Compared with nonsurgical management, upfront appendectomy for neutropenic appendicitis (NA) in children undergoing cancer treatment can lead to lower complication rates, reduced length of stay, and fewer changes to chemotherapy regimens, according to results from a study done in the largest pediatric sample to date.
Results were published in Pediatrics.
“The optimal management of NA in children undergoing chemotherapy remains ill defined, and there is significant practice variation. Numerous studies reveal the safety and efficacy of upfront appendectomy,” wrote lead author Benjamin T. Many, MD, of Northwestern University, Chicago, IL, and fellow researchers.
“The impact of upfront appendectomy versus initial nonoperative management of pediatric NA on delaying or altering oncologic treatment has not been previously reported. These changes or delays in chemotherapy may impact the long-term oncologic outcome, especially if management of NA entails a prolonged hospital course, leading to significant delays in cancer treatment,” they added.
In this 6-year retrospective review, Many and colleagues sought to compare surgical and infectious complications in patients treated with NA and to compare delays or changes to chemotherapy in these children on the basis of their initial treatment.
They reviewed data from 66 children (median age: 11 years; 50% male; 53% non-Hispanic white) with NA from 16 different institutions who had been enrolled in the Pediatric Surgery Oncology Research Collaborative. Presentation did not differ between those undergoing upfront appendectomy and those who had initial nonoperative management, including median ANC, white blood cell count, platelet count, maximum temperature on day of diagnosis, evidence of complicated appendicitis, duration of symptoms, or diagnostic imaging modality used. The most common cancers were leukemia (62%) and brain tumors (12%).
Researchers observed similar rates of abscess or perforation at diagnosis in those treated with upfront appendectomy and nonoperative management (30% vs 24%, respectively; P=0.23).
Upfront appendectomies were performed within 24 hours in 41% of children, and the remaining 56% received nonoperative management. Across the different institutions included, rates of upfront appendectomy ranged from 0% to 100%.
In all, 46% of children who initially had nonoperative management underwent delayed appendectomy during the same hospitalization. In a full 65% of these patients, delayed appendectomy was caused by failure of initial nonoperative management, and in 35%, due to count recovery.
Changes in therapy were required in 22% of patients undergoing upfront appendectomy, and 46% of those undergoing initial nonoperative management (P=0.05). A similar rate of delay or change in chemotherapy regimen occurred in children with perforated vs nonperforated appendicitis (P=0.51).
Delays of over 48 hours in cancer treatment occurred in 36% of patients, including delays of 2-7 days in 14%, 14-21 days in 5%, and greater than 21 days in 6%. One patient required additional changes in chemotherapy regimen.
“It is unknown whether delays or alterations in chemotherapy secondary to treatment of NA result in differences in oncologic outcomes. The effect of chemotherapy alterations or delays in overall survival and disease-free survival is likely related to cancer type and aggressiveness as well as efficacy of available chemotherapy,” commented Many and fellow researchers on the significance of these delays.
Previous studies have shown associations between delayed or interrupted chemotherapy treatment and inferior complete remission rates and increased risk of death in children with acute myelogenous leukemia.
“In our study, at least 7 patients had delays beyond this 10-day threshold, although the delay occurred during treatment rather than at the beginning of therapy. Furthermore, children treated with initial nonoperative management of NA had significantly greater delays in chemotherapy, as compared with those undergoing upfront appendectomy. Taken together, delays in definitive treatment of NA results in delays and alterations in chemotherapy and may potentially impact cancer outcomes,” stressed Many et al.
Initial nonoperative management was also associated with longer hospital stays compared with initial appendectomy (29 vs 12 days, respectively; P=0.01).
Bowel obstruction and resection, abscess, and Clostridioides difficile infection occurred in 7% of children undergoing upfront appendectomy, compared with 27% of patients who had initial nonoperative management (P=0.05). Complication rates were even higher in children who underwent delayed appendectomy after initial nonoperative management (59%; P ˂ 0.01).
Limitations of the study include its retrospective nature and the inclusion of patients from freestanding tertiary or quaternary children’s hospitals.
In an accompanying editorial, authors Kibileri Williams, MD, MSc, of Children’s National Hospital, Washington, DC, and Tolulope A. Oyetunji, MD, MPH, FACS, FAAP, of Children’s Mercy Kansas City, Kansa City, MO, applauded these results from Many and colleagues.
“A major clinical challenge in the care of children with cancer is how to take care of those patients with chemotherapy-induced neutropenia who develop acute appendicitis. How do we weigh the risk of perforation and sepsis against the risk of surgery in these high-risk patients?” they wrote.
“[W]e congratulate the authors on tackling an important question on surgery in neutropenic appendicitis. They have nicely laid the groundwork for a potential algorithm for the management of acute appendicitis in children with neutropenia, in which upfront appendectomy can be safely offered and may likely be preferred in those patients most likely to benefit. Decreases in hospital length of stay, postoperative complications, and, as a result, cost of care in this particularly vulnerable population can only serve to improve the overall quality of care that they receive,” they concluded.
In the largest sample to date of children with appendicitis and neutropenia secondary to cancer treatment, upfront appendectomy was associated with lower complication rates, reduced lengths of stay, and fewer alterations in chemotherapy regimens, compared with upfront nonoperative management.
Children who were initially managed nonoperatively and later underwent delayed appendectomy had increased postoperative complications compared with those treated with upfront appendectomy.
E.C. Meszaros, Contributing Writer, BreakingMED™
Many, Williams, and Oyetunji reported no disclosures.
Cat ID: 138
Topic ID: 85,138,730,188,935,138,192,925,159