Lymph node metastasis occurs in as many as 16% of patients with submucosal invasive colorectal carcinoma. We investigated the association between histopathological factors and lymph node metastases ...in 322 consecutive patients with submucosal invasive colorectal carcinoma who had undergone radical colectomy with lymph node dissection to detect patients at high risk of lymph node metastasis without measuring the depth of submucosal invasion. Lymph node metastasis was found in 46 (14.3%) of 322 patients with submucosal invasive colorectal carcinoma. Univariate analysis showed that each of the following histopathological factors had a significant influence on lymph node metastasis: invasion depth, lymphatic invasion, venous invasion, tumor differentiation, growth pattern of the intramucosal tumor component, complete disruption of the muscularis mucosa due to tumor invasion, and tumor budding at the submucosal invasive front. Multivariate analysis showed that lymphatic invasion (P<0.01), tumor differentiation (P<0.01), and tumor budding (P<0.01) were significantly associated with lymph node metastasis. All 46 cases of lymph node metastasis showed at least one of the following findings: lymphatic invasion, moderately or poorly differentiated tumor grade, tumor budding, or complete disruption of the muscularis mucosa due to tumor invasion. Patients with submucosal invasive colorectal carcinoma that show at least one of three factors--lymphatic invasion, moderately or poorly differentiated tumor grade, or tumor budding--are at high risk for lymph node metastasis. All of the patients with lymph node metastasis, who did not have any of these factors, showed a completely disrupted muscularis mucosa.
Background
Helicobacter pylori
(
HP
) infection potently induces aberrant DNA methylation in gastric mucosae, and its accumulation is associated with gastric cancer risk. Cross-sectional analysis of ...methylation levels (fraction of methylated DNA molecules) and temporal analysis of methylation incidence suggested that methylation levels decrease after
HP
infection discontinues. We aimed to demonstrate the decrease in methylation levels.
Methods
Thirty-five patients with
HP
infection who had undergone curative endoscopic resection and 11 healthy volunteers were recruited. Methylation levels were quantified by real-time methylation-specific PCR. Histology was evaluated according to the updated Sydney System.
Results
In the 20 patients with successful eradication, the
FLNc
methylation level, along with infiltration of inflammatory cells, decreased from 0.6 to 0.4% at 6 weeks (
P
= 0.049) and remained low at 1 year. The
THBD
methylation level (30.1%) remained high at 6 weeks, but decreased to 19.0% at 1 year (
P
= 0.0032). Nine healthy volunteers with successful eradication tended to show a decrease of both
FLNc
and
THBD
at 6 weeks. However, the methylation levels after the decrease were still higher than those of healthy individuals without
HP
infection. In the 15 patients with persistent infection, the methylation levels remained the same. Before eradication, the
THBD
methylation level correlated with the degree of inflammatory cell infiltration (
P
<
0.05).
Conclusions
Methylation levels in gastric mucosae decreased to certain levels after
HP
eradication in profiles unique to individual markers. Involvement of chronic inflammation in methylation induction was suggested.
Diseases of the proximal pathways of the biliary system can be divided into those that affect the interlobular bile ducts and those that affect the bile canaliculi. The former include primary biliary ...cirrhosis, small-duct variant of primary sclerosing cholangitis, graft-versus-host disease, and drug-induced liver injury, whereas the latter include progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis, intrahepatic cholestasis of pregnancy, and drug-induced liver injury.
To summarize the current state of knowledge of diseases of the proximal pathways of the biliary system, with special emphasis on clinical presentation, pathological features, and differential diagnosis.
Clinicopathological information was extracted from pertinent published literature.
Care of the patient with cholestasis hinges on identifying the etiology. Diagnostic steps in cholestatic conditions comprise a thorough patient history, abdominal imaging, distinct serological studies, and liver biopsy. Primary biliary cirrhosis is characterized by distinctive serological and histological findings. The small-duct variant of primary sclerosing cholangitis is very rare and difficult to diagnose; imaging of the bile ducts is not helpful. Graft-versus-host disease is characterized by damage and loss of intrahepatic bile ducts. Drugs can cause injury variably at the level of bile canaliculus or the interlobular bile duct. Loss of bile ducts may be seen with primary biliary cirrhosis, primary sclerosing cholangitis, graft-versus-host disease, and drug-induced liver injury. Progressive familial intrahepatic cholestasis and progressive familial intrahepatic cholestasis represent 2 extreme ends of the spectrum of abnormalities in transporters responsible for bile formation. Intrahepatic cholestasis of pregnancy has a variable incidence in different parts of the world and may be due to abnormalities in transporter molecules.
