症例は67歳，女性．両側異時性乳癌（56歳で左，62歳で右，いずれも浸潤性乳管癌）にて乳房切除術の既往があり，術後化学療法を終了していた．両側ともホルモン受容体は陰性であった．定期的診察にて右大胸筋外縁腋窩部に腫瘤を指摘．乳癌局所再発と術前診断され手術施行したところ，切除標本の所見から副乳原発の神経内分泌癌と病理診断された．術後は右腋窩部を中心に放射線照射を行い，術後約5年を経過した現在まで転移・再発所見は認めず経過観察中である．

The feasibility and efficacy of adriamycin or epirubicin in combination with cyclophosphamide followed by weekly paclitaxel (AC/EC-weekly PAC) as adjuvant chemotherapy for breast cancer was investigated. Patients and Methods: Node-positive breast cancer was treated with AC/EC-weekly PAC, namely AC at 60/600 mg/m(2) or EC at 90/600 mg/m(2) x 4 at three-week intervals, followed by weekly PAC (80 mg/m(2)) x 12, namely four cycles of single weekly administration for three weeks followed by a one-week rest (3x4 PAC) or single weekly administration for 12 consecutive weeks (12 PAC). Results: One hundred and three of 109 consecutive patients enrolled were analyzed, of whom 96 (93.2%) completed the regimen. Grade 314 neutropenia occurred in 52.4% receiving AC/EC, and 10.9% of 55 receiving 12 PAC but only 2.1% of 48 receiving 3x4 PAC. Neuropathy disorders occurred in more than half receiving PAC, which did not improve after one-week rest in 3x4 PAC. Conclusion: AC/EC-weekly PAC is feasible and without serious complications.

症例は64歳，女性．関節リウマチのため10年前よりステロイドを内服していた．平成18年12月，腹痛・悪心嘔吐を主訴として救急外来を受診し，腹部単純X線写真で著明な小腸ガス像を認めたため，腸閉塞の診断で入院となった．第2病日にイレウス管を挿入するも，自覚症状・画像所見はともに改善せず，第6病日に呼吸困難を発症した．胸部単純X線検査・胸部CT検査で右胸腔内に拡張した小腸を認めたため，横隔膜破裂と診断した．第7病日に横隔膜修復術，イレウス解除術を施行した．術後経過は良好で，第25病日に退院となった．横隔膜破裂の原因は外傷が殆どであるが，本例は，ステロイド内服による組織の脆弱化と腸閉塞による腹腔内圧の上昇が原因と考えられた，稀な発症様式の横隔膜破裂例であった．腸閉塞による横隔膜破裂の報告は，検索しうる限り本例が本邦で2例目であった．若干の文献的考察を加えて報告する．

BACKGROUND Preclinical studies have shown that irinotecan (CPT-11) and cisplatin (CDDP) can act synergistically. Several chemotherapy regimens combining CPT-11 and CDDP for advanced gastric cancer have been reported to demonstrate high response rates and high incidence of severe toxicity. PURPOSE We conducted a combination chemotherapy regimen of low-dose CDDP and CPT-11 to prolong the time to progression with less toxicity. PATIENTS AND METHODS Seven patients with histologically-confirmed intestinal type of gastric adenocarcinoma were enrolled in this study. All patients were male, and their age at diagnosis ranged from 52 to 76 with a mean age of 64.8. Six patients received combination chemotherapy with CPT-11 and CDDP after the gastrectomy (stage I b: 1, II : 3, III b: 1, IV: 1). Only chemotherapy was administered in one patient because of a far advanced primary lesion and metastatic tumors. Low-dose CDDP (20 mg/body) and CPT-11 (65 mg/m(2)) were administered intravenously once every two weeks. RESULTS The overall response rate was 43% including 1 complete response and 2 partial responses. One patient had grade 3 myelosuppression. Other adverse reactions were mild. CONCLUSION The combination of low-dose CDDP and CPT-11 has mild therapeutic toxicities and may achieve a prolonged median survival time in patients with intestinal- type gastric adenocarcinoma.

Follow-up colonoscopy of a 25-year-old Japanese man with ulcerative colitis (UC) who had undergone endoscopic mucosal resection twice for early colon cancers revealed the presence of a new 1.5-cm-diameter tumor in the sigmoid colon. It was diagnosed by preoperative biopsy as a poorly differentiated adenocarcinoma. Sigmoidectomy was performed, and the pathological findings revealed lymphoepithelioma-like carcinoma (LEC). In situ hybridization to detect Epstein-Barr virus (EBV)-encoded small RNAs showed positive signals in stromal lymphocytes, but weak signals in the tumor cells. The association between EBV and LEC was obscure in this case. Unlike typical UC-mediated colon cancers, the lesion was poorly differentiated, and negative for p53 signals immunohistochemically. These findings may hint at a novel mechanism of carcinogenesis in UC-mediated colorectal cancer.

