Ismail Oguz Kara

Mucormycosis‐associated fungal infections in patients with haematologic malignancies

Among patients with haematologic disorders, mucormycosis most commonly occurs in those with acute leukaemia or lymphoma who have developed neutropenia due to malignancy or to chemotherapy, and in transplanted patients receiving immunosuppressive treatment. Here, we aim to present a retrospective study conducted over a 5‐year period (2001–2005). The study included 20 patients with haematologic malignancies with a proven mucormycosis admitted in Medical Oncology Divisions in Cukurova University Hospital. The most frequent sites of infection were paranasal sinuses (95%) and lung (5%). Antifungal treatment was empirically administered in 18 (90%) patients; 18 patients underwent radical surgical debridement (90%). The therapy was successful for only eight patients (40%). Eleven patients died within 1 months of the diagnosis of fungal infection: the cause of death was only by mucormycosis in four patients (36.6%), mucormucosis and systematic inflamatuar response syndrome (SIRS) in two patients (18.2%) and progression of haematologic disease in five patients (45.5%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: amphotericin B treatment, neutrophil recovery from postchemotherapy aplasia. At multivariate analysis, the factors that significantly correlated with recovery from infection were the liposomal amphotericin B treatment (p = 0.026), doses of L‐AmB (p = 0.008) and the length of the treatment (p = 0.01), respectively. It seems to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential to improve the prognosis in these patients.

Expression of soluble CD27 and interleukins-8 and -10 in B-cell chronic lymphocytic leukemia: Correlation with disease stage and prognosis

Investigators in this study explored levels of soluble CD27 (sCD27), interleukin (IL)-8, and IL-10 in B-cell chronic lymphocytic leukemia (B-CLL), and the correlation of these levels with disease stage and prognosis. Plasma IL-8, IL-10, and sCD27 levels were assessed with enzyme-linked immunosorbent assay tests in 22 healthy donors and 70 patients with B-CLL (49 men and 21 women). Mean patient age was 61.57 y (range, 44–75 y). Mean healthy donor age was 62.09 y (range, 40–72 y). In the study group, mean values were as follows: plasma IL-8, 284.758 pg/mL (0–1000 pg/mL); plasma IL-10, 26.152 pg/mL (0–100 pg/mL); sCD27, 731.357 U/mL (139.9–1000 U/mL); white blood cell count, 59.9 × 109/L (0.8–250.0 × 109/L); hemoglobin count, 11.2 g/dL (5.0–16.2 g/dL); platelet count, 162.5 × 109/L (29.8–317 × 109/L); B2 microglobulin (B2M) 3350.2 mg/L (274.7–7499.9 mg/L); CD38, 19.5%; and lactate dehydrogenase (count, 497.5 U/L (263.0–1507 U/L). Patients represented all Rai stages, with 22.9% at stage 0, 11.4% at stage I, 11.4% at stage II, 41.4% at stage III, and 12.9% at stage IV. Plasma levels of IL-8, IL-10, and sCD27 were correlated between study and control groups; significantly higher IL-8 (P=.001) and sCD27 (P=.000) levels were found, but the IL-10 level was not significant (P=.139). Plasma IL-10 (P=.01) and sCD27 (P=.008) were positively correlated with Rai stage, but IL-8 was not (P=.146). Levels of sCD27 were significantly correlated with values for B2M (P=.000), hemoglobin (P=.028), lactate dehydrogenase (P=.001), CD19 (P=.03), and IL-10 (P=.000). IL-8 was significantly correlated with white blood cell (P=.000) count, and CD38 (P=.001) and CD5 (P=.006) levels. IL-10 was significantly correlated with B2M (P=.017), CD19 (P=.000), platelet (P=.002), and CD27 (P=.000). In survival distributions for CD27, IL-8 and IL-10 were found to have more significant relationships for all parameters (P=.0000). In conclusion, the authors suggest that sCD27, IL-8, and IL-10 are more significant prognostic factors for B-CLL when compared with others, and these values should correlate with new prognostic factors (eg, zeta-associated protein-70, mutated/unmutated immunoglobulin variable heavy chain).

