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Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma.We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations.This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival.Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.

Cystic brain metastasis is a rare condition that mainly originates from lung or breast adenocarcinomas. By contrast, pulmonary spindle cell carcinoma, a rare type of non-small cell carcinoma, has not been reported with this condition. Cystic brain metastases are characterized by larger tumor sizes with increased peritumoral edema compared with solid metastases. Therefore, specific treatment strategies are required for intracranial disease control. Immunotherapy has recently been demonstrated to be crucial for treating pulmonary sarcomatoid carcinomas based on high programmed cell death-ligand 1 (PD-L1) expression observed in these cancers. The present report describes the case of an 82-year-old man diagnosed with pulmonary spindle cell carcinoma, a rare subtype of sarcomatoid carcinoma. At 7 months after the diagnosis, the patient complained of a walking disturbance for which de novo brain metastasis with peritumoral edema was the causative agent. The brain tumor had a large cystic component, and thus, an Ommaya reservoir catheter was implanted for cyst aspiration but collapsed early without sufficient volume reduction. The patient was transferred to receive twice-split gamma knife treatment, which shrank the solid compartment and reduced the cyst volume, thereby relieving neurological defects. The patient was subsequently treated with immunotherapy targeting programmed cell death-1 based on the high PD-L1 expression in the lung tumor specimen. The thoracic tumors regressed following immunotherapy and progression-free survival was maintained for 16 months. To the best of our knowledge, the present report provides the first description of focal and systemic therapies for pulmonary spindle cell carcinoma with cystic brain metastasis. The report also discusses the treatment strategies for cystic brain metastases and reviews cases of pulmonary spindle cell carcinoma treated with immune checkpoint inhibitors.

Pulmonary sarcoidosis may occasionally present with large bullae, but the clinical implications of this finding remain unclear. We herein report the complete clinical course of a case of pulmonary bullous sarcoidosis. Chest computed tomography initially showed subpleural and peribronchovascular lung opacities, and bullae spontaneously developed in adjacent less-affected regions, probably via a retraction mechanism. Bullae progression was refractory to corticosteroid treatment and associated with deterioration of respiratory symptoms. The later phase involved repeated bacterial and fungal infections of the bullous lungs, eventually causing respiratory failure and mortality. Postmortem examinations revealed aggressive pulmonary Mycobacterium avium infection and diffuse alveolar damage.

Background and aims The current goal of treatment for ulcerative colitis [UC] is endoscopic and ultimately histological mucosal healing. However, there is no consensus on the definition of histological mucosal healing. We evaluated histological risk factors for clinical relapse in UC patients with endoscopically normal mucosa to focus on the importance of histological evaluation. Methods Patients with UC who underwent colonoscopy confirming Mayo endoscopic subscore [MES] ≤ 1 with biopsies were enrolled into this retrospective cohort. Three expert pathologists evaluated the presence or absence of chronic inflammatory cell infiltrate, breaches in the surface epithelium, crypt abscesses, mucin depletion, crypt architectural irregularities and basal plasmacytosis. Clinical relapse was defined as partial Mayo score ≥ 3 or modification of induction treatment. Prediction models of clinical relapse were generated, especially in patients with MES 0. Results A total of 194 UC patients were enrolled. Histological abnormalities existed more frequently in patients with MES 1 than those with MES 0, while the vast majority of patients still possessed at least one abnormality. There was no significant difference in time to relapse between MES 0 and 1. Crypt architectural irregularities and mucin depletion were associated with time to relapse in patients with MES ≤ 1. In patients with MES 0, the presence of mucin depletion was the only factor significantly and independently associated with the risk of relapse (hazard ratio, 2.18 [1.16-5.82]; p = 0.03). Conclusions Mucin depletion was shown to be a histological risk factor for clinical relapse in UC patients with MES 0.

