Surgery in the Transplanted Patient


13 Surgical Considerations in Solid-Organ Transplant Recipients

Pasithorn A. Suwanabol, MD, Joshua D. Mezrich, MD

In 2008, over 27,000 patients received solid-organ transplants in the United States alone.1 Advances in the management and the surgical techniques of solid-organ transplantation have led to a growing number of patients living long term with transplanted organs. In fact, the 5-year survival of living donor renal transplant and liver transplant has been reported at 91% and 79%, respectively.1 As a result, general surgeons have a greater likelihood of encountering a posttransplant patient now than ever before.

Despite commonly held concerns, a large number of studies have demonstrated that immunosuppression is not a contradiction to surgery and good outcomes can be expected in the majority of patients.2–7 Additionally, abdominal surgery in transplanted patients is not infrequent, with reports of up to 10% of renal transplant patients experiencing a severe gastrointestinal (GI) complication within 10 years8 and 24% of liver transplant patients having another surgical procedure within 10 years.9

The extensive medication list of transplant recipients frequently seems complicated to caregivers with limited experience, often causing hesitation in evaluating these patients as surgical candidates. Additionally, it can be a challenging task to determine whether the benefits of the procedure outweigh the risks in this special population of patients. In general, as long as the surgeon adheres to basic surgical principles with frequent reevaluation and a low threshold for operative intervention, the disease processes should be manageable, with good outcomes.

It should be emphasized that these patients often present with surgical diseases in a manner unlike their immunocompetent counterparts and need aggressive intervention to achieve cures. Additionally, an appreciation for the balance between preventing graft rejection and infection or malignancy is essential.

This chapter focuses on special considerations in the solid-organ abdominal transplant patient. The goal of this chapter is to provide information for the practicing surgeon who is not at a transplant center to help decide when to perform an intervention or operation, how to modify standard procedures, and when to consider transfer to a transplant center if possible. It cannot be stressed enough that surgical intervention in these patients ideally should be carried out by the original transplant team. However, because the unstable or noncompliant patient is a reality, knowledge of perioperative management of transplant patients is critical for all nontransplant providers.

Preoperative Considerations
Discharge from the hospital is often met with anxiety in both the recent transplant recipient and his or her family members and can be minimized by assurance and education. The transplant patient should have been counseled in medications, including the doses, functions, side effects and potential drug interactions, and recognition of signs and symptoms of rejection and infection. Therefore, patient participation should not be underestimated.

An extensive and expensive workup is unnecessary for minor ambulatory surgery in this population as there is a small complication rate and a low risk of compromising graft function.9 The surgeon should remember that the workup should focus more on the indicated procedure rather than the patient's immune status.9,10 Nevertheless, a thorough preoperative evaluation and understanding of the special considerations in this population are necessary to reduce risk.11 There is typically no need to change medications around a minor procedure, except in select cases [see:Management of Immunosuppression during the Perioperative Period, below].

When planning a major surgical procedure, it is essential for the surgeon to have knowledge of the patient's graft function. This will aid the surgeon in optimizing perioperative management of fluid and electrolyte status, medications, blood pressure, and ventilation as well as anticipating immediate postoperative care.12 Consideration of transplant patients undergoing major surgery should follow the algorithm shown in Figure 1. Patients should provide a thorough history of symptoms related to their graft. For example, renal transplant patients vary in their ability to concentrate urine, and to avoid further graft dysfunction, it is critical to provide adequate hydration and careful monitoring of serum electrolytes. Liver transplant recipients should be asked about jaundice, pruritus, change in the color of urine or stool, and fluid retention.

Renal transplant patients often have associated multiorgan disease as a result of their primary condition (i.e., diabetes mellitus, hypertension) and should be evaluated for symptoms of underlying disease on a physical examination. Liver transplant recipients should be evaluated for underlying liver dysfunction: asterixis, ascites, and edema. As with renal and liver transplant recipients, pancreas transplant recipients should have a thorough physical examination with particular attention to the abdomen.

In most cases, standard laboratory values are adequate. For instance, in renal transplant recipients, an assessment of creatinine, urine protein/creatinine ratio, and glomerular filtration rate (GFR) may suffice. In liver transplant patients, assessment of coagulation and liver function tests (LFTs) may be adequate. In general, bilirubin and synthetic function becomes normal within 3 months following transplantation, and trends in LFTs should be monitored for abnormalities. Pancreas transplant recipients should have serum amylase and lipase, urine amylase (for bladder-drained transplants), and glucose levels monitored. Additionally, as the nutritional status of any patient is critical to decrease the risk of infection and improve wound healing, it is especially important in this particular patient population.9,11–15 Whenever possible, appropriate specialists (i.e., nephrologists, hepatologists) should follow the patient in the perioperative period.