BACKGROUND:Fine-needle aspiration cytology (FNA) is less traumatic and technically easy to apply to small breast tumors.METHODS:A total of 382 cases of palpable breast lesions that had undergone fine needle aspiration and histopathologic diagnosis were reviewed with an emphasis on the rate of false positive diagnoses in benign breast lesions.RESULTS:A diagnosis of " malignant " was made in 98 of the 382 specimens (25.6%). The predictive value for malignancy was 97.9%. The sensitivity, specificity, and accuracy of FNA were 86.3%, 98.2%, and 93.2%, respectively, when the " suspicious " group was considered positive for malignancy. The histologic subtypes of the 4 false-positive cases were epithelial proliferative lesions, ductal or lobular hyperplasia. None of these 4 cases were definitely diagnosed as " malignant " by radiological studies. Four false-negative cases by FNA were suspicious for malignancy radiologically. There was no specific pathological subtype associated with false-negative status on FNA in this study.CONCLUSION:Palpable breast tumors can be definitively diagnosed based on a combination of physical examination, radiological studies and FNA, when the radiological studies concur with the diagnosis by FNA.

Matrilysin, MMP-7, is an important target for anti-metastasis therapy of colorectal cancer because it is a strong proteolytic factor secreted from the cancer cell itself and it induces tumor angiogenesis. In a previous report, we showed that matrilysin accelerated human umbilical vein endothelial cell (HUVEC) proliferation in low serum conditioned medium. In the present study, we show that matrilysin stimulation decreased VE-cadherin expression, induced accumulation of beta-catenin in the nucleus of the HUVEC, and up-regulated matrilysin mRNA expression. These results compel a hypothesis that matrilysin cleaves VE-cadherin and releases beta-catenin from the VE-cadherin/catenin complex; the free beta-catenin can activate T-cell factor (Tcf) DNA binding protein, which accelerates cell proliferation and matrilysin expression.

Hyperbranched polymer (poly-1a) with sulfonic acid groups at the end of chains was successfully synthesized. Interpenetration reaction of poly-1a with a hyperbranched polymer with acryloyl groups at the end of chains (poly-1b) as a cross-linker afforded a tough electrolyte membrane. The poly-1a and the resulting electrolyte membrane showed the ionic conductivities of 7×10−4 and 8×10−5 S/cm, respectively, at 150 °C under dry condition. The ionic conductivities of the poly-1a and the electrolyte membrane exhibited the VTF type temperature dependence. And also, both poly-1a and the resulting electrolyte membrane were thermally stable up to 200 °C.

Aims: To examine four-node axillary sampling assisted by a blue dye (4NAS/dye) technique as a sentinel node biopsy (SNB) for breast cancer.Methods: Lymphatic mapping was performed by injection of patent blue for 33 consecutive cases with breast cancer. Axillary sampling was performed until four nodes were obtained. This was followed by back-up axillary lymph node dissection to examine the feasibility of 4NAS/dye. The same study with 30 cases was conducted at an independent hospital to confirm the feasibility of this method. This method was then applied to 101 consecutive clinically node-negative patients to avoid axillary-node dissection, with intraoperative diagnosis made by frozen section examination.Results: The median numbers of blue-stained nodes and nodes excised by 4NAS/dye were 1.7 and 3.4, respectively. The identification rate of sentinel lymph nodes (SNs) was 81.8% using the dye atone and 97.0% when the combination was used. Pathological. examination revealed that the nodal status was correctly predicted by the dye alone in 62.5% of cases with metastasis, whereas in 100% by 4NAS/dye. The dye alone was not sufficient to identify SNs, especially in cases with prior excisional biopsy. The identification rate of SNs and the accuracy rate in another feasibility study were 100% and 92.5% in 30 consecutive cases, respectively. 4NAS/dye successfully detected SNs in 100 of 101 cases of the subsequent observational study with an acceptable postoperative axillary morbidity and thus succeeded as an SNB.Conclusions: The 4NAS/dye method is reliable for the detection of SNs. This method could be applied to observational studies without radio-isotope. (C) 2005 Elsevier Ltd. All rights reserved.

