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Purpose The objective of this study is to specify the most reported adverse events as preferred terms (PTs) and to compare the reported adverse events about some properties including the number of report and time-to-onset (TTO) distribution of the originator of filgrastim Neupogen® and its biosimilars in Europe, using VigiBase®. Methods We identified the biosimilar which was reported as the suspected drug in more than 100 individual case safety reports in Europe. Then, we specified the top ranking 10 PTs in the cases reported with Neupogen® or each biosimilar as the suspected drug. We also compared the TTO of the most reported PTs using the data about the onset date of the PT and the start date of filgrastim. We used Kolmogorov–Smirnov method to detect significant difference. Results The total ICSR numbers with Neupogen® and 3 biosimilars, Zarzio®, Nivestim®, and Tevagrastim® were 1,301, 295, 156, and 127, respectively, in Europe. The most reported PTs with Neupogen® were bone pain, pyrexia, and dyspnoea. The TTO of bone pain and pyrexia with Zarzio® (N: 22 and 16, median: 1 and 0.5 days) were significantly shorter than those with Neupogen® (P < 0.01, N: 72 and 33, median: 3.5 and 3 days), respectively. The most reported PTs with biosimilars were drug ineffective and neutropenia. Conclusion The difference in the TTO was identified between originator filgrastim Neupogen and its biosimilar regarding some PTs, which may suggest the difference in their safety profile. Copyright © 2017 John Wiley & Sons, Ltd.

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

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.

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.

Sixty-four cases of malignant lymphoma involving the liver were examined. Of these, 20 cases were histologically confirmed to be primary hepatic B-cell lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12 cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6 (indicating a germinal center phenotype), six were positive for Bcl2, and five were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and HCV RNA. The incidence of HCV infection was significantly higher in the hepatic DLBCL cases than in systemic intravascular large B-cell cases with liver involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19 cases, 5.3%) (p

症例1:74歳女性，上行結腸癌に対し右半結腸切除術を施行し，術後14カ月目に下部消化管内視鏡検査で吻合部再発を認めた．症例2:71歳女性，下行結腸癌に対し左半結腸切除術を施行し，術後42カ月目に下部消化管内視鏡検査で吻合部再発を認めた．共に進行癌で，吻合部を含めた腸管切除術を施行し，いまだ再発を認めていない．開腹し再建を手縫い吻合で行っているが，同吻合が主である当科における過去10年間の結腸癌吻合部再発は当2例であり，再発率は0.92％で文献的統計と差はない．近年器械吻合の機会が増え，吻合部再発の報告が増えている．当科では吻合前腸管洗浄や吻合部へのポビドンヨード塗布は行っていなかったが，implantationが原因である可能性が高いことから，一般的な予防法の確立が望まれる．

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.

We assessed interinstitutional and interobserver consistency of human epidermal growth factor receptor type-2 (HER2) testing using immunohistochemical analysis and fluorescence in situ hybridization (FISH) in a set of 20 breast cancer samples among 10 institutions in Japan and a Herceptin adjuvant study participating laboratory in Germany and identified factors that may lead to discordant results.We found a good agreement in immunohistochemical HER2 scoring between the coordinating institution and 10 participating laboratories (kappa = 0.718) and excellent agreement for FISH (kappa = 0.900). The results of a comparison between 10 Japanese laboratories and the German laboratory was good for immunohistochemical studies (kappa = 0.713) and excellent for FISH (kappa = 0.887). FISH retesting of equivocal samples (2+ immunohistochemically) improved agreement. Discrepancies between results were attributed to the evaluation process in 33.0% of the samples, staining procedures in 25.0%, and a combination of the two in 41.7%. Evaluation of samples according to the American Society of Clinical Oncology/College of American Pathologists guideline increased the number of 2+ immunohistochemical scores. By performing FISH retesting for these samples, consistency among multiple institutions could be archived. The quality of the staining procedures performed and the consistency of evaluations require regular assessment.

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．

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.

