Multiple myeloma in association with second malignancy.

PURPOSE: To look at the frequency of second primary malignancies (SECMAL) in patients with multiple myeloma (MM). METHODS: The medical files of 332 patients with MM (whole group), diagnosed and treated at the University Multiprofile Hospital for Active Treatment "Sv. Georgi" and the Comprehensive Oncology Hospital (Plovdiv) for a 20-year period (1990-2010) were retrospectively analyzed. MM patients with SECMAL constituted the study group. A control group comprised patients with solid tumors associated with SECMAL. This group derived from a sample of 21768 patients with solid tumors. RESULTS: In the study group, SECMAL was diagnosed in 4.52% (N=15) of the patients, while in the control group this figure was 5.09% (N=1108) (p>0.05). The diagnosis of MM preceded the occurrence of SECMAL in 35.71% of the study group patients, the median interval being 6.6 years (range 5-14). More frequently the diagnosis of the solid tumor preceded the occurrence of MM (66.67%). Breast cancer and gastric cancer were encountered with the highest frequency (26.67% each). The median survival (77.2 months, range 44-129) was significantly longer in the group with MM and SECMAL compared to the whole group with MM (median 38.6 months, range 10-58; p<0.05). CONCLUSION: The rate of MM with other malignant diseases is comparable with the frequency of SECMAL in other lymphoproliferative disorders and solid tumors. The occurrence of SECMAL during the clinical course of MM is not a frequent event and is expected in the rare cases with longer survival.

From Virchow's triad to metastasis: circulating hemostatic factors as predictors of risk for metastasis in solid tumors.

Tumor growth is characterized by disturbances of hemostatic mechanisms towards subclinical activation of coagulation. In cancer patients there is an increased risk up to 4-6 fold for developing idiopathic thrombosis due to the tumor-associated prothrombotic status. The molecular basis for the interrelationship between malignant phenotype and hemostatic disbalance includes several specific properties of tumor cells such as production of proinflammatory and proangiogenic cytokines, exhibition of procoagulant / fibrinolytic activities by tumor cells themselves and direct cell-to-cell interactions between tumor cells and cellular components of the hemostatic system. Aberrant tissue factor (TF) expression is a hallmark of human cancers and has been linked to their metastatic potential and neoangiogenesis. TF is a multifunctional molecule which controls the pro-/antiangiogenic balance in tumor tissue both by its procoagulant properties and via coagulation-independent mechanism inducing production of angiogenic cytokines by tumor cells. Components of the fibrinolytic system urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) facilitate targeted proteolysis of the basement matrix in order neovascularization to occur. Overexpression of these factors in tumor tissue has been identified as prognosticator for metastatic spread and overall survival in many human cancers, including breast, gastrointestinal, lung, urological and gynecological malignancies. Measurement of circulating TF and the soluble isoform of uPAR in plasma may be useful for evaluating the risk of cancer metastasis, monitoring for tumor recurrence and prediction of response to cancer therapy.

Non-Hodgkin lymphomas and carrier state of viral hepatitis B and C.

PURPOSE: To establish the characteristics and prognosis of newly diagnosed patients with non-Hodgkin lymphoma (NHL), who were carriers of hepatitis B (HBV) and C (HCV) viral infection. METHODS: 542 patients with NHL, diagnosed and treated in the University Hospital "Sv. Georgi", Plovdiv, were retrospectively analysed. Two NHL patient groups were created - the study group, consisting of 33 patients with NHL positive for HBV and HCV, and the control group, consisting of 40 randomly assigned patients with NHL and negative serology for hepatitis. Study and control groups were compared for basic characteristics and survival. RESULTS: The prevalence of hepatitis B surface antigen (HBsAg) among newly diagnosed patients was 5.72% and of HCV 1.84 %. Association with hepatitis viruses was more frequent in indolent than in aggressive NHLs (p=0.044). Liver dysfunction was registered more often in the study group (p=0.002). Reactivation of HBV infection was registered in 5 patients (12.19%) from the study group. There was no statistically significant difference between survival rate of patients in the study group and in the control group (p=0.738). CONCLUSION: Hepatitis virus carrier state did not alter significantly the clinical course and disease prognosis (remission rates and survival) in our patient group. We recommend the routine testing for hepatitis infection in patients newly diagnosed with NHL in order to collect more data needed for the establishment of a possible causal relationship between hepatitis viruses and NHL. Since antiviral prophylaxis could positively impact the course of lymphoma treatment, national guidelines for the management of patients with hepatitis infection and NHL will prove to be necessary for the clinical practice.

