Can the Pathological Response in Patients with Locally Advanced Gastric Cancer Receiving Neoadjuvant Treatment Be Predicted by the CEA/Albumin and CRP/Albumin Ratios?

Background: The purposes of neoadjuvant chemotherapy are to tumor size to improve the tumor removal rate, extend survival, and prevent metastasis. In this study, the importance of CRP/albumin ratio and CEA/albumin ratio in the prediction of neoadjuvant treatment response in gastric cancer patients was evaluated. Methods: This study retrospectively included 135 gastric cancer patients who received neoadjuvant chemotherapy at Çukurova University Balcali Hospital between January 2018 and December 2023. Preoperative CRP/albumin and CEA/albumin ratios were compared according to treatment response and multivariate logistic regression analysis was performed to determine the potential importance of these ratios in predicting pathological response. Results: The mean age of the 135 patients was 58.79 ± 10.83 (min = 26-max = 78). The CRP/albumin and CEA/albumin ratios were found to be significantly lower in patients who did not respond to neoadjuvant therapy. Each 1-unit increase in the CRP/albumin ratio was associated with a 1.16-fold decrease in the odds of pathological complete response to neoadjuvant therapy. Both CRP/albumin and CEA/albumin ratios were found to be significant in distinguishing neoadjuvant therapy response. The optimal cut-off value was 2.74 for the CRP/albumin ratio (sensitivity = 60%, specificity = 78.4%) and 1.40 for the CEA/albumin ratio (sensitivity = 74.2%, specificity = 67.6%). Values below these cut-off points favored neoadjuvant therapy response. Pathological complete response to neoadjuvant therapy was 4.75 times higher in patients with a CRP/albumin ratio below 2.74 and 5.14 times higher in patients with a CEA/albumin ratio below 1.40. Conclusions: Findings demonstrate that in patients with locally advanced gastric cancer receiving neoadjuvant treatment, CRP/Albumin and CEA/Albumin ratios are significant markers of pathological response.

Exploring the Impact of Cytogenetic Abnormalities on Treatment Responses and Survival Outcomes in Multiple Myeloma: A Single-Centre Experience of 13 Years of Follow-Up.

(1) Background: The introduction of novel therapies has led to a considerable evolution in the management of Multiple Myeloma, and chromosomal abnormalities predict the success of treatment. We aimed to characterize cytogenetic abnormalities for risk stratification in the patient population and to evaluate the predictive and prognostic value of the specified abnormalities in distinct treatment modalities. (2) Methods: This study included patients with Multiple Myeloma who applied to the Internal Medicine Clinic of the Cukurova University Faculty of Medicine. Between 2010 and 2023, 98 cases with cytogenetic abnormality data were identified. We analysed the effects of cytogenetic abnormalities on survival and response rates to first chemotherapies. (3) Results: P53 del was the most prevalent abnormality, and t(11;14) was the most common translocation. There was no significant difference in the mean survival and treatment response rates for specific cytogenetic abnormalities. When chemotherapies based on lenalidomide were initiated, patients' life-death statuses differed significantly from those of treatments without lenalidomide. Regardless of the type of chromosomal aberration, lenalidomide-based treatments independently enhanced average survival 14-fold, while there was no significant difference in overall survival among treatments. (4) Conclusions: In individuals with cytogenetic abnormalities, lenalidomide-based treatments should be started regardless of the chemotherapy to be used for the condition.

Ornidazole suppresses CD133+ melanoma stem cells via inhibiting hedgehog signaling pathway and inducing multiple death pathways in a mouse model.

