PI3-kinase inhibition synergistically promoted the anti-tumor effect of lupeol in hepatocellular carcinoma

Background: Lup-20(29)-en-3H-ol (Lupeol), a dietary triterpene, has been shown to possess multiple pharmacological activities including anti-tumor effects Methods: In the current study, we noted that low doses of lupeol (<40muM) promoted the growth of hepatocellular carcinoma (HCC) cells with a significant activation of the PI3-kinase/Akt signaling pathway. We further investigated the combined anti-tumor effect of lupeol and S14161, a newly identified PI3-Kinase inhibitor in vitro and in vivo Results: The results demonstrated that lupeol and S14161 could exert a synergistic antitumor effect resulting in chemo-sensitization of HCC to low doses of lupeol. Using an in vivo HCC model, we further demonstrated that lupeol and S14161 synergistically inhibited tumor growth without any adverse effects on body weight Conclusion: Our studies showed that the activation of PI3-kinase/Akt pathway resulted in the tumor-promoting effect with low doses of lupeol. Combining PI3-kinase inhibitor with lupeol could synergistically augment the anti-tumor effect of lupeol and might be an applicable strategy for HCC therapy.

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FDG-PET parameter predicts locally advanced lung cancer survival

High post-treatment concentrations of a radioactive imaging marker are predictive of worse overall survival from inoperable, locally advanced non-small-cell lung cancer, prospective study findings suggest.

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Factors associated with receipt of adjuvant chemotherapy among married women with breast cancer

Background: Adjuvant chemotherapies are recommended for most women after breast cancer surgery, and can greatly affect the patients' survival. We describe and evaluate possible factors influencing receipt of postoperative adjuvant chemotherapy among breast cancer patients in China. Methods: A total of 1,431 women diagnosed with breast cancer from 1997 to 2005 were enrolled. We reviewed medical records and abstracted information about these patients. Details on social-demographic factors and clinical-pathological characteristics of participants were collected and analyzed. To meet our objectives, the patient's age at diagnosis, comorbidities, menstrual status, rural/urban status, tumor size, lymph node status, distant metastasis, tumor stage and hormone receptor status were estimated. Results: Overall, 936 of these 1,431 patients (65.41%) received adjuvant chemotherapy. Receipt of chemotherapy was significantly associated with age at diagnosis, rural--urban disparities, and lymph node status of patients, though no significant difference was found between the age <50 and age 50 to 64 groups. Moderate association was also observed between hormone receptor status and receipt of adjuvant chemotherapy, though it was still not statistically significant. Conclusions: Our study suggests that age at diagnosis, rural--urban disparities and lymph node status of breast cancer patients are independent predictors for receipt of adjuvant chemotherapy among married Chinese women. Further investigations are warranted, and related public health education needs to be expanded in China.

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Toxicity limits benefits of bevacizumab–erlotinib NSCLC maintenance therapy

Two targeted anticancer drugs used together after first-line chemotherapy for advanced stage non-small-cell lung cancer improve progression-free survival, the results of a large, prospective study show.

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DNA methylation signature marks recurrence in early stage lung cancer

An international research team has identified a DNA methylation signature that identifies patients with stage I non-small-cell lung cancer who are at high risk for relapse.

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STAT3 mutations are frequent in T-cell large granular lymphocytic leukemia with pure red cell aplasia

T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder and can cooccur in the context of pure red cell aplasia (PRCA). The aim of the current study was to analyze the signal transducer and activator of transcription 3 (STAT3) mutation status and its clinical significance in T-LGLL. We found STAT3 mutations in 21.4% of patients with T-LGLL. High beta2-MG (beta2-microglobulin) levels (P = 0.005), neutropenia (P = 0.018) and PRCA (P = 0.001) all displayed a significant association with STAT3 mutations. In univariate analysis, treatment-free survival (TFS) was affected by STAT3 mutation status (P = 0.008) and beta2-MG (P = 0.006). Our results demonstrate the remarkable correlation of STAT3 mutation with PRCA, neutropenia and beta2-MG.

via Journal of Hematology & Oncology

Breast adenomyoepithelioma: a case report with malignant proliferation of epithelial and myoepithelial elements

Background: Breast adenomyoepithelioma is an unusual tumor characterized by a biphasic proliferation of epithelial and myoepithelial cells. Most breast adenomyoepitheliomas are considered to be benign or to have a low-grade malignant potential, characterized by propensity for local recurrence. Malignant changes arising in this lesion are extremely rare and may involve one or both cellular components.Case report: We discuss a case of a 60 year-old woman who began to experience pain in her right breast in January 2009. Breast ultrasound and mammography were performed showing a rounded, hypoechoic solid lesion with ill-defined margins in the right inner-inferior quadrant, suspicious of malignancy. Quadrantectomy of the inner-inferior quadrant of the right breast with sampling of ipsilateral axillary lymph nodes was performed. The histological analysis confirmed the diagnosis of adenomyoepithelioma with focal malignant change of the epithelial component, associated with high-grade malignant myoepithelial change. The patient was treated with adjuvant radiotherapy and her right breast received a dose of Gy 50 with a boost of Gy 10 to the tumor bed. At present, the patient shows no sign of tumor recurrence. Conclusion: Breast malignant adenomyoepithelioma is a rare tumor which should be considered in the differential diagnosis of other solid breast lesions. Only few cases have been reported in the literature. Diagnosis, optimal therapy and predicting the outcome are problematic issues due to the rarity of this disease which appears to have hematogenous rather than lymphatic spread and usually occurs in primary tumors >= 1.6 cm in size.

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Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts

Background: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts >=100 x 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 x 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 x 109/L are reported. Methods: Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. Results: By week 24, 62% of patients achieved stable doses >=10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts <=75 x 109/L. Seven patients experienced platelet count increases >=15 x 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. Conclusions: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts.Trial registration: ClinicalTrials.gov: NCT01348490.

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FPGS rs1544105 polymorphism is associated with treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia

Background: Folypolyglutamate synthase (FPGS) catalyzes the polyglutamation of folates and antifolates, such as methotrexate (MTX), to produce highly active metabolites. FPGS tag SNP rs1544105C > T is located in the gene promoter. The aim of the present study was to investigate the impact of rs1544105 polymorphism on the treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods: This study enrolled 164 children with BCP-ALL. We genotyped the FPGS SNP rs1544105, and analyzed the associations between its genotypes and treatment outcome. We also examined FPGS mRNA levels by real-time PCR in 64 of the 164 children, and investigated the function of this polymorphism on gene expression. Results: We found significantly poor relapse-free survival (RFS) (p = 0.010) and poor event-free survival (EFS) (p = 0.046) in carriers of CC genotype. Multivariable Cox regression analyses adjusted for possible confounding variables showed that, relative to the CT + TT genotypes, the CC genotype was an independent prognostic factor for poor RFS (hazard ratio [HR], 4.992.; 95% CI, 1.550-16.078; p = 0.007). No association was found between any toxicity and rs1544105 polymorphism. Quantitative PCR results showed that individuals with the T allele had lower levels of FPGS transcripts. Conclusions: Our study indicates that FPGS rs1544105C > T polymorphism might influence FPGS expression and affect treatment outcome in BCP-ALL patients.

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Current drugs may harbor small-cell lung cancer promise

Scientists have identified several existing non-oncology drug classes that may have potential as a treatment for small-cell lung cancer, especially for patients with chemoresistant and metastatic disease.

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Complement protein holds diagnostic, prognostic promise in lung cancer

A complement activation product known as “C4d” may have value as a diagnostic and prognostic biomarker for lung cancer, research suggests.

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CpG oligodeoxynucleotides enhance chemosensitivity of 5-fluorouracil in HepG2 human hepatoma cells via downregulation of the antiapoptotic factors survivin and livin

Background: Recent studies indicated that a synthetic oligonucleotide containing un-methylated CpG oligodeoxynucleotides(CpG-ODN)has a potential function for cancer therapy. In this study, we evaluated the chemosensitizing effects of CpG-ODN in 5-fluorouracil (5-FU)-treated HepG2 human hepatoma cells. Methods: Cell viability assay were utilized to evaluate the direct cytotoxicity of CpG-ODN in the presence or absence of 5-FU in HepG2 cells, and apoptosis as well as cell-cycle was examined by flow cytometry analysis. The mRNA expression of Bcl-2, Livin and Survivin within HepG2 cells treated with CpG-ODN and/or 5-FU were analyzed by Real Time PCR assay in vitro. Results: CpG-ODN in combination with 5-FU could decrease cell viability, increase apoptosis and further induce HepG2 cells cycle arrest at S phase when compared with CpG-ODN or 5-FU. CpG-ODN or 5-FU could down-regulate the mRNA expression of Bcl-2 within HepG2 cells. The mRNA expression of Livin and Survivin decreased in cells treated with CpG-ODN alone but increased in cells treated with 5-FU alone. However, CpG-ODN in combination with 5-FU could down-regulate the mRNA expression of Livin and Survivin within HepG2 cells. Conclusions: Our finding demonstrated that CpG-ODN enhanced the chemosentivity of 5-FU in HepG2 human hepatoma cells at least in part by down-regulating the expression of Livin and Survivin, leading to apoptosis and further inducing cell cycle arrest at S phase. Therefore, CpG-ODN may be a potential candidate as chemosensitizer for human hepatocellular carcinoma.

via Cancer Cell International

Prognostic value of isocitrate dehydrogenase 1, O6-methylguanine-DNA methyltransferase promoter methylation, and 1p19q co-deletion in Japanese malignant glioma patients

Background: To determine the prognostic value of isocitrate dehydrogenase 1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and 1p/19q co-deletion in Japanese patients with malignant gliomas. Methods: We studied 267 malignant gliomas, which included 171 glioblastomas (GBMs), 40 anaplastic astrocytomas (AAs), 30 anaplastic oligodendrogliomas (AOs), and 26 anaplastic oligoastrocytomas (AOAs). These malignant gliomas were divided into 2 groups (Group 1: GBM + AA, Group 2: AO + AOA) according to the presence of the oligodendroglioma component. We examined IDH1 mutation and MGMT promoter methylation in each group by direct sequencing and methylation-specific PCR, respectively. We further examined 1p/19q co-deletion in Group 2 by fluorescence in situ hybridization. Survival between groups was compared by Kaplan--Meier analysis. Results: In Group 1, patients with IDH1 mutations exhibited a significantly longer survival time than patients with wild-type IDH1. However, no significant difference was observed in Group 2, although patients with IDH mutations tended to show prolonged survival. For both Group 1 and Group 2, patients with MGMT methylation survived longer than those without this methylation. Further, patients with 1p/19q co-deletion showed significantly better outcome in Group 2. Conclusions: Our study confirms the utility of IDH1 mutations and MGMT methylation in predicting the prognosis of Group 1 patients (GBM + AA) and demonstrated that IDH1 mutations may serve as a more reliable prognostic factor for such patients. We also showed that MGMT methylation and 1p/19q co-deletion rather than IDH1 mutations were prognostic factors for Group 2 patients (AOA + AO). Our study suggests that patients survive longer if they have IDH1 mutations and undergo total resection. Further, irrespective of MGMT promoter methylation status, the prognosis of glioma patients can be improved if total resection is performed. Moreover, our study includes the largest number of Japanese patients with malignant gliomas that has been analyzed for these three markers. We believe that our findings will increase the awareness of oncologists in Japan of the value of these markers for predicting prognosis and designing appropriate therapeutic strategies for treating this highly fatal disease.

