Nana Hayashi

Endoscopic prediction of deep submucosal invasive carcinoma: validation of the Narrow-Band Imaging International Colorectal Endoscopic (NICE) classification

BACKGROUND A simple endoscopic classification to accurately predict deep submucosal invasive (SM-d) carcinoma would be clinically useful. OBJECTIVE To develop and assess the validity of the NBI international colorectal endoscopic (NICE) classification for the characterization of SM-d carcinoma. DESIGN The study was conducted in 4 phases: (1) evaluation of endoscopic differentiation by NBI-experienced colonoscopists; (2) extension of the NICE classification to incorporate SM-d (type 3) by using a modified Delphi method; (3) prospective validation of the individual criteria by inexperienced participants, by using high-definition still images without magnification of known histology; and (4) prospective validation of the individual criteria and overall classification by inexperienced participants after training. SETTING Japanese academic unit. MAIN OUTCOME MEASUREMENTS Performance characteristics of the NICE criteria (phase 3) and overall classification (phase 4) for SM-d carcinoma; sensitivity, specificity, predictive values, and accuracy. RESULTS We expanded the NICE classification for the endoscopic diagnosis of SM-d carcinoma (type 3) and established the predictive validity of its individual components. The negative predictive values of the individual criteria for diagnosis of SM-d carcinoma were 76.2% (color), 88.5% (vessels), and 79.1% (surface pattern). When any 1 of the 3 SM-d criteria was present, the sensitivity was 94.9%, and the negative predictive value was 95.9%. The overall sensitivity and negative predictive value of a global, high-confidence prediction of SM-d carcinoma was 92%. Interobserver agreement for an overall SM-d carcinoma prediction was substantial (kappa 0.70). LIMITATIONS Single Japanese center, use of still images without prospective clinical evaluation. CONCLUSION The NICE classification is a valid tool for predicting SM-d carcinomas in colorectal tumors.

Efficacy and safety of telaprevir, a new protease inhibitor, for difficult-to-treat patients with genotype 1 chronic hepatitis C.

Summary.  The aims of this phase III study were to assess the efficacy and safety of telaprevir in combination with peginterferon alfa‐2b (PEG‐IFN) and ribavirin (RBV) for difficult‐to‐treat patients who had not achieved sustained virological response (SVR) to prior regimens in Japan. The subjects were 109 relapsers (median age of 57.0 years) and 32 nonresponders (median age of 57.5 years) with hepatitis C virus genotype 1. Patients received telaprevir (750 mg every 8 h) for 12 weeks and PEG‐IFN/RBV for 24 weeks. The SVR rates for relapsers and nonresponders were 88.1% (96/109) and 34.4% (11/32), respectively. Specified dose modifications of RBV that differed from that for the standard of care were introduced to alleviate anaemia. RBV dose reductions were used for 139 of the 141 patients. The SVR rates for relapsers did not depend on RBV dose reduction for 20–100% of the planned dose (SVR rates 87.5–100%, P < 0.05). Skin disorders were observed in 82.3% (116/141). Most of the skin disorders were controllable by anti‐histamine and/or steroid ointments. The ratios of discontinuation of telaprevir only or of all the study drugs because of adverse events were 21.3% (30/141) and 16.3% (23/141), respectively. A frequent adverse event leading to discontinuation was anaemia. Telaprevir in combination with PEG‐IFN/RBV led to a high SVR rate for relapsers and may offer a potential new therapy for nonresponders even with a shorter treatment period.

Warning for unprincipled colorectal endoscopic submucosal dissection: Accurate diagnosis and reasonable treatment strategy

Piecemeal endoscopic mucosal resection (EMR) is generally indicated for laterally spreading tumors (LST) >2 cm in diameter. However, the segmentation of adenomatous parts does not affect the histopathological diagnosis and completeness of cure. Thus, possible indications for piecemeal EMR are both adenomatous homogenous‐type granular‐type LST (LST‐G) and LST‐G as carcinoma in adenoma without segmentalizing the carcinomatous part. Diagnosis of the pit pattern using magnifying endoscopy is essential for determining the correct treatment and setting segmentation borders. In contrast, endoscopic submucosal dissection (ESD) is indicated for lesions requiring endoscopic en bloc excision, as it is difficult to use the snare technique for en bloc excisions such as in non‐granular‐type LST (LST‐NG), especially for the pseudodepressed type, tumors with a type VI pit pattern, shallow invasive submucosal carcinoma, largedepressed tumors and large elevated lesions, which are often malignant (e.g. nodular mixed‐type LST‐G). Other lesions, such as intramucosal tumor accompanied by submucosal fibrosis, induced by biopsy or peristalsis of the lesion; sporadic localized tumors that occur due to chronic inflammation, including ulcerative colitis; and local residual early carcinoma after endoscopic treatment, are also indications for ESD. In clinical practice, an efficient endoscopic treatment with segregation of ESD from piecemeal EMR should be carried out after a comprehensive evaluation of the completeness of cure, safety, clinical simplicity, and cost–benefit, based on an accurate preoperative diagnosis.

Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team.

Many clinical studies on narrow‐band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low‐grade intramucosal neoplasia, high‐grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

NBI magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team (JNET)

Many clinical studies on narrow‐band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low‐grade intramucosal neoplasia, high‐grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

Endoscopic submucosal dissection as total excisional biopsy for clinical T1 colorectal carcinoma.

Background/Aims: Only the depth of submucosal invasion can be estimated prior to determining the indications for endoscopic submucosal dissection (ESD) as a curative treatment for colorectal carcinoma (CRC). Here we evaluated the outcomes of ESD for clinical T1 CRCs. Methods: Of 660 patients who underwent ESD for CRC at the Hiroshima University Hospital between June 2003 and December 2013, we examined the outcomes of 37 (6%; 26 men, 11 women; mean age ± SD, 68 ± 12 years) who underwent ESD as total excisional biopsy for various reasons, in spite of an endoscopic diagnosis of T1 CRC. Results: The mean lesion size was 25 ± 14 mm; 14 lesions were protruding and 23 were superficial. The en bloc resection rate was 100% (37/37). The histological en bloc resection rate was 92% (34/37). ESD resulted in a positive vertical margin in 3 cases. Deep submucosal invasion was seen in 3 cases, 2 of which had severe submucosal fibrosis. Although severe submucosal fibrosis was not found in other cases, pathologic examination of the deepest invasive portion of the tumor revealed poorly differentiated adenocarcinoma. The rates of post-ESD bleeding and perforation were 8% (3/37) and 5% (2/37), respectively. All patients recovered under conservative therapy. No cases of recurrence were noted in patients without additional surgical resection when the lesions satisfied the curative conditions listed in the 2014 Japanese Society for Cancer of the Colon and Rectum guidelines. Conclusion: En bloc resection by ESD as total excisional biopsy for clinical T1 CRC is a highly effective treatment and establishes a precise histological diagnosis.

Relationship between Narrow-Band Imaging Magnifying Observation and Pit Pattern Diagnosis in Colorectal Tumors

Background/Aim: The aim of this study was to examine the relationship between narrow-band imaging (NBI) magnifying observation using the surface pattern as the main evaluation criterion and pit pattern diagnosis on the basis of magnifying observation using a dye in relation to the characteristics of colorectal tumors according to their morphologies. Methods: In this study, NBI observation and pit pattern diagnosis using a dye with magnifying observation were simultaneously performed in our hospital, and the consecutive 786 cases of colorectal lesions (hyperplasia, adenomata and early carcinomas) that had been endoscopically or surgically resected were retrospectively analyzed. NBI magnifying observation was in conformance with the Hiroshima classification and pit pattern diagnosis was in conformance with the Kudo and Tsuruta classification. The relationship between NBI magnifying observation and pit pattern diagnosis and that between NBI magnifying observation and the histological type/invasion depth were examined in relation to colorectal tumor morphology. Results: Type A corresponded to the type II pit pattern, type B corresponded to the type IIIS, type IIIL and type IV regular pit patterns, type C1 corresponded to the type VI slightly irregular pit pattern, type C2 corresponded to the type VI highly irregular pit pattern and type C3 corresponded to the type VN pit pattern. In the protruded type, the irregularity of type C1 or C2 lesions agreed with the type VI slightly or highly irregular pit pattern, respectively, in 114 cases (64.0%). Moreover, the irregularity was higher with NBI magnifying observation than with pit pattern diagnosis in 58 cases (32.6%). In the superficial type, the irregularity of type C1 or C2 lesions agreed with the type VI slightly or highly irregular pit pattern, respectively, in 63 cases (71.6%). Moreover, the irregularity was higher with NBI magnifying observation than with pit pattern diagnosis in 19 cases (21.6%). In the case of type C1 or C2 lesions, the irregularity tended to be higher with NBI magnifying observation than with pit pattern diagnosis in the protruded type compared to the superficial type (p = 0.087). Conclusion: The surface pattern, which was visible in NBI magnifying observation, differed from the pit pattern findings obtained by magnifying endoscopic observation using a dye. Findings were more detailed in pit pattern diagnosis using a dye than in NBI magnifying observation.

