Science.gov

Sample records for advanced epidermoid carcinoma

  1. Effective multimodality treatment for advanced epidermoid carcinoma of the female genital tract

    SciTech Connect

    Kalra, J.; Cortes, E.; Chen, S.; Krumholz, B.; Rovinsky, J.J.; Molho, L.; Seltzer, V.; Papantoniou, P.; Lee, J.Y.

    1985-07-01

    Fifteen patients with advanced or recurrent squamous-cell carcinoma of the cervix, vulva, vagina, and urethra were treated with simultaneous combination chemotherapy (5-fluorouracil infusion and mitomycin C) and radiotherapy (3,000 rad for a period of three weeks). Three to four weeks after completion of radiotherapy, 13 of 15 patients achieved partial or complete tumor shrinkage. Nine of 15 patients are alive, eight of whom (at a median follow-up time of 24 months) have no evidence of disease. The longest survival time was 45 + months. There was minimal toxicity associated with this therapy. The results of this pilot study suggest that the simultaneous administration of radiation and chemotherapy is an effective method of treatment of advanced female genital tract carcinoma.

  2. Natural flavonoid derivatives as oral human epidermoid carcinoma cell inhibitors.

    PubMed

    Gunda, Shravan Kumar; Kongaleti, Sofia Florence; Shaik, Mahmood

    2015-01-01

    Natural flavonoid derivatives against cancer for selective KB cell lines (oral human epidermoid carcinoma) are analysed to determine the relationship between biological activities and structural properties of these molecules. Molecular alignment was performed for 88 natural flavonoid derivatives; out of these 88 molecules, 69 molecules were taken into training set and rest of the 19 molecules were used in test set prediction. We describe our elucidation of their structure activity relation (SAR) using three-dimensional quantitative structure activity relationship (3D-QSAR) models. A predictive comparative molecular field analysis (CoMFA) model of q² = 0.888 and r² = 0.940 was obtained and a comparative molecular similarity indices analysis (CoMSIA) model q² = 0.778 and r² = 0.971 was used to describe the non-linearly combined affinity of each functional group in the inhibitors. The contour maps obtained from 3D-QSAR studies were evaluated for the activity trends of the molecules analysed.

  3. Selective apoptotic effect of Zelkova serrata twig extract on mouth epidermoid carcinoma through p53 activation.

    PubMed

    Kang, Hoe-Jin; Jang, Young-Joo

    2012-06-01

    Apoptosis or programmed cell death plays an essential role in chemotherapy-induced tumor cell killing, and inducers of apoptosis are commonly used in cancer therapy. Treatment with Zelkova serrata extracts was performed in human gingival fibroblast (HGF), mouth epidermoid carcinoma cell (KB), lower gingival squamous cancer cell (YD38) and tongue mucoepidermoid carcinoma cells (YD15). We observed that extract prepared from Zelkova serrata twig selectively inhibited proliferation of various oral cancer cells, but not normal gingival fibroblasts, in a dose-dependent manner. Caspase-8-mediated apoptosis was induced by treatment with the extract only in mouth epidermoid carcinoma and not in other types of cancer cells, including lower gingival squamous cell carcinoma. The selective apoptotic effect of Zelkova serrata twig extract in mouth epidermoid carcinoma was dependent on normal p53 status. Apoptosis was not remarkably induced by treatment with the extract in either lower gingival squamous or tongue mucoepidermoid carcinoma cells, both of which contain abnormalities of p53. Upon treatment with Zelkova serrata twig extract, mouth epidermoid carcinoma cells accumulated in S phase by activation of p21. These data indicate that Zelkova serrata twig extract exerted a cancer type-specific, p53-dependent apoptotic effect and disturbed the cell cycle, which suggests that herbal medicine could be a treatment for specific types of cancers.

  4. Malignant Transformation of an Intracranial Extradural Epidermoid Cyst into Squamous Cell Carcinoma Presented with Cerebrospinal Fluid Leakage

    PubMed Central

    Seif, Bahram; Pourkhalili, Reza; Shekarchizadeh, Ahmad; Mahzouni, Parvin

    2017-01-01

    We report a case of malignant transformation of an intracranial extradural epidermoid cyst into squamous cell carcinoma (SCC), that presented with cerebrospinal fluid (CSF) leakage at the time of recurrence. Intracranial epidermoid cysts are histologically benign and slow-growing neoplasms. They are congenital lesions that develop from ectodermal remnants during neuroembryogenesis. Malignant transformation of epidermoid cysts into SCC is very rare. Various clinical presentations of these tumors after malignant transformation are mentioned in the literature. None of the previous cases, presented with CSF leakage as the recent case did. In cases of malignant transformation, surgical resection and then adjuvant radiation therapy are highly recommended. PMID:28299308

  5. Effect of transforming growth factor-alpha on inositol phospholipid metabolism in human epidermoid carcinoma cells

    SciTech Connect

    Kato, M.; Takenawa, T.; Twardzik, D.R.

    1988-08-01

    Transforming growth factor-alpha (TGF-alpha) stimulates (in a dose-dependent manner) the incorporation of (/sup 32/P)Pi into phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA) in the human epidermoid carcinoma cell line (A431). The effect of TGF-alpha on the incorporation was found to be similar to that of EGF. On the other hand, a striking difference in the activation of diacylglycerol (DG) kinase activity was seen between TGF-alpha and EGF. At least 100 times more TGF-alpha was required to achieve maximal stimulation of DG kinase activity relative to EGF. These results suggest that the activation of DG kinase by TGF-alpha may involve a mechanism independent from or subsequent to activation of the EGF receptor.

  6. Induction of Apoptosis and Antiproliferative Activity of Naringenin in Human Epidermoid Carcinoma Cell through ROS Generation and Cell Cycle Arrest

    PubMed Central

    Jafri, Asif; Ahmad, Sheeba; Afzal, Mohammad; Arshad, Md

    2014-01-01

    A natural predominant flavanone naringenin, especially abundant in citrus fruits, has a wide range of pharmacological activities. The search for antiproliferative agents that reduce skin carcinoma is a task of great importance. The objective of this study was to analyze the anti-proliferative and apoptotic mechanism of naringenin using MTT assay, DNA fragmentation, nuclear condensation, change in mitochondrial membrane potential, cell cycle kinetics and caspase-3 as biomarkers and to investigate the ability to induce reactive oxygen species (ROS) initiating apoptotic cascade in human epidermoid carcinoma A431 cells. Results showed that naringenin exposure significantly reduced the cell viability of A431 cells (p<0.01) with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed statistically significant (p<0.001) dose-related increment in ROS production for naringenin. It also caused naringenin-mediated epidermoid carcinoma apoptosis by inducing mitochondrial depolarization. Cell cycle study showed that naringenin induced cell cycle arrest in G0/G1 phase of cell cycle and caspase-3 analysis revealed a dose dependent increment in caspase-3 activity which led to cell apoptosis. This study confirms the efficacy of naringenin that lead to cell death in epidermoid carcinoma cells via inducing ROS generation, mitochondrial depolarization, nuclear condensation, DNA fragmentation, cell cycle arrest in G0/G1 phase and caspase-3 activation. PMID:25330158

  7. Knockdown of asparagine synthetase by RNAi suppresses cell growth in human melanoma cells and epidermoid carcinoma cells.

    PubMed

    Li, Hui; Zhou, Fusheng; Du, Wenhui; Dou, Jinfa; Xu, Yu; Gao, Wanwan; Chen, Gang; Zuo, Xianbo; Sun, Liangdan; Zhang, Xuejun; Yang, Sen

    2016-05-01

    Melanoma, the most aggressive form of skin cancer, causes more than 40,000 deaths each year worldwide. And epidermoid carcinoma is another major form of skin cancer, which could be studied together with melanoma in several aspects. Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine, and its expression is associated with the chemotherapy resistance and prognosis in several human cancers. The present study aims to explore the potential role of ASNS in melanoma cells A375 and human epidermoid carcinoma cell line A431. We applied a lentivirus-mediated RNA interference (RNAi) system to study its function in cell growth of both cells. The results revealed that inhibition of ASNS expression by RNAi significantly suppressed the growth of melanoma cells and epidermoid carcinoma cells, and induced a G0/G1 cell cycle arrest in melanoma cells. Knockdown of ASNS in A375 cells remarkably downregulated the expression levels of CDK4, CDK6, and Cyclin D1, and upregulated the expression of p21. Therefore, our study provides evidence that ASNS may represent a potential therapeutic target for the treatment of melanoma.

  8. Effect of downregulation of survivin expression on radiosensitivity of human epidermoid carcinoma cells

    SciTech Connect

    Sah, Nand K.; Munshi, Anupama; Hobbs, Marvette B.A.; Carter, Bing Z.; Andreeff, Michael; Meyn, Raymond E. . E-mail: rmeyn@mdanderson.org

    2006-11-01

    Purpose: The expression of survivin, a member of the inhibitor-of-apoptosis protein family, is elevated in many types of human cancer. High survivin expression has been associated with poor patient prognosis and tumor resistance to chemotherapy and radiotherapy. The purpose of this study was to compare the radiosensitizing effects of five agents that target survivin on their relative ability to downregulate survivin expression. Methods and Materials: The human epidermoid carcinoma cell line A431 was treated with adenoviral-mediated wild-type p53, antisense to survivin, the mitogen-activated protein kinase inhibitor PD98059, the cyclin-dependent kinase inhibitor Purvalanol A, or the histone deacetylase inhibitor trichostatin A. The radiosensitizing effects of these treatments were determined by clonogenic survival curve analysis and their abilities to suppress survivin expression by Western blot analysis. Results: All the strategies were shown to radiosensitize A431 cells. This effect correlated with their abilities to downregulate survivin. Conclusion: Expression of survivin appears to confer a radioresistant phenotype that can be overcome using several clinically achievable strategies that target survivin either specifically or nonspecifically.

  9. Cytotoxic Effect of Thymus caramanicus Jalas on Human Oral Epidermoid Carcinoma KB Cells.

    PubMed

    Fekrazad, Reza; Afzali, Mehrad; Pasban-Aliabadi, Hamzeh; Esmaeili-Mahani, Saeed; Aminizadeh, Maryam; Mostafavi, Ali

    2017-01-01

    Identifying new chemotherapeutic agents with fewer side effects is a major concern for scientists today. Thymus caramanicus Jalas (Lamiaceae family) is one of the species of Thymus that grows wild in different regions of Iran. Traditionally, leaves of this plant are used in the treatment of diabetes, arthritis and cancer. Here was investigated the cytotoxic property of Thymus caramanicus essential oil and extract in human oral epidermoid carcinoma KB cells. Cell viability was measured by MTT and neutral red assays. The cells were exposed to different concentrations of essential oil (0.05-1 µL/mL) and extract (25-150 µg/mL) for 24 h. Doxorubicin was used as anticancer control drug. The data showed that the essential oil (IC50=0.44 µL/mL) and extract (IC50=105 µg/mL) induce potent cytotoxic property. Surprisingly, cytotoxic effects of essential oil and extract of this plant on KB cancer cells were greater than those on normal gingival HGF1-PI1 cell line. In addition, Thymus caramanicus could potentiate the effect of doxorubicin in sub-effective concentrations. The results of the present study indicate that essential oils and extracts of Thymus caramanicus have potential anti-proliferative property on KB cells and can be used as pharmaceutical case study for oral cancer treatments.

  10. Pheophorbide a mediated photodynamic therapy against human epidermoid carcinoma cells (A431)

    NASA Astrophysics Data System (ADS)

    Chen, Yi-Chun; Li, Wen-Tyng

    2011-02-01

    The objective of this study was to characterize the death mechanism of human epidermoid carcinoma cells (A431) triggered by photodynamic therapy (PDT) with pheophorbide a. First of all, significant inhibition on the survival of A431 cells (< 20 %) was observed when an irradiation dose of 5.1 J/cm2 combined with 125 ng/ml of pheophorbide a was applied. Survival rate of human keratinocyte cells was over 70 % under the same PDT parameters, suggesting that pheophorbide a killed cancer cells selectively. Mitochondria were the main target sites where pheophorbide a accumulated. Formation of reactive oxygen species (ROS) was detected after PDT. Addition of antioxidant N-Acetyl cysteine prevented ROS production and increased cell survival thereafter. The decrease in cellular ATP level was also observed at 6 hrs after PDT. Typical apoptotic cellular morphology and a collapse of mitochondrial membrane potential occurred after PDT. The loss of mitochondrial membrane potential led to the release of cytochrome c from the mitochondria to the cytosol, followed by activation of caspase-9 and caspase-3. The activation of caspase-3 resulted in poly(ADP-ribose) polymerase (PARP) cleavage in A431 cells, followed by DNA fragmentation. In conclusion, the results demonstrated that pheophorbide a possessed photodynamic action against A431 cells, mainly through apoptosis mediated by mitochondrial intrinsic pathway triggered by ROS.

  11. [Alpha-lipoic acid triggers elimination of cells with abnormal nuclei in human carcinoma epidermoid cell line].

    PubMed

    Kisurina-Evgen'eva, O P; Onishchenko, G E

    2010-01-01

    The skin is usually exposed to adverse environmental conditions that may cause pathological cell proliferation and cellular transformations leading to the formation of malignant cells. Antioxidants may affect these processes and induce the elimination of transformed cell. The purpose of this work was to investigate the effect of alfa-lipoic acid on human carcinoma epidermoid cell line A431. Our results showed that alfa-lipoic acid induced inhibition of cell proliferation or stimulated apoptotic cell death. Cells with abnormal nuclei were eliminated by apoptosis. Electron microscopy showed that survived cells had typical for control cells shape and organization of the nuclei, organization of the cytoplasm and organelles. Thus, alfa-lipoic acid not only triggered apoptosis of carcinoma cells, but it may also activate the mechanism of elimination of cells with abnormal chromosome number.

  12. Density-dependent induction of 92-kd type IV collagenase activity in cultures of A431 human epidermoid carcinoma cells.

    PubMed Central

    Xie, B.; Bucana, C. D.; Fidler, I. J.

    1994-01-01

    We examined the in vitro regulation of the production of two type IV collagenases, MMP-2 and MMP-9, by A431 human epidermoid carcinoma cells. The A431 cells were cultured under sparse or confluent conditions. The addition of transforming growth factor-beta (TGF-beta) or phorbolester-TPA to sparse cultures induced low levels of MMP-9 secretion, whereas in confluent cultures only TGF-beta produced this effect. Neither treatment altered the level of constitutive secretion of MMP-2. Treatment of sparse, actively growing cultures but not confluent stationary cultures with both TGF-beta and TPA produced synergistic induction of MMP-9 but did not affect MMP-2. A431 cells were grown as discrete large monolayer colonies. Radiolabeling with [3H]leucine or [3H]thymidine followed by autoradiography revealed that all the A431 cells in the colonies were metabolically active and only those on the periphery were dividing. Only these dividing A431 cells stained positive by anti-MMP-9 antibodies. Our results demonstrate that the synergistic induction of MMP-9 secretion in A431 cells occurs subsequent to stimulation by external signals in only noncontact-inhibited dividing tumor cells. These regulatory mechanisms may account for the in vivo finding that many proteinases are localized at the invasion front of a neoplasm where tumor cells are dividing and accessible to various environmental signals. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8178929

  13. Regulation of apoptosis by resveratrol through JAK/STAT and mitochondria mediated pathway in human epidermoid carcinoma A431 cells

    SciTech Connect

    Madan, Esha; Prasad, Sahdeo; Roy, Preeti; George, Jasmine; Shukla, Yogeshwer

    2008-12-26

    Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin present mainly in grapes, red wine and berries, is known to possess strong chemopreventive and anticancer properties. Here, we demonstrated the anti-proliferative and apoptosis-inducing activities of resveratrol in human epidermoid carcinoma A431 cells. Resveratrol has cytotoxic effects through inhibiting cellular proliferation of A431 cells, which leads to the induction of apoptosis, as evident by an increase in the fraction of cells in the sub-G{sub 1} phase of the cell cycle and Annexin-V binding of externalized phosphatidylserine. Results revealed that inhibition of proliferation is associated with regulation of the JAK/STAT pathway, where resveratrol prevents phosphorylation of JAK, thereby inhibiting STAT1 phosphorylation. Furthermore, resveratrol treatment actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. Consequently, an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and subsequent cleavage of PARP, thereby shifting the balance in favor of apoptosis. These observations indicate that resveratrol treatment inhibits JAK/STAT-mediated gene transcription and induce the mitochondrial cell death pathway.

  14. Evaluating the promiscuous nature of tyrosine kinase inhibitors assessed in A431 epidermoid carcinoma cells by both chemical- and phosphoproteomics.

    PubMed

    Giansanti, Piero; Preisinger, Christian; Huber, Kilian V M; Gridling, Manuela; Superti-Furga, Giulio; Bennett, Keiryn L; Heck, Albert J R

    2014-07-18

    Deregulation of protein tyrosine kinase signaling has been linked to many diseases, most notably cancer. As a consequence, small molecule inhibitors of protein tyrosine kinases may provide powerful strategies for treatment. Following the successful introduction of imatinib in the treatment of chronic myelogenous leukemia, such drugs are also now evaluated for other types of cancer. However, many developed kinase inhibitors are not very target-specific and therefore may induce side effects. The importance of such side effects is certainly cell-proteome dependent. Understanding the all-inclusive action of a tyrosine kinase inhibitor on each individual cell-type entails the identification of potential targets, combined with monitoring the downstream effects revealing the signaling networks involved. Here, we explored a multilevel quantitative mass spectrometry-based proteomic strategy to identify the direct targets and downstream signaling effect of four tyrosine kinase inhibitors (imatinib, dasatinib, bosutinib, and nilotinib) in epidermoid carcinoma cells, as a model system for skin-cancer. More than 25 tyrosine kinases showed affinity to the drugs, with imatinib and nilotinib displaying a high specificity, especially when compared to dasatinib and bosutinib. Consequently, the latter two drugs showed a larger effect on downstream phosphotyrosine signaling. Many of the proteins affected are key regulators in cell adhesion and invasion. Our data represents a multiplexed view on the promiscuous action of certain tyrosine kinase inhibitors that needs to be taking into consideration prior to the application of these drugs in the treatment of different forms of cancer.

  15. Combinatorial effects of geopropolis produced by Melipona fasciculata Smith with anticancer drugs against human laryngeal epidermoid carcinoma (HEp-2) cells.

    PubMed

    Bartolomeu, Ariane Rocha; Frión-Herrera, Yahima; da Silva, Livia Matsumoto; Romagnoli, Graziela Gorete; de Oliveira, Deilson Elgui; Sforcin, José Maurício

    2016-07-01

    The identification of natural products exerting a combined effect with therapeutic agents could be an alternative for cancer treatment, reducing the concentration of the drugs and side effects. Geopropolis (Geo) is produced by some stingless bees from a mixture of vegetable resins, gland secretions of the bees and soil. It has been used popularly as an antiseptic agent and to treat respiratory diseases and dermatosis. To determine whether Geo enhances the anticancer effect of carboplatin, methotrexate and doxorubicin (DOX), human laryngeal epidermoid carcinoma (HEp-2) cells were treated with Geo alone or in combination with each drug. Cell growth, cytotoxicity and apoptosis were evaluated using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and flow cytometry. Scratch assay was used to analyze cell migration and transmission electron microscopy to observe morphologic alterations. The influence of Geo on drug resistance was also investigated assessing P-glycoprotein (P-gp) action. Geo inhibited cell proliferation and migration. The combination Geo+DOX led to the highest cytotoxic activity and induced apoptosis, leading to loss of membrane integrity. Geo had no effect on P-gp-mediated efflux of DOX. Data indicate that Geo combined with DOX could be a potential clinical chemotherapeutic approach for laryngeal cancer treatment.

  16. Photodynamic therapy-induced apoptosis in epidermoid carcinoma cells. Reactive oxygen species and mitochondrial inner membrane permeabilization.

    PubMed

    Lam, M; Oleinick, N L; Nieminen, A L

    2001-12-14

    Photodynamic therapy (PDT), a novel and promising cancer treatment that employs a combination of a photosensitizing chemical and visible light, induces apoptosis in human epidermoid carcinoma A431 cells. However, the precise mechanism of PDT-induced apoptosis is not well characterized. To dissect the pathways of PDT-induced apoptosis, we investigated the involvement of mitochondrial damage by examining a second generation photosensitizer, the silicon phthalocyanine 4 (Pc 4). By using laser-scanning confocal microscopy, we found that Pc 4 localized to cytosolic membranes primarily, but not exclusively, in mitochondria. Formation of mitochondrial reactive oxygen species (ROS) was detected within minutes when cells were exposed to Pc 4 and 670-675 nm light. This was followed by mitochondrial inner membrane permeabilization, depolarization and swelling, cytochrome c release, and apoptotic death. Desferrioxamine prevented mitochondrial ROS production and the events thereafter. Cyclosporin A plus trifluoperazine, blockers of the mitochondrial permeability transition, inhibited mitochondrial inner membrane permeabilization and depolarization without affecting mitochondrial ROS generation. These data indicate that the mitochondrial ROS are critical in initiating mitochondrial inner membrane permeabilization, which leads to mitochondrial swelling, cytochrome c release to the cytosol, and apoptotic death during PDT with Pc 4.

  17. High prevalence of human papillomavirus infection and possible association with betel quid chewing and smoking in oral epidermoid carcinomas in Taiwan.

    PubMed

    Chang, K W; Chang, C S; Lai, K S; Chou, M J; Choo, K B

    1989-05-01

    Seventeen oral epidermoid carcinomas, three oral papillomas, and 17 normal gingival tissues were tested for the presence of human papillomavirus (HPV) types 6, 11, 16, and 18 sequences by Southern blot hybridization. Episomal HPV-16 sequences in various amounts were detected in 76.4% of the oral carcinomas and in all three cases of papilloma. However, only one of the 17 normal tissues was HPV positive with an unknown type. None of the samples contained HPV-6, -11, or -18 sequences. Examination of the habits of the patients showed that 59% of the patients were betel quid chewers and 82% were smokers. Thus, the concurrent incidence of HPV infection and betal quid chewing and/or smoking habits in oral carcinoma patients observed in Taiwan is consistent with the view that both viral and chemical factors may be involved in the process of carcinogenesis.

  18. Involvement of retinoblastoma (Rb) and E2F transcription factors during photodynamic therapy of human epidermoid carcinoma cells A431.

    PubMed

    Ahmad, N; Gupta, S; Mukhtar, H

    1999-03-11

    Photodynamic therapy (PDT), a promising new therapeutic modality for the management of a variety of solid malignancies and many non-malignant diseases, is a bimodal therapy using a porphyrin based photosensitizing chemical and visible light. The proper understanding of the mechanism of PDT-mediated cancer cell-kill may result in improving the efficacy of this treatment modality. Earlier we have shown (Proc. Natl. Acad. Sci. USA; 95: 6977-6982, 1998) that silicon phthalocyanine (Pc4)-PDT results in an induction of the cyclin kinase inhibitor WAF1/CIP1/p21 which, by inhibiting cyclins (E and D1) and cyclin dependent kinases (cdk2 and cdk6), results in a G0/G1-phase arrest followed by apoptosis in human epidermoid carcinoma cells A431. We have also demonstrated the generation of nitric oxide during PDT-mediated apoptosis (Cancer Res.; 58: 1785-1788, 1998). Retinoblastoma (pRb) and E2F family transcription factors are important proteins, which regulate the G1-->S transition in the cell cycle. Here, we provide evidence for the involvement of pRb-E2F/DP machinery as an important contributor of PDT-mediated cell cycle arrest and apoptosis. Western blot analysis demonstrated a decrease in the hyper-phosphorylated form of pRb at 3, 6 and 12 h post-PDT with a relative increase in hypo-phosphorylated pRb. Western blot analysis also revealed that PDT-caused decrease in phosphorylation of pRb occurs at serine-780. The ELISA data demonstrated a time dependent accumulation of hypo-phosphorylated pRb by PDT. This response was accompanied with down-regulation in the protein expression of all five E2F (1-5) family transcription factors, and their heterodimeric partners DP1 and DP2. These results suggest that Pc4-PDT of A431 cells results in a down regulation of hyper-phosphorylated pRb protein with a relative increase in hypo-phosphorylated pRb that, in turn, compromises with the availability of free E2F. We suggest that these events result in a stoppage of the cell cycle

  19. Fisetin inhibits growth, induces G₂ /M arrest and apoptosis of human epidermoid carcinoma A431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation.

    PubMed

    Pal, Harish C; Sharma, Samriti; Elmets, Craig A; Athar, Mohammad; Afaq, Farrukh

    2013-07-01

    Non-melanoma skin cancers (NMSCs), one of the most common neoplasms, cause serious morbidity and mortality. Therefore, identification of non-toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3',4',7-tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti-oxidant and antiproliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fisetin (5-80 μm) resulted in a significant decrease in cell viability in a dose- and time-dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G₂ /M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti-apoptotic proteins (Bcl2; Bcl-xL and Mcl-1); (ii) increased expression of pro-apoptotic proteins (Bax, Bak and Bad); (iii) disruption of mitochondrial potential; (iv) release of cytochrome c and Smac/DIABLO from mitochondria; (v) activation of caspases; and (vi) cleavage of Poly(ADP-ribose) polymerase (PARP) protein. Pretreatment of A431 cells with the pan-caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs.

  20. Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-{kappa}B pathway in human epidermoid carcinoma A431 cells

    SciTech Connect

    Roy, Preeti; Kalra, Neetu; Nigam, Nidhi; George, Jasmine; Ray, Ratan Singh; Hans, Rajendra K.; Prasad, Sahdeo; Shukla, Yogeshwer

    2009-06-26

    Resveratrol has been reported to suppress cancer progression in several in vivo and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer, is known to induce cell death in cancerous cells. Here, we investigated whether resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced cell death. We examined the combined effect of UVB (30 mJ/cm{sup 2}) and resveratrol (60 {mu}M) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or resveratrol can inhibit cell proliferation and induce apoptosis. However, the combination of resveratrol and UVB exposure was associated with increased proliferation inhibition of A431 cells compared with either agent alone. Furthermore, results showed that resveratrol and UVB treatment of A431 cells disrupted the nuclear factor-kappaB (NF-{kappa}B) pathway by blocking phosphorylation of serine 536 and inactivating NF-{kappa}B and subsequent degradation of I{kappa}B{alpha}, which regulates the expression of survivin. Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701 of the important transcription factor signal transducer activator of transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein LIMK1, which reduced the motility of A431 cells. In conclusion, our study demonstrates that the combination of resveratrol and UVB act synergistically against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic agent against skin carcinogenesis.

  1. Recombinant human tumor necrosis factor alpha does not potentiate cell killing after photodynamic therapy with a silicon phthalocyanine in A431 human epidermoid carcinoma cells.

    PubMed

    Azizuddin, K; Kalka, K; Chiu, S M; Ahmad, N; Mukhtar, H; Separovic, D

    2001-02-01

    Photodynamic therapy (PDT) is a novel cancer treatment utilizing a photosensitizer, visible light and oxygen. PDT with the silicon phthalocyanine Pc 4, a new photosensitizer, is highly effective in cancer cell destruction and tumor ablation. The mechanisms underlying cancer cell killing by PDT are not fully understood. Tumor necrosis factor alpha (TNF) is a multifunctional cytokine that has been implicated in photocytotoxicity. We asked whether recombinant human TNF (rhTNF) affects Pc 4-PDT cytotoxicity in A431 human epidermoid carcinoma cells. Co-treatment of A431 cells with various doses of Pc 4-PDT and a sub-lethal rhTNF dose led to a sub-additive reduction in cell survival. In addition, in the presence of Pc 4-PDT or rhTNF, caspase-3 activity and apoptosis were induced. The combined treatment, however, did not potentiate either caspase-3 activity or apoptosis. Similar to previous findings we observed that Pc 4-PDT initiated a time-dependent extracellular TNF accumulation. The data suggest that: a) PDT and rhTNF induce cancer cell killing through different mechanisms; and b) Pc 4-PDT-induced TNF production is a stress response that may not directly affect photocytotoxicity.

  2. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    SciTech Connect

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C.; Ballestas, Mary E.; Kopelovich, Levy; Elmets, Craig A.; Athar, Mohammad

    2013-01-15

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  3. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  4. Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G(2)/M arrest to apoptosis.

    PubMed

    Bhui, Kulpreet; Tyagi, Shilpa; Srivastava, Amit Kumar; Singh, Madhulika; Roy, Preeti; Singh, Richa; Shukla, Yogeshwer

    2012-03-01

    Bromelain, obtained from pineapple, is already in use clinically as adjunct in chemotherapy. Our objective was to test its ability to act as a sole anti-cancer agent. Therefore, we describe its anti-proliferative, anti-inflammatory and subsequent anti-cancer effects in vitro, against human epidermoid carcinoma-A431 and melanoma-A375 cells. Bromelain exhibited reduction in proliferation of both these cell-lines and suppressed their potential for anchorage-independent growth. Further, suppression of inflammatory signaling by bromelain was evident by inhibition of Akt regulated-nuclear factor-kappaB activation via suppression of inhibitory-kappaBα phosphorylation and concomitant reduction in cyclooxygenase-2. Since, the inflammatory cascade is well-known to be closely allied to cancer; we studied the effect of bromelain on events/molecules central to it. Bromelain caused depletion of intracellular glutathione and generation of reactive oxygen-species followed by mitochondrial membrane depolarization. This led to bromelain-induced cell-cycle arrest at G(2)/M phase which was mediated by modulation of cyclin B1, phospho-cdc25C, Plk1, phospho-cdc2, and myt1. This was subsequently followed by induction of apoptosis, indicated by membrane-blebbing, modulation of Bax-Bcl-2 ratio, Apaf-1, caspase-9, and caspase-3; chromatin-condensation, increase in caspase-activity and DNA-fragmentation. Bromelain afforded substantial anti-cancer potential in these settings; hence we suggest it as a potential prospect for anti-cancer agent besides only an additive in chemotherapy.

  5. Hydroxyl radical (·OH) played a pivotal role in oridonin-induced apoptosis and autophagy in human epidermoid carcinoma A431 cells.

    PubMed

    Yu, Yang; Fan, Si Miao; Song, Jun Ke; Tashiro, Shin-ichi; Onodera, Satoshi; Ikejima, Takashi

    2012-01-01

    Oridonin, a diterpenoid compound extracted and purified from Rabdosia rubescen, has been reported to induce tumor cell apoptosis through tyrosine kinase pathway. To further examine the mechanism of oridonin, we selected human epidermoid carcinoma A431 cell as a test object. Besides apoptosis, oridonin also induced A431 cell autophagy, and this autophagy antagonized apoptosis and played a protective role for A431 cells. Reactive oxygen species (ROS) played a pivotal role in induction of cytotoxicity. Therefore, a ROS scavenger, N-acetylcysteine (NAC) combined with oridonin was appiled. Results of morphologic observation, flow cytometric analysis and Western blot analysis showed that NAC could significantly reverse both ROS generation and down-regulation of mitochondrial membrane potential in oridonin treated cells. NAC inhibited oridonin induced apoptosis through both the intrinsic and extrinsic apoptotic pathways. NAC effectively inhibited both oridonin-induced apoptosis and autophagy by reducing intracellular oxidative stress. To further examine the mechanism of ROS, exogenous enzyme antioxidants (superoxide dismutase (SOD), catalase (CAT)) and non-enzyme antioxidants (glutathione (GSH)) were applied to detect the effect of oridonin on ROS generation. Only GSH exerted a similar role with NAC, suggesting that hydroxyl radical (·OH) played the major role in oridonin-induced cell death. Oridonin could decrease the GSH level in A431 cells in a dose-dependent manner. In addition, after treatment with ·OH donor, Fenton reagent, the changes in A431cells were similar to the results of oridonin treatment. All the results proved that ·OH played the pivotal role in oridonin induced apoptosis and autophagy in A431 cells.

  6. Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells.

    PubMed

    Bhatia, N; Agarwal, C; Agarwal, R

    2001-01-01

    Silibinin, quercetin, and epigallocatechin 3-gallate (EGCG) have been shown to be skin cancer-preventive agents, albeit by several different mechanisms. Here, we assessed whether these agents show their cancer-preventive potential by a differential effect on mitogenic signaling molecules and cell cycle regulators. Treatment of human epidermoid carcinoma A431 cells with these agents inhibited the activation of the epidermal growth factor receptor and the downstream adapter protein Shc, but only silibinin showed a marked inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation. In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Quercetin treatment, however, resulted in a moderate increase in Cip1/p21 with no change in Kip1/p27 and a decrease in CDK4 and cyclin D1. EGCG treatment also led to an induction of Cip1/p21 but no change in Kip1/27, CDK2, and cyclin D1 and a decrease in CDK4 only at low doses. Treatment of cells with these agents resulted in a strong dose- and time-dependent cell growth inhibition. A high dose of silibinin and low and high doses of quercetin and EGCG also led to cell death by apoptosis, suggesting that a lack of their inhibitory effect on mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation possibly "turns on" an apoptotic cell death response associated with their cancer-preventive and anticarcinogenic effects. Together, these results suggest that silibinin, quercetin, and EGCG exert their cancer-preventive effects by differential responses on mitogenic signaling and cell cycle regulators.

  7. Erlotinib for advanced hepatocellular carcinoma

    PubMed Central

    Zhang, Jing; Zong, Yuan; Xu, Gang-Zhu; Xing, Ke

    2016-01-01

    Objectives: To evaluate the efficacy and safety of erlotinib for the treatment of advanced hepatocellular carcinoma (HCC). Methods: A systematic literature search was undertaken in June 2015. Phase II/III trials of erlotinib for the treatment of advanced HCC were included. A descriptive analysis was applied. The study was conducted in College of Medicine, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China, between June 2015 and January 2016. Results: Ten trials, comprising 9 phase II and one phase III trial, were included in the systematic review. The tumor response rate was 0% in 4 of the phase II trials, <10% in 3 of the phase II trials and the phase III trial, and >20% in 2 of the phase II trials. The disease control rate was 42.5-79.6% in most studies. Three studies reported a median progression-free survival (PFS) of 6.5-9.0 months, although PFS was <3.5 months in most studies. Most trials reported a median overall survival of 6.25-15.65 months. The most frequent grade 3/4 toxicities were fatigue (11.9%), diarrhea (10%), increased alanine and aspartate transaminases (7.3%), and rash/desquamation (6.9%). Conclusion: Erlotinib provides efficacious and well-tolerated treatment for advanced HCC. However, more detailed investigations of HCC pathogenesis and evaluation of sensitive patient subsets are needed to improve outcomes of patients with advanced HCC. Additional well-designed, randomized, controlled trials are needed to evaluate the efficacy and safety of erlotinib as monotherapy or combination with other drugs for advanced HCC. PMID:27761555

  8. In vitro motility of cells from human epidermoid carcinomas. A study by phase-contrast and reflection-contrast cinematography.

    PubMed

    Haemmerli, G; Sträuli, P

    1981-05-15

    The motile behavior of six cell lines derived from human squamous carcinomas (two from the larynx, four from the tongue) was studied by cinematography under phase- and reflection-contrast illumination. The recorded cell activities consist in spreading, stationary and translocation motility, and aggregate formation. Within this common pattern, quantitative modifications ("sub-pattern") are stable properties of the individual cells lines. Such modifications are particularly evident with regard to the dynamic texture of the aggregates which ranges from loose, netlike structures to compact islands with smooth borders. Accordingly, the intensity of cell traffic within and around the aggregates varies considerably. It is discussed to what extent the in vitro motility of the carcinoma cell populations reflects their behavior in the organism and thus the significance of cell movements for invasion.

  9. The effect of betel nut extract on cell growth and prostaglandin endoperoxide synthase in human epidermoid carcinoma cells.

    PubMed

    Yang, C Y; Meng, C L; van der Bijl, P; Lee, H K

    2002-04-01

    The objective of this study was to find out whether prostaglandin endoperoxide synthase (PHS) involves the action of betel nut extract (BNE) on the growth of oral cancers. Therefore, growth and PHS activity were examined in two human oral carcinoma cell lines (OEC-M1 and KB) and one normal fibroblast cell line (NF) in the presence of increasing BNE concentration. BNE at concentrations above 50 microg/ml significantly inhibited the cell growth of OEC-M1 after 72 h in culture, of KB and NF after 48 h in culture. The IC50 of BNE in OEC-M1, KB and NF at 24 h in culture was about 406, 37.5 and 140 microg/ml respectively. PHS activity in OEC-M1 was significantly increased by low BNE concentrations (50 microg/ml, 114%; 100 microg/ml, 33%; 150 microg/ml, 30%) but significantly reduced at higher BNE concentrations (300 microg/ml, 33%; 500 microg/ml, 61%). The PHS activity in KB was significantly inhibited by BNE and this effect was intensified as concentrations increased (50 microg/ml, 31%; 100 microg/ml, 24%; 150 microg/ml, 43%; 300 microg/ml, 60%; 500 microg/ml, 92%). Similar to that in OEC-M1, the PHS activity in NF was significantly increased at low BNE concentrations (50 microg/ml, 139%; 100 microg/ml, 87%;150 microg/ml, 77%) but reduced at higher concentrations (300 microg/ml, 55%; 500 microg/ml, 72%). The PHS activity in all cell lines was almost completely blocked by indomethacin (5 x 10(-6) M). We conclude that these findings suggest that PHS may be an important biochemical mediator of the effect of BNE on the growth of two human oral carcinoma cell lines.

  10. New advances in hepatocellular carcinoma

    PubMed Central

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  11. Submental epidermoid cysts in children

    PubMed Central

    Zakrzewska, Anna

    2015-01-01

    Epidermoid cysts are lesions, which form as a result of implantation of the epidermis in the layers of the dermis or the mucous membrane. The lesions are rare in adults with 7% occurring in the head and neck area and most often located in the submental region. In children population submental epidermoid cysts are extremely rare. The differential diagnosis of the lesions is necessary as it affects the choice of treatment methods. Among the pathological conditions occurring in that region, salivary retention cyst (ranula), thyroglossal duct cyst, vascular lymphatic malformation (cystic hygroma), median neck cyst, lymphadenopathy, thyroid gland tumor, laryngeal cyst, epidermoid and dermoid cysts, submental abscess, sialolithiasis and salivary gland inflammation should be considered. The authors of the present report demonstrate two cases of submental epidermoid cysts in children. Differential diagnosis in case of suspected submental epidermoid cyst in a child with proposed clinical practice and literature review is provided.

  12. Hepatocellular carcinoma: Advances in diagnostic imaging.

    PubMed

    Sun, Haoran; Song, Tianqiang

    2015-10-01

    Thanks to the growing knowledge on biological behaviors of hepatocellular carcinomas (HCC), as well as continuous improvement in imaging techniques and experienced interpretation of imaging features of the nodules in cirrhotic liver, the detection and characterization of HCC has improved in the past decade. A number of practice guidelines for imaging diagnosis have been developed to reduce interpretation variability and standardize management of HCC, and they are constantly updated with advances in imaging techniques and evidence based data from clinical series. In this article, we strive to review the imaging techniques and the characteristic features of hepatocellular carcinoma associated with cirrhotic liver, with emphasis on the diagnostic value of advanced magnetic resonance imaging (MRI) techniques and utilization of hepatocyte-specific MRI contrast agents. We also briefly describe the concept of liver imaging reporting and data systems and discuss the consensus and controversy of major practice guidelines.

  13. Brainstem epidermoid cyst: An update

    PubMed Central

    Patibandla, M. R.; Yerramneni, Vamsi Krishna; Mudumba, Vijaya S.; Manisha, Nukavarapu; Addagada, Gokul Chowdary

    2016-01-01

    The incidence of epidermoid tumors is between 1% and 2% of all intracranial tumors. The usual locations of epidermoid tumor are the parasellar region and cerebellopontine angle, and it is less commonly located in sylvian fissure, suprasellar region, cerebral and cerebellar hemispheres, and lateral and fourth ventricles. Epidermoid cysts located in the posterior fossa usually arise in the lateral subarachnoid cisterns, and those located in the brain stem are rare. These epidermoids contain cheesy and flaky white soft putty like contents. Epidermoid cysts are very slow growing tumors having a similar growth pattern of the epidermal cells of the skin and develop from remnants of epidermal elements during closure of the neural groove and disjunction of the surface ectoderm with neural ectoderm between the third and fifth weeks of embryonic life. We are presenting an interesting case of intrinsic brainstem epidermoid cyst containing milky white liquefied material with flakes in a 5-year-old girl. Diffusion-weighted imaging is definitive for the diagnosis. Ideal treatment of choice is removal of cystic components with complete resection of capsule. Although radical resection will prevent recurrence, in view of very thin firmly adherent capsule to brainstem, it is not always possible to do complete resection of capsule without any neurological deficits. PMID:27366244

  14. Accelerated degradation of 160 kDa epidermal growth factor (EGF) receptor precursor by the tyrosine kinase inhibitor herbimycin A in the endoplasmic reticulum of A431 human epidermoid carcinoma cells.

    PubMed Central

    Murakami, Y; Mizuno, S; Uehara, Y

    1994-01-01

    The effect of herbimycin A on the biosynthesis of epidermal growth factor (EGF) receptor was examined in human epidermoid carcinoma A431 cells. Cells were pulse-labelled with [35S]methionine, and EGF receptor biosynthesis was quantified by immunoprecipitation using a monoclonal anti-(EGF receptor) antibody. In the presence of herbimycin A, an immature 160 kDa EGF receptor precursor accumulated in 1 h and disappeared completely in 4 h. Pulse-labelled 160 kDa receptor precursor in the absence of herbimycin A, however, was converted normally into a 170 kDa one by chase with herbimycin A. Herbimycin A affected neither the synthesis of the secreted form of EGF receptor devoid of cytoplasmic domain, nor that of the transferrin receptor in A431 cells. The herbimycin A-induced degradation of 160 kDa EGF receptor precursor was not inhibited by an inhibitor of lysosomal enzymes, NH4Cl. Endoglycosidase H digestion of the 160 kDa precursor converted it into the deglycosylated 130 kDa precursor peptide. These results suggested that herbimycin A selectively acted on the EGF receptor precursor during the synthesis of the 160 kDa form, probably on the cytoplasmic domain, to form an aberrant molecule which was subjected to rapid degradation in the endoplasmic reticulum. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8037692

  15. Antiangiogenic Therapies for Advanced Hepatocellular Carcinoma

    PubMed Central

    Sampat, Keeran R.

    2013-01-01

    Hepatocellular carcinoma (HCC) is a significant cause of death worldwide. HCC is a highly vascular tumor, and proangiogenic cytokines such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor may play crucial roles in this disease. Sorafenib, a multikinase inhibitor that blocks VEGF and PDGF signaling, was the first systemic therapy to demonstrate improved survival in patients with advanced HCC. Several other drugs targeting VEGF are in development. Because of the anticipation of eventual resistance to anti-VEGF therapies, drugs that also target alternative proangiogenic pathways are being investigated. Recent clinical and preclinical data along with ongoing studies are reviewed. PMID:23576483

  16. Advanced treatment for basal cell carcinomas.

    PubMed

    Atwood, Scott X; Whitson, Ramon J; Oro, Anthony E

    2014-07-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists.

  17. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  18. Purification and properties of the alpha-3/4-L-fucosyltransferase released into the culture medium during the growth of the human A431 epidermoid carcinoma cell line.

    PubMed

    Johnson, P H; Donald, A S; Watkins, W M

    1993-04-01

    A soluble alpha-3/4-fucosyltransferase secreted into the growth medium of the human A431 epidermoid carcinoma cell line has been purified 700,000 fold by a series of steps involving chromatography on Phenyl Sepharose 4B, CM-Sephadex C-50 and GDP-hexanolamine Sepharose 4B. The untreated spent culture medium transferred almost ten times more fucose to the subterminal N-acetylglucosamine residue in the Type 1 (Gal beta 1-3GlcNAc) disaccharide than to the subterminal sugar in the Type 2 (Gal beta 1-4GlcNAc) disaccharide; the relative activity with these two substrates remained virtually unchanged throughout the purification procedure. At no stage was any alpha-3-fucosyltransferase species acting solely on N-acetylglucosamine residues in Type 2 chains separated from the bulk of the alpha-3/4-fucosyltransferase activity. The purified enzyme preparation showed insignificant activity with glycoprotein substrates having N-linked oligosaccharide chains with terminal Type 2 sequences but transferred fucose to a mucin-type glycoprotein with O-linked oligosaccharide chains with terminal Type 1 structures. Lactose was a poor substrate but the activity of the enzyme was influenced by the presence of substituents on the terminal beta-galactosyl residue and 2'-fucosyllactose was almost as good an acceptor as the Type 1 disaccharide. The properties of the purified enzyme with regard to specificity, divalent cation requirements, pH optimum, and M(r), closely resembled those of the Lewis-blood-group gene associated alpha-3/4-fucosyltransferase isolated from human milk.

  19. Recurrent craniospinal epidermoid: A case report

    PubMed Central

    Shah, Abhidha; Patil, Manoj; Goel, Atul

    2016-01-01

    We present a rare case of a fourth ventricular epidermoid cyst, which recurred 15 years after the initial radical tumor resection surgery. The recurrence of the tumor extended into the cervical spine. The patient was reoperated and a near-total excision of both the cranial and spinal components of the epidermoid was performed. Our literature search did not reveal any case where there was a simultaneous presence of both the cranial and spinal epidermoid tumors. The possible cause of extension of the cranial epidermoid into the spinal compartment is analyzed. PMID:27041888

  20. Modern management of locally advanced cervical carcinoma.

    PubMed

    Dueñas-Gonzalez, Alfonso; Cetina, Lucely; Mariscal, Ignacio; de la Garza, Jaime

    2003-10-01

    Radiation was until recently the key and only modality for the routine treatment of locally advanced cervical carcinoma. However after years of studying multi-modality treatments as an alternative to radiation alone in randomized phase III trials, the standard treatment has changed to chemo-radiation based on cisplatin. Three recent meta-analyses have confirmed that cisplatin-based chemo-radiation adds an absolute 12% benefit in five-year survival over radiation therapy alone. Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. Despite these encouraging results there remains room for improvement as the five-year survival of patients treated with chemo-radiation ranges from nearly 80% in bulky IB tumours to only 25% in stage IVA disease. Other therapeutic approaches need to be fully evaluated including the use of chemo-radiation after neoadjuvant chemotherapy; the use of new drug combinations and the multi-modality combination of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemo-radiation. Likewise, the addition of radiosensitizers to cisplatin, preoperative chemo-radiation and/or adjuvant chemotherapy may eventually improve the currents results of cisplatin-based chemo-radiation. Nevertheless, it is hard to foresee a dramatic increase in cure rate, even with the most optimal combination of cytotoxic drugs, surgery and radiation, and thus the testing of molecular targeted therapies against cervical cancer is a logical step to follow.

  1. Definitive Chemoradiotherapy for Advanced Pulmonary Sarcomatoid Carcinoma

    PubMed Central

    Takeda, Kazuya; Matsushita, Haruo; Kubozono, Masaki; Tanabe, Takaya; Ishikawa, Yojiro; Yamamoto, Takaya; Kozumi, Maiko; Takahashi, Noriyoshi; Katagiri, Yu; Tasaka, Shun; Fukui, Katsuya; Takeda, Ken; Fujishima, Fumiyoshi; Ichinose, Masakazu; Jingu, Keiichi

    2016-01-01

    Pulmonary sarcomatoid carcinoma is a rare subtype of non-small cell lung cancer with a poor prognosis. We herein report on a case of pulmonary sarcomatoid carcinoma that was treated successfully by concurrent chemoradiotherapy. A 65-year-old man was diagnosed to have pulmonary pleomorphic carcinoma (clinical T4N2M0 stage IIIB). He received concurrent chemoradiotherapy (60 Gy of radiotherapy in 30 fractionations and two courses of chemotherapy with carboplatin and paclitaxel). After chemoradiotherapy, a significant reduction of the tumor size was observed. Two courses of adjuvant chemotherapy were performed. He is currently alive at 15 months after the first treatment without any recurrence or metastasis. PMID:27853077

  2. Advances in the management of cutaneous squamous cell carcinoma

    PubMed Central

    Parikh, Sonal A.

    2014-01-01

    Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas. PMID:25165569

  3. Advances in the pathology of penile carcinomas.

    PubMed

    Chaux, Alcides; Cubilla, Antonio L

    2012-06-01

    The incidence of penile cancer varies from country to country, with the highest figures reported for countries in Africa, South America, and Asia and lowest in the United States and Europe. Causes of this variation are not clear, but they are thought to be related to human papillomavirus infection, smoking, lack of circumcision, chronic inflammation, and poor genital hygiene. Most penile tumors are squamous cell carcinomas, and a variegated spectrum of distinct morphologies is currently recognized. Each one of these subtypes has distinctive pathologic and clinical features. About half of penile carcinomas are usual squamous cell carcinomas, and the rest corresponds to verrucous, warty, basaloid, warty-basaloid, papillary, pseudohyperplastic, pseudoglandular, adenosquamous, sarcomatoid, and cuniculatum carcinomas. Previous studies have found a consistent association of tumor cell morphology and human papillomavirus presence in penile carcinomas. Those tumors composed of small- to intermediate-sized, basaloid ("blue") cells are often human papillomavirus positive, whereas human papillomavirus prevalence is lower in tumors showing large, keratinizing, maturing eosinophilic ("pink") cells. Human papillomavirus-related tumors affect younger patients, whereas human papillomavirus-unrelated tumors are seen in older patients with phimosis, lichen sclerosus, or squamous hyperplasia. This morphologic distinctiveness is also observed in penile intraepithelial neoplasia. The specific aim of this review is to provide a detailed discussion on the macroscopic and microscopic features of all major subtypes of penile cancer. We also discuss the role of pathologic features in the prognosis of penile cancer, the characteristics of penile precursor lesions, and the use of immunohistochemistry for the diagnosis of invasive and precursor lesions.

  4. Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma.

    PubMed

    Lepesant, P; Crinquette, M; Alkeraye, S; Mirabel, X; Dziwniel, V; Cribier, B; Mortier, L

    2015-10-01

    Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

  5. Nursing Management of Advanced Merkel Cell Carcinoma.

    PubMed

    Lowry, Pamela A; Freeman, Morganna L; Russell, Jeffery S

    2016-11-01

    Merkel cell carcinoma (MCC) is a rare and lethal skin cancer with few known treatment options. Management of this disease is challenging, and oncology nurses must understand the medical, physical, and psychosocial burden that MCC places on the patient and family caregivers. Patients must navigate a complex medical and insurance network that often fails to support patients with rare cancers. Nurses must advocate for these patients to ensure quality comprehensive cancer care.

  6. [Epidermoid cyst of the mouth floor].

    PubMed

    Sanjuán Rodríguez, S; Morán Penco, J M; Ruiz Orpez, A; Santamaria Ossorio, J I; Berchi García, F J

    2003-07-01

    The epidermoid cysts are frequent during childhood, however mouth floor location are very unusual, because of their more difficult diagnosis and therapeutic approach. We present a 5 years old male, symptoms free until a week before, when his parents noticed a well defined mass in the mouth floor. A physical examination leaded to the diagnosis of possible epidermoid cyst. The tumor was excised through an introral approach. A review of different diagnostic means and surgical management are undertaken.

  7. Adenoid cystic carcinoma of breast: Recent advances

    PubMed Central

    Miyai, Kosuke; Schwartz, Mary R; Divatia, Mukul K; Anton, Rose C; Park, Yong Wook; Ayala, Alberto G; Ro, Jae Y

    2014-01-01

    Adenoid cystic carcinoma (ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features (i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with the ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features. PMID:25516849

  8. Combination treatment including targeted therapy for advanced hepatocellular carcinoma

    PubMed Central

    Xie, Yuan; Wang, Anqiang; Zhang, Haohai; Yang, Xiaobo; Wan, Xueshuai; Lu, Xin; Sang, Xinting; Zhao, Haitao

    2016-01-01

    Management of advanced hepatocellular carcinoma (HCC), one of the most lethal cancers worldwide, has presented a therapeutic challenge over past decades. Most patients with advanced HCC and a low possibility of surgical resection have limited treatment options and no alternative but to accept local or palliative treatment. In the new era of cancer therapy, increasing numbers of molecular targeted agents (MTAs) have been applied in the treatment of advanced HCC. However, mono-targeted therapy has shown disappointing outcomes in disease control, primarily because of tumor heterogeneity and complex cell signal transduction. Because incapacitation of a single target is insufficient for cancer suppression, combination treatment for targeted therapy has been proposed and experimentally tested in several clinical trials. In this article, we review research studies aimed to enhance the efficacy of targeted therapy for HCC through combination strategies. Combination treatments involving targeted therapy for advanced HCC are compared and discussed. PMID:27626176

  9. Epidermoid cysts of the velum interpositum.

    PubMed

    Bahuleyan, Biji; Daniel, Roy T; Chacko, Geeta; Chacko, Ari G

    2008-10-01

    The cistern of the velum interpositum is a space located between the corpus callosum dorsally and the roof of the third ventricle ventrally. Lesions located within the velum interpositum are rare and include meningiomas, pilocytic astrocytomas, atypical teratoid/rhabdoid tumors and arachnoid cysts. Epidermoid cysts in this location have not been reported previously. We report the clinical and radiological features of two patients with epidermoid cysts located in the velum interpositum. The patients presented with gait difficulty and features of raised intracranial pressure and magnetic resonance imaging demonstrated large tumors in the velum interpositum with intensities suggestive of epidermoid cysts. There was ventral displacement of the internal cerebral veins and dorsal displacement of the corpus callosum in keeping with a mass in the velum interpositum. Tumors of the third ventricle displace the internal cerebral veins dorsally. A transcallosal approach was used in both patients to effectively excise the tumors.

  10. Progress in systemic therapy of advanced hepatocellular carcinoma

    PubMed Central

    Gong, Xin-Lei; Qin, Shu-Kui

    2016-01-01

    Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians. PMID:27547002

  11. Extensive Epidermoid Cyst and Breathing Difficulty

    PubMed Central

    Soares, Ciro Dantas; Gurgel, Alberto Costa; de Souza Júnior, Francisco de Assis; de Oliveira, Samila Neres; de Carvalho, Maria Goretti Freire; Oliveira, Hanieri Gustavo

    2015-01-01

    Epidermoid cysts are common cystic lesions in the skin, ovaries, and testicles, but their occurrence in the oral cavity is uncommon. They consist of cysts delimited by a fibrous capsule without cutaneous annexes and are lined by stratified squamous epithelium. The differential diagnosis includes ranula, dermoid cysts, and lingual thyroid. Despite their benign presentation, these cysts can cause functional limitations, requiring special clinical attention for extensive lesions located in regions that preserve vital structures. This paper aims to report a case of epidermoid cyst in patient with swallowing and breathing difficulty, highlighting the clinical and surgical planning. PMID:26180645

  12. Liver abscess in advanced hepatocellular carcinoma after sorafenib treatment.

    PubMed

    Shin, Seung Kak; Jung, Young Kul; Yoon, Hyun Hwa; Kwon, Oh Sang; Kim, Yun Soo; Choi, Duck Joo; Kim, Ju Hyun

    2014-01-25

    Hepatocellular carcinoma (HCC) is a critical global health issue and the third most common cause of cancer-related deaths worldwide. The majority of patients who present HCC are already at an advanced stage and their tumors are unresectable. Sorafenib is a multi-kinase inhibitor of the vascular endothelial growth factor pathway and was recently introduced as a therapy for advanced HCC. Furthermore, studies have shown that oral sorafenib has beneficial effects on survival. However, many patients experience diverse side effects, and some of these are severe. Liver abscess development has not been previously documented to be associated with sorafenib administration in HCC. Here, we report the case of a HCC patient that developed a liver abscess while being treated with sorafenib.

  13. Sublingual epidermoid cyst in a neonate

    PubMed Central

    Oginni, Fadekemi Olufunmilayo; Oladejo, Taoreed; Braimah, Ramat Oyebunmi; Adenekan, Anthony Taiwo

    2014-01-01

    Epidermoid cysts (EC) in the head and neck region could be considered a rare condition representing only 6.9% of all ECs occurring in the body. They occur rarely in children and neonates. We present a case of sublingual EC in a Nigerian neonate. PMID:24987608

  14. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.

  15. Vismodegib: in locally advanced or metastatic basal cell carcinoma.

    PubMed

    Keating, Gillian M

    2012-07-30

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the US, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Vismodegib selectively and potently inhibits the Hedgehog signalling pathway by binding to Smoothened, thereby inhibiting the activation of Hedgehog target genes. Oral vismodegib was effective in the treatment of patients with locally advanced (n = 63) or metastatic (n = 33) BCC, according to the results of an ongoing, noncomparative, multinational, pivotal, phase II trial (ERIVANCE BCC). In this trial (using a clinical cutoff date of 26 November 2010), the independent review facility overall response rate was 42.9% in patients with locally advanced BCC and 30.3% in patients with metastatic BCC. In both patients with locally advanced BCC and those with metastatic BCC, the median duration of response was 7.6 months and median progression-free survival was 9.5 months. Oral vismodegib had an acceptable tolerability profile in patients with advanced BCC.

