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The detection rate of early-stage esophageal cancer has increased recently. Various types of treatment including endoscopic mucosal resection, blunt dissection, and esophagectomy with extended lymphadenectomy are employed in patients with submucosal esophageal cancer. The purpose of the present study was to analyze prognostic factors in patients with submucosal esophageal cancer. Univariate analysis showed that lymph node metastasis, subdivision of tumor depth, and lymphatic invasion were correlated with prognosis, whereas sex, age, tumor location, surgical procedure, adjuvant therapy, histologic findings, and venous invasion did not affect prognosis. Multivariate analysis demonstrated lymph node metastasis to be the only significant prognostic factor in submucosal esophageal cancer. Although subdivisions of tumor depth did not reach significance as prognostic factors, lymph node metastasis was strongly related to tumor depth. To select the individualized treatment in patients with submucosal esophageal cancer, accurate diagnosis of lymph node metastasis necessitates a combination of imaging methods such as endoscopic ultrasound-guided fine-needle aspiration, computed tomography, and positron emission tomography.

Prior to worldwide acceptance of the sentinel lymph node concept, internal mammary node dissection was regarded as unnecessary for diagnosis of breast cancer. More recently, the impact of internal mammary nodes dissection on the survival of breast cancer patients has come under scrutiny. We have encountered important breast cancer cases involving lymphatic streams that go from the tumor to both the internal mammary chain and axillary node basin simultaneously. Moreover, a lymphatic stream was found to go from the breast tumor to the internal mammary chain via intra-mammary gland lymph nodes. These cases indicate the dual importance of internal mammary sentinel node dissection as well as axillary sentinel node dissection.

Purpose: Outcome for patients with biliary-pancreatic cancer is still poor, despite curative operation. We investigated the clinical significance of molecular detection of circulating cancer cells in the blood as an early indicator of relapse during follow-up of patients who underwent a curative operation for biliary-pancreatic cancer. Patients and Methods: We followed 53 patients who underwent a curative operation for biliary-pancreatic cancer between 1996 and 2001. We used reverse transcription-PCR in the peripheral blood to evaluate carcinoembryonic antigen (CEA) mRNA expression for molecular detection of circulating cancer cells. Follow-up examinations every 3 months after surgery included CEA mRNA expression in the blood, serum CEA, serum carbohydrate antigen 19-9 (CA19-9), and computed tomography or magnetic resonance imaging. Results: Sixteen of 53 patients (30.2%) were diagnosed with a recurrence by imaging studies. The CEA mRNA detection rate in the peripheral blood of these 16 patients was 75% compared with 5.4% in the 37 patients without relapse (P < 0.001). Sensitivity of CEA mRNA, CEA, and CA19-9 serum levels was 75.0%, 50.0%, and 68.8%, respectively. Similarly, specificity was 94.6%, 64.9%, and 81.1%, respectively. CEA mRNA was expressed in the blood, even though tumor markers CEA and CA19-9 were within the normal range in patients with relapse. CEA mRNA expression in the blood, as well as the serum level of CA19-9, tended to be detected a few months earlier than detection by imaging modalities. Conclusions: During the follow-up of patients who undergo a curative operation for biliary-pancreatic cancer, CEA mRNA expression in the peripheral blood might be a useful and early indicator of relapse.

Objective: Esophageal cancer has been reported to be frequently associated with cancer of the head and neck. The iodine dye method is reportedly useful to detect early esophageal cancer. The aim of this study was to clarify clinicopathological and biological characteristics of esophageal squamous cell carcinoma associated with head and neck cancer (HN group). Methods: Thirty-seven patients of the HN group who underwent esophagectomy were examined clinicopathologically compared to 42 patients with esophageal cancer alone (SE group). All resected specimens were histologically studied after iodine dye staining, and p53 and cyclin D1 (CD1) expression were immunohistochemically examined in esophageal cancer. Results: The HN group had more multiple iodine-unstained lesions and multiple primary cancers within the esophagus compared with the SE group (p = 0.0027, p = 0.067, respectively). There was no significant difference in smoking, drinking, family history and the other clinicopathological factors between the HN and SE groups. Coexpression of p53 and CD1 was found to be significant in the HN group (p = 0.03). Conclusions: The coexistence of multiple iodine-unstained lesions, multiple cancers in the esophagus and overexpression of p53 and CD1 is suggested as a risk factor for the HN group.

Background and Objectives It is important to identify the initial lymph node metastasis when performing less invasive surgery. The purpose of the present study was to analyze locations of solitary lymph node metastasis and micrometastasis in esophageal carcinoma. Methods We retrospectively analyzed the initial sites of lymph node metastasis in esophageal cancer. Sixty-five consecutive patients with solitary lymph node metastasis, and 33 pN0 patients with only lymph node micrometastasis detected by immunohistochemistry, were classified according to tumor location and tumor depth. Results The location of lymph node metastasis in the 22 patients with superficial cancer was limited to recurrent nerve nodes (RN) in the upper thoracic esophagus; RN, paraesophageal nodes (PE), or perigastric nodes (PG) in the middle or lower thoracic esophagus. Thirty-six patients with advanced cancer had lymph node metastasis at RN, PE, or PG locations, while in the remaining seven, lymph node metastasis was found in areas far from the primary tumor. Regarding the 33 patients with lymph node micrometastasis, the locations of micrometastasis were similar to those of solitary metastasis. Conclusions Although less invasive surgery, such as reduction of lymphadenectomy, may be suitable for superficial cancer, it should be performed with special care in advanced cancer. J. Surg. Oncol. 2005;89:6–11. © 2004 Wiley-Liss, Inc.

食道異所性胃粘膜に発生した食道穿孔の1例を経験したので報告する. 症例は52歳の男性で, 十二指腸潰瘍で内服加療を受けていた. 突然の心窩部痛が出現し, 激しい嘔吐後に疼痛が増強したため近医を受診し, 上部消化管穿孔を疑われ当院紹介となった. 上部消化管内視鏡検査にて下部食道の潰瘍形成, CT検査で両側胸水を認めた. 食道造影では腹部食道左壁からの造影剤漏出を認めたため, 食道穿孔と診断し, 右開胸開腹による食道切除術と胃管による再建を行った. 病理組織学的検査で, 下部食道異所性胃粘膜部の穿孔と潰瘍の形成が認められた. 術後は縦隔炎に起因する敗血症に陥ったが, 縫合不全や膿瘍形成はみられず救命しえた. 食道の異所性胃粘膜は比較的まれで, ほとんどが無症状である. 内視鏡検査で偶然発見される場合が多いが, 潰瘍の合併も念頭に置きながら定期的な内視鏡検査を行い, 潰瘍の早期発見と治療が必要と考えられた.