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
Clinical proteomics using a large archive of formalin‐fixed paraffin‐embedded (FFPE) tissue blocks has long been a challenge. Recently, a method for extracting proteins from FFPE tissue in the form ...of tryptic peptides was developed. Here we report the application of a highly sensitive mass spectrometry (MS)‐based quantitative proteome method to a small amount of samples obtained by laser microdissection from FFPE tissues. Cancerous and adjacent normal epithelia were microdissected from FFPE tissue blocks of 10 squamous cell carcinomas of the tongue. Proteins were extracted in the form of tryptic peptides and analyzed by 2‐dimensional image‐converted analysis of liquid chromatography and mass spectrometry (2DICAL), a label‐free quantitative proteomics method developed in our laboratory. From a total of 25 018 peaks we selected 72 mass peaks whose expression differed significantly between cancer and normal tissues (P < 0.001, paired t‐test). The expression of transglutaminase 3 (TGM3) was significantly down‐regulated in cancer and correlated with loss of histological differentiation. Hypermethylation of TGM3 gene CpG islands was observed in 12 oral squamous cell carcinoma (OSCC) cell lines with reduced TGM3 expression. These results suggest that epigenetic silencing of TGM3 plays certain roles in the process of oral carcinogenesis. The method for quantitative proteomic analysis of FFPE tissue described here offers new opportunities to identify disease‐specific biomarkers and therapeutic targets using widely available archival samples with corresponding detailed pathological and clinical records. (Cancer Sci 2009; 100: 1605–1611)
No previous reports on lymph-node metastasis (LNM) from superficial squamous cell carcinoma of the esophagus have proposed definite criteria for additional treatment after endoscopic mucosal ...resection (EMR). We investigated the association between histopathological factors and LNM in 464 consecutive patients with superficial squamous cell carcinoma of the esophagus who had undergone a radical esophagectomy with lymph-node dissection (14 ‘M1' lesions: intraepithelial tumors, 36 ‘M2' lesions: tumors invading the lamina propria, 50 ‘M3' lesions: tumors in contact with or invading the muscularis mucosa, 32 ‘SM1' lesions: tumors invading the most superficial 1/3 of the submucosa and 332 ‘SM2/3' lesions: tumors invading deeper than SM1 level). Histopathological factors including invasion depth, size, lymphatic invasion (LY), venous invasion, tumor differentiation, growth pattern, degree of nuclear atypia and histological grade were assessed for their association with LNM in 82 M3 or SM1 lesions to determine which patients need additional treatment after EMR. LNM was found in 0.0, 5.6, 18.0, 53.1 and 53.9% of the M1, M2, M3, SM1 and SM2/3 lesions, respectively. A univariate analysis showed that each of the following histopathological factors had a significant influence on LNM: invasion depth (M3 vs SM1), LY, venous invasion and histological grade. Invasion depth and LY were significantly associated with LNM in a multivariate analysis. Four out of 38 patients (10.3%) with M3 lesions without LY had LNM, whereas five out of 12 patients (41.7%) with M3 lesions and LY had LNM. Only patients with M1/2 lesions are good candidates for EMR. Invading the muscularis mucosa (M3) is a high-risk condition for LNM the same as submucosal invasion, but M3 lesions without LY can be followed up after EMR without any additional treatment.
BACKGROUND: The presence of lymph node metastasis (LNM) is the most important prognostic factor for patients with early gastric cancer (EGC). A D2 gastrectomy has been the gold standard treatment. ...Strict criteria for endoscopic mucosal resection have been widely accepted in Japan. There are some trials aimed at expanding the indications for local treatment, although there has not been a comprehensive review of the risk of LNM with the lesions of EGC.METHODS: We investigated 5265 patients who had undergone gastrectomy with lymph node dissection for EGC at the National Cancer Center Hospital and the Cancer Institute Hospital. Nine clinicopathological factors were assessed for their possible association with LNM.RESULTS: None of the 1230 well differentiated intramucosal cancers of less than 30 mm diameter regardless of ulceration findings, were associated with metastases (95% confidence interval CI, 0-0.3%). None of the 929 lesions without ulceration were associated with nodal metastases (95% CI, 0-0.4%) regardless of tumor size. Similarly to findings for intramucosal cancers, for submucosal lesions, there was a significant correlation between tumor size larger than 30 mm and lymphatic-vascular involvement with an increased risk of LNM. None of the 145 differentiated adenocarcinomas of less than 30-mm-diameter without lymphatic or venous permeation were associated with LNM, provided that the lesion had invaded less than 500 m into the submucosa (95% CI, 0-2.5%).CONCLUSION: Based on our large series of cases, we have been able to clarify the risks associated with EGC and to propose expansion of the criteria for local treatment. However, accurate histological evaluation of the resected specimens is essential to avoid recurrence for such EGCs that should be cured.
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