Search

壁内転移とリンパ節転移を伴った食道多発粘膜癌の1例を経験したので報告する.症例は75歳の男性で, 嚥下困難を主訴として来院し, 内視鏡検査で中部食道の白苔と発赤を指摘され, 生検の結果, 扁平上皮癌と診断された.入院後の超音波内視鏡検査で固有筋層内への浸潤とリンパ節転移が疑われたため, 右開胸・開腹によって食道亜全摘とリンパ節郭清を施行した.切除標本の病理組織学的検索において内視鏡検査で認められた病変は深達度が粘膜内に留まる4個の多発病変であることが判明した.また超音波内視鏡で指摘された病変は粘膜下腫瘍の形態を呈しており, 連続切片を作成して検討した結果, 組織型は低分化扁平上皮癌で, 腫瘍を覆う粘膜の上皮から粘膜筋板まではすべての切片で保たれており, 最終的には食道mm癌からの壁内転移と診断された.食道mm癌の壁内転移はまれであるが, その可能性も十分念頭において術前診断に臨むべきことが示唆された.

Alterations in microRNA (miRNA) and other short or long non-coding RNA (ncRNA) are involved in the initiation, progression, and metastasis of human cancer. The main molecular alterations result from variations in gene expression, which are usually minor but have consequences for a vast number of target protein-coding genes. The causes of the widespread differential expression of ncRNAs in malignant cells compared with normal cells can be explained by the location of these genes in genomic regions associated with cancer, by epigenetic mechanisms, and by alterations in the processing machinery. Expression profiling of human tumors based on the expression of miRNAs and other short or long ncRNAs has identified signatures associated with diagnosis, staging, progression, prognosis, and response to treatment. In addition, profiling has been exploited to identify ncRNAs that may represent downstream targets of activated oncogenic pathways or that target protein-coding genes involved in cancer. Recent studies found that miRNAs and non-coding ultraconserved genes are the main candidates for the elusive class of cancer-predisposing genes and that other types of ncRNAs participate in the genetic puzzle that gives rise to the malignant phenotype. These discoveries could be exploited for the development of useful markers for diagnosis and prognosis in cancer, as well as for the development of new RNA-based cancer therapies.

Recently, the existence of lymph node micrometastasis (LNM), including isolated tumor cells, has been focused on during the development of molecular diagnostic tools for lymph node metastasis in various malignant neoplasms. In particular, immunohistochemistry and reverse transcription-polymerase chain reaction have been reported to be available for the detection of LNM in gastric cancer. However, at present, the clinical significance of LNM remains unclear in patients with gastric cancer. Therefore, we cannot strategically make light of this issue in clinical management. Currently, minimally invasive treatments, such as endoscopic submucosal dissection and laparoscopic surgery with personalized lymphadenectomy, are widely performed in consideration of postsurgical quality of life (QOL). However, it is important to maintain the balance between QOL and curability when selecting surgical treatments for patients with gastric cancer. If minimally invasive surgery based on LNM status was established for patients with early gastric cancer, it could be performed safely. We reviewed the clinical significance of LNM as an important strategic target in patients with gastric cancer.

Background Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified. Methods A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed. Results The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval. Conclusion The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system.

To examine the appearance and distribution of folate receptor β-expressing (FRβ+) macrophages in the pancreatic tumor microenvironment and their relationship to metastasis and prognosis in pancreatic cancer patients. Tumor samples were obtained from 76 patients with pancreatic cancer who underwent curative resection. None of these patients had received any preoperative chemotherapy or radiotherapy. Both FRβ+ and tumor-infiltrating (CD68+) macrophages were examined in each tumor specimen by immunohistochemical and immunofluorescence staining using a newly developed anti-human FRβ monoclonal antibody and CD68 antibody. The appearance, distribution, expression of vascular endothelial growth factor (VEGF) on FRβ-expressing or CD68+ macrophages, and tumor microvessel density (MVD) were assessed. Log rank test and Cox proportional hazard regression were used to investigate the associations among CD68+ or FRβ+ macrophages, clinicopathologic factors, and overall survival. FRβ+ macrophages were prominent in the perivascular regions of the tumor-invasive front and a specific subset with VEGF expression in the CD68+ macrophages. A high number of FRβ+ macrophages showed a positive association with high MVD, a high incidence of hematogenous metastasis, and a poor prognosis in pancreatic cancer patients. FRβ+ macrophages are a novel subset of tumor-associated macrophages in pancreatic cancer and may play an important role in the tumor microenvironment in association with systemic metastasis through the interaction with tumor cells and vessels. FRβ+ macrophages may be promising a targeting therapy for pancreatic cancer.

A prospective feasibility study was planned to clarify the proportion of compliance and adverse events in the administration of capecitabine as adjuvant chemotherapy for colon cancer in Japanese patients.We aimed initially to register 92 cases of R0 stage III colon cancer. Capecitabine (2,500 mg/m(2)/day) was given orally on days 1-14 every 3 weeks for 8 cycles. The proportion of treatments completed as planned was selected as the primary endpoint.Ninety-seven cases were registered and treated between September 2008 and August 2009. The proportion of treatments completed in the full analysis set was 64/97 [66.0%; 95% confidence interval (CI), 55.7-75.3%] and in the per protocol set was 64/91 (70.3%; 95% CI, 59.8-79.5%). Adverse events which led to treatment discontinuation included hand-foot syndrome (HFS) (7), haematotoxicity (5) and increased hepatic damage (4). The proportions of patients with major grade 3/4 adverse events were HFS 22.7%, neutropenia 7.2%, diarrhoea 2.1%, and increased bilirubin 0.0%.This collaborative multi-facility study, the first of its kind in Japan, presented results of a safety confirmation experiment on capecitabine as adjuvant chemotherapy for stage III colon cancer. The results suggest that capecitabine may be administered safely to Japanese patients.