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Inhibition of cancer cell proliferation and apoptosis-inducing activity of fungal taxol and its precursor baccatin III purified from endophytic Fusarium solani

Background: Taxol (generic name paclitaxel), a plant-derived antineoplastic agent, used widely against breast, ovarian and lung cancer, was originally isolated from the bark of the Pacific yew, Taxus brevifolia. The limited supply of the drug has prompted efforts to find alternative sources, such as chemical synthesis, tissue and cell cultures of the Taxus species both of which are expensive and yield low levels. Fermentation processes with microorganisms would be the methods of choice to lower the costs and increase yields. Previously we have reported that F. solani isolated from T. celebica produced taxol and its precursor baccatin III in liquid grown cultures J Biosci 33:259-67, 2008]. This study was performed to evaluate the inhibition of proliferation and induction of apoptosis of cancer cell lines by the fungal taxol and fungal baccatin III of F. solani isolated from T. celebica. Methods: Cell lines such as HeLa, HepG2, Jurkat, Ovcar3 and T47D were cultured individually and treated with fungal taxol, baccatin III with or without caspase inhibitors according to experimental requirements. Their efficacy on apoptotic induction was examined. Results: Both fungal taxol and baccatin III inhibited cell proliferation of a number of cancer cell lines with IC50 ranging from 0.005 to 0.2 muM for fungal taxol and 2 to 4 muM for fungal baccatin III. They also induced apoptosis in JR4-Jurkat cells with a possible involvement of anti-apoptotic Bcl2 and loss in mitochondrial membrane potential, and was unaffected by inhibitors of caspase-9,-2 or -3 but was prevented in presence of caspase-10 inhibitor. DNA fragmentation was also observed in cells treated with fungal taxol and baccatin III. Conclusions: The cytotoxic activity exhibited by fungal taxol and baccatin III involves the same mechanism, dependent on caspase-10 and membrane potential loss of mitochondria, with taxol having far greater cytotoxic potential.

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Up-regulation of miR-224 promotes cancer cell proliferation and invasion and predicts relapse of colorectal cancer

Background: MicroRNAs (miRNAs) are small, non-coding RNAs that can function as oncogenes or tumor suppressors in human cancer. Abnormally expressed miR-224 was found to play a fundamental role in several types of cancer. The aim of this study was to investigate the prognostic and biological values of miR-224 in colorectal cancer (CRC). Methods: Quantitative RT-PCR (qRT-PCR) was used to evaluate expression levels of miR-224. The postoperative survival rate was analyzed with Kaplan--Meier method. The roles of miR-224 in cell proliferation, migration and invasion were analyzed with pre-miR-224 transfected cells. In addition, the regulation of SMAD4 by miR-224 was evaluated by qRT-PCR, Western blotting and luciferase reporter assays. Results: In the present study, we demonstrated that miR-224 was significantly up-regulated in CRC tissue samples and associated with disease relapse and a relative poorer disease-free survival rate. Moreover, ectopic expression of miR-224 potently promoted tumor cell proliferation, migration and invasion in vitro. Furthermore, the over-expression of miR-224 in CRC cell lines decreased SMAD4 expression at the translational level and decreased SMAD4-driven luciferase-reporter activity. Conclusions: Our data suggest that miR-224 could play an oncogenic role in the cellular processes of CRC and represent a novel biomarker for tumor relapse of CRC patients.

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Adjuvant zoledronic acid therapy for patients with early stage breast cancer: an updated systematic review and meta-analysis

Background: Zoledronic acid is a potent inhibitor of osteoclast-mediated bone resorption and has been widely used in bone metastasis malignancies and postmenopausal osteoporosis as a preventive therapy against skeletal-related events. The purpose of this study was to evaluate the clinical outcome of zoledronic acid as an adjuvant therapy for patients with early stage breast cancer.Patients and methodsEntries in the PubMed and EMBASE databases up to 12 July 2013 were systematically reviewed. Online abstracts from the proceedings of the Annual Meetings of the American Society of Clinical Oncology (ASCO) (1992--2013) and the San Antonio Breast Cancer Symposium (SABCS) (2004--2013) were also reviewed. Primary endpoints included overall survival (OS) and disease-free survival (DFS), while secondary endpoints included bone metastasis-free survival (BMFS), distant metastasis-free survival (DMFS), and fracture-free rate (FFR). Results: A total of eight studies including 3,866 subjects and 3,864 controls met our search criteria and were evaluated. The use of zoledronic acid was found to improve OS (relative risk (RR), 0.88; 95% confidence interval (CI), 0.77--1.01; p-value = 0.06) and DMFS (RR, 0.77; 95% CI, 0.60--1.00; p-value = 0.05). Furthermore, statistically significant benefits were associated with BMFS (RR, 0.81; 95% CI, 0.66--0.99; p-value = 0.04) and FFRs (RR, 0.75; 95% CI, 0.61--0.92; p-value = 0.007). In contrast, there was no significant difference in DFS with the application of zoledronic acid (RR, 0.88; 95% CI, 0.72--1.09; p-value = 0.24). Sensitivity analysis further identified the improvement of 5-year OS for the adjuvant zoledronic acid therapy in early stage breast cancer patients (RR, 0.86; 95% CI, 0.75--0.99; p-value = 0.03), while a borderline statistically significant benefit was observed for 5-year DFS (RR, 0.90; 95% CI, 0.81--1.00; p-value = 0.06). Conclusion: Zoledronic acid as an adjuvant therapy appears to improve the 5-year OS rate for early stage breast cancer patients, and was associated with a protective effect for the bone metastases and fractures evaluated in more than 7,000 patients. However, further research is needed to confirm our findings, and sub-group analyses according to menopause status or hormone status may provide further insight.

via Journal of Hematology & Oncology

Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing

Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. This review summarizes data supporting appropriate individualized patient management through careful monitoring of blood counts and dose titration as needed in order to maximize treatment benefit.

via Journal of Hematology & Oncology

High expression of prolactin receptor is associated with cell survival in cervical cancer cells

Background: The altered expression of prolactin (PRL) and its receptor (PRLR) has been implicated in breast and other types of cancer. There are few studies that have focused on the analysis of PRL/PRLR in cervical cancer where the development of neoplastic lesions is influenced by the variation of the hormonal status. The aim of this study was to evaluate the expression of PRL/PRLR and the effect of PRL treatment on cell proliferation and apoptosis in cervical cancer cell lines. Results: High expression of multiple PRLR forms and PRLvariants of 60--80 kDa were observed in cervical cancer cell lines compared with non-tumorigenic keratinocytes evaluated by Western blot, immunofluorecence and real time PCR. Treatment with PRL (200 ng/ml) increased cell proliferation in HeLa cells determined by the MTT assay at day 3 and after 1 day a protective effect against etoposide induced apoptosis in HeLa, SiHa and C-33A cervical cancer cell lines analyzed by the TUNEL assay. Conclusions: Our data suggests that PRL/PRLR signaling could act as an important survival factor for cervical cancer. The use of an effective PRL antagonist may provide a better therapeutic intervention in cervical cancer.

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The flavokawains: uprising medicinal chalcones

Plant-based compounds have been in the spotlight in search of new and promising drugs. Flavokawain A, B and C are naturally occurring chalcones that have been isolated from several medicinal plants; namely the piper methysticum or commercially known as the kava-kava. Multiple researches have been done to evaluate the bioactivities of these compounds. It has been shown that all three flavokawains may hold promising anti-cancer effects. It has also been revealed that both flavokawain A and B are involved in the induction of cell cycle arrest in several cancer cell lines. Nevertheless, flavokawain B was shown to be more effective in treating in vitro cancer cell lines as compared to flavokawain A and C. Flavokawain B also exerts antinociceptive effects as well as anti-inflammation properties. This mini-review attempts to discuss the biological properties of all the flavokawains that have been reported.

