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An arteriovenous malformation (AVM) is defined as a vascular malformation with a short, non-capillary communication between the arteries and veins. Most gastrointestinal AVMs are solitary, occurring predominantly in the stomach, small intestine and right colon, and rarely in the inferior mesenteric artery (IMA) region.A 70-year-old man was first diagnosed with ischemic enteritis two years earlier, and was hospitalized several times with the same diagnosis. He visited our hospital because of left lower abdominal pain and melena. Colonoscopy showed findings suggestive of ischemic enteritis, and contrast-enhanced computed tomography (CT) and IMA angiography showed hyperplasia and dilation of blood vessels from the sigmoid-descending colon junction to the upper rectum. We performed conventional laparoscopic low anterior resection using intraoperative intravenous injection of indocyanine green (ICG). The final diagnosis was arteriovenous malformation in the IMA region. The patient had an uneventful postoperative course and was discharged on the 13th day after the operation.Cases of AVM in the IMA region are relatively rare. This is the first reported case of AVM in the IMA region that was resected under intraoperative ICG fluorescence imaging (FI), which provided useful information on the extent of intestinal resection and mesenteric dissection required, and confirmed the adequacy of intestinal blood flow during and after mesenteric dissection and anastomosis.It is advisable to use ICG FI intraoperatively during resection of AVMs in the IMA region, as with colorectal cancer surgery.

This patient was a 96-year-old woman. She was referred to our hospital with abdominal pain and vomiting. The levels of the tumor markers CEA and CA19-9 were elevated, at 39.47 ng/mL and 918.5 U/mL, respectively. She was diagnosed with peritonitis with digestive tract perforation by abdominal CT and an emergency operation was performed. At laparotomy, dirty ascites was observed in the peritoneal cavity. A perforation, 1 cm in diameter was found in the jejunum 15 cm from the Treitz ligament, and a mass, 2 cm in diameter was also palpated on the mesentery side. We performed jejunectomy including the tumor. The submucosal tumor was 2 cm in size and the mucosal surface of the perforation was ulcerated. Pathohistological inspection of the extracted sample revealed no heteromorphism in the small intestine mucosal plane. A moderately differentiated adenocarcinoma was diagnosed in the submucosal layer of the heterotopic pancreas of Heinrich typeⅡ. No tumor cells were found in the perforation. Thirteen previous cases of ectopic pancreatic cancer have been reported and this was the 14th case.

A 43-year-old man was admitted to our hospital presenting with seizures and syncope. He had a history of a cold with a fever of 39°C occurring three days earlier. Electrocardiography (ECG) showed complete atrioventricular block (AV block) with a maximum pause of 32 seconds, for which temporary pacing was performed. Echocardiography showed mild hypertrophy of the left ventricle (LV) with a normal ejection fraction of 61%. Coronary angiography showed normal coronary arteries. Then, an endomyocardial biopsy was performed, the results of which indicated a diagnosis of acute myocarditis. After admission, the complete atrioventricular block disappeared together with normalization of the LV wall thickness., Internal Medicine, 51(21), pp.3035-3040; 2012

To the Editor,Liver dysfunction is sometimes experienced in the clinical course of rheumatoid arthritis (RA). It is caused by viral hepatitis, autoimmune hepatitis, fatty liver disease and drug-ind...

The air-liquid interface (ALI) is a common microenvironment of the skin, but it is unknown whether the ALI affects melanoma cell behaviors. Using a collagen gel invasion assay, immunohistochemistry, and Western blots, here we show that melanoma cell proliferation in cultures with an ALI is higher than melanoma cell proliferation in submerged cultures. Bromodeoxyuridine (BrdU) uptake, an indicator of cell proliferation, of melanoma cells at the ALI was about 3 times that of submerged cells, while ALI and submerged melanoma cells had similar levels of single-stranded DNA (a marker of apoptosis). The ALI enhanced the expression of Raf-1, MEK-1 and pERK-1/2 components of the mitogen-activated protein kinase (MAPK) cascade, in cells more than the submerged condition did. The increases in BrdU uptake and pERK-1/2 expression promoted by ALI was abolished by the MEK inhibitor, PD-98059. ALI-treated and submerged melanoma cells did not infiltrate into the collagen gel, and they showed no significant difference in the expression of the invasion- and motility-related molecules, matrix metalloproteinase-1 and -9, laminin 5, and filamin A. Our data indicate that the ALI, a skin microenvironment, accelerates the growth, but not the apoptosis or invasion, of melanoma cells through MAPK activation.

Adipose tissue consists of mature adipocytes, preadipocytes and mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. We have recently developed “adipose tissue-organotypic culture system” that maintains unilocular structure, proliferative ability and functions of mature adipocytes for a long term, using three-dimensional collagen gel culture of the tissue fragments. In this system, both preadipocytes and MSCs regenerate actively at the peripheral zone of the fragments. Our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome. Thus, it seems to be a promising model for investigating adipose tissue biology and regeneration. In this article, we introduce adipose tissue-organotypic culture, and propose two theories regarding the mechanism of tissue regeneration that occurs specifically at peripheral zone of tissue fragments in vitro.