The sentinel node (SN) is regarded as the first drainage lymph node, and tumor cells are considered likely to directly affect the SN. However, few reports have identified differences between SNs and non-SNs in cancer patients. Subjects in this study included 27 patients with gastric cancer who underwent curative operation and intraoperative detection of SNs by radioisotope methods. The mean number of SNs was 3.2 (range 1 to 5). Degree of infiltration of natural killer cells, dendritic cells, MIB-1 labeling index, and CD3-zeta expression of lymphocytes in SNs and non-SNs were examined by means of immunohistochemical methods. Degree of infiltration was compared according to depth of invasion and between SNs and non-SNs. Patients with early-stage cancer displayed a greater degree of infiltration of MIB-1 labeling index and CD3-zeta expression than patients with pT2 or pT3 lesions (P0.05). The MIB-1 labeling index in SNs was significantly lower than that in non-SNs (P0.05). However, no significant difference was observed in infiltration of natural killer cells, dendritic cells, or CD3-zeta. Morphologic changes of dendritic cells in SNs were not definite. Our results suggest that SNs in gastric cancer might not be suppressed, unlike in breast cancer and melanoma. SN paralysis may depend on tumor- and organ-specific characteristics or exogenous stimulation from the gastric mucosa. Studies in progress will help to identify immunologic paralysis of the SN in various types of cancer. Attention must therefore be paid to organ specificity.

In gastric cancer, disseminated cancer cells (DCC) can be detected in peripheral blood using bio-molecular techniques. It is known that patients having DCC exhibit a high occurrence of postoperative relapse in gastrointestinal cancer. However, more than half of gastric cancer patients having positive DCC do not show cancer relapse. Sialylated Lewis antigens are considered to be crucial molecules in the metastasis of disseminated cancer. The current study investigated whether combination analysis of DCC and sialylated Lewis antigen are useful in estimating the recurrence risk of gastric cancer.Subjects were 106 consecutive gastric cancer patients who underwent curative gastrectomy. DCC in the peripheral blood were detected using the carcinoembryonic antigen (CEA)-mRNA by RT-PCR method. Sialylated Lewis antigen expression (sLeA and sLeX) of the primary tumor was assessed immunohistochemically.Of 106 gastric cancer patients, 43 (40%) were positive for DCC. Immunohistochemically, 53 (50%) and 49 (46%) patients were positive for sLeA and sLeX, respectively. The presence of DCC did not correlate with sLeA and sLeX expression in gastric cancer. Postoperative tumors were present in 19 patients (7 hematogenous and 12 non-hematogenous), 12 of which were positive for DCC. Six sLeA-positive patients (26%) with DCC and 13 sLeX-positive patients (57%) with DCC suffered from postoperative recurrence of gastric cancer. The p value of CEA-mRNA and sLeX combination analysis was more significant (p0.01) than that of CEA-mRNA alone (p=0.02).Analyzing both DCC and sLeX expression in gastric cancer may enable more accurate prediction of postoperative recurrence.

To identify clinically useful parameters obtainable before treatment of predicting clinical outcomes in patients with esophageal carcinoma.Various factors regarding the biologic state of tumors or the nutritional state of patients have been individually reported to correlate with prognosis. Reliable estimates of life expectancy before treatment are important, and consideration needs to be given not only to tumor-related but also to host-related factors in patients with esophageal carcinoma.The following clinicopathological factors were retrospectively analyzed in 356 consecutive patients with surgical treatment: sex; age; serum C-reactive protein (CRP); proportion of lymphocytes; body weight changes; serum albumin; clinical TNM staging; tumor location; serum squamous cell-related antigen; serum carcinoembryonic antigen; and histology. Factors related to prognosis were evaluated by using univariate and multivariate analyses.According to univariate analysis, significant differences in survival were found for sex, serum CRP, proportion of lymphocytes, body weight change, serum albumin, serum squamous cell-related antigen, and clinical TNM staging. Multivariate analysis demonstrated that CRP levels (P = 0.0285), body weight change (P = 0.0165), and clinical TNM staging (P = 0.0008) displayed independent correlations to prognosis. When serum CRP elevation, body weight loss, and clinical TNM staging III and IV were scored as a combined index, the total score (prognostic index for esophageal cancer, PIEC) demonstrated a good stratification value for prognosis. Moreover, PIEC was superior to the conventional clinical TNM staging by the likelihood ratio test.PIEC based on serum CRP, body weight change, and clinical TNM staging before treatment offers a very simple and informative method for predicting the prognosis of patients with esophageal carcinoma.

Micrometastasis in regional lymph nodes has been observed immunohistochemically, but the biological and clinical roles of minute nodal invasion of carcinoma in gastric cancer remain unclear. We used the anti-cytokeratin (AE1/AE3) antibody to immunohistochemically detect nodal micrometastatic lesions that could not be identified by routine pathological examination. A total of 4203 lymph nodes were examined in 180 gastric cancer patients. Lymph node metastasis was found in 36 of the 180 patients by routine pathological evaluation. Immunohistochemically micrometastasis was detected in the lymph nodes of 19 node-negative patients. Micrometastasis was not detected in any of the mucosal gastric cancer patients who underwent lymph node dissection. Gastric cancer patients with more than six metastatic lymph nodes all had nodal micrometastasis. Patients with micrometastasis had a significantly poorer survival rate than those without micrometastasis ( P < 0.05). Based on the present results the presence of lymph node micrometastasis may provide a more accurate indication for surgical outcome in gastric cancer patients at the same clinical stage.

