Non-specific Type Research Articles

Urinary Protein and Peptide Markers in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a non-specific type of kidney disease that causes a gradual decline in kidney function (from months to years). CKD is a significant risk factor for death, cardiovascular disease, and end-stage renal disease. CKDs of different origins may have the same clinical and laboratory manifestations but different progression rates, which requires early diagnosis to determine. This review focuses on protein/peptide biomarkers of the leading causes of CKD: diabetic nephropathy, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis, and membranous nephropathy. Mass spectrometry (MS) approaches provided the most information about urinary peptide and protein contents in different nephropathies. New analytical approaches allow urinary proteomic–peptide profiles to be used as early non-invasive diagnostic tools for specific morphological forms of kidney disease and may become a safe alternative to renal biopsy. MS studies of the key pathogenetic mechanisms of renal disease progression may also contribute to developing new approaches for targeted therapy.

English

Biomarkers are considered as an innovative tool in the diagnosis and follow-up of breast cancer. The aim of the study was to assess the profile of circulating tumour markers CA 15-3 and CEA in patients under chemotherapy for breast cancer in Ouagadougou. This is a prospective cross-sectional study with a descriptive and analytical aims which was done from July to November 2020. Patients with histologically confirmed malignant breast tumour and under chemotherapy were included. Results revealed that the study was on thirty (30) female patients whose average age was 47.47 ± 2.10 years with a mean BMI of 27.29 ± 1.09 kg/m2. It was a non-specific type of infiltrating carcinoma with SBRm II grade in 90% of the patients. The mean CA 15-3 was 212.98 U/mL before chemotherapy and 165.75 U/mL after it. The CEA mean value was 3.13 ng/L before chemotherapy and 16.14 ng/L after it. Serum CA 15-3 was significantly associated with tumour site, SBRm grade, chemotherapy line and treatment response. Serum CEA level was significantly associated with tumour site and SBRm grade. Despite their lack of sensitivity, tumour markers, particularly CA 15-3 enabled assessment of the response to treatment in patients in this study.   Key words: Tumour markers, CA 15-3, CEA, breast cancer, chemotherapy.

Clinicopathological features and prognosis of male breast cancer.

ObjectiveWe aimed to describe the differences in clinicopathological characteristics and overall survival (OS) between male and female breast cancer patients, and to develop a prognostic nomogram to predict survival in patients with male breast cancer (MBC).MethodsUsing the Surveillance, Epidemiology, and End Results database, we compared age, race, histological type, histological grade, tumor size, lymph node status, metastases, estrogen/progesterone receptor (ER/PR) and HER-2 status between male and female patients, and analyzed their relationships with OS. We established a nomogram and produced a calibration curve to observe its predictive effect.ResultsAge, race, T stage, N stage, bone and lung metastases, and histological type and grade differed between male and female patients. OS in male patients was related to age, tumor size, metastatic site, ER/PR status, and histological grade, but not to race or lymph node status. A nomogram was established, which showed good predictive performance for survival in MBC patients (area under the curve = 0.7).ConclusionMBC has a worse prognosis than female breast cancer, mainly characterized by late onset age, late staging, high proportion of invasive non-specific histological types, high histological grade, and luminal breast cancer.

Ki67 as Proliferative Marker in Patients with Early Breast Cancer and Its Association with Clinicopathological Factors

Introduction: Ki67 as a proliferative marker has prognostic and therapeutic relevance in early breast cancer (EBC). However, standard cutoffs for distinguishing low and high Ki67 do not exist. Material and Methods: Data from all patients treated at the University Hospital Ulm for EBC between January 2013 and December 2015 with documented results for internal Ki67 assessment of the primary (n = 917) tumor were retrospectively analyzed evaluating the associations between Ki67 and other clinicopathological factors. Results: 595 (64.9%) patients had a Ki67 <20% and 322 (35.1%) a Ki67 ≥20%. The median Ki67 was 10% (range 1–90%). Median Ki67 values according to the hormone receptor (HR)/ human epidermal growth factor receptor 2 (HER2) subtypes were 10% for HR-positive/HER2 negative (HR+/HER2−) disease (n = 717), 20% for HR+/HER2+ (n = 76), 30% for HR−/HER2+ (n = 45), and 60% for HR−/HER2− (n = 75). 75.2% or 89.3% of all patients with HER2-positive or triple-negative disease had a Ki67 ≥20%, respectively. Using a multivariable logistic regression with Ki67 (<20% vs. ≥20%) as binary dependent variable, younger age, positive nodal status, higher grading, histological nonspecific type carcinoma, negative HR status, and positive HER2 status were shown to be significantly associated with a higher proliferative index (Ki67 ≥20%). Conclusion: This analysis described Ki67 in different subtypes in EBC and its association with clinicopathological factors. According to more aggressive tumor biology, the respective subgroups also showed higher median Ki67 levels. However, definition of low and high proliferation index itself is difficult. It is essential to interpret Ki67 indices carefully with regard to the own institutional values and other clinicopathological factors.