We report the results of oncoplastic surgery in two Japanese patients with early breast cancer. Their breasts were large and ptotic, and their lesions, which were close to the areola, were considered to be suitable for breast conservative surgery. Oncoplastic surgery involving partial resection of the gland and a periareolar mammoplasty were performed. The technique was easy to perform, and the cosmetic outcome was excellent.

The B7-H4 coregulatory molecule is a member of the B7 family of molecules, which regulate the T-cell-mediated immune response through CD28 receptors. Recently, B7-H4 has been reported to be a negative regulator of the immune response in patients with several malignant diseases. However, few reports have investigated the clinical significance of B7-H4 expression in patients with gastric cancer. In the present study, we analyzed B7-H4 expression and the relationship between its expression and clinicopathological factors including prognosis in gastric cancer.B7-H4 expression in gastric cancer cell lines and clinical gastric cancer specimens was initially assessed with the reverse transcription-polymerase chain reaction (RT-PCR). Moreover, B7-H4 and CD3 expression in 120 resected specimens from gastric cancer patients were evaluated by immunohistochemistry (IHC).B7-H4 expression was identified in the gastric cancer cell lines and clinical tumor tissues by RT-PCR. B7-H4 expression was high in 25.8% (31/120) of resected tumor specimens. B7-H4 expression significantly correlated with tumor stage (P = 0.04). The 5-year survival rate was significantly lower in patients with high B7-H4 expression than in those with low B7-H4 expression (P = 0.001). Multivariate analysis demonstrated that B7-H4 expression was an independent prognostic factor (P = 0.035). Immunohistochemical analysis of CD3 expression showed that B7-H4 expression was inversely correlated with the number of tumor infiltrating T lymphocytes (P0.001).The B7-H4 coregulatory molecule is a novel prognostic marker related to the T-cell-mediated immune response, and its pathway may be a molecular target for controlling tumor progression in patients with gastric cancer.

BACKGROUND AND OBJECTIES: Phenotypic plasticity of cancer cells via epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) is essential for tumor progression and metastasis.Tissue samples were obtained from 76 pancreatic head cancers. We assessed the expression of E-cadherin, vimentin, ZEB-1, and ZEB-2 by immunohistochemical and immunofluorescence staining. Next, 147 metastatic lymph nodes from 45 pancreatic cancers with low expression of E-cadherin were obtained and divided into two categories according to the maximum diameter of the metastases: 2 mm or more and less than 2 mm.High expressions of ZEB-1 and ZEB-2 in the primary tumors were significantly associated with repression of E-cadherin (P = 0.0007), and poorer prognosis (P = 0.0322). Forty-three (29.3%) of the 147 metastatic tumors from pancreatic cancers with low expression of E-cadherin showed high E-cadherin expression. Cancer cells in the larger metastases showed high expression of E-cadherin (P = 0.0061) and low expression of ZEB-1 (P = 0.0170) and ZEB-2 (P = 0.0036) compared with those in the smaller metastases.In primary pancreatic tumors and metastatic lymph nodes, high and low expression of ZEB-1 and ZEB-2 was associated with mesenchymal and epithelial phenotype of cancer cells, respectively.

The expression of desmoglein I (DGI) in both primary turners and metastatic lymph node of esophageal carcinoma was studied immunohistochemically in 102 patients using an anti-DGI monoclonal antibody. Normal squamous epithelial cells strongly expressed DGI at their cell-cell boundaries. DGI expression in the tumors was divided into DGI (++), DGI (+), DGI (-) according to the staining intensity. DGI (+) or DG (-) tumors had lymph node metastases more frequently than DGI (++) tumors (p

AIM: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses. METHODS: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16INK4a expression in HPV-positive and HPV-negative cases was also made. RESULTS: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16INK4a proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and -negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs. CONCLUSION: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.

The limitations of surgical treatment for advanced esophageal cancer have been clarified, although esophagectomy with extended lymph node dissection has been widespread in Japan. Preoperative adjuvant therapy has been investigated in Western countries, and recently preoperative chemoradiotherapy (CRT) has been introduced for the treatment of resectable esophageal cancer. There are several reports of randomized controlled trials (RCTs) comparing CRT followed by surgery and surgery alone. According to the results of a meta-analysis, preoperative CRT is considered to be the standard therapy in Western countries. However, problems in the clinical heterogeneity of meta-analyses include: small number of patients in each RCT; differences in stage grouping; presence of both squamous cell carcinoma and adenocarcinoma; various surgical techniques used; and differences in the amount of radiation administered. Preoperative CRT appears to be a promising method for the treatment of potentially resectable advanced esophageal cancer patients with nodal metastasis. Currently, phase I and II trials of new anticancer agents or molecular targeting agents are ongoing. However, since the surgical procedure in the Western method is still being debated, well-designed RCTs are necessary, especially in esophageal squamous cell carcinoma. The effectiveness of CRT followed by surgery should be clarified based on excellent Japanese surgical techniques.

Breast conservative therapy (BCT) as treatment for early breast cancer usually ensures local control and acceptable cosmetic results. We describe a new technique of using an inframammary adipofascial flap to reconstruct defects caused by lower-pole partial mastectomy, which achieved excellent results (Kijima et al. in Am J Surg 193:789–91 (1); Sakai et al. in Ann Plast Surg 29(2):173–7, 2; Ogawa Am J Surg 193:514–8, 3). We developed this procedure as an oncoplastic technique for a Japanese woman with a similar defect without ptosis. After partial mastectomy, the superior half of the flap is harvested via an initial incision along the inframammary line, and the inferior half is harvested via an additional incision along the caudal edge of the flap, to produce a crescent of de-epithelialized skin. A tongue-shaped flap containing the crescent of de-epithelialized skin, subcutaneous fat, and the fascia of the vertical rectus abdominis muscle is then rotated upwards, gathered, and inserted into the breast defect.

