Safety and Efficacy of Endoscopic Therapy for Nonmalignant Duodenal Duplication Cysts: Case Report and Comprehensive Review of 28 Cases Reported in the Literature.

Analyze efficacy, safety of endoscopic therapy for duodenal duplication cysts (DDC) by comprehensively reviewing case reports.Tandem, independent, systematic, computerized, literature searches were performed via PubMed using medical subject headings or Keywords "cyst" and "duodenal" and "duplication"; or "cyst", and "endoscopy" or "endoscopic", and "therapy" or "decompression"; with reconciliation of generated references by two experts. Case report followed CARE guidelines.Literature review revealed 28 cases (mean = 1.3 ± 1.2 cases/report). Endoscopic therapy is increasingly reported recently (1984-1999: 3 cases, 2000-2015: 25 cases, P = 0.003, OR = 8.33, 95%-CI: 1.77-44.5). Fourteen (54%) of 26 patients were men (unknown-sex = 2). Mean age = 32.2 ± 18.3 years old. Procedure indications: acute pancreatitis-16, abdominal pain-8, jaundice-2, gastrointestinal (GI) obstruction-1, asymptomatic cyst-1. Mean maximal DDC dimension = 3.20 ± 1.53 cm (range, 1-6.5 cm). Endoscopic techniques included cyst puncture via needle knife papillotomy (NKP)/papillotome-18, snare resection of cyst-7, cystotome-2, and cyst needle aspiration/ligation-1. Endoscopic therapy was successful in all cases. Among 24 initially symptomatic patients, all remained asymptomatic post-therapy without relapses (mean follow-up = 36.5 ± 48.6 months, 3 others reported asymptomatic at follow-up of unknown duration; 1 initially asymptomatic patient remained asymptomatic 3 years post-therapy). Two complications occurred: mild intraprocedural duodenal bleeding related to NKP and treated locally endoscopically.A patient is reported who presented with vomiting, 15-kg-weight-loss, and profound dehydration for 1 month from extrinsic compression of duodenum by 14 × 6 cm DDC, underwent successful endosonographic cyst decompression with large fenestration of cyst and endoscopic aspiration of 1 L of fluid from cyst with rapid relief of symptoms. At endoscopy the DDC was intubated and visualized and random endoscopic mucosal biopsies were obtained to help exclude malignant or dysplastic DDC.Study limitations include retrospective literature review, potential reporting bias, limited patient number, variable follow-up.In conclusion, endoscopic therapy for DDC was efficacious in all 29 reported patients including current case, including patients presenting acutely with acute pancreatitis, or GI obstruction. Complications were rare and minor, suggesting that endoscopic therapy may be a useful alternative to surgery for nonmalignant DDC when performed by expert endoscopists.

INTRODUCTION

Symptomatic duodenal duplication cysts (DDC) were traditionally treated surgically, but have been increasingly treated endoscopically to avoid considerable morbidity from surgery.[1] This work comprehensively reviews this subject with review of 28 previous cases, and shows this technique is likely efficacious, relatively safe, and durable. A 29th patient is also reported who presented with severe recurrent vomiting for 1 month from duodenal compression by a huge DDC that was successfully treated by DDC decompression under endosonographic guidance with symptomatic resolution. During decompression at endosonography, the DDC was intubated and biopsied to exclude malignancy/dysplasia. This work suggests that endoscopic treatment is a viable and potentially preferable alternative to surgery for most DCC, provided endoscopic expertise is available and malignancy is excluded.

METHODS

Computerized literature searches independently performed in tandem via PubMed using the medical subject headings (MeSH) or key words of “cyst” and “duodenal” and “duplication”; or “cyst” and “endoscopy” or “endoscopic” or “therapy” and “decompression”; with reconciliation of cited references. One article written in French,[2] and one article written in Spanish[3] were professionally translated. Case report followed CARE guidelines. This review received exemption/approval by William Beaumont Hospital IRB on August 14, 2015.

CASE REPORT

See Appendix 1.

