Correlation between laboratory values and the severity/outcome of injury is poor. A high white blood cell count (> 20000 cells/mm³), elevated serum C-reactive protein, age and the presence of an esophageal ulcer have been considered predictors of mortality in adults[32]; an arterial pH less than 7.22 or a base excess lower than -12 have been considered indication of severe esophageal injury and of emergency surgery[33]. Essentially, laboratory studies are more useful in monitoring and guiding patient management than in predicting morbidity or mortality[34].

Shortly after ingestion, a plain chest radiograph may reveal air in the mediastinum suggesting esophageal perforation, as well as free air under the diaphragm, indicating gastric perforation. If it is felt necessary to confirm a clinically suspected perforation, a water-soluble agent, such as Hypaque™ or Gastrografin™, and less irritant than barium sulphate, should probably be used, though both can be equally irritant[35]. Conversely, barium sulfate should be the preferred contrast agent in late barium swallowing, providing greater radiographic details than water-soluble contrast agents[22].

Evaluation of esophageal wall caustic damage by endoscopic ultrasound (EUS) using a miniprobe seems safe, though prolongs examination time without showing any difference with endoscopy in predicting early complications[36]. The destruction of the muscular layers of the esophagus observed at EUS seems a reliable sign of future stricture formation[37]; furthermore, ultrasound examination with a radial probe may predict the response to dilatation, which usually requires more sessions when the muscolaris propria is involved at EUS, as in Figure 2[38]. In spite of these encouraging reports, the role of US examination in caustic injuries is still under evaluation.

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Figure 2 Endoscopic ultrasound showing involvement of the muscularis propria of esophageal wall. Reproduced from Kamijo et al[37].

A CT scan likely offers a more detailed evaluation than early endoscopy about the transmural damage of esophageal and gastric walls and the extent of necrosis[39]. It is more valuable than endoscopy in assessing threatened or established stomach perforation[29], and a CT grading system (Table 2 and Figure 3) has been proposed to predict esophageal stricture[40,41]. With the advantage of not being invasive, CT scan has a promising role in the early evaluation of caustic injury damage.

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Figure 3 Computed tomography grading of esophageal caustic injuries. A: Grade 1; B: Grade 2; C: Grade 3; D: Grade 4. Reproduced from Ryu et al[40]. Arrows show the esophageal wall.

Esophagogastroduodenoscopy is considered crucial and usually recommended in the first 12-48 h after caustic ingestion, though it is safe and reliable up to 96 h after the injury[13,42]; gentle insufflation and great caution are mandatory during the procedure. Endoscopy and even dilatation have been performed without consequences from 5 to 15 d after corrosive ingestion[43], though potentially hazardous due to tissue softening and friability during the healing period. Adequate sedation (general anesthesia in children) is compulsory, yet endotracheal intubation is strictly required only for patients in respiratory distress. The constraint to stop the endoscope in the presence of a circumferential second or third degree esophageal burn is not mandatory[44,45].

When lip and oropharyngeal injuries are the main clinical findings, esophageal or gastric injuries are generally no greater than grade 1[46]. Although severe esophageal injuries have been reported in 12.0%[47] and 19.3%[48] of asymptomatic children, significant lesions at endoscopy are not usually observed when symptoms are absent after unintentional ingestion of less aggressive substances[24,49], thus making routine post-ingestion endoscopy questionable in this group of patients. All adult patients must undergo endoscopy after suicidal ingestion, because of the larger amount of more corrosive agents swallowed compared with unintentional injuries, where early esophagoscopy has been questioned[50]. Ultimately, though endoscopy is considered by most a cornerstone in the diagnosis of corrosive ingestions, which patients would clearly benefit from it is still debated. Considering that 10%-30% of caustic ingestions globally do not show any upper gastrointestinal injury[22,51], the indication for early endoscopy should be made on a case-by-case basis, with consideration of symptoms, otorhinolaryngeal injuries, and the amount and nature of the ingested substance.

Contraindications to endoscopy are a radiologic suspicion of perforation or supraglottic or epiglottic burns with edema, which may be a harbinger of airway obstruction, therefore indicating endotracheal intubation or tracheostomy. A third degree burn of the hypopharynx is a further contraindication for endoscopy[22].

