Cytologic Diagnosis Of Cancer Research Articles

HYBRID MINIMALLY INVASIVE TECHNOLOGIES IN DIAGNOSING AND ASSESSING THE PROGNOSIS FOR THE COURSE OF THE DISEASE IN PATIENTS WITH BREAST CANCER: PUNCTURE-NEEDLE BIOPSY USING OZONE-OXYGEN MIXTURE AND TISSUE SPECTROPHOTOMETRY TECHNIQUE

Breast cancer is the most common malignant disease in women worldwide. According to the World Health Organization and the International Agency for Research on Cancer, it accounts for 25.1% of all cancer cases in women. Intracystic breast cancer is one of the most rare and difficult to diagnose forms of this disease. Due to this improving existing methods of breast cancer diagnosis and developing new ways for the early detection of this pathology are of great importance. The aim of the study is to evaluate the effectiveness of new methods for breast cancer diagnosis – an improved technique of puncture–needle biopsy under ultrasound control and a hybrid technology for assessing the local metabolism of mammary tumors. Materials and methods. The article presents the results of examining 67 female patients with intracystic breast cancer using the traditional technique of puncture-needle biopsy and a new method of cytological diagnosis of this disease. The article presents the pilot results of using the hybrid technology for evaluating local metabolism of mammary gland tumors in 22 patients with suspected breast cancer to clarify the diagnosis and assess the prognosis using optical diagnostic methods: fluorescence spectroscopy (at wavelengths of fluorescence excitation of 365 and 450 nm) and diffuse reflectance spectroscopy (with a source of polychromatic radiation). Results. The sensitivity of puncture-needle biopsy performed according to the traditional method in the diagnosis of intracystic breast cancer was 81.8%, and the sensitivity of the improved method was 97.06% (p < 0.05). To asses reliably the effectiveness of the hybrid technology for determining the local metabolism of tumors in the diagnosis of breast cancer, examination of a larger number of patients is required. Among the patients examined using the optical diagnostic methods, the following data were obtained: the redox index in the tumor was 0.67±0.10 relative units, in the surrounding tissue – 0.77±0.14, tissue saturation in the tumor – 64±14%, in the surrounding tissue – 68±9%. Two cases of breast cancer in patients prior to the start of treatment and after 6 courses of neoadjuvant polychemotherapy are considered separately. The following data were obtained: the redox index in the tumor in the patient without treatment was 0.53± 0.01 relative units, in the patient after 6 courses of neoadjuvant therapy – 0.81±0.01 relative units; the value of tissue saturation in the tumor in the patient without treatment – 71±1%, in the patient after 6 courses of neoadjuvant therapy – 64± 2%. To asses reliably the effectiveness of the hybrid technology for determining the local metabolism of tumors in the diagnosis of breast cancer and to have the opportunity to assess the prognosis for the disease course, examination of a larger number of patients is required. Conclusions. A new method of cytological diagnosis of cancer in a breast cyst using ozone-oxygen mixture proved to be more effective than the traditional method, which proves the expediency of its use in order to improve the diagnosis of this pathology at the preoperative stage. To solve the question of the expediency of using the technique of spectrophotometry of tumor tissues in patients with breast cancer in order to assess the effectiveness of chemotherapy, a larger number of women under examination and a period of their follow-up for 3–5 years are required.

A phase 1 dose-escalation study to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamic activity of CLN-619 (anti-MICA/MICB antibody) alone and in combination with pembrolizumab in patients with advanced solid tumors.