 
Figure 1 Algorithm for Transplant Patients
As in any surgical procedure, it is essential to know the patient's anatomy and examine previous operative notes if at all possible [see Table 1for a summary of common locations and procedures for each transplant]. This will allow consideration of altered anatomy that can lead to unexpected complications. For instance, in patients who have had kidney transplants, the location of the organ, particularly the ureter, is crucial to avoid injury. A previously transplanted ureter looks remarkably like an adhesion even to the trained eye, and many have been divided during uncomplicated lysis of adhesions. This is particularly likely if the kidney was placed through a midline incision and the surgeon does not know on which side the graft was placed.

In patients who have undergone a pancreas transplant, one must consider if a Roux-en-Y reconstruction for drainage of the duodenum was used (or if the pancreas was bladder drained, although this is far less common in recently transplanted pancreata) or if the vein drains via the superior mesenteric vein or the iliac vein in the recipient. Likewise for the liver, knowledge of any vascular reconstructions is critical.

Diagnostic and Radiologic Considerations
Although the physical examination is critical in the evaluation of any surgical patient, caution must be exercised in the transplant patient, particularly those patients who have been on immunosuppression for many years. It is not unheard of to explore a patient with a near-normal examination and be surprised to find an abdomen full of succus. For this reason, we are aggressive in obtaining abdominal imaging in the majority of transplant patients who are being evaluated for an intra-abdominal process.

Consideration should be made for diagnostic sampling of any fluid collections or free intra-abdominal fluid that is not expected to rule out surgical causes. Fluid is typically sent for Gram stain and culture, bilirubin, amylase, creatinine, and any other biochemical marker that is relevant to the situation. In general, it is acceptable to follow patients conservatively if that is the judgment of the caregiver, but frequent reassessments are necessary. If the patient does not improve quickly, consideration should be made for aggressive intervention or at least reimaging.

When it comes to choosing radiologic imaging, similar algorithms should be used, as in the nontransplant patient. As in their immunocompetent counterparts, immunocompromised patients may undergo ultrasonography to evaluate the biliary tree, kidneys or ureters, and the female reproductive organs. Computed tomography (CT) is the best tool for assessment of intra-abdominal fluid.16

Transplanted patients being evaluated for trauma should be assessed as any other trauma patient.10,17 Kidney transplant patients often have creatinine levels that run higher than those in the nontransplant patient, with values in the range of 2 mg/dL or above even with stable function. Appropriate hydration decreases the risk of nephrotoxicity similar to that of nontransplant patients,17 and standard bicarbonate protocols are similarly helpful. If CT is warranted for safe management of the trauma, it should be conducted. It may be useful to hold the calcineurin inhibitor (cyclosporine or tacrolimus) for a few days following the contrast load as these drugs are nephrotoxic. Holding a calcineurin inhibitor for a few days in the setting of a trauma typically is safe. Depending on the patient, extra steroids (such as the equivalent of 10 to 30 mg of prednisone per day) can be considered during this period, although, again, if use is limited to a few days, it is probably unnecessary. Ideally, this would be done in consultation with an appropriate specialist or transplant center.

Intraoperative Considerations
Since the introduction of minimally invasive techniques, transplant surgeons have been active participants in its use, from ultrasound-guided biopsy to laparoscopic donor nephrectomy. As in immunocompetent patients, the use of minimally invasive techniques in immunocompromised patients is safe and provides the same benefits, such as decreased hospital stay and narcotic use, as well as com parable or even improved complication rates.18–21 A skilled laparoscopic surgeon should always offer the immuno compromised patient the laparoscopic alternative when available and feasible.

During any reoperation following a kidney transplantation, one should always be thinking of the ureter. If one does come across and divide the ureter unexpectedly, the most likely repair will be a ureteroureterostomy, using the patient's native ureter and sewing it end to end over a stent after spatulation. Most commonly, this does not require a native nephrectomy even if the patient's native kidney makes urine, although, in occasional cases, hydronephrosis can follow, requiring a native nephrectomy at a later time point.

As a general rule, similar principles of surgical technique should hold with the transplant patient. Additionally, any procedure that is reasonable in the nontransplant patient can be used in the transplant patient. We do caution the practitioner who has not had a lot of experience with transplant patients that the long-term immunosuppressed patient in particular certainly has an increased risk of poor healing or wound or anastomotic dehiscence. Moreover, the patient will not always show the signs of sepsis that are commonly noted when this happens. Note that there is no real definition of “long term,” and this is an anecdotal observation. In general, those patients who have been immunosuppressed for a decade or more seem to be at higher risk for complications related to healing. Therefore, any transplant patient who simply does not progress and heal in a fashion that seems reasonable should be considered for a complication, and aggressive radiologic assessment is recommended.

