伴淋巴结转移的早期胃癌病理组织形态学研究

目的通过研究早期胃癌发展过程中组织形态学的变迁，预测其淋巴结转移的难易程度。方法以伴淋巴结转移的81例早期胃癌作为转移组，抽取81例不伴淋巴结转移者作为对照组，两组均含11例黏膜内癌，70例黏膜下癌，组织学分类及肿瘤部位相似，具可比性。将各组的肿瘤灶亚分类为表层部、浸润部，各病灶的病理组织形态学依据规范分为分化型、混合型、未分化型。对各病例相关因子进行统计学分析研究。结果浸润部较表层部组织分化程度低下者，转移组为40．7％，较对照组的11．9％为高。转移组表层部的分化型胃癌和未分化型胃癌，其浸润部同一组织学分化程度较对照组为低，其差异有统计学意义（分别为P〈0．01和P〈0．05）。转移组的表层部与浸润部的分化程度合致率为61．7％，明显低于对照组的77．8％，其差异有统计学意义（P〈0．05）。转移组的男女比率为1．9：1，较对照组的3．3：1为低，其差异有统计学意义（P〈0．05）。结论早期胃癌中，癌灶水平方向和浸润先端部的垂直方向组织学分化程度的变化更易出现。浸润部与黏膜同有层癌组织学分化程度不同者，尤其是组织学分化程度趋低下者易出现淋巴结转移。女性较男性更易出现淋巴结转移。     

内镜黏膜下剥离术治疗早期胃癌

目的 探讨内镜黏膜下剥离术(ESD)治疗早期胃癌的有效件及安全性.方法 对20例早期胃癌患者共21处病灶进行ESD治疗,观察治疗的情况及效果.结果 21处病灶一次性整块切除率为95.2%(20/21),组织学治愈性切除率为90.5%(19/21).平均手术时间50.4 min.急性少量出血率4.8%(1/21),术后腹痛发生率为76.2%(16/21),未发生急性大量出血、穿孔、术后延迟出血.2个月时复查胃镜,溃疡愈合率100%.平均随访9.2个月(8～12个月),局部无残留、复发及异时病灶发生.结论 ESD町提高一次性完整切除率和组织学治愈性切除率,是一种治疗早期胃癌的安全有效的方法.     

High proliferative activity is associated with dysplasia in ulcerative colitis

PURPOSE: Ulcerative colitis is associated with an increased risk of colorectal neoplasia. Markers of proliferation are reported to be valuable in the diagnosis of dysplasia in ulcerative colitis. However, it is not known whether dysplastic change or proliferative change occurs first. Whether abnormal proliferation is present in normal-seeming mucosa in ulcerative colitis was investigated. METHODS: Eighteen cancer or high-grade dysplasia specimens and 9 low-grade dysplasia specimens from 5 patients and 51 specimens from 31 patients without neoplasia were studied. Immunostaining with anti-Ki 67 antibody was used to evaluate proliferative activity. Labeling index (in the superficial one-half of crypt) was calculated. Crypts with labeling index more than 0.3 were determined to have abnormal proliferation. RESULTS: The mean ± standard error of the mean labeling index in specimens negative for dysplasia (0.056±0.004) was significantly lower than that in low-grade dysplasia specimens (0.418±0.024) and that in high-grade dysplasia specimens (0.503±0.027;P<0.0001). In specimens negative for dysplasia, only 4 (4 cases) of 339 (1.2 percent) crypts had abnormal proliferation, whereas the ratio of crypts with abnormal proliferation was 76 percent (54/71) in low-grade dysplasia and 92.1 percent (35/38) in high-grade dysplasia. The labeling index in background mucosa was 0.139±0.009, which was significantly higher than that in specimens negative for dysplasia (P<0.001). In background mucosa 15.7 percent of crypts showed abnormal proliferation. A follow-up study revealed that two of four cases developed cancer or high-grade dysplasia one and seven years after proliferative abnormality was detected in nondysplastic specimens. CONCLUSION: Ki-67 immunostaining can be an aid in the diagnosis of dysplasia. High proliferating activity in background mucosa suggests that proliferating activity change precedes dysplasia detected with hematoxylin-and-eosin staining.     

