Gastric Cancer Screening in First-Degree Relatives: A Pilot Study in a Diverse Integrated Healthcare System.

INTRODUCTION: Family history of gastric cancer has been shown as an independent risk factor of gastric cancer development and is associated with increased risk of progression to gastric cancer among patients with gastric intestinal metaplasia (GIM). METHODS: Between 2017 and 2020, we conducted a prospective pilot screening program of patients with a confirmed first-degree relative with gastric cancer to evaluate the feasibility of screening and prevalence of precursor lesions (e.g., GIM or dysplasia) on biopsy. RESULTS: A total of 61 patients completed screening by upper endoscopy with a mapping biopsy protocol: 27 (44%) were found to have GIM and 4 (7%) were found with low-grade dysplasia. DISCUSSION: Our pilot screening program identified a high prevalence of precursor lesions for gastric cancer among asymptomatic patients with a first-degree relative with gastric cancer. Careful endoscopic inspection and standardized biopsy protocols may aid in prompt identification of these precursor lesions in those at risk of gastric cancer.

Endoscopic full-thickness resection of polyps involving the appendiceal orifice: a multicenter international experience.

BACKGROUND: Endoscopic resection of lesions involving the appendiceal orifice remains a challenge. We aimed to report outcomes with the full-thickness resection device (FTRD) for the resection of appendiceal lesions and identify factors associated with the occurrence of appendicitis. METHODS: This was a retrospective study at 18 tertiary-care centers (USA 12, Canada 1, Europe 5) between November 2016 and August 2020. Consecutive patients who underwent resection of an appendiceal orifice lesion using the FTRD were included. The primary outcome was the rate of R0 resection in neoplastic lesions, defined as negative lateral and deep margins on post-resection histologic evaluation. Secondary outcomes included the rates of: technical success (en bloc resection), clinical success (technical success without need for further surgical intervention), post-resection appendicitis, and polyp recurrence. RESULTS: 66 patients (32 women; mean age 64) underwent resection of colonic lesions involving the appendiceal orifice (mean [standard deviation] size, 14.5 (6.2) mm), with 40 (61 %) being deep, extending into the appendiceal lumen. Technical success was achieved in 59/66 patients (89 %), of which, 56 were found to be neoplastic lesions on post-resection pathology. Clinical success was achieved in 53/66 (80 %). R0 resection was achieved in 52/56 (93 %). Of the 58 patients in whom EFTR was completed who had no prior history of appendectomy, appendicitis was reported in 10 (17 %), with six (60 %) requiring surgical appendectomy. Follow-up colonoscopy was completed in 41 patients, with evidence of recurrence in five (12 %). CONCLUSIONS: The FTRD is a promising non-surgical alternative for resecting appendiceal lesions, but appendicitis occurs in 1/6 cases.

Long-term follow-up of branch-duct intraductal papillary mucinous neoplasms with No change in first 5 Years of diagnosis.

BACKGROUND: Discontinuation of branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) surveillance after 5 years of no change remains controversial. Long-term outcomes of BD-IPMN without significant changes in the first 5 years were evaluated. METHODS: We performed a multi-center retrospective analysis of patients with BD-IPMN diagnosis from 2005 to 2011 (follow-up until 2017). Significant changes were defined as pancreatic cancer (PC), pancreatectomy, high-risk stigmata (HRS), worrisome features (WF) and worrisome EUS features (WEUS). RESULTS: Of 982 patients who had no significant changes, 5 (0.5%), 7 (0.7%), 99 (10.1%), 4 (0.4%) patients developed PC, HRS, WF, WEUS, respectively, post-5 years. PC and HRS/WF/WEUS incidences at 12 years were 1.0% and 29.0%, respectively. Patients that developed HRS/WF/WEUS had larger cyst size in first 5 years compared to those that did not [16 (12-23) vs. 12 (9-17) mm, p = 0.0001], cyst size of >15 mm having higher cumulative incidence of HRS/WF/WEUS. PC mortality was 0.8%; all-cause mortality was 32%. Incidence of mortality due to PC was higher in HRS/WF/WEUS group, p < 0.0001. The mortality rate at 12 years for ACCI (age-adjusted Charlson Comorbidity Index) of ≤3, 4-6, and ≥7 were 3.5%, 19.9%, and 57.6% (p < 0.0001), respectively. CONCLUSIONS: Incidence of PC in patients with BD-IPMN without significant changes in first 5 years of diagnosis remains low at 1.0%. Incidence of HRS/WF/WEUS was higher at 29.0%. PC-related mortality was higher in HRS/WF/WEUS group. These risks should be weighed against patients' overall mortality (utilizing scoring systems such as ACCI) when making surveillance decision of BD-IPMN beyond 5 years.