症例は68歳,女性.約5年前に4型の進行胃癌に対し胃全摘術を施行.組織型は印環細胞癌を含む低分化腺癌で, pT3 (se), pN0, H0, P0, M0, Stage II, scirrhous type, ly1, v0,であった.術後補助化学療法として経口抗癌剤5'-DFURを2年間内服した.今回,下腹部痛,腹部膨満感を主訴に当院を受診.下部消化管造影で横行結腸脾彎曲部にapple core signを呈し,下部消化管内視鏡では全周性の高度狭窄を認め,粘膜は発赤浮腫状,易出血性であった.組織生検では印環細胞癌を含む低分化腺癌の診断で,原発性もしくは転移性大腸癌と診断し手術を施行した.術後病理診断は印環細胞癌を含む低分化腺癌であった.免疫組織検査では, CK7, CK19, MUC5ACは陽性で, CK20, MUC1, MUC2は陰性であった.原発巣と考えられる胃癌標本を再検討すると両者の組織型,免疫組織学的染色の結果が一致しており,胃癌の結腸転移と診断した.

Pleomorphic adenomas usually occur in the major salivary glands, and rarely in the nasal septum.We describe here a rare case of a Pleomorphic adenoma originating from the nasal septum treated by endoscopic nasal surgery. A 77-year-old man was admitted to our hospital because of epistaxis. The rhinoscopic examination showed a vascularized nasal polyp-like mass located in the nasal septum. It was elastic in consistency. Endoscopic examination revealed a smooth-surface mass measuring 2 x 2 cm in diameter. Nasal axial contrast-enhanced CT scan demonstrated a well circumscribed solid mass with a slightly enhanced rim in the right nasal cavity with no evidence of bone destruction. The patient underwent adequate surgical excision using nasal endoscopy. On histologic examination, the specimen was found to be a pleomorphic adenoma. Thereafter, the patients showed no evidence of recurrence at more than one year later. It is concluded that endoscopic nasal surgery is a useful option for a pleomorphic adenoma of the nasal cavity.

症例は62歳,女性.健診にて便潜血陽性を指摘され精査目的で当院外来受診.肛門鏡,肛門指針にて肛門部3時の方向に弾性硬の可動性不良の粘膜下腫瘍を認めた.腹部造影CTにて造影効果を伴う腫瘤を認め,肛門部の悪性腫瘍を否定できないため経肛門的腫瘍摘出術を施行した.摘出標本の病理組織診断にて,顆粒状あるいは明るく広い細胞質と類円形核を有する細胞を認め,免疫組織学的にS-100蛋白陽性であり,肛門部に発生した顆粒細胞腫と診断された. 顆粒細胞腫はSchwann細胞由来の良性腫瘍といわれている.胸壁,乳房,頸部の皮下に好発するといわれ消化管では口腔内,食道の報告が多く肛門部の報告は極めて稀といわれる.今回われわれは肛門部に粘膜下腫瘍として発見された顆粒細胞腫の稀な1例を経験したので報告する.

Osteosarcoma is one of the neoplasms that may occur following exposure to radiation. A case of osteosarcoma arising in the craniofacial bone with a short latency period of 3 years after radiotherapy for maxillary squamous cell carcinoma is described. A 64-year-old-man underwent right partial maxillectomy and chemoradiotherapy due to squamous cell carcinoma of his right maxillary sinus. Histologically, the tumor was composed of moderately differentiated squamous cell carcinoma with a component of spindle cell carcinoma. Three years later, osteosarcoma developed in the craniofacial bone within the irradiation field of the first tumor. Detailed histological examination demonstrated that there was no component of osteosarcoma in the first tumor or squamous cell carcinoma in the second tumor. Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy. In this case, osteosarcoma was possibly a radiation-induced osteosarcoma with a short latency period of 3 years.

症例は23歳の女性. 平成13年7月4日より腹痛嘔吐が出現し7月7日当院を受診した. 触診上, 左下腹部に圧痛を伴った鶏卵大腫瘤を触知した. 腹部エコー, CT検査において左下腹部にターゲットサインを認め, また上部小腸の拡張を認めた. 小腸重積症の診断で高圧注腸を試みたが, 整復が困難であったため緊急手術を行った. 回腸末端部より90cm口側の回腸が約15cmにわたって重積を起こしており, 約40cmの回腸を切除した. 重積回腸先進部の粘膜面に径約3cmの腫瘍を認めた. 病理組織学的には, 粘膜下組織と筋層内に平滑筋組織と混在する導管構造を認め, 迷入膵Heinrich分類III型と診断した. 迷入膵は胃, 十二指腸, 空腸などの膵の近傍に好発する疾患で, 回腸に発生することは比較的まれである. 回腸迷入膵は腸重積を引き起こし発症することが多く, 高圧注腸による整復が困難で腸切除を余儀なくされることが多い. 発生部位は回腸末端部より100cmまでの下部回腸に好発する.

Summary Inflammatory myopathy with abundant macrophages (IMAM) has recently been proposed as a new clinical condition. Although IMAM shares certain similarities with other inflammatory myopathies, the mechanisms responsible for this condition remain unknown. Patients with familial Mediterranean fever (FMF) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS) also often develop myalgia. We therefore investigated the polymorphisms or mutations of MEFV and TNFRSF1A genes in patients with IMAM to identify their potential role in this condition. We analysed the clinical features of nine patients with IMAM and sequenced exons of the MEFV and TNFRSF1A genes. The patients with IMAM had clinical symptoms such as myalgia, muscle weakness, erythema, fever and arthralgia. Although none of the patients were diagnosed with FMF or TRAPS, seven demonstrated MEFV polymorphisms (G304R, R202R, E148Q, E148Q-L110P and P369S-R408Q), and one demonstrated a TNFRSF1A mutation (C43R). These results suggest that MEFV gene polymorphisms and TNFRSF1A mutation are susceptibility and modifier genes in IMAM.

