Long-term outcome of regional cooperation pathway after endoscopic submucosal dissection for early detection of new gastric cancer.

OBJECTIVES: The Cancer Control Act requires the maintenance of regional cooperation pathways (RCP) for cancer treatment. In 2008, we started RCP for early detection of new gastric cancer after endoscopic submucosal dissection (ESD). In gastric cancer treatment, RCP after surgical resection had been widely used, but little is known about RCP after ESD. This study aimed to evaluate the effectiveness of RCP after ESD. METHODS: This study included 465 patients on whom our RCP was implemented from 2008 to 2018. A regional family physician performed surveillance endoscopy at 3 months and 1 year after ESD and annually thereafter. We retrospectively evaluated the cumulative incidence and treatment outcomes of new gastric cancer and compared them with previous reports. RESULTS: During a median follow-up period of 70.5 months (3-120 months), 58 patients developed new gastric cancers, and metachronous gastric cancer was detected in 55 patients more than 1 year after ESD. The 5-year cumulative incidence rate was 9.8%. Three patients did not want treatment. Among the remaining 55 patients, the initial treatment was ESD in 51 and surgical resection in 4. Eventually, 50 patients (48 in the ESD group and 2 in the surgical resection group) fulfilled the pathologic criteria for curative ESD. There were no deaths due to gastric cancer. CONCLUSION: Our study was the first to reveal the incidence of new gastric cancer after ESD using RCP. Most lesions were cured with ESD, and no patients died of gastric cancer. Therefore, we consider RCPs to be an option for surveillance after ESD.

Diagnostic Value of Adding Magnifying Chromoendoscopy to Magnifying Narrow-Band Imaging Endoscopy for Colorectal Polyps.

BACKGROUND & AIMS: This study examined the additional value of magnifying chromoendoscopy (MCE) on magnifying narrow-band imaging endoscopy (M-NBI) in the optical diagnosis of colorectal polyps. METHODS: A multicenter prospective study was conducted at 9 facilities in Japan and Germany. Patients with colorectal polyps scheduled for resection were included. Optical diagnosis was performed by M-NBI first, followed by MCE. Both diagnoses were made in real time. MCE was performed on all type 2B lesions classified according to the Japan NBI Expert Team classification and other lesions at the discretion of endoscopists. The diagnostic accuracy and confidence of M-NBI and MCE for colorectal cancer (CRC) with deep invasion (≥T1b) were compared on the basis of histologic findings after resection. RESULTS: In total, 1173 lesions were included between February 2018 and December 2020, with 654 (5 hyperplastic polyp/sessile serrated lesion, 162 low-grade dysplasia, 403 high-grade dysplasia, 97 T1 CRCs, and 32 ≥T2 CRCs) examined using MCE after M-NBI. In the diagnostic accuracy for predicting CRC with deep invasion, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for M-NBI were 63.1%, 94.2%, 61.6%, 94.5%, and 90.2%, respectively, and for MCE they were 77.4%, 93.2%, 62.5%, 96.5%, and 91.1%, respectively. The sensitivity was significantly higher in MCE (P < .001). However, these additional values were limited to lesions with low confidence in M-NBI or the ones diagnosed as ≥T1b CRC by M-NBI. CONCLUSIONS: In this multicenter prospective study, we demonstrated the additional value of MCE on M-NBI. We suggest that additional MCE be recommended for lesions with low confidence or the ones diagnosed as ≥T1b CRC. Trials registry number: UMIN000031129.

Clinical outcome of the delineation-without-negative-biopsy strategy in magnifying image-enhanced endoscopy for identifying the extent of differentiated-type early gastric cancer.

BACKGROUND: The histologic evaluation of biopsy samples collected from the surrounding mucosa has conventionally been used to determine the horizontal extent of early gastric cancer. Recently, optical delineation using magnifying image-enhanced endoscopy (IEE) has been considered an alternative method to histologic evaluation. This study aimed to assess the clinical outcome and efficacy of this method in identifying cancer margins. METHODS: Overall, 921 patients with 1018 differentiated-type early gastric tumors who underwent endoscopic submucosal dissection (ESD) were examined. Before ESD, the lesions were classified based on whether they have clear or unclear margins on magnifying IEE. When the lesions had clear margins, the marking dots were placed outside the margins without a negative biopsy. Successful delineation was defined as lesions with clear margins and accurate delineation based on histopathological examination. The primary outcome was the accuracy of optical delineation without a negative biopsy compared with histopathological diagnosis. Moreover, the clinicopathological factors associated with an unsuccessful delineation were assessed. RESULTS: Of 1018 lesions, 820 had a clear margin and 198 an unclear margin. Of 820 lesions with a clear margin, 817 and 3 had an accurate and inaccurate delineation, respectively, according to the histological examination. Accordingly, the accuracy rate of optical delineation was 99.6% (817/820). The significant independent factors associated with an unsuccessful delineation were absence of Helicobacter pylori infection after eradication, tumor size > 20 mm, and moderate differentiation. CONCLUSIONS: Optical delineation may be an alternative method to histological evaluation in lesions with a clear margin on magnifying IEE.

