Over the last 15 years, the outcome of patients with follicular lymphoma (FL) has dramatically improved mainly as a result of effective therapies and of a better understanding of lymphoma biology. Although progression-free survival is approximately 10 years with standard treatment and overall survival upwards of 20 years, the clinical behavior among individual patients is highly heterogenous, and a significant number of subjects have a higher and earlier risk of dying from FL within a few years from diagnosis. In this article, we provide an overview of available prognostic tools that can be used to identify high-risk patients with FL and describe which therapies are available and can be recommended for this group of hard-to-treat FL patients.
Background and aim of the work: The Lynch Syndrome (LS) is associated with germline mutations in one of the MisMatch Repair (MMR) genes. Most of germline mutations are point variants, followed by large rearrangements that account to 15-55% of all pathogenic mutations. Many study reporting the frequency of large rearrangements in the MLH1 and MSH2 genes were performed, while, little is known about the contribution of large rearrangements in other MMR genes, as PMS2 and MSH6. Therefore, in this study we investigated the involvment of large rearrangements in MSH6 and PMS2 genes in a well-characterized series of 20 LS southern Italian patients. Methods: These large rearrangements are not usually detected by methods of mutation analysis, such as denaturing high-performance liquid chromatography (DHPLC) and direct DNA sequencing, but they are detectable by a known technique as the Multiplex Ligation-Probe Dependent Amplification (MLPA) assay. Results: No large rearrangements were identified in MSH6 gene; instead, a large rearrangement was identified in PMS2 gene. A large duplication including the exons 3 and 4 of the PMS2 gene was identified in a patient who developed a rectum carcinoma at 45 years of age, an endometrial carcinoma and a vaginal cancer at the 65 years of age. Conclusion: We can affirm that the detection of large rearrangements in the MSH6 and PMS2 genes should be included in the routine testing for Lynch syndrome, especially considering the simplicity of the MLPA assay.
Objectives: Primary fallopian tube carcinoma (PFTC) is a rare cancer. Although comparable to epithelial ovarian cancer (EOC), PFTC may have different biology and prognosis than EOC. This single tertiary care hospital based study aims to evaluate the survival outcome and to identify factors that prognosticate the clinical outcome in PFTC patients. Methods: We retrospectively evaluated all the 21 patients diagnosed with PFTC between 2004-2013. We studied clinicopathological data to extract the prognostic factors for recurrence and survival. Kaplan-Meier curves were generated, and survival differences evaluated by using log-rank tests. Results: All the patients had pathologically proven PFTC. The mean age was 53.5 years (range: 36-69 years). Per-vaginal bleeding 11(52.2%) and abdominal pain 5 (23.8%) of average duration of 2.7 months were the commonest symptoms. Stage distribution at presentation, International Federation of Obstetrics and Gynecology (FIGO)-1991 stage I,II,III,IV were 33.3%, 19%, 42%, 4.7% respectively. Commonest histology was serous-papillary carcinoma 18 (86%).Optimal debulking was done in 18 (85.7%) cases. Seventeen (81%) patients received paclitaxol-carboplatin adjuvant chemotherapy. Median follow-up period was 31 months (range: 6-127months). The disease free interval was 23.5 months. Five year Overall survival was 42.8%. Lymphovascular space invasion was associated with advanced stage (p=0.026) and earlier recurrences (p=0.044). Factors prognostic for overall survival were FIGO stage (p=0.008) and lymph node metastasis (p=0.038). Conclusion: Our single institution study results show that presence of advanced stage at diagnosis and lymph nodal metastases results in poor overall survival. Presence of lymphovascular space invasion indicates increased recurrence risk. Future clinical studies are warranted to identify the possible distinct clinical behaviour of PFTC.
Background and aim of the work: The Lynch Syndrome (LS) is associated with germline mutations in one of the MisMatch Repair (MMR) genes, including MLH1, MSH2, MSH6, PMS2, MLH3 and MSH3. The molecular characterization of mutations in these MMR genes facilitates the pre-symptomatic diagnosis of subjects at risk to develop a colon cancer or a cancer LS-related. Methods: DHPLC and direct sequencing were performed for the mutation detection analysis. Results: In this study, we identified a novel frame shift mutation, the named is c.170delT in MSH2 gene that determined a premature stop codon and consequently, the formation of a truncated protein (p. Val56Glyfs*7). This is a novel mutation, as it has not been reported before in the international scientific literature. This mutation was found in two subjects (father and son) belonging to a LS family. However, they showed a different phenotype disease. Conclusion: In this study, we identified and characterized a novel MSH2 mutation; moreover, this study reaffirmed the importance of genetic testing in Lynch syndrome.
Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death which can present with various clinical situations. Hypopituitarism when encountered with NSCLC may be due to diverse etiologies including pituitary metastasis, hypophysitis, pituitary infarction or a consequence of therapeutical interventions such as surgery or radiotherapy. Result: We present an unusual case of hypopituitarism in a NSCLC patient associated with a benign disorder, a sinus mucocele and thereby review the pathogenesis of hypopituitarism accompanying malignant diseases. Conclusion: Our case represents an example of association of a benign disorder with malignancy causing severe deterioration of life quality. Although rare, pituitary metastasis is the initial possible diagnosis in the setting of non-small cell lung cancer.
Background:Breast cancer is the most common cause of cancer death among women worldwide and the second leading cause of tumor-related death for women in westernized countries. Most research efforts to find a breast cancer biomarker have focused on the stage after the cancer is diagnosed. To investigate more deeply into mammary cancer prevention, a study of precancerous lesion development seems a priority. Experimentally-induced mammary tumors in rats constitute a powerful tool for studying the pathogenesis of this cancer and the molecular mechanisms involved in neoplastic progression. Furthermore, in vivo experimental animal models provide information not otherwise available in human populations. 7,12-dimethylbenz[a] anthracene (DMBA) induced rat mammary carcinomas have several similarities with human breast cancers including: histopathology, origination in the ductal epithelial cells, and hormone dependence. To better understand the molecular events associated with mammary carcinogenesis, we used a time-course high throughput gene expression approach on a DMBA-induced mammary cancer model to identify the early precancerous events as well as new potential diagnostic biomarkers.Materials and Methods:Twelve 7 wk-old virgin female Sprague-Dawley rats were randomized into 2 experimental groups: 1) DMBA-treated (40 mg/kg b.w. by intragastric administration (i.g.) in corn oil as the vehicle and 2) treated with corn oil (vehicle) by ig. At 2 and 4 weeks after DMBA administration, 3 animals randomly chosen from each experimental group were sacrificed and necropsied. Total RNA was extracted and the global gene expression patterns from the mammary gland and liver samples collected were used to identify the molecular profile of the precancerous stage genome. Significantly altered genes as evinced by multivariate data analysis were further confirmed by quantitative real time PCR and siRNA knockdown assays.Results and Discussion:Genes involved in cancer progression, migration, proliferation and oxidative stress were identified in this study. MARK, Wnt and Jak-STAT pathway signaling, known to play a major role at the precancerous stage, were also identified. Two novel less known cancer progression/proliferation related genes, Pcbd1 and Ppil1, upregulated in both liver and mammary glands, were also identified.
Nuclear medicine is currently a well-established part of medicine. It is applied in many fields of clinical medicine and science like endocrinology, oncology, cardiology, molecular medicine and engineering, radiopharmacy, physics and information science. Due to its increasing importance and application, several regulation and supervision bodies have been founded to ensure safe usage of radiation and to improve diagnostic and therapeutic procedures. This article reviews the legal requirements of Polish law regarding a fully functional Nuclear Medicine Centre (NMC) and reports on the current situation of nuclear medicine in Poland. It also suggests a model project for NMCs compatible with Polish and European Union regulations.
Purpose: Guidelines on older cancer patients recommend a comprehensive geriatric assessment, preferably including an item on medication management since cancer treatment further increases risks of polypharmacy. So far, little attention is given to non-adherence due to functional changes. We aimed to assess autonomy in medication management after start of therapy in older patients with haematological malignancies. In case of deterioration, we aimed to search for predetermining factors. Methods: Longitudinal single centre cohort study in patients ≥ 70 years. Patients underwent a geriatric evaluation before and two months after start of therapy. Medication was registered both times. Results: Sixty two patients, median age 77 years, were included. At baseline 49 patients (79%) took their long-term medication independently. Independent medication management was significantly higher in patients taking <5 medications (93.7% vs. 63.3%, p < 0.005). After start of therapy, polypharmacy rates increased from 48.3% to 98.3% (n=61) while 55.6% of the initially independent patients became dependent for medication management. Median increase in the number of medications was significantly higher in dependent patients (6 vs. 4.5, p<0.05). Multiple daily doses (80%, n=50), varying doses (59.7%, n=37) and medication splitting (45.3%, n=27) further contributed to regimen complexity. Unlike results at baseline, no correlations were found between autonomy in medication management and medication regimen two months after start of therapy. Conclusion: Haematological patients are confronted with extensive changes in medication. A considerable number becomes dependent for medication management. Emphasis should be put on detection and remediation, taking into consideration the challenges of an ambulatory setting.
