Correlation Between Enhancement Intensity in Contrast Enhancement Spectral Mammography and Types of Kinetic Curves in Magnetic Resonance Imaging.

BACKGROUND Due to the decreased sensitivity of mammography in glandular breasts, new diagnostic modalities, like contrast-enhanced spectral mammography (CESM) and digital breast tomosynthesis (DBT) have been developed. The aim of this study was to compare qualitative enhancement levels on CESM with type of kinetic enhancement curves on MRI examination. MATERIAL AND METHODS Patients qualified for the CESM examination presented some diagnostic doubts - suspected multifocality, multicentricity, or having dense glandular breast tissue. The enhancement level on CESM was described as weak, medium, or strong. Enhancement on achieved MR images was assessed on the basis of enhancement kinetic curves. The level of enhancement on CESM was associated with enhancement curves type on MRI. All lesions detected on CESM and MRI were histopathologically verified. RESULTS The study involved 107 lesions diagnosed in 94 patients: 71 lesions (66%) appeared to be infiltrating on histopathological examination, 9 lesions (8%) were non-infiltrating cancers, and 27 lesions (25%) were benign. Data analysis revealed that lesions with wash-out curve on MRI most often presented strong enhancement on CESM, while in lesions with progressive enhancement curve, strong enhancement on CESM was the rarest. The relationship between enhancement level on CESM and curve type on contrast-enhanced MRI depends on the nature of the lesion. The type of MRI curve was found to be associated with enhancement level on CESM. CONCLUSIONS We compared subjective assessments of contrast enhancement on CESM with enhancement kinetic curves on MRI. The results showed that the level of enhancement on CESM and type of kinetic curves on MRI depends on the lesion type.

The association between lymph node metastases and long-term survival in patients with epithelial ovarian cancer.

INTRODUCTION: A key survival prognosis factor for patients treated for ovarian cancer is complete cytoreductive surgery where all macroscopic neoplastic implants, including enlarged metastatic lymph nodes, are removed. We presume that investigating the involvement of the lymphatic system can result in a more individualized approach to the treatment of ovarian cancer patients. The main aim of our study was to analyze the relationship between the presence, number and types of lymph node metastases and ovarian cancer patient prognosis. MATERIAL AND METHODS: We carried out a retrospective analysis of patients who underwent cytoreduction due to primary ovarian cancer, between 2010 and 2015. We analyzed the number of metastatic lymph nodes, the lymph node ratio defined as the ratio of the number of metastatic lymph nodes to the total number of lymph nodes removed, extracapsular involvement, and the histopathological pattern of metastases. RESULTS: The study group included 651 patients. Of these, 377 had lymphadenectomy, 144 presented with lymph node metastases, and 233 had no lymph node metastases. We also included a group of 274 patients who did not have lymphadenectomy. Patients with more than 4 metastatic lymph nodes and a lymph node ratio of ≥ 0.1 had significantly poorer overall survival. Extracapsular involvement had no relation to patient overall survival. Multivariant survival analysis indicated that a lymph node ratio of ≥ 0.1 was an independent predictor of poor survival. CONCLUSIONS: The analysis of lymph node metastases in ovarian cancer patients can have predictive value for patient overall survival.

Correlation between quantitative assessment of contrast enhancement in contrast-enhanced spectral mammography (CESM) and histopathology-preliminary results.