Antibiotics and Pain Medicine in the Perioperative Period
It is well established that immunocompromised patients encounter many more infections than their immunocompetent counterparts, in particular rare fungal, bacterial, and viral infections.10,15,22–28 Fifty to 70% of transplant patients have at least one episode of bacterial infection, and 30 to 60% have at least one serious viral infection.10,29 In general, posttransplant patients have a predictable infectious course: within the first posttransplant month, infections are comparable to those of their immunocompetent counterparts and are usually bacterial in nature; in months 1 through 6, patients are at risk for opportunistic infections, including Pneumocystis carinii, Listeria monocytogenes, and Aspergillus species; more than 6 months posttransplantation, two thirds of patients suffering from an infection will develop a community-acquired respiratory virus, whereas the remainder will develop chronic viral infections (such as hepatitis B and C viruses). A group at particular risk are those who received excessive amounts of immunosuppression as a result of early rejection or delayed graft function, causing the greatest risk of infection from opportunistic pathogens such as Cryptococcus neoformans, P. carinii, and L. monocytogenes.30,31 Other viruses that are quite well known to transplant physicians are cytomegalovirus and BK virus, which can cause nonspecific symptoms such as fevers or diarrhea but can also cause graft dysfunction or loss of a graft. Certainly, any transplant patient who is suffering from more than an easily diagnosable and treatable urinary tract infection, pneumonia, or line infection should undergo workup for these pathogens, and consideration should be given to transferring to a transplant center.

There is no evidence of prolonged perioperative antibiotic (greater than 24 hours) use despite the widespread use of prophylactic antibiotics in a patient's medication regimen. This is attributable to an increased risk of viral and fungal infections in addition to superinfection with resistant bacteria and/or Clostridium difficile.11,32 Surgical prophylaxis should include therapies against skin flora such as staphylococci and streptococci and, in renal transplant patients, the inclusion of therapies against urine species such as Escherichia coli, Klebsiella, and Proteus. In suspected infection, empirical therapy should be guided by the suspected anatomic site and organism, previous antibiotic therapy, renal and hepatic function, and immunosuppression status. Continued therapy after identification of an organism should be as specific as possible with consideration of renal and hepatic function.

Postoperatively, consideration of hepatic and renal function is necessary when choosing medications such as narcotics and antihypertensives. For example, in patients with suboptimal liver function, morphine, meperidine, or propoxyphene for pain management and clonidine or nifedipine for hypertension are preferred.9

Management of Immunosuppression during the Perioperative Period
Immunosuppression in the solid-organ transplant patient often includes several agents with different mechanisms to use lower doses and decrease potential toxicity.31 Additionally, in the late postoperative period (2 to 6 months), immunosuppression is usually decreased as the allograft is typically functioning well and rates of rejection are highest in the first 6 months, with decreasing incidence thereafter. When considering elective procedures, it may make sense to delay them for up to 6 months after transplantation or at least the point where they are down to their baseline maintenance immunosuppression. This, of course, has to be balanced with the urgency or risk of delaying the surgical procedure.

Immunosuppression is associated with an increased susceptibility to infection and poor wound healing.10,33 However, a balance between preventing graft rejection and anticipating the patient's response to surgical stress must be appreciated. If the procedure is unable to be performed by the original transplant team, the surgeon should not hesitate to consult a transplant service for immunosuppressive guidelines.9

Although historically there has been concern over a immunocompromised patient's ability to undergo surgical procedure, a number of studies demonstrate that these patients are able to undergo a variety of procedures with complication rates similar to those of their immunocompetent counterparts34–37 and without an increased risk of wound healing problems.9,38,39 In general, immunosuppression is not altered during the perioperative period unless the patient is demonstrating significant infection or sepsis. It should be given at the same schedule and dose as the patient's home regimen.9 If the patient is unable to take anything orally, azathioprine and mycophenolate mofetil (MMF) can be safely withheld for 2 to 3 days. Intravenous cyclosporine can be used at one third the total daily oral dose over 4 to 8 hours. Until the patient is able to tolerate immunosuppression by mouth, immunosuppression levels should be checked daily, with the goal of having no variation from baseline greater than 25%.9 There are some exceptions to this, however. Most transplant surgeons would suggest discontinuing sirolimus and changing to a calcineurin inhibitor as sirolimus has been known to impair wound healing.11,40

In our own practice [see Table 2 for a summary of the medicines and recommended adjustments], for minor procedures, we do not recommend any change in immunosuppression. Patients can take their medicines on the morning of surgery and resume them that night or the next morning, depending on how they are feeling. It is important that patients stay well hydrated perioperatively as the calcineurin inhibitors are nephrotoxic, and this is compounded by a prerenal state. Therefore, we are more aggressive about admitting patients for a day or two after surgery or at least following their laboratory results (organ specific labs are drawn as outpatients at their local clinic/hospital, and results are faxed to the transplant unit) as outpatients and seeing them more frequently if admission is not necessary or feasible. For more extensive procedures, particularly those that will require patients to be nihil per os (NPO) for a period of time, we typically hold their calcineurin inhibitor and put them on the equivalent of 20 to 30 mg of intravenous prednisone per day (we typically use dexamethasone, 2 mg every 8 to 12 hours IV, until they can return to their home dose). This obviously depends on what organ they have received, how recent the transplantation was, and what their rejection history is.