  16. Targeting EGFR and sonic hedgehog pathways for locally advanced eyelid and periocular carcinomas

    PubMed Central

    Yin, Vivian T; Merritt, Helen; Esmaeli, Bita

    2014-01-01

    For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. Overexpression of epithelial growth factor receptor was found in squamous cell carcinomas. Vismodegib targets the mutation in the hedgehog pathway identified in basal cell carcinoma and basal cell nevus syndrome. Targeted therapies provide a novel and potentially effective treatment alternative for patients with eyelid carcinoma not amendable for surgery, including those with metastatic, locally advanced disease, advanced age, and significant comorbidities. High cost, need for long-term treatment, and toxicity are relative limitations. PMID:25232546

  17. Technical advances in external radiotherapy for hepatocellular carcinoma

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  18. Advanced primary peritoneal carcinoma: clinicopathological and prognostic factor analyses

    PubMed Central

    Zhang, Chao; Li, Xiao-ping; Cui, Heng; Shen, Dan-hua; Wei, Li-hui

    2008-01-01

    Objective: To investigate the factors favoring a positive prognosis for advanced primary peritoneal carcinoma (PPC). Methods: Twenty-four cases meeting the criteria for PPC were analyzed retrospectively for the clinicopathologic profiles. Immunohistochemistry was used to determine the expressions of p53, Top2α, Ki-67 and Her-2/neu. Then all these clinicopathological factors and molecular markers were correlated with the prognosis. Results: There were 15 cases of primary peritoneal serous papillary carcinoma (PPSPC), 6 cases of mixed epithelial carcinoma (MEC) and 3 cases of malignant mixed Mullerian tumor (MMMT). All patients underwent cytoreductive surgery with optimal debulking achieved in 3 cases. Among those receiving first-line chemotherapy, 13 patients received the TP regimen (paclitaxel-cisplatin or carboplatin) and 7 patients received the PAC regimen (cisplatin-doxorubicin-cyclophosphamide). The median overall survival of all patients was 42 months, while the breakdown for survival time for patients with PPSPC, MMT and MEC was 44, 13 and 19 months, respectively. The expressions of p53, Top2α and Ki-67 were all demonstrated in 11 cases respectively. None showed the expression of Her-2/neu. There were significant differences in the median survival between patients with PPSPC and those with MMMT (44 months vs 13 months, P<0.05), also between patients receiving TP combination and those receiving the PAC regimen (75 months vs 28 months, P<0.05). Another significant difference in the median progression-free survival (PFS) was identified between patients with positive p53 immunostaining and those with negative p53 immunostaining (15 months vs 47 months, P<0.05), whereas age, menopausal status, residual tumor size and the other molecular factors did not significantly impact survival. Conclusion: Patients with PPC should be treated with a comprehensive management plan including appropriate cytoreductive surgery and responsive chemotherapy. Overestimating an

  19. Transcatheter embolization of advanced renal cell carcinoma with radioactive seeds

    SciTech Connect

    Lang, E.K.; deKernion, J.B.

    1981-11-01

    Advanced renal cell carcinoma was treated by transcatheter embolization with radioactive seeds. There were 14 patients with nonresectable or metastatic disease (stage IV) and 8 with stage II tumors treated. In 8 patients the tumor was implanted with radon seeds, complemented by 2,500 rad of external beam therapy, and 10 were treated by embolization with 125iodine seeds. The total dose delivered ranged form 1,600 to 14,000 rad. Several patients also had intra-arterial chemotherapy. Survival was improved over previously reported studies: 13 of 22 (59 per cent) at risk for 2 years and 5 of 15 (33 per cent) for 5 years. Distant metastases did not resolve but significant local palliation was achieved. Tumor size decreased in all patients, 8 of whom subsequently underwent nephrectomy. Other local effects included pain control (10 per cent), weight gain (75 per cent) and control of hemorrhage (88 per cent). Toxicity was minimal and consisted of mild nausea or pain. This approach, using a low energy emitter, allows selective high dose radiation of the tumor, while sparing the adjacent normal tissues. In contrast to renal artery occlusion with inert embolic material, subsequent nephrectomy in patients with disseminated disease is not necessary. Transcatheter embolization with radioactive seeds should be considered a reasonable palliative procedure in patients with nonresectable primary renal cell carcinoma.

  20. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

    PubMed Central

    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  1. Advances in the management of basal cell carcinoma

    PubMed Central

    Carucci, John A.

    2015-01-01

    Basal cell carcinoma (BCC), a malignant neoplasm derived from non-keratinizing cells that originate in the basal layer of the epidermis, is the most common cancer in humans. Several factors such as anatomic location, histologic features, primary or recurrent tumors, and patient characteristics influence the choice of treatment modality for BCC. Mohs micrographic surgery (MMS) facilitates optimal margin control and conservation of normal tissue for the management of BCC; however, other treatment modalities may also be implemented in the correct clinical scenario. Other treatment modalities that will be reviewed include simple excision, electrodesiccation and curettage, cryotherapy, topical immunotherapy and chemotherapy, photodynamic therapy, and radiation therapy. In addition, targeted molecular therapeutic options for the treatment of advanced or metastatic BCC will be discussed in this informal review based on recent literature obtained by using PubMed with relevant search terms. PMID:26097726

  2. Current Management of Advanced Resectable Oral Cavity Squamous Cell Carcinoma

    PubMed Central

    Ow, Thomas J.

    2011-01-01

    The oral cavity is the most common site of head and neck squamous cell carcinoma, a disease which results in significant morbidity and mortality worldwide. Though the primary modality of treatment for patients with oral cavity cancer remains surgical resection, many patients present with advanced disease and are thus treated using a multi-disciplinary approach. Patients with extracapsular spread of lymphatic metastasis and surgical margins that remain positive have been found to be at high risk for local-regional recurrence and death from disease, and are most often recommended to receive both post-operative radiation as well as systemic chemotherapy. The basis for this approach, as well as scientific developments that underly future trials of novels treatments for patients with high-risk oral cavity cancer are reviewed. PMID:21461056

  3. Lenvatinib: a potential breakthrough in advanced hepatocellular carcinoma?

    PubMed

    Oikonomopoulos, Georgios; Aravind, Preetha; Sarker, Debashis

    2016-02-01

    Treatment of advanced hepatocellular carcinoma (HCC) has reached a plateau after the approval of sorafenib in 2007. Several molecularly targeted therapies have failed to show significant improvement in survival outcomes compared with sorafenib, due to flaws in the design of clinical trials or failure to understand and correct for the competing co-morbidity of liver dysfunction. Lenvatinib is a multitargeted tyrosine kinase inhibitor with potent antiangiogenic effects, and has recently been approved for differentiated thyroid cancer. Lenvatinib has shown highly promising response data in Phase I/II clinical trials in HCC, although with some concerns regarding its toxicity profile. The pivotal Phase III REFLECT trial comparing lenvatinib to sorafenib has been completed, and the results of this trial will determine whether lenvatinib represents a breakthrough in the current crisis affecting HCC drug development.

  4. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    PubMed Central

    Dollinger, Matthias M; Behrens, Christa M; Lesske, Joachim; Behl, Susanne; Behrmann, Curd; Fleig, Wolfgang E

    2008-01-01

    Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8–12). Grade 1 local reactions following injection were the only side effects. Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition

  5. Extensive epidermoid cyst of the submental region

    PubMed Central

    Utumi, Estevam Rubens; Araujo, Juliane Pirágine; Pedron, Irineu Gregnanin; Yonezaki, Frederico; Machado, Gustavo Grothe

    2016-01-01

    Epidermoid cysts are malformations that are rarely observed in the submental region. Imaging has an important role in surgical planning according to the size and location of the cyst in relation to geniohyoid and mylohyoid muscles. This article reports the case of a 15-year-old female patient complaining of submental swelling. The differential diagnosis included infection, tumor, ranula, and abnormalities during embryonic development. The lesion was surgically excised using an extra-oral approach. The histopathological examination revealed a cyst wall lined with stratified squamous epithelium with the presence of several horny scales consistent with the diagnosis of an epidermoid cyst. No recurrences were found after 1 year of follow-up. PMID:27547744

  6. Isolated giant molluscum contagiosum mimicking epidermoid cyst

    PubMed Central

    Uzuncakmak, Tugba K.; Kuru, Burce C.; Zemheri, Ebru I.; Zindanci, Ilkin; Turkoglu, Zafer; Kavala, Mukaddes

    2016-01-01

    Molluscum contagiosum is a benign cutaneous viral infection which is caused by double- stranded DNA poxvirus. It affects mainly children and young adults and usually presents with single or multiple umblicated papules or nodules on face, arms, legs and anogenital regions. It may present in atypical size and clinical appearance in patients with altered or impaired immunity and rarely in immuncompetent patients. Herein we present an immuncompetent young adult patient with isolated giant molluscum contagiosum, which was mimicking epidermoid cyst clinically. PMID:27648389

  7. Epidermoid Cyst Arising in the Submandibular Region

    PubMed Central

    Kudoh, Masanori; Harada, Hiroyuki; Omura, Ken; Ishii, Yoshimasa

    2013-01-01

    Dermoid and epidermoid cysts in the oral cavity frequently develop in the midline or sublingual region of the floor of the mouth. Here, we report a rare case of an epidermoid cyst in the submandibular region. The patient was a 69-year-old man with a chief complaint of a mass in the right submandibular region. A mobile, elastic, relatively soft mass without tenderness was palpable in this region. The skin covering the mass was normal. MRI showed a cystic lesion measuring 3.5 × 3.0 cm under the platysma in the right submandibular region. Cystectomy was performed under general anesthesia. There was no adhesion to surrounding tissue and the right submandibular gland was preserved. The surgical specimen was cystic and contained soybean cord-like materials. Histopathologically, the cyst wall was lined by stratified squamous epithelium with no skin appendage, suggesting an epidermoid cyst. The postoperative course was uneventful and without recurrence after 28 months. PMID:24191161

  8. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome.

    PubMed

    Bodzin, Adam S; Busuttil, Ronald W

    2015-05-28

    Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients.

  9. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome

    PubMed Central

    Bodzin, Adam S; Busuttil, Ronald W

    2015-01-01

    Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients. PMID:26019732

  10. Endoscopic Treatment of a Third Ventricular Epidermoid Cyst.

    PubMed

    Paz, Daniel de Araujo; da Costa, Marcos Devanir Silva; Rodrigues, Thiago Pereira; Riechelmann, Guilherme Salemi; Suriano, Ítalo Capraro; Zymberg, Samuel Tau

    2017-03-01

    Epidermoid cyst is a benign and congenital lesion of ectodermal origin. Traditionally, microsurgical techniques are used to treat these lesions, and their occurrence in the third ventricle is rare. Here, the authors report a case of epidermoid cyst in the third ventricle that presented with signs and symptoms of intracranial hypertension, which was treated safely and effectively using neuroendoscopic surgery.

  11. Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

    PubMed

    Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

    2003-10-01

    The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced

  12. Esophageal leukoplakia or epidermoid metaplasia: a clinicopathological study of 18 patients.

    PubMed

    Singhi, Aatur D; Arnold, Christina A; Crowder, Clinton D; Lam-Himlin, Dora M; Voltaggio, Lysandra; Montgomery, Elizabeth A

    2014-01-01

    Oral leukoplakia is a relatively common, painless disorder of the oral mucosa. It predominantly affects middle-aged to elderly men and has a strong association with tobacco smoking and alcohol intake. Concomitant histological findings of hyperorthokeratosis and a well-developed granular cell layer, termed orthokeratotic dysplasia, are often associated with oral squamous cell carcinoma. In contrast, analogous lesions within the esophagus, termed esophageal epidermoid metaplasia, are rarely encountered and poorly described in the literature. To better characterize the clinicopathological features of this entity, we have collected 25 cases from 18 patients. Patients ranged in age from 37 to 81 years (mean, 61.5 years), with a slight female predominance (10/18, 56%). On presentation, a majority of patients complained of dysphagia (10/18, 56%). Past medical history was significant for tobacco smoking or long history of second-hand smoke in 11 (61%) patients and alcohol intake in 7 (39%) patients. Seventeen (94%) patients with esophageal epidermoid metaplasia were located within the middle-to-distal esophagus. Histologically, all cases were sharply demarcated and characterized by epithelial hyperplasia, a thickened basal layer, acanthotic midzone, a prominent granular cell layer, and superficial hyperorthokeratosis. Adjacent high-grade squamous dysplasia and/or squamous cell carcinoma were seen in 3 out of 18 (17%) patients. Follow-up information was available for 13 out of 18 (72%) patients and ranged from 2 to 8.3 years (mean, 2.3 years). Seven of the 13 (54%) patients had persistent disease; however, none of them developed squamous dysplasia or squamous cell carcinoma. In an effort to assess the incidence of esophageal epidermoid metaplasia, 198 consecutive esophageal biopsies were prospectively surveyed over a 6-month period at three academic institutions. No cases were identified within this time frame. In summary, esophageal epidermoid metaplasia is a rare

  13. Epidermoid cyst of the uvula in a child

    PubMed Central

    Daram, Shiva; Ulualp, Seckin O; Uddin, Naseem

    2016-01-01

    Objective: Epidermoid cysts are rarely located in the uvula. To date, epidermoid cyst of the uvula has not been reported in a child at preschool age. We present clinical and histopathological characteristics of an epidermoid cyst in a child with uvula mass. Methods: Retrospective chart review. Results: A 5-year-old boy was seen in the pediatric otolaryngology clinic for assessment of a uvula mass. The mass was detected during a tonsillectomy and adenoidectomy performed for sleep-related breathing disorder. The mass was completely removed and the final diagnosis was epidermoid cyst. Conclusion: Pediatricians, otolaryngologists, and pathologists should be cognizant of the occurrence of uvular epidermoid cyst in preschool children. PMID:28382209

  14. Lenvatinib in Advanced, Radioactive Iodine-Refractory, Differentiated Thyroid Carcinoma.

    PubMed

    Yeung, Kay T; Cohen, Ezra E W

    2015-12-15

    Management options are limited for patients with radioactive iodine refractory, locally advanced, or metastatic differentiated thyroid carcinoma. Prior to 2015, sorafenib, a multitargeted tyrosine kinase inhibitor, was the only approved treatment and was associated with a median progression-free survival (PFS) of 11 months and overall response rate (ORR) of 12% in a phase III trial. Lenvatinib, a multikinase inhibitor with high potency against VEGFR and FGFR demonstrated encouraging results in phase II trials. Recently, the pivotal SELECT trial provided the basis for the FDA approval of lenvatinib as a second targeted therapy for these patients. Median PFS of 18.3 months in the lenvatinib group was significantly improved from 3.6 months in the placebo group, with an HR of 0.21 (95% confidence interval, 0.4-0.31; P < 0.0001). ORR was also significantly increased in the lenvatinib arm (64.7%) compared with placebo (1.5%). In this article, we will review the molecular mechanisms of lenvatinib, the data from preclinical studies to the recent phase III clinical trial, and the biomarkers being studied to further guide patient selection and predict treatment response.

  15. Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

    PubMed Central

    Wehler, Thomas C.; Graf, Claudine; Biesterfeld, Stefan; Brenner, Walburgis; Schadt, Jörg; Gockel, Ines; Berger, Martin R.; Thüroff, Joachim W.; Galle, Peter R.; Moehler, Markus; Schimanski, Carl C.

    2008-01-01

    Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P = .039), tumor dedifferentiation (P = .0005), and low hemoglobin (P = .039). In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma. PMID:19266088

  16. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  17. MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2017-02-08

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  18. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma

    PubMed Central

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-01-01

    Abstract Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and “en bloc” removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of

  19. Acquired dorsal intraspinal epidermoid cyst in an adult female

    PubMed Central

    Singh, Kulwant; Pandey, Sharad; Gupta, Praveen Kumar; Sharma, Vivek; Santhosh, Deepa; Ghosh, Amrita

    2016-01-01

    Background: Epidermoid and dermoid cyst comprise <1% of spinal tumors and may be congenital (hamartoma) or acquired (iatrogenic) in origin. Epidermoid cysts within the neuraxis are rare benign neoplasms that are most commonly located in the intracranial region. Case Description: Here, we report the a case of an acquired intradural extramedullary epidermoid cyst involving the thoracic region in an adult female who had no associated history of an accompanying congenital spinal deformity. Conclusion: Early diagnosis and immediate surgical intervention reduce patient morbidity. Near complete or subtotal excision of the cyst wall is warranted to prevent inadvertent injury to the spinal cord thus minimizing neurological morbidity. PMID:26904369

  20. Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.

    PubMed

    Doval, D C; Pande, S B; Sharma, J B; Pavithran, K; Jena, A; Vaid, A K

    2008-10-01

    In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.

  1. Recent advances in the management of renal cell carcinoma

    PubMed Central

    Molina, Ana M.; Nanus, David M.

    2016-01-01

    Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years with the recent approval of two new agents resulting in prolonged progression-free and overall survival. PMID:27019698

  2. Pineal epidermoid cyst: case report and review of the literature.

    PubMed

    Hassani, Fahd Derkaoui; Bouchaouch, Abdelali; El Fatemi, Nizare; Gana, Rachid; El Abbadi, Najia; Maaqili, Moulay Rachid

    2014-01-01

    Intracranial epidermoid cysts are one of the rare tumors of all intracranial tumors. They represent 0,2 to 1% of intracranial tumors and 7% of tumors in the cerebellopontine angle. The pineal region is exceptionally subject to such kind of tumor. Cushing was the first to report the pineal localization of the epidermoid cyst in 1928. Up to now, 85 cases of pineal epidermoid cyst were cited in the literature. We report a clinical case concerning a 45 years old man who presented an intracranial hypertension during 18 months. The clinical examination found a hemiparesis with a facial hypoesthesis. The MRI showed a process of the pineal region. The patient underwent a surgery with a large resection. The histological examination confirms the epidermoid cyst. Many approaches were described in the literature. The outcome is related to this localization.

  3. Epidermoid Cyst of the Sole - A Case Report

    PubMed Central

    Rajput, Santosh Singh; Gopinathan, Nayar Sajeeth

    2016-01-01

    Epidermoid cysts are common benign subcutaneous lesion also termed as epidermal cysts. Epidermoid cyst are commonly seen in hairy regions of body like scalp, face and scrotum, can be single or multiple, but rarely can occur in glabrous skin of palm and sole. They are known to result from progressive cystic ectasia of the infundibular portion of hair follicle but the pathogenesis in palmo-plantar epidermoid cyst differs that is traumatic sequestration of epidermal elements into dermis. Here, we report a case of 30-year-old female presented with complaints of swelling in her left sole. On examination a palpable firm swelling was noted just below the 2nd web space left foot plantar region, on X-ray foot no osseous lesion or foreign body was detected. Swelling was excised and sent for histopathological examination which confirmed it as epidermoid cyst. PMID:28050432

  4. Treatment of advanced renal cell carcinoma: recent advances and current role of immunotherapy, surgery, and cryotherapy.

    PubMed

    Mennitto, Alessia; Verzoni, Elena; Calareso, Giuseppina; Spreafico, Carlo; Procopio, Giuseppe

    2017-01-21

    Renal cell carcinoma (RCC) is the 10th most common cancer in Western countries. The prognosis of metastatic disease is unfavorable but may be different according to several risk factors, such as histology and clinical features (Karnofsky performance status, time from nephrectomy, hemoglobin level, neutrophils and thrombocytes count, lactate dehydrogenase and calcium serum value, sites and extension of the disease). In this review, we focused on some recent developments in the use of immunotherapy, surgery and cryotherapy in the treatment of advanced disease. While RCC is unresponsive to chemotherapy, recent advances have emerged with the development of targeted agents and innovative immunotherapy-based treatments. Surgical resection remains the standard of care for patients with small renal lesions but in patients with significant comorbidities ablative therapies such as cryoablation and radiofrequency ablation may lead to local cancer control and avoid surgical complications and morbidity. In the setting of metastatic RCC, radical nephrectomy, or cytoreductive nephrectomy, is considered a palliative surgery, usually part of a multimodality treatment approach that requires systemic treatments.

  5. Pediatric epidermoid cysts masquerading as ranulas: A case series.

    PubMed

    Reddy, Abhita; Kreicher, Kathryn L; Patel, Neha A; Schantz, Stimson; Shinhar, Shai

    2016-02-01

    Pediatric neck masses represent a variety of differential diagnoses. A common pathology in pediatric cystic neck tumors include ranulas, mucus retention cysts due to salivary gland obstruction. Epidermoid cysts are lesions infrequently encountered in the pediatric population and may appear similarly to ranulas on computed tomography imaging. MRI more easily differentiates these masses, and should therefore be the preferred imaging modality. Due to their distinct intraoperative management, ranulas and epidermoid cysts should be distinguished preoperatively through proper workup.

  6. Epidermoid tumor within Meckel's cave--case report.

    PubMed

    Nadkarni, T; Dindorkar, K; Muzumdar, D; Goel, A

    2000-01-01

    A rare case of an epidermoid tumor lying within Meckel's cave is reported. A 27-year-old housewife presented with complaints of right facial hypesthesia for two and a half years. On examination she had partial loss of touch sensation in the right trigeminal nerve distribution. Magnetic resonance imaging revealed a tumor located at the right petrous apex and cavernous sinus. The epidermoid tumor was excised through a lateral basal subtemporal approach. The symptoms resolved following surgery.

  7. Epidermoid cyst: Report of two cases

    PubMed Central

    Puranik, Surekha R; Puranik, Rudrayya S; Prakash, Satya; Bimba, M

    2016-01-01

    Epidermoid cysts (ECs) are uncommon, benign cystic lesions derived from the entrapment of surface epithelium or more often from the aberrant healing of infundibular epithelium during an episode of follicular inflammation. ECs occur anywhere on the body, particularly along embryonic fusion lines, most commonly on the face, scalp, neck, chest and upper back. Head and neck ECs constitute only about 7%, whereas only 1.6% of ECs are reported in the oral cavity. They comprise <0.01% of all the oral cysts. Floor of the mouth, tongue, lips, palate, jaws, etc., are some of the reported sites of ECs in the oral cavity. Microscopically, ECs are lined with plain stratified squamous epithelium filled with laminated layers of keratin. Here, we report two rare cases of ECs, one occurring in the gingival aspect and other in the lower third of face. The cases are reported due to rarity of ECs in the head and neck region. PMID:27721628

  8. Splenic epidermoid cyst - a rare entity.

    PubMed

    Rana, Amrit Pal Singh; Kaur, Manjit; Singh, Parvinder; Malhotra, Satish; Kuka, Amarjit Singh

    2014-02-01

    C Splenic epidermoid cysts are relatively uncommon. Most often, they are asymptomatic, but they may present with abdominal discomfort, predominantly at young ages. We are reporting a rare case of 12-years-old female child with history of dull intermittent pain, tender palpable mass in left hypochondrium on physical examination. Ultrasonography (USG) of abdomen showed large cyst in upper pole of spleen, and an X ray of chest revealed slightly raised left hemidiaphragm. Axial sections taken on computerized tomography of abdomen showed a large well defined cystic mass near upper pole of spleen, with a thin septum in it. On laparotomy, open total splenectomy was performed. Sections from cystic wall were processed and histopathological examination revealed fibrous tissue covered by stratified squamous epithelium. Although, now-a-days emphasis is being laid on minimal invasive operative procedures which preserve spleen. This case report favours total splenectomy, considering postoperative outcome. The final diagnosis always depends upon histopathological examination.

  9. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  10. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    PubMed Central

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  11. Vulvar Epidermoid Cyst and Type 2 Radical Genital Mutilation

    PubMed Central

    Birge, Ozer; Ozbey, Ertugrul Gazi; Arslan, Deniz; Erkan, Mustafa Melih; Demir, Feyza; Akgor, Utku

    2015-01-01

    About 100 million women are estimated to be circumcised globally. Various rates of complications have been encountered, especially after circumcision, such as bleeding, infection, shock, menstrual irregularity, difficulty in urination or common urinary tract infections, inguinal pain, difficulty in sexual intercourse, and genital circumcision scar especially at the vulvar region, and cystic or solid character mass in short and long term. Furthermore, the maternal-fetal morbidity and mortality increase due to bleeding and fistula, which develop after prolonged labor, travail, and difficult labors. Our aim in this paper was to discuss a 42-year-old multiparous female case who had undergone type 2 radical genital mutilation (circumcision) when she was 7 years of age, along with the literature, which has been evaluated for the gradually growing mass at the left inguinal canal region in the last 10 years and diagnosed as epidermoid inclusion cyst developing secondary to postcircumcision surgical ground trauma, since there was no other case found in the literature search that had been circumcised at such an early age and developing after circumcision at such advanced age, and, therefore, this is suggested to be the first case on this subject. PMID:26682078

  12. Vismodegib: a guide to its use in locally advanced or metastatic basal cell carcinoma.

    PubMed

    Lyseng-Williamson, Katherine A; Keating, Gillian M

    2013-02-01

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the USA, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. In an ongoing, noncomparative, phase II trial, oral vismodegib was effective in and had an acceptable tolerability profile in the treatment of patients with locally advanced or metastatic BCC.

  13. Coexistence of intracranial epidermoid tumor and multiple cerebral aneurysms

    PubMed Central

    Yao, Pei-Sen; Lin, Zhang-Ya; Zheng, Shu-Fa; Lin, Yuan-Xiang; Yu, Liang-Hong; Jiang, Chang-Zhen; Kang, De-Zhi

    2017-01-01

    Abstract Rationale: There were a few case reports concerning epidermoid tumor coexisted with multiple cerebral aneurysms. Here, we present one case of coexistence of intracranial epidermoid tumor and multiple cerebral aneurysms and performed a literature review. Patient concerns: A 42 years old male patient was admitted to our institution with complaints of headache and dizziness. Interventions: The radiological examinations showed a hypointense lesion in the right parasellar and petrous apex region and an ipsilateral saccular aneurysm originated from the M2–M3 junction of the right middle cerebral artery (MCA) and a saccular aneurysm of the clinoid segment of right internal carotid artery (ICA). Interventions: The patients underwent a right frontotemporal approach for removal of the epidermoid tumor and clipping of the MCA aneurysm in one stage. The aneurysm located at the clinoid segment of ICA was invisible and untreated during operation. Outcomes: No postoperative complications were found in the patient. The patient's follow up after 5 years of surgical treatment was uneventful, and the untreated aneurysm remains stable. Lessons: The coexistence of intracranial epidermoid tumor and cerebral aneurysm is a rare event. The secondly inflammation in cerebral arterial wall may be responsible for the aneurysm formation. Surgical treatment of the intracranial epidermoid tumor and cerebral aneurysm repair may be an optimal scheme in one stage. PMID:28151901

  14. Managing patients receiving sorafenib for advanced hepatocellular carcinoma: a case study.

    PubMed

    Hull, Diana; Armstrong, Ceri

    2010-05-01

    Despite improvements in cytotoxic chemotherapy agents over the last 50 years, the outlook for patients with many of the most common solid tumours has remained poor. However, in recent years a number of targeted therapies have been licensed in the European Union for use in these cancer types. One such therapy, a tyrosine kinase inhibitor (sorafenib) is now used to treat patients with advanced hepatocellular carcinoma (HCC) and metastatic renal cell carcinoma. This article will explore the role of the oncology nurse in managing patients receiving sorafenib for advanced HCC. A brief overview of sorafenib as a current treatment approved for advanced HCC in the palliative setting is presented. This is followed by a case study-based discussion with particular reference to some of the key care coordination challenges facing the oncology nurse. The management of treatment-related adverse events and the importance of using a multidisciplinary team approach is also reviewed.

  15. Nab-paclitaxel as alternative treatment regimen in advanced cholangiocellular carcinoma

    PubMed Central

    Unseld, Matthias; Scheithauer, Werner; Weigl, Roman; Kornek, Gabriela; Stranzl, Nadja; Bianconi, Daniela; Brunauer, Georg; Steger, Guenther; Zielinski, Christoph C.

    2016-01-01

    Background Advanced cholangiocellular carcinoma has a poor prognosis with limited therapeutic options. Nab-paclitaxel has recently been described to be beneficial in metastatic pancreatic cancer improving overall and progression free survival (PFS). The potential antitumor activity of nab-paclitaxel in cholangiocellular carcinoma is hitherto unknown. Methods We retrospectively analyzed an institutional cholangiocellular carcinoma registry to determine the potential biological activity of nab-paclitaxel in advanced intrahepatic cholangiocellular carcinoma. Disease control rate (DCR), PFS and overall survival (OS) upon nab-paclitaxel based treatment, after failure of platinum-containing first-line combination chemotherapy, was assessed. Results Twelve patients were identified. Five of 12 patients (42%) received nab-paclitaxel as second line, and 7 patients (56%) as third-line treatment. The objective DCR with nab-paclitaxel was 83% (10/12 patients). One patient had a complete remission (CR), two patients had a partial remission (PR) and 7 patients had stable disease (SD). Disease was rated progressive in two patients. In all 12 patients receiving nab-paclitaxel the median time to progression was 6 months (range, 2.1–19.5 months). Median OS after initiation of nab-paclitaxel treatment was 9 months (2.1–28.4 months). The median time of survival after diagnosis of advanced disease was 21.5 months, whereby 3 patients were alive at the date of censoring (04/01/2015). Conclusions This is the first report suggesting substantial antitumor activity of nab-paclitaxel in advanced cholangiocellular carcinoma. In this small series, nab-paclitaxel based salvage chemotherapy appears to have a biological activity by controlling the disease and positively affecting survival. Randomized trials in this disease entity and subgroup of patients are urged. PMID:27563449

  16. Intrathoracic impedance monitor alarm in a patient with cardiac resynchronisation therapy and advanced lung carcinoma.

    PubMed

    Cvijić, Marta; Zižek, David; Antolič, Bor; Zupan, Igor

    2013-01-01

    The intrathoracic impedance monitor system measures impedance between the device case and the right ventricular coil and reflects intrathoracic fluid status. It is used to detect early volume overload in patients with chronic heart failure. We report a case of inappropriate activation of the intrathoracic impedance monitor alarm in a patient with epidermoid lung cancer and pleural carcinosis.

  17. Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery

    PubMed Central

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han

    2015-01-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery. PMID:26019766

  18. Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

    PubMed

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-05-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

  19. Sylvian fissure epidermoid cyst presenting with intention tremor

    PubMed Central

    Shah, Abhidha; Makkiyah, Feda; Goel, Atul

    2016-01-01

    Epidermoid tumors are benign tumors which contain keratin, cellular debris, and cholesterol, and are lined with stratified squamous epithelium. They grow in discreet silence sustained over a multitude of years. The tumors most commonly present with headache and seizures. We report the case of a 24-year-old male with a large sylvian fissure epidermoid tumor who presented with intention tremor. The patient was operated, and a near-total excision of the tumor was performed with a resolution of the tremor. PMID:27057232

  20. Advanced oxidation protein products and total antioxidant activity in colorectal carcinoma.

    PubMed

    Avinash, S S; Anitha, M; Vinodchandran; Rao, Gayathri M; Sudha, K; Shetty, Beena V

    2009-01-01

    The present study was designed to assess the levels of advanced oxidation protein products (AOPP) and percent hemolysis (that indirectly indicates the degree of membrane damage secondary to lipid peroxidation) in colorectal carcinoma. Glutathione (GSH), total thiols and albumin were measured to determine the antioxidant status. Considering the dynamic interaction between various antioxidants in the body, we measured the total antioxidant activity (AOA). Globulin was measured to assess the inflammatory response secondary to oxidative stress. Investigations were conducted in 45 cases of recently diagnosed primary colorectal adenocarcinoma. As control, 45 age and sex matched healthy persons were chosen. GSH was estimated in whole blood, percent hemolysis in RBC suspension and other parameters in plasma. We observed a very high significant increase (P<0.001) in AOPP, percent hemolysis and a highly significant increase (P<0.01) in globulin in colorectal carcinoma. We observed a very high significant decrease (P<0.001) in whole blood GSH, total thiols, albumin, AOA and a significant decrease (P<0.05) in plasma GSH in colorectal carcinoma. A very high significant negative correlation between percent hemolysis and AOA and an apparent negative correlation between total thiols and AOPP was seen in colorectal carcinoma. This demonstrated oxidative stress, decreased antioxidant status and secondary inflammatory response in colorectal carcinoma.

  1. Angiogenesis-Related Gene Expression Profile with Independent Prognostic Value in Advanced Ovarian Carcinoma

    PubMed Central

    Redondo, Andrés; Mariño-Enríquez, Adrián; Madero, Rosario; Espinosa, Enrique; Vara, Juan Ángel Fresno; Sánchez-Navarro, Iker; Hernández-Cortes, Ginés; Zamora, Pilar; Pérez-Fernández, Elia; Miguel-Martín, María; Suárez, Asunción; Palacios, José; González-Barón, Manuel; Hardisson, David

    2008-01-01

    Background Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients. Methodology/Principal Findings RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001). Conclusions/Significance It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma. PMID:19112514

  2. [Laparoscopic abdominoperineal resection after preoperative chemoradiotherapy for advanced carcinoma associated with anal fistula].

    PubMed

    Morikawa, Takashi; Yamashita, Kimihiro; Sumi, Yasuo; Kanemitsu, Kiyonori; Yamamoto, Masashi; Kanaji, Shingo; Imanishi, Tatsuya; Nakamura, Tetsu; Suzuki, Satoshi; Tanaka, Kenichi; Kakeji, Yoshihiro

    2014-11-01

    The patient was a 71-year-old man who was diagnosed with anal fistula 50 years previously. He complained of mucous and bloody stools. He was diagnosed with a carcinoma associated with anal fistula after biopsy. Image examination showed that the tumor was filled with mucinous substances and that it had invaded the levator ani muscle, with left external iliac and left inguinal lymph node metastases. Therefore, preoperative chemoradiotherapy for locally advanced cancer was administered. After chemoradiotherapy, the tumor and metastatic lymph nodes reduced in size. We performed laparoscopic abdominoperineal resection. Histopathologically, the tumor was revealed as a mucinous adenocarcinoma, but no cancer cells were present on the surgical margin. This case suggested that preoperative chemoradiotherapy could be effective for locally advanced carcinoma associated with anal fistula.

  3. Combined chemotherapy and radiation therapy for advanced carcinoma of the cervix

    SciTech Connect

    Lipsztein, R.; Kredentser, D.; Dottino, P.; Goodman, H.M.; Dalton, J.F.; Bloomer, W.D.; Cohen, C.

    1987-12-01

    Ten patients with advanced squamous cell carcinoma of the uterine cervix received induction chemotherapy with cis-platinum, mitomycin-C, vincristine, and bleomycin (BOMP) over a 5 week period, followed by radiotherapy with concomitant weekly cisplatinum. Two patients were FIGO stage I-B barrel-shaped, five were stage II-B, and three were III-B. All patients responded to induction chemotherapy with five complete and five partial responses. At the completion of radiation therapy, nine patients had negative biopsies. One patient never reached a complete response and died of distant metastasis. Another underwent total exenteration for a central recurrence and was found to have microscopic paraaortic lymph node involvement. A third recurred in the parametrium. Two patients with barrel-shaped tumors underwent extrafascial hysterectomies; both had negative specimens and tolerated surgery well. Although follow-up is short, this new approach for advanced carcinoma of the cervix yielded excellent results and was well tolerated.

  4. Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma

    PubMed Central

    Schmidinger, M; Wenzel, C; Locker, G J; Muehlbacher, F; Steininger, R; Gnant, M; Crevenna, R; Budinsky, A C

    2001-01-01

    We performed a pilot-study on pegylated liposomal doxorubicin (PLD) for advanced hepatocellular carcinoma. Seventeen patients received 40 mg/m2 PLD intravenously every 4 weeks. A clinical benefit response was achieved in 50% (complete remission 7%, minor remission 7%, stable disease 36%). Toxicities were moderate. In view of these encouraging findings, further studies appear warranted. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11747325

  5. Yttrium-90 Radioembolization of Hepatocellular Carcinoma-Performance, Technical Advances, and Future Concepts.

    PubMed

    Molvar, Christopher; Lewandowski, Robert

    2015-12-01

    Hepatocellular carcinoma (HCC) is a lethal tumor, claiming over half a million lives per year. Treatment of HCC is commonly performed without curative intent, and palliative options dominate, including catheter-based therapies, namely, transarterial chemoembolization and yttrium-90 ((90)Y) radioembolization. This review will showcase the performance of (90)Y radioembolization for the treatment of HCC, focusing on recent seminal data and technical advances. In particular, novel radioembolization treatment concepts are discussed and compared with conventional HCC therapy.

  6. Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma

    PubMed Central

    Huang, Yun-Ching; Chang, Ying-Hsu; Chiu, Kuo-Hsiung; Shindel, Alan W.; Lai, Chia-Hsuan

    2016-01-01

    There is relatively little literature on adjuvant radiotherapy after radical nephroureterectomy with bladder cuff excision (RNU) for patients with upper tract urothelial carcinoma (UTUC). This study was designed to determine the efficacy of adjuvant radiotherapy for patients with pT3N0M0 UTUC. We retrospectively reviewed 198 patients treated with RNU between December 2001 and January 2015. Postoperative radiotherapy was administered in 40 (20.2%) of patients. Patients who received radiotherapy were younger than those that did not (65.2 vs. 70.5 years, p = 0.023). With median follow up of 29.1 months, Kaplan-Meier analysis with the log-rank test demonstrated no significant differences between those omitting vs receiving adjuvant radiotherapy in regards to 2-year rates of overall survival (72.0% vs. 73.4%, p = 0.979), cancer-specific survival (73.2% vs. 75.3%, p = 0.844), and recurrence-free survival (61.2% vs. 66.3%, p = 0.742). However, in multivariable analysis with Cox regression, young age, absence of chronic kidney disease, negative lymphovascular invasion, negative surgical margin, and adjuvant chemotherapy were also associated with better cancer-specific survival. In conclusion, adjuvant radiotherapy did not offer any significant benefit in terms of overall, cancer-specific, and recurrence-free survivals in patients with pT3N0M0 UTUC after RNU. More effective systemic adjuvant chemotherapy is necessary to improve the outcome of these patients. PMID:27910890

  7. Unusually Giant Sublingual Epidermoid Cyst: A Case Report

    PubMed Central

    Nishar, Chintan-C; Ambulgekar, Vijayalaxmi-K.; Gujrathi, Atish-B.; Chavan, Pravin-T.

    2016-01-01

    Introduction: Epidermoid cysts are rare, slow‑growing, benign, developmental cysts, which are derived from abnormally situated ectodermal tissue. Epidermoid cysts of the floor of the mouth represent <0.01% of all oral cysts. So far, only a few cases have been reported. Case Report: Hereby, we present a case of a giant sublingual epidermoid cyst, which was completely asymptomatic upon presentation. However, due to its large size, it pushed the epiglottis posteriorly and created difficulty during intubation. The patient developed respiratory distress after its surgical excision and extubation, requiring tracheostomy post operatively. The patient recovered well and a successful weaning of tracheostomy was performed, giving the patient a healthy life. Conclusion: Epidermoid cyst is a rare differential diagnosis of sublingual swelling that should be kept in mind for large asymptomatic swellings in this region. The only symptom it can cause might be respiratory distress due to its large size. This can happen not only pre-operatively but also post-operatively and the surgeon should be ready for immediate tracheostomy. PMID:27602342

  8. Subconjunctival epidermoid cysts in Gorlin-Goltz syndrome.

    PubMed

    De Craene, S; Batteauw, A; Van Lint, M; Claerhout, I; Decock, C

    2014-08-01

    Epidermoid cysts are common benign cysts which occur particularly on the skin of the face, neck and upper trunk. Subconjunctival location of these cysts is very rare and, until today, only seen in patients with Gorlin-Goltz syndrome. Histopathological examination of these cysts show similarities with odontogenic keratocysts, a typical clinical manifestation of Gorlin-Goltz syndrome.

  9. Epidermoid cyst of the ileum in a miniature dachshund dog

    PubMed Central

    Shimamura, Shunsuke; Kainuma, Risa; Kimura, Ken; Okamura, Yasuhiko; Kobayashi, Saori; Katayama, Masaaki; Sato, Reeko; Yasuda, Jun

    2014-01-01

    A 13-year-old castrated male miniature dachshund dog was presented with chronic vomiting and diarrhea. Contrast radiography and surgical exploration revealed an ileal cyst, which was excised. A diagnosis of epidermoid cyst was made from a combination of the clinical findings and histological examination of the surgical specimen. PMID:24688137

  10. Meckel's cave epidermoid with trigeminal neuralgia: CT findings.

    PubMed

    Kapila, A; Steinbaum, S; Chakeres, D W

    1984-12-01

    An epidermoid tumor of Meckel's cave was found in a middle-aged woman with trigeminal neuralgia. On CT the lesion had negative attenuation numbers of fat and extended from an expanded Meckel's cave through the porous trigeminus into the ambient and cerebellopontine angle cisterns. Surgical excision provided relief of the patient's trigeminal neuralgia.

  11. Phase II Study of Concurrent Chemoradiation in Combination With Erlotinib for Locally Advanced Esophageal Carcinoma

    SciTech Connect

    Li Gang; Hu Wei; Wang Jianhua; Deng Xia; Zhang Ping; Zhang Xuebang; Xie Congyin; Wu Shixiu

    2010-12-01

    Purpose: To investigate the feasibility and efficacy of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma. Methods and Materials: Twenty-four patients with locally advanced esophageal carcinoma were treated with concurrent chemoradiotherapy. A daily fraction of 2.0 Gy was prescribed to a total dose of 60 Gy over 6 weeks. Concurrent paclitaxel (135 mg/m{sup 2}, d{sub 1}) and cisplatin (20 mg/m{sup 2}, d{sub 1-3}) were administered on Day 1 and Day 29 of the radiotherapy. Erlotinib, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, was taken by every patient at the dose of 150 mg daily during the chemoradiotherapy. Results: The median follow-up of the 24 patients was 18.6 months (range, 7.1-29.6 months). The 2-year overall survival, local-regional control, and relapse-free survival were 70.1% (95% CI, 50.4-90%), 87.5% (95% CI, 73.5-100%), and 57.4% (95% CI, 36.3-78.7%), respectively. During the chemoradiotheapy, the incidences of acute toxicities of Grade 3 or greater, such as leucopenia and thrombocytopenia, were 16.7 % (4/24) and 8.3% (2/24). Conclusions: Application of concurrent chemoradiotherapy in combination with erlotinib for locally advanced esophageal carcinoma yielded satisfactory 2-year overall survival and local-regional control. The toxicities were well tolerated.

  12. Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

    SciTech Connect

    Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle; Carroll, William R.; Desmond, Renee; Clemons, Lisa; Spencer, Sharon; Magnuson, J. Scott; Rosenthal, Eben L.

    2013-04-01

    Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.

  13. Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma

    NASA Astrophysics Data System (ADS)

    Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.

    1996-12-01

    Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.

  14. Bilateral Blindness Following Chemoradiation for Locally Advanced Oropharyngeal Carcinoma

    PubMed Central

    Zeng, K. Liang; Kuruvilla, Sara; Sanatani, Michael

    2015-01-01

    Wernicke's encephalopathy is a life-threatening neurologic complication of thiamine deficiency. Though the presentation of symptoms can vary widely, the classical triad is founded on ophthalmoplegia, alteration of mental status, and gait disturbance. We describe a case of Wernicke's encephalopathy in an oncology patient shortly after concurrent 5-fluorouracil, carboplatin, and radiotherapy for locally advanced oropharyngeal cancer, presenting as complete bilateral blindness, ataxia, nystagmus, and confusion. Thiamine was given based on clinical suspicion and rapid improvement of clinical findings occurred. An MRI performed later supported the diagnosis of Wernicke's encephalopathy. A multifactorial etiology of thiamine deficiency from nutritional deficits and neurotoxic effects of chemotherapy are hypothesized. PMID:26623207

  15. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma.

    PubMed

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC.

  16. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

    PubMed Central

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC. PMID:27695345

  17. Advanced carcinoma of the stomach treated with definitive proton therapy

    SciTech Connect

    Koyama, S.; Kawanishi, N.; Fukutomi, H.; Osuga, T.; Iijima, T.; Tsujii, H.; Kitagawa, T. )

    1990-04-01

    We report the case of a 72-yr-old man who suffered from severe chronic emphysema with poor pulmonary function, and who had advanced cancer of the stomach. Proton beam radiotherapy was applied to the lesion, since surgery was contraindicated. The total dose to the stomach lesion was 61 Gy in 7 wk. The tumor on the stomach regressed, with flattening of the round wall of the lesion. The reactive changes of the proton beam radiotherapy, based on the histopathological examination, revealed extensive tumor necrosis and sparing of vital architecture of normal tissue around the irradiated tumor tissue. Only small clusters of vital or devitalized tumor cells with less than approximately 5% of the whole tumor tissue remained after treatment. We suggest that a high dose of radiation delivered by well-defined proton field could result in an improved therapeutic outcome without undue risk of injury to normal tissue.

  18. Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study

    PubMed Central

    André, T; Reyes-Vidal, J M; Fartoux, L; Ross, P; Leslie, M; Rosmorduc, O; Clemens, M R; Louvet, C; Perez, N; Mehmud, F; Scheithauer, W

    2008-01-01

    Advanced biliary tract carcinomas (BTCs) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) has shown promising activity in this setting. This international phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTC received gemcitabine 1000 mg m−2 (day 1) and oxaliplatin 100 mg m−2 (day 2), every 2 weeks. Seventy patients were enroled; 72.9% had metastatic disease. Sixty-seven patients were treated. There were 10 confirmed partial responses (14.9%; 95% confidence interval (CI), 7.4–25.7%) in the treated population (RECIST). Twenty-four patients (35.8 %) had stable disease. The objective response rate was 20.5% in patients with non-gallbladder cancers (9/44 patients) and 4.3% in patients with gallbladder cancers (1/23). Median overall survival for the intent-to-treat population was 8.8 months (95% CI, 6.9–11.1%) and progression-free survival was 3.4 months (95% CI, 2.5–4.6%). Grade 3/4 toxicities included thrombocytopenia (14.9% of patients), alanine aminotransferase elevation (13.4%), anaemia (10.4%), neutropenia (11.9%) and pain (11.9%). In this study, GEMOX demonstrated activity in non-gallbladder carcinoma, but poor activity in gallbladder carcinoma. GEMOX is well tolerated in advanced BTCs. PMID:19238628

  19. High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study.

    PubMed Central

    Sweetenham, J. W.; McKendrick, J. J.; Jones, D. H.; Whitehouse, J. M.; Williams, C. J.

    1990-01-01

    Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered. PMID:2155645

  20. Stereotactic ablative radiotherapy with CyberKnife for advanced thymic carcinoma: a case report.

    PubMed

    Fan, C Y; Huang, W Y; Jen, Y M; Lin, M J; Lin, K T

    2015-10-01

    Thymic carcinoma is a rare but lethal mediastinal cancer. The optimal treatment for advanced thymic carcinoma is not yet established. This report is the first known of stereotactic ablative radiotherapy (sabr) with CyberKnife (Accuray, Sunnyvale, CA, U.S.A.) as definitive therapy for thymic carcinoma. The patient, a 70-year-old woman with thymic carcinoma, invasion into neighboring organs, and pleural metastases-underwent CyberKnife sabr at 40 Gy in 5 fractions for two lesions, one in the thymus and one in the right paraspinal pleura. After 61 months of observation, a partial response was observed in the irradiated fields. However, disease progression in the non-irradiated pleura was noted. The patient underwent salvage CyberKnife sabr for the four initially nonirradiated pleural lesions. Computed tomography images obtained 10 months after the salvage therapy revealed a partial response. The patient is living, with progression-free irradiated lesions and no radiation-related toxicity. CyberKnife sabr is feasible for patients who are unable to undergo either surgery or conventionally fractionated radiation therapy.

  1. Immunotherapy for patients with advanced pancreatic carcinoma: a promising treatment

    PubMed Central

    Liu, Jing; Lian, Zhouyang; Liang, Long; Chen, Wenbo; Luo, Xiaoning; Pei, Shufang; Mo, Xiaokai; Zhang, Lu; Huang, Wenhui; Ouyang, Fusheng; Guo, Baoliang; Liang, Changhong; Zhang, Shuixing

    2017-01-01

    There are limited data on the safety and efficacy of immunotherapy for patients with advanced pancreatic cancer (APC). A meta-analysis of single-arm trials is proposed to assess the efficacy and safety of immunotherapy for APC. Eighteen relevant studies involving 527 patients were identified. The pooled disease control rate (DCR), overall survival (OS), progression free survival (PFS), and 1-year survival rate were estimated as 59.32%, 7.90 months, 4.25 months, and 30.12%, respectively. Subgroup analysis showed that the pooled OS, PFS, and 1-year survival rate were significantly higher for autologous activated lymphocyte therapy compared with peptide-based vaccine therapy (OS: 8.28 months vs. 7.40 months; PFS: 6.04 months vs. 3.86 months; 1-year survival rate: 37.17% vs. 19.74%). Another subgroup analysis demonstrated that the pooled endpoints were estimated as obviously higher for immunotherapy plus chemotherapy compared with immunotherapy alone (DCR: 62.51% vs. 47.63%; OS: 8.67 months vs. 4.91 months; PFS: 4.91 months vs. 3.34 months; 1-year survival rate: 32.32% vs. 21.43%). Of the included trials, seven trials reported no treatment related adverse events , five trials reported (16.6 3.9) % grade 3 adverse events and no grade 4 adverse events. In conclusion, immunotherapy is safe and effective in the treatment of APC. PMID:27992378

  2. Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2012-01-01

    Angiogenesis in general and the vascular endothelial growth factor (VEGF) signaling axis in particular is a validated target in renal cell carcinoma (RCC). Clear-cell carcinoma of the kidney is now recognized as a malignancy that is sensitive to inhibitors of the VEGF pathway. Treatment options for patients with metastatic renal cell carcinoma have evolved in dramatic fashion over the past 6 years, and a new paradigm has developed. The cytokines interferon-α and interleukin-2 were previously utilized for therapy, but since December 2005, six new agents have been approved in the United States for the treatment of advanced RCC. Two are tyrosine kinase inhibitors (TKI's) including sunitinib and recently pazopanib, and the multikinase inhibitor sorafenib. The current review examines the evolving data with the next generation of TKI's, axitinib and tivozanib being developed for the treatment of advanced RCC. These agents were synthesized to provide increased target specificity and enhanced target inhibition. The preclinical and clinical data are examined, an overview of the development of these TKI's is provided, and discussion plus speculation concerning their potential roles as RCC therapy is provided.

  3. [Paratrigeminal epidermoid originated in the meckel's cave (author's transl)].

    PubMed

    Miyasaka, Y; Morii, S; Tachibana, S; Saito, T; Ohwada, T

    1976-05-01

    We have reported a case of paratrigeminal epidermoid originated in the Meckel's cave. A 30 years old man was admitted to the department of neurosurgery with chief complaints of continuous right facial pain and numbness of entire right side of the face of three years duration. The positive neurological findings were hypesthesia over the distribution of the right trigeminal nerve, absence of the right corneal reflex and nystagmus on left lateral gaze. Caloric response was absent on the right side, however the audiogram showed normal. Cerebrospinal fluid examination was within normal limit. Electromyography showed giant spike in the right masseter and temporal muscles. Radiogram of the skull revealed a bone-destroying lesion over the medial florr of the right middle fossa involving the apex of the petrous bone (Fig 1). Right carotid angiography showed straightening and forward displacement of C4- C5 portion of the carotid siphon in the lateral view, and vertebral angiography showed displacement of basilar artery to the left side, upward displacement of the right posterior cerebral and superior cerebellar artery in the frontal view (Fig. 2, 3). At the time of operation, an epidermoid was identified in the Meckel's cave and totally removed microsurgically. Small amount of the tumor extending into the posterior fossa was also removed (Fig. 4, 5, 6, 7). Postoperative course was uneventfull except for an episode of headache and high fever of short duration, suggesting the signs of meningial irritation. Two months postoperativelly patient was relived of facial pain and was discharged with sensory impairment of the right trigeminal nerve distribution. Only 11 cases of paratrigeminal epidermoid, including the cases localized in the Meckel's cave have been reported in the past literatures (Table 1). In this paper we have discussed about the symptomatology and clinical data of paratrigeminal epidermoid and compared with those of trigeminal neurinoma, and meningioma originated

  4. Intramedullary spinal epidermoid cyst of the cervicodorsal region: A rare entity.

    PubMed

    Kumar, Ashok; Singh, Pritish; Jain, Pramod; Badole, C M

    2010-01-01

    Intramedullary spinal epidermoid cysts are rare, with only few cases having been reported in the literature. We are reporting a case of a 10-year-old female child who presented with symptoms of meningitis with progressive paraparesis. Magnetic resonance imaging of the spine revealed an intramedullary epidermoid cyst from C6 to D5. Near-total excision of the tumor was performed. Histopathological report confirmed the diagnosis of epidermoid cyst. The patient showed progressive recovery.

  5. Vismodegib: the first drug approved for advanced and metastatic basal cell carcinoma.

    PubMed

    Dubey, A K; Dubey, S; Handu, S S; Qazi, M A

    2013-01-01

    Treatment of basal cell carcinoma (BCC) usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA). The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  6. Epidermoid cyst of the floor of the mouth

    PubMed Central

    Baliga, Mohan; Shenoy, Nandita; Poojary, Dharnappa; Mohan, Ram; Naik, Ramdas

    2014-01-01

    Dermoid cysts are malformations that are rarely seen in the oral cavity. An intraoral dermoid cyst grows slowly, but may enlarge and interfere with deglutition and speech, or can pose a critical risk to the airway and therefore require immediate surgical intervention. Dermoid cysts may develop above or below the mylohyoid muscle, causing a submental or submandibular swelling. Surgical excision is the treatment of choice and recurrence is rare. An intraoral approach for the treatment of large lesions presenting above the mylohyoid muscle provides good cosmetic and functional results. We report a case of a 26-year-old female who developed an epidermoid cyst presenting as a large sublingual swelling causing speech and swallowing difficulties. The lesion was surgically excised using an intraoral approach. Microscopic examination revealed a dermoid cyst of the epidermoid type. This case shows that dermoid cysts may be successfully diagnosed and managed using a series of simple yet effective clinical procedure. PMID:25298725

  7. Oncology Gold Standard™ practical consensus recommendations 2016 for treatment of advanced clear cell renal cell carcinoma

    PubMed Central

    Batra, U; Parikh, PM; Prabhash, K; Tongaonkar, HB; Chibber, P; Dabkara, D; Deshmukh, C; Ghadyalpatil, N; Hingmire, S; Joshi, A; Raghunath, SK; Rajappa, S; Rajendranath, R; Rawal, SK; Singh, Manisha; Singh, R; Somashekhar, SP; Sood, R

    2016-01-01

    The Oncology Gold Standard (OGS) Expert Group on renal cell carcinoma (RCC) developed the consensus statement to provide community oncologists practical guidelines on the management of advanced clear cell (cc) RCC using published evidence, practical experience of experts in real life management, and results of a nationwide survey involving 144 health-care professionals. Six broad question categories containing 33 unique questions cover major situations in the routine management of RCC. This document serves as a ready guide for the standard of care to optimize outcome. The table of “Take Home Messages” at the end is a convenient tool for busy practitioners. PMID:28032079

  8. Sublingual Epidermoid Cyst Presenting with Distinctive Magnetic Resonance Imaging Findings

    PubMed Central

    Yoshida, Naohiro; Kodama, Kozue; Iino, Yukiko

    2014-01-01

    A case of sublingual epidermoid cyst presenting distinctive magnetic resonance imaging (MRI) findings is described. A 39-year-old man presented to our hospital with a three months progressive left submandibular swelling, difficulty moving his tongue, and snoring. Preoperative evaluation with MRI and fine needle aspiration cytology (FNAC) revealed that the heterogeneous cystic lesion contained the squamous cells, which is compatible with ectodermal tissue. The mass was located above the mylohyoid muscle and spread to the pharyngeal space. By considering the size, infection history, patient age, and location, the cyst was completely resected under general anesthesia via cervical approach without any complication. Histopathologically, the cyst wall was lined by stratified squamous epithelium with no skin appendage, suggesting an epidermoid cyst. Ultrasound (US), MRI and FNAC were very useful of the preoperative diagnosis for oral and sublingual lesion. The postoperative course was uneventful and without recurrence after 24 months. This case showed that epidermoid cysts formed the rarely heterogeneous cystic tumor and it underlined usefulness of preoperative diagnosis, such as US, MRI and FNAC for oral and sublingual tumor. PMID:25332766

  9. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    ClinicalTrials.gov

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  10. Intracranial epidermoid tumor; microneurosurgical management: An experience of 23 cases

    PubMed Central

    Chowdhury, Forhad Hossain; Haque, Mohammod Raziul; Sarker, Mainul Haque

    2013-01-01

    Objectives: An intracranial epidermoid tumor is relatively a rare tumor, accounting for approximately 0.1% of all intracranial space occupying lesions. These are also known as pearly tumor due to their pearl like appearance. In this series, the localization of the tumor, presenting age and symptoms, imaging criteria for diagnosis, surgical management strategy with completeness of excision and overall outcome were studied prospectively. Here, we report our short experience of intracranial epidermoid as a whole. Materials and Methods: Between January 2006 to December 2010, 23 cases of intracranial epidermoid were diagnosed preoperatively with almost certainty by computed tomography (CT) and magnetic resonance imaging (MRI) of brain in plain, contrast and other relevant studies. All of them underwent operation in Dhaka Medical College Hospital and in some Private Hospital in Dhaka, Bangladesh. All patients were followed-up routinely by clinical examination and neuroimaging. Average follow-up was 39 (range-71-11months) months. Patients of the series were prospectively studied. Results: Supratentorial epidermoids were 04 cases and infratemporal epidermoids were 19 cases. Clinical features and surgical strategy varies according to the location and extension of the tumors. Age range was 19-71 years (37.46 years). Common clinical features were headache, cerebellar features, seizure, vertigo, hearing impairment and features of raised intracranial pressure (ICP). Investigation was CT scan or/+ MRI of brain in all cases. Pre-operative complete excision was 20 cases, but post-operative images showed complete excision in 17 cases. Content of tumor was pearly white/white material in all cases except one, where content was putty material. Re-operation for residual/recurrent tumor was nil. Complications included pre-operative mortality one case, persisted sixth nerve palsy in one case, transient memory disturbance one case, and extra dural hematoma one case. One senior patient

  11. Incidental frontal lobe mixed density epidermoid tumor in a patient of head injury: A rare case report

    PubMed Central

    Gupta, Pankaj; Mittal, Radheyshyam; Gandhi, Ashok; Sharma, Achal; Gandhi, Sapna

    2015-01-01

    The incidence of the epidermoid tumor is approximately 0.2–1.8% of all intracranial tumors. Epidermoid tumors are typically intradural, but extra-axial in location and only rarely found within the brain substance. We are reporting the first case of incidental mixed density frontal epidermoid tumor in a patient of head injury. Difficulty in the preoperative diagnosis and uncommon presentation of the intracranial epidermoid tumor prompted us to report this case. PMID:26425171

  12. Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras.