The clinical significance of B7-H3 expression in gastric cancer remains unclear, although the B7 ligand family plays a critical role in the T cell-mediated immune response. We therefore investigated B7-H3 expression as a blood marker of circulating tumor cells and determined correlations with tumor progression in patients with gastric cancer. B7-H3 expression in gastric cell lines was initially evaluated by immunocytochemistry. Furthermore, we used quantitative RT-PCR to assess B7-H3 mRNA expression in four cell lines and in 95 blood specimens from patients with gastric cancer, as well as in 21 samples of peripheral blood lymphocytes from healthy volunteers. B7-H3 expression in cell lines was identified by immunocytochemistry and quantitative RT-PCR. Blood specimens from patients with gastric cancer contained significantly more copies of B7-H3 mRNA than those from healthy volunteers without cancer (P < 0.0001). Levels of B7-H3 expression significantly correlated with overall stage (P = 0.013). The 5-year survival rate was significantly lower in patients with high B7-H3 expression than with low expression (P = 0.02). Multivariate analysis demonstrated that B7-H3 expression was an independent prognostic factor (P = 0.046). Our results indicate that B7-H3 appears to be a useful blood marker for predicting tumor progression in gastric cancer.

A case of an inflammatory pseudotumor arising in the spleen of a 60-year-old Japanese male is described herein. This benign lesion is extremely rare, with only 12 cases, including our own, having been reported in the world literature. We preoperatively diagnosed the splenic tumor as a metastasis, due to the coexistance of advanced stage carcinoma in the sigmoid colon. However, after splenectomy, histopathological examination of the mass revealed an inflammatory process. Inflammatory pseudotumors often pose diagnostic difficulties because the clinical and radiologic findings are suggestive of malignancy. The clinical and pathological features of cases previously reported are reviewed following the presentation of this case.

The 14-3-3 sigma gene is transcriptionally activated by p53 after DNA damage and facilitates DNA repair during G2 arrest. The present study analyzed the clinical significance of 14-3-3 sigma expression in esophageal squamous cell carcinoma.The relationship between 14-3-3 sigma and p53 expressions was investigated immunohistochemically in surgical specimens of primary tumors from 248 patients with esophageal squamous cell carcinoma.The positive expression rates of cytoplasmic and nuclear 14-3-3 sigma were 61.7% and 41.9%, respectively. There was no correlation between 14-3-3 sigma and p53 expression. Positive expression of nuclear 14-3-3 sigma was significantly correlated with depth of invasion, stage, lymphatic invasion, and poor prognosis. Multivariate analysis indicated that negative expression of nuclear 14-3-3 sigma was an independent prognostic factor.Evaluation of the expression of nuclear 14-3-3 sigma proteins may be useful in predicting the outcome in patients with esophageal squamous cell carcinoma.

The postoperative clinical superiority of the interposition of jejunum reconstruction (INT) to Roux-en-Y reconstruction (RY) after total gastrectomy has not been clarified. Postoperative quality of life (QOL) was evaluated between the 2 methods by a multi-institutional prospective randomized trial.A total of 103 patients with gastric cancer were prospectively randomly divided into groups for RY (n = 51) or INT reconstruction (n = 52) after total gastrectomy. They were stratified by sex, age, institute, histology, and degree of lymph node dissection. Postoperatively, body mass index (BMI) and nutritional conditions were measured serially, and QOL and postoperative squalor scores were evaluated at 3, 12, and 60 months and compared between the 2 groups.After removing patients who did not complete the follow-up survey or censured cases, 24 patients in the RY group and 18 patients in the INT group were clinically available and their postoperative status was assessed. QOL scores were increased and complication scores were improved in the postoperative periods (P.01). Postoperative BMI significantly deteriorated compared with preoperative BMI in each group. The postoperative QOL and complication scores at 60 months after surgery were significantly better than those at 3 months after surgery in each group (P.01). However, there was no significant difference of QOL scores and postoperative complication scores between the 2 reconstruction groups. The nutritional condition in the INT group was nearly the same as that in the RY group.Although our patient sample was small and patients who did not complete the follow-up survey were present, we could not identify any clinical difference between INT and RY after total gastrectomy 60 months after surgery. The safer and simpler RY method may be a more suitable reconstruction method than INT after total gastrectomy.

It is important to minimize surgical invasiveness in the therapy of patients with hepatocellular carcinoma (HCC) complicated with cirrhosis. Laparoscopic hepatectomy is feasible for such patients. However, most procedures undertaken at the present time are non-anatomic partial resection or limited resection, except for left hepatectomy and bisegmentectomy 2 and 3. Because anatomic hepatic resection for small HCC yielded more favorable results than non-anatomic resection, we conducted laparoscopic anatomic hepatic resection as image-navigated surgery by referring to portal 3D images.Detailed descriptions of laparoscopic anatomic resection, such as segmentectomy and subsegmentectomy are presented. Preoperative 3D images clarified the anatomical relationships between HCC and its portal territory and enabled determination of the transection line. Laparoscopic anatomic resection was completed with mini-laparotomy or -thoracotomy with equal success to the conventional procedure under an open approach.Five patients with primary HCC with cirrhosis underwent the above procedure between January 2008 and February 2009. There were 2 male and 3 female patients, with a median age of 74.4 (70-80) years. All procedures were successful, with no conversions to open surgery required. The median operation time was 251 min (range: 222-280 min), and the median estimated blood loss was 183 ml (range 50-320 ml). There was no surgical mortality and major morbidity.These procedures contributed reduced invasiveness, even for elderly patients with cirrhosis: low blood loss and no postoperative complication. Laparoscopic anatomic hepatic resection based on navigation of the portal 3D images might be useful not only to facilitate minimally invasive surgery but also to improve the therapeutic efficacy.