OBJECTIVES: Contrast-enhanced spectral mammography (CESM) is a novel method for breast cancer detection. The aim of this study is to check if there is a possibility of quantitative assessment of contrast enhancement in CESM and if there is any correlation between quantitative assessment of contrast enhancement in CESM and histopathology. METHODS: A total of 167 female patients underwent CESM. All subjects previously had suspicious lesions found on mammography, breast ultrasound, or both. After imaging, the following parameters were evaluated: number of enhancing lesions in each breast and size and degree of enhancement of each lesion. Based on the collected data, the percentage signal difference between enhancing lesion and background (%RS) and signal-difference-to-noise ratio (SDNR) were measured for each lesion. RESULTS: The number of lesions detected in the study population was 195. Among all diagnosed lesions, 120 (62%) were assessed to be infiltrating cancers, 16 (8%) non-infiltrating cancers, and 59 (30%) were benign. Thirteen (7%) lesions did not enhance in CESM; all non-enhancing lesions were confirmed to be benign under histopathological examination. Analysis of enhancement indices showed that signal values within lesions and signal values within background ROIs (regions of interest) were similar in CC (craniocaudal) and MLO (mediolateral) projections. Mean %RS values were correlated with the type of enhancing lesion, infiltrating cancers having the highest values, benign lesions the lowest. CONCLUSIONS: This work has demonstrated a significant correlation between the degree of lesion enhancement in CESM and malignancy. Quantitative analysis of enhancement levels in CESM can distinguish between invasive cancers and benign or in situ lesions. KEY POINTS: • There is a possibility of quantitative assessment of contrast enhancement in CESM. • Correlation between quantitative assessment of contrast enhancement in CESM and histopathology was observed.

Selected features of breast and peritoneal cancers diagnosed in BRCA1 carriers after risk-reducing salpingo-oophorectomy.

BACKGROUND: Since more than two decades Risk-reducing salpingo-oophorectomy (RRSO) is recommended and widely accepted by BRCA1/2 carriers as a method reducing ovarian cancer risk and improving survival rate. After RRSO, there remains a risk of breast cancer and peritoneal cancer. The characteristics of these neoplasms are not well known. In this study, we determined the selected parameters such as age at cancer diagnosis, time from RRSO to the diagnosis of cancer, and significance of BRCA1 mutation type in patients diagnosed with breast or peritoneal cancer during postoperative follow-up. METHODS: The material comprised of 195 BRCA1 carriers who performed RRSO between years 1999-2012. In this period, 16 patients developed cancer (6-primary breast cancer, 3-contralateral breast cancer, 5-relapse of breast cancer, 2-peritoneal cancer). They were subject of the further analysis. RESULTS: During the follow-up period mean age of patients after RRSO at the time of cancer diagnosis was 53.19. The mean age of patients diagnosed with primary breast cancer was 50, contralateral breast cancer - 58.67, recurrence of breast cancer - 51 and peritoneal cancer 60. The mean time periods from RRSO to the diagnosis of primary, contralateral, recurrence breast cancer were 53, 58.67 and 25,4 months respectively and of peritoneal cancer 46 months. BRCA1 c.5266dupC mutation carriers demonstrated significantly shorter time of cancer development compared to patients carrying c.181T > G and c.4035delA mutations. Peritoneal cancer was only observed in two c.181T > G BRCA1 mutation carriers. CONCLUSIONS: The mean age of cancer diagnosis and the mean time periods from RRSO to the diagnosis of cancer are similar to those observed by other researchers. The carriers of c.181T > G and c.5266dupC BRCA1 mutation should be the subject further studies in context of breast and peritoneal cancer risk or time of cancer development after RRSO, respectively.

Cobas 4800 HPV detection in cervical samples of Polish women.

INTRODUCTION: Long-term infection with human papillomavirus (HPV) is the cause of cervical cancer and its precursor - cervical intraepithelial neoplasia (CIN). The presence of HPV infection can be presumed in more than 99% of cases of cervical cancer worldwide. The introduction of DNA testing for the presence of HPV has increased the effectiveness of screening programs for the detection of this cancer. This study aimed to analyze the prevalence of high risk HPV DNA (HR HPV) in females from Poland. MATERIAL AND METHODS: The study was performed on 280 cervical smear samples. In this work we used the Roche Cobas 4800 HPV test to detect the HR HPV in cervical smear samples. RESULTS: 56 patients (20%) proved to be positive regarding HPV-16 DNA and 40 patients (14.28%) regarding HPV-18 DNA. In overall assessment, in 94 patients (33.57%) we detected oncogenic HPV subtypes, other than the two mentioned above. In 90 patients (32.14%) no high risk HPV was detected. CONCLUSIONS: The Roche Cobas 4800 HPV test is a viable, effective, easy and quick tool in detecting high risk HPV DNA.

