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Sample records for advanced epidermoid carcinoma

  1. Multimodality approach to surgical management of locally advanced epidermoid carcinoma of the anorectum

    SciTech Connect

    Wanebo, H.J.; Futrell, W.; Constable, W.

    1981-06-15

    Seven patients (five female, two male) had locally advanced epidermoid carcinoma of the anal canal. Three patients had recurrent or persistent disease previously treated and four had advanced primary cancer. Five patients had groin node metastasis. The treatment protocol consisted of chemotherapy with continuous 5-day infusion of 5-fluorouracil, 750 mg/m2, and mitomycin C, 15 mg/m2, by bolus injection and radiation 3000 rads. All patients received one or two cycles of chemotherapy pre-operatively and four (not previously irradiated) received radiation. Tumor regression greater than 50% occurred in five patients, minor regression (25-50%) occurred in one patient and one patient showed no regression (on chemotherapy alone). All patients had total resection of all gross tumor with microscopic clear margins and five had groin dissection. One patient had no residual cancer in specimen and one patient had a microscopic focus only. Four of five patients had residual nodal metastases at groin dissection. Currently three patients are free of disease at 24, 24, and 26 months. Two patients died with disease at 6 months and 34 months, and two patients died of other causes while still free of disease, at 4 and 5 months after resection. Multimodality therapy of locally advanced epidermoid cancer of anal canal can provide effective control and palliation of many of these tumors and, in some, possibly effect cure.

  2. Combined radiotherapy and chemotherapy versus radiotherapy alone in locally advanced epidermoid bronchogenic carcinoma. A randomized study

    SciTech Connect

    Trovo, M.G.; Minatel, E.; Veronesi, A.; Roncadin, M.; De Paoli, A.; Franchin, G.; Magri, D.M.; Tirelli, U.; Carbone, A.; Grigoletto, E. )

    1990-02-01

    Between June 1980 and December 1983, 111 patients with inoperable epidermoid bronchogenic carcinoma (limited disease) were entered into a randomized trial comparing radiotherapy alone versus radiotherapy and combination chemotherapy with cyclophosphamide, Adriamycin (doxorubicin), methotrexate, and procarbazine. Thirty-five of 62 (56.4%) patients treated with 4500 rad in 15 fractions in 3 weeks and 19 of 49 (38.8%) patients treated with the same radiation treatment and chemotherapy had an objective response. The difference in response rate was not significant (P = 0.900). Median time to progression was 5.9 and 7.02 months, respectively, for the radiation treatment and the combined treatment. Median survival was 11.74 and 10.03 months, respectively, without statistically significant differences between the two groups of patients. The toxicity was acceptable and no treatment-related death occurred in either treatment schedule. In this study no significant superiority of combined radiotherapy and chemotherapy treatment over radiation therapy alone was evidenced. Whether different chemotherapy regimens may prove more effective in this context should be clarified by further studies.

  3. Bleomycin, cyclophosphamide and radiotherapy in regionally advanced epidermoid carcinoma of the head and neck

    SciTech Connect

    Seagren, S.L.; Byfield, J.E.; Davidson, T.M.; Sharp, T.R.

    1982-01-01

    Twenty-four patients with squamous carcinoma of the head and neck and advanced regional (N/sub 2-3) disease were treated. The regimen consisted of 3 cycles, each of 28 days. Cyclophosphamide (1 gm/ M/sup 2/ I.V.) was given on day 1, bleomycin (15 u I.M.) on days 2, 4, 9 and 11, and ionizing radiation (/sup 60/Co, 180 rad/fraction) days 1-5, and 8-12. No therapy was given on days 13-28. After three cycles of therapy, 13 patients had a complete response; following further therapy (surgery, interstitial or external beam radiation), 16 patients were free of disease. However, remissions were not durable and 11/16 patients recurred loco-regionally with a median time to recurrence of 5 months; most (7/11) also developed distant metatases. These patients have biologically aggressive disease and may have a worse prognosis than patients who are Stage IV based on a T/sub 4/ primary lesion only.

  4. Bleomycin, cyclophosphamide and radiotherapy in regionally advanced epidermoid carcinoma of the head and neck

    SciTech Connect

    Seagren, S.L.; Byfield, J.E.; Davidson, T.M.; Sharp, T.R.

    1982-01-01

    Twenty four patients with squamous carcinoma of the head and neck and advanced regional (N/sub 2//sub -//sub 3/) disease were treated. The regimen consisted of 3 cycles, each of 28 days. Cyclophosphamide (I gm/m/sup 2/ I.V.) were given on day 1, bleomycin (15 ..mu.. I.M.) on days 2, 4, 9 and 11, and ionizing radiation (/sup 60/Co, 180 rad/fraction) days 1-5, and 8-12. No therapy was given on days 13-28. After three cycles of therapy, 13 patients had a complete response; following further therapy (surgery, interstitial or extenal beam radiation), 16 patients were free of disease. However, remissions were not durable and 11/16 patients recurred loco-regionally with a median time to recurrence of 5 months; most (7/11) also developed distant metastases. These patients have biologically aggressive disease and may have a worse prognosis than patients who are Stage IV based on a T/sub 4/ primary lesion only.

  5. Pulmonary epidermoid carcinoma in a patient with acromegaly: a rare entity

    PubMed Central

    El Aziz, Siham; Chadli, Asma; Obbiba, Atika; El Ghomari, Hassan; Farouqi, Ahmed

    2012-01-01

    A 56-years-old woman was referred to our unit for partially treated acromegaly. She had a high level of insulin growth factor. She did not complain of any pulmonary symptoms and was a non-smoker. Physical examination revealed clinical features of acromegaly. She had a 13 mm pituitary adenoma and was proposed for surgical intervention. Her chest X-ray showed a right paracardiac tumor. Computed tomography scan revealed a large right-sided fowler tumor. Pituitary surgery was cancelled and lobectomy after biopsy with lymph nodes excision was performed through thoracotomy. Histological study of the tumor revealed a medium differentiated epidermoid carcinoma with positive lymph nodes and extension to pleura. She was referred to chemotherapy protocol. Association between carcinoma and acromegaly has previously been reported. Most common tumors are colorectal and thyroid neoplasia. As we see in this case report, we need to consider other carcinomas in acromegalic patients like pulmonary carcinoma, despite their rarity in women. PMID:22891085

  6. [Laryngeal epidermoid carcinoma in a young adult without risk factors: a case report].

    PubMed

    M'barek, Basma; Gargouri, W; Maalej, M

    2005-08-01

    Head and neck carcinomas are rare in young patients without a history of tobacco consution, tho two classical risk factors. Our report is about 20 year-old patient without a history exosure to radiations or of alcohol / tobacco consumption, who presented with repeated episodes of dysphonia that didn't improve under medical treatment. Endoscopy showed a fungating hemilaryngeal lesion with a histology of epidermoid carcinoma stage T3N0. The patient initially 3 courses of cisplatin-5 fluorouracil resulting in a 90% objective response, followed by a loco-regional radiotherapy. 36 months after the diagnosis and 24 after the end of therapy, the patient is still alive and in complete remission. PMID:16238282

  7. 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

  8. Purification of high-molecular-weight subfraction from porcine skin inhibiting proliferation of A431 human carcinoma epidermoid cells.

    PubMed

    Belova, O V; Sergienko, V I; Arion, V Ya; Lukanidina, T A; Moskvina, S N; Zimina, I V; Borisenko, G G; Lutsenko, G V; Grechikhina, M V; Kovaleva, E V; Klyuchnikova, Zh I

    2014-07-01

    Subfraction with a molecular weight >250 kDa isolated from porcine skin and inhibiting the proliferation of A431 human carcinoma epidermoid cells was purified by DEAE 32 anion exchange chromatography with NaCl concentration step-gradient. The effects of the initial subfraction and fractions obtained by separation in DEAE 32 on the proliferation of A431 human carcinoma epidermoid cells were studied in vitro in two tests (MTT and fluorescent test). The more sensitive fluorescent test showed the highest inhibitory activity of fraction No. 2 released from the column at 0.15 M NaCl. One major protein component and a series of minor protein components were detected in this fraction by vertical PAAG-SDS electrophoresis. PMID:25070165

  9. 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. PMID:25858017

  10. In vitro cytotoxic effect of Brazilian green propolis on human laryngeal epidermoid carcinoma (HEp-2) cells.

    PubMed

    Búfalo, Michelle C; Candeias, João M G; Sforcin, José Maurício

    2009-12-01

    Propolis is a sticky dark-colored material showing a very complex chemical composition that honeybees collect from plants. It has been used in folk medicine since ancient times, due to several biological properties, such as antimicrobial, anti-inflammatory, antioxidant and immunomodulatory activities, among others. Its antitumor action in vivo and in vitro has also been reported, using propolis extracts or its isolated compounds. The goal of this work was to evaluate propolis's cytotoxic action in vitro on human laryngeal epidermoid carcinoma (Hep-2) cells. These cells were incubated with different concentrations of this bee product for different time periods, and morphology and the number of viable HEp-2 cells analyzed. Data showed that propolis exhibited a cytotoxic effect in vitro against HEp-2 cells, in a dose- and time-dependent way. Propolis solvent had no effects on morphology and number of viable cells, proving that the cytotoxic effects were exclusively due to propolis components. Since humans have been using propolis for a long time, further assays will provide a better comprehension of propolis's antitumor action. PMID:18955250

  11. 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.

  12. In vitro Cytotoxic Effect of Brazilian Green Propolis on Human Laryngeal Epidermoid Carcinoma (HEp-2) Cells

    PubMed Central

    Búfalo, Michelle C.; Candeias, João M. G.

    2009-01-01

    Propolis is a sticky dark-colored material showing a very complex chemical composition that honeybees collect from plants. It has been used in folk medicine since ancient times, due to several biological properties, such as antimicrobial, anti-inflammatory, antioxidant and immunomodulatory activities, among others. Its antitumor action in vivo and in vitro has also been reported, using propolis extracts or its isolated compounds. The goal of this work was to evaluate propolis's cytotoxic action in vitro on human laryngeal epidermoid carcinoma (Hep-2) cells. These cells were incubated with different concentrations of this bee product for different time periods, and morphology and the number of viable HEp-2 cells analyzed. Data showed that propolis exhibited a cytotoxic effect in vitro against HEp-2 cells, in a dose- and time-dependent way. Propolis solvent had no effects on morphology and number of viable cells, proving that the cytotoxic effects were exclusively due to propolis components. Since humans have been using propolis for a long time, further assays will provide a better comprehension of propolis's antitumor action. PMID:18955250

  13. A clinical report of an oral lichen planus associated to epidermoid carcinoma in contact with metallic restorations.

    PubMed

    Silva, Regina Helena Barbosa Tavares da; Paleari, Andrá Gustavo; Brito, Carolina de Assis Barros; Rocha, Josá Francisco Santos Simões da; Massucato, Elaine Maria Sgavioli; Quishida, Cristiane Campos Costa

    2014-01-01

    The aim of this study was to relate the clinical case of a patient with oral lichen planus (OLP) and a history of epidermoid carcinoma associated with metallic restorations. The etiology of OLP is a mucocutaneous disease, which is poorly understood. Studies point to the potential of malignant transformation of OLP and its association with metallic restorations. The metallic restorations were replaced by crowns with a ceramic covering associated and osseointegrated implants in the edentulous areas. About 1 year later, it was observed a bilateral regression of the tongue lesions. The replacement of metallic restorations can contribute to improvement of OLP. PMID:25707841

  14. Epidermoid carcinoma of the anal canal. A series of 276 cases

    SciTech Connect

    Papillon, J.; Montbarbon, J.F.

    1987-05-01

    During the past ten years, substantial progress has been made in the knowledge of the natural history of epidermoid carcinoma of the anal canal and of the response of the disease to radiotherapy alone or combined with chemotherapy. At the present time, the main problem in the management of this tumor concerns identification of the best modalities to achieve local control and preservation of anal function. From a series of 276 cases, followed for more than three years, the necessity for a careful pretreatment evaluation was stressed. This included a systematic search for pelvic metastatic lymph nodes by palpation and CT scan. All patients were treated initially by irradiation except those who underwent groin dissection for inguinal node metastasis or colostomy for complete anal obstruction. Three groups of patients have been identified: unresectable or disseminated tumors (33 cases), resectable tumors but not suitable for sphincter conservation (21 cases) treated by radiochemotherapy and delayed surgery, and resectable tumors suitable for sphincter conservation (222 cases) which were treated by a split-course regimen combining a short course of carefully planned external beam irradiation (19 days) followed by an iridium 192 implant after a two-month rest. In this group, which represents 80 percent of the whole series, 80 percent of patients have had their cancer controlled and 90 percent of controlled patients have retained normal anal function. The use of chemotherapy during the first days of irradiation is advisable in all cases to reinforce the efficacy of treatment and increase the chance of anal preservation. Results of the split-course regimen, combining external beam and interstitial irradiation, demonstrate a clear superiority over external beam irradiation alone, especially for large infiltrating tumors, which represent the majority of cases.

  15. Combined radiotherapy and chemotherapy with cyclophosphamide, adriamycin, methotrexate, procarbazine (camp) in 64 consecutive patients with epidermoid bronchogenic carcinoma, limited disease: a prospective study. [/sup 60/Co

    SciTech Connect

    Trovo, M.G.; Tirelli, U.; De Paloi, A., et. al.

    1982-06-01

    Sixty-four consecutive patients with inoperable epidermoid bronchogenic carcinoma (limited disease) were treated with radiotherapy to the primary and nodal areas and combination chemotherapy with cyclophosphamide, adriamycin, methotrexate and procarbazine. The overall response rate (CR + PR) to combined treatment was 62%. The median survival time was 12.7 months. The toxicity was acceptable and no treatment-related death occurred.

  16. Effects of resveratrol on the proliferation, apoptosis and telomerase ability of human A431 epidermoid carcinoma cells

    PubMed Central

    ZHAI, XIAO-XIANG; DING, JI-CUN; TANG, ZHI-MING; LI, JING-GUO; LI, YONG-CONG; YAN, YUE-HUA; SUN, JING-CHANG; ZHANG, CUI-XIA

    2016-01-01

    The aim of the present study was to investigate the effect of resveratrol on cell apoptosis, ability of telomerase and the human telomerase reverse transcriptase (hTERT) protein expression in human A431 epidermoid carcinoma cells. A431 cells were treated with different concentrations of resveratrol, and the cell appearance was then observed under a microscope. In addition, the cell proliferation was examined using an MTT assay, and the ability of telomerase was detected using telomeric repeat amplification protocol-polymerase chain reaction-ELISA. Resveratrol significantly inhibited the ability of telomerase and decreased the expression of hTERT protein in a concentration-dependent manner. In conclusion, resveratrol is capable of downregulating the expression of hTERT protein and inhibits the ability of telomerase of A431, which is an important mechanism of action of resveratrol with regard to inhibition of A431 cell proliferation. PMID:27123055

  17. Design and optimization of non-clogging counter-flow microconcentrator for enriching epidermoid cervical carcinoma cells.

    PubMed

    Tran-Minh, Nhut; Dong, Tao; Su, Qianhua; Yang, Zhaochu; Jakobsen, Henrik; Karlsen, Frank

    2011-02-01

    Clogging failure is common for microfilters in living cells concentration; for instance, the CaSki Cell-lines (Epidermoid cervical carcinoma cells) utilizing the flat membrane structure. In order to avoid the clogging, counter-flow concentration units with turbine blade-like micropillar are proposed in microconcentrator design. Due to the unusual geometrical-profiles and extraordinary microfluidic performance, the cells blocking does not occur even at permeate entrances. A counter-flow microconcentrator was designed, with both processing layer and collecting layer arranged in terms of the fractal based honeycomb structure. The device was optimized by coupling Artificial Neuron Network (ANN) and Computational Fluid Dynamics (CFD). The excellent concentration ratio of a final microconcentrator was presented in numerical results. PMID:21053081

  18. 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.

  19. 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. PMID:27261576

  20. [Prognostic value of the immunohistochemical expresion of protein Rb in epidermoid carcinoma of the larynx].

    PubMed

    García Lozano, M C; Orradre Romero, J L; Sánchez Carrión, S; Menéndez Loras, L M; Jiménez Antolín, J; Piris Pinilla, M A

    2005-01-01

    In this paper we carried out an immunohistochemical study of protein Rb (G3-245) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain) for a time of 5 years. In the cases with lymph node metastasis we also studied Rb expression at this level. Furthermore we have analysed the value of Rb expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between Rb expression and other clinic and pathologic parameters. PMID:15929589

  1. [Pronostic value of the immunohistochemical expression of cyclin D1 (DCS6) in epidermoid larynx carcinoma].

    PubMed

    García Lozano, M C; Orradre Romero, J L; Sánchez Carrión, S; Caro Garcia, M; Lasso Luis, O; Piris Pinilla, M A

    2006-01-01

    In this paper we carried out an immunohistochemical study of cyclin D1 (DCS6 ) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain) for a time of 5 years. In the cases with lymph node metastasis we also studied cyclin D1 expression at this level. Furthermore we have analysed the value of cyclin D1 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between cyclin D1 expression and other clinic and pathologic parameters. PMID:16881553

  2. A new approach to the management of epidermoid carcinoma of the anal canal

    SciTech Connect

    Papillon, J.; Mayer, M.; Montbarbon, J.F.; Gerard, J.P.; Chassard, J.L.; Bailly, C.

    1983-05-15

    Until recently most squamous cell carcinomas of the anal canal were treated by radical surgery. Radiation therapy was only considered for palliation in case of inoperable tumors. Important progress has been made in the knowledge of the natural history of the disease and in the field of radiotherapy. Anal canal squamous cell carcinoma should not be treated any longer by the same procedure as adenocarcinoma of the lower rectum, because both these diseases differ markedly. Multimodality therapy with radiotherapy as first approach has been considered. This series of 121 cases treated since 1971 and followed more than three years suggests that three protocols based on irradiation followed or not by surgery should be used according to the extent of the disease. Of the 72 patients with resectable tumor, the five-year survival rate was 65%. Three-quarters of the patients cured had normal anal function. The rate of death from cancer was 18%. The method requires an accurate assessment of the extent of the tumor and of its pelvic lymphatic spread. Great care must be taken in planning treatment in a close cooperation between radiotherapist and surgeon.

  3. Enediyne lidamycin enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, in epidermoid carcinoma A431 cells and lung carcinoma H460 cells.

    PubMed

    Liu, Hong; Li, Liang; Li, Xing-Qi; Liu, Xiu-Jun; Zhen, Yong-Su

    2009-01-01

    Gefitinib, a low-molecular-weight epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is effective in a wide variety of tumor types. Preclinical studies have shown potentiated antitumor efficacies of this agent in combination with chemotherapy or radiotherapy. The antitumor antibiotic lidamycin (LDM) showed extremely potent cytotoxicity in vitro and marked therapeutic effect in vivo. In this report, the cytotoxic and biochemical activity of LDM and gefitinib on human epidermoid carcinoma A431 cells and human large cell lung cancer H460 cells as a single agent or in combination has been evaluated. In the MTT assay, LDM showed much more potent cytotoxicity than gefitinib to both cell lines. A431 cells with a highly EGFR-expressing level were more sensitive to gefitinib than H460 cells, which expressed EGFR at an intermediate level. LDM plus gefitinib showed potentiation of antiproliferative activity and apoptosis induction, which were associated with downregulation of EGFR signaling pathway and nuclear factor-kappa B expression, and the increase of cleaved poly (adenosine diphosphate-ribose) polymerase in the two cell lines, although to a lesser degree in H460 cells. Combined treatment induced G1 phase arrest similar to that of gefitinib alone in A431 cells and intensified G2/M phase accumulation in H460 cells. The above results indicate that LDM potentiates the effects of gefitinib in both gefitinib sensitive and less sensitive cells in association with enhanced inhibition of EGFR-dependent signaling. PMID:19342999

  4. Malignant Transformation of an Epidermoid Cyst in the Cerebellopontine Angle

    PubMed Central

    Chon, Kyu-Hyon; Koh, Eun-Jung; Choi, Ha-Young

    2012-01-01

    Intracranial squamous cell carcinoma is extremely rare, with most of the cases arising from malignant transformation of an epidermoid or a dermoid cyst. The patient presented with facial weakness. Initial magnetic resonance imaging revealed a mass in the right cerebellopontine angle. A subtotal resection was performed via right retrosigmoid suboccipital approach. Histopathological findings were consistent with an epidermoid tumor. Five months later, the patient underwent gamma knife radiosurgery due to highly probable recurrent epidermoid tumor. Two years after, the patient's neurological deficit had been newly developed, and follow-up magnetic resonance imaging demonstrated a large contrast-enhancing tumor in the left cerebellopontine angle, which compressed the brainstem. After resection of the tumor, histopathological examinations revealed a squamous cell carcinoma probably arising from an underlying epidermoid cyst. We report a case of an epidermoid tumor in the cerebellopontine angle that transformed into a squamous cell carcinoma. PMID:23091675

  5. 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.

  6. [Testicular epidermoid cyst: orchiectomy or enucleation resection?].

    PubMed

    Heidenreich, A; Zumbé, J; Vorreuther, R; Klotz, T; Vietsch, H; Engelmann, U H

    1996-01-01

    Our experience with 18 patients with simple epidermoid cysts of the testis is reported. In each patient the tumour was enucleated completely and two biopsies of the adjacent parenchyma were obtained for exclusion of associated germ cell cancer, scars or carcinoma in situ. There was no evidence of malignancy in any of the biopsy specimens. Preoperative evaluation included physical examination, testicular sonography, and determination of AFP and hCG serum levels. Although epidermoid cyst can be strongly suspected on sonography the ultrasound appearance is not specific, and inguinal testicular exploration was required in these patients. In 1 patient multiple epidermoid cysts of the right testis were associated with an adult teratoma containing embryonal carcinoma and choriocarcinoma of the left testis; no similar case has been described in the literature. On the basis of our results and experience we consider tumour enucleation and biopsy of the adjacent parenchyma to be adequate treatment for benign epidermoid cyst. The world literature concerning organ-sparing surgery in testicular epidermoid cyst is reviewed. PMID:8851841

  7. Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis in A431 human epidermoid carcinoma cells.

    PubMed

    Jiang, Zhongyong; Chai, Jin; Chuang, Henry Hon Fung; Li, Shifeng; Wang, Tianran; Cheng, Yi; Chen, Wensheng; Zhou, Deshan

    2012-07-01

    The anticancer effects of artesunate (ART) have been well documented. However, its potential against skin cancer has not been explored yet. Herein we reported that 60 μmol/l ART effectively inhibited A431 (human epidermoid carcinoma cells) growth but not that of HaCaT (normal human keratinocyte cells). Our results revealed that ART induced cell cycle arrest at G0/G1 phase through the downregulation of cyclin A1, cyclin B, cyclin D1, Cdk2, Cdk4, and Cdk6. This correlated with the upregulation of p21 and p27. The 5-bromodeoxyuridine incorporation assay also indicated that ART treatment reduced DNA synthesis in a time-dependent manner. Furthermore, ART induced mitochondrial apoptosis, as evidenced by annexin V/propidium iodide staining and western blot analysis. Interestingly, ART-induced apoptosis diminished under iron-deficient conditions but intensified under iron-overload conditions. Taken together, these findings demonstrated the potential of ART in treating skin cancer through the induction of G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis and supported further investigations in other test systems. PMID:22421370

  8. The beta 2-adrenergic receptors of human epidermoid carcinoma cells bear two different types of oligosaccharides which influence expression on the cell surface.

    PubMed Central

    Cervantes-Olivier, P; Delavier-Klutchko, C; Durieu-Trautmann, O; Kaveri, S; Desmandril, M; Strosberg, A D

    1988-01-01

    The beta 2-adrenergic receptors of the human epidermoid carcinoma A431 cells reside on two polypeptide chains revealed by photoaffinity labelling with [125I]iodocyanopindolol-diazirine. These proteins correspond to two distinct populations of N-asparagine-linked glycoproteins: the 55-52 kDa molecules are associated with complex carbohydrate chain(s), the 65-63 kDa component with polymannosidic carbohydrate chain(s). Both types of receptors are present in preconfluent cells, but only the polymannosidic type is found in the postconfluent cells. Moreover, complex chains appear to be associated with the receptors with the highest affinity for (-)-isoproterenol and polymannosidic chains with the receptors with the lowest affinity for this agonist. the carbohydrate moiety of the beta-adrenergic receptor is involved in the expression and function of the beta 2-adrenergic receptors at the surface of the A431 cells, since tunicamycin and monensin, complete and partial inhibitors of glycosylation respectively, diminish the number of binding sites at the cell surface and increase the total number of sites in the cell. In these conditions a diminution of cyclic AMP accumulation is also observed. Images Fig. 5. PMID:2895638

  9. 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.

  10. Advances in managing hepatocellular carcinoma.

    PubMed

    Reataza, Marielle; Imagawa, David K

    2014-06-01

    Multiple modalities for treatment of hepatocellular carcinoma are available, depending on tumor size and number. Surgical resection remains the gold standard, so long as the residual liver function reserve is sufficient. In patients with advanced cirrhosis, liver transplantation is the preferred option, as these patients may not have adequate hepatic reserve after resection. Salvage liver transplantation has also become an option for a select few patients who recur after surgical resection. Ablative techniques have been used for palliation as well as to either completely destroy the tumor, act as an adjunct to resection, or downstage the tumor to meet Milan criteria such that a patient may be a candidate for liver transplantation. Radiofrequency ablation, microwave ablation, chemoembolization, radioembolization, and irreversible electroporation have all been used in this capacity. Currently, sorafenib is the only US Food and Drug Administration-approved chemotherapeutic for hepatocellular carcinoma. The efficacy of sorafenib, in combination with other agents, transarterial chemoembolization, and surgical resection is currently being investigated. Sunitinib and brivanib, tyrosine kinase inhibitors, have failed as potential first- or second-line options for chemotherapy. Bevacizumab in combination with erlotinib is also currently being studied. Final analysis for ramucirumab and axitinib are pending. Tivantinib, a selective mesenchymal-epithelial transition factor (MET) inhibitor, is also undergoing clinical trials for efficacy in MET-high tumors. This review serves to emphasize the current and new technologies emerging in the treatment of hepatocellular carcinoma. PMID:24810646

  11. Testicular epidermoid cyst

    PubMed Central

    Çakıroglu, Basri; Sönmez, Nurettin Cem; Sinanoğlu, Orhun; Ateş, Lora; Aksoy, Süleyman Hilmi; Özcan, Faruk

    2015-01-01

    Epidermoid cyst of the testis is a benign, non-teratomatous tumour. It is often possible to make the diagnosis pre-operatively, combining typical sonographic features with normal biochemical tumour markers. The accurate pre-operative diagnosis will allow for testis-sparing surgery and prevent unnecessary orchiectomy. An 11-year-old boy with testicular epidermoid cyst who presented with pain in testis was presented in this report. PMID:25659561

  12. 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

  13. New advances in hepatocellular carcinoma.

    PubMed

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    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

  14. Grape seed proanthocyanidins promote apoptosis in human epidermoid carcinoma A431 cells through alterations in Cdki-Cdk-cyclin cascade, and caspase-3 activation via loss of mitochondrial membrane potential.

