＜文献概要＞はじめに 膵癌は最も予後不良な固形癌であり,進行した状態で診断されることが多く,過半数の患者が診断後1年以内に死亡する。近年,日本でも罹患数が増加しており,死亡数は増加の一途をたどっている。膵癌は腫瘍径が2cm以下のTS1膵癌で発見されてもその予後はよいとはいいがたく,予後向上には長期予後が見込める上皮内癌(5年生存率86%)や腫瘍径10mm以下の微小浸潤癌(5年生存率80%)の状態でいかに的確に診断できるかが最重要課題といえる。しかしながら,腫瘍径が1cm以下の早期の膵癌症例では症状の出現に乏しいため発見は困難であり,早期診断のためには,どのような対象にどのような画像検査を含む精査を行うのかを考える必要がある。膵癌の画像診断では,腹部US,造影CT,腹部MRI,EUSなどが用いられる。これらの診断モダリティのなかでもEUSは管腔内走査をすることにより,超音波端子を膵臓に近接し固定することができるため,他のモダリティと比較し空間分解能が非常に高く,膵癌の早期発見において欠かすことのできない画像診断検査である。本稿では,膵癌の早期診断においてEUSが果たしている役割,早期診断の精度や限界について概説する。

BACKGROUND: The Idylla™ EGFR Mutation Test is an ultra-rapid single-gene test that detects epidermal growth factor receptor (EGFR) mutations using formalin-fixed paraffin-embedded specimens. Here, we compared the performance of the Idylla EGFR Mutation Test with the Cobas® EGFR Mutation Test v2. METHODS: Surgically resected NSCLC specimens obtained at two Japanese institutions (N = 170) were examined. The Idylla EGFR Mutation Test and the Cobas EGFR Mutation Test v2 were performed independently and the results were compared. For discordant cases, the Ion AmpliSeq Colon and Lung Cancer Research Panel V2 was performed. RESULTS: After the exclusion of five inadequate/invalid samples, 165 cases were evaluated. EGFR mutation analysis revealed 52 were positive and 107 were negative for EGFR mutation in both assays (overall concordance rate: 96.4%). Analyses of the six discordant cases revealed that the Idylla EGFR Mutation Test was correct in four and the Cobas EGFR Mutation Test v2 was correct in two. In a trial calculation, the combination of the Idylla EGFR Mutation Test followed by a multi-gene panel test will reduce molecular screening expenses if applied to a cohort with EGFR mutation frequency >17.9%. CONCLUSIONS: We demonstrated the accuracy and potential clinical utility of the Idylla EGFR Mutation Test as a molecular screening platform in terms of turnaround time and molecular testing cost if applied to a cohort with a high EGFR mutation incidence (>17.9%).

BACKGROUND: The Biocartis Idylla™ platform is a fully automated, real-time PCR-based diagnostic system. The Idylla™ KRAS and NRAS-BRAF Mutation Tests have been developed for the qualitative detection of mutations in KRAS, NRAS and BRAF genes, facilitating the genomic profiling of patients with colorectal cancer. The aim of the present study was to evaluate clinical performances of these tests in Japan. METHODS: The RAS and BRAF mutation statuses of 253 formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissues were analyzed using the Investigational Use Only Idylla™ KRAS Mutation Test and the Idylla™ NRAS-BRAF Mutation Test and an in vitro diagnostics (IVD) kit (MEBGEN RASKET™-B kit). RESULTS: The success rate for obtaining a valid mutational data without retest of the Idylla tests was 97.6% (247/253): 111 KRAS mutations (43.8%), 9 NRAS mutations (3.6%), and 36 BRAF V600E mutations (14.2%) were detected using the Idylla tests. Compared with the MEBGEN RASKET-B results, the positive concordance rate was 97.4%, the negative concordance rate was 95.7%, and the overall concordance rate was 95.3% (κ = 0.919, 95% CI 0.871-0.967). The average turnaround time to Idylla™ KRAS and NRAS-BRAF Mutation Test was 5.6 working days (range: 3-11 days). CONCLUSION: This result demonstrates a high concordance between the Idylla™ KRAS and NRAS-BRAF Mutation Tests and an existing IVD kit. In this manner, the Idylla™ mutation tests were validated for the detection of clinically significant KRAS, NRAS, and BRAF mutations in FFPE samples from colorectal cancer patients.

BACKGROUND: Pancreatic cancer (PC) exhibits extremely rapid growth; however, it remains largely unknown whether the early stages of PC also exhibit rapid growth speed equivalent to advanced PC. This study aimed to investigate the natural history of early PCs through retrospectively assessing pre-diagnostic images. METHODS: We examined the data of nine patients, including three patients with carcinoma in situ (CIS), who had undergone magnetic resonance cholangiopancreatography (MRCP) to detect solitary main pancreatic duct (MPD) stenosis >1 year before definitive PC diagnosis. We retrospectively analyzed the time to diagnosis and first-time tumor detection from the estimated time point of first-time MPD stenosis detection without tumor lesion. RESULTS: The median tumor size at diagnosis and the first-time tumor detection size were 14 and 7.5 mm, respectively. The median time to diagnosis and first-time tumor detection were 26 and 49 months, respectively. CONCLUSIONS: No studies have investigated the PC history, especially that of early PCs, including CIS, based on the initial detection of MPD stenosis using MRCP. Assessment of a small number of patients showed that the time to progression can take several years in the early PC stages. Understanding this natural history is very important in the clinical setting.

BACKGROUND: The value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for T-staging in patients with extrahepatic bile duct cancer was evaluated. METHODS: This single-center, retrospective study included consecutive patients with extrahepatic bile duct cancer who underwent surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced CT (CE-CT) examinations between June 2014 and August 2017. The capacity of these modalities for T-staging of extrahepatic bile duct cancer was evaluated by assessing invasion beyond the biliary wall into the surrounding tissue, gallbladder, liver, pancreas, duodenum, portal vein system (portal vein and/or superior mesenteric vein), inferior vena cava, and hepatic arteries (proper hepatic artery, right. and/or left. hepatic artery). Blind reading of EUS, CH-EUS, and CE-CT images was performed by two expert reviewers each. RESULTS: 38 patients were eligible for analysis, of which eight had perihilar bile duct cancer and 30 had distal bile duct cancer. Postoperative T-staging was T1 in 6, T2 in 16, and T3 in 16 cases. CH-EUS was superior to CE-CT for diagnosing invasion beyond the biliary wall into surrounding tissue (92.1% vs. 45.9%, P = 0.0002); the ability to detect invasion to other organs did not differ significantly between the two modalities. The accuracy of CH-EUS for T-staging of tumors was better than that of CE-CT (73.7% vs. 39.5%, P = 0.0059). CH-EUS tended to have a better accuracy than EUS for the diagnosis of invasion beyond the biliary wall into the surrounding tissue (92.1% vs. 78.9%, P = 0.074) and T-staging (73.7% vs. 60.5%, P = 0.074). CONCLUSION: CH-EUS is useful for T-staging of extra hepatic bile duct cancer, especially in terms of invasion beyond the biliary wall into the surrounding tissue.

