Intensive endoscopic resection strategy for multiple duodenal polyposis associated with familial adenomatous polyposis.

BACKGROUND AND AIM: Multiple duodenal polyposis associated with familial adenomatous polyposis (FAP) is a high risk of duodenal cancer development. We evaluated the feasibility of intensive endoscopic resection that is a comprehensive treatment strategy combining multiple kinds of endoscopic treatments. METHODS: This is a retrospective observational study. From January 2012 to July 2022, a total of 28 consecutive patients in FAP who underwent endoscopic resection for multiple duodenal polyposis more than twice were included. Various endoscopic treatments, such as cold polypectomy (CP), endoscopic mucosal resection (EMR), underwater EMR (UEMR), endoscopic submucosal dissection (ESD), and endoscopic papillectomy (EP), were applied depending on lesions size and location. We evaluated individual information from patients' medical records, including patient characteristics, lesion characteristics, details of endoscopic treatment, pathologic findings, and Spigelman index (SI). We compared the differences in the number of treatments and observation periods with and without SI decrease. RESULTS: A total of 1040 lesions were removed by 138 sessions of endoscopic resections. The median follow-up period was 3.2 years. At the beginning of the endoscopic intervention, median SI was 9 (6-11) and the proportion of Spigelman stage (SS) IV was 61%. Repeated endoscopic treatments finally reduced SI in 26 patients (93%), and the proportion of SS IV significantly decreased to 13% with every endoscopic treatment. The mean SI change was -4.2 points per year (95% confidence interval: -0.6 to -5.9). There were no patients required surgical duodenectomy during the follow-up period. CONCLUSION: Intensive resection has a potential of downstaging duodenal lesions associated with FAP.

Nonampullary Duodenal Adenomas Rarely Recur after Complete Endoscopic Resection: A Swiss Experience Including a Literature Review.

INTRODUCTION: Duodenal polyps and especially duodenal adenomas are a rare and mostly coincidental finding in patients undergoing upper gastrointestinal endoscopy. Due to their malignant potential, duodenal adenomas should be removed upon diagnosis. So far, the limited available data on the performance of endoscopic polypectomy show conflicting results with regard to adverse events and the adenoma recurrence rate. PATIENTS AND METHODS: After summarizing the currently available data, we retrospectively analyzed all patients undergoing endoscopic resection of nonampullary duodenal adenomas (NAD) at our institution between 2006 and 2016. RESULTS: A total of 78 patients underwent endoscopic polypectomy for NAD adenoma. End-of-treatment success with complete resection requiring a mean of 1.2 interventions was achieved in 91% (n = 71). Procedural hemorrhage occurred in 12.8% (n = 10), whereas delayed bleeding was noted in 9% (n = 7). Duodenal perforation was registered and successfully treated in 2 cases (2.6%). No adenoma recurrence was noted following primary complete adenoma resection after a mean follow-up time of 33 months. Acute post-polypectomy bleeding was statistically significantly associated with large polyp size (p = 0.003) and lack of endoscopic prophylaxis (p = 0.0008). Delayed post-polypectomy bleeding showed a trend in the occurrence of large polyps (p = 0.064), and was statistically significantly associated with familial cancer syndrome (p = 0.019) and advanced histopathology (p = 0.013). CONCLUSION: Our data suggest that endoscopic polypectomy of NAD is well feasible with high success rates. Procedural and delayed hemorrhage seems to be the primary issue rather than adenoma recurrence. We therefore advocate referral of patients with large NAD to experienced centers for endoscopic resection.

Efficacy and safety of eflornithine (CPP-1X)/sulindac combination therapy versus each as monotherapy in patients with familial adenomatous polyposis (FAP): design and rationale of a randomized, double-blind, Phase III trial.