    PubMed

    Meeran, Syed M; Katiyar, Santosh K

    2007-05-01

    Dietary grape seed proanthocyanidins (GSPs) prevent photocarcinogenesis in mice. Here, we report that in vitro treatment of human epidermoid carcinoma A431 cells with GSPs inhibited cellular proliferation (13-89%) and induced cell death (1-48%) in a dose (5-100 mug/ml)- and time (24, 48 and 72 h)-dependent manner. GSP-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest at 24 h, which was mediated through the inhibition of cyclin-dependent kinases (Cdk) Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and simultaneous increase in protein expression of cyclin-dependent kinase inhibitors (Cdki), Cip1/p21 and Kip1/p27, and enhanced binding of Cdki-Cdk. The treatment of A431 cells with GSPs (20-80 mug/ml) resulted in a dose-dependent increase in apoptotic cell death (26-58%), which was associated with an increased protein expression of proapoptotic Bax, decreased expression of antiapoptotic Bcl-2 and Bcl-xl, loss of mitochondrial membrane potential, and cleavage of caspase-9, caspase-3 and PARP. Pretreatment with the pan-caspase inhibitor (z-VAD-fmk) blocked the GSP-induced apoptosis in A431 cells suggesting that GSP-induced apoptosis is associated primarily with the caspase-3-dependent pathway. Together, our study suggests that GSPs possess chemotherapeutic potential against human epidermoid carcinoma cells in vitro, further in vivo mechanistic studies are required to verify the chemotherapeutic effect of GSPs in skin cancers. PMID:17437483

  15. 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. PMID:26632539

  16. Splenic epidermoid cysts.

    PubMed Central

    Robbins, F G; Yellin, A E; Lingua, R W; Craig, J R; Turrill, F L; Mikkelsen, W P

    1978-01-01

    Four patients with splenic masses were operated upon and found to have epidermoid cysts of the spleen, a rare lesion comprising less than 10% of benign, nonparasitic splenic cysts. The patients were young and had vague, non-specific symptoms which were related to the size of the slowly enlarging splenic mass. Three patients had palpable masses. Contrast gastrointestinal studies and intravenous urography will help exclude mass lesions of the gastrointestinal or genitourinary tract. Sonar scan may confirm the cystic nature of the lesion and localize it to the spleen. A review of 42,327 autopsy records at the Los Angeles County--University of Southern California Medical Center revealed 32 benign splenic cysts found incidentally at autopsy. Hemorrhage, infection, rupture, and rarely, malignant change are complications of splenic cysts. Splenectomy is recommended to eliminate the symptoms produced by the cyst and prevent the potential complications. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:637577

  17. Malignant transformation of an epidermoid cyst in the temporal and prepontine region: Report of a case and differential diagnosis

    PubMed Central

    DING, SHENGHAO; JIN, YICHAO; JIANG, JIYAO

    2016-01-01

    Malignant transformation of an epidermoid cyst is rare. The current report presents a case of a 55-year-old female patient with squamous cell carcinoma arising from a benign epidermoid cyst in the left temporal region and prepontine area. She had undergone subtotal resection of an epidermoid cyst 7 months previously. Preoperative imaging findings included a focal enhancing area adjacent to the lesion. Postoperative computed tomography demonstrated an increase in the size of the enhancing area. The patient underwent removal of the lesion and postoperative histological examination revealed a squamous cell carcinoma possibly arising from the epidermoid cyst. Accurate diagnosis of malignant transformation prior to operation is difficult; however, the possibility of an intracranial epidermoid cyst must be considered if a focally enhancing area is visible. Postoperative histological examinations may be used to determine a definite diagnosis, and accurate diagnosis is important for planning a rational therapeutic strategy. PMID:27123070

  18. Brainstem epidermoid cyst: An update.

    PubMed

    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

  19. 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

  20. [Giant intradiploic infratentorial epidermoid cyst].

    PubMed

    Alberione, F; Caire, F; Fischer-Lokou, D; Gueye, M; Moreau, J J

    2007-10-01

    Epidermoid cysts are benign, uncommon lesions (1% of all intracranial tumors). Their localization is intradiploic in 25% of cases, and exceptionally subtentorial. We report here a rare case of giant intradiploic infratentorial epidermoid cyst. A 74-year old patient presented with recent diplopia and sindrome cerebellar. CT scan and MR imaging revealed a giant osteolytic extradural lesion of the posterior fossa (5.2 cm x 3.8 cm) with a small area of peripheral enhancement after contrast injection. Retrosigmoid suboccipital craniectomy allowed a satisfactory removal of the tumor, followed by an acrylic cranioplasty. The outcome was good. Neuropathological examination confirmed an epidermoid cyst. We review the literature and discuss our case. PMID:18008017

  1. Management of advanced primary urethral carcinomas.

    PubMed

    Dayyani, Farshid; Hoffman, Karen; Eifel, Patricia; Guo, Charles; Vikram, Raghu; Pagliaro, Lance C; Pettaway, Curtis

    2014-07-01

    Primary urethral carcinoma (PUC) is a rare malignancy accounting for <1% of genitourinary cancers, with a predilection for men and African-Americans. The sites and histology of urethral carcinoma vary by gender and anatomical location. Squamous cell carcinoma is most common among both genders but adenocarcinomas are noted in 15-35% of cases among women. Obstructive or irritative symptoms and haematuria are common modes of presentation. Clinical evaluation includes cystourethroscopy with biopsy and examination under anaesthesia. Magnetic resonance imaging provides a highly effective method to image the primary tumour while defıning the potential involvement of surrounding structures. Most tumours are localised, with regional metastases to nodal sites seen in up to 30% of cases in both genders, while distant metastases at presentation are rare (0-6%), but occur in up to 40% of cases with recurrent disease. Among men, the two most important prognostic factors are disease location and stage. Low-stage tumours (T1-2) and tumours involving the fossa navicularis or the penile urethra have a better prognosis than higher stage tumours (>T2 or N+) and lesions involving the bulbomembranous urethra. In women, in addition to stage and location, the size of the tumour has also prognostic implications. While surgery and radiation therapy (RT) are of benefit in early stage disease, advanced stage PUC requires multimodal treatment strategies to optimise local control and survival. These include induction chemotherapy followed by surgery or RT and concurrent chemoradiation with or without surgery. The latter strategy has been used successfully to treat other human papillomavirus-related cancers of the vagina, cervix and anus and may be of value in achieving organ preservation. Given the rarity of PUC, prospective multi-institutional studies are needed to better define the optimal treatment approach for this disease entity. PMID:24447439

  2. Treatment of advanced thymoma and thymic carcinoma.

    PubMed

    Rajan, Arun; Giaccone, Giuseppe

    2008-12-01

    Although thymic epithelial tumors are rare, they are relatively common among neoplasms of the anterior superior mediastinum. They usually exhibit indolent behavior, but do have the capacity to invade surrounding structures and metastasize to distant sites. Thymic carcinomas are rare, but are highly aggressive tumors that are associated with a poor prognosis. The mainstay of therapy is complete surgical resection. Locally advanced thymoma and thymic carcinoma require a multimodality treatment approach with a combination of surgery, chemotherapy, and radiation therapy to decrease the chances of recurrence and improve survival. The risk of disease recurrence lasts for a number of years after completion of primary therapy. A majority of cases of recurrent disease present as pleural recurrences. Once again, surgical resection of recurrent disease represents the cornerstone of successful therapy and is critical to long-term survival. In recent years, a better understanding of the biologic basis of thymic epithelial tumors has led to the emergence of targeted therapy directed against this malignancy. PMID:19381821

  3. [Study of the genesis of bronchial epidermoid carcinoma: evolution or the expression of proteins, messenger RNAs and microRNAs at all stages of the process of carcinogenesis].

    PubMed

    Mascaux, C

    2009-01-01

    We characterized the successive and cumulative molecular modifications associated with transition in the histological stages of lung squamous carcinogenesis (normal epithelium from smokers, hyperplasia, metaplasia, mild, moderate and severe dysplasia, in situ carcinoma and invasive carcinoma) to improve our understanding of the mechanisms involved and identify new biomarkers for the early detection of lung squamous cell carcinoma. We employed immunohistochemistry, immunofluorescence, gene expression microarrays and quantitative RT-PCR to successively assess the expression of various proteins involved in cellular proliferation and apoptosis as well as messenger RNAs and microRNAs expression. Based on our data, we have improved the classification of bronchial preneoplastic lesions and furthered our understanding of the pathways involved in early lung carcinogenesis. The large number of biomarkers highlighted in these studies has opened two major and interesting perspectives: 1) the development of non invasive tests based on biomarkers for lung cancer detection at pre-invasive and early invasive stages and 2) new avenues of fundamental research whose goal is to understand the mechanisms underlying lung carcinogenesis. PMID:20666154

  4. Interdural cavernous sinus epidermoid cyst.

    PubMed

    Bonde, Vivek; Goel, Atul

    2008-02-01

    We report a patient with an uncommon interdural epidermoid tumor, located within the confines of dural layers of the lateral wall of the cavernous sinus. The tumor was resected by a basal subtemporal extradural-interdural approach. Following the surgery, the 45-year-old female patient recovered completely from her symptoms of atypical neuralgic facial pains. PMID:18083573

  5. Advances of imaging for hepatocellular carcinoma.

    PubMed

    Choi, Byung Ihn

    2010-07-01

    A variety of imaging modalities, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography, are currently used in evaluating patients with chronic liver disease and suspected hepatocellular carcinoma (HCC). Further technological advancement will undoubtedly have a major impact on liver tumor imaging. Increased speed of data acquisition and consequently shorter scan times in CT and MRI show further improvement in resolution by further reducing motion artifacts. Development of new contrast materials for liver tumor imaging in US and MRI improve tumor detection and characterization by increasing the contrast resolution. Currently available advanced US techniques in the evaluation of HCC are various harmonic imaging techniques with contrast agents, volume imaging, and recently, US elastography, that has been developing and might play a role in characterizing liver nodules in the future. The latest advance in CT is the multidetector (MD) CT scanner where a 256- or 320-detector CT was introduced. Recent studies describe the high sensitivity of double arterial phase imaging in hepatic tumor detection and the usefulness of CT angiography by using MD CT in a detailed assessment of hepatic arterial anatomy using a three-dimensional dataset. In addition, perfusion CT imaging is also being developed and can be used for the characterization and treatment monitoring of HCC. Dual-energy CT with new technology is also continuously progressing. Advances in MR technology, including hardware and pulse sequence implementation, allow acquisition times to be reduced to the time frame of one breathhold, providing multiphasic dynamic MRI. Functional MRI including diffusion-weighted MRI, MR elastography, and new MR contrast agent with dual function have been investigated for the clinical utility of detection and characterization of HCCs. Functional MRI has a potential to be a promising technique for assessing HCC. PMID:20616584

  6. Advances in systemic treatment for nasopharyngeal carcinoma.

    PubMed

    Tan, Wan-Ling; Tan, Eng-Huat; Lim, Darren Wan-Teck; Ng, Quan-Sing; Tan, Daniel Shao-Weng; Jain, Amit; Ang, Mei-Kim

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is a unique disease endemic in Asia. It is etiologically linked to the Epstein-Barr virus and is both radio- and chemo-sensitive. While radiotherapy (RT) remains the primary treatment modality with high cure rates for early stage disease, systemic treatment forms an important integral component in the treatment of NPC, both in the non-metastatic as well as palliative setting. Presently, standard therapy in locally advanced NPC comprises conventional cytotoxic chemotherapy administered concurrently during RT. The role of induction chemotherapy and adjuvant chemotherapy remain to be well-defined. Further research strategies in non-metastatic disease will require better identification of patients with high risk disease, and determining the optimal sequence and combination of chemotherapeutic regimens. In metastatic disease, whilst chemotherapy remains the mainstay of care, resistance inevitably develops. Development of molecularly targeted therapies has not yielded much success to date, and further research has been focused on development of EBV-targeted strategies such as vaccination or administration of cytotoxic T-cells directed towards EBV, as well as evaluation of immune checkpoint inhibition approaches. PMID:27121881

  7. Multimodal therapy in locally advanced breast carcinoma

    SciTech Connect

    Lopez, M.J.; Andriole, D.P.; Kraybill, W.G.; Khojasteh, A. )

    1990-12-01

    Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.

  8. 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

  9. Porfiromycin in the management of epidermoid and transitional cell cancer: a phase II study.

    PubMed

    Panettiere, F J; Talley, R W; Torres, J; Lane, M

    1976-07-01

    Porifiromycin has been tested in many groups of patients over the past several years (1-7). This report is an analysis of greater than 100 patients with epidermoid and urinary tract transitional cell carcinomas treated with this agent. A review of these data and the available literature on this agent shows that porfiromycin offers definite usefulness in disseminated squamous cell carcinomas of the cervix, and definite but lesser effectiveness in epidermoid carcinomas of the lung, the head and neck region, and other sites. Responsiveness was also demonstrated in transitional cell carcinomas of the urinary tract. Toxicity was tolerable and consisted primarily of myelosuppression and local skin necrosis in sites where extravasation had occurred. PMID:795539

  10. Chemotherapy and prognosis in advanced thymic carcinoma patients

    PubMed Central

    Song, Zhengbo; Yu, Xinmin; Zhang, Yiping

    2015-01-01

    OBJECTIVE: The role of chemotherapy in treating advanced thymic carcinoma is unclear. The purpose of the current study was to investigate the efficacy of chemotherapy and the prognostic factors for patients with advanced thymic carcinoma. METHODS: A retrospective review of the medical records of 86 patients treated with chemotherapy for advanced thymic carcinoma was conducted between 2000 and 2012 at our institution. The clinical characteristics, chemotherapy regimens and prognostic factors were analyzed. Survival curves were plotted using the Kaplan–Meier method and the Cox proportional hazard model was used for multivariate analysis. RESULTS: Of the 86 patients, 56 were male and 30 were female. The median survival time was 24.5 months. For the first-line chemotherapy treatment, the objective response rate was 47.7% and the disease control rate was 80.2%. The median progression-free survival for all patients was 6.5 months for first-line chemotherapy. No significant differences in progression-free survival were observed among the different chemotherapy regimens. Multivariate analyses revealed that the prognostic factors for overall survival included performance status (p=0.043), histology grade (p=0.048), and liver metastasis (p=0.047). CONCLUSION: Our results suggest that there is no difference in efficacy between multiagent and doublet regimens. The prognosis of patients with advanced thymic carcinoma can be predicted based on histological grade, liver metastasis and performance status. PMID:26735216

  11. Epidermoid Causing Ischemic Stroke in the Brainstem

    PubMed Central

    Mahore, Amit; Kulkarni, Abhijeet; Rangarajan, Vithal; Patil, Manoj; Kawale, Juhi

    2014-01-01

    Intracranial tumors may rarely cause stroke. We report an epidermoid cyst causing stroke in a pediatric patient. We have also reviewed the literature and pathogenesis of stroke caused by intracranial tumors. PMID:25580320

  12. Aldesleukin in advanced renal cell carcinoma.

    PubMed

    Schmidinger, Manuela; Hejna, Michael; Zielinski, Christoph C

    2004-12-01

    Renal cell carcinoma accounts for 2-3% of all malignancies. The most common subtype [85%] is the clear cell variant. A total of 30% of patients present with metastatic disease at diagnosis and another 30-40% will develop metastases during the course of the disease. Conventional cancer treatment is not effective, but cytokines including recombinant interleukin-2 (aldesleukin) have demonstrated clinical activity of various degrees. This drug profile provides a review of the literature on studies using aldesleukin in patients with metastatic renal cell carcinoma. Aldesleukin has been used in different dose schedules applying various administration routes, as either monotherapy or in combination with other cytokines, chemotherapy, endocrine treatment and adoptive cellular immunotherapy. Although a large number of randomized trials have been performed with different treatment strategies, it still remains uncertain whether the dose or combination of aldesleukin with other agents substantially influence treatment outcome. It appears that factors other than those that are treatment related are responsible for the course of the disease. PMID:15606326

  13. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances

    PubMed Central

    Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R.

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development. PMID:27239288

  14. Recent advances in the imaging of hepatocellular carcinoma

    PubMed Central

    You, Myung-Won; Kim, Kyoung Won; Lee, So Jung; Shin, Yong Moon; Kim, Jin Hee; Lee, Moon-Gyu

    2015-01-01

    The role of imaging is crucial for the surveillance, diagnosis, staging and treatment monitoring of hepatocellular carcinoma (HCC). Over the past few years, considerable technical advances were made in imaging of HCCs. New imaging technology, however, has introduced new challenges in our clinical practice. In this article, the current status of clinical imaging techniques for HCC is addressed. The diagnostic performance of imaging techniques in the context of recent clinical guidelines is also presented. PMID:25834808

  15. 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. PMID:18710812

  16. Atypical Intracranial Epidermoid Cysts: Rare Anomalies with Unique Radiological Features

    PubMed Central

    Law, Eric K. C.; Lee, Ryan K. L.; Ng, Alex W. H.; Siu, Deyond Y. W.; Ng, Ho-Keung

    2015-01-01

    Epidermoid cysts are benign slow growing extra-axial tumours that insinuate between brain structures, while their occurrences in intra-axial or intradiploic locations are exceptionally rare. We present the clinical, imaging, and pathological findings in two patients with atypical epidermoid cysts. CT and MRI findings for the first case revealed an intraparenchymal epidermoid cyst that demonstrated no restricted diffusion. The second case demonstrated an aggressive epidermoid cyst that invaded into the intradiploic spaces, transverse sinus, and the calvarium. The timing of ectodermal tissue sequestration during fetal development may account for the occurrence of atypical epidermoid cysts. PMID:25667778

  17. 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

  18. Orbital Epidermoid Cysts: A Diagnosis to Consider

    PubMed Central

    Eltanamly, Rasha M.

    2014-01-01

    Background. Orbital epidermoids form a rare pathological entity that is separate from dermoid cysts. They have variable clinical and radiological presentations and they should be considered in the differential diagnosis of orbital cystic lesions. This work describes the various clinical and radiological presentations of 17 cases of epidermoid cysts and the surgical outcome. Method. A prospective interventional study was conducted on 17 patients diagnosed with epidermoid cysts. Patients' symptoms and signs were recorded; CT scan was done for all patients. All lesions were removed through anterior orbitotomy and histopathological diagnosis confirmed. Results. Mean age of patients was 16.3 years ±  10.54. Main complaints were lid swelling, masses, ocular dissimilarity, chronic pain, and ocular protrusion. Clinical signs varied from lid swelling and masses in all cases to proptosis, globe displacement, limitation of ocular motility, and scars. Radiological findings ranged from homogenous hypodense masses (58.8%) to homogenous radiolucent (17.6%) and heterogenous masses (23.5%). No recurrences following surgeries were reported throughout the follow-up (mean 18.8 months ±  0.72). Conclusion. Deep orbital epidemoid cysts are a separate entity that can behave like deep orbital epidermoid; however, they usually present at a relatively older age. They can be associated with increased orbital volume but not necessarily related to bony sutures. PMID:25276416

  19. 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

  20. Technical advances in external radiotherapy for hepatocellular carcinoma.

    PubMed

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

    2016-08-28

    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

  1. 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.

  2. Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age

    PubMed Central

    Miyahara, Koji; Nouso, Kazuhiro; Yamamoto, Kazuhide

    2014-01-01

    The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma (HCC). After development of sorafenib and its introduction as a therapeutic agent used in the clinic, several critical questions have been raised. Clinical parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be elucidated. Although it is difficult to know the responders in advance using conventional characteristics of patients, there are specific serum cytokines and/or gene amplification in tumor tissues that have been reported to predict efficacy of sorafenib. Risk and benefits of continuation of sorafenib beyond radiological progression is another issue to consider because no other standard therapy for advanced HCC as yet exists. In addition, effectiveness of the expanded application of sorafenib is still controversial, although a few studies have shed some light on combinational treatment with sorafenib for intermediate-stage HCC. Recently, over 50 relevant drugs have been developed and are currently under investigation. The efficacy of some of these drugs has been extensively examined, but none have demonstrated any superiority over sorafenib, so far. However, there are several drugs that have shown efficacy for treatment after sorafenib failure, and these are proceeding to further studies. To address these issues and questions, we have done extensive literature review and summarize the most current status of therapeutic application of sorafenib. PMID:24764653

  3. 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

  4. 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. PMID:26674766

  5. Dual bradykinin B2 receptor signalling in A431 human epidermoid carcinoma cells: activation of protein kinase C is counteracted by a GS-mediated stimulation of the cyclic AMP pathway.

    PubMed Central

    Liebmann, C; Graness, A; Ludwig, B; Adomeit, A; Boehmer, A; Boehmer, F D; Nürnberg, B; Wetzker, R

    1996-01-01

    Cell membranes of the human epidermoid cell line A431 express classical bradykinin (BK) B2 receptors, as assessed by [3H]BK binding studies. Furthermore, stimulation by BK induced a time-dependent modulation of protein kinase C (PKC) activity in A431 cells: a rapid activation (t1/2 approximately 1 min) is followed by a slow inhibition (t1/2 approximately 20 min) of PKC translocation measured by [3H]phorbol 12,13-dibutyrate binding. In addition, BK stimulated both adenylate cyclase activity in A431 membranes and accumulation of intracellular cyclic AMP (cAMP) in intact cells in a retarded manner. A possible BK-induced activation of the cAMP pathway mediated via PKC, phospholipase D, prostaglandins or Ca2+/calmodulin was excluded. A 35 kDa protein was found in A431 membranes to be specifically phosphorylated in the presence of both BK and protein kinase A (PKA). An anti-alpha s-antibody, AS 348, abolished stimulation of adenylate cyclase activity in response to BK, cholera toxin and isoprenaline, strongly suggesting the involvement of Gs proteins in the BK action. The BK-activated cAMP signalling system might be important for the observed inactivation of PKC slowly evoked by BK: the BK-induced rapid activation of PKC is decreased by dibutyryl cAMP, and the slow inhibition of PKC is prevented by an inhibitor of PKA, adenosine 3':5'-monophosphothioate (cyclic, Rp isomer). The inhibition of PKC translocation might be exerted directly at the level of PKC activation, since stimulation of phosphoinositide hydrolysis by BK was affected by neither dibutyryl cAMP nor forskolin. Thus our results provide the first evidence that A431 cells BK is able to activate two independent signal-transduction pathways via a single class of B2 receptors but two different G proteins. The lagging stimulation of the cAMP signalling pathway via Gs might serve to switch off PKC, which is rapidly activated via Gq-mediated stimulation of phosphoinositide hydrolysis. PMID:8546671

  6. Sunitinib re-challenge in advanced renal-cell carcinoma

    PubMed Central

    Porta, C; Paglino, C; Grünwald, V

    2014-01-01

    Despite offering significant clinical benefits in advanced renal-cell carcinoma (RCC), the effectiveness of targeted therapies eventually declines with the development of resistance. Defining optimal sequences of therapy is therefore the focus of much current research. There is also evidence that treatment ‘re-challenge' may be an effective strategy in some patients. We review evidence to evaluate whether sunitinib may have value as re-challenge therapy in patients who have progressed on prior targeted therapy with sunitinib and/or an alternative tyrosine kinase inhibitor or mammalian target of rapamycin inhibitor. Re-challenge with sunitinib appears to be of clinical benefit, thus representing a feasible therapeutic option for patients with advanced RCC who are refractory to other treatments and are able to receive further therapy. These observations support hypotheses that resistance to targeted agents is transient and can be at least partially reversed by re-introduction of the same agent after a treatment break. Median progression-free survival durations appear to be shorter and response rates lower on re-challenge than following initial treatment, although a wider interval between treatments appears to increase response to sunitinib re-challenge. PMID:24800947

  7. 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

  8. Epidermoids involving the temporal bone: clinical, radiological and pathological aspects.

    PubMed

    Nager, G T

    1975-12-01

    Epidermoids or congenital cholesteatomas arise from aberrant epithelial remnants and are, therefore, considerd blastomatous malformations. Their predilective sites are the intracranial cavity, the diploe of the skull and the spinal canal. In the base of the skull the temporal bone is the most frequent site. Epidermoids account for about 0.2-1.5 percent of all intracranial tumors. The majority originate in the cerebello-pontine angle where they account for 6-7 percent of all tumors. Their age incidence reveals a great scatter from birth to 80 years. The majority are recognized during the third and fourth decades with the onset of clinical symptoms occurring much earlier. They affect males more frequently than females. Their delicate capsule with a whitish mother-of-pearl sheen lends them a typical appearance. Epidermoids are generally slow growing lesions which may remain asymptomatic for years. The irritative effect of their content, however, can produce symptoms of dysfunction and intense inflammation. Malignant changes occur infrequently. Diploic epidermoids are easily recognized, whereas, intradural epidermoids are more difficult to identify. Epidermoids may arise in the vicinity, on the outer aspect or within the temporal bone. Epidermoids originating in any of these locations have certain characteristic features which may arouse suspicion of their presence. Examples of an epidermoid with origin in the typical locations within the temporal bone and cerebello-pontine angle are discussed to portray their individual characteristics. PMID:1207346

  9. Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma

    PubMed Central

    Lee, Victor Ho-Fun; Leung, Dennis KC; Luk, Mai-Yee; Tong, Chi-Chung; Law, Martin WM; Ng, Sherry CY; Wong, Ka-Kin; Poon, Ronnie TP; Kwong, Dora LW; Leung, To-Wai

    2015-01-01

    Background Advanced inoperable hepatocellular carcinoma (HCC) conferring a grave prognosis may benefit from yttrium-90 (90Y) radioembolization. Methods Thirty patients with advanced inoperable HCC including those with any lesion >8 cm in maximal diameter or multiple bi-lobar lesions (totally more than five lesions), or portal vein thrombosis treated with radioembolization were reviewed. Treatment efficacy and safety were evaluated. Univariate and multivariate analyses were performed for identifying potential prognostic factors. Results After a median follow-up of 18.3 months, the response rate was 30.0%, and the disease control rate was 50.0%. Median overall progression-free survival (PFS) and overall survival (OS) were 3.3 months and 13.2 months, respectively. Longer median PFS was noted in those who had transarterial chemoembolization before radioembolization (7.3 months vs 3.1 months; P=0.021) and duration of alfafeto protein (AFP) response ≥6 months (11.8 months vs 3.0 months; P<0.001). Longer median OS was also revealed in those without portal vein thrombosis (17.1 months vs 4.4 months; P=0.015) and those whose duration of AFP response was ≥6 months (21.2 months vs 8.6 months; P=0.001). Seventeen patients (56.7%) developed treatment-related complications including five (16.7%) grade 3 events. Multivariate analysis revealed that treatment responders (P=0.001) and duration of AFP response ≥6 months (P=0.006) were prognostic of PFS, whereas the absence of portal vein invasion (P=0.025), treatment responders (P=0.010), and duration of AFP response ≥6 months (P=0.001) were prognostic of OS. Conclusion 90Y radioembolization is an alternative treatment with a promising outcome for poor-risk advanced inoperable HCC. PMID:26640386

  10. 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

  11. Strain elastography features of epidermoid tumours in superficial soft tissue: differences from other benign soft-tissue tumours and malignant tumours

    PubMed Central

    Park, H J; Lee, S M; Kim, W T; Lee, S; Ahn, K S

    2015-01-01

    Objective: We evaluated ultrasonographic features of superficial epidermoid tumour with a focus on strain elastography (SE) features that will help in the differential diagnosis of epidermoid tumour from other benign and malignant soft-tissue tumours. Methods: We retrospectively evaluated ultrasonographic and SE data of 103 surgically confirmed superficial soft-tissue tumours and tumour-like lesions: 29 cases of epidermoid tumour, 46 cases of other benign tumours and 28 cases of malignant tumour. SE and B-mode imaging were performed at the same time. SE characteristics were assigned into four grades (1–4) according to their elasticity. Interobserver agreement for the four SE scores between the two radiologists was analysed using kappa statistics. We classified each SE finding as a hard lesion (SE Score 3–4) or soft lesion (SE Score 1–2) and compared these findings using the χ2 test to identify whether a significant difference in mass hardness existed among epidermoid tumour, other benign tumour and malignant tumour. Results: Overall interobserver agreement according to the four SE scores was moderate (κ = 0.540), and overall agreement for the hardness [soft (Score 1–2) or hard (Score 3–4)] was almost perfect (κ = 0.825). Malignant tumours showed higher SE scores (3–4, hard nature) than did epidermoid tumour or other benign soft-tissue tumours. There were no differences in SE score between epidermoid tumour and other benign tumours. Conclusion: Superficial epidermoid tumour exhibits a softer nature than does malignant tumour but does not have a different SE pattern from other benign tumours. Advances in knowledge: SE features of epidermoid tumour might be helpful in differentiating from other benign and malignant tumours. PMID:25827206

  12. Chemotherapy in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Gyawali, Bishal; Shimokata, Tomoya; Honda, Kazunori; Ando, Yuichi

    2016-03-01

    Chemotherapy, in combination with a local treatment, has a role in nearly all the settings of locally advanced head and neck squamous cell carcinoma (LAHNSCC) treatment: as definitive, adjuvant or induction therapy. However, despite many years of trials, controversies still exist regarding the best approach to using chemotherapy in the multi-modal treatment of LAHNSCC. Opinions are divided on sequential versus concurrent use of chemotherapy and radiotherapy for unresectable LAHNSCC. More debate exists on whether the addition of induction chemotherapy to concomitant chemoradiotherapy is clinically meaningful. After the approval of cetuximab in combination with radiotherapy for this disease, making treatment choices have become further complicated. Although new data from trials are arriving every year, the results have been inconclusive. In this review, we provide the readers with the latest information on various strategies of using chemotherapy and cetuximab that will help to make an evidence-based decision in the treatment of LAHNSCC, including the approach to larynx preservation. We conclude that with the available information, concurrent chemoradiotherapy should be preferred over induction chemotherapy, except in the setting of larynx preservation. Furthermore, given the paucity of positive data and severe financial toxicity associated with cetuximab, concurrent chemoradiotherapy should be the preferred choice over cetuximab-radiotherapy. Future trials in head and neck cancer should be properly planned to address these controversies and provide clear solutions. PMID:26924194

  13. Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma

    PubMed Central

    Santoni, Matteo; Amantini, Consuelo; Burattini, Luciano; Berardi, Rossana; Santoni, Giorgio; Cascinu, Stefano; Muzzonigro, Giovanni

    2013-01-01

    Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents. PMID:24093097

  14. Recent advances in multidisciplinary management of hepatocellular carcinoma

    PubMed Central

    Gomaa, Asmaa I; Waked, Imam

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

  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. Clinical Characteristics of Epidermoid Cysts of the External Auditory Canal

    PubMed Central

    Kim, Go-Woon; Park, Jang-Hee; Kwon, Oh-Joon; Kim, Dong Hyun

    2016-01-01

    Background and Objectives The epidermoid cyst is a common benign disease of the skin caused by inflammation of hair cortex follicles and proliferation of epidermal cells within the dermis or superficial subcutaneous tissue. The purpose of this study was to investigate the characteristics of epidermoid cysts of the external auditory canal (EAC) by analyzing the clinical and radiologic features. Subjects and Methods The clinical records were retrospectively reviewed for patients diagnosed with epidermoid cyst of the EAC from March 2004 to December 2013. The epidermoid cysts were diagnosed clinically by endoscopy and microscopy examinations and by temporal bone CT images, and were confirmed by histopathologic examination. Characteristics of epidermoid cysts in bony EAC and cartilaginous EAC were compared. Results Eight patients had an epidermoid cyst in the bony EAC and nine patients had one in the cartilaginous EAC. Swelling and otalgia were common symptoms, but 47% of cysts were found incidentally. The mean age of patients was 49.6 years (age range, 26-67 years) in the bony EAC cases and 26.1 years (age range, 6-57 years) in the cartilaginous EAC cases. The mean size of the epidermoid cyst was 3.50 mm (size range, 2-7 mm) in the bony EAC cases and 9.55 mm (size range, 2-20 mm) in the cartilaginous EAC cases. Conclusions Comparison of epidermoid cysts of the bony EAC and the cartilaginous EAC revealed that epidermoid cysts of the bony EAC is usually found incidentally, arose in older patients and had smaller size. PMID:27144232

  18. Giant Pelvic Retroperitoneal Epidermoid Cyst: A Rare Case Report

    PubMed Central

    Fdili Alaoui, F. Z.; Oussaden, A.; Bouguern, H.; El Fatemi, H.; Melhouf, M. A.; Amarti, A.; Ait Taleb, K.

