Colorectal Epithelial Neoplasia Research Articles

"Underwater" endoscopic submucosal dissection: a novel method for resection in saline with a bipolar needle knife for colorectal epithelial neoplasia.

Despite improvements in therapeutic strategy and instrumentation in colorectal endoscopic submucosal dissection (ESD), adverse events sometimes occur. Further advancements in available techniques are required to improve procedural success rates and safety. We developed a novel method for ESD in saline, referred to as "underwater" ESD (UESD). UESD involves using a bipolar needle knife and aims to enable complete resection while minimizing thermal damage to the muscle layer. In this study, we evaluated the safety and efficacy of this new technique. This was a retrospective study using data from two referral centers and included 40 lesions diagnosed as colorectal epithelial neoplasia (> 20mm in diameter or with severe fibrosis) and treated with UESD between December 2015 and March 2017. The main outcome measures were technical success rate, incidence of adverse events, and feasibility of histologic evaluation of the resected specimens. All 40 lesions, including those with submucosal fibrosis, underwent successful en bloc resection using the UESD technique. No procedural adverse events including perforation, delayed bleeding, and electrocoagulation syndrome were observed, and all patients had an uneventful clinical course associated with UESD. In all cases, UESD provided a resected specimen adequate for histological evaluation, without unwarranted burn effect to the tissues. Our UESD technique was safe and effective for complete resection of colorectal epithelial neoplasia.

Recurrence rate of lateral margin-positive cases after en bloc endoscopic submucosal dissection of colorectal neoplasia.

We aimed to evaluate the recurrence rate of colorectal neoplasia showing histologic lateral margin involvement after en bloc endoscopic submucosal dissection (ESD). We reviewed 527 colorectal lesions that were removed by en bloc ESD from 2005 to 2013 and followed by endoscopy. Based on the postprocedural pathologic reports, the lesions were categorized as follows: lesions with clear deep and positive lateral margins (n = 63) and lesions with R0 resection (n = 299). The tumor size was 45.7 ± 21.1mm in the lateral margin-positive group and 30.6 ± 15.1 in the R0 group (P < 0.001). Procedure time was longer in the lateral margin-positive group than in the R0 group (94.3 ± 75.1 vs. 54.1 ± 48.9min; P <0.001). Lateral margin positivity was associated with ESD time ≥ 120min in the multivariate analysis. Compared with 0-I morphology, LST-G was significantly associated with the lateral margin positivity. The volume of ESD experience in endoscopists may also be associated with the lateral margin positivity. Histologic reassessment of the specimen suggested that 32.2% of lateral margin-positive cases based on the initial pathology report were false-positive lateral margin involvement. The 5-year cumulative recurrence rate was 0.6% in the R0 group and 5% in the margin-positive group (P = 0.198). The local recurrence rate was not higher in lateral margin-positive cases than in R0 resection cases if the colorectal epithelial neoplasia was removed in an en bloc manner using ESD. Meticulous pathologic interpretation may reduce unnecessarily frequent surveillance after en bloc ESD.

The nature of the white opaque substance within colorectal neoplastic epithelium as visualized by magnifying endoscopy with narrow-band imaging.

Background and study aims: We previously reported our discovery of a white opaque substance (WOS) that is opaque to endoscopic light inside the epithelium while using magnifying endoscopy (ME) to examine gastric epithelial neoplasia. Histopathologic analysis revealed that the WOS comprises minute lipid droplets (LDs) accumulated within the neoplastic epithelium. In addition, the WOS was found in colorectal epithelial neoplasia, although it was unclear whether this WOS corresponded to an accumulation of LDs, as in the stomach. Therefore, the aim of the current study was to elucidate whether the WOS observed in colorectal epithelial tumors comprises LDs. Patients and methods: A consecutive series of 40 WOS-positive and 40 WOS-negative colorectal epithelial tumors was analyzed. One biopsy specimen was taken from each neoplasm. Cryostat sections were stained with oil red O for LD, and sections after formalin-fixation for LD were immunostained with anti-adipophilin antibody. Results: The prevalence of LDs stained with oil red O in WOS-positive vs. WOS-negative lesions was 47.5 % (19/40) vs. 5 % (2/40), respectively (P < 0.001). Furthermore, the WOS coincided with the expression of adipophilin; the prevalence of LDs stained by anti-adipophilin antibody in WOS-positive vs. WOS-negative lesions was 100 % (40/40) vs. 62.5 % (25/40), respectively (P < 0.001). Conclusions: This study elucidated for the first time that endoscopically visualized WOS in colorectal epithelial neoplasia may be composed of LDs accumulated in the neoplastic epithelium.