Prognostic value of tumor-infiltrating lymphocytes (TILS) and their association with clinicopathological features in breast cancer: A retrospective study involving 53 cases

ObjectiveQuantitative analysis of tumor-infiltrating lymphocytes (TILs) is currently considered as a prognostic factor in several malignant tumors. The aim of our study was to assess the prognostic value of TILs in breast cancers and its association with other clinicopathological prognostic factors in non-specific type (NST) breast carcinoma in Tunisian population. MethodsRetrospective study included 53 women with NST breast carcinoma. The data were collected over a period of 13 months with a follow-up of 40 months for all the patients. The TILs were evaluated according to the 2014 recommendations of the international working group on TILs. ResultsTILs level was between 3% and 60% with mean of 21%. Ten patients had lymphocyte predominant breast cancer (LPBC). Statistical analysis had shown that the TILs level ≤50% was associated with the presence of vascular emboli and the absence of HER2 amplification. Inflammatory-type carcinoma and HER2 amplification significantly worsened OS. Presence of vascular emboli, lymph node metastases, inflammatory type of carcinoma, TILs ≤50%, and absence of estrogen receptors (ER) were associated with reduced RFS. In multivariate analysis, the presence of vascular emboli was an independent factor for OS. TILs ≤50%, inflammatory type of carcinoma and presence of vascular emboli were independent risk factors for RFS. ConclusionThis Tunisian pilot study showed higher level of TILs in NST breast carcinomas is associated with improved RFS. The therapeutic implications will benefit from multiple research studies including ours on the predictive value of TILs for neoadjuvant or adjuvant treatment.

INFECTIOUS COMPLICATIONS AFTER RECONSTRUCTIVE SURGERIES IN BREAST CANCER PATIENTS: A CASE REPORT

Introduction. Currently, there is no global consensus regarding the management of breast cancer patients with implant-associated infections. Some studies clearly recommend their removal and surgical debridement with consecutive antimicrobial treatment, while others prefer long-term antibacterial therapy (at least 1 month) with the effectiveness of such conservative approach of 36–73 %.Case description. A 43-year-old patient suffering from brca1-positive right breast cancer t2n0m0 (invasive carcinoma of non-specific type g3, er – 8, pgr – 0, her-2/neu – 0, ki67 (%) – less than 20 %), underwent radical skin-preserving mastectomy on the right with simultaneous implant reconstruction and preventive subcutaneous mastectomy on the left with simultaneous implant reconstruction. Peri-implant infection in the left breast was observed on the 21st day after surgery.Results. The patient received empirical therapy with cefepim. Microbiological examination of the punctate revealed the causative agent of infection – methicillin-resistant staphylococcus aureus (mrsa) (1×105cfu/ml). Daptomycin 6 mg/kg/day was added to therapy. After 8 weeks, the patient received oral moxifloxacin 400 once daily, for another 3 weeks. A complete response was achieved. The patient has no signs of infection for 3 years.Conclusion. Long-term etiotropic antibacterial therapy with daptomycin followed by oral moxifloxacin resulted in a stable clinical effect.

Identification of Thioflavin T Binding Modes to DNA: A Structure-Specific Molecular Probe for Lasing Applications.

