Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study.

BACKGROUND & AIMS: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. METHODS: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). RESULTS: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. CONCLUSIONS: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.

Gastric cancer detection rates using GI endoscopy with serologic risk stratification: a randomized controlled trial.

BACKGROUND AND AIMS: Efforts have been made to develop an endoscopic screening system incorporating serologic gastric cancer (GC) risk stratification (ABC classification) alongside annual population-based GC screening using barium. We conducted a randomized controlled trial (RCT) to compare GC detection rates between the Ba-Endo group, which underwent annual barium tests for primary screening followed by detailed endoscopic examinations, and the ABC-Endo group, where endoscopy intervals were determined based on individual gastric cancer risk in the ABC classification. METHODS: In total, 1206 individuals from Yurihonjo and Nikaho City, Akita Prefecture, were randomized through the minimization method using sex and age as allocation factors. The intervention study was conducted for both groups over 5 years. The Ba-Endo group received annual barium tests, and the ABC-Endo group underwent EGD at different intervals: group A, EGD only at entry; group B, EGD once every 3 years; group C, EGD once every 2 years; and group D, EGD every year. RESULTS: There were 24 detected GC lesions, with a GC detection rate of 1.9%. GC detection rates in the Ba-Endo and ABC-Endo groups were 2.0% and 1.8%, respectively, with no significant differences between groups (P = 1.0). However, the rate of GC cured by endoscopic resection alone was 41.6% in the Ba-Endo group and was significantly higher at 90.9% in the ABC-Endo group (P = .02). CONCLUSIONS: There were no differences between the Ba-Endo and ABC-Endo groups in GC detection rates. However, the rate of detected GCs that could be cured by endoscopic resection alone was significantly higher in the ABC-Endo group. (Clinical trial registration number: UMIN000005962.).

Sessile serrated lesion prevalence and factors associated with their detection: a post-hoc analysis of a multinational randomized controlled trial from Asia.

BACKGROUND: Sessile serrated lesions (SSLs) are associated with an increased risk of colorectal cancer. Data on the prevalence of SSLs in Asia are limited. We performed this study to estimate the prevalence of SSLs in Asia and to explore endoscopic factors that are associated with SSL detection. METHODS: This is a post-hoc analysis of a multicenter randomized controlled trial from four Asian countries/regions that compared adenoma detection rates using linked-color imaging (LCI) and white-light imaging. Colonoscopies were performed in an average-risk population for screening, diagnostic examination, or polyp surveillance. Patients with SSLs were compared against those without SSLs to evaluate for possible predictors of SSL detection using Firth's logistic regression. RESULTS: 2898 participants (mean age 64.5 years) were included in the analysis. The estimated prevalence of SSLs was 4.0% (95%CI 3.4%-4.8%), with no sex or age group differences. On multivariable analysis, use of LCI (adjusted odds ratio [aOR] 1.63, 95%CI 1.10-2.41), experienced endoscopists (aOR 1.94, 95%CI 1.25-3.00), use of transparent cap (aOR 1.75, 95%CI 1.09-2.81), and longer withdrawal time (aOR 1.06, 95%CI 1.03-1.10) were independently associated with SSL detection. Synchronous adenoma detection (aOR 1.89, 95%CI 1.20-2.99) was also predictive of SSL detection. CONCLUSION: The prevalence of SSLs in Asia is 4.0%. Use of LCI or a transparent cap, greater endoscopist experience, and longer withdrawal time were all associated with increased SSL detection.

Diagnostic performance of linked color imaging for gastric cancer by Helicobacter pylori infection status: A subanalysis of the large-scale, multicenter randomized controlled trial LCI-FIND.

BACKGROUND: Linked color imaging (LCI) is a new image enhancement technology that facilitates the recognition of subtle differences in mucosal color. In the large-scale, multicenter randomized controlled trial LCI-FIND, LCI demonstrated good diagnostic performance for the detection of tumor lesions in the upper gastrointestinal tract. The aim of the present study was to exploratively evaluate the diagnostic performance of LCI according to H. pylori infection status as a subanalysis of LCI-FIND trial. METHODS: The patients were randomly allocated to receive white light imaging (WLI) first, followed by LCI (WLI group), or vice versa (LCI group), and the two groups were compared for the detection of tumors. Data from this trial were analyzed by the presence/absence of H. pylori infection and further analyzed by successful or unsuccessful eradication in the H. pylori infection group. RESULTS: The 752 patients in the WLI group and 750 patients in the LCI group who had participated in the LCI-FIND trial were included. In the successful eradication group, more gastric lesions were detected by primary mode in the LCI group than in the WLI group, indicating that more lesions were missed by WLI. Fisher's exact probability test for the comparison of the WLI and LCI groups yielded a p-value of 0.0068, with missed gastric lesions being detected 0.136 times (95% confidence interval: 0.020-0.923), significantly less with LCI than with WLI. CONCLUSION: The current study suggests that LCI should be used for gastric cancer screening, particularly in patients with successful H. pylori eradication.

