Should we use risk selection tests for HPV 16 and/or 18 positive cases: Comparison of p16/Ki67 and cytology.

Major screening abnormalities in precolposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primary human papillomavirus (HPV)-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Among 30 066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available high-risk types of HPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher positive predictive value for HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p < 0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2.26/2.19 vs. 3.54). Only one HSIL+ case was missed in both triage models with DS incorporation. p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.

p16/Ki67 dual stain triage versus cytology in primary human papillomavirus-based cervical cancer screening with limited genotyping.

The introduction of primary human papillomavirus (HPV) cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high-grade cervical disease without losing diagnostic specificity. From the 30.066 screening tests results, a total of 1086 with available high-risk human papillomavirus (HRHPV) with limited genotyping, cytology, and p16/Ki67 dual-stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. In HPV16/18-positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p < 0.0001; 45.9%/17.0% for CIN3+; p < 0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p = 0.0955; 100.0%/87.5% for CIN3+; p = 0.0832). In other HRHPV-positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p < 0.0001; 44.5%/16.5% for CIN3+; p < 0.0001), with sensitivity (92.3%/74.4% for CIN2+; p = 0.0522; 90.9%/81.8% for CIN3+; p = 0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18-positive cases for CIN2+ (45.4%; 95% confidence interval [CI]: 35.2-55.8; p < 0.0001) and very high NPV in all HPV-positive cases regardless of detected genotype (96.3%-100.0%). The risk (1-NPV) for CIN3+ in HRHPV16/18-positive/p16/Ki67-negative women was 0.0%. Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual-immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in secondary cervical cancer prevention.

Breast carcinoma grading on core needle biopsy - to grade or not to grade?

Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease and the basis for the treatment planning. The concordance rate between CNB and surgical excision specimen in determination of histological grade (HG) varies widely across literature, ranging from 59-91%. The aim of our study was to investigate the level of concordance between CNB and surgical excision specimen for the determination of HG for breast cancer patients. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. The concordance level between core needle biopsy and surgical resection specimen for overall histologic grading was 73%: for tubule formation - 71%, for nuclear pleomorphism - 91%, for the mitotic index - 59%. Our study shows that our institution's histologic grading of CNBs and surgical excisions shows a fairly good correlation and is useful for the planning of treatment.

Dendritic Cell Subpopulations Are Associated with Prognostic Characteristics of Breast Cancer after Neoadjuvant Chemotherapy-An Observational Study.

Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC.

Dendritic Cell Subpopulations Are Associated with Morphological Features of Breast Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is to identify DCIS with significant risk of transformation into BC. Dendritic cells (DC) are professional antigen presenting cells and as such play a pivotal role in the formation of immune cells that infiltrate in breast tumors. The aim of this study was to investigate the relationship between the density of DCs with different superficial antigens (CD1a, CD123, DC-LAMP, DC-SIGN) and various histopathological characteristics of DCIS. Our evaluation indicated that CD123+ and DC-LAMP+ cells were strongly associated with maximal tumor size, grading and neoductgenesis. Together with CD1a+ cells, they were negatively correlated with hormonal receptors expression. Furthermore, the number of DC-LAMP+ cells was higher in DCIS with comedo necrosis, ductal spread, lobular cancerization as well as comedo-type tumors, while CD1a+ cells were abundant in cases with Paget disease. We concluded that different subpopulations of DCs relate to various characteristics of DCIS. Of the superficial DCs markers, DC-LAMP seems particularly promising as a target for further research in this area.

Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden.

BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.

Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial.

OBJECTIVE: DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. METHODS: In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3-6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). RESULTS: Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42-1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20-0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. CONCLUSIONS: DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

Exploring the relationship between the body self and the sense of coherence in women after surgical treatment for breast cancer.