AIMS:We assessed changes in gene expression of hypertrophied liver after portal vein ligation (PL) in a test group of rats compared to a control group, which had the same size liver but no PL. METHODS:The portal veins of the left and median lobes in the test group were ligated in an initial operation. Four days after the PL, the liver volume of the posterior caudate lobe (5%) increased two-fold and comprised 10% of the liver. A 90% hepatectomy was then performed, leaving only the hypertrophied posterior caudate lobe, and leaving the normal anterior and posterior caudate lobes (10%) in the control (sham) group. A comparison of the expression profiles between two groups was performed using cDNA microarrays and the hepatic ATP level was measured. RESULTS:The survival rate for the PL group was significantly higher than for the sham group at 4 days after the hepatectomy (56.3% and 26.7%, P < 0.05). Gene expression of cyclin D1, proliferating cell nuclear antigen, cyclin A and B was upregulated, and the cyclin-dependent kinase inhibitor was downregulated. Increases were observed in: (i) pyruvate dehydrogenase, the tricarboxylic acid cycle cycle regulator, (ii) acyl-CoA dehydrogenase, the oxidation regulator, and (iii) cytochrome oxidases, the oxidative phosphorylation regulator. Hepatic ATP concentration after hepatectomy was better maintained in the PL group than in the sham group (0.48 +/- 0.01 micromol/ml vs. 0.33 +/- 0.01 micromol/ml, P < 0.05). CONCLUSION:The regenerating liver increased tolerance for extended hepatectomy compared to normal liver. It is believed that this is because the induced rapid regeneration of the remaining liver after hepatectomy increases ATP metabolism.

Objectives We assessed the utility of dynamic magnetic resonance imaging (MRI) in differentiating benign from malignant lesions of the breast and then applied MRI to diagnose intraductal breast tumors with nipple discharge. Methods Gadolinium (Gd)-enhanced MR mammography was performed on 74 patients with breast tumors and 8 patients with nipple discharge. Results The steepest slopes of the contrast medium uptake (S slope) s from time-intensity curves were significantly different between malignant and benign lesions. At S slope threshold of 0.95%/second, malignancy was predicted with a sensitivity and specificity of 75%. Six of 8 cases with nipple discharge were successfully identified by MR ductography by injecting Gd-DTPA into discharging ducts. Among them, 2 non-invasive ductal carcinomas were differentiated from benign lesions by the S slope value. Conclusions Dynamic MR mammography is an useful modality for differentiating breast lesions and has potential for evaluating intraductal lesions with nipple discharge.

Purpose Docetaxel is an active agent as first-line chemotherapy in patients with advanced breast cancer at a dosage of 100 mg/m 2 . However, the efficacy of this agent as a first-line drug when used at a lower dosage is unclear. This study was performed to evaluate the clinical efficacy and safety of 60 mg/m 2 docetaxel for the treatment of breast cancer. Patients and Methods This study enrolled 23 patients with advanced and/or metastatic breast cancer, who had not been treated with an anthracycline or taxane previously. Treatment with docetaxel was continued in patients showing a response until there was evidence of disease progression or unacceptable toxicity. Results Among 20 fully evaluated patients, the overall response rate was 50.0% and the median time to progression was 31 weeks. The most commonly observed adverse events were neutropenia (78.2%) and fatigue (60.9%). Fluid retention occurred in only 8.7% of the patients. Adverse events did not cause discontinuation of the treatment. Conclusion Docetaxel achieved good disease control with mild adverse events in first-line treatment at a dosage of 60 mg/m 2 .

Reverse transcriptase-polymerase chain reaction (RT-PCR) has been utilized to detect living micrometastases of cancer cells in the lymph node, ascites or circulation system. However, the method was so sensitive that false-positives happened frequently. Therefore we have developed a quantification of CEA mRNA using real-time PCR to detect living cancer cells in the circulating blood and examined its usefulness as a predictive marker for liver metastases of colon cancer. In cell spiking experiments, it was possible to detect CEA mRNA in 10(1) cancer cells diluted in 10(7) normal lymphocytes. In the blood samples of cancer patients, the CEA mRNA level was significantly higher in Dukes' D patients than in the other clinical stages of colorectal cancer. This indicates that quantification of CEA mRNA is useful for the evaluation of colorectal cancer progress and that the post-operative increase of CEA mRNA can be a predictive marker for micrometastasis.

Brain metastases occur in 15% to 30% of breast cancer patients, usually as a late event. The patterns of metastases to different organs are determined by the tumor cell phenotype and interactions between the tumor cells and the organ environment.