Randomized study of two endo-knives for the traction-assisted endoscopic submucosal dissection of early esophageal squamous cell carcinoma.

Needle-type devices, such as the DualKnife (Olympus, Tokyo, Japan), are widely used for traction-assisted esophageal endoscopic submucosal dissection (ESD) but require a prolonged operation time. An improved model of the ITknife (Olympus), the ITknife nano, may allow faster and easier ESD than the DualKnife. We conducted a randomized study to compare the performances of the DualKnife and the ITknife nano for traction-assisted esophageal ESD. Patients with early esophageal squamous cell carcinoma were eligible for this study. The primary outcome was the total procedure time. The secondary outcomes were submucosal dissection time, en bloc, and complete resection rates, perforation rate, and adverse events. Results Fifty patients were equally divided into two groups: the DualKnife group (D-group) and the ITknife nano group (I-group), and all underwent the assigned treatment. The I-group had significantly shorter total procedure time (36.8 vs. 60.7 min; P < 0.01) and submucosal dissection time (17.2 vs. 35.8 min; P < 0.01) than the D-group. The en bloc and complete resection rates were sufficiently high in both groups (100% and 100% in the D-group and 100% and 96% in the I-group, respectively). Significantly fewer hemostatic procedures due to intraoperative bleeding were performed in the I-group than in the D-group (0.2 vs. 1.4; P < 0.01). Delayed bleeding, perforation, or esophageal stricture did not occur in either group. The ITknife nano exhibited lower procedure time for traction-assisted esophageal ESD than the DualKnife, without increasing adverse events.

Usefulness of cold polypectomy under linked color imaging.

Background and study aims Cold polypectomy is becoming popular for treatment of colon polyps due to its safety and convenience, but there is still the problem of tumor remnants. Because linked color imaging (LCI) improves polyp visibility, cold polypectomy under LCI is anticipated to reduce the tumor remnant rate. Therefore, we investigated the usefulness of this procedure. Patients and methods Fifty patients scheduled to undergo cold polypectomy for treatment of colon polyps < 10 mm and assumed to be adenomas were registered prospectively. After performing cold snare polypectomy (CSP) under LCI, biopsy was performed at two resection margin sites for each polyp to determine the tumor remnant rate. Results A total of 145 lesions were treated by CSP. Of the 139 lesions in which polyps were retrievable and diagnosed as adenomas pathologically, one lesion was recognized as a remnant adenoma on biopsy (remnant rate: 0.7 % [95 % CI: 0.0-4.4]). This remnant rate was extremely low. Treatment results were extremely promising given that en bloc resection, post-procedure bleeding, and perforation rates were 100 %, 0 %, and 0 %, respectively. Conclusion Cold snare polypectomy under LCI may be an effective treatment method capable of reducing the tumor remnant rate. This trial was approved by our Institutional Ethics Committee and registered at the University Hospital Medical Information Network (UMIN 000033690).

Comparison of endoscopic visibility and miss rate for early gastric cancers after Helicobacter pylori eradication with white-light imaging versus linked color imaging.

BACKGROUND AND AIM: We aimed to investigate whether linked color imaging (LCI) improves endoscopic visibility of early gastric cancers (EGC) after Helicobacter pylori eradication, which are often difficult to detect, and reduces the miss rate when compared with white-light imaging (WLI). METHODS: The visibility study used two images, one each with WLI and LCI, from 84 consecutive EGC after H. pylori eradication. Endoscopic visibility was evaluated using a visibility score and color difference (CD) value. To analyze miss rates, we studied a library of recorded videos using both WLI and LCI for 70 other consecutive patients after H. pylori eradication, among whom 19 had EGC. Endoscopic screening was done using the same protocol to map the entire stomach. Six endoscopists reviewed the videos in a randomized order. Miss rates of EGC were compared among the modalities. RESULTS: Mean [(±standard deviation) visibility scores with LCI were significantly higher than those with WLI (3.19 ± 0.84 vs 2.52 ± 0.98, P < 0.001), as were mean CD values (26.3 ± 9.1 vs 13.6 ± 6.3, P < 0.001). Miss rates of the six endoscopists were significantly lower with LCI than with WLI (30.7% vs 64.9%, P < 0.001). Both expert and trainee endoscopists had significantly better results with LCI than with WLI. CONCLUSIONS: Linked color imaging significantly improved the visibility of EGC after H. pylori eradication compared with WLI using both subjective and objective criteria. Furthermore, LCI significantly reduced miss rates of these lesions compared with WLI.