TPS2688 Background: The major histocompatibility complex (MHC) class I-related proteins MICA and MICB are stress-inducible, surface glycoproteins that are up-regulated on human tumors. MICA/MICB are ligands for the activating receptor, Natural Killer Group 2 member D (NKG2D) expressed on Natural Killer (NK) cells, CD8+ T cells, γδ T cells and iNKT cells. Proteases in the tumor microenvironment cleave MICA/MICB from the cell surface which enables tumor cells to evade immune cell recognition and destruction by NKG2D-expressing cells. Increased concentrations of shed MICA have been observed in serum from patients across multiple tumor types and correlate with poor survival. CLN-619 is a humanized, clinical-stage, MICA/MICB-specific IgG1 monoclonal antibody that prevents the proteolytic release of MICA/MICB thereby exposing tumor cells for immune destruction through both NKG2D-mediated and antibody-dependent cell-mediated cytotoxicity (ADCC). The antibody has been shown to restore the MICA/MICB-NKG2D axis to promote NK-mediated tumor cell lysis (AACR Annual Meeting abstract 3506, April 2022). In mice bearing MICA/MICB-expressing human tumor xenografts, CLN-619 treatment yielded robust anti-tumor activity at low doses. MICA/MICB is expressed in a wide range of solid tumors. Therefore, CLN-619 is expected to have broad anti-tumor activity. Methods: CLN-619 is being evaluated in an open-label, non-randomized, dose-escalation (phase 1) study as monotherapy, and in combination with pembrolizumab, in patients with advanced solid tumors. Cohort expansion in patients with specific indications as monotherapy and in combination with pembrolizumab will be conducted. The phase 1 study explores ascending intravenous doses of CLN-619 as monotherapy (0.1, 0.3, 1.0, 3.0, 6.0 and 10.0 mg/kg) and in combination with pembrolizumab (200 mg) in 21-day cycles to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Key eligibility criteria include 1) histological or cytological diagnosis of cancer and 2) refractory metastatic disease, or locally advanced disease not amenable to local therapy. At the RP2D, CLN-619 monotherapy will be evaluated in non-small cell lung and cervical cancer. In parallel, a cohort of patients will be administered CLN-619 in combination with pembrolizumab. Serum levels of soluble MICA/MICB, identity of MICA/MICB alleles, phenotypes of peripheral blood mononuclear cells, cytokines and tumor biopsies will be investigated for correlative pharmacodynamic and predictive biomarkers. This clinical trial is in progress (NCT05117476) and has completed accrual of three participants at the first dose level. Clinical trial information: NCT05117476.

Outer Cutoff Value for the Box-Counting Method for Fractal Analysis of the Nucleus Using Kirsch Edge Detection

Objective: The complexity of chromatin (i.e., irregular geometry and distribution) is one of the important factors considered in the cytological diagnosis of cancer. Fractal analysis with Kirsch edge detection is a known technique to detect irregular geometry and distribution in an image. We examined the outer cutoff value for the box-counting (BC) method for fractal analysis of the complexity of chromatin using Kirsch edge detection. Materials: The following images were used for the analysis: (1) image of the nucleus for Kirsch edge detection measuring 97 × 122 pix (10.7 × 13.4 μm) with a Feret diameter of chromatin mesh (n = 50) measuring 17.3 ± 1.8 pix (1.9 ± 0.5 μm) and chromatin network distance (n = 50) measuring 4.4 ± 1.6 pix (0.49 ± 0.18 μm), and (2) sample images for Kirsch edge detection with varying diameters (10.4, 15.9, and 18.1 μm) and network width of 0.4 μm. Methods: Three types of bias that can affect the outcomes of fractal analysis in cytological diagnosis were defined. (1) Nuclear position bias: images of 9 different positions generated by shifting the original position of the nucleus in the middle of a 256 × 256 pix (28.1 μm) square frame in 8 compass directions. (2) Nuclear rotation bias: images of 8 different rotations obtained by rotating the original position of the nucleus in 45° increments (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°). (3) Nuclear size bias: images of varying size (diameter: 190 pix [10.4 μm], 290 pix [15.9 μm], and 330 pix [18.1 μm]) with the same mesh pattern (network width: 8 pix [0.4 μm]) within a 512 × 512 pix square. Different outer cutoff values for the BC method (256, 128, 64, 32, 16, and 8 pix) were applied for each bias to assess the fractal dimension and to compare the coefficient of variation (CV). Results: The BC method with the outer cutoff value of 32 pix resulted in the least variation of fractal dimension. Specifically, with the cutoff value of 32 pix, the CV of nuclear position bias, nuclear rotation bias, and nuclear size bias were <1% (0.1, 0.4, and 0.3%, respectively), with no significant difference between the position and rotation bias (p = 0.19). Our study suggests that the BC method with the outer cutoff value of 32 pix is suitable for the analysis of the complexity of chromatin with chromatin mesh.