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Osteomyelitis of the femur mimicking bone tumors: a review of 10 cases

Background: The clinical symptoms and radiographic appearance of osteomyelitis can mimic those of bone tumors. Methods: We reviewed 10 patients with osteomyelitis of the femur who were initially diagnosed as having bone tumors and were subsequently transferred to our institution. Results: Nocturnal pain of moderate intensity occurred in seven patients, and all 10 patients had elevated C-reactive protein levels. The radiographic findings included the following: a permeative, moth-eaten osteolytic lesion in six patients, an osteolytic lesion with sclerotic borders in three patients, and cortical destruction with pathological fracture in one patient. Magnetic resonance imaging was performed for eight patients, and only one had a positive penumbra sign. All patients underwent a surgical biopsy to confirm the final diagnosis for histological analysis and cultures. Klebsiella pneumoniae was detected in six patients and Staphylococcus aureus, the most common organism in osteomyelitis, was detected in three. Recurrence of infection occurred in five patients following debridement surgery; of these three had a Klebsiella pneumoniae infection. All patients received antibiotic treatment for an average of 20.4 weeks (range, 4 to 44) and surgical treatment an average of 1.8 times (range, 1 to 4). At the final follow-up, all patients were fully recovered with no signs of infection. Conclusions: When used in combination, clinical examinations, laboratory data, and radiographic findings can reliably distinguishing osteomyelitis from bone tumors.

via World Journal of Surgical Oncology

HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line

Background: Homeobox (HOX) genes deregulation has been largely implicated in the development of human leukemia. Among the HOXB cluster, HOXB1 was silent in a number of analyzed acute myeloid leukemia (AML) primary cells and cell lines, whereas it was expressed in normal terminally differentiated peripheral blood cells. Methods: We evaluated the biological effects and the transcriptome changes determined by the retroviral transduction of HOXB1 in the human promyelocytic cell line HL60. Results: Our results suggest that the enforced expression of HOXB1 reduces cell growth proliferation, inducing apoptosis and cell differentiation along the monocytic and granulocytic lineages. Accordingly, gene expression analysis showed the HOXB1-dependent down-regulation of some tumor promoting genes, paralleled by the up-regulation of apoptosis- and differentiation-related genes, thus supporting a tumor suppressor role for HOXB1 in AML. Finally, we indicated HOXB1 promoter hypermethylation as a mechanism responsible for HOXB1 silencing. Conclusions: We propose HOXB1 as an additional member of the HOX family with tumour suppressor properties suggesting a HOXB1/ATRA combination as a possible future therapeutic strategy in AML.

via Cancer Cell International

Stage and grade dominate RCC outcomes

Tumor grade and American Joint Committee on Cancer stage have emerged as the most important predictors of mortality in a competing risks analysis of patients undergoing nephrectomy for renal cell carcinoma.

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Prognostic factors could aid RCC metastasectomy decisions

Researchers have identified four factors that are associated with survival time in patients who undergo metastasectomy for metastatic renal cell carcinoma.

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P400 predicts RCC outcome

Reduced expression of a senescence-associated protein is associated with worse outcome in patients with renal cell carcinoma, study findings show.

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Retraction: The stem cell factor antibody enhances the chemotherapeutic effect of adriamycin on chemoresistant breast cancer cells

No description available

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Positive association between Interleukin-8 -251A > T polymorphism and susceptibility to gastric carcinogenesis: a meta-analysis

Backgrounds: The associations between the polymorphisms of interleukin-8 (IL-8) gene and gastric carcinogenesis have been extensively investigated in recent years. However, the results remain conflicting rather than conclusive. Methods: A meta-analysis of 18 eligible studies was performed to evaluate the association of IL-8 -251A > T polymorphism with risk of gastric carcinogenesis. A systematic literature search of MEDLINE, Embase, and Web of Science, CNKI databases was conducted. Statistical analysis was performed by using the Revman 5.1 software and the Stata 12.0 software. Results: Of the 293 unique studies identified using our search criteria, 18 studies fulfilled our inclusion criteria and were included in the meta-analysis. These studies cumulatively reported 5,321 cases and 6,465 controls. The combined results based on all studies showed that the IL-8 -251A > T polymorphism was associated with the risk of gastric carciongenesis (A vs. T: OR: 1.14 [1.02, 1.26], P = 0.02), especially gastric cancer (A vs. T: OR: 1.15 [1.03, 1.29], P = 0.02), but not associated with the risk of precancerous lesion (A vs. T: OR: 1.09 [0.99, 1.20], P = 0.08). Analysis stratified by ethnicity may seem that IL-8 -251A > T polymorphism was susceptible to gastric cancer in Asian population, but not in Caucasian population. Conclusions: Our meta-analysis results provide evidence that IL-8 -251A > T polymorphism is significantly associated with increased risk of gastric carcinogenesis in Asian population, particularly in gastric cancer. Further large and well-designed studies are required to confirm this conclusion.

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REGARD VEGF receptor-2 as gastric cancer target

Targeting vascular endothelial growth factor receptor-2 mediated signaling is an effective strategy against advanced gastric cancer, results from the REGARD trial demonstrate.

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BRCA1/2 mutations may alter endometrial, ovarian function

Scientists have detected significant differences in endometrial thickness and hormone levels in women with and without BRCA1/2 mutations that may play a role in cancer susceptibility or development.

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Skin cancer drug shows periocular promise

Early research suggests that patients with periocular basal cell carcinoma may benefit from treatment with a drug targeting the Hedgehog signaling pathway.

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Synchronous primary neoplasms of the bladder, skin and breast in a male patient: a case report

The incidence of multiple primary malignant neoplasms increases with age, reflecting an increase in overall cancer risk in older patients. Cases of two or more concurrent primary cancers are still rare, although its incidence is increasing. Here, we report the case of a 57-year-old man who was referred to our institution with synchronous squamous cell carcinoma of the skin on the forehead, infiltrating ductal carcinoma of the breast, and transitional cell carcinoma of the urinary bladder. To the best of our knowledge, this is the first reported case in literature of this combination of primary neoplasms.

via World Journal of Surgical Oncology

Pulmonary benign metastasizing leiomyoma: report of three cases

Benign metastasizing leiomyoma is very rare and usually occurs in women who undergo hysterectomy and myomectomy for uterine leiomyoma. This is a benign spindle-shaped smooth muscle cell tumor pathologically but metastasizes to the extrauterine organs. Lungs are the most common site of metastasis. We observed three cases of pulmonary benign metastasizing leiomyoma.

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Prognosis of the intrahepatic cholangiocarcinoma after resection: hepatitis B virus infection and adjuvant chemotherapy are favorable prognosis factors

AimThe incidence and mortality associated with intrahepatic cholangiocarcinoma is increasing in many countries and documentation of disease outcome is sparse. The present study was undertaken to investigate the prognostic factors for intrahepatic cholangiocarcinoma (ICC) following surgical resection. The impact of pre-existing HBV virus infection and adjuvant chemotherapy on the overall survival was also evaluated. Methods: Clinical and pathological data were collected retrospectively from 81 patients undergoing surgery for ICC between 2005 and 2011, at The Henan Province Tumor Hospital and the First Affiliated Hospital of Zheng Zhou University. Survival and prognosis were analyzed using the Kaplan-Meier method and COX regression model. Results: The population included 37 patients who were HBsAg + or anti-HBc+, 21 patients who were anti-HBs + positive and 18 patients who received adjuvant chemotherapy. The overall 1- and 3-year survival rates were 51% and 20%, respectively. The median survival was 12.2 months. Univariate analysis identified the following prognostic factors: HBV virus infection or HBV vaccine prior to resection (P = 0.017); adjuvant chemotherapy (P = 0.001); preoperative serum CA19-9 (>200U/mL; P = 0.015); GGT (>64U/L; P = 0.008), ALP (>119U/L; P = 0.01); lymph node metastasis (P = 0.005); radical resection (P = 0.021); intrahepatic metastasis (P = 0.015) and diabetes (P = 0.07). Multivariate analysis identified chronic HBV infection (RR = 0.583; P = 0.041), anti-HBs positivity (RR = 0.680; P = 0.050), adjuvant chemotherapy (RR = 0.227; P < 0.001), lymph node metastasis (RR = 2.320; P = 0.001), and intrahepatic duct stones (RR = 0.473; P = 0.032) as independent prognostic factors. Conclusions: HBV virus infection or HBV vaccination prior to resection, together with adjuvant chemotherapy, were independently associated with improved survival in patients undergoing surgery for ICC.

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Family history of hepatocellulcar carcinoma is not associated with its patients' prognosis after hepatectomy

Background: Family history of liver cancer is a major risk factor for hepatocellular carcinoma (HCC). In this study, we investigated the prognosis of patients with HCC with or without family history. Methods: Data for 1,313 patients who underwent hepatectomy as initial treatment for HCC between 2000 and 2008 at a tertiary cancer center hospital were retrieved from a prospective database. A positive family history was defined as a self-reported history of HCC in first-degree relatives. Clinicopathologic characteristics were compared by family history. Kaplan-Meier method and Cox proportional hazards regressions were applied for overall survival (OS) and disease-free survival (DFS). Results: Of 1,313 patients, 169 patients (12.9%) had first-degree relatives with a history of HCC. There were no significant differences between patients with or without family history in basic clinicopathologic characteristics. In either whole group or each stage according to the TNM staging system, first-degree family history was not associated with survival in all patients, hepatitis B virus-positive patients, as well as male patients. Multivariate analysis revealed that first-degree family history was not a prognostic factor, either for OS or DFS. Conclusion: A first-degree family history of HCC is not associated with its patients' prognosis after hepatectomy.

via World Journal of Surgical Oncology

Benign metastasizing leiomyoma of the lung

Benign leiomyomas of the uterus are uncommonly found in association with benign smooth muscle tumors beyond the confines of the uterus. Benign metastasizing leiomyoma (BML) is a rare disease in which the lung is described to be the most afflicted extrauterine organ. We present a brief review of the literature, along with case reports for four patients who were followed up after resection of a pulmonary lesion or after pathological confirmation by biopsy. The clinical course of BML varies from chronic asymptomatic appearance to rapid progression, leading to respiratory failure and death. Our BML patients did not complain of pulmonary symptoms, such as cough, dyspnea, or chest tightness. Pathology revealed benign leiomyomas with no atypia and mitotic activity <5 per 10 high-power field. Immunohistochemical staining was positive for actin and desmin. A standard treatment for BML has not yet been established. Because of the hormone-sensitive characteristics of BML, treatments are based on hormonal manipulation along with either surgical or medical oophorectomy. Benign metastasizing leiomyoma can be observed in postmenopausal women. We observed four patients who did not receive adjuvant hormonal therapy because they were postmenopausal or perimenopausal. All patients are still healthy and show no evidence of recurrence or progression of the disease.