Current treatment options for advanced choriocarcinoma on the basis of own case and review of the literature.

Choriocarcinoma is one of rare neoplasms of female reproductive organs. In the last decade only a few cases of this disease have been registered in Poland. The paper presents the current principles of diagnosis and treatment options for this rare disease based on the authors' clinical experience (description of the case) and literature review. This paper provides basic information on epidemiology, FIGO classification, and also discusses the chemotherapy regimens used in the medical treatment of choriocarcinoma. Surgical options were also considered. A thematic review of the most important papers published in international journals in recent years has also been made.

Post-Irradiation Bladder Syndrome After Radiotherapy of Malignant Neoplasm of Small Pelvis Organs: An Observational, Non-Interventional Clinical Study Assessing VESIcare®/Solifenacin Treatment Results.

BACKGROUND Radiotherapy is explicitly indicated as one of the excluding factors in diagnosing overactive bladder syndrome (OAB). Nevertheless, symptoms of OAB such as urgent episodes, incontinence, pollakiuria, and nocturia, which are consequences of irradiation, led us to test the effectiveness of VESIcare®/Solifenacin in patients demonstrating these symptoms after radiation therapy of small pelvis organs due to malignant neoplasm. MATERIAL AND METHODS We conducted an observatory clinical study including 300 consecutive patients with symptoms of post-irradiation bladder; 271 of those patients completed the study. The observation time was 6 months and consisted of 3 consecutive visits taking place at 12-week intervals. We used VESIcare® at a dose of 5 mg a day. Every sixth patient was examined urodynamically at the beginning and at the end of the observation period, with an inflow speed of 50 ml/s. RESULTS We noticed improvement and decline in the average number of episodes a day in the following parameters: number of micturitions a day (-36%, P<0.01), nocturia (-50%, P<0.01), urgent episodes (-41%, P<0.03), and episodes of incontinence (-43%, P<0.01). The patients' quality of life improved. The average maximal cystometric volume increased by 34 ml (21%, p<0.01), average bladder volume of "first desire" increased by 42 ml (49%, P<0.01), and average detrusor muscle pressure at maximal cystometric volume diminished by 9 cmH2O (-36%, P<0.03). CONCLUSIONS The substance is well-tolerated. Solifenacin administered long-term to patients with symptoms of OAB after radiotherapy of a malignant neoplasm of the small pelvis organs has a daily impact in decreasing number of urgent episodes, incontinence, pollakiuria, and nocturia.

[Primary diffuse large B-cell lymphoma of the uterine cervix - case report]. / Pierwotny chloniak rozlany z duzych komórek B szyjki macicy - opis przypadku.

We present a case of a 54-year-old woman treated for stage IIAE primary diffuse large B-cell lymphoma (DLBCL) of the uterine cervix. The CHOP chemotherapy regimen was started. After the diagnosis of lymphoma of DLBCL CD20+ type was confirmed, rituximab was added to the therapy. Within systemic therapy, the patient received two cycles of CHOP and six cycles of R-CHOP altogether. After treatment completion, total remission of the lesions was observed on computed tomography. Twenty-four months after therapy completion, the patient is disease-free with no signs of recurrence.

Selected markers of ovarian cancer and their relation to targeted therapy (Review).

