Clinical factors associated with noncurative endoscopic submucosal dissection for the expanded indication of intestinal-type early gastric cancer: Post hoc analysis of a multi-institutional, single-arm, confirmatory trial (JCOG0607).

OBJECTIVES: The multi-institutional, single-arm, confirmatory trial JCOG0607 showed excellent efficacy of endoscopic submucosal dissection (ESD) for the expanded indication of intramucosal intestinal-type early gastric cancer (EGC), which consists of two groups: lesions >2 cm if clinical finding of ulcer (cUL)-negative, or those ≤3 cm if cUL-positive because of the expected low risk of lymph node metastasis. However, the proportion of noncurative resections (NCR) requiring additional surgery was high (32.4%). This post hoc analysis aimed to explore the clinical factors associated with NCR. METHODS: As the expanded indication includes two different groups, we explored the clinical factors associated with NCR separately in cUL-negative (>2 cm) and cUL-positive (≤3 cm) groups using the log-linear model. RESULTS: Two hundred and sixty cUL-negative and 206 cUL-positive EGCs were analyzed. The proportions of NCR were 33.8% in the cUL-negative group and 29.6% in the cUL-positive group. A multivariable analysis demonstrated that moderately differentiated predominant histology diagnosed in pretreatment biopsy (risk ratio [RR] 1.93, 95% confidence interval [CI] 1.34-2.77, P < 0.001) and lesion in the upper stomach (RR 1.75, 95% CI 1.03-2.96, P = 0.038) in the cUL-negative EGCs, and tumor size >2 cm (RR 1.78, 95% CI 1.22-2.58, P = 0.003) and female sex (RR 1.62, 95% CI 1.07-2.44, P = 0.021) in the cUL-positive EGCs were independent factors associated with NCR. CONCLUSIONS: Clinical risk factors associated with NCR were different between cUL-negative and cUL-positive EGCs. To avoid NCR, we need to take these factors into account when deciding expanded indications for ESD.

Pretreatment risk factors for endoscopic noncurative resection of gastric cancers with undifferentiated-type components.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is recommended for the treatment of early gastric cancers with an undifferentiated-type component, clinically diagnosed as intramucosal lesions ≤ 2 cm, without ulceration. In the JCOG1009/1010 trial, ESD could be performed with stomach preservation in 70% of such patients whose pathological findings met the curative resection criteria. However, additional gastrectomy was required for the remaining 30%. We identified the pretreatment risk factors for noncurative resection. METHODS: Post-hoc analysis indicated that 336 patients were identified in the JCOG1009/1010 trial; among them, 243 and 93 patients were categorized into the curative or noncurative resection groups, respectively, based on the pathological findings of the resected specimens. We explored the pretreatment risk factors for noncurative resection and investigated their associated pathological findings. RESULTS: Multivariable analysis revealed that a pretreatment tumor size > 1 cm was an independent risk factor for noncurative resection (odds ratio, 3.538; 95% confidence interval, 2.020-6.198, P < 0.0001). Patients with a pretreatment tumor size > 1 cm (n = 172) had a histological tumor size > 2 cm (22.1% vs 4.3%, odds ratio, 6.313; 95% confidence interval, 2.73-14.599, P < 0.0001) and submucosal invasion (17.4% vs 9.1%, odds ratio, 2.000; 95% confidence interval, 1.032-3.877, P = 0.040) more frequently as noncurative resection findings compared with those with a tumor size < 1 cm (n = 164). CONCLUSIONS: Because pretreatment tumor size > 1 cm is an independent risk factor for noncurative resection, endoscopists should be aware that noncurative resection is not uncommon in ESD and fully explain the potential necessity for additional gastrectomy to patients before the procedure.

Second gastric cancer after curative endoscopic resection of differentiated-type early gastric cancer: post-hoc analysis of a single-arm confirmatory trial.