BACKGROUND: Molecular studies suggest inhibition of colorectal mucosal polyamines (PAs) may be a promising approach to prevent colorectal cancer (CRC). Inhibition of ornithine decarboxylase (ODC) using low-dose eflornithine (DFMO, CPP-1X), combined with maximal PA export using low-dose sulindac, results in greatly reduced levels of normal mucosal PAs. In a clinical trial, this combination (compared with placebo) reduced the 3-year incidence of subsequent high-risk adenomas by >90 %. Familial Adenomatous Polyposis (FAP) is characterized by marked up-regulation of ODC in normal intestinal epithelial and adenoma tissue, and therefore PA reduction might be a potential strategy to control progression of FAP-related intestinal polyposis. CPP FAP-310, a randomized, double-blind, Phase III trial was designed to examine the safety and efficacy of sulindac and DFMO (alone or in combination) for preventing a clinically relevant FAP-related progression event in individuals with FAP. METHODS: Eligible adults with FAP will be randomized to: CPP-1X 750 mg and sulindac 150 mg, CPP-1X placebo and sulindac 150 mg, or CPP-1X 750 mg and sulindac placebo once daily for 24 months. Patients will be stratified based on time-to-event prognosis into one of the three treatment arms: best (ie, longest time to first FAP-related event [rectal/pouch polyposis]), intermediate (duodenal polyposis) and worst (pre-colectomy). Stage-specific, "delayed time to" FAP-related events are the primary endpoints. Change in polyp burden (upper and/or lower intestine) is a key secondary endpoint. DISCUSSION: The trial is ongoing. As of February 1, 2016, 214 individuals have been screened; 138 eligible subjects have been randomized to three treatment groups at 15 North American sites and 6 European sites. By disease strata, 26, 80 and 32 patients are included for assessment of polyp burden in the rectum/pouch, duodenal polyposis and pre-colectomy groups, respectively. Median age is 40 years; 59 % are men. The most common reasons for screening failure include minimal polyp burden (n = 22), withdrawal of consent (n = 9) and extensive polyposis requiring immediate surgical intervention (n = 9). Enrollment is ongoing. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov ( NCT01483144 ; November 21, 2011) and the EU Clinical Trials Register( EudraCT 2012-000427-41 ; May 15, 2014).

Laboratory variation in the grading of dysplasia of duodenal adenomas in familial adenomatous polyposis patients.

To prevent duodenal and ampullary cancer in familial adenomatous polyposis (FAP) patients, a diagnosis of high grade dysplasia (HGD) plays an important role in the clinical management. Previous research showed that FAP patients are both over- and undertreated after a misdiagnosis of HGD, indicating unwarranted variation. We aimed to investigate the laboratory variation in dysplasia grading of duodenal adenomas and explore possible explanations for this variation. We included data from all Dutch pathology laboratories between 1991 and 2020 by retrieving histology reports from upper endoscopy specimens of FAP patients from the Dutch nationwide pathology databank (PALGA). Laboratory variation was investigated by comparing standardized proportions of HGD. To describe the degree of variation between the laboratories a factor score was calculated. A funnel plot was used to identify outliers. A total of 3050 specimens from 25 laboratories were included in the final analyses. The mean observed HGD proportion was 9.4%. The top three HGD-diagnosing laboratories diagnosed HGD 3.9 times more often than the lowest three laboratories, even after correcting for case-mix. No outliers were identified. Moderate laboratory variation was found in HGD diagnoses of duodenal tissue of FAP patients after adjusting for case-mix. Despite the fact that no outliers were observed, there may well be room for quality improvement. Concentration of these patients in expertise centers may decrease variation. To further reduce unwarranted variation, we recommend (inter)national guidelines to become more uniform in their recommendations regarding duodenal tissue sampling and consequences of HGD diagnoses.

Cold snare polypectomy for duodenal adenomas in familial adenomatous polyposis: a prospective international cohort study.

