Combined endocytoscopy with pit pattern diagnosis in ulcerative colitis-associated neoplasia: Pilot study.

OBJECTIVES: Ulcerative colitis-associated neoplasias (UCAN) are often flat with an indistinct boundary from surrounding tissues, which makes differentiating UCAN from non-neoplasias difficult. Pit pattern (PIT) has been reported as one of the most effective indicators to identify UCAN. However, regenerated mucosa is also often diagnosed as a neoplastic PIT. Endocytoscopy (EC) allows visualization of cell nuclei. The aim of this retrospective study was to demonstrate the diagnostic ability of combined EC irregularly-formed nuclei with PIT (EC-IN-PIT) diagnosis to identify UCAN. METHODS: This study involved patients with ulcerative colitis whose lesions were observed by EC. Each lesion was diagnosed by two independent expert endoscopists, using two types of diagnostic strategies: PIT alone and EC-IN-PIT. We evaluated and compared the diagnostic abilities of PIT alone and EC-IN-PIT. We also examined the difference in the diagnostic abilities of an EC-IN-PIT diagnosis according to endoscopic inflammation severity. RESULTS: We analyzed 103 lesions from 62 patients; 23 lesions were UCAN and 80 were non-neoplastic. EC-IN-PIT diagnosis had a significantly higher specificity and accuracy compared with PIT alone: 84% versus 58% (P < 0.001), and 88% versus 67% (P < 0.01), respectively. The specificity and accuracy were significantly higher for Mayo endoscopic score (MES) 0-1 than MES 2-3: 93% versus 68% (P < 0.001) and 95% versus 74% (P < 0.001), respectively. CONCLUSIONS: Our novel EC-IN-PIT strategy had a better diagnostic ability than PIT alone to predict UCAN from suspected and initially detected lesions using conventional colonoscopy. UMIN clinical trial (UMIN000040698).

Small Neuroendocrine Tumors of the Whole Gastrointestinal Tract Performed Endoscopic or Surgical Resections Also Show Positive for Lymphovascular Invasion.

BACKGROUND AND AIMS: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. METHODS: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. RESULTS: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases <5 mm, with a lymphovascular invasion rate of 8.7% for those 5-10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion. CONCLUSIONS: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.

Treatment policy for colonic laterally spreading tumors based on each clinicopathologic feature of 4 subtypes: actual status of pseudo-depressed type.

BACKGROUND AND AIMS: Laterally spreading tumors (LSTs) are originally classified into 4 subtypes. Pseudo-depressed nongranular types (LSTs-NG-PD) are gaining attention because of their high malignancy potential. Previous studies discussed the classification of nongranular (LST-NG) and granular types (LST-G); however, the actual condition or indication for endoscopic treatment of LSTs-NG-PD remains unclear. We aimed to compare the submucosal invasion pattern of LSTs-NG-PD with the other 3 subtypes. METHODS: A total of 22,987 colonic neoplasms including 2822 LSTs were resected endoscopically or surgically at Showa University Northern Yokohama Hospital. In these LSTs, 322 (11.4%) were submucosal invasive carcinomas. We retrospectively evaluated the clinicopathologic features of LSTs divided into 4 subtypes. In 267 LSTs resected en bloc, their submucosal invasion site was further evaluated. RESULTS: The frequency of LSTs in all colonic neoplasms was significantly higher in women (14.9%) than in men (11.0%). Rates of submucosal invasive carcinoma were .8% in the granular homogenous type (LSTs-G-H), 15.2% in the granular nodular mixed type (LSTs-G-M), 8.0% in the nongranular flat elevated type (LSTs-NG-F), and 42.5% in LSTs-NG-PD. Tumor size was associated with submucosal invasion rate in LSTs-NG-F and LSTs-NG-PD (P < .001). The multifocal invasion rate of LSTs-NG-PD (46.9%) was significantly higher than that of LSTs-G-M (7.9%) or LSTs-NG-F (11.8%). In LSTs-NG-PD, the invasion was significantly deeper (≥1000 µm) if observed in 1 site. CONCLUSIONS: For LSTs-G-M and LSTs-NG-F that may have invaded the submucosa, en bloc resection could be considered. Considering that LSTs-NG-PD had a higher submucosal invasion rate, more multifocal invasive nature, and deeper invasion tendency, regardless if invasion was only observed in 1 site, than LSTs-NG-F, we should endoscopically distinguish LSTs-NG-PD from LSTs-NG-F and strictly adopt en bloc resection by endoscopic submucosal dissection or surgery for LSTs-NG-PD. (Clinical trial registration number: UMIN 000020261.).