肝細胞癌に対する経皮的ラジオ波焼灼術（RFA）後に発症した右横隔膜ヘルニアの2症例を経験した．横隔膜の欠損は治療部位に接して生じており，ラジオ波焼灼術による合併症と判断した．RFA治療から発症までの期間は症例1で78週，症例2で112週であった．しかし，横隔膜の断裂は症例1では65週の時点で，症例2では42週の時点でCT上明らかになっていた．横隔膜断裂に加え，肝委縮・腹水貯留・腹圧上昇などにより腸管が横隔膜下腔に入り込むことがヘルニア発症の誘引と考えられた．右葉横隔膜直下の腫瘍に対するラジオ波焼灼術においては，十分量の人工腹水注入や腹腔鏡あるいは開腹下などの横隔膜を損傷しない工夫と治療後の経過観察が重要であると考えられた．

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.

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.

The authors reviewed the computed tomographic (CT) scans and pathologic specimens of 57 histologically proved bronchogenic carcinomas (35 squamous cell carcinomas, 12 small cell carcinomas, and 10 adenocarcinomas) in 47 patients with diffuse pulmonary fibrosis. The patients ranged in age from 61 to 87 years (mean age, 72 years; 42 men and 5 women). On radiography and CT, most tumors (82%) were located in peripheral areas of honeycomb lung. In 50 of the 57 lesions, the tumors were round or lobulated with sharp margins. In seven tumors, including six squamous cell carcinomas and one small cell carcinoma, the tumor invaded the adjacent honeycomb lung and lacked distinct margins. Intratumor lucency was seen in 13 tumors (five solitary and eight multiple). The CT findings, including high-resolution CT scans, were compared with the histologic findings in a subgroup of 29 lesions in 25 patients with available surgical or autopsy specimens. Invasive growth of tumors with unclear margins (four lesions), septal thickening of the contiguous/surrounding honeycombed areas (16 lesions), and discrete masses (nine lesions) with solitary (four of nine) or multiple (five of nine) intratumor lucencies. The lucencies in six of nine patients (67%) with intratumor lucencies were found to represent engulfed cystic airspaces histologically. CT revealed that bronchogenic carcinoma associated with diffuse pulmonary fibrosis has distinct morphologic characteristics that correlate histologically with a specific pattern of tumor growth.

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

乳腺穿刺吸引細胞診において, 常に乳癌との鑑別が問題となるのが線維腺腫や良性乳頭状病変である. 今回, 線維腺腫のなかで特に乳頭腺管癌との鑑別が問題となる乳腺症型線維腺腫について, その細胞像および良悪の鑑別点を乳癌例と対比しながら細胞学的検討を行った. 乳腺症型線維腺腫の細胞像は, 一般的な線維腺腫の細胞像に加え, 乳腺症に出現する細胞集団 (乳頭重積状・節状・充実重積状・クサビ状) が認められる. よって増殖の強い細胞集団を散見する場合, 全体像をよく把握したうえで, 各細胞出現様式について詳細な細胞の観察を行い, 総合的に判断することが重要である.

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.

The occurrence of a collision tumor in the stomach, consisting of adenocarcinoma and malignant lymphoma, is extremely rare. We report herein the case of a patient who had undergone a pancreatoduodenectomy for bile duct cancer 5 year earlier, in whom an ulcerating tumor of the remnant stomach developed and grew rapidly within 5 months. Surgical exploration revealed a tumor in the remnant stomach, multiple liver metastases, and multiple lymph node metastases. Total resection of the remnant stomach was performed, and pathological examination revealed a collision tumor consisting of adenocarcinoma and malignant lymphoma. The patient died of liver metastases and lymph node metastases 7 months after his second operation. The coexistence of both adenocarcinoma and malignant lymphoma of the remnant stomach and the etiology of this unusual combination, never previously reported, is discussed.

