Magnifying Endoscopy, Stereoscopic Microscopy, and the Microvascular Architecture of Superficial Esophageal Carcinoma

Kumagai, Youichi; Inoue, Haruhiro; Nagai, Kagami; Kawano, Tatsuyuki; Iwai, Takehisa

doi:10.1055/s-2002-25285

Cited by 225 publications

(225 citation statements)

References 9 publications

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“…[19][20][21][22] Inoue et al reported the terminal capillary inside the epithelial papillae of the normal squamous epithelium named intra-papillary capillary loop (IPCL).…”

Section: Discussionmentioning

confidence: 99%

“…Japanese endoscopists currently apply these features for diagnosing the depth of tumor invasion, and in this context, high accuracy of preoperative magnifying endoscopy has been reported. [20][21][22] Considering these observations, we compared the four different categories of normal squamous epithelium, LGIN (borderline malignancy), M1 and M2 cancer, and M3 or deeper cancer.Using cancerous and precancerous lesion of the esophagus, Shamma et al 5 reported that the COX-2 immunoreactivity score was highest in high-grade dysplasia, and then gradually decreased according to cancer progression (at the present time, ''highgrade dysplasia'' is considered to be ''high-grade intraepithelial neoplasia'' in the Japanese classification, 1 which is included in ''M1 and M2 cancer'' in the present report). Our present study revealed positive staining for 71.9% of COX-2 and 80.7% of iNOS among M1, M2 regions.…”

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confidence: 99%

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Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma

Kumagai

Sobajima

Higashi

et al. 2015

International Surgery

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Using immunohistochemical staining, the present study was conducted to examine whether cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) affect angiogenesis in early-stage esophageal squamous cell carcinoma (ESCC). We also analyzed the correlation between these two factors. Cyclooxygenase 2, iNOS, and angiogenesis in early-stage ESCC are unclear. Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia (LGIN), and 45 samples of superficial esophageal cancer, we observed the expression of COX-2 and iNOS. We then investigated the COX-2 and iNOS immunoreactivity scores and the correlation between COX-2 or iNOS scores and microvessel density (MVD) using CD34 or CD105. The intensity of COX-2 or iNOS expression differed significantly according to histological type (P , 0.001). The scores of COX-2 and iNOS were lowest for normal squamous epithelium, followed in ascending order by LGIN, carcinoma in situ and tumor invading the lamina propria mucosae (M1-M2 cancer); and tumor invading the muscularis mucosa (M3) or deeper cancer. The differences were significant (P , 0.001). Cancers classified M1-M2 (P , 0.01 and P , 0.05, respectively); M3; or deeper cancer (P , 0.01) had significantly higher COX-2 and iNOS scores than normal squamous epithelium. There was a significant correlation between COX-2 and iNOS scores (P , 0.001, r s ¼ 0.51). Correlations between COX-2 score and CD34-positive MVD or CD105-positive MVD were significant (r s ¼ 0.53, P , 0.001; r s ¼ 0.62, P , 0.001, respectively). Inducible nitric oxide synthase score was also significantly correlated with CD34 MVD and CD105 MVD (r s ¼ 0.45, P , 0.001; r s ¼ 0.60, P , 0.001, respectively). Chemoprevention of COX-2 or iNOS activity may blunt the development of ESCC from precancerous lesions.Key words: COX-2 -iNOS -CD34 -CD105 -Esophageal cancer -Angiogenesis T he depth of invasion of superficial esophageal carcinoma is expressed in accordance with the sub-classification criteria of the Japan Esophageal Society (Guidelines for clinical and pathologic studies on carcinoma of the esophagus). 1Angiogenesis is essential for cancer progression in order to supply nutrients and oxygen, and remove metabolic waste. Understanding the mechanism of angiogenesis, especially during the early stage of cancer progression, may uncover new targets for treatment or prevention.We have previously reported in detail the use of microvessel density (MVD) as a feature of earlystage esophageal squamous cell carcinoma (ESCC) revealed by immunostaining using CD34 and CD105.2 In that report, we mentioned that MVD based on CD34 and CD105 immunostaining increased according to the grade of atypia or depth of ESCC progression, and also that these findings were correlated with the morphological features of microvessels at the surface of superficial ESCC observed by magnifying endoscopy.As a subsequent step, we examined the angiogenic factors that induced these newly recruited capillaries at the early stage of ESCC progression. Based on a revie...

