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Background Lymphovascular invasion (LVI), which includes vascular or lymphatic invasions, is a representative prognostic factor even in patients with resected stage IA non-small cell lung cancer (NSCLC). Because tegafur-uracil is effective on cancers with LVI, we conducted a multi-center single-arm phase II study to estimate the efficacy of adjuvant tegafur-uracil in patients with LVI-positive stage IA NSCLC. Methods Patients with completely resected LVI-positive stage IA NSCLC were registered. LVI was diagnosed by consensus of two of three pathologists. Adjuvant chemotherapy consisted of 2 years of oral tegafur-uracil at 250 mg/m2/day. Fifty-five patients from 7 institutions were enrolled from June 2007 to September 2012. Results Among the 52 eligible patients, 36 (69.2%) completed the treatment course. There were 39 male and 13 female patients. The observation period was calculated as 562 to 3107 days using the reverse Kaplan-Meier method. The 5-year overall and relapse free survival rates were 94.2 and 88.5% respectively, which were significantly better than that of any other studies conducted on patients with LVI-positive stage IA NSCLC. Notably, the overall survival rate was 15% better than that of our prior retrospective study. The retrospective analysis of stage IA NSCLC patients who had received an operation in the same period revealed that the 5-year overall survival rate of the LVI positive group was 73.6% when adjuvant chemotherapy was not applied. Among 55 safety analysis sets, 4 cases of grade 3 hepatic function disorder (9.1%) and 5 cases of grade 2 anorexia (10.9%) were most frequently observed. No grade 4 adverse effects were encountered. Conclusion A 2-year course of oral tegafur-uracil administration is feasible and might have a significant benefit in the adjuvant treatment of LVI-positive stage IA NSCLC. Trial registration UMIN identifier: UMIN000005921; Date of enrolment of the first participant to the trial: 19 June 2007; Date of registration: 5 July 2011 (retrospectively registered).

Background and Aim:Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare neoplasm, and its clinical features and management are still limited. We evaluated the clinicopathological factors, including CDX2 immunohistochemical expression, to predict survival in patients with LCNEC.Patients and Methods:In all, 50 patients with LCNEC who underwent surgery at 4 institutes between 2001 and 2017 were included. Clinicopathological characteristics were evaluated for prognostic factors and statistically analyzed by Kaplan-Meier curve with a log-rank test or Cox regression models. We used immunohistochemical (IHC) analysis to determine the expressions of CDX2 and compared them with clinicopathological factors and survival.Results:Sixteen of the 50 cases (32%) were CDX2 positive. No correlation was found between the CDX2 expression by IHC and clinicopathological factors. Multivariate analysis identified adjuvant chemotherapy (hazard ratio [HR] =2.86, 95% confidence interval [CI] = 1.04-8.16, P = .04) and vascular invasion (HR = 4.35, 95% CI = 1.21-15.63, P = .03) as being associated with a significantly worse rate of recurrence-free survival.Conclusion:CDX2 was expressed in 1/3 of LCNEC but not associated with prognostic factor. Adjuvant chemotherapy and vascular invasion were associated with a negative prognostic factor of LCNEC.

（背景）輸血を受け入れないエホバの証人の患者に対する治療の対応や指針が検討され，現在に至っている．（目的）患者の意思決定を尊重する原則に立って治療を推進していく上で，インフォームドコンセント（IC）の方法とそれを実践する為に必要な他科との医療連携について検討する．（対象と方法）過去十年間にエホバの証人の患者113名（小児3名），128例におこなったICの方法と他科との医療連携の内容を示した．ICの方法は同種輸血拒否と受け入れ可能な代替療法の許容範囲の確認，無輸血治療に伴う合併症の内容の理解と同意であった．医療連携には麻酔科医，放射線科医，消化器内視鏡医との連携が含まれた．（結果と成績）ICの過程で医療者側が治療適応外と認めた症例は無かった．治療症例は110名，125症例で手術治療107例，放射線学的観血治療10例，内視鏡的治療4例，放射線照射化学療法17例をおこなった．緊急手術および治療は15例だった．患者全員が同種血輸血の受け入れを拒否する意思を示したが，4名を除く106名が代替療法として閉鎖回路で連結された希釈式自己血および回収式自己血輸血や血液分画の投与を受け入れた．自己血輸血を29例（23%）に施行し，術中術後の管理を通して，患者の意思により術前に代替治療の適用を定めた許容範囲を超えた症例は無く，無輸血治療が本来の治療の根治性を阻害することはなかった．また手術在院死亡や重篤な合併症の併発を認めなかった．（結論）ICの徹底と院内医療連携による無輸血治療の実践によって個々の患者に対する適切な医療環境と治療成績を提供できた．