OBJECTIVE: Analysis of the relationship between the body self (BS) and the sense of coherence (SOC) in women after breast surgery due to cancer in comparison with a control group. METHODS: A cross-sectional study in a group of 78 women using the body-self questionnaire (BS-Q), and the life orientation questionnaire (SOC-29). Statistics based on the IBM SPSS v.25. RESULTS: Multivariate analysis of variance (MANOVA) has shown significant differences based on groups in experiencing intimacy, manifesting femininity, body acceptance, and manageability. In particular, manifesting femininity and body acceptance showed a big effect size (0.30 < partial ɳ2  < 0.32). Correlation analysis between the BS-Q and SOC-29 subscales and Fisher's r to z transformation determines that the differences between groups were significant in favour of healthy women in two sets of variables: experiencing intimacy/meaningfulness and attitude to food and weight/manageability. CONCLUSIONS: Breast cancer survivors are at greater risk of developing decreased body acceptance and problems in intimacy, and have less correlation than the healthy control group between manageability and meaningfulness with an appropriate attitude to food and intimate relationship with their partner, respectively. A higher manifestation of femininity in the treated group can be considered a positive but socioculturally conditioned coping strategy.

Lymphoid environment in molecular subtypes of breast cancer.

Recently, a large body of evidence has shown that the microenvironment of invasive breast carcinoma affects its development and the patient's outcome, and vice versa - cancer cells express factors that modulate tumour milieu in terms of its composition and function. We performed an immunohistochemical (IHC) staining of 108 formalin-fixed, paraffin-embedded (FFPE) tissue samples to investigate the relationships between T-cell, B-cell, and NK-cell infiltrate, invasive breast carcinomas molecular subtypes, and other prognostic indicators. The main findings of our study were as follows: the significantly higher infiltrate of the analysed immune cell subsets in triple-negative (TNBC), HER2-positive, non-luminal and luminal B/HER2+ breast carcinomas than in luminal A cancers; their higher densities in poorly differentiated lesions; correlations between lymphoid cells and the expression of hormonal receptors, HER2 receptor status, and marker of cancer proliferation. Furthermore, we observed T-cell numbers to be associated with greater tumour diameter. In summary, the results of our study indicate associations between tumoural lymphoid infiltration and the unfavourable intrinsic subtypes as well as other detrimental prognostic factors in invasive breast carcinomas.

The relationship between breast cancer treatment, tumour type and vitamin D level in pre- and postmenopausal women.

OBJECTIVE: Vitamin D deficiency has been linked to a higher risk of cancer. There is insufficient data regarding the influence of treatment on vitamin D status. The aim of this study was to compare pre- and post-treatment levels of 25(OH)D in premenopausal and postmenopausal women with breast cancer with a different receptor status (ER-estrogen receptors, PR-progesterone receptors) and in healthy controls. METHODS: 49 patients with breast cancer (23 premenopausal), and 28 healthy controls matched for age, menopausal status and BMI. RESULTS: The pre-treatment levels of 25(OH)D in patients with breast cancer were significantly lower in comparison to the control group (19 ng/mL vs. 30 ng/mL, p<0.001), the lowest in premenopausal women (18.4 ng/mL). After the treatment period, a significant decrease in 25(OH)D level (mean 15.8 ng/mL) was observed. The pre-treatment level of 25(OH)D was significantly lower in patients with ER (16.1 vs. 23.9 ng/mL, p=0.02) and with PR (15 vs. 24.4 ng/mL, p=0.003). The mean pre- and post-treatment levels of 25(OH)D were lower in patients with Ki67 <21% (16.7 vs. 20.1 ng/mL, p=0.15; 12.5 vs. 18.1 ng/mL, p=0.02 respectively). CONCLUSIONS: 25(OH)D level is lower in patients with breast cancer in comparison to healthy women, regardless of their menopausal status. The lowest levels are found in patients with ER and PR positive tumours. While a significant decrease in 25(OH)D level during the course of therapy is observed, the supplementation of vitamin D should be considered.

Pigmented Paget's disease of the nipple.

Pigmented Paget's disease of the nipple (PPD) is an uncommon variant of Paget's disease. An accumulation of melanin within the lesion imparts a brow color to the affected area, so the lesion might clinically as well as histologically mimic melanoma. We present a case of PPD in a 60-year-old woman.

Fertility-sparing treatment in female genital cancer and breast cancer.