Kliniczne znaczenie rozpoznania zmiany pęcherzykowej bliżej nieokreślonej (grupa III wg Systemu Bethesda) w biopsji aspiracyjnej cienkoigłowej (BAC)

Follicular Lesion of Undetermined Significance (FLUS) belongs to the most controversial category of the Bethesda System. The aim of the study was to specify the risk of malignancy in patients with FLUS diagnosis in the material from the Institute of Oncology in Gliwice. This is the first Polish study specifying the risk of malignant neoplasm presence when Fine-Needle Aspiration Biopsy (FNAB) results in a report of diagnostic category III (DC III). Three hundred and ninety-five primary DC III diagnoses from FNABs of the thyroid gland performed from 2010 to 2015 were analysed. Correspondence of DC III with diagnoses from repeated FNABs and histopathology reports was evaluated. From 395 DC III patients, 27 were treated surgically for clinical indications, receiving six diagnoses of cancer. Repeat FNAB was performed in 180 cases, and primary diagnosis was confirmed in 41 cases. In the second FNAB there was one diagnosis of "Papillary Thyroid Carcinoma" and one "Suspicious for Papillary Thyroid Carcinoma". From eight patients treated surgically in these series prior cytological cancer diagnosis was confirmed in two cases. Forty-six patients were subjected to third and subsequent FNABs; in one case the diagnosis was "Suspicious for Malignancy". In the analysed material the risk of cancer in patients with FLUS is 2.78%. Taking into account all 56 subsequent FNABs in which the primary diagnosis was confirmed, the risk decreases to 2.43%. The diagnosis of FLUS in the absence of clinical indications is not a basis for surgical treatment.

Cytological diagnosis of cancer in serous fluids, secretions and excretions

Cytological diagnosis of cancer in serous fluids, secretions and excretions

Reconfigurable microfluidic integration of a dual-beam laser trap with biomedical applications

A dual-beam fiber laser trap, termed the optical stretcher when used to deform objects, has been combined with a capillary-based microfluidic system in order to serially trap and deform biological cells. The design allows for control over the size and position of the trap relative to the flow channel. Data is recorded using video phase contrast microscopy and is subsequently analyzed using a custom edge fitting routine. This setup has been regularly used with measuring rates of 50-100 cells/h. One such experiment is presented to compare the distribution of deformability found within a normal epithelial cell line to that of a cancerous one. In general, this microfluidic optical stretcher can be used for the characterization of cells by their viscoelastic signature. Possible applications include the cytological diagnosis of cancer and the gentle and marker-free sorting of stem cells from heterogeneous populations for therapeutic cell-based approaches in regenerative medicine.

Joint research project of genetic diagnosis of papillary thyroid cancer between Semipalatinsk Medical Academy and Nagasaki University

The activating point mutation of BRAF gene, BRAF T1799A , is the most common and specific genetic alteration in adult papillary thyroid carcinoma. BRAF T1799A seems to be associated with clinical aggressiveness of papillary thyroid carcinoma. We have established that PCR-RFLP method enables us to detect the BRAF T1799A mutation using DNA extracted from fine-needle aspiration biopsy samples and then applied this proprietary method not only to our clinical practice but also to international medical assistance around the Semipalatinsk Nuclear Testing Site in Kazakhstan. Seventy cases from Japan and one hundred cases from Kazakhstan were examined. There were 14 Japanese and 50 Kazakhstani cases of cytological malignant tumors in all of the examined samples, among which we detected 12 and 14 cases with BRAF T1799A in Japanese and Kazakhstan cases, respectively. Of these cases, we found mutations in two cytological “suspicious” cases and even two pathological “benign” cases (after surgery in Kazakhstan). All of the BRAF mutation-positive cases, including those four, were confirmed as papillary thyroid carcinoma by careful pathological examination including immunohistochemical analysis. In conclusion, our PCR-RFLP method for BRAF T1799A detection using fine-needle aspiration biopsy samples is useful not only for preoperative diagnosis but also for accurate pathological decision of difficult cases as a complementary diagnostic method even after surgery. The introduction of appropriate genetic evaluation together with cytological cancer diagnosis into Kazakhstan makes a novel possibility for our future joint project.

