PURPOSE: This study aimed to provide immunohistochemical evidence of micrometastasis in patients with node-negative Dukes' B colorectal cancer and to evaluate the clinical implications, including prognostic significance, of lymphatic metastasis. METHODS: A retrospective study of 90 patients who underwent a curative operation due to colorectal neoplasms from 1996 to 2001 was performed. Two consecutive sections of lymph nodes were prepared: one for ordinary hematoxylin-eosin staining, and the other for immunohistochemistry with pancytokeratine antibody. All clinical factors, including survival rate, were compared between patients with and without lymph-node metastasis. The mean follow- up period was 36.1 months. RESULTS: Micrometastasis was confirmed in 115 nodes (7.9%) from 32 patients (35.6%). No correlations were observed between micrometastases and prognostic factors, including survival rate, except for lymphatic invasion and postoperative TNM staging. Twenty-six of the 32 (81.3%) patients with micrometastases belonged to stage T3N0M0 (P<0.003). CONCLUSIONS: The immunohistochemical assay may be a useful way to identify micrometastasis in patients with Dukes' B colorectal neoplasms, but we were not able to demonstrate the prognostic significance of micrometastasis.
Colorectal Neoplasms* ; Humans ; Immunohistochemistry ; Lymph Nodes* ; Lymphatic Metastasis ; Neoplasm Metastasis ; Neoplasm Micrometastasis* ; Neoplasm Staging ; Retrospective Studies ; Survival Rate

PURPOSE: Studying the prognostic factors of distant metastasis is quite important for predicting these patients' prognosis and also for providing standards for post-operative adjuvant chemotherapy. Microbiological studies currently enable researchers to look for new predictors of distant metastasis in patients with colon cancers. In this study, the VEGF-C expression and stain rate of D2-40 were investigated as prognostic factors. METHODS: 79 Specimens were collected from the patients who underwent colorectal operation and they were pathologicaly diagnosed with cancer at Chung-Ang University hospital from March, 2003 to Sept. 2005. The specimens were immunohistochemically stained to detect the VEGF-c expression and the D2- 40 stain rate. RESULTS: The VEGF-C expression was related to lymph node metastasis, tumor embolism and the frequency of the T- stage, but it was not related to progression of cancer. The D2-40 stained lymphatic density was significantly increased in the cases with lymph node metastasis and in the tumor embolism cases; furthermore, the density became higher in relation to the increased T-stage and progression of cancer. CONCLUSION: The VEGF-C expression and lymphatic vessel density appear to be prognostic factors for colon cancer.
Chemotherapy, Adjuvant ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Lymph Nodes ; Lymphatic Vessels ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Prognosis ; Vascular Endothelial Growth Factor C

OBJECTIVETo explore the correlations of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) with the clinicopathological characteristics, prognostic events, and survival outcomes in esophageal cancer (EC) patients.

METHODSThe PubMed, Web of Science, Embase database and Cochrane database were searched for studies reporting the outcomes of interest. The studies were selected according to established inclusion/exclusion criteria. Meta-analysis of the studies was performed using Review Manager 5.3 and Stata12.0 software with the odds ratio (OR), risk ratio (RR) , hazard ratio (HR) , and 95% confidence interval (95% CI) as the effect indexes.

RESULTSNineteen studies involving a total of 1766 patients were included in the analysis. Significant correlations of CTCs and DTCs were found with the clinicopathological parameters including the tumor stage (OR=1.95), depth of invasion (OR=1.99), lymph node metastasis (OR=2.44), distal metastasis (OR=5.98), histological differentiation (OR=1.67) and lymphovascular invasion (OR=4.48). CTCs and DTCs were also correlated with the prognostic events including relapse (RR=6.86) and metastasis (RR=3.22) and with the survival outcomes including the overall survival (OS) overall analysis (HR=3.46) and disease-free survival/progression-free survival (DFS/PFS) overall analysis (HR=3.00).