BACKGROUND AND AIMS: Endoscopic resection (ER) for early gastric cancer (EGC) can preserve the stomach; however, the remaining stomach can develop second gastric cancer. Few reports have prospectively investigated the incidence and treatment outcomes of second gastric cancer. METHODS: This post-hoc analysis used the dataset of the single-arm confirmatory trial, JCOG0607. The key inclusion criteria for JCOG0607 were solitary differentiated-type EGC and no previous gastrectomy or endoscopic treatment for EGC. Three hundred seventeen patients who underwent curative ER were included in this study. Surveillance endoscopy was performed 1 to 3 months after the initial ER and subsequently annually for at least 5 years. A lesion detected ≤1 year and >1 year after the initial ER was defined as overlooked gastric cancer (OGC) and metachronous gastric cancer (MGC), respectively. RESULTS: During a median follow-up period of 6.0 years (interquartile range, 5.1-7.0), 30 OGCs and 61 MGCs were detected in 24 and 48 patients, respectively. The cumulative incidence of OGC at 1 year and MGC at 5 years was 7.6% and 12.7%, respectively. ER and gastrectomy were performed in 85 lesions and 6 lesions, respectively. Pathologic evaluation showed 78 mucosal cancers, 12 submucosal cancers, and 1 advanced cancer. Eventually, 28 OGCs and 52 MGCs fulfilled the pathologic criteria for curative ER. CONCLUSIONS: Our study was the first to reveal the actual incidence of second gastric cancer after curative ER for differentiated-type gastric cancer. Most lesions could be treated with ER. Continuous endoscopic surveillance after curative ER is important to detect second gastric cancer.

Incidence and treatment outcomes of metachronous gastric cancer occurring after curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer: Japan Clinical Oncology Group study-post hoc analysis of JCOG1009/1010.

BACKGROUND AND AIMS: A drawback of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is the development of metachronous gastric cancer (MGC). While MGC after ESD for differentiated-type (D-) EGC was well understood, little is known about MGC occurring after ESD for undifferentiated-type (UD-) EGC, because ESD had not been indicated. We evaluated the incidence and treatment outcomes of MGC after ESD of UD-EGC. METHODS: This study is a post hoc analysis of JCOG1009/1010, a multicenter trial to evaluate the efficacy and safety of ESD for UD-EGC. The patients who underwent curative ESD of index solitary UD-EGC were analyzed. Surveillance endoscopy was performed biannually for the first 3 years and thereafter annually. We assessed the time to MGC occurrence after ESD, lesion characteristics, and treatment outcomes of MGC. Time to MGC occurrence was estimated by cumulative incidence function, with death and total gastrectomy as competing risks. RESULTS: A total of 198 patients were included in this study. During a median follow-up period of 5.8 years, 4 patients (2%) developed MGC. Median time to MGC occurrence was 4.5 years (range: 3.1-5.4). Five-year cumulative incidence of MGC was 1.0% (95% CI: 0.2-3.3%). Two MGCs were histologically D-EGC, and the remaining two were UD-EGC. The median tumor size of MGCs was 1.0 cm (range: 0.7-1.7), and the depth of invasion (M/SM1/SM2) was 2/1/1, respectively. Three patients achieved curative resection with repeated ESD. CONCLUSIONS: MGC does not occur commonly after curative ESD of UD-EGC, and repeated ESD could contribute to stomach preservation.

A nonrandomized, single-arm confirmatory trial of expanded endoscopic submucosal dissection indication for undifferentiated early gastric cancer: Japan Clinical Oncology Group study (JCOG1009/1010).

BACKGROUND: While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC. METHODS: The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC. RESULTS: Three hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1-99.8). CONCLUSIONS: ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.

Factors associated with technical difficulty of endoscopic submucosal dissection for early gastric cancer that met the expanded indication criteria: post hoc analysis of a multi-institutional prospective confirmatory trial (JCOG0607).