A novel ability of endocytoscopy to diagnose histological grade of differentiation in T1 colorectal carcinomas.

BACKGROUND AND STUDY AIMS: Endocytoscopic images closely resemble histopathology. We assessed whether endocytoscopy could be used to determine T1 colorectal cancer histological grade. PATIENTS AND METHODS: Endocytoscopic images of 161 lesions were divided into three types: tubular gland lumens, unclear gland lumens, and fused gland formations on endocytoscopy (FGFE). We retrospectively compared endocytoscopic findings with histological grade in the resected specimen superficial layer, and examined the incidence of risk factors for lymph node metastasis. RESULTS: Of the 118 eligible lesions, the sensitivity, specificity, accuracy, negative predictive value, and positive likelihood ratio of tubular or unclear gland lumens to identify well-differentiated adenocarcinomas were 91.0 %, 93.1 %, 91.5 %, 77.1 %, and 13.20, respectively. To identify moderately differentiated adenocarcinomas for FGFE, these values were 93.1 %, 91.0 %, 91.5 %, 97.6 %, and 10.36, respectively. In the 35 lesions with FGFE, the rates of massive invasion, lymphovascular infiltration, and tumor budding were 97.1 %, 60.0 %, and 37.1 %, respectively. CONCLUSIONS: Endocytoscopy could be used to diagnose T1 colorectal cancer histological grade, and FGFE was a marker for recommending surgery.

Artificial intelligence may help in predicting the need for additional surgery after endoscopic resection of T1 colorectal cancer.

BACKGROUND AND STUDY AIMS: Decisions concerning additional surgery after endoscopic resection of T1 colorectal cancer (CRC) are difficult because preoperative prediction of lymph node metastasis (LNM) is problematic. We investigated whether artificial intelligence can predict LNM presence, thus minimizing the need for additional surgery. PATIENTS AND METHODS: Data on 690 consecutive patients with T1 CRCs that were surgically resected in 2001 - 2016 were retrospectively analyzed. We divided patients into two groups according to date: data from 590 patients were used for machine learning for the artificial intelligence model, and the remaining 100 patients were included for model validation. The artificial intelligence model analyzed 45 clinicopathological factors and then predicted positivity or negativity for LNM. Operative specimens were used as the gold standard for the presence of LNM. The artificial intelligence model was validated by calculating the sensitivity, specificity, and accuracy for predicting LNM, and comparing these data with those of the American, European, and Japanese guidelines. RESULTS: Sensitivity was 100 % (95 % confidence interval [CI] 72 % to 100 %) in all models. Specificity of the artificial intelligence model and the American, European, and Japanese guidelines was 66 % (95 %CI 56 % to 76 %), 44 % (95 %CI 34 % to 55 %), 0 % (95 %CI 0 % to 3 %), and 0 % (95 %CI 0 % to 3 %), respectively; and accuracy was 69 % (95 %CI 59 % to 78 %), 49 % (95 %CI 39 % to 59 %), 9 % (95 %CI 4 % to 16 %), and 9 % (95 %CI 4 % - 16 %), respectively. The rates of unnecessary additional surgery attributable to misdiagnosing LNM-negative patients as having LNM were: 77 % (95 %CI 62 % to 89 %) for the artificial intelligence model, and 85 % (95 %CI 73 % to 93 %; P < 0.001), 91 % (95 %CI 84 % to 96 %; P < 0.001), and 91 % (95 %CI 84 % to 96 %; P < 0.001) for the American, European, and Japanese guidelines, respectively. CONCLUSIONS: Compared with current guidelines, artificial intelligence significantly reduced unnecessary additional surgery after endoscopic resection of T1 CRC without missing LNM positivity.