Postponed motherhood is the reason why many women are diagnosed with cancer before they make the decision to conceive a child, but only a small number of the affected patients will receive any information about treatment-related infertility As far as female genital cancer is concerned, cervical cancer continues to be the most frequently diagnosed malignancy in women of childbearing age. In its early stages, it can be treated with surgical procedures which spare the genitals, i.e. surgical conization and vaginal radical trachelectomy with laparoscopic lymphadenectomy The advantages of these procedures have been observed in our experience. Also, a successful conservative 6-month treatment of endometrial cancer limited to the mucous membrane with progestagens following curettage of the uterine cavity has been reported in the literature. This paper also presents our own experience with fertility-sparing surgical treatment of ovarian cancer with borderline malignancy and invasive IA stage. Breast cancer affects over 7% of all cancer patients under the age of 40. Pregnancy after breast cancer treatment has been shown to develop properly and both, pregnancy and breastfeeding have no influence on cancer relapse. Protective shields for the adnexa or relocation of the ovaries should be used during radiotherapy in patients who wish to preserve their fertility In case of chemotherapy application of GnRH analogs has shown promising results in preservation of the ovarian function. Also, the development of new assisted reproductive technology has offered an increasing number of alternatives for young cancer patients who wish to preserve their fertility

[Prevalence of HPV DNA among male sexual partners of women diagnosed with CIN and early invasive cervical cancer]. / Wystepowanie HPV DNA u partnerów seksualnych kobiet ze sródnablonkowa neoplazja szyjki macicy--CIN i wczesnoinwazyjnym rakiem szyjki macicy.

Human Papilloma Virus (HPV) infection is the most common sexually transmitted disease. Chronic HPV infection is indispensable for development of cervical intraepithelial neoplasia and cervical cancer. First data stating that HPV transmission among heterosexual partners is very common appeared in last years. The aim of this study was to estimate the HPV infection prevalence among male sexual partners of women diagnosed with subclinical HPV infection, cervical intraepithelial neoplasia and early invasive cervical cancer. The study was conducted among 289 women aged 25-60 diagnosed with CIN and cervical cancer stage IA; control group consisted of 44 women aged 28-56 HPV testing using the material from retroglandular sulcus was conducted among male sexual partners of women from the study group. Testing was performed with HC2 method. In the study group, HPV infection was stated in 218 (75.43%) women and in 6 (13.63%) in control group. HPV DNA was present in 148 (51.21%) men--sexual partners of women from the study group and only 1 (2.27%) from control group. Additionally, HPV types of high and low oncogenic potential were analyzed with regard to histological diagnosis (SPI, CIN, early invasive cervical cancer). As the analysis shows, HPV infection of male sexual partners of women diagnosed with SPI and CIN is relatively high (9.09-93.33%).

[Assesment of the ongoing changes among patients diagnosed with subclinical changes of an HPV infection (SPI) as well as changes in the type of CIN 1 and CIN 2]. / Zachowanie sie zmian o charakterze subklinicznej infekcji HPV (SPI), sródnablonkowej neoplazji szyjki macicy (CIN) 1 i 2. Badanie prospektywne obserwacyjne.

PURPOSE OF STUDY: The aim of the study was to assess the ongoing changes of the type of regression, progression and steady state among patients diagnosed with subclinical changes of an HPV infection as well as changes in the type of CIN 1 and CIN 2. MATERIALS AND METHODS: The study was conducted in a group of 289 women between the ages of 25-60 with abnormal cytology taking part in the CIN cervical cancer prevention program. RESULTS: The patients were observed over a period of 6 years; no detectable differences were discovered in the frequency of regression between patients with SPI in comparision to patients with CIN1. In addition, no differences were identified in the frequency of regression between groups of patients with CIN1 and CIN2. In contrast, regression was more common in patients with SPI than in patients with CIN2. Steady state was more frequent in patients with CIN1 and CIN 2 than in patients with SPI. The results illustrated no differences in the progression of SPI and the CIN1 to CIN2. The group of patients with CIN2 were frequently associated with progression to CIN3 more than in the group of patients with SPI. The group of patients with CIN2 were frequently associated with progression to CIN3 more than in the group of patients with CIN1. Further investigation of cervical changes associated with SPI, CIN1 and CIN2 were dependent on the presence of transcription genes E6 and E7 of HPV. In 138 cases, the presence of these transcription genes lead to progression in 19.56% of women; more specifically in the introduction of mE6 and E7 RNA. There were changes typical of remission in 56,52% of cases primarily in the absence of transcriptor genes HPV E6 and E7. CONCLUSION: 1. The histological changes of the cervix observed in subclinical HPV infection, CIN1 and CIN2 may be subject to a higher degree of progression of CIN. In addition, these changes may progress to cervical cancer, remain stationary in a steady state, or decline into remission. 2. The types of HPV infection with high oncogenic potential are not only important in initiation of cerival changes but also in the developmental process of carcinogenesis in the cervix by several independent mechanisms.

