EUS followed by EMR for staging of high-grade dysplasia and early cancer in Barrett's esophagus

BACKGROUND: Accurate staging of high-grade dysplasia and of early cancer in Barrett's esophagus is important in the selection of patients for endoscopic therapy. METHODS: Patients with Barrett's esophagus and biopsy specimen proven high-grade dysplasia and adenocarcinoma in focal nodular lesions or in endoscopically unapparent flat lesions in short-segment Barrett's esophagus were initially staged with EUS. In patients with disease limited to the mucosa on EUS, cap-assisted EMR was performed. The depth of tumor invasion on EMR specimens was classified in a similar manner to squamous-cell cancer of the esophagus: m1 (epithelial layer, dysplasia), m2 (lamina propria invasion), m3 (muscularis mucosae invasion), sm (submucosal invasion). RESULTS: EUS was performed in 48 consecutive patients (27 with focal nodular lesions and 21 with microscopic lesions), and submucosal invasion was diagnosed in 8 (confirmed in 7/8 at surgery). EMR was carried out in the remaining 40 patients without significant complications. In the 25 patients with high-grade dysplasia on prior biopsy specimens, EMR confirmed m1 disease in 19; whereas in 6 (24%), invasive adenocarcinoma was detected (to m2 in 4; to m3 in 2). In the 15 patients with invasive cancer on prior biopsy specimens and staged as intramucosal cancer on EUS, intramucosal carcinoma was confirmed in 9 (m2 in 3; m3 in 6); whereas, in 6 patients (40%), submucosal invasion was found. Overall, EUS provided accurate staging in 41/48 patients (85%) with one patient overstaged and 6 patients understaged compared with pathologic staging obtained by surgery or EMR. Of the 34 patients with m1 to m3 staging after EMR, 29 were treated endoscopically and had no evidence of cancer after a mean follow-up of 22.9 months(standard deviation 9.2 months). CONCLUSIONS: EMR provides pathologic staging information that, in addition, may be helpful after EUS if a stage-determined approach is used in the management of high-grade dysplasia and of early cancer in Barrett's esophagus. EMR may be particularly useful for staging of focal nodules or in short-segment Barrett's esophagus with microscopic lesions when endoscopic therapy is an option.     

胃食管高级别上皮内瘤变内镜切除术前后病理结果对比研究

目的 比较胃、食管高级别上皮内瘤变病灶内镜活检与内镜切除标本病理诊断的异同.方法 选取近4年间147例内镜活检诊断为胃、食管黏膜高级别上皮内瘤变、经内镜下切除（EMR或ESD）患者的资料,对切除前后的病理结果进行对照分析.结果 147例患者活检病理均诊断胃、食管上皮内瘤变,其中胃41例,食管106例;内镜术后97例（66%）维持上皮内瘤变诊断,50例（34%）诊断为癌,且有11例已经侵犯到黏膜下层.病理分型腺癌34例,鳞癌16例,其中低-中分化癌22例（44%）.结论 内镜活检诊断胃、食管高级别上皮内瘤变的病例超过三分之一已经癌变,应该采取积极的治疗措施.     

结直肠高级别上皮内瘤变的临床分析38例

目的:研究结直肠高级别上皮内瘤变的临床病理特征,探讨临床合理治疗决策.方法:回顾性总结38例经内镜检查和病理初步诊断为结直肠高级别上皮内瘤变患者的,临床资料,分析其临床表现、内镜形态学、组织病理学特点、预后等,随访观察3-36 mo.结果:38例患者中,最终确诊17例为结直肠癌.21例仍为高级别上皮内瘤变.治疗前后诊断一致性较差(Kappa值为0.376).结直肠高级别上皮内瘤变合并癌的高危因素包括:肿瘤大小、内镜形态特点、症状严重、绒毛状腺瘤合并高级别上皮内瘤变、CEA或CA19-9增高等.结论:使用WHO新的诊断结直肠高级别上皮内瘤变需引起临床医生重视,特别是对于内镜下单纯活检病例.应当谨慎选择治疗方式和随访时间.     