Risk factors of recurrence in T1 colorectal cancers treated by endoscopic resection alone or surgical resection with lymph node dissection.

PURPOSE: The recurrence of T1 colorectal cancers is relatively rare, and the prognostic factors still remain obscure. This study aimed to clarify the risk factors for recurrence in patients with T1 colorectal cancers treated by endoscopic resection (ER) alone or surgical resection (SR) with lymph node dissection, respectively. METHODS: We reviewed 930 patients with resected T1 colorectal cancers (mean follow-up, 52.3 months). Patients were divided into two groups: those who underwent ER alone (298 cases), and those who underwent initial or additional SR with lymph node dissection (632 cases). Group differences in recurrence-free survival were evaluated using the Kaplan-Meier method and log-rank test. Associations between recurrence and clinicopathological features were evaluated in Cox regression analyses; hazard ratios (HRs) were calculated for the total population and each group. RESULTS: Recurrence occurred in four cases (1.34%) in the ER group and six cases (0.95%) in the SR group (p = 0.32). Endoscopic resection, rectal location, and poor or mucinous (Por/Muc) differentiation were prognostic factors for recurrence in the total population. Por/Muc differentiation was prognostic factor in both groups. Female sex, depressed-type morphology, and lymphatic invasion were also prognostic factors in the ER group, but not in the SR group. CONCLUSIONS: Endoscopic resection, rectal location, and Por/Muc differentiation are prognostic factors in the total population. For patients who undergo ER alone, female sex, depressed-type morphology, and lymphatic invasion are also risk factors for recurrence. For such patients, regional en-bloc surgery with lymph node dissection could reduce the risk of recurrence.

Practical problems of measuring depth of submucosal invasion in T1 colorectal carcinomas.

PURPOSE: Submucosal invasion depth (SID) in colorectal carcinoma (CRC) is an important factor in estimating risk of lymph node metastasis, but can be difficult to measure, leading to inadequate or over-extensive treatment. Here, we aimed to clarify the practical aspects of measuring SID in T1 CRC. METHODS: We investigated 568 T1 CRCs that were resected surgically at our hospital from April 2001 to December 2013, and relationships between SID and clinicopathological factors, including the means of measurement, lesion morphology, and lymph node metastasis. RESULTS: Of these 568 lesions, the SID was ≥1000 µm in 508 lesions. SIDs for lesions measured from the surface layer were all ≥1000 µm. Although lesions with SIDs ≥1000 µm were associated with significantly higher levels of unfavorable histologic types and lymphovascular infiltration than shallower lesions, a depth of ≥1000 µm was not a significant risk factor for lymph node metastasis (LNM) (6.7 vs. 9.8 %; P = 0.64), and no lesions for which the sole pathological factor was SID ≥1000 µm had lymph node metastasis. Protruded lesions showed deeper SIDs than other types. CONCLUSIONS: Although we found several problems of measuring SID in this study, we also found, surprisingly, that SID is not a risk factor for lymph node metastasis, and its measurement is not needed to estimate the risk of lymph node metastasis.

Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis.

BACKGROUND AND AIM: Recent advances in endoscopic technology have allowed many T1 colorectal carcinomas to be resected endoscopically with negative margins. However, the criteria for curative endoscopic resection remain unclear. We aimed to identify risk factors for nodal metastasis in T1 carcinoma patients and hence establish the indication for additional surgery with lymph node dissection. METHODS: Initial or additional surgery with nodal dissection was performed in 653 T1 carcinoma cases. Clinicopathological factors were retrospectively analyzed with respect to nodal metastasis. The status of the muscularis mucosae (MM grade) was defined as grade 1 (maintenance) or grade 2 (fragmentation or disappearance). The lesions were then stratified based on the risk of nodal metastasis. RESULTS: Muscularis mucosae grade was associated with nodal metastasis (P = 0.026), and no patients with MM grade 1 lesions had nodal metastasis. Significant risk factors for nodal metastasis in patients with MM grade 2 lesions were attribution of women (P = 0.006), lymphovascular infiltration (P < 0.001), tumor budding (P = 0.045), and poorly differentiated adenocarcinoma or mucinous carcinoma (P = 0.007). Nodal metastasis occurred in 1.06% of lesions without any of these pathological factors, but in 10.3% and 20.1% of lesions with at least one factor in male and female patients, respectively. There was good inter-observer agreement for MM grade evaluation, with a kappa value of 0.67. CONCLUSIONS: Stratification using MM grade, pathological factors, and patient sex provided more appropriate indication for additional surgery with lymph node dissection after endoscopic treatment for T1 colorectal carcinomas.

