はじめに：GISTは消化管由来の間葉系腫瘍の中では最も頻度の高い腫瘍であり，近年分子標的薬イマチニブの登場により治療戦略に大きな変化を遂げたといえる．今回，当院におけるGIST症例の臨床病理学的特徴を検討した．方法：1999年５月から2007年12月の間にsurgical interventionの対象となったGIST症例26例の検討を行った．結果：好発年齢は60歳代であり性差は認めなかった．ほとんどが胃原発であり，免疫組織学的に検査された全例でKITあるいはCD34が陽性であった．高リスク群の５年全生存率は80.0％，その他のリスク群では100％であり，統計学的な有意差は認めなかった．一方で，高リスク群の４年無再発生存率は41.7％であり，その他のリスク群の100％と比較して，有意に不良であった．結語：高リスク群におけるadjuvant療法の重要性が再確認される結果であった．

症例は62歳の男性で心窩部痛と悪寒にて受診．腹部CTにて遊離ガス，腹水および噴門から胃上部の壁肥厚を認め，進行胃癌穿孔を疑い緊急手術を施行した．食道胃接合部（esophagogastric junction：EGJ）と横隔膜が一塊となった腫瘍を認め，穿孔部は胃体上部前壁であった．一期的切除は困難と判断し，経鼻胃管も挿入できなかったため腸瘻を造設した．精査でEGJに高度狭窄を伴う低分化型腺癌を認め，Stage Ⅳ胃癌と診断しS-1とCDDP併用化学療法を行った．経口摂取困難のため，S-1は腸瘻より経腸栄養とともに投与した．２コース施行後の画像検査にて主病変の縮小と腫大したリンパ節の消失を認め，治療効果は部分奏効（PR）と判定し，根治目的にて胃全摘（D2郭清）・脾合併切除術を施行した．組織学的効果判定はGrade 2であった．上部消化管閉塞による内服不能例であっても，積極的に腸瘻を造設しS-1＋CDDP併用化学療法を実施することは，高度進行胃癌に対する治療として検討に値するのではないかと考えられた．

症例は61歳の女性で，3日前に発症した腹痛の増悪にて統合失調症で入院中の精神科病院より受診した．血液検査でWBC数とCRPの上昇を認め，腹部造影CTで横行結腸の著明な拡張を認めたため横行結腸軸捻を疑い注腸造影で確診したが，内科的整復は穿孔の危険性が高いと判断し緊急手術を施行した．横行結腸はほぼ全長が壊死状態に陥っており，中等量の血性腹水も認めた．可及的に壊死腸管を切除し機能的端々吻合術で再建を行った結果，術後経過は良好で術後10日目に精神科病院へ転院となった．結腸軸捻は大腸の機械的な閉塞原因の約3％を占める疾患であるが，9割はS状結腸で発生するため横行結腸軸捻はまれである．自験例では複数の向精神薬を服用しており，慢性便秘であったことが発症要因と考えられた．結腸切除と一期的再建術で経過は良好であったが，病因を踏まえての治療法選択が重要な疾患であり若干の文献的考察を加えて報告する．

症例は70歳の男性で，健診で胃の異常を指摘された．上部消化管内視鏡検査で胃体上部前壁に1型病変を認め，腹部造影CTでは小彎側に腫大したリンパ節腫大を認めた．血液検査ではAFP 15.7ng/mL，HCG 552mIU/mLと上昇を認めた．cStage IIの進行胃癌と診断し胃全摘・脾合併切除，Roux-en Y再建術を施行した．病理組織所見にて充実性構造の低分化型腺癌を認め，それを中心にHCG陽性の絨毛癌様部分，腫瘍細胞が索状配列をとるAFP陽性の肝癌様部分，敷石・シート状配列をとるPALP陽性の胚細胞腫様部分を認めた．現在，術後6年6カ月経過したが再発を認めていない．AFPとHCGが共に高値を示す胃癌はまれであるが，これらの癌関連抗原陽性の胃癌は進行例が多く予後不良とされている．今回，われわれは健診にて発見されたAFP・HCG産生胃癌の1長期生存例を経験したので，若干の文献的考察を加え報告する．