The binding mechanism of thioflavin T (ThT) to DNA was studied using polarized light spectroscopy and fluorescence-based techniques in solutions and in solid films. Linear dichroism measurements showed that ThT binds to DNA duplex by intercalation. Time-resolved fluorescence studies revealed a second binding mode which is the external binding to the DNA phosphate groups. Both binding modes represent the nonspecific type of interactions. The studies were complemented with the analysis of short oligonucleotides having DNA cavities. The results indicate that the interplay between three binding modes—intercalation, external binding, and binding inside DNA cavities—determines the effective fluorescence quantum yield of the dye in the DNA structures. External binding was found to be responsible for fluorescence quenching because of energy transfer between intercalated and externally bound molecules. Finally, amplified spontaneous emission (ASE) was successfully generated in the ThT-stained films and used for detecting different DNA structures. ASE measurements show that ThT-stained DNA structures can be used for designing bioderived microlasers.

Association of pathological clinical characteristics, PD L 1 receptor expression (sp 142), with tumor lymphocytic infiltration cells (TILs) in patients (pts) with triple negative breast cancer (TNBC) in Tucumán, Argentina.

e13049 Background: Breast cancer (BC) is the most prevalent tumor in women and the leading cause of cancer death in women. TNBC has the worst prognosis among BC subtypes and limited treatment options, mainly including chemotherapy. The efficacy of immunotherapy is clear for immunogenic tumors, such as melanoma, kidney cancer, non-lung cancer small cell, among others. BC seems to be less immunogenic. Basal-type TNBC present a prominent infiltration of inflammatory cells, suggesting that an immune pathway plays a role in tumorogenesis. The development of immunotherapy (IO)has reached an important turning point in the history of cancer treatment based on the use of the immune system itself to fight tumor cells. PD-L1 overexpression is the only predictive response biomarker for anti-PD-1 / PD-L1 therapy that is accepted in TNBM. Methods: Retrospectively, 68 cases of TNBC from the Pathological Anatomy Service of the Ntra. Sra. De las Mercedes Maternity Institute, of Tucumán, between 2010 and 2016 were analyzed. VENTANA anti PDL1 sp142 assay platform was used. Tumor-infiltrating immune cells (IC) are scored as the proportion of tumor area that is occupied by PD-L1 staining IC of any intensity. A specimen should be considered to have PD-L1 expression if the specimen exhibits ≥ 1% IC. In addition, carcinomas with a proportion greater than 50% of lymphocytic infiltration and its association with the expression of PD L1 were studied according to the recommendations of the International TILs Working group. Results: The median age of the patients was 56 years (21-80). The predominant histological type was non-specific type ductal carcinoma, reported in 45/68 cases (66%), following the medullar 9 / 68 (13%) lobular in 8/68 (11%), metaplastic 3/68 (4%) and other 4%. The tumor grade (G), half of the cases were G 3 with 34/68 (50%), G 2 with 42%. The largest proportion of pts, 42%, had no lymph node (LN) involvement, 33% had between 1 to 3 positive LN and 25% showed 4 or more LN. Stage II 39/68 patients (58%) in stage III 20/68 (30%), I (9%, 6) and IV (3%, 2). 16% (11/68) of the patients were PD-L1 positive. Tumors with lymphocytic infiltration between 0% and 10% expressed 24% (2/37), no expression was observed in tumors with TIls between 10 and 50% and in cases with lymphocytic infiltration greater than 50% expression of PD L was observed 1 in 9/18 cases (50%) (Fisher's exact test, p &lt; 0.0001). Conclusions: It was demonstrated that there is an association between the stromal lymphocytic infiltrate (TILs) and the expression of PD-L1 in tumor cells, in this population of women from Tucumán, which would help to select patients as candidates for anti PD L1 therapies.

Primary Systemic Therapy for HER2/Neu-Positive Operable Breast Cancer Increases the Number of Breast-Conserving Surgery and Disease-Free Survival: Retrospective Cohort Analysis at Single Institution

