乳腺原発小細胞癌は稀な組織型であり，予後不良とされる．薬物療法に関してエビデンスは乏しいが，進行例に対しては小細胞肺癌に準じた化学療法が行われている．今回，転移・再発の乳腺原発小細胞癌に対して，小細胞肺癌に準じてprogrammed cell death ligand 1阻害薬の併用療法を施行した1例を経験した．症例は52歳，女性．3カ月前から左乳房腫瘤を自覚して受診し，局所進行の化生癌と診断した．術前化学療法後に根治手術を施行し，最終的に乳腺原発小細胞癌と診断した．術後2カ月で左胸壁の皮下再発，多発リンパ節転移，肺転移を認め，左胸壁の皮下再発を組織診で小細胞癌と診断した．Cisplatin+etoposide+durvalumab療法を4サイクル施行後，左腋窩リンパ節を除く転移巣は全て縮小し，左腋窩リンパ節転移も照射で縮小したが，その後病勢進行により初診から19カ月目に永眠した．

Nivolumab induces several immune-related adverse events. Isolated adrenocorticotropic hormone(ACTH)deficiency has low frequency. A 73-year-old woman with gastric cancer metastasis of the peritoneum was treated with nivolumab as the third-line chemotherapy. After 5 courses of nivolumab, she developed hypothyroidism. After completing 12 courses, peritoneal metastasis increased. We evaluated the metastasis as progression of disease, so treatment with nivolumab was discontinued. Two weeks after the last dosage of nivolumab, she developed general fatigue and appetite loss. At first, we considered that these symptoms were caused by peritoneal metastasis, but progression was not indicated in the CT. Blood levels of cortisol and ACTH were very low. We suspected secondary adrenocortical insufficiency induced by nivolumab. Endocrinological examinations and the results of brain MRIsuggested isolated ACTH deficiency. This is the first report of isolated ACTH deficiency induced by nivolumab in a patient with gastric cancer metastasis of the peritoneum. The symptoms of adrenocortical insufficiency induced by nivolumab overlap with those of peritoneal metastasis, and thus, it may be difficult to confirm a differential diagnosis. When adrenocortical insufficiency is suspected, we should check the blood levels of cortisol and ACTH.

A 65-year-old woman was diagnosed with simultaneous hepatic metastasis of rectal cancer with portal venous tumor thrombi(Vp3)that developed in the bifurcation of the portal vein. Four days from the first visit, abdominal dynamic contrastenhanced CT image on the portal venous phase shows that the tumor thrombi progressed in the main trunk of the portal vein (Vp4). We decided that it was a condition of oncologic emergency and initiated FOLFOXIRI plus BV therapy. After 12 courses, tumor shrinkage and regression of the portal venous tumor thrombi were achieved, but conversion surgery was impossible because the collateral circulation of the hepatic portal region remained. The treatment target was changed to the extension of the survival period. The initiation and reinitiation of FOLFOXIRI plus BV therapy and maintenance of 5-FU/l-LV plus BV therapy contributed to disease control in 24 months and survival period of 36months.

症例は49歳，女性．3カ月前からの左乳房のしこりを主訴に当院を受診した．精査の結果，左AC領域の浸潤性乳管癌，病期cT2cN0cM0 cStage IIAであった．左乳房切除術およびセンチネルリンパ節生検を行った．センチネルリンパ節転移陽性で，腋窩郭清術（レベルI）を追加した．術直後より腋窩部ドレーンから漿液性排液を認めた．術後1日目（post operative day1，以下POD1）の夕食摂取後よりドレーンから252mlの白濁した排液を認め，乳糜漏と診断した．POD2より脂肪制限食に変更した．排液量は徐々に減少しPOD5より漿液性となり，POD7にドレーンを抜去し，POD10に退院となった．乳癌術後の乳糜漏は非常に稀な合併症であり，今回，保存的治療により治癒しえた1例を経験したので，その病態や治療法を中心に文献的考察を踏まえて報告する．

