[Diagnostic value of FNDC5 in patients with subclinical diabetic cardiomyopathy].

Objective: To estimate the diagnostic value of fibronectin type Ⅲ-domain containing protein 5 (FNDC5) in subclinical diabetic cardiomyopathy. Methods: A total of 94 patients with type 2 diabetes (T2DM), who were hospitalized from April 2018 to June 2019 in the Third Affiliated Hospital of Soochow University, were enrolled in this study. Patients were divided into T2DM with cardiac dysfunction (subclinical DCM) group (n=47) and T2DM without cardiac dysfunction (non-DCM) group (n=47) according to echocardiography and gated myocardial perfusion imaging results. Basic clinical data and serum FNDC5 level were compared between the two groups. Logistic regression analysis was used to establish predicting models and the diagnostic efficiency of established models was compared by ROC curve analysis. Results: Compared to non-DCM group, patients in subclinical DCM group were older, with longer duration of diabetes, and had higher levels of glycosylated hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) (all P<0.05). Serum FNDC5 level was significantly lower in subclinical DCM group than in non-DCM group (P<0.001). FNDC5 level was positively correlated with ventricular septal e'(r=0.451,P=0.005), mitral valve e'(r=0.291,P<0.001), the ratio of peak early diastolic trans-mitral flow velocity (E) to peak late diastolic trans-mitral flow velocity (A)(r=0.490,P=0.002), while negatively correlated with A(r=-0.399,P<0.001), the average ratio of E/e'(r=-0.490,P<0.001), tricuspid regurgitation velocity(r=-0.567,P<0.001), left atrial volume index(r=-0.491,P<0.001). Univariate ROC analysis showed that the diagnostic efficacy of FNDC5(AUC=0.940,95%CI 0.897-0.982)was superior to age(AUC=0.639,95%CI 0.523-0.752), diabetic duration(AUC=0.663,95%CI 0.555-0.772), HbA1c(AUC=0.740,95%CI 0.638-0.839), TG(AUC=0.661,95%CI 0.547-0.776), TC(AUC=0.675,95%CI 0.563-0.788)and LDL-C(AUC=0.644,95%CI 0.532-0.756). Model 1 was established with subclinical DCM as dependent variable, age, diabetic duration, TG, TC, LDL-C and HbA1c as independent variables. Model 2 was established by adding FNDC5 as independent variable on the basis of model 1. Diagnostic efficacy for subclinical DCM was compared between the two models by ROC analysis. The diagnostic efficiency was better with model 2 (AUC=0.980) than with model 1 (AUC=0.879, P<0.001). When sensitivity was set at 0.617, the specificity of model 2 was higher than that of model 1(0.979 vs. 0.936). When sensitivity was set at 0.532, the sensitivity of model 2 was higher than that of model 1 (1.000 vs. 0.915). Conclusions: Our findings suggest that serum FNDC5 could be used as a novel biomarker for the diagnosis of subclinical DCM.

Positive-Parity Linear-Chain Molecular Band in

An inelastic excitation and cluster-decay experiment ^{2}H(^{16}C,^{4}He+^{12}Be or ^{6}He+^{10}Be)^{2}H was carried out to investigate the linear-chain clustering structure in neutron-rich ^{16}C. For the first time, decay paths from the ^{16}C resonances to various states of the final nuclei were determined, thanks to the well-resolved Q-value spectra obtained from the threefold coincident measurement. The close-threshold resonance at 16.5 MeV is assigned as the J^{π}=0^{+} band head of the predicted positive-parity linear-chain molecular band with (3/2_{π}^{-})^{2}(1/2_{σ}^{-})^{2} configuration, according to the associated angular correlation and decay analysis. Other members of this band were found at 17.3, 19.4, and 21.6 MeV based on their selective decay properties, being consistent with the theoretical predictions. Another intriguing high-lying state was observed at 27.2 MeV which decays almost exclusively to ^{6}He+^{10}Be(∼6 MeV) final channel, corresponding well to another predicted linear-chain structure with the pure σ-bond configuration.

g Factor of the

The gyromagnetic factor of the low-lying E=251.96(9) keV isomeric state of the nucleus ^{99}Zr was measured using the time-dependent perturbed angular distribution technique. This level is assigned a spin and parity of J^{π}=7/2^{+}, with a half-life of T_{1/2}=336(5) ns. The isomer was produced and spin aligned via the abrasion-fission of a ^{238}U primary beam at RIKEN RIBF. A magnetic moment |µ|=2.31(14)µ_{N} was deduced showing that this isomer is not single particle in nature. A comparison of the experimental values with interacting boson-fermion model IBFM-1 results shows that this state is strongly mixed with a main νd_{5/2} composition. Furthermore, it was found that monopole single-particle evolution changes significantly with the appearance of collective modes, likely due to type-II shell evolution.