内镜黏膜下剥离术在治疗胃上皮内瘤变中的应用与评价

目的探讨胃上皮内瘤变行内镜黏膜下剥离术(ESD)的可行性、必要性及疗效。方法对50例内镜下有明确病灶,表现为浅表病变,活检病理为上皮内瘤变的患者,行ESD切除病灶,对比术前术后病理结果,并内镜随访。结果 34例术前活检病理为低级别上皮内瘤变的病灶ESD术后病理诊断为低级别上皮内瘤变22例、高级别上皮内瘤变6例、黏膜内癌4例、黏膜下浅层癌2例。16例术前活检病理为高级别上皮内瘤变的病灶ESD术后病理诊断为慢性炎症肠上皮化生1例、高级别上皮内瘤变5例、黏膜内癌3例、黏膜下层癌7例。结论 ESD治疗内镜下有明确病灶的上皮内瘤变可及时发现早期胃癌,并有效预防胃癌的发生、发展。     

Endoscopic mucosal resection for early esophageal cancer with esophageal varices

Squamous cell carcinomas account for more than 80 % of esophageal malignancies in Germany. Alcohol and tobacco smoke are two of the most important risk factors. In superficial esophageal squamous cell carcinoma, endoscopic mucosal resection (EMR) is a very useful and effective treatment modality. However, in patients with submucosal esophageal cancer, radical esophageal resection is regarded as the gold standard for treatment at present. We report the case of a 71-year-old female patient with alcohol-induced liver cirrhosis with esophageal varices and a - therefore inoperable - early esophageal squamous cell carcinoma. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) seemed not to be an effective treatment modality due to its limited penetration depth (< 2 mm) and the liver toxicity of 5-ALA. PDT using Photofrin(R) with a higher penetration depth seemed to be associated with a high risk of bleeding due to the esophageal varices. Furthermore, this sensitizer is associated with a high rate of strictures and a long-lasting skin sensitivity. In contrast, arguments against an endoscopic mucosal resection (EMR) were endosonographically suspected submucosal tumor growth and a high risk of bleeding. Nevertheless, with respect to the lack alternatives we decided to perform an EMR after ligation of esophageal varices. The tumor could be resected in sano without major bleeding complication. Histology demonstrated a carcinoma in situ without submucosal invasion. After 3 months a second EMR was necessary due to recurrence. Meanwhile after a follow-up period of 18 months only low grade intraepithelial neoplasia without macroscopically suspicious lesions was observed.     

The importance of the concept and histological criteria of “intraepithelial squamous cell carcinoma” of the esophagus: in comparison between Western and Japanese criteria

Background

There are differences in the histological diagnostic criteria for early stage gastrointestinal carcinoma between Western and Japanese pathologists. Western histological criteria of carcinoma are “presence of stromal invasion of neoplastic cells”, while Japanese criteria are “the degree of cytological and structural abnormality of neoplastic cells, regardless of stromal invasion”. The aim of the present study is to clarify and review the present status of the Western and Japanese histological criteria of early stage esophageal squamous cell carcinoma (SCC) and also to clarify their significance and accuracy.

Methods

Twenty-nine Polish, German, and Japanese pathologists participated in this study. A total of 18 histological slides of biopsy, endoscopic submucosal dissection (ESD), and surgical resection of esophageal squamous lesions were diagnosed using a virtual slide system.

Results

Most of noninvasive (intraepithelial) carcinomas diagnosed by Japanese pathologists were diagnosed as high- or low-grade dysplasia (intraepithelial neoplasia) or reactive atypia by the majority of Polish and German pathologists. Diagnoses of not only high-grade dysplasia but also low-grade dysplasia or reactive lesion by Western criteria were given for many biopsy specimens of cases in which the corresponding ESD or surgical specimens showed definite stromal invasion.

Conclusion

There still exist differences in the histological diagnostic criteria for early stage esophageal carcinoma between Western and Japanese pathologists. The Japanese diagnostic criteria could improve agreement of diagnoses between biopsy and resected specimens of esophageal SCC. Moreover, diagnostic approaches using Western criteria may cause delay in the early diagnosis and treatment of esophageal SCC.