BACKGROUND: There are few reports on the technical difficulty of gastric endoscopic submucosal dissection (ESD). The aim of this study was to investigate the factors associated with the technical difficulty of ESD for early gastric cancer (EGC) using the data from the multicenter non-randomized confirmatory trial of expanded indication criteria of ESD (JCOG0607). METHODS: The major inclusion criteria were as follows: (1) histologically proven intestinal-type adenocarcinoma; (2) cT1aN0M0; (3) lesion without finding of ulcer (UL-negative) with > 2 cm in size, or UL-positive with ≤ 3 cm; (4) age 20-75 years. The difficult case was defined as ESD taking ≥ 120 min, piecemeal resection, and/or developing perforation during procedure. RESULTS: Between June 2007 and October 2010, 470 patients were enrolled from 29 institutions. Median procedure time was 79 (range 14-462) min, and it was ≥ 120 min in 127 patients. Twelve patients developed perforation during ESD, and the procedure time was ≥ 120 min in 9 of them. Therefore, 130 patients (27.7%) were identified as difficult cases. Multivariable analysis showed that UL-negative with > 5 cm (vs. UL-negative with ≤ 3 cm, odds ratio, 24.993; 95% CI 6.130-101.897, p < 0.0001) had the largest odds ratio and followed by UL-negative with 3-5 cm upper or middle portion of stomach and age ≤ 60 years were significantly associated with difficulty. CONCLUSIONS: UL-negative lesion with > 3 cm, upper or middle portion of stomach and age ≤ 60 years were independent factors associated with technical difficulty of ESD for EGC. Trial registered number was UMIN000000737.

Prospective real-time evaluation of diagnostic performance using endocytoscopy in differentiating neoplasia from non-neoplasia for colorectal diminutive polyps (≤ 5 mm).

AIM: To clarify the diagnostic performance of endocytoscopy for differentiation between neoplastic and non-neoplastic colorectal diminutive polyps. METHODS: Patients who underwent endocytoscopy between October and December 2016 at Sano Hospital were prospectively recruited. When diminutive polyps (≤ 5 mm) were detected, the lesions were evaluated by endocytoscopy after being stained with 0.05% crystal violet and 1% methylene blue. The diminutive polyps were classified into five categories (EC 1a, 1b, 2, 3a, and 3b). Endoscopists were asked to take a biopsy from any lesion diagnosed as EC1b (indicator of hyperplastic polyp) or EC2 (indicator of adenoma). We have assessed the diagnostic performance of endocytoscopy for EC2 and EC1b lesions by comparison with the histopathology of the biopsy specimen. RESULTS: A total of 39 patients with 63 diminutive polyps were analyzed. All polyps were evaluated by endocytoscopy. The mean polyp size was 3.3 ± 0.9 mm. Among the 63 diminutive polyps, 60 were flat and 3 were pedunculated. The mean time required for EC observation, including the time for staining with crystal violet and methylene blue, was 3.0 ± 1.9 min. Histopathologic evaluation showed that 13 polyps were hyperplastic and 50 were adenomas. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of EC2 for adenoma compared with EC1b for hyperplastic polyp were 98.0%, 92.3%, 96.8%, 98.0% and 92.3%, respectively. There were only two cases of disagreement between the endoscopic diagnosis made by endocytoscopy and the corresponding histopathological diagnosis. CONCLUSION: Endocytoscopy showed a high diagnostic performance for differentiating between neoplastic and non-neoplastic colorectal diminutive polyps, and therefore has the potential to be used for "real-time histopathology".

Additional chromoendoscopy for colorectal lesions initially diagnosed with low confidence by magnifying narrow-band imaging: Can it improve diagnostic accuracy?