The purpose of this retrospective study was to analyze the distribution of lymph node metastases, including micrometastases, according to the location of the gastric cancer with submucosal invasion. A total of 118 patients with submucosal gastric cancer were enrolled in this study. The distribution of lymph node metastases was examined according to tumor location. Immunohistochemical examination using anti-cytokeratin antibody was performed to examine nodal micrometastases in 118 patients. Lymph node metastasis was found in 19.5% (23/118) of the patients. Significant differences were found for tumor size and depth, lymphatic invasion, and venous invasion for patients with and without nodal metastasis. The distribution of lymph node metastasis for tumors at upper or middle portions of the stomach was mainly found along the left gastric artery. The distribution of lymph node metastasis for tumors in the lower and lesser curvature varied. Immunohistochemical analysis found that 15 of 23 patients with lymph node metastasis found by histologic examination had micrometastases. The presence of two or more lymph node micrometastases was found in these 15 patients, and they were distributed in another stations, including distant nodes. The incidence of micrometastasis was 24.2% (23/95) in pN0 patients. Lymph node micrometastases were confined to regional nodes near the primary tumor. When planning minimally invasive treatment for submucosal gastric cancer, it is important to understand the distribution of lymph node metastasis, including micrometastasis, according to tumor location.

Background. The clinical significance of circulating tumor cells in the blood during surgery has not been elucidated in esophageal squamous cell carcinoma (ESCC). We evaluated the relationship between circulating tumor cells and clinicopathologic findings, compared with that of serum squamous cell carcinoma (SCC) antigen and carcinoembryonic antigen (CEA), in ESCC. Methods. Blood samples from 54 consecutive patients were obtained from the peripheral artery and the superior vena cava at three points in time: immediately before surgery, and before and after tumor resection. CEA-specific reverse transcriptase-polymerase chain reaction (RT-PCR), which can quantify circulating tumor cells in blood, was performed. The preoperative values of serum SCC antigen and CEA were also obtained for all patients. Results. CEA messenger RNA (CEA mRNA) was detected in the blood of 31 out of 54 patients (57.4%). CEA mRNA positivity was detected most frequently after tumor resection and correlated with nodal status and stage grouping. The incidence of total recurrence and blood-borne recurrence was significantly greater in patients with CEA mRNA positivity than in those with CEA mRNA negativity ( P =.036 and.0026, respectively). Preoperative serum levels of SCC antigen and CEA did not correlate with clinicopathologic findings and tumor recurrence. Conclusions. CEA mRNA detected by RT-PCR was more predictive of tumor recurrence than serum tumor markers. Effective adjuvant therapy is recommended for patients with CEA mRNA positive expression. (Surgery 2003;133:162-9.)

Background The intraoperative diagnosis of lymph node micrometastasis (LNM) may help guide the area of appropriate lymph node dissection. This study aimed to evaluate the rapid immunohistochemical detection of LNMs using frozen sections during operation for gastro-oesophageal cancer. Methods Rapid immunostaining with anticytokeratin (AE1/AE3) antibody was compared with conventional immunostaining. A total of 210 lymph nodes obtained from 47 patients with oesophageal squamous cell carcinoma and from 32 with gastric adenocarcinoma were examined during operation. Lymph nodes were frozen, sectioned, and examined by histological and immunohistochemical methods. Results It took 30 min to complete the rapid immunostaining procedure; the expression of cytokeratin by rapid immunostaining was similar to that by conventional immunostaining. The incidence of lymph node metastasis detected by histological and immunohistochemical examination was 17 and 23 per cent respectively. LNM was solely detected in 12 lymph nodes by immunostaining: three micrometastases and nine with tumour cell microinvolvement. Conclusion Intraoperative rapid immunostaining is a simple and useful technique for detecting LNMs. Further study should investigate the role of rapid immunostaining during cancer surgery to select appropriate areas for lymphadenectomy.

We investigated the effect of the polymer-drug interaction on the surface morphology of polymer microspheres and in vitro release properties. Polylactide microspheres enclosing the antitumor agent Irinotecan hydrochloride (CPT) were prepared by the solvent evaporation method of the O/O emulsion system in order to control the concentration of drugs in living organisms. The mean diameter of the polylactide microspheres was kept at approximately 50 μm while varying the content of CPT. The enclosing efficiencies in all runs were around 80%, independent of the CPT content. The surface morphology of polylactide microspheres was significantly affected by the content of the enclosing CPT. Furthermore, the degree of unevenness of the surface was increased with an increase in the CPT content in polylactide microspheres. DSC studies have suggested that the glass transition temperature of polylactide microspheres enclosing CPT shifted to lower temperatures with an increasing CPT content. It was assumed from DSC measurements that the morphological change of polylactide microspheres was induced by a polymer-drug interaction. In vitro release experiments suggested that the release rate in the early period increased with an increasing CPT content. From this study, it was pointed out that the drug, miscible with the matrix polymer, induced a change in surface morphology, providing a significant effect on release properties.

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Between 1985 and 2000, 128 esophageal cancer patients underwent esophagectomy with resulting vocal cord paralysis (VCP). They were disease free at least 1 year after surgery. They were divided into Group A (63 patients operated on between 1985 and 1993) and Group B (65 patients operated on between 1994 and 2000). In 1993, we revised our surgical techniques in removing the recurrent nerve lymphatic chains in order to reduce postoperative VCP. Thus, we could compare these two groups of patients. Only two patients (3.1%) of Group B complained of severe hoarseness 1 year after surgery, as compared to 18 patients (28.6%) in Group A. Of the 108 patients who did not complain of severe hoarseness, the mean duration of their difficulty in talking was 3.3 months for Group B and 6.0 months for Group A. The incidence of the persistent VCP 1 year after surgery significantly decreased from 57.1% in Group A to 24.6% in Group B, mainly owing to a recovery from left recurrent nerve palsy. In the group of patients with severe hoarseness 1 year after surgery, daily activity and percentage of ideal body weight at 1 year had deteriorated. Severe hoarseness, therefore, does not seem to be an inevitable consequence of esophagectomy for cancer but rather to surgical maneuver and a poor nutritional state. From the viewpoint of quality of life, the permanent nerve paralysis caused by esophageal cancer surgery is worrisome and a factor in the deterioration of daily activity until it is adequately treated.

microRNA-10b (miR-10b) expression in pancreatic ductal adenocarcinoma (PDAC), as identified by in situ hybridization, is highly correlated with cancer diagnosis, therapy response, and prognosis. If these findings are further confirmed in prospective studies, miR-10b could be used to improve the management of PDAC and decrease the mortality rate of this deadly cancer. Clin Cancer Res; 17(17); 5527–9. ©2011 AACR.