The aim of this study was to elucidate the risk factors for recurrence of Stage IIIa colon and rectosigmoid cancer.The subjects were 93 patients with Stage IIIa colon and rectosigmoid cancer who underwent radical colectomy in this department between 2001 and 2011. Various risk factors for recurrence were examined.The overall recurrence rate was 18% (17/93 cases). Univariate analysis identified a risk factor for recurrence: depth of tumor invasion( ≥serosa exposed[ SE])(hazard ratio[ HR] 10.04, 95% confidence interva[l CI] 3.26-30.89, p0.0001). The rate of 1, 2, and 3-year relapse-free survival of patients with respect to the depth of tumor invasion( ≥SE) were 76%, 61%, and 56%, respectively.Tumor depth SE or serosa infiltrating( SI) was a risk factor for the recurrence of Stage IIIa colon and rectosigmoid cancer.

We report a case of lethal interstitial pneumonia that occurred after neoadjuvant chemotherapy for advanced gastric cancer. A 76-year-old man with no history of interstitial pneumonia received 2 courses of S-1 (100 mg/body) following 1 course of S-1 plus cisplatin( CDDP) from June 2012. He complained of dyspnea on exertion 6 days after completion of the treatment. Chest radiography and computed tomography (CT) revealed diffuse interstitial lesions in bilateral lung fields. Bronchoalveolar lavage( BAL) revealed an increased number of lymphocytes and leukocytes. Transbronchial lung biopsy (TBLB) revealed interstitial pneumonia with fibrous thickening in the alveolar septum. The drug lymphocyte stimulation test (DLST) was positive for S-1 and negative for CDDP. These results suggested that S-1 had induced interstitial pneumonia. Steroid therapy( 40 mg/day prednisolone following 500 mg methylprednisolone pulse therapy) and an antibiotic agent were administered but were ineffective. He rapidly developed respiratory failure and required tracheal intubation and mechanical ventilation on hospital day 24, and died on hospital day 38.

Background Fat cells (stromal tissue cells), not only have the function of lipid metabolism, but produce various cytokines that exert an influence on other cell types through paracrine or endocrine mechanisms. Objectives To elucidate possible roles of fat cells in the skin, we examined their effects on the biological behaviour of keratinocytes and dermal fibroblasts in culture. Methods In the present study, focusing upon fat cell–keratinocyte or fat cell–dermal fibroblast interactions, we used a reconstructed skin system with rat skin cells in a three-dimensional collagen gel matrix culture. Results In this coculture system, fat cells promoted the proliferation and differentiation of keratinocytes. When keratinocytes were seeded directly on the fat cell layer without dermal fibroblasts, they proliferated extensively and formed a thick epidermal layer with a well-differentiated structure. Conversely, fat cells inhibited the proliferation of dermal fibroblasts. These effects of fat cells were presumed to be mediated by cytokines derived from the fat cells. Conclusions The effects of fat cells could not be mimicked by the addition of leptin, tumour necrosis factor-α or insulin-like growth factor-II, suggesting that fat cells are mediating these activities via some other cytokines.

Anencephaly is usually observed without association of severe malformations of other organs. A case of polysplenia, which was experienced in a 20-week-old anencephalic female fetus, was reported. The families of the parents had no history of neural tube defects. There was no consanguinity between the parents. The fetus showed a typical anencephaly with absent cranial vault, exophthalmus, hyperplastic thymus and hypoplastic adrenals. There was an atypical polysplenia consisting of five small spleens, absent gall bladder, short pancreas, small intestinal atresia and Fallot tetralogy. No visceral heterotaxy was observed in bronchi, lungs, liver or stomach. Though no direct association has been recognized between anencephaly and polysplenia, recent progresses in the studies of human fetuses and animal experiments help explain the relationship between anencephaly and heterotaxy syndrome. The mother of the present fetus had no history of hyperthermia, drug take or diabetes mellitus. She also had no infections such as virus and toxoplasma before and during pregnancy. There were no clues that would elucidate the etiology of the present anencephalic fetus with polysplenia. Precise surveillance and records of such cases should be advisable.

We herein report a very rare case of a patient suffering from simultaneous occurrence of three immune disorders, i.e. Hashimoto's thyroiditis, sarcoidosis and minimal change glomerular disease. A 66-year-old man was admitted to our hospital for evaluation of nephrotic syndrome. Six months before admission, he was pointed out as having positive proteinuria, hypoalbuminemia and associated pretibial pitting edema. Initial laboratory data showed high gammaglobulinemia, high titers of both antimicrosomal and antithyroglobulin antibodies with normal thyroid function. Chest X-ray and CT scan revealed bilateral hilar lymphadenopathy with interstitial shadow. Ga-citrate scan disclosed positive accumulation in the thyroid glands, the mediastinum, the lungs and the kidneys. The diagnosis of minimal change nephritic syndrome and pulmonary sarcoidosis was made, based on the findings of transbronchial lung biopsy and kidney biopsy. After one and a half months of admission, thyroid function had gradually deteriorated. The histological findings of the thyroid were consistent with the features of Hashimoto's thyroiditis. Treatment with prednisolone and cyclophosphamide resulted in a decrease in urinary protein excretion, reduction in the size of mediastinal lymphadenopathy and disappearance of positive findings of Ga-citrate scan in the thyroid glands and the kidneys. Simultaneous occurrence of minimal change-glomerular disease, sarcoidosis and Hashimoto's thyroiditis in our case suggests that similar immunological abnormalities may be involved in the pathogenesis of the diseases.