Enrichment technique to allow early detection and monitor emergence of KRAS mutation in response to treatment.

Sensitivity of cell-free circulating tumour DNA (ctDNA) assays is often hampered by the limited quantity of intact mutant nucleotide fragments. To overcome the issue of substrate limitation in clinical applications, we developed an enrichment method utilizing pyrrole-imidazole (PI) polyamides and their ability to bind the minor groove of B-DNA. We present here a proof-of-concept experiment to enrich specific mutant KRAS alleles with biotinylated PI polyamides. We investigated the clinical feasibility of incorporating PI polyamides to detect KRAS mutations in ctDNA from 40 colorectal cancer (CRC) patients, of whom 17 carried mutations in KRAS. After enriching ctDNA with those polyamides, we used digital PCR to detect several common KRAS codon 12 mutations. Enrichment by biotinylated PI polyamides improved the sensitivity of ctDNA analysis (88.9% vs. 11.1%, P < 0.01) in 9 non-metastatic mutation-positive patients. We observed no differences in performance for the 8 metastatic subjects (100% vs. 75%, P = 0.47). In the remaining 23/40 patients with wild type KRAS codon 12, no mutant alleles were detected with or without polyamide-facilitated enrichment. Enriching B-form of ctDNA with PI polyamides significantly improved the assay sensitivity in detecting KRAS mutations in non-metastatic CRC patient samples.

Early gastric cancer diagnostic ability of ultrathin endoscope loaded with laser light source.

BACKGROUND: Conventionally, the low luminous intensity, low image resolution, and difficulty in operation have been reported with the ultrathin endoscope. However, it has markedly advanced recently. The improvement of the diagnostic ability is expected. AIM: To compare the early gastric cancer diagnostic ability of an ultrathin endoscope loaded with a laser light source and that of the conventional endoscope. METHODS: The target subjects were 375 consecutive patients who underwent endoscopy at our hospital for post-endoscopic submucosal dissection follow-up of gastric cancer from January to August 2018. During endoscopy, the ultrathin endoscope was used in 140 patients (37.3%), and the conventional endoscope was used in 235 patients (62.7%). Patient background was adjusted using the propensity score matching method, and gastric cancer detection ability was evaluated in the two groups. RESULTS: The gastric cancer detection rate was 7.8% in the ultrathin endoscope group and 7.0% in the conventional endoscope group, and the mean intragastric observation time was 4.1 ± 1.7 min in the ultrathin endoscope group and 4.1 ± 1.9 min in the conventional endoscope group, showing no significant differences between the groups. Moreover, the biopsy implementation rate was 31.8% in the ultrathin endoscope group and 41.1% in the conventional endoscope group, and the biopsy prediction rate was 17.9% and 13.2%, respectively, showing no significant differences between the groups. CONCLUSION: The gastric cancer diagnostic ability of the ultrathin endoscope loaded with a laser light source was comparable to that of the conventional endoscope. The observation time was also comparable. Thus, endoscopy using the ultrathin endoscope loaded with the laser light source would be the first option in screening examinations of gastric cancer due to its low invasion.

Linked color imaging improves the endoscopic visibility of gastric mucosal cancers.

Background and study aims As a newly developed endoscopy technique, linked color imaging (LCI) provides very bright images with enhanced color tones. With the objective of improving the detection rate of gastric mucosal cancers, which are often difficult to detect, we examined the utility of LCI from the viewpoint of visibility. Patients and methods The current study used 100 consecutive gastric mucosal cancers ≤ 20 mm in diameter. For each lesion, we selected one endoscopic image acquired by white-light imaging (WLI), blue-laser imaging (BLI) -bright, and LCI modes. Four endoscopists interpreted the images; using a previously reported scale, we scored the visibility level on a scale of 1 - 4. Results The mean (±â€ŠSD) visibility scores were 2.54 ±â€Š1.10 for WLI, 3.02 ±â€Š1.07 for BLI-bright, and 3.28 ±â€Š0.97 for LCI. The score was significantly higher for BLI-bright compared with WLI ( P  < .001) and again higher for LCI compared with BLI-bright ( P  < .001). For the experts, the scores for BLI-bright and LCI were similar, but both were significantly higher than the score for WLI. For the trainees, there was no significant difference between the WLI and BLI-bright scores, but LCI score was significantly higher than those for WLI and BLI-bright scores. With regard to clinical characteristics, LCI particularly enhanced visibility of normochromic, flat and depressed lesions, which had the lowest visibility scores of all three modalities compared with those of the other lesions. Conclusion LCI increased visibility and may contribute to early detection of gastric mucosal cancers.

