Treatment outcomes of endoscopic submucosal dissection and surgery for colorectal neoplasms in patients with ulcerative colitis.

OBJECTIVES: This study aimed to clarify the validity and long-term outcomes of colorectal endoscopic submucosal dissection (ESD) of visible lesions (≥20 mm) in patients with ulcerative colitis (UC) and investigate the incidence of undetected lesions in surgical specimens. METHODS: This single-center retrospective study included 11 lesions from nine patients with UC who underwent ESD and 19 lesions from nine patients with UC who underwent colectomy between March 2001 and January 2019. We evaluated the endoscopic findings of scarring, atrophy, and loss of haustra in the ESD group, and we determined the lesion visibility in the colectomy group. We investigated the clinicopathological features of all lesions and examined the follow-up evaluations in the ESD group. RESULTS: The en bloc and curative resection rates of ESDs were 91% and 82%, respectively. Endoscopic findings of scarring, atrophic colitis, and loss of haustra were observed in two (18%), seven (64%), and one (9%) lesions, respectively. The two lesions with scarring showed severe submucosal fibrosis. Mortality and recurrence were not observed during the median follow-up of 25 months. Metachronous lesions ≥20 mm were detected in two patients, which were successfully treated with ESDs. In the colectomy specimens, 21% of the lesions were undetected, 67% had multiple neoplasms, and 33% had multiple invasive cancers. CONCLUSIONS: ESD is feasible and valid for large visible lesions in patients with UC; however, for lesions with endoscopic findings of scarring, technical difficulties in endoscopic resection must be considered. In addition, intensive surveillance colonoscopy is necessary to detect undetected lesions.

Endoscopic characteristics influencing postpolypectomy bleeding in 1147 consecutive pedunculated colonic polyps: a multicenter retrospective study.

BACKGROUND AND AIMS: Postpolypectomy bleeding is the most common adverse event with pedunculated polyps. We clarified the endoscopic characteristics influencing postpolypectomy bleeding for pedunculated colonic polyps. METHODS: We reviewed clinical data for 1147 pedunculated colonic polyps removed by polypectomy in 5 Japanese institutions. Pedunculated polyps were defined as polyps with a stalk length ≥5 mm. Analyzed clinical data were age, sex, polyp location/size, stalk length/width, prophylactic clipping or endoloop before polypectomy, injecting the stalk, closing the polypectomy site, antithrombotic agent use, and endoscopist experience. Postpolypectomy bleeding was classified as immediate bleeding or delayed bleeding. RESULTS: Immediate and delayed bleeding was observed in 8.5% (97/1147) and 2% (23/1147) of polypectomies, respectively. Comparing immediate bleeding with nonbleeding, multivariate analysis showed that stalk width ≥6 mm (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.4) was a significant risk factor for immediate bleeding. For polyp size ≥15 mm, prophylactic endoloop use (OR, .17; 95% CI, .04-.72) was a significant inhibiting factor. Comparing delayed bleeding with nonbleeding, multivariate analysis showed that prophylactic clipping before polypectomy (OR, 4.2; 95% CI, 1.3-13) and injecting the stalk (OR, 4.0; 95% CI, 1.4-12) were significant risk factors for delayed bleeding. CONCLUSIONS: The increased risk for delayed bleeding with injecting the stalk and prophylactic clipping before polypectomy suggests that simple resection with coagulation mode is a suitable strategy in endoscopic resection of pedunculated polyps. Moreover, prophylactic endoloop use was highly likely to inhibit immediate bleeding with polyp size ≥15 mm.

Efficacy of Full-Spectrum Endoscopy to Visualize the Major Duodenal Papilla in Patients with Familial Adenomatous Polyposis.

BACKGROUND AND AIMS: Duodenal cancer is one of the extracolonic malignancies with known mortality in familial adenomatous polyposis (FAP) patients. Visualization of the major duodenal papilla (MDP) with a standard esophagogastroduodenoscopy (EGD) is currently insufficient because of the limited field of view. Full-spectrum endoscopy (FUSE), utilizing double imagers located on the front and side of the endoscopic tip, provides a wider field of view up to 245 degrees. The aim of this study was to evaluate the efficacy of FUSE in visualizing MDP in patients with FAP. METHODS: This study was a single-center retrospective study including 49 FAP patients undergoing surveillance at our institution. EGD was performed by qualified endoscopists using FUSE, and visibility of the MDP was evaluated. All examinations were video-recorded, and the clips for individual patient were edited to forward view images alone (conventional group) and 2-view images of the duodenum (forward and side-view [FUSE group]). Three other qualified external endoscopists independently reviewed the videos and compared the visibility of MDP between the conventional and the FUSE groups. Primary endpoint was the rate of Type 1 visibility (whole area of the papilla) in off-site video reviews. We also assessed MDP visibility on-site as secondary endpoint. RESULTS: The rate of type 1 MDP visibility was significantly higher in the FUSE group than conventional group in both on-site (32.6/100%, p < 0.001) and off-site reviews (8.2, 16.3, 14.3/100, 98, and 100%, p < 0.001). CONCLUSIONS: FUSE is recommended in screening and surveillance EGD to better visualize MDP in FAP patients.