The effect of prophylactic hemoclips on the risk of delayed post-endoscopic mucosal resection bleed for upper and lower gastrointestinal lesions: a retrospective cohort study.

BACKGROUND: Endoscopic mucosal resection (EMR) is a minimally invasive procedure used for the treatment of lesions in the gastrointestinal (GI) tract. There is increased usage of hemoclips during EMR for the prevention of delayed bleeding. This study aimed to evaluate the effect of hemoclips in the prevention of delayed bleeding after EMR of upper and lower GI tract lesions. METHOD: This is a retrospective cohort study using the Kaiser Permanente Southern California (KPSC) EMR registry. Lesions in upper and lower GI tracts that underwent EMR between January 2012 and December 2015 were analyzed. Rates of delayed bleeding were compared between the hemoclip and no-hemoclip groups. Analysis was stratified by upper GI and lower GI lesions. Lower GI group was further stratified by right and left colon. We examined the relationship between clip use and several clinically-relevant variables among the patients who exhibited delayed bleeding. Furthermore, we explored possible procedure-level and endoscopist-level characteristics that may be associated with clip usage. RESULTS: A total of 18 out of 657 lesions (2.7%) resulted in delayed bleeding: 7 (1.1%) in hemoclip group and 11 (1.7%) in no-hemoclip group (p = 0.204). There was no evidence that clip use moderated the effects of the lesion size (p = 0.954) or lesion location (p = 0.997) on the likelihood of delayed bleed. In the lower GI subgroup, clip application did not alter the effect of polyp location (right versus left colon) on the likelihood of delayed bleed (p = 0.951). Logistic regression analyses showed that the clip use did not modify the likelihood of delayed bleeding as related to the following variables: use of aspirin/NSAIDs/anti-coagulants/anti-platelets, pathologic diagnoses (including different types of colon polypoid lesions), ablation, piecemeal resection. The total number of clips used was 901 at a minimum additional cost of $173,893. CONCLUSION: Prophylactic hemoclip application did not reduce delayed post-EMR bleed for upper and lower GI lesions in this retrospective study performed in a large-scale community practice setting. Routine prophylactic hemoclip application during EMR may lead to significantly higher healthcare cost without a clear clinical benefit.

Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer.

BACKGROUND: The risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed in the 2012 international consensus guidelines ("Fukuoka criteria"). METHODS: Retrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest-Risk Group", LRG). RESULTS: After exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001). CONCLUSIONS: This study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with "high-risk stigmata" or "worrisome features" criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk.

Prediction of malignancy in cystic neoplasms of the pancreas: a population-based cohort study.

OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. The aims of this study were to determine the incidence of malignancy and develop an imaging-based system for prediction of malignancy in PCN. METHODS: We conducted a retrospective cohort study of patients ≥18 years of age with confirmed PCN from January 2005 to December 2010 in a community-based integrated care setting in Southern California. Patients with history of acute or chronic pancreatitis were excluded. Malignancy diagnosed within 3 months of cyst diagnosis was considered as pre-existing. Subsequent incidence of malignancy during surveillance was calculated based on person-time at risk. Age- and gender-adjusted standardized incidence ratio (SIR) was calculated with the non-cyst reference population. Recursive partitioning was used to develop a risk prediction model based on cyst imaging features. RESULTS: We identified 1,815 patients with confirmed PCN. A total of 53 (2.9%) of patients were diagnosed with cyst-related malignancy during the study period. The surveillance cohort consisted of 1,735 patients with median follow-up of 23.4 months. Incidence of malignancy was 0.4% per year during surveillance. The overall age- and gender-adjusted SIR for pancreatic malignancy was 35.0 (95% confidence level 26.6, 46.0). Using recursive partitioning, we stratified patients into low (<1%), intermediate (1-5%), and high (9-14%) risk of harboring malignant PCN based on four cross-sectional imaging features: size, pancreatic duct dilatation, septations with calcification as well as growth. Area under the receiver operator characteristic curve for the prediction model was 0.822 (training) and 0.808 (testing). CONCLUSIONS: Risk of pancreatic malignancy was lower than previous reports from surgical series but was still significantly higher than the reference population. A risk stratification system based on established imaging criteria may help guide future management decisions for patients with PCN.

