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Background/aim Irinotecan is rarely used on the metastatic breast cancer (MBC) setting. S-1 is an oral mixture of tegafur, gimeracil and oteracil. We conducted this pilot study to assess efficacy and safty of chemotherapy with combined irinotecan and S-1 (IRIS). Patients and methods Irinotecan was given intravenously at 80 mg/m2 on days 1 and 8 and S-1 was given orally at 80-120 mg/day depending on body surface area for 2 weeks, repeating the cycle every 3 weeks. Results Twenty-two patients were enrolled in the study. Median age was 50.5 years (range=26-72). Nineteen patients were evaluable for response. Median overall survival and progression-free survival were 672 days (95% CI=420-967) and 166 days (95% CI=76-814), respectively. Conclusion The IRIS regimen has an acceptable safety profile and modest efficacy against MBC in patients previously heavily treated with chemotherapy. This regimen has potential to treat MBC.

Background Primary sarcomas of the breast are rare and account for less than 1% of all primary breast malignancies. We experienced a case of extraskeletal osteosarcoma of the breast that had a unique clinical course and remarkable findings of mammography and magnetic resonance imaging (MRI). A review of the case reports published in the past few decades showed no reports of a case in which a calcified lesion was followed up three different times on mammography, making this a valuable case report. Case presentation A 52-year-old woman noticed a right breast mass and underwent a breast examination. Mammography showed a 1.5-cm coarse calcified lesion in the upper outer portion of the right breast. Because fine-needle aspiration (FNA) revealed no suspicion of malignancy, she was followed up. Sixteen months later, the tumor grew progressively to 4.5 cm in size with new calcifications that were fine and irregular in shape and density surrounding an enlarged, coarse calcified lesion. Contrast-enhanced magnetic resonance imaging (MRI) showed a high signal intensity in the periphery of the tumor. Extirpation of the tumor was indicated. The pathological findings were extraskeletal osteosarcoma. She underwent additional resection and latissimus dorsi flap reconstruction at the Department of Orthopedic Surgery. Conclusion The present case suggests that mammography findings of a tumor with coarse calcifications that are not typical of benign lesions may be extraskeletal osteosarcoma. A diagnosis must be made as early as possible in order to improve the prognosis of this disease.

e13005 Background: In Japan, eribulin has been approved for inoperative or recurrent breast cancer, following treatment with an anthracyclines and a taxanes. We reported the efficacy and safety of eribulin as a first-line to third-line treatment in patients with advanced/metastatic breast cancer (MBC) previously treated with anthracylinsanthracyclines and taxanes (Breast 2017). Briefly, the main inclusion criteria were as follows: no history of eribulin administration; an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2,; human epidermal growth factor receptor 2 (HER2)-negative,; 20–75 years; ≥4 weeks from the last dose of chemotherapy, or ≥2 weeks from the last dosing of endocrine or radiation therapy; measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1; sufficient organ function; life expectancy of ≥3 months; and no significant abnormalities on electrocardiogram. Patients in this clinical trial were enrolled between December 1, 2011, and November 30, 2013. Eribulin was administered intravenously at a dose of 1.4 mg/m2 during a 2-5 min infusion on days 1 and 8 every 3 weeks. In contrast, baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) were reported to predict progression-free survival (PFS) or overall survival (OS). However, these reports were mainly retrospective analysis. Therefore, retrospective evaluation of NLR/ALC in a prospective clinical trial is important to understand the association between NLR/ALC and OS/PFS. Methods: Of 47 prospectively enrolled patients in a previous trial, 45 patients were retrospectively evaluated for baseline NLR/ACL and at the time of 3 cycles of eribulin. The association between NLR/ALC and OS/PFS was also were analyzed for association with OS/PFS. The Kaplan-Meier method was used to estimate the OS/PFS distribution. The cut-off values for baseline NLR and ALC were set at 3 and 1500 /ul, respectively. Results: The median OS of patients with a baseline NLR < 3 was significantly longer than that of patients with a baseline NLR ≥ ≧3 (769 days vs. 409 days; log-rank test p = 0.0333). The median OS of patients with a baseline ALC ≥ ≧1500 was also significantly longer than that of patients with a baseline ALC < 1500 (964 days vs.vs 427 days; log-rank test p = 0.0425). Association between baseline NLR/ALC and PFS were not seen, and also association between at the time of 3 cycles of NLR/ALC and OS/PFS were not seen neither. Conclusions: Baseline NLR and ALC in the patients with HER2- negative breast cancer who plan to treat eribulin may predict overall survival. Clinical trial information: UMIN000007121.

The aim of this study was to investigate the validity of the management strategy for intraductal papillary mucinous neoplasms (IPMNs) advocated by the international consensus guidelines 2012 (ICG2012). The medical records of 49 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. According to preoperative imaging, 10 patients (20 %) had main-duct IPMNs, 20 (41 %) had mixed IPMNs, and 19 (39 %) had branch-duct IPMNs, with malignancy frequencies of 80, 15, and 37 %, respectively. Twenty-seven patients had high-risk stigmata and 21 had worrisome features, with malignancy frequencies of 59 and 10 %, respectively. The sensitivity, specificity, and positive and negative predictive values of high-risk stigmata for malignancy were 88, 65, 59, and 91 %, respectively. Lesions were malignant in 88 % of patients with an enhanced solid component, which was significantly correlated with the prevalence of malignancy (P

The aim of this study was to investigate preoperative factors associated with ductal carcinoma in situ (DCIS) upstaged to invasive ductal carcinoma (IDC) and sentinel lymph node (SLN) status in patients who underwent mastectomy for a preoperative diagnosis of DCIS. The medical records of 220 patients who underwent mastectomy for a preoperative diagnosis of DCIS were retrospectively reviewed. Fifty-one (22.6%) of 226 lesions were upgraded to IDC after mastectomy. Preoperative factors associated with upstaging to IDC included patient-reported signs and symptoms, a clinically palpable mass, ultrasound findings classified as category 4 or 5, the ultrasound appearance of a mass or widely distributed non-mass abnormality (NMA), and a high Ki67 index. The prevalence of SLN macrometastasis was 0.9%. IDC was diagnosed for 10.9% of lesions of a preoperative ultrasound category of 0–3, 13.0% of those with no mass or NMA detected by ultrasonography, and 14.1% of lesions preoperatively diagnosed by methods other than core needle biopsy (CNB). Of those lesions, none was associated with SLN metastasis. Routinely performing SLN biopsy for patients undergoing mastectomy for a preoperative diagnosis of DCIS is overtreatment, because the prevalence of SLN metastasis was low. SLN biopsy can be omitted for most patients. In particular, we suggest omitting SLN biopsy for patients who have lesions of ultrasound category 0–3, who have neither a mass nor NMA detected by ultrasound, or whose initial diagnosis was made based on a specimen obtained by methods other than CNB.

