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Endoscopy 2013; 45(02): 127-132
DOI: 10.1055/s-0032-1326177
Review
© Georg Thieme Verlag KG Stuttgart · New York

Endoscopic resection in the duodenum: current limitations and future directions

M. J. Bourke
Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, Australia
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Corresponding author

M. J. Bourke
Suite 106a
151-155 Hawkesbury Road
Westmead
NSW 2145
Australia   
Fax: +61-2-96333958   

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Publikationsdatum:
30. Januar 2013 (online)

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Duodenal lesions that should be considered for endoscopic resection comprise a heterogeneous group of disorders. Most are adenomas, primarily located in the descending duodenum. In comparison to lesions of a similar size elsewhere in the gastrointestinal tract, the risk of major complications from endoscopic resection of duodenal lesions is magnified. The unique anatomical features of the duodenum are largely responsible for this, but despite this we continue to apply conventional endoscopic therapies when a more sophisticated approach is required. Many other important clinical questions in relation to duodenal adenomas remain unanswered. This review aims to identify the gaps in the knowledge base and therapeutic approach and propose some solutions and directions for future research.


 

Introduction

More than lesions at any other site in the gastrointestinal tract, those of the duodenum found at endoscopy comprise a diverse and heterogeneous group of disorders at varying risk of malignant transformation or symptomatic presentation. Most are premalignant adenomas, but other pathologies include benign mass lesions such as large Brunner’s gland hamartomas and submucosal lipomas. These may be subject to prolapse and present with vague obstructive symptoms or iron deficiency anemia secondary to surface ulceration. Submucosal lesions also occur and may be neuroendocrine tumors (e. g., carcinoids, gastrinomas, and gangliocytic paragangliomas, all mostly nonfunctioning) or gastrointestinal stromal tumors [1].

Most duodenal adenomas are sporadic and are found on the posterior or lateral walls of the second part of the duodenum, usually at or below the papilla. Whether this reflects the true anatomical distribution or a detection bias influenced by forward-viewing endoscopes, which poorly visualize the medial and sometimes the anterior wall of the tubular second part of duodenum, is unclear. The distribution of duodenal adenomas appears to be influenced by bile flow and its growth-promoting properties, although 10 % – 20 % of all duodenal adenomas are found in the duodenal cap or the junction of the first and second parts. Duodenal adenomas seem to follow a similar adenoma-to-carcinoma sequence to adenoma of the colon [2]. However, the risk for malignant transformation appears to be reduced in comparison to colonic adenoma, and the time course more prolonged. In addition, endoscopic resection is technically more challenging and is associated with a much greater incidence of complications than comparable pathologies of similar size in the colon, and hence the decision to intervene endoscopically must always be carefully weighed against the age and co-morbidity of the patient. In an older patient, particularly in the setting of substantial co-morbidity that is likely to increase the risk of complications – especially postprocedural bleeding (anticoagulation, chronic kidney disease, ischemic heart disease with obligate antiplatelet therapy) – and/or to diminish the physiological tolerance to such events, the time course to malignant transformation may not exceed the patient’s reasonable life expectancy.

Given the relative infrequency of sporadic duodenal adenomas and the absence of collaborative multicenter and multidisciplinary research, many important clinical and management questions remain unanswered. These include

  • the relationship between sporadic duodenal adenomas and colorectal neoplasia;

  • a clinically relevant morphological classification system;

  • optimal technique of endoscopic resection;

  • recognition, prevention, and management of postresection complications.


 

Relationship between sporadic duodenal adenomas and colorectal neoplasia

Sporadic duodenal adenomas are associated with colorectal neoplasia, which is variously reported with a relative risk of 2.5 – 7.8 times that of average-risk age-matched controls [3] [4]. Thus, all patients with sporadic duodenal adenomas should undergo colonoscopy at some point. Less clear is the association of sporadic duodenal adenomas in younger patients (< 50 years of age) with germline mutations predisposing to colorectal neoplasia, such as Lynch syndrome (hereditary nonpolyposis colorectal cancer) and the autosomal recessive MYH-associated polyposis (MAP) [5]. Amongst patients with MAP, approximately 20 % will have duodenal adenomas, and the lifetime risk of duodenal cancer is 4 % [6]. Thus, a thorough family history in terms of gastrointestinal and genitourinary malignancy is essential, although it may not be informative. All patients in this subgroup should be seen by a familial cancer service and considered for genetic testing.


