Transmission of Genetic Material and Malignant Cells of Cutaneous Origin via Surgical Sutures.

BACKGROUND: Seeding of skin cancer cells following diagnostic or therapeutic surgical procedures can occur and might cause local recurrences. As current preferred therapy for skin malignancy is surgical excision, seeding of tumour cells by manipulating malignant tissue or suturing can be another factor leading to recurrences. OBJECTIVE: To evaluate whether genetic material and malignant cells adhere to standard suture materials. METHODS: This prospective study included patients who underwent excision of skin lesions. Monofilament and braided sutures were examined. Sutures were passed through the observed tumour or healthy skin margins and were examined for DNA material and cells by cytological analysis, cell culture and characterization, and DNA analysis. RESULTS: Twenty-two patients and 148 sutures were included. DNA quantification showed DNA material on all sutures, with no significant difference between braided and monofilament sutures. Cytological analysis showed that all slides prepared from cell blocks contained normal squamous and atypical cells. Cell culture and characterization showed viable cells adhering to the sutures under direct light microscopy. Cell cultures showed rapid proliferation of epithelial cells from squamous cell carcinoma specimens. CONCLUSION: Suture materials carry DNA material and cells, including malignant cells of cutaneous origin and may seed them at distant sites.

High-throughput lipidomic profiles sampled with electroporation-based biopsy differentiate healthy skin, cutaneous squamous cell carcinoma, and basal cell carcinoma.

BACKGROUND: The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time-consuming. We describe the development of a novel approach to high-throughput sampling of tissue lipids using electroporation-based biopsy, termed e-biopsy. We report on the ability of the e-biopsy technique to harvest large amounts of lipids from human skin samples. MATERIALS AND METHODS: Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) providing cSCC, BCC, and healthy skin lipidomic profiles. RESULTS: Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso-phospholipids in cSCC compared to healthy skin tissue samples. CONCLUSION: The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e-biopsy technique for the analysis of lipidomic profiles of human skin tissues.

Exploring multisite heterogeneity of human basal cell carcinoma proteome and transcriptome.

Basal cell carcinoma (BCC) is the most common type of skin cancer. Due to multiple, potential underlying molecular tumor aberrations, clinical treatment protocols are not well-defined. This study presents multisite molecular heterogeneity profiles of human BCC based on RNA and proteome profiling. Three areas from lesions excised from 9 patients were analyzed. The focus was gene expression profiles based on proteome and RNA measurements of intra-tumor heterogeneity from the same patient and inter-tumor heterogeneity in nodular, infiltrative, and superficial BCC tumor subtypes from different patients. We observed significant overlap in intra- and inter-tumor variability of proteome and RNA expression profiles, showing significant multisite heterogeneity of protein expression in the BCC tumors. Inter-subtype analysis has also identified unique proteins for each BCC subtype. This profiling leads to a deeper understanding of BCC molecular heterogeneity and potentially contributes to developing new sampling tools for personalized diagnostics therapeutic approaches to BCC.

Temporal trends in incidence, evaluation and management of neuroendocrine neoplasms of the appendix: 14 years' experience.

BACKGROUND: Information regarding temporal trends in appendiceal neuroendocrine neoplasms (ANEN) is limited. This retrospective study evaluated temporal trends in ANEN incidence and management over a 14-year period. METHODS: Appendectomy pathology reports from a single tertiary center were reviewed. RESULTS: During 2005-2018, 8327 appendectomies were performed and 57 ANENs were diagnosed (average age 31.7 ± 17 years; 70.2% women; 17.5% Arab ethnicity; and 22.8% < 18 years of age). The cohort was divided according to year of diagnosis (Period A 2005-2011; Period B 2012-2018). No differences were found in ANEN incidence (0.75% and 0.62%, respectively, p = 0.104), epidemiologic or pathologic characteristics between periods. In period B, pathology reports were more comprehensive and use of specific imaging and biochemical studies was more prevalent. Hemicolectomy rates and results were similar (8 in Period A, 7 in Period B, p = 0.925). All patients remained alive for the duration of follow-up. CONCLUSIONS: No temporal changes in epidemiological, clinical or pathological features of ANENs were noted. Although clinico-pathological evaluation was more detailed after 2011, there was no change in rates of hemicolectomy or disease prognosis.

Appendiceal tumor incidence and an in-depth look at appendiceal neuroendocrine neoplasm in a cohort of 8,162 appendectomies: Full dataset.