Breast carcinoma arising in a benign fibroepithelial tumor is rare, and is usually discovered incidentally during examination of the breast mass. We evaluated the clinicopathological features, treatment, and prognosis of seven women with breast carcinomas within benign fibroepithelial tumors, diagnosed and treated at a single institution between 2011 and 2015. Seven women, aged 21–64 years, visited our hospital complaining of a breast mass detected by self-checking or screening examination. All patients had well-demarcated movable breast masses. Ultrasonography showed circumscribed masses suggesting benign tumors in all cases, and mammography revealed well-defined, high-density masses, with or without calcification. The masses progressed in two patients. A preoperative histological diagnosis of carcinoma was made following needle biopsy in four patients. Tumorectomy, breast-conserving surgery, and mastectomy were performed in three, two, and two patients, respectively. One patient underwent lymph node dissection and another underwent sentinel node biopsy. Histologically, the masses were diagnosed as invasive ductal carcinoma, ductal carcinoma in situ or lobular carcinoma in situ, arising in a benign phyllodes tumor, fibroadenoma, or fibroadenomatoid mastopathy. Lymph node metastasis was detected in two patients. There was no recurrence in any of the patients. Although a carcinoma within a preexisting benign fibroepithelial tumor is extremely rare, it is important to be aware of the possibility of invasive and metastatic disease.

A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1–2, node metastases (n = 0–3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids and bone markers were measured prior to, and again at 6, 12, and 24 months after initiation of treatment. Changes in serum lipids and bone markers were compared. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and 14.0% of patients, respectively, receiving TOR. Lipid levels did not change in patients administered LET. Significant differences were observed in TC and LDL-C between the two groups at 12 and 24 months. In the TOR group, serum bone-specific alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross-linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months, and these reductions were maintained for at least 24 months. In contrast, in the LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert different effects on serum lipid profiles and bone metabolism markers. The effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism in postmenopausal breast cancer patients are superior to those of LET.

Purpose To validate the safety and efficacy of percutaneous radiofrequency ablation (RFA) of breast carcinomas. Methods This retrospective study was conducted by the Breast Cancer Society for Minimally Invasive Therapy following approval from institutional review boards, and with the written informed consent of patients. A total of 386 patients with breast cancer treated with RFA at 10 institutions between July 2003 and June 2009 were identified and included in the analysis. Patients underwent a standard RFA procedure with ultrasound guidance and were followed up every 6 to 12 months. In this study, feasibility of RFA procedure and related safety and ipsilateral breast tumor recurrence (IBTR) were examined. Fisher exact or χ2 test evaluated associations between clinicopathological factors and IBTR, and local recurrence-free survival was estimated using the Kaplan-Meier method. Results RFA-related adverse events included local pain in 9 patients, skin burns in 15, and nipple retraction in 7. Patients were followed for a median of 50 months. IBTR was more frequently observed in patients with initial tumor sizes > 2 cm (3 of 30, 10%) than in those with initial tumors ≤ 2 cm (8 of 355, 2.3%; P = .015). IBTR-free rates 5 years after RFA were 97%, 94%, and 87% in patients with initial tumor sizes ≤ 1.0 cm, 1.1 to 2.0 cm, and > 2.0 cm, respectively. Conclusions RFA in breast cancer is a safe and promising minimally invasive treatment for tumors ≤ 2 cm in diameter. Further studies are needed to optimize the technique and evaluate its future role as local therapy.

Introduction Endoscopic surgery is reportedly associated with smaller scars and greater patient satisfaction. Herein we evaluate the early results of endoscopy-assisted breast-conserving surgery(E-BCS). Methods Between May 2009 and October 2010, 61 women with breast cancer underwent E-BCS. We performed E-BCS on patients with tumors measuring less than 2 cm, without skin or pectoralis muscles invasion. Any patients with microcalcified lesions or axillary lymph node metastasis were excluded. We used an endoscopic vein retractor to dissect the dorsal layer of the mammary gland from a small axillar incision. We dissected the subcutaneous layer and cut the mammary gland vertically from a periareolar incision. We evaluated the clinicopathological characteristics, the surgical outcomes, and early cosmetic results. Results The mean age of the patients was 58.5 years, and the mean tumor size was 1.4 cm. Sentinel node biopsy was positive in seven patients, all of whom underwent axillary node dissection. An additional intraoperative resection of the breast was performed in 12 patients. The mean length of the operation was 167 min, and the mean blood loss was 27 mL. Eight patients received a boost to the tumor bed. The cosmetic results were satisfactory, and the wound scar was inconspicuous in most patients. Conclusion Herein we demonstrate that E-BCS is a feasible and safe procedure for patients with early breast cancer. It allows for a better cosmetic scar location and offers patients favorable aesthetic results in the short-term follow-up results.

Objective: The aim of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2)-related biomarkers and the treatment outcomes using lapatinib plus capecitabine (LC) and to evaluate the influence of the estrogen receptor (ER) status in trastuzumab-refractory HER2-positive advanced breast cancer. Method: Eighty patients were enrolled in this study. Total HER2, p95HER2, and total HER3 expression were quantified using the VeraTag assays. PTEN (phosphatase and tensin homolog) and p95 expression was evaluated using immunohistochemistry and PIK3CA mutation using direct sequencing. Results: The response rate to LC was 30%, clinical benefit rate was 51.3%, and the median progression-free survival (PFS) was 174.5 days. ER negativity significantly correlated with higher HER2 and p95HER2. The lower HER2 and PIK3CA mutations were often observed in the nonresponders. A high p95HER2 expression correlated with longer PFS especially in the high HER2- and ER-positive cases. Patients without the PIK3CA mutation showed longer PFS in the same subset. Overall survival after LC significantly correlated with the number of recurrence organs. Conclusion: LC therapy is effective in trastuzumab-refractory HER2-positive breast cancer. Moreover, the biomarker expression differed depending on ER status, and a high p95HER2 expression and wild-type PIK3CA gene correlated with longer PFS especially in the ER-positive cases.