症例は82歳の女性で，大腸がん検診で便潜血陽性を指摘された．大腸内視鏡検査で1型下行結腸癌を認め，術前検査で膵尾部癌および早期胃癌を認めた．cStage IIの下行結腸癌，cStage IVaの膵尾部癌の診断にて膵体尾部・脾合併切除，下行結腸部分切除術を施行した．早期胃癌は内科で経過観察となった．術後1年6カ月で多発肝転移にて永眠された．病理組織学的検査所見にて膵癌は粘表皮癌であった．膵粘表皮癌は非常にまれであり，膵癌取扱い規約では腺扁平上皮癌の亜型として分類されている．膵腺扁平上皮癌は膵癌の約2％とまれだが，早期から転移をきたすなど予後不良である．膵癌と他臓器癌の同時性重複は約3％との報告があるが，膵粘表皮癌との同時性重複癌は検索しえた範囲では報告を認めなかった．膵粘表皮癌がまれであるうえに，今回われわれは胃癌と大腸癌の同時性3重複癌の1例を経験したので，若干の文献的考察を加えて報告する．

大腸癌術後４年目に異時性孤立性脾転移を認めた１例を経験した．症例は75歳の男性で，下行結腸癌とそれに伴う閉塞性イレウスに対して，下行結腸切除術（D2）を施行した．Stage Ⅲaであったため，LV/5-FUによる術後補助化学療法を６クール施行し，以後外来にて経過観察していた．術後４年目の血液検査にてCEAの上昇を認め，腹部造影CTにて脾臓に低濃度の占居性病変を認めた．他に転移・再発を疑う所見はなく，上部および下部内視鏡検査を施行したが，原発巣となるような異常を認めなかったため，大腸癌の異時性孤立性脾転移と診断し開腹下で脾臓摘出術を施行した．病理組織学的検査所見は腺癌で，下行結腸癌の転移に矛盾しない所見であった．現在脾摘術後４年８カ月経過したが，再発を疑う所見は認めていない．大腸癌の他臓器への転移を伴わない孤立性脾臓転移は比較的稀であり，若干の文献的考察を加えて報告する．

To improve the poor prognosis in patients with stage IV (StIV) gastric cancer (GC), we conducted a multicenter phase II study of preoperative S-1 plus cisplatin followed by gastrectomy and postoperative S-1 for StIV GC (the protocol is registered at the clinical trial site of the National Cancer Institute; KYUH-UHA-GC03-01, NCT00088816).

This study investigated the expression and functions of ferritin, which is involved in osteoblastogenesis, in the periodontal ligament (PDL). The PDL is one of the most important tissues for maintaining the homeostasis of teeth and tooth-supporting tissues. Real-time PCR analyses of the human PDL revealed abundant expression of ferritin light polypeptide (FTL) and ferritin heavy polypeptide (FTH), which encode the highly-conserved iron storage protein, ferritin. Immunohistochemical staining demonstrated predominant expression of FTL and FTH in mouse PDL tissues in vivo. In in vitro-maintained mouse PDL cells, FTL and FTH expressions were upregulated at both the mRNA and protein levels during the course of cytodifferentiation and mineralization. Interestingly, stimulation of PDL cells with exogenous apoferritin (iron-free ferritin) increased calcified nodule formation and alkaline phosphatase activity as well as the mRNA expressions of mineralization-related genes during the course of cytodifferentiation. On the other hand, RNA interference of FTH inhibited the mineralized nodule formation of PDL cells. This is the first report to demonstrate that ferritin is predominantly expressed in PDL tissues and positively regulates the cytodifferentiation and mineralization of PDL cells.