Endoscopic classification[8] is important for prognosis and management (Table 3). Generally, grade 0 and 1 lesions do not develop delayed sequels, such as esophageal strictures or gastric outlet obstruction, whose incidence increases with the severity of the lesion. Additionally, the degree of esophageal injury at endoscopy is an accurate predictor of systemic complications and death, with each increased injury grade correlated with a 9-fold increase in morbidity and mortality[14]. Emergency surgery can be planned according to the endoscopic degree of burn, though an isolated black eschar does not always indicate full-thickness injury and the need for immediate surgical treatment: such patients may deserve further evaluation and careful observation. Recently, some concerns have been raised about the correlation between endoscopic findings and the extent of necrosis[39]: gastrectomy was considered unnecessary at laparotomy in 12% of patients with gastric injuries staged 3b at endoscopy, while the decision to perform esophagectomy based exclusively on endoscopic findings led to unnecessary esophagectomy in 15% of cases[52], suggesting the need for better criteria to improve patient selection for emergency surgery.

Immediate treatment is usually conservative, as the definitive extent of the injury is determined within minutes after ingestion. Hemodynamic stabilization and adequacy of the patient’s airway are priorities. If the airway is unstable, fiberoptic laryngoscopy allows intubation under direct visualization, avoiding ‘‘blind’’ intubation with the risk of bleeding and additional injuries. In challenging patients, a surgical airway may be required. Gastric lavage and induced emesis are contraindicated for the risk of re-exposure to the corrosive agent and additional injury to the esophagus. The effectiveness of milk and water either as antidotes or to dilute the corrosive agents has never been proven. pH neutralization, with either a weak acid or base, is not recommended for fear of an exothermic reaction, which may increase the damage. Milk and activated charcoal are contraindicated because may obscure subsequent endoscopy. Nasogastric tubes may be applied to prevent vomiting and as stent in severe circumferential burns, but their validity has never be proven. In any case they should not be placed blindly because of the risk of esophageal perforation[53].

To date, the efficacy of proton-pump inhibitors and H₂ blockers in minimizing esophageal injury by suppressing acid reflux has not been proven, though an impressive endoscopic healing after iv omeprazole infusion has been observed in a small prospective study[54].

The utility of corticosteroid is controversial. A meta-analysis of studies between 1991 and 2004, and an additional analysis of the literature over a longer period from 1956 to 2006 did not find any benefit of steroid administration in terms of stricture prevention. Steroids are usually reserved for patients with symptoms involving the airway[55,56].

The administration of broad-spectrum antibiotics is usually advised mainly if corticosteroids are initiated, as well as if lung involvement is identified[53,57].

Patients whose injuries are graded 1 and 2A are permitted oral intake and discharged within days with antacid therapy. In more severe cases (grade 2 or 3), observation in an intensive care unit and adequate nutritional support is required.

Patients with clinical or radiological evidence of perforation require immediate laparotomy, usually followed by esophagectomy, cervical esophagostomy, frequently concomitant gastrectomy and even more extensive resections, and jejunostomy feeding[58-60]. Some patients without features of perforation at admission may later develop necrosis, perforation and massive bleeding with disastrous results. Indications for emergency surgery rely more often on clinical grounds than on radiological findings; in the presence of doubtful clinical features a decision to perform laparotomy is likely more advantageous for patients than a conservative attitude especially in patients who ingested large amounts of corrosive substances[60].

Laboratory and endoscopic criteria for emergency surgery have been suggested, including disseminated intravascular coagulation, renal failure, acidosis and third degree esophageal burns[58,61]. Unfortunately, these are often late findings and surgery may improve mortality and morbidity in grade 3A injuries only[14].

Severe injuries of the stomach at endoscopy require careful monitoring with a low threshold for laparotomy. At surgery, a gastrotomy allows an accurate evaluation of the extent of damage, since mucosal (and transmural) necrosis may be more extensive than what is apparent from the serosal side. There is no role for procedures such as closure of a perforation. Conservative management of severe gastric injuries at laparotomy, with partial or total conservation of the stomach, has been recently advocated by some in the absence of clinical and biological signs of severity[62].

The need to perform surgery for caustic injuries has a persistent long-term negative impact both on survival and functional outcome. Moreover, esophageal resection per se, is an independent negative predictor of survival after emergency surgery[52].