The increasing use of mammographic screening has led to an increased detection of ductal carcinomain situ (DCIS) of the breast. The detailed biological characteristics of DCIS and a new classification of DCIS based on these characteristics are needed. Immunohistochemical studies were performed to assess the expression of c-erbB-2 (ErbB-2), estrogen receptor (ER), p53 and proliferative activity (Ki-67) in 65 patients with pure DCIS and 60 with invasive ductal carcinoma (IDC). We classified pure DCIS tumors using three classifications, the architectural, Nottingham, and Van Nuys classifications. ErbB-2, ER and p53 staining was positive in 34%, 66% and 21% of patients with DCIS, respectively, and 58%, 42% and 33% in patients with IDC, respectively. Ki-67 stained positively in 1.5 % of patients with DCIS and 11.2 % of patients with IDC. The comedo type showed a high rate of positive ErbB-2 and p53 staining. The cribriform and papillary types showed a high rate of positive ER staining. Under the Van Nuys classification, ErbB-2, p53 and Ki-67 expression were highest in the group with high nuclear grade and lowest in the group with non-high nuclear grade without necrosis. Although the biological markers of IDC tended to suggest aggressive behavior more so than those of DCIS, these differences were based on the histological sub-type, comedo or non-comedo. The Van Nuys classification best defined the subgroups of DCIS with a distinct expression pattern of biological markers, and the best candidates for breast-conserving surgery.

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.

Activating missense mutations in the Arg 201 codon of the gene encoding the alpha subunit of Gs, the G protein that stimulates cAMP formation, have been recognized as the cause of many endocrine diseases, McCune-Albright syndrome and isolated fibrous dysplasia of bone. On the other hand, intramuscular myxomas with fibrous dysplasia, so-called Mazabraud's syndrome, have been sporadically reported, but it has not been confirmed whether intramuscular myxoma, with or without fibrous dysplasia, is associated with the Gs(alpha) mutations. We investigated the presence of the Gs(alpha) mutations in intramuscular myxomas with or without fibrous dysplasia by a PCR-SSCP assay, using formalin-fixed, paraffin-embedded tissues. In five of the six intramuscular myxomas (three with and two without fibrous dysplasia), point mutations were detected as aberrant bands by SSCP, which were confirmed by a subsequent sequence analysis (three Arg to His and two Arg to Cys). This result suggests that the Gs(alpha) mutations are related to tumorigenesis in intramuscular myxoma and that intramuscular myxoma is one of the diseases induced by abnormal Gs(alpha) protein.

Protein changes in the neutrophils of patients with Behçet's disease were analyzed by high resolution two-dimensional gel electrophoresis to investigate the pathological features of Behçet's disease. Two clear protein spots were found to be differently expressed between healthy volunteers and patients with Behçet's disease. One was a 53 kDa protein with pI 5.2 that was detected in healthy volunteers but was nearly absent in the patients. The other was a 40 kDa protein with pI 5.2 that was detected in the patients but nearly absent in the healthy volunteers. Analysis of the N-terminal amino acid sequence of the 40 kDa protein revealed that it was a truncated actin with an N-terminus of Met-44. The presence of the truncated actin in the neutrophils of patients was confirmed by Western blot analysis using an antibody to the C-terminus of actin. The 53 kDa protein could not be identified because its N-terminus was blocked. The presence of the truncated actin in the neutrophils of the patients may be important in understanding the pathology of Behçet's disease.

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.

Optimal microbicidal activity of polymorphonuclear leukocytes (PMNs) requires recruitment of a functional nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to the phagosome. In this study, we used a synchronized phagocytosis assay and immunofluorescence microscopy (IFM) to examine the association of cytosolic NADPH oxidase subunits with phagosomes containing opsonized zymosan (OpZ). Ingestion of OpZ began within 30 seconds of particle binding and forming phagosomes were enriched for both F-actin and the actin-binding protein p57. NADPH oxidase subunits p47phox and p67phox were also recruited to forming phagosomes and were retained on mature phagosomes for at least 15 minutes. Colocalization of F-actin, p57, and p47phox on phagosomes was confirmed by immunoblotting. Translocation of p67phox, but not p57, to forming phagosomes was deficient in PMNs lacking p47phox. Surprisingly, we found that in PMNs from six individuals with X-linked chronic granulomatous disease (CGD), p47phox and p67phox accumulated in the periphagosomal area during ingestion of OpZ. However, in marked contrast to normal PMNs, p47phox and p67phox were shed from nascent phagosomes along with F-actin and p57 once OpZ was internalized (≈5 minutes). These data support a model in which flavocytochrome b is required for stable membrane binding of p47phox and p67phox, but not their association with the cytoskeleton or transport to the cell periphery.