Due to the tendency of gastric linitis plastica (GLP) to cause extensive submucosal infiltration, a superficial endoscopic biopsy sometimes yields no evidence of malignancy, hindering definite diagnosis. The present study was a single-center retrospective analysis of 54 consecutive patients diagnosed with GLP between 2016 and 2020 to evaluate EUS-guided fine-needle aspiration (EUS-FNA) biopsy outcomes in patients with negative endoscopic biopsy findings. A pathological GLP diagnosis was achieved by endoscopic biopsy in 40 patients (74.1%). EUS-FNA biopsy with a 22-gauge needle was performed in 13 of the remaining 14 patients, and GLP diagnosis was confirmed in 10 patients, with a median of three needle passes. The remaining four patients were laparoscopically diagnosed with GLP. The diagnostic ability of EUS-FNA biopsy for GLP was 76.9%, and EUS-FNA biopsy contributed to GLP diagnosis in 18.5% (10/54) of all cases. None of the 13 patients exhibited EUS-FNA biopsy-related adverse events. Univariable and multivariable analyses revealed an absence of superficial ulcerations as a predictor of false-negative endoscopic biopsy findings in patients with GLP. These results suggest EUS-FNA biopsy as a minimally invasive and safe alternative diagnostic modality for GLP in cases where conventional endoscopic biopsy fails to verify malignancy, although prospective studies with larger cohorts are warranted to confirm these findings.

Double expressor lymphoma (DEL), defined as overexpression of BCL2 and MYC, is an aggressive subtype of diffuse large B cell lymphoma (DLBCL). Here we report a case of a 64-year-old female diagnosed with abdominal DEL transformed from jejunum follicular lymphoma (FL). 18F-fluorodeoxyglucose (FDG)-positron emission tomography showed diffuse accumulation of FDG into the peritoneum and small bowel wall. Double balloon-assisted enteroscopy revealed whitish submucosal tumors in the proximal jejunum. Aggregation of atypical lymphocytes positive for CD20, CD79a, and BCL2 was seen in the jejunal biopsy samples. These atypical lymphocytes were monoclonal since cell surface expression of Ig light chains was limited to κ chain by flow-cytometry. Thus, immunohistochemical and flowcytometric analyses data were consistent with FL of the jejunum. Neoplastic lymphocytes obtained from ascites were positive for CD10, CD20, CD79a, BCL2, and BCL6. Fluorescence in situ hybridization (FISH) showed formation of BCL2/IgH fusion gene and extra copies of MYC, the former of which is a characteristic chromosomal abnormality of FL. These genetic alterations and protein expression profiles of ascitic fluid cells were consistent with those of DEL transformed from FL. Given that a significant population of patients with indolent FL of the gastrointestinal tract developed into aggressive DLBCL, it is likely that primary FL of the jejunum transformed into the abdominal aggressive DEL in this case. This case is unique in that concurrent occurrence of FL and DEL was confirmed by immunohistochemical and FISH analyses and that abdominal DEL transformed from jejunal FL was highly suspected.

Behçet's disease (BD) is a rare inflammatory condition characterized by oral and genital ulcers, skin lesions, as well as ophthalmological, neurological, and gastrointestinal manifestations. BD involving the gastrointestinal tract is known as intestinal BD. The mucosa of the gastrointestinal tract of patients with intestinal BD exhibits enhanced levels of proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α. These proinflammatory cytokines play pathogenic roles in the development of BD, as evidenced by the fact that biologics targeting these cytokines effectively induce BD remission. It should be noted, however, that the molecular mechanisms by which the blockade of these cytokines suppresses chronic inflammatory responses in BD are poorly understood. Herein, we report a case of intestinal BD resistant to prednisolone that was successfully treated with infliximab (IFX). The induction of remission by IFX was accompanied by a marked elevation of IL-6 and forkhead box P3 (FOXP3) at mRNA level. This case suggests that induction of remission by IFX is mediated not only by the suppression of TNF-α-mediated signaling pathways, but also by the promotion of IL-6 expression and accumulation of regulatory T cells expressing FOXP3.

This study aimed to investigate whether the incorporation of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) into the international consensus guidelines (ICG) for the management of intraductal papillary mucinous neoplasm (IPMN) could improve its malignancy diagnostic value. In this single-center retrospective study, 109 patients diagnosed with IPMN who underwent preoperative CH-EUS between March 2010 and December 2018 were enrolled. We analyzed each malignancy diagnostic value (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) by replacing fundamental B-mode EUS with CH-EUS as the recommended test for patients with worrisome features (WF) (the CH-EUS incorporation ICG) and comparing the results to those obtained using the 2017 ICG. The malignancy diagnostic values as per the 2017 ICG were 78.9%, 42.3%, 60.0%, and 64.7% for Se, Sp, PPV, and NPV, respectively. The CH-EUS incorporation ICG plan improved the malignancy diagnostic values (Se 78.9%/Sp, 53.8%/PPV, 65.2%/NPV 70.0%). CH-EUS may be useful in determining the appropriate treatment strategies for IPMN.

Pulmonary sarcomatoid carcinoma (PSC) is classified as poorly differentiated, and non-small cell lung carcinomas that contained a component of sarcoma or sarcoma-like differentiation are rare. The underlying carcinogenetic mechanism governing PSC remains unclear. The current study investigated the underlying carcinogenetic mechanism of PSC based on the hypothesis that it involves the epithelial-mesenchymal transition (EMT) process. Mutation analysis of PSCs, including carcinosarcoma, pleomorphic carcinoma and epithelial carcinoma specimens, was performed using targeted deep sequencing, whole transcriptome analysis and digital spatial profiling (DSP). PSCs exhibit a distinct mutation profile, with TP53, SYNE1 and APC mutations. Therefore, clustering of the gene expression profiles allowed the PSCs to be distinguished from the epithelial carcinomas. Increased gene expression of fibronectin in PSC was an important contributor to differential profiles. Pathway analysis revealed enhanced activity of the integrin-linked kinase (ILK) signaling pathway in the PSCs. DSP analysis using 56 antibodies of marker proteins confirmed significantly higher expression of fibronectin in PSCs. Intratumor heterogeneity of fibronectin expression was observed in sarcoma components. In conclusion, epithelial-mesenchymal transition process mediated by ILK signaling may be associated with carcinogenetic mechanisms of PSC. Overexpression of fibronectin mediated by ILK signaling appears to serve a role in the EMT involved in the PSC transformation process.

Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC). The composition of the bowel microflora is thought to influence the development of inflammatory bowel disease and irAE colitis. We profiled the gene expressions and microbe compositions of colonic mucosa from patients with solid cancers receiving anti-PD-L1 antibody treatment; we then compared the expression profiles associated with irAE colitis with those associated with UC. The pathway enrichment analysis revealed functional similarities between inflamed regions of irAE colitis and UC. The common enriched pathways included leukocyte extravasation and immune responses, whereas non-inflamed mucosa from patients with irAE colitis was distinct from patients with UC and was characterized by the recruitment of immune cells. A similarity between the microbiota profiles was also identified. A decreased abundance of Bacteroides species was observed in inflamed regions from both irAE colitis and UC based on a microbiota composition analysis of 16S rDNA sequencing. Pathways associated with molecule transport systems, including fatty acids, were enriched in inflamed and non-inflamed irAE colitis and inflamed UC, similar to Piphillin-inferred KEGG pathways. While UC is characterized by local regions of inflammation, ICI treatment extends to non-inflammatory regions of the colonial mucosa where immune cells are reconstituted. This analysis of the similarity and heterogeneity of irAE colitis and UC provides important information for the management of irAE colitis.