SENSITIVITY OF HUMAN COMPLEMENT FACTOR H RELATED PROTEIN (BTA STAT) TEST AND VOIDED URINE CYTOLOGY IN THE DIAGNOSIS OF BLADDER CANCER

We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.

4588 Endoscopic ultrasound as a first-line diagnostic and staging test after ct in patients with suspected or proven lung cancer: yield in 122 consecutive patients.

Background: 50% of lung cancer patients have mediastinal lymph node metastases. Proof of ipsilateral node (N2) or contralateral node (N3) involvement contraindictates surgery as primary treatment, but usually requires mediastinoscopy. EUS-guided fine needle aspiration (FNA) provides access to posterior mediastinal nodes and may therefore prevent mediastinoscopy and document surgically incurable disease. Aim: To verify the yield of EUS as a first-line diagnostic and staging modality in patients with suspected or proven lung cancer by CT and/or bronchoscopy. Methods: EUS-FNA was used as a first-line diagnostic and/or staging test in consecutive patients with suspected or proven lung cancer in whom CT showed mediastinal disease accessable for EUS-FNA. Results: 122 consecutive patients had disease that appeared amenable to EUS-FNA: 70 with suspected and 52 with proven lung cancer. Overall, EUS was attempted in 118 (97%) cases: 10 masses and 108 nodes (47% level 7 [AP window]; 32% level 5 [subcarina]; 15% levels 5 & 7; and 6% other node levels). There were no complications. A cytological diagnosis of cancer was obtained in 46/70 (69%) of suspected cancers. The yield for nodal staging was calculated on an "intent to stage" basis. Mediastinal node involvement was documented cytologically in 73/112 (60%) cases where staging was the aim: 37/112 (33%) N2 and 36/112 (32%) N3 nodes. See Table. Conclusions: 1) EUS has a high yield in patients with suspected or proven lung cancer with mediastinal disease by CT. 2) A cytological diagnosis of cancer is obtained in 2/3 patients with suspected cancer. 3) Cytological proof of mediastinal ipsilateral or contralateral disease is obtained in 2/3 patients.

Diagnostic cytology of the uterine cervix: a major contribution and classic reference in gynecologic cytopathology.

Diagnostic cytology of the uterine cervix: a major contribution and classic reference in gynecologic cytopathology.

Reproducibility and accuracy of interactive segmentation procedures for image analysis in cytology.

The segmentation of nuclear images is a crucial step in the development of procedures using image analysis for the cytological diagnosis of cancer. The purpose of this study is to evaluate the reproducibility and accuracy of several interactive segmentation methods which can be used in this context. Four methods were studied: a thresholding-based method enabling selection of intensity histogram contrast and brightness, manual tracing with a stylus, and arc- and ellipse-fitting routines. Features of nuclear size and shape were derived from nuclei segmented on repeated occasions by several individuals. Variance component models provided a statistical framework for evaluating the intraobserver and interobserver variability of these measurements in terms of their intraclass correlation coefficients. Of the methods tested, the arc-fitting segmentation method gave the most reproducible results, and thresholding the least. Reproducibility was generally very high both between individuals and for repeated segmentations by a single individual. Accuracies of area measurements for the various methods, as determined with respect to point counting, paralleled the reproducibilities of the methods. Sample size requirements were observed to be more dependent on the biological variability of the tissue sampled than on the particular segmentation method or on the number of individuals performing segmentation.