Data describing appendiceal tumor incidence and epidemiology is limited. We collated data from appendectomy pathology reports between 2005 and 2018 in our institution and examined patient epidemiological and appendectomy pathological features [1]. Overall, 8,328 appendectomies were performed at our institution over the pre-specified time period and 8,162 patients had sufficient epidemiological data to be included in the analysis. A total of 153 patients (1.9%) were diagnosed with appendiceal tumors, of which 57 (37.3%) were Appendiceal Neuroendocrine Neoplasm (ANEN), 35 (22.9%) were mucinous cystadenoma and 34 (22.2%) ovarian cancer metastases. We further examined the ANEN cases in order to characterize initial patient and tumor characteristics, to evaluate the performance of further investigations and interventions, and ultimately to study the behavior of these tumors over time.

Addition of chromosomal microarray and next generation sequencing to FISH and classical cytogenetics enhances genomic profiling of myeloid malignancies.

Comprehensive genetic profiling is increasingly important for the clinical workup of hematologic tumors, as specific alterations are now linked to diagnostic characterization, prognostic stratification and therapy selection. To characterize relevant genetic and genomic alterations in myeloid malignancies maximally, we utilized a comprehensive strategy spanning fluorescence in situ hybridization (FISH), classical karyotyping, Chromosomal Microarray (CMA) for detection of copy number variants (CNVs) and Next generation Sequencing (NGS) analysis. In our cohort of 569 patients spanning the myeloid spectrum, NGS and CMA testing frequently identified mutations and copy number changes in the majority of genes with important clinical associations, such as TP53, TET2, RUNX1, SRSF2, APC and ATM. Most importantly, NGS and CMA uncovered medically actionable aberrations in 75.6% of cases normal by FISH/cytogenetics testing. NGS identified mutations in 65.5% of samples normal by CMA, cytogenetics and FISH, whereas CNVs were detected in 10.1% cases that were normal by all other methodologies. Finally, FISH or cytogenetics, or both, were abnormal in 14.1% of cases where NGS or CMA failed to detect any changes. Multiple mutations and CNVs were found to coexist, with potential implications for patient stratification. Thus, high throughput genomic tumor profiling through targeted DNA sequencing and CNV analysis complements conventional methods and leads to more frequent detection of actionable alterations.

Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears.

AIMS: The distinction between benign and malignant thyroid nodules has important therapeutic implications. Our objective was to develop an assay that could classify indeterminate thyroid nodules as benign or suspicious, using routinely prepared fine needle aspirate (FNA) cytology smears. METHODS: A training set of 375 FNA smears was used to develop the microRNA-based assay, which was validated using a blinded, multicentre, retrospective cohort of 201 smears. Final diagnosis of the validation samples was determined based on corresponding surgical specimens, reviewed by the contributing institute pathologist and two independent pathologists. Validation samples were from adult patients (≥18 years) with nodule size >0.5 cm, and a final diagnosis confirmed by at least one of the two blinded, independent pathologists. The developed assay, RosettaGX Reveal, differentiates benign from malignant thyroid nodules, using quantitative RT-PCR. RESULTS: Test performance on the 189 samples that passed quality control: negative predictive value: 91% (95% CI 84% to 96%); sensitivity: 85% (CI 74% to 93%); specificity: 72% (CI 63% to 79%). Performance for cases in which all three reviewing pathologists were in agreement regarding the final diagnosis (n=150): negative predictive value: 99% (CI 94% to 100%); sensitivity: 98% (CI 87% to 100%); specificity: 78% (CI 69% to 85%). CONCLUSIONS: A novel assay utilising microRNA expression in cytology smears was developed. The assay distinguishes benign from malignant thyroid nodules using a single FNA stained smear, and does not require fresh tissue or special collection and shipment conditions. This assay offers a valuable tool for the preoperative classification of thyroid samples with indeterminate cytology.

Diagnostic aspects of fine needle aspiration for lung lesions: series of 245 cases.