 

A clinically relevant morphological classification system

Morphology is increasingly recognized as an important predictor of submucosal invasion and therapeutic outcomes in the endoscopic treatment of advanced mucosal neoplasia (AMN) of the colon [7] [8]. Here, the risk of submucosal invasion (SMI) appears to follow a clear hierarchy [9]. Large sessile colonic polyps and laterally spreading tumors (termed AMN) can be stratified by Paris classification and surface pattern (whether granular, G, or nongranular, NG). Flat (0 – ΙΙa) granular lesions are at very low risk of SMI (1 % – 2 %); if a large nodule (Is component) is present, the risk is intermediate (7 %); whilst nongranular lesions are at greatest risk (15 % – 20 %), especially if there is a depressed area (ΙΙa + c) (> 40 %) [7] [8]. In addition, nongranular lesions more frequently have significant submucosal fibrosis, making endoscopic resection more technically challenging.

Whilst some authors have attempted to classify duodenal adenomas in a similar fashion, this has not yet been shown to be clinically useful, probably because of a lack of sufficient statistical power in any one series and the relative infrequency of SMI [10] [11]. Still, it seems logical that some form of classification system will ultimately prove useful in planning therapy. Prospective multicenter studies from referral centers will be necessary to achieve this.


 

Optimal technique of endoscopic resection

Broadly speaking, the options for endoscopic resection are endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Whilst ESD has the appeal of potential en bloc R0 resection, in the duodenum it is associated with an unacceptable risk of perforation, in excess of 20 % [12]. As the risk of SMI is generally low, the benefits of ESD are marginal and it cannot be justified. An exception can be made for small to medium-sized (< 15 mm) encapsulated submucosal tumors (carcinoids, etc.) where careful staging, including prior endoscopic ultrasound, has excluded muscularis propria involvement or regional disease. These may be safely “shelled out” with ESD by an expert endoscopist, particularly if they are located in the duodenal cap ([Fig. 1]).

Zoom
Fig. 1 a A 12-mm submucosal carcinoid on the anterior wall of the first part of the duodenum. b Circumferential mucosal incision is performed first. c After submucosal injection, careful submucosal dissection is performed. d The lesion has been completely removed en bloc. Muscularis propria of the duodenal cap is visible within the mucosal defect. The patient was able to be discharged the following day.

EMR is familiar to most endoscopists. As a snare-based technique, it uses some form of pretreatment to separate the mucosa and submucosa from the muscularis propria. The options include:

  • Freehand snare resection after prior submucosal injection. As in the colon, this technique works well in the duodenum as the mucosa is relatively loosely attached to the underlying muscularis propria. Comparatively discrete elevations of the target lesion relative to the surrounding uninvolved mucosa can be achieved, particularly if colloidal solutions, which have proven technical advantages, are used [13].

  • Cap-assisted suck and cut. This technique was pioneered in the esophagus [14]. The predictable absence of discrete tissue elevation in this organ meant that a suction component was necessary to facilitate tissue capture. Cap-assisted suck and cut has been used for duodenal adenomas, but prospective data are limited [11] [15]. In the duodenum, less suction is used than when the technique is employed on the more resilient and muscular wall of the esophagus, but even here it is associated with a small but significant risk of perforation. There is insufficient data to confirm its safety in the duodenum.

  • Band mucosectomy. This is generally done without prior submucosal injection. Although it has been described in the duodenum, data are limited and the safety is questionable. The muscular esophagus is generally not entrapped by the band, but entrapment is likely to be a constant risk in the duodenum, with the exception of the duodenal cap.

Large prospective series reporting outcomes and comparing techniques of endoscopic resection for sporadic duodenal adenomas are lacking, and few have enrolled more than 40 subjects [10] [16]. Individual enthusiasts advocate different techniques, but in general the approach has been freehand snare resection after prior submucosal injection, following the well-established principles of colonic EMR. This conventional EMR method seems safe and effective for small to even moderately large lesions, but it is associated with a higher risk of complications, particularly immediate and postprocedural bleeding, compared with lesions of a similar size in other locations such as the colon [10] [15] [17] [18].

The thin-walled, richly vascularized, relatively fixed, retroperitoneal descending duodenum has several unique features that necessitate consideration of site-specific technical aspects before, during, and after endoscopic resection:

  1. The duodenal folds (valves of Kerckring or valvulae conniventes) are reduplications of the mucosal layer, separated by a thin invagination of submucosa. Lesion biopsy will often straddle folds, linking one side with the other, and is thus more likely to result in submucosal fibrosis than biopsy at other luminal sites, increasing the difficulty of subsequent endoscopic resection. If biopsies are necessary prior to endoscopic resection in flat lesions, the forceps should be oriented transversely with its long axis parallel to the folds and the tissue taken gently from between folds.