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“…[19][20][21][22] Inoue et al reported the terminal capillary inside the epithelial papillae of the normal squamous epithelium named intra-papillary capillary loop (IPCL).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma

Kumagai

Sobajima

Higashi

et al. 2015

International Surgery

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“…In the NBI mode, normal laryngeal mucosa consists of submucosal vessels (appearing green) connecting with an arborescent vascular network (appearing dark brown). Abnormalities of these intraepithelial papillary capillary loop (IPCL), located beneath the basement membrane of epithelium, are usually classified in accordance with their shape changes; such changes have been found to predict the depth of superficial cancer invasion (134,135). Classification of laryngeal lesions has been reported in Figure 4.…”

Section: Narrow Band Imaging (Nbi)mentioning

confidence: 99%

Laryngeal preneoplastic lesions and cancer: challenging diagnosis. Qualitative literature review and meta-analysis.

Mannelli

Cecconi

Gallo

2016

Critical Reviews in Oncology/Hematology

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Abstract.Background: Multi-step cancerogenesis guides laryngeal cancer onset and it includes a wide variety of pre-cancerous lesions that are macroscopically challenging to identify and distinguish from initial cancerous foci. Since the treatment of laryngeal cancer and its precursor lesions has a great impact on important laryngeal basic functions, early detection and preoperative assessment are important for a curative and function-preserving therapy. Nowadays, despite the high number of more advanced diagnostic techniques and methods, unfortunately, it is not uncommon for different clinicians to use different nomenclature or to identify different stage for the same laryngeal lesion. From these observations, it is obvious that an instrument offering the possibility to detect precancerous lesions, early cancerous lesions, and satellite foci or second primaries would be the key to improving management and outcome in laryngeal patients. Object. Different modalities of diagnostic techniques of laryngeal lesions exist. Rather than difference between benign and obvious malignant diseases, more difficult is to detect the presence of precancerous epithelial alterations. Not all tests achieve the same diagnostic accuracy, hence this meta-analysis of literature aimed to synthesize the validity of each single diagnostic technique in identifying and staging laryngeal disease. Methods: A systematic review of literature was led searching for articles mentioning the following terms including their various combinations to maximize the yield: larynx, laryngeal precancerous lesions, laryngeal cancer, white light (WL) endoscopy, stroboscopy, contact endoscopy (CE), autofluorescence (AF), ultrasound (US), narrow band imaging (NBI), computed axial tomography (CAT), magnetic resonance imaging (MRI), positron emission tomography (PET), CAT/PET. Then, a quantitative analysis was carried on for paper published after 2005 onward, reporting a minumun series of 10 patients each study, declaring sensitivity and specificity of each diagnostic system. Results: The search identified 7215 publications, of which 3616 published after 2005, with a final results of a total of 214 articles stratified and included by our selection criteria. 42 out of 214 articles were selected for quantitative synthesis. 25 out of 41 studies had a quality score of ≥ 6 (good), 16 presented a score between 4 and 5 (fair). While objections can be raised about the pooling of different diagnostic procedures under the same group and the high level of heterogeneity in the meta-analyses, the inclusion of over 4400 laryngeal lesions makes the results fairly robust. Conclusions: A comprehensive overview of the most recent advances in laryngeal imaging technology combined with all of the information needed to interpret findings and successfully manage patients with voice disorders can be found herein. With these data, clinicians can riskstratify patients and select proper examination modalities in order to provide appropriate care. Moreover, study limitations, together with p...