Background Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue tumor that generally involves the retroperitoneum, pelvis, omentum and mesentery in younger patients. However, extra-abdominal DSRCT is very rare. Case presentation A 49-year-old Japanese man noticed a mass in the right parotid gland. Ultrasound examination revealed a solid tumor about 2 cm in diameter. Computed tomography (CT) of the whole body revealed no other tumors or lymph node swelling. Superficial parotidectomy was performed. Histologically, the tumor was composed of various-sized tumor cell nests in an abundant fibromyxoid and collagenous background. The tumor cells were small to medium-sized. Immunohistochemistry showed that the tumor cells were immunoreactive for epithelial markers and desmin. They also showed strong nuclear staining with a Wilms tumor 1 (WT1) antibody detecting the C-terminal region (C-WT1), but not the N-terminal region (N-WT1). We also performed 3′/5′ expression imbalance assay based on reverse transcription polymerase chain reaction (RT-PCR) to determine whether aberrant WT1 gene expression was present. This tumor was found to lack 5′-regional expression of the WT1 gene, as well as immunoreactivity with the N-WT1 antibody. Finally, fluorescence in situ hybridization (FISH) and RT-PCR analyses revealed the presence of a gene showing fusion between exon 7 of EWSR1 and exon 8 of WT1. The tumor was diagnosed as a DSRCT of the right parotid gland. The patient has been followed for 3 years without recurrence or metastasis. Conclusions Although DSRCT in the salivary gland is extremely rare, it should be included in the differential diagnosis of poorly differentiated salivary gland neoplasms, especially with a fibromyxoid background. Pathologists should bear in mind that DSRCT may occur in major salivary glands and should perform immunohistochemistry with appropriate antibodies, not only those against keratin and desmin, but also one detecting the C-terminal region of WT-1. Furthermore, molecular detection of EWSR1-WT1 fusion gene conclusively confirmed the diagnosis of DSRCT in this uncommon location.

Transformation of human embryonic stem cells (hESC) is of interest to scientists who use them as a raw material for cell-processed therapeutic products. However, the WHO and ICH guidelines provide only study design advice and general principles for tumorigenicity tests. In this study, we performed in vivo tumorigenicity tests (teratoma formation) and genome-wide sequencing analysis of undifferentiated hESCs i.e. SEES-1, -2 and -3 cells. We followed up with teratoma formation histopathologically after subcutaneous injection of SEES cells into immunodeficient mice in a qualitative manner and investigated the transforming potential of the teratomas. Maturity of SEES-teratomas perceptibly increased after long-term implantation, while areas of each tissue component remained unchanged. We found neither atypical cells/structures nor cancer in the teratomas even after long-term implantation. The teratomas generated by SEES cells matured histologically over time and did not increase in size. We also analyzed genomic structures and sequences of SEES cells during cultivation by SNP bead arrays and next-generation sequencing, respectively. The nucleotide substitution rate was 3.1 × 10−9, 4.0 × 10−9, and 4.6 × 10−9 per each division in SEES-1, SEES-2, and SEES-3 cells, respectively. Heterozygous single-nucleotide variations were detected, but no significant homologous mutations were found. Taken together, these results imply that SEES-1, -2, and -3 cells do not exhibit in vivo transformation and in vitro genomic instability.

Pulmonary artery intimal sarcoma (PAIS) is a rare mesenchymal malignancy arising in the pulmonary trunk or proximal pulmonary artery and shows intraluminal growth. Clinical manifestations in PAIS are predominantly related to the pulmonary artery embolism, so cases with initial symptoms related to an extrapulmonary metastasis are unusual. The present report describes an 82-year-old man without any cardiopulmonary symptoms who was detected with an abnormal shadow on chest radiography during a routine health checkup. Contrast medium-enhanced chest computed tomography revealed an enhancing mass in the right pulmonary artery, pulmonary nodules, and a chest wall tumor corresponding to the abnormal shadow observed using chest radiography. A core needle biopsy for the chest wall tumor determined a pathological diagnosis of unclassified sarcoma. The patient was diagnosed with PAIS on the basis of clinical, radiological, and pathological correlations. He was scheduled to receive supportive care, but died of respiratory failure 1 year from the first visit. An autopsy revealed the pleomorphic sarcoma occupying the entire lumen of the right pulmonary artery with the only site of extrapulmonary metastasis in the chest wall. We should be aware of rare cases of asymptomatic PAIS found through routine health checkups.