小腸の高度狭窄を呈した難治性腸閉塞にて発症し, 切除標本の病理学的検索にてアミロイドーシスの診断を得た1例を報告する. 症例は74歳, 女性. 腹痛, 腹部膨満, 嘔吐など腸閉塞症状と下痢症状を繰返し, 保存的加療にて軽快せず, 外科に転科となった. 小腸造影にて中部小腸は高度の狭窄を示した. 腹部造影CTにて小腸の狭窄像とその口側小腸の拡張および壁肥厚を認めた. 絞扼性イレウスは否定的であったが, 小腸狭窄の原因は明らかでなかった. 難治性の腸閉塞にて手術となった. 小腸は全長約200cmと短縮し, 2カ所の高度狭窄を認めた. 小腸切除を施行し, 空腸・横行結腸側々吻合を行った. 病理学的検索にてアミロイドーシスの診断を得た. 消化管アミロイドーシスは, 腸管運動障害にて, 機能的腸閉塞をきたすが, 腸管狭窄による機械的腸閉塞の報告は稀であり, 若干の文献的考察を加え報告する.

肝癌治療中に併発した胆汁性肝嚢胞(biloma)が心嚢内穿破をきたしたまれな症例を報告する.症例は60歳,男性.原発性肝細胞癌に対して,肝拡大右葉切除術を施行した.その後,残肝再発に対して,肝動脈塞栓術(TAE)および経皮的マイクロ波凝固療法を併用し,複数回の治療を繰り返し経過した.術後8カ月目,閉塞性黄疸と胆管炎が出現した. TAE後の胆管壊死が原因と思われる,左肝管基部狭窄およびその末梢肝管の拡張認めたため,チューブステント留置にて改善した.その後,外側区にbilomaが出現するも,経過観察していたところ,術後14カ月目,突然の前胸部痛および呼吸苦が出現した.画像上, bilomaの心嚢内穿破による心タンポナーデと診断し,心嚢穿刺ドレナージ術を施行し,持続低圧吸引を続け, 3日後チューブ抜去が可であった.その後生存中,経皮的膿瘍ドレナージチューブを留置のまま,肝不全による死亡まで術後約20カ月間QOLを維持した生存期間を得た.

今回われわれはマイクロサテライト不安定性(microsatellite instability: MI)を示した,多発大腸癌,胃癌および腎癌からなる同時性3重複癌1治験例を経験したので報告する.症例: 74歳,男性.大腸多発癌(十二指腸浸潤を疑う上行結腸癌と3個の横行結腸多発早期癌),早期胃癌,左腎細胞癌の同時性3重複癌に対して平成12年2月9日,右半結腸切除,膵頭十二指腸切除および左腎摘出術を施行した.重複癌症例におけるミスマッチ修復系異常の関与を知る目的でMIを検討した結果,腎癌および0-I sp型大腸癌においてDNA複製エラーが認められた. 2002年2月に0-I sp型の直腸癌が出現したためEMRを施行したが, 2003年11月現在まで転移再発などなく経過生存中である. MI陽性例では同時性および異時性の多臓器・多発癌の厳重なフォローアップまた十分なチェックが必要であると考えられる.

Our aim is to evaluate whether outcomes differ by admission day of the week in patients with spontaneous pneumothorax. One hundred twenty five patients undergoing video-assisted thoracic surgery(VATS) in Fukuoka Tokusyukai Hospital from 2007 through 2011 for spontaneous pneumothorax were reviewed. The clinical characteristics and outcomes were compared between patients in weekend admission and weekday admission groups. Patients were divided in 2 groups based on admission between Monday thru Friday vs on Saturday or Sunday. Another 2 groups by admission between Sunday thru Thursday vs on Friday or Saturday were also examined. Time to operation was significantly shorter for admission on period between Sunday thru Thursday compared to admission on Friday or Saturday. But there was no difference in the other clinical factors and postoperative outcomes between 2 groups. Patients admitted on the weekend proved to experience delayed operation, but did not have increased adverse outcomes or longer length of hospital stay compared to those admitted on a weekday. No significant "weekend effect" for spontaneous pneumothorax was demonstrated by the present study.