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Expression of epidermal growth factor receptor is an independent prognostic factor for esophageal squamous cell carcinoma

Background: The overall survival of patients with esophageal squamous cell carcinoma (ESCC) remains poor. Prognostic predictions in ESCC are usually based on histological assessment of tumor invasion and lymph node metastasis, but a biomarker with better predictive accuracy could be more useful. Because overexpression of epidermal growth factor receptor (EGFR) has been associated with poor prognosis, this study investigated whether EGFR is an independent prognostic factor for overall survival and disease-free survival of ESCC patients. Methods: ESCC tissue specimens from 243 patients obtained during surgical resection between 1980 and 1997 were retrieved for immunohistochemical analysis of EGFR expression. Results: The data showed that EGFR protein was overexpressed in 187 of 243 (77%) ESCC tissues. Elevated expression was associated with higher pathologic tumor stages (P = 0.001), lymph node metastasis (P = 0.002), and higher Union for International Cancer Control (UICC) stage (P <0.0001), as well as poorer disease-free survival and overall survival of ESCC patients (P <0.0001). A multivariate analysis showed that overexpression of EGFR protein was an independent factor for disease-free survival (P = 0.003) and overall survival (P = 0.001) of these patients. Subgroup analysis of patients with stage IIA (UICC 2002) showed that EGFR overexpression was associated with poorer disease-free survival (P = 0.007) and overall survival (P = 0.010) of the patients in univariate analyses. Conclusions: The current study demonstrated that EGFR overexpression was an independent prognostic factor for overall survival and disease-free survival of ESCC patients. However, targeting of EGFR activity using gefitinib or erlotinib could be useful for clinical treatment of ESCC patients.

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A giant pregnancy-associated intra-abdominal desmoid tumour: not necessarily a contraindication for subsequent pregnancy

Desmoid tumours are rare mesenchymal tumours, often locally invasive and characteristically associated with a high local recurrence rate after resection. A potential aetiological role for female hormones is indicated. Pregnancy-associated desmoid tumours are almost exclusively located in the abdominal wall. An essential issue is how to counsel women who have had a pregnancy-associated desmoid tumour and subsequently wish to bear a child. A considerably rare case of a patient with a resection of a giant pregnancy-associated, 33 cm in diameter, intra-abdominal desmoid tumour is presented. After a subsequent pregnancy, the patient delivered healthy twins 26 months later. Fifty-four months after treatment, there are no signs of recurrent or second desmoid tumour. Although rarely located in the abdomen, pregnancy-associated desmoid tumours should be included in the differential diagnosis of intra-abdominal tumours detected during or shortly after pregnancy. Based on this case and a few others reported in the literature, subsequent pregnancy does not necessarily seem to be a risk factor for recurrent or new disease.

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Brachial plexus palsy after a left-side modified radical mastectomy with immediate latissimusdorsi flap reconstruction: report of a case

Brachial plexus injury is a rare complication during operation and anesthesia; it can occur as a result of various mechanisms such as inappropriate positioning, over-abduction and stretching the upper limbs. Brachial plexus injury can cause the poor function of the upper limb before recovery, and sometimes serious injury is unable to completely recovered the function permanently. Here, we report a female breast cancer patient who sustained a left brachial plexus palsy after modified radical mastectomy with immediate breast reconstruction with latissimusdorsi flap (LDF). The patient had fully recovered with normal function of her left upper limb six months postoperation after conservative treatment.

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Effect of blockade of the EGF system on wound healing in patients vaccinated with CIMAvax(R) EGF

Background: The epidermal growth factor receptor (EGFR) signaling system is frequently unbalanced in human malignancies due to increased ligand production, receptor overexpression, receptor mutations, and/or cross-talk with other receptor systems. For this reason, the EGFR is an attractive target for anticancer therapy. The epidermal growth factor also plays an important role in regulating multiple facets of cutaneous wound healing, including inflammation, wound contraction, proliferation, migration, and angiogenesis. In the Center of Molecular Immunology, a cancer vaccine is produced (CIMAvax(R) EGF) that blocks the binding of EGF to its receptor. This blockade causes a significant inverse association between the anti-EGF antibody titers and EGF concentration. Around 1,500 patients with non-small cell lung cancer have been treated, showing that this vaccine is safe, immunogenic, increases survival and improves quality of life. Taking into account the therapeutic benefits of CIMAvax(R) EGF vaccination and the role of EGF-EGFR system in the wound healing process, we decided to conduct a retrospective research with the aim of determining the effect to the CIMAvax(R) EGF vaccine on the wound healing process in patients undergoing surgical treatment. Methods: Medical records of 452 vaccinated patients were reviewed and only six patients receiving surgical treatment were identified. Further information about these six patients was obtained from source documents, including medical records and operative reports using an observational list that included different variables. Post-surgical wound healing complications were identified using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTC) version 3.0. Results: None of the six patients operated on presented adverse events related to the wound healing, that is to say, no wound dehiscence, wound infection, delayed wound healing, fistula formation, abscess formation or hemorrhage/bleeding associated with surgery during treatment with CIMAvax(R) EGF occurred. Conclusions: These results suggest that the use of CIMAvax(R) EGF does not produce a deleterious effect in the wound healing process.

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Primary medulla oblongata germinomas: two case reports and review of the literature

An intracranial germinoma is a tumor that is sensitive to radiotherapy. As medulla oblongata germinomas are extremely rare, determining an accurate preoperative diagnosis is challenging. Two cases of medulla oblongata lesions were surgically treated, and a postoperative diagnosis of germinoma was determined in both of the cases. The tumor in one patient completely resolved after a treatment course consisting of surgical intervention, radiotherapy and chemotherapy; the other patient, who did not receive any type of adjuvant treatment after surgery, suffered from tumor relapse and died from pneumonia 8 months following surgery. A preoperative diagnosis of medulla oblongata germinoma is difficult because of the lack of specific clinical signs and symptoms. If the correct diagnosis is reached, patients can have a favorable prognosis with proper evaluation and treatment. An invasive operation can potentially lesion and impair the function of the medulla oblongata, which is fatal to the patient.

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Surgical resection should be taken into consideration for the treatment of small gastric gastrointestinal stromal tumors

Background: The National Comprehensive Cancer Network (NCCN) recommends conservative follow-up for gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. The aim of the present study was to investigate the clinical and pathological features of small gastric GISTs, re-evaluate the risk potential, and discuss the treatment strategy of small gastric GISTs. Methods: In this retrospective study, 63 cases of small gastric GISTs (less than 2 cm) were resected surgically from May 2010 to March 2013 in our department. Clinicopathological factors were collected and the malignant potential of small gastric GISTs was analyzed. Results: The mitotic index of 14 out of 63 cases (22.22%) exceeded 5. The malignant potential of small gastric GISTs was related to tumor location (P = 0.0218). The mitotic index of 4 out of 8 GISTs (50%) located in gastric cardia exceeded 5, 8 out 28 GISTs (28.57%) located in the gastric fundus exceeded 5, and only 2 out of 27 GISTs (7.41%) located in the gastric body exceeded 5. We also discovered a good consistency between mitotic index and Ki-67 expression of small gastric GISTs. Conclusions: Gastric GISTs less than 2 cm also have malignant potential. Thus, we recommended surgical resection of all small gastric GISTs once diagnosed.

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MT1-MMP in breast cancer: induction of VEGF-C correlates with metastasis and poor prognosis

Background: Recent evidence suggests that vascular endothelial growth factor-C (VEGF-C)- dependent tumour production promotes lymphangiogenesis, while membrane-type matrix 1 metalloproteinase (MT1-MMP) is involved in the critical steps leading to carcinogenesis. However, the role of MT1-MMP in lymphangiogenesis and lymphatic metastasis remains poorly understood. In the present study, we investigated the relationship between MT1-MMP and VEGF-C in human breast cancer and correlated MT1-MMP and VEGF-C expression with lymphangiogenesis and prognosis. Methods: MT1-MMP and VEGF-C levels were compared in five breast carcinoma cell lines. We used a membrane invasion assay to assess the effect of MT1-MMP and VEGF-C expression, as well as anti-MT1-MMP and VEGF-C antibodies, on cancer cell invasion. We further assessed MT1-MMP and VEGF-C immunoreactivity and lymph vessels in a cohort of human breast cancer specimens (n = 106) and associated MT1-MMP and VEGF-C expression with clinicopathological parameters, such as lymphatic vessel density (LVD), and patient prognosis. Results: MT1-MMP and VEGF-C expression differed among the five breast cancer cell lines and MT1-MMP and VEGF-C expression were correlated with tumour cell invasion. VEGF-C mRNA expression levels and invasive activity of MDA-MB-231 cells was inhibited by an anti-MT1-MMP antibody in a concentration-dependent manner. A significant correlation was found between the expression of MT1-MMP and VEGF-C in breast cancer patient samples and elevated MT1-MMP and VEGF-C expression was associated with higher LVD, lymph node metastasis, cancer stage, and a decline in overall survival rates. Conclusions: Our data demonstrate that MT1-MMP expression is closely correlated with VEGF-C expression, and that MT1-MMP promotes lymphangiogenesis by up-regulating VEGF-C expression in human breast cancer. Thus, elevated MT1-MMP may serve as a significant prognostic factor in breast cancer.

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Pulmonary artery pseudoaneurysm after a left upper sleeve lobectomy

A 55-year-old man was re-admitted for persistent hemoptysis and high fever three weeks after an initial left upper sleeve lobectomy for a central squamous lung cancer tumor. Pulmonary artery pseudoaneurysm and pulmonary infection were confirmed by multidetector computed tomography angiography and subsequent emergency completion pneumonectomy. The development of pulmonary artery pseudoaneurysm, secondary to post-operative pulmonary infection and pulmonary vascular manipulation, is rare and prompt surgical manipulation is mandatory.