Objectives Despite the survival benefit and acceptable tolerability of eribulin for advanced/metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes, there is limited evidence of the clinical benefit of early eribulin use. We investigated the efficacy and safety of first- to third-line eribulin use in patients with MBC. Materials and methods In this phase II, open-label, single-arm study conducted at 14 sites in Kyushu, Japan, women with histologically confirmed human epidermal growth factor receptor 2–negative MBC were enrolled between December 1, 2011 and November 30, 2013 (Data cut-off: November 30, 2014). Objective response rate (ORR; primary endpoint), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety were evaluated. Results Of 53 recruited patients, 47 were enrolled. The ORR was 17.0% (95% confidence interval, 7.6–30.8), DCR was 66.0% (51.2–77.8), median PFS was 4.9 months (3.5–7.0), DOR was 6.6 months (1.9–14.3), and median OS was 17.4 months (10.1–not evaluable). The common grade 3/4 adverse events were neutropenia (25 patients; 53.2%), leucopenia (16 patients; 42.1%) and febrile neutropenia (4 patients; 8.5%). Toxicity did not increase during the long-term treatment. Subgroup analysis indicated that first-line treatment led to higher ORR and prolonged PFS and OS than second-/third-line treatment and that incidence of adverse events in patients of second-/third-line treatment was not higher than that in patients of first-line treatment. Conclusion Eribulin exhibited efficacy and manageable tolerability in Japanese women with pretreated MBC in first- to third-line use. (ID: UMIN000007121).

With an increasing rate of screening mammography for breast cancer that has allowed earlier detection of early-stage small breast cancer, and the desire for improvement in cosmetic outcome, many minimally invasive techniques for the treatment of early-stage breast cancer have been investigated. Ablation therapies with or without surgical resection, including radiofrequency ablation, high-intensity focused ultrasound surgery, and cryoablation, have been reviewed with preliminary and published data, and many points that need to be resolved have been proposed in prospective clinical trials. These techniques have shown promise for small breast cancer without extensive intraductal components in the short-term, but there is no available data of long-term safety and adverse events.

Trastuzumab (T) has contributed to improving the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Although some patients have been unresponsive or resistant to T. Loss of phosphatase and tensin homolog (PTEN) deleted on chromosome 10, PIK3CA mutation and p95HER2 expression have been reported to potentially be responsible for the poor response to T. This is a small-scale pilot study to be followed by a large-scale investigation examining the association between the biomarkers and clinical response. Based on the response to T, patients were divided into 3 groups in terms of progression-free survival (PFS): PFS >8 months (group A, n=15), 3–8 months (group B, n=7) and PFS

We herein report a rare case of primary angiosarcoma of the breast. A 31-year-old pregnant woman noted a progressing mass in her left breast, and it was suspected to be a phyllodes tumor on the basis of images acquired after the delivery. The histological diagnosis by excisional biopsy was well-differentiated angiosarcoma, so she was referred to our hospital for further treatment. CT and MRI suggested that there was a residual lesion in the remnant breast and multiple bone metastases. She underwent a simple mastectomy, and chemotherapy was performed postoperatively. Four months after surgery, liver, ovary, and mandibular gingival metastases became apparent, although these metastatic lesions had not been distinguished at first. They rapidly progressed, and the regimen of chemotherapy was changed from weekly paclitaxel, MAID (mesna/ifosfamide/doxorubicin/dacarbazine) combination therapy, to docetaxel. Radiation therapy to the gingival tumor was relatively effective. However, the liver and ovary metastases continued to progress under chemotherapy and caused a fatal hemorrhage. Early diagnosis is very important in this highly aggressive disease, and a novel strategy for treatment is needed to prolong the survival and maintain the quality of life of such patients.

The potential long-term adverse effects on quality of life have to be considered when selecting agents for adjuvant hormonal treatment for postmenopausal patients with estrogen receptor-positive breast cancer. We performed a 2-year multicenter randomized study to assess the differences in the time course effects between toremifene (TOR) and anastrozole (ANA) on serum lipid profiles and bone metabolism. This study assessed the serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (Apo A1), and apolipoprotein B (Apo B) as lipid profiles and bone-specific alkaline phosphatase (BAP) and the N-telopeptide of type-I collagen (NTX) as bone turnover markers in patients who received daily doses of 40 mg and 1 mg for TOR and ANA, respectively. A decreased serum level of TC, LDL-C, and Apo B was, respectively, observed at 6 months in 6.2, 12.9, and 13.8% of the patients who received TOR compared with the baseline. These decreases were maintained for at least 24 months. These lipid levels were not changed in those who received ANA. In the TOR patients, there was an increase in the serum level of HDL-C and Apo A1 at 6 months in 17.1 and 16.3%, respectively, which was maintained for at least 24 months, whereas these levels were almost stable in the patients who received ANA. Serum BAP decreased by 12.1% at 12 months and further decreased at 24 months and the serum NTX decreased by 22.0% at 6 months, which was maintained for at least 24 months in the patients who received TOR. In contrast, the serum BAP was increased by 26.0% at 6 months and by 29.2% at 12 months and the serum NTX increased by 21.3% at 24 months compared with baseline in those received ANA. However, the serum BAP increase was not significant at 24 months. TOR provides better effects than ANA in terms of lipid profiles and bone metabolism in postmenopausal females with early breast cancer.

Purpose; An endocrine treatment using aromatase inhibitor (AI) is a standard strategy for postmenopausal patients with hormone receptor positive breast cancer. Postmenopausal patients who relapsed during adjuvant AI treatment or progression within a year after completion of AI treatment were prospectively treated with 40 mg/day of toremifene (TOR) in order to examine the effect of the selective estrogen receptor modulator (SERM) in AI-refractory patients. Patients and Methods; Twenty-three postmenopausal breast cancer patients who relapsed during adjuvant AI treatment or relapsed within a year after completion of AI were enrolled in the prospective trial from January 2007 to February 2010. Out of the patients, 14 cases had measurable or evaluable lesions, and the other had only bone metastasis. All patients were treated with toremifene of 40 mg/day. The primary efficacy end point for the trial was clinical response and secondary end point was progression free survival (PFS).Result; The objective response rate in the patients with measurable lesions was 7.1% (1/14) and clinical benefit rate was 28.6%. In the patients with evaluable bone disease, clinical benefit was 44.4%. No serious adverse event was observed except a patient with grade 3 non-hematological toxicity (AST and ALT).Conclusion; The SERM, toremifene (40 mg/day), demonstrated a safe profile and a favorable effect on disease control after adjuvant AI failure.