Despite advances in surgical treatment techniques and chemotherapy-including anti-angiogenic and immune poly (ADP-ribose) polymerase inhibitors, the 5-year survival rate in ovarian cancer (OC) remains low. The reasons for this are the diagnosis of cancer in advanced clinical stages, chemoresistance and cancer recurrence. New therapeutic approaches are being developed, including the search for new biomarkers that are also targets for targeted therapy. The present review describes new molecular markers with relevance to targeted therapy, which to date have been studied only in experimental research. These include the angiogenic protein angiopoietin-2, the transmembrane glycoprotein ectonucleotide pyrophosphatase/phosphodiesterase 1, the adhesion protein E-cadherin, the TIMP metallopeptidase inhibitor 1 and Kruppel-like factor 7. Drugs affecting cancer stem cells (CSCs) in OC, such as metformin and salinomycin, as well as inhibitors of CSCs markers aldehyde dehydrogenase 1 (with the drug ATRA) and the transcription factor Nanog homeobox (microRNA) are also discussed. A new approach to prevention and possible therapies under investigation such as development of vaccines containing a subpopulation of CD117(+) and CD44(+) stem cells with a promising option for use in women with OC was described.

Analysis of RCAS1 immunoreactivity within hydatidiform mole cells and decidual cells according to the applied therapeutic strategy: surgery or surgery followed by chemotherapy.

INTRODUCTION: Trophoblast cells cooperate with both maternal immune cells and decidual cells to help develop the suppressive microenvironment of the endometrium. The maternal immune response against hydatidiform mole depends on this suppressive endometrial profile. Since RCAS1 is one of the molecular factors participating in the development of the suppressive profile of the endometrium we decided to examine the immunoreactivity of the RCAS1 within both the trophoblast and decidual cells during the development of hydatidiform mole. METHODS: We analyzed the immunoreactivity of RCAS1 on both trophoblast and decidual cells derived from patients who underwent curettage because of hydatidiform mole. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. RESULT: We observed significantly lower immunoreactivity levels of both RCAS1 within the complete molar lesions of the patients on whom surgery alone was performed when compared to the levels found in those for whom surgery was followed by chemotherapy. CONCLUSION: RCAS1 staining may provide information regarding the intensity of the immunosuppressive microenvironment of both the molar lesion and the endometrium. This information can prove significant in determining the clinical course of hydatidiform mole.

Irradiation-induced bone sarcoma in a patient treated for cervix cancer 28 years earlier.

AIM OF THE STUDY: To present a case of a patient with cervical carcinoma in stage IIA who was diagnosed with pelvic bone sarcoma 28 years after radiotherapy. CASE PRESENTATION: A 37-year-old woman with IIA cervix cancer was treated with external beam irradiation and brachytherapy. The patient had undergone conventionally fractionated external beam irradiation using the "box" technique, with the total dose of 50 Gy and brachytherapy with radium applicators (intrauterine tube and fornix applicator) with the dose of 60 Gy calculated at point A. After treatment she was followed up for 2 years. Twenty-six years later, inoperable pelvic bone sarcoma was diagnosed within the irradiated field. The clinical course was aggressive and rapid progression during chemotherapy was observed. CONCLUSIONS: For patients receiving radiotherapy, long-term careful follow-up is mandatory due to second cancer risk. In the case of any suspicious symptoms, such patients need proper diagnosis to detect any disease as early as possible.

The Impact of Surgical Treatment with Adjuvant Chemotherapy for Ovarian Cancer on Disorders in the Urinary System and Quality of Life in Women.