A 68-year-old man admitted for pancreatic tumor detected by US was found by computed tomography(CT)to have locally advanced pancreatic cancer invading the portal vein and neural plexus of the superior mesenteric artery without distant metastasis. We conducted preoperative chemoradiation therapy containing S-1 and hyperfractionated accelerated radiation therapy (50 Gy). Reevaluation of CT after chemoradiation therapy showed that the primary tumor reduced 52% without distant metastasis. Based on these findings, we conducted subtotal stomach-preserving pancreaticoduodenectomy with portal vein resection. Pathological examination revealed moderately-differentiated adenocarcinoma. Extensive fibrosis with a small amount of cancer cells was observed in the marginal area of the tumor. The portal vein was surrounded with extensive fibrosis and free from cancer cells. Extrapancreatic nerve plexus invasion and lymph node metastasis were not observed. There were no residual cancer cells (R0). The postoperative course was uneventful, and adjuvant chemotherapy (S-1) was started. The patient remains well without recurrence 12 months after surgery.

Mesothelin expression is found in normal mesothelium, and cancerous mesothelin has been recently reported in ovarian and pancreas cancer. The clinicopathological implications of mesothelin expression have been discussed with respect to antitumor immunological mechanisms. However, there is no information on mesothelin expression in gastric cancer. The purpose of the current study is to identify the clinical significance of mesothelin in gastric cancer.A total of 212 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were enrolled in this study. Mesothelin was detected immunohistochemically and visualized by ABC method. Intensity of cancerous mesothelin was divided into two categories (0-50%: negative group and 51-100%: positive group).Mesothelin expression was detected in the cellular membrane. In accordance with the previous evaluation, patients were divided into two groups [mesothelin-positive group: 124 (59%) and mesothelin-negative group: 88 (41%)]. The mesothelin-positive group had significantly more nodal involvement and significantly deeper tumor invasion than the mesothelin-negative group (P 0.05). However, by analysis confined to the 117 advanced gastric cancer patients, the 5-year survival rate of the mesothelin-positive group was 55%, which was significantly better than that of the mesothelin-negative group. Multivariate analysis revealed that mesothelin expression is one of the independent prognostic factors of gastric cancer.Cancerous mesothelin expression in gastric cancer may be a useful tool to predict patient survival.

We report the results of oncoplastic surgery in a Japanese patient with early breast cancer. Her breasts were ptotic, and her lesion was considered to be suitable for breast-conserving surgery. Oncoplastic surgery involving partial resection of the gland and a horizontal-type mammoplasty was performed. The technique was easy to perform, and the cosmetic outcome was excellent.

The aim of this study was to investigate the significance of lymphangiogenesis in primary pancreatic tumors and in draining lymph nodes during lymphatic metastasis of pancreatic head cancers.Specimens were obtained from 70 patients. To evaluate lymphangiogenesis, we measured lymphatic vessel density (LVD) using D2-40 antibody in the primary tumors and in the draining lymph nodes. AE1/AE3 antibody was used to detect tiny, histologically negative metastases in lymph nodes.Patients with high LVD of primary tumors had significantly higher incidence of node metastasis (P = 0.0006) and lower postoperative survival rate (P = 0.0066) than those with low LVD. Intranodal LVDs increased with increasing size of the intranodal metastases. The LVDs of non-metastatic nodes in patients with node metastasis were also significantly higher than those of non-metastatic nodes in patients without node metastasis (P 0.0001). The LVDs of peripancreatic nodes in patients with paraaortic node metastases were significantly higher than those in patients without paraaortic metastasis (P 0.0001).Lymphangiogenesis in primary tumors and draining lymph nodes is essential for efficient spread of tumor cells through the lymphatic system. Thus, inhibition of lymphangiogenesis could limit lymphatic dissemination of tumor cells.

B7-H4 is a novel molecular B7 ligand that plays an important role as a negative regulator of the T cell-mediated immune response. However, the clinical significance of B7-H4 expression in gastric cancer remains uncertain. Here, we assessed B7-H4 expression in blood of patients with gastric cancer to determine whether or not it can predict tumor progression and prognosis.We measured B7-H4 mRNA expression by quantitative RT-PCR in five gastric cell lines as well as in blood specimens from 94 patients with gastric cancer and from 22 healthy volunteers.Significantly more B7-H4 mRNA copies were found in gastric cell lines and in blood from patients with gastric cancer than in blood from healthy volunteers (P 0.0001 and P 0.0001, respectively). B7-H4 expressed in 71 (75.5%) of 94 patients with gastric cancer significantly correlated with depth of tumor invasion, lymph node metastasis, and overall stage (P = 0.006, P = 0.001, and P 0.001, respectively). The 5-year survival rate was significantly lower in patients with than without B7-H4 expression (P = 0.04).The evaluation of B7-H4 expression in blood is a useful tool for predicting the progression of gastric cancer and prognosis.

The treatment of early breast cancer using breast conservation therapy (BCT) usually ensures local control and acceptable cosmetic results. We report a useful technique involving the use of a thoracodorsal adipofascial cutaneous flap for reconstructing defects in the upper-outer quadrant area after partial mastectomy that has achieved excellent results. We developed this procedure as an oncoplastic technique for treating a Japanese woman with a similar defect and a relatively slim body. In this procedure, partial mastectomy is followed by raising the anterior half of the flap via the same skin incision, and the posterior half is raised via an additional incision posterior to the axillary area to produce a crescent of de-epithelialized skin. A C-shaped flap containing a crescent of de-epithelialized skin composed of subcutaneous fat and the fascia of the latissimus dorsi muscle is then rotated, gathered, and inset into the breast defect.

Background Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis. Objective To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed. Results Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 ( ADH1B ) and rs671 ( ALDH2 ) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10 −40 and OR=4.13, p=8.4×10 −76 , respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk. Conclusions Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.