Human leukocyte antigen (HLA)-F is one of the non-classical HLA class I molecules that protects the fetus in pregnancy. HLA-F expression was immunohistochemically examined and the association between clinical parameters and HLA-F expression was analyzed. Cancerous HLA-F and stromal HLA-F-positive infiltrating cells were detected in 91 (40.0%) and 186 (81.6%) cases, respectively. HLA-F positivity in cancer cells was significantly associated with tumor size (P

Background Sarcoid-like reaction is often seen in various types of carcinoma, not only in the primary tumor, but also in regional lymph nodes, and can occur at any time, not only at the time of diagnosis, but also after treatment. However, few cases of hepatopancreatobiliary carcinoma, and no cases of gallbladder cancer with sarcoid-like reaction involving the lymph nodes have been described. This report is the first report of a sarcoid-like reaction involving the lymph nodes in a case of gallbladder cancer. Case presentation We encountered a rare case of gall bladder cancer with sarcoid-like reaction in the lymph nodes. Since regional lymph node swelling that was difficult to differentiate from metastasis was found preoperatively, swollen nodes were examined histologically using frozen sections. Based on this histology, the swollen nodes were diagnosed as showing sarcoid reaction and therefore extended lymphadenectomy was avoided. The patient did not receive any adjuvant chemotherapy and has shown no recurrence of disease as of 4 years after surgery. Conclusion Distinguishing between metastasis and sarcoid-like reaction in lymph nodes by preoperative imaging is still difficult. The present case shows that it is important to histologically examine swollen nodes by biopsy or by sampling before deciding on the treatment strategy for gall bladder cancer with swollen lymph nodes.

Background Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC). Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes. Methods We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort. Results We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC. Conclusion Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.

The Kyushu Study group of Clinical Cancer (KSCC) conducted phase II trials (KSCC0802-UMIN000001308) concerning liver resectability after first-line treatment of advanced liver-limited colorectal metastases (CRLM) by a prospective, multi-center study.Patients received 6 cycles of mFOLFOX6 with bevacizumab followed by evaluating liver resectability. The primary end-point was liver resection rate.The 40 patients enrolled from September 2008 to August 2010. The median number of administration cycles was 6 (range=1-7). The liver resectability cases were 16/40 (40.0 %) and the number of R0 cases was 10 patients (25.0%). An overall response rate was 30.0% (95% CI=15.2%-44.8%). Median progression-free and overall survival of all patients was 9.7 months and 33.0 months), respectively.mFOLFOX6 with bevacizumab regimen is safe and effective for advanced liver-limited CRLM and might lead to high liver resectability.

An appropriate timing for surgical resection of branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) to achieve sufficient postoperative survival is still unknown.Of 80 patients with histologically proven IPMNs, 61 patients who had BD-IPMN without pancreatic cancer concomitant with IPMN were enrolled in this study. We divided BD-IPMN into four groups according to disease progression: low to intermediate grade of dysplasia (LGD/IGD-IPMN), high grade of dysplasia (HGD-IPMN), minimally invasive IPMN (MI-IPMN: T1a), and invasive IPMN (IN-IPMN: ≥T1b). Indicators of surgical resection were investigated on the basis of pathological findings and postoperative prognosis.Postoperative survival was distinctly worse for patients with IN-IPMN than for patients with MI-IPMN, HGD-IPMN, and LGD/IGD-IPMN. Postoperative disease-specific 5-year survival rate was 100 % in patients with IN-IPMN, HGD-IPMN, and LGD/IGD-IPMN, by contrast, 40 % in patients with IN-IPMN. The presence of two of the three factors (pancreatitis, serum carbohydrate antigen [CA] 19-9 levels13 U/mL, and mural nodules) could distinguish HGD-IPMN from LGD/IGD-IPMN with a sensitivity of 92.9 %, specificity of 90.2 %, positive predictive value of 76.5 %, negative predictive value of 97.4 %, and accuracy of 90.9 %.To manage patients with BD-IPMN and achieve a good postoperative prognosis, surgical resection should be performed before progression to IN-IPMN.

Background Metastasis to the breast from nonmammary malignancies is rare, and mostly involves patients in a pre-terminal condition with systemic metastases outside the breast. Lymphoma and leukemia, melanoma, and lung carcinoma are the most common primary malignancies to cause breast metastasis; metastasis of soft tissue sarcoma to the breast is very rare. Here, we report a case of primary lower-extremity myxoid liposarcoma with the development of a solitary metastasis to the breast. To the best of our knowledge, no isolated case reports of solitary breast metastasis by myxoid liposarcoma have been previously reported in the English-language literature. Case presentation The patient, a 66-year-old woman, had been previously diagnosed with myxoid liposarcoma of the right thigh. At 21 months after complete surgical resection of the primary tumor with negative margins, a palpable tumor was identified in the patient’s left breast. Needle biopsy revealed the presence of metastatic liposarcoma; positron emission tomography/computed tomography examination confirmed the metastasis as solitary, and no local recurrence of the primary tumor was identified. The patient underwent lumpectomy with negative margins and did not provide consent for adjuvant chemotherapy. As with the biopsy specimen and the total cleavage specimen, myxoid liposarcoma with metastasis to the breast was diagnosed. No recurrence or new metastases were observed five years after resection of the metastatic breast lesion. Conclusions We have presented an extremely rare case of a solitary metastatic breast tumor arising from myxoid liposarcoma of the lower limbs. There is no standard treatment for the management of solitary breast metastasis from myxoid liposarcoma. Therefore, treatment should be guided by consideration of an individual patient’s overall condition.

Angiogenic molecular markers such as vascular endothelial growth factor and tumor microvessel density reflect prognosis of human cancers. The present study clarified the usefulness of endothelial marker endoglin (CD 105) by assessing microvessel density in esophageal squamous cell carcinoma (ESCC).We immunohistochemically investigated CD105, CD31, and vascular endothelial growth factor-A VEGF-A expression in primary esophageal squamous cell carcinoma specimens from 142 patients.Microvessel density was 35.9±21.2 for CD105 and 46.3±25.4 for CD31. CD105 microvessel density was significantly associated with tumor length, tumor invasion depth, lymph node metastasis, stage, lymphatic invasion, venous invasion, and VEGF-A expression; its correlation with almost all clinicopathological parameters was stronger than CD31 microvessel density. And significantly better prognosis was achieved in patients with low, compared to high CD105, microvessel density.CD105 microvessel density reflected the degree of angiogenesis and prognosis in patients with esophageal squamous cell carcinoma.