    2012-01-01

    Epidermoid cyst is a frequent benign cutaneous tumor. The pelvic localization does not occur very often. The literature that taps into such cases is very limited in scope. Here is a report of a 27-year-old woman with a giant pelvic retroperitoneal epidermoid cyst. The use of ultrasound exploration and computed tomography has indicated ovarian origins. The surgery also revealed a retroperitoneal epidermoid cyst, uterus and ovaries were all intact. The evacuation of a cyst was found to contain lamellas of keratin. Histology permitted us to confirm the diagnosis. The patient was faring well after two years of followup. PMID:23150734

  19. Giant pelvic retroperitoneal epidermoid cyst: a rare case report.

    PubMed

    Fdili Alaoui, F Z; Oussaden, A; Bouguern, H; El Fatemi, H; Melhouf, M A; Amarti, A; Ait Taleb, K

    2012-01-01

    Epidermoid cyst is a frequent benign cutaneous tumor. The pelvic localization does not occur very often. The literature that taps into such cases is very limited in scope. Here is a report of a 27-year-old woman with a giant pelvic retroperitoneal epidermoid cyst. The use of ultrasound exploration and computed tomography has indicated ovarian origins. The surgery also revealed a retroperitoneal epidermoid cyst, uterus and ovaries were all intact. The evacuation of a cyst was found to contain lamellas of keratin. Histology permitted us to confirm the diagnosis. The patient was faring well after two years of followup. PMID:23150734

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

    ClinicalTrials.gov

    2016-06-03

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

  1. Recent advances in the surgical treatment of hepatocellular carcinoma.

    PubMed

    Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi; Yoshida, Rie; Isetani, Masashi

    2014-10-21

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. PMID:25339825

  2. Recent advances in the surgical treatment of hepatocellular carcinoma

    PubMed Central

    Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi; Yoshida, Rie; Isetani, Masashi

    2014-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. PMID:25339825

  3. Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma.

    PubMed

    Kuten, A; Stein, M; Steiner, M; Rubinov, R; Epelbaum, R; Cohen, Y

    1988-02-01

    One hundred and sixteen patients with advanced ovarian carcinoma, who underwent primary cytoreductive surgery, received 6-11 courses of chemotherapy by cis-platin (50 mg/m2) and adriamycin (50 mg/m2) every 21 days. This was followed by second look laparotomy in 66 patients with no clinical evidence of disease. Consolidation abdominal irradiation was administered to 43 patients. Two techniques of irradiation were employed: between 1980-1983 whole abdominal irradiation was used and patients were to receive 3000 cGy in 4 weeks (Schedule I). Due to myelosuppression only 13 of 26 patients (50%) completed the planned dose of radiation. Between 1983-1985 the target volume was divided into upper and lower parts. First, the lower abdomen received 3000 cGy in 3 weeks, and then the upper abdomen received the same dose (Schedule II). Sixteen of seventeen patients (94%) thus treated, completed the planned dose of radiation. The actuarial survival for all 116 patients was 28% of 5 years. Irradiated patients with negative second look laparotomy had a survival probability of 100% at 24 months. Irradiated patients with microscopic disease at second look operation had an actuarial 5-year survival of 66%. Patients with minimal residual disease at second look laparotomy, receiving consolidation abdominal irradiation, had an actuarial survival of 5% only at 36 months. It is concluded that consolidation radiotherapy is effective in patients with negative or microscopic residual disease at second-look laparotomy. In regard to bone marrow tolerance, split field technique of irradiation is preferred. PMID:3338949

  4. 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

  5. Recent advances in the treatment of advanced renal cell carcinoma: towards multidisciplinary personalized care.

    PubMed

    Bex, Axel; Gore, Martin; Mulders, Peter; Sternberg, Cora N

    2012-11-01

    What's known on the subject? and What does the study add? With recent improvements in the prognosis for patients with metastatic renal cell carcinoma (mRCC), focus is now shifting towards maximising clinical benefit from targeted therapies. Factors other than efficacy data are increasingly being considered when selecting a treatment strategy, with a view towards optimising clinical outcomes. This review examines the development and efficacy of targeted agents for the management of mRCC and discusses the potential factors, including resistance mechanisms, sequential therapy, prognostic and predictive markers of response, and adverse event management, that may contribute to successful individually tallored treatment of patients with this disease. • Targeted agents have substantially improved outcomes for patients with metastatic renal cell carcinoma (mRCC). • Treatment focus is now shifting towards achieving a continuum of care such that long-term benefit and extended survival may be achieved through the optimal use of targeted agents. • To achieve this goal, a number of factors which impact on treatment selection and outcomes need to be considered when treating patients with mRCC, such as the optimal sequence of targeted therapies (and the related issue of resistance mechanisms). • Recent advances are also likely to impact on the future treatment of mRCC. Examples include the identification of predictive biomarkers as well as a consideration of patient risk profiles or the safety profile of the selected targeted agent. In addition, attention is focusing on re-defining the role of surgery for the treatment of RCC in the context of targeted therapies. • This review examines the recent and future advances that offer the potential for personalizing treatment by selecting the most appropriate treatment for each patient with a view towards optimizing clinical outcomes. PMID:22624610

  6. 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

  7. 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. PMID:25489364

  8. Epidermoid cyst of the testis: An atypical sonographic appearance.

    PubMed

    Chen, Shu-Ting; Chiou, Hong-Jen; Pan, Chin-Chen; Shen, Shu-Huei; Chou, Yi-Hong; Tiu, Chui-Mei; Wang, Hsin-Kai; Lai, Yi-Chen; Lin, Yung-Hui; Wang, Jane; Chang, Cheng-Yen

    2016-09-01

    Epidermoid cysts are rare. They represent the most common benign tumor of the testis. The sonographic appearances of testicular epidermoid cysts usually include avascular, mostly lamellated, heterogeneous internal echotexture, with hypoechoic and hyperechoic concentric rings, accounting for the typical onion-ring appearance. On MRI, epidermoid cysts show a low-signal-intensity center, with internal concentric rings of alternating high- and low-signal intensity on T2-weighted images, which correlates with the onion-ring appearance. We report a patient with testicular epidermoid cyst with atypical ultrasound and MRI appearances that led to the erroneous initial diagnosis of "burned-out" tumor. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:448-451, 2016. PMID:27028726

  9. Potentially fatal supramylohyoid sublingual epidermoid cyst.

    PubMed

    Gulati, Ujjwal; Mohanty, Sujata; Augustine, Jayaseelan; Gupta, Shalini R

    2015-03-01

    A case of chronic and slow growing massive lateral neck swelling is presented which gradually resulted in dysphagia to an extent that patient reported in emergency room. Clinical findings were indicative of a cystic swelling or a massive lipoma. Temporary decompression of the lesion was achieved by partially aspirating the contents of the cyst. Nature of aspirate and its microscopic and biochemical analysis excluded lipoma, vascular malformation and salivary phenomenon. The diagnosis tapered to developmental lateral neck cysts. Magnetic Resonance Imaging (MRI) revealed a massive cystic lesion in the left floor of mouth extending to the right lingual aspect of mandible and posteriorly to impinge on the medial wall of pharynx. A combined intraoral and extraoral approach was used to expose and excise the lesion in toto. Final histological diagnosis of the pathology was epidermoid cyst. PMID:25848141

  10. Paclitaxel and cisplatin with concurrent radiotherapy followed by surgery in locally advanced thymic carcinoma.

    PubMed

    Fukuda, Minoru; Obase, Yasushi; Miyashita, Naoyuki; Kobashi, Yoshihiro; Mohri, Keiji; Ueno, Shiro; Hayama, Makio; Shimizu, Katsuhiko; Nishimura, Hironori; Nakata, Masao; Oka, Mikio

    2007-01-01

    Thymic carcinoma is a rare neoplasm with a poor prognosis. We report the clinical course of a patient who received complete surgical resection after effective induction treatment. A 72-year-old woman with advanced thymic carcinoma (squamous cell carcinoma, stage IVb) was considered as nonresectable due to invasion of neighboring organs and mediastinal lymph node metastasis. Two cycles of chemotherapy, consisting of paclitaxel (180 mg/m2) plus cisplatin (80 mg/m2), combined with thoracic radiotherapy (total 54 Gy) were performed concurrently and complete radical resection could then be performed. She is currently alive and ambulatory and has remained disease-free for two years. This multimodal treatment may be a good treatment option for locally advanced thymic carcinoma. PMID:17595782

  11. Splenic Epidermoid Cyst in a Five-Year-Old Child

    PubMed Central

    Garg, Bhavna; Sood, Neena; Singh, Satpal

    2016-01-01

    Splenic epidermoid cysts are rare non-parasitic true cysts affecting the spleen. We report a five-year-old child who presented with an abdominal lump associated with pain of 15 days. Ultrasonography of the abdomen showed a huge cystic lesion of obscure origin. At laprotomy a huge unilocular cyst involving upper part of spleen containing pultaceous fluid was seen and its removal necessitated splenectomy. Histopathological findings were consistent with splenic epidermoid cyst. Thus histopathology helped in elucidating the aetiology and diagnosis.

  12. 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.

  13. Rehabilitation of an Advanced Case of Adenoid Cystic Carcinoma

    PubMed Central

    Volpato, Luiz Evaristo Ricci; Caldas, Lorena Frange; Castro, Paulo Henrique de Souza; de Carvalhosa, Artur Aburad; Volpato, Maria Carmen Palma Faria; Bandéca, Matheus Coelho; Borges, Álvaro Henrique

    2015-01-01

    Adenoid cystic carcinoma is a cancer of the salivary gland that primarily affects the parotid, submandibular, and accessory salivary glands. Its growth is slow and it has infiltrative nature. A 46-year-old female patient coming from the rural area presented a lesion on the palate and reported pain in the region for three years. After incisional biopsy, and histopathological diagnosis of adenoid cystic carcinoma of the cribriform type of minor salivary gland, superior hemimaxillectomy and adjuvant treatment with radiotherapy and maxillofacial prosthetic rehabilitation were performed. PMID:25709844

  14. Vulvar Epidermoid Cyst and Type 2 Radical Genital Mutilation.

    PubMed

    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

  15. 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

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

    PubMed

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

    2016-09-01

    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

  17. 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

  18. Intraductal Carcinoma of the Prostate Gland: Recent Advances.

    PubMed

    Divatia, Mukul K; Ro, Jae Y

    2016-09-01

    Intraductal carcinoma of the prostate (IDC-P) is characterized by prostatic carcinoma involving ducts and/or acini. The presence of IDC-P is usually associated with a high-grade Gleason score, large tumor volume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion. When present, IDC-P is associated with worse outcomes, regardless of treatment status. IDC-P is included in a broader diagnostic category of atypical cribriform lesions of the prostate gland. This category of lesions also includes high-grade prostatic intraepithelial neoplasia (HGPIN), urothelial carcinoma involving prostatic ducts or acini, and prostatic ductal adenocarcinoma, amongst other intraductal proliferations. Differentiating between these entities is important as they have differing therapeutic and prognostic implications for patients, although differential diagnosis thereof is not always straightforward. The present review discusses IDC-P in regards to its morphological characteristics, molecular features, and clinical outcomes. Given the current state of knowledge, the presence of IDC-P should be evaluated and documented correctly in both radical prostatectomy and needle biopsy specimens, and the clinical implications thereof should be taken into consideration during treatment and follow up. PMID:27401634

  19. Trimodality Therapy for an Advanced Thymic Carcinoma With Both Aorta and Vena Cava Invasion.

    PubMed

    Momozane, Tohru; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Okumura, Meinoshin

    2016-08-01

    A case of locally advanced thymic carcinoma that was successfully resected with the great vessels after chemoradiation therapy is reported. A 57-year-old man with Masaoka stage III thymic carcinoma received two cycles of cisplatin/docetaxel and 60 Gy irradiation. The response was stable disease with 19% size reduction, and a radical resection with the ascending aorta and superior vena cava with the patient under circulatory arrest with the use of cardiopulmonary bypass was performed. The postoperative course was uneventful, and the patient has been free of disease for 28 months. Trimodality therapy with use of a cardiovascular surgical procedure might be a valuable option in locally advanced thymic carcinoma. PMID:27449450

  20. Familial epidermoid cysts of the spleen: report of two cases.

    PubMed

    Kubo, Masatoshi; Yamane, Masaomi; Miyatani, Katsuya; Udaka, Tetsunobu; Mizuta, Minoru; Shirakawa, Kazutoyo

    2006-01-01

    The familial occurrence of epidermoid cysts of the spleen is rare, with only six cases having ever been reported, to our knowledge. We recently diagnosed epidermoid cysts of the spleen in a mother and son. First, a 15-year-old boy was admitted to our hospital for management of blunt abdominal trauma. Computed tomography (CT) showed a ruptured large splenic cyst with an intraabdominal hematoma. We performed a splenectomy, and histopathological examination confirmed the existence of an epidermoid cyst of the spleen. About 2 years and 6 months later, the family physician found that the patient's 41-year-old mother had a large splenic cyst, and she was referred to our hospital for further investigation. CT showed a 10 x 8 cm cyst occupying most of the spleen. The patient underwent splenectomy, and a pathological diagnosis of an epidermoid cyst of the spleen was confirmed. Although the etiology of epidermoid cysts of the spleen is unclear, this familial occurrence may support the hypothesis of congenital malformation as a result of genetic change. PMID:16937296

  1. Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma

    ClinicalTrials.gov

    2016-03-10

    Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage III Major Salivary Gland Carcinoma; Stage III Oral Cavity Adenoid Cystic Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Oral Cavity Adenoid Cystic Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Oral Cavity Adenoid Cystic Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Oral Cavity Adenoid Cystic Carcinoma; Tongue Carcinoma

  2. Primary epidermoid cysts of the mastoid: clinical and treatment implications.

    PubMed

    Syed, Mohammed Iqbal; Plodpai, Yuvatiya; Khoo, Seng Guan; Rutka, John A

    2016-04-01

    Epidermoid cysts of the temporal bone are extremely rare and such lesions arising in isolation within the mastoid bone have never been reported in literature. We report and describe the first two unique cases of primary epidermoid cysts arising in the mastoid bone. Of the two cases, one presented with progressive headache and imbalance and the other with unilateral hearing loss and tinnitus. Both cases needed CT and MRI scans and needed surgical management. We review the clinical presentations, histology, pathogenesis, radiological findings and management of these challenging cases. The diagnosis of an epidermoid cyst is based on clinical presentation, physical examination and especially the radiological, histological and intraoperative findings. Total removal of the lesion along with its capsule is recommended to prevent recurrence and to allow for a good long-term prognosis. PMID:25958160

  3. Persistent Uroplakin Expression in Advanced Urothelial Carcinomas: Implications in Urothelial Tumor Progression and Clinical Outcome

    PubMed Central

    Huang, Hong-Ying; Shariat, Shahrokh F.; Sun, Tung-Tien; Lepor, Herbert; Shapiro, Ellen; Hsieh, Jer-Tsong; Ashfaq, Raheela; Lotan, Yair; Wu, Xue-Ru

    2007-01-01

    As the terminal differentiation products of human urothelium, uroplakins (UPs) would be expected to diminish during urothelial tumorigenesis. Surprisingly, recent studies found UPs to be retained even by well-advanced urothelial carcinomas, suggesting that the loss of UPs does not strictly parallel urothelial transformation. Little is known, however, about whether the status of UPs is associated with a particular pathological parameter, tumor’s biological behavior or patient outcome. Here we assessed UP expression by immunohistochemistry on tissue arrays from 285 patients with bladder urothelial carcinomas or non-tumor conditions. UPs were expressed in all 9 normal urothelial specimens, 63/74 (85%) patients with non-muscle-invasive urothelial carcinomas on transurethral resection, 104/202 (51.5%) patients who underwent radical cystectomy for advanced urothelial carcinomas, and 33/50 (66%) lymph node metastases. Normally associated with urothelial apical surface, UPs were localized aberrantly in tumors, including micro-luminal, basal-laminal, cytoplasmic or uniform patterns. In non-muscle-invasive diseases, there was no association between UP expression and disease recurrence, progression or mortality. In contrast, in invasive diseases, absent UP expression was significantly associated with advanced pathologic stage, lymph node metastases, disease recurrence and bladder cancer-specific mortality (p=0.042, p=0.035, p=0.023 and p=0.022, respectively) in univariate analyses. Furthermore, UP status was independent of key cell-cycle regulators, including p53, pRb, p27 and cyclin D1, thus excluding a functional link between these two groups of proteins. Our data demonstrate for the first time that persistent UP expression is associated with a favorable clinical outcome and that UPs may be used as adjunct markers for predicting the prognoses of patients with invasive and metastatic bladder carcinomas. Our results also suggest that UP-positive and –negative carcinomas

  4. 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

  5. Intrascrotal epidermoid cyst with extension into the pelvis.

    PubMed

    Sadler, B T; Greenfield, S P; Wan, J; Glick, P L

    1995-04-01

    An 8-year-old boy presented with an asymptomatic extratesticular, scrotal epidermoid cyst with extension across the urogenital diaphragm into the pelvis. While routine contrast studies and ultrasound were performed, magnetic resonance imaging was most useful in depicting the anatomical boundaries of the lesion, including the intrapelvic extension. Complete excision was performed transcrotally. The lesion is histologically indistinguishable from epidermoid cysts found elsewhere in the external genitalia, that is the penis, scrotum or testis. The etiology is unknown but it may represent a monolayer teratoma of germ cell origin or abnormal embryological closure of the median raphe. PMID:7869526

  6. Imaging diagnosis--intracranial epidermoid cyst in a Doberman Pinscher.

    PubMed

    Steinberg, T; Matiasek, K; Brühschwein, A; Fischer, A

    2007-01-01

    A 4-year-old Doberman Pinscher was evaluated for chronic progressive central vestibular disease and aggressiveness. A cyst-like lesion was identified in the region of the left cerebellopontine angle. The lesion was hypointense on T1-weighted and hyperintense on T2-weighted images. Differentials included an epidermoid or dermoid cyst, cystic neoplasm, and brain abscess. Hyperintensity on subsequent fluid-attenuated inversion recovery images excluded an arachnoid cyst. The histopathologic diagnosis was epidermoid cyst within the fourth ventricle. PMID:17508513

  7. [A CASE OF ADVANCED BLADDER NEUROENDOCRINE CARCINOMA (SMALL CELL CARCINOMA) SIGNIFICANTLY IMPROVED BY LOW DOSE OF ORAL TEGAFUR-URACIL].

    PubMed

    Nomi, Hayahito; Takahara, Kiyoshi; Minami, Koichiro; Maenosono, Ryoichi; Matsunaga, Tomohisa; Yoshikawa, Yuki; Tsujino, Takuya; Hirano, Hajime; Inamoto, Teruo; Yamamoto, Ikuhisa; Tsuji, Motomu; Kiyama, Satoshi; Azuma, Haruhito

    2015-10-01

    A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years. PMID:26717786

  8. 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

  9. 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. PMID:26019766

  10. Complete remission of advanced hepatocellular carcinoma by radiofrequency ablation after sorafenib therapy

    PubMed Central

    Park, Jung Gil; Park, Soo Young; Lee, Hye Won

    2015-01-01

    Sorafenib, a potent multikinase inhibitor, lead to a significant improvement in progression free survival and overall survival in patients with advanced hepatocellular carcinoma (HCC). Though sorafenib has proven its efficacy in advanced stage HCC, there are limited reports on the role of sorafenib allowing for curative treatment by down-staging. We herein report a case of advanced HCC with vascular invasion, which showed treatment response by sorafenib therapy as to allow for radiofrequency ablation as curative treatment. The patient was followed-up for 6 mo without recurrence with continued sorafenib therapy. PMID:25741170

  11. Treatment for Advanced and Recurrent Endometrial Carcinoma: Combined Modalities

    PubMed Central

    Rauh-Hain, J. Alejandro

    2010-01-01

    Women with recurrent or advanced endometrial cancer constitute a heterogeneous group of patients. Depending on previous treatment, women with recurrent endometrial cancer may be appropriate candidates for surgery, radiation therapy, hormonal therapy, or chemotherapy. Women with advanced stage disease at presentation may also be appropriate candidates for systemic and local therapies. We review the treatment options available to treat recurrent and locally advanced endometrial cancer. Treatment choice depends largely on the localization of disease, the patient’s performance status and previous treatment history, as well the tumor’s hormonal receptor status. Radiation therapy is appropriate for isolated vaginal recurrences in patients with no previous history of radiation therapy. Patients with recurrent low-grade tumors overexpressing estrogen and progesterone receptors may be treated with progestin therapy. Systemic therapy is appropriate for patients with disseminate recurrences or advanced stage disease at presentation, or for those with receptor-negative tumors. We review all these different treatment strategies available to patients with advanced or recurrent endometrial cancer. PMID:20660059

  12. Phase II Study of Carboplatin and Paclitaxel in Advanced Thymoma and Thymic Carcinoma

    PubMed Central

    Lemma, Girum L.; Lee, Ju-Whei; Aisner, Seena C.; Langer, Corey J.; Tester, William J.; Johnson, David H.; Loehrer, Patrick J.

    2011-01-01

    Purpose The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. Patients and Methods We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m2) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. Results From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. Conclusion Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma. PMID:21502559

  13. Improvement in the Results of Surgical Treatment of Advanced Squamous Esophageal Carcinoma During 15 Consecutive Years

    PubMed Central

    Ando, Nobutoshi; Ozawa, Soji; Kitagawa, Yuko; Shinozawa, Yotaro; Kitajima, Masaki

    2000-01-01

    Objective To document the clinicopathologic characteristics and survival of patients undergoing esophagectomy for squamous carcinoma of the thoracic esophagus, and to examine the factors contributing to improvements in outcome noted in patients with advanced carcinoma. Summary Background Data Japanese and some Western surgeons recently have reported that radical esophagectomy with extensive lymphadenectomy conferred a survival advantage to patients with esophageal carcinoma. The factors contributing to this improvement in results have not been well defined. Methods From 1981 to 1995, 419 patients with carcinoma of the thoracic esophagus underwent esophagectomy at the Keio University Hospital. The clinicopathologic characteristics and survival of patients treated between 1981 and 1987 were compared with those of patients treated between 1988 and 1995. Multivariate analysis using the Cox regression model was carried out to evaluate the impact of 15 variables on survival of patients with p stage IIa to IV disease. Several variables related to prognosis were examined to identify differences between the two time periods. Results The 5-year survival rate for all patients was 40.0%. The 5-year survival rate was 17.7% for p stage IIa to IV patients treated during the earlier period and 37.6% for those treated during the latter period. The Cox regression model revealed seven variables to be important prognostic factors. Of these seven, three (severity of postoperative complications, degree of residual tumor, and number of dissected mediastinal nodes) were found to be significantly different between the earlier and latter periods. Conclusions The survival of patients undergoing surgery for advanced carcinoma (p stage IIa to IV) of the thoracic esophagus has improved during the past 15 years. The authors’ data suggest that this improvement is due mainly to advances in surgical technique and perioperative management. PMID:10903602

  14. 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

  15. [Rare giant retroauricular epidermoid cyst: a case report].

    PubMed

    Zhou, Enhui; Zhang, Yi; Xue, Xiaocheng

    2016-03-01

    Epidermnoid cysts are henign, cutaneous cysts which commonly occur on face, neck and trunk. Retroauricular epidermoid cyst is rare reported which should be differentiated from auricle pseudocyst, lipoma, steatocystoma and fibroma. The hitopathological examination is a gold standard of diagnosis. Surgery of complete excision is the first choice of treatment methods. PMID:27382692

  16. 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. PMID:6501628

  17. 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

  18. Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

    PubMed Central

    Garg, Minal

    2016-01-01

    Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells. PMID:27621760

  19. Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges.

    PubMed

    Garg, Minal

    2016-08-26

    Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells. PMID:27621760

  20. Neoadjuvant treatment in advanced renal cell carcinoma: current situation and future perspectives.

    PubMed

    Timsit, Marc-Olivier; Albiges, Laurence; Méjean, Arnaud; Escudier, Bernard

    2012-12-01

    Neoadjuvant approaches in renal cell carcinoma are currently under investigation, following the demonstration of targeted therapy efficacy in the metastatic setting. It raises the issues of downsizing locally advanced or nonresectable tumor and offering organ-sparing surgery, safety and its potential role in early micrometastatic disease. Relevant studies of the neoadjuvant setting in renal cell carcinoma with targeted therapies were identified from the literature, clinical trial databases and conference abstracts. To date, a neoadjuvant approach appears feasible in terms of safety. Currently available drugs do not achieve major tumor downsizing with primary tumor diameters response rate of 10%. Neoadjuvants should only be considered in clinical trials or as a litmus test in locally advanced patients. PMID:23253222

  1. Cabozantinib versus everolimus in advanced renal cell carcinoma

    PubMed Central

    Choueiri, Toni K.; Escudier, Bernard; Powles, Thomas; Mainwaring, Paul; Rini, Brian I.; Donskov, Frede; Hammers, Hans; Hutson, Thomas E.; Lee, Jae-Lyun; Peltola, Katriina; Roth, Bruce J.; Bjarnason, Georg A.; Géczi, Lajos; Keam, Bhumsuk; Moroto, Pablo; Heng, Daniel Y. C.; Schmidinger, Manuela; Kantoff, Philip W.; Borgman, Anne; Hessel, Colin; Scheffold, Christian; Schwab, Gisela M.; Tannir, Nizar M.; Motzer, Robert J.

    2016-01-01

    Background Cabozantinib is an oral small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL; each has been implicated in metastatic renal cell carcinoma (RCC) pathobiology or development of resistance to antiangiogenic drugs. This randomized open-label phase 3 trial evaluated the efficacy of cabozantinib compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy. Methods The trial randomized 658 patients to receive cabozantinib at a dose of 60 mg daily, or everolimus at a dose of 10 mg daily. The primary endpoint was progression-free survival. Secondary efficacy endpoints were overall survival and objective response rate. Results Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The risk of progression or death was 42% lower with cabozantinib compared to everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P < 0.001). Objective response rates were 21% with cabozantinib and 5% with everolimus (P < 0.001). A planned interim analysis showed that overall survival was improved with cabozantinib (hazard ratio, 0.67; 95% CI, 0.51 to 0.89; P = 0.005) but did not cross the significance boundary. Adverse events (grade 3 or 4, regardless of causality) were reported in 74% of cabozantinib patients and 65% of everolimus patients. Discontinuation of study treatment for adverse events occurred in 9.1% of cabozantinib patients and 10% of everolimus patients. Conclusions Cabozantinib improved progression-free survival compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy. PMID:26406150

  2. Cost-Effectiveness of Cetuximab for Advanced Esophageal Squamous Cell Carcinoma

    PubMed Central

    Bruno, Marco J.; Polinder, Suzanne; Lorenzen, Sylvie; Lordick, Florian; Peppelenbosch, Maikel P.; Spaander, Manon C. W.