The inflammatory-mechanistic basis of subacute thyroiditis remains unclear. To elucidate the roles of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) in the inflammatory process, their immunoexpression was examined in biopsy specimens of ten cases. At the granulomatous stage, all cases expressed VEGF, bFGF, PDGF, and TGF-beta1 in monocytes/macrophages infiltrating into follicle lumina, and in both epithelioid histiocytes and multinucleated giant cells of the granulomas. In fibroblasts and endothelial cells around the granulomas, all cases displayed VEGF, bFGF, and PDGF, but TGF-beta1 was detected only in fibroblasts in two cases. No cases expressed EGF in any of the above cell types. At the regenerative stage, all cases expressed VEGF, bFGF, and EGF in regenerating thyrocytes, whereas three and no cases displayed PDGF and TGF-beta1, respectively. Ten, seven and six cases expressed PDGF in fibroblasts, endothelial cells, and monocytes, respectively. In these cell types, all cases expressed VEGF and bFGF, whereas no cases displayed TGF-beta1 and EGF. To estimate the roles of these growth factors in thyroid tissue regeneration, their effects on thyroid folliculogenesis and angiogenesis were examined using collagen gel culture of thyrocytes and endothelial cells, respectively. Cell proliferation was also studied by bromodeoxyuridine (BrdU) uptake. EGF decreased follicle formation and TGF-beta1 drastically inhibited it, but the others had no effect. VEGF showed the greatest effect on vessel formation, although all of the others promoted it. EGF and VEGF or bFGF caused the highest BrdU uptake in thyrocytes and endothelial cells, respectively. The data suggest firstly, that at the granulomatous stage of subacute thyroiditis, growth factor-rich monocytes/macrophages infiltrating into follicle lumina trigger the granulomatous reaction, and VEGF, bFGF, PDGF, and TGF-beta1 produced by the stromal cell types tested mediate the reaction; secondly, that at the regenerative stage, EGF serves follicle regeneration through its mitogenic effect on thyrocytes, although some cofactors with EGF are involved in folliculogenesis and the decreased expression of TGF-beta1, a fibrogenic factor, contributes to thyroid tissue repair; and thirdly, that VEGF and bFGF are more responsible for the angiogenesis at both stages than the other factors studied.

The growth of neoplasia is determined by the proliferation and loss of cells. The purpose of this study is to determine the frequency of apoptosis in laryngeal carcinomas and to examine its relationship to the pathological parameters, including ki-67 expression, and to expression of p53, bcl-2, and bax protein. The materials are 67 cases of laryngeal squamous cell carcinomas (SCCs) and 22 cases of squamous dysplasia using biopsy and surgery specimens. Apoptotic cells were determined by the modified TUNEL method. Expressions of p53, bcl-2, and bax, i.e. apoptosis-related genes, and ki-67, a proliferation marker, were immunohistochemically examined. The relationships between apoptosis and the clinicopathological findings were studied. The stage of the carcinoma was not related to the apoptotic index. The expression of p53 was frequently detectable in the advanced carcinomas with T3, T4 and N-positive. The apoptotic index was not significantly related to recurrence, metastasis or histological differentiation. Apoptosis occurred frequently in the cornified areas of well differentiated SCCs. The expressions of ki-67 observed in the poorly differentiated SCCs was significantly higher than that observed in the well differentiated SCCs (P0.01). The apoptotic index increased after irradiation in the carcinoma. No relationship was found between apoptotic index, ki-67 index, and expression of p53, bcl-2 and bax. The apoptotic index obtained form the SCCs was significantly higher than that obtained form squamous dysplasias (P0.05). Various apoptosis-related findings including p53 expression were observed in the advanced type of laryngeal SCCs, and apoptosis of the carcinoma was suggested to be controlled by complicated factors including bcl-2.

A 44-year-old woman presented with a slightly elevated, erythematous lesion, with partially blue-black areas. The nonpigmented area histologically showed a "dissecting" fascicular growth pattern, similar to one of the patterns seen in the cellular type of nerve sheath myxoma. The clinically pigmented part of the lesion consisted of diffusely infiltrating, broad and poorly delineated fascicles often showing nerve sheath differentiation, embedded in a highly myxomatous stroma. No part of the lesion showed the plexiform pattern typical of the classic type of nerve sheath myxoma; rather, the lesion had some common features of neurofibroma, and also was characteristically associated with a considerable number of scattered dermal melanocytes. However, based on the fascicular histologic pattern showing nerve sheath differentiation within mucinous matrix, S-100 protein-negative immunophenotype, and electron microscopic features, we considered the whole lesion in the present case to be an entity within the spectrum of nerve sheath myxoma, either mixed-type nerve sheath myxoma or unusually differentiating immature nerve sheath myxoma, except for the associated dermal melanocytosis. Because of the intimate association of the dermal melanocytes with this nerve sheath myxoma with divergent differentiation, this lesion can also be considered as a distinctive type of benign neoplasm derived from pluripotent neural crest cells.

