Discussion
In this retrospective study we found that pediatric patients with an
active oncologic diagnosis who underwent appendectomy did not have
higher odds of suffering post-operative complications including
superficial or deep SSI’s, superficial or deep wound dehiscence, deep
organ space infections or suture line dehiscence as compared to patients
without cancer. The literature on post-operative morbidity in cancer
patients, particularly in pediatrics, is sparse. Indeed, most have
focused specifically on patients with neutropenia, rather than cancer,
although there is an obvious and nearly 1:1 overlap in these groups
among available studies on appendicitis.
Some studies have suggested an elevated risk of surgical complications
in pediatric neutropenic patients and by extrapolation led to inference
that appendicitis should be treated non-operatively if
possible1,2. Pudela et al. reported a case series of 3
neutropenic patients, all with underlying oncologic diagnoses and each
treated differently – one with antibiotics alone, one with interval
appendectomy after up-front antibiotic therapy, and one with urgent
operation – concluding that therapy should be tailored, but implying
that medical management may be the prudent course1.
Wiegering et al.’s study of 5 neutropenic oncology patients from one
institution reported symptom resolution after antibiotic therapy for
appendicitis in all patients, with 6-month to
3-year-followup2. One patient underwent prophylactic
appendectomy prior to bone marrow transplantation. The acceptance of
these studies is buoyed, in part, by the ample literature demonstrating
that non-operative management of appendicitis with antibiotic therapy
alone can – in the short term – have successful outcomes that approach
those of surgical appendectomy3,4.
Other studies evaluating neutropenic pediatric patients with
appendicitis have come to opposite conclusions, demonstrating relative
safety of surgery in the face of neutropenia, and thus have implied that
surgical treatment is preferable to medical treatment of
appendicitis5,6,7. Mortellaro et al. included 11
neutropenic patients from 2 institutions, all with an oncologic
diagnosis5. All underwent appendectomy and had
hospital lengths of stay comparable to the groups’ previously published
outcomes data on appendectomy in non-neutropenic patients. Although the
paper did not report on any complications in the group of 11, the
authors concluded that appendectomy in neutropenic patients was“tolerated well with a low risk of surgical complications.”Scarpa et al.’s show heterogeneous treatment strategies among 30
neutropenic children with appendicitis (90% of whom had a hematological
malignancy) from 8 French institutions6. Among the 30,
6 underwent immediate operation, 17 underwent delayed operation after
initial antibiotic therapy, while the remaining 7 were treated with
antibiotics alone. Wound complications were reported in 2 patients but
it was unclear to which surgical group they belonged.
All of the available studies were conducted as single institution or
small multi-center data collections, and individually included no more
than 30 patients. They also were very inconsistent and vague in
reporting surgical complications.
The literature on overall surgical intervention in neutropenic patients,
pediatric or adult, is quite sparse. Jolissaint et al. reported on
nearly 250 neutropenic adult patients from a single institution
undergoing abdominal surgery, finding that ANC < 500 and
emergency surgery carried a relatively higher risk of morbidity and
mortality compared to less severe neutrophilia and/or elective
surgery8. Badgwell et al. concluded in a
single-institution study of 60 neutropenic adult patients undergoing
urgent abdominal surgery that delay until severe neutropenia can be
improved – usually by administration of colony-stimulating factors –
may have beneficial effects9. Grant et al., examining
4389 adult patients undergoing chemotherapy for cancer in the NSQIP
database, showed that leukopenia itself was not an independent risk
factor for perioperative morbidity or mortality10. The
authors did not, however, compare these results to the non-cancer
population.
Further muddying the waters is a 2015 report by Gulack et al. using the
NSQIP adult database to examine the association of leukopenia and
perioperative complications in patients undergoing exclusively emergency
surgery11. Among the 20443 included patients
undergoing emergency laparotomy, leukopenia was independently associated
with increased odds of both post-operative morbidity and mortality.
Our study was strengthened by higher overall numbers than other
pediatric reports (95 patients in total with a cancer diagnosis), a
comparison cohort group of patients without cancer that allowed for risk
stratification and multivariable logistic regression to identify
covariates independently significant for increase odds of developing a
wound complication, as well as the unique feature of the NSQIP
database’s reporting structure that actively seeks out evidence of
30-day complications by a trained analyst. In addition to looking for
30-day complications, NSQIP reports 30-day hospital readmissions, which
can also be an important metric to examine. Although quite a high
proportion of the 95 patients with a cancer diagnosis were readmitted
within 30 days of operation, only a scant 5% of readmissions were
related to the surgery itself (compared to the 85% surgery-related rate
among readmissions in the non-cancer cohort); this again suggests that
operating on appendicitis in children with a synchronous oncologic
diagnosis may be safe and prudent.
Our study has several limitations that are worth noting. There are those
relevant to any database study, including its retrospective nature, risk
of coding and reporting error, and missing data points. The last was
addressed by a sensitivity analysis that did not change the overall
outcomes based on missing WBC and ASA Class data points. In addition,
NSQIP-P reports only total WBC counts but does not include neutrophil
counts, so we were unable to include neutropenia specifically as a risk
factor. The flag for cancer diagnosis includes both “active cancer
diagnosis” and “undergoing chemotherapy” so we were unable to
categorize specifically treatment vs overall diagnosis as possible risk
factors. Specific type of cancer diagnosis was also not uniformly
available, further limiting our ability to stratify our findings.
In conclusion, pediatric patients undergoing treatment for cancer do not
have increased odds of suffering post-operative wound complications
following appendectomy compared to the general population. These
findings refute beliefs that surgical risks are prohibitively high in
patients with appendicitis who have a synchronous cancer diagnosis and
support surgical appendectomy as the appropriate first-line treatment.
Further studies may help define any subgroups that are particularly at
risk for surgical complications – such as patients with markedly low
ANCs, those with specific types of cancer – although the feasibility of
these studies is questionable given the small patients numbers involved.