FDG-PETは良悪性の鑑別診断に有効で，近年消化器癌術後の再発診断の精査に用いられる．症例は64歳の女性で，5年前に下行結腸癌，同時性肝転移に対して左半結腸切除術と術前化学療法後に肝部分切除術（S5，S8の2か所）の既往があった．肝切除後4年目の腹部造影CTで肝S8切除部位の近傍に直径15 mmの低吸収域が指摘され，ガドキセト酸ナトリウム造影MRIでも同部位に単発の低信号域が確認された．FDG-PETで同部位に強い集積を認めたため残肝再発と診断し，2回目の肝S8部分切除術を行った．切除標本の病理組織学的検査では悪性所見を認めず，異物巨細胞やリンパ球の集簇および糸様の構造物が確認され異物肉芽腫と診断された．今回，我々は肝転移切除術後の残肝にFDG-PETで偽陽性を呈した1例を経験したので報告する．

症例は81歳の女性で，腹痛と悪心を主訴に受診した．腹部CTで右閉鎖孔に小腸と連続する腫瘤を認め，右閉鎖孔ヘルニア嵌頓と診断した．発症2時間の時点で，超音波検査下に非観血的な整復を行った．整復後第4病日に待機的に大腿アプローチによるメッシュプラグ法で閉鎖孔ヘルニア根治手術を行った．閉鎖孔ヘルニアは緊急開腹手術を要する疾患とされてきたが，非観血的な整復を行うことができれば低侵襲な手術が可能であると考えられる．

636 Background: KRAS status is the therapeutic marker of anti-EGFR drug, and may be the prognostic marker of metastatic colorectal cancer (mCRC). However, there is no consensus whether bevacizumab (anti-VEGF drug) benefits patients with mutated KRAS in mCRC. We investigated the clinical benefits of bevacizumab treatment in mCRC depending on KRAS status, retrospectively. Methods: We investigated 49 patients who received chemotherapies with bevacizumab as first-line treatment for mCRC from May 2008 through June 2013. We evaluated response rate (RR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tumor reduction rate and the adverse events (CTCAE v4.0 - JCOG) depending on KRAS status. Results: The median age of the patients was 66 years (range; 36 - 80). Forty-five patients received oxaliplatin-based chemotherapies with bevacizumab and four patients received irinotecan-based chemotherapies with bevacizumab. KRAS status of 30 patients was wild type and that of 19 patients was mutation type. There was no difference in patient characteristics between KRAS wild type (WT) and mutation type (MT). In all 49 patients, RR was 62.5%. DCR was 91.7%. The median PFS was 10.9 months. In RR, patients with KRAS wild type tumors had better outcome than patients with mutant type tumors (WT : MT, 69.0% : 52.6%, no statistically difference). A similar tendency was seen in DCR (WT : MT, 96.6% : 84.2%, no statistically difference). The average reduction rate in KRAS WT was 42.7% and in KRAS MT was 32.3% (p = 0.309). In the KRAS wild patients, the median PFS was longer than that in the KRAS mutant patients (WT : MT, 11.8 : 8.9 months, Log Rank p = 0.583), but there is no statistically difference between two groups. In median OS, there was no difference between two groups (WT : MT, 21.0 : 20.8 months, Log Rank p = 0.393). The incidence of severe adverse events was not statistically different between KRAS WT group and MT group. Conclusions: Regardless of KRAS status, bevacizumab provides clinical benefits for patients with mCRC.

症例は55歳の女性で，平成20年7月，顔面，手掌の皮疹を主訴に当院を受診．精査にて皮膚筋炎の診断に至り，ステロイド治療が開始された．9月，頸部痛，発熱を認め，食道透視，頸胸部CTにより頸部食道穿孔に伴う縦隔炎と診断し，頸部アプローチにより，頸部・上縦隔洗浄ドレナージを施行した．その後，CTにて右胸腔と後縦隔に液貯留が出現したため，初回手術後7日目に右開胸下に縦隔胸腔ドレナージを施行した．術後，縦隔炎は沈静化したが，頸部食道皮膚瘻の治癒に時間を要した．経管栄養管理の状態で初回手術後162日目に退院し，205日目に瘻孔閉鎖を確認，経口摂取を再開した．皮膚筋炎は消化管潰瘍を合併する報告はあるが，穿孔に至る例はまれである．今回，皮膚筋炎治療中に発症した頸部食道穿孔による縦隔炎に対して段階的な頸部および開胸のドレナージにより救命しえた1例を経験したので報告する．