Background and Objectives Delayed gastric emptying (DGE) is one of main complications after pylorus-preserving pancreaticoduodenectomy (PPPD) with regional lymph node dissection (RLND). The aim of this study was to retrospectively investigate whether subtotal stomach-preserving PD (SSPPD) decreased incidence of DGE. Methods This study included 112 consecutive patients underwent PPPD (n = 48) or SSPPD (n = 64) with/without RLND. DGE was classified into three categories (grades A, B, and C) according to the guideline proposed by the International Study Group of Pancreatic Surgery. Results The incidence of DGE grade B/C in SSPPD with RLND (13.0%) was lower compared with that (34.8%) in PPPD with RLND (P = 0.0326). Consequently, the mean length of postoperative hospital stay of SSPPD with RLND group was significantly shorter than that of PPPD with RLND (P = 0.0476). Conclusions SSPPD could be substituted for PPPD due to decreased postoperative DGE when RLND is involved. A randomized control trial of SSPPD versus PPPD should be considered. J. Surg. Oncol. 2010;102:615–619. © 2010 Wiley-Liss, Inc.

A 65-year-old woman was admitted with upper abdominal pain and pyrexia. She was given a diagnosis of acute pancreatitis and treated with intravenous infusion. After recovering, abdominal enhanced-CT showed a low density area in the head of the pancreas, measuring 2 cm in maximum dimension. Endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) revealed acinar cell carcinoma (ACC). She underwent curative subtotal stomach-preserving pancreaticoduodenectomy. The definitive diagnosis, based on the histopathological examinations including immunohistochemical staining, was ACC. ACC of the pancreas is extremely rare, occurring in approximately 1% of all cases of pancreatic neoplasm. We report a rare case diagnosed as ACC by EUS-FNA prior to surgical treatment.

CD133 expression in cancer cells has been recognised as a putative cancer stem cell (CSC) marker in epithelial malignancies. CD133 expression was evaluated in gastric cancer and the clinical impact of CD133-positive gastric cancer was clarified.Ninety-seven gastric cancer patients who received curative gastrectomy were enrolled. CD133 expression in cancerous tissue was evaluated by immunohistochemistry.CD133 expression positively correlated with tumour extension and the degree of nodal involvement. CD133 expression significantly affected patient postoperative outcome. Multivariate analysis revealed CD133 positivity as an independent prognostic factor superior to the depth of invasion and similar to nodal involvement in gastric cancer (p0.05).Even slight CD133 expression in gastric cancer patients may be a useful prognostic marker via CSC. Further examination of CD133 with respect to CSC markers can enable prediction of the recurrence risk of gastric cancer.

A 67-year-old male was admitted to Kagoshima University Hospital and received distal gastrectomy with D1 lymph node dissection under the diagnosis of early gastric cancer. Five years later, a retroperitoneal tumor 12 cm in diameter was detected by abdominal CT. Although the tumor was curatively resected, rapid recurrence was identified in the same retroperitoneal space. Chemoradiation therapy (radiation 50 Gy and bleomycin) for residual tumor was performed, but the tumor rapidly grew. The patient was given cisplatin (CDDP) and gemcitabine (GEM) following CPT-11 treatment. The recurred tumor was remarkably shrunken and completely regressed after eight courses of the chemotherapy. The retroperitoneal tumor was finally diagnosed as lymph node relapse from undifferentiated gastric cancer. This rare case of undifferentiated gastric cancer showed a complete lymph node response following combination chemotherapy of CDDP and GEM. Combination chemotherapeutic regime with CDDP and GEM seems to be useful for treatment of undifferentiated gastric cancer.

The expression of E-cadherin correlates with the progression and metastasis of gastric cancer. Slug, a member of the snail family of transcriptional factors, is a newly identified factor that represses transcription of the E-cadherin gene. The purpose of the present study was to evaluate the clinical significance of E-cadherin and Slug expression in gastric cancer. Immunohistochemistry was used to investigate the expression of E-cadherin and Slug proteins in 164 patients with gastric cancer. The relationships between the expression of these proteins and clinicopathological factors, including prognosis, were analyzed. Positive expression of E-cadherin and Slug was observed in 43.9 and 29.9% of cases, respectively. Tumors with reduced E-cadherin or positive Slug expression had greater extent of lymph node metastasis, lymphatic invasion, and venous invasion, and were at a worse stage than the tumors with preserved E-cadherin or negative Slug expression. Slug expression was significantly correlated with reduced E-cadherin expression; 37 of the 49 (75.5%) tumors with positive Slug expression had reduced E-cadherin expression (P = 0.0008). Patients with reduced E-cadherin expression or positive Slug expression had poor clinical outcomes. In the group with preserved E-cadherin expression, the 5-year survival rate was better for patients who were negative for Slug expression than for those who were positive for Slug expression (P = 0.0001). However, multivariate analysis indicated that E-cadherin expression and Slug expression were not independent prognostic factors. Evaluation of not only the expression of E-cadherin, but also the coexpression of E-cadherin and Slug in patients with preserved E-cadherin expression would be useful for predicting malignant properties of gastric cancer.

If the sentinel node (SN) concept is established for esophageal cancer, it will be possible to reduce safely the extent of lymphadenectomy. Our objective was to perform SN mapping in esophageal cancer to assess distribution of lymph node metastases with the goal to reduce the need for extensive lymphadenectomy.A total of 134 patients who underwent esophagectomy with lymph node dissection were enrolled. The number of patients with clinical T1, T2, and T3 tumors was 60, 31, and 32, respectively. Eleven patients also received neoadjuvant chemoradiation therapy (CRT). (99m)Tc-Tin colloid was injected endoscopically into the esophageal wall around the tumor 1 day before surgery. SNs were identified by using radioisotope (RI) uptake. RI uptake of all dissected lymph nodes was measured during and after surgery. Lymph node metastases, including micrometastases, were confirmed by hematoxylin eosin and immunohistochemical staining.Detection rates of SNs were 93.3% in cT1, 100% in cT2, 87.5% in cT3, and 45.5% in CRT patients. In the 120 cases where SNs were identified, lymph node metastases were found in 12 patients with cT1, 18 with cT2, 24 with cT3 tumors, and 3 with CRT. Accuracy rate of SN mapping was 98.2% in cT1, 80.6% in cT2, 60.7% in cT3, and 40% in CRT patients. Although one false-negative case had cT1 tumor, the lymph node metastasis was detected preoperatively.SN mapping can be applied to patients with cT1 and cN0 esophageal cancer. SN concept might enable to perform less invasive surgery with reduction of lymphadenectomy.