This randomized controlled trial will compare oral 5-fluorouracil derivatives, TS-1, with intravenous standard chemotherapy such as taxanes in women with metastatic or recurrent breast cancer. Patients with hormone-resistant breast cancer are assigned to either TS-1 (40-60 mg twice daily for 28 consecutive days, followed by a 14-day rest period) or standard chemotherapy (docetaxel 60-75 mg/m(2) at 3- or 4-week intervals, paclitaxel 175 mg/m(2) at 3- or 4-week intervals or paclitaxel 80-100 mg/m(2) weekly, followed by a 1-week rest period). Treatment will be repeated until tumor progression or > or =4 courses for TS-1 and > or =6 courses for taxanes. The primary endpoint is overall survival. Secondary endpoints are progression-free survival, time to treatment failure, adverse events, health-related quality of life and cost-effectiveness. A threshold hazard ratio of 1.333 will be used to determine whether overall survival in the TS-1 group is equivalent (not inferior) to that in the taxane group. The target number of registered patients is 600.

Clinical trials conducted in Western countries have shown that aromatase inhibitors are associated with better disease-free survival (DFS) than tamoxifen in postmenopausal early breast cancer. Because pharmacogenetic differences in drug-metabolizing genes may cause ethnic differences, assessment of the efficacy and tolerability of aromatase inhibitors in non-white women is warranted. This open-label, randomized clinical trial included 706 postmenopausal Japanese women with hormone-receptor-positive breast cancer, who had received tamoxifen for 1 to 4 years as adjuvant therapy. This study was closed early after entry of approximately 28% of the initially planned patients. They were randomly assigned to either switch to anastrozole or to continue tamoxifen for total treatment duration of 5 years. Primary endpoints were DFS and adverse events. At a median follow-up of 42 months, the unadjusted hazard ratio was 0.69 (95% confidence interval, 0.42-1.14; P = 0.14) for DFS and 0.54 (95% CI, 0.29-1.02; P = 0.06) for relapse-free survival (RFS), both in favor of anastrozole. The incidence of thromboembolic events in the tamoxifen group and bone fractures in the anastrozole group was not excessively high. Switching from tamoxifen to anastrozole was likely to decrease disease recurrence in postmenopausal Japanese breast cancer patients. Ethnic differences in major adverse events may be attributable to a low baseline risk of these events in Japanese.

Capecitabine (Xeloda, X) and cyclophosphamide (C) can be given orally and they have synergistic effects with nonoverlapping toxicities in preclinical studies. A phase I study of the XC combination therapy was conducted in patients with metastatic breast cancer (MBC) and determined the recommended dose and schedule of 1657 mg/m/day capecitabine and 65 mg/m/day cyclophosphamide given orally for 2 weeks at a 3-week interval. A phase II study of the oral XC regimen was then conducted. This study enrolled patients with HER2-negative MBC who were earlier treated with anthracyclines. XC was given at the recommended doses on a 3-week schedule for at least six courses unless disease progression or unacceptable toxicities occurred. The primary endpoint was the response rate. Progression-free survival, overall survival, and adverse events were investigated as secondary endpoints. Forty-eight patients with the median age of 58 (range 32-72 years) years were registered. Three patients withdrew by choice before starting the treatment. A complete response was obtained in two of the 45 evaluable patients, and partial response in 14, resulting in an overall response rate of 35.6%. The median progression-free survival and overall survival were 199 (115-231) days and 677 (437 approximately ) days, respectively. Grade 3 neutropenia and leukopenia developed in 11%, and that of anemia and thrombocytopenia in 2% patients. Nonhematological toxicities were mild. Hand--foot syndrome was observed in 14 patients but no one had grade 3-4 toxicity. Oral XC combination is effective with acceptable toxicities in patients with MBC.

右鎖骨下動脈起始異常に伴うnonrecurrent inferior laryngeal nerve（NRILN）の存在を予測できた食道癌症例に対する腹臥位胸腔鏡下食道切除術を経験したので報告する．症例は73歳男性，胸部つかえ感があり，上部消化管内視鏡で胸部中部および下部食道癌と診断された．CTで右鎖骨下動脈起始異常を認め，NRILNの存在が推測された．手術は腹臥位で胸腔鏡下に行い食道後面を横走し右側を上行する右鎖骨下動脈を認め，右迷走神経から反回する神経はなく，頸部操作で右迷走神経から直接分枝するNRILNを確認した．NRILNは右鎖骨下動脈起始異常に伴う先天奇形で比較的まれなものだが，食道癌における反回神経周囲リンパ節郭清は食道癌の手術において非常に重要である．NRILNを伴う食道癌でもCTなどでその存在を推測し慎重にリンパ節郭清を行うことで，術後反回神経麻痺などの重篤な合併症を起こさない安全なリンパ節郭清が可能と思われた．本症例はNRILNを伴う食道癌に腹臥位胸腔鏡下食道切除術を行った本邦初の報告である．

肉眼的腹膜播種のない腹腔内洗浄細胞診陽性（P0cy1）ss以深胃癌の予後因子について検討した．腹腔内細胞診陽性率はP0 5.4％，P1 67％，ss 10％ se 40％ si 29％であった．ss以深胃癌987例のうちP0cy1胃癌は86例で，P0cy0，P0cy1，P1のMST（生存期間中央値），1年，2年，3年，4年，5年生存率は1678日，83％，70％，58％，51％，48％，446日，56％，30％，21％，14％，9.6％，244日，36％，18％，11％，3％，2％であった．P0cy1の予後はP0cy0とP1との中間に位置している．P0cy1胃癌の予後因子は単変量解析では肉眼分類，肝転移，リンパ節転移度，転移リンパ節個数，リンパ節郭清度，PM，DM，間質，INF，リンパ管侵襲，細胞診の細胞数，細胞診の細胞の大きさ，術後化学療法，化学療法の14因子であったが，多変量解析ではDM，リンパ節郭清度，術後化学療法の3因子であった．P0cy1ss以深胃癌の予後は不良だが，切除断端を陰性にし，D2以上のリンパ節郭清を行い，術後化学療法を行うことができれば予後が良好なことが期待される．