    2016-01-01

    Background Costly biologicals in palliative oncology are emerging at a rapid pace. For example, in patients with advanced esophageal squamous cell carcinoma addition of cetuximab to a palliative chemotherapy regimen appears to improve survival. However, it simultaneously results in higher costs. We aimed to determine the incremental cost-effectiveness ratio of adding cetuximab to first-line chemotherapeutic treatment of patients with advanced esophageal squamous cell carcinoma, based on data from a randomized controlled phase II trial. Methods A cost effectiveness analysis model was applied based on individual patient data. It included only direct medical costs from the health-care perspective. Quality-adjusted life-years and incremental cost-effectiveness ratios were calculated. Sensitivity analysis was performed by a Monte Carlo analysis. Results Adding cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma resulted in an the incremental cost-effectiveness ratio of €252,203 per quality-adjusted life-year. Sensitivity analysis shows that there is a chance of less than 0.001 that the incremental cost-effectiveness ratio will be less than a maximum willingness to pay threshold of €40,000 per quality-adjusted life-year, which is representative for the threshold used in The Netherlands and other developed countries. Conclusions Addition of cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma is not cost-effective when appraised according to currently accepted criteria. Cost-effectiveness analyses using outcome data from early clinical trials (i.c. a phase II trial) enable pharmaceutical companies and policy makers to gain early insight into whether a new drug meets the current eligibility standards for reimbursement and thereby potential admittance for use in regular clinical practice. PMID:27100871

  3. 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.

  4. [Heterotopic cloacogenic carcinoma of the lower lip].

    PubMed

    Vulcan, P; Dumitriu, E; Grigore, M

    1994-01-01

    Cloacogenic carcinoma is a tumour which develops from cylindric epithelial cells at the anorectal junction. Besides this usual localization, other sites have been described including the vagina, urethra, sigmoid colon, vulva and perianal skin. We observed a labial localization in a 50-year-old woman. A 15 mm tumorous formation developed rapidly after initial excision without skin or mucosal changes. The clinical diagnosis was epidermoid carcinoma but histological examination revealed an aspect comparable to cloacogenic carcinoma with nodules of basaloid tumour cells showing atypical mitosis within the nodules and the uniformly eosinophilic masses. We considered that this particular histological aspect eliminated the diagnosis of basocellular or epidermoid carcinoma and suggest that the carcinoma developed from embryon reliquats of cloacoanal transition cells in a heterotopic localization. PMID:7979028

  5. 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.

  6. 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

  7. Recent Advancements in Prognostic Factors of Epithelial Ovarian Carcinoma

    PubMed Central

    Ezzati, Mohammad; Abdullah, Amer; Shariftabrizi, Ahmad; Hou, June; Kopf, Michael; Stedman, Jennifer K.; Samuelson, Robert; Shahabi, Shohreh

    2014-01-01

    Ovarian cancer remains the most common cause of gynecologic cancer-related death among women in developed countries. Nevertheless, subgroups of ovarian cancer patients experience relatively longer survival. Efforts to identify prognostic factors that characterize such patients are ongoing, with investigational areas including tumor characteristics, surgical management, inheritance patterns, immunologic factors, and genomic patterns. This review discusses various demographic, clinical, and molecular factors implicating longevity and ovarian cancer survival. Continued efforts at identifying these prognosticators may result in invaluable adjuncts to the treatment of ovarian cancer, with the ultimate goal of advancing patient care.

  8. Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma.

    PubMed

    Macha, Muzafar A; Batra, Surinder K; Ganti, Apar Kishor

    2013-01-01

    Basal cell carcinoma (BCC) is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC. PMID:23940421

  9. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26628883

  11. [Iatrogenic spinal epidermoid tumors. A late complication of spinal puncture].

    PubMed

    Reina, M A; López-García, A; Dittmann, M; de Andrés, J A; Blázquez, M G

    1996-04-01

    INTRODUCTION. Epidermoid tumors in the spinal canal are rare. Whether congenitally or iatrogenically caused, they form as the result of epidermal cells implanted within the spinal channel. Such implantation can occur during a variety of procedures and events such as bullet wounds, surgery, myelography or punctures for diagnosis, anesthesia or treatment. Although this complication is not discussed in books or journals on anesthesiology, we have found it mentioned in over 100 published cases reporting iatrogenically caused spinal epidermoid tumors. ETIOPATHOGENESIS. Iatrogenic epidermoid tumors of the spine derive from the implantation of epidermal tissue transported inside the spinal canal during lumbar punctures without guidance or with inadequate guidance. There is ample evidence that such tumors are iatrogenic. All cases occur in patients with a history of lumbar puncture. They are rarely associated with congenital anomalies. They are extramedullary. They tend to develop near sites of earlier lumbar puncture, usually near the conus medullaris and the cauda equina. Iatrogenic epidermoid tumors of the spine have been reproduced experimentally in two studies in which autologous skin fragments were implanted in the spinal canal. CLINICAL SIGNS. These tumors are well tolerated by patients for extended periods of time, ranging from 2 to 10 years. At the cauda equinus, tumors can grow slowly for long periods without signs of nerve compression. Symptoms are directly related to tumor size and site. All patients with tumors at the cauda equinus report severe pain radiating toward the roots of compressed nerves. Nuclear magnetic resonance makes it possible to detect the tumor without administration of intrathecal contrast. At present gadolinium-DTPA improves the image so that these tumors can be distinguished from other types. The prognosis for epidermoid tumors of the spine is good, as they are histologically benign. Treatment is always surgical. CONCLUSION. Although the

  12. Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

    ClinicalTrials.gov

    2012-09-07

    Hepatocellular Carcinoma Non-resectable; Hepatocellular Carcinoma Recurrent; Carcinoma, Hepatocellular; Liver Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Carcinoma; Liver Neoplasms; Neoplasms; Neoplasms by Site; Digestive System Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial

  13. Perfusion analyses in advanced breast carcinoma during hyperthermia.

    PubMed

    Lagendijk, J J; Hofman, P; Schipper, J

    1988-01-01

    Blood flow in tumours and healthy tissue determines the ability of obtaining satisfactory temperature distributions in clinical hyperthermia, as well as the success of hyperthermia and radiation treatment. During the hyperthermia treatment, diagnostic data related to tissue blood flow can be determined by analysing the relationship between the amount of power absorbed in the tissue and the resulting temperature rise. The interpretation of the perfusion data (PERF) is highly complicated by the lack of an adequate theory to describe the heat transport in vascularized tissues. In vascularized breast tissues about 10 times as much power is needed to maintain therapeutic temperatures as is necessary in a stationary breast phantom. This large difference in maintenance power levels indicates the extreme importance of blood flow in tissue heat transport. PERF has been determined in 23 patients with advanced breast tumours. In this series (a) perfusion typically did not change during the stationary part of the individual hyperthermic sessions, (b) minimum tumour PERF was not related to tumour volume, and (c) there was no relation between tumour PERF and the ability to heat tumours. PERF can both increase and decrease after successful hyperthermia. PMID:3292667

  14. Maxillary sinus carcinoma

    SciTech Connect

    Lee, F.; Ogura, J.H.

    1981-01-01

    Primary site control, anatomical site of failure, survival, and complications of treatment were determined in a retrospective review of primary maxillary sinus carcinoma. Sixty-one patients were treated by radiation followed by surgery and 35 by radiation alone. Primary tumor control was achieved in 69% of patients receiving combined treatment, 14% of patients treated with radiation alone, and 49% of all patients. Local control did not differ with histological type. Virtually all epidermoid and undifferentiated carcinoma recurrences occurred within 2 years, but 27% of adenocarcinomas recurred after 2 years.

  15. Combined surgery and postoperative radiation therapy for advanced laryngeal and hypopharyngeal carcinomas

    SciTech Connect

    Mirimanoff, R.O.; Wang, C.C.; Doppke, K.P.

    1985-03-01

    The survival, pattern of failure and complications in 47 patients with Stage III and IV cancers of the glottis, supraglottis and hypopharynx treated with surgery and postoperative radiotherapy using a new treatment technique referred to as mini-mantle were analyzed. The absolute survival probability of the entire group was 53 and 31% at 3 and 5 years. The local control probability at 3 and 5 years was 63 and 58%, and was higher for the supraglottic/hypopharyngeal than for glottic carcinomas. Five patients developed complications requiring surgical correction, but none experienced mortality. Moderate complications were treated conservatively without lasting sequelae. This technique is a reasonable safe and efficient procedure and can be effectively employed for the management of advanced laryngeal and hypopharyngeal carcinomas after definitive surgery.

  16. Depressive symptomatology and pineal epidermoid cyst: a case report.

    PubMed

    Kontoangelos, Konstantinos; Economou, Marina; Maltezou, Maria; Kandaraki, Anna; Papadimitriou, George N

    2013-08-01

    Introduction Intracranial epidermoid cysts are congenital cysts. They comprise 0.2-1.8% of primary intracranial tumours and are four to nine times as common as dermoid cysts. Case report We here in present the case of a 32-year-old man who reported sudden onset of symptoms of a depressive symptomatology and particularly severe headache, accompanied by fatigue, depressed mood most of the day, marked diminished interest or pleasure in all or almost all activities, insomnia and diminished ability to think or concentrate. Brain magnetic resolution imaging examination revealed a pineal epidermoid cystic lesion, visualised in the posterior part of the third ventricle, with a maximum diameter of ∼2.8 cm and obstructing the aqueduct of Sylvius, causing obstructive hydrocephalus. Discussion Pineal cysts may enlarge over time, because of either increased cyst fluid or intracystic haemorrhage, and become symptomatic. Brain radiological investigations in patients with depressive symptomatology may be substantial. PMID:25287638

  17. 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

  18. Cerebellopontine angle epidermoid cysts: clinical presentations and surgical outcome.

    PubMed

    Hasegawa, Mitsuhiro; Nouri, Mohsen; Nagahisa, Shinya; Yoshida, Koichiro; Adachi, Kazuhide; Inamasu, Joji; Hirose, Yuichi; Fujisawa, Hironori

    2016-04-01

    Epidermoid cysts constitute less than 1 % of intracranial tumors with the majority of them involving cerebellopontine angle (CPA). Although several mechanisms for cranial nerve dysfunction due to these tumors have been proposed, no direct evaluation for hyper- or hypoactive dysfunction has been done. In this case series, pathophysiology of cranial nerve dysfunction in CPA epidermoid cysts was evaluated with special attention to a new mechanism of capsule strangulation caused by stratified tumor capsule. Twenty-two cases with epidermoid cysts of CPA micro-neurosurgically treated in our departments since 2005 were reviewed. Clinical status of the patients before the surgery and post-operative functional outcome were recorded. Available data from the English literature were summarized for comparison. Mass reduction of cyst contents in most cases was usually associated with prompt and marked improvement of the symptoms suggesting neuroapraxia caused by compression of the tumor content and/or mild ischemia. Among them, two cases showed strangulation of the affected nerves by the tumor capsule whose preoperative dysfunction did not improve after surgery in spite of meticulous microsurgical removal of the lesion. Involved facial and abducent nerves in these two cases showed distortion of nerve axis and nerve atrophy distal to the strangulation site. We report the first direct evidence of etiology of cranial nerve dysfunction caused by cerebellopontine angle epidermoid tumors. Young age and rapidly progressive neurological deficit might be the characteristics for strangulation of the affected nerves by the cyst capsule. Even though the number of cases might be limited, immediate decompression and release of the strangulating band might be urged in such patients to prevent irreversible deficits. PMID:26566990

  19. Whole Course Neuroendoscopic Resection of Cerebellopontine Angle Epidermoid Cysts.

    PubMed

    Hu, Zhiqiang; Guan, Feng; Kang, Tiejiang; Huang, Hui; Dai, Bin; Zhu, Guangtong; Mao, Beibei; Kang, Zhuang

    2016-09-01

    Background Epidermoid cysts are the third most common tumor of the cerebellopontine angle (CPA). Diagnosis often occurs after involvement of the sulci and cisterns that surround nerves and blood vessels, making complete resection highly challenging. Objective To determine the efficacy of whole course neuroendoscopic surgery in the management of CPA epidermoid cysts. Methods We performed a retrospective analysis of clinical data of 13 male and 17 female patients (mean age: 42.4 ± 11.4 years) who presented with a CPA epidermoid cyst and underwent whole course neuroendoscopy. Complications and tumor recurrence were assessed at follow-up. Results Clinical manifestations included an initial symptom of headache (n = 21), gait instability (n = 6), intracranial hypertension (n = 13), posterior cranial nerve symptoms (n = 6), ataxia (n = 5), and hydrocephalus (n = 1). All patients tolerated tumor resection with subsequent symptomatic improvement, and the results of the postoperative magnetic resonance imaging scan did not show any remnants of tumor. Mean duration of surgery was 2.61 ± 0.47 hours, mean loss of blood was 96.8 ± 35.4 mL, and the mean duration of hospitalization was 7.5 ± 2.25 days. Postoperative complications (8 of 30 [26.7%]) included fever (n = 5), communicating hydrocephalus (n = 1), facial nerve paralysis (n = 1), and abducens nerve palsy (n = 1). Tumor recurrence was observed in two patients (6.7%). No deaths or intracranial hemorrhage was reported. Conclusions The characteristics of epidermoid cysts make them amenable to whole course neuroendoscopic resection. Use of physiologic/pathologic interspaces and neuroendoscopic angulations decreases traction on the brain, improves complete resection rates, and decreases postoperative complications. PMID:26302403

  20. Long-Term Follow-Up and Prognostic Factors for Advanced Thymic Carcinoma

    PubMed Central

    Wu, Jun-xin; Chen, Hui-qin; Shao, Ling-dong; Qiu, Su-fang; Ni, Qian-yu; Zheng, Bu-hong; Wang, Jie-zhong; Pan, Jian-ji; Li, Jin-luan

    2014-01-01

    Abstract The aim of this study was to evaluate the long-term survival outcomes in patients with advanced thymic carcinoma and identify prognostic factors influencing the survival. We retrospectively analyzed 90 consecutive patients with pathologically confirmed advanced thymic carcinoma (Masaoka III and IV) in our institute, from December 2000 to 2012. Age, sex, clinical characteristics, laboratory findings, Masaoka and tumor node metastasis staging, pathologic grade, and treatment modalities were analyzed to identify prognostic factors associated with the progress-free survival (PFS) and the overall survival (OS) rates. Statistical analysis was conducted using SPSS, version 19.0 (SPSS, Inc, Chicago, IL). A total of 73 (81.1%) male and 17 (18.9%) female patients participated in the study. The median follow-up time was 75 months (range, 20–158 months). The 5-year PFS and OS rates were 23.6% (95% confidence interval [CI], 14.6%–33.8%) and 35.7% (95% CI, 25.1%–46.4%), respectively. The multivariate Cox regression model analysis showed that factors improving the PFS were the normal lactate dehydrogenase (LDH) level (P < 0.001), Masaoka III stage (P = 0.028), and radiotherapy (RT) (P < 0.001). The LDH (P < 0.001), T stage (P < 0.001), and the pathologic grade (P = 0.047) were independently prognostic of OS. Long-term follow-up of the advanced thymic carcinoma showed poor outcomes of PFS and OS. LDH, Masaoka stage, and RT affected the PFS, and LDH, T stage, and pathologic grade seemed to affect the OS. Establishing a better staging system for predicting outcomes would be warranted. PMID:25526488

  1. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD. PMID:25786448

  2. Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

    PubMed Central

    Bouattour, Mohamed; Payancé, Audrey; Wassermann, Johanna

    2015-01-01

    Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimizing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used. PMID:26380650

  3. Recent Advances in Radiofrequency Ablation for the Management of Hepatocellular Carcinoma

    PubMed Central

    Himoto, Takashi; Kurokohchi, Kazutaka; Watanabe, Seishiro; Masaki, Tsutomu

    2012-01-01

    Contexts Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. Because less than 20% of patients with HCC are resectable, various types of non-surgical treatment have been developed. Evidence Acquisition At present, radiofrequency ablation (RFA) is accepted as the standard local treatment for patients with HCC because of its superior local control and overall survival compared to other local treatments. Results New devices for RFA and combination treatments of RFA with other procedures have been developed to improve anti-tumoral effects. Conclusions This review mainly focuses on the status of RFA in the management of HCC and recent advances in RFA treatment technology. PMID:23162600

  4. Immunological Treatment Options for Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Mirandola, Leonardo; Bernardini, Giovanni; Cunha, Nicholas D’; Tijani, Lukman; Nguyen, Diane; Cordero, Joehassin; Jenkins, Marjorie R.; Cobos, Everardo; Kast, W. Martin; Chiriva-Internati, Maurizio

    2014-01-01

    Patients with squamous cell carcinoma of the head and neck (HNSCC) are usually treated by a multimodal approach with surgery and/or radiochemotherapy as the mainstay of local–regional treatment in cases with advanced disease. Both chemotherapy and radiation therapy have the disadvantage of causing severe side effects, while the clinical outcome of patients diagnosed with HNSCC has remained essentially unchanged over the last decade. The potential of immunotherapy is still largely unexplored. Here the authors review the current status of the art and discuss the future challenges in HNSCC treatment and prevention. PMID:22251006

  5. Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Ko, Christine; Citrin, Deborah

    2008-01-01

    Background Squamous cell carcinomas of the head and neck (SCCHN) affect approximately 35,000 people in the United States yearly. Although survival has improved with advances in therapy, patients with advanced stages of SCCHN continue to have a poor prognosis. An understanding of rationale for treatment selection, newer developments in therapy, and treatment toxicity is critical. Methods Standard methods of treating locally advanced SCCHN are reviewed. Advances in medical and radiotherapeutic management are discussed and the toxicities of therapy are described. Results Post-operative chemoradiation is used in patients with high risk characteristics. Induction chemotherapy and altered fractionation radiation treatment have been evaluated as alternatives to definitive chemo-radiotherapy. Targeted agents such as cetuximab may prove to increase survival with minimal increase in toxicity profile. Technological improvements such as the use of intensity modulated radiation treatment (IMRT) have proven to decrease some debilitating side effects from radiation treatment. Conclusions Locally advanced SCCHN continues to present a therapeutic challenge. Survival, local control, and quality of life are all goals of treatment. The optimal method of treating locally advanced SCCHN is the subject of ongoing research. Long term side effects can be minimized with the use of newer technologies and with careful treatment planning. PMID:19036056

  6. [Treatment of advanced ovarian carcinoma: surgery before chemotherapy or chemotherapy before surgery?].

    PubMed

    Piura, Benjamin

    2014-09-01

    The standard of care for advanced epithelial ovarian carcinoma has been primary surgery aspiring for optimal debulking followed by adjuvant chemotherapy. A significant survival advantage has been demonstrated in women having optimal debulking at primary surgery compared to women having less than optimal debulking at primary surgery. With the advent of efficient chemotherapy for ovarian carcinoma (combination of platinum and taxan), the administration of several courses of chemotherapy before surgery (neoadjuvant chemotherapy) has been established as a method for reducing the intra-abdominal tumor burden and, thereby, increasing the probability of optimal debulking at surgery which is usually performed in the interval between course no. 3 and no. 4 of chemotherapy (interval surgery). Higher rates of optimal debulking, Lower rates of surgical complications, but no differences in survival, have been demonstrated in women having chemotherapy before surgery compared to women having surgery before chemotherapy. Obviously, the method of neoadjuvant chemotherapy is the treatment of choice for women in whom the clinical evaluation indicates that there is no high probability of optimal debulking at primary surgery. Nevertheless, there has been a debate on whether or not the method of neoadjuvant chemotherapy should also be applied for women in whom the clinical evaluation indicates that they are fit for optimal debulking at primary surgery. There is a need for more prospective studies to evaluate the role of neoadjuvant chemotherapy in the treatment of ovarian carcinoma. PMID:25417488

  7. [Treatment of advanced ovarian carcinoma: surgery before chemotherapy or chemotherapy before surgery?............... ].

    PubMed

    Piura, Benjamin

    2014-09-01

    The standard of care for advanced epithelial ovarian carcinoma has been primary surgery aspiring for optimal debulking followed by adjuvant chemotherapy. A significant survival advantage has been demonstrated in women having optimal debulking at primary surgery compared to women having less than optimal debulking at primary surgery. With the advent of efficient chemotherapy for ovarian carcinoma (combination of platinum and taxan), the administration of several courses of chemotherapy before surgery (neoadjuvant chemotherapy) has been established as a method for reducing the intra-abdominal tumor burden and, thereby, increasing the probability of optimal debulking at surgery which is usually performed in the interval between course no. 3 and no. 4 of chemotherapy (interval surgery). Higher rates of optimal debulking, Lower rates of surgical complications, but no differences in survival, have been demonstrated in women having chemotherapy before surgery compared to women having surgery before chemotherapy. Obviously, the method of neoadjuvant chemotherapy is the treatment of choice for women in whom the clinical evaluation indicates that there is no high probability of optimal debulking at primary surgery. Nevertheless, there has been a debate on whether or not the method of neoadjuvant chemotherapy should also be applied for women in whom the clinical evaluation indicates that they are fit for optimal debulking at primary surgery. There is a need for more prospective studies to evaluate the role of neoadjuvant chemotherapy in the treatment of ovarian carcinoma. PMID:25507216

  8. Degranulation patterns of eosinophils in advanced gastric carcinoma: an electron microscopic study.

    PubMed

    Caruso, R A; Ieni, A; Fedele, F; Zuccalà, V; Riccardo, M; Parisi, E; Parisi, A

    2005-01-01

    Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and degranulation patterns of eosinophils in the tumor stroma. Seven cases of advanced gastric carcinomas were found to be massively infiltrated by eosinophils and studied by light and electron microscopy. Gastric carcinomas, despite having similar numbers of tissue eosinophils, exhibited markedly different degranulation patterns. In 2 cases, resting nondegranulating eosinophils were found. Piecemeal degranulation was the predominant mode of secretion from eosinophils localized within the tumor stroma in 4 cases. Eosinophil exocytosis and cytolysis were rarely observed. In 1 case, crystals morphologically similar to Charcot-Leyden crystals were observed at the extracellular level as well as in phagosomes of tissue macrophages, confirming active sequestrations of eosinophil Charcot-Leyden protein by macrophages in vivo. In the same case, eosinophils showed characteristic features of early and late apoptotic changes, such as condensed chromatin, focal dilatation of nuclear envelope, and preserved plasma membrane. Morphological association between apoptotic eosinophils and deposition of granules in the tumor stroma was found. Extracellular deposition of intact granules from apoptotic eosinophils was distinct from eosinophilic (necrotic) cytolysis, and has reported previously in experimental studies in vitro. To the knowledge of the authors, this case represents the first report of late apoptotic eosinophils that release their granules within the tumor stroma in a human gastric carcinoma. PMID:15931778

  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. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma

    PubMed Central

    Nghiem, Paul T.; Bhatia, Shailender; Lipson, Evan J.; Kudchadkar, Ragini R.; Miller, Natalie J.; Annamalai, Lakshmanan; Berry, Sneha; Chartash, Elliot K.; Daud, Adil; Fling, Steven P.; Friedlander, Philip A.; Kluger, Harriet M.; Kohrt, Holbrook E.; Lundgren, Lisa; Margolin, Kim; Mitchell, Alan; Olencki, Thomas; Pardoll, Drew M.; Reddy, Sunil A.; Shantha, Erica M.; Sharfman, William H.; Sharon, Elad; Shemanski, Lynn R.; Shinohara, Michi M.; Sunshine, Joel C.; Taube, Janis M.; Thompson, John A.; Townson, Steven M.; Yearley, Jennifer H.; Topalian, Suzanne L.; Cheever, Martin A.

    2016-01-01

    BACKGROUND Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1. METHODS In this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti–PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing. RESULTS A total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patients with at least one evaluation during treatment was 56% (95% confidence interval [CI], 35 to 76); 4 patients had a complete response, and 10 had a partial response. With a median follow-up of 33 weeks (range, 7 to 53), relapses occurred in 2 of the 14 patients who had had a response (14%). The response duration ranged from at least 2.2 months to at least 9.7 months. The rate of progression-free survival at 6 months was 67% (95% CI, 49 to 86). A total of 17 of the 26 patients (65%) had virus-positive tumors. The response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among those with virus-negative tumors (4 of 9 patients). Drug-related grade 3 or 4 adverse events occurred in 15% of the patients. CONCLUSIONS In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors

  11. Fever as a first manifestation of advanced gastric adenosquamous carcinoma: A case report

    PubMed Central

    Ajoodhea, Harsha; Zhang, Ren-Chao; Xu, Xiao-Wu; Jin, Wei-Wei; Chen, Ke; He, Yong-Tao; Mou, Yi-Ping

    2014-01-01

    Gastric adenosquamous carcinoma (ASC) is a rare type of gastric cancer. It is a mixed neoplasm, consisting of glandular cells and squamous cells. It is often diagnosed at an advanced stage, thus carrying a poor prognosis. We describe a case of a 73-year-old male, who presented with refractory fever and an intra-abdominal mass on imaging. He underwent a laparoscopic exploration followed by a successful totally laparoscopic total gastrectomy with D2 lymphadenectomy for gastric cancer. Postoperative pathology revealed primary gastric ASC (T4aN0M0). The patient received adjuvant radiotherapy and chemotherapy with S1 and is alive 20 mo after surgery without recurrence. This is the first case of advanced gastric ASC with fever as the initial presentation treated with totally laparoscopic total gastrectomy reported in the English literature. PMID:25110448

  12. Advanced Basal cell carcinoma in a patient with schizoaffective disorder: constraints and management.

    PubMed

    Taylor, Elise J; Golas, Liliya; Martel, Joseph R; Martel, James B

    2013-01-01

    The approach used by the authors for managing a patient with a schizoaffective disorder and advanced basal cell carcinoma involving the eyelids, orbit, and face is presented. Complexities included the advanced nature of the disease, neglect of the patient's condition due to schizoaffective disorder, the difficulty of obtaining informed consent, the required aggressive surgical intervention, reconstruction, and the necessary management during the postsurgical period. A multidisciplinary team approach with psychiatry, ophthalmology, ear, nose, and throat, plastic surgery, radiation oncology, oncology, legal, and bioethics specialties is required in patients with cognitive disabilities. Curative treatment requires complete excision, reconstruction, and proper postoperative care, which can be prohibitive in a schizophrenic patient from a surgical and ethical perspective. Staging of this condition after proper informed consent with biopsy, computed tomography, and magnetic resonance imaging is presented. The options for management are discussed, including surgical intervention and palliative care. PMID:23235512

  13. Salivary biomarkers for detection of oral squamous cell carcinoma – current state and recent advances

    PubMed Central

    Yakob, Maha; Fuentes, Laurel; Wang, Marilene B.; Abemayor, Elliot; Wong, David T.W.

    2014-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. Detection of OSCC is currently based on thorough clinical oral examination combined with biopsy for histological analysis. Most cases of OSCC are not detected until the cancer has developed into advanced stages; thus, a reliable early stage diagnostic marker is needed. This literature review presents an overview of the status of current advances in salivary diagnostics for OSCC. Though many protein and mRNA salivary biomarkers have been identified that can detect OSCC with high sensitivity and specificity, the most discernable findings occur with the use of multiple markers. Studies that incorporate proteomic, transcriptomic, and potentially additional “omics”, including methylomics, need to be initiated to bring technology to clinical applications and allow the best use of saliva in diagnosing OSCC. PMID:24883261

  14. Percutaneous irreversible electroporation of locally advanced pancreatic carcinoma using the dorsal approach: a case report.