Electrophoretic finding of bisalbuminemia.

BACKGROUND: Bisalbuminemia or alloalbuminemia is a rare inherited or acquired condition characterized by the presence of two albumin fractions during electrophoretical separation of serum proteins. METHODS: Bisalbuminemia was incidentally detected by agarose gel electrophoresis (AGE) during standard laboratory investigation of a 36-year old female patient, referred to our laboratory with the diagnosis of immune thrombocytopenia. RESULTS: The electrophoregram showed dysproteinemia with the presence of two distinct albumin bands. This initiated testing of other family members - mother, father, and son of the patient. CONCLUSIONS: We report a case of inherited bisalbuminemia in a Bulgarian family with two affected members of four investigated. This is the first report of inherited bisalbuminemia in the Plovdiv region and could be of great interest to laboratory practitioners and clinicians providing some new data on the protein evolution and the clinical approach.

Intraperitoneal perfusion chemotherapy with hyperthermia in some malignant ascites.

Intraperitoneal administration of chemotherapeutic drugs with hyperthermia (HIPEC) increases their local effect on malignant peritoneal diseases and reduces systemic cytotoxicity. The most commonly used are cisplatin, doxorubicin, and mitomycin C. A major disadvantage of intraperitoneal chemotherapy is limited penetration of the drug in the tumor lesion depth (1-3 mm). Extended exposure and increased pressure in the abdominal cavity solution increases penetration of the agent into the tumor and hyperthermia has synergy with cytostatic agent on the permeability of cell membranes and metabolism of the drug. Real clinical hyperthermia is achieved at 41 degrees C. Of greatest importance is the concentration of the drug, but crucial for the prognosis is complete cytoreductive surgery. A major disadvantage of the closed technique is the uneven distribution of the perfusion solution in the peritoneal cavity, and the main advantage is better control of the perfusion, keeping of constant hyperthermia of the solution and regular repetition of manipulation, like intravenous chemotherapy. Laparoscopy determines the stage of the tumor process, refines the indications and preoperative selection for HIPEC, monitors the effects of treatment and determines locations for introducing catheters. In the review the results of the inraperitoneal chemotherapy with hyperthermia in gastric, colorectal, ovarian and other cancers are discussed as well as in diffuse malignant peritoneal mesothelioma and others.

Changes of serum prohepcidin, iron status and zinc-protoporphyrin in a random group of patients with malignant diseases.

PURPOSE: To investigate the changes in the serum levels of prohepcidin (pHp) and markers of iron homeostasis for gathering more data on the pathogenesis of anemia in malignancies. METHODS: In 84 patients with advanced solid malignant tumors, but without iron or vitamin B12 and folate deficiency anemia, we measured serum pHp levels and common markers of iron status, erythropoiesis and inflammation. Two months later the same tests were repeated to determine possible changes in the levels of the measured parameters. RESULTS: The first blood sample characterized the group with a moderately low hemoglobin (Hb) and high CRP levels, suggesting anemia in some patients. Two months later higher levels of serum iron (sFe), total iron binding capacity (TIBC), transferrin saturation, ferritin and zinc-protoporphyrine (ZPP) in erythrocytes were found, along with lower pHp and high sensitivity C-reactive protein (hs-CRP). The correlation coefficient (R) between the values of iron-containing substances and pHp were low (R=0.244). Allocations by sex, Hb concentration and pHp showed that the changes in each group were similar, keeping the trend of increased sFe, ferritin and ZPP, decreased hs-CRP and pHp, at a stable hematological state. CONCLUSION: Because of low correlation between sFe and pHp, it seems more likely that the positive two-month change of iron-containing substances in the serum of the studied patients is a result of treatment, impaired liver function or malignant intoxication, rather than of decreased pHp.

[Postoperative survival in patients with inoperable lung cancer].

UNLABELLED: Despite the advances in treatment in the last two decades, the prognosis in lung cancer remains infavourable. Only 20-25% of the patients are suitable for operative treatment. Almost 75% of the patients are inoperable at the time of diagnosis. MATERIAL AND METHODS: We present 148 patients, who underwent non-radical operation for the period 01.01.1997 - 31.12.2005 - 129 men (87.16%) and 19 women (12.84%), age range - 29-65 years (53.67 +/- 0.60). RESULTS: The mean time of survival for the group submitted to radiotherapy is 13.74 months, while for the group without postoperative radiotherapy is 9.31 months. The mean time of survival for the group submitted to chemotherapy is 9.99 months, while for the group without adjuvant chemotherapy is 10.27 months. CONCLUSIONS: The radiotherapy significantly improves the survival in the patients with inoperable lung cancer, while the chemotherapy don't increase the survival.