Randomized controlled trial comparing the costs of gastric cancer screening systems between serological risk-based upper gastrointestinal endoscopy and the existing barium photofluorography: gastric cancer screening labeled by serum examination in place of aged gastric cancer organized screening systems (GALAPAGOS study).

BACKGROUND: Although the risk of gastric cancer can be stratified according to Helicobacter pylori (H. pylori) IgG antibody titer and pepsinogen levels (ABC classification), a population-based gastric cancer screening system combining serological tests and endoscopy has not been introduced. This study aimed to compare the total testing cost per participant between the ABC classification method and the existing protocol. METHODS: Using the minimization method with sex and age as allocation factors, 1206 participants were randomly assigned to the following two methods for a 5-year intervention: barium photofluorography as primary examination followed by detailed examination with upper gastrointestinal endoscopy (Ba-Endo) and risk-based upper gastrointestinal endoscopy by ABC classification (ABC-Endo). The primary endpoint was the total testing cost per participant over a 5-year period. The secondary endpoint was the expense required to detect one gastric cancer. RESULTS: The total testing cost per participant was 39,711 yen in Ba-Endo (604 participants) and 45,227 yen in ABC-Endo (602 participants), with the latter being significantly higher (p < 0.001). During the intervention period, gastric cancer was found in 11 and eight participants in Ba-Endo and ABC-Endo, respectively. The expenses required to detect one gastric cancer were 2,240,931 yen in Ba-Endo and 3,486,662 yen in ABC-Endo. CONCLUSIONS: The testing cost per participant turned out to be higher in the ABC-Endo group than in the Ba-Endo group. This superiority trial, based on the hypothesis that the cost of testing is lower for ABC-Endo than for Ba-Endo, was rejected.

Linked color imaging improves colorectal lesion detection especially for low performance endoscopists: An international trial in Asia.

BACKGROUND AND AIM: Linked color imaging (LCI) is an image-enhanced endoscopy technique that accentuates the color difference between red and white, potentially improving the adenoma detection rate (ADR). However, it remains unclear whether LCI performance in detecting colorectal lesions differs based on endoscopists' experience levels. We aimed to evaluate the differences in LCI efficacy based on the experience levels of endoscopists by conducting an exploratory analysis. METHODS: In this post hoc analysis of an international randomized controlled trial comparing the detection of adenoma and other lesions using colonoscopy with LCI and high-definition white light imaging (WLI), we included patients from 11 institutions across four countries/regions: Japan, Thailand, Taiwan, and Singapore. We retrospectively reviewed differences in the lesion detection of LCI according to endoscopists' colonoscopy history or ADR. RESULTS: We included 1692 and 1138 patients who underwent colonoscopies performed by 54 experts (experience of ≥ 5000 colonoscopies) and by 43 non-experts (experience of < 5000 colonoscopies), respectively. Both expert and non-expert groups showed a significant improvement in ADR with LCI compared to WLI (expert, 61.7% vs 46.4%; P < 0.001; non-expert, 56.6% vs 46.4%; P < 0.001). LCI had no effect on sessile serrated lesion detection rate in non-experts (3.1% vs 2.5%; P = 0.518). LCI significantly improved detection rates in endoscopists with relatively low detection performance, defined as an ADR < 50%. CONCLUSIONS: This exploratory study analyzed data from a previous trial and revealed that LCI is useful for both experts and non-experts and is even more beneficial for endoscopists with relatively low detection performance using WLI.

Analysis of the Characteristics of Coexisting Lesions in Colorectal Cancer Patients in an International Study: A Subgroup Analysis of the ATLAS Trial.