Eleven metachronous early gastric cancers in an elderly woman

We report on a patient with 11 metachronous multiple early gastric cancers treated by gastrectomy after endoscopic resection. An 87-year-old Japanese woman was admitted to our hospital for treatment of four synchronous multiple early gastric cancers detected by endoscopic examination. The patient had a history of two endoscopic treatments for four metachronous early gastric cancers. The pathological findings of four lesions resected by endoscopic resection and four biopsy specimens showed well-differentiated carcinoma. In March 2012, we performed a distal gastrectomy for four lesions. The surgical specimen revealed 3?minute lesions after surgery in addition to these four lesions. Histologically, all seven lesions were intramucosal well-differentiated adenocarcinomas without vascular invasion. Although the incidence of synchronous and metachronous early gastric cancer is reportedly 11?14.5?% and 8.5?14?%, respectively, only two or three lesions are generally present. Moreover, multiple early gastric cancers usually originate as differentiated adenocarcinoma in male elderly patients with intestinal metaplasia. In the present case, there were multiple early gastric cancers, whose origin may be correlated with the background of intestinal metaplasia, in excess of the number generally expected.     

Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT o...     

Predictive factors of lymph node metastasis in patients with undifferentiated early gastric cancers

BACKGROUND: For intramucosal differentiated early gastric cancer that has little risk of lymph node metastasis, local treatment such as endoscopic mucosal resection has been generally accepted as an adequate treatment. We studied clinicopathological characteristics of undifferentiated early gastric cancer at our institution to identify the predictive factors for lymph node metastasis and qualify lesions that should be referred for gastrectomy and not endoscopic mucosal resection. METHODS: We retrospectively analyzed the clinicopathological features (patient age and gender, tumor size, location, macroscopic type and histological type, presence of ulceration, depth of tumor invasion, and lymphatic-vascular involvement) in 332 patients with undifferentiated early gastric cancer who underwent gastrectomy with regional lymph node dissection. RESULTS: Lymph node metastasis was observed in 45 patients (14%). Univariate analysis revealed that depth of tumor invasion (submucosa), tumor size (>30 mm), and lymphatic-vascular involvement (positive) were associated with lymph node metastasis. Only lymphatic-vascular involvement (positive) was found to have a significant association (odds ratio, 7.4; 95% confidence interval, 2.9-19.0) by multivariate analysis. CONCLUSIONS: Lymphatic-vascular involvement was the only independent predictive risk factor for lymph node metastasis. This pathologic factor was not useful for identifying patients at high risk of lymph node metastasis who should be offered gastrectomy rather than endoscopic mucosal resection.     

Overexpression of p53 is not associated with drug resistance of gastric cancers to 5-fluorouracil-based systemic chemotherapy

BACKGROUND/AIMS: Recent in vitro evidence has strongly suggested that most anti-cancer drugs exert their cytotoxic effects via a p53-dependent apoptosis pathway. An intact p53 molecule appears to be a prerequisite for the cancer cells to be susceptible to these drugs. In this study, we specifically examined if overexpression of p53 may confer drug resistance on human gastric cancer. METHODOLOGY: All patients were treated by an empirical HDFL regimen (weekly 24-hour infusion of 5-FU, 2,600 mg/m2 and leucovorin, 300 mg/m2) in a prospective phase II clinical trial. Among them, patients with adequate pre-chemotherapy gastric cancer tissues for immunohistochemical studies were selected for this study. A p53 DO7 monoclonal antibody was used to detect the overexpression of p53. The results were designated as "-" or "+" by the independent interpretation of two pathologists. RESULTS: A total of 30 patients, 18 men and 12 women, with a median age of 61.5 years (range: 32-78 years), were studied. There were 15 responders and 15 non-responders to HDFL chemotherapy. The percentage of p53 overexpression with positive DO7 staining was 20.0% (6 out of 30). There were no significant differences in the pertinent clinicopathologic features between the patients with positive staining of p53 and the patients with negative staining of p53. Three out of 6 (50.0%) patients with positive staining of p53 and 12 out of 24 (50.0%) patients with negative staining of p53 responded to chemotherapy, respectively (p = 1.000 by Fisher's exact test). CONCLUSIONS: Our data suggested that the overexpression of p53 does not predict drug resistance to 5-FU of human gastric cancer.     