    PubMed

    Li, Pengxiang; Wong, Yu-Ning; Armstrong, Katrina; Haas, Naomi; Subedi, Prasun; Davis-Cerone, Margaret; Doshi, Jalpa A

    2016-02-01

    Between December 2005 and October 2009, FDA approved six targeted therapies shown to significantly extend survival for advanced renal cell carcinoma (RCC) patients in clinical trials. This study aimed to examine changes in survival between the pretargeted and targeted therapy periods in advanced RCC patients in a real-world setting. Utilizing the 2000-2010 SEER Research files, a pre-post study design with a contemporaneous comparison group was employed to examine differences in survival outcomes for patients diagnosed with advanced RCC (study group) or advanced prostate cancer (comparison group, for whom no significant treatment innovations happened during this period) across the pretargeted therapy era (2000-2005) and the targeted therapy era (2006-2010). RCC patients diagnosed in the targeted therapy era (N = 6439) showed improved survival compared to those diagnosed in the pretargeted therapy era (N = 7231, hazard ratio (HR) for all-cause death: 0.86, P < 0.01), while the change between the pre-post periods was not significant for advanced prostate cancer patients (HR: 0.97, P = 0.08). Advanced RCC patients had significantly larger improvements in overall survival compared to advanced prostate cancer patients (z = 4.31; P < 0.01). More detailed year-to-year analysis revealed greater survival improvements for RCC in the later years of the posttargeted period. Similar results were seen for cause-specific survival. Subgroup analyses by nephrectomy status, age, and gender showed consistent findings. Patients diagnosed with advanced RCC during the targeted therapy era had better survival outcomes than those diagnosed during the pretargeted therapy era. Future studies should examine the real-world survival improvements directly associated with targeted therapies.

  13. Percutaneous Irreversible Electroporation of Locally Advanced Pancreatic Carcinoma Using the Dorsal Approach: A Case Report

    SciTech Connect

    Scheffer, Hester J. Melenhorst, Marleen C. A. M.; Vogel, Jantien A.; Tilborg, Aukje A. J. M. van; Nielsen, Karin Kazemier, Geert; Meijerink, Martijn R.

    2015-06-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively.

  14. Complete Remission of Locally Advanced Penile Squamous Cell Carcinoma after Multimodality Treatment

    PubMed Central

    Meng, Yifan; Bernie, Helen Levey; Weng, Tzu-Hua; Ling, Dean-An; Messing, Edward M.; Guancial, Elizabeth

    2016-01-01

    Treatment of locally advanced penile squamous cell carcinoma (pSCC) remains highly controversial secondary to disease rarity and lack of prospective randomized controlled trials. The current mainstays of care are multi-modality treatment with neoadjuvant chemotherapy and surgery. However, clinicians often have difficulty making recommendations for patients unable to tolerate chemotherapy or surgery due to scarcity of data to guide clinical decision-making. We report two cases of locally advanced pSCC that achieved complete remission after treatment with cisplatin-based neoadjuvant chemotherapy and surgery in one case, and concurrent cisplatin chemoradiation in a second, supporting the use of chemotherapy as part of first-line multimodal therapy. We also discuss additional treatment options for patients unable to tolerate traditional chemotherapy regimens. PMID:28191294

  15. Uncommon gastrointestinal bleeding during targeted therapy for advanced renal cell carcinoma: A report of four cases

    PubMed Central

    FUJIHARA, SHINTARO; MORI, HIROHITO; KOBARA, HIDEKI; NISHIYAMA, NORIKO; AYAKI, MAKI; OHATA, RYO; UEDA, NOBUFUMI; SUGIMOTO, MIKIO; KAKEHI, YOSHIYUKI; MASAKI, TSUTOMU

    2015-01-01

    Clinically available targeted agents to treat advanced renal cell carcinoma (RCC) include sunitinib, sorafenib and temsirolimus. Sorafenib and sunitinib have been associated with bleeding in selected trials, but clinical and endoscopic characteristics of gastrointestinal bleeding are not well described. Herein, we report four cases of advanced RCC in which endoscopic hemostasis effectively resolved high-grade, life-threatening gastrointestinal bleeding that occurred during targeted therapy. Although stomatitis and mucositis have occurred during targeted therapies, life-threatening gastrointestinal bleeding is less common. In these four patients, the origins of gastrointestinal bleeding were identified, and complete endoscopic hemostasis was achieved. Endoscopies revealed variable characteristics including angiodysplasia, multiple gastric ulcers and oozing bleeding of the normal mucosa. Although the most effective diagnostic and treatment strategies are disputed, endoscopic examinations are best performed before starting targeted therapies. Additionally, these patients should be monitored even for rare life-threatening events. PMID:26722259

  16. Identifying locally advanced basal cell carcinoma eligible for treatment with vismodegib: an expert panel consensus.

    PubMed

    Peris, Ketty; Licitra, Lisa; Ascierto, Paolo A; Corvò, Renzo; Simonacci, Marco; Picciotto, Franco; Gualdi, Giulio; Pellacani, Giovanni; Santoro, Armando

    2015-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Most occur on the head and neck, where cosmetic and functional outcomes are critical. BCC can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for the majority of high-risk lesions. Aggressive, recurrent or unresectable tumors can be difficult to manage. Until recently, no approved systemic therapy was available for locally advanced or metastatic BCC inappropriate for surgery or radiotherapy. Vismodegib provides a systemic treatment option. However, a consensus definition of advanced BCC is lacking. A multidisciplinary panel with expertise in oncology, dermatology, dermatologic surgery and radiation oncology proposes a consensus definition based on published evidence and clinical experience.

  17. Advanced primary pulmonary lymphoepithelioma-like carcinoma: clinical manifestations, treatment, and outcome

    PubMed Central

    Lin, Chun-Yu; Chen, Ying-Jen; Hsieh, Meng-Heng; Wang, Chih-Wei

    2017-01-01

    Background Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. Methods This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. Results Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. Conclusions Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment. PMID:28203414

  18. Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study.

    PubMed

    Nakano, Masahito; Tanaka, Masatoshi; Kuromatsu, Ryoko; Nagamatsu, Hiroaki; Tajiri, Nobuyoshi; Satani, Manabu; Niizeki, Takashi; Aino, Hajime; Okamura, Shusuke; Iwamoto, Hideki; Shimose, Shigeo; Shirono, Tomotake; Koga, Hironori; Torimura, Takuji

    2015-12-01

    Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression-free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child-Pugh class, baseline serum des-gamma-carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long-term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.

  19. The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Sarpel, Umut; Spivack, John H.; Berger, Yaniv; Heskel, Marina; Aycart, Samantha N.; Sweeney, Robert; Edwards, Martin P.; Labow, Daniel M.; Kim, Edward

    2016-01-01

    Background & aims It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. Methods A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. Results Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407–0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236–0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118–161) vs. 247 days (95% CI: 220–289) in the sorafenib plus LRTx arm (P < 0.001). Conclusions These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC. PMID:27154804

  20. Planned preoperative radiation therapy for advanced laryngeal carcinoma. [/sup 60/Co

    SciTech Connect

    Kazem, I.; van den Broek, P.; Huygen, P.L.M.

    1982-09-01

    One hundred ten patients with predominantly advanced laryngeal carcinoma were treated in the period 1969-1978 with planned preoperative radiation therapy followed by surgery. Site distribution was: 63 supraglottic, 26 glottic, 15 transglottic and 6 subglottic. There were 4 Stage II patients, 66 Stage III and 40 Stage IV. Preoperative radiation therapy consisted of Telecobalt irradiation to a total dose of 25 Gy given to a target volume encompassing the larynx and regional neck nodes, given in 5 equal daily fractions of 5 Gy in 5 consecutive days. Surgery was performed 2 days later. Total laryngectomy was performed on 48 patients, total laryngectomy with neck dissection on 55 patients, supraglottic laryngectomy on 5 and supraglottic laryngectomy with neck dissection on 2 patients. Crude actuarial 5 and 10 year survival probability for the whole group is 71 and 61%, respectively. The corrected 5 and 10 year survival is 75%. For patients with T/sub 3/-T/sub 4/-N/sub 0/ tumors 5 and 10 year survival probability is: crude 65 and 58%, and corrected 70% respectively. For T/sub 3/-T/sub 4/-N/sub +/ crude: 75 and 60% and corrected: 78%. Of 110 patients, one died postoperative, three died of intercurrent disease, five died as a result of second malignancy, and 23 died of their larynx carcinoma: 12/23 because of locoregional failure, and 11/23 because of distant metastasis. We concluded that short intensive preoperative radiation therapy and surgery offer a high cure rate in the treatment of advanced resectable laryngeal carcinoma. The merits of this technique are outlined in the text.

  1. Cetuximab concurrent with IMRT versus cisplatin concurrent with IMRT in locally advanced nasopharyngeal carcinoma

    PubMed Central

    Wu, Xin; Huang, Jingwen; Liu, Lei; Li, Hongmei; Li, Ping; Zhang, Jing; Xie, Li

    2016-01-01

    Abstract To evaluate the treatment efficacies and toxicities of concurrent cetuximab-based bioradiotherapy (BRT) or cisplatin-based chemoradiotherapy (CRT) in locally advanced nasopharyngeal carcinoma. :Patients with previously untreated locally advanced nasopharyngeal carcinoma were matched into pairs, and enrolled into the study. All patients were given either BRT or CRT. Survival outcomes, toxicities, and prognostic factors were evaluated. :A total of 112 patients were enrolled. The 5-year overall survival was 79.3% and 79.5% in CRT and BRT arm, respectively (P = 0.797) and the 5-year DFS was 73.5% and 74.6%, respectively (P = 0.953). In toxicity analysis, CRT arm had more significant decrease in white blood cell, platelet, hemoglobin, and severe vomiting, while more severe skin reactions and mucositis were shown in BRT arm. :BRT was not less efficacious than traditional CRT. They lead to different aspects of toxicities. If patients cannot stand more severe toxicities caused by CRT, BRT could be an ideal alternative. PMID:27684830

  2. Salvage surgery for locoregional recurrences of advanced pharyngolaryngeal squamous cell carcinoma after organ preservation failure.

    PubMed

    López Delgado, I; Riestra Ayora, J; Arenas Brítez, O; García López, I; Martínez Guirado, T; Scola Yurrita, B

    2014-12-01

    Organ preservation treatment for advanced head and neck squamous cell carcinoma is associated with poor outcomes due to locoregional recurrences. Salvage surgery is the main therapeutic option for some of these patients. The aim of this study was to analyse the results of salvage surgery for advanced pharyngolaryngeal squamous cell carcinoma previously treated with radiochemotherapy. We performed a retrospective study on 38 patients (36 men, 2 women). The median age at diagnosis was 60 years with a mean follow-up period of 49.8 months. Recurrences were diagnosed at a mean of 395 days after finalising organ preservation treatment. Patients went under different salvage surgeries, including 22 total laryngectomies, 6 partial laryngectomies (3 transoral laser surgeries and 3 opened surgeries), 8 functional neck dissections and 2 tongue base surgeries. Nineteen patients had no postoperative complications after a mean hospital stay of 2 weeks. However, 5 patients died of significant recurrent bleedings. There were 4 salivary fistulas that responded to conservative management, while 7 patients had important pharyngostomas that required reconstruction with either regional or free flaps. The mean hospital stay was of 61.60 days for all patients. Five-year overall survival from diagnosis, overall survival after salvage surgery and survival after salvage surgery were 44.20, 37.90 and 45.70%, respectively. In summary, we conclude that salvage surgery is an optimal treatment for pharyngolaryngeal and regional recurrences and provides improvement in locoregional control and survival, despite the severe complications.

  3. Preoperative radiotherapy followed by radical vulvectomy with inguinal lymphadenectomy for advanced vulvar carcinomas

    SciTech Connect

    Rotmensch, J.; Rubin, S.J.; Sutton, H.G.; Javaheri, G.; Halpern, H.J.; Schwartz, J.L.; Stewart, M.; Weichselbaum, R.R.; Herbst, A.L. )

    1990-02-01

    A therapeutic alternative to exenteration for large locally advanced vulvar carcinoma involving the rectum, anus, or vagina is the use of preoperative radiation followed by radical surgery. Between 1980 and 1988, 13 patients with Stage III and 3 with Stage IV vulvar carcinoma involving the rectum/anus, urethra, or vagina were treated with 4000 rad to the vulva and 4500 rad to the inguinal and pelvic nodes followed by a radical vulvectomy and inguinal lymphadenectomy 4 weeks later. The overall 5 year cumulative survival was 45%. Twelve tumors regressed after radiation with 62.5% of the patients having visceral preservation while in 4 patients there was no major response to radiation and urinary or fecal diversion was required. Of the 6 recurrences 4 were central and 2 distant. Three patients with central recurrences had tumor within 1 cm of the vulvectomy margin. Complications included wet desquamation, inguinal wound separation, lymphedema, and urethral strictures. There were no operative deaths. It is concluded that the use of preoperative radiation followed by radical vulvectomy may be an alternative to pelvic exenteration in selected patients with advanced vulvar lesions.

  4. Detection of Early Tumor Response to Axitinib in Advanced Hepatocellular Carcinoma by Dynamic Contrast Enhanced Ultrasound.

    PubMed

    Lo, Glen M; Al Zahrani, Hassan; Jang, Hyun Jung; Menezes, Ravi; Hudson, John; Burns, Peter; McNamara, Mairéad G; Kandel, Sonja; Khalili, Korosh; Knox, Jennifer; Rogalla, Patrik; Kim, Tae Kyoung

    2016-06-01

    This study aimed to evaluate the utility of dynamic contrast-enhanced ultrasound (DCE-US) in measuring early tumor response of advanced hepatocellular carcinoma to axitinib. Twenty patients were enrolled (aged 18-78 y; median 65). DCE-US was performed with bolus injection and infusion/disruption replenishment. Median overall survival was 7.1 mo (1.8-27.3) and progression free survival was 3.6 mo (1.8-17.4). Fifteen patients completed infusion scans and 12 completed bolus scans at 2 wk. Among the perfusion parameters, fractional blood volume at infusion (INFBV) decreased at 2 wk in 10/15 (16%-81% of baseline, mean 47%) and increased in 5/15 (116%-535%, mean 220%). This was not significantly associated with progression free survival (p = 0.310) or progression at 16 wk (p = 0.849), but was borderline statistically significant (p = 0.050) with overall survival, limited by a small sample size. DCE-US is potentially useful in measuring early tumor response of advanced hepatocellular carcinoma to axitinib, but a larger trial is needed.

  5. [A Case of Successful Curative Resection Following Downsizing Chemotherapy in Initially Unresectable Locally Advanced Gallbladder Carcinoma].

    PubMed

    Shinmura, Kazuyasu; Kaiho, Takashi; Yanagisawa, Shinji; Okamoto, Ryo; Nishimura, Masaki; Kobayashi, Soichi; Okaniwa, Akira; Mun, Yangi; Tsuchiya, Shunichi; Chiba, Ryoji

    2015-11-01

    A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage ⅣB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma.

  6. [Epidermoid cysts in the pineal region--analysis of four cases and review of the literature].

    PubMed

    Laleva, M; Uzunov, K; Gabrovski, N; abrovski, St

    2009-01-01

    Epidermoid cysts represent 0.2-1% of all intracranial tumours. Extremely rare they are found in the pineal region. We present four patients with epidermoid cysts located in the pineal region observed and operated by the senior author (S.G.) during a period of twenty years and review of the literature.

  7. Case study: Epidermoid cyst following percutaneous Topaz coblation for plantar fasciitis.

    PubMed

    Ferguson, Kim; Thomson, Allan George; Moir, John Stuart

    2012-03-01

    An epidermoid cyst is formed when there is proliferation of epidermal cells within an area of the dermis. They may be formed by the traumatic implantation of epidermal cells within the dermis as well as many other mechanisms. We present a case of epidermoid cyst formation following Topaz coblation for plantar fasciitis; a complication we believe is yet to be reported in the literature.

  8. High expression of Wls is associated with lymph node metastasis and advanced TNM stage in gastric carcinomas.

    PubMed

    Zhang, Wei; Tao, Hong; Chen, Xiao; Sugimura, Haruhiko; Wang, Jiandong; Zhou, Ping

    2017-03-01

    The roles of Wnt protein in carcinogenesis have been well documented in human cancers. Wls is a key modulator for the secretion of Wnt protein. We previously found that Wls was aberrantly expressed in colorectal carcinomas. Studies have revealed that dysregulation of Wnt signal transduction plays an important role in gastric carcinoma. We hypothesized that Wls may play a role in the development and progression of gastric carcinoma. In this study, three gastric cancer cell lines MGC-803, SGC-7901, and AGS, and a set of gastric carcinoma tissue specimens were subjected to immunohistochemistry. The relationship between the expression of Wls and clinicopathological parameters was analyzed. Wls was negatively detected in MGC-803, positively detected in SGC-7901 and AGS cell lines. Wls was weakly expressed in 9.7% (15/154), moderately in 33.1% (51/154), and strongly in 57.1% (88/154) of tested gastric carcinoma specimens. High expression of Wls was positively associated with well and moderately differentiated tumors (P = 0.035, rs  = 0.170), lymph node metastasis (P = 0.001, rs  = 0.276), and advanced TNM stage (P = 0.006, rs  = 0.219). Our data suggest that Wls protein is related to tumor metastasis and advanced TNM stage, and may be used as a new marker for prognosis of gastric carcinoma.

  9. Epidermoid Cyst Arising in the Buccal Mucosa: Case Report and Literature Review

    PubMed Central

    Costa, Fábio Wildson Gurgel; Chaves, Filipe Nobre; de Almeida, Stephanie; Alves, Ana Paula Negreiros Nunes; Patrocínio, Régia Maria do Socorro Vidal; Sousa, Fabrício Bitu; Pereira, Karuza Maria Alves

    2015-01-01

    Epidermoid cysts are benign subcutaneous lesions, and the large majority of these cysts affect the floor of the mouth; however, the buccal mucosa is not a usual site of occurrence. To date, only 5 articles have been published with 6 cases of epidermoid cysts arising in the buccal mucosa. Therefore, the aim of this study was to describe the clinical, histopathological and immunohistochemical features of a case of epidermoid cyst located in the buccal mucosa. To our knowledge, this is the first report of an oral epidermoid cyst describing an intense foreign body gigantocellular inflammatory reaction against epithelial keratin component. Although the usual diagnosis for epidermoid cysts is based on histopathological findings, this case report addresses novel information regarding to the immunohistochemical pattern that may be found in these lesions. PMID:27688388

  10. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    PubMed Central

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

    Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

  11. Challenges and new horizons in the management of advanced basal cell carcinoma: a UK perspective

    PubMed Central

    Lear, J T; Corner, C; Dziewulski, P; Fife, K; Ross, G L; Varma, S; Harwood, C A

    2014-01-01

    Basal cell carcinoma (BCC) is a common malignancy with a good prognosis in the majority of cases. However, some BCC patients develop a more advanced disease that poses significant management challenges. Such cases include locally advanced, recurrent or metastatic BCC, or tumours that occur in anatomical sites where surgical treatment would result in significant deformity. Until recently, treatment options for these patients have been limited, but increased understanding of the molecular basis of BCC has enabled potential therapies, such as hedgehog signalling pathway inhibitors, to be developed. A clear definition of advanced BCC as a distinct disease entity and formal management guidelines have not previously been published, presumably because of the rarity, heterogeneity and lack of treatment options available for the disease. Here we provide a UK perspective from a multidisciplinary group of experts involved in the treatment of complex cases of BCC, addressing the key challenges associated with the perceived definition and management of the disease. With new treatments on the horizon, we further propose a definition for advanced BCC that may be used as a guide for healthcare professionals involved in disease diagnosis and management. PMID:25211660

  12. Clinical outcomes of advanced-stage glassy cell carcinoma of the uterine cervix: a need for reappraisal

    PubMed Central

    Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

    2016-01-01

    We performed a retrospective analysis of the clinical features and patient outcomes for advanced-stage glassy cell carcinoma of the uterine cervix. The study was restricted to cases in which the glassy cell features constituted at least 95% of the biopsied specimen. During the study period, 675 patients were diagnosed with primary cervical carcinoma. Five (0.7%) of the 675 patients had cervical glassy cell carcinoma; of these, three were premenopausal, and two were postmenopausal. Abnormal vaginal bleeding was the most frequent presenting symptom. Glassy cell carcinoma presented as a fungating, exophytic, or infiltrative mass. The greatest tumor dimension ranged from 3 to 9 cm. All patients had parametrial extension. Four patients had stage IIB tumors, and one had a stage IIIB tumor. All patients received concurrent chemoradiation therapy. The patient with a stage IIIB tumor died of hypovolemic shock caused by upper gastrointestinal bleeding during radiation therapy. Three patients with stage IIB tumors survived for more than 8 years without tumor recurrence or metastasis. One of these three patients died of pelvic recurrence 10 years after the initial diagnosis. Cervical glassy cell carcinoma has traditionally been considered an aggressive, highly malignant tumor with poor prognosis, but our data suggest that patient survival is not significantly decreased compared with other histological types of cervical carcinoma. It will be necessary to analyze patient outcomes using a larger number of cervical glassy cell carcinoma cases to confirm our findings. PMID:27793022

  13. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

    SciTech Connect

    Pradier, Olivier . E-mail: opradier@gwdg.de; Christiansen, Hans; Schmidberger, Heinz; Martin, Alexios; Jaeckel, Martin C.; Steiner, Wolfgang; Ambrosch, Petra; Kahler, Elke; Hess, Clemens F.

    2005-12-01

    Purpose: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Patients and Methods: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO{sub 2} laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Results: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). Conclusion: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.

  14. Oral squamous cell carcinoma among Yemenis: Onset in young age and presentation at advanced stage

    PubMed Central

    Al-Mohaya, Maha; Abdulhuq, Mahmoud; Al-Mandili, Ahmad; Al-Anazi, Yousef

    2012-01-01

    Objectives: Oral cancer represents a health burden worldwide. Up to 90% of oral cancer cases are squamous cell carcinomas (SCC). The data on oral SCC in Yemen are lacking. The objective of this study therefore was to describe and analyze the demographic, clinical and histological characteristics of Yemeni patients with oral SCC. Study Design: In this cross-sectional study, two sets of retrospective data for Yemeni cancer patients were obtained officially by two different registries. Patients with oral SCC were included. Their ages were dichotomized using 40 and 45 years alternately as individual cut-points for young and old patients. The patients` demographic, clinical and histological characteristics were statistically analyzed. Results: There were 457 Yemenis with oral SCC; 253 patients (55.4%) were men. The overall mean age was 58.15±14.11 years. The tongue was the most affected oral sub-site accounting for 53% of the reported cases. The well and moderately differentiated oral SCC accounted for 55.5% and 25.6% of the total cases respectively. Noteworthy, 62 patients (14%) were affected by the age of ?40; this increased to 105 patients (23%) aged ?45 years. Additionally, a high proportion of oral SCC patients (62%, 283) were diagnosed at advanced tumor stages (regional extension or metastasized). The distributions of histological grades and tumor stages in young and old patients were significantly different (P=0.006 and 0.026 respectively). Conclusion: The relative frequency of oral SCC among Yemeni young people is high. Unfortunately, most of oral SCC patients in Yemen were diagnosed at advanced stage. Key words:Oral squamous cell carcinoma, Yemen, young patients, advanced stage. PMID:24558559

  15. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva.

    PubMed

    Gaudineau, A; Weitbruch, D; Quetin, P; Heymann, S; Petit, T; Volkmar, P; Bodin, F; Velten, M; Rodier, J F

    2012-10-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6-4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6-4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0-6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva.

  16. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva

    PubMed Central

    GAUDINEAU, A.; WEITBRUCH, D.; QUETIN, P.; HEYMANN, S.; PETIT, T.; VOLKMAR, P.; BODIN, F.; VELTEN, M.; RODIER, J.F.

    2012-01-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6–4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6–4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0–6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva. PMID:23205089

  17. A unique bleeding-related complication of sorafenib, a tyrosine kinase inhibitor, in advanced hepatocellular carcinoma: a case report

    PubMed Central

    2014-01-01

    Introduction Sorafenib, a multikinase inhibitor as a standard of care for advanced hepatocellular carcinoma, may lead endothelial cells to an unstable state by blocking the signaling pathway of vascular endothelial growth factor receptor, which may result in the disruption of the architecture and integrity of the microvasculature, and eventually increase the risk of hemorrhage. Hemobilia is a relatively uncommon condition as a consequence of hepatocellular carcinoma and its risk factors remain uncertain. Case presentation Here we report a unique case of hemobilia occurring in a 55-year-old Korean man with hepatitis B virus-related hepatocellular carcinoma on Barcelona Clinic Liver Cancer advanced stage after seven days of treatment with sorafenib. He had received prior radiation therapy. Endoscopy revealed bleeding from the major duodenal papilla and endoscopic retrograde cholangiography revealed an amorphous filling defect throughout the common bile duct. Blood clots were removed by balloon sweeping and a nasobiliary drainage tube was placed. No further bleeding has been detected as of eight months after discontinuation of sorafenib. Conclusion Sorafenib may increase the risk of biliary bleeding in hepatocellular carcinoma patients who were primed with irradiation, by blocking the signaling pathway of the vascular endothelial growth factor receptor. Therefore, sorafenib should be used with caution in patients with advanced hepatocellular carcinoma, especially when combined with radiation therapy. PMID:24571585

  18. [Epidermoid neoplasm of the fourth ventricle. Report of two cases].

    PubMed

    Santos-Franco, Jorge Arturo; Vallejo-Moncada, Cristóbal; Collado-Arce, Griselda; Villalpando-Navarrete, Edgar; Sandoval-Balanzario, M

    2013-01-01

    Introducción: los tumores epidermoides representan 1 % de las neoplasias intracraneales; el ángulo pontocerebeloso es la localización más frecuente y en el cuarto ventrículo son raros. Casos clínicos: caso 1: mujer de 22 años de edad con cefalea intensa de tres meses de evolución. Al ingreso se identificó hipertensión endocraneana. La tomografía mostró hidrocefalia con aumento del volumen del cuarto ventrículo. La paciente fue tratada con derivación ventrículo-peritoneal; posteriormente se extirpó tumoración encapsulada de aspecto perlado. El estudio histológico indicó tumor epidermoide en el cuarto ventrículo. Caso 2: mujer de 44 años de edad con vértigo ocasional de cinco años de evolución, así como con diploplía y disfagia intermitentes de tres años de evolución. Al ingresó se identificó paresia bilateral de los nervios craneales VI y VII. La tomografía computarizada y la resonancia magnética mostraron lesión en el cuatro ventrículo. El manejo fue quirúrgico. Conclusiones: la resonancia magnética es el estudio diagnóstico específico para el diagnóstico del tumor epidermoide del cuarto ventrículo que, sin embargo, puede confundirse con neurocisticercosis. Están indicados la exéresis del quiste y el tratamiento de la hidrocefalia.

  19. Neurofibroma and epidermoid cyst: unexpected findings after first foreskin retraction.

    PubMed

    Ballouhey, Quentin; Longis, Bernard; Couvrat-Carcauzon, Véronique; Gardic, Solène; Piguet, Christophe; Berenguer, Daniel; Fourcade, Laurent

    2013-12-01

    We report here 2 unusual cases of tumor of the glans penis in children. Abnormal findings were found on a 12-year-old and a 13-year-old boy soon after their first foreskin retraction. Initial medical examination suggested inclusions of smegma and they were referred to our Department of Pediatric Urology. Complete resection was performed under general anesthesia. Histologic examination revealed an epidermoid cyst in the first patient and a solitary neurofibroma in the second. These patients represent respectively the third and the second cases of such entities described in the pediatric age group. Cautious examination is required for persistent inclusions of smegma.

  20. Comprehensive Genomic Profiling of Advanced Penile Carcinoma Suggests a High Frequency of Clinically Relevant Genomic Alterations

    PubMed Central

    Pal, Sumanta K.; Wang, Kai; Palma, Norma A.; Sanford, Eric; Bailey, Mark; He, Jie; Elvin, Julia A.; Chmielecki, Juliann; Squillace, Rachel; Dow, Edward; Morosini, Deborah; Buell, Jamie; Yelensky, Roman; Lipson, Doron; Frampton, Garrett M.; Howley, Peter; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.

    2016-01-01

    Background. Advanced penile squamous cell carcinoma (PSCC) is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. Comprehensive genomic profiling (CGP) was performed to identify clinically relevant genomic alterations (CRGAs). Materials and Methods. DNA was extracted from 40 μm of formalin-fixed, paraffin-embedded sections in patients with advanced PSCC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 692× for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. CRGAs were defined as genomic alterations (GAs) linked to targeted therapies on the market or under evaluation in mechanism-driven clinical trials. Results. Twenty male patients with a median age of 60 years (range, 46–87 years) were assessed. Seventeen (85%) cases were stage IV and three cases (15%) were stage III. CGP revealed 109 GAs (5.45 per tumor), 44 of which were CRGAs (2.2 per tumor). At least one CRGA was detected in 19 (95%) cases, and the most common CRGAs were CDKN2A point mutations and homozygous deletion (40%), NOTCH1 point mutations and rearrangements (25%), PIK3CA point mutations and amplification (25%), EGFR amplification (20%), CCND1 amplification (20%), BRCA2 insertions/deletions (10%), RICTOR amplifications (10%), and FBXW7 point mutations (10%). Conclusion. CGP identified CRGAs in patients with advanced PSCC, including EGFR amplification and PIK3CA alterations, which can lead to the rational administration of targeted therapy and subsequent benefit for these patients. Implications for Practice: Few treatment options exist for patients with advanced penile squamous cell carcinoma (PSCC). Outcomes are dismal with platinum-based chemotherapy, with median survival estimated at 1 year or less across multiple series. Biological studies of patients with PSCC to date have principally focused on human papillomavirus status

  1. Advancements in the Management of HPV-Associated Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Zeitlin, Ross; Nguyen, Harrison P.; Rafferty, David; Tyring, Stephen

    2015-01-01

    Head and neck carcinomas have long been linked to alcohol and tobacco abuse; however, within the last two decades, the human papillomavirus (HPV) has emerged as a third etiology and is specifically associated with head and neck squamous cell carcinomas (HNSCC). In this anatomical region, the oncogenic HPV-16 mediates transformation and immortalization of epithelium, most commonly in the oropharynx. Nevertheless, the recent identification of novel HPV mechanisms thought to be specific to oropharyngeal carcinogenesis has coincided with observations that HPV-associated HNSCC has differing clinical behavior—in terms of natural history, therapeutic response, and prognosis—than HPV-negative head and neck tumors. Taken together with the growing incidence of HPV transmission in younger populations, these discoveries have sparked a rapid expansion in both laboratory and clinical studies on the infection and disease. Herein, we review the clinical characteristics of HPV-associated HNSCC, with particular emphasis on recent advancements in our understanding of the management of this infectious malignancy. PMID:26239449

  2. Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

    PubMed Central

    Ruiz-Morales, Jose Manuel; Heng, Daniel Y.C.

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI). It exerts inhibition of MET, vascular endothelial growth factor receptor type 2, AXL, and many other receptor tyrosine kinases that are also implicated in tumor pathobiology, including RET, KIT, and FLT3. MET drives tumor survival, invasion, angiogenesis, and metastasis through several downstream signaling pathways. AXL has recently been described as an essential mediator of cancer metastasis that mediates crosstalk and resistance to TKIs. MET and AXL are thought to be anti-vascular endothelial growth factor receptor (VEGF) resistance pathways and thus cabozantinib represents a logical choice after progression on initial VEGF therapy. Subgroup analyses examining those with good performance status or visceral and bone metastases indicate that the hazard ratios may be better when using cabozantinib versus everolimus. However, there were no clear statistically significant differences between any subgroups. PMID:27904650

  3. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma.

    PubMed

    Chang, Anne Lynn S; Lewis, Karl D; Arron, Sarah T; Migden, Michael R; Solomon, James A; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F; Sekulic, Aleksandar

    2016-11-15

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age.

  4. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma

    PubMed Central

    Chang, Anne Lynn S.; Lewis, Karl D.; Arron, Sarah T.; Migden, Michael R.; Solomon, James A.; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F.; Sekulic, Aleksandar

    2016-01-01

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age. PMID:27764798

  5. Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib

    PubMed Central

    Gardini, Andrea Casadei; Scarpi, Emanuela; Faloppi, Luca; Scartozzi, Mario; Silvestris, Nicola; Santini, Daniele; de Stefano, Giorgio; Marisi, Giorgia; Negri, Francesca V.; Foschi, Francesco Giuseppe; Valgiusti, Martina; Ercolani, Giorgio; Frassineti, Giovanni Luca

    2016-01-01

    We evalueted a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the aim to explored their prognostic value in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. 56 advanced HCC patients receiving sorafenib were available for our analysis. Lymphocyte, neutrophil and platelet were measured before beginning of treatment and after one month. Patient with SII ≥ 360 showed lower median PFS (2.6 vs. 3.9 months, P < 0.026) and OS (5.6 vs. 13.9 months, P = 0.027) with respect to patients with SII < 360. NLR ≥ 3 had a lower median PFS (2.6 vs. 3.3 months, P < 0.049) but not OS (5.6 vs. 13.9 months, P = 0.062) than those with NLR < 3. After adjusting for clinical covariates SII and NLR remained an independent prognostic factor for OS. The SII and NLR represent potential prognostic indicator in patients with advanced HCC treated with sorafenib. PMID:27613839

  6. [Recent advancements in the treatment of renal cell carcinoma--focus on international guidelines].

    PubMed

    Biró, Krisztina; Küronya, Zsófia

    2010-12-01

    Recent advances in understanding the fundamental biology underlying clear-cell RCC have opened the door to a series of targeted agents, such as tyrosine kinase inhibitors (TKIs) or mTOR inhibitors. These new agents have become the standard of care in managing advanced clear-cell RCC. Choice of initial medical management in patients with metastatic clear-cell RCC should be guided by randomised studies. On the evidence available, the first-line therapy in patients with good- or intermediate-risk mRCC should be either sunitinib or pazopanib, or bevacizumab plus interferon. In selected patients sorafenib is an option, as is high-dose interleukin-2 if performance status is good. In patients with poor prognosis, temsirolimus is recommended. In cytokine refractory patients, sorafenib, when patients have progressed on a tyrosine kinase inhibitor everolimus is the agent of choice. Biró K, Küronya Z. Recent advancements in the treatment of renal cell carcinoma - focus on international guidelines.

  7. Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

    PubMed Central

    Deng, Gan-Lu; Zeng, Shan; Shen, Hong

    2015-01-01

    Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis. PMID:25914779

  8. Is Gemcitabine and Cisplatin Induction Chemotherapy Superior in Locoregionally Advanced Nasopharyngeal Carcinoma?

    PubMed Central

    Zheng, Wei; Qiu, Sufang; Huang, Lingling; Pan, Jianji

    2015-01-01

    Objective: To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by chemoradiotherapy. Methods: Between June 2005 and October 2007, 604 patients with locoregionally advanced NPC were analyzed, of whom 399 and 205 were treated with conventional radiotherapy and intensity-modulated radiotherapy (IMRT) respectively. Meanwhile, 153 patients received concurrent chemotherapy, and 520 were given induction chemotherapy. Results: With a median follow-up time of 65 months, the 3-, and 5-year overall survival (OS), locoregional free survival (LRFS), and distant-metastasis free survival (DMFS) rates were 82.5% vs. 72.6%, 90.6% vs. 87.1%, and 82.5% vs. 81.2%, respectively. Induction chemotherapy was not an independent prognostic factor for OS (P=0.193) or LRFS, but there was a positive tendency for DMFS (P=0.088). GP regimen (gemcitabine + cisplatin) was an independent prognostic factor for OS (P = 0.038) and it had a trend toward improved DMFS (P = 0.109). TP regimen (taxol + cisplatin) was only a significant prognostic factor for DMFS (P =0.038). Conclusions: Adding induction chemotherapy had no survival benefit, but GP regimen benefited overall survival and had a trend toward improved DMFS. GP regimen may be superior to TP/FP regimen (fluorouracil + cisplatin) in treating locoregionally advanced NPC. PMID:26430402

  9. Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

    PubMed Central

    Colombo, Giorgio Lorenzo; Cammà, Calogero; Attili, Adolfo Francesco; Ganga, Roberto; Gaeta, Giovanni Battista; Brancaccio, Giuseppina; Franzini, Jean Marie; Volpe, Marco; Turchetti, Giuseppe

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden. Purpose The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated. Results Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed. Conclusion The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage. PMID:26527877

  10. Systemic treatment and targeted therapy in patients with advanced hepatocellular carcinoma

    PubMed Central

    Tazi, El Mehdi; Essadi, Ismail; M’rabti, Hind; Touyar, Anass; Errihani, PR Hassan

    2011-01-01

    Background: Advanced hepatocellular carcinoma (HCC) is a malignancy of global importance: it is the sixth most common cancer and the third most common cause of cancer-related mortality worldwide. Despite decades of efforts by many investigators, systemic chemotherapy or hormone therapy has failed to demonstrate improved survival in patients with HCC.. Ongoing studies are evaluating the efficacy and tolerability of combining Sorafenib with erlotinib and other targeted agents or chemotherapy. Aims: On the basis of placebo-controlled, randomized phase III trials, Sorafenib has shown improved survival benefits in advanced HCC and has set a new standard for future clinical trials. The successful clinical development of Sorafenib in HCC has ushered in the era of molecularly targeted agents in this disease, which is discussed in this educational review. Material and Methods: Many molecularly targeted agents that inhibit angiogenesis, epidermal growth factor receptor, and mammalian target of rapamycin are at different stages of clinical development in advanced HCC. Future research should continue to unravel the mechanism of hepatocarcinogenesis and to identify key relevant molecular targets for therapeutic intervention. Identification and validation of potential surrogate and predictive biomarkers hold promise to individualize patients’ treatment to maximize clinical benefit and minimize the toxicity and cost of targeted agents. Results: Systemic therapy with various classes of agents, including hormone and cytotoxic agents, has provided no or marginal benefits. Improved understanding of the mechanism of hepatocarcinogenesis, coupled with the arrival of many newly developed molecularly targeted agents, has provided the unique opportunity to study some of these novel agents in advanced HCC. Conclusions: The demonstration of improved survival benefits by Sorafenib in advanced HCC has ushered in the era of molecular-targeted therapy in this disease, with many agents

  11. Diffuse large B-cell lymphoma mimicking advanced basal cell carcinoma.

    PubMed Central

    Akinyemi, Emmanuel; Mai, Le; Matin, Abu; Maini, Archana

    2007-01-01

    Primary cutaneous B-cell lymphomas (PCBCLs) are made up of a heterogenous group of B-cell lymphoproliferative diseases confined to the skin at the time of diagnosis with no evidence of extracutaneous involvement. With early diagnosis and adequate treatment, PCBCLs as a group has excellent prognosis, with about a 95% survival rate at five years. We report a case of diffuse large B-cell lymphoma (DLBCL) in a 52-year-old woman presenting as a fungating skin ulcer mimicking advanced basal cell carcinoma. Review of available literature showed most studies of PCBCLs being done on Europeans with no universally acceptable system of classification. Clinical findings, diagnostic evaluations and treatment outcomes of PCBCLs are discussed with emphasis on comparison of European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) Classification of Neoplasms of the Hematopoietic and Lymphoid Tissue classification systems. Images Figure 1 Figure 2 PMID:17722675

  12. Diffuse large B-cell lymphoma mimicking advanced basal cell carcinoma.

    PubMed

    Akinyemi, Emmanuel; Mai, Le; Matin, Abu; Maini, Archana

    2007-08-01

    Primary cutaneous B-cell lymphomas (PCBCLs) are made up of a heterogenous group of B-cell lymphoproliferative diseases confined to the skin at the time of diagnosis with no evidence of extracutaneous involvement. With early diagnosis and adequate treatment, PCBCLs as a group has excellent prognosis, with about a 95% survival rate at five years. We report a case of diffuse large B-cell lymphoma (DLBCL) in a 52-year-old woman presenting as a fungating skin ulcer mimicking advanced basal cell carcinoma. Review of available literature showed most studies of PCBCLs being done on Europeans with no universally acceptable system of classification. Clinical findings, diagnostic evaluations and treatment outcomes of PCBCLs are discussed with emphasis on comparison of European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) Classification of Neoplasms of the Hematopoietic and Lymphoid Tissue classification systems.

  13. Treatment of advanced squamous cell carcinoma of the lung: a review

    PubMed Central

    Mileham, Kathryn F.; Bonomi, Philip D.; Batus, Marta; Fidler, Mary J.

    2015-01-01

    Lung cancer remains the single deadliest cancer both in the US and worldwide. The great majority of squamous cell carcinoma (SCC) is attributed to cigarette smoking, which fortunately is declining alongside cancer incidence. While we have been at a therapeutic plateau for advanced squamous cell lung cancer patients for several decades, recent observations suggest that we are on the verge of seeing incremental survival improvements for this relatively large group of patients. Current studies have confirmed an expanding role for immunotherapy [including programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition], a potential opportunity for VEGFR inhibition, and even future targets in fibroblast growth factor receptor (FGFR) and PI3K-AKT that collectively should improve survival as well as quality of life for those affected by squamous cell lung cancer over the next decade. PMID:26629421

  14. A case report of peritoneal tuberculosis with multiple miliary peritoneal deposits mimicking advanced ovarian carcinoma

    PubMed Central

    Yazdani, Shahla; Sadeghi, Mahmod; Alijanpour, Abolhasan; Naeimi-rad, Mojgan

    2016-01-01

    Background: Peritoneal tuberculosis accounts 1-2% of all forms of tuberculosis. Peritoneal tuberculosis is an important differential diagnosis for ovarian cancer in women with ascites, adnexal mass and elevated cancer antigen 125 (CA125) levels. We report a case of a 32- year -old woman with multiple miliary peritoneal deposits mimicking advanced ovarian carcinoma. Case Presentation: A 32-year-old drug addicted woman presented with menometrorrhagia, fever and shivering, ascites and pelvis mass. Ultrasonography revealed a 53×65 mm cyst in left ovary and ascites. Multiple miliary peritoneal deposits were observed during laparatomy without any mass, histologic examination confirmed tuberculosis of uterus, tubes, omentum, liver and external surfaces of small intestine. Finally, the patient recovered with anti-tuberculosis treatment. Conclusion: These findings highlight considering tuberculosis in the differential diagnosis of any patients with adnexal mass, ascitis and elevated serum CA125 even with negative cytology and bacteriology test results. PMID:26958336

  15. Combination chemotherapy for advanced squamous cell carcinoma of the head and neck.

    PubMed

    Coker, D D; Elias, E G; Chretien, P B; Gray, W C; Coleman, J J; Zentai, T A; Didolkar, M S; Morris, D M; Viravathana, T; Hebel, J R

    1981-01-01

    Fifty-one patients (32 previously untreated, 19 previously treated) with advanced squamous cell carcinoma of the head and neck received a single course of combination chemotherapy consisting of high dose cis-platinum (DDP), bleomycin (Bleo), +/- high dose methotrexate (MTX). Thirty-three (65%) patients responded to therapy; 5 (10%) of these patients had a complete response. Previously untreated patients and those who received the three drugs (DDP, Bleo and MTX) had the highest response rates. The duration of response was 8 to 12 weeks. Seven (15%) patients showed a two-year survival rate. All nonresponders were dead of disease within two years. Three (56%) of the five complete-response patients and 4 (21%) of the partial-response patients survived for two years. The role of preoperative chemotherapy in head and neck cancer is yet to be conclusively defined.

  16. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    PubMed

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  17. Lenvatinib therapy for the treatment of patients with advanced renal cell carcinoma.

    PubMed

    Glen, Hilary

    2016-10-01

    Despite advances in metastatic renal cell carcinoma (mRCC) treatments, patients eventually progress and develop resistance to therapies targeting a single pathway. Lenvatinib inhibits VEGFR1-3, FGFR1-4, PDGFRβ, RET and KIT proto-oncogenes. In a randomized, Phase II trial evaluating patients with mRCC who had progressed after one prior VEGF-targeted therapy, progression-free survival was significantly improved with lenvatinib alone or in combination with everolimus versus everolimus alone. This review summarizes the clinical development of lenvatinib in mRCC, and how simultaneous targeting of multiple pathways involved in carcinogenesis and/or therapeutic resistance may improve patient outcomes. Lenvatinib plus everolimus may be a promising second-line treatment in patients with mRCC.

  18. Molecularly targeted therapy for advanced hepatocellular carcinoma - a drug development crisis?

    PubMed Central

    Thillai, Kiruthikah; Ross, Paul; Sarker, Debashis

    2016-01-01

    Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib, a multi-targeted kinase inhibitor, is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer (HCC), this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase III clinical trials of novel molecularly targeted therapies, warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity, trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC. PMID:26909132

  19. CEP55 overexpression predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma

    PubMed Central

    Jiang, Wenpeng; Wang, Zhou; Jia, Yang

    2017-01-01

    Development of esophageal squamous cell carcinoma (ESCC) involves alterations in multiple genes with corresponding proteins. Recent studies have demonstrated that centrosomal protein 55 (CEP55) shares certain features with oncogenes, and CEP55 overexpression is associated with the development and progression of malignant tumors. The present study aimed to analyze, for the first time, whether CEP55 expression is related to clinicopothalogic features in the esophageal squamous cell carcinoma (ESCC), as well as patient survival. A total of 110 patients with mid-thoracic ESCC who suffered from Ivor-Lewis were enrolled. The CEP55 expression profile of these patients in tumour tissues and corresponding healthy esophageal mucosa (CHEM) was detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction analyses. Correlations between CEP55 expression and clinicopathological factors were analyzed using χ2 test. The log-rank test was employed to calculate survival rate. A Cox regression multivariate analysis was performed to determine independent prognostic factors. The results demonstrated that CEP55 expression in ESCC was significantly higher than that of CHEM (P<0.001). Overexpression of CEP55 was significantly associated with differentiation degree (P=0.022), T stage (P=0.019), lymph node metastasis (P=0.033), clinicopathological staging (P=0.002) and tumor recurrence (P=0.021) in locally advanced ESCC patients. In addition, CEP55 overexpression was significantly associated with reduced overall survival of patients after surgery (P=0.012). The 5-year survival rate of patients without CEP55 overexpression was significantly higher than that of patients with CEP55 overexpression (P=0.012). Therefore, these findings suggest that CEP55 overexpression correlates with poor prognosis in locally advanced ESCC patients. PMID:28123547

  20. [Carcinoma of the esophagus. Palliative treatment with endoscopic prosthesis].

    PubMed

    Sala, T; Pertejo, V; Linares, M; Del Val, A

    1990-08-01

    The efficacy and safety of endoscopically inserted esophageal prosthesis was evaluated in 33 patients with non-operable carcinoma involving the esophagus. In 30 cases, the origin of the tumor was esophageal, and in 3 cases, bronchopulmonary. Esophago-pulmonary fistula was present in 9 patients. Histologic exam of the tumors revealed 11 adenocarcinomas and 22 epidermoid carcinomas. In every case, Atkinson prosthesis was used and previous esophageal dilatation was needed in 21 patients. Normal oral feeding was achieved in 29 patients. Mean hospital stay after insertion of the prosthesis was 5 days. Survival rate was 84.8% at one month, 63.6% at 4-6 months, 42.4% survived more than 6 months, and 21.2% were still alive one year after the procedure. Complications occurred in 3 patients (9%) -esophageal perforation in two cases, and pneumonia in one case. One patient died. In conclusion, in patients with advanced carcinoma involving the esophagus, palliative therapy with endoscopically inserted esophageal prosthesis is effective, relatively safe and cheap.

  1. [A case of epidermoid tumor inside the Meckel's cave].

    PubMed

    Ohta, H; Ottomo, M; Nakamura, T; Yokota, A

    1997-10-01

    An epidermoid tumor inside the Meckel's cave is rare. The symptoms caused by this tumor include trigeminal neuralgia, facial hypesthesia and paresis of the 3rd, 4th and 6th nerves. A case of epidermoid tumor inside Meckel's cave was presented. A 54-year-old female who had complained of 3rd nerve palsy with right facial hypesthesia since 3 years before was referred to our clinic. Magnetic resonance imaging (MRI) showed the tumor at Meckel's cave. The tumor removal was performed using the orbito-zygomatic approach. To avoid injury of the internal carotid artery and nerves inside the cavernous sinus, removal of the tumor inside the capsule was carried out leaving the capsule. Postoperatively, the tumor removal was confirmed by MRI and improvement of the 3rd and the 5th nerve palsy was obtained three months after surgery. This case suggests that the capsule of the tumor inside the Meckel's cave should be allowed to remain to avoid injury of the adjacent 4th, 5th and 6th nerves and of the internal carotid artery.

  2. Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses

    PubMed Central

    Rognoni, Carla; Ciani, Oriana; Sommariva, Silvia; Facciorusso, Antonio; Tarricone, Rosanna; Bhoori, Sherrie; Mazzaferro, Vincenzo

    2016-01-01

    Trans-arterial radioembolization (TARE) is a recognized, although not explicitly recommended, experimental therapy for unresectable hepatocellular carcinoma (HCC). A systematic literature review was performed to identify published studies on the use of TARE in intermediate and advanced stages HCC exploring the efficacy and safety of this innovative treatment. Twenty-one studies reporting data on overall survival (OS) and time to progression (TTP), were included in a meta-analysis. The pooled post-TARE OS was 63% (95% CI: 56-70%) and 27% (95% CI: 21-33%) at 1- and 3-years respectively in intermediate stage HCC, whereas OS was 37% (95% CI: 26-50%) and 13% (95% CI: 9-18%) at the same time intervals in patients with sufficient liver function (Child-Pugh A-B7) but with an advanced HCC because of the presence of portal vein thrombosis. When an intermediate and advanced case-mix was considered, OS was 58% (95% CI: 48-67%) and 17% (95% CI: 12-23%) at 1- and 3-years respectively. As for TTP, only four studies reported data: the observed progression probability was 56% (95% CI: 41-70%) and 73% (95% CI: 56-87%) at 1 and 2 years respectively. The safety analysis, focused on the risk of liver decompensation after TARE, revealed a great variability, from 0-1% to more than 36% events, influenced by the number of procedures, patient Child-Pugh stage and treatment duration. Evidence supporting the use of radioembolization in HCC is mainly based on retrospective and prospective cohort studies. Based on this evidence, until the results of the ongoing randomized trials become available, radioembolization appears to be a viable treatment option for intermediate-advanced stage HCC. PMID:27579537

  3. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  4. Unusually large submandibular epidermoid cyst: A case report, differential diagnosis and therapy

    PubMed Central

    Passi, Deepak; Singh, Geeta; Mehta, Gagan; Singhal, Deepika

    2014-01-01

    Epidermoid cysts are rare, slow-growing, benign, and developmental cysts that are derived from abnormally situated ectodermal tissue. Epidermoid cysts may grow anywhere on the body and about 7% of them are located in the head and neck. These cysts arise from traumatic implantation of epithelium or entrapment of epithelial remnants during embryonic fusion. Histopathologically, they are lined by stratified squamous epithelium and lumen without any skin appendages. Here, we present a case of large epidermoid cyst occurring in submandibular region. PMID:24963258

  5. Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma.

    PubMed

    DA Fonseca, Leonardo Gomes; Barroso-Sousa, Romualdo; Bento, Afonso DA Silva Alves; Blanco, Bruna Paccola; Valente, Gabriel Luis; Pfiffer, Tulio Eduardo Flesch; Hoff, Paulo Marcelo; Sabbaga, Jorge

    2015-07-01

    Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33-5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22-13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.

  6. Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

    PubMed Central

    Ling, Chun-Run; Wang, Rui; Wang, Mo-Jin; Ping, Jie; Zhuang, Wen

    2017-01-01

    As well known, signet-ring cell carcinoma (SRCC) is a rare histological subtype of colorectal adenocarcinoma, which has been associated with poor prognosis and resistant to non-surgery therapy compared with common adenocarcinoma. In this study, we assessed the effect of preoperative radiotherapy (PRT) for locally advanced rectal SRCC in a large patient group from the Surveillance, Epidemiology, and End Results program (SEER, 1988–2011) database. SRCC was found in 0.9% (n = 622) rectal cancer (RC) patients in our study. In the PRT setting, SRCC had significantly worse cancer-specific survival than mucinous adenocarcinoma and nonmucinous adenocarcinoma patients (log-rank, P < 0.001). In terms of SRCC, stage III RC patients benefited from PRT (log-rank, P < 0.001) while stage II did not (P = 0.095). The multivariate Cox proportional hazard model showed that PRT was an independent benefit factor in stage III rectal SRCC patients (HR, 0.611; 95% CI, 0.407–0.919; P = 0.018). In conclusion, SRCC was an independent predictor of poor prognosis in stage III RC patients, but not in stage II. In the PRT setting of locally advanced RC, SRCC patients had significantly worse prognosis. PRT was an independent prognostic factor associated with improved survival in stage III rectal SRCC. PMID:28345614

  7. Oesophageal squamous cell carcinoma (ESCC): Advances through omics technologies, towards ESCC salivaomics.

    PubMed

    González-Plaza, Juan José; Hulak, Nataša; García-Fuentes, Eduardo; Garrido-Sánchez, Lourdes; Zhumadilov, Zhaxybay; Akilzhanova, Ainur

    2015-08-01

    Oesophageal Squamous Cell Carcinoma (ESCC) is one of the two main subtypes of oesophageal cancer, affecting mainly populations in Asia. Though there have been great efforts to develop methods for a better prognosis, there is still a limitation in the staging of this affection. As a result, ESCC is detected at advances stages, when the interventions on the patient do not have such a positive outcome, leading in many cases to recurrence and to a very low 5-year survival rate, causing high mortality. A way to decrease the number of deaths is the use of biomarkers that can trace the advance of the disease at early stages, when surgical or chemotherapeutic methodologies would have a greater effect on the evolution of the subject. The new high throughput omics technologies offer an unprecedented chance to screen for thousands of molecules at the same time, from which a new set of biomarkers could be developed. One of the most convenient types of samples is saliva, an accessible body fluid that has the advantage of being non-invasive for the patient, being easy to store or to process. This review will focus on the current status of the new omics technologies regarding salivaomics in ESCC, or when not evaluated yet, the achievements in related diseases.

  8. Reconstruction With Modified Face Lift and Orbicularis Oculi V-Y Advancement Flap for Sebaceous Carcinoma on Temple Area.

    PubMed

    Lee, Byeong Ho; Kim, Joo Hyun; Park, Seong Hoon; Ahn, Duk Kyun; Suh, In Suck; Jeong, Hii Sun

    2015-09-01

    Extraocular sebaceous carcinoma that occurs on sebaceous gland is a rare malignant cancer with unknown causes and nonspecific clinical characters, but with distinct pathology and immunohistochemical finding. In Kangnam Sacred Heart Hospital, there was a case that the result of preoperative punch biopsy was squamous cell carcinoma and malignant proliferating trichilemmal tumor, but that of postoperative permanent biopsy was sebaceous carcinoma. The type of tumor, differentiation, location, and aesthetic results are considered to get both recurrence-safe and aesthetically pleasing result. Various flaps were considered, and modified face-lift flap, forehead rotation flap, orbicularis oculi V-Y advancement flap were planned. There were no sign of recurrence of cancer or functional and aesthetical deformities 6 months after the surgery.

  9. Rapid hyperfractionated radiotherapy. Clinical results in 178 advanced squamous cell carcinomas of the head and neck

    SciTech Connect

    Nguyen, T.D.; Demange, L.; Froissart, D.; Panis, X.; Loirette, M.

    1985-07-01

    The authors present a series of 178 patients with Stage III or IV squamous cell carcinoma of the head and neck treated by rapid irradiation using multiple and small fractions per day. An initial group of 91 patients (G1) received a total dose of 72 Gy in 80 sessions and 10 days, according to the following split course schedule: J1 to J5, 36 Gy in 40 sessions, eight daily fractions of .9 Gy separated by 2 hours; J6 to J20, rest period; J21 to J25, same as in J1 except that the spinal cord was shielded. This protocol was altered for the following 87 patients (G2) by lessening the total dose to 60 to 66 Gy and the number of fractions to 60. The rest period was lengthened to 4 weeks. All patients but five completed the whole program and the minimal follow-up period was 24 months. At the end of irradiation, 121 patients achieved a total remission, but local recurrences occurred in 56%. Moreover, acute intolerance was considered as severe in 34% of G1 patients, and included extensive mucosal necrosis and bleeding. Although this rate was significantly reduced in G2 patients, late complications were observed in 20 of the 25 survivors, and included trismus, cervical sclerosis, and recurrent laryngeal edema. The crude survival rate is 13% at 2 years. Although this study was not randomized, this particular type of accelerated and hyperfractionated combination of irradiation did not really improve the clinical results in advanced carcinoma of the head and neck. Other schedules and probably other tumors, less extended, should be tested.

  10. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

    PubMed Central

    Pivot, X; Raymond, E; Laguerre, B; Degardin, M; Cals, L; Armand, J P; Lefebvre, J L; Gedouin, D; Ripoche, V; Kayitalire, L; Niyikiza, C; Johnson, R; Latz, J; Schneider, M

    2001-01-01

    This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11531245

  11. Transcatheter Arterial Chemoembolization for Advanced Hepatocellular Carcinoma with Inferior Vena Cava and Right Atrial Tumors

    SciTech Connect

    Chern, M. C. Chuang, V. P. Cheng, T. Lin, Z. H. Lin, Y. M.

    2008-07-15

    Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 {mu}m, N = 9; and (B) 47-180 {mu}m, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/9 patients) for group A and 76.5% for group B (13/17 patients) (p < 0.02). No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 {mu}m) are superior to large ones (>180 {mu}m).

  12. Efficacy, safety, pharmacokinetics and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: A phase II study

    PubMed Central

    Zhu, Andrew X.; Ancukiewicz, Marek; Supko, Jeffrey G.; Sahani, Dushyant V.; Blaszkowsky, Lawrence S.; Meyerhardt, Jeffrey A.; Abrams, Thomas A.; McCleary, Nadine Jackson; Bhargava, Pankaj; Muzikansky, Alona; Sheehan, Susan; Regan, Eileen; Vasudev, Eamala; Knowles, Michelle; Fuchs, Charles S.; Ryan, David P.; Jain, Rakesh K.; Duda, Dan G.