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Inhibition of protein kinase CK2 with the clinical-grade small ATP-competitive compound CX-4945 or by RNA interference unveils its role in acute myeloid leukemia cell survival, p53-dependent apoptosis and daunorubicin-induced cytotoxicity

Background: The involvement of protein kinase CK2 in sustaining cancer cell survival could have implications also in the resistance to conventional and unconventional therapies. Moreover, CK2 role in blood tumors is rapidly emerging and this kinase has been recognized as a potential therapeutic target. Phase I clinical trials with the oral small ATP-competitive CK2 inhibitor CX-4945 are currently ongoing in solid tumors and multiple myeloma. Methods: We have analyzed the expression of CK2 in acute myeloid leukemia and its function in cell growth and in the response to the chemotherapeutic agent daunorubicin We employed acute myeloid leukemia cell lines and primary blasts from patients grouped according to the European LeukemiaNet risk classification. Cell survival, apoptosis and sensitivity to daunorubicin were assessed by different means. p53-dependent CK2-inhibition-induced apoptosis was investigated in p53 wild-type and mutant cells. Results: CK2alpha was found highly expressed in the majority of samples across the different acute myeloid leukemia prognostic subgroups as compared to normal CD34+ hematopoietic and bone marrow cells. Inhibition of CK2 with CX-4945, K27 or siRNAs caused a p53-dependent acute myeloid leukemia cell apoptosis. CK2 inhibition was associated with a synergistic increase of the cytotoxic effects of daunorubicin. Baseline and daunorubicin-induced STAT3 activation was hampered upon CK2 blockade. Conclusions: These results suggest that CK2 is over expressed across the different acute myeloid leukemia subsets and acts as an important regulator of acute myeloid leukemia cell survival. CK2 negative regulation of the protein levels of tumor suppressor p53 and activation of the STAT3 anti-apoptotic pathway might antagonize apoptosis and could be involved in acute myeloid leukemia cell resistance to daunorubicin.

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Association of body mass index and smoking on outcome of Chinese patients with colorectal cancer

Background: The impact of body mass index (BMI) on the prognosis of patients with colorectal cancer remains largely unknown, particularly in Asian populations. Therefore, the aim of this study was to examine the influence of BMI on clinicopathological characteristics and mortality of Chinese colorectal cancer patients. Methods: The study cohort consisted of 525 patients who were diagnosed with colorectal cancer and underwent radical surgery at the second hospital of Harbin Medical University between June 2004 and August 2011. Study participants were divided into two BMI categories: normal weight (BMI <23 kg/m2) and overweight (BMI >=23 kg/m2). Results: Of 525 patients, 208 patients (39.6%) were included in the normal-weight group and 317 patients were included in the overweight group. During the mean follow-up period of 48.8 months, 89 patients had disease recurrence and 131 deaths occurred. High BMI was significantly correlated with younger age, presence of diabetes, alcohol consumption, distal colon tumors, amount of lymph node harvested and pathological stage. No statistically significant correlation was found between high BMI and progression-free survival (PFS) or overall survival (OS) when the total group of patients was considered (P = 0.077 and P = 0.701, respectively). Cigarette-smoking patients had significantly shorter OS than patients who had never smoked (hazard ratio = 1.613, 95% confidence interval = 1.133 to 2.296; P = 0.008), and this difference in OS remained significant in multivariate analysis. Cigarette-smoking patients did not have significantly different PFS compared with patients who had never smoked. Conclusion: There was no significant correlation between obesity and outcomes of patients with colorectal cancer. In addition, our findings support the claims that cigarette smoking may be partially responsible for the divergent mortality of patients with colorectal cancer.

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The in vitro influences of epidermal growth factor and heregulin-beta1 on the efficacy of trastuzumab used in Her-2 positive breast adenocarcinoma

Background: Human epidermal growth factor receptor-2 (Her-2) is over expressed in approximately 25-30% of all primary breast tumors resulting in a distinctive breast cancer subtype associated with a poor prognosis and a decrease in overall survival. Trastuzumab (Herceptin(R)), an anti-Her-2 monoclonal antibody, has dramatically altered the prognosis of Her-2 positive breast cancer. Trastuzumab is, however, associated with primary and acquired resistance.Aim and methods: To investigate the in-vitro effects of trastuzumab on cell viability (tetrazolium conversion assay), cell cycling (propidium iodide staining), apoptosis (executioner caspases and annexin-V) and relative surface Her-2 receptor expression (anti-Her-2 affibody molecule) in Her-2-positive (SK-Br-3) and oestrogen receptor positive (MCF-7) breast adenocarcinoma cells and to determine potential augmentation of these effects by two endogenous ligands, epidermal growth factor (EGF) and heregulin-beta1 (HRG- beta1). Results: Cell viability was in SK-Br-3 cells decreased by exposure to trastuzumab. This was associated with G1 accumulation and decreased relative surface Her-2 receptor density, supporting the cytostatic nature of trastuzumab in vitro. SK-Br-3 cells exposed to EGF and heregulin-beta1 produced differential cell responses alone and in combination with trastuzumab, in some instances augmenting cell viability and cell cycling. Relative surface Her-2 receptor density was reduced substantially by trastuzumab, EGF and heregulin-beta1. These reductions were amplified when ligands were used in combination with trastuzumab. Conclusion: Cell type specific interactions of endogenous ligands appear to be dependent on absolute Her-receptor expression and cross activation of signaling pathways. This supports the notion that receptor density of Her-family members and multiplicity of growth ligands are of mutual importance in breast cancer cell proliferation and therefore also in resistance associated with trastuzumab.

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Immune response after systematic lymph node dissection in lung cancer surgery: changes of interleukin-6 level in serum, pleural lavage fluid, and lung supernatant in a dog model

Background: Systematic nodal dissection (SND) is regarded as a core component of lung cancer surgery. However, there has been a concern on the increased morbidity associated with SND. This study was performed to investigate whether or not SND induces significant immune response. Methods: Sixteen dogs were divided into two groups; group 1 (n = 8) underwent thoracotomy only, and group 2 (n = 8) underwent SND after thoracotomy. We compared interleukin-6 (IL-6) levels in serum, pleural lavage fluid and lung supernatant at the time of thoracotomy (T0) and at 2 h(T1) after thoracotomy (group 1) or SND (group 2). Severity of inflammation and IL-6 expression in lung tissue were evaluated in a semi-quantitative manner. Results: The operative results were comparable. IL-6 was not detected in serum in either group. IL-6 in pleural lavage fluid marginally increased from 4.75 +/- 3.74 pg/mL at T0 to 19.75 +/- 8.67 pg/mL at T1 in group 1 (P = 0.112), and from 7.75 +/- 5.35 pg/mL to 17.72 +/- 8.58 pg/mL in group 2 (P = 0.068). IL-6 in lung supernatant increased from 0.36 +/- 0.14 pg/mL/mg to 1.15 +/- 0.17 pg/mL/mg in group 1 (P = 0.003), and from 0.25 +/- 0.08 pg/mL/mg to 0.82 +/- 0.17 pg/mL/mg in group 2 (P = 0.001). However, the degree of increase in IL-6 in pleural lavage fluid and lung supernatant were not different between two groups (P = 0.421 and P = 0.448). There was no difference in severity of inflammation and IL-6 expression between groups. Conclusions: SND did not increase IL-6 in pleural lavage fluid and lung supernatant. This result suggests that SND could be routinely performed in lung cancer surgery without increasing the significant inflammatory response.

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MiRNA-497 regulates cell growth and invasion by targeting cyclin E1 in breast cancer

Background: MicroRNAs are a class of endogenous single strand non-coding RNAs that are involved in many important physiological and pathological processes. The purpose of this study was to examine the expression levels of miR-497 in human breast cancer and its function in MDA-MB-231 breast cancer cells. Methods: Quantitative polymerase chain reaction was used to measure the expression levels of miR-497 in 40 breast cancer specimens and adjacent normal breast tissues. MTT assays, colony formation assays, wound healing assays, transwell assays and cell cycle assays were used to explore the potential function of miR-497 in MDA-MB-231 breast cancer cells. Dual-luciferase reporter assays were performed to analyze the regulation of putative target of miR-497, and western blot assays were used to validate the dual-luciferase results. Results: The expression of miR-497 in breast cancer specimens was lower than adjacent normal tissues (P < 0.05). Overexpression of miR-497 inhibited cellular growth, suppressed cellular migration and invasion, and caused a G1 arrest. Dual-luciferase reporter assays showed that miR-497 binds the 3[prime]-untranslated region (3[prime]-UTR) of cyclin E1, suggesting that cyclin E1 is a direct target of miR-497. Western blot assays confirmed that overexpression of miR-497 reduced cyclin E1 protein levels. Conclusions: MiR-497 may act as a tumor suppressor gene in breast cancer. Inhibited cellular growth, suppressed cellular migration and invasion, and G1 cell cycle arrest were observed upon overexpression of miR-497 in cells, possibly by targeting cyclin E1. These results indicate miR-497 could be considered a therapeutic target for the development of treatment for breast cancer.

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Microsurgical management of giant malignant peripheral nerve sheath tumor of the scalp: two case reports and a literature review

Malignant peripheral nerve sheath tumors of the scalp are rare lesions of the nervous system. Only 14 cases have been reported to date. The field of neurosurgery has struggled with diagnosing and treating these tumors. In this report, we present two cases of giant malignant peripheral nerve sheath tumors of the scalp and retrospectively analyze the clinical features, imaging findings, pathological features, and prognoses of these two patients. Each underwent microsurgery and radiotherapy. In addition, based on a literature review, we discuss the diagnostic and therapeutic strategies used to treat these unusual lesions.

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First report of granulomatous mastitis associated with Sjogren's syndrome

Granulomatous mastitis is a rare and often considered as idiopathic disease. However, clinical examination and thorough diagnostic investigations have to be carried out in order to identify cases that are secondary to infections or systemic diseases since these forms may be cured with appropriate etiologic treatment. To the best of our knowledge, this report is the first to describe the association of granulomatous mastitis with Sjogren's syndrome. We discuss the clinical, pathological and therapeutic implications of this association.