INTRODUCTION: We investigated coexisting lesion types in patients with invasive colorectal cancer (CRC) in a multinational study for comprehending the adenoma-carcinoma and serrated pathway about the development of CRC. METHODS: We retrospectively reviewed 3,050 patients enrolled in the international randomized controlled trial (ATLAS study) to evaluate the colorectal polyp detection performance of image-enhanced endoscopy in 11 institutions in four Asian countries/regions. In the current study, as a subgroup analysis of the ATLAS study, 92 CRC patients were extracted and compared to 2,958 patients without CRC to examine the effects of age, sex, and coexisting lesion types (high-grade adenoma [HGA], low-grade adenoma with villous component [LGAV], 10 adenomas, adenoma ≥10 mm, sessile serrated lesions [SSLs], and SSLs with dysplasia [SSLD]). Additional analyses of coexisting lesion types were performed according to sex and location of CRC (right- or left-sided). RESULTS: A multivariate analysis showed that HGA (odds ratio [95% confidence interval] 4.29 [2.16-8.18]; p < 0.01), LGAV (3.02 [1.16-7.83], p = 0.02), and age (1.04 [1.01-1.06], p = 0.01) were independently associated with CRC. According to sex, the coexisting lesion types significantly associated with CRC were LGAV (5.58 [1.94-16.0], p < 0.01) and HGA (4.46 [1.95-10.20], p < 0.01) in males and HGA (4.82 [1.47-15.80], p < 0.01) in females. Regarding the location of CRC, SSLD (21.9 [1.31-365.0], p = 0.03) was significant for right-sided CRC, and HGA (5.22 [2.39-11.4], p < 0.01) and LGAV (3.46 [1.13-10.6], p = 0.02) were significant for left-sided CRC. CONCLUSIONS: The significant coexisting lesions in CRC differed according to sex and location. These findings may contribute to comprehending the pathogenesis of CRC.

Clinical features and distribution of the APC variant in duodenal and ampullary polyps in patients with familial adenomatous polyposis: a multicenter retrospective cohort study in Japan.

BACKGROUND: Management of duodenal or ampullary adenomas in patients with familial adenomatous polyposis (FAP) is a major challenge for clinicians. Insufficient data are available to evaluate the clinical manifestations and distribution of adenomatous polyposis coli (APC) variants in these patients. METHODS: We enrolled 451 patients with data regarding duodenal or ampullary polyps from 632 patients with FAP retrospectively registered in a nationwide Japanese multicenter study. Clinicopathological features and distribution of APC variants were compared between patients with and without duodenal or ampullary polyps. RESULTS: Duodenal and ampullary polyps were found in 59% and 18% of patients with FAP, respectively. The incidence of duodenal cancer was 4.7% in patients with duodenal polyps, and that of ampullary cancer was 18% in patients with ampullary polyps. Duodenal polyps were significantly associated with the presence of ampullary polyps and jejunal/ileal polyps. Duodenal polyps progressed in 35% of patients with a median follow-up of 776 days, mostly in those with early Spigelman stage lesions. Ampullary polyps progressed in 50% of patients with a follow-up of 1484 days. However, only one patient developed a malignancy. The proportion of patients with duodenal polyps was significantly higher among those with intermediate- or profuse-type APC variants than attenuated-type APC variants. The presence of duodenal polyps was significantly associated with ampullary and jejunal/ileal polyps in patients with intermediate- or profuse-type APC variants. CONCLUSIONS: Periodic endoscopic surveillance of the papilla of Vater and small intestine should be planned for patients with FAP with duodenal polyps.

An Estimation Formula for Resonance Frequency Using Sex and Height for Healthy Individuals and Patients with Incurable Cancers.

Resonance frequency breathing is a technique that involves breathing that maximizes heart rate variability. It is specific to individuals and is determined through a procedure taking approximately 30 min, using a procedure that is often best carried out at specialized medical institutions. This is a physical and time-consuming burden because of hospital visits and measurements, particularly for patients with cancer. Therefore it would be beneficial if a procedure can be found to determine resonance frequency from the patient's physical characteristics, without the need for special assessment procedures. This exploratory cross-sectional study examined the correlation between individual characteristics and resonance frequency in healthy volunteers. Multiple regression analysis was performed with the measured resonance frequency as the target variable and individual characteristic parameters as explanatory variables. The study aims to build an estimation formula for resonance frequency with some of these parameters and assess its validity. In addition, the validity of the formula's applicability to patients with incurable cancers is assessed. A total of 122 healthy volunteers and 32 patients with incurable cancers were recruited as participants. The median resonance frequency of 154 participants was six breaths per min. Sex and height were selected as explanatory variables associated with the measured resonance frequency in the volunteers. The estimation formula for resonance frequency using individual characteristics was 17.90-0.07 × height for men and 15.88-0.06 × height for women. Adjusted R-squared values were 0.55 for men and 0.47 for women. When the measured resonance frequency in patients with incurable cancers was six breaths per minute or less, the resonance frequency estimated by this formula was slightly larger than the measured ones. Information on individual characteristics, such as sex and height, which can be easily obtained, was useful to construct an estimation formula for resonance frequency.

