Novel Developments In Intestinal Endoscopy prof. Oliver Pech – Gastro Update Europe 2019, Budapest
1 Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
Most western studies on endoscopic resection of early esophageal malignancy are related to adenocarcinoma. Now a new French multicentre study with long-term follow-up of endoscopic resection of 148 squamous cell cancers was presnted, 54% treated with mucosal resection and 46% treated with submucosal dissection. Median lesion size was 20.5 mm; 38% were piece-meal resected; depth of cancerous infiltration was m1–2 in 64% and m3-sm in 36%; the procedure was complicated by bleeding in 2%, perforation in 2% and led to stricturing in 14%. During a median follow-up of 22 months (m), tumour recurrence was observed in 14.2%. Significant risk factors for recurrence, expressed as hazard ratios were: removal by mucosal resection (17); pT1m3-sm (3); need for additional chemoradiotherapy (7); non-curative resection (12). If at all possible piece-meal resection should be avoided and for larger lesions or suspicion for submucosal ingrowth, submucosal dissection is to be preferred. Radiofrequency ablation of early sqamous cancer has also been evaluated in 35 Chinese patients. Complete response was seen in 86%. Tumour recurrencies were observed in 20% but could all be treated with endoscopic resection. Meticulous examination of the resection specimens suggested that initial expansion of cancerous growth in the ductular epithelial lining of the submucosal glands, extending deeper than the muscularis mucosae and therefore not ablated, was the presumed cause of the cancerous recurrence.
Although, it is commonly known that longstanding achalasia is a risk factor for squamous cancer, little is known about the impact of 3 yearly (y) endoscopic screening with lugol staining as evaluated in a cohort of 230 patients followed for a median of 56 m after various treatments (pneumodilation, surgical myotomy, peroral endoscopic myotomy (POEM), proton pump inhibitors (PPI) etc.). Stasis of food or liquids was observed in 27% during one or more endoscopies. In approx. a quarter of the endoscopies reflux esophagitis, usually grade A and B, was detected. Low grade dysplasia was detected in 3% and evolved into cancer in 1.3%, resulting in an overall incidence rate of sqamous cancer of 63/100,000 person-years. The incidence rate of low grade dysplasia started rising after 20 y of achalasia symptoms and cancer after 30 y of symptoms. Stagnant decomposing food and fluid and bacterial overgrowth, leading to chronic mucosal injury and inflammation, are considered to contribute to the oncogenic process and should be the leading target of the various therapies.
Studies continue to be published regarding the therapy with resection and/or usually radiofrequency ablation of neoplastic columnar metaplastic (Barrett) mucosa, confirming studies mentioned in previous highlights. Controversies remain whether patients should be intensively surveilled in the absence of any dysplasia or whether asymptomatic patients should be treated with non-stop PPI antisecretory treatment. Whether there are prognostic phenotypes for esophageal adenocarcinoma was prospectively evaluated in a separate American and British cohort. Interestingly the overall survival in both cohorts was substantially better when intestinal metaplasia was present in the peritumoral mucosa compared to those where intestinal metaplasia was absent. Thus adenocarcinoma without intestinal metaplasia appeared to have a significantly worse outcome. A confounder in the concept of two different types of esophageal adenocarcinoma is the fact that it is almost impossible to rule out overgrowth of intestinal metaplasia by aggressive tumor expansion. All this reminds the ongoing controvesy regarding the requirement of intestinal metaplasia with goblet cells as a prerequisite for proper diagnosis of Barrett type columnar metaplasia.
Usually covered self-expanding metal stents are used for palliation of advanced esophageal carcinoma, largely to prevent cancerous ingrowth. The full covering however favors the risk of migration. Does it help to leave both ends of the stent uncovered? In a controlled Dutch trial, almost 100 patients were randomized to fully vs. partially covered stents. No differences were found between the two stent types regarding technical success and frequency of recurrent obstruction. Recurrent obstruction was more frequent for proximal cancers.
Benign strictures usually respond to bougie/balloon dilation therapy but some are truly recalcitrant and recurrent. Is temporary stenting with a biodegradable stent with chronic dilation while tissue remodeling occurs helpful in such patients with recurrent benign esophageal strictures? In a controlled multicenter trial, 66 patients with esophageal strictures, most often anastomotic strictures, with prior dilation up to at least 16 mm were randomized. During the first 3 m significantly less repeat endoscopic dilations were necessary in the biodegradable stent grou, but significance was no longer seen at 6 m. The median time to the first re-dilation was longer in the stent group (106 days (d)) vs. the control group (42 d). There were two perforations in the control group vs. five stent occlusions, two tracheoesophageal fistulas and one migration in the stent group. I am wondering what the proper indications (if any) are for biodegradable stenting and if radial incision with a needle-knife would not be a more attractive approach for anastomotic stricturing, realising however that no controlled comparative studies are available.