Background Because carcinomatous lymphangitis and carcinomatous pleuritis are the usual forms of metastasis associated with gastric cancer, resection of solitary pulmonary metastases arising from gastric cancer is rarely performed. To clarify the characteristics of pulmonary metastases from gastric cancer, we investigated patients who underwent resection of metastatic solitary lung tumors arising from gastric cancer. Methods Between October 2003 and October 2012, 10 patients underwent pulmonary metastasectomy for metastatic gastric cancer at our institution. We retrospectively evaluated features of the primary gastric cancer and the clinicopathological features of the pulmonary metastases in these cases. Results 70% of the patients had stage II disease. Lymphatic invasion was observed in all cases of primary gastric cancer. The method of pulmonary resection was partial resection in 5 cases, segmentectomy in 1, and lobectomy in 4. On histopathological examination, immunohistochemical staining was negative for thyroid transcription factor-1 and napsin A in all cases. Patients who underwent resection of pulmonary metastases arising from gastric cancer had a good prognosis: the 4-year survival rate was 75%. Conclusions Carefully chosen patients have a good opportunity to obtain benefits from resection of pulmonary metastases arising from gastric cancer.

We encountered a case of delayed subcutaneous metastases of gastric carcinoma. The patient underwent distal gastrectomy for advanced gastric carcinoma 11 years ago. Postoperative pathological diagnosis indicated stage IIIB disease, poorly differentiated adenocarcinoma (scirrhous, T4a, ly2, v2, N2, H0, P0). Three courses of adjuvant chemotherapy with 5-fluorouracil (5-FU)+cisplatin (CDDP) were administered; however, the patient discontinued the treatment. No signs of recurrence were observed for 11 years after the treatment. However, subcutaneous metastases in the front portion of the head and the back and an ovarian tumor were detected after the remission period. The specimen from the resected subcutaneous tumor from the back indicated signet-ring cell carcinoma, and delayed subcutaneous and ovarian metastases of the gastric carcinoma was diagnosed. Therefore, 8 courses of the S-1+CDDP combination therapy were administered. The cutaneous metastases disappeared, but the ovarian tumor progressed and was therefore resected. Analysis of the resected ovarian tumor also indicated signet-ring cell carcinoma. We report a case of delayed recurrence of gastric carcinoma that was effectively treated with chemotherapy.

Background . Recent progress on airway stents has provided sufficient airway patency for patients with airway obstruction; however, when the stenosis exists in the carinal zone, establishing an excellent airway condition is still troublesome because of the anatomic structure. Methods . We treated 15 patients with severe tracheobronchial stenosis involving a carinal bifurcation region, using several types of stenting devices (long T-tube, T-Y tube, wire reinforced Y tracheostomal tube, Freitag Dynamic stent [Karl Storz, Tuttlingen, Germany], and covered metallic stent). All patients had advanced inoperable tumors (lung cancer, n=6; esophageal cancer, n=3; thyroid cancer, n=3; mediastinal tumor, n=3). Results . All but 2 patients had immediate relief of respiratory symptoms. One patient died of respiratory failure caused by pulmonary lymphatic spread 3 days after Dynamic stent insertion. In 1 patient with severe left main bronchial stenosis due to lung cancer, effective palliation was not achieved by insertion of a covered metallic stent because of its insufficient expansion against the stenosis. Mean survival after successful stenting was 4.3 months (range, 1 to 15 months). There were no complications directly attributable to the stents. Conclusions . As evidenced by the clinical effectiveness, airway stenting for inoperable tumor is valuable in such patients. Choosing a stent that will fully cover the lesion and allow sufficient tolerance against compression is important to successful stenting. Benefits such as ease of phonation and stent maintenance should also be considered.

当科でこれまでに経験した非腫瘍性中葉症候群の29例を臨床的に検討した.【結果】男性11例, 女性18例, 年齢は23-85歳 (平均59.6歳), 中葉病変27例, 舌区病変2例, 切除16例, 非切除13例 (切除率55%) であった.好発年齢は50-60歳代 (66%) であり, 40-50歳代全例が切除, 70-80歳代全例が非切除であった.また, 無症状例は全て非切除であった.気管支鏡検査で83%に異常所見 (炎症, 肥厚, 肉芽様変化, 不整狭窄等) を認めたが, 17%は無所見であった.結核由来の症例や気管支壁外性の症例は各1例であった.非切除の理由は保存的治療が奏功 (肺炎への抗生物質 : 10例, 喀血への気管支動脈塞栓術 : 2例), 高齢, 低肺機能 : 5例, 中葉以外に病変が存在 : 2例などであった.【考察】臨床症状, 気管支鏡所見, 経過などから手術適応は慎重に決定すべきである.今後ステントや胸腔鏡下のアプローチが検討課題となると考えられる.