AIM: To evaluate the inhibitory effects of ornidazole on the proliferation and migration of metastatic melanoma cell line (B16F10) in vitro and its anti-cancer effects in vivo using a melanoma mouse model. METHODS: We investigated the effects of ornidazole on cell viability (Crystal Violet and MTT assay) and migration ability (wound-healing assay) of B16F10 melanoma cells, and its ability to trigger DNA damage (Comet assay) in vitro. We also sorted CD133+ and CD133- cells from B16F10 melanoma cell line and injected them subcutaneously into Swiss albino mice to induce tumor formation. Tumor-bearing mice were divided into control and treatment groups. Treatment group received intraperitoneal ornidazole injections. Tumors were resected. Real-time polymerase chain reaction was used to determine the expression of genes involved into Sonic hedgehog (Shh) signaling pathway, stemness, apoptosis, endoplasmic reticulum (ER) stress, ER stress-mediated apoptosis, and autophagy. Shh signaling pathway-related proteins and CD133 protein were analyzed by ELISA. RESULTS: Ornidazole effectively induced DNA damage in CD133+ melanoma cells and reduced their viability and migration ability in vitro. Moreover, it significantly suppressed tumor growth in melanoma mouse model seemingly by inhibiting the Shh signaling pathway and ER-stress mediated autophagy, as well as by activating multiple apoptosis pathways. CONCLUSIONS: Our preclinical findings suggest the therapeutic potential of ornidazole in the treatment of metastatic melanoma. However, larger and more comprehensive studies are required to validate our results and to further explore the safety and clinical effectiveness of ornidazole.

Safety and efficacy of regorafenib in patients with treatment-refractory metastatic colorectal cancer in Turkey: the single-arm, open-label REGARD study.

OBJECTIVES: Regorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC. DESIGN: Open-label, single-arm, phase IIIb study conducted between July 2013 and April 2015. SETTING: 11 tertiary centres in Turkey. PARTICIPANTS: Eligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status ≤1. Patients were excluded if they had previously received regorafenib. Of 139 patients screened, 100 were treated and completed the study, and all 100 were analysed. Fifty-eight per cent were male. INTERVENTIONS: Patients received oral regorafenib, 160 mg once daily, for the first 3 weeks of each 4-week cycle until disease progression, death or unacceptable toxicity. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was safety, assessed by incidence of treatment-emergent adverse events (TEAEs). Progression-free survival (PFS) per investigator was the primary efficacy endpoint. There were no secondary endpoints. RESULTS: The median treatment duration was 2.5 months (range 0.1 to 20.6). Ninety-six per cent of patients had at least one TEAE and 77% had a grade ≥3 TEAE. The most common grade ≥3 regorafenib-related TEAEs were hypophosphataemia (11%), fatigue (8%), hyperbilirubinaemia (6%), hand-foot skin reaction (5%), hypertension (5%), anorexia (5%) and increased alanine aminotransferase (5%). TEAEs led to dose reduction in 30% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17% of patients. Median PFS was 3.1 months (95% CI 2.9 to 3.8). CONCLUSION: The regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC. TRIAL REGISTRATION NUMBER: NCT01853319, ClinicalTrials.gov.

The prognostic analysis of the some clinicopathological parameters and gene protein expressions in malignant mesothelioma.

INTRODUCTION: Mesothelioma is an aggressive tumour that originates in serous surfaces. The primary end point of this study was to invastigate the relationship of progression free survival (PFS) and overall survival (OS) with the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels in the tumour tissue of pleural and peritoneal mesothelioma cases. MATERIALS AND METHODS: The study included 53 patients diagnosed with mesothelioma between 2005 and 2016. The cases were separated into 2 groups as pleural and peritoneal. The effects on OS and PFS were examined of the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels and also clinicopathological parameters and the treatments given. In the statistical analysis of the data obtained, IBM SPSS vn 20.0 software was used. RESULT: Of the 53 patients included in the study, 39 (73.6%) were diagnosed with pleural mesothelioma and 14 (26.4%) with peritoneal mesothelioma. According to the c-Met and mTOR expression, OS and PFS of the peritoneal cases with high expression (2+, 3+) was seen to be significantly better than that of the peritoneal cases with low expression (0, 1+) (p<0.05). According to the PDGFR expression, OS and PFS of the pleural cases with low expression (0, 1+) was seen to be significantly better than that of the pleural cases with high expression (2+, 3+) (p<0.05). CONCLUSIONS: The examination of c-MET, PDGFR-alpha and m-TOR expression in the in the tumor tissue of mesothelioma cases may be important in determining prognosis.