透析導入後間もない慢性腎不全患者に合併した副甲状腺癌の一例を報告する. 45歳, 女性. 17年前より高血圧を指摘されており, 1991年3月腎障害の精査目的にて当院に入院となった. 入院時, 両腎の石灰化があり, 末期腎不全にもかかわらず高カルシウム傾向を認めたため原発性副甲状腺機能充進症 (C-PTH 5.0ng/ml) が疑われた. しかし, 副甲状腺シンチグラフィー (TI-Tc subtraction image) による集積像は認められなかった. 1992年6月より血液透析導入となったが, 3か月後にPTH値および血清Ca値の急激な上昇を認めたため当科に再入院となった. MRIおよびCTにて甲状腺右葉下極から上縦隔に達する巨大な腫瘍を認め, 副甲状腺腫瘍による副甲状腺機能亢進症と考え, 同年11月に腫瘍の摘出術を行った. 同腫瘍は組織学的所見から副甲状腺癌と診断された. 同時に摘出した他の2腺には過形成などの異常所見は認められなかった.こうした所見から, 本症例はこれまで透析患考で報告されている二次性の副甲状腺機能亢進症に合併した副甲状腺癌ではなく, 原発性のものである可能性が高いと思われた.

Collagenase digests from subcutaneous fat tissue of new born rats were cultured on different types of collagen gel containing 50% type I collagen, on fibronectin (Fn) or on laminin (Lm). On day 6, 17% of cells on a plastic substratum differentiated and had multilocular or unilocular cytoplasmic lipid droplets (CLDs). Cells on each type of collagen and on Lm had more CLDs than those on a plastic substratum. The extent of lipogenesis showed the following decreasing order: cells on Lm (80%), on type IV+I collagen (70%), on type I collagen (52%), on type III+I collagen (36%), on type II+I collagen (32%). On day 14, most cells on Lm became unilocular fat cells. Cells on Fn showed delipidation and showed decreased reactivity to insulin stimulation.Immunohistochemically differentiated fat cells were positively stained with antilaminin or anti-type IV collagen antibodies. These results provide evidence that Lm and type IV collagen promote fat cell differentiation, whereas Fn facilitates dedifferentiation into the fibroblast-like fat cell.

Transforming growth factor-β1 (TGFβ1) induces a mesenchyme-like cell shape in some epithelial cell types. To clarify the role of TGFβ1 in the morphological regulation of thyrocytes, we performed collagen gel culture of porcine thyrocytes with serum-free medium. TGFβ1-nontreated cells organized follicles. In contrast, the cells treated with 10 ng/ml TGFβ1 became spindle shaped, i.e. they resembled mesenchymal fibroblasts, and did not form follicles. To characterize the spindle-shaped cells, we examined the fine structures and expression of thyroglobulin (Tg) and cytoskeletal proteins using electron microscopy, immunohistochemistry, and immunoblotting. TGFβ1-nontreated cells had microvilli at the apical side facing follicle lumen and had basal lamina at the basal side in contact with collagen gel. TGFβ1-treated cells showed both microvilli and basal lamina at the basal side. TGFβ1-nontreated cells expressed Tg, whereas TGFβ1-treated cells showed no expression. TGFβ1-nontreated cells barely expressed vimentin, but they expressed enough cytokeratin. TGFβ1-treated cells extensively displayed vimentin along with the change in shape to become spindle-like and retained a decreased expression of cytokeratin. TSH (10 mU/ml) did not essentially influence any TGFβ1 effects on the cells. These results indicate that TGFβ1 induces a mesenchyme-like cell shape accompanied by cytoskeletal molecular change and the loss of both epithelial polarization and a function in thyrocytes, and that it results in inhibiting thyroid folliculogenesis with or without TSH.

There have been few pathological investigations of 45,X embryos and fetuses from a developmental point of view. Since most 45,X embryos and fetuses are lost prenatally, it is important to investigate them morphologically in order to elucidate the pathogenesis of the abnormalities. In this study, 13 45,X fetuses with cervical cystic hygroma were examined between 12 and 23 weeks of pregnancy. Every case had a hypoplastic thymus. The aortic valve was bicuspid in 11 cases and unicuspid in 2 cases. The aortic arch showed tubular hypoplasia between the left carotid artery and the left subclavian artery in 12 cases and type B interruption in one case. Smooth muscle cells and elastic fibers were reduced in number in the hypoplastic aortic arch. These results suggest hypoplastic development of the fourth branchial arch. Combined abnormalities between the aortic arch and aortic valve are not infrequently observed in DiGeorge anomaly. A similar developmental mechanism apparently underlies the pathogenesis of 45,X embryos. Possible genes causing the abnormalities are discussed.

The proliferative ability of fat cells has been studied both in the adipose tissue in vivo and in culture. We studied the proliferation of unilocular fat cells of young rats in a threedimensional collagen gel matrix culture, which provides a physiological environment for fat cells. In this setting, the unilocular fat cells were able to maintain their cellular functions and actively proliferate. In this study using cells derived from 3 to 6-week-old rats, we observed the appearance of very small fat cells at the surface of unilocular fat cells following the division of the nucleus. We concluded that small fat cells were created mostly in a “budding” manner, and then proliferated. Insulin accelerated both the budding and proliferation process. In other unilocular fat cells, lipid droplets divided after the division of the nucleus, and very small fat cells appeared within the unilocular fat cells in a “sharing” manner. Adenosine deaminase, a potent lipolytic factor, accelerated this process. An analysis of the cellular volume by a Coulter counter confirmed the proliferation of small fat cells derived from the unilocular fat cells. These small fat cells grew and developed into unilocular fat cells. It is supposed that not all unilocular fat cells are terminally differentiated, nor do they lose their proliferative activity.