症例は56歳の男性で,15年前より痔瘻と診断され近医で加療されていた.難治性痔瘻増悪の診断で当科を紹介受診された際には,臀部から陰嚢および陰茎にかけて多数の瘻孔と排膿が認められた.肛門管後壁の瘻孔からの生検にて痔瘻癌と診断した.また,腸管同士の瘻孔形成を認め,尿道・膀胱への瘻孔形成が疑われた.痔瘻は広汎かつ深部に及び,会陰部の炎症が強いため,まずS状結腸人工肛門造設術を行い,全身状態と会陰部の炎症所見を改善させたうえで,外性器を含む広汎な会陰皮膚組織切除を伴う骨盤内臓全摘を行い,会陰欠損部に対して腹直筋皮弁形成術を施行した.現在,術後19ヵ月無再発生存中である.本例のように,腸管や尿道・膀胱への浸潤に加え,広汎な会陰部の皮膚浸潤が疑われる局所進展痔瘻癌に対しては,根治のために外性器切除を含めた広範囲の一塊切除が必要であると考えられる.(著者抄録)

Background: This study aimed to evaluate and identify the specific CT findings by focusing on abnormalities in the main pancreatic duct (MPD) and pancreatic parenchyma in patients with small pancreatic cancer (PC) including carcinoma in situ (CIS). Methods: Nine CT findings indicating abnormalities of MPD and pancreatic parenchyma were selected as candidate findings for the presence of small PC ≤ 10 mm. The proportions of patients positive for each finding were compared between small PC and benign MPD stenosis groups. Interobserver agreement between two independent image reviewers was evaluated using kappa statistics. Results: The final analysis included 24 patients with small PC (including 11 CIS patients) and 28 patients with benign MPD stenosis. The proportion of patients exhibiting partial pancreatic parenchymal atrophy (PPA) corresponding to the distribution of MPD stenosis (45.8% vs. 7.1%, p < 0.01), upstream PPA arising from the site of MPD stenosis (33.3% vs. 3.6%, p = 0.01), and MPD abrupt stenosis (45.8% vs. 14.3%, p = 0.03) was significantly higher in the small PC group than in the benign MPD stenosis group. Conclusions: The presence of partial PPA, upstream PPA, and MPD abrupt stenosis on a CT image was highly suggestive of the presence of small PCs including CIS.

OBJECTIVES: Early death in severe acute pancreatitis (SAP) is caused by pancreatic necrosis and multiple-organ failure due to microcirculation disorder. The aim of this study was to prove that recombinant human-soluble thrombomodulin (rTM) has therapeutic effects on SAP by preventing pancreatic necrosis and organ failure. METHODS: Male Wister rats were used. Cerulein was administered intraperitoneally 4 times every 1 hour, and lipopolysaccharide was administered intraperitoneally 3 hours after. One hour after administration of lipopolysaccharide, rTM was injected intravenously. Rats were observed for 24 hours after starting the experiment, and the survival rate was evaluated. All surviving rats were killed, and the blood sample, liver, and pancreas were excised. Serum amylase, aspartate aminotransferase, alanine aminotransferase, and high mobility group box 1 were measured, and the liver and pancreas were examined histologically. For the evaluation of microcirculation, von Willebrand factor staining was performed. RESULTS: Serum amylase, aspartate aminotransferase, and alanine aminotransferase were significantly decreased. The survival rate was significantly improved to 100%. Moreover, serum high mobility group box 1 was decreased. Liver injury and pancreatic necrosis became less severe, and microcirculation was preserved histologically. CONCLUSIONS: Early administration of rTM prevents organ failure by maintenance of microcirculation and improves prognoses of SAP.

We present a case of locally advanced anal fistula cancer that was resected by total pelvic exenteration with genitalia resection and extensive perineal skin tissue resection. The patient was a 56-year-old man with a history of anal fistula treated at another hospital 15 years earlier. He was referred to our hospital for intractable anal fistula exacerbation and presented with many fistulas and drainage from the buttocks to the scrotum and penis. He was diagnosed with anal fistula cancer by biopsies from a fistula in the posterior wall of the anal canal. Preoperative CT and MRI revealed small bowel fistulas and suspected fistulas involving the urethra and bladder, which caused severe inflammation in the perineum. We performed sigmoid colostomy to improve his general condition prior to curative surgery. The patient then underwent total pelvic exenteration with genitalia resection, extensive perineal skin tissue resection, and treatment with a rectus abdominis musculocutaneous flap. He is currently alive without evidence of recurrence 19 months after surgery. For locally advanced anal fistula cancer with massive invasion into surrounding tissues and perineal skin, a wide en bloc resection including external genital resection is the preferred treatment.

AIMS: Stroke-prone spontaneously hypertensive rats (SHRSP) show significantly lower body weight than normotensive Wistar-Kyoto rats (WKY). Our hypotheses are as follows: weight loss of the skeletal muscle is related to hypertension-related diseases, and muscle hypotrophy is useful as a therapeutic target for hypertension and hypertension-related diseases. In this study, we aimed to investigate the pathophysiological characteristics of muscle hypotrophy in SHRSP to determine the therapeutic target molecule(s). MAIN METHODS: The difference in skeletal muscles in the lower leg between WKY and SHRSP was evaluated mainly through weight/tibial length, histological, gene expression, and protein expression analyses. KEY FINDINGS: SHRSP had a significantly lower weight/tibial length in soleus and gastrocnemius, but not in plantaris and tibialis anterior, indicating that muscles consisting of a relatively high amount of slow muscle fiber were affected. This result was confirmed by the histological analysis of soleus, showing that type I fiber mainly decreased the fiber size. Microarray and protein expression analyses showed that the muscle-specific ubiquitin ligase, muscle RING finger 1 (MuRF1), but not atrogin-1, was highly expressed in soleus, but not in plantaris, in SHRSP. TNF-like weak inducer of apoptosis receptor (TWEAKR) was predicted as a MuRF1 up-regulator by Ingenuity Pathway Analysis and immunostained only in type II fiber in WKY but in both type I and II fibers in SHRSP. SIGNIFICANCE: TWEAKR is a type II-specific receptor in the skeletal muscle. Ectopic TWEAKR expression in type I fiber of SHRSP is most likely involved in slow muscle-specific hypotrophy through MuRF1 overexpression.

Copyright© 2018 Japan Gastroenterological Endoscopy Society. All rights reserved. Background and Aim: Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for diagnosis of localized gallbladder lesions. Methods: One hundred and twenty-five patients with localized gallbladder lesions were evaluated by CH-EUS between March 2007 and February 2014. This was a single-center retrospective study. Utilities of fundamental B-mode EUS (FB-EUS) and CH-EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images. Results: In the differentiation between gallbladder lesions and sludge plug, FB-EUS had a sensitivity, specificity, and accuracy of 82％, 100％, and 95％, respectively, whereas CH-EUS had a sensitivity, specificity, and accuracy of 100％, 99％, and 99％, respectively. FB-EUS-based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61-87％, 71-88％, and 74-86％, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH-EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90％, 98 ％, and 96％, respectively. There was a significant difference between FB-EUS and CH-EUS in terms of carcinoma diagnosis. Conclusion: CH-EUS was useful for the evaluation of localized gallbladder lesions.