BACKGROUND: Transthoracic fine needle aspiration (FNA) is one of several methods for establishing tissue diagnosis of lung lesions. Other tissue or cell sources for diagnosis include sputum, endobronchial biopsy, washing and brushing, endobronchial FNA, transthoracic core needle biopsy, biopsy from thoracoscopy or thoracotomy. The purpose of this study was to compare the sensitivity and specificity of FNA and other diagnostic tests in diagnosing lung lesions. MATERIALS AND METHODS: The population included all patients undergoing FNA for lung lesions at Meir Medical Center from 2006 through 2010. Information regarding additional tissue tests was derived from the electronic archives of the Department of Pathology, patient records and files from the Department of Oncology. Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values were calculated for each test. RESULTS: FNA was carried out in 245 patients. Malignant tumors were diagnosed in 190 cases (78%). They included adenocarcinoma (43%), squamous cell carcinoma (15%), non-small cell carcinoma, not otherwise specified (19%), neurondocrine tumors (7%), metastases (9%) and lymphoma (3%). The specificity of FNA for lung neoplasms was 100%; sensitivity and diagnostic accuracy were 87%. CONCLUSIONS: FNA is the most sensitive procedure for establishing tissue diagnoses of lung cancer. Combination with core needle biopsy increases the sensitivity. Factors related to the lesion (nature, degenerative changes, location) and to performance of all stages of test affect the ability to establish a diagnosis.

Evaluation of peritoneal CEA levels following colorectal cancer surgery.

BACKGROUND: Peritoneal carcinoembryonic antigen (pCEA) levels in the early postoperative period following a curative resection of colorectal cancer (CRC) have not been previously studied. METHODS: Postoperative peritoneal fluids of 36 CRC patients followed by 24 benign colonic disease patients were evaluated for CEA levels and tumor cell presence. Serum CEA levels were also evaluated prior and after surgery. RESULTS: Although high postoperative pCEA levels were observed in some benign patients, more CRC patients exhibited significant elevation of postoperative pCEA (>5 ng/ml) compared to benign patients (50% vs. 23%, P = 0.039). Postoperative median pCEA levels of CRC patients were significantly higher compared to benign patients (5.4 vs. 2 ng/ml, P = 0.011). Specifically, pCEA levels in CRC patients were significantly elevated when measured during the first 24 hr after surgery. Postoperative pCEA levels were associated with colon tumor location compared to rectal location. However, no correlation was found with known risk factors for cancer recurrence or with serum CEA levels. CONCLUSIONS: Postoperative pCEA levels may be significantly elevated following a curative resection for CRC. Its significance within patient's prognostic evaluation remains to be studied. Inclusion of patient's follow-up data may reveal the significance of elevated pCEA levels following CRC resection.

[Osteoarthritic changes in hip joint in patients with fractures of femoral neck].

BACKGROUND: Fractures of proximal femur are common among elderly people. They are associated with considerable morbidity and mortality. Identification of etiopathogenetic factors associated with fractures might facilitate prevention. Osteoporosis is commonly present in the heads of femurs. The prevalence of osteoarthritic changes in hip joints is controversial. Some authorities report low prevalence and even speculate on the protective effect of osteoarthritis against fractures. OBJECTIVE: The goal of the study was to examine the association between osteoarthritic changes (radiologic and histologic) and fractures of the neck of the femur. METHODS: The patient population included 41 patients undergoing replacement of femoral head for subcapital fracture; their ages ranged from 61 - 93 years of age. Radiologic criteria for osteoarthritis included: (a)narrowing of joint space (b) subchondral sclerosis (c) deformation of head of femur (d) subchondra cysts and (e] osteophytes. RESULTS: Osteoarthritic changes, usually mild, were present in 22 (54%) patients, regardless of age and gender The frequency of radioLogical changes was similar to the general population. HistoLogic findings included subchondral fibrosis and subchondral cysts. Mild subchondral fibrosis was present in 78% of cases. CONCLUSION: The findings support lack of association between osteoarthritic changes in hip joint and fracture of proximal femur, without a protective effect.

COX-2 expression in uterine carcinosarcoma.