Granulocytic sarcoma of the heart: Extramedullary relapse of acute myeloblastic leukemia after allogeneic stem cell transplantation successfully treated by chemotherapy alone

We present a case of granulocytic sarcoma (GS) of the heart. A 28-year-old man with relapsed acute myelogenous leukemia (AML-M2) had undergone a non-myeloablative allogeneic peripheral stem cell transplantation. Three years following transplantation, masses were evidenced in his heart by echocardiography but had completely disappeared following a common chemotherapy etoposide, mitoxantrone, ara-C (EMA) regimen for relapsed AML. The involvement of the heart with GS is very rare and this is the first case of extramedullary disease in the heart after allogeneic transplantation. Here we present the case history and related literature has been reviewed.

Correlation of serum adiponectin levels and hepatic steatosis in hepatitis c virus genotype 1 infection

Steatosis is an important cofactor in hepatitis C virus (HCV) because it is associated with fibrosis and reduces early and sustained virologic response. Recent studies suggest that HCV genotype 1 is not steatogenic if additional risk factors are not present. Because hypoadiponectinemia was found to be a feature of nonalcoholic steatohepatitis (NASH) independent of insulin resistance, its level in patients with hepatitis C genotype can reveal the optimal therapeutic strategy. This study was conducted to determine the role of the relationship between steatosis and serum adiponectin levels in the progression of liver damage in HCV genotype 1 without known risk factors for NASH. Patients (n=50) with biopsy-proven chronic hepatitis C (CHC), positive HCV RNA, and raised alanine aminotransferase were enrolled. They were carefully selected to rule out possible confounding factors for the presence of steatosis and additional systemic or liver disease. Associations between serum adiponectin levels and grade of steatosis, histologic activity index (HAI), fibrosis grade of liver biopsies, patient age, HCV viral load, and serum transaminase activities were studied. Also, adiponectin levels were compared with those of a control group of 30 healthy volunteers with normal ultrasound findings of the upper abdomen who had no known NASH risk factors. The investigators found that adiponectin levels in patients with CHC genotype 1 were similar to those in healthy subjects. No significant association was found between adiponectin levels and severity of steatosis, HCV RNA levels, HAI, transaminases, and fibrosis. Steatosis was present in 41 patients (82%) with CHC. Multivariate analysis of data on 50 patients revealed that severity of steatosis was independently related to age alone (P=.03). A correlation between HCV RNA load and HAI was observed (P=.02; r=0.712). HAI also was associated with stage of fibrosis (P=.00;r= 0.612). In cases of chronic HCV genotype 1 hepatitis, steatosis is a common histologic feature, although no risk factors are known. Results presented here cannot establish an association between adiponectin and severity of steatosis when risk factors for steatosis are unknown. Additional studies are needed to discover a metabolic treatment that would seek to improve the progression of hepatic steatosis in CHC infection.

Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-α in bone marrow and peripheral blood of patients with multiple myeloma

Angiogenesis is a process that plays an important role in the growth and progression of cancer; growing evidence suggests that neovascularization is important in hematologic malignancies. Increased angiogenic potential has been identified in multiple myeloma (MM). In this study, investigators simultaneously measured the levels of hepatocyte growth factor (HGF), platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-alpha (TGF-/ga) through enzyme-linked immunosorbent assay in the bone marrow (BM) and peripheral blood (PB) of 30 patients with MM and 10 healthy controls. Differences in HGF values in BM sera were significant (P=.001) between patients and controls. In detailed analyses of HGF, PDGF-AB, and TGF-α, according to disease stage, a significant correlation was found between disease stage and BM HGF (P=.047), BM TGF-α (P=.021), and PB PDGF-AB (P=.006), respectively. When correlations between all other parameters were analyzed, significance was noted between PB TGF-α and lactate dehydrogenase (P=.02), PB TGF-α and PB HGF (P=.002), BM TGF-α and CD38 (P=.046), BM TGF-α and BM HGF (P=.000), BM TGF-α and BM PDGF-AB (P=.048), BM HGF and PB HGF (P=.044), and BM PDGF-AB and PB PDGF-AB (P=.000). BM HGF levels had a significant effect on overall survival, with disease severity assessed in terms of disease stage (P=.0018, log-rank test). These data show that in patients with MM, high levels of BM HGF, BM TGF-α, and PB PDGF-AB were associated with advanced disease stage; in addition, HGF played a significant role in disease processing and was related to disease severity. These findings have also led to the concept of a symbiotic relationship between the growth of myeloma cells and HGF, TGF-α, and PDGF-AB in BM.

