Large Population-based Study Exposes Higher Incidence and Mortality in Emergency Surgical Conditions in Transplant Recipients

Improvements in management of solid organ transplant recipients (SOTR) have increased patient and graft survival. In addition, the number of SOT performed worldwide has increased. Consequently, the number of occasions SOTR present with nontransplant emergency general surgical conditions (EGS) is likely increasing. SOTR represents a high-risk group because of multiple factors, including a high burden of comorbidities, chronic immunosuppression, potential drug interactions, and atypical clinical presentations of abdominal surgical conditions.¹ Thus, there is an important need for a precise assessment of risk of EGS in SOTR. Previous studies indicate substantial morbidity and mortality in SOTR with nontransplant abdominal surgical conditions^2-6; however, these studies were mostly single-center studies, with a limited number of cases, no comparison with the general population, limited to recipients of specific transplant organs or specific EGS conditions, or did not specifically analyze emergency conditions. A recent meta-analysis calculated EGS incidence at 2.5% in 71 671 SOTR and EGS mortality in SOTR at 5.5%.⁷ Still, high-quality, systematic analyses comparing the incidence and mortality of EGS in SOTR with that in the general population have been lacking.

In this issue of Transplantation, Gomez et al⁸ fill the knowledge gap by characterizing the incidence and mortality of EGS among SOTR and the general population using large population-based databases in Ontario, Canada. Importantly, the study used data from various sources, including national transplant registry, national inpatient and emergency care and diagnostic and procedural data, as well as health insurance data and linked them at the individual level. Utilizing Institute for Clinical Evaluative Sciences, an established Canadian collaborative institution for provision of health-related data, as a source, Gomez et al provide data with unmatched precision on EGS in SOTR. The study analyzed data from 10 073 SOTR and 12 608 135 non-SOTR in Ontario from 2002 until 2017. SOTR included kidney (66%), liver (19%), lung (10%), and heart (5%) transplant recipients. Of these, 881 SOTRs developed an EGS, which included perforated peptic ulcers, acute cholecystitis, choledocholithiasis, appendicitis, diverticulitis with abscess of perforation, obstructed small bowel, and incarcerated or strangulated hernias, based on ICD10 diagnosis classification.

The authors calculated the standardized incidence rate ratios (SIRRs) using non-SOTR events as a reference and showed an elevated SIRR for EGS in SOTR of 3.56 (95% confidence interval [CI] 3.32-3.82) compared with age-, sex-, and time-matched non-SOTR, with a highly elevated SIRR of small bowel obstruction (SIRR 6.21, 95% CI 5.58-6.89), followed by incarcerated/strangulated hernia (SIRR 5.52, 95% CI 4.49-6.71) and diverticular abscess/perforation (SIRR 4.81, 95% CI 3.65-6.21). Of note, obstructed bowel or incarcerated hernias did not occur more frequently in recipients of abdominal transplant organs compared with those of thoracic transplant organs. There were also no striking differences in relative incidence of EGS between the recipients of different transplanted organs (SIRR 3.24–3.79), except for lung transplant recipients (LuTR), who showed a substantially elevated EGS SIRR of 6.34 (95% CI 5.4-7.73). Importantly, LuTR showed higher SIRR in almost all EGS, but the cause of their underlying higher risk of EGS remains unclear. To explore the relevance of comorbidities, EGS data were stratified according to the John Hopkins Aggregated Diagnosis Groups (ADG) score, a general measure for comorbidity. ADG scores were higher in SOTR than that in non-SOTR, and scores were higher in patients with EGS in both SOTR and non-SOTR. Although socioeconomic and geographical factors showed no impact on EGS, no further potential contributing factors were analyzed in this study.

Moreover, this study documented an elevated 30-d mortality of 7% after EGS in SOTR compared with 4.8% in non-SOTR, equating to an odds ratio (OR) of 1.52 (95% CI 1.15-1.99). After adjusting for age, sex, and comorbidities, the OR for all-SOTR remained significantly elevated at 1.4; however, the increased OR was driven by a disproportionately elevated OR for LuTR (adjusted OR 3.60, 95% CI 1.90-6.82) compared with OR of other SOTR (adjusted OR kidney 1.26, 95% CI 0.87-1.81; adjusted OR liver 1.22, 95% CI 0.59-2.51; adjusted OR heart 0.54, 95% CI 0.07-4.11). Overall, the findings confirm the results of previous smaller and less rigorously performed studies,^2,3,5 but provide more robust reference data.

The report by Gomez et al highlights the contribution of comorbidities to an elevated risk of death related to EGS in nonlung SOTR compared with non-SOTR. Although excess risk in this population has frequently been attributed to immunosuppression, this analysis suggests that the high burden of comorbidities in SOTR is a key determinant of outcome after EGS; however, immunosuppression was not specifically analyzed, and the study excluded SOTR within 3 mo of transplantation, a period with higher amounts of immunosuppression.

The data presented by Gomez et al single out LuTR, who have a disproportionately high incidence and 30-d mortality after EGS compared with other SOTR. This highly elevated risk of LuTx patients after an EGS is particularly noteworthy, although it is not a complete surprise, because overall posttransplant survival is consistently lower in LuTR compared with other SOTR.⁹ A detailed analysis of the causes of mortality after EGS, the related risk factors, and effects of different clinical management strategies of EGS in LuTR may help to mitigate risk and improve outcomes.

In conclusion, this report is an essential first step toward improving the management of EGS in SOTR by firmly establishing an elevated incidence and risk related to these conditions. Beyond it being an important aspect for transplant and nontransplant surgeons to be aware of, it raises important subsequent questions regarding modifiable factors in the management of EGS in SOTR. First, what are the causes of death after EGS in SOTR? Do patients die from postoperative infections, bleeding complications, cardiovascular events, or transplant organ deterioration, or could they not be weaned of ventilators? Second, do differences in outcomes in EGS in SOTR depend on the type of hospital (transplant versus nontransplant center), conservative versus operative management, surgical technique, or other factors, such as the time to diagnosis, time to operating room, or use of contrast-based imaging during emergency evaluation? Critical analyses of such data are urgently needed to identify modifiable aspects of management and form a basis for recommendations. Third, data on complications of EGS, such as rates of postoperative infections, bleeding and wound complications, length of ICU/ventilator-days, but also changes in immunosuppression and allograft function, will be highly useful to guide management in these conditions in SOTR in the future. Although previous evidence identified certain risk factors, such as mTOR inhibitor therapy or high BMI for complications in surgical wounds posttransplant,¹⁰ such evidence is not available for EGS in SOTR. Further studies are urgently needed to address these unanswered questions and meet the identified elevated incidence and mortality of SOTR with EGS with substantiated recommendations for clinical management.