The anti-carcinogenic effect of TAP-144-SR biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent LHRH agonist, TAP-144 (D-Leu 6 -(des-Gly 10 -NH 2 )-LHRH ethylamide, leuprolide acetate) was investigated in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumours. At 50 days of age, all rats were given 20 mg doses of DMBA by gastric intubation. Rats on the Initiation Group were given a single s.c. injection of TAP-144-SR (3 mg/kg) 1 week before DMBA treatment, and rats in the Promotion Group were given repeated s.c. injections every fourth week from 1 week after DMBA treatment until the end of the experiment. In the Initiation Group, tumour incidence and multiplicity were reduced to 20.8% and 15.0% of the Control Group values, respectively. In the Promotion Group, tumour incidence and multiplicity were also reduced to 17.7% and 7.9%, respectively. It was suggested that TAP-144-SR may be a potential candidate as an agent for hormonal chemoprevention in breast cancer.

The importance of tumor angiogenesis in the process of tumor growth and progression in solid tumors has been widely accepted. We have investigated the significance of tumor angiogenesis as a prognostic indicator in a retrospective study including 328 primary breast cancer patients. The postoperative survey demonstrated that the microvessel density (MVD) evaluated by immunocytochemical staining for factor VIII-related antigen is a potent prognostic indicator. The relapse-free survival (RFS) rate of patients with over 100 microvessels/mm2 in a microscopic field was significantly worse compared to that of patients with less than 100 microvessels/mm2 (p

A 72-year-old man was admitted to our hospital complaining of upper abdominal pain and back pain. Advanced gastric cancer was found at the fundus of the stomach, and severe dysplasia was found at the lower esophagus. We proceeded with neoadjuvant chemotherapy (S-1+CDDP) because the lymph nodes in the lesser curvature of the stomach were metastasized and invasion of the pancreas and some vessels was suspected by computed tomography. The tumor size was reduced remarkably, the esophageal dysplasia disappeared after preoperative chemotherapy, and we were able to perform total gastrectomy.

A bloodless surgery was required in the case of simultaneous liver metastases of colon cancer, one of which invaded at the confluence of left hepatic vein and inferior vena cava. In order to assure the safety and curability, hepatic arterial infusion chemotherapy aiming to size reduction was preceded to synchronous liver resection for a 53-year-old Jehovah's witness male. After gaining the reduction of tumor, synchronous liver resection was safely performed under a hemodilutional autotransfusion. The patient has been alive for 6 years under the withdrawal from chemotherapy.

A 59-year-old man realized a left lower abdominal pain and palpable mass about a month ago. He was admitted to our hospital because of the pain and high fever. Blood examinations revealed high levels of white blood cell count and CRP. Ultrasonography showed a wall thickness of the descending colon and 7 cm cystic mass with air around. Moreover, a 6 cm cystic mass was found an outside of the ascending colon. We first treated with antibiotics under the diagnosis of abscesses because of perforation of diverticulum. Colonoscopy revealed an obstructing tumor in descending colon and biopsy specimens of the tumor showed adenocarcinoma. The preoperative diagnosis of the right side tumor was unclear. We performed a partial resection of the descending colon, and the tumor outside of the ascending colon was resected. The pathological diagnosis of the tumors was both mucinous carcinoma of the colon. Mucinous carcinoma tends to be more found in the right side of the colon than in the left side. The rate of lymph node metastasis and dissemination is higher than that in differentiated adenocarcinoma. We report a rare case of mucinous carcinoma originated from the left side of the colon with a solitary dissemination in opposite side of the abdomen.