Ghrelin, an orexigenic peptide, is primarily produced and secreted by the gastrointestinal tract. As far as we are aware of, there is no evidence of ghrelin expression in esophageal squamous cell carcinoma (ESCC).Two hundred and ten patients with ESCC who underwent surgical resection were enrolled in this study. We immunohistochemically investigated ghrelin expression in primary ESCC specimens and analyzed the relationship with clinicopathological factors.High ghrelin expression was observed in 61 patients (29.0%). Depth of tumor invasion and histological differentiation were statistically associated with ghrelin expression. As for depth of tumor invasion, the deeper it was, the higher was the expression of ghrelin. Well-differentiated tumors had a significantly higher proportion of ghrelin-expressing cells than other types.Ghrelin expression correlated with tumor depth and tumor differentiation, suggesting an important role of ghrelin in tumor growth in ESCC.

Epigenetic alterations have been reported to deregulate the expression of many transcripts, including noncoding RNAs that have no apparent protein-coding capacity. Recently, as the result of numerous studies focused on miRNAs, novel sequencing technologies have made available the transcription profile of the entire human genome. miRNAs as drivers of tumor-suppressive and oncogenic functions have been found to be dysregulated in numerous cancer types. However, the functions of epigenetically regulated genetic elements other than protein-coding genes are still a matter of debate. In this review, the authors focus mainly on describing the epigenetic regulation of miRNAs in cancer. They also discuss the role of miRNAs as potential diagnostic and/or prognostic biomarkers.

Cholangiocarcinoma (CCA) is a highly malignant cancer of the biliary tract with a poor prognosis, which often arises from conditions causing long-term inflammation, injury, and reparative biliary epithelial cell proliferation. Several conditions are known to be major risk factors for cancer in the biliary tract or gallbladder, including primary sclerosing cholangitis, liver fluke infection, pancreaticobiliary maljunction, and chemical exposure in proof-printing workers. Abnormalities in various signaling cascades, molecules, and genetic mutations are involved in the pathogenesis of CCA. CCA is characterized by a series of highly recurrent mutations in genes, including KRAS, BRF, TP53, Smad, and p16(INK4a) . Cytokines that are affected by inflammatory environmental conditions, such as interleukin-6 (IL-6), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and platelet-derived growth factor (PDGF), play an important role in cancer pathogenesis. Prominent signaling pathways important in carcinogenesis include TGF-β/Smad, IL-6/STAT-3, PI3K/AKT, Wnt, RAF/MEK/MAPK, and Notch. Additionally, some microRNAs regulate targets in critical pathways of CCA development and progression. This review article provides the understanding of the genetic and epigenetic mechanism(s) of carcinogenesis in CCA, which leads to the development of new therapeutic targets for the prevention and treatment of this devastating cancer.

Stapled esophagogastrostomy is simple and safe reconstruction after proximal gastrectomy. However, this reconstruction is often concomitant with severe reflux esophagitis because of the loss of cardiac function; simple esophagogastrostomy is not preferred reconstruction after proximal gastrectomy. To prevent reflux esophagitis, we established the fundoplication under the endoscopic stent after proximal gastrectomy.After proximal gastrectomy with lymph node dissection, end-to-side esophago-gastrostomy was done with circular suturing instrument. To prevent gastric juice reflux from the remnant stomach, the stomach was rolling around the abdominal esophagus and tightly under the endoscopical stenting. To make renewal His angle and fornix, the stump of greater curvature was fixed to the left side of diaphragmatic crus with some sutures.We performed this type of fudplication for 18 patients with early gastric cancers and gastric submucosal tumors. Almost all patients postoperative course was uneventful. Three patients needed an endoscopic dilatation for the stricture of esophago-gastrostomy. One case revealed asymptomatic reflux esophagitis because of the looseness of the anastomosis. Weight loss was limited, almost all patients recovered preoperative weight.Simple esophagogastrostomy plus this fundoplication with endoscopic stent is safe and satisfactory reconstruction procedure after proximal gastrectomy.

Background Axillary lymph node (ALN) status is an important prognostic factor for breast cancer. We retrospectively used contrast-enhanced computed tomography (CE-CT) to evaluate the presence of ALN, metastasis based on size, shape, and contrasting effects. Methods Of 131 consecutive patients who underwent CE-CT followed by surgery for breast cancer between 2005 and 2012 in our institution, 49 were histologically diagnosed with lymph node metastasis. Maximum Hounsfield units (HU) and mean HU were measured in non-contrasting CT (NC-CT) and CE-CT of ALNs. Results Of 12 examined measurements, we found significant differences between negative and metastatic ALNs in mean and maximum NC-CT HU, and mean and maximum CE-CT HU (P

We have evaluated the safety and feasibility of combining median-to-lateral and anterior-to-median (MLAM) approaches to perform laparoscopic complete mesocolic excision (CME) with radical lymph node dissection along the gastrocolic trunk of Henle (GTH) for right hemicolon cancer. We retrospectively analyzed data obtained from a prospectively maintained database on 31 consecutive patients who had undergone laparoscopic CME with radical lymph node dissection for right hemicolon cancer between January 2010 and December 2013. We used video recordings of the procedure to assess the quality of the surgery and completeness of CME. We also assessed operative data, pathological findings, length of large bowel resected, complications, BMI, operative time by experience of surgeon, and length of hospital stay. All patients had undergone en bloc resection of the enveloped parietal planes and radical lymph node dissection along the surgical trunk without any serious intraoperative complications. Twenty six and five patients graded mesocolic and intra-mesocolic plane, respectively. Five, three, eleven, and thirteen patients had T1, T2, T3, and T4 tumors, respectively. The median number of lymph nodes retrieved was 25, lymph node metastasis being identified in 11 patients. The mean length of large bowel resected was 21.8 cm. The mean operative time and intraoperative blood loss were 269 min and 39 mL, respectively. No intraoperative complications occurred in any patient. Three patients had postoperative complications. The mean BMI was 22.6 kg/m2. The mean operative time for patients stratified by BMI of