Abstract The prognosis of gastric cancer with distant metastasis is very poor. Improvement of chemotherapy and investigation of molecular markers are required. We investigated the characteristics and the prognosis of patients with stage 4 gastric cancer with peritoneal or other distant metastases. 132 patients with stage 4 gastric carcinoma in Kitano hospital in between 2002 and 2009 were evaluated. The prognosis of the patients treated without chemotherapy was very poor. The prognosis of the patients with one factor of stage 4 was better than those with multiple factors. We tried induction chemotherapy with S-1 plus cisplatin for the patients without gastric bleeding or malignant gastric outlet obstruction. Our retrospective analysis demonstrated that induction chemotherapy improved the prognosis compared with adjuvant chemotheray after gastrectomy. In order to develop molecular markers for chemotherapeutic efficacy for advanced gastric cancer, we investigated the gene expression in the gastric carcinoma before treatment. We identified novel markers of gastric cancer using focused microarray analysis, hypoxanthine phosphoribosyltransferase 1 (HPRT1) and transforming growth factor-alpha (TGF-α), low gene expression of which was associated with less malignant potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3213. doi:10.1158/1538-7445.AM2011-3213

107 Background: Prognosis of StIV GC is poor. S-1 plus cisplatin now becomes one of the Japanese standards for unresectable or recurrent GC. We conducted a multicenter phase II study of preoperative S-1 plus cisplatin for StIV GC (KYUH-UHA-GC03-01, NCT00088816 ). In ASCO 2010, we reported early outcomes, indicating that this regimen is feasible and safe. We will report here the results concerning prognosis and recurrence.METHODSEligibility criteria included histologically proven StIV GC according to Japanese classification. Helical CT and staging laparoscopy were mandatory. Patients (pts) received oral S-1 (80-120 mg/body/day, day 1-21) and intravenous cisplatin (60 mg/m2 on day 8) every 5 weeks for 2 courses. After CX, operation was performed. S-1 (80-120 mg/body/day, day 1-14) was administered every 3 weeks for one year postoperatively. The primary endpoint was 2-year overall survival (OS), and the secondary endpoints were progression free survival (PFS), response, pathologic response, R0 resection, surgical complication, the first recurrence sites and toxicities. Sample size was set at 50.RESULTS51 pts were enrolled and all pts were observed more than 2 years after registration. The median age was 63 (range 35-79). PreOp CX was accomplished in 44 cases. Response was 50% (95% CI: 27.2-72.8). 44 (86.3%) pts underwent surgery and R0 resection was done in 26 pts (51%). Adjuvant chemotherarpy was accomplished in 11 cases. Recurrences were observed 14 cases (53.8%). Most frequent recurrence site was peritoneum. 2-Y OS and PFS were 43.1% [96% CI: 29.4-56.1] and 33.3% [20.9-46.2], respectively. R0 in GC with single StIV factor (n = 24) was 79.2% and that in GC with multiple StIV factors (n = 27) was 25.9%, respectively. All pts with only Cy+ (n = 12) showed complete eradication of cancer cell by S-1/CDDP. Pts with only Cy+ showed significantly better prognosis than other pts.CONCLUSIONSAs compared to Japanese national StIV control (OS: 20.8%), this induction CX showed promising survival. Especially, pts with only Cy+ was popular and showed significantly better prognosis by S1/CDDP induction CX. No significant financial relationships to disclose.