BACKGROUND AND AIM: Magnifying chromoendoscopy has been one of the most reliable diagnostic methods for distinguishing neoplastic from non-neoplastic lesions. The aim of this prospective study was to clarify the clinical usefulness of magnifying chromoendoscopy for colorectal polyps initially diagnosed with low confidence (LC) by magnifying narrow-band imaging (NBI). METHODS: Consecutive adult patients who underwent total colonoscopic examination with magnifying NBI between July and December 2016 at Sano Hospital were prospectively recruited. Endoscopists were asked to carry out additional magnifying chromoendoscopy for cases that had been initially diagnosed as Japan NBI Expert Team (JNET) Type 1 or 2A with LC by magnifying NBI. We investigated the diagnostic performance of magnifying NBI for polyps diagnosed as JNET Type 1 or 2A with LC (first phase) and that of subsequent magnifying chromoendoscopy (second phase) in differentiating neoplasia from non-neoplasia. RESULTS: In 50 patients, we analyzed 53 polyps classified as JNET Type 1 or 2A with LC prediction. Accuracy and negative predictive value of magnifying NBI (first phase) were 58.5% (95% CI, 44.1-71.9%) and 66.0% (95% CI, 36.6-77.9%), and those of magnifying chromoendoscopy (second phase) were 66.0% (95% CI, 51.7-78.5%) and 61.1% (95% CI, 43.5-76.9%), respectively. CONCLUSION: Regardless of the findings of additional chromoendoscopy, all polyps should be resected and submitted for histopathological examination when the confidence level in differentiating adenomatous from hyperplastic polyps by magnifying NBI is low.

Clinical and endoscopic evaluations of sessile serrated adenoma/polyps with cytological dysplasia.

BACKGROUND AND AIM: Although sessile serrated adenoma/polyps (SSA/Ps) are considered to be premalignant lesions and rapidly progress to carcinomas after they develop cytological dysplasia (CD), a treatment strategy for SSA/Ps in Asian countries is still being debated and has not yet been established. The present study aimed to propose a treatment strategy for SSA/Ps. METHODS: Histopathological data of patients, who underwent colonoscopy at our center between January 2011 and December 2016, were reviewed. Data of patients with ≥ 1 SSA/P were retrieved, and clinicopathological characteristics were retrospectively analyzed. RESULTS: A total of 281 patients with 326 SSA/Ps, including 258 patients who had 300 SSA/Ps without CD (SSA/Ps-CD[-]) and 23 patients who had 26 SSA/Ps with CD (SSA/Ps-CD[+]), were evaluated in this study. Although SSA/Ps-CD(+) were often found in older female patients and in the proximal colon, there were no significant differences between SSA/Ps-CD(-) and SSA/Ps-CD(+). Endoscopic morphological findings, such as large or small nodules on the surface and partial protrusion of the lesions, were significantly more common in SSA/Ps-CD(+) than in SSA/Ps-CD(-). Although the diagnostic ability of nodule/protrusion in lesions to predict CD within SSA/Ps was very high with an accuracy of 93.9% and a negative predictive value of 95.4%, sensitivity was low at 46.2%. SSA/Ps-CD(+) were significantly larger than SSA/Ps-CD(-), and the rate of CD within SSA/Ps significantly increased with lesion size (≤ 5 mm, 0%; 6-9 mm, 6.0%; ≥ 10 mm, 13.6%). CONCLUSION: The study proposes removing all SSA/Ps ≥ 6 mm in order to remove high-risk SSA/Ps-CD(+), with high sensitivity.

A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer (cT1a): the Japan Clinical Oncology Group study (JCOG0607).