Pancreatic Carcinoma, Thrombosis and Mean Platelet Volume: Single Center Experience from the Southeast Region of Turkey

BACKGROUND The aim of this study was to investigate the general characteristics of patients with deep vein thrombosis (DVT) and pancreatic cancer as well as evaluate the relationship between mean platelet volume (MPV), DVT and survival. MATERIALS AND METHODS Seventy-seven patients with pancreatic cancer, who were admitted to Cukurova University Medical Faculty, Department of Medical Oncology, were enrolled in the study RESULTS The mean age was 59±20. Forty-nine (63.6%) were men and 28 women (36.4%) . Sixty-eight (88.3%) patients had adenocarcinoma and 9 (11.7%) had a malignant epithelial tumor. Thirty-six (46.7%) had liver metastasis at diagnosis. Twenty-six (33.8%) patients were alive, 20 (26%) were dead and in 31 (40.2%) the status was unknown. Only 14 (18.1%) patients had DVT. In 42 (54.5%) patients MPV values were normal, in 28 (36.4%) patients they were above normal, and in 7 (9.1%) patients they were below normal. There was no statistically significant difference between gender, tumour localization, chemotherapy and survival rates (p:0.56, p:0.11, p:0.21). There was no significant difference between DVT, gender, localisation, histological subtype, the presence of metastasis, stage and if the patient had been treated with chemotherapy (p:0.5, p:0.6, p:0.2, p:0.32, p:0.1, p:0.84). There was also no significant difference between MPV and DVT (p:0.57) but there was a significant difference between liver metastasis and DVT (p:0.02). Age, stage, the presence of metastasis and DVT were prognostic in pancreatic cancer patients. CONCLUSIONS Cases of pancreatic cancer with liver metastasis should be studied more carefully as thrombosis is more common in these patients.

Neurofibromatosis type 1, gastrointestinal stromal tumor, leiomyosarcoma and osteosarcoma: Four cases of rare tumors and a review of the literature

BACKGROUND Neurofibromatosis type 1 (NF1) is a genetic syndrome that predisposes patients to benign and malignant tumor development. Patients with NF1 develop multiple neurofibromas that can transform into aggressive sarcomas known as malignant peripheral nerve sheath tumors. In contrast, malignant tumors unrelated to the nervous system rarely coexist with neurofibromatosis. The aim of this article was to present four cases of adult NF1 patients with malignant tumors unrelated to the nervous system as well as a bibliographic search for papers describing these tumors in NF1, focusing on osteosarcomas, gastrointestinal stromal tumors (GISTs), leiomyosarcomas and somatostatinomas and their genetic alterations in NF1. METHODS Search engines such as PubMed and MEDLINE were browsed for English-language articles since 1989 using a list of keywords, as well as references from review articles. Search terms were NF1, osteosarcoma, leiomyosarcoma, somatostatinoma and GIST. Data were summarized in a table at the end of the Results section. RESULTS In our four NF1 cases, there were one osteosarcoma, one leiomyosarcoma, one somatostatinoma and GIST and one GIST. NF1 was diagnosed at an adult age when these patients were admitted to our oncology department. The results generated by the literature search yielded 75 articles about NF and GIST. We summarized the clinical characteristics of 43 patients with NF1 and somatostatinoma. Forty-five articles involving NF and osteosarcoma were found, and of these, 26 involved NF1; from these articles, we identified the clinical features of 8 patients. Twenty-five articles were found concerning NF1 and leiomyosarcoma, and of those, we summarized the clinical features of 15 patients. CONCLUSIONS Here we reviewed somatostatinomas, GISTs, osteosarcomas and leiomyosarcomas occurring in NF1 patients. Patients with NF1 who present with gastrointestinal symptoms, should be carefully evaluated carefully with a high index of suspicion of potential GISTs, periampullary and duodenal tumors. Patients with pathological fractures or bone pain along with NF1 should be carefully screened for malignant bone tumors. Patients with NF1 can develop leiomyosarcoma less frequently than other malignancies, but the association of uterine leiomyoma and NF1 may not be fortuitous. Somatic mutations were defined for frequent tumors, including neurogenic tumors and GISTs but not for sarcomas due to the complexity of underlying mechanisms of the disease and tumorigenesis. Based on the findings; all NF patients can develop malignant tumors, including the less frequently observed ones. Therefore, we recommend that new genetic studies should be performed for rare malignancies in cases of NF1.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman's disease) previously misdiagnosed as Toxoplasma Lymphadenitis.