Objective The aim of this study was to evaluate the efficacy and cardiotoxicity profile, and to reduce the extend of breast cancer surgery in primary systemic therapy (PST) HER2/neu–positive operable breast cancer patients. Materials and Methods A total of 152 patients diagnosed from 2010 to 2015 were included in the study. The PST consisted of a sequential regimen of taxanes and anthracyclines plus trastuzumab. The clinical and pathological responses and the type of breast cancer surgery were evaluated and correlated with clinical and biological factors. The cardiotoxicity profile and long-term benefits were analyzed. Results The median patient age was 47 (37–67) years, with T2 and T3 67 (44.1%) and 85 (55.9%), respectively. Axillary lymph node breast cancer at diagnosis N0 was 104 (68.4%) and N1 and N2 were 28.9% and 2.6%, respectively. A total of 95.7% of patients had nonspecific type of breast cancer, 67% of tumors were hormonal receptor–negative, 75.5% were grade III, 100% Ki67 &gt; 20%, and 90% of tumors were confirmed to be HER2/neu–positive through immunohistochemistry. Following PST, pathological complete response (pCR) rate was achieved in 44.7% evaluable patients. The pCR rate was higher in HR-negative (93.1% vs. 6.9%) cancer and in grade III (86.2%) than in grade I and II (13.8%) cancer; only 75.5% of complete response (CR) on ultrasound and magnetic resonance imaging were also CR on pathology results. Breast conserving surgery was performed in 41.4%. Regarding type of chemotherapy, there were no significant differences between chemotherapy with anthracycline backbone or taxanes to achieved pathological complete response. Despite that, we were unable to demonstrate an association between pCR and better DFS with p = 0.096; HR 5.7 95.0% CI (0.73–45.52). Patients who are hormonal receptor positive tend to have lower disease-free survival (DFS) than those who are hormonal receptor negative; HR = 6.34, 95.0% CI (1.54–26.00) and p = 0.010. Five years DFS was higher for those who achieved pCR compare with those who did not. Even in this research we failed to show it is statistically significant. Conclusion A sequential regimen of taxanes and anthracyclines plus trastuzumab was effective with high pCR rates and increases the possibility to do breast conservation surgery and had tolerable cardiotoxicity profile.

Characterization of microvascular disease in pediatric sickle cell disease using nailfold capillaroscopy

Sickle cell disease (SCD) is a disorder with repetitive vaso-occlusive crises resulting in microvascular obstruction and tissue ischemia that may lead to multi-organ ischemia and dysfunction. Nailfold videocapillaroscopy (NFC) is an imaging technique utilized in clinical rheumatology to visualize capillaries located near the fingertip. To characterize NFC abnormalities in the setting of pediatric SCD, we performed NFC using a video capillaroscope on 8 digits in 44 stable SCD patients and 65 age matched healthy controls. Mean capillary number was lower (6.4 ± 1.3 vs 7.5 ± 1.8, p = 0.001) in the SCD group compared to controls. The percentage of dilated capillaries was similar (7.1 ± 8.3 vs. 5.9 ± 8.2, p = 0.4). The large majority of capillaries visualized in the SCD and control groups were normal capillary types per the EULAR definition, with a similar percentage of normal, nonspecific capillary morphologies and abnormal types. Regarding normal capillary sub-types, the SCD group and controls exhibited similar percentages of stereotype hairpin shapes, and tortuous or once or twice crossing type capillaries. On multivariate analyses, mean capillary number was independently associated with SCD after adjusting for age, body mass index, systolic blood pressure and gender. In conclusion, pediatric SCD is associated with lower capillary number but similar percentage of dilated capillaries and morphology on NFC. In our SCD cohort, capillary number was unrelated to our available markers of disease severity, including history of sickle crises, previous hospitalization for crises or Hemoglobin F levels.

Breast Cancer in Togolese Women: Imaging and Clinicopathological Findings.

Background:Breast cancer is the most common cancer in women, and its incidence and mortality rates are expected to increase significantly over the next few years, particularly in developing countries. The aim of this study was to describe the epidemiological, clinical, radiological, histopathological, and prognostic aspects of breast cancer in Togo.Materials and methods:We retrospectively analyzed at our Department of Pathology of Lomé all cases of breast cancer in women confirmed by histology over a period of 20 years (2000-2019).Results:We collected 804 cases of breast cancer in women. The median age was 46.7 years (range, 12-86 years). Patients aged <40 years represented 48.38% of cases, and the left breast was more affected (51.24%). Most women were sexually active (71.52%) and resided in urban areas (66.29%). Carcinomas represented the predominant histological group (796 cases, 99.00%) with a predominance of invasive nonspecific type carcinoma (92.34%). These cancers were diagnosed at late stage III using Nottingham grading (55.10%). The TNM classification showed a predominance of grades T2NxMx (72.45%) and T4N1Mx (17.76%). The luminal B profile (40.85%) was found mostly, and the mutation of BRCA2 and BRCA1 genes was found in 2.61% of cases. Mastectomy was performed in 7.59%, radiotherapy in 3.61%, and chemotherapy in 18.66%.Conclusion:Breast cancer is a frequent pathology in Togolese women, predominant in young adults, often diagnosed at a late stage with limited possibilities of treatment. The establishment of early care programs is essential.