If the patient is well clinically and at high risk for rejection (young, recent transplant, previous episodes of rejection, African American, kidney transplant recipient), then con sideration can be made for using intravenous cyclosporine if the patient is on that medication or sublingual tacrolimus (typically half the dose of oral). If this is done, levels should be followed daily until they return to the patient's normal oral dose and baseline levels have been achieved. If at all possible, we do recommend at least discussing the plan with the transplant physician prior to the surgery and, ideally, having his or her input in the perioperative period. If the patient is on MMF, we usually continue this drug intravenously. A well-known side effect of this drug is diarrhea or other GI symptoms, so if the procedure is a major GI operation, it may be necessary to hold this until bowel function normalizes.

We would offer caution considering any operation on a patient who is on sirolimus. This drug has a dramatic effect on wound healing, and, ideally, we stop this drug 2 months before an elective procedure, substituting a calcineurin inhibitor if possible. We would prefer that the patient remain off this drug at least 2 months after the procedure, assuming that the wound has healed well. For those patients who have more urgent procedures, we would at least recommend that sirolimus is held postoperatively for 2 months or more, again substituting alternative agents. All of these decisions should be made in concert with the transplant physicians.

A common concern for nontransplant practitioners is the use of stress-dose steroids in the transplant patient population. Although patients on immunosuppressive medications may have abnormalities of the pituitary-adrenal axis, there is no evidence to support the use of increased steroids in the perioperative period.9,33,41 In fact, the use of high-dose steroids promotes poor wound healing, causing both slower healing and decreased strength of the wound.9,10 This effect has been offset by the administration of vitamin A supplementation.10,42 Stress-dose steroids may be indicated when a patient demonstrates adrenocortical insufficiency, as evidenced by clinical symptoms of weakness, nausea, vomiting, and fever.2 To reiterate, the use of stress-dose steroids is not supported or advocated prophylactically in any procedure. It may be reasonable to consider stress-dose steroids in the septic patient or those patients undergoing major surgery with unexplained hypotension or other signs of adrenocortical insufficiency but otherwise may not be necessary.

Complications
Fortunately, the complication rate for elective procedures in this patient population is similar to that of immunocompetent patients. However, emergent procedures are associated with increased morbidity and length of hospital stay.9 Most authors would advocate an aggressive approach to this group of patients, with surgical revision early if possible.11 It is crucial to remember that transplant patients can have very subtle findings even with major postsurgical complications or infections. As a general rule, any patient who is not progressing as expected should undergo aggressive workup for complications, including liberal use of imaging and diagnostic tapping or reoperation in response to unexpected fluid collections. All fevers should be worked up aggressively either for preexisting infections or peri- or postsurgically acquired infections.

Follow-up
Follow-up for the immunocomprised patient after surgery should proceed in the same manner as performed in an immunocompetent patient. Generally, patients are seen 2 weeks after discharge depending on the hospital course and condition of the wound. Patients are continued on their home immunosuppression, and, as stated previously, unless there is a specific reason, antibiotics are not extended. In our practice, wounds are left covered for 48 hours after surgery, and staples are typically removed 3 weeks after surgery to account for slow healing. Obviously, clinical assessment of wounds may override these recommendations. Levels of calcineurin agents (cyclosporine or tacrolimus) should be followed closely for a few weeks after surgery until the preoperative therapeutic range is achieved. It is common for people to have either high or low levels after surgery, particularly until bowel function has returned to normal. There is a risk that rejection can occur in the postoperative period if levels are too low, and if a patient is having difficulty getting the level up quickly, extra steroids (or another agent) may be required for a few weeks while the level is returning to baseline.

When to Consider Transfer to a Transplant Center
The decision on when to transfer a patient to a transplant center will depend on many factors, including geography, comfort level of the caregivers, desires of the patient, size of the procedure, organ that was transplanted, and postoperative course. Many procedures can be conducted safely on transplant patients without specialized care from a transplant center. However, some patients are reluctant to have anyone other than their transplant physicians treat them once they have received a transplant, and some transplant physicians likewise will agree with that. Ideally, a discussion will take place with both the patient and the transplant physician prior to the procedure to make a plan. If a surgeon is comfortable performing a procedure or operation, the same attention to good technique will apply to these patients. All postoperative complaints or findings should be evaluated very carefully, and if at any point a patient is not progressing appropriately, contact should be made with the transplant center with consideration of transfer. A transplant physician or specialist with some comfort in transplant medications or infections should be consulted if at all possible. Discussions with transplant physicians or pharmacists regarding medications and any alterations in them should be conducted daily if possible.