Ovarian cancer is the fourth-most-common cause of death among all malignant cancers in women in Poland. This study aimed to compare the functioning of the urinary system and quality of life in women in the 12-month period following the completion of surgery or adjuvant treatment for ovarian cancer, with patients who underwent a hysterectomy for non-oncological reasons (control group). The study group consisted of 50 patients diagnosed with stage I−III ovarian cancer. Among 38 patients with type II ovarian cancer (group A), surgery followed by first-line chemotherapy was performed. Within this group of patients, 20 had stage I ovarian cancer, while 18 had stage II ovarian cancer. The study was performed at least 6 months after the final chemotherapy cycle, with no clinical, marker or radiological recurrence determined. On the other hand, in 12 patients with stage I type I ovarian cancer, oncological treatment consisted of only surgery, without the need for adjuvant chemotherapy, due to the low stage of the lesions (group B). In turn, the control group consisted of 50 women who underwent uterine removal for non-oncological reasons (group C). The assessment of quality of life was conducted using the questionnaires: Satisfaction with Life Scale (SWLS); Incontinence Impact Questionnaire, short form (IIQ-7); Urogenital Distress Inventory (UDI-6); and the Sexual Satisfaction Scale for 3, 6, 9, and 12 months after the conclusion of oncological treatment. During the follow-up, a significant reduction in the quality of everyday life and sexual life was noted among patients with ovarian cancer, more pronounced in group B, compared to the control group (p < 0.05). The risk of urinary incontinence is independent of the treatment regimen chosen for ovarian cancer. It is necessary to consider comprehensive psychological care and sexual therapy in patients with ovarian cancer and their families.

Quantitative Assessment of Contrast Enhancement on Contrast Enhancement Spectral Mammography (CESM) and Comparison With Qualitative Assessment.

BACKGROUND/AIM: Contrast enhanced spectral mammography (CESM) is a novel method of breast cancer diagnosis. Benign lesions are enhanced after contrast injection on both CESM and breast magnetic resonance imaging (MRI). Kinetic curves on breast MRI facilitate differentiation between benign and malignant lesions, while on CESM there is no such possibility and we need to asses lesions based only on their level of enhancement and its patterns. The aim of this study was to compare two subjective assessments of enhancement level on CESM with numerical values measured using the region of interests (ROIs) and to categorize obtained enhancement level values. PATIENTS AND METHODS: Patients with suspicious findings on previously performed examinations were qualified for CESM. The qualitative assessment was based on the subjective classification of visible contrast enhancement as weak, medium or strong. The quantitative assessment was obtained by measurements of an average enhancement value and sigma value within the ellipsoidal shape ROI, inserted into the evaluated contrast enhancing lesion. RESULTS: The study group included 151 patients with total of 195 lesions diagnosed. It was verified how the classification based on the threshold values of %RS (percentage signal difference between enhancing lesion and background) and SDNR (signal-difference-to-noise Ratio) corresponds to a subjective assessment. CONCLUSION: Quantitative assessment of contrast enhancement on CESM is helpful in making decisions whether a lesion requires a biopsy. This can reduce the number of unnecessary biopsy procedures and reduce the cost of diagnostics.

Role of vitamin D3 in selected malignant neoplasms.

Vitamin D3 is a fat-soluble essential nutrient that affects multiple biologic functions in the organism through calcitriol and the vitamin D3 receptor. This review article focuses on the results of studies on the relationship between the level of vitamin D3 and cancer incidence or mortality, but also on the anticancer properties of vitamin D3 that support its significant role in the prevention, clinical course, and overall survival rates of selected cancers (colorectal, prostate, breast, ovarian, endometrial, bladder, and malignant melanoma). The mechanisms of vitamin D3 action involve, among others, polymorphism of vitamin D3 receptor, cell cycle, caspases, and cancer stem cells. The level of vitamin D3 has been also demonstrated to serve as a biomarker in some cancers, and high levels of vitamin D3 can be conducive to successful cancer therapy.

Metastatic and non-metastatic sentinel inguinofemoral lymph nodes in vulvar cancer show an increased lymphangiogenesis.