CONCLUSIONCTCs and DTCs are significantly associated with an advanced tumor stage, depth of tumor invasion, lymph node metastasis, distant metastasis before therapy, differentiation, lymphovascular invasion, relapse and metastasis in patients with EC. They are also significantly correlated with a poorer survival for OS and DFS/PFS to serve as clinical and prognostic predictors in patients with EC.

Disease-Free Survival ; Esophageal Neoplasms ; diagnosis ; Humans ; Lymphatic Metastasis ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating ; Odds Ratio ; Prognosis ; Proportional Hazards Models ; Survival Analysis

Lymph node metastasis from gastric cancer is one of the most important events in the progress of disease, which may reflect the disease situation and contribute to evaluate accurately prognosis. Although the detailed mechanism of lymph node metastasis from gastric cancer has not been clearly elucidated, nodal metastasis comprise of a series of events involving the alterations of tumor biological characteristics, including changes of cancer cell proliferation, invasion, chemotaxis, and pathway of lymphatic drainage. As we know, assessment of lymph node metastatic status is significantly associated with both therapeutic strategy and prognostic prediction, It is controversial to adopt the optimal category of lymph node metastasis in clinical practice. Category based on the number of lymph node metastasis (e.g. N stage of UICC TNM classification) is considered as a prominent variable to apply for gastric cancer worldwide, nevertheless, category based on extent of lymph node metastasis (e.g. N stage of JGCA classification) is capable of contributing to the appropriate surgical procedure for patients. It has not reached a consensus for the assessment impacts of several special variables on prognostic evaluation in gastric cancer, including nodal micrometastasis, isolated tumor cells (ITCs) in lymph nodes, and skipping metastasis of lymph nodes, which needs further investigations to determining the application values in gastric cancer.
Cell Proliferation ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Neoplasm Micrometastasis ; Neoplasm Staging ; Prognosis ; Stomach Neoplasms ; pathology

BACKGROUND: About 20% of small cell lung cancer (SCLC) patients have bone marrow (BM) metastasis at the time of diagnosis and the remaining patients are also considered with micrometastasis. In an att empt to detect BM micrometastasis, we used cytokeratin (CK)-20 as a molecular marker, which is specific for epithelial cells. METHOD: A sensitive RT-PCR assay was used to compare CK-20 expression both in SCLC cell line H209 and normal leukocyte and to evaluate BM aspirates of 28 SCLC patients. RESULT: H209 cell line showed CK-20 expression but normal leukocyte did not, suggesting CK-20 expression is lung tissue-specific. Of 28 patients (11 limited disease, 17 extensive disease), only 2 (1/11, 1/17) samples tested revealed positive signal for CK-20. Two patients with CK-20 expression had BM metastasis or multiple bone involvement during follow-up. CONCLUSION: Although circulating tumor cells were detected in BM of small portion of patients with bone metastasis, CK-20 doesn't seem to be a reliable marker for the detection of micrometastasis in SCLC. This study emphasizes that identification of more specific marker for micromatastsis is mandatory prior to clinical application.
Bone Marrow* ; Cell Line ; Diagnosis ; Epithelial Cells ; Follow-Up Studies ; Humans ; Keratins ; Leukocytes ; Lung ; Neoplasm Metastasis ; Neoplasm Micrometastasis* ; Neoplastic Cells, Circulating ; Small Cell Lung Carcinoma*

OBJECTIVETo investigate the regional spread of micrometastatic nodules in the mesorectum from low rectal cancer, and provide further pathological evidence to optimize radical resection procedure for rectal cancer.

METHODSA total of 62 patients with low rectal cancer underwent low anterior resection and total mesorectal excision (TME) was included in this study. Surgical specimens were sliced transversely and serial embedded blocks were made at 2.5 mm interval, and paraffin sections were stained with hematoxylin and eosin. The mesorectum on whole-mount sections was divided into three regions: outer region of mesorectum (ORM), middle region of mesorectum (MRM) and inner region of mesorectum (IRM). Microscopic spread were examined microscopically on the sections for the distribution in different mesorectal regions, frequency, types, involvement of lymphatic system and correlation with the primary tumor.