'Head Invasion' Is Not a Metastasis-Free Condition in Pedunculated T1 Colorectal Carcinomas Based on the Precise Histopathological Assessment.

BACKGROUND/AIM: Previous reports stated that pedunculated T1 colorectal carcinomas with 'head invasion' showed almost no nodal metastasis, requiring endoscopic treatment alone. However, clinically, some lesions develop nodal metastasis. We aimed to validate the necessity of distinguishing between 'pedunculated' and 'non-pedunculated' lesions, and also between 'head' and 'stalk' invasions. METHODS: Initial or additional surgery with lymph node dissection was performed in 76 pedunculated and 594 non-pedunculated cases. Among pedunculated lesions, the baseline was defined as the junction line between normal and neoplastic epithelium (Haggitt's level 2). The degree of invasion was classified as 'head invasion' (above the baseline) or 'stalk invasion' (beyond the baseline). Clinicopathological factors were analyzed with respect to nodal metastasis. RESULTS: Nine of 76 (11.8%) pedunculated cases and 52/594 (8.8%) non-pedunculated cases developed nodal metastasis (p = 0.40). No significant differences were found in the rate of nodal metastasis between 'head invasion' (4/30, 13.3%) and 'stalk invasion' (5/46, 10.9%). All the 4 cases with 'head invasion' had at least one pathological factor. CONCLUSIONS: 'Head invasion' was not a metastasis-free condition. Even for pedunculated T1 cancers with 'head invasion', additional surgery with lymph node dissection should be considered if these have pathological risk factors.

Efficiency of endocytoscopy in differentiating types of serrated polyps.

BACKGROUND: Accurate endoscopic criteria are needed to differentiate serrated polyps, including hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA), because some are precursors of colorectal cancers. OBJECTIVE: To determine the endocytoscopic features of each type of serrated polyp, especially the shapes of lumens and nuclei. DESIGN: Retrospective study. SETTING: Single, tertiary-care referral center. PATIENTS: Patients who underwent removal of serrated polyps from May 2005 to December 2012. INTERVENTION: Endocytoscopy was performed. Endocytoscopic images were evaluated by assessing the shapes of the lumens and nuclei of the target lesions. MAIN OUTCOME MEASUREMENTS: The significant endocytoscopic features in differentiating among types of serrated polyps. RESULTS: Of the 58 eligible lesions, 27 were classified as HP, 12 as SSA/P, and 19 as TSA. Most HPs (77.8%) had star-like lumens, and most SSA/Ps (83.3%) had oval lumens. The lumens of TSAs were serrated (31.6%) or villous (68.4%), with both shapes seen only in TSAs. Most HPs (92.6%) and SSA/Ps (75.0%) had small, round nuclei, and all TSAs had fusiform nuclei. Features significantly differentiating TSAs from HPs and SSA/Ps were the presence of fusiform nuclei (P < .001) and villous (P < .001) and serrated (P = .002) lumens. The presence of oval lumens was significantly characteristic of SSA/Ps (P < .001), and the presence of star-like lumens was significantly characteristic of HPs (P < .001). LIMITATIONS: Retrospective design. Single-center study. CONCLUSION: The shape of lumens and nuclei on endocytoscopy can efficiently differentiate among the different types of serrated polyps. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry UMIN000007850.).

Endocytoscopy can provide additional diagnostic ability to magnifying chromoendoscopy for colorectal neoplasms.