Expression of fibroblast growth factor receptor 1, fibroblast growth factor 2, phosphatidyl inositol 3 phosphate kinase and their clinical and prognostic significance in early and advanced stage of squamous cell carcinoma of the lung.

AIM: Non-small cell lung carcinoma is the leading cause of cancer related to death in the world. Squamous cell lung carcinoma (SqCLC) is the second most frequent histological subtype of lung carcinomas. Recently, growth factors, growth factor receptors, and signal transduction system-related gene amplifications and mutations are extensively under investigation to estimate the prognosis and to develop individualized therapies in SqCLC. In this study, besides the signal transduction molecule phosphatidyl inositol-3-phosphate kinase (IP3K) p110α, we explored the expressions of fibroblast growth factor 2 (FGF2) and receptor-1 (FGFR1) in tumor tissue and also their clinical and prognostic significance in patients with early/advanced SqCLC. MATERIALS AND METHODS: From 2005 to 2013, 129 patients (23 early, 106 advanced disease) with a histopathological SqCLC diagnosis were selected from the hospital files of Cukurova University Medical Faculty for this study. Two independent pathologists evaluated FGFR1, FGF2, and PI3K (p110α) expressions in both tumor and stromal tissues from 99 of the patients with sufficient tissue samples, using immunohistochemistry. Considering survival analysis separately for patients with both early and advanced stage diseases, the relationship between the clinical features of the patients and expressions were evaluated by univariate and multivariate analyses. RESULTS: FGFR1 expression was found to be low in 59 (60%) patients and high in 40 (40%) patients. For FGF2; 12 (12%) patients had high, 87 (88%) patients had low expression and for IP3K; 31 (32%) patients had high and 66 (68%) patients had low expressions. In univariate analysis, overall survival (OS) was significantly associated with stage of the disease and the performance status of the patient (P<0.0001 and P<0.001). There was no significant difference in OS of the patients with either low or high expressions of FGFR1, FGF2, and IP3K. When the patients with early or advanced stage disease were separately taken into consideration, the relationship did not differ, either. Any of FGFR1, FGF2 or IP3K expressions was not found predictive for the treatment of early or advanced staged patients. On the other hand, the expressions of both FGFR1 and FGF2 were significantly different with respect to smoking, scar of tuberculosis and scar of radiotherapy (P=0.002; P=0.06 and P=0.05, respectively). DISCUSSION: There has not been identified an effective individualized treatment for SqCLC yet. Therefore, in order to be able to develop such a treatment in the future, it is essential to identify the genetic abnormalities that are responsible for the biological behaviors and carcinogenesis of SqCLC. Although we could not show the prognostic and predictive significance of FGFR1, FGF2 and IP3K expressions in SqCLC, we determined the expression rates of FGFR1, FGF2 and IP3K as a reference for Turkish patients. In conclusion, we want to put some emphasis on the fact that, pulmonary fibrosis which is a late complication of radiotherapy at stage III disease, and the scar of tuberculosis could be associated with FGFR1 and FGF2 expressions.

Effect of the cumulative dose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe bone disease for which the pathogenetic mechanisms and risk factors are not fully understood. The present study evaluated the data of 652 patients with bone metastasis that had undergone treatment with biphosphonates. Subsequently, 24 patients with BRONJ and 20 control patients without BRONJ that were treated with zoledronic acid were enrolled. It was found that BRONJ occurred in 3.6% of patients. The mean age and the administration of dental treatment were found to be significantly associated with BRONJ development (P=0.049 and P=0.013, respectively). The cumulative dose median in the BRONJ group was found to be significantly higher compared with the cumulative dose average in the control group (P=0.037). In addition, at the time of BRONJ development, improvement in the disease was determined to be better in the BRONJ group than in the control group (P=0.031). The present study determined that age, the existence of dental extraction and the cumulative dose of zoledronate were all important risk factors in BRONJ development.