Special Considerations
ACUTE APPENDICITIS

Although the occurrence of acute appendicitis in the general population is widespread, its frequency in transplant recipients is quite rare, with a reported rate of 0.2% in liver, heart, kidney, and pancreas recipients.43–46 Nevertheless, given the rising number of transplant recipients, knowledge of the management of this disease in this patient population is important.

In the past, appendectomies in conjunction with a pancreas transplant were routine to prevent misdiagnosis of transplant pancreatitis. However, the low incidence and reliability of modern imaging in visualizing acute appendicitis no longer make this current practice at most institutions.

Ultimately, transplant recipients found to have acute appendicitis should be managed similarly to nontransplant patients with the use of laparoscopy based on surgeon preference. As with any intra-abdominal pathology in a transplant recipient, clinical signs can be subtle. Therefore, imaging is crucial in securing the diagnosis.

Our institution is aggressive about proceeding with operative management in patients with acute appendicitis. If management of nontransplant patients includes consideration of percutaneous drain placement and interval appendectomy in perforated and walled-off appendicitis, the same can be considered in the transplant patient. These patients do require close monitoring with serial examinations and reimaging. It cannot be stressed enough that the signs and symptoms of progression can be subtle. A low threshold to abandon conservative management in favor of operative intervention should be considered in patients who do not rapidly improve.

SMALL BOWEL OBSTRUCTION

As a result of medical immunosuppression, transplant recipients rarely develop extensive adhesions causing small bowel obstruction. However, it has been hypothesized that transplant and nontransplant patients develop small bowel obstruction similarly, mainly the formation of adhesions following intra-abdominal surgery. Additionally, there have been reports of small bowel obstruction secondary to internal hernias in pancreas transplant recipients.47,48 The increased risk of malignancy in this patient population should also make the surgeon suspicious of a malignant etiology.

As in nontransplant patients, obstruction can be fatal and should be managed similiarly. Conservative management with nasogastric tube decompression, hydration, and close monitoring is appropriate. If the patient does not improve quickly, operative management is imperative.

PEPTIC ULCER DISEASE

Prior to the advent of histamine2 blockers, mortality from peptic ulcer disease in this patient population was as high as 40%49,50 and was even reported to be approximately 4% only a few years ago.51 The cause of peptic ulcer disease in this patient population is multifactorial. There have been reports of up to 62% of living donor liver recipients52,53 and approximately 30% of renal transplant recipients with Helicobacter pylori colonization.8,51,53,54 Additionally, high-dose steroids used to treat rejection have been found to be ulcerogenic,55 and MMF has been found to cause ulcer perforation or bleeding in 3 to 8% of patients within 6 months.56

Transplant patients are typically placed on prophylactic medications in the perioperative period to prevent the development of peptic ulcer disease. Fortunately, in our practice, we have rarely had to operate on this as in our nontransplant patient population. Surgical management, when necessary, should be no different than in the nonimmunosuppressed patient.

BILIARY TRACT PATHOLOGY

Cyclosporine therapy has been associated with biliary calculous disease and primary choledocholithiasis.10 However, studies have demonstrated the safety of cholecystectomy following transplantation despite previously held beliefs regarding immunosuppression and surgery.49

Biliary tract pathology is common in liver transplant recipients, with an incidence of 10 to 30% and the majority seen within the first 6 months posttransplantation.57 Most commonly, anastomatic stricture of the bile duct following duct to duct reconstruction occurs, resulting in patients who present with symptoms of cholangitis. Elevated bilirubin, fevers, and sepsis warrant urgent endoscopic cholangiopancreatography and broad-spectrum antibiotics. Because of the tenuous condition of these patients, transfer to a transplant center is highly recommended.

DIVERTICULITIS

Diverticulitis in the transplant patient population is higher (1% versus 0.02%)58 and more aggressive59 than in the general population. In a study comparing immunosuppressed and immunocompetent patients with acute diverticulitis, immunosuppressed patients were found to have an increased risk of free perforation (43% versus 14%) and postoperative mortality (39% versus 2%).60 Therefore, patients are typically offered surgical intervention following a single episode of uncomplicated diverticulitis if it is safe and once the acute episode resolves.61 Although there is a paucity of data to support this in the literature, the risk of complications from recurrent episodes and difficulty in diagnosing these patients until they progress to a later stage of disease may be an incentive to intervene earlier than in nontransplant patients.

Acute episodes of diverticulitis are managed conservatively with broad-spectrum antibiotics and percutaneous drain placement. However, frequent reassessment and reimaging are critical. Interval surgical intervention should always be considered if the patient does not progress. In our practice, we have been cautious in performing a primary anastomosis in acute complicated diverticulitis in the sigmoid region, particularly in patients on long-term immunosuppression. We favor reestablishing continuity 3 to 6 months later. Of note, great caution should be taken with patients on sirolimus at the time of presentation. These patients are notoriously poor at healing, and strong consideration should be given for diverting these patients in the acute setting.