    PubMed

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

    2015-06-01

    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. PMID:25288173

  15. En bloc resection of the temporal bone and temporomandibular joint for advanced temporal bone carcinoma.

    PubMed

    Kutz, Joe Walter; Mitchell, Derek; Isaacson, Brandon; Roland, Peter S; Allen, Kyle P; Sumer, Baran D; Barnett, Sam; Truelson, John M; Myers, Larry L

    2015-03-01

    Advanced skin malignancies involving the temporal bone can involve the temporomandibular joint and glenoid fossa. Many of these tumors can be removed with a lateral temporal bone resection; however, extensive involvement of the glenoid fossa should include an en bloc resection of the temporal bone, glenoid fossa, and condyle. We describe a novel surgical approach that is an extension of a temporal bone resection that includes the glenoid fossa and condyle in an en bloc resection with the temporal bone. This procedure has been performed in 7 patients with advanced carcinoma of the temporal bone involving the glenoid fossa. There were no short-term complications as a result of the surgical approach. The addition of a middle fossa craniotomy and inclusion of the glenoid fossa and condyle as part of an en bloc resection of the temporal bone can be performed safely. PMID:25616770

  16. 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.

  17. ‘Saddle nose’ deformity caused by advanced squamous cell carcinoma of the nasal septum

    PubMed Central

    Graham, Hamish Edward; Connolly, Cara; Pahal, Gurjinderpal S; Stafford, Francis W

    2014-01-01

    Hidden behind their common garden symptoms, malignant tumours of the nasal cavity are typically advanced when detected. Squamous cell carcinoma (SCC) is the most common histological type of these rare tumours which may simply present with epistaxis or a blocked nose. A 79-year-old woman attended our clinic with a 2-year history of progressive nasal collapse resulting in a ‘saddle nose deformity’. Imaging showed a soft tissue mass with absolute destruction of the nasal septum and bones with hard palate and maxillary involvement. Histology confirmed a poorly differentiated SCC. Following discussion at the local head and neck multidisciplinary team meeting, the patient was offered radiotherapy alone due to her advanced presentation. She has had a good response to treatment with no further disease progression. Nasal septal SCC is far more successfully treated in the early stages. A suspicious clinician is the patients best ally. PMID:25096649

  18. 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. PMID:26645975

  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. [A Case of Long-Term Survival of Advanced Esophageal Basaloid Squamous Carcinoma Invading the Trachea].

    PubMed

    Tokura, Michiyo; Yoshimura, Tetsunori; Murata, Tomohiro; Matsuyama, Takatoshi; Hoshino, Mayumi; Goto, Hiroshi; Kakimoto, Masaki; Koshiishi, Haruya

    2015-11-01

    A woman in her 50s complained of dysphagia and was diagnosed with locally advanced esophageal cancer in the middle and upper thoracic esophagus, invading the tracheal bronchus. The biopsy indicated esophageal basaloid squamous carcinoma. The pretreatment diagnosis was cT4N2M0, cStage Ⅳa. She was treated with systemic chemotherapy consisting of FAP (5-fluorouracil [5-FU], doxorubicin [DXR] and cisplatin[CDDP]), which resulted in significant tumor shrinkage. One year later, the tumor regrew, and nedaplatin (CDGP) plus docetaxel (DOC) was administered as second-line chemotherapy. The patient complained of dysphagia during the course of chemotherapy, and received radiation therapy for the residual tumor, which again significantly shrunk. Four years after the first round of chemotherapy, the patient can take oral nutrition, and is continuing to undergo chemotherapy. This is a case of long-term survival of locally advanced esophageal cancer of basaloid squamous carcinoma. Effective chemotherapy and radiation can improve the treatment outcome. PMID:26805208

  2. [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. PMID:26805152

  3. An unusual presentation of an intraosseous epidermoid cyst of the anterior maxilla: a case report

    PubMed Central

    2014-01-01

    Introduction Intraosseous epidermoid inclusion cysts are rare benign epithelial inclusion cysts in the bone. They are usually found in the cranium and hand phalanges. They are slow growing lesions, and it is difficult to differentiate them from other inflammatory and cystic lesions. Only a few cases of epidermoid inclusion cyst in the jaw have been reported in the literature. This is the fourth case reported as intraosseous epidermoid cyst of the maxilla in the English literature. Case presentation An asymptomatic 59-year-old Caucasian man was referred to our Oral and Maxillofacial Surgery clinic for a unilocular radiolucent area at his anterior maxilla shown on an orthopantomograph. He was scheduled for surgery and underwent cyst extraction surgery. A pathological examination revealed epidermoid cyst. The diagnostic dilemma in this case report in opposition to the presented intraosseous epidermoid cysts in the literature is that there was no trauma history to his upper jaw. Treatment for this cyst is conservative surgical excision and recurrence is uncommon. Conclusions This report presents an unusual case of an intraosseous epidermoid cyst that occurred with no trauma history to the upper jaw. Although only three cases of epidermoid inclusion cyst have been reported in the maxilla, epidermoid inclusion cyst should be considered in the differential diagnosis of radiolucent lesions of the jaws. PMID:25070270

  4. Bleomycin in advanced squamous cell carcinoma: a random controlled trial. Report of Medical Research Council Working Party on Bleomycin.

    PubMed Central

    1976-01-01

    Bleomycin was compared with conventional cytotoxic drugs in the treatment of 70 patients with advanced squamous cell carcinoma; the primary deposit was in the head and neck in 50 patients and in the perineum or skin in 20. Thirty-four patients received bleomycin while 36 received other cytotoxic drugs. No significant difference was detected between the two groups either in the proportion showing tumour regression or in the survival rates. If bleomycin is to advance the treatment of squamous cell carcinoma it can be only in combination with other drugs or with radiotherapy. PMID:55288

  5. Reduced expression of TGF beta is associated with advanced disease in transitional cell carcinoma.

    PubMed Central

    Coombs, L. M.; Pigott, D. A.; Eydmann, M. E.; Proctor, A. J.; Knowles, M. A.

    1993-01-01

    The gene structure and expression of the related peptide regulatory factors TGF beta 1 and TGF beta 2 were studied in a panel of seven urothelial carcinoma cell lines and 40 transitional cell carcinomas. The latter comprised 15 grade 1, 18 grade 2 and 5 grade 3 tumours and two cases of carcinoma in situ. Control tissues included ten matched 'field' biopsies and 17 other biopsies including 11 biopsies of macroscopically normal urothelium, two of which were from patients with no history of bladder cancer. No amplification of rearrangements of either TGF beta 1 or TGF beta 2 were detected in any sample. A complex pattern of expression or the two genes was found in the urothelial cell lines. High, but variable levels of the 2.5 kb TGF beta 1 transcript were detected and lower and more variable levels of the three (4.1 kb, 5.1 kb and 6.5 kb) transcripts of TGF beta 2 were detected. Although those cell lines expressing most TGF beta 1 tended to express less TGF beta 2 transcript there was no clear-cut relationship. In comparison, no TGF beta 2 transcript was identified in any primary transitional cell carcinoma or control tissue. Markedly reduced or undetectable levels of TGF beta 1 transcript were detected in 4/15 (26%) grade 1, 5/18 (28%) grade 2 and 3/5 (60%) grade 3 tumours. There was no clear relationship to tumour stage, lymphocytic infiltration or stromal content of the tumours. Clinical review one year after the 2 year period of tumour collection showed that 6/9 (66%) of patients with tumours with reduced levels of transcript had died or had disease which was not controllable by local resection and 3/9 (33%) had developed tumour re-occurrences. In comparison, in the group with normal levels of expression of TGF beta 1, 3/18 (17%) had disease which was not controllable by local means, 9/18 (50%) had tumour re-occurrence and 6/18 (33%) had no evidence of disease. The association of reduced expression of TGF beta 1 and advanced disease was statistically significant

  6. c-kit mutation-positive advanced thymic carcinoma successfully treated as a mediastinal gastrointestinal stromal tumor: A case report

    PubMed Central

    HIRAI, FUMIHIKO; EDAGAWA, MAKOTO; SHIMAMATSU, SHINICHIRO; TOYOZAWA, RYO; TOYOKAWA, GOUJI; NOSAKI, KANAME; YAMAGUCHI, MASAFUMI; SETO, TAKASHI; TWAKENOYAMA, MITSUHIRO; ICHINOSE, YUKITO

    2016-01-01

    Thymic carcinoma is an exceptionally rare tumor, which has a very poor prognosis, differing from thymoma. Although cytotoxic chemotherapy is commonly used to treat advanced thymic carcinoma, its effectiveness has not been found to be sufficient. There are several reports that thymic carcinoma also harbors an oncogenic driver mutation, similar to lung cancer. A patient with a c-kit mutation-positive thymic carcinoma received imatinib followed by sunitinib consecutively, which are both c-Kit inhibitors. Although the patient had achieved long-term disease control for 21 months, the primary lesion and pulmonary metastases had increased in size by November, 2014. Following failure of imatinib treatment, the patient received sunitinib, a multiple kinase inhibitor, initiated in December, 2014. Following administration of sunitinib, a computed tomography scan revealed a partial response and the disease was effectively controlled with continued sunitinib treatment for 6 months, up to June, 2015. The patient achieved long-term disease control (~27 months) with imatinib followed by sunitinib. The efficacy of consecutive molecular-targeted therapy for thymic carcinoma was demonstrated in this case. Therefore, thymic carcinoma with oncogenic driver mutations should be treated with molecular-targeted agents rather than with cytotoxic drugs, and it may be suitable to treat c-kit mutation-positive thymic carcinoma as a mediastinal gastrointestinal stromal tumor. PMID:27073655

  7. 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

  8. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment response, etiology, Child-Pugh grading, and level of protein induced by the vitamin K antagonist- II (PIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  9. 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.

  10. 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

  11. 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. PMID:23958511

  12. Intra-Arterial Chemotherapy with Doxorubicin and Cisplatin Is Effective for Advanced Hepatocellular Cell Carcinoma

    PubMed Central

    Ma, Ming-Chun; Chen, Yen-Yang; Li, Shau-Hsuan; Cheng, Yu-Fan; Wang, Chih-Chi; Chiu, Tai-Jan; Pei, Sung-Nan; Liu, Chien-Ting; Huang, Tai-Lin; Huang, Chen-Hua; Chen, Yen-Hao; Rau, Kun-Ming

    2014-01-01

    Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m2) and cisplatin (50 mg/m2) infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR) was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I) and those who received several cycles (group II). The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (P < 0.0001). The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (P < 0.0001). The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT. PMID:24967421

  13. Management of inferior vena cava tumor thrombus in locally advanced renal cell carcinoma

    PubMed Central

    Psutka, Sarah P.

    2015-01-01

    The diagnosis of renal cell carcinoma is accompanied by intravascular tumor thrombus in up to 10% of cases, of which nearly one-third of patients also have concurrent metastatic disease. Surgical resection in the form of radical nephrectomy and caval thrombectomy represents the only option to obtain local control of the disease and is associated with durable oncologic control in approximately half of these patients. The objective of this clinical review is to outline the preoperative evaluation for, and operative management of patients with locally advanced renal cell carcinoma with venous tumor thrombi involving the inferior vena cava. Cornerstones of the management of these complex patients include obtaining high-quality imaging to characterize the renal mass and tumor thrombus preoperatively, with further intraoperative real-time evaluation using transesophageal echocardiography, careful surgical planning, and a multidisciplinary approach. Operative management of patients with high-level caval thrombi should be undertaken in high-volume centers by surgical teams with capacity for bypass and invasive intraoperative monitoring. In patients with metastatic disease at presentation, cytoreductive nephrectomy and tumor thrombectomy may be safely performed with simultaneous metastasectomy if possible. In the absence of level one evidence, neoadjuvant targeted therapy should continue to be viewed as experimental and should be employed under the auspices of a clinical trial. However, in patients with significant risk factors for postoperative complications and mortality, and especially in those with metastatic disease, consultation with medical oncology and frontline targeted therapy may be considered. PMID:26445601

  14. Neoadjuvant Chemotherapy for Locally Advanced Squamous Carcinoma of Oral Cavity: a Pilot Study.

    PubMed

    Sadighi, Sanambar; Keyhani, Amanolah; Harirchi, Iraj; Garajei, Ata; Aghili, Mahdi; Kazemian, Ali; Motiee Langroudi, Maziar; Zendehdel, Kazem; Nikparto, Nariman

    2015-01-01

    To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF) induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SPSS version 17 was used for data analysis. Median follow-up was 16 months. The median age of the patients was 62 years old (23-75 years). Man/woman ratio was 1.13. The primary site of the tumor was the tongue in most patients (48%). No significant difference was observed between pathologic characteristics of the two groups. Chemotherapy group showed 16% complete pathologic response to TPF. No significant difference in organ preservation surgery or overall survival was detected. However, the patients in the chemotherapy group had longer progression-free-survival (P=0.014). Surgery followed by chemoradiotherapy with or without TPF induction results in similar survival time. However, progression-free-survival improves with the TPF induction chemotherapy. Studies with more patents and new strategies are recommended to evaluate organ preservation improvement and long-term outcomes. PMID:26069178

  15. 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

  16. Optimized management of advanced hepatocellular carcinoma: Four long-lasting responses to sorafenib

    PubMed Central

    Abbadessa, Giovanni; Rimassa, Lorenza; Pressiani, Tiziana; Carrillo-Infante, Cynthia; Cucchi, Emanuele; Santoro, Armando

    2011-01-01

    The therapeutic options for hepatocellular carcinoma (HCC) have been so far rather inadequate. Sorafenib has shown an overall survival benefit and has become the new standard of care for advanced HCC. Nevertheless, in clinical practice, some patients are discontinuing this drug because of side effects, and misinterpretation of radiographic response may contribute to this. We highlight the importance of prolonged sorafenib administration, even at reduced dose, and of qualitative and careful radiographic evaluation. We observed two partial and two complete responses, one histologically confirmed, with progression-free survival ranging from 12 to 62 mo. Three of the responses were achieved following substantial dose reductions, and a gradual change in lesion density preceded or paralleled tumor shrinkage, as seen by computed tomography. This report supports the feasibility of dose adjustments to allow prolonged administration of sorafenib, and highlights the need for new imaging criteria for a more appropriate characterization of response in HCC. PMID:21633647

  17. 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

  18. 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

  19. Limbal stem cell failure secondary to advanced conjunctival squamous cell carcinoma: a clinicopathological case report

    PubMed Central

    Lyall, Douglas A M; Srinivasan, Sathish; Roberts, Fiona

    2009-01-01

    A 67-year-old man with a history of multiple myeloma (treated with chemotherapy) was referred with a left hyperaemic conjunctival lesion covering almost 360° of the limbus and extending onto the corneal surface. Conjunctival biopsy revealed conjunctival intraepithelial neoplasia. Initial treatment consisted of topical and intralesional injections of interferon α-2b. The patient subsequently developed limbal stem cell deficiency resulting in a persistent non-healing corneal epithelial defect. This was successfully managed with total excisional biopsy of the lesion, combined with limbal stem cell autograft (from the fellow eye) and amniotic membrane transplantation. Histopathology revealed a conjunctival squamous cell carcinoma. The corneal epithelium completely healed postoperatively and there is no evidence of tumour recurrence at 1 year follow-up. This case highlights a rare case of advanced ocular surface neoplasia causing secondary limbal stem cell deficiency. Medical and surgical management of ocular surface neoplasia with limbal stem cell transplantation is effective in treating such cases. PMID:22121391

  20. 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

  1. Rapid sequence treatment of advanced squamous cell carcinoma of the upper aerodigestive tract: A pilot study

    SciTech Connect

    Moloy, P.J.; Moran, E.M.; Azawi, S. )

    1991-01-01

    A review of the literature suggested that prolonged treatment time may lessen the probability of cure for patients with advanced squamous cell carcinoma of the upper aerodigestive tract. To shorten treatment time, rapid sequence treatment (RST) was devised in which chemotherapy, surgery, and irradation were administered in a total treatment time of 8 weeks. Twelve patients were treated and followed 3 years or longer. Medical complications were minor. Osteonecrosis occurred in each of the first five patients and was the only major complication of the protocol. Surgical techniques were modified, and no additional patient developed osteonecrosis. No patient developed local or regional recurrence. Two patients developed distant metastases and three other patients developed second primaries. Absolute survival was 50%. Rapid sequence treatment is an aggressive and potentially hazardous protocol that yielded encouraging results in this pilot study.

  2. 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

  3. Cervical brachytherapy technique for locally advanced carcinoma of the cervix in a patient with septate uterus

    PubMed Central

    Wallace, Charlie; Gondi, Vinai; Das, Rupak; Straub, Margaret; Al-Niaimi, Ahmed; Applegate, Glenn; Bradley, Kristin A.

    2014-01-01

    Purpose To describe an approach to cervical brachytherapy in a patient with congenital septate uterus and locally advanced cervical carcinoma. Material and methods The patient is a 34-year-old female with septate uterus presenting with pelvic pain. Workup demonstrated a stage IIB cervical adenocarcinoma with imaging evidence of an involved right external iliac lymph node. The patient received whole pelvic radiation, with concurrent weekly cisplatin (40 mg/m2), to a dose of 45 Gy in 25 fractions followed by a parametrial boost of 5.4 Gy and an additional nodal boost of 9 Gy. Results The patient was initiated on cervical brachytherapy following fraction 23 of pelvic radiation. To conform to her septated uterus, a Rotte-Y tandem was used. Additionally, 2 CT-compatible ovoids were placed in the vaginal apex to enhance dose distribution and coverage of the target volume. Each fraction of brachytherapy was performed with CT-based planning. A high-risk clinical target volume (HR-CTV) and normal structures were defined and constrained per American Brachytherapy Society (ABS) and Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines. The brachytherapy dose was 27.5 Gy in 5 fractions of 5.5 Gy each, prescribed to the HR-CTV. Conclusions Herein, we report the first documented case of cervical brachytherapy in a patient with septate uterus and locally advanced cervical carcinoma. Using CT-guided planning, in conjunction with the ABS and GEC-ESTRO guidelines, the patient was effectively treated with adapted cervical brachytherapy, meeting criteria for HR-CTV coverage and normal tissue tolerances. PMID:24790625

  4. Treatment of Locally Advanced Adenoid Cystic Carcinoma of the Trachea With Neutron Radiotherapy

    SciTech Connect

    Bittner, Nathan; Koh, W.-J.; Laramore, George E.; Patel, Shilpen; Mulligan, Michael S.; Douglas, James G.

    2008-10-01

    Purpose: To examine the efficacy of fast neutron radiotherapy in the treatment of locally advanced adenoid cystic carcinoma (ACC) of the trachea and to compare outcomes with and without high-dose-rate (HDR) endobronchial brachytherapy boost. Methods and Materials: Between 1989 and 2005, a total of 20 patients with ACC of the trachea were treated with fast neutron radiotherapy at University of Washington. Of these 20 patients, 19 were treated with curative intent. Neutron doses ranged from 10.7 to 19.95 Gy (median, 19.2 Gy). Six of these patients received an endobronchial brachytherapy boost using an HDR {sup 192}Ir source (3.5 Gy x 2 fractions). Median duration of follow-up was 46 months (range, 10-121 months). Results: The 5-year actuarial overall survival rate and median overall survival for the entire cohort were 89.4%, and 97 months, respectively. Overall survival was not statistically different among those patients receiving an endobronchial boost compared with those receiving neutron radiotherapy alone (100% vs. 68%, p = 0.36). The 5-year actuarial locoregional control rate for the entire cohort was 54.1%. The locoregional control rate was not statistically different among patients who received an endobronchial boost compared with those who received neutron radiotherapy alone (40% vs. 58%, p 0.94). There were no cases of Grade {>=}3 acute toxicity. There were 2 cases of Grade 3/4 chronic toxicity. Conclusions: Fast neutron radiotherapy is an effective treatment for locally advanced adenoid cystic carcinoma of the trachea, with acceptable treatment-related toxicity.

  5. DWI findings in a iatrogenic lumbar epidermoid cyst. A case report.

    PubMed

    Manzo, G; De Gennaro, A; Cozzolino, A; Martinelli, E; Manto, A

    2013-08-01

    Epidermoid cysts comprise less than 1% of intraspinal tumors. They can be congenital, frequently associated with other spinal malformations, or iatrogenic, resulting from the implantation of epidermal cells within the spinal canal during the execution of a variety of procedures such as spinal puncture. At MR imaging epidermoid tumors can mimic cystic lesions with fluid content such as arachnoid cysts. DWI can help obtain a correct diagnosis. We describe a case of iatrogenic lumbar epidermoid cyst with DWI findings in a young woman who had undergone epidural anesthesia for Cesarean section three years before the onset of symptoms. PMID:24007735

  6. Cytodiagnosis of Epidermoid Cyst of the Upper Lip: A Common Lesion in an Uncommon Site

    PubMed Central

    Phukan, Jyoti Prakash; Sinha, Anuradha; Pal, Subrata; Jalan, Shilpa

    2014-01-01

    Epidermoid cyst and dermoid cysts are developmental pathologies thought to derive from aberrant ectodermal tissue. They are uncommon in the head and neck region. Rarely, they can be found in the oral cavity and buccal mucosa. However, epidermoid cyst is extremely uncommon in the upper lip and is rarely reported. In this study, we report an uncommon case of epidermoid cyst occurring in the upper lip diagnosed by fine-needle aspiration cytology (FNAC). We present this case because of its extremely rare site of presentation and also to highlight the role of FNAC to in the pre-operative diagnosis of this benign lesion. PMID:24696565

  7. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial

    PubMed Central

    Kawata, S; Yamasaki, E; Nagase, T; Inui, Y; Ito, N; Matsuda, Y; Inada, M; Tamura, S; Noda, S; Imai, Y; Matsuzawa, Y

    2001-01-01

    Chemotherapy is not effective for hepatocellular carcinoma (HCC). HMG-CoA redutase inhibitors have cytostatic activity for cancer cells, but their clinical usefulness is unknown. To investigate whether pravastatin, a potent HMG-CoA reductase inhibitor, prolongs survival in patients with advanced HCC, this randomized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital. 91 consecutive patients <71 years old (mean age 62) with unresectable HCC were enroled in this study. 8 patients were withdrawn because of progressive liver dysfunction; 83 patients were randomized to standard treatment with or without pravastatin. All patients underwent transcatheter arterial embolization (TAE) followed by oral 5-FU 200 mg−1d for 2 months. Patients were then randomly assigned to control (n = 42) and pravastatin (n = 41) groups. Pravastatin was administered at a daily dose of 40 mg. The effect of pravastatin on tumour growth was assessed by ultrasonography. Primary endpoint was death due to progression of HCC. The duration of pravastatin administration was 16.5 ± 9.8 months (mean ± SD). No patients in either group were lost to follow-up. Median survival was 18 months in the pravastatin group versus 9 months in controls (P = 0.006). The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival. Pravastatin prolonged the survival of patients with advanced HCC, suggesting its value for adjuvant treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11286466

  8. The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

    PubMed Central

    Borregales, Leonardo D.; Adibi, Mehrad; Thomas, Arun Z.; Wood, Christopher G.; Karam, Jose A.

    2015-01-01

    In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC. PMID:27034725

  9. Recent Advances in CT and MR Imaging for Evaluation of Hepatocellular Carcinoma

    PubMed Central

    Lee, Jeong Min; Yoon, Jeong-Hee; Joo, Ijin; Woo, Hyun Sik

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Accurate diagnosis and assessment of disease extent are crucial for proper management of patients with HCC. Imaging plays a crucial role in early detection, accurate staging, and the planning of management strategies. A variety of imaging modalities are currently used in evaluating patients with suspected HCC; these include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography. Among these modalities, dynamic MRI and CT are regarded as the best imaging techniques available for the noninvasive diagnosis of HCC. Recent improvements in CT and MRI technology have made noninvasive and reliable diagnostic assessment of hepatocellular nodules possible in the cirrhotic liver, and biopsy is frequently not required prior to treatment. Until now, the major challenge for radiologists in imaging cirrhosis has been the characterization of small cirrhotic nodules smaller than 2 cm in diameter. Further technological advancement will undoubtedly have a major impact on liver tumor imaging. The increased speed of data acquisition in CT and MRI has allowed improvements in both spatial and temporal resolution, which have made possible a more precise evaluation of the hemodynamics of liver nodules. Furthermore, the development of new, tissue-specific contrast agents such as gadoxetic acid has improved HCC detection on MRI. In this review, we discuss the role of CT and MRI in the diagnosis and staging of HCC, recent technological advances, and the strengths and limitations of these imaging modalities. PMID:24159569

  10. Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

    PubMed Central

    Shao, Yu-Yun; Hsu, Chih-Hung; Cheng, Ann-Lii

    2015-01-01

    Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However, efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2, hepatocyte growth factor, insulin-like growth factor-1, and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast-enhanced magnetic resonance imaging, and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC. PMID:26420960

  11. The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma.

    PubMed

    Borregales, Leonardo D; Adibi, Mehrad; Thomas, Arun Z; Wood, Christopher G; Karam, Jose A

    2016-04-01

    In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC. PMID:27034725

  12. Advanced mass spectrometry-based multi-omics technologies for exploring the pathogenesis of hepatocellular carcinoma.

    PubMed

    Nie, Wenna; Yan, Leyu; Lee, Yie H; Guha, Chandan; Kurland, Irwin J; Lu, Haitao

    2016-05-01

    Hepatocellular carcinoma (HCC) is one of the primary hepatic malignancies and is the third most common cause of cancer related death worldwide. Although a wealth of knowledge has been gained concerning the initiation and progression of HCC over the last half century, efforts to improve our understanding of its pathogenesis at a molecular level are still greatly needed, to enable clinicians to enhance the standards of the current diagnosis and treatment of HCC. In the post-genome era, advanced mass spectrometry driven multi-omics technologies (e.g., profiling of DNA damage adducts, RNA modification profiling, proteomics, and metabolomics) stand at the interface between chemistry and biology, and have yielded valuable outcomes from the study of a diversity of complicated diseases. Particularly, these technologies are being broadly used to dissect various biological aspects of HCC with the purpose of biomarker discovery, interrogating pathogenesis as well as for therapeutic discovery. This proof of knowledge-based critical review aims at exploring the selected applications of those defined omics technologies in the HCC niche with an emphasis on translational applications driven by advanced mass spectrometry, toward the specific clinical use for HCC patients. This approach will enable the biomedical community, through both basic research and the clinical sciences, to enhance the applicability of mass spectrometry-based omics technologies in dissecting the pathogenesis of HCC and could lead to novel therapeutic discoveries for HCC. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:331-349, 2016. PMID:24890331

  13. Management of locally advanced carcinoma of the breast by primary radiation therapy

    SciTech Connect

    Harris, J.R.; Sawicka, J.; Gelman, R.; Hellman, S.

    1983-03-01

    A retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy is presented. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54% 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.

  14. HER2 status in advanced gastric carcinoma: A retrospective multicentric analysis from Sicily

    PubMed Central

    IENI, A.; BARRESI, V.; GIUFFRÈ, G.; CARUSO, R.A.; LANZAFAME, S.; VILLARI, L.; SALOMONE, E.; ROZ, E.; CABIBI, D.; FRANCO, V.; CERTO, G.; LABATE, A.; NAGAR, C.; MAGLIOLO, E.; BROGGI, B.; FAZZARI, C.; ITALIA, F.; TUCCARI, G.

    2013-01-01

    According to the ToGA trial, HER2 has been shown to be predictive for the success of treatment with trastuzumab in advanced gastric cancer (AGC). A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma and identified the rate of HER2 positivity to be markedly varied. To date, the prevalence of HER2 overexpression in Sicilian people with AGC is unknown. Therefore, in the present study, a retrospective immunohistochemical analysis of HER2 was performed in a cohort of 304 AGC samples that were obtained from the archives of 10 Sicilian anatomopathological diagnostic units in order to verify the positive rate of HER2-positive cases. Furthermore, the characteristics of histotype, grade, stage and Ki-67 expression were also analyzed. HER2 overexpression was encountered in 17.43% of all the gastric adenocarcinomas, which was consistent with the results that have been reported elsewhere in the literature. A progressive increase in HER2 overexpression was observed, from the poorly cohesive histotype to the tubular adenocarcinomas and gastric hepatoid adenocarcinomas. HER2 overexpression was significantly associated with a high grade, advanced stage and high Ki-67 labeling index. Further investigations performed jointly by pathologists and oncologists within the geographical area of the present study should confirm that the association of trastuzumab with chemotherapy results in an improvement of survival in patients with AGC. PMID:24260051

  15. Phase II Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)

    ClinicalTrials.gov

    2016-07-20

    Stage II Lymphoepithelioma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

  16. Surgical monotherapy may be a suitable therapeutic strategy for advanced collecting (Bellini) duct carcinoma: A case report and literature review

    PubMed Central

    Zhu, Liang; Wang, Zijian; Pan, Cizhong; Peng, Ran; Wei, Xiong; Zhong, Zhaohui

    2016-01-01

    Collecting duct carcinoma (CDC), which is also known as Bellini duct carcinoma, accounts for less than 1% of all renal cell carcinoma, which has a poor prognosis. Predominantly, clinicians recognize this disease due to past experience and case reports, and a standard treatment is yet to be established. The present case report describes a 57-year-old male patient with CDC who was successfully treated with a left laparoscopic radical nephrectomy without any adjuvant therapy and compares the present patient's clinical presentation with previously reported cases. By analyzing the differences between these cases, the findings of the present case report and literature review suggested that surgery alone remains the only suitable choice for patients with advanced CDC. PMID:27446340

  17. 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.