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.

A new approach to the treatment of metastatic paraganglioma: sorafenib.

Paragangliomas are relatively rare chromaffin cell tumors which may be cured through resection. Patients with paragangliomas may develop metastatic diseases. There is no consensus regarding refractory chemotherapy for treatment of metastatic disease. In this report, we presented a case of a 43-year-old woman who was admitted to the hospital with a history of episodic headaches, diaphoresis, and weakness. Elevated plasma catecholamine levels and a right paraaortic mass were observed on computed tomography. The mass was excised, and a diagnosis of paraganglioma was confirmed. After 20 months of follow-up, local recurrence and metastases were detected in the thorax, abdomen, and skeletal system. Plasma and urinary catecholamine levels were high. Chemotherapy was administered, and no improvement was observed. Therefore, following this palliative conventional chemotherapy, sorafenib was administered for three months, and, finally, positron emission tomography showed that the patient's lesions had completely regressed.

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.

Malignant mixed Mullerian tumor of the ovary with two cases and review of the literature.

INTRODUCTION: Malignant mixed Müllerian tumor (MMMT) of the ovary is a rare and highly aggressive tumor. It accounts <1% of all ovarian carcinomas. It is characterized by the presence of both carcinomatous and sarcomatous components and tends to occur in low parity postmenopausal woman. These are mixed, mostly monoclonal tumors, and the predominance of the stromal component aggravates the prognosis. The staging system for ovarian and primary peritoneal cancer is also used for MMMT. After complete surgical staging, patient with stage II-IV at the time of surgery should have postoperative chemotherapy. Chemotherapy can be considered for stage I MMMT. Its optimal treatment is debatable. Taxane and platinum combination is standard for the epithelial ovarian carcinoma. There is very limited literature reporting this combination therapy in ovarian MMMTs. CASE 1 AND CASE 2: We presented two cases of stage III primary ovarian MMMT. The patients were treated with the taxane/platin combination, without adverse events following surgery, and remained in clinical remission in Case 1 at follow-up. Case 2 has progressed after first line taxane/platin regimen and treated like epithelial ovarian carcinoma. Case 1 was in complete remission in the follow-up visit 2 years later. Case 2 died 14 months later after the tumor was initially diagnosed. CONCLUSION: Predominating carcinomatous or sarcomatous component should be taken into consideration in predicting the response and planning the chemotherapy protocol.

Primary cutaneous small-cell carcinoma: a case report.

Most commonly arising in the gastrointestinal and genitourinary tracts, extrapulmonary small-cell carcinoma is quite rare. Although its prognosis is very poor, complete remission or even cure can be achieved by combination of different treatment modalities. We report here a 32-year-old woman with a cutaneous gluteal mass diagnosed as small-cell carcinoma of the skin. Combination chemotherapy containing cisplatin and etoposide was started. Radiotherapy was administered after two courses of chemotherapy. Following radiotherapy, additional 4 courses of chemotherapy were given. She has been in remission for three years with no evidence of tumor recurrence.

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.

Levels of serum and cerebrospinal fluid soluble CD27 in the diagnosis of leptomeningeal involvement of hematolymphoid malignancies.

