Efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients: a single-centre experience.

PURPOSE: Data on efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients are scarce. We therefore performed this retrospective study to analyse our experience with radiotherapy exclusively to infradiaphragmal fields. MATERIALS AND METHODS: we retrospectively evaluated 101 patients treated between 2003 and 2014. Median dose was 36 Gy, range 4 to 54 Gy. Medium dose per fraction was 2 Gy, range 1.5 to 7 Gy. RESULTS: After a median follow-up of 66 months (range 1-211 months), we observed lymphoma recurrence in 38 patients (38%), five in the RT field and 33 out-of-field. Recurrences were significantly more frequent in the salvage group (17 out-of-field and 4 in-field in 31 patients) than in adjuvant group (16 out-of-field and 1 in-field in 70 patients; p < 0.001). The 2-, 5- and 10-year event-free survival (EFS) rates were 62%, 56% and 54%. The 2-, 5- and 10-year overall survival (OS) rates for the entire group of patients are 73%, 60% and 54%, respectively. Acute side effects occurred in 43 (43%) patients, most frequent gastrointestinal in 26 (26%) patients. Late side effects occurred in 12 (12%) of all patients, 6 of 23 (26%) followed up for more than 10 years. Six patients developed secondary cancers, four gastrointestinal disturbances, two diabetes mellitus and three renal failure. CONCLUSION: Radiotherapy is an effective and safe treatment option for patients with infradiaphragmatic lymphoma providing excellent local disease control with minimal late toxicity. Infradiaphragmatic lymphoma localization should not be regarded as a contraindication for use of radiotherapy. However, patients should be monitored for a secondary malignancy.

Gender Difference in Distribution of Estrogen and Androgen Receptors in Intestinal-type Gastric Cancer.

BACKGROUND: Gender difference in survival of patients with gastric cancer is not well investigated. The aim of this study was to analyze the gender-related distribution of estrogen receptor alpha (ERα) and androgen receptor (AR) in the epithelium and stroma of intestinal-type gastric cancer. MATERIALS AND METHODS: Immunohistochemical analysis was performed in 60 patients (42% females). RESULTS: In gastric cancer patients, frequency of ERα-positive cells was lower in epithelium than in healthy individuals, but not significantly. In stroma and epithelium, AR-positive cells were absent from samples of women with T1 and T2 stage disease, while in men, their frequency was significantly increased in stroma of those with T3 and T4 stages and was significantly higher compared to women. AR-positive cells in stroma were fibroblasts, myofibroblasts and mast cells. CONCLUSION: To our knowledge, this study is the first to show gender differences in the distribution and frequency of AR-positive cells in neoplastic stroma of gastric cancer.

Age and sex differences in genome damage between prepubertal and adult mice after exposure to ionising radiation.

The mechanisms that lead to sex and age differences in biological responses to exposure to ionising radiation and related health risks have still not been investigated to a satisfactory extent. The significance of sex hormones in the aetiology of radiogenic cancer types requires a better understanding of the mechanisms involved, especially during organism development. The aim of this study was to show age and sex differences in genome damage between prepubertal and adult mice after single exposure to gamma radiation. Genome damage was measured 24 h, 48 h, and 72 h after exposure of 3-week and 12-week old BALB/CJ mice to 8 Gy of gamma radiation using an in vivo micronucleus assay. There was a significantly higher genome damage in prepubertal than in adult animals of both sexes for all sampling times. Irradiation caused a higher frequency of micronuclei in males of both age groups. Our study confirms sex differences in the susceptibility to effects of ionising radiation in mice and is the first to show that such a difference occurs already at prepubertal age.

Connexin 43 Expression in Primary Colorectal Carcinomas in Patients with Stage III and IV Disease.

BACKGROUND/AIM: Protein connexin 43 (Cx43), a part of intercellular gap junctions, is frequently down-regulated in tumors. The aim of the study was to compare Cx43 expression in primary colorectal tumors of patients with stage III and IV disease. PATIENTS AND METHODS: Immunohistochemical expression of Cx43 was analyzed in 50 colorectal adenocarcinomas from surgically-treated patients of stage pT3N1-2 without metastases (M0) and 50 specimens of the same pTN stage from patients with synchronous liver metastases (M1). Association of Cx43 expression with clinicopathological factors and tumor site was also analyzed. RESULTS: There was no significant difference in Cx43 expression between M0 and M1 tumor specimens (p=0.817), as well as in Cx43 expression between colonic and rectal tumors (p=0.116), respectively. Stromal expression of Cx43 was higher in M1 than in M0 tumors (p=0.004). CONCLUSION: Stromal Cx43 expression is possible indicator of metastatic potential of colorectal adenocarcinoma.