BACKGROUND AND AIM: Pit pattern (PIT) diagnosis with magnifying chromoendoscopy is effective diagnostic method for predicting a massively invasive submucosal colorectal cancer (SMm) which has possibility of metastasis, whereas endocytoscopy (EC) is recently reported to provide excellent diagnostic ability by enabling in vivo cellular visualization. The aim was to assess the additional diagnostic value of EC to PIT for diagnosing colorectal lesions. METHODS: We conducted a retrospective comparative analysis using a prospectively recorded database in a referral hospital. The subjects were 538 patients who were detected of a colorectal lesion with use of a magnifying colonoscope with EC capability. Each detected lesion was initially diagnosed by PIT findings followed by EC diagnosis by the on-site endoscopist. The diagnostic abilities in predicting neoplastic change and SMm were compared between PIT and PIT plus EC. RESULTS: Overall, 514 lesions from 455 patients were available for analysis. Of them, there were 58 non-neoplastic lesions, 352 adenomas, 15 slightly invasive submucosal cancers, and 89 SMm. The diagnostic abilities of predicting neoplastic change were comparable between PIT and PIT plus EC: sensitivity was 97.8% versus 97.4%, specificity was 91.4% versus 89.7%, and accuracy was 97.1% versus 96.5%. Regarding those of predicting SMm, PIT plus EC showed additional specificity and accuracy to PIT: specificity was 99.1% versus 97.6% (P = 0.041), and accuracy was 96.3% versus 93.8% (P = 0.004). CONCLUSIONS: Though PIT has feasible diagnostic ability for predicting both neoplastic change and SMm, EC provides additional diagnostic value to PIT diagnosis for predicting SMm.

Double staining with crystal violet and methylene blue is appropriate for colonic endocytoscopy: an in vivo prospective pilot study.

BACKGROUND AND AIM: Endocytoscopy (EC) at ultra-high magnification enables in vivo visualization of cellular atypia of gastrointestinal mucosae. Clear images are essential for precise diagnosis by EC. The aim of the present study was to evaluate the optimal staining method for EC in the colon. METHODS: Thirty prospectively enrolled patients were allocated 1:1:1 to three distinct staining methods: 0.05% crystal violet (CV) alone, 1% methylene blue (MB) alone, or CV+MB (CM double). Normal rectal mucosae were stained with each dye and videos of EC images were recorded. Visibility of nuclei and gland formation after staining were evaluated as 'recognizable' or 'not recognizable'. Time for each parameter to become 'recognizable' was measured, and the average times for the three staining regimens were compared. RESULTS: MB alone and CM double staining resulted in 'recognizable' (102 ± 27 vs 89 ± 22 s, P=0.263) nuclei within comparable periods of time, whereas CV alone was unable to identify nuclei. Gland formation became 'recognizable' sooner after CM double staining than after MB alone (61 ± 16 vs 108 ± 24 s, P<0.001). CONCLUSIONS: Double staining with CV and MB, which rapidly provided recognizable images of both nuclei and gland formation, is an appropriate staining regimen for colonic EC.

Clinical usefulness of pit patterns for detecting colonic lesions requiring surgical treatment.

BACKGROUND: The number of patients suffering from colorectal cancer is increasing. According to Japanese guidelines, lesions with a submucosal invasive depth >1,000 µm should be treated with radical proctocolectomy. We propose and evaluate a new clinical classification for pit patterns that uses endoscopy to assess lesion depth for determination of the appropriate therapeutic approach for early colorectal cancers and adenomas. METHODS: Endoscopic images of colorectal adenomas and early cancer cases with type V(I) pit pattern, resected surgically or endoscopically from April 2002 to April 2007 at Showa University Yokohama Northern Hospital, were utilized for analysis. Each image was retrospectively analyzed for (A) pit narrowness, (B) irregular pit margins, and (C) indistinct stromal staining. Sensitivity, specificity, and predictive value were evaluated as major outcomes, using pathological results as the standard. RESULT: In total, 186 cases were assessed. With all features considered (A, B, and C), the sensitivity, specificity, and positive and negative predictive values were 47.8%, 86.3%, 66.0%, and 74.2%, respectively. When limited to two features (A and B), these values were 75.3%, 81.2%, 70.2%, and 84.8%, respectively. CONCLUSION: Our results suggest that the established criteria can, to a certain degree, distinguish between high and low irregularity in colorectal lesions with V(I) pit pattern indicating submucosal cancer infiltration of more or less than 1,000 µm with the clinical consequence of surgery versus endoscopic mucosal resection/endoscopic mucosal dissection.