The therapeutic advances in breast cancer have improved the survival of patients with early disease; however, survival improvement of patients with recurrent disease remains ambiguous. In this retrospective study, we examined whether disparities in survival improvement exist in patients with recurrent breast cancer with distant metastasis.The survival time of 126 patients who experienced recurrence at distant sites from 1990 through 1996 was compared to that of 195 patients who did from 1997 through 2003.A significant survival improvement was observed in the patients who experienced recurrence in the period of 1997-2003 in comparison to the other period in the subsets with estrogen receptor (ER)-positive disease, those who received adjuvant hormonal therapy, and those with a disease-free interval (DFI) of 24 months or more. However, no significant survival improvement was observed in each counterpart. The median survival time (MST) from the first relapse of patients with ER-positive disease in the recurrence period of 1997-2003 was 18.8 months longer than that in the recurrence period of 1990-1996 (46.6 months vs. 27.8 months). The MST of patients with a DFI of 24 months or more in 1997-2003 was 20.3 months longer than that in the other time period (47.2 months vs. 26.9 months).The survival of recurrent breast cancer has improved with disparities. The ER status and the DFI are associated with a survival improvement of women with recurrent breast cancer with distant metastases.

Background: Anthracyclines and taxanes are major cytotoxic drugs against breast cancer. To develop a combination of epirubicin (EPI) and docetaxel (DTX) in Japan, dose escalation and pharmacokinetic studies were performed in patients with advanced or recurrent breast cancer. Methods: Twenty patients received EPI (40, 50 or 60 mg/m2) as 5-min intravenous infusion, followed by DTX infusion (50 or 60 mg/m2) over 1 h in cohorts of 3–6 patients. The maximum tolerated dose (MTD) was defined during the first cycle when more than 2 of 3 or 3 of 6 patients suffered a dose-limiting toxicity (DLT). The DLT was based on febrile neutropenia (FN), prolonged neutropenia, thrombocytopenia and grade 3–4 nonhematological toxicity during the first cycle. Plasma sampling was performed to assess the pharmacokinetic study of these drugs. Results: The second level (EPI/DTX 50/50 mg/m2) was found to be a maximum tolerated dose because of a short duration of FN with no distress. Subsequently, the protocol was modified to permit a new DLT definition including FN lasting for more than 72 h. At the following levels of EPI/DTX 50/50, 50/60 or 60/60 mg/m2, the dose escalation study revealed a high incidence of grade 4 neutropenia (100%) and FN (67%), which did not reach DLT. However, the safety committee decided not to go further because of too high an incidence of FN lasting 3 days, although a little less than 72 h. The pharmacokinetic study with a combination of EPI and DTX showed comparable blood levels of DTX and EPI in relation to those seen when given alone. Conclusion: For further evaluation, the recommended dose and schedule of this combination is EPI 60 mg/m2 and DTX 60 mg/m2, given every 3 weeks to patients without prior chemotherapy and EPI 50 mg/m2 and DTX 50 mg/m2 given to patients with prior chemotherapy, respectively. The pharmacokinetic study indicates no interaction between EPI and DTX.

目的：マンモグラフィ（MMG）で微小円形または淡く不明瞭な石灰化のみを呈した乳癌の超音波検査による石灰化巣の描出能とその病理学的所見の関係を検討する．方法：術前MMGで微小円形または淡く不明瞭な石灰化のみを示した非浸潤性乳管癌あるいは微小浸潤癌14例を対象に，超音波像での高エコースポットの明瞭さを3段階に分類した．組織亜型をcomedo typeとnon-comedo typeに分類，さらに組織学的因子として石灰化径，管腔拡張の程度，管腔密度，管腔内細胞量を3段階に分類した．結果：組織亜型では，comedo typeを有するものは8例中7例で高エコースポットが描出されたが，non-comedo typeのみの病変では6例中5例で描出は不能であり，comedo typeを有するものは有意に高エコースポットの描出が明瞭であった（P＝0.007）．組織学的所見では，石灰化径の大きいもの（P＝0.02），管腔拡張程度が大きいもの（P＝0.003），管腔密度が高いもの（P＝0.01）が有意に高エコースポットの描出が明瞭であったが，管腔内細胞量と高エコースポットの描出に有意な相関は認めなかった（P＝0.58）．結論：comedo typeでは高エコースポットが良好に描出された．組織学的所見として，石灰化径が大きい，管腔が拡張している，管腔密度が高いほど高エコースポットの描出が明瞭であった．

症例は40歳，女性．1996年4月繰り返す黒色便を主訴に当院を受診した．血液検査にてHb5.3g/dlと著名な貧血を認めた．出血シンチグラフィーにて右下腹部にRIの血管外漏出およびテクネシウムシンチグラフィーにて骨盤内右側に異常集積を認めたためMeckel憩室からの出血を疑い緊急開腹術を施行した．開腹所見ではMeckel憩室は存在せず，回腸末端より160cmの小腸腸間膜対側に径7cmの管外性に発育した腫瘍を認め，小腸部分切除術を施行した．病理組織学的にGISTと診断された．その後，約7年間に3回の肝転移を認め，肝切除術を施行した．2003年8月より2年間メシル酸イマチニブ（以下グリベック）の投薬を行った．その間再発は認めなかった．グリベック休薬11カ月後，残肝に転移が出現し，4回目の肝切除を施行した．診断から10年以上経過した現在生存中である．

一般に予後不良とされているAFP産生のS状結腸癌の1例を経験したので報告する. 症例は61歳の女性で, 前医にてS状結腸癌に対しS状結腸切除術を施行された. 術後8か月目に肝S5を主体に右葉を占居する長径9cmの肝転移を認めたため, 当院へ入院し拡大肝右葉切除術を施行した. 術前の腫瘍マーカーは, CEAが6.6ng/ml, CA19-9が239.4U/mlと上昇し, さらに血清AFP値は1,463.7ng/mlと異常高値を示していた. 病理組織学的検査においては, 原発巣および肝転移巣ともに, 中分化型腺癌でAFP の免疫染色が陽性であった. Hepatoid differentiationは肝転移巣で認められた. これらより, AFP産生大腸癌の肝転移と診断した. AFP産生大腸癌の報告は極めてまれである. また, 免疫組織学的検査所見において, chromogranin A染色陽性部分は原発巣およびリンパ節転移巣に比べ, 肝転移巣でより広範囲に認められた. このことは腫瘍が分化・増殖に伴い, 神経内分泌性分化を呈していった可能性を示唆するものであった. AFP産生腫瘍で, かつ神経内分泌性分化を伴った大腸癌の症例はさらにまれである.