Cytologic diagnosis of malignant mesothelioma, with particular emphasis on the epithelial noncohesive cell type.

The effusion cytologies from 21 cases of malignant mesothelioma (MM) (15 pleural, 6 peritoneal) diagnosed at the Indiana University Medical Center during 1990-1997 were reviewed. Using the classification of Tao (Acta Cytol 1979;23:209-213), 13 cases of MM were of the epithelial cohesive cell type and 8 were of the epithelial noncohesive cell type. While the epithelial cohesive cell type has been discussed in the literature, the epithelial noncohesive cell type has not. The cytomorphologic features for both types are presented with particular emphasis on the noncohesive cell type. The differential diagnosis and use of ancillary confirmatory laboratory tests are briefly discussed. Because of its resemblance to florid reactive mesothelial hyperplasia and the general lack of awareness of the existence of the single-cell pattern of mesothelioma, this diagnosis can often be missed.

Fine-needle aspiration biopsy using a newly-developed pencil-grip syringe holder.

Until now, commercially available syringe holders for fine-needle aspiration (FNA) were designed to be held in a pistol-grip manner. A newly developed, pencil-grip syringe holder, the Tao Aspirator, was tested. The device is equipped with a release button for automatically drawing back the syringe plunger and a regulating knob for adjusting negative pressure for the aspiration. After direct smears were made for on-site examination, the remaining aspirated material was collected by rinsing the needle and syringe with CytoRich red fixative. Hettich cytocentrifuge preparations were then prepared. The quality of the first 150 FNA specimens procured by this device and prepared with liquid fixation was evaluated in terms of adequacy of specimen, amount of obscuring blood, preservation of cells, and ease of screening and interpretation. These 150 specimens included 32 from thyroids; 34 from breasts; 40 from lymph nodes; 24 from subcutaneous nodules; and 20 from salivary glands. There were no unsatisfactory specimens. In Hettich preparations, red blood cells were lysed, making interpretation easier. All cellular elements and tissue fragments were adequately fixed, showing excellent cellular morphology. Specimens fixed in liquid fixative yielded uniform cell suspensions, resulting in cytocentrifuge preparations with evenly distributed cells, and so the screening was also easier. The aspiration techniques using pistol-grip and pencil-grip FNA syringe holders were also compared in terms of control in tissue sampling, ease of use, and safety. The pencil-grip syringe holder allowed greater tactile sensation of the texture of the lesion, and enabled the operator to use a single hand to place a needle into a target lesion with minimal error. This device placed the hand relatively close to the needle tip while the hand was in a position of natural function, imparting more control in tissue sampling. It was more easily manipulated, and could prevent dripping when cystic fluid was aspirated. Specimen collection using the Tao Aspirator and processing with liquid fixation in addition to direct smear preparations allowed the laboratory to consistently produce adequate cytologic preparations and cell blocks.

Hepatic angiosarcoma: aspiration biopsy cytology and immunocytochemical contribution.

In the absence of previously documented sarcoma, the initial diagnosis of angiosarcoma (AS) on fine-needle aspiration (FNA) biopsy of the liver is difficult. However, awareness of its occurrence and the assistance of immunocytochemical stains may aid in arriving at the correct diagnosis. In this paper, a 59-yr-old smoker and alcoholic woman presented after a syncopal episode and was found to have a palpable right abdominal mass. An abdominal CT scan confirmed multiple centrally necrotic liver masses, from which an FNA biopsy was obtained. The smears were bloody with groups of relatively dishesive and singly dispersed spindle cells in a somewhat necrotic background. The nuclei were elongated to ovoid-round with small nucleoli. The cytoplasm was ample and ill-defined. The cells were reactive for factor VIII-related antigen and CD31 but negative for cytokeratin immunocytochemical stains, and a diagnosis of "suspicious for angiosarcoma" was entertained. The patient declined further studies or treatment but presented 4 mo later with light-headedness and hypoglycemia. Laparoscopic tissue biopsies of the liver/abdominal masses were obtained and revealed AS. Rarely, liver masses may represent AS. Pathologists should be aware of their cytomorphology and characteristic immunostaining to avoid their misinterpretation.