A 59-year-old woman was referred to our hospital with the finding of an incidentaloma in her right kidney. Computed tomographyand magnetic resonance imaging showed a solid tumor, approximately8 cm in diameter, at the lower pole of the right kidney. Partial nephrectomy was performed without a renal vessel clamp. Histopathologically, fibroblast-like spindle cells were proliferating with rich collagenous fibers, and tumor cells were infiltrated into the renal parenchyma. The tumor cells were stained positive with CD34, CD99, and bcl-2. The tumor was diagnosed as solitaryfibrous tumor originating from the kidney based on these histopathological findings. The patient was followed 3 years after surgery with neither recurrence nor metastasis.

Objectives: Salivary gland cancer is a rare cancer that has no effective drug therapy available. It comprises salivary duct carcinoma (SDC) as a major histology, which resembles high-grade breast ductal carcinoma and often overexpresses HER2. The purpose of this study is to evaluate the efficacy and safety of trastuzumab and docetaxel therapy in patients (pts) with HER2-positive salivary gland carcinoma. Methods: We conducted a multicenter, single-arm Phase II study of trastuzumab and docetaxel for pts with HER2-positive recurrent and/or metastatic salivary gland carcinoma pursuant to the J-GCP. HER2 positivity was defined as immunohistochemistry (IHC) 3+ or IHC 2+/dual color in situ hybridization (DISH) +. Eligible pts were treated with trastuzumab 6 mg/kg (loading dose 8 mg/kg) and docetaxel 70 mg/m2 every 3 weeks up to 8 cycles. The primary endpoint was overall response rate (ORR) using RECIST v1.1 assessed by the blinded independent review committee (BIRC). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. This study required 16 pts, with ORR of 25% considered non-promising and 70% promising (two-sided alpha = 0.05; beta = 0.1) and with 2 withdrawal pts. Results: Sixteen pts were recruited in this trial. The median age was 59 (range 26-72), 3 pts were female, and all pts had performance status 0-1. All pts had carcinomas histologically compatible with SDCs by central pathology review of samples used for HER2 evaluation, 14 of which were readily confirmed as SDCs. All pts had HER2 IHC 3+ tumors. Two pts were previously untreated and had metastatic disease. The remaining 14 pts had recurrence after surgery that was followed by adjuvant chemoradiotherapy in 5 pts and by adjuvant radiotherapy in 6 pts. No pts were previously treated with chemotherapy alone. After excluding a pt without measurable lesions evaluated by BIRC, ORR by BIRC was 60% (9/15; 95% CI, 32.3~83.7) with one complete response. Median PFS was 8.5 months (95% CI, 6.0~12.7). Median OS was not reached at a median follow-up of 17.9 months in survivors. Common grade 3/4 adverse events (> 10%) were neutropenia (16 pts, 100%), leukopenia (15 pts, 93.8%), lymphopenia (3 pts, 18.8%), and febrile neutropenia (2 pts, 12.5%). Treatment-related death occurred in 1 pt (6.3%) due to hypoalbuminemia. Conclusions: This study demonstrated a promising efficacy with predictable toxicities. Trastuzumab and docetaxel therapy may be an effective treatment option in pts with HER2-positive recurrent and/or metastatic salivary gland carcinoma. Citation Format: Ichiro Kinoshita, Satoshi Kano, Yasushi Shimizu, Naomi Kiyota, Yuichiro Tada, Kei Ijichi, Tmoko Yamazaki, Akihiro Homma, Yoichi M. Ito, Kota Ono, Keiko Kobayashi, Toshiyuki Isoe, Yutaka Hatanaka, Hitoshi Tsuda, Shojiroh Morinaga, Yoshihiro Matsuno, Hirotoshi Dosaka-Akita. Phase II study of trastuzumab and docetaxel therapy in patients with HER2-positive recurrent and/or metastatic salivary gland carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT137.

