Discussion
This survey of practice reflected the general level of NEC surgical treatment provided in China at present and brought to light the lack of consensus on certain NEC management issues. As many of the current NEC definitions include subjectively chosen criteria, multicenter prospective studies, ideally on a global scale, should be conducted to develop a consensus definition.
In China, patients with NEC are more concentrated in large central specialized hospitals, as seen by the higher annual admission volumes of patients with NEC for these hospitals in our survey (figure 3A). NEC is co-managed by the department of neonatal surgery and department of neonatology in most centers, and multidisciplinary treatment is currently adopted since it offers greater benefits.
Figure 3(A) The number of children’s specialized and comprehensive hospitals with different numbers of patients with necrotizing enterocolitis (NEC) enrolled per year. (B) The relative percentage of children’s specialized and comprehensive hospitals with different certainty of identifying the presence of localized intestinal necrosis preoperatively (before intestinal perforation).
Growing evidence has demonstrated that abdominal radiographs and abdominal ultrasound (AUS) are both the cornerstones of NEC diagnosis and management; nevertheless, the first-line use of AUS has been minimal.9 Recently, surgeons have gradually realized the importance of AUS in NEC, and AUS is more sensitive and can predict whether surgery is needed earlier to improve the prognosis.10–12 A total of 81.3% of surgeons reported the use of AUS in this survey, which was higher than that reported previously.5 9 10 The signs that surgeons concern are typically those relate to the timing of operation, such as portal venous gas. In the future, more standardized ultrasound examination or a more accurate diagnostic model combined with ultrasound may be beneficial.9–11 Although a CT scan is not a suitable choice for neonates, 26.1% of surgeons ordered it.
Neutropenia, thrombocytopenia, metabolic acidosis, and elevated CRP levels are common signs in infants with NEC.7 8 The great majority of surgeons indeed relied on these parameters for the assessment of severity in our study. It is noteworthy that surgeons have paid less attention to hyponatremia because it is an independent predictor of bowel ischemia and reflects the severity of inflammation.7 13 Interpretation of electrolyte disorders should be given more attention.13 WBC, CRP, PCT, and IL-6 are all non-specific mediators of inflammation; CRP is the most commonly used biomarker as a late-warning biomarker, whereas IL-6, an early-warning biomarker, has not been frequently employed in clinical settings because many hospitals do not have relevant detection capability.14 15 Since the cut-off values for fecal calprotectin cannot be identified and it is significantly influenced by gestational and postnatal age, it is rarely used in routine clinical practice.14
No agreement has been achieved about the empirical use of broad-spectrum antibiotics for medical NEC, which is also represented in the questionnaire. According to the severity of the disease, antibiotics should be applied for 7–14 days, varying from 7-10 days for mild cases to 10–14 days for severe cases.16 17 Currently, ampicillin, gentamycin, and metronidazole are widely used abroad, while carbapenems, penicillin and cephalosporins, and nitroimidazole are the most used antibiotics in China.17 18 There is no consensus on the best combination of antibiotics.19 Aminoglycosides are not commonly used in China due to ototoxicity and nephrotoxicity. Another essential component of treatment is fasting, which is typically advised for 7–10 days.1 Some surgeons would choose to fast for a shorter period of time. Currently, some studies indicate that fasting for fewer than 7 days does not increase the risk of NEC recurrence, intestinal stenosis, or mortality in infants with non-surgical NEC.1 20 21
A proportion of NEC infants ultimately require surgical intervention. In this survey, it is considered that the judgment of the timing of the surgery is the most challenging. For patients with NEC who do not have intestinal perforation or who have a small anount of pneumoperitoneum but have an uncertain intestinal perforation, DAP is recommended to make a certain diagnosis to help determine the timing of surgery.22 Several results are commonly specific to surgical exploration: (1) fecal ascites which indicates intestinal perforation, (2) hemorrhagic one which even implies intestinal necrosis, and (3) purulent one which reminds severe abdominal infection and peritonitis.22 Pierro et al originally proposed the diagnostic use of laparoscopy for infants with NEC, and he suggested that laparoscopy provides information regarding intestinal viability, which can guide further surgical management even in critically ill neonates weighing less than 1000 g.23 Some case reports and animal models support this opinion.24 25 Surprisingly, pediatric surgeons are enthusiastic about laparoscopy in China, with 40.2% of surgeons considering laparoscopy for the diagnosis and/or treatment of NEC, which is significantly higher than the international level.5 The indications for laparoscopy in NEC are still unclear, and evidence-based guidelines are currently absent. At present, it is only clear that laparoscopy should not be performed on newborns who have unstable circumstances. It is also questionable whether the surgeons performed laparoscopic surgery too early, which was not the appropriate timing of this intervention for NEC.