Parathyroid cysts are rarely located in the mediastinum. This report describes a 45-year-old man with a mediastinal parathyroid cyst. Video-assisted thoracic surgery was successfully performed to remove the cyst.

We report herein an unusual case of a composite glandular-neuroendocrine carcinoma of the hilar bile duct. A 71-year-old Japanese woman was admitted to our hospital suffering from general fatigue, progressive jaundice, and a high fever. Computed tomography and angiography findings revealed a solid hypervascular mass in the hepatic hilus. Thus, a subsegmentectomy of the liver (S4, S5) and bile duct resection with lymph node dissection were performed. A tumor measuring 6.0 x 3.0 cm was found to be located in the bile duct of the hepatic hilus. Histologically, the tumor was composed of well-differentiated adenocarcinoma and small cell neuroendocrine carcinoma cells, with a histological transition between the two components. Grimelius' method revealed the presence of diffuse positive tumor cells in neuroendocrine carcinoma. The neuroendocrine tumor cells were also diffusely immunoreactive to chromogranin A. To the best of our knowledge, only 22 previous cases of composite glandular-neuroendocrine carcinoma in the biliary tract have been reported; however, this is the first case report of a clearly composite tumor of the hilar bile duct.

Immunoglobulin G4-related disease, a newly emerging systemic autoimmune disorder, can potentially involve the cardiovascular system. The standard treatment for immunoglobulin G4-related cardiovascular disease has not been established. We encountered a very rare case of an immunoglobulin G4-related inflammatory abdominal aortic aneurysm coexisting with a coronary artery aneurysm and periarteritis. The patient underwent surgical resection for the abdominal aortic aneurysm, followed by successful corticosteroid therapy for the coronary artery lesions. This is the first report of steroid-sensitive immunoglobulin G4-related coronary artery disease. A carefully planned treatment strategy for the multiple cardiovascular lesions was invaluable in the present case.

It was previously reported that vaccination with synthetic peptides corresponding to the CDR2 or CDR3 region of T cell receptor (TCR) protected susceptible animals from the development of experimental autoimmune encephalomyelitis (EAE). However, recent studies by several research groups have revealed that TCR peptide therapy often confers little or no protection from autoimmune disease. In the present study, we attempted to find more appropriate peptides that is capable of conferring effective protection against the development of EAE. Four peptides corresponding to parts of the V beta region (13-23, 24-36, 39-59, and 64-74) were selected by epitope scanning and hydrophilicity searching, and their protective abilities were tested. All these peptides were, however, ineffective in protecting rats from the disease. We also generated three different synthetic peptides corresponding to the TCR J region of encephalitogenic T cells. Vaccination with the J-region peptides did not protect animals from the development of EAE. Rather, one of the peptides (V beta-DSS-J beta 2.6) enhanced the clinical severity of EAE and induced fatal disease in some rats. Taken together, TCR peptide therapy appears to be generally ineffective and elucidation of the mechanism by which EAE is enhanced after TCR peptide vaccination should provide insight into the pathogenesis of this disease.

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

Thirty two patients (1.04%) with malignant lymphoma of the stomach were selected from 3074 patients with malignant tumor of the stomach. They were 14 men and 18 women with a mean age of 56.4 years. Stage (Ann Arbor, p=0.0030), lymph node metastasis (p=0.0076), histological subtype (0.0037), histological grade (Working Formation, p=0.0004) and lymphoma surface marker (T or B, p=0.0021) were correlated with survival. Multvariate analysis using Cox regression method showed no parameter reached the statistical significance. The stage I patient without lymph node metastasis revealed favorable prognoses. Lymph node metastases were observed in 15 (50%) of 30 resected cases, even in 1 (17%) of 6 submucosal lesion. In the patients with positive lymph node metastases, the survival of the patients received adjuvant chemotherapy was better than those without it (16.2 years vs. 2.4 years, p=0.1615). These results showed the radical surgical resection with lymph node dissection was enough for stage I patients, and the postoperative adjuvant chemotherapy was useful in stage II or more stage patients. We think that lymph node dissection is necessary for achieving a curative resection as well for assessing the prognostic factors.