Matrix metalloproteinases (MMP) are considered to play important roles in angiogenesis. In angiogenic processes, endothelial cells secrete MMP-2 or MMP-1 to dissolve the basement membrane or connective tissue around the vessels. MMP-7 (matrilysin) is secreted from the neovasculars induced by cancer and is a metastatic factor of colorectal cancer. The effect of matrilysin on angiogenesis is still unclear, however. We therefore examined the effect of MMP-7 on the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro. Our results showed that recombinant MMP-7 (rMMP-7) accelerated the proliferation of endothelial cells dose-dependently, and did so for endothelial cells cultured not only on type IV collagen, but also on type I collagen. MMP-7 also upregulated MMP-1, -2 secretion, but did not stimulate vascular endothelial growth factor (VEGF) secretion. From this study, we conclude that MMP-7 directly induces angiogenesis, and that therefore MMP-7 would be a good target of cancer therapy.

The efficacy of a phosphorothioate antisense oligonucleotide (ASO) for KDR/Flk-1 (KDR/Flk-1-ASO), an endothelial cell–specific vascular endothelial growth factor (VEGF) receptor, was investigated on the peritoneal dissemination and angiogenesis of a human gastric cancer cell line in nude mice. Green fluorescent protein (GFP)–transduced NUGC-4 (NUGC-4-GFP) human gastric cancer cells were implanted into the peritoneal cavity of nude mice. KDR/Flk-1-ASO, -SO, or phosphate-buffered saline was administrated from days 7 to 14, 200 μg/mouse, once a day. The mice were sacrificed on day 28. Disseminated peritoneal tumor nodules expressing GFP were visualized by fluorescence microscopy. KDR/Flk-1-ASO significantly decreased the extent of peritoneal dissemination of the tumors. The number of cells undergoing apoptosis was significantly increased in the KDR/Flk-1-ASO–treated tumors. Microvessel density was significantly reduced in the KDR/Flk-1-ASO–treated tumor nodules. The KDR/Flk-1 antisense strategy, therefore, decreases tumor dissemination apparently by inhibiting angiogenesis.

We studied the expression profiles of various stages of colorectal tumors (adenoma (AD), seven samples; carcinoma (CA), 16 samples) by using cDNA microarrays and developed ADMS (algorithm for diagnosing malignant state) method, selecting 335 clones characteristic of CA state. We, then, applied ADMS to 12 additional samples (five from primary lesions with metastasis and seven metastases); all 16 CAs and 12 metastatic tumors were diagnosed correctly as cancerous states. Although three of the seven ADs were diagnosed as "cancerous," the large size of two of these tumors suggested their potential malignancy. Our strategy for selecting clones characteristic of the malignant state is widely applicable to diagnosis and for predicting the stage of progression during multistep carcinogenesis. Of the 335 clones we selected, 135 were known genes. Included in the 135 genes were tumor suppressor and growth factor-related genes and were consistent with the literature. ADMS is a reliable means for identifying genes useful for the diagnosis of cancer.

Bone resorption markers have become available for the diagnosis of bone metastasis. We evaluated cross-linked collagen C-and N-telopeptides (ICTP and NTx) in diagnosing bone metastasis from breast cancer. For a threshold of 4.5 ng/ml of 1CTP and 55.0 pmol BCE/micromol of NTx, bone metastasis could be predicted with an accuracy of 84% and 63%, respectively. All the patients who had metastatic lesions, but showed lower than 4.5 ng/ml of ICTP, had a solitary lesion of bone metastasis. Although ICTP is not sensitive enough to detect an early stage of bone metastasis, it is a better biochemical marker than NTx for detecting bone metastasis from breast cancer.

We report a 35-year-old woman with locally advanced mucinous carcinoma of the breast with sudden growth acceleration. A pea-sized mass developed into an ulcerated large tumor within 1 month. After the combination of chemotherapy, radiation and hyperthermia, a radical mastectomy was performed, followed by repair of the skin defect by latissimus dorsi and rectus abdominis musculocutaneous flaps. Histological examination revealed a pure mucinous carcinoma with axillary lymph node involvement. Estrogen and progesterone receptors were not detected in the tumor. Twenty-five months after treatment, there is no sign of recurrent disease. Pure mucinous carcinoma generally has a less aggressive growth pattern as defined by tumor size, adherence to the overlying skin/bottom fasciae, estrogen and progesterone receptor positive and primary lymph axillary lymph node metastases. This case showed completely opposite features to all of these typical biological features of pure mucinous carcinomas.