Prognostic significance of tumour infiltrating lymphocytes in different molecular subtypes of invasive breast carcinoma

Metastasis is the main cause of death from cancer, including breast cancer, so the search for simple and effective prognostic parameters is becoming a priority for researchers. The number of tumor-infiltrating lymphocytes is a proven prognostic factor for triple negative and Her2-positive, but not luminal, molecular subtypes of breast cancer. Possible reasons for the failure of this prognostic parameter for luminal subtypes of breast cancer may be the tumor morphological heterogeneity. Objective: to assess the prognostic significance of the tumor-infiltrating lymphocytes number in the invasive breast carcinoma of a non-specific type (IC NST) of various molecular subtypes, taking into account its morphological heterogeneity. 152 patients with IC NST (T1-3N0-2M0) aged 29 to 75 years were enrolled in the study. The molecular subtype was determined using immunohistochemical analysis of the expression of estrogen and progesterone receptors, Ki-67 and Her2/neu. TILs were assessed in accordance with the recommendations of the International TILs Working Group. It was shown that TILs near the structures of various types is heterogeneous only in patients with the luminal Her2-negative subtype of IC NST. In addition, was found that the development of hematogenous metastases and worse metastatic-free survival in this cohort of patients is associated with a high TILs near solid structures and also depended on Ki-67 level. Thus, TILs near solid structures is a potential prognostic factor for the development of distant metastasis in the luminal Her2-negative and Ki-67 level less 20% subtype of IC NST.

Real-world testing compliance to NCCN guideline and factors of underutilization in U.S. community clinics.

e21592 Background: Over the last 10 years, guideline recommendations for testing advanced non-small cell lung carcinomas (aNSCLC) have rapidly evolved with the identification of driver mutations and associated therapies. A retrospective study of the testing rates for ALK was initiated to understand real world adherence to guidelines. Methods: A retrospective study of the testing rates (negative category = not tested/unknown testing status) for ALK utilizing the nationwide Flatiron Health electronic record-derived de-identified database was initiated. Patients diagnosed with NSCLC (Stage IIIB-IV) were initially included (41,728 patients from Jan 2012 to May 2019) to describe the trend of ALK testing in community setting. An increase in ALK testing was seen from 59.5% to 84.1% of NCCN guideline eligible patients from 2012-2019. There was also an increase in the number of ineligible patients (smokers with squamous histology) tested (15.6% in 2012 to 50.8% in 2019). This 2012-2019 patient population was then limited to diagnosis from Jan 2015 to May 2019 to assess factors related to test utilization. In 26,617 aNSCLC patients, 75% were ALK testing eligible (by NCCN guidelines) with one quarter ineligible. Multivariable logistic regression analysis was used to assess clinical and demographic factors for impact on testing rates. Results: Both histology type and smoking status played an important role impacting ALK testing rate. Compared to non-squamous non-smokers (9.3% ALK-positive, 87.9% testing rate), non-smokers with squamous cell histology had a relatively high rate of ALK mutation (3.3%) but a low testing rate (55.03%) (Odds ratio (OR) 7.6, 95% CI 5.6-10.4). Other histology type and smoking status also had lower testing rate, including non-smoker with NSCLC non-specific type (OR 1.8, 95% CI 1.1-3.2), and smoker with non-squamous type (OR 1.5, 95% CI 1.3-1.7). Additional factors related to underutilization were patients with poorer ECOG scores and earlier stage at diagnosis. Demographic characteristics that also played a role in underutilization were older age ( &gt; 50 yrs), non-commercial insurance, male, and patients diagnosed before 2017. Conclusions: This analysis of real world data shows that test utilization has increased but there remains room for improvement. While testing ineligible patients is an inefficient use of resources (smokers with squamous histology), smokers with a small biopsy should be tested as they might be harboring an actionable driver mutation. Eligible patients still remain untested and potentially missing therapeutic options.