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A meta-analysis: neoadjuvant chemotherapy versus primary surgery in ovarian carcinoma FIGO stageIII and IV

Background: The purpose of the current study is to analyze the existing data comparing neoadjuvant chemotherapy with primary debulking surgery (PDS) in patients with advanced ovarian carcinoma. Methods: Patients with stage IIIC and IV ovarian cancer were identified from articles in Medline, PubMed, Cochrane Library, and EMBASE database (1989 to February 2013). Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration's risk of bias tool was used. Meta-analysis on literatures was conducted by using RevMan 5.2 software. Results: Two high-quality randomized controlled trials (RCTs) met the inclusion criteria. These multicenter trials randomized 1,220 women with stage IIIc/IV ovarian cancer to NACT or PDS followed by chemotherapy. There were no significant differences between the study groups with regard to overall survival (OS) (1,120 women; HR 0.98; 95% CI 0.85 to 1.14) or progression-free survival (PFS) (1,120 women; HR 1.03; 95% CI 0.91 to 1.16). Conclusion: There was no statistical difference in median OS and PFS between the two treatment groups. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account respectability, age, histology, stage, and performance status.

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Palliative chemoradiation boosts survival, QoL in poor-prognosis NSCLC

C hemoradiation is superior to chemotherapy alone with respect to both survival and quality of life in patients with inoperable non-small-cell lung cancer, a phase III trial has found.

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HIV infection heralds worse outcomes in NSCLC

Infection with HIV is an indicator of poor prognosis in patients with non-small-cell lung cancer, analysis of epidemiologic data indicates.

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Identification of exon 19 and 21 mutations of EGFR gene in Chinese patients with esophageal squamous cell carcinoma

Background: Although epidermal growth factor receptor (EGFR) inhibitor treatment showed modest response in several clinical trials in esophageal squamous cell carcinoma (ESCC) patients, it has been reported that the frequency of EGFR mutations varied largely. The aim of this study was to investigate the existence of EGFR mutations in Chinese esophageal squamous cell carcinomas. Methods: Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 127 randomly selected Chinese patients with ESCC. The most common EGFR mutations, including in-frame deletions in exon 19 and base substitutions in exon 21, were detected by denaturing high performance liquid chromatography (DHPLC) and direct sequencing simultaneously. K-RAS mutations in codons 12 and 13 were detected by direct sequencing. Results: In this study, L858R missense mutations of the EGFR gene were found in 8 out of 127 patients (6.3%) by DHPLC but no mutation was observed by direct sequencing. In addition, K-RAS mutation was detected in 2 out of 127 (1.6%) patients by direct sequencing. Conclusions: The incidence of EGFR mutations was relatively high using DHPLC method but no mutation with direct sequencing in Chinese ESCC patients.

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IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells

Background: The role of IGF binding protein 2 (IGFBP2) in cancer development is intriguing. Previously we identified IGFBP2 as an extrinsic factor that supports the activity of hematopoietic stem cells (HSCs).Methods and results: Here we investigated the role of IGFBP2 in in human leukemia cells and in the retroviral AML1-ETO9a transplantation acute myeloid leukemia (AML) mouse model. Results: IGFBP2 is highly expressed in certain human AML and acute lymphoblastic leukemia (ALL) cells. Inhibition of expression of endogenous IGFBP2 in human leukemia cells led to elevated apoptosis and decreased migration and, consistently, to decreased activation of AKT and other signaling molecules. We also studied the effects of IGFBP2 knockout in the retroviral AML1-ETO9a transplantation AML mouse model. The deletion of IGFBP2 in donor AML cells significantly decreased leukemia development in transplanted mice. Lack of IGFBP2 resulted in upregulation of PTEN expression and downregulation of AKT activation, in the mouse AML cells. The treatment of IGFBP2 deficient AML cells with a PTEN inhibitor restored the wild-type colony forming ability. The deletion of IGFBP2 also led to decreased AML infiltration into peripheral organs and tissues, suggesting that IGFBP2 is required for the migration of AML cells out of bone marrow. Conclusion: IGFBP2 is a critical cell-autonomous factor that promotes the survival and migration of acute leukemia cells.

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New clinical application of high-intensity focused ultrasound: local control of synovial sarcoma

High-intensity focused ultrasound (HIFU) is playing an increasingly important role in cancer therapy. Primary synovial sarcomas of the chest wall are extremely rare. We report the first case of noninvasive HIFU therapy for the control of synovial sarcoma. A 51-year-old man was diagnosed with spindle cell sarcoma on the left chest wall through lumpectomy. After four cycles of chemotherapy, local recurrence of the sarcoma was detected. Subsequent extended resection confirmed synovial sarcoma. After five cycles of a new chemotherapy option, the sarcoma relapsed again. Then the patient received five courses of HIFU; this completely ablated the sarcoma without complications. No chemotherapy, radiotherapy, or biological therapy has been applied since. Now the patient is stable and has a high quality of life.

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BMP4, a new prognostic factor for glioma

Background: The expression status of bone morphogenetic protein 4 (BMP4) in gliomas is still unclear by now. We try to investigate the relationship between BMP4 expression and the biological behavior of gliomas in order to lay a foundation for the management of these tumors. Methods: A total of 630 patients with glioma were enrolled in the study from January 2002 to January 2008. The expression status of BMP4 in gliomas was evaluated by RT-PCR and immunohistochemistry. The relationships between BMP4 expression and clinicopathological parameters and between BMP4 expression and prognosis were also studied. Results: The expression of BMP4 in tumor tissues was significantly lower than that in the paracancer tissues at both mRNA and protein levels (P = 0.01 and 0.001, respectively). Univariate analysis showed that BMP4 expression was closely related to extent of resection, Ki-67 expression, and the WHO grade (P = 0.001, 0.001, and 0.001, respectively), but it was not related to age, sex, or the Karnofsky Performance Status (KPS) score (P = 0.099, 0.472, and 0.201, respectively). Finally, Ki-67 expression and the WHO grade were found to be related to BMP4expression using logistic regression (P = 0.001 and 0.001, respectively). Interestingly, we found that the expression of BMP4 was significantly related to distant glioma metastasis. Cox regression analysis identified the KPS score, extent of resection, Ki-67 expression, WHO grade, and BMP4 expression as independent prognostic factors (P = 0.044, 0.010, 0.002, 0.001, and 0.001, respectively). Conclusions: BMP4 is differentially expressed in glioma patients and is closely related to the biological behavior of gliomas. BMP4 expression was found to be a strong predictor of distant metastasis and postoperative prognosis.

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Successful combination chemotherapy with irinotecan hydrochloride and cisplatin for primary gastric small cell carcinoma: report of a case

Primary gastric small cell carcinoma is a rare and aggressive malignant disease with a poor prognosis that was first reported in 1976 by Matsusaka et al. The incidence is very low and the clinicopathological features are similar to those of small cell lung carcinoma.We herein report a case of successful treatment by combination chemotherapy consisting of irinotecan hydrochloride and cisplatin for primary gastric small cell carcinoma. The patient was a 71-year-old male who was admitted to a local hospital with anemia. Gastrointestinal endoscopy revealed the presence of advanced gastric carcinoma at the upper region of the stomach. The patient underwent surgery, and the pathological diagnosis was small cell carcinoma due to the presence of the typical features of small round cells with scant cytoplasm that were positive for synaptophysin and chromogranin A in the resected specimen. The patient underwent subsequent combination chemotherapy, which provided him with over 1 year of survival and a good quality of life. We also present a review of the literature regarding chemotherapy for primary gastric small cell carcinoma.

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Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs

Background: Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-beta1-induced NSCLC cells that are reminiscent of EMT cells. Methods: Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled receptor smoothened in the Hh pathway. Not all NSCLC patients are likely to benefit from EGFR-TKIs and, therefore, cisplatin was used to further demonstrate a role of inhibition of Hh signaling in sensitization of resistant EMT cells. Specific pre- and anti-miRNA preparations were used to study the mechanistic involvement of miRNAs in drug resistance mechanism. Results: siRNA-mediated inhibition as well as pharmacological inhibition of Hh signaling abrogated resistance of NSCLC cells to erlotinib and cisplatin. It also resulted in re-sensitization of TGF-beta1-induced A549 (A549M) cells as well the mesenchymal phenotypic H1299 cells to erlotinib and cisplatin treatment with concomitant up-regulation of cancer stem cell (CSC) markers (Sox2, Nanog and EpCAM) and down-regulation of miR-200 and let-7 family miRNAs. Ectopic up-regulation of miRNAs, especially miR-200b and let-7c, significantly diminished the erlotinib resistance of A549M cells. Inhibition of Hh signaling by GDC-0449 in EMT cells resulted in the attenuation of CSC markers and up-regulation of miR-200b and let-7c, leading to sensitization of EMT cells to drug treatment, thus, confirming a connection between Hh signaling, miRNAs and drug resistance. Conclusions: We demonstrate that Hh pathway, through EMT-induction, leads to reduced sensitivity to EGFR-TKIs in NSCLCs. Therefore, targeting Hh pathway may lead to the reversal of EMT phenotype and improve the therapeutic efficacy of EGFR-TKIs in NSCLC patients.

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Obstructive jaundice due to ampullary metastasis of renal cell carcinoma

Renal cell carcinoma is often characterized by the presence of metachronous metastases in unusual sites. The presence of isolated metastases is treated with surgical excision with good anticipated results. On the other hand, systemic chemotherapy is administered in the context of metastatic spread, usually sunitib or sorafenib. In such cases, however, the presence of symptomatic foci calls for minimal intervention.We present a case of a 77-year-old patient who presented with obstructive jaundice due to an ampullary mass. Endoscopic excision and biopsy set the diagnosis of metastatic renal cell carcinoma. Consequently, imaging studies revealed the presence of multiple foci in the lungs and bone. Therefore, pancreatoduodenectomy was excluded and the patient underwent endoscopic ampullectomy and was set to oral sunitinib. Interestingly, despite generalized spread, local control was achieved until the patient succumbed to carcinomatosis.Painless obstructive jaundice in a patient with history of renal cancer and negative computed tomography scanning for pancreatic or other causes of obstruction should alert for prompt investigation for an ampullary metastasis.