     

Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions

There is uncertainty regarding the value of endoscopic biopsy surveillance in Barrett's esophagus because, in retrospective studies, some patients with high-grade dysplasia in endoscopic biopsy specimens have had unexpected advanced adenocarcinoma discovered at the time of esophageal resection. We compared the accuracy of preoperative endoscopic biopsy diagnoses with the final pathologic diagnoses in esophagectomy specimens in 4 patients who had both high-grade dysplasia and intramucosal carcinoma and 4 other patients who had only high-grade dysplasia preoperatively. The histologic lesions in all 8 patients were documented in intact mucosa with no gross evidence of neoplasia by endoscopy. The preoperative diagnoses were defined with an endoscopic biopsy protocol in which specimens were taken with large-channel biopsy forceps at least every 2 cm throughout the length of Barrett's epithelium. Final pathologic diagnoses derived from detailed analysis of the resected specimens confirmed high-grade dysplasia without carcinoma in 4 patients and intramucosal carcinoma in 2 patients. The remaining 2 patients with a preoperative diagnosis of intramucosal carcinoma had focal submucosal invasion by carcinoma in the resected specimens, but no involvement of the muscularis propria or adventitial lymph nodes. Because the natural history of high-grade dysplasia is not known, the decision to operate on patients with this lesion must be carefully weighed and individualized for each patient. Two of our patients who underwent esophageal resection for high-grade dysplasia without cancer died, one immediately postoperatively and the other 9 mo later after a postoperative stroke. Once intramucosal carcinoma is documented, surgery should be considered if the patient is an acceptable operative risk. We conclude that systematic preoperative endoscopic biopsy of intact mucosa in Barrett's esophagus can correctly detect high-grade dysplasia, either alone or in combination with early, treatable adenocarcinoma.     

EMR for Barrett's esophagus-related superficial neoplasms offers better diagnostic reproducibility than mucosal biopsy

BACKGROUND: EMR of Barrett's esophagus (BE)-related superficial neoplasms represents an efficacious staging modality. It also allows for better pathologic grading compared with mucosal biopsy specimens. However, the interobserver variation in the interpretation of EMR specimens has not been tested. OBJECTIVE: To evaluate consistency in the diagnosis of BE-related neoplasia on EMR specimens. DESIGN: Nine pathologists reviewed 25 esophageal EMR specimens and corresponding biopsy specimens independently. Each pathologist classified the cases as either non-neoplastic BE, low-grade dysplasia, high-grade dysplasia, intramucosal adenocarcinoma, or invasive adenocarcinoma. Interobserver concordance for both specimens from EMRs and biopsies was measured by intraclass correlation and Kendall's coefficient of concordance. The proportion of agreement was also calculated for each specimen and compared for EMR and biopsy by using the Wilcoxon signed rank test. SETTING: Teaching hospitals. PATIENTS: Twenty-five patients who underwent EMR for BE-related neoplasia. RESULTS: The intraclass correlation and the Kendall's coefficient for the 25 biopsy specimens was 0.938 (95% CI 0.880-0.965) and 0.677, respectively; for the 25 EMRs, these were significantly improved, at 0.977 (95% CI 0.957-0.987) and 0.831, respectively. In addition, the proportion of agreement for EMR specimens was significantly better compared with biopsy specimens (P = .015). CONCLUSIONS: Interobserver agreement of BE-related neoplasia on EMR specimens is significantly higher compared with biopsy specimens. The results may relate to the larger tissue sampling compared with biopsy specimens and the ability to evaluate mucosal landmarks, such as double muscularis mucosae. Thus, we suggest that EMRs, in addition to being a staging and therapeutic procedure, improve diagnostic consistency.     