膵・胆管合流異常に合併した共通管内乳頭状腫瘍の1例を報告する.症例は75歳の男性で,6ヵ月間に2度の急性膵炎を発症し保存的加療で軽快した.急性膵炎の原因精査および加療目的で当院へ紹介となった.ERCPでは膵・胆管合流異常を認め,共通管内に7mmの結節様陰影欠損像を認めた.上部内視鏡検査では乳頭部からの粘液排出は認めず,超音波内視鏡検査では共通管内に乳頭状の腫瘍が描出された.造影CTでは膵頭部に拡張した共通管と内部に増強効果を持つ8mmの腫瘤を認めた.尾側の主膵管の拡張は認めなかった.膵・胆管合流異常に合併した共通管内乳頭状腫瘍と診断し,亜全胃温存膵頭十二指腸切除術を施行した.病理肉眼所見では共通管内に発育する有茎性の乳頭状腫瘍で,組織像は管状構造増生を主体とする腺腫であった.免疫組織学的染色ではMUC1,MUC2陰性,MUC5AC陽性で胃型腺腫と最終診断した.(著者抄録)

症例は67歳、女性。上腸間膜動静脈浸潤および遠隔リンパ節転移を伴う膵頭部癌に対し、S-1による化学療法を施行した。2コース終了後に腫瘍マーカーの正常化、主病変の著明な縮小を認めた。化学療法を継続したが、増悪所見を認めず治療開始から8ヵ月後に亜全胃温存膵頭十二指腸切除術を施行した。切除後の病理診断では、主腫瘍は著明な線維性変化と軽度異型細胞をわずかに認めるのみでリンパ節転移も認めず、組織学的完全奏効と診断した。術後10ヵ月現在、無再発生存中である。(著者抄録)

NEW FINDINGS: What is the central question of this study? An inverse correlation between circulating adiponectin and many diseases has been reported, but some studies have found no correlation. To evaluate this controversy, we investigated the relationship between heart-bound adiponectin and hypertension or cardiac hypertrophy, compared with serum adiponectin. What is the main finding and its importance? Using hypertensive and normotensive rats, we found that heart-bound adiponectin was inversely correlated with cardiac hypertrophy, suggesting that heart-bound adiponectin has a more important function in preventing cardiac hypertrophy than circulating adiponectin. Our study provides new insights regarding the role of adiponectin in diseases. The inverse correlation between circulating adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. In addition to circulating adiponectin, adiponectin is also bound to tissues such as the heart and skeletal muscle. In this study, we investigated the relationship of serum adiponectin and heart-bound adiponectin with hypertension and cardiac hypertrophy. Four types of hypertensive rats presenting different blood pressure levels were used at different ages, as follows: normotensive Wistar-Kyoto rats (WKYs); two sub-strains (strains C and B2, having low and high blood pressure, respectively) of spontaneously hypertensive rats (SHRs); and stroke-prone SHRs (SHRSPs). Blood pressure, heart-to-body weight ratio, serum adiponectin and heart-bound adiponectin were determined. Histopathological analysis of the heart was carried out to evaluate the relationship with heart-bound adiponectin. Serum adiponectin concentration was not inversely correlated with blood pressure or heart-to-body weight ratio. In contrast, heart-bound adiponectin levels were significantly lower in SHRSPs than in other strains at respective ages. This resulted from a decrease in T-cadherin expression, which induced adiponectin binding to tissues. No significant difference in heart-bound adiponectin among WKYs and SHRs (C and B2) was detected, indicating that heart-bound adiponectin is not related to hypertension. In addition, differences in heart-bound adiponectin did not affect AMP-activated protein kinase in the traditional adiponectin activation cascade. Histopathological analysis revealed that heart-bound adiponectin was inversely correlated with cardiomyocyte hypertrophy and left ventricular wall thickness and, in part, with cardiac fibrosis. These results suggest that the decreased level of heart-bound adiponectin in SHRSPs is more related to their cardiac hypertrophy than circulating adiponectin.

背景:アレルギー性気管支肺アスペルギルス症(allergic bronchopulmonary aspergillosis:ABPA)は、気管支喘息患者の気管支にアスペルギルスが持続的に腐生し、これに対するI型とIII型アレルギーが成立して発症する疾患群である。臨床像、血清検査、画像をもとに診断されることが多く、気管支内容物の細胞診を見る機会は少ない。今回ABPAの1例を経験し、その特徴的な細胞像について報告する。症例:79歳、女性。喘息発作で入院した。Rosenbergの診断基準を満たし、ABPAと診断された。気管支肺胞洗浄液細胞診で、粘液を背景に好酸球が孤立性および集団で認められ、隔壁を有するY字状分岐菌糸が散在し、シャルコー・ライデン結晶も認められた。培養でAspergillus属真菌が分離された。結論:気管支内容物の細胞診で、粘液を背景に好酸球の集団と隔壁を有するY字状分岐菌糸を認めた場合、ABPAを鑑別する必要がある。(著者抄録)

AIM: To report the magnetic resonance imaging (MRI) and corresponding histopathological features of squamous cell carcinoma (SCC) originating in the parotid gland. MATERIALS AND METHODS: The MRI images of seven patients with histopathologically proven SCC originating in the parotid gland were reviewed retrospectively, with an emphasis on tumour size, shape, contour definition, extraparotid infiltration, signal characteristics, and the presence of central necrosis. These were correlated with the microscopic findings of the surgical specimens. RESULTS: The tumours ranged in size from 3.9-7 cm (mean 4.7 cm). All tumours had an ill-defined margin with extraparotid infiltration, which seemed to reflect the invasive growth of the tumour cells on histopathological examination. The solid portions of the tumours showed predominantly low to intermediate signal intensities on T2-weighted images, which seemed to reflect the high cellularity, intercellular bridges, and/or keratin pearl formation observed at histopathological examination. Five of the seven tumours had central necrosis. CONCLUSION: A relatively large tumour with central necrosis is a useful imaging feature of SCCs originating in the parotid gland, in addition to the well-recognized indicators of parotid malignancy, such as an ill-defined margin, extraparotid infiltration, and low to intermediate signal intensity on T2-weighted images. (C) 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

本邦ではじめて経験されたConidiobolus属真菌感染症剖検例で，生前に得られた気管支吸引細胞診での真菌形態について報告した。

背景：病理組織実習における学生の積極性を引き出す方法が模索されていた。携帯電話やスマートフォン内蔵デジタルカメラを用いた顕微鏡画像撮影を勧奨することは学生の積極性を引き出すのに役立つかどうか観察した。
方法：学生に自由に内臓デジタルカメラで顕微鏡画像を接眼部から撮影させた。病理組織実習に対する学生の態度の変化を観察記録した。
結果：学生は顕微鏡画像撮影に積極的であった。撮影された画像を画面上で見ながら質問・説明が可能であった。学生は自ら撮影した画像を整理して復習に利用した。
結論：学生一人一人が自ら顕微鏡画像を撮影することで病理組織実習への積極的な参加を誘導できた。

Cystic lesions of the pancreas are sometimes difficult to diagnose. We report a case of a gastric duplication cyst (GDC) of the pancreas in an adult. A 45-year-old woman was admitted to our department for the investigation of anemia. Abdominal ultrasonography revealed a large cystic lesion, measuring about 40 × 70 mm with calcification in the tail of the pancreas. Contrast-enhanced computed tomography of the abdomen revealed a non-enhanced cystic lesion with non-enhanced wall. Endoscopic retrograde pancreatography revealed a mild extended main pancreatic duct and an aberrant pancreatic duct, but there was no communication with the cyst. We could not deny the malignancy, so distal pancreatectomy was performed. The pathological examination revealed that the inner wall of the cyst consisted of columnar epithelium and smooth muscle layer. Immunohistochemical analysis revealed the columnar epithelium to be immunopositive for cytokeratin 7 (CK7) and immunonegative for cytokeratin 20 (CK20) and the glands to be immunonegative for CK 7 and immunopositive for CK 20. Therefore, a diagnosis of GDC of the pancreas was made. On imaging, a GDC usually mimics a pancreatic pseudocyst or a cystic neoplasm of the pancreas. Therefore, even though it is rare, a GDC should be considered in the differential diagnosis of cystic tumors of the pancreas.