Cyclin-dependent kinase subunit 2 (CKS2) is a cyclin-dependent kinase subunit (CKS) family member that participates in cell cycle regulation. Few studies have investigated its involvement in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to assess the clinical significance of CKS2 in ESCC. We used immunohistochemistry to study the clinicopathologic significance of CKS2 protein expression in 121 patients with ESCC. Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we examined the expression of CKS2 mRNA in tumors and the corresponding normal esophageal tissues that were obtained from 62 patients. Finally, siRNA-mediated attenuation of CKS2 expression was examined in vitro. CKS2 protein expression was significantly correlated with depth of tumor invasion, clinical stage, lymphatic invasion and distant metastasis (p=0.033, 0.028, 0.041 and 0.009, respectively). CKS2 mRNA expression was higher in cancer tissue than in corresponding normal tissue (p

Invariant chain (Ii) is a chaperone molecule that inhibits the binding of endogenous antigens to HLA class II. The tumor cell with overexpressed Ii chain is thought to escape attacking cytotoxic lymphocytes by suppressing the host immune. However, the relationship between Ii expression by the tumor and clinicopathological factors in gastric cancer remains unclear. We studied 126 patients with gastric cancer who had undergone curative gastrectomy at Kagoshima University Hospital between 1988 and 1997. In order to detect Ii and HLA-DR expression by tumor cells, immunohistochemical staining with anti-CD74 and anti-HLA-DR antibodies were performed by avidin-biotin peroxidase complex method. The 126 patients studied were divided into two groups based on Ii expression. Ii and HLA-DR were expressed both on the surface and in the cytoplasm of tumor cells and tumor infiltrating lymphocytes. A total of 48 patients were identified as Ii positive, while the remaining 78 patients were Ii negative. Ii expression negatively correlated with the depth of invasion of the tumor as well as the patients’ clinical stage. Ii expression was negatively correlated with HLA-DR expression. Patients with Ii negative expression had significantly better surgical outcomes than those with Ii positive expression (P

The clinicopathologic significance of micrometastasis (MM) and tumor cell microinvolvement (TCM) in regional lymph nodes as identified by immunohistochemical staining for cytokeratin expression was evaluated in patients with node-negative gastric cancer.MM was defined as tumor cells with stromal reaction, and TCM was defined as individual tumor cells without stromal reaction. We investigated 1761 lymph nodes obtained from 67 gastric cancer patients whose diagnosis showed no lymph node metastasis by routine histological examination. The depth of tumor invasion was T1 (submucosa) in 33 patients and T2 (muscularis propria and subserosa) in 34 patients. The lymph nodes were examined immunohistochemically for the presence of tumor cells using anti-cytokeratin AE1/AE3 monoclonal antibody. Both the biopsy tumor specimens obtained prior to surgery and the resected primary tumors were immunostained with E-cadherin (E-cad) monoclonal antibody.Thirty (1.5%) of the 1761 lymph nodes showed MM and/or TCM. MM with or without TCM was found in 10 patients, and TCM alone was found in 4 patients; 6 (18.2%) of the 33 patients with T1 tumor and 8 (23.5%) of the 34 patients with T2 tumor had occult lymph node metastasis. The 5-year survival rate was worse among those with MM with or without TCM, than among those without MM. Nearly all of the patients with MM and/or TCM had reduced or negative E-cad expression in the primary tumor.We demonstrated that the incidence of MM and/or TCM in the lymph nodes of patients with gastric cancer is quite high, and that such metastasis is associated with the prognosis of patients with pN0. Examination of E-cad expression in biopsy tumor specimens may be useful for predicting MM and/or TCM.

Blood-borne metastasis, including liver metastasis, is one of several important prognostic factors in patients with gastric cancer undergoing curative resection. 1,2 Even in patients with early gastric cancer, blood-borne metastasis occurs. 3–5 In animal studies, cancer cells have been observed to shed into the bloodstream during surgical manipulation of a primary tumor. 6,7 In turn, this shedding of cancer cells into the bloodstream enhanced the distant metastasis. 8,9 Circulating cancer cells are now easily detectable with polymerase chain reaction (PCR) or reverse transcriptase–polymerase chain reaction (RT-PCR). There have been several studies on the detection of circulating cancer cells in the blood by PCR or RT-PCR. 10–15 Eschwege et al 16 showed the dissemination of prostatic epithelial cells during radical prostatectomy in patients with prostatic cancer by RT-PCR. Brown et al 17 detected tumor cell dissemination during surgery in patients with breast cancer using RT-PCR. However, relatively few reports have examined the presence of cancer cells in blood samples from various sites or investigated the relation between the detection of circulation of cancer cells and blood-borne metastases. Gerhard et al 18 established carcinoembryonic antigen (CEA)-specific RT-PCR in 1994. Mori et al 19 detected circulating cancer cells in patients with gastric cancer by CEA-specific RT-PCR. Funaki et al 20 detected CEA-mRNA in the circulating peripheral blood in patients with gastric cancer using their own CEA-specific RT-PCR method. Thus, the CEA-specific RT-PCR method is useful for detecting circulating cancer cells in patients with gastric cancer. We performed CEA-specific RT-PCR on blood samples from several vessels to investigate the relation between the detection of circulating cancer cells during surgery and blood-borne metastases. Thus, the present study examines circulating cancer cells from various sites according to the time course during a surgical procedure and attempts to determine the relation between the appearance of cancer cells in blood as a result of surgical maneuvers and liver metastasis in patients with gastric cancer.

胃粘膜下層癌 (以下, SM胃癌) 120例を対象として胃癌取扱い規約の深達度亜分類 (SM1, SM2) の有用性を検討した. SM1は50例, SM2は70例であった. リンパ節転移はそれぞれSM1: 6例, SM2: 20例であり, 有意差が認められた (p

To demonstrate the association of Epstein-Barr virus (EBV) with primary epithelial neoplasms in the south part of Kyushu, Japan, 761 carcinomas consisting of 75 lung, 61 breast, 107 esophagus, 102 colon, 58 pancreas, 45 thyroid, and 313 gastric cancers were examined by EBER-1 in situ hybridization. EBER-1 was detected in 23 cases (7.3%) out of 313 gastric carcinomas, while none of the other carcinomas was positive for EBER-1. Twenty-eight (9.4%) out of 313 gastric carcinomas were differentiated poorly to moderately carcinomas with prominent lymphoid cell infiltration, similar to so-called lymphoepithelioma-like carcinoma, and 19 cases (67.9%) were positive for EBER-1. Although two (2.6%) and 11(10.3%) out of 75 lung and 107 esophagus carcinomas were so-called lymphoepithelioma-like carcinomas, respectively, but EBER-1 was not detected in other epithelial neoplasms that originated from the lung, esophagus, breast, colon, pancreas, and thyroid in the south of Kyushu, Japan. As a result, EBV was associated with only some gastric carcinomas but not with other epithelial neoplasms originating from the lung, esophagus, breast, colon, pancreas, and thyroid in southern Japan.