[Stage of disease as a prognostic factor in radically operated patients with non-small cell lung cancer].

UNLABELLED: Despite the better diagnostic and therapeutic opportunities, lung cancer is still the major cause for cancer mortality. The surgical-pathological TNM-stage is known as the most reliable prognostic factor for survival in patients with lung cancer. MATERIAL AND METHODS: We present 440 patients with non-small cell lung cancer, radically operated in the Clinic of Thoracic and abdominal surgery of University Hospital "St.George" - Plovdiv for the period 01.01.1997 - 01.09.2004 - 378 men (85.91%) and 62 women (14.09%), age range 23-82 years. RESULTS: The mean time of survival according to the stage is as follows: IA - 77 months, IB - 67, IIA - 55, IIB - 42, IIIA - 33 IIIB - 14, IV - 27 months. CONCLUSIONS: The stage of the disease is an important prognostic factor for patients with lung cancer. We found the lowest survival in stage IIIB. For selected patients in stage IV, the operative treatment leads to good results.

[Extent of resection as a prognostic factor in patients with non-small cell lung cancer].

UNLABELLED: Despite the new methods of treatment during the last two decades, prognosis in lung cancer remains unfavourable. Only 20-25% of the patients are suitable for surgery, and the surgical resection is the unique alternative with curable intent. The extent of resection is an important prognostic factor in lung cancer patients. MATERIAL AND METHODS: We present 440 patients with non-small cell lung cancer, radically operated in the Clinic of Thoracic and abdominal surgery of University Hospital "St.George" - Plovdiv for the period 01.01.1997 - 01.09.2004.191 underwent lobectomy, 12 - limited resection, 39 - bilobectomy, and 198 - pneumonectomy. RESULTS: 63 patients underwent lobectomy for stage I, and the 5-year survival was 63.49%. For the 12 patients with limited resection we found mean time of survival of 50 months, and the 5-year survival was 50%.331 of our patients were in stage II and III. 123 of them underwent lobectomy--the 5-year survival was 28.46%. 208 patients underwent bilobectomy and pneumonectomy--the 5-year survival in this group was 17.79%. CONCLUSIONS: In conclusion we found that the extent of resection is an important prognostic factor for lung cancer patients in stage I. The patients submitted to lobectomy have better survival compared with those submitted to limited resection. The survival is better for the group of patients who underwent lobectomy,compared with the one for the group with bilobectomy and pneumonectomy, which is probably due to the earlier stage of the disease.

Risk index score for bacteremia in febrile neutropenic episodes in children with malignancies.

PURPOSE: To prospectively determine risk factors for bacteremia in febrile neutropenic children with malignancies. PATIENTS AND METHODS: We studied 199 episodes of febrile neutropenia in 80 children with malignancies, treated by conventional chemotherapy for a 4-year period (2000 - 2004). A standardized computer database with a set of variables for each febrile neutropenic episode was used. C-reactive protein (CRP) was measured at the first febrile episode and on the 3rd and 5th day from the beginning of antibiotic therapy by immunoturbidimetric method. Blood cultures were taken at the onset of fever and before initiation of antibiotic therapy. RESULTS: Multivariate logistic regression analysis determined 5 variables as independent risk factors for bacteremia: the underlying malignant disease (leukemia, non - Hodgkin's lymphoma / NHL, stage IV), chills, perianal cellulitis, presence of central venous catheter and CRP rise >or=34.5 mg/L between the onset of fever and the 3rd day of empiric antibiotic therapy. Thus we identified a low-risk group for bacteremia of 19.1%. CONCLUSION: Serial measurement of CRP allows for definite risk stratification of febrile neutropenic episodes on the 3rd day from the onset of fever. The low-risk group could be eligible for sequential empiric antibiotic therapy.

Therapy-related acute promyelocytic leukemia after treatment with radioiodine for thyroid cancer: case report with literature review.