Significance of neoplastic involvement of margins obtained by endoscopic mucosal resection in Barrett's esophagus

OBJECTIVES: Although EMR has been used for elimination of neoplasia in BE, the significance of positive carcinoma margins and depth of invasion on endoscopic resection pathology has not been assessed using a valid standard. The aim of this study was to assess the accuracy of tumor staging by EMR using esophagectomy as the standard. METHODS: Medical records of patients, who underwent endoscopic resection for esophageal carcinoma or high-grade dysplasia in BE followed by esophagectomy, were reviewed. Data were abstracted from a prospectively maintained EMR database. Endosonography and endoscopic resection were performed by a single experienced endoscopist. Two experienced GI pathologists interpreted all histological results. Standard statistical tests were used to compare continuous and categorical variables. RESULTS: Twenty-five patients were included in the study. Three patients had mucosal carcinoma and 16 had submucosal carcinoma following endoscopic resection. Surgical pathology staging was consistent with preoperative EMR staging in all patients. No patient with negative mucosal resection margins had residual tumor at the resection site at esophagectomy. In patients with submucosal carcinoma, 8 had residual carcinoma at the EMR site at surgery and 5 patients had metastatic lymphadenopathy. CONCLUSIONS: Tumor staging using EMR pathology is accurate when compared with surgical pathology following esophagectomy. Negative margins on EMR pathology correlate with absence of residual disease at the EMR site at esophagectomy. Submucosal carcinoma on EMR specimens was associated with a high prevalence of residual disease at surgery (50%) and metastatic lymphadenopathy (31%).     

Lugol's dye spray chromoendoscopy establishes early diagnosis of esophageal cancer in patients with primary head and neck cancer

OBJECTIVE: Patients with primary head and neck cancer show a predisposition to develop esophageal cancer. The aim of this study was to investigate in these patients: the prevalence of esophageal cancer comparing the value of chromoendoscopy using Lugol's solution examination to standard endoscopy, in the early diagnosis of esophageal cancer. METHODS: Prospective observational study at a state general university hospital in Sao Paulo, Brazil. 326 consecutive adult patients with primary head and neck cancer were evaluated. A standard endoscopy was performed, followed by a 2% Lugol's dye spray chromoendoscopy and histopathologic study. The prevalence of esophageal cancer was defined. The results of the two endoscopic methods were compared. RESULTS: Twenty-four patients with esophageal cancer and high-grade intraepithelial neoplasia were detected and had a prevalence of 7.36%. Chromoendoscopy and standard endoscopy were equivalent to the diagnosis of advanced and invasive esophageal cancer. However, standard endoscopy diagnosed 55% of high-grade intraepithelial neoplasia, in comparison to chromoendoscopy that detected 100%. CONCLUSIONS: Patients with primary head and neck cancer should be considered as high risks for the presence of esophageal cancer. Lugol's dye chromoendoscopy diagnosed high-grade intraepithelial neoplasia, which went unnoticed with standard endoscopy. It permits a more exact detection of lesion boundaries and facilitates a more precise targeting of biopsy fragments.     

Metachronous squamous cell carcinoma of the esophagus arising after endoscopic mucosal resection

BACKGROUND: Endoscopic mucosal resection (EMR) is being used increasingly to treat early stage esophageal carcinoma. However, the preserved esophageal mucosa may be the source of new lesions. The aims of this study were to analyze the frequency of metachronous esophageal carcinoma after EMR and to determine whether minute iodine unstained areas often associated with squamous cell carcinoma develop into carcinoma. METHODS: Eighty-two patients with esophageal squamous cell carcinoma who underwent EMR were studied. Based on the iodine staining pattern at initial EMR, they were divided into those with uniform (group U) and scattered (group S) types of background mucosa. Patients were followed by endoscopy with iodine staining (group U: median 39 months, range 12 to 71 months; group S: median 38 months, range 14 to 68 months). RESULTS: In total, 12 (14.6%) of 82 patients were found to have metachronous esophageal carcinoma during follow-up, including 6 (37.5%) of 16 patients in group S. The cumulative proportion of metachronous carcinoma-free subjects was significantly lower in group S than group U (p = 0.0048). CONCLUSIONS: Primary esophageal carcinoma develops frequently in patients who have undergone EMR for esophageal squamous carcinoma. The high frequency of metachronous carcinoma may be attributed to field carcinogenesis. Careful long-term endoscopic observation is required for patients who undergo EMR for esophageal carcinoma, especially those with scattered-type iodine staining of the background mucosa.     

