Fertility options after chemotherapy in young premenopausal patients.

Context: Infertility affects more and more younger patients nowadays. Life-saving cancer treatments - chemotherapy and radiation therapy unfortunately damage oocytes and reduce the window of fertility in women. There were an estimated 14.1 million cases of cancer worldwide in 2012, of which 6.7 million were in women. Aim: We are reviewing fertility options and treatments for women fighting oncological diseases. It is important to promote that there is a possibility for these patients to know all they can do in order to preserve their fertility and our government should help all these young patients.The trend of delayed childbearing has increased worldwide duet o increased life costs, difficulty of finding a suitable partner and carier options, while the number of women facing a cancer diagnosis is rising. Material and methods: We describe a review regarding the impact of these treatments for the fertility of these patients. Results: Show that informed patients can better cope with their diagnostic and have a better prognosis. Conclusions: Improving survival rates and current data have created a new medical field oncofertility. The term was first introduced in 2015 and is being used all over clinics that treat young patients nowadays.

Malignant arterial hypertension in a 2-month-old girl: Etiological diagnosis and treatment.

A 2-month-old girl presented with malignant arterial hypertension revealing bilateral renal artery stenosis secondary to neurofibromatosis type 1 (NF1). Life-supporting care was initiated immediately. High-dose peripheral vasodilator therapy induced life-threatening toxicity; vascular surgery was therefore performed. Technical difficulties due to the young age and low body weight of the patient resulted in fatal bleeding. Renovascular disease is an important cause of pediatric hypertension. NF1-associated renovascular hypertension in young pediatric patients is rare, and its highly specialized management is best delivered via a multidisciplinary approach. The long-term prognosis remains poor.

FSH RECEPTOR AND FSH BETA CHAIN POLYMORPHISM INVOLVEMENT IN INFERTILITY AND ENDOMETRIOSIS DISEASE.

OBJECTIVES: The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.-280G>T) polymorphisms and endometriosis in Romanian women. MATERIAL AND METHODS: We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). RESULTS: There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.-280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). CONCLUSIONS: FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.

LARGE CELL METASTATIC PANCREATIC NEUROENDOCRINE CARCINOMA TREATED WITH SOMATOSTATIN ANALOGUES - CASE REPORT AND LITERATURE REVIEW.

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient's health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. CONCLUSION: This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

A Primary Retroperitoneal Diffuse Large B-Cell Lymphoma: A Challenging Diagnosis.

Although quite rare, retroperitoneum can harbour malignant limphomas. On the grounds that the anatomical location is uncommon and the symptoms are scarce, the diagnosis is usually late and challenging. Imaging methods such as magnetic resonance imaging, computed tomography (CT) and positron emission tomography-computed tomography (PET-CT), can characterize and locate the tumor while endoscopic ultrasound fine needle aspiration (EUS-FNA) may provide pathological confirmation. We present the clinical case of a fifty-five-year-old female that is admitted to our hospital with epigastric discomfort, nausea and vomiting. CT showed a homogenously enhancing mass lesion that encased the pancreas, in contact with the portal vein, inferior vena cava, invading splenomesenteric confluence. To investigate further, EUS-FNA was decided and it revealed lymphocyte proliferation suggestive for the diagnosis of lymphoma. Hereinafter, surgical intervention was performed and immunohistochemical analysis and sub classification of lymphoma was obtained. The final diagnosis was non-Hodgkin lymphoma, Diffuse Large B-Cell Lymphoma (DLBCL). Poly-chemotherapy with R-CHOP was initiated. At the end of the treatment fluorodeoxyglucose positron emission tomography (FDG-PET) was performed and no pathological findings were found. A brief review of literature is also provided.

PROGNOSTIC FACTORS IN PATIENTS WITH SURGICAL RESECTION OF PANCREATIC NEUROENDOCRINE TUMOURS.

CONTEXT: Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. OBJECTIVE: The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. SUBJECTS AND METHODS: The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. RESULTS: Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. CONCLUSIONS: Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%.

Chronic venous leg ulcers: Effects of foam sclerotherapy on healing and recurrence.