Direct intrauterine sampling: the IUMC Endometrial Sampler.

Endometrial cytology has been studied for more than 25 years, and a variety of cytologic devices have been developed for direct sampling of the endometrium. The quality of endometrial samples procured by various devices is markedly different and greatly affects the diagnostic accuracy. A new endometrial sampling device, the IUMC Endometrial Sampler, was developed at the Indiana University Medical Center and approved by the Food and Drug Administration for general medical use. This device is intended for the early detection of endometrial carcinoma and its precursors. It can be used to monitor the endometrial condition of patients receiving estrogen replacement therapy or tamoxifen. It is also useful for the procurement of uncontaminated endometrial samples for microbiologic studies from patients with suspected endometritis. It has the potential to be used for endometrial dating for patients with infertility disorders. In our clinical trials and sampling tests using hysterectomy specimens, adequate and representative endometrial samples without contamination from endocervix and vagina were consistently obtained by this device. The procedure of endometrial sampling using this device and the preparation techniques for endometrial brushing specimens are discussed and illustrated.

Vimentin-positive spider-shaped Kupffer cells. A new clue to cytologic diagnosis of primary and metastatic hepatocellular carcinoma by fine-needle aspiration biopsy.

The identification of Kupffer cells highlighted by positive immunostaining for vimentin on direct smears was found to play an important role in the diagnosis of primary and metastatic hepatocellular carcinoma by fine-needle aspiration biopsy. The Kupffer cell, identified by vimentin staining, is spider- or star-shaped with multiple elongated and slender cytoplasmic processes. Direct smears obtained by fine-needle aspiration biopsy from 14 cases of hepatocellular carcinoma and 15 cases of metastatic carcinoma were stained with vimentin. The cytologic diagnoses were verified by histologic and/or clinical follow-up. All 14 cases of hepatocellular carcinoma, including 9 primary and 5 metastatic, contained significant number of vimentin-positive spider cells within tumor clusters. There were at least three spider cells present within each tumor cluster, involving at least 50% of the tumor clusters. The spider cells were not only found in the well-differentiated type but also in the poorly differentiated and pleomorphic large cell types of the hepatocellular carcinoma. However, the tumor cells from 15 metastatic carcinomas contained no or few spider cells in the tumor clusters. The presence of numerous vimentin-positive spider-shaped Kupffer cells within tumor clusters constitutes strong evidence in favor of a diagnosis of hepatocellular carcinoma.

Cytomorphologic appearances of normal endometrial cells during different phases of the menstrual cycle: a cytologic approach to endometrial dating.

From 1988 to 1992, 156 endometrial cytologic preparations were procured by directly brushing hysterectomy specimens from premenopausal women with normal endometrium and regular menstruation. These brushing smears were obtained by using the cytobrush and/or the endometrial brush. The cytologic findings were correlated with histologic endometrial dating. Of these, 56 cases were classified as proliferative phase endometrium; 89, secretory phase; and 11, menstrual phase. The cytomorphologic features of endometrial glandular and stromal cells at different stages of the menstrual cycle are summarized and compared. On the basis of the different cytomorphologic features of glandular and stromal cells seen during various phases of the cycle, cytologic differentiation between proliferative phase and secretory phase endometria can be readily established. It appears possible to date the endometrium by direct endometrial brushing technique. It is also possible to determine if the glandular and/or stromal cells seen in the endocervical smears procured by the cytobrush are normal endometrial cells from cytobrush extraction, and are consistent with the date of the menstrual cycle, which should be made clear in the cytology report.

Fine needle aspiration cytology of a male breast carcinoma exhibiting neuroendocrine differentiation. Report of a case with immunohistochemical, flow cytometric and ultrastructural analysis.

We present the cytologic, immunohistochemical, flow cytometric and ultrastructural findings of a case of invasive ductal carcinoma of the breast with features of neuroendocrine differentiation occurring in an 83-year-old male. Fine needle aspiration (FNA) cytology of the patient's tumor demonstrated a markedly cellular specimen to discohesive tumor cells, present primarily singly, with occasional loose groups. The cells were relatively large, with pleomorphic, eccentrically placed, round to oval nuclei. The cytoplasm was abundant and contained prominent red granules (Papanicolaou stain) that were also argyrophilic. Immunohistochemical studies performed on the aspirate and the subsequently excised malignant breast tissue revealed positive staining for neuron-specific enolase, chromogranin A, synaptophysin and gastrin. Also, the majority of the tumor stained positive with antibodies to both estrogen and progesterone hormone receptors. DNA flow cytometry demonstrated an aneuploid stemline population with a DNA index of 1.73 and an S-phase fraction of 4.5%. Electron microscopy was performed on the FNA material, and numerous variable-sized, membrane-bound, dense-core granules diffusely scattered within the cytoplasm of the neoplastic cells were identified. The specific cytologic features of this tumor, along with the immunocytochemical and ultrastructural features, can aid the pathologist in rendering an accurate FNA diagnosis of this specific subtype of breast carcinoma.