Clinical significance of immunohistochemical expression of cancer/testis tumor-associated antigens (MAGE-A1, MAGE-A3/4, NY-ESO-1) in patients with non-small cell lung cancer.

AIMS AND BACKGROUND: This paper deals with the clinical significance of the immunohistochemical expression of MAGE-A1, MAGE-A3/4 and NY-ESO-1 antigens in patients with non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: The study included 80 patients with NSCLC (40 with adenocarcinoma, 40 with squamous cell carcinoma) who had undergone surgery. MAGE-A1 and MAGE-A3/4 antigen expression was determined by an immunohistochemical method using the monoclonal antibody 57B, and NY-ESO-1 antigen expression was determined with the addition of the B9.8.1.1 antibody. The expression of these antigens was compared with the clinicopathological features of the tumors and the survival of the patients. RESULTS: MAGE-A1, MAGE-A3/4 and NY-ESO-1 were expressed in 17.3%, 44.4% and 18.5% of NSCLC patients, respectively. A statistically higher immunohistological expression rate of MAGE-A3/4 was found in squamous cell carcinoma (P <0.001) and a significantly higher amount of tumor necrosis was observed in tumors with MAGE-3 expression (P = 0.001), but no correlation with positive lymph nodes was found. There was a statistically significant correlation between MAGE-A1 expression in adenocarcinoma and the presence of tumor necrosis (P = 0.05). Furthermore, there was a significant correlation between NY-ESO-1 expression and positive lymph nodes in adenocarcinoma, but not in squamous cell carcinoma. No statistically significant difference in patient survival was found with regard to tumor type and the observed histopathological characteristics except tumor size. Statistically significantly better survival was found in the group of patients with adenocarcinomas who had positive expression of MAGE-A3/4 (P = 0.012). CONCLUSIONS: This study demonstrated that the expression of MAGE-A3/4 antigen might be a valuable prognostic factor regarding survival in patients with NSCLC.

[Lymphoma diagnosis and treatment - second Croatian consensus]. / Dijagnostika i lijecenje limfoma - drugi hrvatski konsenzus.

New, extended and modernized recommendations for diagnostics and treatment of lymphomas were accepted at a meeting held in March 2012 with the participation of major Croatian experts. They encompass morphological, radiological and nuclear diagnostics, systemic treatment, radiotherapy and follow-up of most tumors of lymphoid tissues occurring in adults. The recommendations were agreed upon by consensus. Reporters presented data and suggested recommendations which had been first discussed in working groups and then agreed upon on the plenary session.

Leptomeningeal and intramedullary metastases of glioblastoma multiforme in a patient reoperated during adjuvant radiochemotherapy.

Despite huge advances in medicine, glioblastoma multiforme (GBM) remains a highly lethal, fast-growing tumour that cannot be cured by currently available therapies. However, extracranial and extraneural dissemination of GBM is extremely rare, but is being recognised in different imaging studies. To date, the cause of the GBM metastatic spread still remains under discussion. It probably develops at the time of intracranial progression following a surgical procedure. According to other hypothesis, the metastases are a consequence of spontaneous tumour transdural extension or haematogenous dissemination. We present a case of a 59-year-old woman with symptomatic leptomeningeal and intramedullary metastases of GBM who has been previously surgically treated with primary subtotal resection and underwent a repeated surgery during adjuvant radiotherapy and chemotherapy with temozolomide. Today, the main goal of surgery and chemoradiotherapy is to prevent neurologic deterioration and improve health-related quality of life. With this paper, we want to present this rare entity and emphasise the importance of a multidisciplinary approach, a key function in the management of brain tumour patients. The prognosis is still very poor although prolongation of survival can be obtained. Finally, although rare, our case strongly suggests that clinicians should be familiar with the possibility of the extracranial spread of GBM because as treatment improvements provide better control of the primary tumour and improving survival, metastatic disease will be increasingly encountered.