Reportedly, soluble CD27 (sCD27) is a sensitive and specific marker for leptomeningeal involvement (LI) of CD27-expressing lymphoproliferations, such as B-cell non-Hodgkin's lymphoma and chronic B-lymphocytic leukemia. On morphologic analysis of cerebrospinal fluid (CSF), one third of patients suspected of LI have false negatives, so a diagnostic marker for LI in B-cell non-Hodgkin's lymphoma or B-lymphocytic leukemia would be extremely valuable. sCD27 was detected in the serum and CSF samples from 35 selected patients in whom 18 cases of acute lymphoblastic leukemia (ALL) (3 with LI), 7 of non-Hodgkin's lymphoma, and 5 of acute myelogenous leukemia (3 with LI) were submitted for (immuno)morphologic detection of malignant cells and intrathecal therapy, along with samples from 5 control patients (2 submitted for epidural hemorrhage, 3 for lumbar disc protrusion). Concentrations of CSF-sCD27 were determined by enzyme-linked immunosorbent assay (PeliKine Compact Human Soluble CD27 ELISA Kit, Cat. No. M1960; Research Diagnostics Inc., Concord, Mass). The cutoff value was 350 U/mL. Serum and CSF-sCD27 concentrations above the cutoff value were not detected. Although it is unlikely that LI would be present in patients with chronic lymphoproliferation who have normal sCD27 concentrations in CSF samples, the determination of CSF-sCD27 is not sufficiently specific to allow it to serve as a reliable tumor marker.

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 x 10(9)/L (0.8-250.0 x 10(9)/L) hemoglobin count, 11.2 g/dL (5.0-16.2 g/dL) platelet count, 162.5 x 10(9)/L (29.8-317 x 10(9)/L) B(2) microglobulin (B(2)M) 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 B(2)M (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).

Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-alpha 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 (PDGFAB), and transforming growth factor-alpha (TGF-alpha) 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-alpha, according to disease stage, a significant correlation was found between disease stage and BM HGF (P=.047), BM TGF-alpha (P=.021), and PB PDGF-AB (P=.006), respectively. When correlations between all other parameters were analyzed, significance was noted between PB TGF-alpha and lactate dehydrogenase (P=.02), PB TGF-alpha and PB HGF (P=.002), BM TGF-alpha and CD38 (P=.046), BM TGF-alpha and BM HGF (P=.000), BM TGF-alpha 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-alpha, 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-alpha, and PDGFAB in BM.

Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction.

Palmar-plantar erythrodysesthesia (PPE) is a distinctive and relatively frequent toxic reaction related to some chemotherapeutic agents. Doxorubicin, cytarabine, docetaxel, fluorouracil, and capecitabine are the most frequently implicated agents. Recently, taxanes, especially docetaxel, have been widely used in combination with capecitabine in patients with metastatic breast cancer (MBC). A high percentage of PPE has been seen in patients undergoing this combination therapy. PPE seems to be dose dependent and both peak drug concentration and total cumulative dose determine its occurrence. Withdrawal or dose reduction of the implicated drug usually gives rise to amelioration of the symptoms. Supportive treatments such as topical wound care, elevation, and cold compresses may help to relieve the pain. Use of systemic corticosteroids, pyridoxine (vitamin B6), blood flow reduction, and, recently, topical 99% dimethyl-sulfoxide have been used with variable outcomes. Vitamin E treatment has not been published before, especially without dose reduction of docetaxel-capecitabine therapy. Here we present five MBC patients treated with docetaxel-capecitabine combination therapy in whom PPE was observed during the clinical follow-up period. In all patients grade 2-3 PPE was observed. Vitamin E therapy was started at 300 mg/day p.o. without dose reduction of therapy and after 1 week of treatment PPE began to disappear. We suggest that it could be of interest to consider vitamin E as a preventive drug when drugs with a strong association with PPE are going to be administered.

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.

Breast cancer and concomitant primary hyperparathyroidism: description of two patients.

Breast cancer is the malignant neoplasm most commonly associated with hypercalcemia. In breast cancer the majority of the hypercalcemia cases result from osteolytic metastatic bone disease of the primary tumor. In a few patients hypercalcemia results from other conditions like primary hyperparathyroidism. Here, we present two female patients who were treated for breast cancer. Hypercalcemia in these two patients was diagnosed as being due to primary hyperparathyroidism. One of them was submitted to surgery and the calcium level dropped to the normal level thereafter. The other one refused surgery and was treated with biphosphonate and calcitonin. We suggest that when hypercalcemia occurs in breast cancer, primary hyperparathyroidism should be considered as possible cause.