INTRODUCTION: Ultrasound-guided foam sclerotherapy is a minimally invasive treatment option used for ablation of axial and perforator reflux for chronic venous ulceration. Active ulceration presents a significant health burden in both the primary and secondary care setting. The objective of this study is to determine ulcer healing rates at 24 weeks and 12 months, and ulcer recurrence rates at one year for chronic venous ulcers after ultrasound-guided foam sclerotherapy. METHODS: Between 2007 and 2012, 54 patients underwent ultrasound-guided foam sclerotherapy for clinical, aetiological, anatomical and pathological C6 ulcers. All patients were followed up clinically, and venous duplex was performed on all legs before and after treatment. A prospectively maintained database was analysed to determine venous truncal occlusion rates, 24-week and 12-month healing and recurrence rates (using Kaplan-Meier survival analysis). RESULTS: Fifty-seven ulcerated legs, 39 primary and 18 with recurrent superficial venous reflux were analysed. Median time of active ulceration at presentation was 15.2 months (range 5 months to 17 years). At a median follow-up of 2.7 months, 90% (51 legs) achieved full truncal occlusion after one session, 4% (2) short segment occlusion and 5% (3) failed to occlude and one patient died and was lost to follow-up; 13/57 (23%) required a second session of treatment for completion of treatment, recanalisations and to treat perforator disease, 88% (50/57) ulcers healed at a median of 5.3 months (interquartile range 2.9-8.4 months) following their first ultrasound-guided foam sclerotherapy treatment. The 24-week and 12-month estimated healing rates were 53% and 72%, respectively. The estimated 12-month recurrence rate was 9.2%. There were no reported incidences of deep venous thrombosis or neurological symptoms. CONCLUSION: This study affirms the role of ultrasound-guided foam sclerotherapy as a safe and effective option for abolition of superficial reflux.

Allogeneic and autologous stem cell transplantation for hepatosplenic T-cell lymphoma: a retrospective study of the EBMT Lymphoma Working Party.

The objective of this registry study was to analyse the outcome of patients who underwent allogeneic or autologous haematopoietic stem cell transplantation (HSCT) for hepatosplenic T-cell lymphoma (HSTL), a rare and extremely aggressive peripheral T-cell lymphoma subtype. Patients were eligible if they had histologically verified HSTL and underwent HSCT between 2003 and 2011. Seventy-six patients were identified in the European Society for Bone and Marrow Transplantation database. Additional baseline and follow-up information could be obtained from the referring centres for 36 patients. Eleven of these were excluded following histopathology review, leaving 25 patients in the final study cohort (alloHSCT 18, autoHSCT 7). With a median follow-up of 36 months, 2 patients relapsed after alloHSCT, resulting in a 3-year progression-free survival of 48%. After autoHSCT, 5 patients relapsed and subsequently died. This study indicates that graft-versus-lymphoma activity conferred by alloHSCT can result in long-term survival for a substantial proportion of patients with HSTL.

Management of hepatocellular carcinoma -- experience of a single center.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer-related death. We aim to study the diagnosis and treatment options for HCC. METHODS: We used standard methods of diagnosis for HCC:radiology, determining serum alpha fetoprotein (AFP). We included 190 patients diagnosed with HCC between April 2011 and May 2012. RESULTS: All patients were classified and treated according to the BCLC staging. Our study included 43 patients with early stage HCC, 58 patients with intermediate stage HCC (Stage B) and 89 patients with advanced stage HCC (Stage C). Most patients in the early stage underwent local ablation, while TACE was preferred in 46 patients in the intermediate stage.Systemic therapy was the most frequent treatment for patients in the advanced stage (48 patients), followed by Sorafenib (16 patients). 21 patients with end-stage disease did not receive treatment. Survival rates depended on the HCC stage: 2 - 18 months in the intermediate stage and 1 - 12 months in the advanced stage. CONCLUSION: Early diagnosis of HCC is essential in improving the patients outcomes, as there are several classic therapeutic options and new emerging ones addressing patients with early stage disease.

Fludarabine, low-dose cyclophosphamide and rabbit antithymocyte globulin allowed stable engraftment after allogeneic peripheral blood stem cell transplantation for poly-transfused dyskeratosis congenita patient: case report.