混合型肝癌は原発性肝癌の0.54%を占める稀な疾患で,胆管細胞癌に類似した進展形式をとり予後不良とされている.当院では1979年から2004年の間に423例の原発性肝癌に対して肝切除を行い,そのうち4例(0.95%)が混合型肝癌と診断された.平均年齢67.5歳,男女比3:1で4例中3例が腫瘍最大径5cm以上であり, HBs抗原陰性, HCV抗体陰性のものが2例, HCV抗体陽性が1例, HBs抗原陽性が1例であった.術前診断は画像所見,腫瘍マーカーなどより2例で混合型肝癌を疑い,残りの2例は肝細胞癌であった.それぞれ術後5カ月後死亡, 3年8カ月後死亡, 1年10カ月後死亡, 5カ月後生存,と予後は不良であった.再発形式はリンパ節,肝,骨,肺,心などであり,残肝再発に対しては,従来の肝動注化学療法や肝動脈化学塞栓療法がやや有効であった.

横隔膜原発粘液線維肉腫の稀な1例を経験したので報告する.症例は45歳,女性,左季肋部の鈍痛を自覚し近医を受診した.腹部エコーで左上腹部に腫瘤を指摘され,当院紹介となった. CT・MRIでは,左上腹部に約17cm大の境界明瞭な腫瘤を認め,胃・脾・膵・左腎を著明に圧排していた.血管造影では左下横隔動脈より腫瘍への栄養血管を認めた.手術所見より,横隔膜原発腫瘍と判断し,脾臓・横隔膜の一部と共に腫瘍を切除した.病理組織学的には粘液線維肉腫(粘液型悪性線維性組織球腫)と診断された.術後化学療法としてMAID療法 (MESNA+ADM+IFM+DTIC) を施行中であり,術後2ヵ月目の現在,無再発である.

目的:膵癌は切除術を施行しても治療成績はいまだに悪く有効な補助療法の併用が不可欠だと考えられている.そこで今回,膵癌切除後の補助療法として術中放射線照射療法の有効性について検討した.方法: 1991年1月から2003年12月までの13年間に当院で行った膵管癌切除症例69例を術中放射線照射(以下IORT)施行群38例と非施行群31例に分けて各群における局所再発率と生存率を検討した.さらに臨床・病理学的因子ごとに両群間の生存率を比較し, IORTがどのような症例に対して有用かについて検討を行った.結果: IORT施行群では非施行群と比べて有意に局所再発が低く(IORT群7.8%, 非施行群22.6%, p

症例は60歳,女性.右腎細胞癌(clear cell type)の根治術術後4年で,左内下部に腫瘤を自覚し,徐々に増大のため当科紹介. 2.6cmの腫瘤に対し, core needle biopsy (CNB)施行し,腎細胞癌からの転移が強く疑われた.他部位に転移はみられず,乳房円状部分切除とセンチネルリンパ節生検(SNB)を施行した.病理診断は腎細胞癌からの転移でリンパ節転移はみられなかった.術後無治療で経過観察中である.腎細胞癌からの乳腺転移は非常に稀のため,文献的考察を加える.

A variety of innumerable clinical trials are now carried out all over the world. However, there are few high evidence level results which are usable in actual practice. Moreover, there are very few cases participating in clinical trials, especially in Japan, and the evidence level is becoming low.

症例は50 歳の女性で, 全身倦怠感を主訴に近医を受診した. 腹部超音波検査で膵体部に径1cm の腫瘍を認め, 当院紹介となった. 腹部CT では膵体部に造影効果のある径1cm の腫瘍を認め膵内分泌腫瘍が疑われたが, 腹部MRI ではT1, T2強調像ともに低信号であり, 膵内分泌腫瘍としては非典型的な所見であった. 血清CA19-9が1,459.2U/ml と高値であり, 膵管癌の可能性も否定できず, 外科的切除を施行した. 病理組織検査で腫瘍細胞は膵島類似の索状配列をなし, 一部に腫瘍細胞と連続して腺管構造を伴っていた. また, 間質が高度に線維化しており, これがMRI T2強調像で腫瘍が低信号を示した原因と考えられた. 免疫染色では内分泌細胞の部分がグルカゴンに陽性, 腺管構造の部分がCA19-9染色に陽性を示し, 非機能性膵内分泌腫瘍と診断した. 膵内分泌腫瘍の起源に関しては諸説有るが, 内分泌腫瘍細胞と腺管組織が連続性を持つことより膵内分泌腫瘍の起源として多分化能を持つ膵管上皮が考えられた.

症例は初診時64歳の女性. 1990年2月右乳癌(潜在癌)の診断で拡大乳房切除術施行した(Stage III,充実腺管癌).術後はタモキシフェン, UFT®を5年間内服.1998年5月(71歳)性器出血から子宮体癌と診断,同年7月準広汎子宮全摘術施行され,組織検査では小細胞癌(Stage IIIc)であった.術後補助化学療法としてカルボプラチン+エトポシドを6コース施行. 1998年12月(72歳)子宮癌の経過観察中腹部超音波検査で膵体部癌を発見され, 1999年3月膵体尾部切除術,術中放射線照射25Gy施行された(Stage II,高分化腺癌).膵癌術後5年10カ月経過したが,無再発生存中である.本症例では子宮体癌術後の経過観察中に膵癌を比較的早期に発見できたことが長期生存の大きな要因と考えた.