Nationwide epidemiological survey of polyarteritis nodosa in Japan in 2020.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that predominantly affects medium-sized arteries. With advances in our understanding of the pathogenesis and classification of vasculitis, PAN and microscopic polyangiitis (MPA), a disease of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), were separated from the group of diseases previously diagnosed as periarteritis nodosa (PN) at the Chapel Hill Consensus Conference (CHCC) in 1994 (1).

Association between continuous cessation or reduction of drinking alcohol and improvement of multiple dysplastic lesions in patients with esophageal squamous cell carcinoma after endoscopic resection.

BACKGROUND: Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated. METHODS: We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6 months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6 months. RESULTS: Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7-153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2-6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04-0.7, p = 0.009). CONCLUSIONS: This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development. CLINICAL TRIALS REGISTRY NUMBER: UMIN000001676.

Genotype-phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.

Linked-Color Imaging Detects More Colorectal Adenoma and Serrated Lesions: An International Randomized Controlled Trial.

BACKGROUND & AIMS: Effects of linked-color imaging (LCI) on colorectal lesion detection and colonoscopy quality remain controversial. This study compared the detection rates of adenoma and other precursor lesions using LCI vs white-light imaging (WLI) during screening, diagnostic, and surveillance colonoscopies. METHODS: This randomized controlled trial was performed at 11 institutions in 4 Asian countries/regions. Patients with abdominal symptoms, a primary screening colonoscopy, positive fecal immunochemical test results, or undergoing postpolypectomy surveillance were recruited and randomly assigned in a 1:1 ratio to either the LCI or high-definition WLI group. The primary outcome was adenoma detection rate (ADR). Secondary outcomes were polyp detection rate, advanced ADR, sessile serrated lesion (SSL) detection rate, and the mean number of adenomas per colonoscopy. The recommended surveillance schedule distribution after trial colonoscopy was analyzed. RESULTS: Between November 2020 and January 2022, there were 3050 participants (LCI, n = 1527; WLI, n = 1523) recruited. The LCI group ADR was significantly higher than the WLI group ADR using intention-to-treat (58.7% vs 46.7%; P < .01) and per-protocol analyses (59.6% vs 46.4%; P < .01). The LCI group polyp detection rates (68.6% vs 59.5%; P < .01), SSL detection rates (4.8% vs 2.8%; P < .01), and adenomas per colonoscopy (1.48 vs 1.02; P < .01) also were significantly higher. However, the advanced ADR was not significantly different (13.2% vs 11.0%; P = .06). Significantly more patients in the LCI group had shorter recommended surveillance schedules than the WLI group (P < .01). CONCLUSIONS: Compared with WLI, LCI improved adenoma and other polyp detection rates, including SSLs, resulting in alteration of the recommended surveillance schedule after screening, diagnostic, and postpolypectomy surveillance colonoscopies. TRIAL REGISTRATION NUMBER: UMIN000042432 (https://www.umin.ac.jp/ctr/index.htm).

Long-term Outcomes After Endoscopic Submucosal Dissection for Large Colorectal Epithelial Neoplasms: A Prospective, Multicenter, Cohort Trial From Japan.