4124 Background: Prognosis of StIV GC is poor due to unresectability and high frequency of peritoneal dissemination. S-1 plus cisplatin now becomes one of the Japanese standards for unresectable or recurrent GC. Therefore, we conducted a multicenter phase II study of preoperative S-1 plus cisplatin for StIV GC confirmed by helical CT and staging laparoscopy (KYUH-UHA- GC03-01, NCT00088816). Methods: Eligibility criteria included histologically proven StIV GC according to Japanese staging system; no prior therapy; PS 0,1; 20- 80 years old. Helical CT and staging laparoscopy were mandatory in all cases. Patients (pts) received oral S-1 (80-120 mg/body, b.i.d., day 1-21) and intravenous cisplatin (60 mg/m2 on day 8) every 5 weeks for 2 courses. After CX, gastrectomy with D2 lymph node dissection was performed. S-1 (80-120 mg/body, b.i.d., day 1-14) was administered every 3 weeks for one year postoperatively. The primary endpoint was %2-year overall survival, and the secondary endpoints were time to progression, %response, %pathologic response, %R0 resection, surgical complication, the first recurrence sites and toxicities. Sample size of 46 was required to show significant improvement of this therapy compared with our historical control (one-sided alpha: 0.025, power: 0.80). Results: 51 pts were enrolled in this study. The median age was 63 (range 35-79); male/female: 29/22; PS0/1: 44/7. CX was accomplished in 44 cases (ave. 1.80 cycles). Grade 3/4 neutropenia was observed 25%. In 20 cases with the measurable lesions, response was CR in 2, PR in 8, %response was 50% (95%CI 27.2-72.8%). 44 (86.3%) pts underwent surgery and R0 resection was done in 26 pts (51%). %R0 in GC with single StIV factor (n = 24) was 79.2% and that in GC with multiple StIV factors (n = 27) was 25.9%, respectively. No treatment related death was observed. Operative morbidity was 18.2%. Conclusions: The combination of S-1 and cisplatin was feasible and promising as preoperative chemotherapy regimen for patients with St.IV GC. No significant financial relationships to disclose.

In this study, we analyzed the effects of tensile mechanical stress on the gene expression profile of in vitro-maintained human periodontal ligament (PDL) cells. A DNA chip analysis identified 17 up-regulated genes in human PDL cells under the mechanical stress, including HOMER1 (homer homolog 1) and GRIN3A (glutamate receptor ionotropic N-methyl-d-aspartate 3A), which are related to glutamate signaling. RT-PCR and real-time PCR analyses revealed that human PDL cells constitutively expressed glutamate signaling-associated genes and that mechanical stress increased the expression of these mRNAs, leading to release of glutamate from human PDL cells and intracellular glutamate signal transduction. Interestingly, exogenous glutamate increased the mRNAs of cytodifferentiation and mineralization-related genes as well as the ALP (alkaline phosphatase) activities during the cytodifferentiation of the PDL cells. On the other hand, the glutamate signaling inhibitors riluzole and (+)-MK801 maleate suppressed the alkaline phosphatase activities and mineralized nodule formation during the cytodifferentiation and mineralization. Riluzole inhibited the mechanical stress-induced glutamate signaling-associated gene expressions in human PDL cells. Moreover, in situ hybridization analyses showed up-regulation of glutamate signaling-associated gene expressions at tension sites in the PDL under orthodontic tooth movement in a mouse model. The present data demonstrate that the glutamate signaling induced by mechanical stress positively regulates the cytodifferentiation and mineralization of PDL cells.

Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients.

A case of an intracystic adenomyoepithelioma of the breast mimicking intracystic carcinoma is described. Preoperative examination with mammography, sonography, computed tomography, and magnetic resonance imaging showed an intracystic tumor with an indistinct margin and several swollen lymph nodes in the ipsilateral axilla. Because the results of fine-needle aspiration cytology of the tumor were interpreted as carcinoma, partial mastectomy with dissection of the axillary nodes was performed. Histopathologic and immunohistochemical examination revealed an intracystic adenomyoepithelioma without nodal involvement. The imaging features of this rare tumor may vary widely, which may result in an incorrect diagnosis of breast carcinoma. Indeed, adenomyoepithelioma has metastatic potential; however, lymphatic spread is rare and axillary intervention may be over-treatment for most cases. While the imaging descriptions of intracystic adenomyoepitheliomas are very limited, this tumor should be considered in the differential diagnosis to avoid unnecessarily aggressive treatment.

