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.