Endoscopic submucosal dissection vs laparoscopic colorectal resection for early colorectal epithelial neoplasia.

To compare the short term outcome of endoscopic submucosal dissection (ESD) with that of laparoscopic colorectal resection (LC) for the treatment of early colorectal epithelial neoplasms that are not amenable to conventional endoscopic removal. This was a retrospective cohort study. The clinical data of all consecutive patients who underwent ESD for endoscopically assessed benign lesions that were larger than 2 cm in diameter from 2009 to 2013 were collected. These patients were compared with a cohort of controls who underwent LC from 2005 to 2013. Lesions that were proven to be malignant by initial endoscopic biopsies were excluded. Mid and lower rectal lesions were not included because total mesorectal excision, which bears a more complicated postoperative course, is not indicated for lesions without histological proof of malignancy. Both ESD and LC were performed by the same surgical unit with a standardized technique. The patients were managed according to a standard protocol, and they were closely monitored for complications after the procedures. All hospital records were reviewed, and the following data were compared between the ESD and LC groups: patient demographics, size and location of the lesions, procedure time, short-term clinical outcomes and pathology results. From 2005 to 2013, 65 patients who underwent ESD and 55 patients who underwent LC were included in this study. The two groups were similar in terms of sex (P = 0.41) and American Society of Anesthesiologist class (P = 0.58), although patients in the ESD group were slightly older (68.6 ± 9.4 vs 64.6 ± 9.9, P = 0.03). ESD could be accomplished with a shorter procedure time (113 ± 66 min vs 153 ± 43 min, P < 0.01) for lesions of comparable size (3.0 ± 1.2 cm vs 3.4 ± 1.4 cm, P = 0.22) and location (colon/rectum: 59/6 vs colon/rectum: 52/3, P = 0.43). ESD appeared to be associated with a lower short-term complication rate, but the difference did not reach statistical significance (10.8% vs 23.6%, P = 0.06). In the LC arm, a total of 22 complications occurred in 13 patients. A total of 7 complications occurred in the ESD arm, including 5 perforations and 2 episodes of bleeding. All perforations were observed during the procedure and were successfully managed by endoscopic clipping without emergency surgical intervention. Patients in the ESD arm had a faster recovery than patients in the LC arm, which included shorter time to resume normal diet (2 d vs 4 d, P = 0.01) and a shorter hospital stay (3 d vs 6 d, P < 0.01). ESD showed better short-term clinical outcomes in this study. Further prospective randomized studies will be required to evaluate the efficacy and superiority of colorectal ESD over LC.

Expression of podoplanin/D2-40 in pericryptal stromal cells in superficial colorectal epithelial neoplasia

The aim of this study is to investigate the distribution and roles of podoplanin/D2-40-positive pericryptal stromal cells in superficial colorectal epithelial neoplasia. A total of 105 superficial colorectal epithelial tumors were examined: 65 tubular/tubulovillous adenomas, 32 adenocarcinomas in situ, and 8 submucosally invasive adenocarcinomas. Immunohistochemical analysis was performed using the monoclonal antibody to podoplanin/clone D2-40, which is reactive in both lymphatic endothelial cells and activated stromal cells, but negative in vascular endothelial cells. We found 50 (78%) of 65 tubular/tubulovillous adenomas, 30 (94%) of 32 adenocarcinomas in situ, and all 8 (100%) submucosally invasive adenocarcinomas had podoplanin/D2-40-positive pericryptal stromal cells, whereas all normal colorectal mucosae had no podoplanin/D2-40-positive pericryptal stromal cells. The presence of podoplanin/D2-40-positive pericryptal stromal cells is associated with epithelial tumorigenesis in the colorectum.