Hyphae are usually the only fungal elements found in tissue of mucormycosis, and other fungal elements are quite rarely encountered. We found chlamydospores in bronchial lumina in autopsied tissue of pulmonary mucormycosis of a diabetic patient. Chlamydospores are thick-walled, asexually produced spores arising from the modification of a hyphal segment. This is the first histologic demonstration of chlamydospores in mucormycosis in which the causative fungus is culturally identified to species level. Rhizopus microsporus var. rhizopodiformis was isolated from the present autopsied pulmonary tissue. A literature review of human infection by this fungus found 27 cases with histopathologic evidence.

稀であるが近年増加傾向にあるアレルギー性真菌性副鼻腔炎の細胞診での特徴について報告した。

75歳男性。約2年前より全身の紫斑、そう痒感が出現し近医皮膚科を受診、経過観察中であった。今回、労作時呼吸困難をはじめ全身倦怠感、起坐呼吸の増悪を主訴に心不全の診断で著者らの施設にある循環器内科入院後、皮膚症状について皮膚科へ紹介となった。初診時、上眼瞼、腋窩、側腹部に紫斑がみられ、皮膚生検の結果、全身性ALアミロイドーシスと診断された。また、循環器内科で行われた心筋生検でも間質にアミロイドの沈着が証明された。以上より、心不全症状に対しては飲水制限や利尿薬の投与などの対症療法が行われ、皮膚症状に対しては抗ヒスタミン薬の内服や副腎皮質ステロイド外用、保湿剤の外用が行われた。その結果、そう痒感は若干ではあるが落ち着いた。

Background: Anti-angiogenic agents are now being clinically evaluated for the treatment of pancreatic cancer and a detailed investigation of the angiogenic profile of pancreatic cancer is needed. The aim of this study was to evaluate the plasma concentrations of angiogenesis-related molecules in patients with pancreatic cancer, compared with those with other diseases.Methods: Plasma samples obtained from 45 patients with pancreatic cancer were analyzed and compared with those from 9 patients with pancreatitis, 16 patients with benign hepatobiliary diseases and 58 patients with colorectal cancers. The plasma levels of angiogenesis-related molecules including angiopoietin-2, follistatin, granulocyte-colony stimulating factor, hepatocyte growth factor, interleukin-8, leptin, platelet-derived growth factor beta polypeptide, platelet endothelial cell adhesion molecule-1 and vascular endothelial growth factor were determined using an antibody suspension bead arrays system.Results: The plasma levels of all the angiogenesis-related molecules were not increased in patients with pancreatic cancer, compared with those with pancreatitis and benign hepatobiliary diseases, whereas the levels of those with colorectal cancer were markedly increased. The plasma interleukin-8 concentration was significantly elevated in patients with distant metastases and was associated with a poor treatment outcome of chemotherapy in patients with pancreatic cancer.Conclusions: The plasma levels of angiogenesis-related molecules were not elevated in patients with pancreatic cancer, compared with those with benign diseases or colorectal cancer. The plasma interleukin-8 level may be a novel biomarker for the response to chemotherapy in patients with pancreatic cancer and warrants further prospective study.

OBJECTIVES: Endoscopic ultrasonography (EUS)-guided celiac plexus neurolysis (EUS-CPN) is safe and effective but not beneficial for some patients with extended abdominal cancer. We compared the effectiveness of standard EUS-CPN and EUS-guided broad plexus neurolysis (EUS-BPN) that extends over the superior mesenteric artery (SMA) using a 25-gauge needle. METHODS: Consecutive patients referred to our quaternary EUS centers were eligible for inclusion. To evaluate the neurolytic spread, contrast was mixed with the neurolytic agent and post-procedure computed tomography scanning was performed. The regions containing the celiac, superior, and inferior mesenteric arteries were divided on the frontal plane into six areas: upper right and left, middle right and left, and lower right and left. The number of contrast-bearing areas after EUS-CPN and EUS-BPN were related to the degree of pain relief achieved. RESULTS: A total of 67 patients with advanced abdominal cancer were included (34 EUS-CPN and 33 EUS-BPN). The qualitative variables of the two groups did not differ significantly. The EUS-BPN group had more patients with six contrast-bearing areas (42%) than the EUS-CPN group (0%). These patients had significantly better short-term and long-lasting pain relief than patients with less than five contrast-bearing areas. EUS-BPN patients exhibited significantly greater reductions in days 7 and 30 visual analog pain scale scores than EUS-CPN patients. CONCLUSIONS: Our preliminary data suggested that EUS-BPN using a 25-gauge needle provides patients with advanced abdominal cancer with better pain relief than standard EUS-CPN, and without incurring serious complications. Moreover, it seems that broad neurolysis over the SMA may provide superior analgesia.

68歳の男性。平成19年に近医で血圧が高値であったため、降圧薬が開始となった。その際の血液検査では低K血症を認め、血漿アルドステロン濃度の上昇と血漿レニン活性の低下を伴っていたため、原発性アルドステロン症の疑いで当科に紹介された。画像所見上は両側副腎腫瘍が認められた。入院にて更に内分泌学的検査を行ったところ、尿中アルドステロンの上昇と血中DHEA-Sの正常低値もあり、カプトプリル負荷試験では陽性基準を満たした。また、コルチゾールの簡易日内変動と1mg・8mgデキサメサゾン抑制試験を施行したところ、日内変動は消失しており1mg・8mgのデキサメサゾン抑制試験は陽性であったため、サブクリニカルクッシング症候群を合併した原発性アルドステロン症と診断した。その後、コルチゾールとアルドステロンのそれぞれにおける局在診断のために、131I-アドステロールシンチグラフィと選択的副腎静脈サンプリングを行ったところ、両ホルモンは右副腎で高値であったため、当院泌尿器科にて腹腔鏡下右副腎摘出術を施行した。術後は血清K値の低下はなく経過し、降圧薬も当初の薬剤に変更して退院となった。(著者抄録)

Small cell carcinoma (SCC) of the pancreas is a rare entity, with only a few cases reported in the literature. The aim of this study was to evaluate the effectiveness of combination chemotherapy with carboplatin and etoposide (CE) in SCC of the pancreas. We performed a retrospective analysis of four patients diagnosed with SCC among 279 patients with malignant pancreatic tumors treated between 2000 and 2007. All patients were treated with combination chemotherapy using a schedule consisting of intravenous (IV) carboplatin (150 mg/m(2)) on day 1 and IV etoposide (80 mg/m(2)) on days 1, 2, and 3 every 28 days. Pathological diagnosis was confirmed by endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in all patients. Three patients treated with the combination chemotherapy achieved remission, two with a complete response and one with a partial response. The remaining one patient showed no change. One of the two patients with a complete response survived for 56 months following the diagnosis. Combination chemotherapy with CE may be effective for the treatment of SCC of the pancreas; EUS-FNA plays an important role in distinguishing SCC from other pancreatic malignancies, leading to the appropriate treatment being given.