62歳の男性。約4ヵ月前に頭頂部に自覚症状のない軟性腫瘤が出現した。Pilar cystを疑い, 皮膚切開したところ皮下に血管腫様暗紅色の嚢腫様腫瘤があり, また同部の骨欠損が認められた。生検標本の病理組織像で, 顆粒状の細胞質と大型の異型核を有する類円形の腫瘍細胞がシート状に増殖し, 肝癌の転移が疑われた。頭部CTで右頭頂部に境界明瞭な骨融解と腫瘤が, 体部CTで肝内に腫瘤が認められた。血液検査で軽度ないし中等度の肝機能異常と腫瘍マーカー(CEA, AFP, CA19-9)の高値が認められた。以上から本症例は肝癌が頭蓋骨へ転移し, 骨を破壊して皮下腫瘤として出現したものと考えられた。肝癌の頭蓋骨への転移は非常に稀であるが, このような悪性腫瘍が皮膚良性病変に類似する臨床像を呈することがあり日常の診察において充分注意が必要であると思われる。

SummaryCatamenial pneumothorax (CP) is a rare entity of spontaneous, recurring pneumothorax in females. Although it has been known to be associated with thoracic endometriosis, varying clinical course and the lack of consistent intraoperative findings have led to conflicting etiological theories. We herein discuss the etiology, clinical course, and surgical treatment of three patients with CP. Three females (aged 40 years, 28 years, and 34 years) had recurrent right-sided spontaneous pneumothoraces that coincided with their menses. They had undergone video-assisted thoracoscopic surgery (VATS) previously. Blueberry spots in the right diaphragm were detected in all three cases. Two patients had recurrence, postoperatively. The other patient, who received luteinizing hormone-releasing hormone analog therapy for an abdominal endometriosis in the perioperative period and postoperative chemical pleurodesis to prevent recurrence, has been free of recurrence for 15 months, postoperatively. However, pelvic endometriosis was detected in this patient only. Therefore, CP should be suspected in ovulating females with spontaneous pneumothorax, even in the absence of any symptoms associated with pelvic endometriosis. In addition, while performing VATS, careful inspection of the diaphragmatic surface is important. In complicated cases, hormonal suppression therapy and chemical pleurodesis might also be helpful adjunct modalities.

Anaplastic thyroid carcinoma (ATC) is a tumor with bad prognosis and long-term survival is very low. However, appropriate combinations of chemotherapy, surgery, and radition have been reported to potentially improve the treatment results for ATC. We describe a case of refractory ATC successfully treated with high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT). There has not been any evidence of recurrence for 10 years after auto-PBSCT. To the best of our knowledge, this is the first case of ATC that has been followed up for a long-term period after HDC with auto-PBSCT. This case suggests that intensive therapeutic approach such as HDC with auto-PBSCT may be useful.

We report a case of isoechoic axillary lymph node metastasis of mucinous carcinoma (so-called pure mucinous carcinoma) of the breast. A 47-year-old premenopausal woman was referred to our hospital with a 2 years history of mass and distortion of her left breast and with recent worsening of her symptoms. Ultrasonography demonstrated a well-circumscribed mass, about 5 cm in diameter, which was isoechoic compared to the surrounding fat tissue. Distal enhancement was also recognized. A left axillary ultrasonographic scan demonstrated four nodules, which were indistinct because of their isoechogenicity compared to the surrounding tissue. Based on a preoperative diagnosis of mucinous carcinoma of the left breast with left axillary lymph nodes metastases, left mastectomy and left axillary nodal dissection were performed. Mucinous carcinoma with axillary lymph node metastases was diagnosed histologically. The lymph node metastases showed histological findings identical to those of the primary tumor, which was considered to be the reason for their isoechogenicity. Although lymph node metastasis of mucinous carcinoma of the breast is rare, ultrasonographers should perform careful scanning when the primary breast mass is suspicious for mucinous carcinoma, because lymph node metastases of mucinous carcinoma can be more indistinct and difficult to detect than those of other types of breast cancer.