We report an atypical case of non-sebaceous lymphadenoma (NSL) of the parotid gland showing serous acinic cell differentiation. NSL is a rare benign salivary gland tumor with intermingled lymphoid and epithelial tissues without sebaceous differentiation. Since the first description of a case designated by Auclair et al. as 'non-sebaceous lymphadenoma' in 1991, to our best knowledge, only 37 cases have been reported, and no differentiation of tumor cells into serous acinic cell lineage has been described so far. In this paper, we present a case of NSL with serous acinic cell differentiation. The patient was a 78-year-old female with the complaint of a painless mass in the left parotid gland. The surgically resected tumor was encapsulated and measured 13 × 9 × 9 mm. Histologically, the tumor had the features of NSL, and an unusual finding of this case was the presence of epithelial cells with serous acinic cell differentiation. Dense cytoplasm packed with basophilic granules in those cells was positive in periodic acid Schiff reaction after diastase digestion (D-PAS), which was compatible with the feature of serous acinic cell differentiation. Possible differentiation of the epithelial component into serous acinic cell in this rare entity is warranted to avoid confusion in the diagnosis.

Low-grade cribriform cystadenocarcinoma (LGCCC) is a recently described rare tumor of the salivary gland; this tumor most frequently arises from the parotid gland. Here, we describe a case of LGCCC arising from a minor salivary gland in the buccal mucosa. A 72-year-old man had a small mass on the left buccal mucosa. The mass was completely resected, and the postoperative course was uneventful. Histopathologically, the tumor comprised a single cyst with intraductal proliferation. Based on these histopathological findings along with immunohistochemistry a diagnosis of LGCCC arising from a minor salivary gland was made. (J Oral Sci 58, 145-149, 2016).

Background— A myocardial bridge (MB) that partially covers the course of the left anterior descending coronary artery (LAD) sometimes causes myocardial ischemia, primarily because of hemodynamic deterioration, but without atherosclerosis. However, the mechanism of occurrence of myocardial infarction (MI) as a result of an MB in patients with spontaneously developing atherosclerosis is unclear. Methods and Results— One hundred consecutive autopsied MI hearts either with MBs [MI(+)MB(+) group; n=46] or without MBs (n=54) were obtained, as were 200 normal hearts, 100 with MBs [MI(−)MB(+) group] and 100 without MBs. By microscopy on LADs that were consecutively cross-sectioned at 5-mm intervals, the extent and distribution of LAD atherosclerosis were investigated histomorphometrically in conjunction with the anatomic properties of the MB, such as its thickness, length, and location and the MB muscle index (MB thickness multiplied by MB length), according to MI and MB status. In the MI(+)MB(+) group, the MB showed a significantly greater thickness and greater MB muscle index ( P P P Conclusions— In the proximal LAD with an MB, MB muscle index is associated with a shift of coronary disease more proximally, an effect that may increase the risk of MI.

Background and Aim: The effect of polaprezinc, a zinc-carnosine chelate compound, on the development of non-alcoholic steatohepatitis (NASH) was investigated in dietary methionine and choline deficient (MCD) mice. Methods: Mice were fed the MCD diet with or without polaprezinc (2.2 g/kg diet) for 10 weeks. Liver histopathology, triglyceride and lipid peroxide levels, and the expression of genes linked to fibrosis were then assessed. Results: MCD mice developed steatohepatitis accompanied by mild fibrosis with an increase in lipid peroxidation, hepatic stellate cell (HSC) activation, and the augmented mRNA expression of tumor necrosis factor-α, transforming growth factor-β1 and procollagen α1(I). The mRNA expression levels of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were also enhanced. Histopathologically, polaprezinc supplementation did not influence the development of steatosis but it apparently attenuated fibrosis. Polaprezinc slightly reduced lipid peroxidation and suppressed HSC activation as well as the mRNA expression of pro-inflammatory cytokines. Polaprezinc affected the MCD diet-enhanced expression of TIMP-1 even when administered relatively late. Conclusion: These results suggest that polaprezinc attenuates fibrosis in NASH by reducing inflammation and lipid peroxidation and, during a later phase, promoting fibrolysis via the inhibition of TIMP expression in the liver. Further investigation is required to clarify the clinical efficacy of polaprezinc in patients with NASH.