    2013-01-01

    Purpose We performed a single-arm phase II study of cediranib, a pan-VEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods Patients with histologically confirmed measurable advanced HCC and adequate hematologic, hepatic, and renal functions received cediranib 30-mg orally once daily (4 weeks/cycle). The primary endpoint was progression-free survival (PFS) rate at 3 months. Other endpoints included response rates, overall survival (OS), pharmacokinetics (PK) and biomarkers for cediranib. Results Cediranib treatment resulted in an estimated 3-month-PFS rate of 77% [60%, 99%]. Median PFS was 5.3 [3.5,9.7] months, stable disease was seen in 5/17 patients (29%), and median OS was 11.7 [7.5–13.6] months. Grade 3 toxicities included hypertension (29%), hyponatremia (29%) and hyperbilirubinemia (18%). Cediranib PK were comparable to those seen in cancer patients with normal hepatic function. Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2 and Ang-2 decreased after cediranib treatment. PFS was inversely correlated with baseline levels of VEGF, sVEGFR2, and bFGF and with on-treatment levels of bFGF and IGF-1, and directly associated with on-treatment levels of IFN-γ. OS was inversely correlated with baseline levels of sVEGFR1, Ang-2, TNF-α, CAIX and CD34+CD133+CD45dim circulating progenitor cells and on-treatment levels of sVEGFR2. Conclusions Despite the limitations of primary endpoint selection, cediranib at 30-mg daily showed a high incidence of toxicity and preliminary evidence of antitumor activity in advanced HCC. Hepatic dysfunction did not appear to affect the steady-state PK of cediranib. Exploratory studies suggested pro-angiogenic and inflammatory factors as potential biomarkers of anti-VEGF therapy in HCC. PMID:23362324

  13. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma

    PubMed Central

    Wahid, Mohd; Jawed, Arshad; Dar, Sajad Ahmad; Mandal, Raju K; Haque, Shafiul

    2017-01-01

    Patients suffering from advanced basal cell carcinoma (BCC) have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee) that corresponds to 43% (95% confidence interval [CI]: 28–59) and 38% (95% CI: 28–48) in their respective categories. Disease control was found in 93% (39 patients) and 80% (74 patients) of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance), nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. PMID:28182134

  14. Intraosseous epidermoid cyst of the distal phalanx reconstructed with synthetic bone graft.

    PubMed

    Sasaki, Hiromi; Nagano, Satoshi; Shimada, Hirofumi; Nakashima, Takayuki; Yokouchi, Masahiro; Ishidou, Yasuhiro; Setoguchi, Takao; Komiya, Setsuro

    2017-01-01

    Intraosseous epidermoid cysts are exceedingly rare. Known as pseudotumors, not true neoplasms, intraosseous epidermoid cysts usually involve the phalanges, the skull, and the toes. Intraosseous epidermoid cysts typically present as destructive osteolytic lesions on X-ray, mimicking malignant bone tumors. Here, we present two cases of an intraosseous epidermoid cyst in the distal phalanx treated with curettage and synthetic bone graft, followed by a review of the relevant literature. In both cases, the patient presented with a painful enlargement of the fingertip following a minor trauma. Magnetic resonance imaging demonstrated lesions involving the distal phalanx that had a low signal on T1-weighted imaging (WI) and a high intensity on T2-WI. In both cases, the lesions were not enhanced by gadolinium. Good remodeling and functional recoveries were obtained. For physically active patients with substantial bone defects, synthetic bone graft may be recommended.

  15. Multiple epidermoid cysts located in the pineal and extracranial regions treated by neuroendoscopy.

    PubMed

    Kurosaki, Kunikazu; Hayashi, Nakamasa; Hamada, Hideo; Hori, Emiko; Kurimoto, Masanori; Endo, Shunro

    2005-04-01

    A 22-year-old woman presented with a rare case of multiple epidermoid cysts located in the pineal and extracranial regions. Magnetic resonance (MR) imaging showed a lesion in the pineal region as hypointense on the T(1)-weighted image and hyperintense on the T(2)-weighted image, without enhancement. Neuroendoscopic treatment was performed under a diagnosis of pineal cyst. However, the cyst wall was too thick to perforate, although third ventriculostomy was performed. Diffusion-weighted MR imaging demonstrated the lesions in the pineal and extracranial regions as marked hyperintensity. The diagnosis was epidermoid cyst. Subsequently, neuroendoscopic treatment of the pineal epidermoid cyst was performed. Careful preoperative diagnosis of epidermoid cysts based on diffusion-weighted MR imaging is required.

  16. [Outcome of treatment with surgical resection of the remaining tumor after modified M-VAC treatment for advanced urothelial carcinoma].

    PubMed

    Narita, Shintaro; Nakano, Masahiro; Matsuzaki, Masato; Watanabe, Jyunichi; Morikawa, Hiroshi; Murata, Hirokatsu; Oda, Hiroyuki; Komatsu, Hideki

    2005-03-01

    We retrospectively evaluated the effect of the surgical resection of the remaining tumor after modified M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) (m-M-VAC) treatment for locally advanced or metastatic urothelial carcinoma. In m-M-VAC therapy, methotrexate and vinblastine on 15 and 22 days were omitted from the classical M-VAC to avoid the discontinuation and the dose reduction, and duration of 1 course was shortened to 21 days from 28 days of the classical M-VAC. Seven patients with locally invasive or metastatic carcinoma of the renal pelvis, ureter, and bladder, 6 males and 1 female, with a median age 64.1 years, ranging from 49 to 77 years received m-M-VAC chemotherapy without severe side effects. In all patients, the residual viable carcinoma was completely resected and they achieved complete remission. The median survival time was 20 months (range, 7 to 61). Five of these 7 patients were still alive. Two patients had no recurrence and achieved long-term survival (survival duration; 61 and 39 months). Although further studies and long-term follow up are required, these results suggest that patients who present with locally advanced or metastatic urothelial carcinoma may benefit from surgical resection after m-M-VAC.

  17. Nonbacterial thrombotic endocarditis with embolic cerebral vascular accidents in a patient with advanced, recurrent clear cell carcinoma of the ovary: A case report.

    PubMed

    Liang, Lusha W; Perez, Alexander R; Cangemi, Nicholas A; Young, Robert J; Makker, Vicky

    2016-04-01

    •Nonbacterial thrombotic endocarditis can occur in ovarian clear cell carcinoma.•We report on NBTE-associated embolic cerebrovascular infarcts in advanced OCCC.•Further NBTE-associated embolic events can be prevented with anticoagulant therapy.

  18. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  19. Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up

    PubMed Central

    Colagrande, Stefano; Regini, Francesco; Taliani, Gian Giacomo; Nardi, Cosimo; Inghilesi, Andrea Lorenzo

    2015-01-01

    Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of

  20. Helical tomotherapy and larynx sparing in advanced oropharyngeal carcinoma: a dosimetric study.

    PubMed

    Gielda, Benjamin T; Millunchick, Cheryl H; Smart, Joseph P; Marsh, James C; Turian, Julius V; Coleman, Joy L

    2010-01-01

    Intensity-modulated radiation therapy (IMRT) is gaining acceptance as a standard treatment technique for advanced squamous cell carcinoma (SCC) of the oropharynx. Dose to the uninvolved larynx and surrounding structures can pose a problem in patients with significant neck disease, potentially compromising laryngeal function and quality of life. Tomotherapy may allow greater laryngeal sparing. Seven patients with stage IV SCC of the oropharynx were replanned using Tomotherapy version 3.1. All contours/planning target volumes (PTVs) from the original plans were preserved, with the exception of the larynx, which was drawn to include all soft tissue encompassed by the thyroid/cricoid cartilage. A simultaneous integrated boost technique was used with PTV 1, 2, and 3 receiving 69.96, 59.40, and 54.00 Gy, respectively in 33 fractions. Dosimetry was evaluated via the Pinnacle treatment planning system (TPS). Equivalent uniform dose (EUD) was calculated from the dose volume histogram (DVH) using the general method with "a" = 5.0. Mean larynx dose for all patients was 24.4 Gy. Mean EUD to the larynx was 34.2 Gy. Homogeneity was adequate; average maximum dose was 109.7% of the highest prescription. All other organs at risk (OAR) were adequately spared. Tomotherapy can spare the uninvolved larynx in the setting of advanced SCC of the oropharynx to levels that are similar to or better than those reported with other techniques. Sparing is achieved without compromising target coverage or other OAR sparing. The clinical benefit of this sparing remains to be determined in a prospective study.

  1. Helical Tomotherapy and Larynx Sparing in Advanced Oropharyngeal Carcinoma: A Dosimetric Study

    SciTech Connect

    Gielda, Benjamin T.; Millunchick, Cheryl H.; Smart, Joseph P.; Marsh, James C.; Turian, Julius V.; Coleman, Joy L.

    2010-10-01

    Intensity-modulated radiation therapy (IMRT) is gaining acceptance as a standard treatment technique for advanced squamous cell carcinoma (SCC) of the oropharynx. Dose to the uninvolved larynx and surrounding structures can pose a problem in patients with significant neck disease, potentially compromising laryngeal function and quality of life. Tomotherapy may allow greater laryngeal sparing. Seven patients with stage IV SCC of the oropharynx were replanned using Tomotherapy version 3.1. All contours/planning target volumes (PTVs) from the original plans were preserved, with the exception of the larynx, which was drawn to include all soft tissue encompassed by the thyroid/cricoid cartilage. A simultaneous integrated boost technique was used with PTV 1, 2, and 3 receiving 69.96, 59.40, and 54.00 Gy, respectively in 33 fractions. Dosimetry was evaluated via the Pinnacle treatment planning system (TPS). Equivalent uniform dose (EUD) was calculated from the dose volume histogram (DVH) using the general method with 'a' = 5.0. Mean larynx dose for all patients was 24.4 Gy. Mean EUD to the larynx was 34.2 Gy. Homogeneity was adequate; average maximum dose was 109.7% of the highest prescription. All other organs at risk (OAR) were adequately spared. Tomotherapy can spare the uninvolved larynx in the setting of advanced SCC of the oropharynx to levels that are similar to or better than those reported with other techniques. Sparing is achieved without compromising target coverage or other OAR sparing. The clinical benefit of this sparing remains to be determined in a prospective study.

  2. Role of transarterial chemoembolization in relation with sorafenib for patients with advanced hepatocellular carcinoma

    PubMed Central

    Ha, Yeonjung; Lee, Danbi; Shim, Ju Hyun; Lim, Young-Suk; Lee, Han Chu; Chung, Young-Hwa; Lee, Yung Sang; Park, Sook Ryun; Ryu, Min-Hee; Ryoo, Baek-Yeol; Kang, Yoon-Koo; Kim, Kang Mo

    2016-01-01

    Background Although sorafenib is considered standard therapy for advanced hepatocellular carcinoma (HCC), actual treatments vary. We evaluated the effects of different treatment strategies on overall survival. Methods A retrospective study of sorafenib-treated patients with advanced HCC was conducted. The primary outcome was overall survival. Prognostic factors were analyzed using multivariate Cox-proportional hazards model. Results A total of 658 patients (mean age, 54.5 years; 83.3% male) were analyzed; 293, 129, and 236 patients were treated with sorafenib, a combination therapy of sorafenib and transarterial chemoembolization (TACE), and TACE followed by sorafenib, respectively. Overall, 51.2% of patients treated under the combination strategy had portal vein invasion, whereas 89.9% of patients receiving sorafenib monotherapy had distant metastasis. Median overall survival durations were comparable (11.8 months for sorafenib, 16.2 months for the combination therapy, and 13.5 months for TACE followed by sorafenib; P = 0.13). However, among portal vein invasion cases, combination (25.7 months, P = 0.002) and TACE followed by sorafenib (14.0 months, P = 0.030) treatments were associated with longer overall survival duration compared with than sorafenib monotherapy (5.5 months). In a multivariate model, sorafenib duration (hazard ratio [HR], 0.96, P < 0.001) and TACE (HR, 0.24, P < 0.001) along with Child-Pugh stage (HR, 1.83, P = 0.005) were associated with better survival. Conclusions In patients with portal vein invasion, TACE performed concurrently with or before sorafenib administration is associated with better survival. PMID:27494871

  3. Combined-modality treatment for advanced oral tongue squamous cell carcinoma

    SciTech Connect

    Fan, K.-H.; Lin, C.-Y. |; Kang, C.-J.; Huang, S.-F.; Chen, I.-H.; Liao, C.-T. |; Wang, H.-M. |; Cheng, A.-J. |; Chang, J.T.-C. ||. E-mail: jtchang@adm.cgmh.org.tw

    2007-02-01

    Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.

  4. Relationship of ethnicity and overall survival in patients treated with sorafenib for advanced hepatocellular carcinoma

    PubMed Central

    Renouf, Daniel J.; Gill, Sharlene; Cheung, Winson Y.; Lim, Howard J.

    2014-01-01

    Background Although both the SHARP and the Asian-Pacific trials showed improved overall survival (OS) for sorafenib, the magnitude of benefit was substantially less for Asians, who have a higher prevalence of hepatitis B viral (HBV) infection. Whether the worse prognosis is related to ethnicity or to the etiology of hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to identify prognostic factors among patients with HCC who received sorafenib in British Columbia (BC), which has a sizeable Asian population. Methods A total of 255 consecutive patients with advanced HCC who initiated sorafenib from January 2008 to February 2013 were identified using our pharmacy database. Clinicopathological variables and outcomes were retrospectively collected. Prognostic factors were assessed by univariate and multivariate analyses. Results Median age was 63 years, 80.2% were men, and 38% were Asian. Among them, 34.5% had HBV and 29.8% had hepatitis C viral (HCV) infection. In addition, 68.6% had cirrhosis and 45.9% had liver-limited disease. Median progression-free and OS were 3.7 [95% confidence interval (CI): 3.3-4.2] and 7.5 months (95% CI: 5.7-9.2), respectively. On multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) and HCV positivity correlated with better OS (P<0.001 and 0.04, respectively), but ethnicity did not (P=0.622). Conclusions When treated with sorafenib at the same institution, Asians and Caucasians with advanced HCC had similar OS. ECOG PS and HCV were the only significant prognostic factors. A higher proportion of HCV positivity might explain why the SHARP trial achieved better OS when compared to the Asian-Pacific trial. PMID:25083298

  5. Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up.

    PubMed

    Colagrande, Stefano; Regini, Francesco; Taliani, Gian Giacomo; Nardi, Cosimo; Inghilesi, Andrea Lorenzo

    2015-05-18

    Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of

  6. Clinical Benefit Assessment of Vismodegib Therapy in Patients With Advanced Basal Cell Carcinoma

    PubMed Central

    Basset-Seguin, Nicole; Caro, Ivor; Yue, Huibin; Schadendorf, Dirk

    2014-01-01

    Purpose. Vismodegib was approved for the treatment of advanced basal cell carcinoma (aBCC) based on the pivotal ERIVANCE BCC study. The primary endpoint (objective response rate [ORR]) was assessed 9 months after the last patient was enrolled. To confirm the clinical benefit of vismodegib, an additional analysis was performed 12 months after the primary analysis. Materials and Methods. ERIVANCE BCC was a multicenter, nonrandomized, two-cohort study of 104 patients with histologically confirmed aBCC. Patients received 150 mg oral vismodegib daily until disease progression, intolerable toxicity, or withdrawal. An independent review panel comprising three expert clinicians reviewed patient photographs individually and as a consensus panel to evaluate baseline disease severity and clinical benefit after vismodegib treatment in 71 patients with locally advanced BCC (laBCC). Results. Sixty-three patients were efficacy evaluable; baseline and postprogression photographs for 61 were available for review. Baseline disease severity was judged as 5 or 4 (very severe or moderately severe) in 71.4%. Clinical benefit was observed in 76.2% (significant: 65.1%; some: 11.1%). Interpanelist agreement (maximum difference ≤1 point among panelists’ scores in 65.1% and 87.3% of patients for clinical benefit and baseline disease severity, respectively) and correlation between individual and panel reviews were strong. Clinical benefit scores showed good concordance with the protocol-specified ORR obtained by an independent review facility and with investigator-assessed response. Conclusion. Clinical benefit assessed by independent review based on expert clinical judgment provides strong evidence that treatment with vismodegib results in clinically meaningful and durable responses in patients with laBCC. PMID:25001266

  7. Non-coding RNAs deregulation in oral squamous cell carcinoma: advances and challenges.

    PubMed

    Yu, T; Li, C; Wang, Z; Liu, K; Xu, C; Yang, Q; Tang, Y; Wu, Y

    2016-05-01

    Oral squamous cell carcinoma (OSCC) is a common cause of cancer death. Despite decades of improvements in exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. The difficulty of early diagnosis and the high prevalence of metastasis associated with OSCC contribute to its dismal prognosis. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest in the research for predictive biomarkers. Non-coding RNAs (ncRNAs) are promising biomarkers. Among numerous kinds of ncRNAs, short ncRNAs, such as microRNAs (miRNAs), have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. In contrast to miRNAs, long non-coding RNAs (lncRNAs) are much less known concerning their functions in human cancers especially in OSCC. The present review highlighted the roles of miRNAs and newly discovered lncRNAs in oral tumorigenesis, metastasis, and their clinical implication.

  8. Chemotherapies and targeted therapies in advanced hepatocellular carcinoma: from laboratory to clinic.

    PubMed

    Voiculescu, Mihai; Winkler, Robert E; Moscovici, Marius; Neuman, Manuela G

    2008-09-01

    Chronic liver diseases alone or in conjunction with other risk factors result in increased liver damage leading to inflammation and fibrosis of the liver and rising rates of liver cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). This review will address the determinants of liver injury at the initiation of the tumor and the risk factors for rapid disease progression. Regardless of the etiology, the unifying feature of these tumors are their propensity to arise upon a background of inflammation and fibrosis. Liver disease is often associated with enhanced hepatocyte apoptosis, which is the case in viral and autoimmune hepatitis, cholestatic diseases, and metabolic disorders. Disruption of apoptosis is responsible for HCC. The mechanisms by which apoptosis occurs in the liver might provide insights into HCC and suggest possible treatments. We aim to better understand the factors that distinguish a relatively long course of HCC from one with rapid progression. We will accomplish this task with three integrated ideas: 1 - the role of epidemiology in establishing the risk factors of co-morbidity with alcohol and hepatitis viruses; 2 - the role of apoptosis and anti-apoptotic signals in the progression of HCC; and 3 - the role of new advancements that have emerged in the field of molecular-directed chemotherapeutics in HCC in recent years. This review will also aim to describe the molecular targeted therapies of non-resectable HCC and the ways of effective combination in this otherwise chemo-resistant tumor.

  9. Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2010-05-01

    Treatment options for patients with metastatic renal cell carcinoma (RCC) have changed dramatically, and a new paradigm has evolved. IFN-alpha and IL-2 were previously mainstays of therapy, but since December 2005, six new agents have been approved in the USA for the treatment of advanced RCC. Three of these new agents are multitargeted kinase inhibitors, including sunitinib, sorafenib, and recently pazopanib, two target the mTOR (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with IFN-alpha) that targets VEGF. Sunitinib has emerged as the standard of care for treatment-naive RCC patients, with the recently approved bevacizumab and IFN-alpha combination providing an additional option for this population. The recent approval of pazopanib, based on the results from sequential Phase II and III clinical trials demonstrating improved overall response rates and progression-free survival, provides yet another option for front-line therapy. The current article examines the pazopanib preclinical and clinical data, provides an overview of the development of this tyrosine kinase inhibitor, and provides some speculation concerning its role in RCC therapy.

  10. Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

    PubMed

    Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D

    2001-01-01

    The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.

  11. Safety and long term efficacy of porfimer sodium photodynamic therapy in locally advanced biliary tract carcinoma

    PubMed Central

    Pereira, Stephen P; Aithal, Guruprasad P; Ragunath, Krish; Devlin, John; Owen, Faye; Meadows, Helen

    2012-01-01

    Background In patients with unresectable cholangiocarcinoma, photodynamic therapy (PDT) with porfimer sodium promotes biliary drainage and may improve survival and quality of life. Aim To prospectively evaluate the safety and efficacy of PDT in patients with locally advanced biliary tract carcinoma. Methods Eligible patients had unresectable, histologically confirmed disease, a Karnofsky performance status of ≥30% and life expectancy >12 weeks. Patients received 2mg/kg i.v. of porfimer sodium, followed by endobiliary laser activation and stent replacement 48 hrs later. Patients were assessed clinically and radiologically before treatment and on day 28, and followed up thereafter at three-monthly intervals until death. Results 36 patients were entered over an 18 months period: 14 males, 22 females, with a median age of 65 (30-79) yr and performance status of 80 (50-100). PDT was technically successful in all cases and was generally well tolerated; there was no grade 4 toxicity and no treatment-associated mortality. The median survival was 12 (1-84) months. Conclusions Porfimer sodium PDT can be delivered safely to patients with biliary tract cancer and is suitable for testing in phase III studies (UKCRN ID 1218). PMID:23200007

  12. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    PubMed Central

    Jain, Sachin; Song, Ruolan; Xie, Jingwu

    2017-01-01

    The Hedgehog (Hh) pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC), medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA) approved sonidegib, a smoothened (SMO) antagonist, for treatment of advanced BCC (aBCC) after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles)? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. PMID:28352196

  13. Induction chemotherapy for the treatment of non-endemic locally advanced nasopharyngeal carcinoma

    PubMed Central

    Zhao, Lina; Xu, Man; Jiang, Wen; Pan, Haitao; Zang, Jian; Luo, Shanquan; Wang, Jianhua; Zhou, Yongchun; Shi, Mei

    2017-01-01

    Background The role of induction chemotherapy is less clear in non-endemic locally advanced nanopharyngeal carcinomas (NPC). Results With a total of 233 eligible patients and a median follow-up of 36 months, 3-year overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) were 84.5%, 94.9%, 78.6% and 69.2%, respectively. The overall failure rate was 21.0% and distant metastasis occurred in 17.2% patients. Multivariate analyses showed that retropharyngeal and bilateral neck lymph node metastasis were significant prognostic factors for DFS and OS. Moreover, patients receiving both GP (gemcitabine+cisplatin) and TP (docetaxel+cisplatin) regimes had significantly higher DFS and OS compared with PF (cisplatin+5-FU) regime. GP regimes lead to significantly improved OS than TP/PF in some subgroup of patients. No severe toxicities were observed. Materials and Methods We retrospectively analyzed stage III-IVb NPC patients treated between Jan 2006 and Dec 2014, with induction chemotherapy followed by concurrent chemoradiation (IC-CCRT). Statistical analyses were performed on survival and failure patterns. Conclusions These results suggested IC-CCRT was safe and effective for NPCs from non-endemic region. The choice of induction regimen appeared to affect patient outcomes. PMID:28036270

  14. Advanced imaging techniques in the therapeutic response of transarterial chemoembolization for hepatocellular carcinoma

    PubMed Central

    Yang, Ke; Zhang, Xiao-Ming; Yang, Lin; Xu, Hao; Peng, Juan

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in patients with chronic liver disease. Transarterial chemoembolization (TACE) can significantly improve the survival rate of patients with HCC and is the first treatment choice for patients who are not suitable for surgical resections. The evaluation of the response to TACE treatment affects not only the assessment of the therapy efficacy but also the development of the next step in the treatment plan. The use of imaging to examine changes in tumor volume to assess the response of solid tumors to treatment has been controversial. In recent years, the emergence of new imaging technology has made it possible to observe the response of tumors to treatment prior to any morphological changes. In this article, the advances in studies reporting the use of computed tomography perfusion imaging, diffusion-weighted magnetic resonance imaging (MRI), intravoxel incoherent motion, diffusion kurtosis imaging, magnetic resonance spectroscopy, magnetic resonance perfusion-weighted imaging, blood oxygen level-dependent MRI, positron emission tomography (PET)/computed tomography and PET/MRI to assess the TACE treatment response are reviewed. PMID:27239110

  15. Nonsurgical treatment options for basal cell carcinoma - focus on advanced disease.

    PubMed

    Goldenberg, Gary; Hamid, Omid

    2013-12-01

    Basal cell carcinoma (BCC) is the most common cancer in the world. It is typically slow growing and usually effectively managed with surgery. However, BCCs in some patients are unsuitable for surgery or the patient may prefer a nonsurgical treatment. Radiotherapy is a nonsurgical option for the primary treatment of either low- or high-risk BCCs. It is associated with high cure rates, albeit somewhat lower than those observed with Mohs micrographic surgery for high-risk BCCs. Not all patients with BCCs are suitable for radiotherapy. Superficial therapies for BCC include topical imiquimod or 5- fluorouracil and photodynamic therapy (PDT). These therapies are generally associated with somewhat lower clearance rates and/or higher recurrence rates than surgery or radiotherapy, although they may be suitable in patients with low-risk BCCs when surgery or radiotherapy are impractical or less appropriate. An appealing feature of PDT is excellent cosmesis, but PDT is not currently approved by the Food and Drug Administration (FDA), and regimens are not well standardized. Vismodegib is a first-in-class hedgehog pathway inhibitor and recent addition to the armamentarium for the treatment of advanced BCC.

  16. Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma

    SciTech Connect

    Kwong, Dora L.W. . E-mail: dlwkwong@hkucc.hku.hk; Sham, Jonathan S.T.; Leung, Lucullus H.T.; Cheng, Ashley C.K.; Ng, W.M.; Kwong, Philip W.K.; Lui, W.M.; Yau, C.C.; Wu, P.M.; Wei, William; Au, Gordon

    2006-02-01

    Purpose: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). Methods and Materials: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). Results: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. Conclusions: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.

  17. Present and future perspectives on immunotherapy for advanced renal cell carcinoma: Going to the core or beating around the bush?

    PubMed Central

    Kimura, Yasunori

    2015-01-01

    Metastatic lesions of renal cell carcinoma (RCC) occasionally regress spontaneously after surgical removal of the primary tumor. Although this is an exceptionally rare occurrence, RCC has thus been postulated to be immunogenic. Immunotherapies, including cytokine therapy, peptide-based vaccines, and immune checkpoint inhibitors have therefore been used to treat patients with advanced, metastatic RCC. We review the history, trends, and recent progress in immunotherapy for advanced RCC and discuss future perspectives, with consideration of our experimental work on galectin 9 and PINCH as promising specific immunotherapy targets.

  18. Honokiol, a chemopreventive agent against skin cancer, induces cell cycle arrest and apoptosis in human epidermoid A431 cells.

    PubMed

    Chilampalli, Chandeshwari; Guillermo, Ruth; Kaushik, Radhey S; Young, Alan; Chandrasekher, Gudiseva; Fahmy, Hesham; Dwivedi, Chandradhar

    2011-11-01

    Honokiol is a plant lignan isolated from bark and seed cones of Magnolia officinalis. Recent studies from our laboratory indicated that honokiol pretreatment decreased ultraviolet B-induced skin cancer development in SKH-1 mice. The aim of the present investigation was to study the effects of honokiol on human epidermoid squamous carcinoma A431 cells and to elucidate possible mechanisms involved in preventing skin cancer. A431 cells were pretreated with different concentrations of honokiol for a specific time period and investigated for effects on apoptosis and cell cycle analysis. Treatment with honokiol significantly decreased cell viability and cell proliferation in a concentration- and time-dependent manner. Honokiol pretreatment at 50 μmol/L concentration induced G0/G1 cell cycle arrest significantly (P < 0.05) and decreased the percentage of cells in the S and G2/M phase. Honokiol down-regulated the expression of cyclin D1, cyclin D2, Cdk2, Cdk4 and Cdk6 proteins and up-regulated the expression of Cdk's inhibitor proteins p21 and p27. Pretreatment of A431 cells with honokiol leads to induction of apoptosis and DNA fragmentation. These findings indicate that honokiol provides its effects in squamous carcinoma cells by inducing cell cycle arrest at G0/G1 phase and apoptosis.

  19. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma.

    PubMed

    Axelson, Michael; Liu, Ke; Jiang, Xiaoping; He, Kun; Wang, Jian; Zhao, Hong; Kufrin, Dubravka; Palmby, Todd; Dong, Zedong; Russell, Anne Marie; Miksinski, Sarah; Keegan, Patricia; Pazdur, Richard

    2013-05-01

    The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.

  20. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    PubMed Central

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  1. A useful treatment for patients with advanced mixed-type small cell neuroendocrine carcinoma of the prostate: A case report.

    PubMed

    Uemura, Kei-Ichiro; Nakagawa, Go; Chikui, Katsuaki; Moriya, Fukuko; Nakiri, Makoto; Hayashi, Tokumasa; Suekane, Shigetaka; Matsuoka, Kei

    2013-03-01

    Treating extended prostatic small cell neuroendocrine carcinoma (PSCNC) is extremely difficult and no standard treatment has yet been established. We experienced a case of advanced mixed-type PSCNC in which the patient achieved long-term survival and local control following combined therapy. Locally advanced PSCNC causing lower urinary obstruction was detected during androgen-ablation therapy for stage D2 mixed adenocarcinoma PSCNC. The patient was treated with intra-arterial infusion chemotherapy using a reservoir system and external-beam radiotherapy (EBRT) to the whole pelvis and local tumor. After chemoradiotherapy, the patient's lower urinary obstruction was reduced and did not return during the remaining 40 months of the patient's life. The patient survived for 70 months following the start of the androgen-ablation therapy. The present study reports a useful treatment for advanced mixed-type PSCNC, androgen-ablation therapy and chemoradiotherapy. The present results also suggest that the prognostic factors for advanced mixed-type PSCNC are the sensitivity of the conventional adenocarcinoma to androgen-ablation therapy, degree of metastasis and extent of the small cell neuroendocrine carcinoma component.

  2. Effects of an oral iron chelator, deferasirox, on advanced hepatocellular carcinoma

    PubMed Central

    Saeki, Issei; Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Maeda, Masaki; Fujisawa, Koichi; Iwamoto, Takuya; Matsumoto, Toshihiko; Hidaka, Isao; Ishikawa, Tsuyoshi; Uchida, Koichi; Tani, Kenji; Sakaida, Isao

    2016-01-01

    AIM To evaluate the inhibitory effects of deferasirox (DFX) against hepatocellular carcinoma (HCC) through basic and clinical studies. METHODS In the basic study, the effect of DFX was investigated in three hepatoma cell lines (HepG2, Hep3B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day. The duration of a single course of DFX therapy was 28 consecutive days. In the event of dose-limiting toxicity (according to the Common Terminology Criteria for Adverse Events v.4.0), DFX dose was reduced. RESULTS Administration of DFX inhibited the proliferation of hepatoma cell lines and induced the activation of caspase-3 in a dose-dependent manner in vitro. In the murine model, DFX treatment significantly suppressed the development of liver tumors (P < 0.01), and significantly upregulated the mRNA expression levels of hepcidin (P < 0.05), transferrin receptor 1 (P < 0.05), and hypoxia inducible factor-1α (P < 0.05) in both tumor and non-tumor tissues, compared with control mice. In the clinical study, anorexia and elevated serum creatinine were observed in four and all six patients, respectively. However, reduction in DFX dose led to decrease in serum creatinine levels in all patients. After the first course of DFX, one patient discontinued the therapy. We assessed the tumor response in the remaining five patients; one patient exhibited stable disease, while four patients exhibited progressive disease. The one-year survival rate of the six patients was 17%. CONCLUSION We demonstrated that DFX inhibited HCC in the basic study, but not in the clinical study due to dose-limiting toxicities. PMID:27833388

  3. Analysis of Prognostic Factors After Yttrium-90 Radioembolization of Advanced Hepatocellular Carcinoma

    SciTech Connect

    Inarrairaegui, Mercedes; Martinez-Cuesta, Antonio; Rodriguez, Macarena; Bilbao, J. Ignacio

    2010-08-01

    Purpose: To analyze which patient-, tumor-, and treatment-related factors may influence outcome after {sup 90}Y radioembolization ({sup 90}Y-RE) for hepatocellular carcinoma (HCC). Patients and Methods: Seventy-two consecutive patients with advanced HCC treated with {sup 90}Y-RE were studied to detect which factors may have influenced response to treatment and survival. Results: Median overall survival was 13 months (95% confidence interval, 9.6-16.3 months). In univariate analysis, survival was significantly better in patients with one to five lesions (19 vs. 8 months, p = 0.001) and in patients with alpha-fetoprotein <52 UI/mL (24 vs. 11 months, p = 0.002). The variation in target tumor size and the appearance of new lesions were analyzed among 50 patients with measurable tumors. A decrease in target tumor size was observed in most patients, and the intensity of such decrease was not associated with any of the factors under study. Patients who developed new lesions in the treated liver (and also in the nontargeted liver) at month 3 more frequently had more than five nodules, bilobar disease, and alpha-fetoprotein >52 UI/mL, and their survival in the multivariate analysis was significantly worse (hazard ratio, 4.7; 95% confidence interval, 13-1.73) (p = 0.002). Conclusions: Yttrium-90 radioembolization results in control of target lesions in the majority of patients with HCC but does not prevent the development of new lesions. Survival of patients treated with {sup 90}Y-RE seems to depend largely on factors related to the aggressiveness of the disease (number of nodules, levels of alpha-fetoprotein, and presence of microscopic disease).

  4. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients.

  5. A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma

    PubMed Central

    Yan, Li; Chen, Yong-Liang; Su, Ming; Liu, Tian; Xu, Kai; Liang, Feng; Gu, Wan-Qing; Lu, Shi-Chun

    2016-01-01

    Background: Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. Methods: Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. Results: All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. Conclusions: IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy. PMID:27958223

  6. Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma

    PubMed Central

    Salman, A.; Simoneau, E.; Hassanain, M.; Chaudhury, P.; Boucher, L.M.; Valenti, D.; Cabrera, T.; Nudo, C.; Metrakos, P.

    2016-01-01

    Background and Aims In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc). Methods The study, conducted prospectively during 2009–2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6–8 weeks before 90Y treatment. Safety and tolerability were assessed. Results Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months. Conclusions Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit. PMID:27803608

  7. A Recent Advance in Image-Guided Locoregional Therapy for Hepatocellular Carcinoma

    PubMed Central

    Shi, Yaoping; Zhai, Bo

    2016-01-01

    Background Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Hepatic resection and liver transplantation are considered to be the preferred treatment for HCC. However, as novel therapeutic options such as image-guided locoregional therapies have emerged and been refined, the manner in which HCC is treated has changed dramatically compared with what it was considered just 2 decades earlier. Summary This study reviews the current results of various image-guided locoregional therapies for treating HCC, especially focusing on thermal ablative and transarterial techniques. Key Message Advances in image-guided locoregional therapies, including local ablative therapy and transarterial therapy, have led to a major breakthrough in the management of HCC. Both survival rates and cure rates of patients with HCC have improved markedly since the introduction of these techniques. Practical Implications Radiofrequency ablation is currently considered as an alternative to surgical resection for patients with early-stage HCC. A newer technique of ablation such as microwave ablation is increasingly being used, especially for large HCC. Transarterial chemoembolization has become a standard care for asymptomatic patients with multinodular tumors in intermediate-stage disease, and transarterial radioembolization has become the method of choice in HCC cases with portal vein thrombosis. Moreover, combination treatment modalities, such as thermal-based ablation combined with transarterial chemoembolization or 125I seed implant brachytherapy, may further broaden their clinical indications for HCC. Moreover, use of localized radiation in combination with thermal ablation has been reported to improve tumor control and long-term survival. PMID:27904861

  8. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2017-01-19

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  9. Benefit of percutaneous endoscopic gastrostomy in patients undergoing definitive chemoradiotherapy for locally advanced nasopharyngeal carcinoma

    PubMed Central

    Xu, Yun; Guo, Qiaojuan; Lin, Jin; Chen, Bijuan; Wen, Jiangmei; Lu, Tianzhu; Xu, Yuanji; Zhang, Mingwei; Pan, Jianji; Lin, Shaojun

    2016-01-01

    Background and aim To evaluate the impact of percutaneous endoscopic gastrostomy (PEG) tube on nutritional status, treatment-related toxicity, and treatment tolerance in patients with locally advanced nasopharyngeal carcinoma (NPC) who underwent chemoradiotherapy. Patients and methods We enrolled 133 consecutive non-metastatic NPC (III/IV stage) patients, who were treated with prophylactic PEG feeding before the initiation of concurrent chemoradiotherapy (CCRT) between June 1, 2010 and June 30, 2014. Meanwhile, another 133 non-PEG patients, who were matched for age, gender, and tumor, node, metastases stage, were selected as historical control cohort. Weight and nutritional status changes from pre-radiotherapy to the end of radiotherapy were evaluated, and treatment tolerance and related acute toxicities were analyzed as well. Results We found that significantly more patients (91.73%) in the PEG group could finish two cycles of CCRT, when compared with those in the non-PEG group (57.89%) (P<0.001). We also indicated that more patients (50.38%) in the non-PEG group experienced weight loss of ≥5%, while the phenomenon was only found in 36.09% patients in the PEG group (P=0.019). In addition, the percentage of patients who lost ≥10% of their weight was similar in these two groups. Changes in albumin and prealbumin levels during radiotherapy in the non-PEG group were higher than those obtained for the PEG group with significant differences (P-values of 0.023 and <0.001, respectively). Furthermore, patients in the PEG group had significantly lower incidence of grade III acute mucositis than those in the non-PEG group (22.56% vs 36.84%, P=0.011). Tube-related complications occurred only in 14 (10.53%) patients in the PEG group, including incision infection of various degrees. Conclusion PEG and intensive nutrition support may help to minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced NPC who

  10. Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma.

    PubMed

    Gu, Mo-Fa; Liu, Li-Zhi; He, Long-Jun; Yuan, Wen-Xin; Zhang, Rong; Luo, Guang-Yu; Xu, Guo-Liang; Zhang, Hua-Man; Yan, Chao-Xian; Li, Jian-Jun

    2013-01-01

    We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.

  11. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma: A Case Report and Literature Review.

    PubMed

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-05-01

    Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches.A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy.The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery.Patients with advanced stage tumors of the

  12. Prevention of Hepatitis B Virus Reactivation With Lamivudine in a Patient With Advanced Renal Cell Carcinoma Treated With Everolimus.

    PubMed

    D'Aniello, Carmine; Maruzzo, Marco; Basso, Umberto

    2016-01-01

    Anticancer agents may trigger reactivation of hepatitis B virus infection ensuing in asymptomatic to severe liver damage. Preemptive administration of antiviral agents such as lamivudine to patients receiving cytotoxic chemotherapy has been shown to inhibit viral replication and prevent such events. No data are available so far concerning the coadministration of antiviral agents and everolimus, an oral mammalian target of rapamycin inhibitor recently approved for the treatment of advanced renal cell carcinoma. We present in this study the first case to our knowledge of a hepatitis B surface antigen-positive patient with metastatic renal cell carcinoma who has been successfully treated with prophylactic lamivudine and everolimus. Long-term depletion of viral replication was obtained along with stabilization of lung and bone metastases. Hepatitis B surface antigen positivity may be found in up to 10% of cancer patients but should not be considered a contraindication to treatment with everolimus.

  13. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2017-03-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  14. Intracranial germinoma in the pineal region arising after subtotal resection of epidermoid cyst: case report.

    PubMed

    Walker, Amanda J; Huynh-Le, Minh-Phuong; Nauen, David; Malayeri, Ashkan A; Jallo, George; Terezakis, Stephanie A

    2014-05-01

    We present an unusual case of a germinoma of the pineal region arising adjacent to an epidermoid cyst in a 16-year-old male. Initial imaging findings were classic for epidermoid cyst. The patient underwent two partial resections at an outside institution, each specimen demonstrating pure epidermoid cyst. Follow-up imaging over a period of 24 months showed an area of progressive contrast enhancement adjacent to the initial lesion, suggesting the development of a neoplasm. Given the area of contrast enhancement in addition to worsening headaches and visual changes, he underwent a third and final resection at our institution. Pathology revealed a mixed germ cell tumor with prominent germinoma component in addition to a well-differentiated epidermoid cyst. Details of his imaging and pathologic findings are presented, and possible explanations for these findings are explored, the most likely of which is lack of complete resection at the onset failed to identify the whole of the neoplasm. We conclude that pediatric epidermoid cysts of the pineal region should always receive close follow-up, particularly when total resection is not performed.

  15. Acquired Encephalocele With Hydrocephalus and Pineal Region Epidermoid Cyst.

    PubMed

    Toktaş, Zafer Orkun; Yilmaz, Baran; Ekşi, Murat Şakir; Bayoumi, Ahmed B; Akakin, Akin; Yener, Yasin; Demir, Mustafa Kemal; Kiliç, Türker

    2016-07-01

    A combination of trauma and a missed inflammatory response (nasal operation) concomitant with hydrocephalus and tumor in secondary encephalocele has not been described in the English literature yet. A 38-year-old man was admitted to the clinic with rhinorrhea that started 3 months ago. In his medical history, nothing abnormal was present except a nasal operation performed 1 year ago. Brain magnetic resonance imaging depicted left frontal encephalocele concomitant with obstructive hydrocephalus caused by an epidermoid cyst originated from the pineal region. A 2-staged surgery was planned. In the first stage, a ventriculoperitoneal shunt insertion was conveyed successfully. In the second-stage surgery, the herniated brain tissue was excised, and the frontal sinus was cleansed with serum saline combined with antibiotic. The bony defect and the dura defect were repaired. The patient's presenting complaint recovered fully, and he was discharged to home in a well condition. Acquired encephalocele is a rare entity. In case of rhinorrhea and encephalocele, even in the presence of prior history of nasal surgery, intracranial evaluation should be conveyed to exclude the presence of hydrocephalus and/or tumor. The cranial defect should be repaired to prevent future infections and brain tissue damage.

  16. Treatment of epidermoid tumors with gamma knife radiosurgery: Case series

    PubMed Central

    Vasquez, Javier A. Jacobo; Fonnegra, Julio R.; Diez, Juan C.; Fonnegra, Andres

    2016-01-01

    Background: Epidermoid tumors (ETs) are benign lesions that are treated mainly by means of surgical resection, with overall good results. External beam radiotherapy is an alternative treatment for those recurrent tumors, in which a second surgery might not be the best choice for the patient. A little information exists about the effectiveness of gamma knife radiosurgery for the treatment of newly diagnosed and recurrent ETs. We present three cases of ETs treated with gamma knife radiosurgery. Case Description: Case 1 is a 21-year-old female with an ET located in the left cerebellopontine angle (CPA) with symptoms related to VIII cranial nerve dysfunction. Symptom control was achieved and maintained after single session radiosurgery with gamma knife. Case 2 is a 59-year-old female patient with the history of trigeminal neuralgia secondary to a recurrent ET located in the left CPA. Significant pain improvement was achieved after treatment with gamma knife radiosurgery. Case 3 is a 29-year-old male patient with a CPA ET causing long lasting trigeminal neuralgia, pain relief was achieved in this patient after gamma knife radiosurgery. Conclusion: Long-term symptom relief was achieved in all three cases proving that gamma knife radiosurgery is a good and safe alternative for patients with recurrent or nonsurgically treated ETs. PMID:26958427

  17. A case of polypoid and papillary cystitis mimicking an advanced bladder carcinoma with invasion of perivesical fat.

    PubMed

    Ozaki, Kumi; Kitagawa, Kiyohide; Gabata, Toshifumi; Matsui, Osamu

    2014-01-01

    A rare case of polypoid and papillary cystitis without a history of catheterization is reported. A 69-year-old man was admitted to our hospital because of pain during urination and gross hematuria. The cystscopic and imaging findings including ultrasound, CT, and MR image showed an irregular wall thickening and stranding in the perivesical fat, which indicated an advanced bladder carcinoma, but histopathological findings obtained by transurethral resection revealed polypoid and papillary cystitis. Such benign lesions need to be discussed in the differential diagnosis of patients with bladder tumor to avoid excessive resection.

  18. A case of polypoid and papillary cystitis mimicking an advanced bladder carcinoma with invasion of perivesical fat

    PubMed Central

    Ozaki, Kumi; Kitagawa, Kiyohide; Gabata, Toshifumi; Matsui, Osamu

    2014-01-01

    A rare case of polypoid and papillary cystitis without a history of catheterization is reported. A 69-year-old man was admitted to our hospital because of pain during urination and gross hematuria. The cystscopic and imaging findings including ultrasound, CT, and MR image showed an irregular wall thickening and stranding in the perivesical fat, which indicated an advanced bladder carcinoma, but histopathological findings obtained by transurethral resection revealed polypoid and papillary cystitis. Such benign lesions need to be discussed in the differential diagnosis of patients with bladder tumor to avoid excessive resection. PMID:24669128

  19. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy.

    PubMed

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-09-05

    Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children.

  20. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy

    PubMed Central

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-01-01

    Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children. PMID:27746885

  1. Congenital Epidermoid Cyst of the Oral Cavity: Prenatal Diagnosis by Sonography

    PubMed Central

    Park, Seung Wan; Chae, Soo Ahn; Yoo, Byoung Hoon; Kim, Gwang Jun; Lee, Sei Young

    2013-01-01

    Epidermoid cysts are benign developmental anomalies that are rarely observed in the oral cavity of neonate. If large in size, especially in the developing fetus or newborn infant, they can cause swallowing difficulty and occasionally respiratory difficulty. We report a case of epidermoid cyst in the oral cavity detected prenatal sonography. The sonographic finding was large cystic mass, measuring 30×25 mm. In this case, supplies and equipment for an emergency tracheostomy were made available prior to the delivery. However, the infant did not require intervention to secure the airway. The lesion was surgically excised, and histologic diagnosis was epidermoid cyst. After 6 months of follow up, the cyst had not recurred. This case illustrates the value of accurate prenatal diagnosis and planned perinatal management using a team approach. PMID:24069525

  2. Unusual site and uncommon presentation of epidermoid cyst: a rare case report and review of literature

    PubMed Central

    Sahoo, Manash Ranjan; Gowda, Manoj S; Behera, Syam Sundar

    2013-01-01

    Epidermoid cyst of gastrointestinal tract is very rare, and only a few cases of epidermoid cyst of the caecum have been reported in the literature. We report the first case of epidermoid cyst of the caecum in an elderly man, mimicking mesenteric cyst clinically. It was treated by laparoscopic excision of the cyst. The cyst was spherical, extending from and expanding the serosal surface of the caecum with no communication through the muscularis wall. Histologically, the inner lining of the cyst was composed of benign, mature, keratinised and stratified squamous epithelium with a well-formed granular layer. On opening, the cyst contained pultaceous cheesy material. No calcification, hair, teeth or bone elements were detected. PMID:23302551

  3. Maintenance Peginterferon Therapy and Other Factors Associated with Hepatocellular Carcinoma in Patients with Advanced Hepatitis C

    PubMed Central

    Lok, Anna S.; Everhart, James E.; Wright, Elizabeth C.; Di Bisceglie, Adrian M.; Kim, Hae-Young; Sterling, Richard K.; Everson, Gregory T.; Lindsay, Karen L.; Lee, William M.; Bonkovsky, Herbert L.; Dienstag, Jules L.; Ghany, Marc G.; Morishima, Chihiro; Morgan, Timothy R.

    2010-01-01

    Background & Aims Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C anti-viral long-term treatment against cirrhosis (HALT-C) trial showed that 4 years of maintenance therapy with peginterferon does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer post-treatment follow-up period. Methods The study included 1,048 patients with chronic Hepatitis C (Ishak fibrosis scores ≥3) who did not have a sustained virological response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed for a median 6.1 (maximum 8.7) years. Results Eighty-eight patients developed HCC (68 definite, 20 presumed): 37/515 that were given peginterferon (7.2%) and 51/533 controls (9.6%; P=0.24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR]=0.45; 95% confidence interval [CI]: 0.24–0.83); in treated and control patients with fibrosis they were 8.3% and 6.8%, respectively (HR=1.44; 95% CI: 0.77–2.69). Treated patients with a ≥2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs. 9.4%; P=0.03). Conclusions Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk for HCC than controls. PMID:21129375

  4. Successful Treatment of Advanced Primary Cutaneous Apocrine Carcinoma on the Scrotum with Systemic Chemotherapy and Radiotherapy Followed by Denosumab

    PubMed Central

    Furudate, Sadanori; Fujimura, Taku; Tsukada, Akira; Sato, Yota; Hidaka, Takanori; Tanita, Kayo; Kambayashi, Yumi; Haga, Takahiro; Hashimoto, Akira; Aiba, Setsuya

    2017-01-01

    Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive cutaneous adnexal type of tumor that has a high metastasis rate and a poor prognosis. Although there are several case reports describing the successful treatment of PCAC with chemoradiotherapy or molecular targeting therapy, no standard therapy for the treatment of advanced PCAC has been established yet. Since receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed in cancers of apocrine origin, leading to immunosuppression at the tumor site, we hypothesized that targeting RANKL with denosumab might be useful for the treatment of PCAC. In this report, we describe a case with advanced PCAC on the scrotum successfully treated with systemic chemotherapy using carboplatin and paclitaxel, and radiotherapy followed by denosumab. PMID:28203164

  5. Alternative treatments in advanced hepatocellular carcinoma patients with progressive disease after sorafenib treatment: a prospective multicenter cohort study

    PubMed Central

    Nakano, Masahito; Tanaka, Masatoshi; Kuromatsu, Ryoko; Nagamatsu, Hiroaki; Satani, Manabu; Niizeki, Takashi; Okamura, Shusuke; Iwamoto, Hideki; Shimose, Shigeo; Shirono, Tomotake; Noda, Yu; Koga, Hironori; Torimura, Takuji

    2016-01-01

    Sorafenib is an oral multikinase inhibitor that has been approved to treat advanced hepatocellular carcinoma (HCC), though it is unclear how much benefit advanced HCC patients with progressive disease (PD) derive from sorafenib treatment. This study aimed to assess survival risk factors and evaluate therapeutic strategies for advanced HCC patients with PD after sorafenib treatment. We analyzed the clinical data and treatment outcomes for 315 consecutive advanced HCC patients treated with sorafenib. Univariate analyses of overall survival identified therapeutic effect as an independent risk factor in all patients. Among all patients, 141 developed PD. Of those, 58 (41%) were treated with sorafenib monotherapy, 70 (50%) with agents other than sorafenib, and 13 (9%) were not treated at all. The median survival time was 6.1 months for PD patients with sorafenib monotherapy and 12.2 months for those administered alternative treatments (p < 0.0001). Our results indicated that sorafenib treatment may have negative long-term therapeutic effects in advanced HCC patients with PD, and that alternative treatments should be considered for these patients after sorafenib administration. PMID:27462865

  6. Radical irradiation and misonidazole in the treatment of advanced cervical carcinoma: results of a phase II trial

    SciTech Connect

    Girinski, T.; Pejovic, M.H.; Haie, C.; Bonnay, M.; Gerbaulet, A.; Mazeron, J.J.; Malaise, E.; Chassagne, D.

    1985-10-01

    Between February 1979 and January 1982, a Phase II study of misonidazole as a radiosensitizer was performed in 34 patients with advanced carcinoma of the uterine cervix. Twenty-nine patients were treated with conventional fractionated radiation and five patients with a twice daily fractionation schedule, 3 days a week. The total dose to the whole pelvis was 5000 cGy delivered in 5.5 weeks. Intracavitary curietherapy delivered an additional boost to the tumor. Misonidazole was given to all patients during external radiation and to 25 patients during intracavitary treatment for a total dose of 11 to 14 g/mS. All patients were followed for at least 28 months after treatment with a median follow-up of 52 months. Misonidazole toxicity included peripheral neuropathy (18%) and central nervous system toxicity (3%). The 3-year survival rate is 74% and the 3-year disease-free survival is 57%. When compared to our historical group survival, 42 and 12% for Stage III and IV, respectively, our data suggest that there is a probable advantage from using misonidazole in advanced carcinoma of the cervix.

  7. The influence of genetic variants of sorafenib on clinical outcomes and toxic effects in patients with advanced renal cell carcinoma

    PubMed Central

    Qin, Chao; Cao, Qiang; Li, Pu; Wang, Shangqian; Wang, Jian; Wang, Meilin; Chu, Haiyan; Zhou, Liqun; Li, Xuesong; Ye, Dingwei; Zhang, Hailiang; Huang, Yiran; Dong, Baijun; Sun, Xiaofeng; Zou, Qing; Cai, Hongzhou; Sun, Lijiang; Zhu, Jian; Liu, Fade; Ji, Junbiao; Cui, Li; Wang, Xiaoxiang; Zhou, Hai; Zhao, Hu; Wu, Bin; Chen, Jianchun; Jiang, Minjun; Zhang, Zhengdong; Shao, Pengfei; Ju, Xiaobing; Yin, Changjun

    2016-01-01

    The purpose of the present study was to investigate whether genetic variants that influence angiogenesis and sorafenib pharmacokinetics are associated with clinical outcomes and toxic effects in advanced renal cell carcinoma patients treated with this drug. One hundred patients with advanced renal cell carcinoma were enrolled. Forty-two polymorphisms in 15 genes were selected for genotyping and analyzed for associations with progression-free survival, overall survival, and toxic effects. We found that rs1570360 in VEGF and rs2239702 in VEGFR2 were significantly associated with progression-free. Specifically, patients carrying the variant genotypes (AG + AA) of these two polymorphisms both had an unfavorable progression-free. In addition, compared with those with the rs2239702 GG genotype, patients with the AG + AA genotype suffered an unfavorable OS. We found that the VEGF rs2010963 CG + GG genotypes had a significantly increased risk of hand-foot syndrome, and the ABCB1 rs1045642 CT + TT genotypes had an increased risk of high blood pressure. Our results suggest that polymorphisms in VEGF and VEGFR2 are associated with sorafenib clinical outcomes, and polymorphisms in VEGF and ABCB1 are associated with sorafenib-related toxicities. Larger studies are warranted to validate our findings. PMID:26830973

  8. The predictive value of MRI in detecting thyroid gland invasion in patients with advanced laryngeal or hypopharyngeal carcinoma.

    PubMed

    Lin, Peiliang; Huang, Xiaoming; Zheng, Chushan; Cai, Qian; Guan, Zhong; Liang, Faya; Zheng, Yiqing

    2017-01-01

    The aim of this study was to evaluate the predictive value of magnetic resonance imaging (MRI) in detecting thyroid gland invasion (TGI) in patients with advanced laryngeal or hypopharyngeal carcinoma. In a retrospective chart review, 41 patients with advanced laryngeal or hypopharyngeal carcinoma underwent MRI scan before total laryngectomy and ipsilateral or bilateral thyroidectomy during the past 5 years. The MRI findings were compared with the postoperative pathological results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Among the 41 patients, 3 had thyroid gland invasion in postoperative pathological results. MRI correctly predicted the absence of TGI in 37 of 38 patients and TGI in all 3 patients. The sensitivity, specificity, PPV, and NPV of MRI were 100.0, 97.4, 75.0, and 100 %, respectively, with the diagnostic accuracy of 97.6 %. In consideration of the high negative predictive value of MRI, it may help surgeons selectively preserve thyroid gland in total laryngectomy and reduce the incidence of hypothyroidism and hypoparathyroidism postoperatively.

  9. The association of nutritional assessment criteria with health-related quality of life in patients with advanced colorectal carcinoma.

    PubMed

    Thoresen, L; Frykholm, G; Lydersen, S; Ulveland, H; Baracos, V; Birdsell, L; Falkmer, U

    2012-07-01

    Health-related quality of life (QoL) is a goal in nutritional oncology but the association between nutritional status and QoL is rarely explored. The aim of the study was to investigate the association of nutritional assessment criteria with QoL in 50 patients with advanced colorectal carcinoma. A second aim was to investigate changes in body weight and QoL during a 3-month follow-up. Muscle mass, nutritional risk, malnutrition and cachexia according to three different criteria were assessed, as well as health-related QoL. At inclusion, 36 patients experienced weight loss, 10 patients sarcopenia, 25 were at nutritional risk, 16 were malnourished and 11, 14 and 31 patients had cachexia according to different criteria. All nutritional assessment criteria discriminated between groups of patients with worse or better QoL to varying degrees. Malnutrition and cachexia defined by the European Palliative Care Research Collaborative and adjusted for recent gain or stabilisation of body weight discriminated on most QoL scores. Weight loss at follow-up was associated with a decrease in several QoL scores. Recognition of weight loss as well as diagnosing malnutrition and cachexia should be the first steps in an interventional pathway to enhance nutritional status and QoL in patients with advanced colorectal carcinoma.

  10. Treatment Outcomes of Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy

    PubMed Central

    Chen, Yen-Hao; Lu, Hung-I.; Chien, Chih-Yen; Lo, Chien-Ming; Wang, Yu-Ming; Chou, Shang-Yu; Su, Yan-Ye; Shih, Li-Hsueh; Li, Shau-Hsuan

    2017-01-01

    The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3–4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3–4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival. PMID:28134308

  11. [Pre- and postoperative radiotherapy of oral carcinoma of a locally advanced stage. An analysis of the results and complications].

    PubMed

    Zini, G; Barbieri, E; Campobassi, A; Dallera, P; Emiliani, E; Frezza, G; Marchetti, C; Neri, S; Romagnoli, D; Silvano, M

    1989-01-01

    The combination of radiotherapy and surgery in the treatment of advanced oral carcinoma (T3 and T4 lesions) yields good possibilities of recovery; whether radiotherapy should be given before or after surgery is still debated. Fifty patients with advanced oral carcinomas were analyzed: 24 of them were irradiated before and 26 after surgery; doses ranged from 40 to 56 Gy for the first group of patients, and from 50 to 68 Gy for the second one. The disease-free survival 48 months after the diagnosis was 36% in patients who received preoperative irradiation, and 53.6% in patients who received postoperative radiotherapy; the latter allowed local control of the disease to be significantly improved (chi 2 3.99, 0.01 less than p less than 0.05). The quality of survival was worse in the group receiving preoperative irradiation, because of radiation-induced surgical complications, which were especially observed in patients with diffuse disease. Our findings suggest that postoperative radiotherapy may be advisable if the tumor is resectable, since tolerance and local control rate were acceptable. On the contrary, nearly inoperable masses and massive neck diseases often require preoperative irradiation.

  12. Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update.

    PubMed

    Chen, Leon; Silapunt, Sirunya; Migden, Michael R

    2016-09-01

    The Hedgehog inhibitors are promising alternative for patients with advanced basal cell carcinoma that are not amenable to radiotherapy or surgery. Sonidegib, also known as LDE225, is an orally available SMO antagonist that was recently approved by the US FDA for the treatment of patients with locally advanced basal cell carcinoma. This article will provide an overview of the pharmacology and pharmacokinetics of sonidegib and in-depth analysis of the BOLT trial with additional data from the 12-month update. The present challenges associated with Hedgehog inhibitors will also be discussed.