  18. Intranasal epidermoid cyst causing upper airway obstruction in three brachycephalic dogs.

    PubMed

    Murgia, D; Pivetta, M; Bowlt, K; Volmer, C; Holloway, A; Dennis, R

    2014-08-01

    This case report describes three brachycephalic dogs with intranasal epidermoid cysts that were causing additional upper airway obstruction. Although epidermoid cysts have been described in several locations in dogs, to the authors' knowledge intranasal epidermoid cysts have not been previously reported. All dogs had mucopurulent to haemorrhagic nasal discharge. Magnetic resonance imaging of the head revealed the presence of unilateral or bilateral intranasal cystic lesions obstructing the nasal cavities partially or completely, with atrophy of the ipsilateral nasal turbinates. The cystic lesions were surgically excised in all dogs using a modified lateral alveolar mucosal approach to the affected nasal cavity. Aerobic, anaerobic and fungal culture of the cystic contents were negative and histology of the excised tissue was consistent with a benign intranasal epidermoid cyst in each dog. Upper airway obstruction was clinically improved in two dogs. PMID:24697627

  19. Epidermoid cyst radiologically mistaken as a left sided subpulmonic effusion.

    PubMed

    Sameh, Ibrahim Sersar; Gewaeli, NourEldeen Noaman; Hamza, Usama Ali; Awadalla, Mohammed Mounir el-said

    2003-09-01

    A 33-year-old female had a left sided chest pain for the last 3 months. Chest X-ray showed a left basal opacity. Computed tomography chest suggested a left sided subpulmonic effusion (17.5x12.2x13 cm) with thick enhanced walls with marked collapse of the left lower lobe and displacement of the heart and mediastinum to the right side. Trial of thoracocentesis was done and it was positive. Trial of intercostal tube insertion was done with a sense of very thick pleura and the patient developed a vasovagal attack. Accordingly, exploratory thoracotomy was decided. Intraoperative assessment showed a huge anterosuperior mediastinal cyst attached to the pericardium and was successfully resected. The pathological findings were compatible with epidermoid cyst. PMID:17670071

  20. 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).

  1. FDA Approval Summary: Temsirolimus as Treatment for Advanced Renal Cell Carcinoma

    PubMed Central

    Prowell, Tatiana M.; Ibrahim, Amna; Farrell, Ann T.; Justice, Robert; Mitchell, Shan Sun; Sridhara, Rajeshwari; Pazdur, Richard

    2010-01-01

    This report summarizes the U.S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel®), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review. A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-α versus those receiving temsirolimus alone or in combination with IFN-α. In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-α arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-α did not lead to a significant difference in OS compared with IFN-α alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-α arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001). Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed. Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-α and provides an additional treatment option for patients with advanced RCC. PMID:20332142

  2. Metronomic Capecitabine in Advanced Hepatocellular Carcinoma Patients: A Phase II Study

    PubMed Central

    de Rosa, Francesco; Agostini, Valentina; di Girolamo, Stefania; Andreone, Pietro; Bolondi, Luigi; Serra, Carla; Sama, Claudia; Golfieri, Rita; Gramenzi, Annagiulia; Cucchetti, Alessandro; Pinna, Antonio Daniele; Trevisani, Franco; Biasco, Guido

    2013-01-01

    Background. Anti-angiogenic treatment with targeted agents is effective in advanced hepatocellular carcinoma (HCC). This trial evaluated the safety and efficacy of metronomic capecitabine in patients with HCC. Methods. This single-institution phase II trial included 59 previously untreated patients with advanced HCC and 31 patients resistant to or intolerant of sorafenib. The treatment schedule was capecitabine 500 mg twice daily until progression of disease, unacceptable toxicity level, or withdrawal of informed consent. Progression-free survival (PFS) was chosen as the primary endpoint. Results. A total of 59 previously untreated and 31 previously treated patients with HCC were enrolled. The first cohort achieved a median PFS of 6.03 months and an overall survival (OS) of 14.47 months. Two patients achieved a complete response, 1 patient achieved partial response, and in 30 patients, stable disease was the best outcome. The second cohort achieved a median PFS of 3.27 months and a median OS of 9.77 months. No complete or partial responses were observed, but 10 patients had stable disease. An unscheduled comparison of the first cohort of patients with 3,027 untreated patients with HCC from the Italian Liver Cancer (ITA.LI.CA) database was performed. One-to-one matching according to demographic/etiologic/oncologic features was possible for 50 patients. The median OS for these 50 capecitabine-treated patients was 15.6 months, compared with a median OS of 8.0 months for the matched untreated patients (p = .043). Conclusion. Metronomic capecitabine is well tolerated by patients with advanced HCC and appears to have activity both in treatment-naive patients and in those previously treated with sorafenib. PMID:24232581

  3. 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

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

    PubMed

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

    2016-05-28

    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

  5. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

    PubMed

    Sangro, B; Mazzolini, G; Ruiz, M; Ruiz, J; Quiroga, J; Herrero, I; Qian, C; Benito, A; Larrache, J; Olagüe, C; Boan, J; Peñuelas, I; Sádaba, B; Prieto, J

    2010-12-01

    The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹⁰ to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient. PMID:20689572

  6. [Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy].

    PubMed

    Troussier, I; Huguet, F; Servagi-Vernat, S; Benahim, C; Khalifa, J; Darmon, I; Ortholan, C; Krebs, L; Dejean, C; Fenoglietto, P; Vieillot, S; Bensadoun, R-J; Thariat, J

    2015-04-01

    The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed. PMID:25770884

  7. [Plasma Biomarkers as Predictive Factors for Advanced Hepatocellular Carcinoma with Sorafenib].

    PubMed

    Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Matsukiyo, Yasushi; Kogame, Michio; Shinohara, Mie; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

    2016-07-01

    We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival. PMID:27431630

  8. 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

  9. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI

    PubMed Central

    Joo, Ijin; Lee, Jeong Min

    2016-01-01

    Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID:26989660

  10. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI.

    PubMed

    Joo, Ijin; Lee, Jeong Min

    2016-02-01

    Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID:26989660

  11. Treatment of advanced squamous carcinoma of the maxillary sinus by irradiation

    SciTech Connect

    Frich, J.C. Jr.

    1982-08-01

    Between 1959 and 1972, there were 23 patients with advanced squamous carcinoma of the maxillary sinus treated by radiation therapy as the only modality. Eighteen of these patients had not shown evidence of metastasis and were locally extensive being classified as T/sub 3-4/N/sub 0/M/sub 0/. They received 60-75 Gy (6000-7500 rad) in 6 to 7 1/2 weeks using an anterior portal with opposed lateral wedge pairs to give a homogenous dose. No treatment was given to the neck. Of 10 patients with tumors presenting in the suprastructures, six are living 5 years with no evidence of disease (NED), one is dead of intercurrent disease, one died of metastatic disease with no evidence of tumor at the primary site, and two died of recurrent primary tumor. With suprastructure presentation, radiation therapy as a sole treatment was able to control the primary tumor in eight out of 10 patients. It is concluded that in extensive tumors of suprastructure, radiation may be the only modality required to control the primary tumor (80%). In the infrastructure, radiation has failed in 75% of the patients so that surgery may also be required as a planned part of treatment in order to control the primary tumor. Metastatic disease accounted for three of the 10 deaths as a result of tumor.

  12. [Treatment of advanced renal cell carcinoma with interferon alpha and OK-432 (streptococcal preparation)].

    PubMed

    Shinoda, M; Naide, Y

    1992-11-01

    A total of 12 patients with advanced renal cell carcinoma received interferon alpha (3 million units intramuscularly 6 times weekly) and OK-432 (5 KE (Klinische Einheit) intramuscularly twice weekly). Metastatic lesions appeared before operation in six patients and after operation in six patients. Among them 5 patients had received interferon therapy and this combination therapy was started after the judgment of progressive disease for interferon therapy. Eleven pulmonary and 5 bone metastases were evaluable. The median duration of the combination therapy was 89.3 weeks. There were 4 partial responses and no complete responses among the 12 patients, giving a response rate of 33.3%. The median duration of response was 25 months, with a range of 6 to 54 months. Responses were seen predominantly in patients in whom metastases appeared after operation (3 of 4 responders). However, regarding the individual organs, two complete and 2 partial responses were observed among 11 pulmonary metastases and 2 partial responses among 5 bone metastases. The survival period after discovery of the metastasis was 10 to 67 months and the 5-year survival rate was 70.5%. Almost all patients had fever and induration at the injection site. Other side effects included leukopenia, anorexia, and depression. This combination therapy is thought to be effective against bone or other organs metastasis resistant to interferon alone. PMID:1485585

  13. 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. PMID:26370423

  14. 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.

  15. 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.

  16. Simultaneous Multitarget Irradiation Using Helical Tomotherapy for Advanced Hepatocellular Carcinoma With Multiple Extrahepatic Metastases

    SciTech Connect

    Jang, Jeong Won Kay, Chul Seung You, Chan Ran; Kim, Chang Wook; Bae, Si Hyun.; Choi, Jong Young; Yoon, Seung Kew; Han, Chi Wha; Jung, Hyun Suk; Choi, Ihl Bong

    2009-06-01

    Purpose: The prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases is extremely poor. Helical tomotherapy, an image-guided, intensity-modulated radiotherapy system, can allow for simultaneous and precise targeting of multiple cancerous lesions, while sparing normal tissues. This study evaluated the feasibility and outcome of tomotherapy for advanced HCC with metastases. Patients and Methods: A total of 42 consecutive HCC patients with metastases were treated with tomotherapy using the Hi-Art system. A total of 152 intra- and extrahepatic lesions (3.5 lesions/patient) were treated simultaneously, with a dose of 51.03 Gy (range, 30-57.61) in 10 fractions. Transarterial chemolipiodolization using epirubicin (50 mg) and cisplatin (60 mg) was repeated in patients with intrahepatic HCC (mean size, 9.0 cm) after tomotherapy. Results: An objective response (complete response and partial response) was achieved in 45.2% of patients with intrahepatic tumors, 68.4% of patients with pulmonary lesions, 60.0% of patients with lymph node/adrenal lesions, and 66.7% of patients with soft-tissue metastases. The complete response rate for those with pulmonary and lymph node/adrenal metastases was 26.3% and 5.0%, respectively. The overall survival rate at 1 and 2 years was 50.1% and 14.9%, respectively, with a median survival of 12.3 months. The actuarial in-field tumor control rate for {<=}1 year was 79.0%. No cases of Grade 4-5 acute toxicity occurred. Conclusion: The results of this study have shown that helical tomotherapy is safe and feasible without major toxicities for the treatment of advanced HCC and results in excellent tumor control and a potential survival benefit. This approach is expected to be a useful palliative option for selected HCC patients with metastases.

  17. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Objective. Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. Methods. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. Results. The 16W-DCR was 42% (95% confidence interval, 27%–57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3–4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. PMID:22707516

  18. High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis.

    PubMed

    Oh, Bong-Kyeong; Kim, Haeryoung; Park, Young Nyun; Yoo, Jeong Eun; Choi, Jinsub; Kim, Kyung-Sik; Lee, Jae Jung; Park, Chanil

    2008-02-01

    Telomerase reactivation and telomere maintenance are crucial in carcinogenesis and tumor progression. In this study, the relationships between telomere parameters, chromosomal instability and clinicopathological features were evaluated in hepatocellular carcinomas (HCCs). Telomere length (TL), telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA levels were measured in 49 hepatitis B virus (HBV)-related HCCs and corresponding non-tumorous tissues. The results were compared with clinicopathological data, including differentiation, multipolar mitosis (MM), anaphase bridge, immunohistochemical stain results for cytokeratin 19 (CK19) and patient outcome. TL of HCCs ranged from 4.7 to 13.1 kb, and 44.4% of HCCs showed telomere lengthening. hTERT mRNA levels and TA were closely related (P=0.008), and were significantly higher in HCCs than non-tumorous tissues. TL was significantly higher in HCCs with strong TA (P=0.048), high hTERT mRNA levels (P=0.001) and poor differentiation (P=0.041). Frequent MM was associated with poor differentiation (P=0.007) and advanced stage (P<0.001). TA was positively correlated with MM, anaphase bridges and advanced stage (P=0.019, P=0.017 and P=0.029). Thirteen (28.3%) HCCs were CK19+ and demonstrated longer telomeres than CK19- HCCs (P=0.046). Overall survival was poor in HCCs with MM >0.4 per field (P=0.016), high TA (P=0.009) and high TL ratio (HCC/non-HCC) >0.8 (P=0.044). Our results show that long telomeres, high TA and high mitotic instability are poor prognostic markers for HBV-related HCCs and their close association suggests that telomere maintenance may be important for the progression of HCCs with high chromosomal instability to more aggressive ones. PMID:18158557

  19. Determinants of esophageal varices bleeding in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Iavarone, Massimo; Primignani, Massimo; Vavassori, Sara; Sangiovanni, Angelo; La Mura, Vincenzo; Romeo, Raffaella

    2015-01-01

    Background and aims Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), yet treatment safety may be challenged by portal hypertension. We therefore assessed the prevalence, risk factors and clinical consequences of esophageal varices (EVs) in sorafenib-treated patients with HCC. Methods Starting in 2008, all compensated patients with advanced or intermediate HCC not eligible for other therapies were consecutively enrolled in a prospective evaluation of sorafenib therapy, all with pretreatment by upper-gastrointestinal endoscopy (UGE). Results A total of 150 patients received sorafenib for 4.6 (95% CI, 3.3–5.6) months. At baseline, 61 (41%) patients were EV free (group A), 78 (52%) had EVs (61 small EVs (group B), 17 medium/large EVs (group C)) and 11 (7%) previously endoscopically treated EVs (group D). Propranolol was given to all patients with medium/large EVs and those with previous bleeding. Twelve patients (8%) bled from EVs after 36 (18–260) days of sorafenib. During sorafenib, bleeding occurred in six of 26 group B patients with neoplastic portal vein thrombosis (nPVT), three of nine group C patients with nPVT, two of five group D patients with nPVT and one of six without nPVT (p < 0.0001), nPVT being the strongest independent predictor of bleeding by multivariate analysis (HR = 15.4, 95% CI 1.84–129.6). Conclusion UGE screening is worthwhile in HCC patients allocated to sorafenib since it identifies patients with EVs at risk of bleeding during therapy, particularly those with nPVT.

  20. Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma.

    PubMed Central

    Nakamura, M.; Katano, M.; Kuwahara, A.; Fujimoto, K.; Miyazaki, K.; Morisaki, T.; Mori, M.

    1998-01-01

    It has been generally accepted that transforming growth factor beta1 (TGF-beta1) has both negative and positive effects on tumour growth and progression. This study analysed the prognostic value of TGF-beta1 mRNA in advanced gastric carcinoma. A reverse transcriptase-polymerase chain reaction analysis (RT-PCR) was used for TGF-beta1 in endoscopic biopsy specimens from 42 advanced gastric carcinomas. Thirty specimens expressed TGF-beta1 mRNA while 12 specimens did not. The follow-up duration ranged from 4 to 37 months (mean 22.8 months). TGF-beta1-positive group demonstrated a shorter overall survival compared with the TGF-beta1 -negative group (P=0.0014). A significant correlation was also found in the 32 patients who underwent curative resection (P=0.0048). Significant correlations were found between TGF-beta1 mRNA expression and both stage (P=0.0015) and nodal involvement (P=0.0060). Multivariate analysis demonstrated that only TGF-beta1 mRNA expression (P=0.0306) was an independent prognostic factor. All of ten patients who underwent non-curative resection expressed TGF-beta1 mRNA. Expression of TGF-beta1 mRNA in gastric biopsy specimens may be an important preoperative prognostic variable for advanced gastric carcinoma. Images Figure 1 PMID:9823982

  1. 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. PMID:21908486

  2. Carcinoma of the cervical esophagus: changing therapeutic trends

    SciTech Connect

    Collin, C.F.; Spiro, R.H.

    1984-10-01

    Carcinoma of the cervical esophagus is a lethal tumor because of its advanced stage at the time of diagnosis. The records of 71 patients with this disease treated at Memorial Sloan-Kettering Cancer Center from 1965 through 1980 have been reviewed herein. Epidermoid carcinoma was the prevailing histologic finding, and extramural penetration was present in 77 percent of the evaluable patients. Tracheal invasion and vocal cord paralysis were noted in 35 and 24 percent of the patients, respectively and were predictive of significantly decreased survival. Primary radiotherapy in doses greater than 5,000 rads produced short lived responses in 13 of 21 patients (62 percent). Surgery was performed in 45 patients (63 percent), including 35 esophagectomies for cure and palliative procedures in the 10 other patients. There were five operative deaths (11 percent), but only two followed esophageal resection (5.6 percent). Locoregional treatment failure, present in 46 of 52 evaluable patients (88 percent) at last follow-up, continues to be a major problem. Overall, the 5 year survival rate was 9.6 percent. The longest survival and best palliation was achieved with aggressive resection and immediate reconstruction using the transposed stomach (gastric pullup).

  3. Nasopharyngeal carcinoma in children: review of 16 cases

    SciTech Connect

    Jereb, B.; Huvos, A.G.; Steinherz, P.; Unal, A.

    1980-04-01

    Of fifty two children with nasopharyngeal tumors who were registered and treated a Memorial Sloan-Kettering Cancer Center (MSKCC), from 1961 through 1977, 16 had carcinoma. The results of retrospective analysis of these patients are presented here. There were 7 girls and 9 boys between 12 and 16 years of age. One patient had a Stage I tumor; one had a Stage II tumor and 14 had Stage IV tumors. The histology was poorly differentiated epidermoid carcinoma in all patients. All patients had radiotherapy to the primary site. Six patients received chemotherapy for distant metastases, and 2 had adjuvant chemotherapy. Of the 13 patients who were treated initially with radiation alone, 2 were alive and free of disease at 12 and 14 years respectively. Of the 3 patients who had chemotherapy at initial treatment, one was alive and free of disease 18 months from diagnosis and one patient died of treatment without tumor. Bone was the common site of distant metastases. While radiation therapy alone appears to be adequate treatment for early tumors, adjuvant chemotherapy should be tried to improve results in advanced tumors.

  4. Phase I Dose-Escalation Study of Docetaxel, Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma

    PubMed Central

    Satomura, Hitoshi; Nakajima, Masanobu; Sasaki, Kinro; Yamaguchi, Satoru; Domeki, Yasushi; Takahashi, Masakazu; Muroi, Hiroto; Kubo, Tsukasa; Kikuchi, Maiko; Otomo, Haruka; Ihara, Keisuke; Kato, Hiroyuki

    2015-01-01

    A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m2 DOC plus 70 mg/m2 CDDP on day 1 plus 700 mg/m2 5-FU on days 1–5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started. PMID:26414837

  5. 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

  6. Sequence of treatment in locally advanced and metastatic renal cell carcinoma

    PubMed Central

    Fischer, Stefanie; Gillessen, Silke

    2015-01-01

    The spectrum of drugs that have shown activity in advanced or metastatic renal cell carcinoma (RCC) has led to a debate on the optimal sequence of treatments. There is agreement on recommending targeted agents as the standard of care in this disease. Uncertainty, however, remains on the best first-line drug choice. Physicians and patients may select sunitinib, bevacizumab in combination with interferon-alpha (IFN-α), pazopanib, or—in poor risk patients—temsirolimus. There are also a variety of therapies with proven efficacy on hand in the second-line setting: sorafenib, pazopanib, axitinib, and everolimus. While most randomized RCC trials assessed progression free survival (PFS) as primary endpoint, some agents were shown to improve median overall survival (OS), and given in sequence they have extended the life expectancy of RCC patients from 13 months in the cytokine era to over 30 months. Despite the progress made, there are sobering aspects to the oncologic success story in RCC, as the new treatments do not obtain an objective response or disease stabilization (SD) in all patients. There are also as yet no predictors to select patients who might benefit and those who are primary resistant to specific drugs, and ultimately almost all patients will experience disease progression. Bearing inevitable treatment failure in mind, availability of further drugs and switching therapy while the patient is in a condition to continue pharmacotherapy is essential. Of note, depending on the setting, only 33-59% of patients receive second-line treatment. In this review we present data on first-, second-, and third-line treatment in RCC, and discuss the difficulties in their interpretation in the context of treatment sequence. We summarize biological aspects and discuss mechanisms of resistance to anti-angiogenic therapy and their implications for treatment selection. PMID:26816832

  7. [Treatment of advanced renal cell carcinoma with a combination of interferon alpha and gamma].

    PubMed

    Naito, S; Yasumasu, T; Kumazawa, J; Hiratsuka, Y; Sakamoto, K; Iguchi, A; Masaki, Z; Hasui, Y; Osada, Y; Kurozumi, T

    1995-08-01

    A total of 29 patients with advanced renal cell carcinoma entered a pilot study of combination therapy with interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma). IFN-alpha (HLBI: 3 x 10(6) IU, BALL 1:5 x 10(6) IU, IFN-alpha-2a: 9 x 10(6) IU or IFN-alpha-2b: 6 x 10(6) IU) was given intramuscularly every day and IFN-gamma (IFN-gamma-1a: 3 x 10(6) JRU) was given intravenously by drip infusion 3 times a week (every 2-3 days). The treatment was continued for 3 months as the induction therapy, and then the tumor response was evaluated. Of the 22 evaluable patients, 4 achieved a partial response (PR), 10 showed no change (NC), and in 8 the disease had progressed (PD) during the therapy. Thus, the overall response rate was 18.2% [95% confidence interval (CI) 2.1-34.3%]. A favorable response tended to be obtained in patients with good performance status or small pulmonary metastases, or in those who had no prior therapy with IFN-alpha, who received this treatment immediately subsequent to radical nephrectomy, or who received IFN-gamma as much as possible according to this regimen. Toxicity was evaluated in 28 patients: fever, general fatigue, anorexia, leukocytopenia and impaired liver function were frequently noted, and 3 patients were withdrawn from the study because of such adverse effects. In patients who had a PR or NC, the same dosage of IFN-alpha was continued to be given intramuscularly 2-3 times a week (every 2-4 days) as the maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7474618

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

    ClinicalTrials.gov

    2016-03-11

    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. 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

  10. 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. PMID:27315314

  11. 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. PMID:24221216

  12. 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

  13. Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option

    PubMed Central

    Meulendijks, D; Dewit, L; Tomasoa, N B; van Tinteren, H; Beijnen, J H; Schellens, J H M; Cats, A

    2014-01-01

    Background: Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for patients with rectal cancer receiving chemoradiotherapy. Its place in the treatment of locally advanced anal carcinoma (AC), however, remains undetermined. We investigated whether capecitabine is as effective as 5-FU in the treatment of patients with locally advanced AC. Methods: One hundred and five patients with squamous cell AC stage T2-4 (T2>4 cm), N0-1, M0 or T1-4, N2-3, M0, were included in this retrospective study. Forty-seven patients were treated with continuous 5-FU (750 mg m−2) on days 1–5 and 29–33, mitomycin C (MMC, 10 mg m−2) on day 1, and radiotherapy; 58 patients were treated with capecitabine (825 mg m−2 b.i.d. on weekdays), MMC (10 mg m−2) on day 1, and radiotherapy. The primary end points of the study were: clinical complete response rate, locoregional control (LRC) and overall survival (OS). Secondary end points were: colostomy-free survival (CFS), toxicity and associations of genetic polymorphisms (GSTT1, GSTM1, GSTP1 and TYMS) with outcome and toxicity. Results: Clinical complete response was achieved in 41/46 patients (89.1%) with 5-FU and in 52/58 patients (89.7%) with capecitabine. Three-year LRC was 76% and 79% (P=0.690, log-rank test), 3-year OS was 78% and 86% (P=0.364, log-rank test) and CFS was 65% and 79% (P=0.115, log-rank test) for 5-FU and capecitabine, respectively. GSTT1 and TYMS genotypes were associated with severe (grade 3–4) toxicity. Conclusions: Capecitabine combined with MMC and radiotherapy was equally effective as 5-FU-based chemoradiotherapy. This study shows that capecitabine can be used as an acceptable alternative to 5-FU for the treatment of AC. PMID:25167226

  14. Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence

    PubMed Central

    Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

    2015-01-01

    Background: There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. Methods: All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. Results: The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. Conclusion: The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma. PMID:26131062

  15. The continuing role of epidermal growth factor receptor tyrosine kinase inhibitors in advanced squamous cell carcinoma of the lung

    PubMed Central

    Tan, Wan Ling

    2016-01-01

    Squamous cell carcinoma (SCC) of the lung represents about 20-30% of non-small cell lung cancers (NSCLC) and is associated with a poorer prognosis with limited treatment options. Erlotinib is an approved, standard second-line therapy in this setting, besides docetaxel. The LUX-Lung 8 study has shown superior overall survival (OS), progression-free survival (PFS), as well as disease control rates for treatment with afatinib compared to erlotinib in this head-to-head trial in patients with previously treated advanced SCC of the lung, with manageable side effect profile. This is the first and largest prospective phase III trial comparing two different tyrosine kinase inhibitors in patients with advanced SCC of the lung. Whether the results would be practice-changing remains to be seen, especially with the advent of novel immunotherapeutic agents such as nivolumab, which is recently approved for advanced lung SCC. PMID:26958503

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

    ClinicalTrials.gov

    2016-06-17

    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

  17. Phase I Study of Lenalidomide and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

    PubMed Central

    Loehrer, Patrick J.; Clark, Romnee S.; Spittler, A. John; Althouse, Sandra K.; Chiorean, E. Gabriella

    2016-01-01

    Lessons Learned Combination therapies in patients with hepatocellular carcinoma can be associated with overlapping toxicity and are therefore poorly tolerated. Using sorafenib at the maximum tolerated dose can lead to a higher incidence of toxicities. Consequently, combination studies might evaluate sorafenib at alternative schedules or doses to improve tolerance, recognizing this could affect sorafenib efficacy. Although this combination was poorly tolerated, it does not exclude further evaluation of new-generation immunomodulator drugs or immune checkpoint inhibitors in the hope of optimizing tolerance and safety. Background. Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC), and to date, no combination therapy has demonstrated superior survival compared with sorafenib alone. The immunosuppressive microenvironment in HCC is a negative predictor for survival. Lenalidomide is an immunomodulator and antiangiogenic agent, with limited single-agent efficacy in HCC. Based on these data, we designed a phase I study of sorafenib plus lenalidomide to determine the safety and preliminary antitumor activity of this combination. Methods. This was an open-label, phase I study with a 3+3 dose escalation/de-escalation design. The starting dose of sorafenib was 400 mg p.o. b.i.d. and of lenalidomide was 15 mg p.o. daily with a planned dose escalation by 5 mg per cohort up to 25 mg daily. Dose de-escalation was planned to a sorafenib dose of 400 mg p.o. daily combined with two doses of lenalidomide: 10 mg p.o. daily for a 28-day cycle (cohort 1) and 10 mg p.o. daily for a 21- or 28-day cycle (cohort 2). Patients with cirrhosis, a Child-Pugh score of A-B7, and no previous systemic therapy were eligible. Results. Five patients were enrolled. Their median age was 56 years (range 39–61), and the ECOG status was 0–2. Four patients were treated at dose level (DL) 1. Because of the poor tolerance to the combination associated with grade 2 toxicities

  18. Epidermoid cysts of the rumen in a Holstein-Friesian steer.

    PubMed

    Ohfuji, S

    2014-07-01

    Epidermoid cysts were identified in the rumen of a 2-year-old Holstein-Friesian steer. Small nodules (<4 mm diameter) filled with paste-like, friable, white material were scattered in the rumen wall. Microscopically, the nodules were located in the submucosal connective tissue and comprised of cysts lined by stratified squamous epithelium surrounding keratin debris, exhibiting features identical to those of epidermoid cysts. The cysts were surrounded by chronic inflammation. The ruminal mucosa contained vesicles or cystic cavities filled by inflammatory exudate, in addition to empty cystic spaces lined by flattened endothelial cells, which were possibly of lymphatic origin. The development of these epidermoid cysts might have resulted from implantation of exfoliated squamous epithelial cells from damaged ruminal epithelium into the submucosal connective tissue, although the precise aetiology of this anomaly remains to be defined. PMID:24679853

  19. Primary intradural sacral epidermoid in a nondysraphic spine: Case report and review of literature

    PubMed Central

    Sivaraju, Laxminadh; Thakar, Sumit; Ghosal, Nandita; Hegde, Alangar S

    2016-01-01

    The occurrence of epidermoids within the spinal canal is uncommon. Most of the reported spinal epidermoids (SEs) have been described in the thoracic or lumbar regions. They occur either following trauma or in the setting of coexistent spinal dysraphism. The authors describe an unusual case of a 28-year-old lady who presented with long-standing back pain and urinary incontinence. Magnetic resonance imaging (MRI) of her spine demonstrated a sacral SE without any coexistent spinal dysraphism. The diagnosis of an epidermoid was confirmed by histopathological examination following laminectomy and excision. To the authors’ best knowledge, this is the third case of a sacral SE occurring in a non-dysraphic spine. The case is discussed in the light of a relevant literature review. PMID:27217657

  20. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy

    PubMed Central

    2015-01-01

    Background/Aims Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. Methods In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A survey was conducted to collect data on patients who experienced CR after sorafenib monotherapy, and their medical records and follow-up data were analyzed. The tumor response and recurrence rates were assessed by radiologic study, based on modified response evaluation criteria in solid tumors. Results Seven patients with advanced HCC experienced CR after sorafenib therapy. The median time to tumor disappearance and the median disease-free survival time were 3 months and 9 months, respectively. HCC recurrence was identified in three cases (42.9%). Of these, two patients discontinued sorafenib before or after achieving CR and the other patient continued sorafenib after achieving CR. HCC recurred at 3, 10, and 42 months after CR in these three patients. Three patients needed dose reduction for toxicity and adverse events. Conclusions Though CR was achieved after sorafenib therapy in patients with advanced HCC, the recurrence rate was relatively high. Subsequent strategies to reduce a chance of recurrence after sorafenib therapy are required to investigate. PMID:26527250

  1. Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy

    PubMed Central

    2014-01-01

    Background Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear survival advantage over gemcitabine alone and has become a new standard in advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX) combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have shown efficacy in phase II trials and there is no comparative study between different platinum salts. We assessed the efficacy and safety of different platinum-based chemotherapies at first line in aBTC patients. We also analysed the second-line chemotherapy. Methods Sixty-four consecutive patients with aBTC diagnosed between 1998 and 2010 were included for analysis. At first line chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 Day 1, every 2 weeks), and 20 patients received Gem/Carb regimen (gemcitabine at 1000 mg/m2 Days 1 and 8 with carboplatin delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks). At second line, a total of 16 patients received a fluoropyrimidine-based chemotherapy. Results With GEMOX regimen, median progression-free survival (PFS) was 3.7 months (95%CI, 2.4 to 5) and median overall survival (OS) was 10.5 months (95%CI, 6.4 to14.7). The main toxicity was peripheral neuropathy (20% grade 2 and 7% grade 3). Grade 3/4 haematological toxicities were rare. With Gem/Carb regimen, PFS was 2.5 months (95%CI, 2.1 to 3.7) and OS was 4.8 months (95%CI, 3.7 to 5.8). The main grade 3/4 toxicities were haematological: anaemia (45%), thrombocytopenia (45%), and neutropenia (40%). At second-line, fluoropyrimidine-based chemotherapy was feasible in only a fourth of the patients. The median OS was 5.3 months (95%CI, 4.1 to 6.6), and median PFS was 4.0 months (95%CI, 2.6 to 5.5). Conclusions One day GEMOX regimen has a favourable toxicity profile and could be an alternative to standard Gem/CDDP regimen, in particular in unfit patients for CDDP. At second

  2. Recurrence pattern in patients with locally advanced renal cell carcinoma: The implications of clinicopathological variables

    PubMed Central

    Sameh, Wael M.; Hashad, Mohammed M.; Eid, Ahmed A.; Abou Yousif, Tamer A.; Atta, Mohammed A.