Histological criteria for subclassification of intraductal papillary mucinous tumor (IPMT) and mucinous cystic tumor (MCT) of the pancreas remain ambiguous in the absence of apparent invasion or metastasis. To elucidate this issue, we evaluated clonality and K- ras mutations in 11 cystic tumors of the pancreas from female patients, including 7 IPMTs and 4 MCTs. The analyses were performed on DNA from laser microdissected epithelia showing different degrees of atypia as well as normal-appearing epithelia (NAE) in the individual tumors. The grades of atypia were classified into three groups on conventional hematoxylin-eosin staining. Clonality was assessed using the methylation-induced polymorphic inactivation of the X-linked phosphoglycerate kinase gene. The incidence of monoclonality increased with the grades of atypia: 27% for NAE, 43% for grade 1, and 100% for grades 2 and 3. In three of four MCTs, foci of NAE were polyclonal, while monoclonality was seen in each one of grades 1 and 2. The frequency of K- ras mutation depended on the grades of atypia: 0% for NAE, 29% for grade 1, 50% for grade 2, and 75% for grade 3. Polyclonal epithelia were devoid of K- ras mutation in 92% of sites, while monoclonality was associated with both wild and mutational types in an approximately equal ratio. Both IPMT and MCT seem to arise from polyclonal epithelia and to be replaced by monoclonal neoplastic cells as they undergo dysplastic changes and K- ras mutation. These data suggest that the monoclonal expansion precedes K- ras mutation.

目的:唾液腺上皮筋上皮癌の細胞像の特徴と多様性を明らかにすることを目的とした.方法:穿刺吸引細胞診施行後に切除された唾液腺上皮筋上皮癌4例を用いて, 細胞像と切除標本の組織像を対比した. また, 切除標本に対して, 種々の抗体を用いて, 免疫組織化学的に検討したほか, 細胞診標本については, ケラチン (KL-1) と平滑筋アクチン (α-smooth muscleactin, α-SMA) の二重免疫染色を施行して検討した.成績:組織学的に問質の硬化が少なく筋上皮細胞成分の多い定型的な症例では, 異型の乏しい上皮細胞集塊とともに, 背景に多数の裸核状の筋上皮細胞がみられた. 組織学的に乳頭状構造を持つものは細胞診標本でも乳頭状構造が認められた. 腺様嚢胞癌に類似した節状構造が部分的にみられた症例では, 細胞診標本にも粘液球が見出された. 二重免疫染色では, 細胞集塊の中心部がKL-1陽性, 辺縁部と背景の裸核細胞がα-SMA陽性を示した.結論:本腫瘍には特徴的な細胞像がみられたが, 同時に多様性もみられ, 細胞診のみでの診断は困難と思われた. パパニコロウ染色では, 上皮細胞と筋上皮細胞との区別が困難な場合があったが, 二重染色により両成分の分布が明瞭に染め分けられた.

Type 2 diabetes (T2D) is a metabolic disease affecting >370 million people worldwide. It is characterized by obesity-induced insulin resistance, and growing evidence has indicated that this causative link between obesity and insulin resistance is associated with visceral adipose tissue inflammation. However, using anti-inflammatory drugs to treat insulin resistance and T2D is not a common practice. We recently applied a bioinformatics methodology to open public data and found that CD44 plays a critical role in the development of adipose tissue inflammation and insulin resistance. In this report, we examined the role of CD44 in T2D by administering daily injections of anti-CD44 monoclonal antibody (mAb) in a high-fat–diet mouse model. Four weeks of therapy with CD44 mAb suppressed visceral adipose tissue inflammation compared with controls and reduced fasting blood glucose levels, weight gain, liver steatosis, and insulin resistance to levels comparable to or better than therapy with the drugs metformin and pioglitazone. These findings suggest that CD44 mAb may be useful as a prototype drug for therapy of T2D by breaking the links between obesity and insulin resistance.

Gastrointestinal stromal tumor (GIST) is currently considered to be derived from the interstitial cells of Cajal (ICC). To test the hypothesis that omental mesenchymal tumor is also a type of GIST, we evaluated the expression of specific molecules in GIST, and c-kit gene mutation in omental mesenchymal tumors, and we identified a possible counterpart of ICC in the omentum. Immunohistochemically, all of the omental mesenchymal tumors (n = 5) were positive for both KIT and CD34, and three of the five tumors were also positive for an embryonic form of smooth-muscle myosin heavy chain (SMemb). Polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing revealed mutations in c-kit gene exon 11 in all five tumors. As for the ICC counterparts in the omentum, there were some KIT-positive mesenchymal cells resembling ICC at the surface of the omentum. Double fluorescence immunostaining, using anti-KIT polyclonal antibodies and monoclonal antibodies against other molecules, demonstrated that KIT-, CD34- and SMemb-positive cells were present just beneath the mesothelial cells of the omentum. These results show that omental mesenchymal tumor corresponds to GIST of the omentum, and that KIT-positive bipolar mesenchymal cells may be a counterpart of ICC in the gastrointestinal tract. Identification of a new type of KIT-positive mesenchymal cell in the omentum may lead to the discovery of a new physiological role for this organ.