  13. Case report of complicated epidermoid cyst of the floor of the mouth: Radiology-histopathology correlation

    PubMed Central

    Mirza, Salman; Fadl, Shaima; Napaki, Sarbar; Abualruz, AbdulRahman

    2014-01-01

    Epidermoid cysts, true dermoid cysts and teratoid cysts compose the spectrum of cystic teratomas, which are defined as neoplasms whose tissue are derivatives of more than one germ layer, foreign to that part of the body from which the tumor arises. Epidermoid cysts of the floor of the mouth are rare lesions and are much less common than dermoid cysts in the head and neck. This case reports a 43-year-old male patient who presented with a longstanding midline swelling in the submental region. Initial imaging was done using ultrasound followed by computed tomography (CT) scan. Biopsy was taken and revealed a cyst wall lined with epidermal squamous epithelium along with areas of focal ulceration suggesting chronic inflammatory changes of the wall of the epidermoid cyst. There are characteristic and even pathognomonic imaging features of epidermoid cysts at the floor of the mouth in ultrasound and CT scan. Imaging has an important role in the surgical management plan according to the size and location of the cyst in relation to geniohyoid and mylohyoid muscles. PMID:25320687

  14. A case of epidermoid median raphe cyst traversing the corpora cavernosa

    PubMed Central

    Yu, Alice; Capolicchio, John-Paul

    2017-01-01

    Median raphe cysts are congenital lesions that typically have a superficial appearance. We present a very unusual case of a deep perineal mass in a six-year-old boy. The lesion extends into the corpus cavernosum, suggesting that the anomaly was an early embryological event. Histopathological features are consistent with an epidermoid type of median raphe cyst. PMID:28360959

  15. FDA Approval Summary: Nivolumab in Advanced Renal Cell Carcinoma After Anti-Angiogenic Therapy and Exploratory Predictive Biomarker Analysis.

    PubMed

    Xu, James Xunhai; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Pazdur, Richard

    2017-03-01

    On November 23, 2015, the U.S. Food and Drug Administration approved nivolumab (OPDIVO, Bristol-Myers Squibb Company) for patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. The approval was based on efficacy and safety data demonstrated in an open-label, randomized study of 821 patients with advanced RCC who progressed after at least one anti-angiogenic therapy. Patients were randomized to nivolumab or everolimus and followed for disease progression. The primary end point was overall survival. Subsequent therapies, including everolimus for patients who developed progressive disease on the nivolumab arm, were allowed, but no cross-over was permitted. The median overall survival was 25.0 months on the nivolumab arm and 19.6 months on everolimus arm (hazard ratio: 0.73; 95% confidence interval: 0.60-0.89). The confirmed response rates were 21.5% versus 3.9%; median durations of response were 23.0 versus 13.7 months, and median times to response were 3.0 versus 3.7 months in the nivolumab and everolimus arms, respectively. A statistically significant improvement in progression-free survival was not observed in this trial. The safety profile of nivolumab in renal cell cancer was similar to that in other disease settings. However, the incidence of immune-mediated nephritis appeared to be higher in patients with RCC. The Oncologist 2017;22:311-317 IMPLICATIONS FOR PRACTICE: The overall benefit/risk profile demonstrated in trial CA209025 supported the approval of nivolumab as an additional treatment option for patients with advanced renal cell carcinoma after anti-angiogenic therapy. The use of nivolumab in patients who had received vascular endothelial growth factor-targeted therapy resulted in a 5.4 month improvement in median overall survival compared with the everolimus arm. This difference is statistically significant and clinically meaningful.

  16. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  17. [Moderately differentiated squamous cell carcinoma associated pilonidal cyst].

    PubMed

    Cruz-Mendoza, Irma; Hernández-Jesús, Bernal; López-Pérez, Eva; Flores-Cobos, Ada Elisa; García-Rodríguez, Francisco

    2014-01-01

    Antecedentes: la degeneración maligna es una complicación rara, observada principalmente en enfermedad pilonidal crónica recurrente y se asocia con muy mal pronóstico. En la bibliografía mundial se encuentra como una entidad poco frecuente. En España se revisaron 367 pacientes afectados de quiste pilonidal, simple o complicado. Entre ellos se encontraron tres casos (0.81%) de carcinoma epidermoide con quiste pilonidal. Caso clínico: paciente masculino de 60 años de edad, con cuadro clínico de 50 años de evolución de un tumor sacro. Luego de la exéresis el reporte histopatológico fue de quiste pilonidal; la evolución fue tórpida en la cicatrización, con bordes necróticos que se resecaron y el reporte fue: carcinoma epidermoide. Conclusión: el carcinoma epidermoide de sinus pilonidal es una enfermedad infrecuente asociada con muy mal pronóstico.

  18. NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy

    PubMed Central

    Hudes, Gary R.; Carducci, Michael A.; Choueiri, Toni K.; Esper, Peg; Jonasch, Eric; Kumar, Rashmi; Margolin, Kim A.; Michaelson, M. Dror; Motzer, Robert J.; Pili, Roberto; Roethke, Susan; Srinivas, Sandy

    2015-01-01

    The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion. PMID:21335444

  19. Improved local control for advanced oropharyngeal carcinoma following twice daily radiation therapy

    SciTech Connect

    Wang, C.C.

    1985-12-01

    This paper presents the results of treatment on 99 patients with squamous cell carcinoma of the oropharynx irradiated by the twice-a-day radiation therapy program at the Massachusetts General Hospital. The program consisted of 1.6 Gy per fraction, two fractions per day with 4 hours between fractions, for 12 days, 5 days a week. After 38.4 Gy, the patients were given a 2 week break and then resumed twice-a-day radiation therapy for a total of 64 Gy and occasionally 67.2 Gy. Fifty-two patients had carcinoma of the faucial tonsil and 47 patients had carcinoma of the base of the tongue. For the entire group of patients, the 36 month actuarial local control rate was 58%, and for the T1-2 and T3-4 lesions, the rates were 77% and 48% respectively. In comparison with patients treated by once-a-day radiation therapy for a few years immediately prior to the twice-a-day program, the local control rates were improved to a statistically significant level. Likewise, the results as compared to those published in the literature were no worse and perhaps superior to those of patients treated by the once-a-day schedule.

  20. Hepatocellular carcinoma.

    PubMed

    Macdonald, G A

    1999-05-01

    Hepatitis C infection is associated with the development of hepatocellular carcinoma, and progress has been made in a number of areas. Transgenic mice lines expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and hepatocellular carcinomas, with no significant hepatitis or fibrosis. This implies that hepatitis C can lead directly to malignant transformation. A new lesion, irregular regeneration, has been described in chronic hepatitis C infection and is associated with a 15-fold increase in the relative risk of developing hepatocellular carcinoma. A minority of patients with hepatitis C-related hepatocellular carcinoma have intense lymphocytic infiltration of the cancer, a feature associated with a better prognosis. Several studies have confirmed the association between large cell dysplasia and hepatocellular carcinoma. However, large cell dysplasia may not be a premalignant lesion and instead may be a marker for premalignant alterations elsewhere in the liver. Oral contraceptives previously have been linked to an increased risk of hepatocellular carcinoma. A large multicenter European case-control study has shown minimal increased risk of hepatocellular carcinoma with use of steroidal contraception. Tamoxifen had shown promise in the management of advanced hepatocellular carcinoma. However, a randomized placebo-controlled study of 477 patients with hepatocellular carcinoma found no benefit from tamoxifen. In a preliminary study, however, octreotide has shown improved survival and quality of life in patients with advanced hepatocellular carcinoma. Finally, interferon treatment continues to be linked to a reduced risk of hepatocellular carcinoma in patients with hepatitis C. These studies generally are not randomized, and a randomized prospective study is required to address this issue.

  1. Treatment Modalities and Outcomes in Patients with Advanced Invasive Thymoma or Thymic Carcinoma: A Retrospective Multicenter Study

    PubMed Central

    Modh, Ankit; Rimner, Andreas; Allen, Pamela K.; Greenfield, Brad; Marom, Edith M.; Rice, David; Huang, James; Rosenzweig, Kenneth E.; Komaki, Ritsuko; Gomez, Daniel R.

    2016-01-01

    Introduction We investigated relationships between treatment characteristics and long-term outcomes in patients with locally advanced thymoma or thymic carcinoma. Methods We retrospectively reviewed 146 patients treated in 1980–2011 at two tertiary cancer care centers, 110 with Masaoka-Koga stage III–IVa invasive thymoma and 36 with stage I–IVa thymic carcinoma. Survival probabilities were estimated with the Kaplan-Meier method. Risk factors related to survival were identified by univariate and multivariate competing risk analysis, with overall survival (OS) as the competing risk. Cox regression analysis was used to identify risk factors for OS. Results Median follow-up time for all patients was 64 months. At 5/10 years, rates of OS and freedom from recurrence (FFR) were 81/58% and 81/65%, respectively. Of patients who underwent surgery, trimodality treatment produced better survival compared to less aggressive treatment among patients with stage III disease (p=0.03). Among patients who underwent trimodality treatment, patients with stage III disease had better OS (p=0.03) and FFR (p<0.001) than those with stage IVA disease. On Cox regression analysis, decreased OS was associated with thymic carcinoma (hazard ratio [HR]=7.36, 95% CI=2.38–22.77, p=0.001), R2/unresectable disease (HR=8.45, 95% CI=1.44–49.42, p=0.02) and an Eastern Cooperative Oncology Group performance score of 1 (HR=8.14, 95% CI=1.55–42.75, p=0.01) or 2–3 (HR=29.60, 95% CI=4.0–218.98, p=0.001) versus 0. Conclusion Aggressive treatment with chemotherapy, surgical resection, and postoperative radiation therapy can produce long-term survival for patients with invasive thymic malignanices. PMID:24390276

  2. Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment

    PubMed Central

    Nakanishi, Hiroyuki; Kurosaki, Masayuki; Tsuchiya, Kaoru; Yasui, Yutaka; Higuchi, Mayu; Yoshida, Tsubasa; Komiyama, Yasuyuki; Takaura, Kenta; Hayashi, Tsuguru; Kuwabara, Konomi; Nakakuki, Natsuko; Takada, Hitomi; Ueda, Masako; Tamaki, Nobuharu; Suzuki, Shoko; Itakura, Jun; Takahashi, Yuka; Izumi, Namiki

    2016-01-01

    Objectives This study aimed to build a prediction score of prognosis for patients with advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods A total of 165 patients with advanced HCC who were treated with sorafenib were analyzed. Readily available baseline factors were used to establish a scoring system for the prediction of survival. Results The median survival time (MST) was 14.2 months. The independent prognostic factors were C-reactive protein (CRP) <1.0 mg/dL [hazard ratio (HR) =0.51], albumin >3.5 g/dL (HR =0.55), alpha-fetoprotein <200 ng/mL (HR =0.45), and a lack of major vascular invasion (HR =0.39). Each of these factors had a score of 1, and after classifying the patients into five groups, the total scores ranged from 0 to 4. Higher scores were linked to significantly longer survival (p<0.0001). Twenty-nine patients (17.6%) with a score of 4 had a MST as long as 36.5 months, whereas MST was as short as 2.4 and 3.7 months for seven (4.2%) and 22 (13.3%) patients with scores of 0 and 1, respectively. Conclusions A novel prognostic scoring system, which includes the CRP level, has the ability to stratify the prognosis of patients with advanced stage HCC after treatment with sorafenib. PMID:27781198

  3. Phase II clinical trial of cisplatin, 5-fluorouracil, and ifosfamide as treatment for advanced locoregional head and neck carcinoma.

    PubMed

    Sánchez Parra, M; Churruca, C; Paredes, A; Lacasta, A; López de Argumedo, G; Alvárez, I; Abad, T; Egana, L; Guimón, E; Piera, J M

    1999-02-01

    The association of ifosfamide with cisplatin and 5-fluorouracil for the management of advanced squamous cell carcinoma of the head and neck was assessed in this trial. Ifosfamide was given initially to 12 patients in combination with standard fixed doses of cisplatin and 5-fluorouracil, at 1,000 mg/m2 daily on days 2, 3, and 4. Two patients died of neutropenia and severe infection, and the authors recruited seven more patients who were treated with a lower dose of ifosfamide, 800 mg/m2 daily on days 2, 3, and 4. One of the seven patients died of neutropenia and severe infection. Three complete remission were observed in 18 patients evaluable for efficacy. The study was closed early because of the severe toxicity profile demonstrated by this scheme and because of no clear advantage in efficacy versus cisplatin plus 5-fluorouracil combinations.

  4. Hsp90 Inhibitor AT13387 in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2017-01-31

    Human Papillomavirus Infection; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  5. Impact of Adding Concomitant Chemotherapy to Hyperfractionated Accelerated Radiotherapy for Advanced Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Nuyts, Sandra Dirix, Piet; Clement, Paul M.J.; Poorten, Vincent Vander; Delaere, Pierre; Schoenaers, Joseph; Hermans, Robert; Bogaert, Walter van den

    2009-03-15

    Purpose: To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m{sup 2}) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 73) treated with the same schedule, but without concomitant Cx, between 2001 and 2004. Results: The locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2-year disease-free survival rates were 74% and 60%, respectively. In comparison with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall survival (p = 0.09) was observed. All patients were treated to full radiation dose according to protocol, although the Cx schedule had to be adjusted in 12 patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3 acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p < 0.001) were significantly higher in the chemoradiotherapy group compared with patients treated with RT alone. Conclusion: With this chemoradiotherapy regimen, excellent LRC and survival rates were achieved, with acceptable acute toxicity.

  6. Evaluation of the Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy for the Treatment of Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, O. Kusunoki, S.; Kudoh, K.; Takamori, H.; Tsuji, T.; Kanemitsu, K.; Yamashita, Y.

    2006-06-15

    Purpose. To evaluate the effects of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in patients with advanced pancreatic carcinoma. Methods. CTAI was performed in 17 patients with stage IV pancreatic cancer with (n = 11) or without (n = 6) liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The inferior pancreatic artery (IPA) was embolized to achieve delivery of the pancreatic blood supply through only the celiac artery. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. Treatment effects were evaluated based on the primary tumor size, liver metastasis, and survival time and factors such as tumor size, tumor location, and stage of pancreatic carcinoma; the embolized arteries were analyzed with respect to treatment effects and prognosis. Results. A catheter was fixed in the gastroduodenal artery and splenic artery in 10 and 7 patients, respectively. Complete peripancreatic arterial occlusion was successful in 10 patients. CT showed a decrease in tumor size in 6 of 17 (35%) patients and a decrease in liver metastases in 6 of 11 (55%) patients. The survival time ranged from 4 to 18 months (mean {+-} SD, 8.8 {+-} 1.5 months). Complete embolization of arteries surrounding the pancreas was achieved in 10 patients; they manifested superior treatment effects and prognoses (p < 0.05). Conclusion. In patients with advanced pancreatic cancer, long-term CTAI with systemic chemotherapy appeared to be effective not only against the primary tumor but also against liver metastases. Patients with successfully occluded peripancreatic arteries tended to survive longer.

  7. Esophageal squamous cell carcinoma (ESCC): advance in genomics and molecular genetics.

    PubMed

    Chen, J; Kwong, D L; Cao, T; Hu, Q; Zhang, L; Ming, X; Chen, J; Fu, L; Guan, X

    2015-01-01

    Esophageal cancer is aggressive and has poor prognosis. Esophageal squamous cell carcinoma (ESCC) is histologically the most prevalent type of esophageal cancer and ranked as the sixth leading cause of cancer death worldwide. In recent years, cancer has been widely regarded as genetic disease, as well as epigenetic abnormalities including DNA methylation, histone deacetylation, chromatin remodeling, gene imprinting and noncoding RNA regulation. In this review, we will provide a general overview of genes, proteins and microRNAs that are involved in the development of ESCC, which aims to enhance our understanding of molecular mechanisms implicated in ESCC development and progression.

  8. Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: a prospective randomized trial of the International Atomic Energy Agency

    PubMed Central

    2014-01-01

    Abstact Background The purpose was to determine whether a brachytherapy boost improves outcomes in patients with advanced nasopharyngeal carcinoma treated with standard chemo-radiotherapy. Methods Patients with nasopharyngeal carcinoma WHO grades I-III and TNM stages III or non-metastatic stage IV were eligible for this phase III study. Patients were randomized to either arm (A) induction chemotherapy, followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n = 139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in arm (B) was given by either low dose-rate (LDR – 11 Gy) or high dose-rate (HDR – 3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall survival (OS) and secondary endpoints were: local control, regional control, distant metastasis and grade 3–4 adverse events. Results 274 patients were randomized between September 2004 and December 2008. The two arms were comparable with regard to age, gender, stage and grade. 273 patients completed treatment. Median follow-up was 29 months (0.2-67 months). The effect of treatment arm, country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and chemotherapy on overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p = 0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None of the other factors studied were significant. The 3-year LRFS was 60.5% and 54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in Arm B (67

  9. Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma

    PubMed Central

    Dréno, Brigitte; Ascierto, Paolo Antonio; Dummer, Reinhard; Basset-Seguin, Nicole; Fife, Kate; Ernst, Scott; Licitra, Lisa; Neves, Rogerio I.; Peris, Ketty; Puig, Susana; Sokolof, Jonas; Sekulic, Aleksandar; Hauschild, Axel; Kunstfeld, Rainer

    2016-01-01

    Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1–2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy. Implications for Practice: The hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life

  10. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma

    SciTech Connect

    Sangro, Bruno . E-mail: bsangro@unav.es; Bilbao, Jose I.; Boan, Jose; Martinez-Cuesta, Antonio; Benito, Alberto; Rodriguez, Javier; Panizo, Angel; Gil, Belen; Inarrairaegui, Mercedes; Herrero, Ignacio; Quiroga, Jorge; Prieto, Jesus

    2006-11-01

    Purpose: To investigate the antitumor effect of resin microspheres loaded with 90-yttrium against hepatocellular carcinoma and their safety in the setting of liver cirrhosis. Patients and Methods: Data from 24 consecutive patients with hepatocellular carcinoma (HCC) treated by radioembolization in the period from September 2003 to February 2005 were reviewed. Patients received no further antineoplastic therapy. A comprehensive evaluation was performed to prevent the risk of damage due to microsphere misplacing. Patients were discharged the day after microspheres injection. Results: Serious liver toxicity observed among cirrhotic patients in a first period was subsequently prevented by modifying the selection criteria and the method for calculating the activity to be administered. Among 21 patients evaluable for response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions was observed in all but 1 patient. When considering only target lesions, disease control rate and response rate were 100% and 23.8%, respectively. However, 43% of patients progressed in the liver in the form of new lesions appearing a median time of 3 months after radioembolization. Conclusion: Our experience in these series of patients indicates that radioembolization using resin microspheres has a significant antitumor effect against HCC and that using stringent selection criteria and conservative models for calculating Radiation activity to be administered, radioembolization can be performed safely even in cirrhotic patients.

  11. Hepatocellular carcinoma

    SciTech Connect

    Nakashima, T.; Kojiro, M.

    1986-01-01

    With the remarkable recent diagnostic and therapeutic advances and the discovery of a possible pathogenetic role of hepatitis B virus, the study and treatment of hepatocellular carcinoma are entering a new era. Parallel developments in the pathological study of this malignancy are also to be expected. To coincide with this new era, this book presents the authors' accumulated pathomorphological knowledge of hepatocellular carcinoma. The detailed coverage is based on the examination findings of 439 cases of hepatocellular carcinoma autopsied at the authors' department in the last twenty years.

  12. Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial

    PubMed Central

    Ikeda, M.; Shimizu, S.; Sato, T.; Morimoto, M.; Kojima, Y.; Inaba, Y.; Hagihara, A.; Kudo, M.; Nakamori, S.; Kaneko, S.; Sugimoto, R.; Tahara, T.; Ohmura, T.; Yasui, K.; Sato, K.; Ishii, H.; Furuse, J.; Okusaka, T.

    2016-01-01

    Background Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. Patients and methods We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5–7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4–6 weeks) or Sor (400 mg bid). The primary end point was overall survival. Results A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38–0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. Conclusion SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. Clinical Trial registration UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703. PMID:27573564

  13. Immunohistochemical markers of advanced basal cell carcinoma: CD56 is associated with a lack of response to vismodegib.

    PubMed

    Castillo, Jean-Marie; Knol, Anne-Chantal; Nguyen, Jean-Michel; Khammari, Amir; Saint-Jean, Mélanie; Dreno, Brigitte

    2016-10-01

    Vismodegib is an effective treatment for advanced basal cell carcinoma (BCC), but primary resistance to vismodegib remains to be elucidated. Alternative approaches are warranted to help selecting patients most likely to be responsive to treatment. The identification of immunohistochemical markers may support this perspective, as well as better understanding of resistance mechanisms. To determine the level of expression of CD56, PDGF-R, CD117, MMP9, TIMP3, and CXCR4 in advanced BCC, and explore whether expression levels are associated with non-response to vismodegib. A cross-sectional study was conducted. Immunohistochemical markers were selected based on their roles in tumour proliferation and/or migration in skin tumours. Tissue samples included pretreatment advanced BCC samples from patients treated with vismodegib, with an available response after six months of treatment. Regression optimised models were used to build hypotheses regarding a possible association between expression levels and non-response to vismodegib, which was then tested by logistic regression. Twenty-three patients were included. The percentage of samples expressing markers ranged from 43.5% (CD117) to 91.3% (CXCR4). CD56 expression was significantly associated with an increased risk of non-response to vismodegib (OR = 5.5; CI 95%: 3.4-29.8; p = 0.0488); a similar association was suggested for CXCR4 (p = 0.066), but not identified for other markers. These results provide a better understanding of the expression of immunohistochemical markers in advanced BCC. Further detailed analysis of CD56 expression may provide insights into guiding further investigation of the correlation between this marker and non-response to vismodegib.

  14. Treatment algorithm based on the multivariate survival analyses in patients with advanced hepatocellular carcinoma treated with trans-arterial chemoembolization

    PubMed Central

    Prajapati, Hasmukh J.

    2017-01-01

    Purpose To develop the treatment algorithm from multivariate survival analyses (MVA) in patients with Barcelona clinic liver cancer (BCLC) C (advanced) Hepatocellular carcinoma (HCC) patients treated with Trans-arterial Chemoembolization (TACE). Methods Consecutive unresectable and non-tranplantable patients with advanced HCC, who received DEB TACE were studied. A total of 238 patients (mean age, 62.4yrs) was included in the study. Survivals were analyzed according to different parameters from the time of the 1st DEB TACE. Kaplan Meier and Cox Proportional Hazard model were used for survival analysis. The SS was constructed from MVA and named BCLC C HCC Prognostic (BCHP) staging system (SS). Results Overall median survival (OS) was 16.2 months. In HCC patients with venous thrombosis (VT) of large vein [main portal vein (PV), right or left PV, hepatic vein, inferior vena cava] (22.7%) versus small vein (segmental/subsegmental PV) (9.7%) versus no VT had OSs of 6.4 months versus 20 months versus 22.8 months respectively (p<0.001). On MVA, the significant independent prognostic factors (PFs) of survival were CP class, eastern cooperative oncology group (ECOG) performance status (PS), single HCC<5 cm, site of VT, metastases, serum creatinine and serum alpha-feto protein. Based on these PFs, the BCHP staging system was constructed. The OSs of stages I, II and III were 28.4 months, 11.8 months and 2.4 months accordingly (p<0.001). The treatment plan was proposed according to the different stages. Conclusion On MVA of patients with advanced HCC treated with TACE, significant independent prognostic factors (PFs) of survival were CP class, ECOG PS, single HCC<5 cm or others, site of VT, metastases, serum creatinine and serum alpha-feto protein. New BCHP SS was proposed based on MVA data to identify the suitable advanced HCC patients for TACE treatments. PMID:28170405

  15. Maspin and MCM2 immunoprofiling in salivary gland carcinomas

    PubMed Central

    2011-01-01

    Background The pathogenesis of salivary gland carcinomas is very complex and prognostic markers are difficult to find in these carcinomas of which the different subtypes have varying malignant potential. The study was conducted to examine the cellular distribution of maspin and MCM2 in salivary gland carcinomas and their value to predict lymph node metastasis. Materials and methods Fifty three paraffin blocks of different lesions (15 muco-epidermoid carcinoma, 14 adenoid cystic carcinoma, 3 epi-myoepithelial carcinoma, 5 salivary duct carcinoma, 5 malignant pleomorphic adenoma, 6 polymorphous low grade adenocarcinoma and 5 acinic cell carcinoma) were prepared for immunohistochemical staining with maspin and MCM2 antibodies. ANOVA and Pearson correlation tests were used for the statistical analysis of the results. Results All salivary gland carcinomas express maspin and MCM2 with variable cellular localization. There was a significant difference in the expression of each antibody between mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. No association was found between examined markers and lymph node metastasis. Conclusions Salivary gland carcinomas express maspin and MCM2 with variable levels and cellular localization, consisting important markers of biological behavior in these tumors. The level of MCM2 expression can be used in the differential diagnosis of adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Further study with large sample size is recommended to assess their value in prediction of lymph node metastasis. PMID:21943228

  16. Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma: A case series.

    PubMed

    Nemoto, Tomoyuki; Matsuda, Hidetaka; Nosaka, Takuto; Saito, Yasushi; Ozaki, Yoshihiko; Hayama, Ryoko; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Ohtani, Masahiro; Hiramatsu, Katsushi; Suto, Hiroyuki; Nakamoto, Yasunari

    2014-11-01

    Sorafenib and hepatic arterial infusion chemotherapy (HAIC) are both indicated for unresectable hepatocellular carcinoma (HCC). In this study, we compared the efficacy and safety of HAIC to that of sorafenib in elderly patients with HCC. Eligible patients included those aged ≥70 years, with histologically or clinically confirmed advanced HCC. A total of 12 patients received sorafenib (800 mg per day) and 8 patients received HAIC with 5-fluorouracil (300 mg/m(2) on days 1-5 and 8-12) with or without cisplatin (20 mg/m(2) on days 1 and 8), with interferon-α (3 times per week for 4 weeks). The response rate was significantly higher in patients treated with HAIC (37.5%) compared to that in patients treated with sorafenib (no response). The median overall survival (18.6 and 11.7 months) and progression-free survival (4.0 and 5.0 months) were similar between the sorafenib and HAIC groups, respectively. In the sorafenib group, 58.3% of the patients discontinued treatment compared to none in the HAIC group. The most frequent adverse event leading to discontinuation of sorafenib was anorexia. Similar to sorafenib, HAIC appears to be a feasible treatment and may also have the advantage of an adequate safety profile for elderly patients with advanced HCC. Further study of HAIC in a larger population of elderly patients is required to assess its potential as an alternative to sorafenib for HCC.

  17. Anatomic and dosimetric changes during the treatment course of intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

    PubMed

    Wang, Xin; Lu, Jiade; Xiong, Xiaopeng; Zhu, Guopei; Ying, Hongmei; He, Shaoqin; Hu, Weigang; Hu, Chaosu

    2010-01-01

    Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.

  18. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model.

    PubMed

    Vinh, Nguyen Quoc; Naka, Shigeyuki; Cabral, Horacio; Murayama, Hiroyuki; Kaida, Sachiko; Kataoka, Kazunori; Morikawa, Shigehiro; Tani, Tohru

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC.

  19. Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma

    PubMed Central

    Lin, Dong; Ma, Longfei; Ye, Ting; Pan, Yunjian; Shao, Longlong; Song, Zuodong; Jiang, Shujun

    2017-01-01

    Background For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). Methods We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. Results A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. Conclusions Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation. PMID:28275480

  20. Anatomic and Dosimetric Changes During the Treatment Course of Intensity-Modulated Radiotherapy for Locally Advanced Nasopharyngeal Carcinoma

    SciTech Connect

    Wang Xin; Lu Jiade; Xiong Xiaopeng; Zhu Guopei; Ying Hongmei; He Shaoqin; Hu Weigang; Hu Chaosu

    2010-07-01

    Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.

  1. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma.

    PubMed

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC.

  2. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    PubMed Central

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

  3. "Exploratory" surgery for advanced carcinoma of the larynx: a relatively safe approach.

    PubMed

    Tucker, H M

    1998-05-01

    Between the years 1970 and 1986, the author managed 132 patients with T3 glottic carcinoma. Over half of these patients were explored in an effort to safely perform subtotal laryngectomy. Twenty-seven of them were found to have extension of tumor that required immediate conversion to total laryngectomy. Five-year survival rates were essentially the same for all three groups: immediate total laryngectomy, subtotal laryngectomy, and total laryngectomy following attempted subtotal laryngectomy. I conclude that carefully selected patients with T3 glottic cancer may be candidates for subtotal laryngectomy after surgical exploration, since conversion to total laryngectomy yields local control rates as satisfactory as those of initial total laryngectomy. When subtotal laryngectomy is possible, local control of tumor and recurrence rates are as satisfactory as those of total laryngectomy.

  4. Epidermoid Cyst in the Floor of the Mouth of a 3-Year-Old

    PubMed Central

    Pascual Dabán, Rossana; García Díez, Eloy; González Navarro, Beatriz; López-López, José

    2015-01-01

    Epidermoid cysts are a rare entity in the oral cavity and are even less frequent in the floor of the mouth, representing less than 0.01% of all the cases. We present the case of a 3-year-old girl with a growth in the floor of the mouth with 2 months of evolution and without changes since it was discovered by her parents. The lesion was asymptomatic; it did not cause dysphagia, dyspnea, or any other alteration. A CT scan with contrast was done which revealed the location and exact size of the lesion, allowing an intraoral approach for its excision. The histological examination confirmed the clinical speculation of an epidermoid cyst. PMID:25694831

  5. Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts.

    PubMed

    Koh, Kwang-Joon; Park, Ha-Na; Kim, Kyoung-A

    2016-12-01

    Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome.

  6. Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts

    PubMed Central

    Park, Ha-Na; Kim, Kyoung-A

    2016-01-01

    Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome. PMID:28035305

  7. Epidermoid tumors of Meckel's cave: case report and review of the literature.

    PubMed

    Miyazawa, N; Yamazaki, H; Wakao, T; Nukui, H

    1989-12-01

    Lesions of Meckel's cave are extremely uncommon and difficult to diagnose. The symptoms and signs are variable, and the lesions may not appear on routine roentgenographic or computed tomographic examination. A patient with a small epidermoid tumor of Meckel's cave that was diagnosed by magnetic resonance imaging is herein reported. The epidermoid appeared as a low-intensity mass on the T1-weighted image and as a high-intensity mass on the T2-weighted image. Coronal sections defined the anatomic relationship to the trigeminal nerve. Preoperative recordings of the trigeminal sensory evoked response may be predictive of postoperative recovery of neurological deficits. Furthermore, intraoperative recording was extremely useful in avoiding inadvertent neurological injury. Review of the literature confirms the rarity of this lesion and the usefulness of magnetic resonance imaging in diagnosing it, although based on a limited number of cases.

  8. Chemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients

    SciTech Connect

    Baujat, Bertrand; Audry, Helene; Bourhis, Jean; Chan, Anthony T.C.; Onat, Haluk; Chua, Daniel T.T.; Kwong, Dora L.W.; Al-Sarraf, Muhyi; Chi, K.-H.; Hareyama, Masato; Leung, Sing F.; Thephamongkhol, Kullathorn; Pignon, Jean-Pierre . E-mail: jppignon@igr.fr

    2006-01-01

    Objectives: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. Methods and Materials: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. Results: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. Conclusion: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT.

  9. Trigeminal Neuralgia Due to a Small Meckel's Cave Epidermoid Tumor: Surgery Using an Extradural Corridor.

    PubMed

    Furtado, Sunil V; Hegde, Alangar S

    2009-09-01

    Tumors at the petrous apex are associated with a variety of symptoms, which most often involve the trigeminal nerve. The authors present a rare case of a small epidermoid tumor in Meckel's cave that caused medically refractory trigeminal neuralgia. The surgical challenge associated with approaches to such lesions is discussed. The skull base tumor was excised completely through a small temporal craniotomy. The practicality of neuronavigation in reaching the petrous apex using a small extradural window is presented.

  10. Phase I Study of Everolimus in Combination with Gemcitabine and Split-Dose Cisplatin in Advanced Urothelial Carcinoma

    PubMed Central

    Abida, Wassim; Milowsky, Matthew I.; Ostrovnaya, Irina; Gerst, Scott R.; Rosenberg, Jonathan E.; Voss, Martin H.; Apolo, Andrea B.; Regazzi, Ashley M.; McCoy, Asia S.; Boyd, Mariel E.; Bajorin, Dean F.

    2016-01-01

    Background: Cisplatin-based combination chemotherapy is standard first-line treatment for patients with advanced urothelial carcinoma (UC). Molecular profiling studies reveal that the PI3K/AKT/mTOR pathway is altered in a significant percentage of UCs. Objective: We conducted a phase I trial to evaluate the feasibility of combining the mTOR inhibitor everolimus with gemcitabine and split-dose cisplatin (GC) in advanced UC in the first-line setting. Methods: Patients received gemcitabine 800 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 of 21-day cycles for a total of 6 cycles in combination with everolimus at increasing dose levels (DL1:5 mg QOD, DL2:5 mg daily, DL3:10 mg daily) following a standard 3+3 design. Responses were assessed every 2 cycles. Patients with at least stable disease (SD) continued everolimus until progression. Goals were to establish dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for the combination. Results: 12 patients were enrolled, 3 at DL1, 3 at DL2, and an additional 6 at DL1 *(DL1 following de-escalation). 3/3 patients at DL2 had DLTs during cycle 1. 2/8 evaluable patients at DL1/DL1 * had DLTs during cycle 1. DLTs were primarily hematologic. Further toxicities, also primarily hematologic, were observed during later treatment cycles, leading to 8 chemotherapy dose reductions overall. Partial responses were observed in 4/10 evaluable patients, and SD in 5/10. Median overall survival was 10.8 months (95% CI 6.9, not reached). Conclusions: The maximum tolerated dose was reached at the lowest dose level, 5 mg QOD, for everolimus in combination with gemcitabine and split-dose cisplatin in advanced UC. The regimen was limited by hematologic toxicity. PMID:27376132

  11. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy

    PubMed Central

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil

    2016-01-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3–12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10–22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  12. Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy

    PubMed Central

    2011-01-01

    Background To establish recurrence patterns among locally advanced head and neck non-nasopharyngeal squamous cell carcinoma (HNSCC) patients treated with radical (chemo-) radiotherapy and to correlate the sites of loco-regional recurrence with radiotherapy doses and target volumes Method 151 locally advanced HNSCC patients were treated between 2004-2005 using radical three-dimensional conformal radiotherapy. Patients with prior surgery to the primary tumour site were excluded. The sites of locoregional relapses were correlated with radiotherapy plans by the radiologist and a planning dosimetrist. Results Median age was 59 years (range:34-89). 35 patients had stage III disease, 116 patients had stage IV A/B. 36 patients were treated with radiotherapy alone, 42 with induction chemotherapy, 63 with induction and concomitant chemoradiotherapy and 10 concomitant chemoradiotherapy. Median follow-up was 38 months (range 3-62). 3-year cause specific survival was 66.8%. 125 of 151 (82.8%) achieved a complete response to treatment. Amongst these 125 there were 20 local-regional recurrence, comprising 8 local, 5 regional and 7 simultaneous local and regional; synchronous distant metastases occurred in 7 of the 20. 9 patients developed distant metastases in the absence of locoregional failure. For the 14 local recurrences with planning data available, 12 were in-field, 1 was marginal, and 1 was out-of-field. Of the 11 regional failures with planning data available, 7 were in-field, 1 was marginal and 3 were out-of-field recurrences. Conclusion The majority of failures following non-surgical treatment for locally advanced HNSCC were loco-regional, within the radiotherapy target volume. Improving locoregional control remains a high priority. PMID:21609453

  13. Isolated thoracic (D5) intramedullary epidermoid cyst without spinal dysraphism: A rare case report

    PubMed Central

    Mishra, Sudhansu Sekhar; Satapathy, Mani Charan; Deo, Rama Chandra; Tripathy, Soubhagya Ranjan; Senapati, Satya Bhusan

    2015-01-01

    Spinal epidermoid cyst, congenital or acquired, is mainly congenital associated with spinal dysraphism, rarely in isolation. Intramedullary epidermoid cysts (IECs) are rare with less than 60 cases reported so far; isolated variety (i.e., without spinal dysraphism) is still rarer. Complete microsurgical excision is the dictum of surgical treatment. A 14-year-old boy presented with 4-month history of upper backache accompanied with progressive descending paresthesia with paraparesis with early bladder and bowel involvement. His condition deteriorated rapidly making him bedridden. Neurological examination revealed upper thoracic myeloradiculopathy probably of neoplastic origin with sensory localization to D5 spinal level. Digital X-ray revealed no feature suggestive of spinal dysraphism. Contrast magnetic resonance imaging (MRI) characteristics clinched the presumptive diagnosis. Near-total microsurgical excision was done leaving behind a small part of the calcified capsule densely adhered to cord. Histopathological features were confirmative of an epidermoid cyst. Postoperatively, he improved significantly with a gain of motor power sufficient to walk without support within a span of 6 months. Spinal IECs, without any specific clinical presentation, are often diagnosed based upon intraoperative and histopathological findings, however early diagnosis is possible on complete MRI valuation. Complete microsurgical excision, resulting in cessation of clinical progression and remission of symptoms, has to be limited to sub-total or near-total excision if cyst is adherent to cord or its confines. PMID:26167216

  14. Epidermoid cyst in Meckel's cave with unusual computed tomography and magnetic resonance imaging findings. Case report.

    PubMed

    Arai, Atsushi; Sasayama, Takashi; Koyama, Junji; Fujita, Atsushi; Hosoda, Kohkichi; Kohmura, Eiji

    2010-01-01

    A 27-year-old woman presented with headache and occasional numbness over her right face. Computed tomography revealed a hypodense mass in the middle cranial fossa and another adjacent hyperdense mass in the posterior fossa with erosion of the right petrous apex. Magnetic resonance imaging revealed the lesion in the middle cranial fossa as iso- to hypointense on T(1)-weighted and hyperintense on T(2)-weighted imaging, with peripheral enhancement after gadolinium administration, and the adjacent lesion in the posterior fossa as hyperintense on T(1)-weighted and hypointense on T(2)-weighted imaging. During surgery, these lesions mimicking two adjacent distinct tumors were revealed to connect through Meckel's cave. The hypodense lesion in the middle cranial fossa consisted of pearly-like solid contents, and the hyperdense lesion in the posterior cranial fossa consisted of viscid dark-green materials. The tumors were gross totally resected with endoscopic assistance. Histological examination confirmed that the tumor was an epidermoid cyst. The present case cyst indicates that although the diffusion-weighted imaging sequence is useful for detection of intracranial epidermoid cysts, epidermoid cysts including viscous materials with unusual radiological findings could complicate the preoperative diagnosis.

  15. Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I-type II study from the GINECO group.

    PubMed

    Heudel, P-E; Fabbro, M; Roemer-Becuwe, C; Kaminsky, M C; Arnaud, A; Joly, F; Roche-Forestier, S; Meunier, J; Foa, C; You, B; Priou, F; Tazi, Y; Floquet, A; Selle, F; Berton-Rigaud, D; Lesoin, A; Kalbacher, E; Lortholary, A; Favier, L; Treilleux, I; Ray-Coquard, I

    2017-01-01

    Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma.

  16. Development of hepatocellular carcinoma in chronic hepatitis B patients with advanced fibrosis is independent of viral genotype.

    PubMed

    Kumar, Rajneesh; Testoni, Barbara; Fresquet, Judith; Lim, Tony Kiat Hon; Hao, Ying; Tan, Hui Hui; Chow, Wan Cheng; Zoulim, Fabien

    2017-05-01

    Hepatitis B is leading cause of liver related morbidity in Asia with predominant genotypes B and C in East-Asia. Data on Serum, intrahepatic viral-markers, and long-term follow-up of prevalent genotypes (GT) B and C in patients with biopsy proven advanced fibrosis are sparse. To compare serum, intrahepatic viral-markers and development of hepatocellular carcinoma (HCC) in GT-B and C in patients with advanced fibrosis (Ishak ≥ 4). Sixty-three treatment-naïve patients identified with advanced fibrosis on liver-biopsy performed between 1998 and 2000 at Singapore General Hospital. FFPE tissue was available for 59 patients and serum for 42 patients. HBV-DNA was quantified in serum and liver while qHBsAg quantified in serum. Patients were followed-up till December 2015. The median age was 47 ± 16 years, with 77.7% males. About 19 were GT-B, 43 patients were GT-C, and 1 had both GT-B and C. Mean follow-up was 13.5 years. The median serum HBV-DNA was 6.25 ± 2.17 and 6.58 ± 1.85 log IU/ml, serum HBsAg was 3.29 ± 0.80 and 3.45 ± 1.85 log IU/ml, and intrahepatic HBV-DNA was 0.52 ± 3.73 copies/cell and 0.4 ± 1.37 copies/cell in the GT-B and C, respectively (P > 0.1 in all). Complete cirrhosis (Ishak-6) was present in 47.6%, Ishak-5 fibrosis in 33.3%, and Ishak-4 fibrosis in 19% at recruitment. On follow-up HCC developed in 8/43 in GT-C and in 3/19 GT-B (P = 0.86). Advanced age and cirrhosis were significant factors for development of HCC. No difference in serum HBV-DNA, qHBsAg or intrahepatic HBV-DNA was seen in the two genotypes. HCC development seen over long-term follow-up was independent of genotypes in patients with advanced fibrosis. J. Med. Virol. 89:845-848, 2017. © 2016 Wiley Periodicals, Inc.

  17. Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients with Advanced Hepatitis C

    PubMed Central

    Sterling, Richard K.; Wright, Elizabeth C.; Morgan, Timothy R.; Seeff, Leonard B.; Hoefs, John C.; Di Bisceglie, Adrian M.; Dienstag, Jules L.; Lok, Anna S.

    2013-01-01

    Background Prospective studies of serum HCC biomarkers in patients with advanced hepatitis C are lacking. Aims To determine frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. Methods Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. Results 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20-199, while 2.3% had at least one AFP value ≥200 ng/mL; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90-149, and 14.7% had at least one DCP value ≥150 mAU/mL. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP >20 ng/mL. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/mL had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/mL had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. Conclusions Mild-moderate elevations in total AFP and DCP but not AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. PMID:21931376

  18. Usefulness of human epididymis protein 4 in predicting cytoreductive surgical outcomes for advanced ovarian tubal and peritoneal carcinoma

    PubMed Central

    Tang, Zhijian; Chang, Xiaohong; Ye, Xue; Li, Yi; Cheng, Hongyan

    2015-01-01

    Objective Human epididymis protein 4 (HE4) is a promising biomarker of epithelial ovarian cancer (EOC). But its role in assessing the primary optimal debulking (OD) of EOC remains unknown. The purpose of this study is to elucidate the ability of preoperative HE4 in predicting the primary cytoreductive outcomes in advanced EOC, tubal or peritoneal carcinoma. Methods We reviewed the records of 90 patients with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at the Department of Obstetrics and Gynecology of Peking University People’s Hospital between November 2005 and October 2010. Preoperative serum HE4 and CA125 levels were detected with EIA kit. A receiver operating characteristic (ROC) curve was used to determine the most useful HE4 cut-off value. Logistic regression analysis was performed to identify significant preoperative clinical characteristics to predict optimal primary cytoreduction. Results OD was achieved in 47.7% (43/48) of patients. The median preoperative HE4 level for patients with OD vs. suboptimal debulking was 423 and 820 pmol/L, respectively (P<0.001). The areas under the ROC curve for HE4 and CA125 were 0.716 and 0.599, respectively (P=0.080). The most useful HE4 cut-off value was 473 pmol/L. Suboptimal cytoreduction was obtained in 66.7% (38/57) of cases with HE4 ≥473 pmol/L compared with only 27.3% (9/33) of cases with HE4 <473 pmol/L. At this threshold, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing suboptimal debulking were 81%, 56%, 67%, and 73%, respectively. Logistic regression analysis showed that the patients with HE4 ≥473 pmol/L were less likely to achieve OD (odds ratio =5.044, P=0.002). Conclusions Preoperative serum HE4 may be helpful to predict whether optimal cytoreductive surgery could be obtained or whether extended cytoreduction would be needed by an interdisciplinary team. PMID:26157328

  19. Reducing the Risk of Xerostomia and Mandibular Osteoradionecrosis: The Potential Benefits of Intensity Modulated Radiotherapy in Advanced Oral Cavity Carcinoma

    SciTech Connect

    Ahmed, Merina; Hansen, Vibeke N.; Harrington, Kevin J.; Nutting, Christopher M.

    2009-10-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 {+-} 0.8 Gy for 3DCRT and 59.8 {+-} 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 {+-} 6 Gy for 3DCRT and 15.3 {+-} 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 {+-} 0.8 Gy for 3DCRT and for IMRT was 54.2 {+-} 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 {+-} 3.2 Gy vs. 30.7 {+-} 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 {+-} 2.7 Gy for IMRT and 42.0 {+-} 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

  20. Reducing the risk of xerostomia and mandibular osteoradionecrosis: the potential benefits of intensity modulated radiotherapy in advanced oral cavity carcinoma.

    PubMed

    Ahmed, Merina; Hansen, Vibeke N; Harrington, Kevin J; Nutting, Christopher M

    2009-01-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 +/- 0.8 Gy for 3DCRT and 59.8 +/- 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 +/- 6 Gy for 3DCRT and 15.3 +/- 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 +/- 0.8 Gy for 3DCRT and for IMRT was 54.2 +/- 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 +/- 3.2 Gy vs. 30.7 +/- 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 +/- 2.7 Gy for IMRT and 42.0 +/- 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

  1. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Montejo, Michael E.; Shrieve, Dennis C.; Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O.; Agarwal, Neeraj; Hitchcock, Ying J.

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  2. Pim1 kinase synergizes with c-MYC to induce advanced prostate carcinoma

    PubMed Central

    Wang, Jie; Kim, Jongchan; Roh, Meejeon; Franco, Omar E.; Hayward, Simon W.; Wills, Marcia L.; Abdulkadir, Sarki A.

    2010-01-01

    The oncogenic PIM1 kinase has been implicated as a cofactor for c-MYC in prostate carcinogenesis. Here we show that in human prostate tumors, coexpression of c-MYC and PIM1 is associated with higher Gleason grades. Using a tissue recombination model coupled with lentiviral-mediated gene transfer we find that Pim1 is weakly oncogenic in naïve adult mouse prostatic epithelium. However, it cooperates dramatically with c-MYC to induce prostate cancer within 6-weeks. Importantly, c-MYC/Pim1 synergy is critically dependent on Pim1 kinase activity. c-MYC/Pim1 tumors showed increased levels of the active serine-62 (S62) phosphorylated form of c-MYC. Grafts expressing a phosphomimetic c-MYCS62D mutant had higher rates of proliferation than grafts expressing wild type c-MYC but did not form tumors like c-MYC/Pim1 grafts, indicating that Pim1 cooperativity with c-MYC in vivo involves additional mechanisms other than enhancement of c-MYC activity by S62 phosphorylation. c-MYC/Pim1-induced prostate carcinomas demonstrate evidence of neuroendocrine (NE) differentiation. Additional studies, including the identification of tumor cells coexpressing androgen receptor and NE cell markers synaptophysin and Ascl1 suggested that NE tumors arose from adenocarcinoma cells through transdifferentiation. These results directly demonstrate functional cooperativity between c-MYC and PIM1 in prostate tumorigenesis in vivo and support efforts for targeting PIM1 in prostate cancer. PMID:20140016

  3. Advances of multidetector computed tomography in the characterization and staging of renal cell carcinoma

    PubMed Central

    Tsili, Athina C; Argyropoulou, Maria I

    2015-01-01

    Renal cell carcinoma (RCC) accounts for approximately 90%-95% of kidney tumors. With the widespread use of cross-sectional imaging modalities, more than half of RCCs are detected incidentally, often diagnosed at an early stage. This may allow the planning of more conservative treatment strategies. Computed tomography (CT) is considered the examination of choice for the detection and staging of RCC. Multidetector CT (MDCT) with the improvement of spatial resolution and the ability to obtain multiphase imaging, multiplanar and three-dimensional reconstructions in any desired plane brought about further improvement in the evaluation of RCC. Differentiation of RCC from benign renal tumors based on MDCT features is improved. Tumor enhancement characteristics on MDCT have been found closely to correlate with the histologic subtype of RCC, the nuclear grade and the cytogenetic characteristics of clear cell RCC. Important information, including tumor size, localization, and organ involvement, presence and extent of venous thrombus, possible invasion of adjacent organs or lymph nodes, and presence of distant metastases are provided by MDCT examination. The preoperative evaluation of patients with RCC was improved by depicting the presence or absence of renal pseudocapsule and by assessing the possible neoplastic infiltration of the perirenal fat tissue and/or renal sinus fat compartment. PMID:26120380

  4. Nivolumab in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

    PubMed Central

    Mennitto, Alessia; Grassi, Paolo; Ratta, Raffaele; Verzoni, Elena; Prisciandaro, Michele; Procopio, Giuseppe

    2016-01-01

    Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α). Strategies of tumor immune evasion include T-cell suppression by negative signals deriving from the interaction between programmed death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells. Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus reversing T-cell suppression and activating antitumor responses. The aim of this review is to summarize the safety and efficacy data of nivolumab in mRCC. Objective responses and safety profile of single-agent nivolumab are favorable in both previously treated and treatment-naïve mRCC patients. Despite toxic effects, combination therapies with nivolumab have shown promising results, indicating a potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to-patient basis represents a major challenge for the future. PMID:27695530

  5. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract.

    PubMed

    Thar, Yu Yu; Patel, Poras; Huang, Tiangui; Guevara, Elizabeth

    2016-01-01

    Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck.

  6. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract

    PubMed Central

    Guevara, Elizabeth

    2016-01-01

    Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck. PMID:27529044

  7. Advances of Salivary Proteomics in Oral Squamous Cell Carcinoma (OSCC) Detection: An Update

    PubMed Central

    Sannam Khan, Rabia; Khurshid, Zohaib; Akhbar, Shazia; Faraz Moin, Syed

    2016-01-01

    Oral cancer refers to malignancies that have higher morbidity and mortality rates due to the late stage diagnosis and no early detection of a reliable diagnostic marker, while oral squamous cell carcinoma (OSCC) is amongst the world’s top ten most common cancers. Diagnosis of cancer requires highly sensitive and specific diagnostic tools which can support untraceable hidden sites of OSCC, yet to be unleashed, for which plenty of biomarkers are identified; the most recommended biomarker detection medium for OSCC includes biological fluids, such as blood and saliva. Saliva holds a promising future in the search for new clinical biomarkers that are easily accessible, less complex, accurate, and cost effective as well as being a non-invasive technique to follow, by analysing the malignant cells’ molecular pathology obtained from saliva through proteomic, genomic and transcriptomic approaches. However, protein biomarkers provide an immense potential for developing novel marker-based assays for oral cancer, hence this current review offers an overall focus on the discovery of a panel of candidates as salivary protein biomarkers, as well as the proteomic tools used for their identification and their significance in early oral cancer detection. PMID:28248250

  8. Functional NBS1 polymorphism is associated with occurrence and advanced disease status of nasopharyngeal carcinoma.

    PubMed

    Zheng, Jian; Zhang, Chun; Jiang, Lan; You, Yonghe; Liu, Yuehui; Lu, Jiachun; Zhou, Yifeng

    2011-09-01

    As a component of the MRN (MRE11/RAD50/NBS1) complex, NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with nasopharyngeal carcinoma (NPC) in Chinese population has not been investigated. Moreover, there is no report about the association between NBS1 3'UTR variant rs2735383 and the risk of NPC. A multiple center case-control analysis was performed to assess the association between NBS1 polymorphisms and NPC risk in Eastern and Southern Chinese population. The genotypes and haplotypes were determined in 1052 cases and 1168 controls and the associations with risk of NPC were estimated by logistic regression. Cell migration assays were performed in 24-well transwell chambers to detect the effects of NBS1 E185Q SNP on cell migration. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (P(trend) < 0.0001). The C allele increases the risk for invasive disease or metastatic disease, compared with G allele. More over, CNE-2 cells (NPC cell line) transfected with pcDNA-NBS1-185Q (8360CC) had significantly higher migration levels than those transfected with pcDNA-NBS1-185E (8360GG) (P = 0.024). These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for the occurrence and aggression of NPC.

  9. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    SciTech Connect

    Du, Zhongli; Zhang, Wencheng; Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen; Xiao, Zefen; Tan, Wen; and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  10. Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma

    PubMed Central

    KAWANO, SHINTARO; ZHENG, YANQUN; OOBU, KAZUNARI; MATSUBARA, RYOTA; GOTO, YUICHI; CHIKUI, TORU; YOSHITAKE, TADAMASA; KIYOSHIMA, TAMOTSU; JINNO, TEPPEI; MARUSE, YASUYUKI; MITATE, EIJI; KITAMURA, RYOJI; TANAKA, HIDEAKI; TOYOSHIMA, TAKESHI; SUGIURA, TSUYOSHI; NAKAMURA, SEIJI

    2016-01-01

    The administration of pre-operative chemotherapy with S-1 and concurrent radiotherapy at a total dose of 30 Gy was clinicopathologically evaluated as a treatment for locally advanced oral squamous cell carcinoma (OSCC) in the present study. The participants comprised 81 patients with OSCC, consisting of 29 patients with stage II disease, 12 patients with stage III disease and 40 patients with stage IV disease. All patients received a total radiation dose of 30 Gy in daily fractions of 2 Gy, 5 times a week, for 3 weeks, and the patients were concurrently administered S-1 at a dose of 80–120 mg, twice daily, over 4 consecutive weeks. Radical surgery was performed in all cases at 2–6 weeks subsequent to the end of pre-operative chemoradiotherapy. The most common adverse event was oropharyngeal mucositis, but this was transient in all patients. No severe hematological or non-hematological toxicities were observed. The clinical and histopathological response rates were 70.4 and 75.3%, respectively. Post-operatively, local failure developed in 6 patients (7.4%) and neck failure developed in 2 patients (2.5%). Distant metastases were found in 7 patients (8.6%). The overall survival rate, disease-specific survival rate and locoregional control rate at 5 years were 87.7, 89.9 and 90.6%, respectively. Locoregional recurrence occurred more frequently in patients that demonstrated a poor histopathological response compared with patients that demonstrated a good response (P<0.01). These results indicate that pre-operative S-1 chemotherapy with radiotherapy at a total dose of 30 Gy is feasible and effective for patients with locally advanced OSCC, and that little or no histopathological response may be a risk factor for locoregional recurrence in this treatment. PMID:27123119

  11. Relationship between level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Xing, Yan; Zhang, Jianjun; Lin, Heather; Gold, Kathryn A.; Sturgis, Erich M.; Garden, Adam S.; Lee, J. Jack; William, William N.

    2015-01-01

    Background The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. We sought to investigate the impact of level of lymph node metastasis (LNM) on survival Methods The Surveillance, Epidemiology, and End Results (SEER) registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. Multivariate Cox proportional hazards model was used to evaluate whether level of LNM is an independent prognostic factor. Site-specific recursive-partitioning analysis (RPA) was performed to classify patients into different risk groups. Results Totally, 14,499 patients including OC (N=2,463), OP (N=8,567), LAR (N=2,332) and HP (N=1,137) were analyzed. Both AJCC N classification and level of LNM showed significant effects on overall survival (OS) in patients with OC, OP or LAR, but not in HP. In patients with N2 disease, AJCC subclassification (N2a, N2b, N2c) was significantly associated with OS of patients with OP and LAR, but not OC or HP, while level of LNM (primary, secondary, and tertiary) was significantly associated with OS in patients with OC, OP and LAR, but not HP. Using RPA, we designed a simple, primary site-specific prognostic tool integrating AJCC T classification, N classification, and level of LNM that can be easily utilized by health care providers in clinic. Conclusions Level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classification in patients with locally advanced HNSCC. PMID:26554754

  12. Clinical implication of computed tomography findings in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Ryu, In Sun; Lee, Jeong Hyun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Cho, Kyung-Ja

    2015-10-01

    Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72%) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73%) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80%, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78%. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP.

  13. Effectiveness of combined (131)I-chTNT and radiofrequency ablation therapy in treating advanced hepatocellular carcinoma.

    PubMed

    Tu, Jianfei; Ji, Jiansong; Wu, Fazong; Wang, Yonghui; Zhang, Dengke; Zhao, Zhongwei; Ying, Xihui

    2015-03-01

    To investigate the effectiveness of monoclonal antibody ((131)I-chTNT) and radiofrequency ablation (RFA) combination therapy in treating middle-advanced stage hepatocellular carcinoma (HCC). Thirty-four patients diagnosed with HCC patients, divided into two groups comprised of 22 and 12 cases were included in this retrospective study. The two groups received RFA with or without ((131)I-chTNT) therapy, respectively. The patients in these groups were followed up for a median of 31 and 35 months, respectively. Patient survival was evaluated using Kaplan-Meier method and safety profiles were determined by analyzing liver, thyroid, and bone marrow toxicities. This retrospective study showed that survival time of the patients who received combination therapy was significantly longer than that of the RFA group (P = 0.052). The median progress-free survival of patients in the two groups was 23 and 7 months, respectively, and the difference was significant (P = 0.04). Tumor recurred in 3.5-8.7 months in four of the combination group patients, among which three had newly developed lesions. The red blood cells and platelets counts were not altered on day 7 and 1 month of the treatment, however, number of white blood cells was significantly increased on day 7 which was reversed back to the normal range in 2 weeks. The ALT and AST were also not significantly altered on day 7 and 1 month of therapy. In middle-advanced stage HCC patients, the combination of (131)I-chTNT and RFA therapy was found to be significantly more effective than the RFA treatment alone as assessed in short-term follow-up. However, the dose we used was insufficient to completely block the local recurrence of the lesions with a diameter of 5 cm or larger.

  14. Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

    PubMed Central

    Echarri, María José; Lopez-Martin, Ana; Hitt, Ricardo

    2016-01-01

    Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing. PMID:26927178

  15. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

    PubMed Central

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  16. Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

    PubMed Central

    Liang, Zhong-Guo; Chen, Xiao-Qian; Lin, Guo-Xiang; Yu, Bin-Bin; Chen, Kai-Hua; Zhong, Qiu-Lu; Nong, Si-Kai; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Zhu, Xiao-Dong

    2017-01-01

    The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. PMID:28150694

  17. Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

    PubMed Central

    Takino, Jun-ichi; Nagamine, Kentaro; Hori, Takamitsu; Sakasai-Sakai, Akiko; Takeuchi, Masayoshi

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus (HCV), and non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products (AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs (TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs (RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC. PMID:26483867

  18. Subcutaneous administration of interleukin 2 and interferon-alpha-2b in advanced renal cell carcinoma: a confirmatory study.