This study clarified the difference in the effects on serum lipids between toremifene (TOR) and tamoxifen (TAM). To remove influencing factors, we investigated adjuvant therapy for hormone receptor-positive patients with breast cancer without lymph node metastasis. The subjects were 65 patients who were enrolled in a multicenter randomized comparative study between April 1997 and March 2001. As adjuvant therapy, 20 mg of TAM or 40 mg of TOR was administered for 1 year. The levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (Apo A-1), apolipoprotein A(Apo B), and lipoprotein a (Lp(a)) were measured prior to administration and 3, 6, and 12 months after the start of administration. TC, LDL-C, Lp(a) and Apo B significantly decreased from the third month of administration compared with values before the start of administration in both the TOR and TAM groups. HDL-C significantly increased from the third month only in the TOR group. TG significantly increased in the TAM group but significantly decreased in the TOR group in the 12th month of administration. When these two groups were compared, HDL-C was significantly higher (p < 0.01) and TG was significantly lower (p < 0.01) in the TOR group in the 12th month. Improvement of abnormal values of TG, HDL-C and LDL-C was better in the TOR group than in the TAM group after administration for 12 months. The effect on lipid metabolism showed different profiles between the two selective estrogen receptor modulators (SERMs), and TOR gave better results than TAM.

Background and Objectives Although studies have focused on modulating the bioavailability of 5-FU through inhibition of dihydropyrimidine dehydrogenase (DPD) to improve efficacy of the drug, activity of this enzyme in breast cancer has not been thoroughly examined. We measured DPD activity in primary and metastatic lesions and benign breast tumors to evaluate the clinical significance of this enzyme in the treatment of breast cancer. Methods DPD activity was measured by catalytic assay and compared in 100 primary tumors (95 invasive carcinomas, 5 intraductal carcinomas), 26 uninvolved adjacent breast tissue specimens, 6 metastatic sites, and 7 intraductal papillomas. Results The enzyme level in the carcinomas was 4-fold that of adjacent uninvolved breast tissues (101 vs 23 pmol/min/mg protein, P

The purpose of this study was to determine the most appropriate tests and procedures to detect disease progression effectively during the postoperative follow-up of patients with early breast cancer. We reevaluated our current surveillance protocol which involves the intensive follow-up of 643 patients with stage I disease. With the exception of one case of bone metastasis, all cases of recurrence (97%) were suspected from abnormal results detected during surveillance involving physical examination, serial determination of tumor markers, and chest roentgenography. Among 15 patients with asymptomatic distant metastasis, disease recurrence was suspected in 12 (80%) because of increased levels of serum tumor markers. No disease recurrence was detected by routine complete blood counts or automated chemistry studies alone. Our experience indicates that an effective follow-up regimen for patients with early breast cancer may include careful history-taking, physical examination, and the determination of serum tumor markers every 3-6 months for the first 3 years, then less frequently thereafter, and chest roentgenography every 6 months for 5 years, in addition to annual mammography. Serial determination of the tumor markers tumor polypeptide antigen, NCC-ST-439, and either carcinoembryonic antigen or carbohydrate antigen 15-3, seems to be of value for the selection of patients who should undergo radiologic exploration. The health benefits and cost-effectiveness of a follow-up focused on the measurement of serum tumor markers need to be evaluated in large prospective randomized trials.

Background Endoscopic resection was recommended as treatment for mucosal epithelium or lamina propria mucosae lesions not exceeding two-thirds of the circumference. The aim of this study was to verify the outcomes of endoscopic resection and surgery for early and superficial carcinoma of the esophagus.

The surgical treatment of esophageal cancer affects both the physical and psychological condition of the patients, and it is often associated with severe complications after the operation. Education concerning potential postoperative conditions during the early preoperative period might reduce anxiety associated with the operation and allow patients to manage their situation preoperatively. Preoperative instruction video orientation systems (OR) were introduced, and the changes in the patients’ anxiety, the time period after leaving a state of bed rest, and the occurrence of postoperative respiratory complications in the intensive care unit (ICU) were investigated. Seventeen patients underwent curative surgical treatment of esophageal carcinoma in our institute from February to November, 2008. The original orientation video was introduced on the first hospitalization day, just 1 week before the operation. A questionnaire was administered to the patients on the first day to evaluate the patients’ anxiety using the Hospital Anxiety Depression Scale (HADS) and again on the fourth day before surgery. HADS score was significantly reduced to 3.9 ± 2.8 after OR from 4.7 ± 2.7 before OR (P < 0.01). The time required to be able to walk was 2.5 ± 0.6 days following the operation. There were no respiratory complications or any episodes of emotional instability in the ICU. The OR is considered to be effective for the prevention of respiratory complications because it reduces the anxiety in preoperative patients and eases postoperative nursing care (by early ambulation).

We reviewed the clinical and pathologic features of pure tubular carcinoma of the breast with particular emphasis on the reported risk factors associated with local recurrences and survival following breast-conserving therapy. Of 1653 cases of invasive breast cancer, 12 (0.7%) were identified as pure tubular carcinoma. Clinical/pathologic features of pure tubular carcinoma were compared with those of T1 invasive carcinoma of all other histologic types (T1 IC). Of the 12 patients with pure tubular carcinoma (median tumor diameter 1.4 cm; range 0.5-3.0 cm), a multicentric association was identified in one patient while a multifocal association was seen in two. One patient had nodal metastatic disease out of the ten who underwent axillary dissection. No lymphatic vessel invasion was identified in any tumors (P < 0.1 vs T1 IC). In addition, extensive intraductal spread was not present in any tumors (P < 0.05 vs T1 IC). This study shows that patients with pure tubular carcinoma are appropriate candidates for breast-conserving therapy based on the clinical/ pathologic features. When a multifocal association is suspected preoperatively, either a wide local excision or a quadrantectomy which includes other lesions is thus recommended.

As the incidence of ductal carcinomain situ (DCIS) is increasing, it is necessary to make a guideline for the pathological examination and diagnosis of DCIS, by creating criteria based on clinical and biological aspects of the disease. We collected biopsy specimens originally diagnosed as benign lesions, from patients who subsequently developed invasive carcinoma in the ipsilateral breast. The histology of the biopsy specimens was re-evaluated principally according to the 1995 Philadelphia Consensus on DCIS. Histopathological agreement on each biopsy specimen was made by the JBCS Study Group members under a multiviewer microscope. In the course of making conclusive agreements among the pathologists, we developed a consensus for the histopathological diagnosis of DCIS, especially non-comedo types. DCIS is defined as a carcinoma of ductal epithelial origin, without any evidence of stromal invasion. It is necessary to note the methods of pathologic examination required to diagnose DCIS. Stromal invasion is an important prognostic factor, and should be diagnosed with caution. Classification of proliferative ductal lesions as benign or malignant (DCIS), the subtype of DCIS (nuclear grade, architecture, and necrosis), and the histological grading of DCIS are proposed and recommended Although we have made a new proposal according to current concepts, there are still several unresolved problems. Thus further examination and modification will be necessary in the future.