BACKGROUND & AIMS: To determine the long-term outcomes after colorectal endoscopic submucosal dissection (ESD), we conducted a large, multicenter, prospective cohort trial with a 5-year observation period. METHODS: Between February 2013 and January 2015, we consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. Patients with noncurative resection (non-CR) lesions underwent additional radical surgery, as needed. After the initial treatment, intensive 5-year follow-up with planned multiple colonoscopies was conducted to identify metastatic and/or local recurrences. Primary outcomes were overall survival, disease-specific survival, and intestinal preservation rates. The rates of local recurrence and metachronous invasive cancer were evaluated as the secondary outcomes. RESULTS: The 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. Patients with CR lesions had no metastatic occurrence, and patients with non-CR lesions had 4 metastatic occurrences. Kaplan-Meier curves revealed that overall survival and disease-specific survival rates were significantly higher in patients with CR lesions than in those with non-CR lesions (P > .001 and P = .009, respectively). Local recurrence occurred in only 8 lesions (0.5%), which were successfully resected by subsequent endoscopic treatment. Multiple logistic regression analyses revealed that piecemeal resection (hazard ratio, 8.19; 95% CI, 1.47-45.7; P = .02) and margin-positive resection (hazard ratio, 8.06; 95% CI, 1.76-37.0; P = .007) were significant independent predictors of local recurrence after colorectal ESD. Fifteen metachronous invasive cancers (1.0%) were identified during surveillance colonoscopy, most of which required surgical resection. CONCLUSIONS: A favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000010136.

Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III): a multicenter prospective interventional study.

BACKGROUND: Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP. METHOD: A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period. RESULTS: 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %-5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %-94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %-92.4 %). CONCLUSION: IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed.

Efficacy and safety of intensive downstaging polypectomy (IDP) for multiple duodenal adenomas in patients with familial adenomatous polyposis: a prospective cohort study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) risk developing multiple duodenal adenomas (MDAs), leading to duodenal cancer and death. We investigated the efficacy and safety of intensive downstaging polypectomy (IDP) for MDAs integrated with new-generation procedures. METHODS: This prospective phase II study, conducted at a tertiary cancer center, enrolled patients with FAP who had MDAs. We performed IDP including cold snare/forceps polypectomy (CSP/CFP) and underwater endoscopic mucosal resection (UEMR). The primary end point was the downstaging of Spigelman stage at 1-year follow-up. RESULTS: 2424 duodenal polyps in 58 patients with FAP underwent IDP, including 2413 CSPs in 57 patients, seven CFPs in one patient, and four UEMRs in four patients. Only one major adverse event was observed (grade 3 hyperamylasemia) without clinical manifestations. We performed additional UEMR, CSP, and CFP for one, 12, and 22 patients, respectively, during initial follow-up. Overall, 55 patients completed protocol examination; the Spigelman stage was significantly reduced at the 1-year follow-up endoscopy (P < 0.001), with downstaging observed in 39 patients (71 %). Among the 26 patients with Spigelman stage IV at initial examination and protocol completion, 23 (88 %) showed downstaging. There was no major change in Spigelman stages from 1-year follow-up esophagogastroduodenoscopy to a median of 37 months (range 3-56). CONCLUSIONS: IDP, including new-generation procedures, showed significant downstaging with acceptable adverse events for MDA in patients with FAP, even those with advanced-stage disease. Lesion selection for different resection techniques may be important for suitable and sustainable management of MDA in patients with FAP.

Metachronous primary gastric cancer after endoscopic resection in patients with esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to evaluate the risk factors for developing metachronous primary Gastric Cancer (GC) after Endoscopic Resection (ER) for esophageal Squamous Cell Carcinoma (SCC). METHODS: We studied 283 patients with esophageal SCC who underwent ER. The study outcomes were as follows: (1) incidence of metachronous primary GC after ER; and (2) predictors for the development of metachronous primary GC after ER by the Cox proportional hazards model. RESULTS: The median follow-up was 43.1 months (1.81-79.1), and the 3-year cumulative incidence of metachronous primary GC was 6.5% (95%CI: 4.1-10.4). The incidence of metachronous primary GC during the follow-up period was 2.31 per 100 person-years. The frequencies of severe gastric atrophy and macrocytosis at the timing of ER were significantly higher in patients with than without metachronous primary GC (91.7% vs. 73.2%, p = 0.0422, 20.8% vs. 5.2%, p = 0.0046, respectively). Severe gastric atrophy was associated with the development of metachronous primary GC (sex-and-age adjusted hazard ratio (HR) [95%CI] = 4.12 [0.95-27.78], p = 0.0093). Macrocytosis was associated with the development of metachronous primary GC (sex-and-age adjusted HR = 4.76 [1.75-13.0], p = 0.0012) and found to be an independent predictor for metachronous primary GC by multivariate Cox proportional hazards analysis (HR [95%CI] = 4.35 [1.60-11.84], p = 0.004). CONCLUSIONS: Severe gastric atrophy and macrocytosis should be noted in the development of metachronous primary GC after ER for esophageal SCC. In particular, macrocytosis at the timing of ER was considered an important predictor. CLINICAL TRIALS REGISTRY NUMBER: UMIN000001676.

Linked color imaging provides enhanced visibility with a high color difference in upper gastrointestinal neoplasms.

BACKGROUND AND AIM: The aim of this post-hoc analysis in a randomized, controlled, multicenter trial was to evaluate the visibility of upper gastrointestinal (UGI) neoplasms detected using linked color imaging (LCI) compared with those detected using white light imaging (WLI). METHODS: The visibility of the detected UGI neoplasm images obtained using both WLI and LCI was subjectively reviewed, and the median color difference (ΔE) between each lesion and the surrounding mucosa according to the CIE L*a*b* color space was evaluated objectively. Multivariate logistic regression analysis was performed to identify factors associated with neoplasms that were missed under WLI and detected under LCI. RESULTS: A total of 120 neoplasms, including 10, 32, and 78 neoplasms in the pharynx, esophagus, and stomach, respectively, were analyzed in this study. LCI enhanced the visibility 80.9% and 93.6% of neoplasms in pharynx/esophagus and stomach compared with WLI, respectively. LCI also achieved a higher ΔE of enhanced neoplasms compared with WLI in the pharynx/esophagus and stomach. The median WLI ΔE values for gastric neoplasms missed under WLI and later detected under LCI were significantly lower than those for gastric neoplasms detected under WLI (8.2 vs 9.6, respectively). Furthermore, low levels of WLI ΔE (odds ratio [OR], 7.215) and high levels of LCI ΔE (OR, 22.202) were significantly associated with gastric neoplasms missed under WLI and later detected under LCI. CONCLUSION: Color differences were independently associated with missing gastric neoplasms under WLI, suggesting that LCI has an obvious advantage over WLI in enhancing neoplastic visibility.

Risk factors for the development of second primary esophageal squamous-cell carcinoma after endoscopic resection for esophageal squamous-cell carcinoma according to genetic polymorphisms related to alcohol and nicotine metabolism.

BACKGROUND: Multiple development of esophageal squamous-cell carcinoma is explained by field cancerization and is associated with alcohol consumption and smoking. We investigated the association between the development of second primary esophageal squamous-cell carcinoma after endoscopic resection for esophageal squamous-cell carcinoma and genetic polymorphisms related to alcohol and nicotine metabolism. METHODS: The study group comprised 56 patients with esophageal squamous-cell carcinoma after endoscopic resection. The main variables were the following: (i) cumulative incidence and total number of second primary esophageal squamous-cell carcinoma according to genetic polymorphisms in alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and cytochrome P450 2A6; and (ii) risk factors of second primary esophageal squamous-cell carcinoma identified using a multivariate Cox proportional-hazards model. The frequencies of alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and cytochrome P450 2A6 genetic polymorphisms in the buccal mucosa were analyzed. RESULTS: The median follow-up was 92.8 months (range: 2.7-134.2). Slow-metabolizing alcohol dehydrogenase 1B was associated with a higher 7-year cumulative incidence of second primary esophageal squamous-cell carcinoma (fast-metabolizing alcohol dehydrogenase 1B vs slow-metabolizing alcohol dehydrogenase 1B: 20.5% vs 71.4%, P = 0.006). Slow-metabolizing alcohol dehydrogenase 1B (relative risk [95% confidence interval]: 3.17 [1.49-6.73]), inactive aldehyde dehydrogenase 2 (2.17 [1.01-4.63]) and poorly-metabolizing cytochrome P450 2A6 (4.63 [1.74-12.33]) had a significantly higher total number of second primary esophageal squamous-cell carcinoma per 100 person-years. In the multivariate Cox proportional-hazards model, slow-metabolizing alcohol dehydrogenase 1B was a significant risk factor of the development of second primary esophageal squamous-cell carcinoma (hazard ratio 9.92, 95% confidence interval: 2.35-41.98, P = 0.0018). CONCLUSIONS: Slow-metabolizing alcohol dehydrogenase 1B may be a significant risk factor for the development of second primary esophageal squamous-cell carcinoma. In addition, inactive aldehyde dehydrogenase 2 and poorly-metabolizing cytochrome P450 2A6 may be important factors.

Clinical Guidelines for Diagnosis and Management of Peutz-Jeghers Syndrome in Children and Adults.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. SUMMARY: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. KEY MESSAGES: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.