Background and study aims In patients with familial adenomatous polyposis (FAP), endoscopic resection of duodenal adenomas is commonly performed to prevent cancer and prevent or defer duodenal surgery. However, based on studies using different resection techniques, adverse events (AEs) of polypectomy in the duodenum can be significant. We hypothesized that cold snare polypectomy (CSP) is a safe technique for duodenal adenomas in FAP and evaluated its outcomes in our centers. Patients and methods We performed a prospective international cohort study including FAP patients who underwent CSP for one or more superficial non-ampullary duodenal adenomas of any size between 2020 and 2022. At that time, this technique was common practice in our centers for superficial duodenal adenomas. The primary outcome was the occurrence of intraprocedural and post-procedural AEs. Results In total, 133 CSPs were performed in 39 patients with FAP (1-18 per session). Median adenoma size was 10 mm (interquartile range 8-15 mm), ranging from 5 to 40 mm; 27 adenomas were ≥20 mm (20%). Of the 133 polypectomies, 109 (82%) were performed after submucosal injection. Sixty-one adenomas (46%) were resected en bloc and 72 (54%) piecemeal. Macroscopic radical resection was achieved for 129 polypectomies (97%). Deep mural injury type II occurred in three polyps (2%) with no delayed perforation after prophylactic clipping. There were no clinically significant bleeds, perforations or other post-procedural AEs. Histopathology showed low-grade dysplasia in all 133 adenomas. Conclusions CSP for (multiple) superficial non-ampullary duodenal adenomas in FAP seems feasible and safe. Long-term prospective research is needed to evaluate whether protocolized duodenal polypectomies prevent cancer and surgery.

Long-Term Outcomes of Pancreas-Sparing Duodenectomy for Duodenal Polyposis in Familial Adenomatous Polyposis Syndrome.

BACKGROUND: Pancreas-sparing duodenectomy (PSD) offers definitive therapy for duodenal polyposis associated with familial adenomatous polyposis (FAP). We reviewed the long-term complications of PSD and evaluated the incidence of high-grade dysplasia (HGD) and cancer in the remaining upper gastrointestinal tract. METHODS: Forty-seven FAP patients with duodenal polyposis undergoing PSD from 1992 to 2019 were reviewed. Long-term was defined as > 30 days from PSD. RESULTS: All patients were treated with an open technique, and 43 (91.5%) had Spigelman stage III or IV duodenal polyposis. Median follow-up was 107 months (IQR, 26-147). There was no 90-day mortality. Seven patients died at a median of 10.5 years (IQR, 5.4-13.3) after PSD, with one attributed to gastric cancer. Pancreatitis occurred in 10 patients (21.3%), and two required surgical intervention. Seven patients (14.9%) developed an incisional hernia, and all underwent definitive repair. Forty-one patients (87.2%) had postoperative surveillance endoscopy over a median follow-up of 111 months (IQR, 42-138). Three patients (6.4%) developed adenocarcinoma (two gastric, one jejunal), and four (8.5%) had adenomas with HGD (two gastric, two jejunal) with a median of 15 years (IQR, 9-16) from PSD. One patient with gastric adenocarcinoma and all patients with HGD or adenocarcinoma of the jejunum required surgical intervention. CONCLUSION: PSD can be performed with a low but definable risk of long-term morbidity. Risk of gastric and jejunal carcinoma rarely occurs and was diagnosed decades after PSD. This demonstrates the need for lifelong endoscopic surveillance and educates us on the risk of carcinoma in the remaining gastrointestinal tract.

Pancreas- and Pylorus-Preserving Duodenectomy for Advanced Familial Duodenal Polyposis.

Most patients with familial adenomatous polyposis (FAP) will develop duodenal polyps and 5% progress to cancer. Those with Spigelman stage IV have a 36% risk of cancer at 10 years. Endoscopic surveillance is necessary with local ablation for early disease. Unresectable duodenal disease and severe dysplasia are an indication for prophylactic radical surgery by pancreaticoduodenectomy or pancreas-sparing duodenectomy. Some preliminary results have shown better outcomes with duodenectomy. A 45-year-old female with FAP had restorative proctocolectomy at 24 years, desmoid of the mesentery with regression after sulindac, two pregnancies, and at the age of 37 years had duodenal polyposis stage III carpeting the periampullary region. Endoscopic papillectomy and extensive piecemeal mucosectomy was performed but was unsuccessful due to recurrence. After 7 years of regular endoscopic surveillance, focal high-grade dysplasia was diagnosed at the last evaluation. Some diminutive polyps were seen in the small-bowel capsule endoscopy. MRCP showed a normal biliary and pancreatic duct without visualization of the Santorini duct. A pancreas and pylorus-preserving duodenectomy was performed with 3 main steps: (1) duodenectomy with preservation of the pancreas and the pylorus; (2) reconstruction with an advanced jejunal limb and duodenojejunostomy; (3) reimplantation of the biliary and pancreatic duct in the jejunal loop. The patient was discharged on the 11th postoperative day without complications. In conclusion, pancreas- and pylorus-preserving duodenectomy is a promising alternative to pancreaticoduodenectomy for advanced duodenal polyposis that allows complete endoscopic surveillance.

