DISCUSSION
All of our hematopoietic stem cell transplant patients were successfully treated for appendicitis utilizing surgical and/or medical management depending on their clinical scenario. Appendectomy, whether open or laparoscopic, remains the overall gold standard for treatment of appendicitis and in line with treatment guidelines of the American College of Surgeons and World Society of Emergency Surgery [7, 8]. The use of open vs laparoscopic appendectomy in the general population is not in the scope of this review, however, there are proponents of using laparoscopic appendectomy among patients who are immunocompromised [7, 9, 10].]. Others advocate for laparoscopic appendectomy in patients with pancytopenia as it has been associated with decreased postoperative infection, hemorrhagic complications, and a lower mortality rate [10]. One particular case series involving children with acute leukemia showed mixed use of open and laparoscopic appendectomy in patients with a mean absolute neutrophil count of 800 cells/m3 and boasted no intraoperative or postoperative complications [11]. There is no data large enough to determine statistical efficacy of appendectomy among adult transplant patients, and the use of appendectomy in HCT remains anecdotal but an effective treatment for patients in various stages of hematopoietic recovery [2, 4, 5]. Still, appendectomy in this patient population is not without its risk of infection, delayed healing, hemorrhagic complications or operative risk based on severity of systemic disease. A multidisciplinary team should carefully consider these risks when determining whether to pursue appendectomy or conservative therapy.
Medical management without surgery is an alternative approach to the treatment of appendicitis. Medical management normally consists of bowel rest, pain management, intravenous fluids and broad spectrum antibiotics with both gram-negative and anaerobic bacteria coverage [12, 13]. Multiple retrospective and randomized controlled trials have evaluated the efficacy of conservative antibiotic treatment compared to surgery in the general population. A large retrospective cohort involving 231,678 patients with appendicitis found 3,236 patients who were managed nonsurgically. Only 5.9% of these patients had subsequent treatment failure which had no impact on overall mortality. After risk adjustment, mortality rates were not statistically significant between the surgical and nonsurgical patients at 0.1% and 0.3% respectively. However, hospital duration was statistically longer among the nonoperative patients (2.1 vs 3.2 days; p < 0.001) [14]. A meta-analysis involving 741 patients in four randomized controlled trials showed higher efficacy in the patients receiving surgery compared to conservative management (OR = 6.01, 95% CI = 4.27–8.46). However, surgery was associated with statistically significant higher complication rates (OR = 1.92, 95% CI = 1.30–2.85) [12]. Another meta-analysis involving 59,448 patients in 20 retrospective studies evaluated outcomes in patients with appendiceal abscess or phlegmon who received both surgical and nonsurgical treatment. Treatment failure was noted in 7.2% of the patients who received nonsurgical therapy. Immediate surgery was associated with higher complications compared to nonsurgical treatment (OR, 3.3, CI = 1.9-5.6, p < 0.001) [15]. It is difficult to interpret how these results would apply to patients who additionally have neutropenia and/or immunosuppression. A case series involving five children with acute leukemia and neutropenia reported successful conservative treatment of acute appendicitis without the need for surgery. However, one patient did pursue elective appendectomy prior to bone marrow transplantation [13].
Our experience showed that 3 of the 4 patients with neutropenia and/or on immunosuppression were successfully treated with nonsurgical management. None of these patients had recurrence or complications associated with appendicitis. The patient who failed nonsurgical therapy ultimately was found to have perforation with abscess requiring pelvic drain placement and culture revealing ESBL E. coli . The patient was maintained on ertapenem and ultimately received elective appendectomy after hematopoietic recovery and prior to transplant. The final patient received a preemptive laparoscopic appendectomy for dilated appendix which ultimately was discovered to be a benign mucinous adenoma after histologic review. As seen here, management of appendicitis in the peri-transplant setting depends on the clinical scenario.
In pre-transplant patients with appendicitis, elective appendectomy should be considered as a means of source control prior to transplant. Though no data exists in this particular scenario it is important to manage existing infections to reduce the risk of further infectious complications throughout the peri-transplant period. One could argue for laparoscopic surgery in this case to decrease morbidity and potentially mitigate further delay. It is reasonable to provide a trial of nonsurgical therapy, including broad spectrum antibiotics, if the pre-transplant patient is still recovering from cytopenias with prompt surgical resection upon recovery.
The pre-engraftment patient may very well have confounding diagnoses to include mucositis, neutropenic enterocolitis, or other infectious colitis. This was the case in two of our patients: one who was suffering from mucositis and the other who was subsequently discovered to haveC. diff colitis. These patients would likely benefit from a trial of nonsurgical therapy as well given the potential therapeutic overlap of broad spectrum antibiotics and higher risk of surgical complications in the setting of pancytopenia. Reevaluation of these patients following should be considered to determine if elective appendectomy if indicated.
Post-transplant patients may also be considered for a trial of nonsurgical therapy if they are still requiring either prophylactic or therapeutic immunosuppression for GVHD. Our post-transplant patient had complete recovery with radiographic resolution of findings and appendicolith. However, the severity of immunosuppression varies greatly from patient to patient during this time period. There is retrospective data that notes safety among immunocompromised patients [9] and thus a lower threshold to pursue appendectomy in these patients is reasonable.
It is important in any of these scenarios to remain vigilant for signs of clinical deterioration. These include persistent or worsening localized abdominal pain and peritoneal signs, lack of clinical improvement with medical treatment, or hemodynamic instability/septic physiology. Further invasive therapies such as percutaneous drainage or surgical exploration may be warranted.