MALIGNANCY

Clinicians should have an appreciation for the increased risk of cancer associated with immunosuppression. Although the exact risk remains controversial, the incidence of malignancy in transplant recipients is increasing, and there are estimates that after 10 years of chronic immunosuppression, the incidence of malignancy is 20%.62 The risk of malignancy can vary based on the medication and type of cancer and is believed to be closely associated with overall exposure to immunosuppression.62

In general, solid-organ tumors of the GI tract have an approximately 1.25 to 5 times and lymphomas a 10 times greater incidence in transplant patients.63 In solid-organ transplant recipients, nonmelanotic skin cancers are extremely common,64,65 with transplant patients at a 65-fold increased risk of developing squamous cell carcinoma.66 For this reason, all patients should be followed by a dermatologist.

As with nontransplant patients, transplant patients with solid tumors should be followed under the same oncologic principles. Multidisciplinary teams including transplant physicians, oncologists, and surgeons are necessary for the care of these patients.

A special note should be made regarding posttransplantation lymphoproliferative disorder (PTLD). PTLD is the second most common malignancy seen in renal transplant patients67 and the most common malignancy in liver transplant patients.68 It can have variable presentations, including abdominal pain, small bowel obstruction, weight loss, and GI bleed. The presence of masses on a CT scan is suggestive of PTLD, with 25% involving the small bowel and 6% involving the colon.69 PTLD may cause bowel obstruction, necessitating emergent surgery. Interestingly, simply reducing immunosuppression can sometimes cause eradication of disease. Additionally, as the majority of cases are B cell in nature and associated with Epstein-Barr virus, B cell–directed therapies such as anti-cd20 antibody rituximab, may eliminate the disease. Consequently, patients with PTLD should be managed at a transplant center where graft loss or mortality can be minimized by the modification of immunosuppression and other therapies.

GASTROINTESTINAL PROBLEMS

Immunosuppressants often have GI effects that modify symptoms and therefore the presentation of GI diseases.49 It is quite common for transplant patients to develop diarrhea, sometimes severe episodes. This can sometimes be related to transplant medications, and a careful drug history should be the initial step in evaluating a transplant patient with diarrhea. For example, up to 50% of patients on MMF develop GI complaints.70 Ruling out other causes, particularly infections, is important and can be challenging. Infectious processes often seen in the transplant population include C. difficile superinfection, cytomegalovirus colitis, more common GI viruses, and opportunistic infections. The initial workup should be no different from that for the nontransplant patient but may ultimately require colonscopy and biopsy to rule out the above.

Summary
General surgeons can certainly have some level of comfort with the knowledge that with careful attention to medications and symptoms, general principles will hold true with transplant patients. Minor procedures can usually be conducted without much modification, and more major procedures may require some adjustment of medication regimen. The most important point is to watch these patients closely as their physical examination, including vital signs and laboratory studies, can be misleading, and frequent reassessment with imaging may be necessary. If a patient does not proceed along the expected recovery, attention must be given to a possible complication. Most transplant centers have a program for following up with their patients and a contact to call for questions about their care and organ function. It is always recommended to communicate with a program. Consideration for transfer to a transplant center may be appropriate in complicated cases or in the setting of complications.

Financial Disclosures: None Reported

References
1. U.S. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation. 2009 annual report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: transplant data. 1999–2008. Washington, DC: U.S. Department of Health and Human Services; 2009.

2. Yee J, Christou NV. Perioperative care of the immunocompromised patient. World J Surg 1993;17:207–14.

3. Deziel DJ, Hyser MJ, Doolas A, et al. Major abdominal operations in acquired immunodeficiency syndrome. Am Surg 1990;56:445–50.

4. Wilson SE, Robinson G, Williams RA, et al. Acquired immune deficiency syndrome (AIDS). Indications for abdominal surgery, pathology, and outcome. Ann Surg 1989;210:428–33; discussion 433–4.

5. Steed DL, Brown B, Reilly JJ, et al. General surgical complications in heart and heart-lung transplantation. Surgery 1985;98:739–45.

6. Meyer AA. The surgical management of AIDS and HIV-infected patients. Adv Surg 1989;22:57–73.

7. Merrell SW, Ames SA, Nelson EW, et al. Major abdominal complications following cardiac transplantation. Utah Transplantation Affiliated Hospitals Cardiac Transplant Program. Arch Surg 1989;124:889–94.

8. Sarkio S, Halme L, Kyllonen L, et al. Severe gastrointestinal complications after 1,515 adult kidney transplantations. Transpl Int 2004;17:505–10.

9. Testa G, Goldstein RM, Toughanipour A, et al. Guidelines for surgical procedures after liver transplantation. Ann Surg 1998;227:590–9.

10. Johnston TD, Katz SM. Special considerations in the transplant patient requiring other surgery. Surg Clin North Am 1994;74:1211–21.