A maioria dos doentes portadores de polipose adenomatosa familiar (FAP) vem a desenvolver pólipos duodenais que poderão degenerar em 5% dos casos. Os casos que apresentem um estádio IV de Spigelman têm um risco de degenerescência de 36% ao fim de 10 anos. É necessária vigilância endoscópica e excisão das lesões iniciais. Os pólipos considerados irressecáveis e com displasia de alto grau têm indicação para exérese cirúrgica radical através de duodenopancreatectomia ou de duodenectomia com conservação do pâncreas. Existem alguns resultados preliminares a revelar melhores resultados com a duodenectomia. Uma doente de 45 anos portadora de FAP efetuou proctocolectomia reconstrutiva aos 24 anos. Desenvolveu tumor desmoide mesentérico após um ano e que regrediu com sulindac, teve dois filhos e aos 37 anos apresentou polipose duodenal, em toalha periampular, com estádio III. Foi submetida a papilectomia endoscópica e mucosectomia fragmentada da lesão circundante tendose verificado recorrência. Durante 7 anos procedeu-se a vigilância endoscópica regular com presença de displasia de alto grau focal na última avaliação. Na cápsula endoscópica foram observados alguns pólipos diminutos no intestino delgado. A CPRM revelou normalidade nos canais pancreático e biliar, sem evidência do Santorini. Foi efetuada uma duodenectomia com conservação do pâncreas e do piloro cujos passos cirúrgicos principais foram: (a) duodenectomia com conservação do pâncreas e do piloro; (b) reconstrução com ansa jejunal e duodenojejunostomia; (c) reimplantação dos canais biliar e pancreático à ansa jejunal. A doente teve alta ao 11o dia pós-operatório sem complicaçõs. Em conclusão, a duodenectomia com conservação do pâncreas e do piloro constitui uma boa alternativa à duodenopancreatectomia permitindo vigilância endoscópica completa.

Pancreas-sparing total duodenectomy for Spigelman stage IV duodenal polyposis associated with familial adenomatous polyposis: experience of 10 cases at a single institution.

Duodenal cancer is a leading cause of death in patients with familial adenomatous polyposis (FAP). In patients with Spigelman's classification (SC) stage IV duodenal polyposis (DP), careful endoscopic surveillance by specialists or surgical intervention is mandatory. We herein report the surgical and pathological outcomes of FAP patients with SC stage duodenal polyposis undergoing pancreas-sparing total duodenectomy (PSTD), which has been rarely reported but seems optimal in such patients. PSTD and distal gastrectomy with Billroth-I type reconstruction in ten consecutive FAP patients with SC stage IV DP are reported. The median duration of surgery was 396 min (range 314-571 min) and the median estimated blood loss was 480 mL (range 100-975 mL). Significant postoperative complications included wound infection in 1 patient, pancreatic fistula [International Study Group on Pancreatic Fistula definition (ISGPF) grade B] in 4 patients. Histopathologic examinations revealed a well-differentiated carcinoma in situ in 3 patients and others were all adenomas. Over a median follow-up period of 15 months (range 9-29 months), 1 patient developed a stomal ulcer which improved with medical treatment. There were no patients with a body weight loss of ≥10 % relative to the preoperative body weight. No recurrence were experienced during the follow up period. Patients were free from postoperative diabetes mellitus. PSTD is a feasible and acceptable procedure in FAP patients with SC stage IV DP, in terms of surgical, pathological and clinical outcome. However, accumulation of the patients and long-term follow up study is necessary.