RESULTS

Epidemiology and Anatomy

DDC are extremely rare congenital anomalies, with a prevalence of less than 1 per 100,000 live births.[4] DDC are the least common small bowel duplication cysts, preceded by ileal and jejunal duplication cysts.[5] In a comprehensive meta-analysis, 47 DDC were reported from 1999 to 2009.[4] About 60% of cases are diagnosed during infancy and childhood, and 40% are diagnosed in adulthood.[4-8]

By definition, a DDC must adhere to the duodenum, contain a smooth muscle layer in its walls, and be lined by duodenal epithelium.[5,6,9-11] DDC usually share the blood supply with the rest of the duodenum.[6] DDC are usually filled with clear fluid, but can contain bile, pancreatic fluid, or gallstones if they connect to the pancreaticobiliary ducts.[12-15] DDC can occur in any duodenal segment, but most commonly arise in the second or third parts of the duodenum. They usually arise on the mesenteric side.[5,13]

DDC can communicate directly with the true lumen via the duodenum, or via the pancreaticobiliary ducts, or have no communication.[4-6,9,16] About 30% of DDC communicate with the pancreaticobiliary ducts.[4] DDC are also classified according to shape as cystic or elongated/tubular.[13] DDC are most commonly cystic.[5,12]

Clinical Course

DDC are usually asymptomatic and incidentally discovered during radiologic imaging or esophagogastroduodenoscopy (EGD).[6,7] They can remain clinically silent for many years.[6] Symptoms, when present, most commonly include abdominal pain, followed by nausea in 80%, and vomiting in 40%.[4] The most common complication is acute pancreatitis.[4,12] Other complications include: jaundice, biliary obstruction, cyst infection, intussusception, cholestasis, and hepatitis.[4,14-20] DDC may contain ectopic pancreatic or gastric tissue that can cause duodenal ulcers, gastrointestinal (GI) bleeding, or rarely duodenal perforation.[6,11,21,22] DDC are usually benign, but are occasionally malignant.[7,23-25]

Diagnosis

DDC are strongly suggested by characteristic radiologic imaging findings, but imaging findings are occasionally misleading.[12,18] Twin major goals of radiologic imaging are to determine that the lesion is fluid-filled and to locate the cyst attachment site.[13] Contrast radiographs reveal a submucosal or extrinsic mass or filling defect.[4] Abdominal computerized tomography (CT), ultrasound (US), and magnetic resonance imaging (MRI) are commonly used to detect DDC. DDC appear as discrete, fluid-filled structures attached to the duodenal wall.[4,13] CT is useful to depict cyst location and dimensions, potential communications, and other anomalies.[26] On CT scan, the wall of duplication shows contrast enhancement, but the cyst content has a density of 0–20 Hounsfield units without contrast enhancement.[13] On US, DDC are highly suspected when an outer hypoechoic muscular layer and an inner echogenic mucosal layer is detected, a phenomenon called the “double-wall” or “muscular rim” sign.[5,13,26,27] Cysts may contain keratin and desquamated cells, which can appear solid on US.[17] MRI typically shows low attenuation signals in T1- and T2-weighted images.[13] A Meckel's technetium scan is used to exclude ectopic gastric tissue within DDC.[13] Magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) can also be used diagnostically, and to exclude cyst communication with the pancreaticobiliary ducts.[4,16,28,29] If the choledochus drains into the DDC, only the pancreatic duct fills with contrast during ERCP.[16] A meta-analysis revealed false negative rates for DDC of 23% with US and 9% with CT or MRI/MRCP.[4] Three-dimensional virtual cholangioscopy has been used to exclude communication between DDC and pancreaticobiliary ducts.[7,30]

Definitive diagnosis requires EGD with endosonographic confirmation, or surgery with pathologic analysis of resected tissue.[22,29,31-34] At EGD, DDC appear as a duodenal bulge with normal overlying mucosa, or as a variably long diverticulum. DDC usually have a smooth, regular, mucosal appearance. Other cystic masses in the differential diagnosis include: choledochal cyst, cystic dystrophy of duodenal wall, pancreatic pseudocyst, duodenal polyp, cystic pancreatic tumors, lymphatic malformation, mesenteric cyst, omental cyst, and gastrointestinal stromal tumor.[13,35-37] Endoscopic ultrasonography (EUS) can confirm the presence of muscular layer continuity between the duodenum and its duplication.[9,13,38] Fine needle aspiration can be performed during EUS if the diagnosis is uncertain, but aspiration occasionally results in cyst infection.[17,39-42]

Therapy

Asymptomatic cysts are usually managed expectantly, but some authorities recommend intervention based upon potential complications, including malignant transformation,[5] especially in patients who are unlikely to follow-up.[4,43] Prospective studies of the natural history of DDC are, however, unavailable. Symptomatic DDC generally mandate endoscopic or surgical therapy. Moreno et al,[44] however, reported one case of medical management of a symptomatic DDC with prokinetic therapy, and recommended annual follow-up with EGD or abdominal US, if a symptomatic cyst is managed medically. Some authorities recommend complete surgical resection of symptomatic DDC,[7,19,45,46] whereas others recommend therapeutic endoscopy to establish free drainage.[6,46-48] Surgical extirpation entails higher morbidity, and appreciable mortality as compared with endoscopic therapy, but eliminates the risk of malignant cyst degeneration.[6,7] Pancreaticoduodenectomy is sometimes necessary intraoperatively if the DDC is too close to the pancreaticobiliary ducts.[7] Less invasive, surgical techniques, including partial cyst resection, internal derivation,[19] and marsupialization,[4] have become obsolete.