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Metastatic Merkel cell carcinoma (MCC) of pancreas and breast: a unique case

Merkel cell carcinoma (MCC) is a rare potentially fatal skin tumor affecting older and immunosuppressed individuals. It is highly malignant with high rates of metastasis and poor survival.We present a case of a 67-year-old woman with a palpable mass in the upper abdomen. An abdominal CT revealed a mass in the tail of the pancreas. Two weeks before, lumpectomy of a 3.5 cm tumor of the left breast had been performed. Histology showed a primary neuroendocrine carcinoma of the mammary gland. The patient's medical history was significant for a 0.7 x 0.9 cm MCC removed from her left forearm 2.5 years ago. There was no evidence of vascular involvement or peritoneal disease and by all criteria was resectable. A somatostatin receptor scintigraphy showed an enhanced uptake in the pancreatic tail region. The tumor was immunohistochemically strong staining for synaptophysin and CD56. The diagnosis of a metastatic-MCC in the tail of the pancreas was made. Further histological investigation of the prior removed neuroendocrine breast tumor and the MCC of the left forearm confirmed neuroendocrine origin and identical histology to the previously resected MCC of the left forearm. In this article, we aim to highlight that MCC has the potential to spread even in unusual organs, such as pancreas or breast, and therefore a diligent follow-up should be applied in patients with MCC.

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Investigating citrullinated proteins in tumour cell lines

Background: The conversion of arginine into citrulline, termed citrullination, has important consequences for the structure and function of proteins. Studies have found PADI4, an enzyme performing citrullination, to be highly expressed in a variety of malignant tumours and have shown that PADI4 participates in the process of tumorigenesis. However, as citrullinated proteins have not been systematically investigated in tumours, the present study aimed to identify novel citrullinated proteins in tumours by 2-D western blotting (2-D WB). Methods: Two identical two-dimensional electrophoresis (2-DE) gels were prepared using extracts from ECA, H292, HeLa, HEPG2, Lovo, MCF-7, PANC-1, SGC, and SKOV3 tumour cell lines. The expression profiles on a 2-DE gel were trans-blotted to PVDF membranes, and the blots were then probed with an anti-citrulline antibody. By comparing the 2-DE profile with the parallel 2-D WB profile at a global level, protein spots with immuno-signals were collected from the second 2-DE gel and identified using mass spectrometry. Immunoprecipitation was used to verify the expression and citrullination of the targeted proteins in tumour cell lines. Results: 2-D WB and mass spectrometry identified citrullinated alpha-enolase (ENO1), heat shock protein 60 (HSP60), keratin 8 (KRT8), tubulin beta (TUBB), T cell receptor chain and vimentin in these cell lines. Immunoprecipitation analyses verified the expression and citrullination of ENO1, HSP60, KRT8, and TUBB in the total protein lysates of the tumour cell lines. Conclusions: The citrullination of these proteins suggests a new mechanism in the tumorigenic process.

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Surgical management of hepatocellular carcinoma with tumor thrombi in the inferior vena cava or right atrium

Background: The prognosis for advanced hepatocellular carcinoma (HCC) with tumor thrombi in the inferior vena cava (IVC) or right atrium (RA) is poor, and there is no established effective treatment for this condition. Thus study aimed to evaluate the efficacy of surgical resection and prognosis after surgery for such cases. Methods: Between January 1990 and December 2012, 891 patients underwent hepatectomy for HCC at our institution. Of these, 13 patients (1.5%) diagnosed with advanced HCC with tumor thrombi in the IVC or RA underwent hepatectomy and thrombectomy. Data detailing the surgical outcome were evaluated and recurrence-free and overall survival rates were calculated using the Kaplan-Meier method. Results: Seven patients had an IVC thrombus and six had an RA thrombus. Extra-hepatic metastasis was diagnosed in 8 of 13 patients. Surgical procedures included three extended right lobectomies, three extended left lobectomies, five right lobectomies, and two sectionectomies. Right adrenal gland metastases were excised simultaneously in two patients. All IVC thrombi were removed under hepatic vascular exclusion and all RA thrombi were removed under cardiopulmonary bypass (CPB). Four patients (30.8%) experienced controllable postoperative complications, and there was no surgical mortality. The mean postoperative hospital stay for patients with IVC and RA thrombi was 23.6 +/- 12.5 days and 21.2 +/- 4.6 days, respectively. Curative resection was performed in 5 of 13 cases. The 1- and 3-year overall survival rates were 50.4%, and 21.0%, respectively, and the median survival duration was 15.3 months. The 1- and 3-year overall survival rates for patients who underwent curative surgical resection were 80.0% and 30.0%, respectively, with a median survival duration of 30.8 months. All patients who underwent curative resection developed postoperative recurrences, with a median recurrence-free survival duration of 3.8 months. The 1-year survival rate for patients who underwent noncurative surgery and had residual tumors was 29.2%, with a median survival duration of 10.5 months. Conclusions: Aggressive surgical resection for HCC with tumor thrombi in the IVC or RA can be performed safely and may improve the prognoses of these patients. However, early recurrence and treatment for recurrent or metastatic tumors remain unresolved issues.

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Changing trends in symptomatology, diagnostics, stage and survival of prostate cancer in Northern Finland during a period of 20 years

Background: Prostate cancer is the most common cancer among men in many countries. The aim of the present study was to find out how the symptoms leading to a diagnosis, diagnostic procedures and stages of the disease among prostate cancer patients have changed over a period of 20 years. Methods: This retrospective chart review consisted of 421 prostate cancer patients whose treatment was started in the years 1982, 1987, 1992, 1997 and 2002 at the Oulu University Hospital. Earlier prostatic disorders, specific urological symptoms, diagnostic procedures, the TNM classification and histological grade were recorded. Results: The number of symptom-free prostate cancer patients increased over the 20 years, as did the number of men suffering from chronic prostatitis, although the latter increase was not statistically significant. A drop in the number of clinical T4 cases and increase of clinical T1 and clinical T2 cases was recorded but no clear change in the histological distribution occurred. The 5-year prostate cancer-specific survival improved significantly over the 20 years. The urologist was found to be the person who was contacted first most often. Conclusions: Our data indicate that the number of prostate cancer patients has increased hugely over the period from 1982 to 2002 and although the clinical T stage has moved towards earlier stages, the proportion of well differentiated cancers remains low, so that most patients have clinically significant cancer with the need of some form of therapy. Further, prostate cancer-specific survival improved significantly over the period.

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Endoscopic and clinicopathological patterns of esophageal cancer in Tanzania: experiences from two tertiary health institutions

Background: Esophageal cancer is one of the most serious gastrointestinal cancer worldwide, owing to its rapid development and fatal prognoses in most cases. There is a paucity of published data regarding esophageal cancer in Tanzania and the study area in particular. This study was conducted to describe the endoscopic and clinicopathological patterns of esophageal cancer in this part of the world. The study provides baseline local data for future comparison. Methods: This was a retrospective study of histologically confirmed cases of esophageal cancer seen at Bugando Medical Center and Muhimbili National Hospital between March 2008 and February 2013. Data were retrieved from medical record computer database and analyzed using SPSS computer software version 17.0. Results: A total of 328 esophageal cancer patients were enrolled in the study, representing 25.3% of all malignant gastrointestinal tract tumors. The male to female ratio was 2.2:1. The median age of patients at presentation was 47 years. The majority of patients (86.6%) were peasants coming from the rural areas. Smoking and alcohol consumption were documented in 74.7% and 61.6% of patients respectively. Family history of esophageal cancer was reported in 4.6% of cases. The majority of patients (81.7%) presented late with advanced stage of cancer. Progressive dysphagia and weight loss were the most common presenting symptoms occurring in all patients. The middle third esophagus (58.5%) was the most frequent anatomical site for esophageal cancer followed by lower third (27.4%) and upper third esophagus (10.4%). Squamous cell carcinoma (96.0%) was the most common histopathological type. Adenocarcinoma occurred in 13 (4.0%) patients. TNM staging was documented in only 104 (31.7%) patients. Of these, 102(98.1%) patients were diagnosed with advanced esophageal cancer (Stages III and IV). According to tumor grading, most of tumors were moderately differentiated accounting for 56.1% of cases. Distant metastasis was documented in 43.3% of patients. Conclusion: Esophageal cancer is not uncommon in this region and shows a trend towards a relative young age at presentation and the majority of patients present late with advanced stage. There is a need for screening of high-risk populations and detecting esophageal cancer at an early stage in order to improve chances for successful treatment and survival.

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A safe anastomotic technique of using the transorally inserted anvil (OrVilTM) in Roux-en-Y reconstruction after laparoscopy-assisted total gastrectomy for proximal malignant tumors of the stomach

Background: To explore the safety and feasibility of the transorally inserted anvil (OrVilTM) in laparoscopy-assisted total gastrectomy for gastric cancer. Methods: From December 2010 to June 2011, a total of 28 patients underwent laparoscopy-assisted total gastrectomy with a Roux-en-Y-esophagojejunostomy anastomosis with OrVilTM. Perioperative treatments, intraoperative data, postoperative complications and hospital length of stay were evaluated. Results: There were no conversions to the open gastrectomy. The mean operation time was 143 minutes and the mean blood loss was 70 ml. Patients resumed an oral liquid diet on postoperative days 4 to 5. Two patients (7 %) who suffered postoperative aspiration pneumonia were cured by conservative treatment. The median hospital length of stay was 9.6 days (8 to 11 days), with no inhospital mortalities. The median follow-up time was 14.8 months (12 to 18 months), and postoperative endoscopic examination revealed no anastomosis stenosis in patients who had dysphagia. Conclusion: The use of the OrVilTM is technically feasible and relatively safe for Roux-en-Y reconstruction after laparoscopy-assisted total gastrectomy.