Previous authors have suggested that a diverticulum of the vermiform appendix has a higher risk of perforation than acute appendicitis. Therefore, this study compared appendiceal diverticulitis with acute appendicitis to explain the characteristics of appendiceal diverticulitis.Data for this study came from a retrospective analysis at the Department of Surgery at Fukuoka Tokushukai Hospital from January 2005 to June 2008. Twelve cases of appendiceal diverticulitis and 378 cases of acute appendicitis were analyzed.The patients with appendiceal diverticulitis were older than those with acute appendicitis (42.7 ± 15.4 vs. 29.1 ± 17.7; p = 0.009). The white blood cell (WBC) level was lower (11332 ± 4658 vs. 14236 ± 3861; p = 0.011) and the CRP level was higher (8.65 ± 8.94 vs. 4.34 ± 6.34, p = 0.022) in those with appendiceal diverticulitis than in those with acute appendicitis. A preoperative diagnosis for appendiceal diverticulitis was made in 4 out of 12 (33.3%) by ultrasonography (US). The perforation rate was higher in appendiceal diverticulitis than that in acute appendicitis (33.3 vs. 9.8%; p = 0.009).Appendiceal diverticulitis is more likely to perforate over the progression of the clinical course, which would mandate appendectomy when appendiceal diverticulitis is detected by US, even if the patient has no severe abdominal pain.

A 71-year-old man began feeling a lower abdominal pain at bowel movement about one year ago. He was found to have a pelvic tumor during a health examination and referred to our hospital for further evaluation. CT and MRI scans demonstrated a giant pelvic tumor, 10 cm in size, which compressed the rectum. The likely preoperative diagnosis was leiomyosarcoma from the rectum or neurilemoma. To regulate intraoperative hemorrhaging and to reduce the tumor size, angiography was performed at two days before the operation and embolization of the tumor vessels was done. He had a tumor resection and a low anterior resection of the rectum and a transient colostomy of the ascending colon without blood transfusion. The resected tumor was covered with thin yellowish-white capsule with smooth surface, elastic hard on palpation, and was measured 10.5 × 9 × 10.5 cm, and weighted 320 g. The pathological diagnosis was neurilemoma (schwannoma) consisting both Antoni type A and Antoni type B sections.

Background. Recently, the authors reported that membrane-associated phospholipase A2 (M-PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. Methods. M-PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method. Results. Tissue levels of M-PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-PLA2 and clinicopathologic factors showed that tissue M-PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M-PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-PLA2 showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-PLA2 concentration could be a powerful prognostic factor in predicting such survival rates. Conclusions. M-PLA2 is closely related to the malignant potential of breast cancers, and the M-PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer.

This study was undertaken to determine if primary breast tumor plasminogen activator expression correlates with skeletal metastasis in breast cancer. Total plasminogen activator activity was significantly lower in tumors of patients with recurrence than in recurrence-free patients. Similarly, the primary tumors of patients with skeletal metastasis contained considerably less enzyme activity compared with those of patients surviving without skeletal metastasis. When patients with skeletal metastasis were categorized in terms of their recurrence pattern, those who had skeletal metastasis without other organ metastasis had significantly less tissue-type plasminogen activator antigen in their primary breast tumors than did those who had metastasis to other organs. Furthermore, a significantly lower level of tissue-type plasminogen activator antigen was found in primary tumors associated with axial bone metastasis than in those associated with appendicular bone metastasis. These results suggest that tissue-type plasminogen activator is involved in skeletal metastasis formation by its effects through the vertebral venous plexus.

A 66-year-old woman, complaining of anal bleeding with anemia, was examined and diagnosed as advanced rectal cancer. Hemoglobin level at admission was 8.8 g/dL. Abdominal CT and MRI revealed a solid tumor of 43x45 mm in diameter. Colostomy was preceded for the purpose of bleeding control under the blood-augmented treatment on the 7th day of hospitalization. Preoperative chemoradiation was performed (a total of 40 Gy radiation+FOLFOX4 for 1 cycle) and obtained a significant size reduction of the tumor (reduction rate 75%). Abdomino-perineal resection of rectum was performed with 550 mL of hemodilutional autotransfusion 3 months after the initiation of treatment. Pathological findings showed moderately differentiated adenocarcinoma with Stage III a. Vaginal fistula as an irradiation associated with complication was healed by duly performed debridement. The patient has survived for 31 months with no recurrence, which indicates that preceded colostomy and preoperative chemoradiation enabled a curative resection safely for the Jehovah's Witness patient with bleeding advanced rectal cancer.