  2. The most medial aspect of the lesion must always be visualized and the relationship with the major and minor papilla established using a side-viewing instrument (duodenoscope) if necessary. If the lesion involves the major papilla, consideration will need to be given to performing endoscopic retrograde cholangiopancreatography (ERCP) and ampullectomy concurrently during endoscopic resection. If it is within 1 cm of the major papilla, prophylactic pancreatic stent placement should be considered to prevent postresection pancreatitis, which can be severe [10].

  3. The margins of flat lesions can be especially difficult to discern, possibly reflecting that duodenal adenomas generally have tubulovillous histology and normal duodenal mucosa is villiform. Where appropriate, chromoendoscopy with a nonabsorptive dye such as indigo carmine should be considered to avoid incomplete resection, and dye should be incorporated in the submucosal injectate.

  4. The choice of endoscope is crucial; more than one may be required for extensive pathology. For lesions on the anterior or medial walls, a side-viewing instrument is optimal as this gives the best en face access to the lesion, particularly when it is located within 5 cm of the major papilla. With more distal locations, the utility of the side viewer diminishes. For lesions on the posterior and lateral wall, a pediatric colonoscope is preferable. The 6-o’clock orientation of the working channel most closely duplicates the standard approach with colonoscopic polypectomy, and the general principles employed there apply in the duodenum. The longer insertion length is also advantageous for more distal locations and specimen retrieval.

  5. The duodenal folds ensure that 0 – IIa (flat) duodenal adenomas have a more varied topography than the morphological equivalent elsewhere in the gastrointestinal tract. Hence, great care is necessary to avoid entrapping muscularis propria during endoscopic resection. A large-volume injection of colloidal solution may assist by everting the pseudodepressed convolutions between the folds ([Fig. 2]). It is also helpful where possible to orient the snare in alignment with the folds, rather than the long axis, of the duodenum. With this approach, tissue capture is along the folds and not across them, which minimizes the risk of entrapment of muscularis propria if tissue elevation is suboptimal. Otherwise, endoscopic resection for duodenal adenomas should follow the systematic approach and technical principles which have proven to be safe and very effective for treating AMN of the colon [7] [9] [19].

  6. Every attempt should be made to completely resect the lesion in a single session without compromising safety. Residual islands of adenoma within areas of submucosal fibrosis encountered at follow-up procedures are very difficult to resect. Careful endoscopic follow-up is important as the recurrence/residual often grows across the scar. This is easily managed when the recurrence/residual is small, but is a significant challenge if it is extensive. We advocate an endoscopy with photodocumentation and biopsy of the scar at intervals of 4 – 6 months and 12 months.

  7. The advanced endoscopist should be aware that the duodenal cap is different to other duodenal sites. It has thicker mucosa, more like the stomach, so tissue transection with a snare requires greater energy and is substantially slower. Access to the proximal posterior and inferior walls can be a challenge and a side-viewing scope may be necessary.

Zoom
Fig. 2 a A 40-mm hemicircumferential nongranular laterally spreading tumor of the distal second part of the duodenum. The lesion has a characteristic white reticulated appearance on the surface consistent with partial obstruction of lacteals. b Closer assessment with narrowband imaging. c A submucosal injection with indigo carmine dye has been made in preparation for endoscopic resection. d Complete endoscopic resection has been achieved with clear margins. There are several small (< 0.3 mm) submucosal vessels within the mucosal defect, with a larger vessel in the foreground of the defect.

 

Recognition, prevention, and management of postresection complications

Major complications are a constant threat with advanced endoscopic resection in the duodenum, and the risks must always be carefully weighed against the benefits. If definitive therapy is deemed appropriate, endoscopic resection is generally the most attractive option, as surgery for neoplasia in the upper gastrointestinal tract even in high-volume centers carries a significant risk of perioperative mortality and long-term digestive morbidity due to disruption of the underlying physiology and anatomy [20] [21]. However, effective therapies to prevent endoscopic complications have not yet been developed. Wide-field endoscopic resection exposes numerous submucosal vessels, which may bleed during or after endoscopic resection ([Fig. 2], [Fig. 3]). Persistent bleeding points can be treated with coagulating forceps with low-voltage (or bipolar) current, but great care should be taken to avoid deep thermal injury or excessive coagulation ([Fig. 3 d]), which risks delayed perforation with disastrous consequences. Postprocedural bleeding is the main complication, occurring in up to 30 % [10] [15] [17] [22] [23], and is due to the extensive second-order arterial blood supply. Whilst it is possible to close small defects, which theoretically may decrease delayed bleeding, those at greatest risk (large hemicircumferential defects) cannot be effectively closed. In addition, as the descending duodenum is fixed, attempting to draw large areas of exposed muscularis propria together may tear this layer. Prophylactic endoscopic coagulation of visible vessels is possible, but the benefits are unproven in similar sites such as the colon [9] and, again, the risks of deep injury in the duodenum are substantial. Thus, other, novel approaches to bleeding after endoscopic resection need to be developed. It may be possible to incorporate a hemostatic agent in the submucosal injectate, or to apply an adherent hemostatic gel at the end of the procedure [24]. Ultimately it may be feasible to predict risk of post-endoscopic-resection bleeding based on the features of the post-EMR defect, and thus to stratify risk to improve outcomes.