P99. Preliminary accuracy and interobserver agreement among surgeons for the diagnosis of colorectal epithelial neoplasia, following video tutorial on pattern recognition in probe-based confocal laser endomicroscopy

P99. Preliminary accuracy and interobserver agreement among surgeons for the diagnosis of colorectal epithelial neoplasia, following video tutorial on pattern recognition in probe-based confocal laser endomicroscopy

Long-term outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms

Endoscopic submucosal dissection (ESD) provides a high en bloc resection rate with less invasiveness than surgical resection for large or scarring gastrointestinal neoplasms. However, detailed outcomes in colorectal ESD are still lacking. The aim of our study was to elucidate short- and long-term outcomes of colorectal ESD. 310 consecutive colorectal epithelial neoplasms (146 adenomas, 164 carcinomas), in 290 patients, which fulfilled our indication criteria and were treated with ESD between July 2000 and December 2008 were studied. ESD was done by three skilled endoscopists. As short-term outcomes, rates of en bloc resection, en bloc plus R0 resection, and major complications were analyzed. As long-term outcomes, disease-free and overall survival were assessed in 224 patients. Rates of en bloc resection and en bloc plus R0 resection were 90.3 % and 74.5 %, respectively. Eight patients underwent additional colectomy due to histopathologically proven possible node-positive cancer. Intraoperative perforations occurred with 14 lesions (4.5 %), which were treated successfully only by endoscopic clipping. Emergent surgery was needed for one case of postoperative perforation. Blood transfusion due to intraoperative massive bleeding was required in 1 case (0.3 %). Postoperative bleeding occurred with four lesions (1.3 %), and was endoscopically managed without blood transfusion. Local recurrence was detected in 4 lesions (4/202 patients, 2.0 %); resection had been piecemeal in all 4. During a median follow-up of 38.7 months (range 12.8 - 104.2), the 3- and 5-year overall/disease-specific survivals were 97.1/100 % and 95.3/100 %, respectively. Colorectal ESD showed favorable long-term outcomes. It may largely replace colectomy for node-negative colorectal epithelial neoplasia.

Fundic gland polyps (Elster's cysts) of the gastric mucosa. A marker for colorectal epithelial neoplasia?

The results of several retrospective studies allow us to conclude that the detection of fundic gland polyps (Elster's cysts) is associated with an increased incidence of colorectal tumors. In this survey, we present the results of a prospective study investigating such a possible relationship. A total of 144 patients were investigated, of whom 80 had fundic gland polyps of the gastric corpus mucosa. Sixty-four of these patients underwent a colonoscopy, whereas the other 64 patients belonged to a sex- and age-matched control group with no fundic gland polyps. In the group with known fundic gland polyps, colorectal neoplasias were found in 29 (45.3%) patients. Eight of these patients had (12.5%) adenocarcinomas, 3 (4.7%) had high-grade intraepithelial neoplasia, and 18 (28.1%) had tubular adenomas. In one patient, a synchronous carcinoma of the rectum and the colon was detected. In comparison, 6 patients of the control group (9.3%) developed tubular adenomas and 9 (14.1%) had hyperplastic polyps of the colonic and rectal mucosa. Our results suggest that it is necessary to conduct a careful diagnostic work-up of the colon in patients with gastric fundic gland polyps.

Can Paneth cell metaplasia in cecum indicate the presence of colorectal epithelial neoplasia?

The main purpose of the present study was to investigate the relationship between the incidence of Paneth cells in cecal mucosa and the incidence of colorectal epithelial neoplasias. Using endoscopic biopsy specimens, obtained from cecum of 375 subjects in cases of total colonoscopy, we examined the incidence of Paneth cells in the cecal mucosa. In the present study, Paneth cells were present in the human cecal mucosa (47.7%, 179/375 subjects) regardless of age. Paneth cells were found more frequently in the subjects with colorectal epithelial neoplasia (57.3%, 90/157 subjects) than in the subjects without colorectal epithelial neoplasia (40.8%, 89/218 subjects) (p<0.01, chi(2) test). Our results suggest that the incidence of Paneth cells in cecal mucosa indicate some changes in the environment with tumorigenesis of the colorectal region according to the function of Paneth cells, proposed by other investigators.