Systematic Literature Review of Therapeutic EGD

Systematic literature review revealed 28 reported cases of endoscopic therapy (Table 1     ,[3,8,45-63] number of case reports per publication = 1.3 ± 1.2). Endoscopic therapy is increasingly reported recently: 3 cases reported from 1984 to 1999, versus 25 cases reported from 2000 to 2015 (P = 0.003, OR = 8.33, 95%-CI: 1.77–44.5, Fisher exact test). Among 26 patients in whom the sex was reported, 14 (54%) were men. The mean patient age = 32.2 ± 18.3 years old. Procedure indications included: acute pancreatitis-16 (first episode-10, recurrent-6), abdominal pain-8, jaundice-2, upper GI obstruction-1, and asymptomatic cyst-1 (Table 1     ). Two patients had two simultaneous clinical syndromes: including one patient presenting with acute pancreatitis and chronic GI blood loss (patient-4[48]), and one patient presenting with obstructive jaundice and RUQ abdominal pain (patient-25[61]). Only 1 patient had chronic GI blood loss attributed to DDC (patient-4[48]). The rarity of this presentation is likely because DDC are uncommonly inflammatory, invasive, or malignant. Patients typically presented with symptoms, signs, and laboratory abnormalities suggestive of the presenting syndrome (e.g., acute pancreatitis), but without clinical features suggesting that the underlying cause was DDC. DDC was, however, generally diagnosed by radiologic imaging, including EUS, CT, ERCP, or MRCP. The mean maximal diameter of the reported DDC = 3.20 ± 1.53 cm.

TABLE 1

Clinical Presentation and Endoscopic Therapy for Duodenal Duplication Cysts: Comprehensive Review of 28 Cases Reported in the Literature with Patient Outcomes

Systematic literature review demonstrates that endoscopic treatment is safe and effective, avoiding the morbidity associated with laparotomy[57]. Endosonographic therapeutic techniques included cyst puncture via needle knife papillotomy (NKP) or papilotome-18, snare resection of cyst-7, cystotome-2, and cyst needle aspiration and ligation-1. Endosonographic therapy was successful in all 28 prior cases (Table 1     ). Only 2 complications (7.1%) were reported. Both complications were relatively mild: GI bleeding, related to NKP, that were easily managed without any permanent clinical sequelae by dilute subcutaneous epinephrine injection and placement of a cyst catheter for drainage that was removed after 48 hour (patient-17[54]), or by leaving a cyst drain for 3 days for tamponade and monitoring the bleeding (patient-19[56]). All patients remained asymptomatic during variable follow-up. Among 25 patients in whom the length of follow-up was reported, all were asymptomatic during mean follow-up of 35.1 ± 48.1 months. Three other patients were reported as asymptomatic at follow-up, but follow-up duration was not reported (patients 23,24,27[59-61]). One patient who had presented with an asymptomatic DDC remained asymptomatic for 3 years after endoscopic therapy (patient 29[63]). These data suggest that endoscopic therapy may be durable without symptomatic recurrences. Table 3 summarizes the key findings of this comprehensive review of endosonographic therapy for DDC.

TABLE 1 (Continued)

Clinical Presentation and Endoscopic Therapy for Duodenal Duplication Cysts: Comprehensive Review of 28 Cases Reported in the Literature with Patient Outcomes

Advantages of endoscopic therapy include no visible abdominal scars, decreased post-operative pain, and shorter hospitalization.[45] Surgery is necessary if a symptomatic cyst cannot be approached endoscopically.[4] Before therapeutic endosonography, the patient should be advised of a potential need for traditional surgery if therapeutic endoscopy fails.[45]

Comprehensive review of 93 gastric duplication cysts reported in the literature revealed 7 cases treated endoscopically. In all these cases the endsocopic therapy was successful without complications (Table 2   A).[9,64-69] Comprehensive review of 80 esophageal duplication cysts reported in the literature revealed 7 cases treated endoscopically. In all these 7 cases the endoscopic therapy was successful (Table 2Table 2   B).[70-75] Two minor endoscopic complications occurred: minor esophageal mucosal laceration without GI bleeding in 1, and minor infection at the cyst incision site successfully treated by irrigation and cyst opening extension at repeat EGD in 1. The number of gastric or esophageal duplication cysts treated endoscopically is relatively small. However, these literature reviews on gastric or esophageal duplication cysts further support the efficacy and safety of therapeutic endoscopy for upper gastrointestinal duplication cysts.