BACKGROUND: Dyskeratosis congenita (DC) is characterized by the clinical triad of reticular skin pigmentation, oral leukoplakia, and nail dystrophy associated with bone marrow failure (BMF) and an high risk to develop cancer and pulmonary complications. The only curative treatment for patients with DC and BMF is stem cell transplantation. Due to the rarity of the disease, the best transplant procedure is not yet known. The use of myeloablative procedures has been associated with high mortality. In the last 2 decades, encouraging results have been obtained with nonmyeloablative procedures. Heavily transfused patients have an additional risk of graft failure. CASE REPORT: Herein we have reported a 4-year-old boy with DC and severe BMF at the time of transplantation, who had been transfused with nonleucodepleted blood products for 18 months. He experienced a favorable outcome after nonmyeloablative transplant conditioning using low-dose cyclophosphamide (40 mg/kg), fludarabine (180 mg/kg), and rabbit antithymocyte globulin (10 mg/kg). The patient received a peripheral stem cell graft containing 7.52 × 10(6) CD34/kg from an HLA identical sister. Graft versus host disease (GVHD) prophylaxis consisted of a short-term combination of cyclosporine and methotrexate. RESULTS: We observed rapid neutrophil engraftment on day +21 and for platelets on day +40. No early or late complications were recorded during 15 months follow-up. The patient developed only grade I skin GVHD. On day +30, chimerism assay showed 100% donor cells. CONCLUSION: Long-term follow-up is essential to establish the efficacy and safety of this procedure.

Cytokine gene polymorphisms support diagnostic monitoring of Romanian multiple myeloma patients.

INTRODUCTION: Cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine gene polymorphism in Romanian multiple myeloma patients. MATERIAL AND METHODS: Cytokine genotyping was performed in 80 patients and 100 healthy blood donors using molecular biology methods (SSP-Invitrogen, USA). RESULTS: Analyzing each polymorphic site, there was an increased frequency of the following genotypes in patients compared to control group: Interleukin-1beta (IL-1ß) pos.+3962 TT, IL-12 pos.-1188 CC, gamma-Interferon (γ-IFN) pos.+874 AA, Transforming Growth Factor- beta1 (TGF- ß1) codon10 TT, IL-2 pos.-330 TG and pos.+166 TT, Interleukin-4Receptor alpha (IL-4Rα) pos.-33 TC, IL-10 pos.-1082 GG and pos.-592 CC, IL-6 pos.-174 GG. It should be noted that almost one third of multiple myeloma patients had IL-6 pos.-174 GG genotype and 62% IL-10 GCC haplotype. These identified haplotypes are high interleukins producer, and this fact was confirmed by serum IL-6 and IL-10 levels performed by ELISA and enhanced chemiluminiscence methods. CONCLUSION: These markers could be successfully used, together with other specific clinical and biological parameters, as reliable individualized prognostic factors in multiple myeloma patients.

Total body irradiation prior to bone marrow transplantation--the experience of the Institute of Oncology Prof. Dr. Al. Trestioreanu Bucharest.

PURPOSE: To present the technique of total body irradiation (TBI), applied for the first time in Romania, at the Institute of Oncology Bucharest, as part of stem cell transplantation for hematological malignancies. PATIENTS AND METHODS: The total dose administered was 12 Gy at the reference point, 2 Gy/fraction, one fraction per day, 6 consecutive days, with a total dose of 8 - 11.4 Gy delivered to the lung, using Mevatron Primus linear accelerator (6 MV & 15 MV, 200-300 cGy/min in isocenter), in vivo dosimetry detectors and equipment for the reference dosimetry, personalized blocks for lung shielding sustained by polymethylmethaacrylate (PPMA) plate, Simulix HP simulator, and computer tomographic (CT) scans. Techniques used were: a) two parallel opposed anteroposterior / posteroanterior (AP/PA) fields with the patient in prone and supine position; b) two parallel opposed lateral fields with the patient placed on a lateral table, at 320 cm from the source. The percentage depth dose, tissue maximum ratio (TMR), off axis ratio (OAR) and the reference dose rate were measured for every patient's geometrical characteristics, with an uncertainty of +/- 2.2% and were used to calculate monitor units and to evaluate the dose in organs at risk (lungs, gonads, eyes etc). RESULTS: 5 patients (3 with the AP/PA technique and 2 with the lateral technique) were irradiated. All patients completed their irradiation in good clinical condition. The acute side effects were minimal (WHO grade 1: nausea/ vomiting--all patients; diarrhea--1 patient; headache--2 patients; photophobia and diplopia--1 patient; head and neck skin erythema--all patients). Because of the short follow-up period no safe evaluation of late side effects can be done. However, during this period one patient developed a non-aggressive form of chronic liver graft vs. host disease (GVHD) and one patient died due to acute GVHD. CONCLUSION: TBI as part of stem cell transplantation for hematological malignancies was successfully realized at our Institute, with favorable clinical results. This technique is easy to carry out and reproducible.

Nonclinical and early clinical development of tacrolimus ointment for the treatment of atopic dermatitis.

Tacrolimus ointment, formulated for the treatment of atopic dermatitis, is the first in a class of topical immunomodulators. Its mechanism of action is based on calcineurin inhibition, which results in suppression of antigen-specific T-cell activation and inhibition of inflammatory cytokine release. Animal and human studies have shown that topically applied tacrolimus is minimally absorbed into the systemic circulation, the fraction that is absorbed is extensively distributed, and tacrolimus does not accumulate in tissues following repeated topical application. In addition, tacrolimus ointment is not inherently irritating, sensitizing, phototoxic, or photoallergenic when applied to intact skin. Unlike some topical corticosteroids, tacrolimus ointment does not cause a decrease in collagen synthesis or skin thickness, nor does it produce skin abnormalities or depigmentation. In animal studies, repeated daily application of tacrolimus ointment up to 1 year is associated with dermal findings similar to those following vehicle application (mild to moderate dermal irritation and microscopic findings of acanthosis, hyperkeratosis, and superficial inflammation). In a 52-week study with Yucatan micropigs, no noteworthy macroscopic or microscopic changes (either dermal or systemic) related to the application of tacrolimus ointment (0.03% to 0.3% concentrations) were observed. Tacrolimus ointment was shown to be safe and effective in phase 2 and early phase 3 studies. Significant improvements in atopic dermatitis were observed in the majority of patients treated with tacrolimus ointment. The most common adverse events associated with its use were a transient burning sensation and pruritus at the site of application. Blood tacrolimus concentrations were below the limit of quantitation in most patients.

Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children.

BACKGROUND: Tacrolimus is a potent immunosuppressant used in organ transplant recipients; an ointment formulation is being developed as a therapeutic agent for atopic dermatitis. OBJECTIVE: Our purpose was to define the pharmacokinetics and evaluate tacrolimus 0.3% ointment as therapy for moderate to severe atopic dermatitis. METHODS: Thirty-nine patients, 5 to 75 years of age, received 14 applications over 8 days. Serial blood samples were collected on days 1 and 8, with predose samples collected on days 2 through 7. Overall response and signs/symptoms were rated daily on days 1 through 11. Incidence of adverse events and laboratory profile were determined. RESULTS: Mean area under the curve (0.9 to 42.5 ng x hr/ml) was highly variable and appeared to be related to size of application area. No systemic accumulation of tacrolimus was observed. Comparison to historical intravenous data indicates that absolute bioavailability of topical tacrolimus was less than 0.5%. Ninety-five percent of patients showed at least good improvement. All adverse events were transient. Burning was the most common application site adverse event and vasodilatation ("flushing/warmth") was the most common nonapplication site adverse event. No drug-related changes in laboratory profile were observed. CONCLUSION: The results of this study suggest that tacrolimus 0.3% ointment may be a safe and effective therapy for atopic dermatitis.

Simultaneous determination of tiaramide and its metabolites by high performance liquid chromatography.

A simultaneous quantitative HPLC assay was developed for tiaramide hydrochloride (4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl) acetyl]-1-piperazine ethanol hydrochloride) and its main metabolites, namely, 1 - [ (5-chloro-2-oxo-3 (2H) -benzothiazolyl) -acetyl]-piperazine (DETR) and 4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl) acetyl] -piperazine acetic acid (TRAA). The assay was employed to determine plasma levels of tiaramide and its main metabolite, TRAA, after intravenous administration of tiaramide hydrochloride to rabbits.