Narrow-banding images and structures of microvessels of colonic lesions.

BACKGROUND: Magnifying colonoscopy with NBI has been shown to be useful for the differential diagnosis of tumors. However, the relationship between findings on NBI magnification and the microvessel architecture of colorectal lesions remains to be clarified. AIMS: The aim of this study was to clarify the correlation between NBI findings and the microvascular architecture of colorectal lesions according to the depth of microvessels from the mucosal surface. METHODS: A total of 22 colorectal lesions (11 tubular adenomas and 11 hyperplasia) obtained from 22 patients were studied. These lesions were analyzed microscopically on tissue specimens immunostained with CD34. Three-dimensional images were reconstructed from serial sections of tubular adenomas, hyperplasia, and normal mucosa. RESULTS: Three-dimensional reconstructed images of tubular adenoma and normal mucosa to a depth of less than 150 µm from the mucosal surface showed similar structures to images obtained by NBI magnification. Microvessel diameter was significantly larger in tubular adenoma than in normal mucosa (P = 0.002) and hyperplasia (P = 0.034), and microvessel area was significantly larger in tubular adenoma than in normal mucosa (P < 0.001) and hyperplasia (P < 0.001) only in the superficial mucosal layer (to a depth of less than 150 µm). CONCLUSIONS: TA was characterized by thicker microvessels and higher volume of microvessels than NM and HP. Compared with white light, NBI can more accurately depict the characteristics of microvessels because it uses light with short wavelengths, thereby contributing to high diagnostic capability.

Endoscopic characteristics of colorectal serrated lesions.

BACKGROUND/AIMS: With the recent changes of pathological concepts, colorectal serrated lesions can be now divided into traditional serrated adenoma, typical hyperplastic polyp and sessile serrated polyp. The aim of this study is to clarify the endoscopic differences among these three groups. METHODOLOGY: A total number of 362 serrated lesions larger than 5mm were evaluated. These were detected with ordinary view and observed also with magnifying chromoendoscopic view. The final pathologic diagnosis of the resected specimens was made blinded. RESULTS: There were significant differences between traditional serrated adenoma and sessile serrated polypconcerning location, configuration and color. In chromoendoscopy, most of sessile serrated polyps and typical hyperplastic polyps showed star-like pattern, in contrast with traditional serrated adenomas most of which had fernor pinecone-like pattern. The differential diagnosis between traditional sessile polyp and the other two was possible with high accuracy. On the other hand, endoscopic distinction between sessile serrated polyp and typical hyperplastic polyp was not easy, except that the location and size were significantly different. CONCLUSIONS: We can endoscopically differentiate between traditional serrated adenoma and sessile serrated polyp or typical hyperplastic polyp, but it is difficult to differentiate between the latter two.

Vascular pattern classification of colorectal lesions with narrow band imaging magnifying endoscopy.

Magnifying narrow band imaging (NBI) has enabled to observe the vascular pattern of colorectal lesions. Their broad findings have been divided into six groups according to endoscopical vascular features: normal, faint, network, dense, irregular and sparse. Most hyperplastic polyps show a faint pattern. The vascular patterns of adenomas are mainly network or dense ones. The predominant vascular patterns of cancer were irregular and sparse. Indeed, irregular pattern has found to be characteristic for protruded or flat-elevated cancer, whereas sparse pattern unique for depressed cancer. Through NBI, neoplastic lesions could be differentiated from those non-neoplastic with sensitivity of 83.5%, specificity of 98.7% and accuracy of 98.2%. It was able to distinguish between massively submucosal invasive cancers and slightly submucosal invasive cancers by using the vascular pattern with 91.0% sensitivity and 79.4% specificity. The overall accuracy was 88.3%. NBI system has showed to be a valuable technique for distinguishing neoplastic from non-neoplastic lesions, as well as massively from slightly submucosal invasive cancer. Therefore, vascular pattern analysis might be a promising tool for determining treatment selection, whether endoscopical or surgically.

