Delayed perforation after endoscopic resection of a colonic laterally spreading tumor: A case report and literature review

Abstract

BACKGROUND

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been widely used for the treatment of early gastrointestinal cancer. Endoscopic piecemeal mucosal resection (EPMR) is derived from the combination of EMR and ESD. Delayed perforation with peritonitis after colonic EPMR is a rare but severe complication, sometimes requiring surgery. There are some associated risk factors, including patient- (location, diameter, and presence of fibrosis) and procedure-related factors. Early recognition and timely treatment are crucial for its management.

CASE SUMMARY

We report a case in which delayed perforation with peritonitis was treated using endoscopic closure. A 54-year-old man was diagnosed with a 30-mm-diameter laterally spreading tumor in the colonic hepatic curvature. Fifteen hours after endoscopic resection, peritonitis caused by delayed perforation occurred and gradually aggravated. Conservative treatment was ineffective and no obvious perforation was observed. After timely endoscopic closure, the patient was discharged on postoperative day 4.

CONCLUSION

In occasion of localized peritonitis aggravating without macroscopic perforation, endoscopic closure is an effective treatment for delayed perforation with stable vital signs in the early stage.

Key Words: Endoscopic mucosal resection, Endoscopic submucosal dissection, Endoscopic piecemeal mucosal resection, Delayed perforation, Endoscopic closure, Case report

Core tip: We report a case in which delayed perforation occurred 15 h after colonic endoscopic resection of a laterally spreading tumor in the colonic hepatic curvature. Peritonitis aggravated progressively without macroscopic perforation and conservative treatment had no effect. Micro-perforation was successfully closed under endoscopy with clips to avoid worse complications and surgical intervention.

INTRODUCTION

Endoscopic mucosal resection (EMR) is a common treatment for gastrointestinal mucosal lesions worldwide. Developed on the basis of EMR, endoscopic submucosal dissection (ESD) makes en bloc resection possible and endoscopic piecemeal mucosal resection (EPMR) is suitable for large tumors. Endoscopic therapy requires complicated technology and is associated with a high risk of complications[1]. Perforation is one of the most severe complications; there is both intraoperative perforation and delayed perforation. The latter is often associated with severe systemic symptoms or signs once found; therefore, it requires immediate diagnosis and managements[2].

Here, we report a case in which delayed perforation occurred after colonic endoscopic resection of a laterally spreading tumor (LST) in the hepatic flexure of the colon and peritonitis aggravated progressively. This case is being reported because delayed perforation was identified in a timely fashion and endoscopic closure was performed without macroscopic perforation to avoid worse complications and surgical intervention. We discuss the clinical course of this rare case about micro-perforation and also review the relevant literature.

CASE PRESENTATION

Chief complaints

A 54-year-old man complained of aggravating abdominal pain 15 h after endoscopic resection of a colonic LST.

History of present illness

The patient was referred to our hospital for endoscopic resection of an LST measuring 30 mm that was diagnosed as an adenoma on pathology in the medial side of the colonic hepatic curvature. The patient was placed on a low-fiber diet on the day prior to endoscopic surgery. Adequate bowel preparation (BBPS: 3 points) was achieved using a spilt regimen of 4 L of polyethylene glycol solution and simethicone. During the procedure, our experienced team performed ESD for this lesion at first. When damage to the muscular layer caused by poor scope operability was observed, we changed into EPMR to quickly finish the operation. Prophylactic closure with clips was performed at the damage site. The tumor was removed without residue, and the wound was treated quite well without obvious perforation or hemorrhage. There was no abdominal pain after resection, and the patient was in a good condition. Routine antibiotics and intravenous nutrition were used in consideration of the large mucosal defect. Fifteen hours after endoscopic resection, the patient passed gas and then suddenly experienced severe abdominal pain that aggravated progressively over time without any alleviation.

History of past illness

The patient had a history of diabetes for 10 years without a regular oral hypoglycemic treatment. He had no history of other chronic diseases like cardiovascular disease and hypertension, and no history of trauma, surgery, or blood transfusion. He had no history of food and drug allergy.

Personal and family history

The patient occasionally drank alcohol and denied a history of smoking. He had no family history of intestinal tumors.

Physical examination

Physical examination showed intolerable compression pain and rebound pain localized in the right abdomen, suggesting the presence of peritonitis.

Laboratory examinations

Emergency blood analysis showed that neutrophil proportion increased slightly (79.9%) with normal white blood cell count, hemoglobin, and red blood cell count.

Imaging examinations

Emergency computed tomography (CT) revealed a small amount of pneumoperitoneum and substantial exudate (Figure 1).