Therapy-related acute promyelocytic leukemia (t-APL) is a rare but known complication of chemotherapy and/or radiation therapy. Approximately 200 cases of t-APL have been reported in the literature up until now. The development of t-APL after radioiodine therapy is very rare, keeping in mind the very low doses of radiation exposure of the patient. We present a case of a 47-year-old woman with t-APL t15;17(q22;q21) developed after radioiodine treatment for thyroid carcinoma. The patient was treated with chemotherapy and achieved complete response lasting for 3(+) years. The patient's excellent response to treatment supports the data of the relevant literature that t-APL is associated with a better therapeutic result than the other subtypes of secondary acute myeloid leukemia (AML).

The prognostic value of clinical and laboratory parameters in patients with chronic lymphocytic leukemia.

PURPOSE: Chronic lymphocytic leukemia (CLL) is heterogeneous in its clinical course. The aim of the present study was to identify some clinical and laboratory parameters with prognostic value in relation to survival of patients with CLL. PATIENTS AND METHODS: One hundred thirty one patients with CLL, treated in the Clinic of Hematology, Plovdiv, between 1992 and 2003 were studied. The patients' survival was analyzed by using the Kaplan-Meier method. Log-rank test was used to compare cumulative survival functions between different groups of patients. The parameters studied were: age, sex, Rai clinical stage, ECOG Performance status (PS), FAB morphological type, mediastinal lymphadenopathy, abdominal nodal mass, extranodal localization, absolute lymphocyte count, autoimmune hemolytic anemia, and response to therapy. RESULTS: The mean survival of patients was 76 months (95% Confidence Interval, 64-87). The following factors were found to carry significant prognostic value in relation to survival: Rai clinical stage, ECOG PS, mediastinal lymphadenopathy, extranodal localization, FAB morphological type and response to initial standard treatment. CONCLUSION: The prognostic factors identified in the present study can be easily applied in the clinical practice and may be used as a basis for creating mathematical prognostic models.

New options in the treatment of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a heterogeneous group of progressive chronic hematopoietic disorders, usually presenting as refractory anemia or cytopenia, with an approximately 25% risk of progression toward acute myeloid leukaeima (AML), and no proven curative treatment. Novel biological treatment strategies targeting both the malignant blood cell and its microenvironment can overcome resistance to current therapies, and represent a promising treatment paradigm for improving patient outcome. Many of these agents have multiple biologic activities. The objective of this article is to present a comparative review of classification systems in MDS and to discuss the evolving trends in the treatment of MDS (immunosuppresive therapy, immunomodulatory drugs, arsenic trioxide, proteasome inhibitors, epigenetic therapy).

Cancer and venous thromboembolism.

Clinical examples of coagulation abnormalities may occur from single or multiple abnormailties and include both inherited and acquired defects. Risk factors that further increase clotting include obesity, recent surgery, pregnancy and cancer. Venous thrombosis is a common complication in patients with malignant diseases. The estimates of the prevalence of cancer among patients with venous thrombosis vary from 3 to 18%. Since cancer is a common disorder in the aging population, it may be responsible for a considerable proportion of all cases of thrombosis. The pathogenic mechanisms of thrombosis in the cancer patient involve a complex interaction between the tumor cell, the patient, and the hemostatic system. These include activation of the coagulation system, platelet activation, endothelial damage, indwelling venous access devices, direct effects of chemotherapy/hormonal therapy, and host inflammatory responses. Furthermore, local peritumoral activation of coagulation may have important effects on the biology of cancer. In recent years there have been many new developments in understanding basic mechanisms and optimizing clinical care of thrombosis in cancer patients. Subcutaneous low-molecular weight heparin LMWH) has replaced intravenous unfractionated heparin (UFH) for the initial treatment of thrombosis. In the search for new agents matching the "ideal" anticoagulant profile, a number of different steps in the coagulation cascade have been targeted, including direct thrombin inhibition, and inhibition of factor Xa, factor IXa, the factor VIIa-tissue factor complex and the factor Va-factor VIIIa complex. Such agents could potentially improve thrombosis magement in cancer patients.

Philadelphia variant, t(5;9;22)(q13;q34;q11), in a case with chronic myeloid leukemia.

In this paper we report on a case of chronic myeloid leukemia (CML) with a Philadelphia variant involving chromosome 5 as a second change of the standard Philadelphia chromosome (Ph). Molecular analysis found a fusion gene BCR-ABL with participation of exons b3 and a2, respectively (b3a2). The molecular variant of the fusion gene BCR/ ABL or the rare involvement of chromosome 5 could possibly explain the mild course of the disease.

Biomechanical measurement of skin distensibility in scleredema of Buschke associated with multiple myeloma.