Radiological investigation of the mucosae around early gastric cancers

Background To clarify the corresponding histological structures, double-contrast images of mucosae around early gastric cancers were examined. Methods A total of 332 areas of double-contrast images of the gastric mucosae around early gastric cancers and corresponding specimens resected in operations were selected. The size, shape, and regularity of the granules in the images were inspected. Bull's-eye shadows and dot shadows in the images were also investigated. These findings were compared with the severity of mucosal atrophy, hyperplasia of lymph follicles, and intestinal metaplasia in the corresponding specimens. Results In fundic gland mucosae, granules which were small, oval, irregular, or unaccompanied by bull's-eye shadows indicated severe atrophy. Granules which were irregular or accompanied by dot shadows indicated severe intestinal metaplasia. Granules which were small, oval, or irregular indicated severe hyperplasia of lymph follicles. In pyloric gland mucosae, oval or irregular granules accompanied by dot shadows indicated severe mucosal atrophy and severe intestinal metaplasia. Diamond-shaped granules indicated severe hyperplasia of lymph follicles. Conclusions The histological structure of normal gastric mucosae around gastric cancers can be inferred from the size, shape, and regularity of granules, and the presence of bull's-eye or dot shadows in double-contrast images.     

Lymphocyte-activating gene-3 expression is associated with tumor-infiltrating lymphocyte levels in HER2-positive breast cancers

Lymphocyte-activating gene-3 (LAG-3, CD223) is the third inhibitory receptor targeted for immunotherapy. Several clinical trials investigating the use of interventions targeting LAG-3 are underway. The exact signaling mechanism downstream of LAG-3 is largely unknown, especially in breast cancer. The prognostic significance of tumor-infiltrating lymphocytes (TILs) in breast cancer has been previously determined.Among 167 human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, 90 and 78 patients were positive and negative for the hormone receptor, respectively. LAG-3 mRNA and protein expression levels in TILs were evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, among 12 and 167 HER2-positive breast cancer samples, respectively.High expression of LAG-3 in TILs was significantly correlated with high levels of TILs (P = .003) and an abundance of tertiary lymphoid structures around invasive components (P = .014). In addition, high expression of LAG3 was significantly associated with positivity for programmed death-ligand 1 (PD-L1) in tumor cells, a high immunostaining score of PD-L1 in TILs, and a high total immunostaining score for PD-L1 in tumor cells and TILs (all, P < .001). High expression levels of LAG-3 mRNA were associated with high levels of TILs (P = .091).LAG-3 protein expression was not a prognostic factor in HER2-positive breast cancers, and LAG-3 expression in TILs was significantly associated with the levels of TILs in HER2-positive breast cancer, although it was not a prognostic factor.     

Diagnosis of undifferentiated type early gastric cancers by magnification endoscopy with narrow-band imaging

Background and Aims: The diagnostic use of magnification endoscopy with narrow‐band imaging (ME‐NBI) to assess histopathologically undifferentiated‐type early gastric cancers (UD‐type EGCs) is not well elucidated. The purpose of this study was to examine the comparative relationship between ME‐NBI images and histopathological findings in UD‐type EGCs. Methods: We analyzed 78 consecutive cases of UD‐type EGCs ≤ 20 mm in diameter that underwent ME‐NBI ≤ 2 weeks prior to resection. The ME‐NBI images were compared with histopathological findings following either endoscopic submucosal dissection (ESD) or surgery. Applying the comparative results, we prospectively evaluated the success of identifying the lateral extent of UD‐type EGCs resected by ESD in additional consecutive cases. Results: Lesions with preserved but irregular surface microstructures (S‐type based on ME‐NBI) showed mucosal atrophy and corresponded histologically to the non‐whole‐layer type of intramucosal cancer (24/24, 100%). Lesions with an irregular microvasculature type (V‐type, for example, corkscrew pattern) or mixed type upon ME‐NBI corresponded histopathologically to the non‐whole‐layer type of intramucosal cancer (15/54, 27.8%), the whole‐layer type of intramucosal cancer (27/54, 50.0%) or submucosal (sm) invasion cancer (12/54, 22.2%). Applying these comparative results, we used ME‐NBI to successfully predict the lateral extent of cancer, which corresponded to the histopathological lateral extent in all 18 additional consecutive UD‐type EGCs resected by ESD. Conclusions: ME‐NBI images of UD‐type EGCs were very closely related to the histopathological findings. Thus, ME‐NBI can be useful in the pretreatment assessment of the histopathological patterns of cancer development and the lateral extent of such lesions.