BACKGROUND: Endoscopic resection has been limited to intestinal-type gastric cancer (cT1a) with a low risk of lymph node metastasis (T1a ≤2 cm, without ulcers). This single-arm confirmatory trial evaluated the efficacy and safety of endoscopic submucosal dissection (ESD) for >2 cm ulcer-negative and ≤3 cm ulcer-positive intestinal-type gastric cancer (cT1a). METHODS: The eligibility criteria included endoscopically diagnosed cT1a, a single primary intestinal-type gastric adenocarcinoma, an ulcer-negative lesion of any size or a ≤3 cm ulcer-positive lesion, cN0M0, and no prior treatment. If ESD resulted in noncurative resection, surgical resection was added. The primary endpoint was the 5-year overall survival (OS) (planned sample size was 470, with a one-sided alpha level of 2.5%). The threshold 5-year OS was 86.1%. RESULTS: We enrolled 470 early gastric cancer patients [median tumor size, 25 (5-130) mm] from 29 institutions between June 2007 and October 2010. These patients had 152 ulcer-negative lesions (>2 and ≤3 cm), 111 ulcer-negative lesions (>3 cm), and 207 ulcer-positive lesions (≤3 cm). The success rate for en block resection was 99.1% (466/470). Additional gastrectomy was conducted in 131 patients (28%) who did not fulfill the curative resection criteria. The 5-year OS of all patients was 97.0% (95% confidence interval, 95.0-98.2%), which was higher than the threshold 5-year OS (86.1%). The 317 patients who satisfied the curative resection criteria had no recurrence. There were no ESD-related grade 4 adverse events. CONCLUSION: ESD for early gastric cancers that met the expanded criteria for intestinal-type gastric cancer (cT1a) was acceptable and should be the standard treatment instead of gastrectomy.

Post-colonoscopy colorectal cancer rate in the era of high-definition colonoscopy.

AIM: To investigate the post-colonoscopy colorectal cancer (PCCRC) rate for high-definition (HD) colonoscopy compared with that for standard-definition colonoscopy reported previously. METHODS: Using medical records at Sano Hospital (SH) and Dokkyo Medical University Koshigaya Hospital (DMUKH), we retrospectively obtained data on consecutive patients diagnosed as having CRC between January 2010 and December 2015. The definition of PCCRC was diagnosis of CRC between 7 and 36 mo after initial high-definition colonoscopy that had detected no cancer, and patients were divided into a PCCRC group and a non-PCCRC group. The primary outcome was the rate of PCCRC for HD colonoscopy. The secondary outcomes were factors associated with PCCRC and possible reason for occurrence of early and advanced PCCRC. RESULTS: Among 892 CRC patients, 11 were diagnosed as having PCCRC and 881 had non-PCCRC. The PCCRC rate was 1.7% (8/471) at SH and 0.7% (3/421) at DMUKH. In comparison with the non-PCCRC group, the PCCRC group had a significantly higher preponderance of smaller tumors (39 mm vs 19 mm, P = 0.002), a shallower invasion depth (T1 rate, 25.4% vs 63.6%, P = 0.01), a non-polypoid macroscopic appearance (39.0% vs 85.7%, P = 0.02) and an earlier stage (59.7% vs 90.9%, P = 0.03). Possible reasons for PCCRC were "missed or new" in 9 patients (82%), "incomplete resection" in 1 (9%), and "inadequate examination'" in 1 (9%). Among 9 "missed or new" PCCRC, the leading cause was non-polypoid shape for early PCCRC and blinded location for advanced PCCRC. CONCLUSION: The PCCRC rate for HD colonoscopy was 0.7%-1.7%, being lower than that for standard-definition colonoscopy (1.8%-9.0%) reported previously employing the same methodology.

Polyp Detection, Characterization, and Management Using Narrow-Band Imaging with/without Magnification.

Narrow-band imaging (NBI) is a new imaging technology that was developed in 2006 and has since spread worldwide. Because of its convenience, NBI has been replacing the role of chromoendoscopy. Here we review the efficacy of NBI with/without magnification for detection, characterization, and management of colorectal polyps, and future perspectives for the technology, including education. Recent studies have shown that the next-generation NBI system can detect significantly more colonic polyps than white light imaging, suggesting that NBI may become the modality of choice from the beginning of screening. The capillary pattern revealed by NBI, and the NBI International Colorectal Endoscopic classification are helpful for prediction of histology and for estimating the depth of invasion of colorectal cancer. However, NBI with magnifying colonoscopy is not superior to magnifying chromoendoscopy for estimation of invasion depth. Currently, therefore, chromoendoscopy should also be performed additionally if deep submucosal invasive cancer is suspected. If endoscopists become able to accurately estimate colorectal polyp pathology using NBI, this will allow adenomatous polyps to be resected and discarded; thus, reducing both the risk of polypectomy and costs. In order to achieve this goal, a suitable system for education and training in in vivo diagnostics will be necessary.