Cytopathology of papillary carcinoma of the thyroid with anaplastic transformation. A case report.

A case of papillary carcinoma of the thyroid with anaplastic transformation was diagnosed by fine needle aspiration. The atypical history and presentation of this case, the initially problematic cytologic and immunohistochemical findings, and the definitive cytologic and histologic features are described. The diagnostic problems posed by papillary carcinoma of the thyroid with anaplastic transformation are discussed. This diagnosis must be included in the differential diagnosis of poorly differentiated tumors of the neck.

Endosonography-guided real-time fine-needle aspiration biopsy.

Twenty-six patients were prospectively evaluated with endosonography-guided real-time fine-needle-aspiration biopsy. This cohort comprised 14 patients with a pancreatic mass revealed by CT or a stricture of the main pancreatic duct seen at ERCP, 7 patients with mediastinal lymphadenopathy, 3 patients with extrapancreatic abdominal masses, and 2 patients with subepithelial or infiltrative lesions. Endosonography-guided real-time fine-needle-aspiration biopsy was diagnostic in 18 of 20 patients in whom surgical confirmation was available or in whom malignancy was found and confirmed by clinical follow-up (accuracy of 90%). In the subgroup of patients with pancreatic lesions, 3 had previously undergone nondiagnostic CT-guided fine-needle-aspiration biopsy and 2 did not have evidence of a mass by CT. Real-time fine-needle-aspiration biopsy was diagnostic for malignancy in 4 of these individuals. In the 7 patients with mediastinal lymph nodes, 2 had nondiagnostic transbronchial biopsy and 2 had no evidence of mediastinal lymphadenopathy by CT scan. Endosonography-guided real-time fine-needle-aspiration biopsy diagnosed malignancy in both individuals with nondiagnostic transbronchial studies and was able to identify mediastinal lymphadenopathy in the 2 patients with negative CT scans (malignancy confirmed with real-time fine-needle-aspiration biopsy in 1). Overall, in 9 of 10 lesions in which visualization by CT was not possible (5), CT-guided fine-needle aspiration was unsuccessful (3), or prior nonsurgical biopsy techniques were unsuccessful (2), real-time fine-needle-aspiration biopsy was diagnostic.(ABSTRACT TRUNCATED AT 250 WORDS)

An expert system for teaching cytopathologic diagnosis of lung cancers.

An expert system for teaching cytopathologic skills is described. It uses Tao's cytologic criteria as graded feature parameters for comparison against a set of expert descriptors of known carcinomas. The system scores each diagnosis according to the degree of agreement along each feature axis. The system also allows the user to compare his/her description with that of the expert for any of the tumor entities. The expert knowledge base is abstracted into a numerical matrix within the system. This matrix is used for parameter comparison and score interpretation. This design is simple and compact, allowing portability and broad compatibility for small personal computers. Although testing is only at the initial stages, preliminary studies have shown that the system provides reproducible, consistent results. It is useful as a teaching tool for students, residents and staff pathologists.

Combined endosonography and fine-needle aspiration cytology in the evaluation of gastrointestinal lesions.

Fifty consecutive patients with extrinsic or submucosal masses, gastric ulcers, or surgical anastomoses suspected of malignancy but with previously negative findings on conventional forceps biopsy or brush cytology underwent endoscopic ultrasonography followed by fine-needle aspiration cytology. Diagnostic cytology results were obtained in 37 of 50 (74%) patients. In 11 of the 13 patients with negative fine-needle aspirates, the endosonographic findings supported the final diagnosis as assessed by clinical follow-up or surgical pathology findings. In all patients, endosonography was useful for identifying the extent of the lesion and detailing regional anatomy to permit an assessment of the safest and most appropriate site for needle biopsy. The highest yield was found in evaluating tumors extrinsic to the gastrointestinal tract that were impinging on the lumen (14 of 15 or 93%). In 14 patients who underwent subsequent surgical therapy, the accuracy of fine-needle aspiration cytology was 86% (12 of 14). No complications occurred in any of the patients. EUS combined with fine-needle aspiration cytology appears to be useful in the evaluation of extrinsic or submucosal masses and suspicious appearing ulcerative lesions and surgical anastomoses of the gastrointestinal tract when conventional biopsy and brush cytology techniques have been unsuccessful.

