total. On five occasions. pathogens from the intestinal lumen pro-duced septicemias (translocation). Augmented immunosuppressive therapy resulted in complete resolution of the syndrome. Rejection caused sloughing of all identifiable mucosa in two cases. Control of rejection resulted in regeneration. Liver rejection occurred in five cases (Table 2). When liver rejection was contemporaneous to the intestine. the liver allograft responded to treatment and resumed normal No. of InfectIOUS Episodes Viral Fungli T ranliDc8llon 0tIw' SignticIIIt ComPllCabona 0 1 1 Noncompliant 1 0 2 Refusec1 to eat 0 0 0 PancreatItIS. gastrIC stony + m~K pseuoomem-branous calms 2 0 2 Pylorospasm 2 0 0 Prolonged aSSIsted venblation a 0 0 Died of POSSIble acute GVHD a 0 0 None 0 0 None 0 a 0 Pancreatitis function before the intestine. Patient 4 developed five liver rejections not accompanied by intestinal rejection. GRAFT-VERSUS-HOST DISEASE (GVHD) Patient 6 died of GVHD. The patient had an unsuspected Pneumocystis pneumonitis at the time of transplantation and developed an anastomotic leak at the gastrojejunos-tomy. Fear of fatal infection prompted reduction of the FK 506 dosage. At approximately I week postoperatively. she devel· oped cellulitis of the abdominal wall. Skin biopsies at day 11 failed to reveal GVHD. Repeated skin biopsy at post-operative day 20 showed unequivocal histological evi-dence of the disease. The patient went on to develop a multiorgan failure in spite of aggressive immunosuppres-sive treatment. INFECTION All patients with longer follow-ups (cases I to 5) developed at least one episode of infection during the postoperative course.7 On five occasions. the cause was thought to be translocation. because the same organisms. bacterial in 4 and fungal in I. which were found in the lumen of the intestine. produced septicemia 1 to 2 days later. One patient (2) developed CMV enteritis. which re-solved with reduction of immunosuppression and IV DHPG treatment. Patient 5 developed Adenovirus enteritis which also is thought to have resolved. ENTERAL ALIMENTATION Enteral alimentation was attempted within a few weeks of transplantation. All patients with long follow-ups (cases 1 to 5) have been independent of IV nutrition and gained weight on enteral alimentation for various periods of time. ;: ,. 1240 Nevenheless.IV nutrition is a remote memory in only two patients. who live at home and enjoy eating. Failure to maintain enteral nutrition long term has been due to: I. Rejection. Rejection resulted in dysmotility and mal-absorption which necessitated interruption of the enteral feedings. Enteral nutrition could be reinsti-tuted after the rejection was controlled. 2. Infection. Systemic infections resulted in ileus which necessitated interruption of enteral nutrition. CMV or adenovirus enteritis had the same result. Resolu-tion of these complications allowed resumption of enteral alimentation. 3. Refusal to eat. It was assumed that. given the choice. all patients would prefer to eat rather than be fed IV or enterally with feeding tubes. Contrary to this assumption. the pediatric patients in panicular dem-onstrated a recalcitrant refusal to eat. even if this meant a well-understood inconvenience of IV line placement and insenion or maintenance of nasal feeding tubes. The cause of this phenomenon probably lies with the unpleasant experience which the patients have had in association with food preoperatively or lack of experience with feeding. An adult patient (3) described that. although she forced herself. she had no desire to eat whatsoever for 7 months after transplantation and did not enjoy eating until after then. In one of our pediatric patients (2). refusal was followed by hesitation over a period of 4 to 5 months. and she has now developed normal eating patterns which she seems to enjoy. RENAL FAILURE Two patients (cases I and 9) have required hemodialysis within the first week after surgery. The first patient's renal failure was thought to be the result of a complicated postoperative course and the use of nephrotoxic agents. primarily antibiotics and FK 506. The same causes are suspected in case 9. in addition to the fact that the patient lost function of the left kidney at the time of the injury which necessitated the transplant. Patient 9 subsequently recovered from renal failure and patient I is awaiting kidney transplantation. All patients developed some renal dysfunction during the postoperative course which responded to reduction of FK 506 and withdrawal of other nephrotoxic agents. Inability to administer therapeutic doses of FK 506 because of renal dysfunction was the main cause of adju-vant treatment with azathioprine. TZAKIS. TODO. REYES ET AL OTHER IATROGENIC COMPLICATIONS This group of patients suffered an unprecedented number of iatrogenic complications. which precipitated a cascade of life-threatening or compromising events. Patient 3 developed a pseudoaneurysm of the left fem-oral artery as a result of an anerial line. Repair of the pseudoaneurysm resulted in recurrence. presumably due to suture line infection which necessitated an extraanalOm-icaJ bypass. There is no permanent disability. Patient 4 developed paraplegia after a spinal tap. The spinal tap was performed 6 months after transplantation to rule out meningitis and resulted in a hematoma of the spinal cord. Emergency decompression was performed. but the prognosis for recovery is poor. Patient 5 developed paralysis of the right hemidia-phragm presumably due to right phrenic nerve injury at the time of transplantation. He has been ICU-bound since the time of transplantauon and is currently intermittently respirator dependent. Patient 8 developed hemobilia after a percutaneous liver biopsy which necessitated bile duct reconstruction for evacuation of clots. COSTS The cost of transplantation of these patients has or is expected to exceed 5500.000 per case. Considering the high cost of IV nutrition and its com"li-cations. a successful intestinal transplant should still offer a savings in the long run. Nevenheless. the cost of these transplants has been extraordinarily high and may limit access to the procedure by the less wealthy patients. CONCLUSIONS Successful intestinal transplantation is now possible. Wide clinical application is tempered by the complex postoper-ative course. Rejection. infection. inability to eat. and other compli-cations seemingly unrelated to the procedure caused sig-nificant morbidity. GVHD was most likely the cause of the only mortality in our series and stemmed from a technical complication. REFERENCES I. Starzi TE. Todo S. TZalas A. et aI: Surg Gynecol Obstct 172:335. 1991 2. Todo S. Fung JJ. Stant TE. et aI: Ann Surg 212:295. 1990 3. Todo S. Tzakis A. Reyes J. et aI: Tl'lIJ1S1)iant Proc (in press) 4. Tzakis AG. Todo S. Reyes J. et aI: Transplantation Sci 1:27. 1991 5. Tzakis A. Todo S. Starzi TE: Ann Surg 210:649. 1989 6. Abu-Elmagd KM. Fung JJ, Alessiani M. et al: TranaplaDt Proc (in press) 7. Reyes J. Abu-Elmagd K. Nour B: Transplant Proc (in press) 

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