CLINICAL USEFULNESS OF HIGH‐FREQUENCY ULTRASOUND PROBES FOR NEW INVASION DEPTH DIAGNOSIS IN SUBMUCOSAL COLORECTAL CARCINOMA

Recently it has become very important to diagnose more precisely the invasion depth of submucosal carcinoma prior to endoscopic mucosal resection (EMR) whether selecting lesion is with or without indications for EMR. This study aimed to evaluate the usefulness of high‐frequency ultrasound probes (HFUP) for preoperative diagnosis of vertical invasion depth < 1000 µm or not in superficial and sessile type submucosal colorectal carcinomas. Twenty‐seven cases of superficial and sessile type submucosal colorectal carcinoma were examined with high‐frequency ultrasound probes (HFUP; 15 or 20 MHz radial‐scan ultrasound probes; Olympus Optical, Tokyo, Japan and Fujinon Omiya, Saitama, Japan) at Hiroshima University Hospital and analyzed. Diagnostic accuracy was confirmed by comparing the ultrasonic with the pathologic vertical invasion depth of specimens resected either by EMR or surgical resection. Histologic depth of submucosal invasion was defined as the distance from muscularis mucosae measured microscopically with a micrometer. When muscularis mucosae in the tumor could not be detected, we measured the invasion depth from the surface of the carcinoma to the apex of the deepest invasive portion. As a result, invasion depth between ultrasonic image and histologic findings showed a significantly close correlation. HFUP diagnosis was demonstrated as useful in determining the distance of vertical invasion and for planning a therapeutic strategy against submucosal colorectal carcinomas.     

Prevalence of Perianal Intraepithelial Neoplasia in HIV-Infected Patients Referred for High-Resolution Anoscopy

Purpose This study was designed to describe perianal disease in a cohort of HIV-infected patients referred for high-resolution anoscopy. Methods A retrospective chart review was performed on 52 HIV-infected patients referred for high-resolution anoscopy from 2001 to 2005. All patients underwent anal canal and perianal high-resolution anoscopy in the office with biopsy of suspicious areas. Patients with high-grade intraepithelial perianal lesions underwent multiple biopsies under general anesthesia in the operating room to rule out malignancy. Results Of the 52 patients, 19 (37 percent) had perianal abnormalities noted on high-resolution anoscopy and underwent punch biopsy. The mean duration of known HIV infection in these 19 patients (15 males) was 10.6 years, with 17 on highly active antiretroviral therapy for the last 3-month period. Mean CD4 count was 371 cells/μl. Office perianal biopsies diagnosed two patients with invasive squamous-cell carcinoma and nine with high-grade squamous intraepithelial lesion. Seven of the nine patients with perianal high-grade squamous intraepithelial lesion on office biopsy were submitted to multiple biopsies under general anesthesia. One of these seven had an occult perianal squamous-cell carcinoma. Conclusions Perianal disease was common in this group of HIV-infected patients; 11 patients (21 percent of total) were diagnosed with squamous-cell carcinoma or high-grade squamous intraepithelial lesion. Because only 19 patients had clinically suspicious perianal lesions biopsied, this may be an underestimate. Our data suggest that anal canal neoplasia often is accompanied by perianal disease and illustrates the need for biopsy of any suspicious perianal lesions. Presented at the meeting of the American Society for Colposcopy and Cervical Pathology, Las Vegas, Nevada, March 12 to 17, 2006. Reprints are not available.     

SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA WITH BULKY GASTRIC HIATUS LYMPH NODE METASTASIS: A CASE REPORT

In patients with superficial esophageal cancer, especially in those with tumor invasion above the muscularis mucosae, lymph node metastasis is very rare. We report a case of superficial esophageal cancer who presented with lymph node metastasis. In another hospital a 49‐year‐old man was found to have a bulky tumor adjacent to the cardiac area of the stomach and a total gastrectomy was carried out. Postoperatively, the tumor was identified as a lymph node containing metastatic squamous cell carcinoma. The main lesion could not be identified on fluorodeoxyglucose positron emission tomography. On esophagogastric endoscopy, using the iodine spray technique, we found an unstained lesion about 32 cm from the incisor teeth. The tumor was removed using endoscopic mucosal resection. The entire resected specimen was examined histopathologically; the depth of the tumor was above the muscularis mucosae. Thirty‐four months after endoscopic mucosal resection, there is no sign of tumor recurrence or metastasis.     

High prevalence of anal squamous intraepithelial lesions and squamous-cell carcinoma in men who have sex with men as seen in a surgical practice

INTRODUCTION: Anal high-grade squamous intraepithelial lesions are probable invasive anal squamous-cell cancer precursors, and although unproved, treatment of high-grade squamous intraepithelial lesions may prevent progression to anal squamous-cell cancer. Men who have sex with men are often treated for benign anorectal disorders without consideration given to the possibility of concurrent high-grade squamous intraepithelial lesions or anal squamous-cell cancer. We determined the prevalence of anal high-grade squamous intraepithelial lesions and anal squamous-cell cancer in an urban surgical practice of men who have sex with men referred for treatment of anal condyloma and other benign noncondylomatous anal disorders. METHODS: One hundred thirty-one HIV-positive and 69 HIV-negative men who have sex with men referred for surgical treatment of presumed benign anorectal disease were evaluated by anal cytology, high-resolution anoscopy, and biopsy. Anal cytology and histology were reported with a modified Bethesda classification. RESULTS: One hundred fifty-seven patients (79 percent) were referred for condyloma, 4 (2 percent) for anal squamous intraepithelial lesions (anal high-grade squamous intraepithelial lesions) diagnosed by primary care providers, and 39 (19 percent) for other benign anorectal disorders. One hundred forty-three patients (93 percent) had abnormal anal cytology, with 107 (54 percent) having high-grade squamous intraepithelial lesions on cytology. Biopsy results revealed 120 patients (60.0 percent) with high-grade squamous intraepithelial lesions and 5 patients (3 percent) with invasive squamous-cell carcinoma. Four of five men with anal squamous-cell cancer were HIV positive. Fourteen men (36 percent) who have sex with men referred for noncondylomatous benign anal disorders had high-grade squamous intraepithelial lesions, and three (8 percent) had anal squamous-cell cancer. High-grade squamous intraepithelial lesions and anal squamous-cell cancer were seen most often at the squamocolumnar junction. CONCLUSIONS: Men who have sex with men referred for treatment of either condyloma or noncondylomatous benign anorectal disease had a high prevalence of anal high-grade squamous intraepithelial lesions and anal squamous-cell cancer. All men who have sex with men referred for treatment of benign anorectal disease should have high-resolution anoscopy and aggressive biopsy of all abnormal areas. Treatment of external lesions alone could miss high-grade squamous intraepithelial lesions or anal squamous-cell cancer.     

Endoscopic and histopathological characteristics suggesting the presence of gastric mucosal high grade neoplasia foci in cases initially diagnosed as gastric mucosal low grade neoplasia by forceps biopsy in Korea

Background

As biopsy sites may miss coexisting gastric mucosal high grade neoplasia (HGN) foci, making a diagnosis of gastric mucosal low grade neoplasia (LGN) based only on forceps biopsy specimens can be inaccurate. Therefore, to achieve an accurate diagnosis, endoscopic mucosal resection (EMR) of the entire lesion is required. However, EMR can cause serious complications such as perforation or bleeding. Considering these points, it is necessary to identify the characteristics suggesting coexisting HGN foci in cases initially diagnosed as LGN by forceps biopsy.

Methods

Three hundred and five lesions from 282 consecutive patients were initially diagnosed as LGN by forceps biopsy and later resected using EMR. The still photographs from endoscopies and pathology slides of these lesions were reviewed.