症例は58歳男性. 主訴は心窩部痛. 腹部全体に強い腹膜刺激症状を認め, CTにて腹腔内に多量の液貯留を認めたため汎発性腹膜炎を疑い緊急手術を施行した. 開腹すると消化管穿孔は認めず, 約700ml の新鮮血および凝血塊を認めた. 腹腔内を検索すると, 左三角間膜内に存在する25×20mm大の腫瘤が破裂し出血を来していた. この腫瘤は肉眼的には肝との連続性は認めなかった. 病理組織検査では高分化型肝細胞癌と診断された. 従って, 左三角間膜内に発生した異所性肝細胞癌が自然破裂, 出血したものと考えられた. 異所性肝細胞癌は非常に稀な疾患であり, なかでも破裂を伴ったものは本症例を含めて4例のみという稀有な症例であった.

症例は56歳,男性で,黄疸・発熱が出現し入院. CTで膵頭部に直径20mm大の腫瘍を認め,鈎部にも直径25mm大の腫瘍を認めた.胆道造影所見では総胆管末端の途絶と主膵管の拡張を認めた. Vater乳頭は乳頭直下に潰瘍性病変を認め,生検でneuroendocrine cell carcinomaと診断され,幽門輪温存膵頭十二指腸切除術を施行した.摘出標本では膵頭部上部に直径21×15mmの腫瘍を認め,膵鈎部にも腫瘍を認めた.組織所見では膵組織内に腫瘍が大部分存在しており,膵鈎部の腫瘍は,リンパ節転移であった. TS2,結節型pT3{pCH(+), pDU(+), pS(-), pRP(-), pPV(-), pA(-), pPL(-), pOO(-)} pN3, sM0 fStage IVbであった.免疫染色ではsynaptophysin, chromogranin, NSE染色が全て陽性であった.以上より膵原発neuroendocrine cell carcinomaと診断した.術後5カ月で大動脈周囲リンパ節,肺転移をきたし,化学療法を施行中である.

Background: No reports have yet precisely determined corticotropin (ACTH) responsiveness in virilizing adrenocortical adenoma. Methods: Five women with an androgen-secreting adrenal adenoma were reviewed. Three of them were examined by in vitro steroidogenesis. Two of these 3 patients were studied by immunohistochemistry of steroidogenic enzymes and for the gene expression of ACTH receptor by Northern blot analysis. Results: In preoperative hormonal determinations plasma and urine androgens had increased. Dexamethasone did not suppress plasma and urinary androgens, nor did ACTH increase them. In vitro steroidogenesis revealed that the adenoma cells produced mainly dehydroepiandrosterone and a small amount of testosterone. ACTH did not increase the in vitro production of androgens. In immunohistochemical staining 5 enzymes involved in adrenal steroidogenesis were all expressed, especially 17α-hydroxylase, which was strongly expressed in tumor cells. ACTH receptor messenger RNA was not detected in virilizing tumor tissues, whereas it was expressed in attached adrenal tissues. Conclusions: The lack of response to ACTH is the result of a deficiency of ACTH receptor expression in the virilizing tumor cells. Androgens were autonomously produced in adrenal adenoma cells without ACTH regulation. (Surgery 1999;125:396-402.)

症例は64歳, 男性. 肝腫瘤にて入院. 入院時検査成績でCEA7.9ng/mlと高値であった. 腹部USで肝前区域に径3cmの低エコー腫瘤を認め, 腹部CT上, ring enhancementを示した. 腹部血管造影上淡い腫瘍濃染像を認め, 胆管細胞癌と診断し, 肝前区域部分切除術を行った. 摘出標本は軟らかく, 褐色調を呈し, H-E染色上では確診が困難で, 各種の特殊染色にて胆管由来の神経内分泌癌と確診された. 進行度はstage I. であった. 術後52日目に第VII胸椎以下の両側完全麻痺を来し, 胸椎X-P, 骨シンチ, MRIにて第VII胸椎転移を認めた. 放射線治療にて麻痺は軽快したが, 術後5カ月目に左上肢の強直性間代性痙攣を来し, 頭部CTにて多発性脳転移を認めた. 現在, 対症療法にて経過観察中である. 以上, 組織診断に難渋したstage I. の胆管由来の神経内分泌癌で術後早期に, 急速な遠隔転移を来した1例を報告する.