Prospective evaluation of the proportion of sessile serrated adenoma/polyps in endoscopically diagnosed colorectal polyps with hyperplastic features.

BACKGROUND AND STUDY AIMS: Sessile serrated adenoma/polyps (SSA/Ps) are considered precursors of colorectal cancers with microsatellite instability. However, it is still difficult to differentiate SSA/Ps from hyperplastic polyps endoscopically; therefore, the prevalence of SSA/Ps remains uncertain in clinical practice. This study aimed to clarify the proportion of SSA/Ps in endoscopically diagnosed colorectal polyps with hyperplastic features (E-HPs). PATIENTS AND METHODS: Patients aged ≥ 40 years undergoing colonoscopy for standard clinical indications at our center were prospectively enrolled between June 2013 and May 2014. During colonoscopy, 0.05 % indigo carmine dye was sprayed throughout the colorectum to highlight lesions. All detected lesions were diagnosed by high definition magnifying narrow-band imaging and were resected endoscopically or surgically, apart from rectosigmoid E-HPs ≤ 5 mm. The number of rectosigmoid E-HPs ≤ 5 mm was recorded, and some were resected for use as tissue samples. RESULTS: A total of 343 patients (male: 42.9 %; mean age: 61.5 years) were included. Among 3838 E-HPs (distal: 96.4 %) detected in 294 patients, 792 were resected and analyzed. All of 21 SSA/Ps identified in 17 patients were included in E-HPs, and the overall proportion of SSA/Ps in E-HPs was 2.7 %. However, this proportion increased with the size of E-HPs (≤ 5 mm: 0.7 %; 6 - 9 mm: 29.0 %; ≥ 10 mm: 70 %) and was higher in the proximal colon than in the distal colorectum (10.9 % vs. 0.9 %). In addition, no SSA/P was found in the rectum, and no SSA/P had cytological dysplasia. CONCLUSIONS: The overall proportion of SSA/Ps in E-HPs was 2.7 %, although this proportion was higher in the proximal colon and increased with the size of E-HPs. SSA/Ps were common in routine colonoscopy, with a prevalence of at least 5.0 %. STUDY REGISTRATION: UMIN000010832.

The addition of high magnifying endoscopy improves rates of high confidence optical diagnosis of colorectal polyps.

BACKGROUND AND STUDY AIMS: The real-time optical diagnosis of colorectal polyps with high confidence predictions can achieve high levels of accuracy. Increasing the rates of high confidence optical diagnosis can improve the clinical application of real-time optical diagnosis in routine practice. The primary aim of this prospective study was to evaluate whether high magnifying endoscopy improves the rates of high confidence narrow-band imaging (NBI) - based optical diagnosis for differentiating between neoplastic and non-neoplastic colorectal lesions according to the NBI international colorectal endoscopic (NICE) classification. PATIENTS AND METHODS: Consecutive adult patients undergoing colonoscopy with a high magnifying (maximum, × 80) colonoscope between April and August 2012 were recruited. The optical diagnosis for each polyp was evaluated during colonoscopy in two consecutive stages by the same endoscopist, who first used NBI with non-magnifying endoscopy (NBI-NME), then NBI with magnifying endoscopy (NBI-ME). A level of confidence was assigned to each prediction. RESULTS: The analysis included 124 patients (mean age, 56.4 years; male-to-female ratio, 72:52) with 248 polyps smaller than 10 mm. Of the 248 polyps, 210 were 1 to 5 mm in size and 38 were 6 to 9 mm in size; 77 polyps were hyperplastic, 4 were sessile serrated adenomas/polyps, 160 were low grade adenomas, 5 were high grade adenomas, and 2 were deep submucosal invasive carcinomas. The rate of high confidence optical diagnosis when NBI-ME was used was significantly higher than the rate when NBI-NME was used for diminutive (1 - 5 mm) polyps (92.9 % vs 79.5 %, P < 0.001) and for small (6 - 9 mm) polyps (94.7 % vs 84.2 %, P = 0.048). CONCLUSION: High magnifying endoscopy significantly improved the rates of high confidence NBI-based optical diagnosis of diminutive and small colorectal polyps. STUDY REGISTRATION: UMIN 000007608.

Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions.

AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the "resect and discard" policy. METHODS: Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancers and their endoscopic features were assessed. RESULTS: In total, we found 681 cases of diminutive (1-5 mm) lesions in 402 patients and 197 cases of small (6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal (SM) scanty invasive carcinomas, 1 and 1 were SM-d carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically. CONCLUSION: The risk of failing to detect diminutive and small colorectal invasive cancer with the "resect and discard" strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy.

Feasibility of a "resect and watch" strategy with endoscopic resection for superficial pharyngeal cancer.

BACKGROUND: After endoscopic resection (ER) for superficial pharyngeal cancer (SPC), additional treatments such as radical surgical resection or radiation therapy may be needed in cases of possible incomplete resection. However, the benefit of prophylactic additional treatment is unclear. OBJECTIVE: To evaluate the feasibility of a "resect and watch" strategy with ER for SPC. DESIGN: Retrospective, single-center cohort study. SETTING: Tertiary cancer center. PATIENTS: A total of 32 patients with 47 SPCs were eligible. INTERVENTION: A "resect and watch" strategy of initial ER and observation until development of secondary diseases, including local recurrence, neck lymph node metastasis (LNM), and metachronous pharyngeal cancer. MAIN OUTCOME MEASUREMENTS: Complications, tumor recurrence, development of metachronous pharyngeal cancer, overall survival, and cause-specific survival. RESULTS: There were no severe complications related to ER. Median length of follow-up was 43 months (range, 7-76 months). Cumulative development of secondary diseases at 5 years was 44% (95% CI, 24.5%-63.8%). Local recurrence (N = 4) and neck LNM (N = 5) were successfully treated by local resection (2 partial surgical resections and 2 additional ERs) and neck dissection, respectively. Metachronous pharyngeal cancers (N = 6) were completely removed by ER. The overall survival and cause-specific survival rates at 5 years were 84.4% (95% CI, 70.0%-98.8%) and 100%, respectively. No patient needed radical surgery as an additional therapy. Thus, the larynx and its function were preserved in all patients. LIMITATIONS: Retrospective nature, single-center setting, relatively small sample size. CONCLUSIONS: A "resect and watch" strategy with ER for SPC is feasible and rational.

A phase II clinical trial of endoscopic submucosal dissection for early gastric cancer of undifferentiated type: Japan Clinical Oncology Group study JCOG1009/1010.

A Phase II clinical trial has been initiated to evaluate the efficacy and safety of endoscopic submucosal dissection for intramucosal (cT1a) gastric cancer of undifferentiated type. Patients with cT1a gastric cancer with undifferentiated-type adenocarcinoma are eligible for the study. The tumor size should be 2 cm or less without ulceration. The study will enroll a total of 325 patients from 51 institutions over a 4-year period. The primary endpoint is proportion of 5-year overall survival (% 5-year overall survival) in patients with undifferentiated dominant type. The secondary endpoints are overall survival, relapse-free survival, distant metastasis-free survival, % 5-year overall survival without either recurrence or gastrectomy, % en-bloc resection with endoscopic submucosal dissection, % pathological curative resection with endoscopic submucosal dissection, % 5-year overall survival in patients with differentiated dominant type, % 5-year overall survival in patients with pathologically curative resection with endoscopic submucosal dissection and adverse events.

Risk of lymph node metastases from intramucosal gastric cancer in relation to histological types: how to manage the mixed histological type for endoscopic submucosal dissection.