Objective: Endobronchial benign tumors are rarely seen in lung cancers or in pulmonary benign tumors. In recent years, endoscopic treatment has increasingly been used to treat benign endobronchial lesions. Methods: Data from all adult patients diagnosed with a histologically proven endobronchial hamartoma and lipoma were collected between 2009 and 2014 at our clinic in the Yedikule Chest Diseases Education and Research Hospital. Results: 9 patients were included in the study; 6 patients were diagnosed with endobronchial hamartoma(66%) and 3 had endobronchial lipoma. Six patients were symptomatic. All patients underwent rigid bronchoscopy and biopsies taken during treatment were diagnostic in all cases. Lesions were mostly located at the lobar bronchus. Seven (77%) cases were successfully treated and there were no complications because of the procedure. Two patients was sent for lobectomy because of inadequate debulking. Recurrence was not seen in any patient. Conclusion: Interventional bronchoscopic techniques may be a safe and effective method for diagnosing and treating endobronchial benign tumors.
Aim: To evaluate prognostic factors impacting on the survival of 70 women with ovarian sex cord stromal tumors (SCST). Study Design: A retrospective single-institution review of all patients with SCST from 1982 to 2008 at our own service. Data were collected on patient characteristics, clinical findings, and all treatments received. Kaplan–Meier and Cox proportional hazard analyses were used to determine the predictors for survival. Results: SCST constituted 5.8% of all ovarian cancers in our institution during the study period. The median age was 51 years (range 15–95). Adult granulosa cell tumors (n=52) were the most frequent histological subtype. In addition, there were 14 patients with Sertoli-Leydig cell tumors, two with Juvenile granulosa cell tumors, one with sex cord tumor with annular tubules, and one with steroid cell tumor. The median follow-up period was 58 months (range 1–362). Fifty cases were stage I, two stage II, 15 stage III and three stage IV. There were two cases of persistent disease following surgery, 18 cases of recurrence and six cases of disease-related death. The median time to relapse was 75 months (range: 18–208). The 5-year overall and disease-free survivals were 76% and 68%, respectively. By univariate analysis, factors affecting recurrence were FIGO stage (p=0.02) and postoperative residual tumor (p=0.002), while age, tumor size, extent of surgery (standard staging/conservative staging), lymphadenectomy, histology and grade were not. On multivariate analysis, only postoperative residual tumor (p=0.002) remained significant prognostic factors for improved disease-specific survival. Conclusion: Postoperative residual tumor and early-stage disease are important predictors for improved disease-free survival in patients with SCST. If there are no residuals, fertility-sparing surgery for early staged patients with SCST wishing to preserve fertility appears to be a safe alternative.
Background and aim of the work: Fine needle aspiration biopsy (FNAB) of thyroid is an indispensable procedure in the evaluation of patients with thyroid nodules. The aim of this study was to evaluate the benefit of ultrasonography (USG)-guided FNAB compared to the conventional method. Methods: In this comparative cross-sectional study FNAB samples were collected in 1984 (G1) and 2011 (G2). In G1 (113 patients) FNAB was performed by palpation, and in G2 (1,049 patients) it was USG-guided. Statistical analysis included sensitivity, specificity, positive/negative predictive value, and likelihood ratio. Associations were considered statistically significant when p-value≤0.05. Results: The percentage of unsatisfactory material was 24% in G1 and 7.8% in G2. The sensitivity/specificity in G1 were 40% / 71%, and in G2, 83% / 94.7%. In G2, it was possible to select 77.7% of malignant nodules for surgery, while in G1 only 10%. In G2, the frequency of malignancies was similar between nodules smaller and larger than 1cm (Fisher’s exact test p-value=0.33). Conclusions: Our data confirm that FNAB is a valid technique for screening malignant thyroid nodules, especially when guided by USG. Since subcentimetric nodules harbor malignancy as much as larger nodules, we recommend performing FNAB in all thyroid nodules, regardless of size.
Background: Choroidal metastasis is rare and ocular examination is not routinely recommended as part of staging work up in breast cancer management. Clinical picture: We present a case of choroidal metastasis in female breast cancer. Breast imaging and staging evaluation suggested multicentric breast cancer without lymph node metastasis or systemic metastasis. After total right mastectomy with sentinel lymph node biopsy, the final pathologic stage was pT2N0, ER (+), PR (+), c-erbB2 (2+), and FISH (-). On the third day following surgery, she complained of blurred vision in her left eye. Ophthalmologic evaluation showed choroidal metastasis from breast cancer. The visual acuity in her left eye was 20/50. Result: After concomitant delivery of chemoradiation therapy, the choroidal lesions improved dramatically and vision acuity in her left eye recovered to 20/20. Conclusion: Clinicians should consider the possibility of choroidal metastasis when breast cancer patients complain of ocular symptoms.