Clinicopathological features and prognosis of synchronous bilateral breast cancers

Objective: To study the clinicopathologic characteristics and relevant factors affecting prognosis of patients with synchronous bilateral breast cancer. Methods: The clinical data, pathologic characteristics and immunohistochemical expression characteristics of 151 patients with synchronous bilateral breast cancers diagnosed in Peking Union Medical College Hospital from 2008 to 2018 were collected and analyzed. The factors affecting the prognosis were analyzed by Log rank test, Kaplan-Meier survival analysis, Cox regression and other methods. Results: Synchronous bilateral breast cancer cases accounted for 1.2% (151/12 239) of all breast cancer patients in the same period, and 14.6% (22/151) had a family history. The patients' age range was 22-88 years, mainly female, with a mean survival of 42.5 months. There were 106 patients with synchronous bilateral invasive breast cancers, 6 patients with synchronous bilateral breast cancer in situ, and 39 patients with unilateral invasive breast cancer and unilateral breast cancer in situ. In synchronous bilateral invasive breast cancers, the histological type was mainly non-specific type (84.9%, 180/212), the histological grade was mainly Grade 2 (60.8%,129/212), the TNM stage was mainly stage Ⅰ (50.5%, 107/212), the tumor size was mainly T1 (68.9%, 146/212), and the regional lymph node was mainly N0 (61.8%, 131/212). The molecular subtypes were mainly Luminal A-like (38.1%, 75/197) and Luminal B-like (43.7%, 86/197); ER (78.2%, 154/197) and PR (72.1%,142/197)were mainly positive, and HER2 was mainly negative (91.9%, 181/197). There were 85 (80.2%) patients and 75 (70.8%) patients with the same histological type and histological grade on both sides, respectively. The concordance of tumor size T stage and the regional lymph nodes N stage were 58.5% (62/106) and 55.7% (59/106), respectively. The concordance of molecular subtype was 54.9% (50/91), and the concordance of ER, PR, HER2 and Ki-67 were 83.5% (76/91), 76.9% (70/91), 89.0% (81/91) and 59.3% (54/91), respectively. The expression of ER and PR in synchronous bilateral invasive breast cancer was significantly correlated with prognosis (P<0.05). Conclusions: Among patients with synchronous bilateral breast cancers, bilateral invasive breast cancer is the most common, the prognosis is the worst, and the pathologic characteristics of bilateral breast cancer tend to be consistent. The expression of ER and PR in synchronous bilateral invasive breast cancer is significantly correlated with prognosis, that is, best for bilateral ER-positive patients, worst for bilateral ER-negative patients, and intermediate for unilateral ER-positive patients, thus suggesting the importance of ER and PR detection in synchronous bilateral invasive breast cancers.

THE MODERN ASPECTS OF THE BREAST CONSERVING SURGERY AFTER NEOADJUVANT CHEMOTHERAPY IN PATIENTS WITH BREAST CANCER CT1-3N0-3M0

Introduction. While the “no tumor on ink” approach is generally accepted for breast-conserving surgery (BCS) in patient with breast cancer, it remains unclear whether it is oncologically safe for BCS after neoadjuvant chemotherapy therapy (NACT). The aim of the study is to investigate the optimal width of the resection edges in BCS after NALT and the influence on disease-free and overall survival in patients with breast cancer. Materials and methods. Retrospectively, the medical documentation of 76 patients with breast cancer, who were performed BCS after NACT, was studied. The distribution by stage of breast cancer was as follows: I St. -5 patients, II St. - 55, III St. - 16 (excluded IIIB St.). Invasive cancer of non-specific type was diagnosed in 81.6% of cases, in 6.5% - lobular cancer, in 1.3% - combined breast cancer. Radical breast resections in the classic version were performed in 28 cases, and oncoplastic resections in various modifications were performed in 48 Cases. Results. We present the retrospective data of 76 patients with breast cancer who underwent OSA after NALT in the Department of breast and skin cancer OF the Moscow Institute of medical research. P. A. Herzen. The results of our study demonstrated the oncological safety of OSO with respect to new sizes of tumor nodes after NALT followed by remote radiotherapy. The method of “absence of tumor cells” at the edges of resection demonstrated a high percentage of 1, 3, 5-year relapse - free and overall survival, the frequency of relapse was 2.6%. There was no statistically significant difference in 1, 3, 5-year relapse-free and overall survival when the width of the resection edges was more or less than 1 mm. Conclusion. The results of numerous studies have demonstrated that the breast- conserving surgery is the safe method of surgical treatment from an oncological point of view and is an alternative for radical mastectomies for patients with the breast cancer after neoadjuvant chemotherapy.

