Yasuhiko Watarai

Comparison of urine cytology between the ileal conduit and Indiana pouch

OBJECTIVE To compare the cytomorphologic features of urine obtained from two different kinds of urinary diversions constructed after total bladder resection. STUDY DESIGN The smears of urine from 11 ileal conduits and 6 Indiana pouches were evaluated. All patients underwent total bladder resection due to transitional cell carcinoma (TCC) or other kinds of cancer before urine diversion. RESULTS The cytologic features of Indiana pouch urine include degenerated, small, round cells without columnar cells derived from intestinal epithelium. In ileal conduit urine, well-preserved columnar cells and degenerated, small, round cells were frequently observed. The columnar cells in ileal conduit urine exhibited cytologic features that should be distinguished from TCC cells. CONCLUSION The method of reconstructing the urinary tract is important in urine cytology from urine diversions because the cytomorphologic features of urine are different between the two kinds of urinary diversions. Since columnar cells in ileal conduit urine might lead to misdiagnosis as TCC, special consideration is required to examine ileal conduit urine.

Apurinic/apyrimidinic endonuclease-1 is associated with angiogenesis and VEGF production via upregulation of COX-2 expression in esophageal cancer tissues.

Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme responsible for DNA base excision repair and is also a multifunctional protein such as redox effector for several transcriptional factors. Our study was designed to investigate APE-1 expression and to study its interaction with cyclooxygenase (COX)-2 expression and VEGF production in the esophageal cancer. The expression of APE-1, COX-2, monocyte chemoattractant protein (MCP)-1, CC-chemokine receptor (CCR)2, and VEGF were evaluated by immunohistochemistry in 65 human esophageal squamous cell carcinoma (ESCC) tissues. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of APE-1 and p-signal transducer and activator of transcription 3 (STAT3) expression in MCP-1-stimulated ESCC cell lines (KYSE 220 and EC-GI-10). siRNA for APE-1 was treated to determine the role of APE-1 in the regulation of COX-2 expression, VEGF production, and antiapoptotic effect against cisplatin. In human ESCC tissues, nuclear localization of APE-1 was observed in 92.3% (60/65) of all tissues. There was a significant relationship (P = 0.029, R = 0.49) between nuclear APE-1 and cytoplasmic COX-2 expression levels in the esophageal cancer tissues. In KYSE 220 and EC-GI-10 cells, MCP-1 stimulation significantly increased mRNA and protein expression of APE-1. Treatment with siRNA for APE-1 significantly inhibited p-STAT3 expression levels in MCP-1-stimulated cells. Furthermore, treatment of siRNA for APE-1 significantly reduced COX-2 expression and VEGF production in MCP-1-stimulated esophageal cancer cell lines. Treatment with APE-1 siRNA significantly increased apoptotic levels in cisplatin-incubated KYSE 220 and EC-GI-10 cells. We concluded that APE-1 is overexpressed and associated with COX-2 expression and VEGF production in esophageal cancer tissues.