Thrombomodulin expression impacts the recurrence and long-term survival in pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most aggressive digestive cancers. The tumor expression of thrombomodulin (TM) is correlated with favorable prognosis in several types of cancer. However, this correlation has not been confirmed in hepato-pancreato-biliary cancer. The aim of this study was to evaluate the prognostic value of TM expression in resected pancreatic ductal adenocarcinoma. METHODS: The data of patients who underwent pancreatic resection for pancreatic invasive ductal adenocarcinoma were obtained from a prospectively maintained database. A total of 131 patients were included. Paraffin sections of tumor tissues were stained immunohistochemically using TM antibody. The patients were divided into two groups: the TM-positive or TM-negative group. RESULTS: The specimens were TM-positive in 72 cases. TM expression was a significant factor of favorable prognosis in univariate analysis for disease-free (DFS) and overall survival (OS). The median OS in the TM-positive patients was 32.9 mo, which was better than the 20.0 mo in TM-negative patients (P =.006). TM positivity retained its significance on multivariate analysis for DFS (hazard ratio [HR] 0.651, 95% confidence interval [CI] 0.433-0.979, P =.039) and OS (HR 0.569, 95% CI 0.376-0.862, P =.008). CONCLUSIONS: The tumor expression of TM is a favorable factor for OS in resected pancreatic invasive ductal adenocarcinoma.

Multicenter prospective in vivo study of an endocytoscope system (ECS) for superficial esophageal cancer.

BACKGROUND: Endocytoscope systems (ECS) can visualize cellular nuclei of the mucosa of the gastrointestinal tract and are predicted to provide real-time microscopic diagnosis. However, their practical diagnostic performance remains unclear. Therefore, we conducted a multicenter prospective study to evaluate the visualization of superficial esophageal neoplasm in vivo using an ECS, and its diagnostic capability. METHODS: The study target was histologically confirmed squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN). An integrated ECS was used to obtain ECS images. In each patient, three ECS images of cancerous and corresponding noncancerous regions were selected for evaluation. A pathological review board of five certified pathologists made the final diagnosis of the images. The primary endpoint was the sensitivity of ECS diagnosis by pathologists. RESULTS: ECS images of 68 patients were assessed: 42 lesions were mucosal SCC, 13 were submucosal SCC, and 13 were HGIN. The rate of assessable images was 96% (95% CI 87.6-99.1). The sensitivity of ECS diagnosis by pathologists was 88% (95% CI 77.2-94.5). CONCLUSIONS: ECS can provide high-quality images of cancerous lesions and a high diagnostic accuracy by pathologists, and could be useful for real-time endoscopic histological diagnosis of SCC and HGIN. TRIAL REGISTRATION: The UMIN Clinical Trials Registry Identification Number: 000004218.

Transition from low-grade endometrial stromal sarcoma to high-grade endometrial stromal sarcoma.

We report on a case of a primary low-grade endometrial stromal sarcoma (ESS) that progressed to a secondary high-grade ESS. In the secondary tumor, the immunohistochemical profile and focal tumor cell proliferation pattern suggested that this tumor was not truly undifferentiated, but possessed features of endometrial stroma. Low-grade ESS of our patient's primary tumor showed p53 protein overexpression, which is unusual in low-grade ESS, and her secondary high-grade ESS showed more prominent p53 immunoreactivity. This indicates that low-grade ESS that shows p53 immunoreactivity might progress to high-grade ESS, and it is considered that such cases of low-grade ESS should pay attention to the prognosis. Immunoreactivity for epidermal growth factor receptor was observed in both tumors, suggesting a relationship between the primary and secondary tumors in our case. Further study requires more immunohistochemical data for cases in which low-grade ESS transitions to high-grade ESS; in particular, data on epidermal growth factor receptor expression are necessary to define new therapeutic strategies for ESS.