Endoscopic excision of large colorectal polyps as a viable alternative to surgical resection.

OBJECTIVE: To determine the outcome of endoscopic excision of large colorectal polyps. DESIGN: Retrospective medical record review. SETTING: Kaiser Permanente, a large health care maintenance organization. PATIENTS: One hundred four consecutive patients with large colorectal lesions deemed not amenable to endoscopic resection at initial colonoscopy and referred for surgical resection. INTERVENTION: Endoscopic excision under intravenous sedation by 2 interventional endoscopists. MAIN OUTCOMES MEASURES: Endoscopic success (the ability to completely eradicate the original or recurrent lesion endoscopically at the index procedure or at reintervention), procedure-related complications, disease recurrence, endoscopic reintervention, and surgical intervention. RESULTS: We included 48 men (46%) and 56 women (54%) with a mean age of 67 (range, 29-92) years for analysis. Anatomic distribution of the lesions included the colon (68%) and rectum (32%). Thirty-nine patients (37%) had carcinoma. The median size of the lesions was 3.0 (range, 1-9) cm. The endoscopic success rate was 83% and was highest in patients with noncarcinoma histologic findings compared with carcinoma (P < .001). The morbidity rate was 7%, and all complications occurred in the ascending colon (P = .06). Endoscopic reintervention occurred in 25 of 92 patients (27%). Surgical intervention was undertaken in 14% of all patients. During a mean follow-up of 14 (median, 12) months, recurrent disease was noted in 10 of 86 patients (12%) and occurred more frequently in rectal lesions (P = .002). All recurrences were eradicated endoscopically. CONCLUSIONS: Endoscopic excision of large colorectal polyps is a viable alternative to surgical resection in a select group of patients and can be performed safely with a good success rate.

NSAID inhibition of RGM1 gastric monolayer wound re-epithelialization: comparison of selective Cox-2 versus non-selective Cox inhibitors.

Clinical studies indicate that specific cyclooxygenase-2 (Cox-2) inhibitors are less ulcerogenic than their non-selective predecessors (e.g. indomethacin). However, Cox-2 inhibitors may also interfere with ulcer healing. Re-epithelialization is a crucial factor in both gastrointestinal mucosal injury and ulcer healing. This study was aimed to compare the effects of selective Cox-2 inhibitor (NS398) versus non-selective Cox inhibitor (indomethacin) on basal and basic fibroblast growth factor (bFGF) - stimulated gastric wound re-epithelialization. In-vitro epithelial wounds were created in confluent monolayers of RGM1 rat gastric epithelial cells by a razor blade scrape. Following wounding there was a significant re-epithelialization by 24 hrs. Indomethacin (0.25 mM and 0.5 mM) significantly inhibited basal wound re-epithelialization in a dose dependent manner. In contrast, selective Cox-2 inhibitor NS398 did not inhibit the basal re-epithelialization process. Basic FGF treatment produced significant enhancement of wound re-epitheliazation at the various concentrations [10, 20, 30, 40, 50 and 70 ng/ml] studied. Both indomethacin and NS398 inhibited bFGF stimulated wound re-epithelialization, with indomethacin having a greater inhibitory effect. The extent of NS398 inhibition was limited to the bFGF-stimulated component, whereas indomethacin inhibition extended to both the bFGF-stimulated and the basal re-epithelialization components. These findings indicate that specific Cox-2 inhibitor (NS398) does not interfere with the basal re-epithelialization but significantly inhibits the bFGF - stimulated re-epithelialization, whereas indomethacin interferes with both the basal as well as the bFGF-stimulated wound re-epithelialization.