Deoxyribonucleic Acid Ploidy Enhances the Cytological Prediction of Recurrent Transitional Cell Carcinoma of the Bladder

Purpose We determined whether deoxyribonucleic acid (DNA) ploidy analysis by image analysis cytometry enhances the cytological diagnosis of recurrent transitional cell carcinoma of the bladder. Materials and Methods A retrospective study was performed during a 5-year period to evaluate the cytological diagnosis and DNA ploidy analysis of 469 patients with previously diagnosed superficial transitional cell carcinoma. Cytological and DNA ploidy analysis was performed on 1,034 urine and bladder wash specimens, and the patients were monitored with cystoscopy and biopsies as clinically indicated. Cytology results were classified as normal, atypical, dysplastic or cancerous, and DNA ploidy was defined as normal if the diploid index was 1.2 or less, the S phase - G2M fraction was less than 21% or if there were 3% or less hyperploid cells, or abnormal if there was an increased S phase - G2M fraction, an aneuploid peak on the histogram or tetraploidy or hyperploidy was present. Results The majority of patients (85 of 88, 97%) with a cytological diagnosis of cancer had an abnormal DNA ploidy, and in 60 of 85 of these patients (71%) recurrence was diagnosed within 6 months. Only 5 of 284 specimens (2%) with normal cytology had abnormal DNA ploidy and 1 of these 5 (20%) heralded transitional cell carcinoma recurrence. However, in 145 patients with atypical cytological findings 29 (20%) with abnormal DNA ploidy had a recurrence, compared to 20 of 391 (5%) with normal DNA ploidy (p < 0.0001). Similarly, in 101 patients with dysplastic cytological findings 39 (39%) with abnormal DNA ploidy had transitional cell carcinoma recurrence compared to 4 of 25 with normal ploidy (p = 0.033). Conclusions Abnormal DNA ploidy determined by image analysis significantly enhances the detection of bladder tumor recurrence in patients with atypical or dysplastic cytology but not in those with normal cytology or frank carcinoma on cytological findings.

Deoxyribonucleic acid ploidy enhances the cytological prediction of recurrent transitional cell carcinoma of the bladder.

We determined whether deoxyribonucleic acid (DNA) ploidy analysis by image analysis cytometry enhances the cytological diagnosis of recurrent transitional cell carcinoma of the bladder. A retrospective study was performed during a 5-year period to evaluate the cytological diagnosis and DNA ploidy analysis of 469 patients with previously diagnosed superficial transitional cell carcinoma. Cytological and DNA ploidy analysis was performed on 1,034 urine and bladder wash specimens, and the patients were monitored with cystoscopy and biopsies as clinically indicated. Cytology results were classified as normal, atypical, dysplastic or cancerous, and DNA ploidy was defined as normal if the diploid index was 1.2 or less, the S phase+G2M fraction was less than 21% or if there were 3% or less hyperploid cells, or abnormal if there was an increased S phase+G2M fraction, an aneuploid peak on the histogram or tetraploidy or hyperploidy was present. The majority of patients (85 of 88, 97%) with a cytological diagnosis of cancer had an abnormal DNA ploidy, and in 60 of 85 of these patients (71%) recurrence was diagnosed within 6 months. Only 5 of 284 specimens (2%) with normal cytology had abnormal DNA ploidy and 1 of these 5 (20%) heralded transitional cell carcinoma recurrence. However, in 145 patients with atypical cytological findings 29 (20%) with abnormal DNA ploidy had a recurrence, compared to 20 of 391 (5%) with normal DNA ploidy (p < 0.0001). Similarly, in 101 patients with dysplastic cytological findings 39 (39%) with abnormal DNA ploidy had transitional cell carcinoma recurrence compared to 4 of 25 with normal ploidy (p = 0.033). Abnormal DNA ploidy determined by image analysis significantly enhances the detection of bladder tumor recurrence in patients with atypical or dysplastic cytology but not in those with normal cytology or frank carcinoma on cytological findings.