[Surgical and radiotherapy in treatment of postauricular keloids--case report]. / Kirurska i iradijacijska terapija u lijecenju postaurikularnih keloida.

Treatment of keloid remains a great challenge for clinicians, in spite of numerous therapeutic regimens reported in the literature to date. Earlobe or postauricular regions are predominant locations for postoperative keloids due to the treatment of lop ears. There are several treatments that include intralesional steroid injections, surgical excision, cryotherapy, laser therapy, radiotherapy and pharmacotherapy. A case is presented with fourth recurrence of keloids after surgical treatment of lop ears with final satisfactory outcome after combined therapy that included surgical excision, skin flap transposition and radiotherapy. It is concluded that interdisciplinary approach that includes a combination of surgery and radiotherapy results in a satisfactory outcome of keloid treatment.

Immunohystochemical expression of cancer/testis antigens (MAGE-A3/4, NY-ESO-1) in non-small cell lung cancer: the relationship with clinical-pathological features.

The aim of this study was to explore the expression of cancer/testis tumor associated antigens (C/T TAAs) MAGE-A 3/4 and NY-ESO-1 in lung squamous cell carcinoma and adenocarcinoma, and to evaluate their association with the standard clinical-pathological features of surgically treated lung cancer patients. The study included 80 patients with non-small cell lung cancer (40 adenocarcinomas, 40 squamous cell carcinomas) who had undergone surgery in the period between 2002 and 2005. The MAGE-A3/4 and NY-ESO-1 antigen expression was analyzed immunohistochemically (IHC). The results showed MAGE-A3/4 and NY-ESO-1 positive staining in 65.1% and 23.3% of squamous cell carcinomas and 18.9% and 10.8% of adenocarcinomas, respectively. A statistically higher MAGE-A3/4 expression was observed in planocellular bronchial carcinoma (p < 0.001), while no difference was found in the expression of NY-ESO-1 in adenocarcinoma and planocellular carcinoma (p = 0.144). A significant association was found between the MAGE-A3/4 expression and presence of tumor necrosis in squamous cell cancer specimens (p = 0.001), but not in adenocarcinoma (p = 0.033). A statistically significant association was noted between the NY-ESO-1 expression and positive hilar and mediastinal lymph nodes in adenocarcinoma (p = 0.025) whereas it was not the case in squamous cell carcinoma. Non-small cell lung cancer frequently expresses cancer/testis tumor associated antigens. Our results demonstrate that the MAGE-A3/4 and NY-ESO-1 expression was significant associated with prognostic factors of poor outcome of disease (presence of tumor necrosis and lymph node metastasis). As C/T antigens are important for inducing a specific immune reaction in lung cancer patients, there is an intention to form a subgroup of patients in the future, whose treatment would be enhanced by specific immunotherapy based on the observed scientific results.

Chromosome damage and cancer risk in the workplace: the example of cytogenetic surveillance in Croatia.

The use of cytogenetic assays in the surveillance of populations occupationally exposed to genotoxic carcinogens originates from the assumption that chromosomal alterations might be causally involved in early stages of carcinogenesis. Historical cohort studies have since 1990s consistently reported an association between the level of chromosomal aberrations (CA) in peripheral lymphocytes of healthy subjects and the risk of cancer. Only in few cases, have these results been transformed into a regulatory tool for improving occupational safety. The cytogenetic surveillance program adopted for more than two decades in the Republic of Croatia is one of these few examples. Croatian workers exposed to genotoxic agents were systematically screened for CA, to identify occupational settings needing a priority intervention. Significant increases of mean CA frequency were observed in groups exposed to ionizing radiation, chemical agents, and mixed exposures when compared with a group of unexposed referents. CA data on 736 men and 584 women, monitored between 1987 and 2000, have been associated with cancer incidence. Although the small size of the cohort did not allow for reaching statistical significance, the medium tertile of the CA frequency distribution was associated with a doubling of cancer incidence rate ratio (IRR=2.40; 95% CI 0.85-6.77) when compared with the lowest tertile. For chromosome-type CA, IRR was non-significantly increased for both the medium (IRR 1.53, 95% CI 0.58-3.99) and high categories (IRR 1.69; 95% CI 0.61-4.72). Recommendations for future strategies comprise the inclusion of predictive biomarkers in surveillance programs, the definition of a regulatory framework, and their possible use for the identification of individual risk profiles.