Laparoscopy has been proposed when gastric perforation is highly suspected[63], but the mini-invasive approach has two caveats: unless in very expert hands, it is not a substitute for a comprehensive abdominal exploration, particularly in the posterior aspects of the stomach and duodenum, and it can extend the operative time excessively in a situation where time is a major determinant of outcome. However, it might be considered a useful tool when the stomach cannot be evaluated by endoscopy. Some authors have proposed routine laparoscopic examination in all injuries of second degree or greater[63,64] but the experience is still limited and laparoscopy may be neither feasible nor helpful in such dramatic circumstances.

All injured organs must be resected, if possible, during the first operation. Minimal resection followed by a planned second-look procedure is not recommended. However, secondary extension of caustic burns is unpredictable and re-exploration is indicated when in doubt. An extended resection to adjacent abdominal organs, even the pancreas, does not necessarily carry a prohibitive risk of death in referral centers[60], but an extensive colon resection may compromise future reconstruction and require vascular surgery for atypical transplants. A massive intestinal necrotic injury represents a reasonable limit for resection.

Emergency surgery may be required in the case of severe, uncontrolled late gastric bleeding, usually 1-2 wk after ingestion. Total gastrectomy may be necessary. In duodenal hemorrhages, under-running of the bleeding vessel through a duodenotomy is advised[29].

Acute surgery is quite exceptional in the pediatric population and most authors recommend exhausting all resources to try to preserve the child’s native esophagus[25].

Following a grade 2B and a grade 3 esophageal burn, stricture incidence may be 71%[14] and 100%, respectively[45,53]. Strictures usually develop within 8 wk after the ingestion in 80% of patients, but it can happen as early as after 3 wk or as late as after 1 year. Obviously, ingestion of powerful caustic substances (e.g., sodium hydroxide) is followed by severe, long-standing strictures and dramatically altered esophageal motility[65].

Late sequelae of corrosive gastric injury include intractable pain, gastric outlet obstruction, late achlorhydria, protein-losing gastroenteropathy, mucosal metaplasia and development of carcinoma[66]. Gastric outlet obstruction has an incidence of 5%[67], mainly in the prepyloric area, where prolonged contact with the antral mucosa due to pyloric spasms and to resulting pooling of the caustic agent in this region[55] usually results in stricture in more than 60% of patients[68]. When the volume of the corrosive substance ingested is large, the entire stomach is scarred leading to a diffusely contracted stomach.

Steroids: Systemic administration of steroids seems ineffective in preventing strictures[55,56], especially in patients with 3^rd degree esophageal burns. Intralesional triamcinolone injections have been proposed to prevent strictures[69], but optimal dose, frequency, and best application techniques are still to be defined[70].

Antibiotics: Though an old study reports a marked decrease in stricture formation with the use of antibiotics[71], no prospective trial evaluated their utility, and their value in the setting of caustic ingestion, in the absence of concomitant infection, is unknown[18]. There is a consensus that patients treated with steroids should also be treated with antibiotics, but prophylactic antibiotics to prevent strictures, in the absence of steroid therapy, has not been advocated[72].

Nasogastric tube: Though a nasogastric tube may be helpful to ensure patency of the esophageal lumen, the tube itself can contribute to the development of long strictures and routine use is not uniformly recommended[22]. Any esophageal catheterization may be a nidus for infection and nasogastric placement may worsen gastroesophageal reflux in this patient population, with a consequent delay in mucosal healing. However, enteral nutrition through a nasogastric tube has been demonstrated to be as effective as jejunostomy feeding in maintaining nutrition in such patients, with a similar rate of stricture development[73]. Moreover, positioning a nasogastric tube has the advantage of providing a lumen for dilatation should a tight stricture develops. Therefore, after caustic injuries the placement of a nasogastric tube may be considered, but the decision should be made with caution and done on a case-by-case basis.

Mitomycin C: Mitomycin C, a chemotherapeutic agent with DNA crosslinking activity, when injected or applied topically to the esophageal mucosa, may be valuable in preventing strictures, but this drug has deleterious adverse effects, especially if systemic absorption occurs across the intact mucosa[74]. A recent systematic review indicated encouraging results in the long term[75], but prospective studies are clearly mandatory to determine the most effective concentration, duration and frequency of application[76]. The theoretical risk of secondary long-term malignancy should also be taken into account[77].