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Clinical significance of cytogenetic aberrations in bone marrow of patients with diffuse large B-cell lymphoma: prognostic significance and relevance to histologic involvement

Background: Although knowledge of the genetics of diffuse large B-cell lymphoma (DLBCL) has been increasing, little is known about the characteristics and prognostic significance of cytogenetic abnormalities and the clinical utility of cytogenetic studies performed on bone marrow (BM) specimens. To investigate the significance of isolated cytogenetic aberrations in the absence of histologic BM involvement, we assessed the implication of cytogenetic staging and prognostic stratification by a retrospective multicenter analysis of newly diagnosed DLBCL patients. Methods: We analyzed cytogenetic and clinical data from 1585 DLBCL patients whose BM aspirates had been subjected to conventional karyotyping for staging. If available, interphase fluorescence in situ hybridization (FISH) data were also collected from patients. Results: Histologic BM involvement were found in 259/1585 (16.3%) patients and chromosomal abnormalities were detected in 192 (12.1%) patients (54 patients with single abnormalities and 138 patients with 2 or more abnormalities). Isolated cytogenetic aberrations (2 or more abnormalities) without histologic involvement were found in 21 patients (1.3%). Two or more cytogenetic abnormalities were associated with inferior overall survival (OS) compared with a normal karyotype or single abnormality in both patients with histologic BM involvement (5-year OS, 16.5% vs. 52.7%; P < 0.001) and those without BM involvement (31.8% vs. 66.5%; P < 0.001). This result demonstrated that BM cytogenetic results have a significant prognostic impact that is independent of BM histology. The following abnormalities were most frequently observed: rearrangements involving 14q32, 19q13, 19p13, 1p, 3q27, and 8q24; del(6q); dup(1q); and trisomy 18. In univariate analysis, several specific abnormalities including abnormalities at 16q22-q24, 6p21-p25, 12q22-q24, and -17 were associated with poor prognosis. Multivariate analyses performed for patients who had either chromosomal abnormalities or histologic BM involvement, revealed IPI high risk, >= 2 cytogenetic abnormalities, and several specific chromosomal abnormalities, including abnormalities at 19p13, 12q22-q24, 8q24, and 19q13 were significantly associated with a worse prognosis..->. Conclusions: We suggest that isolated cytogenetic aberrations can be regarded as BM involvement and cytogenetic evaluation of BM improves staging accuracy along with prognostic information for DLBCL patients.

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Clinical features and outcomes of neck lymphatic metastasis in ovarian epithelial carcinoma

Background: Neck lymph node metastasis (NLNM) in epithelial ovarian cancer (EOC) is rare and treated as advanced stage cancer. However, ovarian cancer with lymphatic metastasis may manifest a different clinical course from peritoneal carcinomatosis. Methods: The authors retrospectively assessed 20 patients with EOC and pathologically diagnosed as NLNM between January 2001 and December 2010. The patients were divided into two groups according to the time of NLNM identification. Statistical methods included Kaplan-Meier, log-rank, and Cox regression analysis. Results: Eleven patients were diagnosed with NLNM at the same time of surgical exploration of EOC (Group A) and nine patients at cancer recurrence 43.3 months after initial surgery (Group B). In Group A, patients with tumors confined to the pelvic cavity had no recurrence or had isolated lymph node recurrence (ILNR), and survived longer than patients with abdominal tumor spreading (P = 0.0007). In Group B, 2 patients showed ILNR. The median survival time after NLNM was 42 months in Group A and 6 months in Group B (P = 0.01). Cox model demonstrated that non-serous histology, brain metastasis, and NLNM identified at cancer recurrence were major predictors for poor overall survival (Hazard ratio [HR] = 18.67, 6.93, and 4.52; P = 0.01, 0.02, and 0.04, respectively). Conclusions: A subgroup of EOC patients with NLNM who presented limited pelvic cancer had much better overall survival than patients who had cancer spreading beyond the pelvic cavity or were diagnosed with NLNM at cancer recurrence.

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Pituitary apoplexy induced by Gonadotropin-releasing hormone agonists for treating prostate cancer-report of first Asian case

We present the first Asian case of a 77-year-old man who developed pituitary apoplexy (PA) soon after gonadotropin-releasing hormone agonist (GnRHa) (leuprorelin) injection to treat prostate cancer. Headache, ophthalmoplegia, visual field deficit, nausea, and vomiting are the typical characteristics of pituitary apoplexy. Though the occurrence rate is rare, the consequence of this condition can vary from mild symptoms such as headache to life-threatening scenarios like conscious change. Magnetic resonance imaging is the best imaging modality to detect PA and sublabial trans-sphenoid pituitary tumor removal can resolve most of PA symptoms and is so far the best solution in consensus. We also review 11 previous reported cases receiving GnRHa for androgen deprivation therapy of prostate cancer, and hope to alert clinicians to use GnRHa with caution.

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Esophageal schwannoma: report of a case

Most tumorous lesions of the esophagus are esophageal cancers. Benign primary tumors of the esophagus are uncommon, and account for approximately 2% of all esophageal tumors. More than 80% of benign esophageal tumors are leiomyomas, with schwannomas being rare. A 55-year-old woman visited our internal medicine department with complaints of palpitations and discomfort during swallowing. A chest computed tomography scan showed a lobulated tumor (75 x 57 x 80 mm) in the upper to middle mediastinum, with homogenous inner opacity, compressing the esophagus. Upper gastrointestinal endoscopy revealed a smooth-surfaced elevated lesion covered with normal mucosa, and a schwannoma was diagnosed based on the biopsy result. The tumor was large. It was thus considered to be difficult to repair the esophagus by direct anastomosis after tumor resection. Therefore, subtotal esophagectomy and esophagogastrostomy in the right thorax were performed. Histopathological examination revealed spindle-shaped cells in a fasciculated and disarrayed architecture and nuclei in a palisading pattern. Immunohistochemical studies revealed S100 protein positivity and the absence of staining for alpha smooth muscle actin (alphaSMA), CD34 and CD117, thereby establishing the diagnosis of benign schwannoma. Her postoperative course was uneventful and there has been no evidence of recurrence to date.

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Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases

Background: Pulmonary sarcomatoid carcinoma is a diagnostically challenging group of tumors. It's a rare histologic subtype of non-small cell lung cancer.There are five subgroups of pulmonary sarcomatoid carcinoma, they are identified as pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. We explored the clinicopathologic features and prognostic factors of this tumor. Methods: We analyzed retrospectively the clinicopathological data of 51 patients with pulmonary sarcomatoid carcinoma who were treated in the First Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital and Henan People Hospital from January 2005 to December 2012. The correlation between prognosis and age, sex, smoking history, tumor size, TNM staging, and treatment modality was analyzed by the statistical software SPSS 17.0. The survival analysis was conducted using the Kaplan-Meier method. The factors influencing survival were analyzed using univariate (Log-rank) and multivariate (Cox) models. Results: The overall survival rates at 1, 2, 3 and 5 years were 45.5%, 35.8%, 28.2% and 20.1%, respectively. Cox univariate analyses revealed that age, tumor size, T stage, M stage, surgery or not, and postoperative chemotherapy or not, were prognostic factors. Cox multivariate analysis found that tumor size and M stage were independent prognostic factors for PSC. Conclusions: Due to its rarity and the lack of large-scale clinical trial evidence, few studies about PSC have been reported, its clinical and pathological characteristics remain unclear, and its preoperative diagnosis and investigation of novel treatment approaches are imperative. In our study, the main factors affecting the prognosis of tumor size and M staging are the crucial prognostic factors for PSC. Surgical resection and postoperative adjuvant chemotherapy might result in better prognosis.

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A retrospective analysis on the diagnostic value of ultrasound-guided percutaneous biopsy for peritoneal lesions

Background: Routine examinations have a low specificity and a low positive rate for the diagnosis of peritoneal lesions. This study aimed to evaluate the diagnostic value and safety of ultrasound-guided percutaneous peritoneal lesion biopsies in patients with ascites and/or abdominal distension with unclear causes. Methods: A retrospective analysis was performed in 153 consecutive patients with ascites and/or abdominal distension with unclear causes. All of the patients showed abnormalities of the peritoneum or greater omentum after ultrasonography, and underwent ultrasound-guided percutaneous biopsies using a Bard auto-biopsy gun with 18- or 16-gauge biopsy needles. Results: The success rate of the procedures was 100% (153/153) and the satisfaction rate of the tissue specimens in the biopsy was 91.5% (140/153). A specific histopathological diagnosis was made in 142 out of 153 patients, with an overall diagnostic accuracy of 92.8%. Among the diagnosed patients, 62 were peritoneal metastatic adenocarcinoma, 49 were peritoneal tuberculosis, 11 were peritoneal malignant mesothelioma, 8 were chronic peritoneal infections, 7 were pseudomyxoma peritonei, and 5 were primary peritoneal lymphoma. Only 11 patients did not get a pathologic diagnosis due to the lack of sufficient tissue specimen. No serious complications occurred. Conclusions: Ultrasound-guided percutaneous biopsy could be a simple, safe and accurate diagnostic method in patients with ascites and/or abdominal distension with unclear causes.

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Measures of health-related quality of life and socio-cultural aspects in young patients who after mandible primary reconstruction with free fibula flap

Background: The reconstruction of mandibular defects after trauma or tumor resection is one of the most challenging problems facing reconstructive surgeons. Although the primary intended outcome of surgery to treat head-and-neck malignancies is still the disease-free survival of the patient, health-related quality of life (HRQOL) is now seen as an essential secondary outcome. This study aims to evaluate HRQOL outcomes in young patients undergoing primary mandible reconstruction with free fibula flap and to collect information about their socio-cultural situation. Methods: The HRQOL outcomes of 25 young patients after primary mandible reconstruction with free fibula flap for mandible malignancies were assessed using the Medical Outcomes Study-Short Form-36 (MOS SF-36) and University of Washington Quality of Life (UW-QOL) questionnaires 12 months postoperatively. Results: Using the UW-QOL questionnaire, the best-scoring domain was 'pain', whereas 'chewing' and 'anxiety' were given the lowest scores. Using the MOS SF-36 questionnaire, the best-scoring domain was 'physical functioning', while 'bodily pain' and 'general health' also scored well. Conclusions: Mandible reconstruction with fibula flap will significantly influence a young patient's HRQOL. Young patients pay more attention to postoperative facial appearance; this should be considered in surgical planning. The socio-cultural data show a fairly low level of education for the majority of patients.

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