Germline mutations in the RET proto‐oncogene are responsible for multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Point mutations or in‐frame deletions of exons 10, 11, 13, 14 and 16 are associated with sporadic medullary thyroid carcinoma (MTC). To understand further the role of the RET gene in sporadic MTC, we examined mutations in exons 12 and 15 of RET in patients with sporadic MTC. DNAs were extracted from 39 formalin‐fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes. DNA sequencing was used to identify mutations in exons 12 and 15 of RET. In this study, one novel somatic mutation was found in exon 12 and five novel mutations or deletions were found in exon 15. Of the patients with mutations, one had an in‐frame 12‐bp deletion (nt. 2625‐2636), one had point mutations in both codons 884 and 908, and the remaining three had point mutations in codons 748, 876 and 901, respectively. Together with our previous identification of somatic mutations in exons 10, 11, 13, 14 and 16, somatic alterations were found in 10 out of 39 (25.6%) sporadic MTCs. There was no association of RET gene mutations with tumor recurrence or prognosis. These results suggest that mutations occur frequently in the RET coding region in addition to the previously reported mutation hot spots, and there is a different spectrum of mutations between sporadic and hereditary MTC.

BACKGROUND: A tumor 30 mm or less in diameter is a standard candidate for breast conserving surgery (BCS) in Japan. Axillary lymph node metastases (ALNM) is the most important prognostic factor for survival in patients with breast cancer, but the role of axillary node dissection has been controversial. Histopathological predictive factors of axillary lymph node involvement have not been established. The purpose of this study was to determine the association between the incidence of ALNM and histopathological factors by univariate and multivariate analysis METHODS: Sixty-five patients with noninvasive ductal carcinoma, and 993 patients with tumors 30 mm or less in diameter who underwent axillary dissection between 1988 and 1997 at our institute were reviewed. The association between ALNM and 13 histopathological factors (size, age, histological subtype, histological invasiveness, lymphatic invasion, vascular invasion, macroscopic classification, histological daughter mass, ductal spread, ER, PgR, p-53, and c-erbB-2) were analyzed by univariate and, when significant, by multivariate analysis. RESULTS: Only one patient with noninvasive ductal carcinoma had ALNM, and 33.1% of 993 patients with a tumor 30 mm or less in size had ALNM. Multivariate analysis identified six factors as independent predictors for ALNM: lymphatic invasion, size, histological invasiveness, macroscopic classification, age and histological daughter mass. CONCLUSION: Axillary lymph node dissection can be omitted in patients with noninvasive ductal carcinoma. Histopathological features of tumors 30 mm or less in diameter can be used to estimate the risk of ALNM, and routine axillary node dissection might be spared in selected patients at minimal risk of ALNM, if the treatment decision is not influenced by lymph node status, such as in elderly patients.

1988年より1995年までの8年間の1,180例の乳癌症例中, 非浸潤癌は76例 (6.4%) で, 石灰化を伴った乳管癌22例について検討した。年齢は検診機会の多い40歳代が最も多かった。部位は外上が14例と最も多く, 次に内上6例であった。症状は腫瘤10例, 乳頭分泌3例で, 検診で発見された症例が8例 (36.4%) みられたが, 非浸潤癌の石灰化のパターンを孤在型7例, 散在型6例, 密集型4例, び漫型5例の4型に分類すると, 検診で発見された症例のほとんどは孤在, 散在型であった。診断法別では, MMGではすべて癌と診断されているが, 触診で7例 (31.8%) は異常を認めていなく, 特に孤在, 散在型では約半数を占めていた。超音波でも同様で47.6%に異常を認めていなく, その大部分は孤在, 散在型であった。しかし小strong echoが多数見られるという特徴が見られた。手術法でPateyが27.2%, Halsted以上が13.6%もあり, またR2の郭清が81.9%にも行われていた。特に密集, び漫型で著明であった。病理組織学的には, 孤在型で管内進展なしの症例が半数以上占め, またnon-comedo typeが28.6%見られた。リンパ節転移は1例も見られなかった。以上より, 石灰化, 超音波像より非浸潤癌が疑われた場合, 生検などで確認し, QOLの観点からもover surgeryを避けなければならない。

Four hundred and sixty-four patients with solitary intramucosal gastric cancer were subjected to a study of risk factors of lymph node metastases and the recurrence. Lymph node metastases were recognized in 6 cases (1.3%, n1 2, n2 4). The largest diameters of these tumors ranged from 1 cm to 10 cm (mean 5.6 cm). They showed macroscopically depressed types including 3 IIc types, IIc+III type, 3 type and 5 type. Histology revealed all the tumors contained foci of poorly differentiated adenocarcinoma including 3 por, 2 sig and tub 2. Intramucosal gastric cancers with lymph node metastases were characterized by larger diameter, more often associated ulceration and more often overstimated serosal invasion than those without lymph node metastases. Three of 6 patiens with lymph node metastases died of cancer recurrence at 25, 61 and 71 months after surgery. The 4 recurrent cases died of cancer and had larger diameter (more than 4 cm) and were more often associated with ulceration and lymph node metastases than nonrecurrent 399 cases. We conclude that the depressed poorly differentiated gastric cancer with ulceration, even if it is an intramucosal cancer, can metastasize to lymph nodes; such a cancer should be treated by gastrectomy with lymph node dissection; and postoperative adjuvant chemotherapy should be mandatory, if lymph node metastases exist.

A retrospective analysis was carried out on 379 patients who had experienced an internal mammary lymph node dissection among 2244 patients with breast cancer from 1969 to 1994. Seventy one (18.7%) patients were found to have metastatic internal mammary nodes. The 10-year survival rate of the internal mammary node-positive patients was worse than that of node-negative group (43% vs 72%, p