OBJECTIVE: To assess cyclooxygenase-2 (COX-2) expression in the carcinomatous and sarcomatous elements of uterine carcinosarcoma. DESIGN: Retrospective study. SETTING: Medical center. SAMPLE: Twenty-seven consecutive uterine specimens with carcinosarcoma. METHODS: COX-2 expression assessment by immunohistochemistry was performed on deparaffinized sections of paraffin-embedded tissue blocks. Analysis of all stained tissue sections was done by means of light microscopy counting 10 high power fields with a minimum of 1,000 cells per slide. Analysis of the stained tissue sections was done by pathologists blinded to the clinical data and the follow-up course of the malignancy. MAIN OUTCOME MEASURES: Staining of more than 10% of the cells was considered positive. Staining intensity was graded on a 0-3 scale. A scoring index was calculated by multiplying the intensity grade by the percentage of stained cells and considered low when it was < or =1 and high when it was >1. COX-2 expression was associated with prognostic factors and survival. RESULTS: COX-2 immunohistochemical staining was positive in 74% of the carcinomatous component of carcinosarcoma and a high staining score was observed in 48.2%. Staining parameters were significantly lower in the sarcomatous component. No significant association between COX-2 expression with stage, grade, depth of myometrial invasion, lymphvascular involvement or with survival was observed. CONCLUSIONS: COX-2 is expressed in a high percentage of uterine carcinosarcoma, but does not seem to be associated with prognostic factors or survival.

Horizon in random matrix theory, the Hawking radiation, and flow of cold atoms.

We propose a Gaussian scalar field theory in a curved 2D metric with an event horizon as the low-energy effective theory for a weakly confined, invariant random matrix ensemble (RME). The presence of an event horizon naturally generates a bath of Hawking radiation, which introduces a finite temperature in the model in a nontrivial way. A similar mapping with a gravitational analogue model has been constructed for a Bose-Einstein condensate (BEC) pushed to flow at a velocity higher than its speed of sound, with Hawking radiation as sound waves propagating over the cold atoms. Our work suggests a threefold connection between a moving BEC system, black-hole physics and unconventional RMEs with possible experimental applications.

Jumps in current-voltage characteristics in disordered films.

We argue that giant jumps of current at finite voltages observed in disordered films of InO, TiN, and YSi manifest a bistability caused by the overheating of electrons. One of the stable states is overheated and thus low resistive, while the other, high-resistive state is heated much less by the same voltage. The bistability occurs provided that cooling of electrons is inefficient and the temperature dependence of the equilibrium resistance R(T) is steep enough. We use experimental R(T) and assume phonon mechanism of the cooling taking into account its strong suppression by disorder. Our description of the details of the I-V characteristics does not involve adjustable parameters and turns out to be in quantitative agreement with the experiments. We propose experiments for more direct checks of this physical picture.

The cyclin-dependent kinase inhibitor, p27, has no correlation with the malignant potential of GIST.

BACKGROUND: Tumor size and mitotic activity are characteristically associated with the malignant potential and prognosis of gastrointestinal stromal tumors (GIST). However, since neither small tumor size nor low mitotic activity can rule out malignancy, additional factors that may predict malignant behavior have been suggested. AIM: To evaluate the correlation between the cyclin-dependent kinase inhibitor (CDI), p27kip1, expression and the malignant potential of GIST. METHODS: Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67 in surgical material obtained from 36 patients with GIST. p27kip1 staining intensity and the percentage of positive cells were investigated for association with the malignancy risk, pathological features, overall survival, and disease-free survival. Histologic grade was assigned by spindle vs. epithelioid cell histology, mucosal invasion, tumor cell necrosis or atypia and the number of mitoses. RESULTS: In the multivariate model, p27kip1 expression was not significantly associated with any of the variables examined except Kit protein-CD117 (r = 0.37, p = 0.03). Comparative evaluation of p27kip1 expression in GIST cells revealed higher levels of p27kip1 in patients who died compared to those who survived (2.04 +/- 0.54 vs. 1.3 +/- 0.99, p = 0.1). CONCLUSION: The CDI p27kip1 was not associated with malignancy of GISTs and did not serve as a predictor of survival.

Quadrivalvular heart disease: transition from congenital pulmonary stenosis to rheumatic disease.

The case is reported of a 36-year-old male patient suffering from congenital pulmonary stenosis who previously had undergone pulmonary balloon valvuloplasty. During the past nine years, he had experienced recurrent attacks of rheumatic fever that gradually damaged all four heart valves. The patient underwent aortic, mitral and pulmonary valve replacement with tricuspid valve annuloplasty and pulmonary artery reconstruction. Histologically, all heart valves--including the pulmonary--had similar changes that corresponded to chronic rheumatic disease.

Leiomyosarcoma of the superior vena cava: Resection with vascular reconstruction - case report and review of the literature.

The present report describes a case of pedunculated intraluminal leiomyosarcoma of the superior vena cava, extending to the right atrium, that was successfully resected surgically. Superior vena cava reconstruction was performed using bovine pericardial graft, saving the sinus node. The pathological variants of this neoplasm according to the anatomical site of the tumour are described.