Les cancers héréditaires du sein vus par le pathologiste

Breast cancers occurring in the context of a hereditary mutation of a predisposition gene represent 5 to 10% of all breast cancers, 20 to 25% of which being due to a mutation in the BRCA1 or BRCA2 genes. Authorization to market PARP inhibitors for breast cancer patients with hereditary BRCA1 and 2 mutations has recently been obtained. Given the annual frequency of breast cancer, morphological identification could facilitate the patient care process to limit the search for BRCA1 and 2 mutations to patients whose tumors have very specific characteristics. However, only a few morphological features have been recognized and differ depending on the mutated genes. Breast cancer occurring as part of a mutation in the BRCA1 gene is in 85% of cases of high-grade non-specific type invasive carcinomas with very limited contours, contain numerous lymphocytes in the stroma and are of triple-negative phenotype. Carcinomas associated with mutations in the BRCA2 genes and genes more recently recognized as associated with a risk of development of breast cancer (CHECK2, BMPR1A, BRIP1, PALB2, MUTYH) are most often non-specific invasive carcinomas, although other histological types are possible, grade III, luminal B phenotype. Breast cancer occurring in the context of a constitutional mutation of TP53 occurs in women under 35 years old are of non-specific histological type and with an amplification of HER2 in two thirds of the cases. Those associated with a PTEN mutation are readily of the apocrine type. Finally, very rarely, certain lobular-type breast cancers can occur in the context of a constitutional mutation of the CDH1 gene, which codes for the protein E-cadherin. The morphological and phenotypic characteristics may suggest to the pathologist a carcinoma of the breast occurring in a context of hereditary mutation. However, at the present time the only situations where a morphological sorting makes it possible to accelerate the genetic analysis are those of an invasive carcinoma of non-specific type of triple-negative phenotype in a woman of less than 50 years or that of a diagnosis of HER2 breast cancer amplified in a woman under 31 years of age (Chompret criteria). Family background and personal history are of great importance in the genetic counseling indication decision trees. Unfortunately, to date, no quality antibody has been developed against BRCA1 and 2 to help the pathologist identify hereditary cases. The immunohistochemical analysis of RAD51 could facilitate the identification of tumors possibly sensitive to PARP inhibitors. Progress to identify hereditary cancers is expected thanks to the development of artificial intelligence algorithms from digitized histological slides.

Photophysical and theoretical studies on the solvatochromic effects and dipole moments evaluation of substituted 1-phenyl-3-naphthyl-5- (4-ethyl benzoate)-2-pyrazoline

Abstract The solvatochromic behavior of four 1-phenyl-3-naphthyl-5-(4-ethylbenzoate)-2-pyrazoline with various electron donating and withdrawing substituents on N1-phenyl group were investigated in nonpolar, polar aprotic and protic solvents experimentally and theoretically. The photophysical behavior of pyrazoline in solvents was attributed to the intramolecular charge transfer (ICT) of the compound along with the specific and non-specific interactions with the solvent molecules. On view of the effect of different types of interactions on the optical properties, the Stokes shift of each compound in various solvents was correlated to various parameters such as orientation polarity parameter (Δƒ), microscopic solvent polarity parameter (ET 30), and linear solvation regression of the absorption and emission with specific and non-specific types of interaction. The dipole moments of these compounds in the ground and excited state were also explored and compared using different methods, and the results showed greater stabilization of the studied pyrazoline molecules in the excited state. The DFT and TDDFT calculations supported and explained the experimental data, by obtaining the absorption and emission energies, HOMO/LUMO energies and the dipole moments for each compound in various solvents. Analysis of electron-hole distribution suggests that the intense fluorescent of these molecules originates from a hybrid local excitation charge-transfer state (HLCT).