Vertical transmission of HPV in pregnancy. A prospective clinical study of HPV-positive pregnant women.

INTRODUCTION: Human papillomavirus (HPV) is the most common sexually transmitted infection. Data reporting vertical transmission of HPV from the mother to the fetus are inconsistent and scant. Vertical transmission may occur by hematogenic route (transplacental), or by ascending contamination, or through the birth canal, which may result in the dreaded and rare laryngeal papillomatosis. Infected sperm at fertilization is a potential route of infection, too. OBJECTIVE: The objective of the study was to evaluate the rate of vertical transmission of HPV in HPV-positive pregnant women to their newborn infants, as well as the risk factors of HPV vertical transmission. MATERIAL AND METHODS: The clinical material was provided by 136 pregnant women, aged 18-45 years. Out of this group, 30 (22.05%) women with abnormal Pap test and positive DNA HPV test were prospectively observed Neonatal status, i.e. DNA HPV from the nasopharyngeal smear was recorded in all infants during the perinatal period. The conventional Pap test was performed with the cervix brush in all women. The Bethesda 2011 classification system was applied. RESULTS: An average C Reactive Protein (CRP) concentration in the studied pregnant women was 711.6083 (Std Dev--12.93). The most frequent cytological findings in the cervical smears from the examined women were ASCUS, n = 13 (43.3%), then--LSIL, n = 10 (33.3%), HSIL--n = 5 (16.7%) and AGC--n = 2 (6.7%). In the neonates, the presence of LR HPV DNA was detected in 9 cases (30.0%) and HR HPV DNA in 7 cases (23.3%). Fourteen neonates (46.7%) tested HPV DNA negative in the perinatal period. CONCLUSIONS: HPV infection (incidental or chronic) is observed in approximately 22% of pregnant women from the Matopolska province. Neonatal HPV infection in HPV-positive women was observed in 53.3% of the subjects. CRP concentration > 10 mg/dl in the serum of pregnant women statistically significantly (p 0.001) reduces the risk of vertical transmission of HPV from the mother to the fetus.

[Significance of vitamins A and E in the cervical intraepithelial neopiasia--CEN]. / Rola witaminy A i witaminy E w zachowaniu sie sródnablonkowej neoplazji szyjki macicy (CIN).

UNLABELLED: Cervical intraepithelial neoplasia--CIN affects women in their repro- ductive life period. CIN may proceed squamous cervical cancer. CIN is divided into: CIN1, CIN2, CIN3. CIN3 comprises cervical cancer in situ- CIS which is the true precancer state within the cervix. CIN, depending on grade may progress, regress or persist for many years. According to a few publication vitamins C, E and A may protect against carcinogenesis within the cervix. The aim of this paper was evalua- tion of vitamins A and E serum concentration of cervical intraepithelial neoplasia patients. The study material consisted of 289 women aged 25-60 years diagnosed with CIN and early invasive cervical cancer IA. The subjects of the study were selected amongst participants of National Cervical Cancer Screen- ing Program attending Department of Gynecology and Oncology of Jagiellonian University Medical College in Krakow. The control group consisted of 44 women aged 28-56 years diagnosed and treated in the same centre and period due to a non oncologic gynecologic conditions. Serum vitamin A and E was measured with HPLC method with ultraviolet detector (UV) (254 nm). RESULTS: Medium serum vitamin A concentration in the study group was 2.67 ± 1.15 mg/l and was significantly (p < 0.001) lower than in control group -3.81 ± 1.62 mg/l. Mean serum vitamin E concentration in the study group was 3.95 ± 1.93 mg/l and was also significantly (p < 0.001) lower than in control group (8.63 ± 2.84 mg/l). To conclude, the observed significantly lower vitamins A and E serum concentrations may be related to the cervical neoplasia process. The normal vitamin A and E serum levels may have a protective effect against cervical carcinogenesis.