A number of studies have reported the presence of human papillomavirus (HPV) in lung carcinoma. Interestingly, its detection rate appears to differ histologically and geographically. The present study examined 30 adenocarcinomas and 27 squamous cell carcinomas of the lung in a southern area of Japan, and detected high-risk HPV genome in 9 (30%) adenocarcinomas and 2 (7%) squamous cell carcinomas, using PCR with SPF10 primers and INNO-LiPA HPV genotyping assay. The difference of HPV detection rates in adenocarcinomas and squamous cell carcinomas was statistically significant (P=0.044, Fisher's exact test). HPV-16 was the most prevalent HPV genotype, and was detected in 27% (8/30) of adenocarcinomas and in 7% (2/27) of squamous cell carcinomas. High-risk-HPV positive carcinomas had decreased proportions of pRb (P=0.107) and significantly increased proportions of p16INK4a expressing cells (P=0.031) when compared to HPV-negative lung carcinomas. All HPV-16-positive cases were considered to have an integrated form of HPV-16 but its viral load was low (geometric mean = 0.02 copy per cell). In 20 additional adenocarcinomas treated with gefitinib, a tyrosine kinase inhibitor specific for epidermal growth factor receptor, the presence of HPV was examined. Note that East Asian ethnicity is a predictive factor of gefitinib response. High-risk HPV genome was found in 75% (6/8) of adenocarcinomas with complete or partial response to gefitinib but was not found in the remaining 12, which did not respond to gefitinib. In conclusion, the present study suggests that high-risk HPV may be more strongly related to adenocarcinomas, particularly gefitinib-responsive adenocarcinomas, when compared to squamous cell carcinomas. However, its low viral load makes it difficult to determine the etiological significance of these findings.

A 56-year-old man with abnormal chest X-P and stool occult bleeding was admitted. Colonoscopy detected rectal cancer and sigmoid al polyps. The biopsy results suggested that the rectal lesion was well- to moderately-differentiated adenocarcinoma and the sigmoidal polyp contained well -differentiated adenocarcinoma. CT scan revealed multiple lung, liver and lymph node metastasis. We judged the case to be inoperable and decided to start systemic chemotherapy (FOLFOX4). After treatment with chemotherapy, the tumor shrank and metastatic lesions disappeared. Low anterior resection was done, and final pathological examination revealed a complete response of the main tumor by treating with FOLFOX4.

A 62-year-old man developed a refractory duodeno-cutaneous fistula after undergoing an operation for postoperative adhesion. Five previous simple anastomotic closure failed at another hospital. He underwent long-term intraveous parental hyperalimentation and showed hypoablbuminemia. We started elementary diet and performed an adhesiotomy electively. After successful dissection of postoperative adhesion, the duodenal defect was covered with elevated jejunum, and side-to-side duodeno-jejunostomy was performed. To facilitate decompression of he duodenum, a cholecystostomy and insertion of a cannula into the pancreatic duct was carried out. His postoperative course was uneventful. The large duodenal defect was a good candidate for a side to side anastomosis using elevated jejunal segment in such as this case.

Objective: To analyze the impact on prognosis of the number of axillary lymph node metastases (LNM) detected by ultrasound (US) in patients with breast cancer. Methods: One-to-one comparison of LNM was performed between the ultrasound and histologic diagnosis in 380 patients. Results: The accuracy of preoperative ultrasound diagnosis was 79.7%. According to the subdivision of number of LNM (0, 1–3, 4–9, 10+), the accuracy rates associated with LNM were 82%, 49%, 34%, and 86%, respectively. The disease-free-survival curves according to the number of LNM were similar in them. Conclusion: Preoperative ultrasound can determine axillary involvement and may be useful for predicting prognosis.

The purpose of this study was to estimate the usefulness of positron emission tomography (PET) in dividing the uptake with and without the main tumor for the treatment of patients with pancreatic cancer.Ninety-eight patients with primary pancreatic cancer were evaluated with 18F-FDG-PET. For the main tumor, the maximum standardized uptake values(SUVmax)were compared with clinicopathological factors and analyzed. We examined the site of accumulation and the rate of malignancy without the main tumor.For the accumulation of FDG in the main tumor, the high SUVmax level was significantly correlated with T-category in TNM classification (p=0. 003), tumor invasive size (3 cm) (p0. 001), CA19-9 levels100 U/mL) (p=0. 002). The overall survival of the group in which SUVmax was less than 7. 5 was better than that of the group in which it was more than 7. 5 (p=0. 03). Meanwhile, 58 patients (59%) showed the accumulation of FDG except for the main tumor. Lymph node uptake was shown in 44% of them. As for visceral accumulation, the liver was 11, lung 10, pancreas except main tumor 9, thyroid 7, peritoneal wall 3, colon 2, gall bladder 2, and bone 1. As for the rate of malignancy among them, the liver was 100%, lung 50%, pancreas except main tumor 0%, thyroid 29%, peritoneal wall 67%, colon 50%, gall bladder 50%, and bone 0%.We conclude that FDG-PET is a useful tool for predicting the prognosis in pancreatic cancer, and for detection of distant metastases and hidden malignant disease. FDG-PET has an important clinical impact on the selection of proper treatment.

Esophagectomy with three-field lymphadenectomy has been performed for esophageal cancer. Detailed analysis of cause of death and mode of recurrence is required to determine the need for further adjuvant therapy and follow-up. A total of 208 patients who underwent esophagectomy through right thoracotomy with three-field lymphadenectomy were enrolled into the present study. Mode of first recurrence was divided into four groups: lymph node, hematogenous, mixed, and local recurrence. Excluding 16 hospital deaths, the number of deaths and 5-year survival rates were 104 patients and 7.8% for cancer recurrence, 12 patients and 53.8% for second primary cancers in other organs, and 34 patients and 31.0% for causes of death unrelated to carcinoma. In the 104 patients with relapse, 5-year survival rate of patients was 14.3% with lymph node recurrence (n = 29), 9.1% with hematogenous recurrence (n = 32), 3.1% with mixed recurrence (n = 35), and 12.5% with local recurrence (n = 8). To improve outcomes for esophagectomy with three-field lymphadenectomy, early detection of recurrent disease and regular examination of the entire body for secondary cancer is necessary.