CHARACTERIZATION OF THE ABILITY OF TUMOR CELLS OF VARIOUS MORPHOLOGICAL STRUCTURES TO MODULATE IMMUNE-INFLAMMATORY REACTIONS IN INVASIVE BREAST CARCINOMA

The aim of the study was to assess the ability of tumor cells of invasive breast carcinoma of a non-specific type (IC NST) which forming various morphological structures to modulate their nearest microenvironment. Material and methods. An analysis was carried out of the data on the expression of the immune system (cytokines, including chemokines, and their receptors, pattern-recognizing molecules and growth factors) genes placed in the GEO database (Gene Expression Omnibus, number GSE80754). Results. The largest number of overexpressing genes that functionally provide parenchymal-stromal relationships is observed in discrete tumor cells. The spectrum of genes that contributed to the polarization in Th2 type of the immuno-inflammatory response was a characteristic for tumor cells building trabecular structures. Cells of tubular structures are characterized by overexpression of the IL15 gene, which attracts NK cells. Alveolar and solid structures do not have a pronounced ability to modulate their microenvironment. Conclusion. Tumor elements of various morphological structures of IC NST are characterized by functional heterogeneity in their ability to influence the type of immuno-inflam-matory reactions in their microenvironment.

Dizziness in patients with early stages of Parkinson's disease: Prevalence, clinical characteristics and implications.

The clinical features and implications of dizziness in patients with Parkinson's disease (PD) remain little known. This study aimed to investigate the clinical characteristics of dizziness, and the association of dizziness with motor and non-motor symptoms in early stages of PD. Demographics and clinical characteristics of patients with early PD (disease duration ≤5 years) were retrospectively assessed. The characteristics of dizziness were surveyed in each parkinsonian patient according to existence, frequency, duration and nature. Not only motor symptoms, but also non-motor scales for global cognition, anxiety, depression and fatigue were evaluated to identify risk factors of dizziness. Of a total of 80 patients with early PD, 37 (46.3%) had dizziness. The characteristics of dizziness included short duration (seconds to minutes) and frequent occurrence (several times in a day or a week). The most common type of dizziness was orthostatic (40.5%), followed by non-specific and disequilibrium type. Among many scales for motor and non-motor symptoms, dizzy patients with early PD showed lower scores of Montreal Cognitive representing global cognition than non-dizzy people. A lower Montreal Cognitive Assessment score was the only factor significantly related to dizziness in patients with early PD. We found that dizziness frequently occurs in early parkinsonian patients. It is highly linked to low Montreal Cognitive Assessment scores in patients with early PD, inferring that dizziness might be a potential non-motor symptom associated with cognitive decline in PD. Geriatr Gerontol Int 2020; 20: 443-447.

Datia Langhans cells as tuberculous lymphadenitis diagnose parameter based on chemical reaction

The incidence of tuberculosis in Indonesia increases every year, resulted in increased cases of tuberculous lymphadenitis. The histopathological picture is often similar to other types of lymphadenitis. This study was an in-depth exploration of the anatomical pathology of Langhans datia cells and necrosis in tuberculous lymphadenitis. This research used secondary data from medical record of the lymph node paraffin blocks in the Anatomical Pathology Department of Sadikin Hasan General Hospital Bandung from January to December 2017. There are 322 medical records of tuberculosis lymphadenitis patients, consisting of 179 types of tuberculous lymphadenitis, 144 types of non-lymphadenitis specific, and nine types of granulomatous lymphadenitis. In all kinds of lymphadenitis, necrosis shows a general picture, whereas datia Langhans are more dominant in the tuberculous and granulomatous lymphadenitis type. The description of necrosing in lymphadenitis is tuberculous type 176(98.3%), non-specific type 120(83.3%), and granulomatous type 7(77.8%), while datia Langhans cells are more common in 132(73.7%) tuberculosis lymphadenitis, and granulomatous lymphadenitis 7(77.8%), compared with non-specific lymphadenitis 42(29.2%). This study concludes that there is necrosis in almost every type of lymphadenitis, whereas datia Langhans cells are lower in the tuberculous and granulomatous lymphadenitis.