Figure 1 Emergency computed tomography. A: Free air can be seen under the diaphragm; B: Free air can be found surrounding the endoscopic resection site.

FINAL DIAGNOSIS

The final diagnosis was a perforation after endoscopic resection.

TREATMENT

The attempt of placing gastrointestinal decompression did not relieve the symptoms. Emergent colonoscopy with carbon dioxide insufflation was performed. No obvious perforation was observed. We believed that there was a micro-perforation, and the wound was closed using clips (Figure 2). It only took 2 h from the beginning of abdominal pain to achieve successful endoscopic closure. The patient was asked to maintain a semi-recumbent position and was treated with fasting and broad-spectrum antibiotics.

Figure 2 Emergent colonoscopy with carbon dioxide insufflation was performed. A: No obvious delayed perforation was seen at the wound site; B: The wound was closed using clips.

OUTCOME AND FOLLOW-UP

During the night after endoscopic closure, the patient experienced a fever of 38.3°C, but the pain was slightly relieved. Three days after endoscopic closure, the patient’s abdominal pain totally subsided, and after tolerating oral diet, he was discharged on the 4^th day after endoscopic closure (Figure 3).

Figure 3 Timeline of the patient. EPMR: Endoscopic piecemeal mucosal resection.

No recurrence occurred in the follow-up. The patient was content with our timely treatment, and informed consent was obtained.

DISCUSSION

In the present case, delayed perforation occurred 15 h after colonic endoscopic resection of LST in the hepatic flexure of colon. Peritonitis aggravated progressively without obvious perforation and conservative treatment had no effect. Micro-perforation was successfully closed under endoscopy with clips, which had not been reflected in the previous cases ever.

EMR is effective for lesions < 20 mm, and ESD is recommended for lesions > 20 mm with limited submucosal invasion[3]. Nevertheless, there remain no definitive guidelines for treatment of lesions > 20 mm with no invasion or invasion limited in the mucosal layer. We were planning to perform ESD according to anticipatory judgment; however, poor scope operability causing damage to the muscular layer caused us to change to EPMR. Fortunately, no perforation or obvious hemorrhage occurred throughout the procedure, suggesting that our strategy was reasonable.

Perforation is considered one of the most serious complications of therapeutic colonoscopy. Because of intraperitoneal leakage of the intestinal fluid with digestive enzymes and fecal fluid with large amounts of bacteria, peritonitis caused by colorectal perforation is more serious than gastroesophageal perforation[4]. The probability of perforation after ESD is higher than that after EMR, accounting for 1.4%-14.0%[4-6]. Endoscopic perforation is classified as intraoperative and delayed perforation; the latter is even rarer, with reported rates of 0.3%-0.7%[7] and is defined as perforation within 48 h after endoscopic surgery. All previously reported ten cases occurred within 48 h after ESD or EMR[8-12], accompanied by peritonitis of various degrees. Delayed perforation in our case took place in 15 h and caused progressively increasing peritonitis, which is even rarer because of the aggravating peritonitis and our earlier recognition compared with previous case reports.

Several studies have demonstrated that many factors contribute to the occurrence of delayed perforation. Kang et al[13] reported that LSTs were the most common type of lesions causing endoscopic perforation. The most common location was the right colon, including the cecum, ascending colon, and transverse colon, because colonoscopy might be technically complicated there. Of the reported ten cases, 70% occurred in the right colon. The other risk factors include large tumor diameter, presence of fibrosis, and procedure-related factors[7,13]. Our present case is partly consistent with these reports in terms of tumor diameter and tumor location.

The mechanism of immediate colonic perforation is believed to be associated with unintended deep dissection. Delayed perforation is thought to result from thermal injury, that is to say, immoderate thermocoagulation damages both the submucosal and muscular layers, leading to small perforations over time[14,15]. In our present case, neither an obvious perforation nor a small perforation was observed during the subsequent emergent endoscopy. Therefore, we believed that there was a micro-perforation where there was deep dissection or thermal injury of the muscular layer during the procedure.

Several studies have emphasized that prompt and accurate diagnosis is essential for appropriate management and favorable prognosis after delayed perforation[2,15]. Symptoms and signs should be recorded and evaluated carefully. Abdominal pain is one of the earliest and most common symptoms, accompanied by peritoneal irritation signs. Abdominal distention, fever, tachycardia, tachypnea, and subcutaneous emphysema also raise the index of suspicion for delayed perforation. To obtain a definitive diagnosis, plain abdominal radiography or abdominal computed tomography is recommended to detect subdiaphragmatic free air and fluid leak with high accuracy. Laboratory indicators such as complete blood counts are useful to estimate the degree of abdominal contamination. In our case, when perforation was suspected, a CT scan was performed emergently, which finally indicated pneumoperitoneum and exudation, thereby confirming our suspicion.