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“…Kumagai et al examined surgically resected specimens of superficial esophageal cancer by stereoscopic microscopy, using the Microfil injection technique (2). Furthermore, they histomorphometrically measured the caliber of superficial blood vessels of esophageal tumors and found that vessel caliber gradually increased in parallel to the depth of invasion (16).…”

Section: Discussionmentioning

confidence: 99%

Microvascular architecture of early esophageal neoplasia

Kaga

Inoue²,

Kudo³

et al. 2011

Oncol Rep

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Abstract. Progress in magnifying endoscopy has allowed endoscopic atypia to be evaluated on the basis of the presence or the absence of microvascular hyperplasia in a tumor. We focused our attention on intra-epithelial papillary capillary loops (IPCLs) and studied 20 cases of esophageal neoplasia (IPCL type III, 10 cases; IPCL type IV, 10 cases) and 99 vessels (IPCL type III, 24 vessels; IPCL type IV, 75 vessels). We evaluated the histopathological findings and measured vessel caliber, distance from the basement membrane, distance between blood vessels and thickness of the epithelium. According to the Vienna classification, the histological findings in the 10 patients with IPCL type III lesions were classified as category 1 (negative for neoplasia/dysplasia) in 8 patients and category 3 (non-invasive low grade neoplasia) in 2 patients. The histological findings in the 10 patients with IPCL type IV lesions were classified as category 1 in 1 patient, category 3 in 4 patients and category 4 (non-invasive high grade neoplasia) in 5 patients. The vessel caliber of IPCL type IV lesions (mean, 5.9±2.7 µm) was significantly larger than that of IPCL type III lesions (mean, 4.8±1.5 µm) (P= 0.013). The distance from the basement membrane of IPCL type IV lesions (mean, 99.9±34.4 µm) was significantly greater than that of IPCL type III lesions (mean, 58.0±36.2 µm) (P=1.52562E -06 ). The distance between blood vessels and the thickness of the epithelium did not differ significantly between IPCL type III and IPCL type IV lesions. Our results revealed that changes in vessels of IPCL type IV lesions involve two factors: increased vessel caliber and prolongation of IPCLs toward the surface. These vascular changes appear to be associated with increased atypia of blood vessels. IntroductionIn category 3 of the Vienna classification (non-invasive low grade neoplasia-low grade adenoma/dysplasia), neoplasia is present, but it is associated with a low risk of progression to invasive carcinoma. Therefore, clinicians may consider local treatment of the lesion or opt for follow-up. In category 4 (noninvasive high grade neoplasia), the risks of invasion and the development of metastases are increased. Local treatment such as endoscopic mucosal resection or local surgical treatment is therefore indicated (1). Therefore, the ability to distinguish category 3 lesions from category 4 lesions endoscopically would be beneficial. We previously noted that category 3 and category 4 lesions differ with respect to changes in blood vessels, i.e., the formation of intra-epithelial papillary capillary loops (IPCLs) (2-4).Superficial blood vessels in the esophageal mucosa are branching vessels that extend horizontally immediately above the lamina muscularis mucosa. Intrapapillary capillaries arise from these branching vessels in epithelial papillae and form single loops referred to as IPCLs (Fig. 1). Branching vessels are observed as we approach the normal mucosa on conventional endoscopy. Using magnifying endoscopy with a scope which can magnify objects...

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Magnifying Endoscopy, Stereoscopic Microscopy, and the Microvascular Architecture of Superficial Esophageal Carcinoma

Abstract: Observation of the microvascular architecture of superficial esophageal carcinoma is useful in the diagnosis of the depth of invasion.

Cited by 225 publications

References 9 publications

Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma

Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma

Laryngeal preneoplastic lesions and cancer: challenging diagnosis. Qualitative literature review and meta-analysis.

Microvascular architecture of early esophageal neoplasia

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