Here we describe a case of Rosai-Dorfman Disease (RDD) in a 25-year-old female patient from Turkey who was previously misdiagnosed with Toxoplasma Lymphadenitis, and review the manifestations and treatment of this rare entity. To the best of our knowledge this is the third description of RDD [Sinus Histiocytosis with Massive Lymphadenopathy (SHML)], involving bilateral cervical lymphadenopathy and nephromegaly previously misdiagnosed as Toxoplasma Lymphadenitis. Representative clinical, radiographic and histological findings are presented. Its etiology, diagnosis and management are also reviewed. Sinus Histiocytosis with Massive Lymphadenopathy is a rare disorder of unknown etiology, usually associated with lymph node enlargement in various superficial or deep sites. The key histologic feature of SHML is the presence of various numbers of large, pale histiocytic cells that contain within their cellular borders apparently engulfed lymphocytes (emperipolesis); these distinctive large, pale cells are S-100 protein positive CD-68 positive and CD1a negative by immunostaining. According to the literature the most effective treatment found was surgical debulking.

Expression of Mesenchymal, Hematopoietic, and Biliary Cell Markers in Adult Rat Hepatocytes After Partial Hepatectomy

BACKGROUND AND PURPOSE It has been suggested that liver regeneration can occur either by differentiated adult hepatocytes which retain the capability for several rounds of replication or by hepatic progenitor cells, depending on the number of hepatocytes lost. We sought to study the differentiation potential of hepatocytes following partial hepatectomy (PH) in rats. METHODS Using immunohistochemistry and confocal microscopy we studied the distribution of cytokeratin 7 (CK7), CK19, vimentin, desmin, CD34, and c-kit among adult rat liver hepatocytes after PH at various times just after hepatectomy and after 8, 16, 24, 36, 48, and 60 hour and 6 and 16 days. RESULTS Vimentin, c-kit, and desmin positivity were observed in regenerating hepatocytes in the early stages. Desmin and vimentin staining were also demonstrated in stellate cells. Staining enhancement in stellate cells progressed from day 3 to day 6. No liver sections were stained positive for CD34, CK19, or CK7. CONCLUSION After PH, mature hepatocytes revealed their potential to regain the markers that they do not express when they are quiescent. This result supported the plasticity and differentiation potential of adult hepatocytes during regeneration.

Expression of c-kit protooncogen in hepatitis B virus-induced chronic hepatitis, cirrhosis and hepatocellular carcinoma: has it a diagnostic role?

Aim:  There are more than 350 million people worldwide chronically infected with hepatitis B virus (HBV), who are at high risk for the development of hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Because of the conflicting results about c‐kit expression in HCC and the key role played by c‐kit in gastrointestinal stromal tumours (GIST) and other solid tumours, the aim of this study was to determine c‐kit expression in the course of hepatitis B infection.