A diagnosis of low-grade fibromyxoid sarcoma (LGFMS) remains problematic because of its bland-looking histologic features that can be potentially confused with other benign or low-grade fibromyxoid lesions. Recent cytogenetic and molecular analyses have shown that most LGFMSs have a characteristic chromosomal abnormality, t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. However, such assays have only rarely been used to analyze formalin-fixed, paraffin-embedded tumor samples. In the present study, we conducted a reverse transcription-polymerase chain reaction assay to detect the FUS-CREB3L2 fusion transcripts using formalin-fixed, paraffin-embedded tumor tissue specimens from 16 LGFMSs including 3 cases with giant collagen rosettes. The primers were newly designed to specifically amplify most of the junctional regions of the FUS-CREB3L2 fusion gene transcripts previously reported. The FUS-CREB3L2 fusion gene transcripts were detected in 14/16 (88%) cases of LGFMS. A nucleotide sequence analysis of the PCR products revealed that different portions of the FUS exon 6 or 7 were fused with various sites of the CREB3L2 exon 5, resulting in 12 different nucleotide sequences. We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case. The FUS-CREB3L2 fusion transcripts were not detected in any of the 123 other soft-tissue tumors, including desmoid-type fibromatoses, myxofibrosarcomas, soft-tissue perineuriomas, and congenital or adult fibrosarcomas. These data suggest that our reverse transcription-polymerase chain reaction assay is a reliable method to detect FUS-CREB3L2, which can thus help in accurately diagnosing LGFMS.

Background The optimum sentinel node biopsy (SNB) mapping method for breast cancer remains to be determined. No matter which mapping agents are used, 2-site injection may be superior to 1-site injection in limiting the false-negative rate. Methods We examined whether a double-mapping method with subareolar injection of blue dye and peritumoral injection of green dye would decrease the false-negative rate of dye-only SNB in 145 patients with early breast cancer. Results The identification rate for blue-dyed and/or green-dyed (including mixed color-dyed) lymph nodes was 96.6% (140/145). Sensitivity and specificity were 95.1% (39/41) and 100% (99 of 99), respectively. Accuracy was 98.6% (138/140) with a false-negative rate of 4.9% (2/41). There were 4 patients in whom nodes of each color were found, but nodes of only 1 color were shown to be positive. The primary tumors of these 4 patients and of the 2 patients with false-negative results were located in the upper-outer quadrant of the breast. When only blue-dyed or green-dyed nodes (including mixed color-dyed nodes) were counted, the false-negative rates were 10.3% (4/39) for the subareolar mapping technique and 10.0% (4/40) for the peritumoral mapping technique. Conclusions The double-mapping method based on subareolar and peritumoral injections decreases the false-negative rate of dye-only SNB for early breast cancer. Variations in lymphatic channels may exist in the lateral half of the breast and thus may influence identification of positive sentinel nodes. This finding should be taken into account in cases of multicentric breast cancer.

The presence of rhabdoid cells has been reported in various types of malignant neoplasms and has been determined to be a predictor of aggressive behavior of neoplasms regardless of tumor histogenesis. One hundred and thirteen cases of leiomyosarcoma, selected from 1800 soft tissue sarcomas, were reviewed on hematoxylin and eosin sections, and immunohistochemical staining when available, and seven cases with rhabdoid features were retrieved. Clinicopathologic differences were analyzed to compare between cases with rhabdoid features and those without rhabdoid features. In the seven cases with rhabdoid features, two were intra-abdominal, and the others arose in external soft tissues including muscle, subcutis, and cutis. Patient age ranged from 33 to 84 years, three were female, and four were male. Tumor size ranged from 3 to 22 cm. Clinical evidence showed no differences from those cases without rhabdoid features. Histologically, one of the abdominal cases was epithelioid leiomyosarcoma. Two of the 7 cases were better subclassified as pleomorphic leiomyosarcoma, in which rhabdoid cells are diffusely scattered. In cases other than those with pleomorphic leiomyosarcomas, foci of anaplastic areas were observed, and collections of rhabdoid cells were present in those areas. Immunohistochemical examination of the cases confirmed myogenic differentiation, and showed rhabdoid cells being positive for vimentin and desmin in the inclusion bodies, and diffusely so for muscle actin in the cytoplasm. After dividing all the cases of leiomyosarcoma by their location, prognostic analysis was performed. Leiomyosarcoma of external soft tissue with rhabdoid cells showed a tendency for poorer prognoses than cases without rhabdoid features. On the contrary, retroperitoneal cases did not. This study indicates that rhabdoid features are associated with aggressive biological behavior in leiomyosarcoma of the external soft tissue.