TABLE 1 (Continued)

Clinical Presentation and Endoscopic Therapy for Duodenal Duplication Cysts: Comprehensive Review of 28 Cases Reported in the Literature with Patient Outcomes

DISCUSSION

The currently reported patient was unusual in that the DDC was 14 cm long, more than twice as long as the previously reported longest DDC of 6.5 cm, and that the DDC caused GI obstruction by compressing the duodenal lumen, as demonstrated by abdominal CT and EGD. Only 1 previously reported patient treated endoscopically had presented with GI obstruction (patient-27: gastric outlet obstruction[62]). However, two children treated surgically had presented with gastric outlet obstruction from compression by pyloroduodenal duplication cysts.[76,77]

This current case illustrates that even an extremely long DDC can be adequately drained by therapeutic endosonography, without recurrence at least during 1 month of follow-up, and that adequate DDC decompression can reverse nausea, vomiting, and weight loss from the DDC. The key requirement is adequate DDC drainage and decompression to relieve extrinsic compression of the duodenal lumen causing the severe vomiting. The currently reported patient also had acute pancreatitis, likely from pancreatic ductular hypertension from the DDC. The key findings in the currently reported DDC are compared with those in the previously reported DDCs in Table 3.

Keratinized cysts are lined by keratinized squamous mucosa and tend to have thicker and more viscous fluid within individual cysts than non-keratinized cysts. DDC are generally non-keratinized because they are lined by columnar epithelium and tend to have thinner and less viscous fluid within the cyst. The currently reported cyst was non-keratinized histologically and the cyst fluid was thin and, therefore, relatively easy to aspirate.

The current case report adds to the literature by reporting endoscopic intubation and visualization of the DDC with random mucosal endoscopic biopsies. We speculate that this endoscopic maneuver might prove helpful to exclude potential malignancy or dysplasia in a DDC, which would preclude endoscopic therapy.

Limitations of this review include incorporation of retrospectively reported case reports, potential reporting bias in that successful therapeutic endoscopy might have been preferentially reported, variable follow-up, and review of only 29 reported cases of DDC. Review strengths include performance of a systematic literature review; use of tandem, independent, investigators for the literature search with subsequent reconciliation of references to minimize omissions or biases; relatively long mean follow-up of 35.1 months in 25 cases; and illustration of endosonographic therapy to successfully reverse severely symptomatic duodenal compression from one extremely long DDC.

TABLE 1 (Continued)

Clinical Presentation and Endoscopic Therapy for Duodenal Duplication Cysts: Comprehensive Review of 28 Cases Reported in the Literature with Patient Outcomes

TABLE 1 (Continued)

Clinical Presentation and Endoscopic Therapy for Duodenal Duplication Cysts: Comprehensive Review of 28 Cases Reported in the Literature with Patient Outcomes

TABLE 1 (Continued)

Clinical Presentation and Endoscopic Therapy for Duodenal Duplication Cysts: Comprehensive Review of 28 Cases Reported in the Literature with Patient Outcomes

TABLE 2

Clinical Presentation, Endoscopic Therapy, and Patient Outcomes for Gastric or Esophageal Duplication Cysts: Comprehensive Review of the Literature

TABLE 2 (Continued)

Clinical Presentation, Endoscopic Therapy, and Patient Outcomes for Gastric or Esophageal Duplication Cysts: Comprehensive Review of the Literature

TABLE 2 (Continued)

Clinical Presentation, Endoscopic Therapy, and Patient Outcomes for Gastric or Esophageal Duplication Cysts: Comprehensive Review of the Literature

TABLE 2 (Continued)

Clinical Presentation, Endoscopic Therapy, and Patient Outcomes for Gastric or Esophageal Duplication Cysts: Comprehensive Review of the Literature

TABLE 3

Key Findings in Endoscopic Therapy of Duodenal Duplication Cysts: 28 Previously Reported Cases vs. Currently Reported Case