Oncoplastic techniques, which combine the concepts of oncologic and plastic surgery, are becoming more common, especially in Western countries, however, only a few case reports have been published in Japan. We report the results of oncoplastic surgery for Japanese patients with early breast cancer in the lateral quadrant area. In eight patients, their breasts were ptotic, and each lesion was diagnosed to be suitable for breast-conservative surgery, we performed oncoplastic surgery combining reduction-type partial mastectomy with nipple–areola recentralization. The total operation period ranged from 112 to 290 min with the mean period being 189 min. For the six patients who received contralateral mirror image reduction surgery and recentralization of the nipple–areola complex, the reconstruction period ranged from 80 to 230 min with the mean period being 102 min. For two patients who underwent oncoplastic surgery to the treated breast only, the reconstruction periods were 40 and 60 min, respectively. The weights of the resected tissue of the treated breast ranged from 60 to 306 g whereas that of the contralateral breast ranged from 70 to 302 g. Postoperative seroma after axillary dissection was observed in one case. Oncoplastic surgery for patients with ptotic breasts was successfully performed and may become more popular in Japan in the near future.

Background Twist is a basic helix-loop-helix (bHLH) transcriptional factor that has been identified to play an important role in epithelial-mesenchymal transition (EMT)-mediated metastasis through the regulation of E-cadherin expression. However, few authors have examined the expression of Twist and E-cadherin and their prognostic value in patients with esophageal squamous cell carcinoma (ESCC). The purpose of this study is to evaluate the clinical significance of Twist and E-cadherin expression in ESCC. Methods We immunohistochemically investigated the relationship between their expression and clinicopathological factors including prognosis in surgical specimens of primary tumors in 166 patients with ESCC. Results The expression rate of high Twist was 42.0% and that of preserved E-cadherin was 40.4%. The expression of high Twist and reduced E-cadherin was significantly associated with depth of tumor invasion, lymph node metastasis, distant nodal metastasis, stage and lymphatic invasion, and poor prognosis. High Twist expression significantly correlated with reduced E-cadherin expression. In the preserved E-cadherin group, the 5-year survival rate was better for patients who were low for Twist expression than for those who were high for Twist expression. Multivariate analysis indicated that the combination of low Twist and preserved E-cadherin expression was an independent prognostic factor along with tumor depth, distant nodal metastasis and E-cadherin expression. Conclusions Evaluation of Twist and E-cadherin expressions should be useful for determining tumor properties, including prognosis, in patients with ESCC.

Although breast-conserving therapy (BCT) is the standard form of treatment for early-stage breast cancer, in patients with small breasts cosmetic results can be poor, especially when the lesion is located on the inner upper quadrant area. This study analyzes our use of autologous free dermal fat grafts (FDFGs) for immediate breast reconstruction. A total of 23 patients who received a partial mastectomy for an inner upper quadrant lesion from 1992 to 2006 at Kagoshima University Hospital were retrospectively divided into three groups according to the reconstructive procedure that was used for the defect after partial mastectomy: immediate reconstruction using an autologous FDFG from the lower abdomen (group FDFG); patients receiving only rotation and fixation of the parenchymal adipose tissue or gland to repair the defect (group GL); and a third group who underwent immediate reconstruction using a miniflap of the latissimus dorsi (group LD). The total duration of surgery in group FDFG was significantly shorter than in group LD (P < 0.01). The mean volume of blood lost in group FDFG was significantly lower than in group LD (P < 0.01). The breast retraction assessment (BRA) of group FDFG was significantly better than for the patients in groups GL and LD (P < 0.01). The total score using the ABNSW system for cosmetic assessment was significantly better in group FDFG than in group GL (P < 0.01). Similarly, the total score in group FDFG using the assessment by the Japanese Breast Cancer Society was significantly higher than that in group GL (P < 0.01). Immediate breast reconstruction for a defect after a partial mastectomy of an upper inner quadrant malignant lesion using FDFG can be especially useful for patients with small breasts.

The chemokine receptors CCR7 and CXCR4 play a major role in the mechanism of lymph node metastasis from primary tumor cells. We postulated that their expression in gastric tumor cells could predict lymph node status including lymph node micrometastasis (LNMM). We assessed CCR7 and CXCR4 expression in 93 resected gastric tumor specimens by immunohistochemistry. Dissected lymph nodes were examined by reverse transcription-polymerase chain reaction and immunohistochemistry using cytokeratin monoclonal antibody to detect LNMM in addition to hematoxylin-eosin (H&E) staining. Levels of CCR7 and CXCR4 expression were high in 26.9% (25/93) and in 32.3% (30/93), respectively of tumor cells and the levels significantly correlated with lymph node metastasis according to H&E staining (P=0.0212 and P=0.0115, respectively). We identified LNMM in 25 of 83 (30.1%) node-negative patients. Both CCR7 and CXCR4 expression significantly correlated with lymph node status including LNMM (P=0.0092 and P=0.0075, respectively). Furthermore, levels of combined CCR7 and CXCR4 expression significantly correlated with lymph node metastatic status (P=0.0021). Assessment of CCR7 and CXCR4 expression in gastric cancer is a useful tool for predicting lymph node metastatic status including LNMM.