Nonocclusive mesenteric ischemia after off-pump coronary artery bypass surgery: a word of caution.

We present a series of five cases of off-pump coronary artery bypass surgery complicated with fatal nonocclusive mesenteric ischemia. We review a total of 489 patients aged 65 and older (mean age 74.9 +/- 3.2 years) who underwent off-pump coronary artery bypass surgery. The diagnosis of nonocclusive mesenteric ischemia was confirmed by computed tomography-angiography and/or selective angiography of the superior mesenteric artery, or intraoperatively. Three patients underwent laparotomy with bowel resection. In two cases, resection of bowel was not feasible. Of the possible predisposing factors, we found that four of the patients (two preoperative and two perioperative) had received epinephrine and two had an intra-aortic balloon counter pulsation due to acute myocardial infarction and cardiogenic shock. All patients were over 65 years of age, and all had acute anterior wall myocardial infarction and hemodynamic instability or post-myocardial infarction unstable angina. Nonocclusive mesenteric ischemia is a difficult clinical entity to recognize, has no clear-cut effective management, has a poor prognosis as a result of low cardiac output, and can be aggravated by off-pump coronary artery bypass grafting.

S100P is selectively upregulated in tumor cell lines challenged with DNA cross-linking agents.

Bifunctional alkylating agents that cross-link DNA are implicated in the pathogenesis of therapy related myelodysplastic syndromes (MDS) and MDS related acute myeloid leukemia (MDR-AML). We exposed HL60 cells to the highest level of bifunctional alkylating nitrogen mustard mechlorethamine (HN2) that was consistent with recovery following suppressed growth. Microarray analyses showed minor changes in transcripts in HN2 treated cells. A moderate up-regulation of S100P mRNA was consistently observed after 1 day of exposure to bifunctional alkylating agents and expression was not induced with monofunctional agents. Elevated S100P protein/antigen was not detected until days later in a subset of non-mitotic G2 cells. Elevated S100P protein persisted over the course of a delayed recovery phase. The results confirm recent reports indicating that S100P is a survival factor. In addition, our results indicate that S100P has a specific role in G2 cell function associated with a prolonged phase of recovery after exposure to bifunctional alkylating agents.

p27kip1 expression is inversely related to the grade of gastric MALT lymphoma.

BACKGROUND: Decreased or lost expression of the cyclin-dependent kinase inhibitor p27kip1 protein has been found to be a poor prognostic factor in many cancers, including gastric cancer. AIM: To evaluate p27kip1 expression in gastric mucosa-associated lymphoid tissue (MALT) and gastric B-cell lymphoma. METHODS: Fifty-two cases of gastric lymphoma, mean age 68.7 yr (range 23-90 yr), 11 of chronic Helicobacter pylori-associated gastritis, and 5 of normal gastric mucosa were studied. Patients were classified into two groups. Stage IE gastric lymphomas were defined as local gastric lymphoma of MALT and more advanced stages as advanced gastric lymphoma. Twenty-three patients diagnosed as stage IE, 13 of these were low-grade and 10 diffuse large B-cell lymphoma (DLBL). Twenty-nine patients were at stage IIE or above, 18 with low-grade and 11 with DLBL. Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67. RESULTS: The proliferative index was higher in gastric DLBL than in low-grade MALT lymphomas, 57.1+/-31.2 vs 17.3+/-20.6 (p=0.0001). The mean p27kip1 expression score for high-grade patients was significantly lower compared with that of low-grade patients, 0.5+/-0.4 and 1.6+/-0.8, respectively (p=0.001). Comparative evaluation of p27kip1 expression in malignant lymphoid cells revealed that B cells of the localized gastric DLBL patients expressed the least p27kip1, 0.36+/-0.32. This value was lower than that of malignant lymphoid cells of patients with advanced DLBL, 0.64+/-0.53, advanced low-grade MALT lymphoma, 1.59+/-0.79, and localized low-grade MALT lymphoma, 1.59+/-0.84. In the multivariate model in which all p27kip1 variables were entered, the expression of p27kip1 in malignant lymphoid cells was inversely correlated with the grade of the lymphoma irrespective of the stage of the disease (p=0.0001), and significantly predicted grade: OR:0.07, 95% CI 0.07-0.31, p=0.0001. CONCLUSION: p27kip1 may be a putative distinct molecular marker to differentiate between low-grade and high-grade gastric lymphoma.