A 65-year old man presented with complaints of sclerosis of skin and numbness in the extremities. During last 10 year, he had developed monoclonal gammopathy, Raynaud's phenomenon, ischemic heart disease, sigmoid colon cancer, hyperkalemia, polyneuropathy and scleroderma-like skin changes. Laboratory examinations revealed a monoclonal protein (IgA-lambda) and an elevated serum level of IL-6. Subsequently a diagnosis of POEMS syndrome was made based on the clinical features and laboratory findings which were characteristic of this syndrome. Further examinations showed the presence of glomerulonephritis and brain tumor. These various complications are of great interest in understanding the pathogenesis of POEMS syndrome.

A 58-year-old Japanese man was admitted complaining of abdominal pain. An abdominal computed tomography examination demonstrated a tumor in the head of the pancreas and multiple calcifications. A laparotomy was performed and the tumor was removed by Whipple's operation. Histologically, the neoplasm that invaded the duodenal wall and the papilla of Vater was composed of nests of malignant squamous cells with intercellular bridges and showed the formation of keratinized pearls with a small area of concurrently neoplastic glandular and squamous elements. On the basis of these features, the diagnosis of adenosquamous carcinoma of the pancreas was made. The patient died 18 months after the operation. The neoplastic behavior of this rare primary pancreatic carcinoma is similar to that of duct cell carcinoma as well as pure squamous cell carcinoma of the pancreas. As the pancreas can be the target of metastases of squamous carcinomas from other organs it is wise to be aware of this rare entity.

Thyroid follicles in vivo are embedded in extracellular matrix (ECM). The composing epithelial cells are in close contact with ECM at the basal side. To examine cell-to-ECM interactions, we studied adhesion, proliferation and differentiation of porcine follicle cells monolayer-cultured on type I and IV collagen, fibronectin or laminin. At 3 h in culture, laminin had the lowest rate of cell adhesion. In proliferation, type IV collagen induced the highest level of nuclear bromodeoxyuridine intake. In a functional differentiation, laminin had about 3 times as much triiodothyronine production as the other ECM molecules. In confluent, culture cells, we also examined an expression of c-fos protein, a transcription factor that plays crucial roles in signal transduction. Immunocytochemistry detected the protein mainly in the nuclei. Western blot showed that laminin induced the highest level of its expression. Thyrotropin (TSH, 10 mU/ml) did not affect adhesion of the cells on any of the substrata or proliferation of the cells on fibronectin ; nor did TSH affect c-fos protein expression of the cells on the substrata except for fibronectin. Our results suggest that type IV collagen and laminin, major components of basement membrane, play positive roles in proliferation and differentiation of follicle cells, respectively, while laminin has no positive effect on adhesion of the cells at early culture ; that the cells express c-fos protein even in contact inhibition of growth and its expression is regulated in part by ECM ; and that ECM controls some behaviors of the cells in a TSH-dependent or TSH-independent manner.

A rare case of primary choriocarcinoma of the lung in a male is described with immunohistochemistry for human chorionic gonadotropin (hCG), epidermal growth factor (EGF) and EGF-receptor. The extragonadal trophoblastic origin of this pulmonary carcinoma was definitely confirmed by an autopsy examination, and hCG-production and hCG-positive staining of the tumor cells. Furthermore, the tumor cells clearly expressed EGF and its receptor which play an important role in the proliferation and differentiation of normal and neoplastic trophoblasts of the uterus. Our present case suggests that EGF may act in an autocrine manner in the tumor cells of primary pulmonary choriocarcinoma.

Shuji Toda1, Shigehisa Aoki1, Kazuyoshi Uchihashi1, Aki Matsunobu1, Mai Yakushiji1, Akifumi Ootani2, Eisuke Koike3 and Nobuhisa Yonemitsu4 1Department of Pathology & Microbiology, Faculty of Medicine & Graduate School of Medicine, Saga University, Saga 849-8501, 2Department of Internal Medicine Faculty of Medicine & Graduate School of Medicine, Saga University, Saga 849-8501, 3Department of Surgery, Koike Hospital, Saga 840-0861, 4Department of Pathology, Sasebo Chuo Hospital, Nagasaki 857-1195 Japan

Some follicle cells organize thyroid follicles through proliferation of single cells in collagen gel culture. The aim of this study was to clarify whether two or more (plural) cells can form follicles through aggregation and linkage in this culture system. To address this question, we performed collagen gel culture of porcine follicle cells, using cell labeling with PKH 2 dye. A mixture of dye-labeled and nonlabeled cells was cultured in collagen gel. Organized follicles consisted of both dyed and nondyed cells. This suggested that plural cells reconstructed follicles through aggregation and linkage. To further confirm this finding, cells embedded in collagen gel were cultured in inhibition of cell proliferation with 2 micrograms/ml aphidicolin. Forty to 60 percent of the cells formed follicles, which did not grow larger. Electron microscopy showed that intracytoplasmic cavities appeared in the cells. In contrast, 20-30% of the embedded cells developed into cavity-embracing single cells, which remained signet rings. These results indicate that follicle cells organize follicles in collagen gel culture by two means: through cell division of cavity-embracing single cells and through aggregation and linkage of plural cells.