RESULTSMicroscopic spread of the tumor in mesorectum and ORM was observed in 38.7% (24/62) and 25.8% (16/62) of the patients, respectively. Circumferential resection margin (CRM) involved by microscopic tumor foci occurred in 6.5% (4/62) of the patients, and distal mesorectum (DMR) involvement was recorded in 6.5% (4/62) with a spread extent within 3 cm of distal border of the main lesions. Most (20/24) of the patients with microscopic spread in mesorectum were in TNM stage III.

CONCLUSIONResults of the present study support that complete excision of mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, and an optimal DMR clearance resection margin should not be less than 4 cm.

Adenocarcinoma ; pathology ; surgery ; Adult ; Aged ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Mesentery ; pathology ; surgery ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasm, Residual ; Neoplastic Cells, Circulating ; pathology ; Peritoneal Neoplasms ; pathology ; surgery ; Rectal Neoplasms ; pathology ; surgery ; Rectum ; surgery

PURPOSE: The aim of this study was to determine the rate of lymph node (LN) micrometastasis in patients with stage I and II rectal cancer.METHODS: One hundred eighty patients with either stage I or II rectal carcinoma who underwent curative resection between 1995 and 2010 were included. Forty-eight patients received neoadjuvant chemoradiotherapy. Two sections from each LN were stained with hematoxylin and eosin (H&E) and with CK20 by immunohistochemistry (IHC), respectively.RESULTS: A total of 2,257 LNs with a median of 12.5 LNs per patient were examined. For IHC staining, CK20-positive neoplastic cells were found in 4 of the 2,257 LNs (0.2%) from 3 of the 180 patients (1.7%), and all corresponding H&E re-stained sections confirmed that these neoplastic cells were present. Three of four neoplastic cells were micrometastasis, and one was macrometastasis. All occult neoplastic cells were found in 3 of the 85 patients (3.5%) with stage II disease.CONCLUSION: We observed a 3.5% rate of occult neoplastic cells in stage II rectal cancer. Interestingly, the results of IHC staining corresponded with those of H&E re-stained sections, suggesting that the examination of H&E stained section by a competent pathologist may replace IHC staining.
Chemoradiotherapy ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Immunohistochemistry ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Micrometastasis ; Rectal Neoplasms

PURPOSE: Lymph-node metastasis is one of the most important prognostic factors in gastric cancer. However, it can be missed with conventional histologic examination with hematoxylin-eosin staining. Several methods have been introduced to improve the detection rate of micrometastasis. Among them, immunohistochemical staining with the anti-cytokeratin antibody is known to be an easy and useful method. METHODS: We used immunohistochemical staining with the anti-cytokeratin antibody to evaluate the incidence of micrometastasis in 48 patients with advanced gastric cancer who had been diagnosed as lymph-node negative by H&E, and its relationship to various clinicopathologic factors. RESULTS: Lymph-node micrometastasis (anti-cytokeratin antibody positive) was found in 15 (31.3%) of the 48 patients and in 33 (1.75%) of 1884 lymph nodes. Among the clinicopathologic variables, only lymphatic invasion was significantly associated with micrometastasis status. The gender, the age, the tumor size, the location of the tumor, the histologic type, and the depth of invasion were not significantly associated with micrometastasis status. During the average follow-up period of 21 months, 6 patients suffered a recurrence, and 2 of these patients died of the cancer recurrence. The recurrence and mortality rates were not significantly associated with micrometastasis status. CONCLUSION: Micrometastasis in stomach cancer was frequent when the primary tumor had invaded the lymphatic vessels.
Follow-Up Studies ; Humans ; Incidence ; Keratins ; Lymph Nodes* ; Lymphatic Vessels ; Mortality ; Neoplasm Metastasis ; Neoplasm Micrometastasis* ; Recurrence ; Stomach Neoplasms*

PURPOSE: The Sentinel lymph node (SLN) is the first draining node from the primary lesions, and is the first site of lymph node metastasis in malignancies. The aim of this study was to determine the feasibility of a SLN biopsy in patients with gastric cancer to assess the regional lymph node status. METHODS: A SLN biopsy was performed in 46 consecutive gastric cancer patients, with preoperative imaging stages of T1/T2, N0 and M0. Three hours prior to each operation, a (99m)Tc tin-colloid (2.0 ml, 1.0 mCi) was endoscopically injected into the gastric submucosa around the primary tumor. Subsequently, serial lymphoscintigraphy was performed using a dual head gamma camera. After the SLN biopsy had been performed using a gamma probe, the patients underwent a radical gastrectomy (D2 or D2+ alpha). The SLNs were cut and immediately frozen-sectioned. A paraffin block was then produced for permanent hematoxylin-eosin staining and immunohistochemistry (IHC). RESULTS: SLNs were successfully identified in 43 of the 46 patients (success rate, 93.5%), at an average of 2 (range, 1~8) per patient. The positive and negative predictive values, sensitivity and specificity of the SLN biopsy were 100 (11/11), 93.8 (30/32), 84.6% (11/13) and 100% (30/30), respectively. SLNs were located at the level I, I+II and II lymph nodes in 38 (88.4%), 2 (4.7%) and 3 (7.0%), respectively. No micrometastases of the SLNs was found on the IHC for cytokeratin. CONCLUSION: A sentinel lymph node (SLN) biopsy, using a radioisotope, in patients with gastric cancer is a technically feasible and accurate technique, and is a minimally invasive approach for assessing the nodal status in patients.
Biopsy* ; Gamma Cameras ; Gastrectomy ; Head ; Humans ; Immunohistochemistry ; Keratins ; Lymph Nodes ; Lymphatic Metastasis ; Lymphoscintigraphy ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Paraffin ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy ; Stomach Neoplasms*

PURPOSE: A 25% rate of recurrence after performing complete resection in node-negative colon cancer patients suggests that their nodal staging is frequently suboptimal. Moreover, the value of occult cancer cells in tumor-free lymph nodes still remains uncertain. The authors evaluated the prognostic significance of the pathologic parameters, including the lymph node occult disease (micrometastases) detected by immunohistochemistry, in patients with node-negative colon cancer. MATERIALS AND METHODS: The study included 160 patients with curatively resected stage I or II colon cancer and they were without rectal cancer. 2852 lymph nodes were re-examined by re-do hematoxylin and eosin (H-E) staining and immunohistochemical staining. The detection rates were compared with the clinicopathologic characteristics and with the cancer-specific survival. RESULTS: Occult metastases were detected in 8 patients (5%). However, no clinicopathologic parameter was found to be correlated with the presence of micrometastasis. Twenty patients developed recurrence at a median follow-up of 45.7 months: 14 died of colon cancer and 9 died from noncancer-related causes. Univariate analysis showed that lymphatic invasion and the number of retrieved lymph nodes significantly influenced survival, and multivariate analysis revealed that the stage, the number of retrieved lymph nodes and lymphatic invasion were independently related to the prognosis. CONCLUSIONS: Inadequate lymph node retrieval and lymphatic invasion were found to be associated with a poorer outcome for node-negative colon cancer patients. The presence of immunostained tumors cells in pN0 lymph nodes was found to have no significant effect on survival, but these tumor were identified by re-do H-E staining. Maximal attention should be paid to the total number of lymph nodes that are retrieved during surgery for colon cancer patients.
Colon ; Colonic Neoplasms ; Eosine Yellowish-(YS) ; Follow-Up Studies ; Hematoxylin ; Humans ; Immunohistochemistry ; Lymph Nodes ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Rectal Neoplasms ; Recurrence