Aspiration biopsy cytology of smooth muscle tumors. A cytologic approach to the differentiation between leiomyosarcoma and leiomyoma.

From 1970 to 1991, 51 cases of smooth muscle tumors were diagnosed by fine needle aspiration biopsy. All were verified histologically and/or clinically, with no false-positive results. Of the 51 tumors, 41 were leiomyosarcoma and 10 leiomyoma. Among the 41 cases of leiomyosarcoma, 29 were the well-differentiated type; 8, poorly differentiated type; and 4, epithelioid type. Of the 10 cases of leiomyoma, 2 were the epithelioid type. The cytomorphologic features and cytologic patterns of various types of smooth muscle tumors observed in aspirate preparations are presented and compared in order to establish the cytologic criteria for differentiating malignant from benign smooth muscle tumors. Cytomorphologically the various types of smooth muscle tumors were different, and their cytologic features were sufficiently distinctive to distinguish one from the others. It appears possible to differentiate a well-differentiated leiomyosarcoma from a leiomyoma on the basis of cytologic findings observed in aspirate preparations. The recognition of different cytomorphologic features of various types of smooth muscle tumors is important in establishing an accurate cytologic diagnosis, which may be of practical significance to clinical management.

Are oral contraceptive-associated liver cell adenomas premalignant?

From January 1977 to June 1990, 1,670 patients with a liver mass or masses underwent transabdominal fine needle aspiration biopsy of the liver. Of those cases, 99 were diagnosed cytologically as "hepatocellular carcinoma" and 9 as "consistent with liver cell adenoma." Among the 99 patients with hepatocellular carcinoma, 3 were users of oral contraceptives. The nine patients with liver cell adenoma were all users of oral contraceptives. Of them, two developed foci or areas of liver cell dysplasia within the adenomas. The mean periods of oral contraceptive use among these three groups of patients were different. It appeared that patients started to develop liver cell adenoma after five years of oral contraceptive use (mean, 6.3 years). Foci or areas of liver cell dysplasia began to arise within liver cell adenomas after 8 years of oral contraceptive use (mean, 9 years), and the patients started to develop hepatocellular carcinoma after 10 years of contraceptive use (mean, 11 years). The cytologic features of liver cell dysplasia strikingly mimicked those of hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas foci or areas of liver cell dysplasia within the adenomas are irreversible, premalignant changes and may transform into hepatocellular carcinoma.

Restoration of broken cytology slides and creation of multiple slides from a single smear preparation.

A technique was developed for restoring broken cytology slides so that they are close to their original condition and for making multiple slides from a single smear preparation. The method is applicable to both cytologic preparations and histologic sections. In this study the fragmented smear preparation was treated with Pro-Texx, which penetrated, impregnated and solidified the full thickness of the pieces of the smear, enabling them to be lifted from the pieces of the broken slide. The removed pieces of the smear preparation were reassembled onto a new slide, which was then restained and coverslipped. In preparing multiple teaching slides, the treated smear preparation was divided as planned, with each portion mounted onto a separate slide, which was then restained and coverslipped. Ten other fine needle aspiration cases with broken slides have been restored, and more teaching slides were prepared from a single smear preparation using the same technique. All were equally successful. This technique provides an excellent method of smear transfer in cases of broken slides and creation of multiple slides from a single smear preparation for cytology teaching. This is particularly useful for unusual cases.

Endoscopic ultrasonography as an adjunct to fine needle aspiration cytology of the upper and lower gastrointestinal tract.

Twenty consecutive patients with either extrinsic or submucosal masses or gastric ulcers suspicious for malignancy with previously negative conventional forceps biopsies and/or brush cytology underwent a combined approach of endoscopic ultrasound (EUS) followed by fine needle aspiration cytology. Diagnostic results were obtained in 17 of 20 patients. The three patients with indeterminate aspirates had EUS findings strongly supportive of the final diagnosis. EUS combined with fine needle aspiration cytology appears to be of value in the evaluation of extrinsic, submucosal, and ulcerative lesions of the gastrointestinal tract.