A 54-year-old woman underwent mastectomy and axillary lymph node dissection for infiltrating ductal carcinoma with multiple lymph node involvement. The patient received adriamycin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) (AC) followed by weekly paclitaxel 80 mg/m(2) and external irradiation to the local lymph node regions as adjuvant treatment. After 1 year and 5 months, the patient suffered her first recurrence, developing multiple brain and meningeal metastases. CNS involvement was well controlled by oral capecitabine (2400 mg twice daily, on days 1-21 of a 28-day cycle) and external whole brain irradiation of 50 Gy with minimal toxicity. We suggest that capecitabine contributed to the favorable clinical course in this patient and believe that, as an oral agent, this drug may benefit patients with CNS metastases of breast cancer by allowing home-based therapy.

Sentinel node status was evaluated using preoperative lymphoscintigraphy in a 43-year-old woman who presented with an invasive ductal carcinoma in the lower outer quadrant of the right breast. Two strong hot nodules were visualized in the affected axillary basin on an early image, and a faint accumulation of radioactive tracer was lying between the cancer in the right lower outer quadrant and the axillary hot nodules on the lymphoscintigram taken at 90 min. The faint accumulation was considered to represent a small paramammary node on thin-slice computed tomography (CT) and was confirmed by node biopsy to be a sentinel node grossly involved with tumor cells. Immediate axillary dissection and adjuvant chemotherapy was subsequently performed. Careful evaluation using lymphoscintigraphy and thin-slice CT may be associated with increased localization of true sentinel nodes.

BACKGROUND The present study investigated the efficacy of oral doxifluridine (5'-DFUR) by comparing the survival between patients who received 5'-DFUR at 800 mg/body daily for 1 or 3 years after surgery for stage 1, 2 or 3 breast cancer. PATIENTS AND METHODS Ninety-two patients were enrolled from January 1995 to December 1997, of whom 87 were eligible. The patients were stratified into pre-menopausal and post-menopausal groups, and then each group was further stratified into 1-year or 3-year administration groups. All patients were given endocrine therapy, with gosereline acetate (3.6 mg/body, monthly) for the pre-menopausal patients and tamoxifen (20 mg/day, daily) for the post-menopausal patients for 3 years. RESULTS The median follow-up duration was 9.5 years. Although no differences were found in the overall or disease-free survivals between the administration groups, subset analysis demonstrated that, in the pre-menopausal patients, the 3-year administration group showed a significantly higher overall survival rate than the 1-year administration group, but not in post-menopausal patients. A multivariate analysis also indicated that the administration duration of 5'-DFUR was a significant factor for disease-free survival. CONCLUSION The present study supports the usefulness of 5'-DFUR for adjuvant chemotherapy against breast cancer, especially for pre-menopausal patients; however, further clinical study with a much larger sample size is necessary to reach a conclusive result.

A 38-year-old woman underwent mastectomy and axillary lymph node dissection for invasive ductal carcinoma with multiple lymph node involvement. The patient received adriamycin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 followed by weekly paclitaxel 80 mg/m 2 (without interruption) as adjuvant treatment. After receiving ten courses of paclitaxel, the patient developed motor neuropathy, with difficulty in ascending stairs and rising from a chair. A nerve conduction study demonstrated impairment of bilateral peroneal nerve function, although the sural sensory nerves were intact. After 2 weeks of withholding paclitaxel treatment, the motor neuropathy was alleviated and the scheduled doses were completed. A pharmacokinetic study of paclitaxel showed the possibility of elimination delay at the last infusion. We suggest that a dose-dense schedule of paclitaxel may be a significant risk factor for this kind of motor neuropathy.

Standard treatment for highly advanced gastric cancer (AGC) has not been established yet. Neoadjuvant chemotherapy (NAC) represents a promising approach, which may improve the prognosis of AGC. In this study, we analyzed the feasibility and efficacy of NAC with S-1 (TS-1)/cisplatin CDDP in order to design appropriate clinical trials for AGC.