Gain-of-function mutation in c-kit proto-oncogene exon 11 has been described in about 20 -- 50% of gastrointestinal stroma tumor (GIST). Recently, additional mutational hot-spots in exon 9 and exon 13 of the c-kit gene have been reported in GISTs without mutations of exon 11, but a subsequent report in a Western population indicated that only a small portion of GISTs (eight of 200 GISTs, 4%) showed mutations in these regions. In this study, we evaluated mutations in exon 9 and exon 13 of the c-kit gene by both polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing in 48 GISTs in a Japanese population, for which the clinicopathological and immunohistochemical features and mutations in exon 11 had previously been reported. C-kit gene mutation in exon 9, representing insertion of GCC TAT, was identified in only 4 of 48 GISTs (8%), and none of the GISTs had mutations in exon 13. All four GISTs with mutation in exon 9 were high-risk, and the patients died of multiple tumor metastasis. Mutations in exon 9 and exon 13 of the c-kit gene were also rare events in Japanese GISTs and were related to a poor prognosis. These results in Japanese are consistent with those in Western populations, although a preferential occurrence of GISTs with exon 9 mutation in the small intestine, which was suggested in a previous report, was not observed.

The pathologic features of silent hyperintense white matter lesions in T2-weighted images on MRI were studied in patients with no neurologic signs or symptoms. The small patchy hyperintense white matter lesions represented myelin pallor associated with vessels showing hypertension and arteriosclerotic changes. 'Caps' also showed myelin pallor with dilated perivascular spaces. There were no lacunar infarcts in these lesions. Some of 'caps' was shown to be elongated normal lateral ventricle. 'Rims' of early stage revealed subependymal gliosis that was a part of normal aging processes.

To elucidate the mechanism of tumor extension in human pulmonary adenocarcinoma, we immunohistochemically investigated the expression of cell cycle regulator proteins in 54 small adenocarcinomas less than 3 cm in diameter. The Ki-67-labeling index was significantly higher in the periphery of the tumor nodule than in the center. This proliferative potential correlated well with coexpression of cdk2 and cyclin A. p27, one of the cdk inhibitors, was highly expressed in normal bronchial epithelial cells. Peripherally located tumor cells expressed p27 at an intermediate level, but at a higher frequency and level than those in the center. Expression of p21 was also predominant in the periphery. Furthermore, the expression patterns of p21 and p27 were reciprocal. In vitro kinase assays further demonstrated higher cdk2 kinase activity in the periphery. These results suggest that: (i) within an emerging extension made up of peripherally located tumor cells, their high proliferative potential gradually wanes as their relative topographical position becomes more central in the expanding tumor; (ii) peripherally located tumor cells maintain their proliferative potential by higher cyclin A-cdk2 complex activity; and (iii) intermediate expression of p21/p27 in the peripherally located cells promotes higher cyclin A-cdk2 kinase activity, whereas high p21/p27 expression in nonneoplastic cells inhibits kinase activity.

胸腔鏡下生検において肺癌の診断効率を向上させるために胸腔鏡下あるいは開胸生検された30mm以下の肺末梢限局性陰影122例の生検理由を中心に検討した.肺癌44例と炎症性腫瘤 (結核, 非特異的炎症) 40例の間で生検理由が画像上の悪性所見であった頻度に差はなかった.以前のX-Pと比較して肺癌は炎症性腫瘤より陰影の増大が多く新たに出現したものが少なかった (P

A 56-year-old man was referred to our hospital for evaluation of episodic disturbance of consciousness. Hypoglycemic symptoms were noted and Whipple's triad was satisfied. The 75 g OGTT and the glucagon test revealed a high baseline insulin level and hyperreactivity to glucagon. A pancreatic tumor and liver metastases were found by abdominal computed tomography (CT). Based on the finding of liver biopsy, the final diagnosis was malignant insulinoma with liver metastasis. He selected conservative treatment and no hypoglycemic crisis has occurred for one year since discharge. Early diagnosis and long-term follow-up is necessary since this tumor is slow growing.