    PubMed Central

    Facendola, G.; Locatelli, M. C.; Pizzocaro, G.; Piva, L.; Pegoraro, C.; Pallavicini, E. B.; Signaroldi, A.; Meregalli, M.; Lombardi, F.; Beretta, G. D.

    1995-01-01

    Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur. PMID:8519672

  19. Positron Emission Tomography for Neck Evaluation Following Definitive Treatment with Chemoradiotherapy for Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Bar-Ad, Voichita; Mishra, Mark; Ohri, Nitin; Intenzo, Charles

    2013-01-01

    Objectives The objective of the current review was to assess published data on the role of Positron Emission Tomography (PET) for evaluation of nodal residual disease after definitive chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods Studies were identified by searching PubMed electronic databases. Only studies using a post-chemoradiotherapy PET for nodal residual disease evaluation were included in the present review. Both prospective and retrospective studies were included. Information regarding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET for detecting nodal residual disease after definitive chemoradiotherapy for HNSCC was extracted and analyzed. Results Twenty published studies were included in the present review. Existing data suggest that a negative post-chemoradiotherapy PET scan is associated with a negative predictive value up to 100%. The sensitivity of PET in detecting nodal residual disease is greater for scans performed ≥ 10 weeks after definitive treatment with chemoradiotherapy for HNSCC. Conclusions Further studies are needed to quantify the reliability of PET in detecting nodal residual disease after chemoradiotherapy for locoregionally advanced HNSCC. The optimal timing of PET imaging after chemoradiotherapy remains to be defined. PMID:21864252

  20. Phase I study of TAC-101, an oral synthetic retinoid, in Japanese patients with advanced hepatocellular carcinoma.

    PubMed

    Okusaka, Takuji; Ueno, Hideki; Ikeda, Masafumi; Takezako, Yoriko; Morizane, Chigusa

    2012-08-01

    Preclinical models have shown that TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has antitumor activity in hepatocellular carcinoma (HCC). We conducted a phase I study in Japanese patients with advanced HCC to examine the pharmacokinetics, recommended dose, safety, and efficacy of TAC-101. The administered dose of TAC-101 was 10 mg/day in four patients (level 1), 20 mg/day in six (level 2), and 30 mg/day in three (level 3). There was no dose-limiting toxicity at level 1. Only one patient each had dose-limiting toxicity at level 2 (grade 2 fatigue, recovery requiring eight or more consecutive days of rest) and at level 3 (grade 3 splenic vein thrombosis). Level 3 (30 mg/day) was considered the maximum tolerated dose and 20 mg/day the recommended dose by a panel of medical experts, placing maximum emphasis on safety. The most frequent adverse events were fatigue, headache, and dermal symptoms such as rash. Pharmacokinetic parameters in Japanese patients with HCC were similar to those in patients in the United States, most of whom were Caucasian. Although no patient had a complete or partial response, the disease control rate was 38.5%. In conclusion, the recommended dose of TAC-101 for patients with HCC is 20 mg/day. TAC-101 had an acceptable toxicity profile, warranting further evaluation in clinical trials.

  1. Toxicity of abdominopelvic radiation in advanced ovarian carcinoma patients after cisplatin/cyclophosphamide therapy and second-look laparotomy

    SciTech Connect

    Shelley, W.E.; Starreveld, A.A.; Carmichael, J.A.; O'Connell, G.; Roy, M.; Swenerton, K.

    1988-03-01

    Twenty-seven advanced ovarian carcinoma patients who had received six courses of cyclophosphamide/cisplatin and had either microscopic disease (15 patients) or no pathologically detectable disease (12 patients) after second-look laparotomy were treated with abdominopelvic radiation (2250 cGy to the abdomen and pelvis and a 2250-cGy pelvic boost). Acute myelosuppression or gastrointestinal toxicity prevented completion of treatment in only three patients. However, bowel obstruction occurred in 13 (48%), ten of whom required surgery. Five of these ten had recurrent tumor, but the other five did not. Subsequently two of the latter five did develop a recurrence, one in the lung and one in the liver. A third patient died as an indirect result of radiation damage to the bowel. Median follow-up duration is 17 months from completion of radiation. So far, 13 (48%) have developed progressive disease: four (33%) of the 12 who had a negative second-look laparotomy and nine (60%) of the 15 who had microscopic disease before radiation. While acute toxicity is tolerable, the incidence of serious chronic bowel toxicity is high. Efforts should be made to alter this therapy in order to decrease the frequency of long-term morbidity.

  2. Transcript Profiling Identifies Iqgap2−/− Mouse as a Model for Advanced Human Hepatocellular Carcinoma

    PubMed Central

    Gnatenko, Dmitri V.; Xu, Xiao; Zhu, Wei; Schmidt, Valentina A.

    2013-01-01

    It is broadly accepted that genetically engineered animal models do not always recapitulate human pathobiology. Therefore identifying best-fit mouse models of human cancers that truly reflect the corresponding human disease is of vital importance in elucidating molecular mechanisms of tumorigenesis and developing preventive and therapeutic approaches. A new hepatocellular carcinoma (HCC) mouse model lacking a novel putative tumor suppressor IQGAP2 has been generated by our laboratory. The aim of this study was to obtain the molecular signature of Iqgap2−/− HCC tumors and establish the relevance of this model to human disease. Here we report a comprehensive transcriptome analysis of Iqgap2−/− livers and a cross-species comparison of human and Iqgap2−/− HCC tumors using Significance Analysis of Microarray (SAM) and unsupervised hierarchical clustering analysis. We identified the Wnt/β-catenin signaling pathway as the top canonical pathway dysregulated in Iqgap2−/− livers. We also demonstrated that Iqgap2−/− hepatic tumors shared genetic signatures with HCC tumors from patients with advanced disease as evidenced by a 78% mouse-to-human microarray data set concordance rate with 117 out of 151 identified ortholog genes having similar expression profiles across the two species. Collectively, these results indicate that the Iqgap2 knockout mouse model closely recapitulates human HCC at the molecular level and supports its further application for the study of this disease. PMID:23951254

  3. The Prognostic Value of Baseline Lymphocyte, Neutrophil, and Monocyte Counts in Locally Advanced Cervical Carcinoma Treated with Radiation

    PubMed Central

    Himler, Justin; Nagel, Christa I.; Resnick, Kimberly

    2017-01-01

    Background. To determine the prognostic significance of pretreatment levels of circulating lymphocyte (CLC), neutrophil (CNC), and monocyte (CMC) counts in patients with locally advanced cervical carcinoma (CC) treated with definitive radiation. Methods. A retrospective, dual-institution review of patients with Stage IB2-IVA CC from 2005 to 2015. Progression-free (PFS) and Overall Survival (OS) were determined for high and low CLC, CNC, and CMC groups. Multivariate analysis was used to confirm prognostic value of baseline leukocyte counts. Results. 181 patients were included. Median follow-up time was 26 (3–89) months. CNC had no effect on PFS or OS. PFS was similar between CMC groups; however, OS was significantly improved for patients with low CMC (62.5 versus 45.3 months, p = 0.016). High CLC was associated with improved PFS (48.5 versus 27.8 months, p = 0.048) and OS (58.4 versus 34.9 months, p = 0.048). On multivariate analysis, high CNC was associated with increased relapse risk (HR 1.12, p = 0.006) and low CLC was associated with increased mortality risk (HR 0.67, p = 0.027). Conclusion. This study demonstrates that leukocyte values can provide prognostic information in CC. These hypothesis-generating findings warrant further prospective investigations. PMID:28239396

  4. Phase II trial of biweekly docetaxel, cisplatin, and 5-fluorouracil chemotherapy for advanced esophageal squamous cell carcinoma.

    PubMed

    Tanaka, Yoshihiro; Yoshida, Kazuhiro; Yamada, Atsuko; Tanahashi, Toshiyuki; Okumura, Naoki; Matsuhashi, Nobuhisa; Yamaguchi, Kazuya; Miyazaki, Tatsuhiko

    2016-06-01

    The prognosis of esophageal cancer patients is still unsatisfactory. Although a docetaxel, cisplatin, and 5-Fu (DCF) regimen has been reported, it is often difficult to accomplish because of severe toxicity. Therefore, we developed a new biweekly DCF (Bi-DCF) regimen and previously reported the recommended dose in a phase I dose-escalation study. We then performed a phase II study of Bi-DCF for advanced esophageal squamous cell carcinoma (SCC). Patients with clinical stage II/III were eligible. Patients received 2 courses of chemotherapy: docetaxel 35 mg/m(2) with cisplatin 40 mg/m(2) on days 1 and 15 and 400 mg/m(2) 5-fluorouracil on days 1-5 and 15-19 every 4 weeks. After completion of the chemotherapy, patients received esophagectomy. The primary endpoint was the completion rate of protocol treatment. Thirty-two patients were enrolled. The completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery) was 100 %. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (31.3 %). No treatment-related death was observed, and the incidence of operative morbidity was tolerable. The overall response rate after the chemotherapy was 90.3 %. This Bi-DCF regimen was well tolerated and highly active. This trial was registered with the University Hospital Medical Information Network (No. UMIN 000014625).

  5. Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan

    PubMed Central

    Matsuda, Satoru; Kawakubo, Hirofumi; Ando, Nobutoshi; Kitagawa, Yuko

    2016-01-01

    Multidisciplinary treatment comprising surgery, chemotherapy, and radiotherapy for resectable esophageal squamous cell carcinoma (ESCC) is widely used with improved prognosis. Transthoracic esophagectomy (TTE) with extended lymph node (LN) dissection, known as three field LN dissection, has been recommended for ESCC using open thoracotomy or the thoracoscopic approach. The Japan Clinical Oncology Group (JCOG) trial (JCOG1409) is investigating the patients’ long term survival using the thoracoscopic approach that has been shown to reduce the incidence of postoperative respiratory complication. For perioperative treatment, neoadjuvant chemotherapy using cisplatin plus 5-fluorouracil (5-FU), has been accepted as the standard of care in Japan based on the JCOG9907 trial. In Western countries, neoadjuvant chemoradiotherapy was shown to prolong overall survival for esophageal cancer, including ESCC. Although surgery has been recognized as an initial curative treatment for esophageal cancer, definitive chemoradiotherapy is an alternative treatment for patients who are unable to undergo thoracotomy or who decline to undergo surgery. This article reviews multidisciplinary treatment advances for ESCC. However, current standard treatments are country dependent and the ongoing trial may help standardize ESCC treatment across various societies. PMID:27384595

  6. [Presurgical treatment of axitinib reduced operation risk by downsizing the vena cava tumor thrombus in advanced renal cell carcinomas: two case reports].

    PubMed

    Hamada, Akihiro; Yamasaki, Toshinari; Negoro, Hiromitsu; Kobayashi, Takashi; Terada, Naoki; Sugino, Yoshio; Matsui, Yoshiyuki; Inoue, Takahiro; Kamba, Tomomi; Yoshimura, Koji; Ogawa, Osamu

    2014-12-01

    In cases of advanced renal cell carcinoma with inferior vena cava (IVC) thrombus, surgical resection of both tumor and thrombus contributes to the improvement of patient's prognosis, but the risk of perioperative complication is still high. We experienced two cases of advanced renal tumors with IVC tumor thrombus down-sized by presurgical treatment of axitinib. Axitinib treatment showed a marked tumor reduction effect without any severe adverse event. We could remove both tumor and thrombus without perioperative complications. In these two cases, downsizing of IVC thrombus enabled us to reduce the extent of the surgery.

  7. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-02-14

    Head and Neck Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  8. Could preoperative short-course radiotherapy be the treatment of choice for localized advanced rectal carcinoma?

    PubMed Central

    Ciria, Juan Pablo; Eguiguren, Mikel; Cafiero, Sergio; Uranga, Intza; Diaz de Cerio, Ivan; Querejeta, Arrate; Urraca, Jose Maria; Minguez, Julian; Guimon, Elena; Puertolas, Jose Ramón

    2014-01-01

    Short-course preoperative radiotherapy (RT) is widely used in northern Europe for locally advanced resectable rectal cancer, but its role in the era of advanced imaging techniques is uncertain. Here, we reviewed articles and abstracts on SCRT published from 1974 through 2013 with the goal of identifying patients who might be best suited for short-course RT. We included relevant articles comparing surgery with or without preoperative radiation published before and after the advent of total mesorectal excision. We also analyzed two randomized trials directly comparing short-course RT with conventionally fractionated chemoradiation (the Polish Colorectal Study Group and the Trans-Tasman Radiation Oncology Group) that compared short-course RT with conventional chemoradiotherapy. We conclude from our review that short-course RT can be generally applied for operable rectal cancer and produces high rates of pelvic control with acceptable toxicity; it reduces local recurrence rates but does not increase overall survival. SCRT seems to be best used for tumors considered “low risk,” i.e., those that are >5 cm from the anal margin, without circumferential margin involvement, and involvement of fewer than 4 lymph nodes. Whether sequential chemotherapy can further improve outcomes remains to be seen, as does the best time for surgery (immediately or 6–8 weeks after RT). We further recommend that selection of patients for short-course RT should be based on findings from magnetic resonance imaging or transrectal ultrasonography. PMID:25535578

  9. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    SciTech Connect

    Chen, Shang-Wen; Lin, Li-Ching; Kuo, Yu-Cheng; Liang, Ji-An; Kuo, Chia-Chun; Chiou, Jeng-Fong

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  10. A Phase II Study of Sorafenib in Advanced Uterine Carcinoma / Carcinosarcoma: A Trial of the Chicago, PMH, and California Phase II Consortia

    PubMed Central

    Nimeiri, Halla S.; Oza, Amit M.; Morgan, Robert J.; Huo, Dezheng; Elit, Laurie; Knost, James A.; Wade, James L.; Agamah, Edem; Vokes, Everett E.; Fleming, Gini F.

    2010-01-01

    Objectives To determine the efficacy and safety of single agent sorafenib, an oral multi-targeted tyrosine kinase inhibitor, in patients with advanced uterine carcinoma and carcinosarcoma. Methods This multi-institutional non-randomized phase II trial enrolled two cohorts: patients with uterine carcinoma (cohort A) and uterine carcinosarcoma (cohort B). Eligibility criteria included measurable disease, 0–1 prior chemotherapy regimens, and ECOG performance status ≤ 2. Sorafenib at a dose of 400 mg was administered orally twice daily. A cycle was defined as 28 days. Objective tumor response was the primary endpoint and was assessed following every two cycles. Results Fifty–six patients (40 with carcinoma, 16 with carcinosarcoma) were enrolled between March 2005 and August 2007. Two (5%) patients with uterine carcinoma had a partial response (PR) and 17 (42.5%) achieved stable disease (SD). Five had SD lasting at least 4 months. The 6-month progression free survival rate for patients with carcinoma was 29%, and the median overall survival was 11.4 months. No patients with carcinosarcoma had an objective response. Four (25%) had SD, and one had SD lasting 18 months. The 6-month progression free survival rate was 13%, and the median overall survival was 5.0 months. Grade 3/4 drug related toxicities included: hypertension (13%), hand-foot syndrome (13%), hypophosphatemia (7%), anemia (5%), rash (5%), diarrhea (5%), thrombosis (5%), fatigue (5%) and bleeding (5%). Conclusion Sorafenib had minimal activity in patients with uterine carcinoma. Predictive factors for potential benefit are needed. PMID:20117828

  11. Mycobacterium conceptionense Bloodstream Infection in a Patient with Advanced Gastric Carcinoma.

    PubMed

    Yaita, Kenichiro; Matsunaga, Mototsugu; Tashiro, Naotaka; Sakai, Yoshiro; Masunaga, Kenji; Miyoshi, Hiroaki; Oshima, Koichi; Chikamatsu, Kinuyo; Takaki, Akiko; Mitarai, Satoshi; Watanabe, Hiroshi

    2017-01-24

    A 65-year-old Japanese male farmer with advanced gastric adenocarcinoma and multiple hepatic metastases was admitted to our hospital. Blood culture results were positive on day 5, and Gram-positive rods were detected. According to the results of Ziehl-Neelsen staining and a cultured colony of this bacterium, we suspected a mycobacterial infection. Suspecting a rapidly growing mycobacterium (RGM), we started multidrug therapy with levofloxacin, clarithromycin, and ethambutol, and the patient recovered from the bloodstream infection. Further gene examination (16S rRNA, hsp65, and sodA) revealed an isolate of Mycobacterium conceptionense. M. conceptionense was first identified as an RGM in 2006. Among previous case reports of M. conceptionense infections, bone and soft tissue infections in hosts with a disorder of the normal structure (e.g., surgical sites) were dominant. We report the characteristics of M. conceptionense infection in this first Japanese case report and a review of the literature.

  12. Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

    PubMed Central

    Bayraktar, Soley; Rocha-Lima, Caio M

    2013-01-01

    Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death in both men and women in the United States. Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease. Improvements in overall survival and quality of life have been modest. Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics, thus changing the treatment paradigm for many NSCLC patients. In this review, we present a summary of many of the currently investigated biologic targets in NSCLC, discuss their current clinical trial status, and also discuss the potential for development of other targeted agents. PMID:23696960

  13. Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma of the uterine cervix

    SciTech Connect

    Kato, Shingo . E-mail: s.kato@nirs.go.jp; Ohno, Tatsuya; Tsujii, Hirohiko; Nakano, Takashi; Mizoe, Jun-etsu; Kamada, Tadashi; Miyamoto, Tadaaki; Tsuji, Hiroshi; Kato, Hirotoshi; Yamada, Shigeru; Kandatsu, Susumu; Yoshikawa, Kyosan; Ezawa, Hidefumi; Suzuki, Michiya

    2006-06-01

    Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. Methods and Materials: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had Stage IIIB disease, and 14 patients had Stage IVA disease. Median tumor size was 6.5 cm (range, 4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalents (GyE) (2.2-3.0 GyE per fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose, 68.8 or 72.8 GyE). Results: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were {>=}60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rate for patients in the first and second studies was 45% and 79%, respectively. When treated with {>=}62.4 GyE, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors {>=}6.0 cm (64%). Conclusions: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to <60 GyE to avoid major complications. Although the number of patients in this study was small, the results support continued investigation to confirm therapeutic efficacy.

  14. Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

    PubMed Central

    2010-01-01

    Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12) were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol. Results Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. Trial Registration Current Controlled Trials ISRCTN64487365. PMID:20735834

  15. Budget impact analysis of first-line treatment with pazopanib for advanced renal cell carcinoma in Spain

    PubMed Central

    2013-01-01

    Background Due to economic constraints, cancer therapies are under close scrutiny by clinicians, pharmacists and payers alike. There is no published pharmacoeconomic evidence guiding the choice of first-line therapy for advanced renal cell carcinoma (RCC) in the Spanish setting. We aimed to develop a model describing the natural history of RCC that can be used in healthcare decision-making. We particularly analyzed the budget impact associated with the introduction of pazopanib compared to sunitinib under the Spanish National Healthcare System (NHS) perspective. Methods We developed a Markov model to estimate the future number of cases of advanced RCC (patients with favorable or intermediate risk) resulting either from initial diagnosis or disease progression after surgery. The model parameters were obtained from the literature. We assumed that patients would receive either pazopanib or sunitinib as first-line therapy until disease progression. Pharmacological costs and costs associated with the management of adverse events (AE) were considered. A univariate sensitivity analysis was undertaken in order to test the robustness of the results. Results The model predicted an adult RCC prevalence of 7.5/100,000 (1-year), 20.7/100,000 (3-year) and 32.5/100,000 (5-year). These figures are very close to GLOBOCAN reported RCC prevalence estimates of 7.6/100,000, 20.2/100,000 and 31.1/100,000, respectively. The model predicts 1,591 advanced RCC patients with favorable or intermediate risk in Spain in 2013. Annual per patient pharmacological costs were €32,365 and €39,232 with pazopanib and sunitinib, respectively. Annual costs associated with the management of AE were €662 and €974, respectively. Overall annual per patient costs were €7,179 (18%) lower with pazopanib compared to sunitinib. For every point increase in the percentage of patients treated with pazopanib, the NHS would save €67,236. If all the 1,591 patients predicted were treated with pazopanib, the

  16. Integrated Analysis of Long Noncoding RNA and mRNA Expression Profile in Advanced Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Lian, Meng; Ma, Hongzhi; He, Ning; Liu, Honggang; Wang, Haizhou; Fang, Jugao

    2016-01-01

    Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the expression pattern and function of lncRNAs in laryngeal squamous cell carcinoma (LSCC) are still unclear. To investigate the aberrantly expressed lncRNAs and mRNAs in advanced LSCC, we screened lncRNA and mRNA expression profiles in 9 pairs of primary Stage IVA LSCC tissues and adjacent non-neoplastic tissues by lncRNA and mRNA integrated microarrays. Gene Ontology and pathway analysis were performed to find out the significant function and pathway of the differentially expressed mRNAs, gene-gene functional interaction network and ceRNA network were constructed to select core mRNAs, and lncRNA-mRNA expression correlation network was built to identify the interactions between lncRNA and mRNA. qRT-PCR was performed to further validate the expressions of selected lncRNAs and mRNAs in advanced LSCC. We found 1459 differentially expressed lncRNAs and 2381 differentially expressed mRNAs, including 846 up-regulated lncRNAs and 613 down-regulated lncRNAs, 1542 up-regulated mRNAs and 839 down-regulated mRNAs. The mRNAs ITGB1, HIF1A, and DDIT4 were selected as core mRNAs, which are mainly involved in biological processes, such as matrix organization, cell cycle, adhesion, and metabolic pathway. LncRNA-mRNA expression correlation network showed LncRNA NR_027340, MIR31HG were positively correlated with ITGB1, HIF1A respectively. LncRNA SOX2-OT was negatively correlated with DDIT4. qRT-PCR further validated the expression of these lncRNAs and mRNAs. The work provides convincing evidence that the identified lncRNAs and mRNAs are potential biomarkers in advanced LSCC for further future studies. PMID:28033431

  17. Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-07-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  18. [A successful case of systemic chemotherapy followed by liver resection for advanced hepatocellular carcinoma with highly vascular invasion and multiple pulmonary metastases].

    PubMed

    Mizukami, Tatsuzo; Kamiyama, Toshiya; Nakanishi, Kazuaki; Taniguchi, Masahiko; Yokoo, Hideki; Tahara, Munenori; Kakisaka, Tatsuhiko; Kamachi, Hirofumi; Matsushita, Michiaki; Todo, Satoru

    2011-05-01

    The prognosis for hepatocellular carcinoma with extrahepatic metastasis or vascular invasion is very poor. We treated a case successfully by combining chemotherapy and liver resection for hepatocellular carcinoma with multiple pulmonary metastases and vascular invasion. A 56-year-old man who complained of abdominal pain in his right side was transported to the hospital by ambulance. Because CT scan revealed the rupture of hepatocellular carcinoma, he underwent emergency transcatheter arterial embolization (TAE). A close examination revealed tumor thrombus in the inferior vena cava and posterior segment of the portal vein branch, with multiple pulmonary metastases. We conducted right hepatic lobectomy and removal of the inferior vena cava tumor thrombus. After the operation, pulmonary metastatic lesions gradually grew larger, so the oral administration of S-1 at 120 mg per day was started. At the end of the first course, the CT scan revealed that multiple pulmonary metastases were significantly reduced, and treatment was maintained until the end of 4 courses. A prolongation of survival could be expected by combining systemic chemotherapy and liver resection for advanced hepatocellular carcinoma such as the present case.

  19. Two Cases of an Epidermoid Cyst Developing in an Intrapancreatic Accessory Spleen Identified during Laparoscopic Distal Pancreatectomy

    PubMed Central

    Fujii, Masakuni; Yoshioka, Masao; Shiode, Junji

    2016-01-01

    Epidermoid cysts presenting within an intrapancreatic accessory spleen are rare non-neoplastic cysts typically occurring in the pancreatic tail. This entity is difficult to diagnose given there are many types of pancreatic neoplastic cysts. We herein describe two cases of an epidermoid cyst within an intrapancreatic accessory spleen for which we performed a resection by laparoscopic distal pancreatectomy. Epidermoid cysts in an intrapancreatic accessory spleen should therefore be considered in the differential diagnosis of pancreatic tail cystic lesions. Laparoscopic distal pancreatectomy can be a useful, minimally invasive surgical approach for treating these cysts as well as for the treatment of benign or low-grade malignant tumors located in the pancreatic body or tail. PMID:27803407

  20. Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck

    SciTech Connect

    Giri, P.G.; Gemer, L.S. )

    1991-09-01

    The authors treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.

  1. Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma

    PubMed Central

    Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek

    2016-01-01

    Aim of the study Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Results Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved – without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Conclusions Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM. PMID:27095938

  2. Cine MRI of swallowing in patients with advanced oral or oropharyngeal carcinoma: a feasibility study.

    PubMed

    Kreeft, Anne Marijn; Rasch, Coen R N; Muller, Sara H; Pameijer, Frank A; Hallo, Eeke; Balm, Alfons J M

    2012-06-01

    Treatment of oral and oropharyngeal cancer may cause dysphagia. Purpose is to examine whether cine magnetic resonance imaging (MRI) yields additional information compared to standard examination in the evaluation of posttreatment dysphagia and mobility of oral and oropharyngeal structures. Thirty-four cine MRIs were made in 23 patients with advanced oral and oropharyngeal cancer, consisting of an MR image every 800 ms during swallowing which is compared to videofluoroscopy and quality of life questionnaires. A scoring system was applied to assess mobility on cine MR and videofluoroscopy leading to a score ranging from 9 to 17. Cine MRI of the swallowing in a midsagittal plane visualized the tumor (if located in the same plane), important anatomic structures and surgical reconstructions. Posttreatment mobility on cine MRI and videofluoroscopy was significantly diminished compared to pretreatment, mean pretreatment cine MRI score was 10.8 and posttreatment 12.4 (p = 0.017). Impaired mobility on cine MRI was significantly correlated to more swallowing problems (Spearman's correlation coefficient 0.73, p = 0.04), on videofluoroscopy not. Cine MRI is a promising new technique as an adjunct to standard examinations for evaluation of swallowing in patients with oral and oropharyngeal cancer. Cine MRI directly visualizes the dynamics of swallowing and allows evaluation of pre- and posttreatment differences. Abnormal findings are significantly correlated with subjective swallowing complaints of patients.

  3. Up-regulation of miR-187 modulates the advances of oral carcinoma by targeting BARX2 tumor suppressor

    PubMed Central

    Lin, Shu-Chun; Kao, Shou-Yen; Chang, Jennifer Chen-Yu; Liu, Ying-Chieh; Yu, En-Hao; Tseng, Ssu-Hsueh; Liu, Chung-Ji; Chang, Kuo-Wei

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Aberrations in miRNA regulation are known to play important roles in OSCC pathogenesis. miR-187 was shown to be up-regulated in head and neck malignancies in our previous screening. This study further investigated the oncogenic potential, clinical implications, and targets of miR-187 in OSCC. We observed that miR-187 increased oncogenicity, particularly migration, of OSCC cells. miR-187 expression increased the xenografic tumorigenicity and metastasis in mice. In addition, metastatic human OSCC had higher miR-187 expression than did non-metastatic tumors. Through vigorous screening, we confirmed BarH-like Homeobox 2 (BARX2) gene as an miR-187 target. BARX2 expression suppressed the migration, invasion, anchorage-independent colony formation, and orthotopic tumorigenesis of OSCC cells. The migratory phenotype and neck metastasis induced by miR-187 was rescued by BARX2 expression. BARX2 expression was down-regulated in the vast majority of OSCC, and this down-regulation was particularly conspicuous in tumors with advanced nodal metastasis. In addition, plasma miR-187 was significantly higher in OSCC patients than in normal individuals. This study highlights the roles of miR-187-BARX2 in driving the carcinogenesis of OSCC. The results suggest that miR-187 is a potential serological marker for OSCC and that targeting of miR-187 might prove effective in attenuating nodal metastasis. PMID:27542258

  4. Preoperative Intensity Modulated Radiation Therapy and Chemotherapy for Locally Advanced Vulvar Carcinoma: Analysis of Pattern of Relapse

    SciTech Connect

    Beriwal, Sushil; Shukla, Gaurav; Shinde, Ashwin; Heron, Dwight E.; Kelley, Joseph L.; Edwards, Robert P.; Sukumvanich, Paniti; Richards, Scott; Olawaiye, Alexander B.; Krivak, Thomas C.

    2013-04-01

    Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IV{sub A} (stage I, n=3; stage II, n=13; stage III, n=23; stage IV{sub A}, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13 of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.

  5. Proteomic Analysis of Matched Formalin-Fixed, Paraffin-Embedded Specimens in Patients with Advanced Serous Ovarian Carcinoma

    PubMed Central

    Smith, Ashlee L.; Sun, Mai; Bhargava, Rohit; Stewart, Nicolas A.; Flint, Melanie S.; Bigbee, William L.; Krivak, Thomas C.; Strange, Mary A.; Cooper, Kristine L.; Zorn, Kristin K.

    2013-01-01

    Objective: The biology of high grade serous ovarian carcinoma (HGSOC) is poorly understood. Little has been reported on intratumoral homogeneity or heterogeneity of primary HGSOC tumors and their metastases. We evaluated the global protein expression profiles of paired primary and metastatic HGSOC from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: After IRB approval, six patients with advanced HGSOC were identified with tumor in both ovaries at initial surgery. Laser capture microdissection (LCM) was used to extract tumor for protein digestion. Peptides were extracted and analyzed by reversed-phase liquid chromatography coupled to a linear ion trap mass spectrometer. Tandem mass spectra were searched against the UniProt human protein database. Differences in protein abundance between samples were assessed and analyzed by Ingenuity Pathway Analysis software. Immunohistochemistry (IHC) for select proteins from the original and an additional validation set of five patients was performed. Results: Unsupervised clustering of the abundance profiles placed the paired specimens adjacent to each other. IHC H-score analysis of the validation set revealed a strong correlation between paired samples for all proteins. For the similarly expressed proteins, the estimated correlation coefficients in two of three experimental samples and all validation samples were statistically significant (p < 0.05). The estimated correlation coefficients in the experimental sample proteins classified as differentially expressed were not statistically significant. Conclusion: A global proteomic screen of primary HGSOC tumors and their metastatic lesions identifies tumoral homogeneity and heterogeneity and provides preliminary insight into these protein profiles and the cellular pathways they constitute.

  6. Survival analysis of patients with advanced-stage nasopharyngeal carcinoma according to the Epstein-Barr virus status

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Guo, Rui; Li, Wen-Fei; Mao, Yan-Ping; Tan, Ling-Long; Sun, Ying; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Ma, Jun

    2016-01-01

    Purpose The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV). Results Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC. Methods and Materials Data on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared. Conclusions EBV status was an independent prognostic factor for patients with stage III–IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients. PMID:27008701

  7. Second-line ramucirumab therapy for advanced hepatocellular carcinoma (REACH): an East Asian and non-East Asian subgroup analysis

    PubMed Central

    Park, Joon Oh; Ryoo, Baek-Yeol; Yen, Chia-Jui; Kudo, Masatoshi; Yang, Ling; Abada, Paolo B.; Cheng, Rebecca; Orlando, Mauro; Zhu, Andrew X.; Okusaka, Takuji

    2016-01-01

    Purpose REACH investigated second-line ramucirumab therapy for advanced hepatocellular carcinoma. Results Median overall survival was 8.2 months for ramucirumab and 6.9 months for placebo (HR, 0.835; 95% CI, 0.634–1.100; p = 0.2046) for East Asians, and 10.1 months for ramucirumab and 8.0 months for placebo (HR, 0.895; 95% CI, 0.690–1.161; p = 0.4023) for non-East Asians. Median overall survival in patients with baseline alpha-fetoprotein ≥ 400 ng/mL was 7.8 months for ramucirumab and 4.2 months for placebo (HR, 0.749; 95% CI, 0.519–1.082; p = 0.1213) for East Asians (n = 139), and 8.2 months for ramucirumab and 4.5 months for placebo (HR, 0.579; 95% CI, 0.371–0.904; p = 0.0149) for non-East Asians (n = 111). The most common grade ≥ 3 treatment-emergent adverse events in East Asians and non-East Asians included hypertension and malignant neoplasm progression. Materials and methods A post-hoc analysis of East Asians (N = 252) and non-East Asians (N = 313) in the intent-to-treat population was performed. Conclusions In East Asians and non-East Asians, ramucirumab did not significantly prolong overall survival. In patients with baseline alpha-fetoprotein ≥ 400 ng/mL, a potentially larger survival benefit was observed in both subgroups. Safety for East Asians was similar to non-East Asians. PMID:27776351

  8. Prevalence of regional and distant metastasis in cats with advanced oral squamous cell carcinoma: 49 cases (2005-2011).

    PubMed

    Soltero-Rivera, Maria M; Krick, Erika L; Reiter, Alexander M; Brown, Dorothy C; Lewis, John R

    2014-02-01

    The objective of this study was to evaluate the prevalence of regional and distant metastasis in cats with advanced oral squamous cell carcinoma (SCC) in a retrospective case series. Forty-nine cats with cytologically- or histopathologically-confirmed oral SCC presented to the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania. History, clinical and laboratory results, diagnostic imaging findings and survival times were obtained from the medical records of patients who received diagnostic evaluation for metastasis. The prevalence of metastasis was assessed by means of mandibular lymph node cytology and three-view thoracic radiography. The prevalence of mandibular lymph node metastasis was 31% (15/49). Evidence of possible thoracic metastasis was seen in 10% (5/49) of cases. Of the patients with mandibular lymph node metastasis, 53% (8/15) were maxillary, 27% mandibular (4/15), 13% sublingual (2/15) and 7% caudal pharyngeal (1/15). Pulmonary metastasis was seen in three mandibular, one maxillary and one sublingual mass. Forty-one patients died or were euthanased owing to progression of local disease, and seven patients were lost to follow-up. The prevalence of regional metastasis in this study was more common than most previously reported studies, while the rate of pulmonary metastasis was higher than has previously been published. Although significant conclusions cannot be drawn, control of the primary tumor, regardless of tumor size at diagnosis, appears to be an important factor in improving survival time, and therefore treatment of metastasis may be important in those cases where long-term control of the primary tumor is possible.

  9. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-12-30

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  10. Dumbbell-shaped intradiploic epidermoid cyst involving the dura mater and cerebellum.

    PubMed

    Ichimura, Shinya; Hayashi, Toshiyuki; Yazaki, Takahito; Yoshida, Kazunari; Kawase, Takeshi

    2008-02-01

    A 55-year-old woman presented with an epidermoid cyst extending to the cerebellum manifesting as headaches and pain in the left eye. Magnetic resonance imaging showed an intradiploic part with ring enhancement and an intracerebellar part. Intraoperative inspection revealed erosion of the occipital bone and defective dura mater. The tumor was located both epidurally and subdurally and the cyst consisted of pearly white keratin. The tumor was totally removed and the patient was discharged with no neurological deficit. The intradiploic part of the tumor formed the body and the intracerebellar part was caused by inflammatory reaction, which resulted in the atypical enhancement of the intradiploic part.

  11. Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report

    PubMed Central

    Bezpalko, Kseniya; Mohamed, Mohamed A.; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth

    2015-01-01

    Introduction At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. Presentation of case A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. Discussion The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Conclusion Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. PMID:26275738

  12. Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2.

    PubMed

    Mir, Olivier; Coriat, Romain; Dhooge, Marion; Perkins, Géraldine; Boudou-Rouquette, Pascaline; Brezault, Catherine; Ropert, Stanislas; Durand, Jean-Philippe; Chaussade, Stanislas; Goldwasser, François

    2012-08-01

    The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.

  13. Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-05-02

    Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  14. The apoptosis effect of hispolon from Phellinus linteus (Berkeley & Curtis) Teng on human epidermoid KB cells.

    PubMed

    Chen, Wei; He, Fei-Yu; Li, Yong-Quan

    2006-04-21

    Phellinus linteus (Berkeley & Curtis) Teng, a well-known fungus of the genus Phellinus in the family of Hymenochaetaceae, is being increasingly used to treat a wide variety of disease processes such as oral ulcer, gastroenteric disorder, inflammation, lymphatic disease, and various cancers. However, the mechanism underlying its anti-oral cancer effect is poorly understood. In the present study, we prepared the ethanol extract of Phellinus linteus as a crude drug, and then obtained the active component hispolon by bioassay-guided isolation. Hispolon showed a dose-dependent inhibition of human epidermoid KB cell proliferation with IC50 of 4.62+/-0.16 microg/ml. Furthermore, it was revealed that hispolon could induce human epidermoid KB cell apoptosis with the characteristic of a DNA ladder, and with a significant increase of sub-G1. This process was accompanied by the collapse of mitochondrial membrane potential, the release of cytochrome c and the activation of Caspase-3. These results demonstrated that hispolon induced the death of KB cells through a mitochondria mediated apoptotic pathway. We propose that Phellinus linteus and its effective components could be used as an anti-oral cancer drug for future studies.

  15. Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-08

    Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

  16. Unusual coexistence of an epidermoid cyst with an atypical meningioma: Case report and review of the literature

    PubMed Central

    Karekezi, Claire; El Fatemi, Nizare; Egu, Komi; Ibrahimi, Mohamed; El Maaqili, Moulay Rachid; El Abbadi, Najia

    2016-01-01

    Background: Coexistence of multiple primary intracranial tumors of different cell types has rarely been documented; the association of a meningioma and a glioma has been reported as the most common combination. Hereby, we report an unusual case of a temporal epidermoid cyst coexisting with an atypical meningioma. Case Presentation: A 37-year-old male presented with progressive symptoms of raised intracranial progression with progressive loss of vision without any neurological deficit. On admission, magnetic resonance imaging (MRI) revealed a right frontal lesion appearing hypointense T1, hyperintense T2 slightly enhanced after gadolinium and a second right temporal, isointense T1, hyperintense T2 non-enhancing lesion. A right frontotemporal craniotomy was performed that revealed two distinct lesions: The whitish temporal lesion with the pearl appearance reminding of an epidermoid cyst, the second lesion was extraaxial fibrous lesion arising from the falx. Pathology confirmed an atypical meningioma WHO Grade II and an epidermoid cyst. Conclusion: The simultaneous occurrence of primary intracranial tumors of different cell types is rare. Epidermoid cysts are slow growing lesions believed to arise from inclusion of ectodermal elements during neural tube closure, while meningiomas arise from arachnoidal cells; their association has rarely been reported previously. PMID:27069741

  17. Epidermoid tumour (tumor perlée, cholesteatoma) of the fourth ventricle: case report and review of literature

    PubMed Central

    Scott, Michael

    1974-01-01

    The history, clinical course, and the 17 year follow-up after surgery are reported in a patient who had an epidermoid tumour removed from the fourth ventricle. The gross appearance of the contents of the tumour showed multiple tissue aggregates, with the classical pearl-like appearance. Previous cases reported in the literature are collated. Images PMID:4448996

  18. Does MRI-detected cranial nerve involvement affect the prognosis of locally advanced nasopharyngeal carcinoma treated with intensity modulated radiotherapy?

    PubMed

    Zong, Jingfeng; Lin, Shaojun; Chen, Yunbin; Wang, Bingyi; Xiao, Youping; Lin, Jin; Li, Rui; Pan, Jianji

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is one of the common cancers in South China. It can easily invade into cranial nerves, especially in patients with local advanced disease. Despite the fact that the magnetic resonance imaging (MRI) findings are not always consistent with the symptoms of CN palsy, MRI is recommended for the detection of CN involvement (CNI). However, the prognostic impact of MRI-detected CNI in NPC patients is still controversial. To investigate the prognostic value of MRI detected CNI, we performed a retrospective analysis on the clinical data of 375 patients with NPC who were initially diagnosed by MRI. All patients had T3-4 disease and received radical intensity modulated radiation therapy (IMRT) as their primary treatment. The incidence of MRI-detected CNI was 60.8%. A higher incidence of MRI-detected CNI was observed in T4 disease compared with T3 disease (96.8% vs. 42.8%, P<0.001), and a higher incidence was also found in patients with Stage IV disease compared with those with Stage III disease (91.5% vs. 42.3%; P<0.001). The local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) of patients with T3 disease, with or without MRI-detected CNI, was superior to that of patients with T4 disease (P<0.05). No significant differences in LRFS, DMFS or OS were observed between T3 patients with or without MRI-detected CNI. The survival of Stage III patients with or without MRI-detected CNI was significantly superior to that of Stage IV patients (P<0.01), but there was no significant difference between Stage III patients with or without MRI-detected CNI for all endpoints. Therefore, when treated with IMRT, MRI-detected CNI in patients with NPC does not appear to affect the prognosis. In patients with clinical T3 disease, the presence of MRI-detected CNI is not sufficient evidence for defining T4 disease.

  19. SERUM SOLUBLE B7x IS ELEVATED IN RENAL CELL CARCINOMA PATIENTS AND IS ASSOCIATED WITH ADVANCED STAGE

    PubMed Central

    Thompson, R. Houston; Zang, Xingxing; Lohse, Christine M.; Leibovich, Bradley C.; Slovin, Susan F.; Reuter, Victor E.; Cheville, John C.; Blute, Michael L.; Russo, Paul; Kwon, Eugene D.; Allison, James P.

    2008-01-01

    B7x is the newest member of the B7-CD28 family and is thought to dampen immune responses via negative costimulation. Tumor expression of B7x was recently described in renal cell carcinoma (RCC) and was associated with poor outcome. We developed an assay to detect serum soluble B7x (sB7x) and investigated 101 patients with clear cell RCC who underwent nephrectomy between 2003 and 2007. For controls, we obtained serum from 101 sex-matched blood donors within the same age range. Following an Enzyme-Linked Immunosorbent Assay for sB7x, detectable levels (>0.1ng/ml) of sB7x were observed in 53 RCC patients compared with 18 controls (padvanced tumor stage. These early results merit further investigation of this serum marker for potential diagnostic and prognostic purposes. PMID:18676826

  20. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  1. A Prospective Comparative Study of the Toxicity Profile of 5-Flurouracil, Adriamycin, Cyclophosphamide Regime VS Adriamycin, Paclitaxel Regime in Patients with Locally Advanced Breast Carcinoma

    PubMed Central

    Pillai, Pradeep Sadasivan; Jayakumar, Krishnan Nair Lalithamma

    2015-01-01

    Introduction A 5-flurouracil, Adriamycin, Cyclophosphamide (FAC) and Adriamycin, Paclitaxel (AT) are two popular chemotherapeutic regimens for treatment of breast carcinoma. The most time tested and popular regimen is FAC. It is extensively studied for efficacy and toxicity. But data regarding toxicity profile and efficacy of AT regimen is sparse. Aim To study the toxicity profile, severity of toxicities and clinical response rate of FAC and AT regimens in patients with locally advanced breast carcinoma. Materials and Methods A prospective observational study with 50 patients in each treatment arm. Study duration was 12 months from November 2012 to October 2013. Consecutive patients with locally advanced breast carcinoma receiving treatment with either FAC or AT regimen, satisfying inclusion criteria were enrolled into the study after getting informed written consent. Prior to initiation of treatment detailed medical history was taken from all patients. General clinical examination, examination of organ systems and local examination of breast lump were done. After each cycle of chemotherapy and after completion of treatment patients were interviewed and examined for clinical response and toxicities. Toxicities were graded with WHO toxicity grading criteria. All data were entered in a structured proforma. At least 50% reduction in tumour size was taken as adequate clinical response. Statistical Analysis Data was analysed using Chi-square test with help of Excel 2007 and SPSS-16 statistical software. Results Different pattern of toxicities were seen with FAC and AT regimens. Anaemia, thrombocytopenia, stomatitis, hyperpigmentation, photosensitivity and diarrhoea were more common with patients receiving FAC regimen. Leucopenia, peripheral neuropathy, myalgia, arthralgia, vomiting and injection site reactions were more common in AT regimen. Both FAC and AT regimens gave 100% clinical response. Conclusion FAC and AT regimens are equally efficacious but have different

  2. A Trial of PT2977 Tablets In Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-12-22

    Advanced Solid Tumors; Solid Tumor; Solid Carcinoma; Solid Tumor, Adult; ccRCC; RCC, Clear Cell Adenocarcinoma; RCC; Kidney Cancer; Clear Cell Renal Cell Carcinoma; Renal Cell Carcinoma, Metastatic; Renal Cell Carcinoma Recurrent; Renal Cell Carcinoma, Clear Cell Adenocarcinoma

  3. A Phase I Trial of Oblimersen Sodium in Combination With Cisplatin and 5-Fluorouracil in Patients with Advanced Esophageal, Gastroesophageal Junction and Gastric Carcinoma

    PubMed Central

    Raab, Rachel; Sparano, Joseph A.; Ocean, Allyson J.; Christos, Paul; Ramirez, Mark; Vinciguerra, Vincent; Kaubisch, Andreas

    2012-01-01

    Purpose To determine the maximum tolerated dose of oblimersen, an antisense oligonucleotide directed to the Bcl-2 mRNA, in combination with cisplatin and 5-flourouracil in patients with advanced gastric and esophageal carcinoma. Methods Patients were treated with escalating doses of oblimersen administered by continuous intravenous infusion (CIVI) days 1 to7, CIVI 5-fluorouracil (5-FU) days 4 to 7, and cisplatin on day 4 every three weeks. Results Fifteen patients received a total of 49 courses of oblimersen at doses of 3, 5, or 7 mg/kg/d given as a seven day CIVI in combination with 4 or 5 day CIVI of 5-FU (1000 or 750 mg/m2/d) plus intravenous cisplatin (100 or 75 mg/m2 over 2 hours). The recommended phase II dose of oblimersen was 5 mg/kg/day in combination with 5-FU (750 mg/m2/day for 4 days) and cisplatin (75 mg/m2). The most common grade 3 to 4 adverse events that occurred in at least 10% of patients at all dose levels included neutropenia (33%), hypokalemia (27%), infection (20%), and mucositis, fatigue, dizziness, thrombosis, and dehydration (in 13% for each category). Conclusion The combination of oblimersen with 5-FU and cisplatin chemotherapy is feasible in patients with advanced upper gastrointestinal cancer, with antitumor activity observed in gastric carcinoma. PMID:19738454

  4. Defining the concept of locally advanced squamous cell carcinoma of the vulva: a new perspective based on standardization of criteria and current evidence.

    PubMed

    Aragona, Alejandro M; Soderini, Alejandro H; Cuneo, Nicasio A

    2014-10-01

    The phrase "locally advanced carcinoma of the vulva" has often been mentioned in the literature, though not accurately defined, or even leading to the interpretation overlapping. Grounded on cervical cancer experience, we are able to state that designing a tailored primary strategy based on clinically measurable adverse prognostic factors represents the cornerstone of therapy. This fact urged us to rethink about the real usefulness of the concept of locally advanced squamous cell carcinoma of the vulva. We will refer to this concept as a clinical entity emerging from a rigorous workup which is a valuable guiding tool in the context of a thorough debate about the best primary treatment approach to be used. Furthermore, bulky tumors of the vulva have been associated with a worse prognosis on several occasions. Some authors have questioned the fact that tumor size has not been considered in the staging system. Finally, a standardized definition will help us compare the results obtained, which is extremely necessary given the worldwide low prevalence of this disease.

  5. Defining the concept of locally advanced squamous cell carcinoma of the vulva: a new perspective based on standardization of criteria and current evidence

    PubMed Central

    Soderini, Alejandro H.; Cuneo, Nicasio A.

    2014-01-01

    The phrase "locally advanced carcinoma of the vulva" has often been mentioned in the literature, though not accurately defined, or even leading to the interpretation overlapping. Grounded on cervical cancer experience, we are able to state that designing a tailored primary strategy based on clinically measurable adverse prognostic factors represents the cornerstone of therapy. This fact urged us to rethink about the real usefulness of the concept of locally advanced squamous cell carcinoma of the vulva. We will refer to this concept as a clinical entity emerging from a rigorous workup which is a valuable guiding tool in the context of a thorough debate about the best primary treatment approach to be used. Furthermore, bulky tumors of the vulva have been associated with a worse prognosis on several occasions. Some authors have questioned the fact that tumor size has not been considered in the staging system. Finally, a standardized definition will help us compare the results obtained, which is extremely necessary given the worldwide low prevalence of this disease. PMID:25142626

  6. Phase II Trial Of PS-341 (Bortezomib) In Patients With Previously Treated Advanced Urothelial Tract Transitional Cell Carcinoma

    ClinicalTrials.gov

    2013-06-04

    Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Stage IV Urethral Cancer; Transitional Cell Carcinoma of the Bladder; Ureter Cancer

  7. Ruptured pediatric cerebellopontine angle epidermoid cyst: a case report detailing radiographic evolution and clinical course.

    PubMed

    Guan, Zhe; Hollon, Todd; Bentley, J Nicole; Garton, Hugh J L

    2015-08-21

    Epidermoid cysts (ECs) are uncommon pediatric tumors that often occur in the cerebellopontine angle. Although cyst rupture is a recognized complication, the radiographic evolution of an EC following rupture and the resultant parenchymal brainstem edema have not been reported. The authors present the case of a 13-year-old female with a newly diagnosed cerebellopontine angle EC who presented with worsening headaches, photophobia, and emesis. Magnetic resonance imaging demonstrated significant pericystic brainstem edema and mass effect with effacement of the fourth ventricle. Refractory symptoms prompted repeat imaging, revealing cyst enlargement and dense rim enhancement. Resection of the EC resolved both her symptoms and the brainstem edema. This case documents the radiographic evolution of EC rupture and subsequent clinical course.

  8. Case Report: Delayed presentation of penile epidermoid cyst following reconstruction for Peyronie’s disease

    PubMed Central

    Smith-Harrison, Luriel I.; Farhi, Jacques; Costabile, Raymond A.; Smith, Ryan P.

    2015-01-01

    Penile masses are a concerning finding for both patient and clinician upon initial presentation. There is a wide differential for penile masses from the benign (fibrous plaques, cysts, ulcerative lesions, benign penile pearly papules, etc.) to more concerning malignant lesions. A proper history and physical is the first step to determining the etiology of the mass and any future clinical interventions. In this paper, we review a case of a 73-year-old male who is found to have an enlarging mass during work-up for possible placement of inflatable penile prosthesis. Fortunately, the mass was determined to be a benign epidermoid cyst presenting thirty years after reconstruction for Peyronie’s disease using dermal penile skin graft. With this unique presentation we review the scant literature on penile mass formation following Peyronie’s repair. PMID:26835001

  9. Systematic review of vismodegib toxicity profile in the treatment of advanced basal cell carcinomas compared to other systemic therapies in dermatology.

    PubMed

    Juhasz, Margit L W; Marmur, Ellen S

    2014-06-01

    Vismodegib is a first-in-class, hedgehog-signal inhibitor that is FDA-approved for use with advanced basal cell carcinomas (BCCs) that cannot be removed by either surgical resection or treated with radiation. Release of the drug was fast-tracked because of need for this type of drug, and its overall efficacy in clinical trial by producing either regression or even resolution of advanced BCCs. Compared to placebo, patients using vismodegib have arrested BCC progression, reduced size of BCC, and decreased recurrence of BCC. Unfortunately, vismodegib has notable adverse effects (especially those of alopecia, gastrointestinal, muscle spasms, and dysguesia) that make dermatologists reluctant to prescribe the drug and patients unwilling to undergo therapy. In this article, we tackle this dilemma by comparing the toxicity profile of vismodegib to the adverse effect profiles of other dermatologic chemotherapeutics, immunomodulators, retinoids, and biologics. Considering that many of these drugs carry their own risks and those drugs used to treat advanced melanoma have similar toxicity profiles to that of vismodegib, we hope dermatologists and patients alike will be more willing to try vismodegib as a treatment option for advanced BCCs in the future.

  10. Treatment of Advanced or Recurrent Endometrial Carcinoma with Doxorubicin in Patients Progressing after Paclitaxel/Carboplatin: Memorial Sloan-Kettering Cancer Center (MSKCC) Experience from 1995-2009

    PubMed Central

    Makker, Vicky; Hensley, Martee L.; Zhou, Qin; Iasonos, Alexia; Aghajanian, Carol. A.

    2013-01-01

    Objective Long-term survival for patients with advanced endometrial carcinoma is poor, and limited options exist for the management of recurrent disease. Our goal was to investigate the activity of doxorubicin in the second-line setting in patients who progressed after paclitaxel/carboplatin adjuvant treatment. Methods We conducted a retrospective analysis of patients with recurrent endometrial carcinoma who were treated at Memorial Sloan-Kettering Cancer Center from 1995-2009, and who received paclitaxel/carboplatin adjuvant chemotherapy followed by second-line doxorubicin therapy at time of recurrence. The median PFS and OS times following paclitaxel/carboplatin and following second-line doxorubicin therapy were estimated using the Kaplan-Meier method. Toxicity was assessed by the treating physician at each visit and graded using version 4.0 of Common Terminology Criteria for Adverse Events (CTCAE). Patient presentation, treatment, patterns of recurrence, and patient outcomes were summarized. Results Seventeen patients were included in study analyses. The median PFS from completion of paclitaxel/carboplatin was 8.0 months (95% CI: 4.5-13.6 months). At the time of recurrence, all 17 patients were treated with doxorubicin as second-line therapy. No patient achieved objective response of stable disease. The median PFS of this cohort following doxorubicin treatment was 2.1 months (95% CI: 0.95-2.7) months. Median OS was 5.8 months (95% CI: 1.0-15.0 months). There is only one patient still alive; her median follow-up time is 49.4 months. Predominant doxorubicin-related grade 2 toxicities included nausea/vomiting (18.8%), fatigue (18.8%), and neutropenia (12.5%). No grade 3 or 4 toxicities occurred. Conclusions Among patients with advanced endometrial carcinoma who had received adjuvant paclitaxel/carboplatin, treatment with doxorubicin at time of disease recurrence failed to achieve any objective responses and was associated with a very short (2 months) time to

  11. Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma (Cancer) of the Head and Neck

    ClinicalTrials.gov

    2013-01-23

    Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Salivary Gland Adenoid Cystic Carcinoma; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer

  12. 18F-FDG PET/CT can predict survival of advanced hepatocellular carcinoma patients: A multicenter retrospective cohort study.

    PubMed

    Na, Sae Jung; Oh, Jin Kyoung; Hyun, Seung Hyup; Lee, Jeong Won; Hong, Il Ki; Song, Bong-Il; Kim, Tae-Sung; Eo, Jae Seon; Lee, Sung Won; Yoo, Ie Ryung; Chung, Yong An; Yun, Mijin

    2016-10-27

    Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) consists of a heterogeneous group of patients with a wide range of survival times, requiring further prognostic stratification to facilitate treament allocation. We evaluated the prognostic value of (18)F-flurodeoxyglucose ((18)F-FDG) uptake on positron emission tomography/computed tomography (PET/CT) at the time of presentation in patients with BCLC stage C HCC.

  13. [Successful Management by Immunoglobulin for Sunitinib-Induced Thrombocytopenia in a Patient with Advanced Metastatic Renal Cell Carcinoma].

    PubMed

    Okazaki, Satoshi; Hori, Jun-ichi; Watanabe, Masaki; Hashizume, Kazumi; Kobayashi, Shin; Azumi, Makoto; Kita, Masafumi; Iwata, Tatsuya; Matsumoto, Seiji; Kakizaki, Hidehiro

    2016-02-01

    An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-week-on, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×10(9)/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.

  14. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation

    PubMed Central

    Oh, Jinju; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2016-01-01

    Objective The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. Methods A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. Results Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). Conclusion Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival. PMID:27462593

  15. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    ClinicalTrials.gov

    2017-03-10

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  16. ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay

    NASA Astrophysics Data System (ADS)

    DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Samkoe, Kimberley S.; Anand, Sanjay; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopictomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025μg/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by exvivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth.

  17. Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck

    SciTech Connect

    Christiansen, Hans . E-mail: hchrist@gwdg.de; Hermann, Robert Michael; Martin, Alexios; Florez, Rodrigo; Kahler, Elke; Nitsche, Mirko; Hille, Andrea; Steiner, Wolfgang; Hess, Clemens F.; Pradier, Olivier

    2006-07-15

    Purpose: The aim of this study was to evaluate the efficacy of adjuvant radiotherapy after transoral laser microsurgery for advanced recurrent head-and-neck squamous cell carcinoma (HNSCC). Patients and Methods: Between 1988 and 2000, 37 patients with advanced local recurrences (23 local and 14 locoregional recurrences) of HNSCC without distant metastases were treated in curative intent with organ-preserving transoral laser microsurgery and adjuvant radiotherapy (before 1994 split-course radiotherapy with carboplatinum, after 1994 conventional radiotherapy). Initial therapy of the primary (8.1% oral cavity, 35.1% oropharynx, 13.5% hypopharynx, and 43.3% larynx) before relapse was organ-preserving transoral laser microsurgery without any adjuvant therapy. Results: After a median follow-up of 124 months, the 5-year overall survival rate was 21.3%, the loco-regional control rate 48.3%, respectively. In multivariate analysis, stage of original primary tumor (Stage I/II vs. Stage III/IV), and patient age (<58 years vs. {>=}58 years) showed statistically significant impact on prognosis. In laryngeal cancer, larynx preservation rate after treatment for recurrent tumor was 50% during follow-up. Conclusion: Our data show that organ-preserving transoral laser microsurgery followed by adjuvant radiotherapy is a curative option for patients who have advanced recurrence after transoral laser surgery and is an alternative to radical treatment.