Clinical analysis of metaplastic breast carcinoma with distant metastases: A multi­centre experience.

Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population.

[The changes in complete blood count in patients treated with sunitinib malate for metastatic clear cell renal cell carcinoma]. / Zmiennosc parametrów morfotycznych krwi u pacjentów leczonych sunitynibem z powodu raka jasnokomórkowego nerki w stadium uogólnienia.

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies. For stage I - III RCC surgery is the primary treatment. Systemic therapy is used in the patients with disseminated disease (stage IV). Sunitinib malate is commonly used in the patients with clear cell renal cell carcinoma (ccRCC) rated as 'low' or 'intermediate' risk according to the Motzer scale. Treatment with sunitinib malate is associated with myelotoxicity. To assess its clinical significance we conducted a pilot study in a group of 10 patients. We noticed a gradual decrease in the mean haemoglobin level during subsequent treatment cycles. Alternations in the platelet count were of no clinical significance. Episodes of the neutropenia were noticed in the study group. In some patients neutrophil count decreased to the level that put them at risk of the infectious complications.

Triage Strategies for Non-16/Non-18 HPV-Positive Women in Primary HPV-Based Cervical Cancer Screening: p16/Ki67 Dual Stain vs. Cytology.

BACKGROUND: In the context of primary HPV cervical cancer screening, the identification of minor screening abnormalities necessitates triage tests to optimize management and mitigate overtreatment. Currently, reflex cytology and reflex p16/Ki67 dual-stain (DS) are under scrutiny for their applicability in primary HPV-based screening. However, there remains a dearth of comprehensive data for comparing their performance. METHODS: Among 30,066 results from liquid-based cervical cancer screening tests, a cohort of 332 cases was meticulously selected based on available high-risk human papillomavirus (HPV) test results, limited genotyping for HPV 16 and 18, liquid-based cytology, DS, and histology outcomes from standardized colposcopy with biopsy. For cases positive for 12 other high-risk HPV genotypes, three retrospective triage approaches were analyzed. We computed the positive predictive value (PPV) for the detection of high-grade squamous intraepithelial lesions or worse (HSIL+). RESULTS: Both triage models employing DS (reflex cytology followed by DS and reflex DS alone in all cases) exhibited significantly higher PPV for HSIL+ compared to the strategy with reflex cytology alone (35.9%/33.3% vs. 18.8%; p < 0.0001). Additionally, these DS-based models showed higher negative predictive values (NPV) (100%/96.2% vs. 69.2%; p = 0.0024/0.0079). In the DS-inclusive models, fewer colposcopies were necessitated (103/102 vs. 154), and fewer cases of HSIL+ were overlooked (0/3 vs. 8). CONCLUSIONS: Our findings suggest that p16/Ki67 dual-stain, either as a standalone or combined triage test, holds promise for the effective detection of HSIL+ in patients with minor screening abnormalities in primary HPV-based cervical cancer screening.

Neoductgenesis in Ductal Carcinoma In Situ Coexists with Morphological Abnormalities Characteristic for More Aggressive Tumor Biology.

Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that is generally indolent, however, could advance to invasive carcinoma in more than one-third of cases if left untreated. Thus, there is continuous research to find DCIS characteristics that would enable clinicians to decide if it could be left without intensive treatment. Neoductgenesis (i.e., formation of the new duct of improper morphology) is a promising, but still not sufficiently evaluated indicator of future tumor invasiveness. We gathered data from 96 cases of DCIS (histopathological, clinical, and radiological) to assess the relationship between the neoductgenesis and well-established features of high-risk tumor behavior. Furthermore, our intention was to determine which degree of neoductgenesis should be considered clinically significant. Our major finding was that neoductgenesis is strictly related to other characteristics that indicate the invasive potential of the tumor and, to achieve more accurate prediction, neoductgenesis should be accordingly recognized to less strict criteria. Therefore, we conclude that neoductgenesis is another important revelator of tumor malignancy and that it requires further investigation during prospective controlled trials.