It has previously been reported that RAGE plays a role in resisting hypoxia in cancer cells. Here the mechanism of resistance of RAGE-transfected Cos7 cells to hypoxia is investigated from the standpoint of apoptosis.RAGE-transfected and mock-transfected Cos7 cells were subjected to hypoxia for 12, 24 and 36 h in an MTT assay. The expression of the apoptosis-regulatory proteins, hypoxia inducible factor-1(HIF-1a) and p53 in them was assessed by Western blotting.RAGE-transfected Cos7 cells showed better survival than mock-transfected Cos7 cells during hypoxia. The expression of many apoptosis-regulatory proteins was not affected. However, the expression of HIF-1a and p53 was weaker in RAGE-transfected Cos7 cells than in mock-transfected Cos7 cells.The presence of RAGE might suppress HIF-1a protein expression, which in turn might induce an anti-apoptosis effect in RAGE-transfected Cos7 cells. Moreover, the p53 suppression induced by HIF-1a may lead to malignant potential in RAGE-transfected Cos7 cells.

A new marker, CD208, was recently explored as a mature interdigitating dendritic cell (DC), and the correlation between the infiltration of CD208-positive cells and clinical factors has been reported in various types of cancers. In this study, we tried to clarify the clinical implication of CD208-positive cell infiltration in gastric cancer immunohistochemically. A total of 128 gastric cancer patients who underwent a curative operation were enrolled. DCs in tumor nests were identified with two DC markers, CD208 and S-100 protein (S100), by immunohistochemistry. The correlation between clinicopathological features and the CD208- or S100-positive cell infiltration degree was analyzed. Infiltration of S100-positive cells did not correlate with the degree of CD208-positive cell infiltration. Patients with high CD208-positive cell infiltration in the peritumor had a poorer surgical outcome than those with low CD208 infiltration (p

Summary Human serum contains thousands of proteolytically derived low-molecular-weight peptide fragments (serum peptidome). The concept of utilizing the serum peptidome for cancer diagnosis has been developed. A pathological serum peptidome appears when the homeostatic balance between proteases and protease inhibitors is disrupted. We hypothesize if analyses of the serum peptidome are of diagnostic value as information on which molecules are disrupted, and the pathological course it will take in unknown pathological conditions and disseminated intravascular coagulation (DIC). We analyzed the serum peptidome in 3 stages (early stage, pre-DIC and DIC stages) in one patient with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome, an intractable disease with unknown pathology, using a 1-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization-mass spectrometry (1-DE/MS)-based rapid quantitative approach. A very large number of peptide fragments appeared in the DIC stage, compared to pre-DIC. In addition, we identified fragments of transthyretin (ALGISPFHEHAEVVFTANDSGPR, m/z 2451.18) and α1-antitrypsin (EDPQGDAAQKTDTSHHDQDHPTFN, m/z 2691.02) that significantly increased in the DIC stage, compared to those in the pre-DIC stage. Rapid analyses of the serum peptidome may lead to a diagnostic method that can predict on-going protease activated pathological conditions and help to decide on multilateral strategies including nutritional support and drug therapy.

If the sentinel node (SN) concept is established in esophageal cancer, SN navigation surgery (SNNS) will be clinically useful. Individualized treatment will become possible, such as fewer lymphadenectomies in the upper mediastinal and cervical regions, SN sampling with endoscopic therapy, and targeted radiotherapy for SNs. Since the dye method is difficult to use for SN detection because of the complicated lymphatic flow in the esophagus and anthoracosis in the lymph nodes, the radioisotope method is used in esophageal cancer. When SNNS is introduced clinically, accurate diagnosis of nodal metastases, including micrometastases, will be essential. At present, there are few reports on the SN concept in esophageal cancer, and sufficient clinical evidence has not yet accumulated. In our experience, the detection rate was 93% in clinical NO patients with superficial esophageal cancer, and the accuracy rate was 100% for nodal metastases, including micrometastases. A clinical trial of SNNS has started in elderly patients with preoperative complications and in poor-risk patients. In the near future, a multicenter trial will be necessary to establish a standard for individualized therapy.

Chemoradiotherapy for the unresectable pancreatic cancer and biliary cancer has been used for improving survival. In this study, we examined its safety and efficacy in cases with the local recurrence of pancreatic or biliary cancer after primary resection. Seven consecutive patients with recurrence of carcinoma of pancreas (n=3) and biliary system (n =4) were treated chemoradiotherapy. Local recurrence occurred around the portal vein in 6 patients and remnant pancreas in one patient respectively. Disease free survival after primary surgery was 22 months (range: 5-84). All patients received 50 Gy of conformal three-dimensional radiotherapy with concurrent 5-FU, Gemcitabine or S-1. Grade 3 of anorexia and elevation of transaminase level occurred in one patient respectively. Local tumor response was observed in two patients of pancreatic and biliary cancer respectively. Median survival calculated from the start of the chemoradiotherapy was 14.5 months (range: 6.4-23.9) in pancreatic cancer and 13.5 months (range: 10.8-19.8)in biliary cancer. Our data suggest that chemoradiotherapy is feasible and effective treatment option in patients who present local recurrence after primary surgery in pancreatic or biliary cancer.

One representative microsection from each lymph node was carefully surveyed for metastasis in a routine examination. To scrutinize the existence of occult metastasis, three additional sections were then made from half of the remaining lymph node. A total of 1,698 lymph nodes taken from 55 patients with carcinoma of the esophagus, stomach, colon, thyroid or breast were thus reexamined histologically. The initial examination was not able to prove any metastasis in these lymph nodes. Upon reexamination, however, involvement by cancer cells was detected in 10 nodes of 7 patients. The maximum diameter of the metastatic foci varied from 0.2 mm to 1.3 mm and was less than 0.5 mm in more than half of the nodes. The metastatic patterns in the nodes were classified into three types, i.e., marginal sinus type, medullary sinus type and mixed type. The marginal sinus type was the most frequent, with the mixed type being next and the medullary sinus type being found in only one node. Accordingly, surgeons should keep the possibility of occult metastasis in mind and the marginal sinus of the lymph node should be carefully examined in order to detect any small foci of metastasis.