Early tumor shrinkage as a predictor of favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX.

There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in pancreatic cancer. We therefore investigated whether the ETS will predict outcomes in 59 patients with advanced pancreatic cancer treated with FOLFIRINOX therapy. The association of ETS with progression-free survival (PFS) and overall survival (OS) was evaluated but also we addressed to the correlation between outcomes and DpR. ETS was defined as a reduction ≥ 20% of target lesions' diameters measured at 6 to 8 weeks from treatment start. DpR was percentage of maximal tumor shrinkage observed at the nadir diameter compared with baseline. Among 47 evaluable patients for the ETS, 12 (25.5%) patients experienced ETS. The ETS was significantly associated with better PFS (9.0 vs. 4.2 months) as well as OS (24.0 vs. 9.1 months); moreover, the association had a statistically significance for PFS but a strong trend for OS in multivariate analysis. The DpR was statistically significantly but weakly associated with OS. In conclusion, this is the first report that the early response to chemotherapy may predict favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX therapy.

Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

BACKGROUND: Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs). METHODS: We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI]) and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48 non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10 small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance. RESULTS: S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs) (P<0.001). By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P<0.007). We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P<0.005). Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05). PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41). CONCLUSION: We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.

A new index of abdominal obesity which effectively predicts risk of colon tumor development in female Japanese.

BACKGROUND: A relation between abdominal obesity and colorectal tumor development has been reported repeatedly, and is believed to be more remarkable in man than in women. However, the details vary depending on scientific reports. This may be due at least partly to the selected surface anthropometric index in addition to the influence of gender and ethnic groups. To cope with this, we considered a new index of abdominal obesity and evaluated its risk prediction potential. MATERIALS AND METHODS: Six hundred ninety five Japanese (262 women and 433 men) who had a colonoscopy were studied. The new index was named as waist circumference to height index (WHI) and was calculated by the formula of waist circumference (cm)/height (m)/height (m). Biochemical and lifestyle factors were investigated preceding the colonoscopy. Statistical analysis was performed using SPSS for Windows. RESULTS: Increase of WHI was associated with altered metabolism of carbohydrate and lipid in both women and men. WHI was positively related with the development of colon tumor of women, while not with that of men. Logistic regression analysis performed for stratified age groups (45-54, 55-64 and 65-74 years) showed that WHI significantly increased odds ratio to 1.31 (CI 1.05-1.64 p=0.01) in women of 55-65 years. In contrast, in men this index WHI reduced the odds ratio insignificantly, while low density lipoprotein and triglyceride significantly increased the odds ratio to 1.01 (CI 1.00-1.03 p=0.02) in the 55-65 year group and to 1.02 (CI 1.00-1.03 p=0.02) in the 45-55 year group. CONCLUSIONS: In Japanese the risk factors for colon tumor development are different between women and men. WHI is a simple and efficient predictor of colon tumor risk in Japanese women and may be used to select those who should have colonoscopy.

Molecular features of colorectal polyps presenting Kudo's type II mucosal crypt pattern: are they based on the same mechanism of tumorigenesis?

BACKGROUND AND STUDY AIMS: The molecular features of serrated polyps (SPs) with hyperplastic crypt pattern, also called Kudo's type II observed by chromoendoscopy, were evaluated. METHODS: The clinicopathological and molecular features of 114 SPs with a hyperplastic pit pattern detected under chromoendoscopy (five dysplastic SPs, 63 sessile serrated adenoma/polyps (SSA/Ps), 36 microvesicular hyperplastic polyps (MVHPs), and 10 goblet cell-rich hyperplastic polyps (GCHPs)) were examined. The frequency of KRAS and BRAF mutations and CpG island methylator phenotype (CIMP) were investigated. RESULTS: Dysplastic SPs and SSA/Ps were frequently located in the proximal colon compared to others (SSA/Ps vs. MVHPs or GCHPs, P < 0.0001). No significant difference was found in the frequency of BRAF mutation among SPs apart from GCHP (60 % for dysplastic SPs, 44 % for SSA/Ps, 47 % for MVHPs, and 0 % for GCHPs). The frequency of CIMP was higher in dysplastic SPs or SSA/Ps than in MVHPs or GCHPs (60 % for dysplastic SPs, 56 % for SSA/Ps, 32 % for MVHPs, and 10 % for GCHPs) (SSA/Ps vs. GCHP, P = 0.0068). When serrated neoplasias (SNs) and MVHPs were classified into proximal and distal lesions, the frequency of CIMP was significantly higher in the proximal compared to the distal SNs (64 % vs. 11 %, P = 0.0032). Finally, multivariate analysis showed that proximal location and BRAF mutation were significantly associated with an increased risk of CIMP. CONCLUSIONS: Distinct molecular features were observed between proximal and distal SPs with hyperplastic crypt pattern. Proximal MVHPs may develop more frequently through SSA/Ps to CIMP cancers than distal MVHPs.