We treated a patient with breast cancer associated with McCune-Albright syndrome. A 40-year-old woman with a history of precocious puberty visited our hospital complaining of a mass in the upper lateral quadrant of the right breast. Although bone scintigraphy revealed multiple high uptake of99mTc, plain X-ray demonstrated ground-glass appearance, suggesting fibrous dysplasia rather than bone metastases. Serum levels of tumor markers and alkaline phosphatase were within the normal range. Breast cancer associated with McCune-Albright syndrome was diagnosed, and she subsequently underwent breast conserving surgery, excision of abdominal wall myxoma and bone biopsy of the left clavicula. The bone lesion was histologically confirmed as fibrous dysplasia. Although McCune-Albright syndrome is a rare clinical entity, it should be considered as a possible differential diagnosis of bone metastasis in patients with breast cancer. As recent molecular studies have suggested genetic mutations in McCune-Albright syndrome, this syndrome may possibly predispose patients to breast cancer.

To find out whether macroscopic classification of the tumour margin is predictive of axillary lymph node metastases and to identify a combination of clinical and pathological findings by which axillary node status can be predicted accurately in small carcinomas (T1) of the breast.Retrospective study.Municipal referral centre, Japan.All 1003 patients with T1 invasive carcinoma of the breast who had axillary lymph node dissection between January 1970 and December 1996 as part of their treatment.The association between the incidence of axillary lymph node metastases and 10 clinical and pathological factors (age, palpability and size of tumour, macroscopic classification of tumour margin, clinical axillary status, radiating spiculation on a mammogram, histological type, lymphatic invasion, oestrogen and progesterone receptor status) were analysed.Clinical axillary node status, macroscopic classification of tumour margin, lymphatic invasion, and age of the patient were significant predictors of axillary lymph node metastases (p0.01 in each case). Among 47 patients aged 65 or more whose tumours had well-defined margins and with a clinical N0 status in the axillae, the incidence of histological axillary lymph node metastasis was only 6% (n = 3) whereas it was 65% in 57 patients with tumours of ill-defined margins whose axillae were N1 or N2.Macroscopic classification of tumour margins is an independent predictor of axillary lymph node metastases for patients with small carcinomas of the breast. However, even with combinations of the examined predictors of axillary node metastases, the subgroup of patients at minimal risk of metastasis was less than 5% in T1 breast cancer, whereas three-quarters of the patients had clear axillary lymph nodes. Most patients with T1 breast cancer will need surgical staging of the axillae by methods such as sentinel node biopsy.

Background and Objectives Medullary carcinoma of the breast has generally been considered to result in better prognosis than ordinary invasive ductal carcinoma, which would seem to be discrepant when one considers its anaplastic histology and high mitotic rate. We attempted to elucidate the prognostic implications of apoptosis and cell proliferation in medullary carcinoma of the breast. Methods Formalin-fixed, paraffin-embedded specimens of 50 cases of typical medullary carcinoma (MC) of the breast and those of 50 control cases of non-medullary invasive ductal carcinoma (N-MC), which were matched to the MC cases in both age and TNM classification, were investigated utilizing the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemistry for p53, bcl-2, and Ki-67. Results Mean values of the apoptotic index (AI), the proliferative index (PI), and the ratio of AI to PI (AI/PI) were significantly higher in MC than in N-MC (P < 0.0001). MC exhibited significantly lower positivity for bcl-2 than N-MC (P = 0.00003), while there was no significant difference in p53 positivity between MC and N-MC. Conclusions A high frequency of apoptosis may be related to a favorable prognosis in MC, even though it demonstrates a high proliferative activity, exhibiting a rapid cell turnover. J. Surg. Oncol. 1999;70:209–216. © 1999 Wiley-Liss, Inc.