Automated Primary Screening Devices

failure might vary widely. During the past year there has been a lull in the previously very active promotion of primary screening devices. It appears that economic projections for the manufacturers did not materialize. This offers a good opportunity to assess the situation and to suggest where the development might go from here. The first question to be raised requires that we return to the beginning. What is the problem that automation of primary screening is to solve? The often-quoted Wall Street Journal article (Bogdanich W: The pap test misses much cervical cancer through lab’s errors. Nov 2, 1987) called attention to several concerns. There were concerns about the reliability of the reading of a Pap smear, about the possibility of shortages in highly trained personnel and about labor costs. The resulting availability of capital for technology development undoubtedly responded to the need to support the control of cervical cancer, but one has to consider that a prime motivation was the potential for economic gain. There is nothing wrong with that notion in principle, but inevitably it had major consequences. The first consequence was that technical solutions to the problem were explored almost entirely with the medical/economic situation in the United States in mind. A device had to process a slide within a very short time frame so that system throughput would meet revenue projections. Device costs were weighed against amortization schemes, projected unit sales and return on investment capital. There were discussions about acceptable false negative rates and how these might be pegged to revised estimates of false negative rates in current laboratory practice. There were serious and justified concerns about the risk of lawsuits in the United States. One cannot help, though, particularly on the ocAfter 35 years of basic research and development, automated screening devices for cervical cancer went into clinical trials and entered clinical practice. The results have been encouraging and might be called a success in several ways. The United States FDA approved two devices; both proved to perform at a level equal to or better than claimed by the manufacturers. Beyond that the field tests established that it should be possible to design systems that might find approval by the cytopathology community. The devices in the clinical trials were, after all, only first-generation designs. There is no complex technology that performs at the level of its potential until several generations of designs have evolved. As first-generation devices, given the very substantial difficulties of the problem and the circumstances under which their development took place, they performed remarkably well. Eliminating design compromises dictated either by the state of technology at the time of development or by the development climate concomitant with venture capital financing would produce the next generation of primary screening systems that come much closer to a performance level well respected by medical professionals. One might hear the argument that since performance of the first-generation devices was critically assessed by the FDA in the United States, why should the profession call for improvements? It is true that the FDA approved these devices. However, one has to understand that the FDA here merely certified that the devices perform at the level claimed by the manufacturer. If one wanted to be unkind, one might suggest that the industry set its own standard. In practice it would essentially be the laboratory director who decides whether a claimed performance level can be maintained and is acceptable or not. The extent to which such a decision would be based on a thorough understanding

Apurinic/apyrimidinic endonuclease-1 (APE-1) is overexpressed via the activation of NF-κB-p65 in MCP-1-positive esophageal squamous cell carcinoma tissue

Apurinic/apyrimidinic endonuclease-1 (APE-1), a key enzyme responsible for DNA base excision repair (BER), has been linked to cancer chemoradiosensitivity. The phosphorylation of p65 plays a role in the activation of this pathway. In this study, we investigated APE-1 expression and its interaction with p65 in esophageal squamous cell carcinoma (ESCC) tissue. The expression of APE-1, p65, p65 nuclear localization sequence (p65-NLS), and monocyte chemoattractant protein-1 (MCP-1) was assessed by immunohistochemical analysis in 67 human ESCC tissue samples. Real-time PCR and western blotting were also performed. p65 siRNA was evaluated to determine the role of p65 in the regulation of APE-1 expression. We found nuclear localization of APE-1 in 89.6% (60/67) of ESCC tissue samples. We also observed the colocalization of p65-NLS and APE-1 in esophageal cancer tissue. In KYSE220 cells, pretreatment of MG-132 significantly abrogated upregulation of p65 and APE-1 levels induced by MCP-1, and treatment with 10 and 20 nM p65 siRNA significantly inhibited APE-1 mRNA expression. siRNA for p65 treatment significantly increased the apoptotic index in 5-FU-treated KYSE220 cells. We conclude that APE-1 is overexpressed and mainly localized in the nuclear compartment of cancer cells, and partly regulated by p65 in the NF-κB pathway in ESCC tissue.

Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants

Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants.

Fine needle aspiration cytology of the papillary thyroid carcinoma with a solid component: A cytological and clinical correlation

Solid variant of papillary thyroid carcinoma is a rare subtype of papillary thyroid carcinoma (PTC) containing a solid component (SC), and thus its cytological and clinicopathological features remain elusive. We examined fine needle aspiration (FNA) cytological features of PTC with variable degrees of SC (20‐80% of the tumor)(PTCSC) in comparison to well‐differentiated PTC (WPTC).

Mucinous carcinoma of the breast: a comparative study on cytohistological findings associated with neuroendocrine differentiation.

Mucinous carcinoma (MCA) may show neuroendocrine differentiation (ND), but the cytological features characteristic of ND remains elusive. We compared fine needle aspiration (FNA) findings of MCA between cases with high and low degrees of ND.