Roux-en-Y reconstruction after total gastrectomy is a simple and safe procedure; however, it eliminates the gastric reservoir function and markedly changes the postoperative digestive physiology. The patients therefore suffer from insufficient food intake and malabsorption. It has been reported that jejunal pouch reconstruction increases food intake and improves the nutritional status. We established a novel Roux-en-Y reconstruction with stapled distal jejunal pouch after total gastrectomy. A jejunal pouch, 8 cm in size, was attached at the jejunojejunostomy. We performed this novel reconstruction for 20 gastric cancer patients after total gastrectomy with lymph node dissection as a feasible study. One year after operation, the average percentage weight was maintained in more than 90 per cent and 17 (85%) of these patients were in the normal range of the body mass index. This procedure may improve postoperative malnutrition after total gastrectomy according to our feasible study. A multicenter randomized trial of this approach comparing with Roux-en-Y reconstruction without a pouch is ongoing.

BACKGROUND Tumor involvement of regional lymph nodes has a crucial impact on the prognosis of patients with adenocarcinoma of the esophagogastric junction (AEG). Although additional tumor cell deposits can be detected by sensitive methods (e.g., immunohistochemistry and polymerase chain reaction), their prognostic significance is uncertain. METHODS Using immunohistochemistry for cytokeratins (AE1/AE3 antibody), the authors studied 3987 regional lymph nodes from 145 patients with completely resected adenocarcinoma of the esophagus (AEG I; n = 46 patients), cardia (AEG II; n = 79 patients), and subcardial region (AEG III; n = 20 patients). The newly detected cells were categorized with tumor cell microinvolvement (TCM) or with micrometastases (MM) based on tumor size and histology. RESULTS Of the 75 pathologic lymph node negative (pN0) patients, 3 of 30 patients in the AEG I group (10%) and 8 of 45 patients in the AEG II and III groups (18%) had TCM (no significant difference). MM was found in 2 of 30 tumors in the AEG I group (7%) and in 11 of 45 tumors in the AEG II and III groups (24%), a significantly lower rate that that in the AEG I group (P 0.05). For the AEG II and III tumors, MM (new lymph node positive [pN+] cases) had a prognostic impact similar to metastases found by routine methods, with reclassification based on MM resulting in improvement in the pN0 group from 72.8 months to 82.6 months, but almost no change was seen in the pN+ group (49.9–49.2 months). TCM had no adverse impact on survival in any tumor type. CONCLUSIONS These results highlight important differences between AEG I tumors and AEG II and III tumors and argue for different lymphadenectomy strategies for patients with these tumor types. Cancer 2000;89:1874–82. © 2000 American Cancer Society.

The p53 gene is associated with G1 arrest during the cell cycle and with apoptosis. To evaluate the preoperative chemotherapeutic effect in esophageal squamous cell carcinoma, we retrospectively investigated the apoptotic index (AI) and Ki-67 labeling index (Ki-67LI) in relation to the expression of p53. Thirty patients with esophageal carcinoma who had received chemotherapy prior to surgery were examined using the terminal deoxynucleotidyl-transferase-mediated in-situ end-labeling (TUNEL) method for evaluating AI and immunohistochemical staining with anti Ki-67 and anti p53 antibody for evaluating Ki-67LI and p53 expression, respectively. The histological response rate of chemotherapy was 20.0%. A significant correlation between p53-negative expression and response to chemotherapy was found (P0. 01). The AIs and Ki-67LIs in p53-negative tumors with ineffective responses to chemotherapy were significantly higher than those in p53-positive tumors with ineffective responses (P0.05). The AIs and Ki-67LIs were significantly lower in p53-negative tumors with effective responses to chemotherapy than those in p53-negative tumors with ineffective responses (P0.05 and P0.01, respectively). Furthermore, significant correlations were found between AIs and Ki-67LIs in p53 negative tumors (r=0.60, P0.05). In esophageal carcinoma, p53-negative tumors with highly proliferative cells might be susceptible to apoptosis induced by chemotherapy.

Intratumoral natural killer cells (NKC) and dendritic cells (DC) may affect the clinical features of various gastrointestinal cancers. However, the relationship between intratumoral NKC and DC remains unclear. We examined 169 patients with gastric cancer who underwent gastrectomy at Kagoshima University Hospital. Immunohistochemical staining of CD57 and S-100-protein was performed to evaluate NKC and DC infiltration, respectively. A total of 25 areas containing pericancerous tissue were selected for determining the number of NKC and DC under high power microscopy (x400). Patients were classified into two groups according to NKC and DC population. Intratumoral lymphocytic infiltration was also calculated in 15 areas with a high power (x400) objective. The degree of NKC and DC infiltration was gradually decreased according to the progression of nodal involvement. Patients with many NKC infiltration had a lower positivity of lymph node metastasis and lymphatic invasion than patients with little NKC infiltration. DC infiltration was also negatively correlated with depth of invasion, lymph node metastasis and curativity. DC infiltration was positively correlated with lymphocytic infiltration (P=0.01. r=0.6). The 5-year survival rates of patients with many NKC infiltration and patients with DC many infiltration were 75 and 78%, respectively, both of which were significantly better than that of patients with little NKC and DC infiltration (P

A prospective study was performed to clarify the surgical outcome of patients with esophageal carcinoma who would benefit from induction chemotherapy followed by surgery. Of 55 eligible patients, 42 (76.3%) agreed to randomization with either chemotherapy followed by surgery (n = 21) or surgery alone (n = 21). The other 13 refused. The chemotherapy consisted of cisplatin, 5-fluorouracil and leucovorin. All 55 patients underwent esophagectomy with two- or three-field resection, including two (3.6%) hospital mortalities. Of the 21 patients receiving chemotherapy, the response rate was 33.3% after the first course and 60% after the second course. A complete response was not obtained. Responders to the first course showed a prolonged survival, however time to treatment failure did not differ between patients treated with chemotherapy followed by surgery or surgery alone. This chemotherapy offered a worse surgical outcome for patients with pretreatment diagnosis of T3. Multivariate analysis identified a partial response to the first course of chemotherapy to be a favorable prognostic indicator. Preoperative chemotherapy does not give a survival benefit over surgery alone for patients with advanced tumor (T3). Initial response to the first dose of chemotherapy is deemed to be a prognostic factor for patients with less advanced tumor (T1/T2).