Pneumoperitoneum and failure of conservative treatment are absolute surgical indications, and pneumatosis intestinalis and/or portal venous gas and MD7 ≥3 are relative surgical indications.7 26 Despite the fact that pneumatosis intestinalis and portal venous gas are the two most significant signals that surgeons rely on in imaging examination, they were not used widely to estimate the timing of surgery. This might be because imaging examinations, particularly AUS, are subjective and need to be performed at certain times, which results in frequent re-examination. Once intestinal necrosis has been diagnosed, surgery should be performed as quickly as feasible to treat the acute phase of NEC.26 The lack of specialized equipment forces surgeons to rely on their clinical experience to evaluate whether the intestine is necrotic. Surgeons in large-scale, specialized hospitals are more confident in their ability to detect localized intestinal necrosis preoperatively (before intestinal perforation) (figure 3B).
Regardless of the infant’s weight, most surgeons opt to perform an exploratory laparotomy. Furthermore, larger proportions of surgeons choose laparoscopic exploration for higher weights and PPD for lower weights. PPD is typically used on ELBW infants who cannot withstand laparotomy exploration; however, it is still controversial whether PPD would improve the prognosis compared with laparotomy exploration.27 28 According to our survey, 26.97% of surgeons use PPD in their practice for ELBW infants.
Despite personal experience, there have been several instructive principles of surgery in NEC: removal of necrotic intestine, control of intra-abdominal infection, and preservation of residual intestinal length to the greatest extent.29 Nevertheless, surgical strategy varies on the basis of surgeons’ preference and perspectives. The majority of surgeons choose bowel resection and anastomosis in cases of a single perforation or area of necrosis, regardless of China or Europe, whereas stoma formation predominates in cases with multiple perforations or areas of necrosis. Currently, bowel resection followed by stoma is the most recognized and feasible surgical method.26 NEC totalis remains the most challenging and controversial. Additionally, surgeons in China rarely perform the clip and drop technique, which is frequently used in Europe.
The type and location of the stoma are also up for debate.30 31 The double barrel reduces the risk of subsequent prolapse and may represent the preferred approach.30 Although the timing of stoma closure should be individualized depending on the infant’s weight, we usually recommend 6–12 weeks since stoma formation.32 Early stoma reversal at lower weight may be acceptable because of complications such as failure to thrive. Most surgeons opt for a contrast examination of the distal bowel prior to surgery, which assists them in estimating the bowel’s morphology and continuity.
In the postoperative period, early feeding promotes intestinal adaptation. A meta-analysis concluded that early feeding within 7 days is safe, and the risk of NEC recurrence and intestinal strictures will not increase.21 33–35 Following surgery, human milk is recommended as the first choice for nutrition in newborns.35 36 Extensively hydrolyzed formula is particularly advised for infants with who are intolerant of human milk.37 In the absence of human milk, the best type of formula milk to use is still debatable, and some experts recommend hydrolyzed formulas.37–39 Bovine milk-based products may increase the risk of NEC recurrence.38 In general, no specific implementation protocol is available.
Following discharge, NEC survivors have the risk of developing various medical and surgical conditions, including intestinal stenosis and failure to thrive. It is recommended that the patients should be monitored jointly by the departments of neonatal surgery and neonatology. Most surgeons uppatients, but not for a long period, so neurodevelopmental outcomes do not receive the intended attention.40
There are some limitations in our study. Although our survey has guiding significance for the treatment of surgical NEC in China, it cannot be used as evidence-based medical evidence. We explored the diagnostic and surgical options for NEC. Laparoscopic exploration is a prevalent diagnostic and treatment approach in China; however, its application, indications, and benefits still need to be researched more through multicenter prospective studies in the future.
In conclusion, the most challenging aspect of surgical NEC is evaluating the timing of surgery. Relative surgical indications for NEC have not yet been agreed, but specialized hospitals are relatively more experienced. It is worth noting that AUS has been extensively used in China, which will help to better judge the timing of surgery in the future. In surgical aspects, the surgical treatment for NEC totalis is controversial, and the indications for laparoscopic surgery need to be further clarified. In China, few patients with NEC are followed up for more than 5 years after discharge, and neurodevelopmental outcomes do not receive enough attention. Surgical NEC and medical NEC differ little in feeding, antibiotic therapy and so on. More multicenter prospective studies are needed in the future to develop surgical guidelines for NEC.