Towards safer and appropriate application of endoscopic submucosal dissection for T1 colorectal carcinoma as total excisional biopsy: Future perspectives

According to the Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for the Treatment of Colorectal Cancer, cases with T1 colorectal carcinoma should be considered for additional colectomy with lymph node dissection when histologically complete en bloc resection is endoscopically carried out and when one of the four risk factors listed below is present. These four risk factors are: (i) submucosal (SM) invasion depth ≥1000 μm; (ii) positive vascular invasion; (iii) poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous carcinoma; and (iv) grade 2/3 budding at the deepest part of SM invasion. However, the probability of lymph node metastasis is extremely low if none of these risk factors are present, with the exception of SM invasion depth ≥1000 μm. Consequently, it is assumed that there will be an increasing number of cases where no additional surgery is done, or cases of moderate invasive carcinoma in which endoscopic treatment is carried out to achieve an excisional biopsy, for which complete resection is applicable. In these cases, the preoperative diagnosis, resection techniques such as endoscopic submucosal dissection, features of resected specimens, and the accuracy of pathological diagnosis are all extremely important.

Endoscopic Assessment of Colorectal Cancer with Superficial or Deep Submucosal Invasion Using Magnifying Colonoscopy

Among early colorectal carcinoma, endoscopic treatment is generally indicative for cases with intramucosal to submucosal (SM) superficial invasion, because cases with SM deep invasion should be treated surgically due to the risk of lymph node metastasis. It is important, therefore, to distinguish between superficial and deep SM invasion in early colorectal carcinoma prior to treatment. In this review we assessed the clinical usefulness and knack of pit pattern and narrow band imaging (NBI) diagnosis using magnifying observation. VN type pit pattern, type C3 in NBI Hiroshima classification and NBI type 3 in NBI international colorectal endoscopic (NICE) classification are useful predictors of SM deep invasion. In NBI magnifying observation evaluation of both the vascular pattern and surface pattern are important. We have to use pit pattern diagnosis and NBI magnifying diagnosis as the situation demands with the knowledge of both advantage and disadvantage in each diagnostic method.

Clinical impact and characteristics of the narrow-band imaging magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team.

BACKGROUND AND AIMS The Japan NBI Expert Team (JNET) was established in 2011 and has proposed a universal narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors. The aim of this study was to evaluate the clinical usefulness of the JNET classification for colorectal lesions. METHODS We analyzed 2933 colorectal lesions, which were diagnosed by NBI magnifying observation before endoscopic treatment or surgery. The colorectal lesions consisted of 136 hyperplastic polyps/sessile serrated polyps (HPs/SSPs), 1926 low-grade dysplasia (LGD), 571 high-grade dysplasia (HGD), 87 superficial submucosal invasive (SM-s) carcinomas, and 213 deep submucosal invasive (SM-d) carcinomas. We evaluated the relationship between the JNET classification and the histologic findings of these lesions. RESULTS The sensitivity, specificity, positive and negative predictive values, and accuracy of Type 1 lesions for the diagnosis of HP/SSP were, respectively, 87.5%, 99.9%, 97.5%, 99.4%, and 99.3%; of Type 2A lesions for the diagnosis of LGD were 74.3%, 92.7%, 98.3%, 38.7%, and 77.1%; of Type 2B lesions for the diagnosis of HGD/SM-s carcinoma were 61.9%, 82.8%, 50.9%, 88.2%, and 78.1%; for Type 3 lesions for the diagnosis of SM-d carcinoma were 55.4%, 99.8%, 95.2%, 96.6%, and 96.6%, respectively. CONCLUSIONS Types 1, 2A, and 3 of the JNET classification were very reliable indicators for HP/SSP, LGD, and SM-d carcinoma, respectively. However, the specificity and positive predictive value of Type 2B were relatively lower than those of others. Therefore, an additional examination such as pit pattern diagnosis using chromoagents is necessary for accurate diagnosis of Type 2B lesions.