Intraluminal stent: Specially designed silicone rubber[78] or, more recently, polyflex stents[79] have been found helpful in preventing stricture formation but the efficacy is less than 50%, with a high migration rate (25%). Patient selection remains a challenge and the development of hyperplastic tissue is a concern. Home-made polytetrafluoroethylene stents have shown promising results with a 72% efficacy[80] at 9-14 mo, similar to home-made silicone stents positioned by endoscopy[81] or through laparotomy[82] for 4-6 mo. Biodegradable stents (poly-L-lactide or polydioxanone) are under evaluation for benign strictures[83,84], with a 45% success rate at 53 mo in a patient population with only two caustic strictures, a migration rate of around 10%, and a significant hyperplastic tissue response. Experimentally, biodegradable stents were not able to prevent strictures in pigs after circumferential submucosal resection[85]. Moreover, cost and minimal experience in caustic strictures make the use of biodegradable devices questionable, especially in developing countries.

Other modalities for stricture prevention under evaluation: Intraperitoneal injection of 5-fluorouracil has been effective in preventing strictures experimentally[86]. Anti-oxidant treatment (vitamin E, H₁ blocker, mast cell stabilizer, methylprednisolone) and phosphatidylcoline[87,88] inhibit collagen production and stricture formation by decreasing tissue hydroxyproline, the ultimate product of collagen degradation, but no human study is available. Octreotide and interferon-alfa-2b have been shown in animals to depress the fibrotic activity in the second phase of wound healing of the esophageal wall after a corrosive burn[89]. Cytokines have also been used experimentally with success to prevent stricture formation[90]. Until now, none of the above approaches, albeit appealing, has been tested in humans.

Endoscopic dilatation: Timely evaluation and dilatation of the stricture play a central role in achieving a good outcome[91]. Late management is usually associated with marked esophageal wall fibrosis and collagen deposition[5], which makes dilatation more complex. Maximal esophageal wall thickness, observed at CT scan, was associated with a higher number of sessions required for adequate dilatation[92], and recurrent strictures were significantly more frequent after delayed dilatation (Figure 4)[93-95]. Moreover, delayed presentation and treatment have been found to be strong predictors of future esophageal replacement[96]. This issue, which may entail different management strategies[3] for early or late patients, may be crucial in developing countries, where late presentations are more than 50%[2,97,98].

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Figure 4 Significantly higher hazard of re-dilatation in patients submitted to late dilatation. P = 0.0008. Reproduced from Contini et al[97].

Dilatation can be carried out with balloon or bougies (usually Savary) without a clear advantage for each method[70]. However, the failure rate after pneumatic dilatation is higher in caustic ingestion-related strictures than in other benign strictures[99]; Savary bougies are considered more reliable than balloon dilators in consolidated and fibrotic strictures such as old caustic stenosis or in long, tortuous strictures[100,101], and may offer the operator the advantage of feeling the dilatation occurring under his hands[102]. Dilatation should be avoided from 7 to 21 d after ingestion for the risk of perforation, though early, prophylactic dilatation with bougienage has been reported to be safe and effective even in this period[43]. The perforation rate after dilatation of benign esophageal strictures varies between 0.1% and 0.4%[70], but for caustic strictures it fluctuates from 0.4% to 32.0%, dropping from 17.6% to 4.5% with increased experience[103]. The 5%-8% perforation rate after balloon dilatation[104] may be as high as 32% in caustic strictures[105]. Indeed, radiological intramural and well-contained transmural esophageal ruptures were observed in 30% of balloon dilatation procedures[106]. In addition, balloon inflation may cause either extrinsic mechanical compression of the trachea or obstruction at the endotracheal tube tip[107]. Therefore, the use of the balloon catheter in children entails careful intraoperative monitoring and likely requires greater endoscopic skill and experience than for Savary bougies. If these requirements are not met, as is often the case in developing countries, pneumatic dilatations will carry a considerable risk and then require extra caution, so that bougie dilatation is preferred.

The interval between dilatations varies from less than 1 to 2-3 wk and usually 3-4 sessions are considered sufficient for durable results, although the number of dilatations required may be unpredictable and quite high[103]. In challenging strictures, a nylon thread left between the nose and the gastrostomy maintains luminal access and facilitates further dilatations when an expert endoscopist is not available[108,109]. A cut-off value for unsuccessful dilatation treatment may be difficult to define, especially in developing countries, where alternative surgical options are not widely available.