Serum levels of protein 1 (P1), a Clara cell protein known to have an antiinflammatory effect, were studied in 33 patients with lung cancer before surgery, and 3, 7, 14, 21 days, and 2 months after surgery. The preoperative P1 values of the lung cancer patients were compared with those of 66 healthy controls matched by sex and age. The postoperative changes in P1 which occurred in the lung cancer patients were compared with those in 16 patients who underwent laparotomy for gastric or colon cancer. There was no significant difference in the P1 values between the lung cancer patients and the healthy controls; however, the postoperative P1 values showed a significant decrease 3, 7, (P0.001), and 14 days (P0.05) postoperatively, recovering to normal within 2 months after surgery. One patient who died of postoperative pneumonia showed decreasing serum P1 levels until death. None of the laparotomy patients showed any decrease in P1 serum levels. Thus, we conclude that: (a) serum P1 levels do not differ between lung cancer patients and healthy individuals; (b) serum P1 levels significantly decrease in the early postoperative period, but recover within 2 months after lung resection; and (c) the postoperative changes that occur in serum P1 levels could provide important information about recovery from intraoperative lung damage.

Serum levels of protein 1 (P1), a Clara cell secretory protein, were studied in 942 healthy subjects in relation to sex, age, and smoking habits and in 117 patients with bacterial pneumonia in relation to prognosis. P1 values in bacterial pneumonia patients at disease onset were compared with those in 234 healthy control subjects matched by sex and age. P1 values in healthy males were highest in those 30 to 39 yr of age and highest in healthy femalesor = 70 yr of age but lowest in those 30 to 49 yr of age. P1 values in healthy males were significantly higher than those in females in the 30- to 39-yr age group (p0.05). Male smokers showed higher P1 values than nonsmokers, but without a significant difference. P1 values in patients with pneumonia were significantly lower than in control subjects (p0.0001). P1 values were significantly lower in patients treated with a respirator than in in patients treated without a respirator (p0.05). In 59 patients, whose P1 values could be followed up until the outcome of pneumonia, all 37 recovered patients showed significantly increased P1 values after recovery (p0.001), and all 22 who died of their illness showed significantly decreased P1 values just before death (p0.01). We thus conclude that P1 serum levels were significantly affected by sex and by the degree of seriousness in bacterial pneumonia.

長期CAPDを可能にするためには腹膜機能の長期保持は重要な問題と考えられる. 今回, 我々はCAPD歴3年で適正透析処方していたにもかかわらず, 徐々に全身倦怠感, 貧血の進行, 皮膚〓痒感増強, 血清尿素窒素濃度 (SUN) 上昇などのいわゆる透析不足状態 (underdialysis) と思われる症状が進行した症例を経験した. 本症例は腹膜平衡試験 (PET) で限外濾過能がよく保たれ, 溶質除去能のみの低下が証明された. テンコフカテーテル抜去時に腹膜組織の採取を行い, 線維性肥厚とフィブリンの析出および軽度のリンパ球浸潤を観察し得た. 本症例においては腹膜面積の減少や交換透析液量不足などの原因は認められず, 溶質除去能の低下は腹膜機能自体に起因するものと考えられた. このためCAPDを断念し血液透析 (HD) へ移行した.現在までに腹膜機能低下によるCAPD中止症例の多くは除水能 (限外濾過能) 低下を示す症例であり, 溶質除去能低下のみでCAPD中止に至った症例は稀であるため若干の知見を加えて報告する.

A surgical case of teratoma with malignant transformation (TMT) of the mediastinum in a 66-year-old man is reported. The unilocular, cystic, mediastinal mass, which had been seen in a chest radiograph 7 years earlier, was extirpated. The mass was histologically revealed to be a mature cystic teratoma containing skin and respiratory epithelial tissues, with some areas of well-differentiated adenocarcinoma. Surgical cases of TMT in the mediastinum, which have not received any preoperative chemotherapy or radiation therapy, are rare. By reviewing the previous literature on TMT in various organs, the authors distinguished two types of TMT, chemotherapy- or radiotherapy-induced TMT and naturally occurring TMT. The pathogenesis of these two types are discussed.