Results

After EMR, 272 lesions (89.2%) were finally diagnosed as LGN and 33 lesions (10.8%) were diagnosed as having HGN foci, including 1 intramucosal carcinoma. Univariate analysis showed that lesions >1.0?cm on endoscopy and lesions with tubulovillous or villous histology on forceps biopsy specimens were significantly more frequently found in cases with HGN than in LGN cases. Multivariate analysis demonstrated that lesion size >1.0?cm on endoscopy and findings of tubulovillous or villous histology on forceps biopsy specimens were independent risk factors for coexisting HGN foci in cases initially diagnosed as LGN by forceps biopsy.

Conclusions

If the lesions diagnosed as LGN by forceps biopsy are >1.0?cm on endoscopy or show tubulovillous or villous histology, EMR might be considered to avoid the risk of missing HGN foci.     

Efficacy of the revised Vienna Classification for diagnosing colorectal epithelial neoplasias

AIM： To prospectively investigate the efficacy of the revised Vienna Classification for diagnosing colorectal epithelial neoplastic lesions in cold biopsy specimens.METHODS： Patients were selected for inclusion if they had colorectal epithelial lesions that were not considered suitable for direct endoscopic resection,These included colorectal polyps ≥ 10 mm and lesions suspected of being carcinomas capable of invading the colorectal submucosa or beyond, including strictures, based on the cold biopsies obtained from each lesion prior to resection. We investigated the relationship between diagnoses based on cold biopsy samples using the revised Vienna Classification and resected specimens of the same lesions, and the therapeutic implications of diagnoses made using the revised Vienna Classification. The same cold biopsy specimens were also examined using the Japanese Group Classification guidelines, and compared with the resected specimens of the same lesions for reference.RESULTS： A total of 179 lesions were identified. The sensitivity, specificity, positive and negativepredictive values of the revised Vienna Classification for distinguishing between intramucosal lesions and submucosal invasive carcinomas in cold biopsy specimens was 22.2%, 100%, 100%, and 71.4%,respectively, and for distinguishing between intramucosal lesions and those invading the submucosa or beyond was 59.7%, 100%, 100%, and 37.6%,respectively. The sensitivity, specificity, positive and negative predictive values of the Japanese Group Classification for distinguishing between intramucosal lesions and submucosal invasive carcinomas in cold biopsy specimens was 83.3%, 91.4%, 83.3%. and 91.4%, respectively, and for distinguishing between intramucosal lesions and those invading the submucosa or beyond was 95.1%, 91.4%, 97.9%, and 82.1%, respectively. A total of 137 of 144 carcinomas that had invaded the submucosa or beyond and three high-grade intraepithelial neoplasias were diagnosed as ＂carcinoma＂ using the Japanese Group Classification system.CONCLUSION： The revised Vienna Classification for cold biopsy specimens has high positive predictive value in the diagnosis of colorectal carcinoma invasive to the subrnucosa or beyond.     

Low‐grade dysplasia component in early invasive squamous cell carcinoma of the esophagus

Background and Aims: It has not been determined whether low‐grade squamous dysplasia (LGD) of the esophagus is a precancerous lesion or not. If LGD progresses to squamous cell carcinoma, early carcinoma lesions that have such a natural history might contain a remaining LGD component. Methods: The lesions in the 68 patients with early invasive squamous cell carcinoma who underwent endoscopic mucosal resection were examined for the presence of an LGD component. If LGD components were observed, the degrees of architectural and cytological abnormalities of LGD components and those of tumor invasive fronts in the same lesions were studied. The degrees of abnormalities of 28 small LGD lesions were also studied. Results: Histological examination of resected specimens confirmed LGD components in 43% of the squamous cell carcinoma lesions. The lesions of lamina propria mucosae (m2) cancer contained a significantly broader area of LGD component than did the lesions of muscularis mucosae (m3) and submucosal layer (sm) cancer (P = 0.037). Mean score for the degrees of cytological abnormalities of LGD component was similar to that of tumor invasive front (P = 0.457) and significantly higher than that of small LGD lesions (P < 0.001). Conclusion: Our results indicate the possibility that the lesion was formed by a combination of small lesions that arose as a multicentric occurrence of squamous cell carcinoma and dysplasia. Our results also suggest that an LGD component would transform to carcinoma along with tumor progression. However, the concept of ‘basal cell layer type carcinoma in situ’ may be suitable for squamous cell lesions with a high degree of cytological abnormalities confined to the lower half of the epithelium.     