We report a case of scleredema of Buschke associated with IgG kappa monoclonal hypergammaglobulinaemia. After myeloma polychemotherapy an improvement in skin involvement was observed and confirmed by means of noninvasive skin elasticity measurements. This suggests a relationship between the two diseases. The bioengineering method used can be useful for early detection and monitoring the skin involvement in patients with this disease association.

Pulmonary, gastrointestinal and liver vascular malformations in Rendu-Osler disease.

Hereditary hemorrhagic telangiectasia (HHT) is an angiodysplastic disorder transmitted in autosomal dominant fashion. This case report describes a 46-year-old woman with multiple arteriovenous malformations that eventually caused multiorgan failure. The diagnosis was made in the early childhood based on frequently recurring episodes of severe epistaxis. Telangiectases were found in the skin, the visible mucosal linings, gastrointestinal and bronchial mucosa and liver. Episodes of severe hemoptysis necessitated partial resection of the right lung middle lobe at the age of 22. Liver dysfunction associated with the primary disease was diagnosed by the characteristic clinical picture, laboratory findings and instrumental examinations including abdominal ultrasonography, upper endoscopy, liver CT venography.

A study of Helicobacter pylori infection in patients with pernicious anemia.

INTRODUCTION: Chronic atrophic gastritis presents with atrophy of the gastric mucosa, hypochlorhydria or achlorhydria and unstable gastrin level. Type A chronic atrophic gastritis associated with hypergastrinemia is regarded as the principle causative factor for pernicious anemia. AIM: The study aimed at evaluation of the incidence of H. pylori infection in patients with pernicious anemia and analyze its relation to the severity of gastritis. MATERIAL AND METHODS: Forty patients with pernicious anemia (group 1) were examined for presence of H. pylori infection. Sex- and age-matched patients with gastric ulcer (group 2) and chronic superficial gastritis (group 3) were used as controls. Three antral forceps biopsies were obtained from all patients during videogastroscopy. The presence of H. pylori was verified by urease test, histological and microbiological examination. RESULTS: All patients with pernicious anemia had chronic atrophic gastritis and several times lower incidence of H. pylori infection than the patients with gastric ulcer. Chronic atrophic gastritis was not diagnosed in group 3 patients. Statistically significant difference in Helicobacter pylori infection was found between groups 1 and 2 (P < 0.001) but not between groups 1 and 3 (P > 0.05). CONCLUSIONS: Atrophic gastritis was diagnosed in all patients with pernicious anemia. These patients showed significantly lower incidence of H. pylori infection than the gastric ulcer patients. The patients with pernicious anemia had lower gastritis index and quantitatively less expressed infection than the other two groups.

Acute hemolytic anemia as an initial clinical manifestation of Wilson's disease.

Wilson's disease is an inherited disorder of copper transport in the organism, transmitted in autosomal recessive fashion. It is caused by dysfunction in homologous copper-transporting adenosine triphosphatases. The main clinical symptoms are usually due to hepatic (42%) or/and neurologic (34%) involvement, which is the reason for the name hepatolenticular degeneration. Described in this report are four cases--the first three demonstrate an unusual form of manifestation of Wilson's disease in clinical practice--glucose-6-phosphate dehydrogenase deficiency hemolytic anemia. The fourth case concerns acute intravascular hemolysis that was provoked by the disease and presented without erythrocyte enzyme disturbances. Hemolytic anemia is a recognized but rare (10-15%) complication of the disease. Most often Coombs' negative acute intravascular hemolysis occurs as a consequence of oxidative damage to the erythrocytes by the higher copper concentration. A literature review with discussion of the possible mechanisms for the development of this phenomenon is done.

[Skin symptoms in malignant hemopathies]. / Kozhnye proiavleniia pri gemoblastozakh.

AIM: To investigate specific and non-specific skin lesions in malignant hemopathies. MATERIAL AND METHODS: The study enrolled 862 patients (394 females and 468 males) with hematological malignancies treated in the hematological clinic from 1990 to 1998. The patients were divided into three groups according to the primary disorder: lymphoproliferative processes (541 patients), myeloproliferative processes (296 patients) and bone marrow hypoplasia (25 patients). RESULTS: The non-specific skin lesions showed high variability in morphology, location. Combinations of different lesions were also present. Specific lesions were less variable and more characteristic for lymphoproliferative processes. Skin lesions (specific or non-specific) were not found related to a particular disease. CONCLUSION: Skin lesions in oncohematological disorders appear in great variability. They are essential for diagnosis and may appear a single initial diagnostic marker in these conditions.