Objective Anatomic properties of myocardial bridge (MB) are sometimes responsible for myocardial infarction (MI) through the changes in the atherosclerosis distribution in the left ascending coronary artery (LAD). The purpose of this study was to investigate histopathologic profiles of atherosclerotic lesions resulting from the MB presence in the LAD in the MI cases. Methods In 150 consecutive autopsied MI hearts either with MBs [MI(+)MB(+); n = 67] or without MBs [MI(+)MB(−); n = 83] and 100 normal hearts with MBs [MI(−)MB(+)], LADs were consecutively cross-sectioned at 5-mm intervals. The most advanced intimal lesion and unstable plaque-related lesion characteristics (UPLCs) in each section were histopathologically evaluated in conjunction with the anatomic properties of the MB, such as its thickness, length, location, and MB muscle volume burden (MMV: the total volume of MB thickness multiplied by MB length). Results The MB showed a significantly greater thickness ( P = 0.0090), length ( P = 0.0300), and MMV ( P = 0.0019) in MI(+)MB(+) than in MI(−)MB(+). Mean age of acute MI cases was significantly younger ( P = 0.0227) in MI(+)MB(+) than in MI(+)MB(−). Frequency of plaque fissure/rupture in the proximal LAD was significantly higher in acute MI cases of MI(+)MB(+) than in MI(+)MB(−). UPLCs tended to be located proximally in MI(+)MB(+) and frequent 2.0 cm or more proximal to the MB entrance in MI(+)MB(+). Conclusion In MI(+)MB(+), UPLCs tend to be located more proximally, and a plaque in the LAD proximal to the MB is prone to rupture, resulting in MI at younger age.

An expandable metallic stent was used in 9 patients with tracheobronchial stenosis. Of the 8 patients with malignant stenosis, 6 had extrinsic compression and 2 had intraluminal tumor invasion. The 1 patient with nonmalignant stenosis had postreconstruction bronchomalacia and granulation tissue affecting different parts of the tracheobronchial tree. The expandable metallic stent successfully dilated tracheobronchial stenosis due to extrinsic tumor compression and malacia. However, it was not effective for stenosis due to intraluminal tumor invasion or granulation tissue because of the growth of tumor or granulation tissue between the wires of the stent. However, an expandable metallic stent covered with Dacron mesh was effective in 1 patient with intraluminal tumor invasion because tumor growth was blocked by the mesh. We conclude that an expandable metallic stent is effective for tracheobronchial stenosis due to extrinsic tumor compression, but not for stenosis due to intraluminal tumor invasion or granulation tissue.

A 44-year-old man with neurofibromatosis suffered from severe diarrhea and progressive hypoproteinemia. Enteric protein loss was confirmed by an alpha 1-antitrypsin clearance test. An x-ray study showed irregular mucosa in the distal segment of the ileum. Protein loss has subsided after ileocecal resection. Laparotomy and radiological examinations failed to demonstrate neurofibroma or other tumors in the abdomen. The resected ileum revealed marked edema of the wall and a pseudomembranous enteritis-like appearance in the luminal surface. Microscopically, lymphatic vessels in the intestinal wall were dilated. Marked thickening of the intima with spindle cell proliferation was observed in the mesenteric arteries and veins. This finding is consistent with vascular changes in neurofibromatosis. These vascular changes in the mesentery due to neurofibromatosis may cause protein-losing enteropathy by altering the hemodynamic state and microvascular permeability in the intestine.

We appreciate Dr Poullis’ interest in our study on myocardial bridge (MB) predisposing to myocardial infarction.1 The MB-positive group without myocardial infarction in that study included case subjects who had short and thin MBs and atherosclerosis was more extensive in the left anterior descending coronary artery proximal to MBs that were long and thick.2 Hemodynamic change by retrograde …

Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically, and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II. The amount of adenocarcinoma component did not affect the survival rate, although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors. The histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants.