Abstract: Advanced thymic carcinoma (TC) is a very aggressive disease. To date there are no established treatment options for the refractory and recurrent disease and only a few prospective trials have been conducted in patients with TC. Here we present a case of a relapsed TC patient, who, by using combination chemotherapy, showed a positive response to sorafenib with C-KIT exon 11 mutation.
Abstract: The management of the patients with carcinoma of an unknown primary represents a difficult challenge in oncology. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has provided new insights in the diagnosis, staging, and follow-up of oncological patients.
Abstract: Hand-foot syndrome (HFS), the most common toxicity of capecitabine, is characterized by tingling, numbness, pain, erythema, dryness, rash, swelling, increased pigmentation, and/or pruritus of the palmar and/or plantar surfaces of the hands and/or feet. HFS is usually seen in both the hands and the feet, with varying severity. We have previously published a case report of dihydropyrimidine dehydrogenase (DPD) deficiency that manifested a variant of HFS.
Abstract: Fludarabine is a nucleoside analogue used in the treatment of low-grade lymphoproliferative disorders and in conditioning regimens of non-myeloablative allogeneic stem cell transplantation. This is a relatively safe drug for clinical use but may cause side effects, some of which may be life-threatening. Here a case of severe pulmonary toxicity associated with fludarabine and a possible contribution of rituximab is presented and the literature reviewed.
Abstract: Survivin (S) is a member of inhibitor of apoptosis family (IAP) and is expressed in the majority of malignant tumors but undetectable in normal differentiated adult tissues. S is an encouraging target for cancer therapy. TSP-1 is a multifunctional protein regulating cell growth, motility and apoptosis in both physiological and pathological conditions. The role of TSP-1 in cancer progression remains controversial. We aimed to determine the pathogenetic and prognostic role of TSP-1 and S in non-Hodgkin's lymphomas (NHL). S and TSP-1 expressions were looked for in 177 cases with NHL. S was found to be positive in 94 of the cases (53%). TSP-1 was found to be positive in 31 of the cases (17.5%). There was a strong association between S and TSP-1 and also aggressive histology with S and TSP-1. The overall survival (OS) times were longer in cases without S expression than cases with S expression (p=0.0514). Although the OS was shorter in TSP-1 expressing cases as compared with TSP-1 (-) cases, difference was not significant (p=0.2428). In conclusion, S and TSP-1 expressions were detected in 53 and 17.5% of the cases with NHL, and are associated with aggressive histology and shorter OS.
Abstract: In spite of the development of new antifungal drugs, amphotericin B deoxycholate (d-AMB) remains the gold standard in the treatment of severe fungal infections in immunosuppressed hosts. However, d-AMB is a toxic drug, the most important dose-limiting toxicities being nephrotoxicity and infusion-related allergic reactions. Lipid and liposomal formulations of d-AMB have relatively lower toxicity and are considered alternative choices. However, the routine use of these formulations is limited by their higher cost. Using retrospective analysis, we explored the incidence of nephrotoxicity and allergic reactions requiring the cessation of conventional d-AMB in 113 cases treated with the drug. In contrast to knowledge in the relevant literature, we did not detect significant toxicity, which would have required discontinuation of the d-AMB treatment. Mean serum creatinine levels were 0.72 +/- 0.25 and 0.84 +/- 0.31 mg dl(-1) before and after therapy, respectively. Although the difference between creatinine levels before and after d-AMB is statistically significant, the creatinine level increased twofold in only eight cases. Mean serum potassium levels were 3.8 +/- 0.54 and 3.6 +/- 0.7 mmol l(-1) before and after d-AMB respectively. Potassium levels below 3 mmol l(-1) were found in 7 and 17 cases before and after d-AMB respectively. Potassium levels were statistically lower in cases with fungal mucositis. Severe infusion-related allergic reactions were observed in three cases. Antihistamine and corticosteroid were added to the treatment in these cases. With these findings, we can conclude that d-AMB is a tolerable, low cost drug which can be safely used provided there is suitable premedication and monitoring of blood urea nitrogen, serum potassium and magnesium levels.
Abstract: The aim of this study is to detect the biologic and/or prognostic significance of survivin (S) and effector protease receptor 1: EPR-1 (E) expression in acute leukemias (34 ALL and 40 AML) by using RT-PCR. S and E expressions were found in 83.8 and 20.3% of the cases, respectively. S was detected in 90%, 76.5% and E was detected in 17.5%, 23.5% of the cases with AML and ALL, respectively. There was a significant correlation between S and E (r=0.30 p=0.01). Mortality rate was higher in E(-) cases than E(+) cases (83.1 % versus 66.7%) (p=0.04). The median DFS and OS rates were shorter in S(+) and E(-) cases. In subgroup analysis, there was not a significant difference for OS between S(-) and S(+) cases and E(-) and E(+) cases in ALL group. The median OS rate was significantly longer in S(-) cases than S(+) cases, and longer in E(+) cases than E(-) in AML groups (p=0.04, 0.001, respectively). OS and DFS rates were longest in S(-) E(+) cases and shortest in S(+) E(-) cases (p=0.04 and 0.03, respectively). In multivariate analyses EPR1 negativity was found to be an independent poor risk factor for survival (OR: 2.4, p=0.02). In conclusion S expression is a bad prognostic indicator in cases with acute leukemia especially in AML. S negativity and E positivity show good clinical outcome in acute leukemias. E expression is important due to its property of the possible natural anti-sense of the S.
Abstract: The aim of this study was to determine the expression of Gravin (a tumor suppressor gene belonging to the A kinase anchoring protein family) in samples of acute leukaemia and to explore its association with the prognosis. The study group consisted of 162 people (137 patients with acute leukaemia and 25 volunteers as control). Real-time quantitative PCR was used to determine the gene expression and beta Actin used as a control gene. The results were evaluated with Comparative Ct method. Gravin beta-Actin DeltaCt was statistically different between patients and controls (p value < 0.001). The Gravin expression was found to be decreased 11-fold when compared with controls and was found to be decreased in 106 cases (77.5%). There was an inverse correlation between gravin expression and overall survival. The Gravin expression was found to be decreased in samples of acute leukaemia and was associated with an inferior overall survival. Because of paradoxical results, there is a need for more studies exploring gravin isoforms and other related gene expressions.
Abstract: Retroperitoneal fibrosis (RF) is a clinical entity characterized by the progressive proliferation of connective tissue that rarely forms a mass involving the periaortic area of the abdomen, which may be idiopathic as well as a result of an inflammatory process after aneurysmal dilatation of the aorta. This fibrotic tissue may cover both aorta and iliac arteries, reach the retroperitoneum and surrounding ureters, and cause serious obstructions and renal insufficiency in three-quarters of patients. Most of the patients are known to have atherosclerosis and local inflammation against the antigens of the plaques. A systemic autoimmune disease presenting with retroperitoneal fibrosis seems to be pronounced more frequently nowadays because of the elevated acute-phase reactant levels, positive autoantibodies, and concurrent autoimmune diseases affecting other organs in majority of the diagnosed patients. Ultrasonography, computed tomography, magnetic resonance imaging, positron emission tomography, and retroperitoneal biopsy are useful in diagnosing and assessing the full extent of the disease. Surgical interventions such as ureterolysis and aneurysm repair are frequently performed, but medical therapy including steroids and immunosuppressants is often needed because of the inflammatory and chronic-relapsing nature of the disease. In this paper, we described two cases diagnosed with RF secondary to hemilaminectomy and hypothyroidism, and we summarized the literature related to RF.
Abstract: We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin, and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed acute leukemia patients. Patients were treated with fludarabine phosphate 25 mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was given subcutaneously from sixth day until absolute neutrophil count (ANC) >500/microL. One third of the acute myeloblastic leukemia (AML) and 45% of acute lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML patients, complete remission (CR) was achieved in 15 cases (53.6%). One case showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte recovery time was 16 days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Stem cell transplantation was performed in 5 patients and all achieved CR, 2 autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8 (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%) cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting, and mucositis and could be controlled by supportive therapy. Autologous transplantation was performed in 1 patient, but relapse disease occurred after 5 weeks. There was no correlation between response rate and leukemia subtype (AML versus ALL), leukocyte count, age, sex, disease status (de novo versus secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was 16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3 patients are alive and 2 of these are in continuous remission. The rest of the patients died. In conclusion, Ida-FLAG is a good choice in cases with refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a low-toxicity profile are preferable properties of this regimen, and this regimen has been found to be useful for cytoreduction, especially in candidates for allo-SCT.
Abstract: Transfusion-associated graft-versus-host disease (TA-GVHD) is a relatively rare and interesting entity. Despite a range of pathophysiological and therapeutic approaches, it has a high mortality. It is possible to prevent the disease by prophylaxis only. It is possible to miss the entity in routine clinical practice and reach a different diagnosis due to its non-specific signs and symptoms. Four patients with signs and symptoms suggestive of TA-GVHD were evaluated and the literature reviewed. The transfusion history was of great importance, as was the exclusion of other conditions that may present with similar signs and symptoms (fever, skin rash, diarrhea, pancytopenia, icterus and renal failure). Confirmation of TA-GVHD was by skin biopsy. TA-GVHD must be considered as a differential diagnosis in patients who present with fever, pancytopenia, diarrhea, skin rash and icterus, and the transfusion history must be questioned. Mortality is very high despite various therapeutic approaches. This makes prophylaxis essential. TA-GVHD can be prevented by irradiation of blood products and by avoiding the use of blood transfusions from family donors.
Abstract: It is well known that angiogenesis and lymphangiogenesis play important roles in tumor occurrence and progression. The vascular endothelial growth factor (VEGF) family is the most important family of proteins involved in angiogenesis, and VEGF-C is the most important molecule in lymphangiogenesis. Lymphangiogenesis plays an important role in lymphovascular invasion, metastasis to regional lymph nodes, and distant organ metastasis. In this study, the rate of VEGF-C was investigated in 217 patients with breast cancer. VEGF-C was evaluated by immunohistochemistry and its expression was compared with that of well-known prognostic indicators, such as tumor stage and grade, axillary lymph node involvement, estrogen and progesterone receptor status, c-erb-B2 expression, and extent of lymphovascular invasion. The patient population included 8 men, in addition to women before (n=108), during (n=9), and after (n=92) menopause. Patients had been diagnosed with invasive ductal (n=181) or invasive lobular (n=22) carcinoma, mixed (n=8) or medullary (n=1) carcinoma, or ductal carcinoma in situ (n=5). Tumors ranged from stage 0 to IV and grade I to III and the distribution of estrogen-positive (n=100) and estrogen-negative (n=110) receptor tumors was almost equal. The number of patients with c-erbB2 tumors ranged from 21 to 49 for each tumor stage, and the number of patients with VEGF-C-negative tumors ranged from 28 to 59 for each tumor stage. No important association between VEGF-C expression and other prognostic indicators was found. However, this may be a result of the lack of standardization among the methods used to determine VEGF-C expression. Also, the lymphangiogenic effect may not be overt because of the variety of VEGFR-3 variants, which included nonfunctional variants. To determine the relationship among angiogenesis, lymphangiogenesis, and prognosis, more standardized methods to demonstrate the angiogenesis, and prospective studies to cover a larger, more homogenous patient population are needed.
Abstract: The PRAME (preferentially expressed antigen of melanoma) gene has been shown to be expressed in high levels in some solid tumors and hemopoietic neoplasias but not or only weakly expressed in normal tissues. It encodes an antigen recognized by autologous cytolytic T lymphocytes. PRAME is a good candidate for tumor immunotherapy and is a useful marker gene for detection of minimal residual disease (MRD). In this study, PRAME mRNA using real-time RT-PCR was studied in 74 adult cases with acute leukemia-68 had de-novo acute leukemia, 3 had chronic myeloid leukemia-blastic crisis (CML-BC), and 3 had myelodysplastic/myeloproliferative syndrome-blastic transformation (MDS/MPD-BT)-and the results were compared with 30 age-matched healthy volunteers. Nineteen of 74 cases with leukemia expressed PRAME, while only 2 controls showed weak expression. The prevalence of PRAME expression in AML and ALL cases was 30% and 17%, respectively. We did not find any important correlation between PRAME expression and clinical characteristics, such as age, sex, organomegaly/lymphadenopathy, Hb, WBC count, platelet count, LDH level, alkaline phosphatase, albumin, cell-surface antigens, response to therapy, or progression-free and overall survival. PRAME was monitored in 15 cases during remission and/or relapse. There was a good correlation between PRAME mRNA and hematological remission and/or relapse. Interestingly, PRAME was very high in one case with AML but was not found 3 months after allogeneic transplantation. PRAME mRNA is observed in about one-third of AML cases; it may be a useful marker to detect MRD, and it may also be a good predictor for the timing of donor lymphocyte infusions (DLI) in the post-transplant period in cases of molecular relapse.
Abstract: Granulocytic sarcoma (GS) or chloroma is a neoplasia of immature myeloid cells. Bones, skins, soft tissues and lymph nodes are the most frequently involved organs with this entity and not infrequently it is diagnosed histopathologically as non-Hodgkin's lymphoma (NHL). Ovarian granulocytic sarcoma is a rare entity in daily practice. Here we report an ovarian granulocytic sarcoma, initially diagnosed as NHL, and review the literature.
Abstract: Extranodal involvement in non-Hodgkin's lymphoma (NHL) is not really that rare, but prostatic infiltration is uncommon and rarely detected clinically. Prostatic involvement by lymphoma can cause signs and symptoms of prostatic obstruction. Here we report a patient with prostatic infiltration due to NHL diagnosed 7 years earlier. The literature is also reviewed.
Abstract: Proinflamatory and profibrotic cytokines may be responsible for the cyclosporine A nephrotoxicity. Increased levels of apoptosis, free oxygen redicals, and transforming growth factor beta (TGF-beta), may play an important roles in the pathogenesis of nephrotoxicity. In this experimental animal study, we sought to investigate the effects of colchicine on the cyclosporine nephrotoxicity.
Abstract: The aim of this study is to detect the possible role of hepatitis C Virus (HCV) in lymphomagenesis. HCV-RNA and anti-HCV antibodies were studied in tissue and serum samples taken from patients with non-Hodgkin's Lymphoma (NHL). The prevalence of HCV, the clinical presentation of these cases, and association with histologic subtypes were determined. RT-PCR was used to detect the HCV-RNA in serum and tissue samples. The anti-HCV antibodies were tested with microparticle enzyme immunoassay. Immunohistochemistry with the ABC method was used to detect the HCV core protein in HCV-RNA(+) cases. RNA could be detected in 30 of 35 cases, and other tests were performed in these 30 samples. HCV-RNA was detected in 11 tissue samples (11/30, 37%). HCV core protein was studied in 10 of 11 HCV-RNA(+) cases, and 1-3% nuclear staining was found in only 2 samples. Serologically, HCV-RNA was detected in 7 of 30 samples (23.3%) and anti-HCV antibody was detected in 3 of 30 samples (10%). Detection of HCV-RNA in 37% of the lymphoma tissue samples suggests that HCV may have a role or is a contributing factor in the pathogenesis of lymphoma. The very low HCV core protein in lymphoma tissues may be due to the low viral load in lymphoid tissues and/or higher sensitivity of the PCR method. Detection of anti-HCV antibody in only three cases may be associated with undetectable levels of antibodies due to the immune deficiency in cases with NHL.
Abstract: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloblastic leukemia with specific clinical, morphologic and genetic features and a good response to all trans retinoic acid (ATRA). However, extramedullary (EM) relapse is an interesting feature of these cases, especially those treated with ATRA. Recently, we have encountered an EM relapse in the pleura in a case with APL receiving an ATRA containing regimen. This case is reported and the relevant literature is reviewed.
Abstract: All trans retinoic acid is the drug of choice in the treatment of acute promyelocytic leukemia. But this drug has some side effects, some of which may be life-threatening. Retinoic acid syndrome is the most frequent and dangerous side effect of this differentiation inducing agent. Other side effects include Sweet's syndrome, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum, granulomatous proliferation and some pulmonary complications. Here, we report vasculitis in a case with APL treated with ATRA and review the literature.
Abstract: Leukemias are systemic hematopoietic neoplasias and not infrequently cause ocular findings. Serous retinal detachment (SRD) is one of these manifestations and even may be the first sign of the underlying leukemia. Here we reported a case with chronic lymphocytic leukemia (CLL) presenting with SRD and discussed the clinical importance and therapeutic options.
Abstract: Hepatitis C virus (HCV) is an RNA virus in the Flaviviridae family. It displays lymphotropism in addition to hepatotropism and extrahepatic manifestations are very well known. There are many studies showing an association between HCV infection and non-Hodgkin's lymphomas (NHL). In this study the evidence for HCV infection was studied in cases with NHL. To this end, anti-HCV antibody and HCV-RNA were screened in serum samples of cases with NHL using third-generation ELISA and RT-PCR. Anti-HCV antibody was studied in 223 patients and was found to be positive in 18 cases (8.1%). Anti-HCV antibody positivity was compared with our blood bank/blood donor population. There was an important increased risk of HCV infection--the common odds ratio was 34.56 and corrected odds ratio was 19.07. HCV-RNA was studied in 67 of 223 serum samples. HCV-RNA was found to be positive in 21 of 67 samples (31.3%). When compared with clinico-demographic parameters for anti-HCV and HCV-RNA, including age, nodal status, and grade (in evaluable cases), except age in cases with or without HCV-RNA, we did not find an important correlation with HCV status and clinical findings (P=0.155; 0.442; 0.288 for anti-HCV and 0.027; 0,558; 0.126, respectively). These results suggest that HCV infection may be an important risk factor for lymphomagenesis and HCV-RNA is more useful for the detection of HCV infection in these immunosuppressed cases. Simultaneous detection of anti-HCV and HCV-RNA will be more informative in this population.
Abstract: Antiapoptotic signals are important in the development, progression and prognosis of malignant tumors. The aim of this study was to determine the two distinct antiapoptotic signals-survivin and aven-in acute leukemias and compare them with clinical and hematological findings and response to therapy. Real-time quantitative PCR was used and survivin and aven were detected at the messenger (m)RNA level.