    2012-01-01

    Objectives Recurrence rates for patients with locally advanced renal cell carcinoma (LARCC) remain high. To date the predictors of recurrence in those patients remain controversial. The aim of the present study was to assess the relapse pattern in those patients and identify predictors for recurrence. Patients and methods We evaluated retrospectively 112 consecutive patients who underwent surgery for LARCC (T3–T4N0M0) between January 2000 and December 2010. Clinical and pathological data were collected from hospital medical records and compiled into a computerized database. Studied variables were age, mode of presentation, Tumour-Node-Metastasis (TNM) stage, Fuhrman nuclear grade, histological subtype, tumour size, venous thrombus level, collecting-system invasion and sarcomatoid differentiation. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method. Univariate and multivariate analyses were conducted. Results Patients were followed for a mean and median follow-up of 33 and 24 months, respectively, after surgery. During the follow-up, recurrences (distant and/or local) were recorded in 58 patients, representing 52% of the cohort. The mean and median times to recurrence were 25 and 13 months, respectively. Sites of recurrence were multiple in 36 patients (62%), lung only in 14 (24%), and local in eight (14%). RFS rates at 1, 2, and 5 years were 50%, 43% and 34%, respectively, while the median RFS was 23.7 months. Using univariate analysis, RFS after nephrectomy was significantly shorter in patients aged <70 years, symptomatic at presentation, with larger tumours, higher nuclear grade, collecting-system invasion, and/or sarcomatoid differentiation. After multivariate analysis, T-stage, nuclear grade and sarcomatoid differentiation retained their power as independent predictors of RFS (P = 0.032, <0.001 and 0.003, respectively). Conclusions For patients with LARCC, T-stage, grade and sarcomatoid differentiation independently dictate the

  3. Papillomavirus antigen in the epidermoid cyst of the sole. Immunohistochemical and ultrastructural study.

    PubMed

    Yanagihara, M; Sumi, A; Mori, S

    1989-12-01

    An epidermoid cyst of the sole was studied immunohistochemically and ultrastructurally. Papillomavirus particles were present in the horny layer and in the upper layers of the epidermis of the cyst and within the acrosyringeal epithelium overlying the cyst. Thickened basal lamina-like structures similar to those found in the eccrine sweat duct tumors such as in cylindroma and eccrine spiroadenoma existed at the epidermal-dermal junction of the cyst wall. Carcinoembryonic antigen was immunohistochemically demonstrated in the center of the epidermoid cyst and the DAB reaction products took the shape of a circle resembling that of the sweat ducts in the horny layer. PMID:2559111

  4. Effect of adjuvant perioperative desmopressin in locally advanced canine mammary carcinoma and its relation to histologic grade.

    PubMed

    Hermo, Guillermo A; Turic, Esteban; Angelico, Daniel; Scursoni, Alejandra M; Gomez, Daniel E; Gobello, Cristina; Alonso, Daniel F

    2011-01-01

    Desmopressin (DDAVP) is a vasopressin peptide analog with hemostatic properties that has been successfully used during surgery in patients with bleeding disorders. Recently published experimental and clinical data indicate that perioperative administration of DDAVP can minimize spread and survival of residual mammary cancer cells. The central aim of this study was to explore the effect of perioperative DDAVP and its relation to histologic grade in bitches with locally advanced mammary carcinoma. Of the 32 dogs initially recruited, 28 intact bitches with mammary carcinoma tumors stage III or IV were ultimately included. These dogs were randomized to receive DDAVP at intravenous doses of 1 μg/kg (n=18) or saline solution as placebo (n=10). En bloc mastectomy of the affected gland(s) was performed. Tumor malignancy was graded by the method of Elston and Ellis into well-differentiated (grade 1), moderately differentiated (grade 2), or poorly differentiated (grade 3). DDAVP therapy significantly prolonged the disease-free survival (P<0.001) and overall survival (P<0.01) in bitches with grade 2 or 3 carcinomas compared with bitches in the control group. No significant difference in disease-free period or overall survival was found between treatment groups in bitches with grade 1 tumors. The present data suggest that DDAVP may be an excellent candidate as a surgical adjuvant in the management of aggressive cancers in small animals. More research in this field is warranted. PMID:21164169

  5. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established. PMID:26805098

  6. HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma

    PubMed Central

    Huang, Xinqiong; Liu, Miaomiao; Sun, Hong; Wang, Fengjun; Xie, Xiaoxue; Chen, Xiang; Su, Juan; He, Yuxiang; Dai, Youyi; Wu, Haijun; Shen, Liangfang

    2015-01-01

    The mechanism by which overexpression of hexokinase 2 (HK2) indicates locally advanced cervical squamous cell carcinoma (LACSCC) with radio-resistance is still unknown despite being an independent biomarker of poor prognosis. Here, we retrospectively analyzed 132 female patients receiving radiotherapy for cervical squamous cell carcinoma including 85 radiation-sensitive cases and 47 radiation-resistant cases. The expression of HK2 was examined by immunohistochemistry. The percentage of high HK2 expression in the radiation-resistant group differed from the radiation-sensitive group with statistical significance (P < 0.001) even if divided into three subgroups including a lower 5-year progression free survival group (PFS) for comparison (P < 0.001). The Kaplan Meier curve analysis showed that there were differences between the two groups (P < 0.001). Therefore, this study proves a close relationship between HK2 expression and radio-resistance. Multivariate Cox regression analysis implied that HK2 was an independent prognostic indicator of cervical squamous carcinoma (HR (95% CI), 2.940 (1.609, 1.609); P = 0.002). PMID:26097593

  7. Intratumoral PV701 in Treating Patients With Advanced or Recurrent Unresectable Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-23

    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; 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 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

  8. EGFR monoclonal antibodies in locally advanced head and neck squamous cell carcinoma: What is their current role?

    PubMed

    Alorabi, Mohamed; Shonka, Nicole A; Ganti, Apar Kishor

    2016-03-01

    Treatment options for locally advanced squamous cell carcinoma of the head and neck (SCCHN) include either surgical resection followed by radiation or chemoradiation, or definitive chemoradiation for which single-agent cisplatin is the best studied and established. The increasing understanding of the molecular biology of SCCHN has led to an interest in the development of targeted therapies. The epidermal growth factor receptor (EGFR) is over-expressed in nearly 80-90% of cases of SCCHN and correlates with poor prognosis and resistance to radiation. Preclinical evidence showed that blocking EGFR restores radiation sensitivity and enhances cytotoxicity. This finding led to clinical trials evaluating this class of agents and the approval of cetuximab in combination with radiation for the treatment of locally advanced SCCHN. This review is focused on the anti-EGFR monoclonal antibodies and their role either with radiotherapy or chemoradiation in unresectable LA SCCHN. PMID:26797287

  9. Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    PubMed Central

    Premkumar, Sumana; Dedeepiya, Vidyasagar Devaprasad; Terunuma, Hiroshi; Senthilkumar, Rajappa; Srinivasan, Thangavelu; Reena, Helen C.; Preethy, Senthilkumar; Abraham, Samuel J. K.

    2013-01-01

    Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life. PMID:23653878

  10. New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions.

    PubMed

    Chuma, Makoto; Terashita, Katsumi; Sakamoto, Naoya

    2015-10-01

    Hepatocellular carcinoma (HCC) can be lethal due to its aggressive course and lack of effective systemic therapies for advanced disease. Sorafenib is the only systemic therapy that has demonstrated an overall survival benefit in patients with advanced HCC, and new agents for treatment of advanced HCC are needed. The multiple pathways involved in HCC oncogenesis, proliferation and survival provide many opportunities for the development of molecularly targeted therapies. Molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for treatment of advanced HCC. Agents targeting vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-mesenchymal-epithelial transition factor-1 and mammalian target of rapamycin signaling have been actively explored. This article focuses on the evaluation of molecular agents targeting pathogenic HCC and provides a review of recently completed phase III drug studies (e.g. involving sorafenib, sunitinib, brivanib, linifanib, erlotinib, everolimus, ramucirumab or orantinib) and ongoing drug studies (e.g. involving lenvatinib, regorafenib, tivantinib or cabozantinib) of molecularly targeted agents in advanced HCC, including a brief description of the biologic rationale behind these agents. PMID:25472913

  11. State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma.

    PubMed

    Ried, Michael; Marx, Alexander; Götz, Andrea; Hamer, Okka; Schalke, Berthold; Hofmann, Hans-Stefan

    2016-06-01

    In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC. PMID:26670806

  12. Investigating the Pretreatment miRNA Expression Patterns of Advanced Hepatocellular Carcinoma Patients in Association with Response to TACE Treatment

    PubMed Central

    El-Halawany, Medhat S.; Ismail, Heba M.; Zeeneldin, Ahmed A.; Elfiky, Ammar; Tantawy, Marwa; Kobaisi, Mohamed H.; Hamed, Ikram; Abdel Wahab, Abdel Hady A.

    2015-01-01

    Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents—doxorubicin and cisplatin—is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer. PMID:25811030

  13. Combined levamisole with recombinant interleukin-2 (IL-2) in patients with advanced renal cell carcinoma: a phase II study.

    PubMed

    Creagan, E T; Hestorff, R D; Suman, V J; Mailliard, J A; Nair, S; Krook, J E; Kugler, J W; Marschke, R F; Michalak, J C; Tschetter, L K

    1998-04-01

    Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells is an antineoplastic modality in which immune-activated cells are administered to a host having cancer in an attempt to mediate tumor regression. Levamisole (LEV), an immune stimulant, has been suggested as having therapeutic effectiveness in a variety of cancers. After a phase I trial of recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in patients who had advanced renal cell carcinoma. The regimen was IL-2 at 3 x 10(6) U/m2 daily x 5 plus LEV at 50 mg/m2 perorally three times a day x 5. Only one of the 22 eligible patients had a regression. It was a partial regression, 85 days in duration. The median time to treatment failure (refusal, progression, or off study because of toxicity) was 36 days. The only grade 4 toxicity reported was lethargy. This regimen is not recommended for further testing in patients who have advanced renal cell carcinoma. PMID:9537198

  14. Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix

    PubMed Central

    Loncaster, J A; Cooper, R A; Logue, J P; Davidson, S E; Hunter, R D; West, C M L

    2000-01-01

    The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy. © 2000 Cancer Research Campaign PMID:10944602

  15. Progression of Intravesical Condyloma Acuminata to Locally Advanced Poorly Differentiated Squamous Cell Carcinoma.

    PubMed

    Khambati, A; Bhanji, Y; Oberlin, D T; Yang, X J; Nadler, R B; Perry, K T; Kundu, S D

    2016-07-01

    Condyloma acuminata (CA) is a common sexually transmitted disease caused by Human Papilloma Virus (HPV) infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC) arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition. PMID:27335797

  16. 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. PMID:27189494

  17. A Rare Cause of Headache in the Emergency Department: Intraventricular Epidermoid Cyst Rupture With Hydrocephalus

    PubMed Central

    Yigit, Mehmet; Seyithanoglu, Mehmet Hakan; Dundar, Tolga Turan; Sogut, Ozgur; Yigit, Eda

    2016-01-01

    Lateral intraventricular tumors are not frequently observed. Since these tumors grow linearly rather than exponentially, they grow gradually and thus do not cause mass effects and hydrocephalus. This study is the case report of a rare great volume left intraventricular epidermoid cyst rupture. The tumor was found to be associated with mass effect on neighboring structures and hydrocephalus. PMID:27298668

  18. A Rare Cause of Headache in the Emergency Department: Intraventricular Epidermoid Cyst Rupture With Hydrocephalus.

    PubMed

    Yigit, Mehmet; Seyithanoglu, Mehmet Hakan; Dundar, Tolga Turan; Sogut, Ozgur; Yigit, Eda

    2016-07-01

    Lateral intraventricular tumors are not frequently observed. Since these tumors grow linearly rather than exponentially, they grow gradually and thus do not cause mass effects and hydrocephalus. This study is the case report of a rare great volume left intraventricular epidermoid cyst rupture. The tumor was found to be associated with mass effect on neighboring structures and hydrocephalus. PMID:27298668

  19. Epidermoid cyst of the coronal sulcus mimicking penile cancer: a case report

    PubMed Central

    2014-01-01

    Introduction Epidermoid cysts represent common benign tumors occurring anywhere in the body but very rarely in the penis. Only a few cases of penile localization have been reported in the literature so far, most of them being congenital and/or idiopathic, usually presenting in children as slow-growing, solitary, well-delimited cystic lesions. Here, we describe the case of a patient with a penile epidermoid cyst presenting as an ulcerated lesion of the coronal sulcus, thus mimicking penile cancer. Case presentation A 36-year-old Caucasian man presented with a three-month history of a rapidly growing asymptomatic ulcerated lesion in the ventral portion of the penile coronal sulcus. At surgical exploration, the area under the ulcerated lesion had a well-demarcated cystic shape; following its wide excision, an intraoperative histological examination revealed an epidermoid cyst. No recurrence had occurred at nine years of follow-up. Conclusions Rare benign tumors of the penis, like the described epidermoid cyst, may mimic cancer. Nevertheless, penile ulcerated lesions should always be surgically explored as wide excision and intraoperative histological examination remain the only means of obtaining a precise disease definition and, consequently, administering the appropriate treatment. PMID:24906506

  20. Advanced small cell carcinoma of the bladder: clinical characteristics, treatment patterns and outcomes in 960 patients and comparison with urothelial carcinoma.

    PubMed

    Geynisman, Daniel M; Handorf, Elizabeth; Wong, Yu-Ning; Doyle, Jamie; Plimack, Elizabeth R; Horwitz, Eric M; Canter, Daniel J; Uzzo, Robert G; Kutikov, Alexander; Smaldone, Marc C

    2016-02-01

    To describe the clinical characteristics, treatment patterns and outcomes in advanced small cell bladder cancer (aSCBC) patients and compare to those with urothelial carcinoma (UC). Individuals in the National Cancer Data Base with a diagnosis of either nodal (TxN+M0) or distant metastatic (TxNxM1) disease were identified from 1998 to 2010. We assessed the relationships between stage, treatment modalities and survival in the aSCBC cohort and compared these to UC patients. In the 960 patient aSCBC cohort (62% M1), 50% received palliative therapy alone, 68% in M1 versus 21% in M0 groups (P < 0.0001). Single modality local therapy (15%) and surgical (21%) or radiation-based (14%) multimodal therapy (MMT) were used in the other 50%. Cystectomy-based MMT was utilized in 45% of N+M0 versus 6.4% of NxM1 patients (P < 0.0001). Median overall survival (OS) for aSCBC patients was 8.6 months; 13.0 months in N+M0 versus 5.3 months in NxM1 patients (P < 0.0001). Survival was similar between TxN1M0 and TxN2-3M0 patients (14.8 months vs. 12.1 months, P = 0.15). Urothelial carcinoma patients (n = 27,796, 45% M1) lived longer compared to aSCBC patients in the N+M0 group (17.3 months vs. 13.0 months, P = 0.0007). There were not clinically significant differences in OS between UC and aSCBC patients in the M1 group. Advanced SCBC is a rare disease with a poor survival and palliative therapy is common, especially in M1 patients. In comparison to UC, the outcomes for aSCBC patients are worse in those with lymph node only involvement but similar in those with distant disease. PMID:26679712

  1. A case of successful preoperative chemotherapy with cisplatin and irinotecan followed by curative-intent surgery for locally advanced thymic carcinoma.

    PubMed

    Suzuki, Shigeki; Horio, Hirotoshi; Hato, Tai; Harada, Masahiko; Okuma, Yusuke; Hishima, Tsunekazu

    2013-03-01

    The optimal chemotherapy for thymic carcinoma has yet to be determined based on clinical evidence because of the rarity of this pathological entity. We report the case of a patient with locally advanced thymic carcinoma in whom radical excision was achieved with intensive preoperative chemotherapy followed by curative-intent surgery. A 59-year-old woman was diagnosed with Masaoka-Koga stage III thymic cancer showing squamous cell carcinoma histology. Invasion to the ascending aorta and left brachiocephalic vein was suspected from imaging, so preoperative chemotherapy with three cycles of cisplatin and irinotecan was administered. Partial response to chemotherapy was achieved and the residual tumor was completely resected with subsequent surgery. Histopathological examination of the resected specimen demonstrated stage II thymic carcinoma. The patient has shown no evidence of recurrence or surgical complications as of 46 months after completing preoperative chemotherapy. PMID:22760255

  2. 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.

  3. Recent advances in head and neck squamous cell carcinoma--a review.

    PubMed

    Safdari, Yaghoub; Khalili, Masoumeh; Farajnia, Safar; Asgharzadeh, Mohammad; Yazdani, Yaghoub; Sadeghi, Mahnaz

    2014-09-01

    The current review presents the results of the most recent studies performed on different aspects of human head and neck squamous cell carcinoma, including radiosensitivity induction, efficiency improvement of monoclonal antibodies using low-intensity ultrasound, chemical compounds such as toll-like receptor (TLC) agonists, dasatinib, resveratrol and niclosamide, nuclear inhibition of cancer using STAT3 decoy oligonucleotide, efficiency of anti-EGFR monoclonal antibodies in detection of head and neck cancers and other related issues. PMID:24912050

  4. Efficacy of RetroNectin-activated cytokine-induced killer cell therapy in the treatment of advanced hepatocelluar carcinoma

    PubMed Central

    LI, WEI; WANG, YAOMEI; KELLNER, DANIEL B.; ZHAO, LINGDI; XU, LINPING; GAO, QUANLI

    2016-01-01

    The present study aimed to investigate the efficacy of RetroNectin-activated cytokine-induced killer cell (R-CIK) therapy in advanced hepatocellular carcinoma patients as compared with conventional chemotherapy, a comparison that has not yet been thoroughly studied. From January 2010 to October 2013, 74 patients with an initial diagnosis of advanced hepatocelluar carcinoma were enrolled in the study. Patients were assigned to one of two treatment arms: patients in arm 1 (n=37) received R-CIK treatment as the first line therapy, whereas those in arm 2 (n=37) received chemotherapy as the first line treatment. The primary end point measured in this study was median overall survival (mOS). Median progression-free survival time (mPFS) and 1- and 2-year survival rates were recorded as secondary end points. Kaplan-Meier analysis was performed on all mOS and mPFS data, and treatment hazard ratios were established using the Cox proportional hazards model. The 1-year survival rate in treatment arm 1 was 42.47% vs. 24.89% in arm 2 (95% CI, 24.91–59.01% vs. 12.10–40.02%, P=0.066); the 2-year survival rates were 21.24 and 5.53% (95% CI, 4.60–45.86 vs. 0.46–21.06%, P=0.106) in arms 1 and 2, respectively; the mPFS in arm 1 was 4.37 vs. 3.90 (x2=0.182, P=0.670) in arm 2; and the mOS in arm 1 was 14.03 months vs. 9.46 months(x2=4.406, P=0.036) in arm 2. Calculations of univariate analyses of arm 1, R-CIK cycles ≥6, KPS >70, AFP ≤400 ng/ml, and findings of no vascular invasion and no extra-hepatic metastasis were potential predictive factors (P<0.05). Calculations from multivariate analyses similarly identified these factors as potentially having predictive value (P<0.05). The main adverse effects of R-CIK therapy included fever and headache pain. R-CIK treatment may prolong mOS in advanced hepatocellular carcinoma patients compared with conventional chemotherapy. Patients who underwent ≥6 cycles of R-CIK, had KPS scores >70, AFP ≤400 ng/ml, displayed no evidence of

  5. 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

  6. [Bronchial mucoepidermoid carcinoma].

    PubMed

    Bregante, J I; Rituerto, B; Font de Mora, F; Alonso, F; Andreu, M J; Figuerola, J; Mulet, J F

    1998-07-01

    We submit the case of a child afflicted with a mucoepidermoid bronchial tumor. The patient is a boy, aged seven, who after undergoing antibiotic treatment for six weeks because of a fever and atelectasia-condensation in the right lower lobe showed no signs of clinical improvement and was sent to our department to undergo further study and treatment. A bronchoscopy performed shows a polypoid mass that partially blocks the main bronchial tube a few milimiters under the access to the right upper lobe. A biopsy is carried out and the anatomopathological test shows there is a low degree epidermoid carcinoma. We decide to perform a lobectomy which for the tumor location and the lung condition has to be medium and lower right. We proceed to remove the adenopaty of hilium not affected by the tumor. The postoperative period develops without incidents. A check-up bronchoscopy performed three months later shows two polypoid masses in the right bronchial tube which, once a biopsy is performed, proved to be granulation tissue. Twelve months after undergoing surgery, the patient's condition is good, there is no evidence of tumor relapse and the breathing capacity is adequate, though there is an obstructive restrictive pattern in the espirometry. Even taking into consideration that lung tumors are extremely unusual, the epidermoid carcinoma is the one which most frequently occurs. The tumor's low malignancy is a sign that points to a good prognosis. Performing conservative surgery by means of bronchoplasty should be taken into account so as to keep the sequelae on the lung condition to a minimum, even though in this case the tumor location made it impossible. PMID:12602035

  7. Petrous bone epidermoid cyst caused by penetrating injury to the external ear: Case report and review of literature.

    PubMed

    Kalfas, Fotios; Ramanathan, Dinesh; Mai, Jeffrey; Schwartz, Seth; Sekhar, Laligam N

    2012-04-01

    Epidermoid cysts are histologically benign, slow-growing congenital neoplasms of the central nervous system that may arise from retained ectodermal implants. The epidermoid lesions are generally caused during the 3(rd) to 5(th) week of gestation by an incomplete cleavage of the neural tissue from the cutaneous ectoderm, though it can also happen later in life due to introduction of skin elements by skin puncture, trauma or surgery. We present this unique case of a petromastoid epidermoid cyst associated with ipsilateral cerebellar abscesses, presenting 20 years after a penetrating trauma to the external auditory canal. Radical excision of both lesions and revision of the previous fistulous tract was performed. We present the diagnostic challenge and the operative treatment of this unique case, which to our knowledge is the first where an epidermoid cyst and an adjacent brain abscess occurred as a result of a single traumatic event. PMID:22870161

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

    ClinicalTrials.gov

    2016-08-24

    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

  9. A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

    PubMed Central

    Siegel, Abby B.; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S.; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Flaig, Thomas W.; Tsai, Wei Yann; Wu, David P. H.; Lee, Valerie; Greenlee, Heather

    2013-01-01

    Purpose To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests. PMID:23757319

  10. The role of surgery in locally advanced carcinoma of cervix after sub-optimal chemoradiation: Indian scenario

    PubMed Central

    Kundargi, Rajshekar S.; Guruprasad, B.; Hanumantappa, Nikesh; Rathod, Praveen Shankar; Devi, Uma K.; Bafna, U. D.

    2013-01-01

    Background: Standard treatment of advanced cervical cancer is concurrent chemoradiation. Radical radiotherapy for carcinoma cervix includes pelvic external beam radiotherapy (EBRT) with the concomitant platinum based chemotherapy followed by intracavitary brachytherapy (ICBT) to boost central disease. Management of patients who are suboptimally treated, especially, after unsuccessful ICBT insertion is not well-defined. This study explores the role of hysterectomy in these patients. Materials and Methods: From January 2006 to December 2011, 38 patients with locally advanced cervical cancer, in whom ICBT insertion was unsuccessful, were analyzed retrospectively. Operable patients with no parametrial involvement underwent hysterectomy and outcomes (recurrence free and overall survival) were noted. Results: The major complications in post operative period were wound infection, paralytic ileus and bladder atony all of which were conservatively managed with no mortality. At median follow-up of 36 months (range 12-60 months) there was no recurrence in patients with stage 1B2 and stage IIA, 25 out of 38 (65.8%) were event free and the overall survival was 71%. Conclusion: Many patients in Indian scenario receive suboptimal therapy in locally advanced cervical cancer. EBRT with chemotherapy followed by type 1 extra-fascial hysterectomy can be a good alternative for these patients. PMID:24455590

  11. Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition.

    PubMed

    Finn, Richard S

    2012-11-01

    Hepatocellular carcinoma (HCC) is a common cancer that has the third highest cancer-related mortality rate worldwide. Although potentially curable by transplantation if detected early, the majority of cases are diagnosed at an advanced stage of disease for which limited treatment options are available. The only proven systemic therapy for advanced HCC is sorafenib, a multi-kinase inhibitor that has demonstrated modest efficacy and reasonable tolerability in patients with advanced HCC. Five years after the approval of sorafenib, no other agent has been proven to be beneficial in the first- or second-line setting in advanced HCC. While molecular studies have highlighted various potential targets in HCC, the mammalian target of rapamycin (mTOR) has emerged as an exciting target for cancer therapy including HCC. Laboratory data have linked the phosphatidylinositol 3-kinase/AKT/mTOR axis to various oncogenic processes, including survival and angiogenesis. Historically, mTOR inhibitors have been used for their immunosuppressive properties, but more recently they have been approved as anticancer agents. Retrospective HCC studies suggest that the inclusion of mTOR inhibition as part of an immunosuppressant regimen after transplantation may reduce HCC recurrence compared with other immunosuppressive agents such as calcineurin inhibitors. More recently, single-arm, phase I/II studies have shown that mTOR inhibitors also have activity as monotherapy in cases of recurrent HCC or de novo advanced HCC. This article will review the rationale for targeting the mTOR pathway in HCC, and the currently available clinical data supporting its development for HCC. PMID:24159589

  12. 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.