Cancer is essentially a disease of genes. Accumulation of molecular alterations in the genome of somatic cells is at the basis of tumorigenesis and underlies tumor response to therapy. Common cancers such as those arising in the lung, colon, breast, skin and prostate harbor a cocktail of mutated (or otherwise altered) oncogenes and tumor suppressors that work in concert to determine the molecular pathways that lead to their genesis, maintenance, and progression (1). Oncology research has benefited immensely from the worldwide efforts to characterize the genomes of all major cancer types. Technologic and analytic advances have enabled a comprehensive catalogue of cancer genes that can be exploited as diagnostic, prognostic and predictive biomarkers. The implementation of genomics-driven oncology also known as precision oncology involves several stages: initially, genomes and transcriptomes of patient tumors must be analyzed using state-ofthe-art technologies; second, the molecular profiles of each patient must be integrated using sophisticated bioinformatics tools with knowledge of existing and emerging anticancer drugs; finally, an annotated list of genomic alterations must be provided to the medical oncologist so that it can be incorporated into clinical decision making (2). This seemingly straightforward process is ridden by several challenges. To begin with, high-quality genomic information must be obtained consistently in the diagnostic setting often from sparse amounts of archival tumor tissue. Secondly, different layers of data (genomic, transcriptional and epigenetic profiles) must be annotated and interpreted. Finally, scientists often trained in different fields and clinicians should work in multi-disciplinary teams so that genomic information can be used for evidence-based therapies and innovative clinical trials. I will briefly review here the steps undertaken as well as the hurdles that we have encountered to build an infrastructure which could support genomics-driven cancer medicine for clinical practice and research purposes at our institution. In order to analyze and interpret next-generation sequencing (NGS) data, we formed a multi-skilled team composed of scientists with a background in biology, informatics, pharmacology, mathematics, medicine or engineering. The team met regularly once every 1-2 weeks to set tasks and worked together to develop NGS data analytical pipelines. No golden standard or validated commercial software exist to analyze complex tumor NGS data. Therefore, we strived to build internal pipelines to identify point mutations, copy number changes as well as more complex structural variations. All pipelines include a first mapping step, during which reads are aligned against the reference human genome and attributed the best genomic coordinates. Our first home-built pipeline allows the identification and annotation of single nucleotide variants by comparing the base present at each position in the tumor DNA with the germ-line DNA of the same patient. The user has the option to sieve variants at a-given threshold. When sequencing at a depth of 100x (this means that each nucleotide is sequenced on average 100 times), we usually filter out the variants EUR. J. ONCOL.; Vol. 20, Suppl n. 1, pp. 5-6, 2015 © Mattioli 1885 Proceeding Master Class in Oncology
Aim: It has been reported that derivatives from the chromene family have potent anti-leukemic activity. Differentiation therapy is a promising treatment for myeloid leukemia. Herein, we evaluated inhibition of growth, differentiation induction and apoptosis in human myeloid leukemia K562 cells by the novel derivatives of dihydropyrano[c]chromenes. Methods: K562 cells were treated with different concentrations of the new dihydropyrano[c]chromenes (20-260 μM) derivatives for 3 days. To investigate growth inhibition and viability of the cells, a trypan blue exclusion assay was applied. Differentiation was investigated morphologically by wright-Giemsa staining and latex particle phagocytosis assay. Apoptosis was observed by morphological criteria, the acridine orange/ethidium bromide (AO/EtBr) double staining method, as well as DNA ladder formation. Results: The IC50 values of the 4-PC, 4-NC, 4-CNC and 4-HC after 48 h of exposure was 240±4.5, 60±3.5, 180±4.2 and 160±5.5 μM for K562 cells, respectively. 4-NC was found to be the most effective compound and was chosen for further studies. 4-NC inhibited growth and proliferation in a dose- and time-dependent manner. Moreover, our evidence showed that the 4-NC effects on K562 cells resulted in differentiation toward a monocyte/macrophage lineage. The data from the AO/EtBr and DNA fragmentation assay confirmed qualitatively that K562 cell treatment with 4-NC induces apoptosis. Conclusion: Based on our current observations, these compounds can be valuable candidates for effective chemotherapy acting through differentiation induction and apoptosis.