Concerning the suppressive effect of inorganic iodine on the growth of 7,12-dimethyl-benz(a)anthracene (DMBA)-induced breast tumor in female Sprague-Dawley (SD) rats, we previously reported that although iodine itself had a suppressive effect on the tumor growth, its effect was not as strong as that of MPA (medroxy-progesterone acetate). However, the combined medication of iodine at a low concentration + MPA showed a stronger effect than MPA alone. The purpose of the present study is to elucidate this mechanism of action by determining the uptake of the administered iodine into breast tumor tissue. Breast tumors were induced with DMBA in female SD rats, and these animals were treated with MPA + inorganic iodine at various concentrations for 4 weeks to determine tumor growth and tumor iodine content. In the comparison of tissue iodine content in growth-suppressive tumors with that in nonsuppressive tumors, the former showed a much higher iodine content. This suggests that direct uptake of inorganic iodine by breast tumors led to the suppression of tumor growth. (C) 1996 Wiley-Liss, Inc.

To clarify the precise function of incidentally discovered adrenocortical adenoma, immunohistochemical and dispersed adrenal cell studies were performed. We have recently seen five patients with so-called nonfunctioning adrenocortical adenoma. Diurnal variation in plasma cortisol and suppression of plasma cortisol and urine 17-hydroxycorticosteroids in response to dexamethasone administration revealed adrenocortical function within normal limits in all cases, and no signs or symptoms of adrenal steroid hormone excess were evident. Since a high uptake of iodomethylnorcholesterol was recognized in each adrenal mass, it was supposed that these adrenal tumors produced steroid hormone to a certain extent, and each patient received unilateral adrenalectomy. P450c17, a key enzyme involved in cortisol production, was expressed in the tumor region in all cases in an immunohistochemical study. Upon in vitro steroidogenesis with dispersed adrenal cells in two cases, all steroid hormones measured except for aldosterone (progesterone, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolone, 11-deoxycortisol, cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, dehydroepiandrosterone and androstenedione) were produced in a culture medium. The results indicated that these tumors possessed the capacity for cortisol production, which was in agreement with the results of an iodomethyl-norcholesterol scintigraphy. All patients with mild hypertension or diabetes mellitus had no signs or symptoms of steroid hormone excess, but they could potentially develop a steroid excess syndrome such as Cushing's syndrome in the future.

Patients with Cushing syndrome (n = 122) who underwent adrenalectomy from 1957 through 1993 were reviewed for survival and complications. Of the 122 patients, 70 had adrenocortical adenoma, 30 Cushing's disease, 6 primary pigmented nodular adrenocortical disease (PPNAD), 7 other types of primary nodular hyperplasia, 5 adrenocortical carcinoma, and 4 ectopic ACTH syndrome. Sixty-five patients with adrenocortical adenoma are alive, and the survival rate was equal to the age-matched control population, when patients who died of the postoperative complication were excluded. Of the patients with Cushing's disease, 20 are alive; and 10 of 16 patients (63%) who were followed-up and evaluated had skin pigmentation. Four of sixteen patients (25%) developed Nelson's syndrome. Four PPNAD patients and five with other types of nodular hyperplasia are alive. Most of these patients underwent bilateral total adrenalectomy, but some patients remitted after unilateral adrenalectomy. All of five adrenocortical carcinoma patients and four with ectopic ACTH syndrome died within 2 years after operation. The prognosis for patients with adrenocortical adenoma after unilateral adrenalectomy is excellent, though it is important to avoid operative complications. The rapid cure of signs and symptoms of glucocorticoid excess after total adrenalectomy is ensured, and prognosis is satisfactory under careful glucocorticoid replacement, making total adrenalectomy an alternative treatment for Cushing's disease.