  18. Phase II study of concurrent selective lymph node late course accelerated hyper-fractionated radiotherapy and pemetrexed and cisplatin for locally advanced oesophageal squamous cell carcinoma

    PubMed Central

    Fu, C; Guo, L; Li, H; Huang, W; Gong, H; Sun, M; Wang, Z; Zhou, T; Liu, C

    2014-01-01

    Objective: To determine the clinical efficacy and toxicity of pemetrexed combined with low-dose cisplatin (CDDP) concurrent with late-course accelerated hyperfractionated (LCAF) intensity-modulated radiation therapy (IMRT) in patients with inoperable locally advanced oesophageal squamous cell carcinoma (ESCC). Methods: Patients with locally advanced ESCC (less than or equal to 75 years of age, clinical stages IIB–IVA and Karnofsky performance status ≥70) were enrolled into the study. A target group size of 22 was projected based on the estimation that 2-year overall survival (OS) would increase from 20% to 40%. Patients were treated with pemetrexed, low-dose CDDP and LCAF IMRT concurrently. The main objective of the study was for a 2-year OS, and the secondary objectives were progression-free survival (PFS), objective response, locoregional failure rate, and acute and late toxicities. Results: 25 patients were recruited from October 2008 to July 2011. The median OS was 21 months, with 2- and 5-year OS rates of 44% and 44%, respectively. The median PFS was 18.2 months. The objective response rate was 96% (24/25), with 11 complete responses and 13 partial responses. The locoregional failure rate was 16%. Grades 4 and 5 acute toxicity rates were 8% and 4%, respectively, while no Grade 3 or greater late toxicity was observed. Conclusion: The findings of this Phase II study indicated that the therapeutic regimen appears to achieve an excellent response rate and favourable survival for locally advanced ESCC. However, the severe acute side effects should be considered cautiously in further studies. Advances in knowledge: To our knowledge, this is the first study that introduced pemetrexed and low-dose CDDP combined with LCAF IMRT to treat locally advanced ESCC. The 5-year OS rate was as high as 44%, which was more favourable than other studies. PMID:24666012

  19. Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence

    PubMed Central

    Liao, Yadi; Zheng, Yun; He, Wei; Li, Qijiong; Shen, Jingxian; Hong, Jian; Zou, Ruhai; Qiu, Jiliang; Li, Binkui; Yuan, Yunfei

    2017-01-01

    Sorafenib is the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC); however, its therapeutic value in patients with HCC following resection remains controversial. The current retrospective study was undertaken to assess the effects of sorafenib treatment following surgical resection in patients with advanced HCC disease who were at a high risk for recurrence. Between July 2010 and July 2013, a consecutive cohort of 42 patients with advanced HCC and at a high risk of recurrence (i.e., those with portal vein tumor thrombosis, adjacent organ involvement or tumor rupture) who underwent resection were analyzed. The patients were categorized into the sorafenib group (n=14) or the best supportive care (BSC) group (n=28). Although the histological grade, Barcelona Clinic Liver Cancer Stage, tumor size, nodule number and proportion of patients with high serum α-fetoprotein levels were comparable between the sorafenib and BSC groups, those receiving sorafenib following resection had significantly longer disease-free survival (DFS) of 5.2 months [95% confidence interval (CI), 1.2–9.2 months] compared with the BSC group [1.8 months (95% CI, 0.6–3.0 months)]. No differences in overall survival were noted between the groups. Furthermore, no drug-related adverse events resulted in discontinuation of sorafenib therapy. Univariate log-rank analysis revealed that sorafenib treatment (P=0.002) and treatment prior to resection (P=0.012) were significantly associated with longer DFS; however, sorafenib therapy (P=0.027) and tumor size (P=0.028) were associated with longer DFS by multivariate analysis. Furthermore, sorafenib was well-tolerated and improved DFS in patients with advanced HCC who underwent hepatic resection. Thus, tumor resection followed by sorafenib therapy may represent an effective therapeutic strategy for patients with advanced HCC. This possibility should be confirmed in larger, multicenter studies. PMID:28356989

  20. [Gangliosides in the serum in lung carcinoma].

    PubMed

    Fumić, K; Vladović-Relja, T; Karada, J; Kracun, I; Stavljenić, A; Kubat, M; Cosović, C; Oberman, B

    1990-01-01

    In this study, tumor and serum gangliosides were analyzed in patients bearing lung planocellular carcinoma (LPC) before and after operative therapy. Tumor tissue, pathohistologically characterized as carcinoma planocellulare corneum (Ca. epidermoide, type 8070/3, WHO, Geneva, 1981), showed an elevated concentration of gangliosides in comparison to normal tung tissue. The composition of gangliosides in LPC tissue varied from one tumor sample to another, however, two general features were observed. First, LPC contained an increased amount of GM3 and a decreased amount of GD3 gangliosides. Second, an elevated proportion of gangliosides migrating as polysialogangliosides (x3, x5, x6) characterized the majority of LPC tissues. On the other hand, serum of patients with LPC contained an elevated amount of gangliosides (15.8 +/- 0.3 mumols/L) in comparison to control serum (6.1 +/- 0.8 mumols/L) (P less than 0.01). However, analyzing the composition of serum gangliosides by thin-layer chromatography, all serum gangliosides were more or less elevated. By day 21 after the surgical removal of LPC, serum gangliosides dropped by approximately 50% approaching the normal values. It seems that elevated serum gangliosides in LPC patients were secreted from carcinoma cells, because they normalized after surgical removal of LPC. Thus, serum gangliosides might be a useful biochemical tool for diagnosis and therapy monitoring of this carcinoma.

  1. Complete endoscopic resection of a pituitary stalk epidermoid cyst using a combined infrasellar interpituitary and suprasellar endonasal approach: case report.

    PubMed

    Nakassa, Ana C I; Chabot, Joseph D; Snyderman, Carl H; Wang, Eric W; Gardner, Paul A; Fernandez-Miranda, Juan C

    2017-04-14

    Intracranial epidermoid cysts are benign lesions of epithelial origin that most frequently present with symptoms of mass effect. Although they are often associated with a high rate of residual tumor and recurrence, maximal safe resection usually leads to good outcomes. The authors report a complete resection of an uncommon pituitary stalk epidermoid cyst with intrasellar extension using a combined suprasellar and infrasellar interpituitary, endoscopic endonasal transsphenoidal approach. The patient, a 54-year-old woman, presented with headache, visual disturbance, and diabetes insipidus. Postoperatively, she reported improvement in her visual symptoms and well-controlled diabetes insipidus using 0.1 mg of desmopressin at bedtime and normal anterior pituitary gland function. One year later, she continues to receive the same dosage of desmopressin and is also taking 50 mcg of levothyroxine daily after developing primary hypothyroidism unrelated to the surgical procedure. A combined infrasellar interpituitary and suprasellar approach to this rare location for an epidermoid cyst can lead to a safe and complete resection with good clinical outcomes.

  2. Effectiveness of capecitabine with or without docetaxel therapy for the treatment of patients with advanced urothelial carcinoma: a single-institution experience

    PubMed Central

    Cao, Ye; Chen, Tanhuan; Yang, Wei; Deng, Yingfei; Han, Hui; Teng, Xiaoyu; Zhou, Fangjian; Shi, Yanxia

    2016-01-01

    Purpose The purpose of this study was to evaluate the effectiveness and toxicity of capecitabine (C) chemotherapy regimen with or without (w/o) docetaxel (D) in patients with advanced urothelial carcinoma (UC). Results Clinical benefit rate were similar in two arms (C arm vs DC arm: 38.9% vs 45.5%, p = 0.411). There were two cases achieved partial response in DC arm. In C arm, the median PFS was 3.0 months (95% CI 2.5–3.5 months) and median OS was 11.3 months (95% CI 8.6–14.1 months). In DC arm, the median PFS was 2.2 months (95% CI 1.7–2.7 months) and median OS was 18 months (95% CI 6.8–29.9 months). Adverse events were mostly acceptable, including myelosuppession, hand-foot syndrome and mucositis. Anemia and leukopenia was found more in the DC arm than in the C arm. Materials and Methods This is a one-center, observational, retrospective study. From April 2009 to March 2015, a total of 29 patients with metastatic UC were included in the study. Survivals, response rates and toxicities were collected retrospectively. Conclusions The result showed the activity and toxicity of C w/o D. As DC treatment did not reveal better outcome, C or D single-agent might be an option in platinum-failed patients with advanced urothelial carcinoma. Further clinical trials are warranted. PMID:27577082

  3. SU-E-T-809: Volumetric Modulated Arc Radiotherapy Vs. Intensity-Modulated Radiotherapy for Locally Advanced Laryngeal Carcinoma: A Dosimetric Study

    SciTech Connect

    Lu, J-Y; Huang, B-T; Zhang, W-Z; Yan, L-J

    2015-06-15

    Purpose: To compare volumetric modulated arc radiotherapy (VMAT) technique with fixed-gantry intensity-modulated radiotherapy (IMRT) technique for locally advanced laryngeal carcinoma. Methods: CT datasets of eleven patients were included. Dual-arc VMAT and 7-field IMRT plans, which were created based on the Eclipse treatment planning system, were compared in terms of dose-volume parameters, conformity index (CI) and homogeneity index (HI) of planning target volume (PTV), as well as organ-at-risk (OAR) sparing, planning time, monitor units (MUs) and delivery time. Results: Compared with the IMRT plans, the VMAT plans provided lower D2% and better CI/HI for the high-risk PTV (PTV1), and provided better CI and comparable HI for the low-risk PTV (PTV2). Concerning the OAR sparing, the VMAT plans demonstrated significantly lower Dmax of the spinal cord (planning OAR volume, PRV) and brainstem (PRV), as well as lower Dmean and V30Gy of the right parotid. No significant differences were observed between the two plans concerning the doses delivered to the thyroid, carotid, oral cavity and left parotid. Moreover, the VMAT planning (147 ± 18 min) consumed 213% more time than the IMRT planning (48 ± 10 min). The MUs of the VMAT plans (556 ± 52) were 64% less than those of the IMRT plans (1684 ± 409), and the average delivery time (2.1 ± 0.1 min) was 66% less than that of the IMRT plans (6.3 ± 0.7 min). Conclusion: Compared with the IMRT technique, the VMAT technique can achieve superior target dose distribution and better sparing of the spinal cord, brainstem and right parotid, with less MUs and less delivery time. It is recommended for the radiotherapy of locally advanced laryngeal carcinoma.

  4. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    SciTech Connect

    Boscolo-Rizzo, Paolo; Gava, Alessandro; Baggio, Vittorio; Marchiori, Carlo; Stellin, Marco; Fuson, Roberto; Lamon, Stefano; Da Mosto, Maria Cristina

    2011-05-01

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age ({+-}5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m{sup 2}, and a continuous infusion of 5-fluorouracil, 1,000 mg/m{sup 2}/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  5. Concurrent Chemoradiotherapy With Paclitaxel and Nedaplatin Followed by Consolidation Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix: Preliminary Results of a Phase II Study

    SciTech Connect

    Zhang Meiqin; Liu Suping; Wang, Xiang-E.

    2010-11-01

    Purpose: To evaluate the efficacy and toxicities of concurrent chemoradiotherapy (CCRT) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma. Methods and Materials: Patients with LASCC (FIGO Stage IIB-IIIB) were treated with pelvic external beam radiotherapy (45 Gy for Stage IIB and 50 Gy for Stage III) and high-dose-rate intracavitary brachytherapy (50 Gy for Stage IIB and 35 Gy for Stage III). The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III. Concurrent chemotherapy with paclitaxel (35 mg/m{sup 2}) and nedaplatin (20 mg/m{sup 2}) was given every week for 6 weeks. Consolidation chemotherapy with paclitaxel (135 mg/m{sup 2}) and nedaplatin (60 mg/m{sup 2}) was administered every 3 weeks for 4 cycles. Results: All patients completed CCRT, and 28 of 34 patients completed consolidation chemotherapy. The complete response rate was 88% (95% CI, 73-96%). The most common Grade 3 or higher toxicities were leukopenia/neutropenia (10.9% of the cycles). During a median follow up of 23 months (range, 14-30 months), 5 patients had locoregional failure and 1 patient had distant metastasis. The estimated 2-year progression-free survival and overall survival were 82% (95% CI, 68-95%) and 93% (95% CI, 83-100%), respectively. Grade 3 late complications occurred in 3 patients (9%). Conclusions: CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma. Further randomized trials of comparing this regimen with the standard treatment are worth while.

  6. Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity.

    PubMed

    Saxena, Chitrapriya; Aggarwal, Pooja; Wadhwan, Vijay; Bansal, Vishal

    2015-01-01

    Squamous cell carcinoma (SCC) arising from the wall of an odontogenic cyst (also known as primary intraosseous carcinoma) is a rare tumor which occurs only in jaw bones. This tumor was first described by Loos in 1913 as a central epidermoid carcinoma of the jaw. Primary intraosseous carcinomas (PIOC) may theoretically arise from the lining of an odontogenic cyst or de novo from presumed odontogenic cell rests. According to the new histological classification of tumors of the World Health Organization, odontogenic keratocyst is nowadays considered a specific odontogenic tumor and the PIOC derived from it is considered as a specific entity which is different from other PIOCs derived from the odontogenic cysts. The following report describes a case of such extremely rare entity that is primary intraosseous SCC of the mandible derived from an OKC in a 60-year-old male patient with brief review of literature.

  7. Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity

    PubMed Central

    Saxena, Chitrapriya; Aggarwal, Pooja; Wadhwan, Vijay; Bansal, Vishal

    2015-01-01

    Squamous cell carcinoma (SCC) arising from the wall of an odontogenic cyst (also known as primary intraosseous carcinoma) is a rare tumor which occurs only in jaw bones. This tumor was first described by Loos in 1913 as a central epidermoid carcinoma of the jaw. Primary intraosseous carcinomas (PIOC) may theoretically arise from the lining of an odontogenic cyst or de novo from presumed odontogenic cell rests. According to the new histological classification of tumors of the World Health Organization, odontogenic keratocyst is nowadays considered a specific odontogenic tumor and the PIOC derived from it is considered as a specific entity which is different from other PIOCs derived from the odontogenic cysts. The following report describes a case of such extremely rare entity that is primary intraosseous SCC of the mandible derived from an OKC in a 60-year-old male patient with brief review of literature. PMID:26980976

  8. Clinical characteristics and outcome of patients with stage III esophageal carcinoma: a single-center experience from Turkey.

    PubMed

    Ugur, Vahide I; Kara, Sakire P; Kucukplakci, Bulent; Demirkasimoglu, Taciser; Misirlioglu, Cem; Ozgen, Aytul; Elgin, Yesim; Sanri, Ergun; Altundag, Kadri; Ozdamar, Nadi

    2008-01-01

    Esophageal carcinoma is an extremely deadly disease, and prognosis is poor. We retrospectively evaluated stage III esophageal carcinoma patients in our center. Median age of the patients was 52. Men to women ratio were 3/1. Epidermoid carcinoma was the major histology. Incidence of esophageal carcinoma was higher in the distal and middle third of the esophagus. In 19 patients tumor size was more than 5 cm. In total of 17 of the patients were operated. About 58 patients were irradiated. About 45 of the patients were irradiated with curative intent, 31 of them were primarily irradiated and 14 of them were irradiated postoperatively. Only 13 of the patients received concurrent chemoradiotherapy. Overall 1, 2, 3, and 4 year survival rates were 38.9%, 11.1%, 5.6%, and %1.9, respectively and median survival was 12 months. Median survival for tumors located in cervical esophageal, middle esophagus, and distal esophagus were 23, 8, and 14 months, respectively. One, 2, 3, 4 year survival rates of operated patients were 58.8%, 29.4%, 17.6%, 5.9%, respectively and median survival was 23 months. For inoperable patients 1 and 2 year survival rates were 29.7% and 2.7% and median survival was 8 months. Differences between operable and inoperable patients were statistically significant (P: 0.0003). One, 2, 3, 4 years survival results of patients treated with surgery and postoperative radiotherapy was 62.5%, 25%, 12.5%, 12.5% and median survival was 21 months, 1, 2, 3, 4 years survival results of patients treated with surgery and concurrent chemoradiotherapy was 55.6%, 33.3%, 22.2%, and 0% and median survival was 27 months. There was no statistically significant difference between groups (P: 0.5390). During the therapy, disphagia was the major side effect observed in seven patients. Fatigue, pain, and mild weight loss were the other side effects. Three patients could not tolerate the treatment and left the therapy. We demonstrated that stage III esophageal carcinoma is an extremely

  9. Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy

    PubMed Central

    Lee, Sang Ho; Hayano, Koichi; Zhu, Andrew X.; Sahani, Dushyant V.; Yoshida, Hiroyuki

    2015-01-01

    Background To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy. Methods Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (γ), arterial blood flow (BFA), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (vI), extraction fraction, mean intracellular water molecule lifetime (τC), and fractional intracellular volume (vC) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing. Results The WX-TK-model-derived γ (P = 0.022) and vI (P = 0.010), and WX-ETK-model-derived τC (P = 0.023) and vC (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BFA (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived vC (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS. Conclusions The WX-ETK-model-derived vC was an effective prognostic biomarker for advanced HCC treated with sunitinib. PMID:26366997

  10. Nal-IRI With 5-fluorouracil (5-FU) and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Biliary-tract Cancer

    ClinicalTrials.gov

    2017-02-03

    Adenocarcinoma Metastatic; Biliary Tract Cancer; Adenocarcinoma of the Biliary Tract; Adenocarinoma Locally Advanced; Non-Resectable Hepatocellular Carcinoma; Intrahepatic Bile Duct Carcinoma; Extrahepatic Bile Duct Carcinoma

  11. A case-control study of carcinomas of the nose and paranasal sinuses in the woolen textile manufacturing industry.

    PubMed

    Magnani, C; Comba, P; Ferraris, F; Ivaldi, C; Meneghin, M; Terracini, B

    1993-01-01

    A population-based case-control study was conducted in Biella, which is located in northwestern Italy, to investigate the reported association between sinonasal carcinomas and woolen fabrics production. The study included 33 cases diagnosed during 1976-1988 (14 adenocarcinomas, 11 epidermoid carcinomas, 3 other specified carcinomas, 1 unspecified carcinoma, and 4 cases without histologic confirmation) and 131 controls. No association was found with smoking. As reported previously, excess risks were observed in wood and furniture workers (odds ratio [OR] = 4.4, 95% confidence interval [95% CI] = 1.41-13.4) and in the leather industry (OR = 3.5, 95% CI = 0.6-20.3). Odds ratios in the wood and furniture industry were 22.0 (95% CI = 4.4-124.0) for adenocarcinomas and 0.9 (95% CI = 0.4-8.3) for epidermoid carcinomas. No association was found with the woolen textile or garment industries (OR = 0.8, 95% CI = 0.2-2.8), nor with farming, construction, metal works, and transport. Odds ratios for the textile industry did not vary with length of exposure or histologic type. Power for detecting an odds ratio of 3.0 at the 95% level of significance was 40%.

  12. Dysregulation of MALAT1 and miR-619-5p as a prognostic indicator in advanced colorectal carcinoma

    PubMed Central

    Qiu, Gu; Zhang, Xiu-Bing; Zhang, Shu-Qing; Liu, Pei-Long; Wu, Wei; Zhang, Jin-Ye; Dai, Shi-Rong

    2016-01-01

    The present study aimed to detect the expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and microRNA (miR)-619-5p in colorectal carcinoma (CRC), and to evaluate the significance of MALAT1 and miR-619-5p expression in the clinical diagnosis and prognosis of CRC. Quantitative polymerase chain reaction was used to detect MALAT1 and miR-619-5p expression in 120 colorectal carcinoma and 120 adjacent normal tissue samples. The expression levels of MALAT1 and miR-619-5p were significantly different between colorectal carcinoma and adjacent normal tissues (P<0.05). MALAT1 exhibited an average 2.52-fold increase in colorectal adenoma when compared with adjacent normal tissues, while miR-619-5p exhibited an average 5.79-fold decrease in colorectal adenoma when compared with adjacent normal tissues. There was a significant difference between the MALAT1 expression in CRC tissues obtained from men and women (P=0.027), and in tumor-node-metastasis (TNM) stage II and stage III lesions (P=0.019). MALAT1 expression was associated with lymphovascular invasion (P=0.047) and perineural invasion (P=0.012). In addition, miR-619-5p expression was also significantly different between men and women (P=0.032), and between TNM stage II and stage III lesions (P=0.012). miR-619-5p expression was also associated with lymphovascular invasion (P=0.023) and perineural invasion (P=0.009). Patients with high expression of MALAT1 and low expression of miR-619-5p demonstrated significantly shorter disease-free survival (DFS) (P=0.002) and overall survival (OS) times (P=0.004) compared with patients with low MALAT1 expression and high miR-619-5p expression. Patients with perineural invasion demonstrated significantly shorter DFS (P=0.001) and OS times (P=0.003) compared with patients without perineural invasion. In addition, there was a negative correlation between MALAT1 expression and miR-619-5p expression (r=−0.415, P=0.004) in CRC tissues. In conclusion, MALAT1 and mi

  13. CT-Based Evaluation of Tumor Volume After Intra-Arterial Chemotherapy of Locally Advanced Carcinoma of the Oral Cavity: Comparison with Clinical Remission Rates

    SciTech Connect

    Rohde, Stefan Turowski, Bernd; Berkefeld, Joachim; Kovacs, Adorjan F.

    2007-02-15

    Purpose. To assess the volume of locally advanced tumors of the oral cavity and the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of computed tomography and to compare these data with clinically determined treatment response of the same patient population. Methods. Eighty-eight patients with histologically proven, advanced carcinoma of the oral cavity and/or the oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with cisplatin as part of a multimodal therapeutic regimen, comprising (1) local chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after the intervention, residual disease was evaluated radiologically by measurement of the tumor volume and clinically by inspection and palpation of the primary tumor according to WHO criteria. Results. Comparison of treatment response according to radiological and clinical criteria respectively revealed complete remission in 5% vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs. 58%, and tumor progression in 5% vs. 2%. Conclusion. Radiological volumetry and clinical evaluation found comparable response rates after local chemotherapy. However, in patients with good response after local treatment, volumetric measurement with CT may help to distinguish between partial and complete remission. Thus, radiological tumor volumetry provides precise and differentiated information about tumor response and should be used as an additional tool in treatment monitoring after local chemotherapy.

  14. Neutrophil-to-lymphocyte ratio as a prognostic biomarker for patients with locally advanced esophageal squamous cell carcinoma treated with definitive chemoradiotherapy

    PubMed Central

    Zhou, Xi-Lei; Li, Yong-Qiang; Zhu, Wei-Guo; Yu, Chang-Hua; Song, Ya-Qi; Wang, Wan-Wei; He, Dong-Cheng; Tao, Guang-Zhou; Tong, Yu-Suo

    2017-01-01

    The present study evaluated the clinical and prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (dCRT). A total of 517 patients with ESCC were enrolled and analysed retrospectively. The NLR was calculated at three time points: baseline, post-treatment, and at the time of tumor progression. Elevated NLR was defined as a ratio ≥5. High NLR at baseline was present in 204 (39%) patients and was significantly correlated with larger tumour size, advanced TNM stage, worse ECOG performance status, and dCRT response (p < 0.05). At a median follow-up of 17 months, patients with higher NLR at baseline had poorer progression-free survival (PFS) and overall survival (OS). On multivariate analysis, elevated NLR at baseline was independently associated with PFS and OS (HR = 1.529, p < 0.001 for PFS; HR = 1.856, p < 0.001 for OS). In addition, patients with high pre- and post-treatment NLR demonstrated worse clinical outcomes than other groups. Our results suggest that NLR is an independent prognostic indicator for patients with ESCC undergoing dCRT and changes in NLR level with treatment may indicate therapeutic benefit. PMID:28195186

  15. Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multicenter randomized phase II clinical trial

    PubMed Central

    Tang, Chunyuan; Wu, Fang; Wang, Rensheng; Lu, Heming; Li, Guisheng; Liu, Meilian; Zhu, Haisheng; Zhu, Jinxian; Zhang, Yong; Hu, Kai

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is highly incident in southern China. Metastasis is the major cause of death in NPC patients. Concurrent chemoradiotherapy (CCRT) has been accepted as standard in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, induction chemotherapy (IC) also has benefits in this disease, especially in the patients with certain high-risk factors such as bulky and/or extensive nodal disease. It has been presented that adding IC to CCRT might be a reasonable approach and need more work to confirm. The optimal chemotherapeutic regimen combined with radiotherapy has not been determined so far. It is important to explore high effective and low toxic chemotherapy for the patients. In the multicenter prospective study, 223 patients with locoregionally advanced untreated NPC were randomized into experimental group and control group. The patients received two cycles of induction chemotherapy (IC) with docetaxel (DOC) plus nedaplatin (NDP) in experimental group every 3 weeks, followed by IMRT concurrent with weekly NDP for six cycles, and NDP was replaced by cisplatin (CDDP) in control group. More patients in experimental group could receive full courses of IC and concurrent chemoradiotherapy (CCRT) (P=0.013). There was no significant difference between the two groups in the percentage of reduction of GTVnx and GTVnd after IC (P=0.207 and P=0.107) and CR rate three months after completion of chemoradiotherapy (P=0.565 and P=0.738). With a mean follow-up of 35.1 months, no statistically significant difference in the 3-year OS, LRFS, RRFS, DMFS, and PFS was found. During IC, more patients suffered vomiting in control group (P=0.001). During CCRT, grade 3/4 neutropenia/thrombocytopenia were more common in experimental group (P=0.028 and P=0.035); whereas, severe anemia and vomiting were more common in control group (P=0.0001 and P=0.023). In conclusions, patients with locoregionally advanced NPC showed good

  16. A rapidly growing epidermoid cyst in an intrapancreatic accessory spleen treated by laparoscopic spleen-preserving distal pancreatectomy: Report of a case.

    PubMed

    Kumamoto, Yusuke; Kaizu, Takashi; Tajima, Hiroshi; Kubo, Hidefumi; Nishiyama, Ryo; Watanabe, Masahiko

    2015-06-02

    Epidermoid cysts arising in an intrapancreatic accessory spleen are exceedingly rare, furthermore the natural course of them is hardly known. We report a case correctly diagnosed with epidermoid cyst in an intrapancreatic accessory spleen, followed by 1 year observation, finally underwent surgical treatment. The patient presented with diarrhea. Contrast-enhanced computed tomography (CT) revealed a pancreatic cyst 20 mm in diameter, surrounded by a solid component showing the same enhancement as the spleen, suggesting the presence of an epidermoid cyst in an intrapancreatic accessory spleen. One year later, back discomfort developed, and a CT scan revealed that the cyst had grown to 38 mm in diameter. To obtain a definitive diagnosis, we performed a laparoscopic spleen-preserving distal pancreatectomy. The histopathological diagnosis was compatible with an epidermoid cyst in an intrapancreatic accessory spleen, which is benign. The postoperative course was uneventful. This case demonstrates that an epidermoid cyst arising in an intrapancreatic accessory spleen can rapidly grow, even if it is benign. Laparoscopic spleen-preserving distal pancreatectomy can be a useful procedure, with the advantages of low invasiveness and organ preservation, for the treatment of benign or low-grade malignant tumors located in the pancreatic body or tail.

  17. Cabozantinib in the treatment of advanced renal cell carcinoma: design, development, and potential place in the therapy

    PubMed Central

    Grassi, Paolo; Verzoni, Elena; Ratta, Raffaele; Mennitto, Alessia; de Braud, Filippo; Procopio, Giuseppe

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) has markedly improved over the last few years with the introduction of several targeted agents in clinical practice. Nevertheless, either primary or secondary resistance to inhibition of VEGF and mTOR pathways has limited the clinical benefit of these systemic treatments. Recently, a better understanding of the involvement of MET and its ligand HGF in many biological processes made this signaling pathway an attractive therapeutic target in oncology, particularly in mRCC. Herein, we review the development of cabozantinib, a recently approved inhibitor of multiple tyrosine kinase receptors, including MET, VEGFRs, and AXL, which has proven to increase progression-free survival and overall survival when compared to everolimus in mRCC patients who had progressed after VEGFR-targeted therapy. Finally, we discuss the potential role of cabozantinib within the current treatment landscape for mRCC. PMID:27462141

  18. Expression of P53 and HSP70 in Chronic Hepatitis, Liver Cirrhosis, and Early and Advanced Hepatocellular Carcinoma Tissues and Their Diagnostic Value in Hepatocellular Carcinoma: An Immunohistochemical Study

    PubMed Central

    Wang, Zhi; Gou, Wenbin; Liu, Ming; Sang, Wei; Chu, Hui; Zhang, Wei

    2015-01-01

    Background Tumor protein (P53) and heat shock protein 70 (HSP70) play key roles in chronic liver diseases. This study aimed to characterize P53 and HSP70 expression in chronic hepatitis (CH), liver cirrhosis (LC), early and advanced HCC, and to analyze their diagnostic value in hepatocellular carcinoma (HCC). Material/Methods Immunohistochemical staining was conducted to evaluate the expression of P53 and HSP70 in 200 human liver tissue specimens, with advanced HCC (n=80), early HCC (n=30), CH (n=30), LC (n=30), and Controls (n=30). Results P53 expression levels were lower in LC than those of HCC, but remained on par with those of CH and Controls. HSP70 expression levels were higher in HCC than those of LC, CH, and Controls. The sensitivity and specificity for HCC diagnosis were: 50.9% and 98.9% for P53, and 78.2 and 77.8% for HSP70, respectively. The sensitivity and specificity of different combinations were: 95.5% and 85.5% with either P53 or HSP70 being positive, and 33.6% and 98.9% if both were positive. Among the differentiation stages marked low, intermediate, and high in HCC, the P53 positive rate was higher in the low than in the intermediate, which was higher than that in the high. HSP70 positive rate was higher in the low and the intermediate than in the high, but no obvious changes were found between the low and the intermediate. Conclusions P53 and HSP70 could be potential biomarkers for HCC diagnosis, and proper combinations of these 2 markers could improve diagnostic accuracy. PMID:26494212

  19. Carcinoma gallbladder.

    PubMed

    Biswas, P K

    2010-07-01

    Carcinoma gallbladder (CaGb) is a rare disease. The aetiology of CaGb is yet not known. However the risk of CaGb is increased in anomalous pancreaticobiliary duct junction (APBDJ), gall stones, xanthogranulomatus cholecystitis, calcified or porcelain gallbladder, cholelithiasis with typhoid carriers, gallbladder adenoma, red meat consumption and tobacco uses. There are protective effects of vegetables on CaGb. Most of the cases present with advanced disease. In early carcinoma of a gallbladder sign and symptoms mimic benign disease. The diagnosis is established by ultrasonography, computerized tomography and guided fine needle aspiration cytology (FNAC). Biochemical tests are of very little value in making a diagnosis. The treatment depends on the clinical stage at presentation. Surgery offers the best chance of cure. In stage T1a, laparoscopic or open cholecystectomy alone is curative, and in T1b, cholecystectomy with hepatoduodenal lymph node dissection without combined resection of an adjacent organ is required. Segment S4a+5 hepatectomy combined with extrahepatic bile duct resection (BDR) and D2 lymph node dissection is a highly recommended operation for the treatment of T2 and T3 CaGb. The dye injection method is useful in determining the appropriate extent of hepatic resection for advanced CaGb. Resurgery is required only in those cases where tumour has invaded the serosa and/ or adjacent structures when diagnosed postoperatively. Biliary bypass is required for palliation. Prognosis depends on early diagnosis and appropriate surgical excision.

  20. Weekly Low-Dose Docetaxel-Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma: A Retrospective, Single-Institution Study

    SciTech Connect

    Fukada, Junichi; Shigematsu, Naoyuki; Takeda, Atsuya; Ohashi, Toshio; Tomita, Toshiki; Shiotani, Akihiro; Kunieda, Etsuo; Kawaguchi, Osamu; Fujii, Masato; Kubo, Atsushi

    2010-02-01

    Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m{sup 2}]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade >=3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

  1. Short-term and long-term efficacy of 7 targeted therapies for the treatment of advanced hepatocellular carcinoma: a network meta-analysis

    PubMed Central

    Niu, Meng; Hong, Duo; Ma, Teng-Chuang; Chen, Xiao-Wei; Han, Jin-Hang; Sun, Jun; Xu, Ke

    2016-01-01

    Abstract Background: A variety of targeted drug therapies in clinical trials have been proven to be effective for the treatment of hepatocellular carcinoma (HCC). Our study aims to compare the short-term and long-term efficacies of different targeted drugs in advanced hepatocellular carcinoma (AHCC) treatment using a network meta-analysis approach. Methods: PubMed, Embase, Ovid, EBSCO, and Cochrane central register of controlled trials were searched for randomized controlled trials (RCTs) of different targeted therapies implemented to patients with AHCC. And the retrieval resulted in 7 targeted drugs, namely, sorafenib, ramucirumab, everolimus, brivanib, tivantinib, sunitinib, and sorafenib+erlotinib. Direct and indirect evidence were combined to evaluate stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR), overall response ratio (ORR), overall survival (OS), and surface under the cumulative ranking curve (SUCRA) of patients with AHCC. Results: A total of 11 RCTs were incorporated into our analysis, including 6594 patients with AHCC, among which 1619 patients received placebo treatment and 4975 cases had targeted therapies. The results revealed that in comparison with placebo, sorafenib, and ramucirumab displayed better short-term efficacy in terms of PR and ORR, and brivanib was better in ORR. Regarding long-term efficacy, sorafenib and sorafenib+erlotinib treatments exhibited longer OS. The data of cluster analysis showed that ramucirumab or sorafenib+erlotinib presented relatively better short-term efficacy for the treatment of AHCC. Conclusion: This network meta-analysis shows that ramucirumab and sorafenib+erlotinib may be the better targeted drugs for AHCC patients, and sorafenib+erlotinib achieved a better long-term efficacy. PMID:27930578

  2. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-01-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment. PMID:24403269

  3. A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial chemoembolization using doxorubicin for intractable, advanced hepatocellular carcinoma

    PubMed Central

    Kim, Hee Yeon; Kim, Jin Dong; Park, Jun Yong; Han, Kwang Hyub; Woo, Hyun Young; Choi, Jong Young; Yoon, Seung Kew; Jang, Byoung Kuk; Hwang, Jae Seok; Kim, Sang Gyune; Kim, Young Seok; Seo, Yeon Seok; Yim, Hyung Joon; Um, Soon Ho

    2010-01-01

    Background/Aims Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC. Methods The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m2 on days 1~3) and cisplatin (60 mg/m2 on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks. Results Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group. Conclusions High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC. PMID:21415578

  4. Long-Term Outcomes After Maximal Surgical Resection and Intraoperative Electron Radiotherapy for Locoregionally Recurrent or Locoregionally Advanced Primary Renal Cell Carcinoma

    SciTech Connect

    Hallemeier, Christopher L.; Choo, Richard; Davis, Brian J.; Pisansky, Thomas M.; Gunderson, Leonard L.; Leibovich, Bradley C.; Haddock, Michael G.

    2012-04-01

    Purpose: To report outcomes of a multimodality therapy combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. Methods and Materials: From 1989 through 2005, a total of 22 patients with LR recurrent (n = 19) or LR advanced primary (n = 3) RCC were treated with this multimodality approach. The median patient age was 63 years (range 46-78). Twenty-one patients (95%) received perioperative external beam radiotherapy (EBRT) with a median dose of 4,500 cGy (range, 4,140-5,500). Surgical resection was R0 (negative margins) in 5 patients (23%) and R1 (residual microscopic disease) in 17 patients (77%). The median IOERT dose delivered was 1,250 cGy (range, 1,000-2,000). Overall survival (OS) and disease-free survival (DFS) and relapse patterns were estimated using the Kaplan-Meier method. Results: The median follow-up for surviving patients was 9.9 years (range, 3.6-20 years). The OS and DFS at 1, 5, and 10 years were 91%, 40%, and 35% and 64%, 31%, and 31%, respectively. Central recurrence (within the IOERT field), LR relapse (tumor bed or regional lymph nodes), and distant metastases at 5 years were 9%, 27%, and 64%, respectively. Mortality within 30 days of surgery and IOERT was 0%. Five patients (23%) experienced acute or late National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) Version 4 Grade 3 to 5 toxicities. Conclusions: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach of perioperative EBRT, maximal surgical resection, and IOERT yielded encouraging results. This regimen warrants further investigation.

  5. MicroRNA Expression Profiling of Peripheral Blood Samples Predicts Resistance to First-line Sunitinib in Advanced Renal Cell Carcinoma Patients12

    PubMed Central

    Gámez-Pozo, Angelo; Antón-Aparicio, Luis M; Bayona, Cristina; Borrega, Pablo; Gallegos Sancho, María I; García-Domínguez, Rocío; de Portugal, Teresa; Ramos-Vázquez, Manuel; Pérez-Carrión, Ramón; Bolós, María V; Madero, Rosario; Sánchez-Navarro, Iker; Fresno Vara, Juan A; Arranz, Enrique Espinosa

    2012-01-01

    Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC), but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood samples were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC. miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data. Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression. Blood samples from 38 patients and 287 miRNAs were evaluated. Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment. Predictive models identified populations with differences in the established end points. In the poor response group, median time to progression was 3.5 months and the overall survival was 8.5, whereas in the prolonged response group these values were 24 and 29.5 months, respectively. Ontology analyses pointed out to cancer-related pathways, such angiogenesis and apoptosis. miRNA expression signatures, measured in peripheral blood, may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib, improving diagnostic accuracy. After proper validation, these signatures could be used to tailor therapy in this setting. PMID:23308047

  6. VESPRO: An Individual Patient Data Prospective Meta-Analysis of Selective Internal Radiation Therapy Versus Sorafenib for Advanced, Locally Advanced, or Recurrent Hepatocellular Carcinoma of the SARAH and SIRveNIB Trials

    PubMed Central

    Gibbs, Emma; Gandhi, Mihir; Chatellier, Gilles; Dinut, Aurelia; Pereira, Helena; Chow, Pierce KH; Vilgrain, Valérie

    2017-01-01

    Background Untreated advanced hepatocellular carcinoma (HCC) has an overall poor prognosis. Currently there are 2 ongoing prospective randomized controlled trials that are evaluating the efficacy and safety of sorafenib and selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres in patients with advanced HCC. The SorAfenib versus Radioembolisation in Advanced Hepatocellular carcinoma (SARAH; 459 patients) trial is being performed in Europe and the SIRt VErsus SorafeNIB (SIRveNIB; 360 patients) trial in the Asia Pacific region. Prospectively combining the results, these trials will not only allow for increased precision to estimate efficacy (in terms of survival), but will also provide increased statistical power for subgroup analyses. Objective To ensure the prospectivity and transparency of the meta-analysis. Methods The sirVEnib and SARAH merge PROject (VESPRO) is an individual, patient-data prospective meta-analysis of the SIRveNIB and SARAH randomized trials. The VESPRO protocol includes prespecified hypotheses, inclusion criteria, and outcome measures. The primary outcome measure is overall survival and secondary outcomes include tumor response rate, progression-free survival, progression in the liver as first event, and disease control in the liver. Pooling of toxicity results will allow for robust safety profiles to be established for both therapies, and provides increased statistical power to investigate treatment effects in key subgroups. Analyses will be performed in the intent-to-treat population stratified by trial. Results Both studies are expected to demonstrate a survival benefit for SIRT together with a better toxicity profile compared with sorafenib. It is also anticipated that liver progression as the first event would be longer in the intervention compared with the control. Conclusions As the results of the 2 trials are not yet known, the methodological strength is enhanced, as biases inherent in conventional meta

  7. Unusual mucoepidermoid carcinoma of the liver misdiagnosed as squamous cell carcinoma by intraoperative histological examination

    PubMed Central

    2014-01-01

    As rare condition, mucoepidermoid carcinoma may occur in liver although its etiology and pathogenesis is still unclear. We report here a case of intrahepatic mucoepidermoid carcinoma misdiagnosed as cholangiocarcinoma and squamous cell carcinoma by preoperative radiologic and intraoperative histological examinations, respectively. A 60-year-old woman presented with a 1-month history of progressive jaundice, epigastric discomfort, and weight loss with slightly increased carbohydrate antigen 19-9 (CA19-9). Computed tomography (CT) showed a large tumor, 8.0 cm in diameter, in the left lobe of the liver. A preliminary diagnosis of a cholangiocarcinoma of the liver was made. In the intraoperative histological examination, a diagnosis of squamous cell carcinoma was made based on predominantly invasive epidermoid cells with abundant keratinization and absence of mucin-producing cell component. However, postoperative histological diagnosis of the lesion was mucoepidermiod carcinoma of liver by thoroughly microscopical inspection and the presence of mucin-producing cells confirmed by Alcian blue staining. Despite surgical excision and chemotherapy, the tumor showed very aggressive malignancy with tumor recurrence. The patient died shortly afterward, surviving 6 months after surgery. Due to its rarity and distinct morphological features, mucoepidermoid carcinoma might be erroneously interpreted as squamous cell carcinoma by those who were not familiar with this condition in unusual locations. Therefore, removal of sufficient tissue from different portions of the lesion is essential for the surgeons and pathologists to make a precise diagnosis in the intraoperative histological examination. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4956311271136060 PMID:24475740

  8. Oxaliplatin Plus Dual Inhibition of Thymidilate Synthase During Preoperative Pelvic Radiotherapy for Locally Advanced Rectal Carcinoma: Long-Term Outcome

    SciTech Connect

    Avallone, Antonio; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Petrillo, Antonella; Scott, Nigel; Marone, Pietro; Aloi, Luigi; Sandomenico, Claudia; Lastoria, Secondo; Iaffaioli, Vincenzo Rosario; Scala, Dario; Iodice, Giovanni; Budillon, Alfredo; Comella, Pasquale

    2011-03-01

    Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of {<=}5 cm from the anal verge and/or with a circumferential resection margin (CRM) of {<=}5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m{sup 2}; raltitrexed (RTX), 2.5 mg/m{sup 2} on day 1, and 5-fluorouracil (5-FU), 900 mg/m{sup 2} (31 patients) or 800 mg/m{sup 2} (32 patients); levo-folinic acid (LFA), 250 mg/m{sup 2} on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results: Overall, neutropenia (40%) and diarrhea (13%) were the most common grade {>=}3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group. Conclusions: OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.

  9. Outcomes and prognostic factors of chemotherapy for patients with locally advanced or metastatic pulmonary squamous cell carcinoma

    PubMed Central

    Minami, Seigo; Ogata, Yoshitaka; Ihara, Shouichi; Yamamoto, Suguru; Komuta, Kiyoshi

    2016-01-01

    Background Pulmonary squamous cell carcinoma has not benefited from improvements in chemotherapy over the past decade, compared with non-squamous non-small-cell lung cancer. Nowadays, treatment strategies differ between squamous and non-squamous non-small-cell lung cancers. This study aimed to investigate the percentage of patients treated with first-, second-, or third-line chemotherapy and the characteristics of patients for whom chemotherapy has been beneficial. Method Data on patients with stage IIIB or IV squamous cell carcinoma diagnosed between June 2007 and March 2015, and on patients who had received first-, second-, or third-line chemotherapy between June 2007 and November 2015 at our hospital, were retrospectively extracted from our institutional medical charts. We also compared patients who were treated with chemotherapy (chemotherapy group) and patients who were not (non-chemotherapy group) using multivariate logistic regression and multivariate Cox hazard analyses, respectively. Results During the study period, 103, 63, and 32 patients received first-, second-, and third-line chemotherapy, respectively. Fifty-one patients did not receive chemotherapy. Factors predicting unlikely chemotherapy included age ≥75 years, Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ≥2, Charlson comorbidity index ≥2, hemoglobin <12.2 g/dL, red cell distribution width ≥13.9%, and serum sodium <140 mEq/L. Factors predicting survival for each line of chemotherapy included the following: ECOG-PS ≥2 for first-line; ECOG-PS ≥2 and lymphocyte count for second-line; and ECOG-PS ≥2, body mass index <18.5 kg/m2, and hemoglobin and lactate dehydrogenase levels for third-line. Conclusion Approximately 66% of patients received first-line chemotherapy. Of those, 66% and 33% received second- and third-line chemotherapy, respectively. ECOG-PS was always an essential prognostic factor when considering introducing chemotherapy and proceeding with additional

  10. Epidermoid cyst at a rare location, as a content of inguinal hernia: A case report with a review of the literature

    PubMed Central

    Meher, Sadananda; Baijal, Manish; Soni, Vandana; Sharma, Anil; Khullar, Rajesh; Chowbey, Pradeep

    2016-01-01

    Epidermoid cysts can occur in a variety of locations including the face, trunk, neck, extremities, and scalp. No case of epidermoid cyst as content of inguinal hernia has been reported so far; however, cases with dermoid, teratoma, lipoma, lymphangioma and leiomyoma as content of inguinal canal have been reported. A 29-year-old female presented with a lump in the left inguinal region that was clinically diagnosed as left inguinal hernia. The patient was planned for laparoscopic inguinal hernia repair after routine investigation. Intraoperatively, a cystic mass was found to be attached to the left round ligament that was excised completely. Histopathological report was consistent with epidermal inclusion cyst. Inguinal epidermoid cyst mimicking inguinal hernia is a rare entity. If such a cyst is encountered during operation, it should be completely excised. PMID:27279405

  11. The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study.

    PubMed

    Solomon, Monica Charlotte; Vidyasagar, M S; Fernandes, Donald; Guddattu, Vasudev; Mathew, Mary; Shergill, Ankur Kaur; Carnelio, Sunitha; Chandrashekar, Chetana

    2016-12-01

    Oral squamous cell carcinomas comprise a heterogeneous tumor cell population with varied molecular characteristics, which makes prognostication of these tumors a complex and challenging issue. Thus, molecular profiling of these tumors is advantageous for an accurate prognostication and treatment planning. This is a retrospective study on a cohort of primary locally advanced oral squamous cell carcinomas (n = 178) of an Indian rural population. The expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of primary locally advanced oral squamous cell carcinomas was evaluated. A potential biomarker that can predict the tumor response to treatment was identified. Formalin-fixed paraffin-embedded tumor blocks of (n = 178) of histopathologically diagnosed cases of locally advanced oral squamous cell carcinomas were selected. Tissue microarray blocks were constructed with 2 cores of 2 mm diameter from each tumor block. Four-micron-thick sections were cut from these tissue microarray blocks. These tissue microarray sections were immunohistochemically stained for EGFR, p53, Bcl-2, cyclin D1 and p16. In this cohort, EGFR was the most frequently expressed 150/178 (84%) biomarker of the cases. Kaplan-Meier analysis showed a significant association (p = 0.038) between expression of p53 and a poor prognosis. A Poisson regression analysis showed that tumors that expressed p53 had a two times greater chance of recurrence (unadjusted IRR-95% CI 2.08 (1.03, 4.5), adjusted IRR-2.29 (1.08, 4.8) compared with the tumors that did not express this biomarker. Molecular profiling of oral squamous cell carcinomas will enable us to categorize our patients into more realistic risk groups. With biologically guided tumor characterization, personalized treatment protocols can be designed for individual patients, which will improve the quality of life of these patients.

  12. Fractionated intravesical radioimmunotherapy with (213)Bi-anti-EGFR-MAb is effective without toxic side-effects in a nude mouse model of advanced human bladder carcinoma.

    PubMed

    Fazel, Julia; Rötzer, Silvia; Seidl, Christof; Feuerecker, Benedikt; Autenrieth, Michael; Weirich, Gregor; Bruchertseifer, Frank; Morgenstern, Alfred; Senekowitsch-Schmidtke, Reingard

    2015-01-01

    Gold standard in therapy of superficial, non-muscle invasive urothelial tumors is transurethral resection followed by intravesical instillation therapies. However, relapse is commonly observed and therefore new therapeutic approaches are needed. Application of (213)Bi-immunoconjugates targeting EGFR had shown promising results in early tumor stages. The aim of this study was the evaluation of fractionated application of (213)Bi-anti-EGFR-MAb in advanced tumor stages in a nude mouse model. Luciferase-transfected EJ28 human bladder carcinoma cells were instilled intravesically into nude mice following electrocautery. Tumor development was monitored via bioluminescence imaging. One day after tumor detection mice were treated intravesically either 2 times with 0.93 MBq or 3 times with 0.46 MBq of (213)Bi-anti-EGFR-MAb. Therapeutic efficacy was evaluated via overall survival and toxicity toward normal urothelium by histopathological analysis. Mice without treatment and those treated with the native anti-EGFR-MAb showed mean survivals of 65.4 and 57.6 d, respectively. After fractionated treatment with 0.93 MBq of (213)Bi-anti-EGFR-MAb animals reached a mean survival of 141.5 d and 33% of the animals survived at least 268 d. Fractionated treatment with 0.46 MBq (213)Bi-anti-EGFR-MAb resulted in a mean survival of 131.8 d and 30% of the animals survived longer than 300 d. Significant differences were only observed between the control groups and the group treated twice with 0.93 MBq of (213)Bi-anti-EGFR-MAb. No toxic side-effects on the normal urothelium were observed even after treatment with 3.7 MBq of (213)Bi-anti-EGFR-MAb. The study demonstrates that the fractionated intravesical radioimmunotherapy with (213)Bi-anti-EGFR-MAb is a promising approach in advanced bladder carcinoma.

  13. Fractionated intravesical radioimmunotherapy with 213Bi-anti-EGFR-MAb is effective without toxic side-effects in a nude mouse model of advanced human bladder carcinoma

    PubMed Central

    Fazel, Julia; Rötzer, Silvia; Seidl, Christof; Feuerecker, Benedikt; Autenrieth, Michael; Weirich, Gregor; Bruchertseifer, Frank; Morgenstern, Alfred; Senekowitsch-Schmidtke, Reingard

    2015-01-01

    Gold standard in therapy of superficial, non-muscle invasive urothelial tumors is transurethral resection followed by intravesical instillation therapies. However, relapse is commonly observed and therefore new therapeutic approaches are needed. Application of 213Bi-immunoconjugates targeting EGFR had shown promising results in early tumor stages. The aim of this study was the evaluation of fractionated application of 213Bi-anti-EGFR-MAb in advanced tumor stages in a nude mouse model. Luciferase-transfected EJ28 human bladder carcinoma cells were instilled intravesically into nude mice following electrocautery. Tumor development was monitored via bioluminescence imaging. One day after tumor detection mice were treated intravesically either 2 times with 0.93 MBq or 3 times with 0.46 MBq of 213Bi-anti-EGFR-MAb. Therapeutic efficacy was evaluated via overall survival and toxicity toward normal urothelium by histopathological analysis. Mice without treatment and those treated with the native anti-EGFR-MAb showed mean survivals of 65.4 and 57.6 d, respectively. After fractionated treatment with 0.93 MBq of 213Bi-anti-EGFR-MAb animals reached a mean survival of 141.5 d and 33% of the animals survived at least 268 d. Fractionated treatment with 0.46 MBq 213Bi-anti-EGFR-MAb resulted in a mean survival of 131.8 d and 30% of the animals survived longer than 300 d. Significant differences were only observed between the control groups and the group treated twice with 0.93 MBq of 213Bi-anti-EGFR-MAb. No toxic side-effects on the normal urothelium were observed even after treatment with 3.7 MBq of 213Bi-anti-EGFR-MAb. The study demonstrates that the fractionated intravesical radioimmunotherapy with 213Bi-anti-EGFR-MAb is a promising approach in advanced bladder carcinoma. PMID:26177233

  14. Relationship of smoking status to genomic profile, chemotherapy response and clinical outcome in patients with advanced urothelial carcinoma

    PubMed Central

    Joshi, Monika; Vasekar, Monali; Grivas, Petros; Emamekhoo, Hamid; Hsu, JoAnn; Miller, Vincent A.; Stephens, Philip J.; Ali, Siraj M.; Ross, Jeffrey S.; Zhu, Junjia; Warrick, Joshua; Drabick, Joseph J.; Holder, Sheldon L.; Kaag, Matthew; Li, Min; Pal, Sumanta Kumar

    2016-01-01

    Smoking has been linked to urothelial carcinoma (UC), but the implications on genomic profile and therapeutic response are poorly understood. To determine how smoking history impacts genomic profile and chemotherapy response, clinicopathologic data was collected for patients with metastatic UC (mUC) across 3 academic medical centers and comprehensive genomic profiling (CGP) was performed through a CLIA-certified lab. Unsupervised hierarchical clustering based on smoking status was used to categorize the frequency of genomic alterations (GAs) amongst current smokers (CS), ex-smokers (ES) and non-smokers (NS), and survival was compared in these subsets. Fisher's exact test identified significant associations between GAs and smoking status. Amongst 83 patients, 23%, 55% and 22% were CS, ES, and NS, respectively, and 95% of patients had stage IV disease. With a median follow up of 14.4 months, the median overall survival (OS) was significantly higher in NS and ES (combined) as compared to CS (51.6 vs 15.6 months; P = 0.04). Of 315 cancer-related genes and 31 genes often related to rearrangement tested, heatmaps show some variations amongst the subsets. GAs in NSD1 were more frequent in CS as compared to other groups (P < 0.001). CS status negatively impacts OS in patients with mUC and is associated with genomic alterations that could have therapeutic implications. PMID:27213592

  15. Concomitant consumption of marijuana, alcohol and tobacco in oral squamous cell carcinoma development and progression: recent advances and challenges.

    PubMed

    Lopes, Caio Fabio Baeta; de Angelis, Bruno Brandão; Prudente, Henrique Maciel; de Souza, Bernardo Vieira Goulart; Cardoso, Sérgio Vitorino; de Azambuja Ribeiro, Rosy Iara Maciel

    2012-08-01

    Oral squamous cell carcinoma (OSCC) corresponds to 95% of all malignant tumours of the mouth. The association between alcohol and tobacco is the major risk factor for this disease, increasing the chances for the development of OSCC by 35-fold. The plant, Cannabis sativa is smoked as cigarettes or blunts and is commonly used in association with tobacco and alcohol. Any type of smoking habit exposes individuals to a wide range of carcinogens or pro-carcinogens, such as polycyclic aromatic hydrocarbons, as well as some ethanol derived substances such as acetaldehyde (AA), and all are genotoxic in the same way. In addition, ethanol acts in the oral mucosa as a solvent and therefore increases the cellular membrane permeability to carcinogens. Carcinogens found in tobacco are also concentrated in marijuana, but the latter also contains high levels of cannabinoids, bioactive compounds responsible for several effects such as euphoria and analgesia. However, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the major psychotropic cannabinoid found in plants, causes a reduction of cellular metabolism and induction of apoptosis, both of which are anti-neoplastic properties. Apart from limited epidemiologic and experimental data, the effects of concomitant chronic exposure to marijuana (or Δ(9)-THC), tobacco and alcohol in OSCC development and progression is poorly known. This paper reviews the most recent findings on the effects of marijuana over cellular proliferation, as well as in the risk for OSCC, with emphasis on its interaction with tobacco and ethanol consumption.

  16. Fumonisin B1 does not prevent apoptosis in A431 human epidermoid carcinoma cells after photosensitization with a silicon phthalocyanine.

    PubMed

    Nagy, B; Chiu, S M; Separovic, D

    2000-09-01

    Photodynamic therapy with the phthalocyanine photosensitizer Pc 4 (Pc 4-PDT), an apoptosis inducer, is associated with accumulation of ceramide in various cell lines. The role of ceramide in Pc 4-PDT-induced apoptosis was investigated in A431 cells. Caspase-3 (casp-3) was activated and TUNEL positive cells began to appear 30 and 60 min post-Pc 4-PDT, respectively. A rapid increase (10 min) in cellular ceramide levels was observed after Pc 4-PDT. Induced ceramide accumulation was maintained over 60 min, Acid sphingomyelinase, a ceramide-generating enzyme, was inhibited after photosensitization with Pc 4, suggesting that the enzyme was not required for stimulated ceramide accumulation. Co-treatment of A431 cells with fumonisin B1, a ceramide synthase inhibitor, and Pc 4-PDT led to a decrease in ceramide levels without any effect on induced casp-3 activity or apoptosis. In the presence of zVAD, a pan-caspase inhibitor, apoptosis was abolished, while ceramide levels remained elevated after Pc 4-PDT. Exposure of A431 cells to exogenous C6-ceramide for 22 h, led to induction of apoptosis, and the process was abrogated by zVAD. In conclusion, C6-ceramide-, like Pc 4-PDT-induced apoptosis, is zVAD-sensitive. Furthermore, Pc 4 photosensitization can lead to apoptosis without FB-sensitive elevation in ceramide levels upstream of caspases.

  17. The American Brachytherapy Society Treatment Recommendations for Locally Advanced Carcinoma of the Cervix Part II: High Dose-Rate Brachytherapy

    PubMed Central

    Viswanathan, Akila N.; Beriwal, Sushil; De Los Santos, Jennifer; Demanes, D. Jeffrey; Gaffney, David; Hansen, Jorgen; Jones, Ellen; Kirisits, Christian; Thomadsen, Bruce; Erickson, Beth

    2012-01-01

    Purpose This report presents the 2011 update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer. Methods Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder or interstitial applicators for locally advanced cervical cancer were revised based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy. Results The Cervical Cancer Committee for Guideline Development affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion prior to treatment delivery. Applicator placement, dose specification and dose fractionation must be documented, quality assurance measures must be performed, and follow-up information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2 Gray (Gy) per fraction radiobiologic equivalence (EQD2) is 80–90 Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed. Conclusion These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011. PMID:22265437

  18. Epidermoid Cyst in an Intrapancreatic Accessory Spleen: Case Report and Literature Review of the Preoperative Imaging Findings

    PubMed Central

    Kato, Shin; Mori, Hideki; Zakimi, Moriya; Yamada, Koki; Chinen, Kenji; Arashiro, Masayuki; Shinoura, Susumu; Kikuchi, Kaoru; Murakami, Takahiro; Kunishima, Fumihito

    2016-01-01

    An epidermoid cyst arising within an intrapancreatic accessory spleen (ECIAS) is rare, and also difficult to correctly diagnose before surgery. It is mostly misdiagnosed as a cystic tumor, such as a mucinous cystic neoplasm or as a solid tumor with cystic degeneration, such as a neuro endocrine tumor. We herein report a case of ECIAS and also perform a literature review of 35 reports of ECIAS. Although the preoperative diagnosis of ECIAS using conventional imaging is relatively difficult to make, careful preoperative examinations of the features on computed tomography and magnetic resonance imaging could lead to a correct preoperative diagnosis of ECIAS which might thereby reduce the number of unnecessary resections. PMID:27904107

  19. The Changes of Lipid Metabolism in Advanced Renal Cell Carcinoma Patients Treated with Everolimus: A New Pharmacodynamic Marker?