Usefulness of close observation with non-magnified blue laser imaging for determining cold polypectomy indications.

PURPOSE: To examine the usefulness of non-magnified close observation with blue laser imaging (BLI) using a colonoscope with close observation capability in determining indications for cold polypectomy. METHODS: We conducted an image evaluation study on 100 consecutive colorectal lesions of 10 mm or less which were observed endoscopically without magnification using BLI mode prior to treatment. Two experts and two non-experts reviewed the images using the Japan NBI expert team (JNET) classification and the diagnostic accuracy was analyzed. RESULTS: The final pathological diagnoses of the 100 lesions were hyperplastic/sessile serrated polyp (HP/SSP), low grade dysplasia (LGD), high grade dysplasia (HGD) and deep submucosal invasive cancer (dSM), respectively, in 12, 79, 9 and 0 lesions. When JNET classification type 1 corresponds to HP/SSP; 2A to LGD; 2B to HGD; and 3 to dSM; the overall diagnostic accuracy was 84.3%. Accuracy was 90.5% for experts and 78.0% for non-experts. High confidence rate was 67.5% for experts and 48.0% for non-experts. In diagnostic accuracy for HGD, the sensitivity, specificity, PPV and NPV were, respectively, 77.8%, 98.9%, 87.5% and 97.8% for experts; and 66.6%, 92.3%, 46.2% and 96.6% for non-experts. CONCLUSIONS: The diagnostic accuracy of unmagnified close observation with BLI using a colonoscope with close observation capability is similar to that reported for magnifying endoscopy and is useful in predicting the histological diagnosis of colorectal polyps of 10 mm or less although the effectiveness may be limited for non-experts. This modality is a potentially useful tool in deciding indications for cold polypectomy.

Feasibility of endoscopic submucosal dissection for cecal lesions.

BACKGROUND: The treatment results of endoscopic submucosal dissection (ESD) for colorectal lesions have improved markedly, but some lesions remain difficult to treat. Hence the cecum is considered a technically challenging site for ESD. We examined the feasibility of ESD for cecal lesions. METHODS: Among a total of 708 colorectal ESD performed in our hospital between March 2006 and December 2016, 549 procedures performed after April 2012 were studied, at a time when the techniques of ESD had stabilized and the procedure was covered by health insurance in Japan. Among 549 cases, 61 were cecal lesions and 488 were noncecal lesions. The treatment outcomes were analyzed. RESULTS: For cecal lesions, the en bloc resection rate was 95.1%, R0 resection rate was 91.8%, perforation rate was 0%, delayed bleeding rate was 6.6%, median diameter of resected specimen was 32 mm (16-65 mm), median time of the procedure was 44 minutes (8-140 min). The corresponding results for noncecal lesions were 97.3%, 95.5%, 0.4%, 2.7%, 30 mm (10-109 mm), and 37 min (7-225 min). No significant differences were observed and the good treatment results were seen. When the outcomes were analyzed for cecal sites considered to be particularly challenging; proximity to appendiceal orifice, the ileocecal valve, and the bottom of cecum, the treatment results were not inferior to other sites. CONCLUSIONS: ESD is safe and effective even for cecal lesions considered challenging to treat. ESD is feasible for cecal lesions.

Magnified endoscopic observation of small depressed gastric lesions using linked color imaging with indigo carmine dye.

BACKGROUND AND STUDY AIMS: Magnifying linked color imaging with indigo carmine dye (M-Chromo-LCI) enables sterically enhanced and color image-magnified observation of the superficial gastric mucosa. This study investigated the usefulness of M-Chromo-LCI for the differential diagnosis of gastric lesions. PATIENTS AND METHODS: 100 consecutive small depressed lesions were examined with conventional white-light imaging (C-WLI), magnifying blue-laser imaging (M-BLI), and M-Chromo-LCI. Endoscopic images were reviewed by three experts and three non-experts. Diagnostic accuracy and interobserver agreement were compared among the modalities. RESULTS: For experts, M-BLI showed a significantly higher diagnostic accuracy than C-WLI (82.7 % vs. 67.0 %; P < 0.001). The diagnostic accuracy of M-Chromo-LCI was not different from M-BLI (87.7 % vs. 82.7 %; P = 0.31). For non-experts, M-BLI showed a significantly higher diagnostic accuracy than C-WLI (69.3 % vs. 52.3 %; P < 0.001). M-Chromo-LCI additionally showed a significantly higher diagnostic accuracy than M-BLI (79.7 % vs. 69.3 %; P = 0.005). M-Chromo-LCI had the highest interobserver agreement for each group. CONCLUSIONS: M-Chromo-LCI is expected to become a useful modality for the accurate diagnosis of gastric lesions.