11. Graeb C, Jauch KW. Surgery in immunocompromised patients. Br J Surg 2008;95:1–3.

12. Keegan MT, Plevak DJ. The transplant recipient for nontransplant surgery. Anesthesiol Clin North Am 2004;22:827–61.

13. Becker BN, Becker YT, Heisey DM, et al. The impact of hypoalbuminemia in kidney-pancreas transplant recipients. Transplantation 1999;68:72–5.

14. Guijarro C, Massy ZA, Wiederkehr MR, et al. Serum albumin and mortality after renal transplantation. Am J Kidney Dis 1996;27:117–23.

15. Rubin RH, Schaffner A, Speich R. Introduction to the Immunocompromised Host Society consensus conference on epidemiology, prevention, diagnosis, and management of infections in solid-organ transplant patients. Clin Infect Dis 2001;33 Suppl 1:S1–4.

16. Kaiser LR, Hiatt JR. Surgical considerations in the management of the immunocompromised patient. Crit Care Clin 1988;4:193–208.

17. Urquhart CK, Hawkins ML, Wynn JJ, et al. Management of the injured renal transplant recipient. South Med J 1991;84:524–6.

18. Krajewski E, Soriano IS, Ortiz J. Laparoscopy in transplantation. JSLS 2006;10:426–31.

19. Tichansky DS, Madan AK. Laparoscopic Roux-en-Y gastric bypass is safe and feasible after orthotopic liver transplantation. Obes Surg 2005;15:1481–6.

20. Kennealey PT, Johnson CS, Tector AJ 3rd, et al. Laparoscopic incisional hernia repair after solid-organ transplantation. Arch Surg 2009;144:228–33; discussion 233.

21. Yannam GR, Gutti TL, High R, et al. Experience of laparoscopic incisional hernia repair in kidney and/or pancreas transplant recipients. Am J Transplant 2011;11:279–86.

22. Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med 1998;338:1741–51.

23. Patel R, Paya CV. Infections in solid-organ transplant recipients. Clin Microbiol Rev 1997;10:86–124.

24. Patel R, Snydman DR, Rubin RH, et al. Cytomegalovirus prophylaxis in solid organ transplant recipients. Transplantation 1996;61:1279–89.

25. Evans PC, Soin A, Wreghitt TG, et al. An association between cytomegalovirus infection and chronic rejection after liver transplantation. Transplantation 2000;69:30–5.

26. Humar A, Gillingham KJ, Payne WD, et al. Association between cytomegalovirus disease and chronic rejection in kidney transplant recipients. Transplantation 1999;68:1879–83.

27. Grattan MT, Moreno-Cabral CE, Starnes VA, et al. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA 1989;261:3561–6.

28. Keenan RJ, Lega ME, Dummer JS, et al. Cytomegalovirus serologic status and post operative infection correlated with risk of developing chronic rejection after pulmonary transplantation. Transplantation 1991;51:433–8.

29. Ho M. Laboratory evaluations of infections in immunosuppressed transplant patients. Clin Lab Med 1991;11:715–31.

30. Rubin RH. Gastrointestinal infectious disease complications following transplantation and their differentiation from immunosuppressant-induced gastrointestinal toxicities. Clin Transplant 2001;15 Suppl 4:11–22.

31. Littlewood KE. The immunocompromised adult patient and surgery. Best Pract Res Clin Anaesthesiol 2008;22:585–609.

32. Kotloff RM, Ahya VN, Crawford SW. Pulmonary complications of solid organ and hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2004;170:22–48.

33. Bromberg JS, Baliga P, Cofer JB, et al. Stress steroids are not required for patients receiving a renal allograft and undergoing operation. J Am Coll Surg 1995;180:532–6.

34. Prabhakar G, Testa G, Abbasoglu O, et al. The safety of cardiac operations in the liver transplant recipient. Ann Thorac Surg 1998;65:1060–4.

35. Martin-Conejero A, Serrano-Hernando FJ, Reina-Gutierrez T, et al. Surgery for aortoiliac aneurysm after kidney transplant. Transplant Proc 2003;35:2953–7.

36. Lacombe M. Surgical treatment of aortoiliac aneurysms in renal transplant patients. J Vasc Surg 2008;48:291–5.

37. Velanovich V, Ezzat W, Horn C, et al. Surgery in heart and lung transplant patients. Am J Surg 2004;187:501–4.

38. Lee AB, Dupin CL, Colen L, et al. Microvascular free tissue transfer in organ transplantation patients: is it safe? Plast Reconstr Surg 2008;121:1986–92.

39. Papadopoulos O, Konofaos P, Chrisostomidis C, et al. Reconstructive surgery for kidney transplant recipients. Transplant Proc 2005;37:4218–22.

40. Mehrabi A, Fonouni H, Wente M, et al. Wound complications following kidney and liver transplantation. Clin Transplant 2006;20 Suppl 17:97–110.