Expression of apoptosis-related antigen Le(Y) in superficial colorectal adenoma and adenocarcinoma

To investigate the characteristics of superficial type colorectal epithelial neoplasia (SN) (adenoma, SAd; adenocarcinoma, SCa; superficial-elevation type, E; superficial-depression type, D), the expression of Lewis y (Le(Y)), a marker of apoptosis, and the labeling index of proliferative cell nuclear antigen staining (PCNA-LI) in the intramucosal regions of 56 SN lesions were investigated. Expression of Le(Y) was observed in cytoplasm or cell membrane from the surface to deep within some tubules in SN lesions. Le(Y) was detected at higher rates in SCa lesions than in SAd lesions, in SCa lesions greater than 11 mm in diameter than in those less than 10 mm in diameter, in SCa-E lesions than in SCa-D lesions, in SCa lesions deeper than middle third of the submucosal layer, and was not related to size or macroscopical appearance of SAd lesions. PCNA-LI rate was higher in SCa lesions than in SAd lesions, in SCa lesions with carcinoma invasion to the submucosal layer than in SCa lesions with carcinoma invasion limited to the propria mucosa, and that of SAd lesions was inversely correlated with tumor size although that of SCa lesions was positively correlated with tumor size. There was a relationship between the high degree of expression of Le(Y) and PCNA-LI. In SCa lesions apoptosis and cell proliferation reflected that the enlargement and/or deeper invasion of carcinomatous tissue and in SAd lesions apoptosis had no relationship to tumor size although the cell proliferation inversely correlated with tumor size. This suggested that SCa-D lesions and the SCa-E with much higher proportions of apoptotic cells progressed to the ulcerative advanced cancer, and the size of many SAd lesions had a limit.

Use of Nucleolar Organizer Regions in the Histopathological Diagnosis of Colorectal Epithelial Neoplasia

The AgNOR technique, specific staining for nucleolar organizer regions, was applied to twenty-seven lesions (sixteen tubular adenomas with low grade atypia and eleven well-differentiated adenocarcinomas invading the submucosa) of colorectal epithelial neoplasia, to examine the possibility of its application to histopathological diagnosis. The mean AgNOR number per adenoma nucleus (2.62 +/- 0.16) was significantly higher (P less than 0.01) than that per carcinoma nucleus (2.28 +/- 0.25). The mean cross-sectional area and the maximum diameter of carcinoma AgNORs (1.91 +/- 0.20 micron2 and 1.89 +/- 0.09 micron, respectively) were significantly larger than those of adenoma (1.15 +/- 0.17 and 1.45 +/- 0.11, respectively). The result of the discriminant analysis using these two variants corresponded to the pathological diagnosis with an accuracy of 96.3% (26/27). We thus concluded the AgNOR technique to be one of use in the histopathological diagnosis of colorectal epithelial neoplasia.

Cellular localisation of C‐myc product in human colorectal epithelial neoplasia

Aberrant expression of c-myc has been implicated in the development of colorectal carcinomas. We have used monoclonal antibodies 6E10 and 9E10, raised against mid-sequence and C-terminal peptides of the c-myc protein, to study the distribution of myc protein in normal and diseased bowel at the light microscope and ultrastructural levels. Normal mucosa showed staining only of some nuclei in the proliferative zones of crypts. In adenomas, staining varied from predominantly nuclear to pancellular to focal or pancytoplasmic. Moderately well differentiated areas of carcinomas gave strong focal cytoplasmic staining, while in poorly differentiated tumours staining was pancytoplasmic. Electron microscopy with these antibodies detected myc protein associated with dense chromatin and, where cytoplasmic staining occurred, with polyribosomes. Tumours showed a reduced staining of nuclear pores compared with normal tissue. Comparison of staining patterns with 6E10 and 9E10 in normal tissue, adenomas, and tumours suggests that tumour progression is associated with an accumulation of cytoplasmic c-myc protein, perhaps resulting from alterations to the C-terminus which reduce the efficiency of nuclear targeting of the protein and thus disrupt the regulation of the cell cycle.