Safety and efficacy of endoscopic submucosal dissection using IT knife nano with clip traction method for early esophageal squamous cell carcinoma.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is an accepted and established treatment for early esophageal squamous cell carcinoma (EESCC), it is technically difficult, time consuming, and less safe than endoscopic mucosal resection. To perform ESD safely and more efficiently, we proposed a new technique of esophageal ESD using an IT knife nano with the clip traction method. This study aimed to evaluate the efficacy and safety of ESD using this new technique. METHODS: We retrospectively reviewed all consecutive cases of esophageal ESD performed using an IT knife nano with the clip traction method at our hospital between March 2013 and January 2017. Therapeutic efficacy and safety were also assessed. RESULTS: A total of 103 patients underwent esophageal ESD using the IT knife nano with the clip traction method. In all cases, we performed en bloc resection. Complete resection was achieved in 100 cases (97.1%). The median operating time was 40 (range 13-230) min. No cases of perforation or delayed bleeding occurred. Although two cases (2.0%) of mediastinal emphysema occurred without visible perforation at endoscopy, all were successfully managed conservatively. CONCLUSIONS: The new technique of esophageal ESD using the IT knife nano with the clip traction method appears to be feasible, effective, and safe for EESCC treatment.

A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

BACKGROUND: Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. CASE PRESENTATION: We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. CONCLUSION: In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

Linked-color imaging improves endoscopic visibility of colorectal nongranular flat lesions.

BACKGROUND AND AIMS: As a newly developed image-enhanced endoscopy (IEE) technique, linked-color imaging (LCI) provides very bright images with enhanced color tones. With the objective of improving the detection rate of colorectal flat tumor lesions, which are difficult to detect, we examined the usefulness of LCI from the viewpoint of visibility. METHODS: Fifty-three consecutive nongranular flat tumors were used in this study. Endoscopic images were acquired by white-light imaging (WLI), blue-laser imaging (BLI)-bright, and LCI modes. For each lesion, we selected 1 image each acquired by WLI, BLI-bright, and LCI modes. Six endoscopists interpreted the images. By using a previously reported visibility scale, we scored the visibility level on a scale of 1 to 4. RESULTS: The mean (± standard deviation) visibility scores were 2.74 ± 1.08 for WLI, 2.94 ± 0.97 for BLI-bright, and 3.36 ± 0.72 for LCI. The score was significantly higher for BLI-bright compared with WLI (P < .001) and again higher for LCI compared with BLI-bright (P < .001). When we compared between experts and trainees, the corresponding scores of experts were 2.83 ± 1.06, 3.17 ± 0.88, and 3.40 ± 0.74, with a tendency similar to the scores of all endoscopists. For the trainees, there was no difference between the scores for WLI (2.65 ± 1.10) and BLI-bright (2.71 ± 1.00), but the score for LCI (3.31 ± 0.69) was significantly higher than that for WLI or BLI-bright (P < .001). When only sessile serrated adenoma/polyp lesions were analyzed, LCI remained significantly higher than the other 2. CONCLUSIONS: The present findings suggest that LCI increases the visibility of colorectal flat lesions and contributes to improvement of the detection rate for these lesions.

Frequent Presence of Lymphovascular Invasion in Small Rectal Neuroendocrine Tumors on Immunohistochemical Analysis.

Rectal neuroendocrine tumors (RNETs) have become common in recent years and are good candidates for endoscopic resection (ER). To achieve clear resection margins, more advanced techniques such as endoscopic submucosal dissection, endoscopic submucosal resection with a ligation device, and cap-assisted endoscopic mucosal resection are available for ER. After ER, lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis. Previous studies have shown that small RNETs with LVI were uncommon (0-8.3%). However, using immunohistochemical analysis, a recent study revealed the frequent occurrence of LVI in small RNETs in a systematic manner (46.7%). There is a possibility that the actual detection rate of LVI in small RNETs is not always evaluated accurately because of the limited detection sensitivity of conventional hematoxylin-eosin staining. In addition, the correlation between LVI detected using immunohistochemical analysis and the development of metastasis remains unclear. Further prospective studies are required to clarify the role of LVI detected using immunohistochemical analysis.