Bleeding in the upper gastrointestinal tract remains a challenge, particularly for recurrent bleeding of peptic ulcers. To find out whether over-the-scope (OTSC) clips are superior to standard therapy with clipping or coagulation, 66 patients were randomized in a multicenter study. Persistent bleeding or recurrent bleeding within 7 d was significantly lower in the OTSC group (15%) vs. the control group (58%). Ulcer type, Forrest type, Rockall score, anticoagulation and type of prior endoscopic therapy had no significant impact. OTSC clipping requires adequate anatomic targeting of the bleeding area which may occasionally be challenging; perhaps monopolar hemostatic forceps may be helpful in such circumstances. A consecutive cohort of 112 Turkish patients with bleeding gastroduodenal ulcers were randomized to treatment with monopalar hemostatic forceps with soft coagulation vs. hemoclipping. Hemostasis was obtained in resp. 98 vs. 80% with a median of three clips. Monopolar hemostatic forceps was successful in all clip failures (persistent or recurrent bleeding within 7 d). Hemostatic forceps were more effective than hemoclips independent from ulcer and bleeding type. Other studies have confirmed the usefulness of hemostatic forceps in the treatment of acute bleeding.
POEM has become the minimally invasive treatment of choice for achalasia in many centers. A well documented adverse consequence is the high frequency and often severe nature of reflux disease, sometimes insufficiently controlled with acid suppressant therapy. Surgical Heller-type myotomy is often combined with partial (Dor-type) fundoplication. Is a comparable combination possible by endoscopic means? This was attempted in a rather provocative proof of concept study by Inoue, the inventor of POEM. Distal to the myotomy, the proximal stomach was perforated, allowing endoscopic entry into the peritoneal cavity, positioning of a large endoloop over de fundus, anchoring the most distal and proximal part of the loop with clips and final closing the loop creating a partial fundoplication. There were no complications and the complication appeared endoscopically detectable in almost all patients 2 m later. Obviously many questions remain to be answered but such attempt is a nice illustration of the ongoing exploration of novel therapeutic possibilities.
Using the submucosal tunnel space to approach the muscle layer is not limited to the esophageal sphincter. A logical extension was to cut the obstructing gastric pyloric sphincter complex, called gastric peroral endoscopic myotomy to ameliorate refractory gastroparesis. A meta-analysis of seven studies, involving almost 200 such patients was presented. Clinical success was seen in 82% and the gastroparesis cardinal symptom index decreased significantly in parallel, with scintigraphic emptying studies. Obviously large controlled trials are required now to identify the subset of patients where this novel therapy would be most appropriate, also with long-term follow-up.
All endoscopists are aware of the difficulties in getting permanent optimal cleaning/desinfection of the endoscopic equipment. What is insufficiently realised is the risk of bacterial exposure of the face of the endoscopist during the procedure through exposure to blood and body fluids. Swabs of plastic face shields worn by the endosocpist or positioned on the suite wall were cultured before and after the procedure. The number of bacterial colony forming units was low before the endoscopy but rose substantially post-procedure in 46% of the face shields worn by the endoscopists and in 21% hanging on the suite wall. Unrecognized face exposure occurs 5.6× per 100 half-d endoscpic procedures and individuals standing up to six feet away from the patient may still be exposed at a rate of 3.4 per 100 half-d presence in the endoscopy suite. The authors of that study make a plea for routine face protection for the endoscopist and assisting staff. Uncleaned suite surfaces may aid in patient-to-patient transmission of pathogens.
A major drawback of endoscopic (mucosal) resection of usually large laterally spreading colonic adenomas is the high recurrence rate of up to 30%, especially after piece-meal resection, as discovered during surveillance after 3–6 m. Can thermal ablation of the resection margin reduce this high recurrence rate? This was investigated in a large multicenter controlled trial in Australia in laterally spreading lesions, more than 2 cm in diameter. Piece-meal resection was followed by snare tip soft coagulation of the entire resection margin (soft coag effect 4.80 watts). Surveillance endoscopy, performed at 5–6 and 18 m, included meticulous inspection of the scar with white light and narrow band imaging with biopsies of the scar center and margin and of any suspicious area. Close to 400 patients with over 400 lesions were included. Endoscopic recurrence was observed in approx. 7% in the ablation arm vs. approx. 21% in the control arm, and histologic recurrence in approx. 5 vs. 23%, resp. Endoscopic assessment had a sensitivity of approx. 92%, a specificity of approx. 97% and a negative predictive value of approx. 99% for correctly identifying recurrence at the post-resection scar. The value of ablation of the margins has now been confirmed in other studies. Even in studies evaluating the usefulness of cold snare resection, the advice is usually given to include a generous surrounding tissue margin to decrease the risk of local recurrence. A remaining challenge for endoscopists is the detection of deep submucosal cancerous invasion in polypoid lesions. Up to now, T1 colorectal polyps with one or more risk factors for lymph node metastasis are considered endoscopically unresectable. Can narrow band imaging (NBI) be helpful in identifying deep malignant invasion? A large multicenter prospective Spanish study explored the usefulness of NBI in over 1,600 patients with well over 200 polyps larger than 1 cm. Pointers for deep invasion were brown/dark brown discoloration with/without whiter patches; areas of disrupted/missing vessels; amorphous/absent surface pattern. Of the lesions 4.2% had features of deep invasion and 4.3% were considered endoscopically unresectable. The NBI based prediction of deep malignant infiltration had a sensitivity 58%, a specificity of 96% and a positive and negative predictive value of respectively 42 and 98%. Beyond a doubt such results are encouraging but there is still room for improvement. We live certainly in exciting times, now that experts are exploring removal of (well differentiated) rectal lesions extending up to the muscularis propria by dissecting the plane between the circular and longitudinal muscle. The endoscopic boundaries keep moving.
The Gastro Update Europe 2020 will be held on September 4–5, 2020 in Bratislava, Slovakia. For more information visit www.gastro-update-europe.eu.
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