Heterotransplantation of human parathyroid tissues into nude mice was performed to investigate the characteristics of grafted tissues. Grafts prepared from hyperplasia, adenoma and normal glands which were resected at operation were implanted in the gluteus muscle of the recipient mice (female, KSNnu/nu strain). Graft function was evaluated by measuring human intact PTH concentrations in sera of the mice. Serum PTH concentrations 12 weeks after transplantation were correlated with the tissue volume in the mice which received one, two, four or eight pieces of 1 mm(3) hyperplastic tissues. Changes in graft function were examined in the mice which received four grafts prepared from hyperplasia, adenoma or normal glands. Transplantation of parathyroid tissues resulted in an increase in PTH concentrations for 4 weeks, reaching a plateau thereafter. The level remained unchanged for 8 weeks. Serum PTH levels in the mice with grafts prepared from hyperplasia or adenoma were significantly higher than in those with grafts from normal glands, though without a significant difference between the mice with grafts from adenoma and from hyperplasia. Serum calcium levels were similar in all three groups. We also observed the response of grafted parathyroid tissue to a low calcium level in sera: there was higher PTH secretion four weeks after the administration of the low calcium diet. The success of heterotransplantation was histologically proven by the presence of grafts which were not atrophic in the muscle 12 weeks after transplantation. Nucleoli were found more frequently, and nuclear pleomorphism was observed in the cells of heterografts.

Using anti-S100α and S100β antibodies without any cross reactivity which were purified by affinity chromatography, an immunohistochemicalstudy was conducted on 72 benign breast lesions (from 34 cases of mastopathy and38 cases of fibroadenoma) and 72 malignant breast lesions (invasive ductal carcinoma). Both S100α- and S100β-positive cells occupied more than 30% of proliferation in all the benign lesions. On the other hand, malignant lesion with S100α-positive cells occupied more than 30% of proliferation was confirmed in 70 cases (97.2%), but the lesion with S100β-positive cells in more than 30% of occupation rate was found only in 3 cases (4.2%). These findings indicate that there is a decreasing tendency of S100β-positive cells in breastcancers. We think that this exploration using such very specific antibodies capable of clarifying hidden findings from usual antibody tests can be an adjuvantexamination for breast lesions which present difficulty in differential diagnosis only by HE staining.

From 1979 through 1992, we have conducted operations for differentiated thyroid carcinoma in 392 cases, 18 of which were under the age of 20. As in the case of adults, the same basic surgical approach was used for the young patients: 1) total thyroidectomy, 2) bilateral lymph node dissection, and 3) parathyroid autotransplantation. We attempted to determine the strengths and weaknesses of our operative approach by comparing for diameter of neoplasms, lymph node metastases and the like with adults, including the Quality of Life in the postoperative course. Tumor diameter was more than t2 in 80% of the cases, and in 60% of adults. Lymph node metastases were found in about 90% of the patients, and in 76% of the adults. Evidence of progressive carcinoma was found operatively in more young persons than adults, but there was no recurrence in all 18 cases. Postoperative complications included only a mildly lowered parathyroid function in one case and postoperative cheloid in 3 cases. No problem whatsover was noted in growth or development of the patients less than 10 years of age; 3 females who had come of age had children. Thus our surgical approach is considered appropriate, and promises sufficient radicality and favorable postoperative course.

Background. For papillary thyroid carcinoma, we have used our standard operative method consisting of total thyroidectomy, bilateral lymph node dissection, and parathyroid autotransplantation. Our special parathyroid transplantation method involves transplantation of the minced glands into the pectoralis major muscle. We investigated whether this method is useful for preserving parathyroid function.Methods. In 17 patients who underwent our standard operation for papillary thyroid carcinoma, the intact parathyroid hormone (PTH) and serum calcium levels were determined for 4 weeks after the operation.Results. In all cases the intact PTH levels fell below detectable limits immediately after operation and then recovered to the preoperative level about 2 weeks after the operation. The same recovery patterns were observed in two groups undergoing transplantation of two glands and three or four glands.Conclusions. These recovery patterns of intact PTH levels seem to indicate that the glands were grafted successfully and recovered their function. Our method is thought to be useful for preserving parathyroid function after surgery.