Zoom
Fig. 3 a A 40-mm nongranular laterally spreading lesion on the posteromedial wall of the second part of the duodenum. b Several submucosal vessels and intraprocedural bleeding. c Submucosal injection strategically placed distally to elevate the lesion towards the endoscope d Persistent bleeding controlled with coagulating forceps. The bleeding vessel is gently tented away from the duodenal wall and low-voltage current is employed (soft coagulation). Once tissue desiccation occurs, tissue resistance rises rapidly and current flow ceases. In the thin-walled duodenum it is important to have a significant submucosal fluid cushion to act as a heat sink and minimize the risk of deep thermal injury. e Successful coagulation of the bleeding vessel. f The final mucosal resection defect is almost hemicircumferential. Numerous nonbleeding submucosal blood vessels are evident in the defect.

It is currently unknown which patients who present with postprocedural bleeding should be subjected to repeat endoscopy, as many will settle spontaneously after resuscitation. Reintervention carries significant risks. The acute iatrogenic cautery ulcer is not as resilient or perforation-resistant as a peptic ulcer, and the available hemostatic tools are not as effective or as safe in the duodenum as in other locations. At the Westmead Hospital (Sydney, Australia) we tend to reserve endoscopy for those who have ongoing or a second episode of bleeding. Angiographic embolization may also be considered in those with adequate renal function, particularly if bleeding is massive and endoscopically uncontrollable.

Perforation or muscularis propria injury predisposing to delayed perforation is a significant risk and, unlike in the colon [9], intraprocedural detection is not readily accomplished. Improved means of early detection and risk stratification are required. In addition, endoscopic clip closure is not as effective as in the colon because it is difficult to draw together the relatively fixed wall of the descending duodenum, which may be torn in the process. The over-the-scope clip may have an advantage here, particularly for larger defects, by incorporating extramural tissue in the defect closure [25]. In the event of a perforation, carbon dioxide insufflation is advantageous. This gas is absorbed 150 times faster than air, thus lessening the risk of tension pneumoperitoneum and, theoretically, also the degree of extramural contamination. It has been demonstrated to improve outcomes after advanced endoscopic resection in the colon, and its routine use for endoscopic resection in the duodenum seems logical [26].

In this issue of Endoscopy, three short retrospective reports in the Case Report/Series section confirm the observations made above. Matsumoto and co-workers report their ESD experience with 14 comparatively small lesions (mean size 13 mm) in 13 patients, where mean procedure time was 90 minutes and there were three perforations [27]. In a separate report from Korea, the duodenal ESD experience of high volume ESD experts (> 300 prior upper GI cases each) with 14 relatively small (mean size 17 mm) non-ampullary duodenal adenomas is described [28]. Again perforation was unacceptably high at 36 % (5 cases), 2 of which were delayed making endoscopic management essentially impossible. Ultimately 2 patients required surgery. The authors correctly acknowledge the stark contrast with ESD perforation risk at other luminal sites. This risk is approximately 2 and 5 % in the stomach and colon respectively and even so amongst this perforation subgroup the risk of surgical conversion is still low at less than 3 and 7 % respectively. Iatrogenic perforation is readily recognized in the stomach and colon and thus endoscopic closure can be performed and surgery avoided in the majority. This is not the case in the duodenum and this aspect greatly compounds the morbidity of the already elevated baseline risk. By contrast, Maruoka and co-workers report their experience with 26 lesions of overall slightly larger size removed by EMR. In keeping with other duodenal EMR reports, complications were infrequent and in this seriesno perforations were encountered [29]. ESD for duodenal adenomas, particularly beyond the first part, cannot be justified.