A good nutritional state is crucial for a successful outcome, especially in children, and both an improvement in nutritional status and sustained esophageal patency should be considered reference points for a successful dilatation[3]. Changes in feeding practices may be required in order to maintain an adequate nutritional status[110]. In developing countries, delayed presentation and severity of strictures due to the more corrosive substances usually ingested, together with poor nursing and surgical care make this target quite challenging. In such a scenario, feeding by nasogastric tube for long periods may be tolerated with difficulty and a gastrostomy is more effective and often necessary to attain an acceptable nutritional state. Moreover, gastrostomy allows a retrograde approach for dilatation, which is usually easier and safer[111,112].

Surgery for non-responding esophageal strictures: When esophageal dilatation is not possible or fails to provide an adequate esophageal caliber in the long-term, esophageal replacement by retrosternal stomach or, preferably, right colonic interposition should be considered. Mortality and morbidity are low in expert hands[119,120]. The more demanding pharyngoesophageal strictures may be treated with acceptable results, provided considerable expertise is available[121]. The native esophagus can be left or removed. Though resection of the scarred esophagus may be performed without a substantial increase in morbidity and mortality compared to by-pass[120], a 13% incidence of esophageal cancer after by-pass[93], the risk of infected esophageal mucocele in 50% of the patients after 5 years[94], and the impossibility of endoscopic follow-up for cancer are all arguments favoring esophageal resection. Removal of the native esophagus seems advisable in children because of the risk of cancer in a long life period. Conversely, the doubled mortality rate (11.0% vs 5.9%) of resection vs by-pass[122], the possible damage to the trachea and laryngeal nerve, and the low reported incidence (3.2%) of esophageal malignancy, could support a conservative strategy. In children, reconstruction with gastroplasty seems easier, and more functional failures can be expected with coloplasty[123-125]. In developing countries, experienced pediatric surgical centers are not widely available and this should be considered before abandoning the conservative approach of dilatation.

Surgery for stomach injuries: The timing and type of elective surgery for gastric outlet obstruction is still controversial. Early surgery has been advised to decrease mortality and morbidity[67,126]. Conversely, elective surgery earlier than 3 mo has been considered risky because of poor nutritional state and the presence of adhesions and the edematous gastric wall[27]. Moreover, assessment of the limits of the gastric resection may be difficult, due to ongoing fibrosis. Endoscopic balloon dilatation and/or intralesional steroid injection have been proposed as alternatives[127,128]. However, endoscopic gastric dilatation should be considered a temporary substitute for surgical resection because gastric wall fibrosis usually diminishes the long-term functional result[129,130]. Moreover, although dilatation averts surgery in less than 50% of patients[127], perforation can occur in strictures longer than 15 mm[131]. Pyloroplasty has been recommended for moderate strictures[67], but progressive fibrosis causing recurrent stricture occurs frequently. Gastrojejunostomy is a safer alternative to gastric resection in the presence of extensive perigastric adhesion, an unhealthy duodenum, and poor general condition; marginal ulceration is rarely reported[27,132] possibly due to physiologic antrectomy resulting from mucosal damage[66]. Partial gastric resection is preferred by many[133,134] for the long-term risk of malignant transformation, though the need for gastric resection as prophylaxis against future malignancy has been overstated in the literature[29]. Previous reports of gastric carcinomas after acid ingestion are usually old and limited[135,136]. Regular follow-up and surveillance endoscopy is a more reliable approach.

Late reconstructive surgery after emergency esophagectomy: When the stomach has been removed or shows chronic injuries, the use of a gastric tube for esophageal reconstruction is obviously precluded. Reconstruction is probably advisable at the end of the evolving scarring process, usually after 6 mo, although the optimal timing of reconstruction has been reported from 2 mo to years[94,137,138]. The functional success rate after colon reconstruction at 5 years is 77% and the severity of the initial insult or a delay more than 6 mo, may strongly influence the outcome[119]. Coloplasty dysfunction is responsible for half of the failures, with an overall 70% success rate after revision surgery in expert hands. An emergency tracheostomy may have an adverse impact on the outcome of a colopharyngoplasty[139]. Secondary esophagocoloplasty should be considered with good results if intraoperative colon necrosis occurs at the time of primary reconstruction[140].