The aim of this prospective study was to compare fine-needle aspiration guided by endoscopic ultrasonography (EUS-FNA) using 25-gauge and 22-gauge needles with the EUS-guided 19-gauge Trucut needle biopsy (EUS-TNB) in patients with solid pancreatic mass. Twenty-four consecutive patients with pancreatic mass underwent biopsies by both EUS-FNA and EUS-TNB. Three needles were compared with respect to technical success rate, tissue size obtained, overall diagnostic accuracy and accuracy for histological and cytological diagnosis. The 25-gauge EUS-FNA was technically easier and obtained superior overall diagnostic accuracy than the 22-gauge and Trucut needles, especially in lesions of the pancreas head and uncinate process. Overall accuracy for the 25-gauge, 22-gauge and Trucut needle was 91.7%, 79.7% and 54.1%, respectively. Accuracy for cytological diagnosis irrespective the site of lesions with 25-gauge, 22-gauge and Trucut needles was 91.7%, 75.0%, and 45.8%, respectively. For uncinate masses, it was 100%, 33.3%, and 0.0%, respectively. These differences were significant. Among technically successful patients, the accuracy for histological diagnosis using the 25-gauge was significantly inferior (P < 0.05) to 22-gauge and Trucut needles and the rates were 45.8%, 78.9% and 83.3%. The 25-gauge FNA needle was significantly superior in terms of technical success rate and overall diagnostic accuracy, especially for the head and uncinate lesions, compared to the 22-gauge and Trucut needles and could be considered 'the best choice needle for cytological diagnosis' of solid pancreatic lesions. If histological diagnosis is required, the 22-gauge FNA needle and Trucut needle may be advantageous for use in head/uncinate and body/tail lesions, respectively.

Background. Recently. contrast agents for ultrasonography (US) such as Levovist have been introduced for routine clinical use. The contrast-enhanced US with Levovist permits evaluation of the intratumoral vascularity of hepatic and pancreatic tumors and is useful for their differential diagnosis. The purpose of the present study was to assess tumor vessels and the parenchymal flow of oastrointestinal stromal tumors (GISTs) by contrast-enhanced coded phase-inversion harmonic US and to evaluate whether vascularity is related to the malignant grade of the GISTs. Methods. Thirteen patients with GISTs were included in the present study. Tumors were observed in a real-time fashion of contrast-enhanced coded phase-inversion harmonic US after the injection of Levovist (400 mg/ml). The Vascular patterns were compared with tumor size, histological diagnosis. KIT mutations, and clinical findings such as metastasis. Results. The contrast-enhanced US images of the GISTs were classified into two types according to the blood flow area of the tumors as seen by real-time continuous imaging of the tumor vessels. The image pattern "Poor" represented vessels flowing only in the peripheral part of the tumor, and "Rich" represented abundant vessels flowing from the periphery to the central part of the tumor. According to the contrast-enhanced US images, five GISTs were classified as "Poor" and the others as "Rich." Based on the final diagnosis, all tumors with "Poor" images were determined to be benign GISTs. and the rest tumors except one with "Rich" images were determined to be malignant GISTs. Conclusions. Contrast-enhanced US image is more closely correlated with the final diagnosis than the histological findings.

69歳、女性の胃粘膜下に発生した腫瘍で由来不明な悪性間葉系腫瘍の１例を報告した。組織学的に異型細胞は類上皮様で異型が著明であった。免疫染色の結果、平滑筋系、神経系の抗体およびCD34,CD117のいずれも陰性で、電顕でも特徴となる所見に乏しかった。

Objective: Magnetic resonance imaging (MRI) was used to investigate the therapeutic effects of imidapril, a newly synthesized angiotensin converting enzyme (ACE) inhibitor, on cerebral stroke lesions. Design: Pretreatment with ACE inhibitors is known to prevent stroke in stroke-prone spontaneously hypertensive rats, prolonging their lifespan. Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) were treated with imidapril after the onset of stroke. Methods: M-SHRSP with proved stroke were divided into two groups. One group received 40 mg/kg per day imidapril and the other group was used as a control. For 4 weeks, neurological symptoms were scored daily, and MRI images were taken and scored once a week. Results: In the control group the MRI score for cerebral lesions increased during the experiment, and seven out of eight control rats died within 17 days. In rats treated with imidapril the major finding was that imidapril rapidly ameliorated the damage to the blood-brain barrier and resolved brain oedema within 1 week. At the same time the neurological symptoms observed after stroke disappeared. Furthermore, none of the rats treated with imidapril showed recurrence of stroke, and their survival rate was improved. Conclusion: These results suggest that imidapril has therapeutic effects on stroke lesions, as well as prophylactic effects on the recurrence of stroke.

Apparent diffusion coefficients (ADCs) of tissue water were determined in chronic brain lesions of a rat stroke model, the stroke-prone spontaneously hypertensive rat, and compared with histology. ADCs increased in the order normal < edema < gliosis < cyst. The differences between individual groups were statistically significant. The increase in ADC is thought to mainly reflect a relative increase in the extracellular space in brain tissue. ADC may be a new parameter for tissue characterization.

Memory performances of SHRSP with chronic stroke were examined on the three-panel runway task in addition to the histological evaluation and magnetic resonance imaging (MRI) of the brain. After recovery from the neurological symptoms with stroke. SHRSP were subjected to acquisition training on the memory tasks, and they exhibited both a delay and a persistent impairment of acquisition on the memory tasks, compared to the non-stroke SHRSP. T2-weighted MRI with the stroke SHRSP suggested marked edematous formation in the cortex, caudate putamen and/or thalamus, preferentially in the frontal and/or occipital cortex. The histological evaluation showed edematous degeneration such as edema, gliosis and cyst preferentially in the cortex, but no degeneration in the hippocampus. Thus, SHRSP with chronic stroke was found to exhibit impairment of learning and memory, which may be due to the cortical edematous degeneration.

Apparent diffusion coefficients (ADCs) of tissue water were determined in chronic brain lesions of a rat stroke model, stroke-prone spontaneously hypertensive rats and compared with histology. ADCs increased in the order control < edema < gliosis < cyst. The differences between individual groups were statistically significant. The increase in ADC is thought to mainly reflect a relative increase in the extracellular space in brain tissue. ADC values may be a clinically useful parameter for tissue characterization.

Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) are a useful animal model for studying juvenile malignant hypertension. Using M-SHRSP males, the effects of SQ 29,852 {(S)-1-[6-amino-2-[[hydroxy (4-phenylbutyl) phosphinyl]oxy]-1-oxo-hexyl]-L-proline; 30-40 mg/kg per day}, captopril (30-40 mg/kg per day), hydralazine hydrochloride (10-15 mg/kg per day) and a 33% fish meal diet on the prevention and therapy of malignant hypertension were examined. Drugs and diet were given separately, beginning at weaning, maturity or adulthood. Observed effects included antihypertension, prolonged life span and prevention and/or reversal of angionecrosis. Each treatment resulted in an antihypertensive effect, but some adult rats seemed treatment-resistant. SQ 29,852 was the most effective treatment for reducing blood pressure. The life span of animals in the treated groups was extended significantly beyond that of the controls. In particular, those rats treated with either captopril or SQ 29,852 lived in excess of 500 days. This included not only those in which treatment resulted in a lowering of blood pressure, but also those whose severe hypertension was not so reduced. Angionecrosis was observed in the organs of many of the non-treated animals, including the brain, heart, kidneys and testes. Both hydralazine and the fish meal diet had a limited effect, if any, on the prevention or reversal of angionecrosis. In contrast, almost none of the rats given either captopril or SQ 29,852 showed cerebrovascular lesions or angionecrosis of the brain, heart and kidneys; angionecrosis in adult. M-SHRSP kidneys disappeared within 10 or 18 days after the initiation of SQ 29,852 or captopril, respectively. This data seems to support a possible role for these two drugs not only in prevention, but also in repair, of angionecrosis independent of markedly high blood pressure in M-SHRSP. Based on our overall observations, SQ 29,852 was seen as the most effective of the treatments studied.