Endoscopic cytology of cancer of the esophagus and cardia: a long-term evaluation

Between January 1979 and December 1986, 858 endoscopic cytological examinations of the esophagus were performed, including 309 patients with confirmed malignancies. A positive cytological diagnosis of cancer was made in 289 (93.5%). Adequate biopsies were obtained in 269 instances (87.0%), being positive in 238 cases (overall positivity of biopsy, 77.02%). The combined use of biopsy and cytology provided a correct diagnosis in 98.0% of cases. The cytological examinations were positive in 30 of 40 patients (75.0%) with obstructing lesions in whom no satisfactory biopsies could be obtained. No false positive diagnosis was made among the 550 patients with benign conditions. In this series, cytology increased the yield of biopsy by 20.8%.

Lucy Wortham James Award. Cytologic detection and diagnosis of cancer. Its contributions and limitations.

The use of cytology for the detection and diagnosis of cancer has been a rapidly developing area of pathology. Cytology has been used for mass screening of asymptomatic people, for selective screening of individuals at high risk, and for diagnosis in patients suspected of having cancer. The only area in which mass screening has proved to be cost effective in reducing morbidity and mortality rates is cancer of the uterine cervix. Selective high risk screening has been proposed for endometrium, lung, urinary tract, gastrointestinal tract and oral cavity. Field trials have been performed for each site and some are still operational. While a degree of success has been achieved in identifying patients with early and asymptomatic cancer, cost effectiveness has not as yet been demonstrated and it seems unlikely that it will be. The cytologic diagnosis of cancer of these sites in symptomatic patients is highly effective for lung and bladder cancer. It has been somewhat less effective for gastrointestinal cancer. It is also of value in identifying cancer cells in effusions and for cancer staging. Fine-needle aspiration biopsy for the diagnosis of cancer has been used for over half a century, but in more recent years it has gained wider usage and is now used to diagnose tumors of almost any organ. It is highly cost effective, does not require hospitalization or anesthetic, and is rapid and accurate. Some of the indications and limitations of cellular diagnosis of cancer are presented.

Ultrasound-guided percutaneous fine-needle aspiration cytology in pancreatic cancer.

Fifty-five patients underwent ultrasound-guided fine-needle aspiration from the pancreas. Adequate material was obtained from 33 of the 41 patients with pancreatic malignancy. A cytological diagnosis of cancer was made in 31 (94%) of these; the overall clinical success rate was 75.6%. There were no false-positive results or complications. The sensitivity of the procedure may be increased by repeating the punctures.

Sonographically Guided Fine-Needle Aspiration of Liver Lesions

FINE-needle percutaneous aspiration biopsy of the liver and other intraabdominal organs has been shown to be a safe and accurate method for the cytological diagnosis of cancer.^1-4When combined with an imaging modality such as ultrasound, computed tomography, or fluoroscopy, the diagnostic yield has been reported to be from 85% to 100%.^1-4The liver is easily depicted sonographically. With present-day ultrasound equipment, lesions as small as 2 cm can be imaged. Since 1978 the radiologists in this group of authors have used ultrasound as a guide in aspirating focal masses in the liver. This method has provided rapid and accurate diagnoses in 45 of 59 patients, thus eliminating other more costly and time-consuming studies. <h3>Materials and Methods</h3> The chief indication for performing a guided percutaneous thin-needle aspiration was the demonstration of a focal solid or semisolid liver mass on an initial diagnostic scan (Figure). Before the aspiration biopsy

Book Review: The Cytologic Diagnosis of Cancer

Book Review: The Cytologic Diagnosis of Cancer

Cytological diagnosis of cancer of the biliary tract pancreas and duodenum with duodeno-fiberscope.

Cytological diagnosis of cancer of the biliary tract pancreas and duodenum with duodeno-fiberscope.

Book ReviewThe Cytologic Diagnosis of Cancer.

Book ReviewThe Cytologic Diagnosis of Cancer.