 

Summary

The last decade has seen dramatic and at times remarkable progress in advanced endoscopic resection throughout the gastrointestinal tract. Most superficial mucosal neoplasms, no matter how great the lateral extent, can now be removed with excellent safety and great efficacy. Real-time endoscopic histology is accurate, and complications can be detected early and mostly effectively managed endoscopically. Advanced endoscopic resection in the duodenum clearly lags behind. It is possible for expert endoscopists to remove very extensive, almost circumferential lesions ([Fig. 4], [Fig. 5]) in a high-volume tertiary setting, but many questions remain unanswered. Only by collaborative, prospective multicenter research, that acknowledges the unique anatomical features and challenges of the duodenum, will we overcome these significant gaps in the knowledge base over the next 10 years.

Zoom
Fig. 4 a  Large laterally spreading papillary adenoma. b The lateral components have been resected after submucosal injection and the papilla is now isolated and now ready for papillectomy. c Papillectomy has been performed and a 5-French pancreatic stent has been placed to prevent pancreatitis. d The final resection defect as seen from above occupies approximately two-thirds of the duodenal circumference. The patient had melena for 2 days, but reintervention was not required and the patient was able to be discharged on the 3 rd postprocedural day.
Zoom
Fig. 5a A Paris 0-IIa, almost completely circumferential nongranular laterally spreading tumor of the distal second part of the duodenum. b The lesion was removed with both side-viewing and forward-viewing instruments. Anterior and medial walls were removed by standard inject-and-resect technique using the side viewer. A pediatric colonoscope was used for the posterior and lateral walls. c The final mucosal resection defect has clean margins and is almost circumferential. Numerous submucosal vessels are evident in the mucosal defect. Prophylactic endoscopic coagulation was not applied as the benefits are unproven and the risk of deep injury with potential delayed perforation is significant. The patient had minor melena but no serious sequelae.

 

 

Competing interests: None


Corresponding author

M. J. Bourke
Suite 106a
151-155 Hawkesbury Road
Westmead
NSW 2145
Australia   
Fax: +61-2-96333958   


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Zoom
Fig. 1 a A 12-mm submucosal carcinoid on the anterior wall of the first part of the duodenum. b Circumferential mucosal incision is performed first. c After submucosal injection, careful submucosal dissection is performed. d The lesion has been completely removed en bloc. Muscularis propria of the duodenal cap is visible within the mucosal defect. The patient was able to be discharged the following day.
Zoom
Fig. 2 a A 40-mm hemicircumferential nongranular laterally spreading tumor of the distal second part of the duodenum. The lesion has a characteristic white reticulated appearance on the surface consistent with partial obstruction of lacteals. b Closer assessment with narrowband imaging. c A submucosal injection with indigo carmine dye has been made in preparation for endoscopic resection. d Complete endoscopic resection has been achieved with clear margins. There are several small (< 0.3 mm) submucosal vessels within the mucosal defect, with a larger vessel in the foreground of the defect.
Zoom
Fig. 3 a A 40-mm nongranular laterally spreading lesion on the posteromedial wall of the second part of the duodenum. b Several submucosal vessels and intraprocedural bleeding. c Submucosal injection strategically placed distally to elevate the lesion towards the endoscope d Persistent bleeding controlled with coagulating forceps. The bleeding vessel is gently tented away from the duodenal wall and low-voltage current is employed (soft coagulation). Once tissue desiccation occurs, tissue resistance rises rapidly and current flow ceases. In the thin-walled duodenum it is important to have a significant submucosal fluid cushion to act as a heat sink and minimize the risk of deep thermal injury. e Successful coagulation of the bleeding vessel. f The final mucosal resection defect is almost hemicircumferential. Numerous nonbleeding submucosal blood vessels are evident in the defect.
Zoom
Fig. 4 a  Large laterally spreading papillary adenoma. b The lateral components have been resected after submucosal injection and the papilla is now isolated and now ready for papillectomy. c Papillectomy has been performed and a 5-French pancreatic stent has been placed to prevent pancreatitis. d The final resection defect as seen from above occupies approximately two-thirds of the duodenal circumference. The patient had melena for 2 days, but reintervention was not required and the patient was able to be discharged on the 3 rd postprocedural day.
Zoom
Fig. 5a A Paris 0-IIa, almost completely circumferential nongranular laterally spreading tumor of the distal second part of the duodenum. b The lesion was removed with both side-viewing and forward-viewing instruments. Anterior and medial walls were removed by standard inject-and-resect technique using the side viewer. A pediatric colonoscope was used for the posterior and lateral walls. c The final mucosal resection defect has clean margins and is almost circumferential. Numerous submucosal vessels are evident in the mucosal defect. Prophylactic endoscopic coagulation was not applied as the benefits are unproven and the risk of deep injury with potential delayed perforation is significant. The patient had minor melena but no serious sequelae.