Dasatinib is indicated for chronic myeloid leukemia (CML) patients with resistance or intolerance to imatinib or as a first line therapy in chronic or blastic phase of the disease; it has 325-fold increase potency compared to imatinib and is active in mutated and unmutated resistant patients. Pleural effusions are therapy-related events that can occur in all subset of patients treated with this drug. Aim of this paper is to draw up clinical guidelines on the management of pleural effusions associated with dasatinib treatment. Recommendations are based upon the published data and clinical personal experience from a number of different centres. Incidence of pleural effusions in different dasatinib trials, the related pathogenetic mechanisms and the associated risk factors are discussed. Practical recommendations to manage pleural effusions were finally composed. Adequate monitoring of patients with predisposing factors is necessary in order to early identify subjects at risk of developing such complications as well as to correctly manage them.
Aim: Intraoperative radiotherapy (IORT) is now an acceptable option for low risk early stage breast cancers, allowing patients not to undergo a full course of external radiotherapy. It is not clear, however, whether IORT, providing radiations very close to the chest wall, may produce heart damage. In this study we tried to evaluate if acute or chronic heart damage in early stage breast cancer patients treated with breast conservative surgery (BCS) and IORT, can be assessed by ultra-sensitive cardiac Troponine I (TnI) levels or N-terminal proB-type natriuretic peptide (NT-proBNP), respectively. Materials and methods: We enrolled 43 patients who received IORT for breast cancer, as part of a TARGIT-A trial. Twenty-two patients had left and 21 right breast cancer. TnI levels were measured immediately before surgery, and six hours after the end of IORT; both TnI and NT-proBNP levels were measured after 12 months. For the patients with left breast cancer, a little tungsten sheet was placed under the major pectoralis muscle, on the chest projection of the X-ray source, in order to protect the heart. Results: None of the patients showed altered serum levels of TnI before surgery, or after IORT procedure and NT-proBNP during follow-up. No difference in TnI and NTproBNP values was noticed between right-sided and left-sided breast cancers treated with BCS and IORT. Conclusions: IORT for early stage breast cancer treatment does not increase TnI and NT-proBNP levels, suggesting that the procedure does not determine acute or chronic heart damage.
Telomerase activation has been found in a variety of human cancers, including brain tumors to prevent the telomere from progressive shortening, but telomeres are transcribed into a non-coding RNA called telomeric repeat-containing RNA or TERRA which acts as a natural inhibitor of telomerase activity. Considering meningioma and astrocytoma are the most common tumors of the CNS, the aim of this study was to evaluate TERRA expression level in meningioma, astrocytoma tumors and nontumor (NT) controls. Furthermore, expression levels of TERRA were compared between different grades of meningioma and astrocytoma. Additionally, we analyzed the correlation of TERRA expression and improvement outcome. The total RNA of 51 brain tumor samples and 4 samples as nontumor (NT) controls was extracted and SYBR Green real-time reverse transcription–polymerase chain reaction assays for quantitation of total TERRA levels were developed. Tumor samples from 25 patients with meningiomas and 26 patients with astrocytoma were assessed. We demonstrated the correlation between total TERRA levels of expression with different grades of brain tumors and improvement outcome. According to our study, TERRA may be a prognostic marker in meningioma and astrocytoma tumors.
Non-small cell lung cancer (NSCLC) is the second tumor in incidence worldwide and, at present, remains the leading cause of cancer death. According to the Italian Drug governance, although the incoming knowledge reached during these years, the backbone treatment of the advanced stages of lung cancer remains standard chemotherapy. Platinum-based chemotherapy, prolonged from four to six cycles, is the standard therapy for all the subtypes of NSCLC without Epidermal Growth Factor Receptor (EGFR) mutation. According to the several guidelines, second line therapy must be composed by a single agent drug. During recent years a great attention has been given to the chemotherapy free window which existed between the first and the second line, in case of stable disease (SD) or objective response (OR). Several therapeutic maintenance strategies have been studied, both in continuing the strategy chosen for the first line and in changing the drug, with a no cross-resistant agent, stopping the platinum salt anyway. Although a number of these studies demonstrated that maintenance therapy improved progression free survival (PFS) compared with observation, only few had a significant overall survival (OS) benefit. Pemetrexed, utilized both in patients treated with this drug in first line and as switch maintenance, and bevacizumab, in continuation maintenance setting, are the only drugs which have been shown able to prolong OS in adenocarcinoma histology. Despite these positive results, implementation of maintenance therapy in NSCLC remains debated, and at this moment there are no data comparing continuation and switch maintenance treatment.