M-SHRSP rats appear to be a useful animal model for studying juvenile human malignant hypertension. Using M-SHRSP, the present study was conducted. Drugs selected for use were captopril, SQ 29,852 and hydralazine hydrochloride. The rats were also fed a 33% fish meal diet. When given separately, all three drugs were shown to be anti-hypertensive. However, using the fish meal diet combined with hydralazine was more effective than were any of the drugs given separately, while the effect of hydralazine combined with captopril or SQ 29,852 was even greater than that of the combined fish meal diet and hydralazine treatment. Some rats treated with captopril or SQ 29,852 separately were resistant to treatment, however even for these rats life spans were significantly prolonged and hypertensive vascular lesion incidence rates were drastically lowered. It was also found that even such vascular lesions as angionecrosis seemed to disappear with captopril or SQ 29,852 treatment. © 1991 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

M-SHRSP rats appear to be a useful animal model for studying juvenile human malignant hypertension. Using M-SHRSP, the present study was conducted. Drugs selected for use were captopril, SQ 29,852 and hydralazine hydrochloride. The rats were also fed a 33% fish meal diet. When given separately, all three drugs were shown to be anti-hypertensive. However, using the fish meal diet combined with hydralazine was more effective than were any of the drugs given separately, while the effect of hydralazine combined with captopril or SQ 29,852 was even greater than that of the combined fish meal diet and hydralazine treatment. Some rats treated with captopril or SQ 29,852 separately were resistant to treatment, however even for these rats life spans were significantly prolonged and hypertensive vascular lesion incidence rates were drastically lowered. It was also found that even such vascular lesions as angionecrosis seemed to disappear with captopril or SQ 29,852 treatment.

Captopril, SQ 29852, hydralazine or a combination therapy was administered to 11-week-old male M-SHRSP and 20- to 25-week-old male SHRSP all of which evidenced angionecrosis in verious organs. Blood pressures for captopril or SQ 29852 or hydralazine groups slightly lowered to about 220mmHg, and those of combination therapy groups decreased within normal range. In captopril, SQ 29852 and combination group, fibrinoid substances of blood vessels were absorbed and disappeared, and vacuoles were found in vessel wall, and smooth muscle cells proliferated and, then, blood vessels repaired. These latter effects were not seen in the rats given hydralazine.

The time for the onset of angionecrosis in the ocular vessels was slightly later than that in the brain, kidneys, heart and adrenal glands, but was the same as that in the testes. Retinal and cerebral vessel hyperpermeability (tracer leakage) was observed almost at the same time.

内臓カンジダ症の診断目的で穿刺吸引細胞診が行われることがあるが，症例数が少ないため得られた標本中のカンジダ形態については十分に解析されていない。そこで，剖検時に内臓カンジダ病巣から得られた材料から細胞診標本を作製し，PAS染色を実施してカンジダ形態を解析した。これまで言われていたように出芽分生子，仮性菌糸が認められるが，真性菌糸が見られた場合でもその一部に出芽分生子を見いだすことで他の糸状菌との鑑別が可能と考えられた。

炎症性皮膚疾患のうちの肉芽腫性疾患のなかでも鑑別疾患の多い非感染性肉芽腫について，特に環状肉芽腫（granuloma annulare，GA）を中心にして実際の症例の呈示とともにAckermanやWeedonらの方法を元に，代表的な疾患の鑑別について解説した．GAの4症例の呈示と鑑別疾患として，リポイド類壊死症，リウマトイド結節，類壊死性黄色肉芽腫，弾力線維融解性環状巨細胞肉芽腫などをGAと比較し重要な鑑別点を提示した．

77歳，女性の中枢神経系変性疾患で，解剖の承諾が得られ組織学的に詳細に検討できた貴重な症例を経験したので報告した．脳梗塞を合併しており多彩な臨床像を示していた．小脳，橋の著しい萎縮がみられ，同部を中心に，組織学的には，ガリアス染色で陽性を示す房状アストロサイトやグリアのコイル状小体が明瞭に多数認められた．

33歳，女性の胸壁に発生した稀な血管腫瘍の症例を報告した． 類円形核を有した異型細胞が血管様構造をとって増殖しており，一部では嚢胞様拡張を伴っていた．免疫染色ではCD34陽性, S-100, NSE一部陽性であり，総合的にpolymorpharous hemangioendotheliomaと診断された．

皮膚病理診断研究会がコンパニオンミーティングとして皮膚の軟部腫瘍をテーマにシンポジウムを行った。そのうち「平滑筋腫瘍」の項目を担当し、解説した。

高齢者の皮下腫瘍で、高度のmyxoid changeを伴った症例を報告した。免疫染色の結果、脂肪肉腫であった。HE染色で判断が難しい症例であった。

皮膚病変のうち、悪性黒色腫との鑑別が必要な良性皮膚色素性病変の概説をした。特に手掌、足底、爪の色素性疾患のうちで、病理組織学的に特に悪性黒色腫との鑑別を要する疾患を説明した。

悪性脳卒中易発症性高血圧自然発症ラット（M-SHRSP）を用いて，緑茶成分エピガロカテキンガレート（EGCG）慢性投与の血圧及び脳卒中に対する影響について検討した．M-SHRSPに対して，EGCGの投与は血圧上昇を抑制し，脳卒中発症を有意に遅延させた．血圧上昇の抑制機構として，レニン-アンジオテンシン-アルドステロン系の抑制が考えられた．また，以前の研究により，脳卒中発症時に血清NOx濃度が急激に上昇することを認めており，EGCGはその上昇を抑制することにより，脳障害の抑制に働いていると考えられた．以上の結果より，緑茶の摂取が脳卒中発症の予防に有効であることが示唆された．

73歳，女性の症例で，膵頭部の被膜を有する径2,5cm大の腫瘤が認められた．組織学的に類円形核と好酸性胞体とを有する異型細胞が索状，胞巣状を呈し増殖していた．Synaptophysin, S-100やglucagon, somatostatinなどが陽性であったが，insulin,gastrinは陰性であった．膵内分泌腫瘍でparaganglioma typeと考えられた．良性としたがfollow upが必要と思われた．

皮膚血管性病変の基礎的な知識として必要な解剖学的組織所見と他臓器と皮膚との血管の差異などについて説明した。

腹部CTにて左腎腫瘍を指摘されて当院泌尿器科受診。腹部CTでは均一で骨格筋と同程度のCT値であり、内部に小さな石灰化がみられた。脂肪成分は指摘できず。造影CT早期相では均一によく造影されて、後期相では周囲の腎よりも低吸収であったがtime density curve 上は漸増性を示していた。MRI T2強調画像では骨格筋と同程度の低信号であり、chemical shift imageでは微少脂肪成分は指摘できず、in phase, opposed phaseとも腫瘤は腎実質よりも高信号を示していた。Dynamic studyではCT同様均一に造影されている。T2強調画像で腫瘍そのものが低信号を示しており、被膜の同定は不可能であった。脂肪成分が少ない血管筋脂肪腫との鑑別に苦慮したが、clear cell carcinoma以外の悪性腫瘍の可能性も考え、左腎摘出術を施行。Gerota筋膜表面の血管は強く怒張し、易出血性であった。左腎上極の癒着も著しかった。割面は灰白色で均一であった。組織診断はgranurlar cell carcinomaであった。