Adipose tissue exists in the gastric submucosa and subserosa. Thus, adipose tissue stromal cells (ATSCs), which include mesenchymal stem cells (MSCs), seem critical for the progression of gastric cancer but their interaction with the cancer cells is unknown. We demonstrated an interaction between these cells, using immunohistochemistry, Western blot and the collagen gel invasion assay system, in which the adenocarcinoma cells (well and poorly differentiated types, MKN28 and MKN45, respectively) were cultured on a ATSC-embedded or ATSC-non-embedded gel. ATSCs promoted the expression of the growth marker, proliferation cell nuclear antigen but inhibited that of the apoptosis marker, single-stranded DNA, in the cancer cell types. ATSCs accelerated the invasion of only MKN28 into the gel and promoted the expression of mitogen-activated protein kinase (MAPK, pERK-1/2) but decreased that of the molecularly targeted protein, HER2, in the cancer cells. ATSCs did not affect the expression of the prostaglandin biosynthetic enzyme cyclooxgenase-2 (COX-2) in the cancer cells. The COX-2 inhibitor celecoxib did not affect the morphology or invasion of the cancer cells. The cancer cell types in turn promoted the display of the myofibroblast marker, α-smooth muscle actin, whereas they decreased that of some MSC markers, e.g., CD44 and CD105, in ATSCs. The data suggest that (1) ATSCs influence the progression of gastric cancer by increasing their growth/invasion and decreasing their apoptosis through MAPK activation in a COX-2-independent way; (2) ATSCs adversely affect HER2-targeted therapy; (3) the cancer cells induce the cancer-associated myofibroblast phenotype in ATSCs.

A 69-year-old woman was admitted to our hospital with complaint of epigastric discomfort in February 2006. The detailed examination had revealed type 4 advanced gastric cancer. An exploratory laparotomy was performed for the unresectable case due to peritonitis cartinomatoza. Postoperative S-1 monotherapy (100 mg/body, 4 weeks on, 2 weeks off) was started as an outpatient in April 2006. After 3-course, partial response (PR) was observed for the primary lesion by gastrointestinal endoscopy. In April 2007, the regimen was changed to S-1 (100 mg/body, 3 weeks on, 2 weeks off)+CDDP (60 mg/m2, days 8) combined chemotherapy, then the primary lesion showed a slight increase. Thereafter, the regimen was changed to S-1 monotherapy in March 2008, and S-1+CDDP combined therapy in July 2008 again. PR was kept observed for three years successfully after the exploratory laparotomy. A case of type 4 unresectable gastric cancer was reported that the postoperative chemotherapy of S-1 was effective.

The patient was an 85-year-old man who underwent a rt-hemicolectomy, cholecystectomy and choledocholithotomy for cecum cancer and bile duct stone. The tumor was a well differentiated adenocarcinoma, type 2 in the Japanese classification of colorectal carcinoma. The tumor was considered to be in stage II (ss, ly2, v0, n (-), P0, H0, M (-)). He did not receive any adjuvant chemotherapy. After 2 years and 3 months from the surgery, an abdominal MRI and an abdominal CT scan revealed a 30 mm hepatic nodule lesion. We diagnosed with liver metastasis of the cecum cancer. The patient refused both surgery and radio-frequency ablation therapy. We chose radiotherapy for liver metastasis. He was given a total dose of 50 Gy/25 fractions. After 3 months from the radiotherapy, the tumor was reduced gradually and tumor marker (CEA) was normalized. The disease was diagnosed as CR because no tumors were detected. There has been no liver recurrence. But after 4 years and 6 months from the surgery, 20 mm lung nodules in rt-lower lung were revealed by chest X-ray. Once more, we chose radiotherapy for lung tumor. He was given a total dose of 66 Gy/33 fractions. At present, the tumor was reduced gradually. There has been no recurrence since his irradiation. If the case was made a good choice, radiation therapy appears to be effective for liver and lung tumors from the colorectal cancer.

Subcapsular small cortical cells (SC cells) and subcapsular large cortical cells (LC cells) of bovine adrenal cortex were cultured separately after purification by unit gravity sedimentation, and then compared with inner half layer cells (IL cells) prepared by the same method. Both SC and LC cells were polygonal in shape and their mitochondria were elongated with lamellar cristae. SC cells became as large as LC cells on day 6 of culture with increased cytoplasmic lipid droplets, whereas IL cells showed no change in size. IL cells were spindle-shaped and had mitochondria with tubulovesicular cristae. Both SC and LC cells produced 11β deoxycorticosterone, corticosterone, aldosterone and small amounts of 17α hydroxy progesterone (17 α OH Prog) and Cortisol (F). IL cells produced much more 17α-OH Prog and F than SC or LC cells. When stimulated with ACTH, cortical cells in each group showed cellular retraction and their mitochondria became spherical. The amounts of 17. OH Prog and F increased in all groups, especially in IL cells. These results show that LC cells have similar characteristics to SC cells in both morphology and function, and that they differ from IL cells, which correspond to classical fasciculata reticularis cells. Acta Pathol Jpn 41: 428–436, 1991.

We report two cases of advanced gastric cancer with severe postoperative complications after neo-adjuvant chemotherapy (NAC). The first case is a 60-year-old man who was diagnosed as a type 2 advanced gastric cancer with paraaortic lymph node metastases and the elevation of serum CA19-9 level. NAC was started, but no reductions were noted after 3 courses. Palliative total gastrectomy with distal pancreatectomy, splenectomy, cholecystectomy, and partial hepatectomy for T4 gastric cancer exhibiting obstruction were performed in June 2007. On postoperative day 10, abdominal CT scan revealed left subphrenic abscess, then CT-guided percutaneous drainage was performed. A culture of the abscess yielded Candida albicans and Candida glabrata. The second case is a 58-year-old man who was diagnosed as a type 2 advanced gastric cancer with multiple lymph node metastases and the elevation of serum CA19-9 level. NAC were performed, but no reductions were noted. A distal gastrectomy was performed in January 2008. On the first postoperative day, a severe abdominal distension was appeared suddenly and increasingly. An emergency laparotomy was undergone, but no findings of the bowel obstruction were observed. On postoperative day 2, a rise of serum beta-D-glucan level was recognized. Both cases were improved by an antifungal drug therapy.