Endoscopic mucosal resection for early esophageal cancer and esophageal dysplasia

BACKGROUND/AIMS: Advances in diagnostic technology have led to increased detection of early esophageal cancer, which is suitable for endoscopic treatment. We performed endoscopic esophageal mucosal resection of such cancer and dysplasia using the endoscopic esophageal mucosal resection tube and evaluated the clinical benefit of this technique. METHODOLOGY: Twenty-nine patients with esophageal mucosal cancer (27 cases with 33 lesions) or dysplasia (2 cases with 2 lesions) diagnosed between September 1992 and March 1998 were assessed endoscopically for the depth and extent of invasion by double staining with toluidine blue and iodine. Endoscopic ultrasonography was also performed to assess the depth of invasion in 22 cases with 22 lesions. RESULTS: The 35 esophageal lesions comprised 27 esophageal carcinomas and 8 areas of dysplasia. Twenty of the 35 lesions were resected en bloc and 15 were resected piecemeal. Subsequent surgery was performed for 5 cases with 7 lesions out of 10 cases with 15 lesions that were histopathologically diagnosed as m3 or more invasive. No recurrence has been detected in 24 evaluable cases (including 1 who died of another disease, 2 in whom surgery could not be performed due to complications, and 3 who refused subsequent surgery). No patients died of esophageal cancer after a mean follow-up period of 30.9 +/- 18.9 months. The 4-year survival rate was 100% in the m2 or less invasive group of 19 cases with 20 lesions, 75% in the m3 or higher invasive group of 5 cases with 8 lesions and 100% in the surgery group of 5 cases with 7 lesions (NS). No serious complications occurred except for 1 patient. Circumferential mucosal resection was done in this patient, resulting in esophageal stenosis, which responded to esophageal dilation. CONCLUSIONS: Esophageal mucosal resection using the endoscopic esophageal mucosal resection tube is safe and beneficial for early esophageal cancer and dysplasia.     

Programmed cell death 4 nuclear loss and miR-21 or activated Akt overexpression in esophageal squamous cell carcinogenesis

The programmed cell death 4 (PDCD4) tumor suppressor is down-regulated in several malignancies, and the (subcellular) expression of its protein product is modulated by both oncomiR miR-21 and protein kinase B (Akt). PDCD4 and activated Akt (phosphorylated Akt [pAkt]) expression were assessed immunohistochemically in 53 tissue samples obtained from 25 endoscopic esophageal mucosal resections performed for squamous intraepithelial neoplasia (IEN) or squamous intramucosal carcinoma (IM-SSC). In total, 33 IEN (low-grade = 15; high-grade = 15) and 20 IM-SSC specimens were considered; 50 additional tissue samples of histologically proven normal esophageal mucosa were considered as normal controls. To further validate the results achieved, miR-21 expression (as assessed by quantitative real-time polymerase chain reaction and in situ hybridization) was tested in another series of 15 normal esophageal tissue samples, 15 high-grade IEN, and 15 IM-SCCs. Normal suprabasal squamous epithelial layers consistently featured strong PDCD4 nuclear immunostaining, which was significantly lower (P < 0.001) in IEN (both low-and high-grade) and in IM-SSC. Conversely, pAkt and miR-21 expression was significantly up-regulated in the whole spectrum of preneoplastic/neoplastic lesions considered. PDCD4 down-regulation, as assessed by immunohistochemistry, is a reliable biomarker of early-stage squamous cell esophageal neoplasia, providing additional information in the histological assessment of these lesions.