    PubMed Central

    Pantano, Francesco; Santoni, Matteo; Procopio, Giuseppe; Rizzo, Mimma; Iacovelli, Roberto; Porta, Camillo; Conti, Alessandro; Lugini, Antonio; Milella, Michele; Galli, Luca; Ortega, Cinzia; Guida, Francesco Maria; Silletta, Marianna; Schinzari, Giovanni; Verzoni, Elena; Modica, Daniela; Crucitti, Pierfilippo; Rauco, Annamaria; Felici, Alessandra; Ballatore, Valentina; Cascinu, Stefano; Tonini, Giuseppe; Carteni, Giacomo; Russo, Antonio; Santini, Daniele

    2015-01-01

    Background Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC. Methods 177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated. Results Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis. Conclusion C+T raise is an early predictor for everolimus efficacy for patients with mRCC. PMID:25885920

  20. A dosimetric analysis of dose escalation using two intensity-modulated radiation therapy techniques in locally advanced pancreatic carcinoma

    SciTech Connect

    Brown, Michael W.; Ning, Holly; Arora, Barbara; Albert, Paul S.; Poggi, Matthew; Camphausen, Kevin; Citrin, Deborah . E-mail: citrind@mail.nih.gov

    2006-05-01

    Purpose: To perform an analysis of three-dimensional conformal radiation therapy (3D-CRT), sequential boost intensity-modulated radiation therapy (IMRTs), and integrated boost IMRT (IMRTi) for dose escalation in unresectable pancreatic carcinoma. Methods and Materials: Computed tomography images from 15 patients were used. Treatment plans were generated using 3D-CRT, IMRTs, and IMRTi for dose levels of 54, 59.4, and 64.8 Gy. Plans were analyzed for target coverage, doses to liver, kidneys, small bowel, and spinal cord. Results: Three-dimensional-CRT exceeded tolerance to small bowel in 1 of 15 (6.67%) patients at 54 Gy, and 4 of 15 (26.7%) patients at 59.4 and 64.8 Gy. 3D-CRT exceeded spinal cord tolerance in 1 of 15 patients (6.67%) at 59.4 Gy and liver constraints in 1 of 15 patients (6.67%) at 64.8 Gy; no IMRT plans exceeded tissue tolerance. Both IMRT techniques reduced the percentage of total kidney volume receiving 20 Gy (V20), the percentage of small bowel receiving 45 Gy (V45), and the percentage of liver receiving 35 Gy (V35). IMRTi appeared superior to IMRTs in reducing the total kidney V20 (p < 0.0001), right kidney V20 (p < 0.0001), and small bowel V45 (p = 0.02). Conclusions: Sequential boost IMRT and IMRTi improved the ability to achieve normal tissue dose goals compared with 3D-CRT. IMRTi allowed dose escalation to 64.8 Gy with acceptable normal tissue doses and superior dosimetry compared with 3D-CRT and IMRTs.

  1. Outcomes in a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma

    SciTech Connect

    Paly, Jonathan J.; Hallemeier, Christopher L.; Biggs, Peter J.; Niemierko, Andrzej; Roeder, Falk; Martínez-Monge, Rafael; Whitson, Jared; Calvo, Felipe A.; Fastner, Gerd; Sedlmayer, Felix; Wong, William W.; Ellis, Rodney J.; Haddock, Michael G.; Choo, Richard; Shipley, William U.; Zietman, Anthony L.; Efstathiou, Jason A.

    2014-03-01

    Purpose/Objective(s): This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT). Methods and Materials: Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance. Results: IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P<.01), presence of sarcomatoid features (HR 3.7-6.9, P<.05), and higher IORT dose (HR 1.3, P<.001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P=.03). For locally recurrent tumors, positive margin status (HR 2.6, P=.01) was associated with decreased OS. Conclusions: We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to

  2. Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

    PubMed Central

    Hu, Guofang; Wang, Zhehai; Wang, Yuan; Zhang, Qingqing; Tang, Ning; Guo, Jun; Liu, Liyan; Han, Xiao

    2016-01-01

    Background To retrospectively evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (dCRT) with cisplatinum/paclitaxel versus cisplatinum/5-fluorouracil in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received nonsurgical treatment. Methods This study retrospectively evaluated 202 patients with locally advanced ESCC treated at Shandong Cancer Hospital between January 2009 and December 2013. All the patients initially received dCRT, including platinum and paclitaxel or 5-fluorouracil, with concurrent 1.8 or 2 Gy/fraction radiation (total dose, 54–60 Gy). The patient population was divided into two treatment groups: 105 patients who received the cisplatinum/paclitaxel regimen were allocated to group A, and 97 patients who received the cisplatinum/5-fluorouracil regimen were allocated to group B. We compared the progression-free survival (PFS) and overall survival (OS) by various clinical variables, including prior treatment characteristics, major toxicities (mainly in grade 3 and 4 hematological), and response to dCRT. We used the receiver operating curve analysis to determine the optimal cutoff value of clinical stage and radiation dose. The Kaplan–Meier method was used for survival comparison and Cox regression for multivariate analysis. Results Median PFS and OS in group A were significantly better compared with group B (median PFS, 15.9 versus 13.0 months, P=0.016 and median OS, 33.9 versus 23.1 months, P=0.014, respectively). The 1- and 2-year survival rates of the two groups were 82.9% versus 76.3%, and 61.9% versus 47.6%, respectively. The complete response and response rate were 17.1% versus 7.2% (P=0.032) and 52.4% versus 30.9% (P=0.042) in group A and B, respectively. Meanwhile, group B was associated with a significantly lower rate of grade 3/4 overall toxicity than group A (P=0.039). Conclusion Our data showed that patients with locally advanced ESCC in group A had longer PFS and OS compared with

  3. NON-METASTATIC SQUAMOUS CELL CARCINOMA WITHIN A RATHKE’S CLEFT CYST

    PubMed Central

    O’Neill, Brian T.; Segkos, Konstantinos; Kasper, Ekkehard M.; Pallotta, Johanna A.

    2015-01-01

    Primary intracranial and sellar squamous cell carcinoma is an extremely rare entity, usually caused by malignant transformation of epidermoid cysts, or very rarely other non-malignant epithelial cysts. Malignant transformation of a Rathke’s cleft cyst has never been described. We present a 49-year-old male patient who presented with a 3-month history of progressive frontotemporal headaches. Imaging revealed a 1.2 cm cystic pituitary mass consistent with a hemorrhagic Rathke’s cleft cyst. The patient underwent trans-sphenoidal resection of the pituitary cyst, and pathologic analysis revealed a squamous cell carcinoma lining a Rathke’s cleft cyst. Extensive imaging and otorhinolaryngologic evaluation revealed no primary source for metastasis. We feel this represents the first case of a patient with a pituitary lesion in which presentation and MRI imaging were consistent with Rathke’s cleft cyst, yet histology revealed squamous cell carcinoma in situ. PMID:25715776

  4. SU-E-T-275: Radiobiological Evaluation of Intensity Modulated Radiotherapy Treatment for Locally Advanced Head and Neck Squamous Cell Carcinomas

    SciTech Connect

    Rekha Reddy, B.; Ravikumar, M.; Tanvir Pasha, C.R; Anil Kumar, M.R; Varatharaj, C.; Pyakuryal, A; Narayanasamy, Ganesh

    2014-06-01

    Purpose: To evaluate the radiobiological outcome of Intensity Modulated Radiotherapy Treatment (IMRT) for locally advanced head and neck squamous cell carcinomas using HART (Histogram Analysis in Radiation Therapy; J Appl Clin Med Phys 11(1): 137–157, 2010) program and compare with the clinical outcomes. Methods: We have treated 20 patients of stage III and IV HNSCC Oropharynx and hypopharynx with accelerated IMRT technique and concurrent chemotherapy. Delineation of tumor and normal tissues were done using Danish Head and Neck Cancer Group (DAHANCA) contouring guidelines and radiotherapy was delivered to a dose of 70Gy in 35 fractions to the primary and involved lymph nodes, 63Gy to intermediate risk areas and 56 Gy to lower risk areas, Monday to Saturday, 6 Days/week using 6 MV Photons with an expected overall treatment time of 6 weeks. The TCP and NTCP's were calculated from the dose-volume histogram (DVH) statistics using the Poisson Statistics (PS) and JT Lyman models respectively and the Resultwas correlated with clinical outcomes of the patients with mean follow up of 24 months. Results: Using HART program, the TCP (0.89± 0.01) of primary tumor and the NTCP for parotids (0.20±0.12), spinal cord (0.05±0.01), esophagus (0.30±0.2), mandible (0.35±0.21), Oral cavity (0.37±0.18), Larynx (0.30±0.15) were estimated and correlated with clinical outcome of the patients. Conclusion: Accelerated IMRT with Chemotherapy is a clinical feasible option in the treatment of locally advanced HNSCC with encouraging initial tumour response and acceptable acute toxicities. The correlation between the clinical outcomes and radiobiological model estimated parameters using HART programs are found to be satisfactory.

  5. Subsite, T Class, and N Class Cannot be Used to Exclude the Retropharyngeal Nodes From Treatment De-Intensification in Advanced Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Spector, Matthew E.; Chinn, Steven B.; Bellile, Emily; Gallagher, K. Kelly; Kang, Stephen Y.; Moyer, Jeffrey S.; Prince, Mark E.; Wolf, Gregory T.; Bradford, Carol R.; McHugh, Jonathan B.; Carey, Thomas E.; Worden, Francis P.; Eisbruch, Avraham; Ibrahim, Mohannad; Chepeha, Douglas B.

    2016-01-01

    Importance Understanding the drainage patterns to the retropharyngeal nodes is an important consideration in oropharyngeal squamous cell carcinoma (OPSCC) because treatment of these nodes is related to increased morbidity. Prediction of these drainage patterns could not only help minimize treatment morbidity, but could also prevent failures in at-risk patients, as de-escalation trials are underway for this disease. Objective To evaluate the prevalence of pathologic retropharyngeal adenopathy (RPA) in OPSCC relative to involvement of the oropharyngeal subsite, number of neck nodes, T classification and N classification. Design Retrospective review from 2003–2010 Setting Academic Referral Center Participants 205 previously untreated, advanced stage (III, IV), pathologically confirmed patients with OPSCC Exposure: Concurrent chemoradiation Main Outcome Measures Radiologic evidence of pathologic RPA was tabulated and related to involvement of the oropharyngeal subsite, number of neck nodes, T classification and N classification. Results Pathologic RPA was identified in 18% of patients. There were pathologic retropharyngeal lymph nodes in 12/89 (13%) base of tongue cancers, 24/109 (22%) tonsil cancers, and 1/7 (14%) other oropharyngeal subsite cancers. Increasing prevalence of RPA was positively correlated with closer proximity to the posterior tonsillar pillar. A multivariate predictive regression model using the oropharyngeal subsite, involvement of the posterior tonsillar pillar, number of metastatic nodes, T classification, and N classification, showed that the number of metastatic nodes was statistically significant with an odds ratio of 1.436 (p=0.0001, 95% confidence interval: 1.203 – 1.714). Conclusions and Relevance The prevalence of pathologic RPA in this cohort was 18% and patients with multiple nodes had the highest risk for pathologic RPA, followed by involvement of the posterior tonsillar pillar. However, this data suggests that there is no clear

  6. Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Herchenhorn, Daniel; Dias, Fernando L.; Viegas, Celia M.P.; Federico, Miriam H.; Araujo, Carlos Manoel M.; Small, Isabelle; Bezerra, Marcos; Fontao, Karina M.D.; Knust, Renata E.; Ferreira, Carlos G.; Martins, Renato G.

    2010-11-01

    Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.

  7. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    SciTech Connect

    Tan, Terence; Lim, Wan-Teck; Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim; Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel; Ong, Whee-Sze; Tan, Sze-Huey; Yip, Connie; Quah, Daniel; Soo, Khee-Chee; Wee, Joseph

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  8. Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

    PubMed Central

    Lv, Xing; Xia, Wei-Xiong; Ke, Liang-Ru; Yang, Jing; Qiu, Wen-Zhe; Yu, Ya-Hui; Liang, Hu; Huang, Xin-Jun; Liu, Guo-Yin; Zeng, Qi; Guo, Xiang; Xiang, Yan-Qun

    2016-01-01

    Objective Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC). This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC) or 5-fluorouracil plus carboplatin (FC) followed by concurrent radiation therapy in patients with NPC. Methods Patients (N=88) were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy) with two cycles of carboplatin (area under the curve =5 mg·h/L). Patients were followed up for 8 years. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy) to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5%) was higher than in the FC group (10.7%). Neutropenia and leukopenia were the most common grade 3–4 adverse events in the TC group, and mucositis was the most common in the FC group. Conclusion These data indicate that TC and FC therapies have similar efficacy in treating locally advanced NPC and both are well tolerated. PMID:27574453

  9. Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Tinhofer, Ingeborg; Hristozova, Tsvetana; Stromberger, Carmen; KeilhoIz, Ulrich; Budach, Volker

    2012-08-01

    Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.

  10. Ionizing radiation promotes advanced malignant traits in nasopharyngeal carcinoma via activation of epithelial-mesenchymal transition and the cancer stem cell phenotype

    PubMed Central

    SU, ZHONGWU; LI, GUO; LIU, CHAO; REN, SHULING; TIAN, YONGQUAN; LIU, YONG; QIU, YUANZHENG

    2016-01-01

    Post-irradiation residual mass and recurrence always suggest a worse prognosis for nasopharyngeal carcinoma (NPC). Our study aimed to investigate the malignant behaviors of post-irradiation residual NPC cells, to identify the potential underlying mechanisms and to search for appropriate bio-targets to overcome this malignancy. Two NPC cell lines were firstly exposed to 60 Gy irradiation, and residual cells were collected. In our previous study, colony formation assay detected the radioresistance of these cells. Here, the CCK-8 assay examined the cell sensitivity to paclitaxel and cisplatin. Wound-healing and Transwell assays were performed to investigate cell motility and invasion capabilities. Inverted phase-contrast microscopy was used to observe and photograph the morphology of cells. Expression levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot assay in NPC cells and tissues. The mRNA levels of cancer stem cell (CSC)-related genes were detected via qRT-PCR. The results revealed that residual NPC cells exhibited enhanced radioresistance and cross-resistance to paclitaxel and cisplatin. Higher capacities of invasion and migration were also observed. An elongated morphology with pseudopodia formation and broadening in the intercellular space was observed in the residual cells. Downregulation of E-cadherin and upregulation of vimentin were detected in the residual NPC cells and tissues. CSC-related Lgr5 and c-myc were significantly upregulated in the CNE-2-Rs and 6-10B-Rs radioresistance cells. Higher proportions of Lgr5+ cells were observed in radioresistant cells via immunofluorescent staining and flow cytometry. In conclusion, our study demonstrated that residual NPC cells had an advanced malignant transition and presented with both EMT and a CSC phenotype. This provides a possible clue and treatment strategy for advanced and residual NPC. PMID:27108809

  11. The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization

    PubMed Central

    Liu, Lei; Zhao, Yan; Jia, Jia; Chen, Hui; Bai, Wei; Yang, Man; Yin, Zhanxin; He, Chuangye; Zhang, Lei; Guo, Wengang; Niu, Jing; Yuan, Jie; Cai, Hongwei; Xia, Jielai; Fan, Daiming; Han, Guohong

    2016-01-01

    This retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [ΔAFP(%)] greater than the cutoff point. The ΔAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2–66.9). A level of 46% was chosen as the threshold value for ΔAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG ≥ 1 (HR = 1.95; 95% CI 1.24–3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15–2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy. PMID:26831408

  12. Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma.

    PubMed

    Yau, Thomas; Cheng, Paul N; Chan, Pierre; Chen, Li; Yuen, Jimmy; Pang, Roberta; Fan, Sheung Tat; Wheatley, Denys N; Poon, Ronnie T

    2015-04-01

    This study was designed to evaluate the efficacy, safety profile, pharmacokinetics, pharmacodynamics and quality of life of pegylated recombinant human arginase 1 (Peg-rhAgr1) in patients with advanced hepatocellular carcinoma (HCC). Patients were given weekly doses of Peg-rhAgr1 (1600 U/kg). Tumour response was assessed every 8 weeks using RECIST 1.1 and modified RECIST criteria. A total of 20 patients were recruited, of whom 15 were deemed evaluable for treatment efficacy. Eighteen patients (90%) were hepatitis B carriers. Median age was 61.5 (range 30-75). Overall disease control rate was 13%, with 2 of the 15 patients achieving stable disease for >8 weeks. The median progression-free survival (PFS) was 1.7 (95% CI: 1.67-1.73) months, with median overall survival (OS) of all 20 enrolled patients being 5.2 (95% CI: 3.3-12.0) months. PFS was significantly prolonged in patients with adequate arginine depletion (ADD) >2 months versus those who had ≤2 months of ADD (6.4 versus 1.7 months; p = 0.01). The majority of adverse events (AEs) were grade 1/2 non-hematological toxicities. Transient liver dysfunctions (25%) were the most commonly reported serious AEs and likely due to disease progression. Pharmacokinetic and pharmacodynamic data showed that Peg-rhAgr1 induced rapid and sustained arginine depletion. The overall quality of life of the enrolled patients was well preserved. Peg-rhAgr1 is well tolerated with a good toxicity profile in patients with advanced HCC. A weekly dose of 1600 U/kg is sufficient to induce ADD. Significantly longer PFS times were recorded for patients who had ADD for >2 months.

  13. A Phase 1, Open–label Study of Trebananib Combined With Sorafenib or Sunitinib in Patients With Advanced Renal Cell Carcinoma

    PubMed Central

    Hong, David S.; Gordon, Michael S.; Samlowski, Wolfram E.; Kurzrock, Razelle; Tannir, Nizar; Friedland, David; Mendelson, David S.; Vogelzang, Nicholas J.; Rasmussen, Erik; Wu, Benjamin M.; Bass, Michael B.; Zhong, Zhandong D.; Friberg, Gregory; Appleman, Leonard J.

    2016-01-01

    Background Trebananib, an investigational peptibody, binds to angiopoietin–1/–2, thereby blocking their interaction with Tie2. Patients and Methods This open–label phase 1 study examined trebananib 3 mg/kg or 10 mg/kg IV QW plus sorafenib 400 mg BID or sunitinib 50 mg QD in advanced renal cell carcinoma (RCC). Primary endpoints were adverse event incidence and pharmacokinetics. Results Thirty–seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (71%), diarrhea (71%), hypertension (65%), and fatigue (65%); grade ≥ 3 TRAEs (41%); and 14% of patients had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (74%), fatigue (68%), hypertension (58%), and decreased appetite (58%); grade ≥ 3 TRAEs (68%); and 42% of patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib). Conclusions The toxicities of trebananib IV 3 mg/kg or 10 mg/kg plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed. PMID:24365125

  14. Prognostic significance of catalase expression and its regulatory effects on hepatitis B virus X protein (HBx) in HBV-related advanced hepatocellular carcinomas.

    PubMed

    Cho, Mi-Young; Cheong, Jae Youn; Lim, Wonchung; Jo, Sujin; Lee, Youngsoo; Wang, Hee-Jung; Han, Kyou-Hoon; Cho, Hyeseong

    2014-12-15

    Hepatitis B virus X protein (HBx) plays a role in liver cancer development. We previously showed that ROS increased HBx levels and here, we investigated the role of antioxidants in the regulation of HBx expression and their clinical relevance. We found that overexpression of catalase induced a significant loss in HBx levels. The cysteine null mutant of HBx (Cys-) showed a dramatic reduction in its protein stability. In clonogenic proliferation assays, Huh7-X cells produced a significant number of colonies whereas Huh7-Cys- cells failed to generate them. The Cys at position 69 of HBx was crucial to maintain its protein stability and transactivation function in response to ROS. Among 50 HBV-related hepatocellular carcinoma (HCC) specimens, 72% of HCCs showed lower catalase levels than those of surrounding non-tumor tissues. In advanced stage IV, catalase levels in non-tumor tissues were increased whereas those in tumors were further reduced. Accordingly, patients with a high T/N ratio for catalase showed significantly longer survival than those with a low T/N ratio. Together, catalase expression in HCC patients can be clinically useful for prediction of patient survival, and restoration of catalase expression in HCCs could be an important strategy for intervention in HBV-induced liver diseases.

  15. Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma

    PubMed Central

    Lee, Li-Yu; Lin, Chien-Yu; Wang, Hung-Ming; Ng, Shu-Hang; Chen, Shu-Jen; Yen, Tzu-Chen

    2016-01-01

    TP53 mutations have been linked to reduced survival in patients with oral cavity squamous cell carcinoma (OSCC). However, the impact of different types of TP53 mutations remains unclear. Here, we demonstrate that the carriage of missense mutations in the TP53 DNA binding domain (DBD missense mutations) is associated with decreased disease-specific survival (DSS) compared with wild-type TP53 (P=0.002) in a cohort of 345 OSCC patients. In contrast, DSS of patients bearing all of the remaining TP53 mutations did not differ from that observed in wild-type TP53 patients (P=0.955). Our classification method for TP53 mutations was superior to previously reported approaches (disruptive, truncating, Evolutionary Action score, mutations in L2/L3/LSH) for distinguishing between low- and high-risk patients. When analyzed in combination with traditional clinicopathological factors, TP53 DBD missense mutations were an independent prognostic factor for shorter DSS (P=0.014) alongside with advanced AJCC T- and N-classifications and the presence of extracapsular spread. A scoring system that included the four independent prognostic factors allowed a reliable patient stratification into distinct risk groups (high-risk patients, 16.2%). Our results demonstrate the usefulness of TP53 DBD missense mutations combined with clinicopathological factors for improving the prognostic stratification of OSCC patients. PMID:27283772

  16. Prognostic Value of Neutrophil-Related Factors in Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin-Based Concurrent Chemoradiotherapy.

    PubMed

    Wang, Yan-Yang; Bai, Zhou-Lan; He, Jian-Li; Yang, Yan; Zhao, Ren; Hai, Ping; Zhe, Hong

    2016-01-01

    The aim of this study was to explore the relationship between neutrophil-related factors, including neutrophil-lymphocyte ratio (NLR) and the responses of neutrophil to granulocyte colony-stimulating factors (RNG), and the prognosis of patients with locally advanced cervical squamous cell carcinoma (LACSCC) undergoing cisplatin-based concurrent chemoradiotherapy (CCCRT). A total of sixty LACSCC patients were enrolled in this study. We analyzed the association of NLR or RNG with clinicopathologic characteristics of these patients. The prognostic factors were evaluated by univariate and multivariate survival analysis. The optimal cut-off value of the NLR was determined to be 2.0 for the overall survival (OS). A higher level of the NLR was associated with younger age (P = 0.017) and higher baseline platelet count (P = 0.040). NLR was identified to be the only independent prognostic factor for OS by multivariate analysis (P = 0.037). The median RNG was 3.01, with a range of 1.19-16.84. RNG level was significantly associated with lymph node metastasis of these patients (P = 0.023). And higher RNG was identified as being a closely independent poor prognostic factor for OS (P = 0.055). This study showed that NLR and RNG may be used as potential biomarkers for survival prediction in patients with LACSCC receiving CCCRT.

  17. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: Results of a phase II study

    SciTech Connect

    Vrdoljak, Eduard . E-mail: eduard.vrdoljak@st.hinet.hr; Prskalo, Tomislav; Omrcen, Tomislav; Situm, Kristina; Boraska, Tihana; Frleta Ilic, Nives; Jankovic, Stjepan; Hamm, Wolfgang

    2005-03-01

    Purpose: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). Methods and materials: Forty-four patients with biopsy-proven LASCC were enrolled. FIGO Stages IB2 bulky to IVA were entered into this study. Patients were assigned to receive external radiotherapy (50 Gy in 25 fractions); then ifosfamide 2 g/m{sup 2} plus cisplatin 75 mg/m{sup 2} was applied during two low-dose-rate brachytherapy applications, and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy. The planned dose to point A was 85 Gy. Results: All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy. The average duration of radiation was 45.1 days. The clinical complete response rate was 100%. Grade 3 and 4 leukopenia occurred in 25% and 11% of the cycles, respectively. After a median follow-up of 34 months (range, 20-54 months), the recurrence-free and the overall survival rates were 84% and 91%, respectively. Major delayed local complications occurred in 7 cases (16%). Conclusions: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri. A randomized trial is planned.

  18. Use of targeted therapies for advanced renal cell carcinoma in the Asia-Pacific region: opinion statement from China, Japan, Taiwan, Korea, and Australia.

    PubMed

    Ye, Dingwei; Eto, Masatoshi; Chung, Jin Soo; Kimura, Go; Chang, Wen-Cheng; Chang, Yen-Hwa; Pang, See-Tong; Lee, Jae Lyun; Niu, Yuanjie; Gurney, Howard; Uemura, Hirotsugu

    2014-08-01

    Rates of renal cell carcinoma (RCC) morbidity and mortality vary widely by geography, with increasing incidence in most countries. Interestingly, RCC incidence is significantly lower in Asian countries relative to other regions, which is attributed to environmental and genetic influences. Additionally, it has been demonstrated that different ethnic groups differ in their RCC characteristics which might lead to varied responses to therapy. In this review, physicians drawn from countries across the Asia-Pacific region--China, Japan, Taiwan, Republic of Korea, and Australia--take all available data into consideration to develop the first opinion statement on treatment of advanced RCC in the region. We have sought to determine what factors influence treatment patterns and availability of therapeutic agents in our respective countries, discussed whether these factors are fully justified or should be modified, and considered what additional efforts should be undertaken to optimize treatment outcomes in RCC. Additionally, we have addressed the limitations on treatment of RCC in the region, capturing the restrictive situations of targeted therapy use in the Asia-Pacific region, mainly because of drug availability and treatment reimbursement. Often this illustrates the gap between Western and regional or even among local guidelines, the opinions of leading physicians regarding the treatment, and the realistic access to agents for most patients. Proposals made in this document are based on clinical experience and data from clinical trials of RCC therapies in which Asian patients have been included.

  19. Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma.

    PubMed

    Lapke, Nina; Lu, Yen-Jung; Liao, Chun-Ta; Lee, Li-Yu; Lin, Chien-Yu; Wang, Hung-Ming; Ng, Shu-Hang; Chen, Shu-Jen; Yen, Tzu-Chen

    2016-07-12

    TP53 mutations have been linked to reduced survival in patients with oral cavity squamous cell carcinoma (OSCC). However, the impact of different types of TP53 mutations remains unclear. Here, we demonstrate that the carriage of missense mutations in the TP53 DNA binding domain (DBD missense mutations) is associated with decreased disease-specific survival (DSS) compared with wild-type TP53 (P=0.002) in a cohort of 345 OSCC patients. In contrast, DSS of patients bearing all of the remaining TP53 mutations did not differ from that observed in wild-type TP53 patients (P=0.955). Our classification method for TP53 mutations was superior to previously reported approaches (disruptive, truncating, Evolutionary Action score, mutations in L2/L3/LSH) for distinguishing between low- and high-risk patients. When analyzed in combination with traditional clinicopathological factors, TP53 DBD missense mutations were an independent prognostic factor for shorter DSS (P=0.014) alongside with advanced AJCC T- and N-classifications and the presence of extracapsular spread. A scoring system that included the four independent prognostic factors allowed a reliable patient stratification into distinct risk groups (high-risk patients, 16.2%). Our results demonstrate the usefulness of TP53 DBD missense mutations combined with clinicopathological factors for improving the prognostic stratification of OSCC patients.

  20. Physical considerations in the treatment of advanced carcinomas of the larynx and pyriform sinuses using 10 MV x rays

    SciTech Connect

    Doppke, K.; Novack, D.; Wang, C.C.

    1980-09-01

    A technique for treating patients who have advanced tumors of the larynx and pyriform sinus was developed using isocentric anterior and posterior opposed fields with 10 MV x rays. This technique can be used to deliver a tumor dose of 45 Gray to the primary site and regional nodes and approximately 40 Gray to the spinal cord. The method eliminates problems of multi-field junctures and lowers the daily spinal cord dose when compared to the standard parallel opposed lateral portals and anterior neck fields.

  1. Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma

    SciTech Connect

    Ma, Brigette; King, Ann; Lo, Y.M. Dennis; Yau, Y.Y.; Zee, Benny; Hui, Edwin P.; Leung, Sing F.; Mo, Frankie; Kam, Michael K.; Ahuja, Anil; Kwan, Wing H.; Chan, Anthony . E-mail: anthony@clo.cuhk.edu.hk

    2006-11-01

    Purpose: Plasma Epstein-Barr virus DNA (pEBV DNA) is an important prognostic marker in nasopharyngeal carcinoma (NPC). This study tested the hypotheses that pEBV DNA reflects tumor burden and metabolic activity by evaluating its relationship with tumor volume and {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) uptake in NPC. Methods and Materials: Pre-treatment pEBV DNA analysis, {sup 18}F-FDG positron emission tomography-computed tomography scan (PET-CT) and magnetic resonance imaging (MRI) of the head and neck were performed in 57 patients. Net volume (cm{sup 3}) of the primary tumor (T{sub vol}) and regional nodes (N{sub vol}) were quantified on MRI. {sup 18}F-FDG uptake was expressed as the maximum standardized uptake value (SUV{sub max}) at the primary tumor (T{sub suv}) and regional nodes (N{sub suv}). Lesions with SUV{sub max} {>=} 2.5 were considered malignant. Relationship between SUV{sub max}, natural logarithm (log) of pEBV DNA, and square root (sq) of MRI volumes was analyzed using the Wilcoxon test. A linear regression model was constructed to test for any interaction between variables and disease stage. Results: Log-pEBV DNA showed significant correlation with sq-T{sub vol} (r = 0.393), sq-N{sub vol} (r = 0.452), total tumor volume (sq-Total{sub vol} = T{sub vol} + N{sub vol}, r = 0.554), T{sub suv} (r = 0.276), N{sub suv} (r = 0.434), and total SUV{sub max} (Total{sub suv} = T{sub suv} + N{sub suv}, r = 0.457). Likewise, sq-T{sub vol} was correlated to T{sub suv} (r 0.426), and sq-N{sub vol} with N{sub suv} (r = 0.651). Regression analysis showed that only log-pEBV DNA was significantly associated with sq-Total{sub vol} (p < 0.001; parameter estimate = 8.844; 95% confidence interval = 3.986-13.703), whereas Sq-T{sub vol} was significantly associated with T{sub suv} (p = 0.002; parameter estimate = 3.923; 95% confidence interval = 1.498-6.348). Conclusion: This study supports the hypothesis that cell-free plasma EBV DNA is a marker of tumor burden in EBV

  2. Expression of parathyroid hormone-related protein confers malignant potential to mucoepidermoid carcinoma

    PubMed Central

    NAGAMINE, KYOSUKE; KITAMURA, TETSUYA; YANAGAWA-MATSUDA, AYA; OHIRO, YOICHI; TEI, KANCHU; HIDA, KYOKO; HIGASHINO, FUMIHIRO; TOTSUKA, YASUNORI; SHINDOH, MASANOBU

    2013-01-01

    Parathyroid hormone-related protein (PTHrP) is known to induce bone resorption by activating RANKL as well as PTH. PTHrP plays a central role in humoral hypercalcemia, and its expression has been reported to be closely associated with bone metastasis of breast carcinoma. PTHrP expression in oral squamous carcinoma cell lines was investigated, and PTHrP was expressed in oral squamous cell carcinoma cell lines similar to that in a prostate carcinoma cell line. Mucoepidermoid carcinoma is the most common malignant salivary gland tumor composed of different types of cells including a squamous component. Its clinical behavior is highly variable and ranges from slow-growing and indolent to locally aggressive and highly metastatic. We examined the PTHrP expression in mucoepidermoid carcinoma and assessed the significance of its correlation with clinicopathological features. Immunohistochemical detection of PTHrP was carried out in 21 cases of mucoepidermoid carcinoma in the head and neck region. PTHrP was highly detectable in intermediate and epidermoid cells, and abundant expression of PTHrP in intermediate cells had a significant association with cancer malignancy, including lymph node metastasis and/or tumor recurrence. These results suggest that PTHrP expression can be used as a prognostic factor for mucoepidermoid carcinoma. PMID:23588777

  3. Vismodegib in basal cell carcinoma.

    PubMed

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  4. Axitinib: A Review of its Safety and Efficacy in the Treatment of Adults with Advanced Renal Cell Carcinoma

    PubMed Central

    Gross-Goupil, Marine; François, Louis; Quivy, Amandine; Ravaud, Alain

    2013-01-01

    Over the last seven years, seven targeted agents have been approved in the treatment of advanced or metastatic renal cell cancer, changing the therapeutic approach and prognosis of the disease dramatically. The latest agent with demonstrated efficacy is axitinib (Inlyta®). This new generation of tyrosine kinase agent differs from previously existing agents by its greater activity potency of inhibition of vascular endothelial growth factor-receptor (VEGFR1-3). This efficacy has been tested in phase II and III clinical trials. Axitinib is the only targeted agent that benefits from recommended titration, with intra-patient dose escalation. The toxicity profile of the drug is tolerable. This paper reviews the mechanism of action of axitinib, its metabolism, and its pharmacokinetic profile. Clinical data of efficacy and safety is also detailed. The agent has been integrated in the international therapeutic guidelines, as a standard in treatment of renal cell cancer patients, previously treated through antiangiogenic therapy. PMID:24250243

  5. Simultaneous Integrated Boost–Intensity Modulated Radiation Therapy With Concomitant Capecitabine and Mitomycin C for Locally Advanced Anal Carcinoma: A Phase 1 Study

    SciTech Connect

    Deenen, Maarten J.; Dewit, Luc; Boot, Henk; Beijnen, Jos H.; Schellens, Jan H.M.; Cats, Annemieke

    2013-04-01

    Purpose: Newer radiation techniques, and the application of continuous 5-FU exposure during radiation therapy using oral capecitabine may improve the treatment of anal cancer. This phase 1, dose-finding study assessed the feasibility and efficacy of simultaneous integrated boost–intensity modulated radiation therapy (SIB-IMRT) with concomitant capecitabine and mitomycin C in locally advanced anal cancer, including pharmacokinetic and pharmacogenetic analyses. Methods and Materials: Patients with locally advanced anal carcinoma were treated with SIB-IMRT in 33 daily fractions of 1.8 Gy to the primary tumor and macroscopically involved lymph nodes and 33 fractions of 1.5 Gy electively to the bilateral iliac and inguinal lymph node areas. Patients received a sequential radiation boost dose of 3 × 1.8 Gy on macroscopic residual tumor if this was still present in week 5 of treatment. Mitomycin C 10 mg/m{sup 2} (maximum 15 mg) was administered intravenously on day 1, and capecitabine was given orally in a dose-escalated fashion (500-825 mg/m{sup 2} b.i.d.) on irradiation days, until dose-limiting toxicity emerged in ≥2 of maximally 6 patients. An additional 8 patients were treated at the maximum tolerated dose (MTD). Results: A total of 18 patients were included. The MTD of capecitabine was determined to be 825 mg/m{sup 2} b.i.d. The predominant acute grade ≥3 toxicities included radiation dermatitis (50%), fatigue (22%), and pain (6%). Fifteen patients (83% [95%-CI: 66%-101%]) achieved a complete response, and 3 (17%) patients a partial response. With a median follow-up of 28 months, none of the complete responders, and 2 partial responders had relapsed. Conclusions: SIB-IMRT with concomitant single dose mitomycin C and capecitabine 825 mg/m{sup 2} b.i.d. on irradiation days resulted in an acceptable safety profile, and proved to be a tolerable and effective treatment regimen for locally advanced anal cancer.

  6. Hypofractionated Accelerated Radiotherapy With Concurrent Chemotherapy For Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Sanghera, Paul; McConkey, Chris; Ho, Kean-Fatt; Glaholm, John; Hartley, Andrew . E-mail: andrew.hartley@uhb.nhs.uk

    2007-04-01

    Purpose: To investigate the tumor control rates in locally advanced head-and-neck cancer using accelerated hypofractionated radiotherapy with chemotherapy. Methods and Materials: The data from patients with squamous cell cancer of the larynx, oropharynx, oral cavity, and hypopharynx (International Union Against Cancer Stage II-IV), who received accelerated hypofractionated radiotherapy with chemotherapy between January 1, 1998, and April 1, 2005, were retrospectively analyzed. Two different chemotherapy schedules were used, carboplatin and methotrexate, both single agents administered on an outpatient basis. The endpoints were overall survival, local control, and disease-free survival. Results: A total of 81 patients were analyzed. The 2-year overall survival rate was 71.6% (95% confidence interval [CI], 61.5-81.8%). The 2-year disease-free survival rate was 68.6% (95% CI, 58.4-78.8%). The 2-year local control rate was 75.4% (95% CI, 65.6-85.1%). When excluding patients with Stage II oral cavity, larynx, and hypopharynx tumors, 68 patients remained. For these patients, the 2-year overall survival, local control, and disease-free survival rate was 67.6% (95% CI, 56.0-79.2%), 72.0% (95% CI, 61.0-83.0%), and 64.1% (95% CI, 52.6-75.7%), respectively. Conclusion: Accelerated hypofractionated radiotherapy and synchronous chemotherapy can achieve high tumor control rates while being resource sparing and should be the subject of prospective evaluation.

  7. Early and late radiotherapeutic morbidity in 442 consecutive patients with locally advanced carcinoma of the uterine cervix

    SciTech Connect

    Pedersen, D.; Bentzen, S.M.; Overgaard, J.

    1994-07-30

    The purpose of this study was to evaluate the early and late radiotherapeutic morbidity after combined external and intracavitary radiotherapy to the uterine cervix. Early morbidity was most frequently seen in the rectosigmoideum (61%) and urinary bladder (27%). Medication for early morbidity was required 68% and hospitalization in 10% of the patients. The frequencies of each late morbidity grade did not differ in relation to FIGO State while the actuarial estimates increased significantly with increasing stage. This reflects the poor prognosis in the more advanced stages, where few patients survived to develop late morbidity, and also points to the importance of latency in reporting late radiotherapeutic morbidity. In Stage IVA patients, the ratios between the actuarial estimate and the frequency of late severe rectosigmoid and urinary bladder morbidity were as high as 2.5 and 3, respectively. The highest 5-year risk ({+-} 1 SE of the estimate) of late severe morbidity were found for the rectosignoideum (28% {+-} 3), small intestine (13% {+-} 2) and urinary bladder (10% {+-} 2). Rectosigmoid and urinary bladder complications constituted the most important part of the combined organ morbidity. Almost half of the patients developing late moderate rectosigmoid and one-third of those developing late moderate bladder complications, did so within one year after radiotherapy. Almost all complications were developed within 3 to 4 years after radiotherapy. The probability of surviving without recurrence and/or severe combined rectosigmoid and urinary bladder morbidity was low (23% {+-} 2). Actuarial estimates rather than frequencies should be reported to avoid underestimation of the risk of late radiotherapeutic morbidity in long-term survivors. 29 refs., 5 figs. 7 tabs.

  8. Concomitant Chemoradiotherapy With Mitomycin C and Cisplatin in Advanced Unresectable Carcinoma of the Head and Neck: Phase I-II Clinical Study

    SciTech Connect

    Strojan, Primoz Karner, Katarina; Smid, Lojze; Soba, Erika; Fajdiga, Igor; Jancar, Boris; Anicin, Aleksandar; Budihna, Marjan; Zakotnik, Branko

    2008-10-01

    Purpose: To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck. Patients and Methods: Treatment consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m{sup 2} IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m{sup 2}/d IV, applied during the last 10 fractions of irradiation ('chemoboost'). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m{sup 2}/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m{sup 2}/d (Phase I study), which was tested in the subsequent Phase II study. Results: All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m{sup 2}/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m{sup 2}/d, the corresponding rates were 40%, 20%, and 22%, respectively. Conclusion: Concomitant chemoradiotherapy with mitomycin C and cisplatin 'chemoboost' at 14 mg/m{sup 2}/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.

  9. A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma

    PubMed Central

    2013-01-01

    Background Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of ‘in situ’ tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC. Methods Patients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety. Results Three intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year. Conclusions Intratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of this in situ tumor vaccination are warranted. PMID:24131485

  10. Receptor for advanced glycation end product blockade enhances the chemotherapeutic effect of cisplatin in tongue squamous cell carcinoma by reducing autophagy and modulating the Wnt pathway.

    PubMed

    Zhao, Ziming; Wang, Hongyu; Zhang, Liao; Mei, Xifan; Hu, Jing; Huang, Keqiang

    2017-02-01

    Tongue squamous cell carcinoma (TSCC) is one of the most severe types of cancer with poor outcomes. Cisplatin is used widely to treat cancer cells, but many patients develop acquired drug resistance. The receptor for advanced glycation end products (RAGE) is expressed widely in TSCC and associated with drug-induced chemotherapy resistance. However, the effect of RAGE and cisplatin on Tca-8113 cells remains unknown. We assayed the combined use of RAGE blockade and cisplatin effect on Tca-8113 cells' viability by MTT and apoptosis rate of Tca-8113 cells on RAGE blockade+cisplatin treatment; cisplatin alone; or RAGE blockade alone by flow cytometry. We observed the expressions of autophagy-related proteins beclin1, LC3II, p62; Wnt signaling-related proteins β-catenin, GSK3β, WNT5A, ROR-2; and apoptosis-related protein cleaved caspase-3, bcl-2-associated X proteins using western blot. We determined WNT5A and beclin1 expression on Tca-8113 cells by immunofluorescence. We further observed autophagy vacuoles by monodansylcadaverine staining. We found that RAGE blockade and cisplatin significantly decreased cell viability and increased the cell apoptosis rate compared with cisplatin alone. Furthermore, RAGE blockade suppressed the canonical Wnt pathway proteins β-catenin and GSK-3β, but upregulated noncanonical WNT5A and receptor ROR-2. We show that RAGE blockade suppressed the levels of autophagy-related protein LC3II/I, beclin1, accelerated degradation of autophagy for the increasing p62 expression, and increased cell apoptosis for the increasing expressions of cleaved caspase-3 and bcl-2-associated X proteins. We observed the location of WNT5A and beclin1 expressions on cells by immunofluorescence and their trends were consistent with western blotting. Taken together, our findings suggested that RAGE blockade+cisplatin improved chemotherapeutic effects by reducing autophagy and regulating Wnt/β-catenin to suppress the progression of TSCC.

  11. Phase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat in advanced renal cell carcinoma and other solid tumors

    PubMed Central

    Zibelman, Matthew; Wong, Yu-Ning; Devarajan, Karthik; Malizzia, Lois; Corrigan, Alycia; Olszanski, Anthony J.; Denlinger, Crystal S.; Roethke, Susan K.; Tetzlaff, Colleen H.; Plimack, Elizabeth R.

    2015-01-01

    Background Drugs inhibiting the mammalian target of rapamycin (mTOR) are approved in the treatment of renal cell carcinoma (RCC), but resistance inevitably emerges. Proposed escape pathways include increased phosphorylation of Akt, which can be down regulated by histone deacetylase (HDAC) inhibitors. We hypothesized that co-treatment with the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat may abrogate resistance in RCC. Methods This phase 1 study evaluated the co-administration of ridaforolimus and vorinostat in patients with advanced solid tumors. The primary objective was to determine the maximum tolerated dose (MTD) in RCC patients. Although all solid tumors were allowed, prior cytotoxic chemotherapy was limited to 1 regimen. Using a modified 3+3 dose escalation design, various dose combinations were tested concurrently in separate cohorts. Efficacy was a secondary endpoint. Results Fifteen patients were treated at one of three dose levels, thirteen with RCC (10 clear cell, 3 papillary). Dosing was limited by thrombocytopenia. The MTD was determined to be ridaforolimus 20mg daily days 1–5 with vorinostat 100mg BID days 1–3 weekly, however late onset thrombocytopenia led to a lower recommended phase II dose: ridaforolimus 20mg daily days 1–5 with vorinostat 100mg daily days 1–3 weekly. Two patients, both with papillary RCC, maintained disease control for 54 and 80 weeks, respectively. Conclusions The combination of ridaforolimus and vorinostat was tolerable at the recommended phase II dose. Two patients with papillary RCC experienced prolonged disease stabilization, thus further study of combined HDAC and mTOR inhibition in this population is warranted. PMID:26091915

  12. Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

    SciTech Connect

    Sher, David J.; Posner, Marshall R.; Sarlis, Nicholas J.; Haddad, Robert I.; Holupka, Edward J.; Devlin, Phillip M.

    2011-12-01

    Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

  13. Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion

    SciTech Connect

    Hou Jiazhou; Zeng Zhaochong; Zhang Jianying; Fan Jia; Zhou Jian; Zeng Mengsu

    2012-10-01

    Purpose: The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods and Materials: We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. Results: The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher {alpha}-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). Conclusions: In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.

  14. Cost‐effectiveness of neoadjuvant concurrent chemoradiotherapy versus esophagectomy for locally advanced esophageal squamous cell carcinoma: A population‐based matched case‐control study

    PubMed Central

    Lin, Chen‐Yuan; Fang, Hsin‐Yuan; Feng, Chun‐Lung; Li, Chia‐Chin

    2015-01-01

    Abstract Background Neoadjuvant concurrent chemoradiotherapy (NCCRT) is often considered for locally‐advanced esophageal squamous cell carcinoma (LA‐ESCC) patients; however, no data regarding the cost‐effectiveness of this treatment is available. Our study aimed to evaluate the cost‐effectiveness of NCCRT versus esophagectomy for LA‐ESCC at population level. Methods We identified LA‐ESCC patients diagnosed within 2008–2009 and treated with either NCCRT or esophagectomy through the Taiwan Cancer Registry. We included potential confounding covariables (age, gender, residency, comorbidity, social‐economic status, disease stage, treating hospital level and surgeon's experience, and the use of endoscopic ultrasound before treatment) and used propensity score (PS) to construct a 1:1 population. The duration of interest was three years within the date of diagnosis. Effectiveness was measured as overall survival. We took the payer's perspective and converted the cost to 2014 United States dollars (USD). In sensitivity analysis, we evaluated the potential impact of an unmeasured confounder on the statistical significance of incremental net benefit at suggested willingness‐to‐pay. Results Our study population constituted 150 PS matched subjects. The mean cost (2014 USD) and survival (year) were higher for NCCRT compared with esophagectomy (US$91,460 vs. $75,836 for cost; 2.2 vs. 1.8 for survival) with an estimated incremental cost‐effectiveness ratio of US$39,060/life‐year. Conclusions When compared to esophagectomy, NCCRT is likely to improve survival and is probably more cost‐effective. Cost‐effectiveness results should be interpreted with caution given our results were sensitive to potential unmeasured confounder(s) in sensitivity analysis. PMID:27148413

  15. Transcatheter Arterial Chemoembolization Plus 131I-Labelled Metuximab versus Transcatheter Arterial Chemoembolization Alone in Intermediate/Advanced Stage Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhu, Ze-xin; Liao, Ming-heng; Wang, Xiao-xue

    2016-01-01

    Objective The aim of the study was to compare transcatheter arterial chemoembolization (TACE) plus 131I-labelled metuximab with TACE alone for hepatocellular carcinoma (HCC). Materials and Methods A comprehensive search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Chinese BioMedical Literature Database with published date from the earliest to February 29th, 2016. No language restrictions were applied, but only prospective randomized controlled trials (RCTs) or non-RCTs were eligible for a full-text review. The primary outcome was the overall survival (OS) and effective rate (the rate of partial atrophy or complete clearance of the tumor lesion). The odds ratios (ORs) were combined using either the fixed-effects model or random-effects model. Results Eight trials (3 RCTs and 5 non-RCTs) were included, involving a total of 1121 patients. Patients receiving combined therapy of TACE plus 131I-labelled metuximab showed significant improvement in effective rate {OR = 4.00, (95% confidence interval [CI]: 2.40–6.66), p < 0.001}, 1-year OS (OR = 2.03 [95% CI: 1.55–2.67], p < 0.001) and 2-year OS (OR = 2.57 [95% CI: 1.41–4.66], p = 0.002]. Conclusion TACE plus 131I-labelled metuximab is more beneficial for treating advanced HCCs than TACE alone in terms of tumor response and OS. Large, multi-center, and blinded randomized trials are required to confirm these findings. PMID:27833404

  16. Relationship between response to induction chemotherapy and disease control in patients with advanced laryngeal carcinoma included in an organ preservation protocol.

    PubMed

    León, Xavier; Valero, Cristina; Rovira, Carlota; Rodriguez, Camilo; López, Montserrat; García-Lorenzo, Jacinto; Quer, Miquel

    2017-03-27

    The aim of the study is to analyze the relationship between the degree of response to induction chemotherapy and the disease control in patients with locally advanced laryngeal carcinomas candidates to total laryngectomy. This retrospective study includes 389 patients with T3-T4 laryngeal tumors candidates to total laryngectomy, diagnosed between 1985 and 2013, treated with induction chemotherapy in an organ preservation protocol. Five-year local recurrence-free survival for patients receiving conservative treatment with radiotherapy after a complete response to induction chemotherapy was 75.4%; for patients with partial response greater than 50%, it was 62.0%; and for patients with the absence of response, it was 32.7%. There were significant differences in local recurrence-free survival and laryngeal dysfunction-free survival according to the response to induction chemotherapy (P = 0.0001) at the expense of patients with absence of response to induction chemotherapy. Patients with partial response greater than 50% treated with radiotherapy had a tendency to have worse local recurrence-free survival and laryngeal dysfunction-free survival than patients with complete response, but the differences did not reach statistical significance. Patients with the absence of response after induction chemotherapy had significant differences in disease-specific survival according to the second treatment: for patients treated with surgery it was 70.2%, whereas for patients treated with radiotherapy, it was 28.2% (P = 0.0001). In patients with the absence of response to induction chemotherapy, conservative treatment with radiotherapy implies a significant decrease in survival.

  17. pERK/pAkt phenotyping in circulating tumor cells as a biomarker for sorafenib efficacy in patients with advanced hepatocellular carcinoma.

    PubMed

    Li, Jun; Shi, Lehua; Zhang, Xiaofeng; Sun, Bin; Yang, Yefa; Ge, Naijian; Liu, Huiying; Yang, Xia; Chen, Lei; Qian, Haihua; Wu, Mengchao; Yin, Zhengfeng

    2016-01-19

    Sorafenib is a multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC). However, therapeutic response to sorafenib was not equal among HCC patients. Here we present a novel system to provide quantitative information concerning sorafenib-related targets by simultaneous detection of phosphorylated ERK (pERK) and pAkt expressions in circulating tumor cells (CTCs) isolated from HCC patients. Our results showed that 90.0% of patients had a molecular classification of tissues concordant with that of CTCs. CTC counts showed a shaper decline in patients with pERK+/pAkt- CTCs after two weeks of sorafenib treatment (P < 0.01). Disease control rates were significantly different between patients with pERK+/pAkt- CTCs (11/15; 73.3%) and those without (13/44; 29.5%) (P < 0.05). Univariate and multivariate analysis indicated pERK+/pAkt- CTCs as an independent predictive factor of progression-free survival (PFS) (hazard ratio = 9.389; P < 0.01). PFS correlated with the proportion of pERK+/pAkt- CTCs (r = 0.968, P < 0.01), and was higher in patients with ≥ 40% pERK+/pAkt- CTCs compared to those with < 40% (8.4 vs. 1.3 mo; P < 0.05). In a validation set of twenty HCC patients, CTCs from patients with ≥ 40% pERK+/pAkt- CTCs had significantly higher inhibition rates of spheroid formation compared to those with < 40% (61.2 vs. 19.8%; P < 0.01). Our findings demonstrated that CTCs can be used in place of tumor tissue for characterization of pERK/pAkt expression. pERK+/pAkt- CTCs are most sensitive to sorafenib and an independent predictive factor of PFS in HCC patients treated with sorafenib.

  18. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study

    PubMed Central

    2014-01-01

    Background In Europe, gastric cancer remains diagnosed at advanced stage (serosal and/or lymph node involvement). Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of T3 and/or N + patients remain under 30%. More than 50% of recurrences are peritoneal and/or locoregional. The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences, was extensively evaluated by several randomized trials conducted in Asia. Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival. As it was previously done for the evaluation of the extension of lymph node dissection, it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia. Methods/design GASTRICHIP is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing, treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy. Peroperatively, at the end of curative surgery, patients will be randomized after preoperatively written consent has been given for participation. Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up (5 years). Secondary endpoint will be 3- and 5-year recurrence-free survival, site of recurrence, morbidity, and quality of life. An ancillary study will compare the incidence of positive peritoneal cytology pre- and post-gastrectomy in two arms of the study

  19. c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

    SciTech Connect

    Baschnagel, Andrew M.; Williams, Lindsay; Hanna, Alaa; Chen, Peter Y.; Krauss, Daniel J.; Pruetz, Barbara L.; Akervall, Jan; Wilson, George D.

    2014-03-01

    Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16

  20. Endocervical ultrasound applicator for integrated hyperthermia and HDR brachytherapy in the treatment of locally advanced cervical carcinoma

    PubMed Central

    Wootton, Jeffery H.; Hsu, I-Chow Joe; Diederich, Chris J.

    2011-01-01

    Purpose: The clinical success of hyperthermia adjunct to radiotherapy depends on adequate temperature elevation in the tumor with minimal temperature rise in organs at risk. Existing technologies for thermal treatment of the cervix have limited spatial control or rapid energy falloff. The objective of this work is to develop an endocervical applicator using a linear array of multisectored tubular ultrasound transducers to provide 3-D conformal, locally targeted hyperthermia concomitant to radiotherapy in the uterine cervix. The catheter-based device is integrated within a HDR brachytherapy applicator to facilitate sequential and potentially simultaneous heat and radiation delivery. Methods: Treatment planning images from 35 patients who underwent HDR brachytherapy for locally advanced cervical cancer were inspected to assess the dimensions of radiation clinical target volumes (CTVs) and gross tumor volumes (GTVs) surrounding the cervix and the proximity of organs at risk. Biothermal simulation was used to identify applicator and catheter material parameters to adequately heat the cervix with minimal thermal dose accumulation in nontargeted structures. A family of ultrasound applicators was fabricated with two to three tubular transducers operating at 6.6–7.4 MHz that are unsectored (360°), bisectored (2×180°), or trisectored (3×120°) for control of energy deposition in angle and along the device length in order to satisfy anatomical constraints. The device is housed in a 6 mm diameter PET catheter with cooling water flow for endocervical implantation. Devices were characterized by measuring acoustic efficiencies, rotational acoustic intensity distributions, and rotational temperature distributions in phantom. Results: The CTV in HDR brachytherapy plans extends 20.5±5.0 mm from the endocervical tandem with the rectum and bladder typically <8 mm from the target boundary. The GTV extends 19.4±7.3 mm from the tandem. Simulations indicate that for 60 min

  1. Endocervical ultrasound applicator for integrated hyperthermia and HDR brachytherapy in the treatment of locally advanced cervical carcinoma

    SciTech Connect

    Wootton, Jeffery H.; Hsu, I-Chow Joe; Diederich, Chris J.

    2011-02-15

    Purpose: The clinical success of hyperthermia adjunct to radiotherapy depends on adequate temperature elevation in the tumor with minimal temperature rise in organs at risk. Existing technologies for thermal treatment of the cervix have limited spatial control or rapid energy falloff. The objective of this work is to develop an endocervical applicator using a linear array of multisectored tubular ultrasound transducers to provide 3-D conformal, locally targeted hyperthermia concomitant to radiotherapy in the uterine cervix. The catheter-based device is integrated within a HDR brachytherapy applicator to facilitate sequential and potentially simultaneous heat and radiation delivery. Methods: Treatment planning images from 35 patients who underwent HDR brachytherapy for locally advanced cervical cancer were inspected to assess the dimensions of radiation clinical target volumes (CTVs) and gross tumor volumes (GTVs) surrounding the cervix and the proximity of organs at risk. Biothermal simulation was used to identify applicator and catheter material parameters to adequately heat the cervix with minimal thermal dose accumulation in nontargeted structures. A family of ultrasound applicators was fabricated with two to three tubular transducers operating at 6.6-7.4 MHz that are unsectored (360 deg.), bisectored (2x180 deg.), or trisectored (3x120 deg.) for control of energy deposition in angle and along the device length in order to satisfy anatomical constraints. The device is housed in a 6 mm diameter PET catheter with cooling water flow for endocervical implantation. Devices were characterized by measuring acoustic efficiencies, rotational acoustic intensity distributions, and rotational temperature distributions in phantom. Results: The CTV in HDR brachytherapy plans extends 20.5{+-}5.0 mm from the endocervical tandem with the rectum and bladder typically <8 mm from the target boundary. The GTV extends 19.4{+-}7.3 mm from the tandem. Simulations indicate that for 60

  2. Anal carcinoma and HIV infection: is it time for screening?

    PubMed

    Herranz-Pinto, P; Sendagorta-Cudós, E; Bernardino-de la Serna, J I; Peña-Sánchez de Rivera, J M

    2014-03-01

    A 38-year-old white man had a 10-year history of human immunodeficiency virus (HIV) infection (A3), with no episodes of opportunistic diseases and in good immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while on HAART. He presented with a two-month history of mild anal symptoms, including pruritus and episodic bleeding. He referred past episodes of anal warts, self-treated with several topical compounds, all proven unsuccessful. Perianal examination showed erythema and scratching. A 0.5cm sized tumor, with infiltration at the base was detected on digital exam, located at 15mm from the anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a final diagnosis of infiltrative epidermoid carcinoma. Might that neoplasia have been prevented?

  3. Long-term evaluation of asymptomatic patients operated on for intracranial epidermoid cysts. Comparison of the diagnostic value of magnetic resonance imaging and computer-assisted cisternography for detection of cholesterin fragments.

    PubMed

    Lunardi, P; Fortuna, A; Cantore, G; Missori, P

    1994-01-01

    Magnetic resonance imaging (MRI) and/or computer-assisted cisternography (CAc) assessment of latent late recurrences in long-term asymptomatic patients surgically treated for intracranial epidermoid cyst is here presented. MRI was exclusively utilized in one patient; CAc was exclusively employed in three patients with metalic operative clips; both CAc and MRI were employed in another four patients. CAc appears to be more reliable than MRI in detecting cholesterin fragments in asymptomatic patients operated on for intracranial epidermoid cyst.

  4. Early Clinical Outcomes and Toxicity of Intensity Modulated Versus Conventional Pelvic Radiation Therapy for Locally Advanced Cervix Carcinoma: A Prospective Randomized Study

    SciTech Connect

    Gandhi, Ajeet Kumar; Sharma, Daya Nand; Rath, Goura Kisor; Julka, Pramod Kumar; Subramani, Vellaiyan; Sharma, Seema; Manigandan, Durai; Laviraj, M.A.; Kumar, Sunesh; Thulkar, Sanjay

    2013-11-01

    Purpose: To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). Methods and Materials: Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m{sup 2}. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was graded according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. Results: Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85