Currently, there are no guidelines on the management of delayed perforation after colonic endoscopic resection. Delayed perforation after therapeutic colonoscopy is a rare event; however, it is severe, and emergent surgery is the most common treatment for this situation, especially in the context of peritonitis[12]. With the development of endoscopic techniques[11,16-19], timely endoscopic closure may be a good option, if delayed perforation occurs in the patient’s fasting period with local peritonitis. In the present case, although there was no obvious perforation, peritonitis increased over time and conservative treatment was ineffective. Micro-perforation was diagnosed and successfully closed using clips with carbon dioxide insufflation under colonoscopy. Fasting and intravenous broad-spectrum antibiotics were also administered to avoid the need for surgical rescue.

In the English literature, only five other reports (10 cases) of delayed perforation after EMR and ESD with non-surgical management have been reported[8-12] (Table 1). The decision to conduct an endoscopic operation also depends on the perforation size, endoscopist’s experience, and instruments available[2,15,20-23]. During endoscopic closure, carbon dioxide insufflation is generally preferred to prevent barotrauma because this gas is absorbed more quickly than air[24]. Inoki et al[9] reported a case in which delayed perforation after EMR was closed with endoscopic clips. Currently, increasing numbers of endoscopic techniques and equipment have been used. Both through-the-scope-clip and over-the-scope-clip are widely used for endoscopic repair, the former for smaller perforations and the latter for larger ones. Xiao et al[11] demonstrated an endoscopic method called the overtube approach. Nagami et al[10] demonstrated that polyglycolic acid sheets and fibrin glue were effective for endoscopic closure of delayed perforation. Subsequent conservative treatment after closure is indispensable, including fasting, intravenous antibiotics, gastrointestinal decompression, and nutrition support[25]. Kawashima et al[8] described completely conservative treatment, including transnasal decompression, as a method to manage delayed perforation. Nevertheless, not all cases can be treated endoscopically. Delayed perforation with general peritonitis, hemodynamic disorder, and failure in endoscopic closure require immediate surgical treatment[26].

Table 1 Summary of previous reports of delayed perforation with non-surgical management.

Ref.	Case	Age (yr)	Sex	Morphology	Location	Tumor diameter (mm)	Endoscopic therapy	Time of delayed perforation (h)	Perforation size (mm)	Treatment	Hospital stay (d)
Kawashima et al[8], 2018	1	66	Male	LST	Cecum	40	ESD	Within 24	10	Transnasal decompression, antibiotics	26
Inoki et al[9], 2016	2	73	Male	LST	Transverse colon	18	EMR	Within 24	NM	Endoscopic closure with clips, antibiotics	9
Nagami et al[10], 2019	3	81	Male	LST	Ascending colon	40	ESD	Within 48	NM	Endoscopic closure with clips, polyglycolic acid sheets and fibrin glue, antibiotics	16
Xiao et al[11], 2014	4	49	Female	LST	Sigmoid colon	NM	ESD	Within 24-48	3	Endoscopic closure with clips, overtube, nasobiliary tube, antibiotics	29
Xiao et al[11], 2014	5	77	Male	LST	Ascending colon	NM	ESD	Within 24-48	6	Endoscopic closure with clips, overtube, nasobiliary tube, antibiotics	12
Xiao et al[11], 2014	6	41	Female	Polyp	Transverse colon	NM	EMR	Within 24-48	5	Endoscopic closure with clips, overtube, nasobiliary tube, antibiotics	7
Iwatsubo et al[12], 2019	7	45	Male	Protruded	Descending colon	10	ESD	24	NM	Conservative therapy, antibiotics	13
Iwatsubo et al[12], 2019	8	53	Male	Flat	Transverse colon	22	ESD	19	NM	Conservative therapy, antibiotics	12
Iwatsubo et al[12], 2019	9	74	Female	Protruded	Rectum	110	ESD	14	NM	Conservative therapy, antibiotics	14
Iwatsubo et al[12], 2019	10	58	Male	Protruded	Ascending colon	55	ESD	24	NM	Conservative therapy, antibiotics	13

NM: Not mentioned; ESD: Endoscopic submucosal dissection; EMR: Endoscopic mucosal resection; LST: Laterally spreading tumor.

CONCLUSION

Delayed perforation with peritonitis after endoscopic operation is an uncommon but serious complication. Endoscopists should operate carefully throughout the procedure, especially for LSTs in the right colon. If delayed perforation occurs and localized peritonitis exacerbates, even without macroscopic perforation, endoscopic closure is an alternative for patients with stable vital signs in the early stage.