INTRODUCTION AND OBJECTIVE: Lymph node involvement is a strong predictor of disease recurrence and patient survival in vulvar cancer. The aim of the study was to evaluate the feasibility of sentinel lymph node (SLN) screening, the incidence of skip metastases, and lymph node lymphangiogenesis. MATERIAL AND METHODS: Fifty-five patients participated in this prospective, single centre study. A double SLN screening method was employed using radiocolloid (technetium-99 sulfur colloid) and 1.0% Isosulfan Blue. Immunohistochemistry, using a mouse monoclonal antibody against D2-40, was used to evaluate lymphatic vessel density (LVD). All calculations were performed using STATISTICA software v. 10 (StatSoft, USA, 2011); p < 0.05 was considered significant. RESULTS: Using both methods of SLN detection, 100% accuracy was achieved, and skip metastases were diagnosed in only one woman (1.82%). Peri-tumour median LVD was significantly increased compared with matched intra-tumour samples (p < 0.001), while median LVD was significantly lower in negative, compared with positive SLN, regardless of whether matched non-SLN were negative (p < 0.001) or positive (p = 0.005). Metastatic SLN exhibited significantly higher median LVD compared with matched negative non-SLN (p = 0.015), while no significant difference in median LVD was detected between positive SLN and matched positive non-SLN. However, negative SLN had a significantly higher median LVD compared with matched negative non-SLN (p = 0.012). CONCLUSIONS: SLN detection is a safe and feasible procedure in vulvar cancer. In patients without nodular involvement, SLN, compared with non-SLN, exhibited significantly higher median LVD, which may be an indication of its preparation to host metastases, and thus requires further investigation.

The potential predictive value of serum srCaS1 levels for overall survival in endometrial cancer.

OBJECTIVES: The main aim of the study was to evaluate the impact of levels of serum soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) on the overall survival (OS) rates in patients with endometrial cancer. Furthermore, we analyzed sRCAS1 levels according to the clinicopathological characteristics of the disease. MATERIAL AND METHODS: The study group comprised 43 patients who were being treated for endometrial cancer. We included 10 low-risk, 20 intermediate-risk and 13 high-risk endometrial cancers using the criteria of the European Society for Medical Oncology (ESMO), the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Gynaecological Oncology (ESGO). Serum sRCAS1 levels were obtained before and after surgery. Serum sRCAS1 levels were assessed using the ELISA method. RESULTS: In our univariate analysis, both the pre- and post-surgery high sRCAS1 groups of patients with endometrial cancer indicated a shortened OS. However, in our multivariate analysis, when patients' age and disease-related risk was taken into consideration, only the post-surgery sRCAS1 levels remained as independent prognostic factors of a poor OS. Pre-treatment serum sRCAS1 levels were statistically significantly higher than post-surgery sRCAS1 levels; however, the difference between pre- and post-surgery sRCAS1 levels did not influence the patients' OS rate. Pre- and post-surgery sRCAS1 levels did not differ according to tumor grade, stage of the disease or the disease-related risk group. CONCLUSIONS: High post-surgery serum sRCAS1 levels seem to be an independent indicator of shortened overall survival in patients with endometrial cancer.

Comparison of chromosomal radiosensitivity of normal cells with and without HRS-like response and normal tissue reactions in patients with cervix cancer.

PURPOSE: In our previous study, using the micronucleus (MN) assay, the low- and high-dose radiation response of fibroblasts and keratinocytes from cancer patients was assessed. We reported that a hyper-radiosensitivity (HRS)-like phenomenon was observed for fibroblasts of two and keratinocytes of four of the 40 patients studied. In this paper, we report the comparison of these in vitro results and normal tissue reactions in patients with cervix cancer and answer the question of the predictive value of the MN assay. MATERIALS AND METHODS: Of the 40 patients with cervix cancer whose cells were previously studied in vitro, 32 received radiotherapy. The treated group included two patients with HRS-like positive fibroblasts and four patients with HRS-like positive keratinocytes. In 26 patients both types of cells were HRS-like negative. The in vitro results (MN induction measured in patients' fibroblasts and keratinocytes after in vitrogamma-irradiation with doses ranging from 0.05-4 Gy) were compared with the maximum grade of acute and late reactions. RESULTS: Five of the six patients whose cells demonstrated low-dose chromosomal hypersensitivity in vitro, did not suffer from any mild or severe side effects after radiotherapy. Although individual variations in the grade scores of normal-tissue reactions were observed in cancer patients, no significant relationship was found between MN induction, either in fibroblasts or keratinocytes, and acute and late effects. CONCLUSION: Since the MN assay showed no predictive value, it is rather impossible that the severe late complication observed in one of the six HRS-like positive patients reflects her low-dose chromosomal hypersensitivity in vitro.