Breast carcinoma with osteoclast-like giant cells: A cytological-pathological correlation with a literature review

Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare disease characterized by the infiltration of OGCs in the tumor; however, cytological aspects of this tumor type remain elusive. We examined the cytological features in fine needle aspiration (FNA) biopsy smears obtained from 5 patients who were histologically diagnosed with breast carcinoma with OGCs. We compared FNA and clinicopathological findings with results from the published literature. Histological assessment of the resected samples showed that all tumors exhibited a histological grade 1 phenotype with a predominant cribriform architecture. Four patients were estrogen receptor positive, and 1 patient showed a triple negative phenotype. All patients survived without tumor recurrence. In the FNA smears, tumor cells were arranged in loosely cohesive clusters, characterized by varying degrees of OGCs infiltration and rare formation of solid tumor nests. Occasionally, 2- or 3-dimensional clusters of tumor cells were found, accompanied by OGCs at the peripheral regions. In all patients, tumor cells were small without severe nuclear atypia. None of the patients showed significant background necrosis. In summary, cytological features of breast carcinoma with OGCs are characterized by loose aggregates of low grade tumor cells, the presence of OGCs, and the absence of necrosis, all of which were consistent with features reported previously. This peculiar form of breast tumors should be included in the differential diagnosis, when physicians encounter FNA findings including low grade ductal carcinoma with the admixture of multinucleated giant cells or OGCs.

3 cases of invasive carcinoma with neuroendocrine features of the breast.

背景:神経内分泌細胞への分化neuroendocrine features (以下NEF) を伴う浸潤性乳癌は比較的まれであるが, 細胞診が診断に有用であった3症例を経験したので報告する.症例:全例女性, 症例1は28歳, 右前胸部打撲後腫瘤形成, 血性分泌が持続し来院. 症例2は45歳, 右乳房に約2cm大の腫瘤に気づき来院. 症例3は右乳房に自潰する約10cm大の腫瘤を認めた. これらの腫瘤の細胞診では, 結合性の比較的緩い小-中集塊ならびに不完全なロゼット様構造がみられた. 腫瘍細胞は軽度の大小不同を伴う中型の類円型細胞が主体で, クロマチンは細顆粒状で増量しN/C比大, 核型は軽度不整, 核小体は腫大していた. 細胞質は比較的豊富で重厚感と細顆粒状変化, 混濁したライトグリーン好染性を特徴とし浸潤性乳癌の所見とともにNEFを疑った. しかし, 各症例では, 多数のOsteoclast様多核巨細胞の出現, 背景に粘液成分を認めるなど, 多彩な所見もみられた. 組織所見でも, 同様な所見を認め, さらに, 腫瘍細胞では, Grimelius染色陽性, 免疫組織化学的に, Chromogranin AなどのNEFのマーカーが陽性となり, NEFを伴う浸潤性乳癌と診断された.結論:乳癌の細胞診においてもNEFの存在とその組織型の多彩さを念頭に置き診断することが必要と思われた.

Cytological evaluation of atypical lymphocytes in bronchoalveolar lavage fluid of hypersensitivity pneumonitis.

In hypersensitivity pneumonitis (HP), bronchoalveolar lavage (BAL) sometime show atypical lymphocytes (AT). We compared lymphocytes from (5 patients) with BAL flui from small lymphocytic lymphoma and leukemia (LL from 6 patients). In a Giemsa-stained specimen, 500 lymphocytes per case were categorized as N (normal), A (smaller than a neutrophil, atypical nuclear shape), AS (A with abnormal chromatin), and AL (larger than a neutrophil, with atypia), then calculated the ratio of each category. AT accounted for 14 to 22%(A + AS, AL= 0%) in HP, but LL showed a high A+AS ratio (>51.7%) with AL (>0.2%). Thus, calculating the ratio of small AT is important to avoid misinterpretation of BAL samples when AT is observed.In hypersensitivity pneumonitis (HP), bronchoalveolar lavage (BAL) sometime show atypical lymphocytes (AT). We compared lymphocytes from (5 patients) with BAL flui from small lymphocytic lymphoma and leukemia (LL from 6 patients). In a Giemsa-stained specimen, 500 lymphocytes per case were categorized as N (normal), A (smaller than a neutrophil, atypical nuclear shape), AS (A with abnormal chromatin), and AL (larger than a neutrophil, with atypia), then calculated the ratio of each category. AT accounted for 14 to 22%(A + AS, AL= 0%) in HP, but LL showed a high A+AS ratio (>51.7%) with AL (>0.2%). Thus, calculating the ratio of small AT is important to avoid misinterpretation of BAL samples when AT is observed.