Osteosarcoma is one of the neoplasms that may occur following exposure to radiation. A case of osteosarcoma arising in the craniofacial bone with a short latency period of 3 years after radiotherapy for maxillary squamous cell carcinoma is described. A 64-year-old-man underwent right partial maxillectomy and chemoradiotherapy due to squamous cell carcinoma of his right maxillary sinus. Histologically, the tumor was composed of moderately differentiated squamous cell carcinoma with a component of spindle cell carcinoma. Three years later, osteosarcoma developed in the craniofacial bone within the irradiation field of the first tumor. Detailed histological examination demonstrated that there was no component of osteosarcoma in the first tumor or squamous cell carcinoma in the second tumor. Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy. In this case, osteosarcoma was possibly a radiation-induced osteosarcoma with a short latency period of 3 years.

F9 teratocarcinoma stem cells treated with retinoic acid (RA) differentiate into visceral endoderm, and this process affects the expression of some extracellular matrix (ECM) proteins. As the direct influence of ECM molecules on the differentiation of F9 stem cells has not been studied, we investigated the effects of various ECM proteins on the early differentiation of these cells. Monolayers of F9 stem cells were cultured on dishes coated with various ECM, such as type I or IV collagen, fibronectin, or laminin. They aggregated and formed spheroid bodies in the absence of RA only on type IV collagen. The outer layer cells of the spheroid bodies exhibited numerous microvilli, junctional complexes and mature cell organelles. Alpha-fetoprotein was positive in the outer layer cells. A small amount of laminin was detected in the matrix of the spheroid bodies. These data suggest that type IV collagen promoted the early stage of the differentiation of F9 stem cells without RA. The other ECM molecules failed to induce them to form spheroid bodies. The reversibility of the structure of the spheroid bodies to a monolayer was also examined. When the spheroid bodies were reseeded only on fibronectin- or laminin-coated culture dishes, they broke down and the cells spread to the surface in the absence of RA. The differentiation of F9 stem cells induced by type IV collagen seemed to be reversible and to take place at an early stage of their morphogenesis. These findings suggest that type IV collagen plays an important role in early embryogenesis.

The localization and biological roles of the multifunctional cell type mast cells remain unclear in subacute thyroiditis that is characterized by both epithelioid granuloma formation and thyroid tissue repair. We examined their immunolocalization with tryptase of a mast cell marker, using the biopsy specimens from 12 cases. In the epithelioid granuloma, no mast cells were detected in any of the cases, although a small number of them (4.6 +/- 2.4) were seen at the fibrous stroma around the granuloma in all cases. By contrast, in all cases, increased mast cells (28 +/- 7.2) localized at the thyroid tissue-regenerative site where both thyroid folliculogenesis and angiogenesis take place. To elucidate possible roles of mast cells in the disease, we also examined their immunoexpressions of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF), which affect thyroid folliculogenesis and angiogenesis. In all 12 cases, mast cells displayed all of these growth factors in a manner not specific to the infiltrating site. The data suggest that growth factor-expressing mast cells may play crucial roles in the thyroid tissue repair of subacute thyroiditis, modulating thyroid folliculogenesis and angiogenesis; and that the multifunctionality of the cells may be partly dependent on their expressions of various growth factors.

Subepithelial tissue cell types in vivo are separated from air by the surface-covering epithelial layer of various organs, e.g., the skin, cornea, and respiratory and upper alimentary tracts. The epithelial defect caused by inflammatory, traumatic or surgical injury would be expected to expose the subepithelial tissue-localized fibroblasts to influx air. However, it is unclear what effects air stimulation elicits in fibroblast growth, which is critical for wound healing. To address this question, we examined the proliferation of 3T3 fibroblasts with bromodeoxyuridine (BrdU) uptake, using fibroblast-embedded collagen gel culture with or without air exposure. The BrdU intake of air-exposed fibroblasts was about 6 times that of air-nonexposed cells. To further characterize this fibroblast growth, we examined the expression of mitogen-activated protein kinase (MAPK) cascade, which plays a key role in the growth-signaling pathway of various cell types. Immunohistochemistry and Western blotting showed that air exposure increased MAPK cascade expression of the cells more strongly than air nonexposure. The data indicate that air exposure promotes MAPK cascade-associated fibroblast growth, suggesting in turn that in wound repair air stimulation itself may be involved in the basic mechanisms of subepithelial fibroblast proliferation and that it may be related to the pathogenesis of excessive fibroplasia through fibroblast overgrowth.

We describe a rare case of papillary carcinoma with extensive proliferation of stromal cells. The stromal cells were immunocytochemically positive for vimentin, alpha-smooth muscle actin and desmin, but negative for cytokeratin, epithelial membrane antigen, S-100, thyroglobulin and CD34. These results and the ultrastructure of the stromal cells, which exhibited the characteristics of both fibroblasts and smooth muscle cells, indicated an origin from myofibroblasts. We conclude that myofibroblastic proliferation may contribute to the stromal response in the slow growth of the papillary carcinoma.