41. Mathis AS, Shah NK, Mulgaonkar S. Stress dose steroids in renal transplant patients undergoing lymphocele surgery. Transplant Proc 2004;36:3042–5.

42. Trujillo EB. Effects of nutritional status on wound healing. J Vasc Nurs 1993;11:12–8.

43. Savar A, Hiatt JR, Busuttil RW. Acute appendicitis after solid organ transplantation. Clin Transplant 2006;20:78–80.

44. Ceulemans P, Wybaillie E, Monbaliu D, et al. Acute appendicitis after liver transplantation: a case report and review of the literature. Acta Chir Belg 2010;110:335–8.

45. Abt PL, Abdullah I, Korenda K, et al. Appendicitis among liver transplant recipients. Liver Transpl 2005;11:1282–4.

46. Verzaro RM, Khan A, Falcone JL, et al. Acute appendicitis in a kidney-pancreas transplant recipient: report of a case. Transplant Proc 2006;38:3144–6.

47. Agarwal A, Maglinte DD, Goggins WC, et al. Internal hernia after pancreas transplantation with enteric drainage: an unusual cause of small bowel obstruction. Transplantation 2005;80:149–52.

48. Linhares MM, del Grande L, Gonzalez A, et al. Intestinal obstruction due to internal hernia following pancreas transplantation. Transplant Proc 2010;42:3660–2.

49. Gautam A. Gastrointestinal complications following transplantation. Surg Clin North Am 2006;86:1195–206, vii.

50. Owens ML, Passaro E Jr, Wilson SE, et al. Treatment of peptic ulcer disease in the renal transplant patient. Ann Surg 1977;186:17–21.

51. Ponticelli C, Passerini P. Gastrointestinal complications in renal transplant recipients. Transpl Int 2005;18:643–50.

52. Hosotani Y, Kawanami C, Hasegawa K, et al. A role of Helicobacter pylori infection in the development of duodenal ulcer after adult living-related liver transplantation. Transplantation 2003;76:702–4.

53. Ueda Y, Chiba T. Helicobacter pylori in solid-organ transplant recipient. Curr Opin Organ Transplant 2008;13:586–91.

54. Sarkio S, Rautelin H, Kyllonen L, et al. Should Helicobacter pylori infection be treated before kidney transplantation? Nephrol Dial Transplant 2001;16:2053–7.

55. Chen KJ, Chen CH, Cheng CH, et al. Risk factors for peptic ulcer disease in renal transplant patients—11 years of experience from a single center. Clin Nephrol 2004;62:14–20.

56. Bjarnason I. Enteric coating of mycophenolate sodium: a rational approach to limit topical gastrointestinal lesions and extend the therapeutic index of mycophenolate. Transplant Proc 2001;33:3238–40.

57. Wojcicki M, Milkiewicz P, Silva M. Biliary tract complications after liver transplantation: a review. Dig Surg 2008;25:245–57.

58. Hwang SS, Cannom RR, Abbas MA, et al. Diverticulitis in transplant patients and patients on chronic corticosteroid therapy: a systematic review. Dis Colon Rectum 2010;53:1699–707.

59. Stocchi L. Current indications and role of surgery in the management of sigmoid diverticulitis. World J Gastroenterol 2010;16:804–17.

60. Tyau ES, Prystowsky JB, Joehl RJ, et al. Acute diverticulitis. A complicated problem in the immunocompromised patient. Arch Surg 1991;126:855–8; discussion 858–9.

61. Qasabian RA, Meagher AP, Lee R, et al. Severe diverticulitis after heart, lung, and heart-lung transplantation. J Heart Lung Transplant 2004;23:845–9.

62. Buell JF, Gross TG, Woodle ES. Malignancy after transplantation. Transplantation 2005;80(2 Suppl):S254–64.

63. Chapman JR, Webster AC. Cancer after renal trans plantation: the next challenge. Am J Transplant 2004;4:841–2.

64. Dreno B, Mansat E, Legoux B, et al. Skin cancers in transplant patients. Nephrol Dial Transplant 1998;13:1374–9.

65. Gupta AK, Cardella CJ, Haberman HF. Cutaneous malignant neoplasms in patients with renal transplants. Arch Dermatol 1986;122:1288–93.

66. Jensen P, Hansen S, Moller B, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol 1999;40(2 Pt 1):177–86.

67. Penn I. Cancers in renal transplant recipients. Adv Ren Replace Ther 2000;7:147–56.

68. Penn I. Posttransplantation de novo tumors in liver allograft recipients. Liver Transpl Surg 1996;2:52–9.

69. Pickhardt PJ, Siegel MJ. Posttransplantation lymphoproliferative disorder of the abdomen: CT evaluation in 51 patients. Radiology 1999;213:73–8.

70. Behrend M. Mycophenolate mofetil: suggested guidelines for use in kidney transplantation. BioDrugs 2001;15:37–53.

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