Natural killer (NK) cells are a group of effector cells that act nonspecifically against tumor cells. The correlation between intratumoral NK cell infiltration and clinicopathologic features remains unclear.The authors selected 146 patients with gastric carcinoma who underwent gastrectomy at Kagoshima University Hospital between 1985-1995. Immunohistochemical staining with the CD57 antibody was performed for the evaluation of NK cell infiltration. A total of 25 areas containing CD57 positive cells were selected and the number of NK cells were counted (magnification, x200). The patients were divided into 2 groups: patients with a high level of NK infiltration (n = 39) (25 NK cells/25 high-power fields [HPF]) and patients with a low level of NK infiltration (n = 107) (25 NK cells/25 HPF). Intratumoral lymphocytic infiltration also was counted in 25 areas at a magnification of x200. Patients were classified into a high infiltrating lymphocyte (IL) group (n = 69) (150 cells/HPF) and a low IL group (n = 77) (150 cells/HPF). The Kaplan-Meier curve was used to analyze surgical outcome. Multivariate analyses were performed to evaluate prognostic factors.Patients with a high level of NK infiltration had a higher rate of early gastric carcinoma, fewer metastases to the lymph nodes (P0.01), and less lymphatic invasion (P0.05) than patients with a low level of NK infiltration. NK cell infiltration also was found to correlate with depth of invasion, clinical stage, and venous invasion. There was no correlation between NK cells and lymphocytic infiltration (P = 0.07; correlation coefficient = 0.15). The 5-year survival rate of patients with a high rate of NK infiltration was 78%, which was significantly better than that of patients with a low level of NK infiltration (P0.01). Multivariate analysis did not show NK cell infiltration to be a significant prognostic factor. Combination analysis of the number of NK cells and lymphocytic infiltration was shown to be an independent prognostic factor (P = 0.02; hazard ratio = 1.32).Patients with a high level of NK infiltration were found to have a better prognosis than those with a low level of NK infiltration. Combination analysis with lymphocytic infiltration may provide useful information regarding the immunologic condition of patients with gastric carcinoma.

胃癌術後に発症したサイトメガロウイルス (以下, CMV) 肺炎の2治験例を経験した. 症例1は63歳の男性. 4型胃癌に対して術前腹腔内にシスプラチンを投与し, 胃全摘術を施行した. 術後間質性肺炎を発症した.CMV肺炎を疑い, 抗ウイルス剤を先行投与し, 軽快治癒した. 原因検索の結果, CMV肺炎と診断された. 症例2は66歳の男性. 左肺癌と早期胃癌の重複癌で, 術前放射線療法を受けていた. 幽門側胃切除術施行後, 間質性肺炎をきたした. 抗ウイルス剤投与にて治癒しえた. 治療後にCMVが同定された. 両症例とも肺炎発症時にリンパ球数は低下しており, 術前の化学療法あるいは放射線療法による免疫能低下がCMV肺炎発症に関与したと推定された. 抗ウイルス剤による治療後に起因ウイルスが同定された. CMV肺炎の治療成績は不良であり, 本疾患が強く疑われる場合, 抗ウイルス剤の早期投与は有用と考えられた.

Using 2 anti-mucin 1 (MUC1) monoclonal antibodies (MAbs), DF3 and BCP8, we examined MUC1 expression immunohistochemically in 192 esophageal squamous-cell carcinomas (SCCs). In normal squamous epithelium of the esophagus, DF3 was not expressed, but BCP8 was expressed on the cell membrane, mainly in the surface layer. In esophageal SCCs, DF3 and BCP8 were expressed mainly on the cell membrane of SCC cells, but also in the cytoplasm in several cases. To analyze the correlation of MUC1 expression and the prognosis of the patients, the 192 cases were divided into 2 groups: high-expression group (HEG, >50% of the neoplastic cells stained) and low-expression group (LEG

Background: Lymphatic invasion is a risk factor for lymph node metastases in patients with gastric cancer. No studies have been reported, however, on the correlation between lymphatic invasion and lymph node metastasis in early gastric cancer invading into the submucosa. Methods: We performed a retrospective analysis of lymphatic invasion in 170 patients with early gastric cancer invading into the submucosa. Results: Lymphatic invasion was found in 76 patients. Lymphatic invasion correlated significantly with the presence of lymph node metastasis and vascular invasion (P < .05) and with the degree of cancerous submucosal involvement (P < .05). The presence of lymph node metastasis also correlated with the grade of submucosal invasion and lymphatic invasion. The 5-year survival of patients with lymphatic invasion was poorer than that of patients without lymphatic invasion (P < .05). Node-negative patients had similar survival, regardless of the presence of lymphatic invasion. All patients with severe lymphatic invasion had sm3 invasion and lymph node metastases. Conclusion: Although lymphatic invasion is the first stage of lymph node metastasis, lymphatic invasion in itself does not have clinical importance except for severe invasion in early gastric cancer. It is possible to predict lymph node metastases from the combined evaluation of degree of lymphatic invasion and submucosal involvement of the tumor in patients with early gastric cancer invading into the submucosa.

We report a rare case of synchronous quintuple advanced carcinoma of the colon. A 73-year-old man was admitted to the hospital because of discomfort of the anus. Gastrointestinal fiberscopy revealed five protruding lesions in the cecal, transverse, descending, sigmoid colon and upper rectum. During operation, five lesions were suspected to have serosal invasion. Cecal and sigmoid lesions were resected with D 2 lymphadenectomy and the other three lesions were extirpated with D 1 lymphadenectomy. Histologically sigmoid colon cancer invaded the mp layer and the other 4 lesions invaded subserosal layer. Regional lymph node metastases were found in the cecal carcinoma. p53 expression was positive in the tumors of the cecum and sigmoid colon, whereas p 21 expression was negative in the all tumors. These findings suggested that there that there were some differences in proliferation among these tumors. Six months after the operation, since multiple liver me-tastases were detected by CT examination, chemotherapy via hepatic artery has been performed. Synchronous quintuple advanced cancer of the colon is rare. Considering the total volume of all five tumors, some strategy for hematogenous metastasis which must occur in early stage would be needed.