A 23-year-old man without a history of tuberculosis presented with right lower abdominal pain and a fever. An increased inflammatory response was found, and abdominal computed tomography showed a diffuse enlargement and wall thickening in the appendix. An ileocecal abscess and perforating appendicitis were suspected. Therefore, an emergency operation was performed. The surgery revealed a diffuse enlargement with adhesion to the retroperitoneum, which was suspected to be a neoplastic lesion of the appendix, thus an ileocecal resection including the appendix was performed. A histopathological examination revealed a number of epithelioid granulomas having Langerhans giant cells with caseous necrosis in the appendix, in addition to many granulomas without caseous necrosis in the regional lymph nodes. No tubercle bacilli were detected by Ziehl-Neelsen staining. Further examination revealed no tubercular lesions in other organs, thus leading to the diagnosis of primary tuberculosis of the appendix. This is an extremely rare disease reported in Japan.

In vitro and animal studies, the effect of loss of p53 function on radiosensitivity is controversial. p21Waf1/Cip1 is a potent inhibitor of cyclin-dependent kinases and p21 gene polymorphisms are associated with some human cancers. We sought to determine whether p53 mutations or p21 polymorphisms affect response to radiotherapy in patients with recurrent non-small cell lung carcinoma (NSCLC). Thirty-four patients with NSCLC who underwent radiotherapy for recurrent tumors after potentially curative resection were studied. Gene alterations or polymorphisms were analyzed in DNA from the primary tumor tissue, and the response to radiotherapy was based on the metastatic lesion. Mutations in exons 5–8 of the p53 gene were detected by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. p21 gene polymorphisms were identified by restriction digestion (BsmAI or PstI) of PCR products. Mutations in p53 were found in 13 of 34 pat6ients (38.2%). The response rates (complete plus partial) were 15.4% for patients with tumors having p53 mutations and 61.9% for patients with wild-type p53 (P=0.013). There was no significant difference between p21 polymorphisms and response to radiation. p53 gene mutations predict response to radiotherapy in NSCLC. Our results provide clinical support for the in vitro model that loss of p53 function decreases radiosensitivity.

BACKGROUND Recent clinical studies have demonstrated that tumor angiogenesis is a potent prognostic indicator for breast cancer patients. The quantitation of endothelial growth factors is thought to be useful to assess angiogenic phenotype in the tumor. Among the many new endothelial growth factors, vascular endothelial growth factor (VEGF) is known to be particularly responsible for promoting the neovascularization in human breast cancer. METHODS Intratumoral protein levels of VEGF were measured by enzymatic immunoassay in 135 primary breast cancer tissues. The VEGF levels were compared with the microvessel density evaluated by immunostaining the endothelial antigen and also were compared with intratumoral protein levels of other endothelial growth factors, including basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). RESULTS Intratumoral VEGF concentrations varied from 3.3 pg/mg protein to 2032 pg/mg protein (average 148 pg/mg protein). An immunocytochemical analysis using anti-VEGF antibody confirmed that VEGF was located mainly in the cytoplasm of the tumor cells. The VEGF concentrations were significantly higher in vascularly rich tumors than in vascularly poor tumors. No significant association was found between VEGF concentrations and the two other endothelial growth factor concentrations. CONCLUSIONS The quantitation of intratumoral VEGF levels seems to be useful for assessing the activity of tumor angiogenesis. Cancer 1996;77:1101-6.

A rare case of carcinoma of the breast in a 6-year-old Japanese girl is reported together with a review of the Japanese literature of this disease in childhood, totalling 17 patients, which confirms the good prognosis in the majority of cases. It is proposed that surgery, at least initially, should be conservative.

Recent reports have suggested that tissue-type plasminogen activator activity is regulated by estrogen in 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma type I cells but is not necessarily regulated by estrogen in type II mammary carcinoma cells. We have compared the biological features of these two types of mammary carcinoma cells and have found that, although there is no difference in estrogen receptor content between these two cell types, the plasminogen activator activity markedly differs. Tissue-type plasminogen activator activity is significantly higher in type I carcinoma than in type II carcinoma, urokinase-type activity is significantly higher in type II carcinoma than in type I carcinoma. When these two types were compared in terms of rate of tumor growth, type II carcinomas clearly showed more rapid growth than type I carcinomas. Survival studies showed significantly shorter survival of type II tumor-bearing rats compared with type I tumor-bearing rats. Furthermore, type II carcinomas contained a greater proportion of aneuploid cells than type I carcinomas. These results suggest that type II carcinoma cells, in which estrogen is unable to regulate tissue-type plasminogen activator activity, are considered to be of a higher grade of malignancy than type I carcinoma cells.