BACKGROUND: The behavior of early gastric cancer (EGC) with mixed-type histology (differentiated and undifferentiated) is incompletely understood. This study aimed to clarify the clinicopathological features of EGC with mixed-type histology in relation to lymph node (LN) metastasis. METHODS: Clinicopathological data from 410 patients who underwent surgical resection for intramucosal EGC were reviewed. Lesions were classified into four types according to the proportion of differentiated and undifferentiated components at histopathology: pure differentiated (PD) type, mixed predominantly differentiated (MD) type, mixed predominantly undifferentiated (MU) type, and pure undifferentiated (PU) type. We examined the clinicopathological differences between PD and MD, and between PU and MU, and the rate of LN metastasis according to tumor size and ulceration. RESULTS: Moderately differentiated adenocarcinoma was the primary component in MD relative to PD (90.7 vs. 46.1 %). Signet ring cell carcinoma was the main component in PU relative to MU (81.5 vs. 33.3 %). LN metastasis was more common in MU than PU (19.0 vs. 6.0 %). For intramucosal tumors larger than 20 mm without lymphovascular invasion and without ulceration, the rate of LN metastasis was 0 % for MD and 24 % for MU. For intramucosal lesions less than 30 mm with ulceration but without lymphovascular invasion, the rate of LN metastasis was 0 % for MD and 20 % for MU. CONCLUSIONS: Histologically mixed-type EGC with a predominantly undifferentiated component should be managed as an undifferentiated-type tumor. Further investigation is required to determine whether mixed-type EGC with a predominantly differentiated component could be managed the same way as a differentiated-type EGC.

Autoimmune pancreatitis with response to chemoradiation therapy.

Autoimmune pancreatitis (AIP) sometimes mimics pancreatic cancer, and is rarely resected under this misdiagnosis. However, there is no report in the literature regarding a case of AIP, which was misdiagnosed as an inoperative stage of pancreatic cancer and which received systemic chemotherapy with or without radiation. We report a 59-year-old man with a mass-forming lesion at the pancreatic head involving the common hepatic artery and portal vein, initially diagnosed as locally advanced pancreatic cancer and treated with chemoradiation therapy. After a month of continuous infusion of low dose 5-fluorouracil with concurrent local radiation (50.4 Gy), the pancreatic lesion diminished in size. However, the pancreatic body gradually enlarged and a capsule-like limb appeared in the following year. Serological markers and endoscopic retrograde cholangiopancreatography were compatible with those of AIP. No neoplastic tissue was identified on the fine needle aspiration biopsy of the pancreas. The pancreatic lesion responded well to steroid therapy and the patient remained in remission for one year after the withdrawal of steroids. Similar to pancreatic cancer, this current case of AIP responded to chemoradiation. Both serological and histological examinations were essential for images equivocal for either locally advanced pancreatic cancer or AIP.

Palliative radiotherapy for bleeding from advanced gastric cancer: is a schedule of 30 Gy in 10 fractions adequate?

PURPOSE: To evaluate the effectiveness of short-course radiotherapy (RT) with 30 Gy in 10 fractions for bleeding from advanced gastric cancer. METHODS: We reviewed the data for all patients with gastric cancer requiring blood transfusions due to gastric bleeding who were treated with RT at the Shizuoka Cancer Center Hospital between September 2002 and March 2007. Patients with curative-intent chemoradiotherapy or previous irradiation were excluded. RT was planned to deliver a total of 30 Gy at 3 Gy per fraction. We defined RT as effective if the patients did not require blood transfusions for 1 or more months after RT. RESULTS: Twenty-two out of 30 patients (73%) responded to RT, and rebleeding occurred in 11 (50%) of 22 patients responding to RT. The median actuarial time to rebleeding was 3.3 months. Twelve patients received concurrent chemoradiotherapy and had a significantly lower rebleeding rate than patients undergoing RT alone (P = 0.001). Among patients receiving CRT, 1 with grade 3 non-hematological toxicity and 5 with grade 3-4 hematological toxicity were observed. No Grade 3 or higher adverse events were observed in patients treated with RT alone. CONCLUSIONS: RT with 30 Gy in 10 fractions is an adequate treatment for bleeding from advanced gastric cancer, especially in patients with poor prognosis.