症例は55歳，女性．中結腸動脈に動脈瘤が認められ手術的に切除された．組織学的には動脈壁全層にfibrinoid壊死をきたしていた．結節性多発性動脈炎に類似する点がみられるが，内弾性板の断裂がみられた．さらに，非病変部でも中膜平滑筋細胞に空胞変性が著明であり，分節性動脈中膜解離と診断された． 原因不明な稀な症例であり，症例数の蓄積が期待される．

中結腸動脈破裂で緊急手術をされた症例で、病理組織学的に検討した結果、中結腸動脈に発生したsegmental arterial mediolysisであることが判明した。本疾患は報告例が少なく原因究明には更なる症例の蓄積が必要と考えられた。

平成6年頃より胆道感染症を繰り返すも、保存的加療を続けていた。 平成15年10月と平成16年1月に化膿性胆管炎を併発したため再度受診。精査の結果，粘液産生腫瘍が疑われた。ため当院紹介となった。 まれな腫瘍であり、大量の粘液産生により閉塞性黄疸や繰り返す胆道感染症を引き起こす。 悪性腫瘍、良性腫瘍、過形成など様々な組織が混在することが多い。 腫瘍は小さくCT やMRI では指摘できないこともある。 通常の胆管癌に比して長期予後が望める。 粘液産生肝内胆管癌を経験したので報告した。 術前に充実成分を指摘できたが、それ以上に乳頭状病変が広がっていた。 切除範囲決定には空間分解能に優れた超音波検査が有用と考えられる。

74歳，男性．肝内胆管腫瘍が疑われ摘出術が施行された．肉眼的には多房性腫瘍で，組織学的には乳頭状粘液産生腫瘍であった．多くは良性病変の組織型であったが，その一部に核異型，構造異型がみられ免疫染色の結果を考慮して一部に悪性化を伴ったものと判断された．

血栓症の1例として、腫瘍によりなくなられた患者にみられた肺塞栓症をマクロ画像、組織画像をまじえて解説した。

肝門部の胆管内に腫瘍が認められた症例を報告した。胆管内乳頭状粘液産生腫瘍であった。組織学的にその一部で悪性と思われる所見が見られ、免疫染色で証明した。この疾患は膵管内の乳頭状粘液産生腫瘍との関連性が指摘されており、究明には更なる症例集積が望まれる。

BNCTは腫瘍選択性照射が期待される放射線治療である。悪性グリオーマ6症例に8回の照射を行った。初期効果は全例PRであった。照射後摘出しえた標本から神経組織への腫瘍選択的効果を示唆する所見をえた。

２学年の病理学コースのなかで，37回の講義について毎回，学生による教員評価を行った。被評価者は教授１，助教授１，講師４で，担当時間数は異なっている（最高９，最低３）。評価項目は１０項目で，５段階評価，無記名とした。平均回収率は58％であった。以下に項目ごとの結果を示す。数値は教員ごとの平均の最高，最低および全教員の平均を示している。１．説明が明快で全体としてまとまりがある（最高4.5，最低3.2 平均4.0）２．よく準備している（最高4.5，最低3.7 平均4.2）３．重点をうまく要約してくれる（最高4.5，最低3.2 平均4.0）４．授業を静粛に保つ配慮をしてくれる （最高4.2，最低3.6 平均3.9）５．教師の意見と違った別の見方も紹介してくれる（最高3.8，最低3.2 平均3.6）６．授業が興味深く触発されることが多い（最高4.1，最低3.1 平均3.7）７．学生に対して関心が深い（最高4.3，最低3.4 平均3.8）８．担当科目に情熱を持っている（最高4.

症例は84歳，男性．全身倦怠感で入院，腹部CTで偶然に両側副腎腫瘤が認められた．経過観察となったが退院2ヶ月後，全身状態が悪化し死亡された．解剖の結果，真菌感染が考えられ，免疫染色，遺伝子検索の結果，Histoplasma capsulatumと診断された．海外渡航歴はなく，国内に定着している可能性が疑われた．

84歳、男性。４ヶ月前から食欲不振、全身倦怠感出現し、腹部CTにて両側副腎腫瘤が指摘された。治療検査目的で入院したが、高齢のため経過観察となっていた。２ヶ月後状態悪化し再入院し治療するも改善なく死亡し病理解剖が施行された。目立った合併症、悪性腫瘍はなく海外渡航歴はなかった。剖検では両側副腎を含む全身臓器に真菌の播種が認められた。免疫染色、遺伝子検索の結果Histoplasma capsulatumと同定された。本疾患は大部分は輸入感染症と認識されているが近年ごく稀に国内発生例と思われる報告がみられる。

悪性神経膠腫に対しBNCTを行った。BNCTは硼素化合物を使用し、腫瘍選択的治療として期待される。病理学的に神経組織に対し腫瘍選択性が認められたが、脈管への影響もあり効果の検討を考慮する必要がある。

症例は53歳、女性。労作時胸痛出現のため受診し精査目的で入院。その後のfollow中に内視鏡検査において食道全体に多数の黄白色斑状病変がみられ一部に小隆起性病変が認められた。生検の結果、食道にはまれな異所性皮脂腺とsteatocytoma様嚢胞と考えられた。

40歳台、男性の診断に苦慮した肝腫瘍の１例を報告した。腹部CTにて多発性肝SOLを指摘され内分泌癌と診断されたが原発は不明であった。抗癌剤治療中に敗血症を併発し死亡。病理解剖の結果、肝臓と胆嚢には直接浸潤像はないが胆嚢原発の腺内分泌細胞癌が考えられた。

症例は52歳，女性．虫垂間膜に嚢胞性病変がみられ，内腔に漿液の貯留がみられた．嚢胞は虫垂，結腸との連続性は認められなかった．上皮に異型はみられず，浸潤像もみられなかった．特染，免疫の結果，上皮細胞は中皮由来と考えられた．鑑別診断，文献的考察を加えて報告した．

53歳，女性の患者で，内視鏡検査で偶然見つかった多発性食道異所性皮質腺の症例を報告した．皮膚腫瘍のsteatocystomaと酷似する組織像であった．異所性皮質腺は全身で報告例があるが，いずれも稀であり，その存在を認識しておく必要があると思われた．

52歳、女性。虫垂根部に腸間膜嚢胞の形成が認められた稀な症例を経験したので報告した。嚢胞は虫垂、結腸との連続性はなくmesentric cystが考えられた。組織学的検索、免疫染色等での検索の結果中皮由来が考えられた。鑑別診断や文献的考察を加えて報告した。

69歳，女性の胃粘膜下腫瘍で稀な組織型を呈した症例を報告した．胃亜全摘が施行され，組織学的にGISTに類似した組織であった．免疫染色ではvimentin陽性で，CD117, CD34は陰性であった．電顕観察を加え総合的に判断するもGISTのどの分類にも当てはまらず，悪性間葉系腫瘍と診断した．

症例は64歳，男性．検査の結果，胃癌と診断され胃全摘出術が施行された．組織学的には中分化型腺癌であり，一部はhCG陽性を示した．間質の一部に著明な好酸性無構造物質の沈着が認められ，PAS(+), PTAHで赤褐色を呈し，電顕では大量の線維状物質が認められた．本態は不明であるが，腫瘍細胞が産生する特異な所見と思われた．