Perivascular epithelioid tumor (PEComa) of the falciform/ broad ligament.

PEComas localized in the region of falciform ligament and broad ligament are exceedingly rare. Most of them are built of spindle neoplastic cells. We report a case of epithelioid PEComa of the falciform ligament and/or broad ligament. There is only one report of such neoplasm in English-language literature. Histologically, the tumor was composed of nests of epithelioid clear cells stained positively for vimentin, HMB45, and SMA. Because of morphological features of the tumour (4 mitoses /20HPF, focal necrosis, and vascular invasion) we assess the neoplasm as potentially malignant.

The response of primary keratinocytes and fibroblasts from cancer patients to multiple low-dose irradiations.

In our previous study, using the micronucleus (MN) assay, a hyper-radiosensitivity (HRS)-like phenomenon was observed after single low doses for fibroblasts from two and keratinocytes from four of the 40 patients studied. In this paper, we report the response of primary keratinocytes from 23 and fibroblasts from 21 of these cancer patients to multiple low-dose irradiations and answer the question regarding whether the patients with an HRS-like response after single low doses also demonstrate chromosomal hypersensitivity after multiple low doses. The cells were irradiated with three doses of 0.25 Gy separated by 4-h intervals, and MN induction was compared with that after the same total dose given as a single fraction of 0.75 Gy. Similarly, the effect of three doses of 0.5 Gy was compared with that of a single dose of 1.5 Gy. For fibroblasts from two and keratinocytes from four patients who demonstrated a single-dose HRS-like response, a significant inverse effect of fractionation (greater MN induction after three doses of 0.25 Gy than after a single dose of 0.75 Gy) was observed, which suggests a repeated hypersensitive response after each dose of 0.25 Gy. Such an effect was not seen for the cells from 19 patients who were single-dose HRS-like negative. In conclusion, an inverse fractionation effect for MN induction that was observed in fibroblasts from two and keratinocytes from four patients after three doses of 0.25 Gy (but not 3 x 0.5 Gy) reflects the chromosomal hyper-radiosensitivity seen in the same patients in response to single low doses.

Low-dose radiation response of primary keratinocytes and fibroblasts from patients with cervix cancer.

The aim of the present study was to examine, using the micronucleus (MN) assay, the low-dose radiation response of normal skin cells from cancer patients and to determine whether the hyper-radiosensitivity (HRS)-like phenomenon occurs in cells of these patients. Primary skin fibroblasts and keratinocytes derived from 40 patients with cervix cancer were studied. After in vitro gamma irradiation with single doses ranging from 0.05 to 4 Gy, MN induction was assessed. For each patient, the linear-quadratic (LQ) model and the induced repair (IR) model were fitted over the whole data set. In fits of the IR model, an HRS-like response after low doses (seen as the deviation over the LQ curve) was demonstrated for the fibroblasts of two patients and for the keratinocytes of four other patients. The alpha(s)/alpha(r) ratio for the six patients ranged from 2.7 to 15.4, whereas the values of the parameter d(c) ranged from 0.13 to 0.36 Gy. No relationship was observed between chromosomal radiosensitivity of fibroblasts and keratinocytes derived from the same donor in the low-dose (0.1-0.25 Gy) region. In conclusion, the fact that low-dose chromosomal hypersensitivity was observed for cells of only six of the patients studied suggests that it is not a common finding in human normal cells and can represent an individual characteristic.