  13. Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma.

    PubMed

    Shi, Wei-hong; Wu, Qing-quan; Li, Su-qing; Yang, Tong-xin; Liu, Zi-hao; Tong, Yu-suo; Tuo, Lei; Wang, Shan; Cao, Xiu-Feng

    2015-04-01

    Recent studies reveal that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. This study aimed to assess the potential role of PCAT-1 specifically in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PCAT-1 in matched cancerous tissues and adjacent noncancerous tissues from 130 patients with ESCC, 34 patients with non-small cell lung cancer (NSCLC), and 30 patients with gastric carcinoma (GC). The correlation of PCAT-1 with clinicopathological features and prognosis were also analyzed. The expression of PCAT-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (70.8%, p < 0.01), and the high level of PCAT-1 expression was significantly correlated with invasion of the tumor (p = 0.024), advanced clinical stage (p = 0.003), lymph node metastasis (p = 0.032), and poor prognosis. However, PCAT-1 mRNA expression had no significant difference between paired primary cancerous tissues and the adjacent noncancerous tissues in 34 cases of NSCLC (p = 0.293) and 30 cases of GC (p = 0.125). High expression of PCAT-1 was specifically correlated with invasion of cancer tissues, metastasis of lymph node, and advanced tumor stage of ESCC. High expression of PCAT-1 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Adjuvant therapy targeting PCAT-1 molecule might be effective in treatment of ESCC. PMID:25731728

  14. 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.

  15. The systemic inflammatory response as a prognostic factor for advanced hepatocellular carcinoma with extrahepatic metastasis

    PubMed Central

    AINO, HAJIME; SUMIE, SHUJI; NIIZEKI, TAKASHI; KUROMATSU, RYOKO; TAJIRI, NOBUYOSHI; NAKANO, MASAHITO; SATANI, MANABU; OKAMURA, SHUSUKE; SHIMOSE, SHIGEO; MIYAHARA, KENSUKE; TORIMURA, TAKUJI

    2016-01-01

    Several indices have been proposed to evaluate the systemic inflammatory response (SIR), which has been reported to be a useful prognostic factor in various types of cancer. We investigated the usefulness of the Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in patients with advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis (stage IVB). Between April, 1997 and March, 2013, a total of 434 HCC patients who developed extrahepatic metastasis were enrolled in the present study. The GPS was defined on the basis of pretreatment C-reactive protein (CRP) and albumin (Alb) levels, and the subjects were grouped according to GPS 0–2. The NLR was calculated as the neutrophil count/lymphocyte count, and the PLR was calculated as the platelet count/lymphocyte count. A comparative examination was performed using a survival analysis with approximate median values to determine the cut-off value for both ratios. The median survival time (MST) of the 434 patients overall was 7.3 months, with cumulative survival rates of 31.8, 14.5 and 7.7% at 1, 2 and 3 years, respectively. The patient backround was as follows: The male:female ratio was 363:71, with a median age of 67.0 years (range, 15.0–92.0 years). Hepatitis B virus patients:hepatitis C virus patients:non-B, non-C hepatitis patients = 75:303:56. Child-Pugh class A:B:C = 218:153:63. As regards T stage, ≤T2:T3:T4 = 60:190:181. The median white blood cell count was 4,650/l (range, 1,400-20,500/l); the platelet count was 11.1×104/µl (range, 3.1×104-45.5×104/µl); the aspartate aminotransferase level was 40.0 U/l (range, 7.0–338.0 U/l) and the alanine aminotransferase level 64.5 U/l (range, 16.0–407.0 U/l); the α-fetoprotein level was 622.1 ng/ml (range, 1.5–3,311,794.0 ng/ml); and the des-gamma-carboxyprothrombin level was 1,285.0 mAU/ml (range, 8.0->75,000 mAU/ml). The principal sites of metastasis included the lungs

  16. Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma

    PubMed Central

    Baur, Johannes; Ritter, Christian O; Germer, Christoph-Thomas; Klein, Ingo; Kickuth, Ralph; Steger, Ulrich

    2016-01-01

    Purpose In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE). Patients and methods In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever. Results No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference. Conclusion No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE. PMID:27382341

  17. 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.

  18. Analysis of adverse events of sunitinib in patients treated for advanced renal cell carcinoma

    PubMed Central

    Cedrych, Ida; Jasiówka, Marek; Niemiec, Maciej; Skotnicki, Piotr

    2016-01-01

    Introduction Treatment of the metastatic stage of renal cell carcinoma is specific because classical chemotherapy is not applicable here. The treatment is mainly based on molecularly targeted drugs, including inhibitors of tyrosine kinases. In many cases the therapy takes many months, and patients often report to general practitioners due to adverse events. In this article, the effectiveness and side effects of one of these drugs are presented. The aim of the study was to analyse of the toxicity and safety of treatment with sunitinib malate in patients with clear cell renal cell carcinoma in the metastatic stage. Material and methods Adverse events were analyzed using retrospective analysis of data collected in a group of 39 patients treated in the Department of Systemic and Generalized Malignancies in the Cancer Center in Krakow, Poland. Results Toxicity of treatment affected 50% of patients. The most common side effects observed were hypertension, thrombocytopenia, stomatitis, diarrhea and weakness. Grade 3 serious adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4 affected up to 10% of patients. The most common serious adverse events were hypertension and fatigue. Conclusions Sunitinib malate is characterized by a particular type of toxicity. Knowledge of the types and range of adverse events of this drug is an important part of oncological and internal medicine care. PMID:27186181

  19. 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

  20. Epidermoid cyst in the floor of the mouth of a 3-year-old.

    PubMed

    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

  1. Planned preoperative radiation therapy vs. definitive radiotherapy for advanced laryngeal carcinoma

    SciTech Connect

    Kazem, I.; van den Broek, P.

    1984-10-01

    In the period 1970-1980 inclusive, 191 patients with T3T4 laryngeal carcinoma (glottic: 63 and supraglottic: 128) received either definitive radiation therapy (RT) (60-65 Gy in 6-7 weeks) or planned preoperative radiation therapy (25 Gy in 5 equal daily fractions of 5 Gy) followed by laryngectomy with or without neck dissection (RT + S). Selection for RT vs. RT + S was based on medical operability and/or patient's refusal to undergo surgery. All patients are evaluable with minimum of 2 years observation. Crude 5 and 10-year survival probability for 32 patients with glottic localization who received RT is 55% and 38% vs. 65% and 65% respectively for 31 treated with RT + S. For 52 patients with supraglottic site who received RT, the 5 and 10-year survival is 44% and 44% vs. 82% and 60% for 76 patients treated with RT + S.

  2. Potential Approaches and Recent Advances in Biomarker Discovery in Clear-Cell Renal Cell Carcinoma

    PubMed Central

    Majer, Weronika; Kluzek, Katarzyna; Bluyssen, Hans; Wesoły, Joanna

    2015-01-01

    The early diagnosis and monitoring of clear-cell Renal Cell Carcinoma (ccRCC), which is the most common renal malignancy, remains challenging. The late diagnosis and lack of tools that can be used to assess the progression of the disease and metastasis significantly influence the chance of survival of ccRCC patients. Molecular biomarkers have been shown to aid the diagnosis and disease monitoring for other cancers, but such markers are not currently available for ccRCC. Recently, plasma and serum circulating nucleic acids, nucleic acids present in urine, and plasma and urine proteins gained interest in the field of cancer biomarker discovery. Here, we describe the applicability of plasma and urine nucleic acids as cancer biomarkers with a particular focus on DNA, small RNA, and protein markers for ccRCC. PMID:26516358

  3. A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma

    PubMed Central

    Tannir, Nizar M.; Plimack, Elizabeth; Ng, Chaan; Tamboli, Pheroze; Bekele, Neby; Xiao, Lianchun; Smith, Lisa; Lim, Zita; Pagliaro, Lance; Araujo, John; Aparicio, Ana; Matin, Surena; Wood, Christopher G; Jonasch, Eric

    2013-01-01

    Background Sunitinib is a standard of care treatment in advanced clear-cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell RCC (nccRCC). Objective To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC. Design, Setting, and Participants This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥ 20 percent sarcomatoid histology, performance status 0–2, measurable disease, maximum 2 prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors. Intervention Patients received sunitinib 50 mg daily on a 4-week on, 2-week off schedule. Outcome Measurements and Statistical Analysis Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints were safety and overall survival (OS). Results and Limitations Fifty-seven patients were eligible [papillary (27), chromophobe (5), unclassified (8), collecting duct or medullary carcinoma (6), sarcomatoid (7), others (4)]. Median PFS for 55 evaluable patients was 2.7 months [95% CI: 1.4, 5.4]. Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5% ORR). Median PFS for patients with papillary histology was 1.6 months (95% CI: 1.4, 5.4). Median PFS for patients with chromophobe histology was 12.7 months (95% CI: 8.5, NA). Median OS for all patients was 16.8 months (95% CI: 10.7, 26.3). Treatment emergent adverse events were consistent with sunitinib’s mechanism of action. The non-randomized design and small number of patients are limitations of this study. Conclusions The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short

  4. Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial

    PubMed Central

    Boige, V; Raoul, J-L; Pignon, J-P; Bouché, O; Blanc, J-F; Dahan, L; Jouve, J-L; Dupouy, N; Ducreux, M

    2007-01-01

    Evaluation of new drug combinations is needed to improve patients' prognosis in advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of the capecitabine–oxaliplatine combination (XELOX) in HCC patients. First-line chemotherapy with XELOX regimen consisting of a 3-week cycle of intravenous oxaliplatin (130 mg m−2) on Day 1, and oral capecitabine twice daily from Days 1–14 (1000 mg m−2) was administered in patients with measurable, unresectable HCC. Fifty patients (male, 88%; median age, 68 years) received a total of 295 cycles (median, 6) of treatment. Disease control (three partial responses, 29 stable diseases) rate was 72% (95% CI 57–83%). Median overall and median progression-free (PFS) survival was 9.3 months and 4.1 months, respectively. Progression-free survival rates at 6 and 12 months were 38% (95% CI 26–52%) and 14% (95% CI 7–26%), respectively. Main grade 3–4 drug-related toxicities included diarrhoea (16%), elevation of aminotransferases and/or bilirubin (16%), thrombocytopenia (12%), and neurotoxicity (6%). Capecitabine plus oxaliplatin regimen showed modest anti-tumour activity with tolerable toxicities in patients with advanced HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further attention for this convenient, outpatient-based chemotherapy regimen. PMID:17876335

  5. Rapid long-lasting biochemical and radiological response to sorafenib in a case of advanced hepatocellular carcinoma.

    PubMed

    Gerardi, Assunta Maria Teresa; Stoppino, Luca Pio; Liso, Arcangelo; Macarini, Luca; Landriscina, Matteo

    2013-03-01

    The multikinase inhibitor sorafenib has demonstrated an overall survival benefit in phase III hepatocellular carcinoma (HCC) trials and has become the new standard of care for advanced stages of this disease. However, in clinical practice, the vast majority of patients obtain disease stabilization and occasionally tumor shrinkage. Furthermore, the appropriate timing of sorafenib therapy initiation, in order to maximize its clinical activity, remains under debate. We report a case of 4-year sorafenib treatment in a patient with an advanced hepatitis C virus (HCV)-related HCC with extensive infiltration of the inferior vena cava. Sorafenib treatment induced a rapid complete biochemical response and a long-term favorable outcome. Additionally, no major toxicities or detrimental effects on quality of life were observed. Thus, it is likely that a subgroup of human HCC may be highly sensitive to sorafenib; new molecular determinants are required to select those patients who may benefit from this therapy. Furthermore, a prompt initiation of treatment when the hepatic function is not compromised is a prerequisite for maximizing the clinical activity of sorafenib. PMID:23426789

  6. Rapid long-lasting biochemical and radiological response to sorafenib in a case of advanced hepatocellular carcinoma

    PubMed Central

    GERARDI, ASSUNTA MARIA TERESA; STOPPINO, LUCA PIO; LISO, ARCANGELO; MACARINI, LUCA; LANDRISCINA, MATTEO

    2013-01-01

    The multikinase inhibitor sorafenib has demonstrated an overall survival benefit in phase III hepatocellular carcinoma (HCC) trials and has become the new standard of care for advanced stages of this disease. However, in clinical practice, the vast majority of patients obtain disease stabilization and occasionally tumor shrinkage. Furthermore, the appropriate timing of sorafenib therapy initiation, in order to maximize its clinical activity, remains under debate. We report a case of 4-year sorafenib treatment in a patient with an advanced hepatitis C virus (HCV)-related HCC with extensive infiltration of the inferior vena cava. Sorafenib treatment induced a rapid complete biochemical response and a long-term favorable outcome. Additionally, no major toxicities or detrimental effects on quality of life were observed. Thus, it is likely that a subgroup of human HCC may be highly sensitive to sorafenib; new molecular determinants are required to select those patients who may benefit from this therapy. Furthermore, a prompt initiation of treatment when the hepatic function is not compromised is a prerequisite for maximizing the clinical activity of sorafenib. PMID:23426789

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

    PubMed Central

    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. PMID:26203241

  8. 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.

  9. 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. PMID:26203241

  10. Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Gan, Hua; Denniston, Kyle A.; Li, Sicong; Tan, Wenyong; Wang, Zhaohua

    2014-01-01

    Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs. PMID:24587184

  11. Congenital dermal sinuses, dermoid and epidermoid cysts of the posterior fossa.

    PubMed

    Schijman, E; Monges, J; Cragnaz, R

    1986-01-01

    Dermal sinuses are abnormal communications between the skin and deeper tissues. Seven cases are presented of occipital dermal sinuses associated with dermoid or epidermoid cysts of the posterior fossa. The cysts were interdural, subdural and intracerebellar. Although they are benign lesions, there is a high incidence of complications, especially infections such as bacterial or aseptic meningitis and cerebellar abscess. The clinical features, radiological and tomographical characteristics, and the relationship to meningeal structures, dural sinuses and cerebellar parenchyma are described. PMID:3731173

  12. Experience with combination of nimotuzumab and intensity-modulated radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma

    PubMed Central

    Zhai, Rui-ping; Ying, Hong-mei; Kong, Fang-fang; Du, Cheng-run; Huang, Shuang; Zhou, Jun-jun; Hu, Chao-su

    2015-01-01

    Aim To evaluate the efficacy and safety of using nimotuzumab in combination with intensity-modulated radiotherapy (IMRT) in the primary treatment of locoregionally advanced nasopharyngeal carcinoma. Methods Between December 2009 and December 2013, 38 newly diagnosed patients with stage III–IV nasopharyngeal carcinoma were treated with IMRT and nimotuzumab concomitantly. The distribution of disease was stage III in 20 (52.6%), stage IV A in 9 (23.7%), and stage IV B in 9 (23.7%). All the patients received at least two cycles of cisplatin-based neoadjuvant chemotherapy followed by nimotuzumab 200 mg/week concurrently with IMRT. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. Results With a median follow-up of 39.7 months (range, 13.3–66.5 months), the estimated 3-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, progression failure-free survival, and overall survival rates were 92.8%, 92.9%, 89.5%, 78.7%, and 87.5%, respectively. The median cycle for nimotuzumab addition was 6 weeks. Grade 3 radiation-induced mucositis accounted for 36.8% of treated people. No skin rash and infusion reaction were observed, distinctly from what is reported in cetuximab-treated patients. Conclusion Nimotuzumab plus IMRT showed promising outcomes in terms of locoregional control and survival, without increasing the incidence of radiation-related toxicities for patients. PMID:26604795

  13. Treatment of advanced head and neck carcinoma with synchronous irradiation and methotrexate

    SciTech Connect

    Pointon, R.C.; Askill, C.S.; Hunter, R.D.; Wilkinson, P.M.

    1981-01-01

    Thirty-four patients with advanced head and neck cancer were treated by synchronous radiotherapy and methotrexate (MTX) (100 mg/m2). Complete resolution of disease was obtained in 18 patients, the median remission of patients being 17 months. In general, treatment was well tolerated, although mucosal reaction was prolonged in 50% of patients. Drug-induced hematological toxicity was observed in six patients (18%) and one patient died. As a result of these findings, a random clinical trial to compare X-ray therapy with X-ray therapy and MTX in advanced head and neck cancer has been commenced.

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

    PubMed

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

    2016-09-01

    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

  15. 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

  16. 18F-FDG PET/CT of advanced gastric carcinoma and association of HER2 expression with standardized uptake value

    PubMed Central

    Kim, Jin Suk; Young Park, Shin

    2014-01-01

    Objective(s): Expression of HER2 in gastric carcinoma has direct prognostic and therapeutic implications in patient management. The aim of this study is to determine whether a relationship exists between standardized uptake value (SUV) and expression of HER2 in advanced gastric carcinoma. Methods: We analyzed the 18F-FDG PET/CT results of 109 patients that underwent gastrectomy for advanced gastric carcinoma. The 18F-FDG PET/CT imaging was requested at the initial staging before surgery. The examinations were evaluated semi-quantitatively, with calculation of maximum standardized uptake values (SUVmax). The clinicopathologic factors, including HER2 overexpression, were determined from tissue obtained from the primary tumor. Metabolic and clincopathologic parameters were correlated using a t-test, one way ANOVA and chi-square test. Results: Immunohistochemically, 26 patients (23.8%) showed HER2 overexpression. This overexpression was significantly associated with high SUV level (P=0.02). The SUV level was significantly correlated with tumor size (P=0.02) and differentiation (P<0.001), and Lauren histologic type (P=0.04). Multivariate analysis showed HER2 overexpression, large tumor size, and differentiation (P=0.022, P=0.002, P<0.001) were significantly correlated with the high level of SUV in advanced gastric carcinoma. No association was found between SUV and T stage and lymph node metastasis. A receiver-operating characteristic curve demonstrated a SUVmax of 3.5 to be the optimal cutoff for predicting HER2 overexpression (sensitivity; 76.9%, specificity; 60.2%). Conclusion: An association exists between high SUV and HER2 overexpression and 18F-FDG PET/CT could be a useful tool to predict the biological characteristics of gastric carcinoma.

  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. Hyperfractionated radiotherapy in advanced squamous cell carcinoma of the head and neck

    SciTech Connect

    Nguyen, T.D.; Panis, X.; Legros, M.; Froissart, D.

    1983-03-01

    From January, 1976 to January, 1980, 141 patients (135 males and 6 females) with Stage III and IV squamous cell carcinoma of the head and neck received a split course of hyperfractionated radiotherapy (HFR). In the first group, involving 91 patients, the therapeutic schedule was as follows: first and fourth week, 7.2 Gy per day in 8 sessions of .9 Gy from Monday to Friday, the second and third week no irradiation was given. Thus, patients were given 72 Gy total dose, fractionated into 80 sessions. Mucosal necrosis and severe hemorrhage were responsible for the death of 26 patients (28%). Therefore the therapeutic protocol was altered for the 50 patients of the second group: during the first and sixth week 6.6 Gy per day in 6 sessions of 1.1 Gy from Monday to Friday. The total dose was thus reduced to 66 Gy fractionated into 60 sessions, resulting in the decrease of toxicity. Regardless of the therapeutic protocol and site of primary, 114 patients (80%) achieved a complete remission and 8 showed a partial remission (>50%), whereas no change was seen for the 19 remainders. Local recurrence appeared in 60 patients (48%). Acute mucositis and laryngeal edema regularly occurred a week after every course of HFR and were considered severe in 40 patients. In spite of toxicity, the median survival is 14 months and 22 patients are still alive in November 1981: 19 without disease, and 8 of these patients have a survival time of at least 3 years.

  19. Clinical experience and critical evaluation of the role of everolimus in advanced renal cell carcinoma

    PubMed Central

    Sun, Maxine; Abdollah, Firas; Schmitges, Jan; Jeldres, Claudio; Shariat, Shahrokh F; Perrotte, Paul; Karakiewicz, Pierre I

    2011-01-01

    The efficacy of sequential everolimus, an orally administered inhibitor of mammalian target of rapamycin (mTOR), was proven in a placebo-controlled phase III study, where median progression-free survival was 4.9 vs 1.9 months for placebo (hazard ratio: 0.33, P < 0.001). Placebo crossovers (80%) contaminated overall survival data. Adverse event discontinuation rate was of only 10% and health-adjusted quality-of-life was sustained. These data represent the first placebo-controlled evidence of efficacy for a sequentially used targeted agent. Everolimus resulted in the strongest hazard ratio ever recorded for progression-free survival, despite it being tested in a population with the most aggressive natural history ever recorded in all available phase III metastatic renal cell carcinoma trials. Everolimus use after exclusively one prior antivascular endothelial growth factor failure resulted in an even longer progression-free survival time (5.4 months) than in the entire population (4.9 months). These benefits should also be considered in the light of sustained and unimpaired health-related quality of life. Use in first line other than second or subsequent lines remains to be validated. PMID:24198635

  20. Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma

    SciTech Connect

    Willett, C.G.; Shellito, P.C.; Tepper, J.E.; Eliseo, R.; Convery, K.; Wood, W.C. )

    1991-03-15

    A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.

  1. 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

  2. Continuous infusion of 5-fluorouracil with alpha 2b interferon for advanced colorectal carcinoma.

    PubMed Central

    Ferguson, J. E.; Hulse, P.; Lorigan, P.; Jayson, G.; Scarffe, J. H.

    1995-01-01

    Thirty patients with symptomatic colorectal carcinoma were commenced on treatment with 5-fluorouracil (2.5 g week-1) administered by continuous intravenous infusion and alpha 2b interferon (3 x 10(6) U s.c. three times a week). Six out of 30 patients (20%) achieved a partial response. Three patients (10%) had stable disease and 21 patients (70%) progressed on treatment. Twenty patients (67%) completed ten or more weeks of treatment. In nine patients, treatment was withdrawn after 2-9 weeks because of disease progression or death. One patient's treatment was interrupted by emergency surgery. The median survival for all patients was 210 days (7 months). The principal side-effects were oral mucositis (12/30 patients), nausea (8/30 patients) and transient diarrhoea (4/30 patients), and initial constitutional symptoms due to alpha 2b interferon. The combination of low-dose continuous infusional 5-fluorouracil and low-dose alpha 2b interferon is well tolerated but has no obvious advantage over alternative infusional regimens using 5-fluorouracil as a single agent. PMID:7599051

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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. PMID:19647632

  8. [Esophageal intubation for palliative treatment in advanced carcinoma of the esophagus and cardia].

    PubMed

    Domene, C E; Cecconello, I; Volpe, P; Zilberstein, B; Sakai, P; Ishioka, S; Pinotti, H W

    1998-01-01

    This is a report of 121 cases of advanced esophageal and cardia cancer managed by endoscopic and surgical esophageal intubation. They were submitted to surgical intubation 69 (53%) patients, and 52 (47%) to endoscopic intubation. There were 32.5% of technical complications in endoscopic intubation and 26.5% in surgical intubation. Perfuration was more frequent (11.5%) in endoscopic intubation than surgical group. Mortality rate was 17.3% for endoscopic and 5.8% for surgical intubation. Perfuration was the main cause of death in endoscopic intubation. Survival rate was 3.5 months for endoscopic and 4.7 months for surgical intubation. The majority of patients died of cancer evolution--caquexia (55.5%), carcinomatosis (4.5%) and brain methastasis (1.1%). The results of endoscopic and surgical intubation in this group of patients recommend its use in patients with advanced esophageal and cardic cancer. PMID:9699358

  9. Locally advanced hypopharyngeal squamous cell carcinoma: single-institution outcomes in a cohort of patients curatively treated either with or without larynx preservation*

    PubMed Central

    Reis, Isabel; Aguiar, Artur; Alzamora, Cristiana; Ferreira, Carolina; Castro, Vera; Soares, André; Lobão, Marisa

    2016-01-01

    Objective The present study was aimed at describing a single-institution experience in the curative treatment of patients diagnosed with locally advanced hypopharyngeal squamous cell carcinoma. Materials and Methods Data concerning all patients treated for locally advanced hypopharyngeal squamous cell carcinoma between January 2006 and June 2012 were reviewed. Results A total of 144 patients were included in the present study. The median follow-up period was 36.6 months. Median survival was 26 months, and 2-year and 5-year overall survival rates were, 51% and 30.5%, respectively. Median recurrence-free survival was 18 months and 2-year and 5-year recurrence-free survival rates were 42.8% and 28.5%, respectively. Conclusion The outcomes in the present series are in line with the literature. PMID:26929457

  10. Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches

    PubMed Central

    Swiecicki, Paul L; Malloy, Kelly M; Worden, Francis P

    2016-01-01

    Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus (HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease. PMID:26862488

  11. Use Of Yttrium-90 Microspheres In Patients With Advanced Hepatocellular Carcinoma & Portal Vein Thrombosis

    PubMed Central

    Tsai, Andrea L.; Burke, Charles T.; Kennedy, Andrew S.; Moore, Dominic T.; Mauro, Matthew A.; Dixon, Robert D.; Stavas, Joseph M.; Bernard, Stephen A.; Khandani, Amir H.; O'Neil, Bert H.

    2010-01-01

    Purpose Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma (HCC) have limited treatment options due to increased disease burden and diminished hepatic perfusion. 90Y-microspheres may be better tolerated than chemoembolization in these patients. Here we review the safety and efficacy of 90Y-microsphere use for HCC with major PVT. Materials and Methods A retrospective review of HCC with main (n=10) or first (n=12) branch PVT treated with 90Y-microspheres (n=22) was conducted. CLIP scores ranged from 2 to 5 with 18% scoring 4 or greater. Response was determined 8-12 weeks following treatment using magnetic resonance or computed tomography and RECIST criteria. Overall survival was estimated by the Kaplan-Meier method. Results 32 treatments (26 glass, 6 resin) were administered to 22 patients. Common grade 1–2 toxicities included abdominal pain (38%), nausea (28%), fatigue (22%). Four post-therapy hospitalizations occurred, all <48hrs in duration. 1 death occurred 10 days following therapy Response data: 2 partial responses, progressive disease 42%, stable disease 50% of treatments. Median overall survival (OS) was 7 months from time of initial 90Y-microsphere treatment. Child-Pugh A patients had a median OS of 7.7 months; B and C = 2.7 months (p = 0.01). Median OS for CLIP scores 2–3 was 7 months versus 1.3 months for scores 4–5 (p = 0.04). Conclusions 90Y-microspheres are tolerated in patients with HCC and major PVT. Compared with chemoembolization, rates of severe adverse events appear low. Radiographic response rates are low. Median OS of 7 months is promising and warrants further study versus systemic therapy. PMID:20691606

  12. 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.

  13. Metastasectomy Following Targeted Therapy in Patients with Advanced Renal Cell Carcinoma

    PubMed Central

    Karam, Jose A.; Rini, Brian I.; Varella, Leticia; Garcia, Jorge A.; Dreicer, Robert; Choueiri, Toni K.; Jonasch, Eric; Matin, Surena F.; Campbell, Steven C.; Wood, Christopher G.; Tannir, Nizar M.

    2015-01-01

    Purpose Metastasectomy is often incorporated in the overall management of patients with metastatic renal cell carcinoma (mRCC). While this approach has been studied in the immunotherapy era, only a few cases have been described in the targeted therapy era. Therefore, we evaluated the role of metastasectomy in patients with mRCC who received prior targeted therapy. Patients and Methods Patients who underwent consolidative metastasectomy following targeted therapy at three institutions from 2004 to 2009 were evaluated in this retrospective study. All patients received at least one cycle of targeted therapy prior to surgical resection of all visible disease. Results Twenty-two patients were identified. Sites of metastasectomy included the retroperitoneum in 12 patients, lung in 6 patients, adrenal gland in 2 patients, bowel in 2 patients, and mediastinum, bone, brain, and IVC thrombus in 1 patient each. A total of 6 postoperative complications were observed in 4 patients within 12 weeks from surgery, all of which resolved with appropriate management. Postoperatively, nine patients received at least one targeted therapy. Eleven patients recurred at a median of 42 weeks from metastasectomy and another eleven patients have not experienced a recurrence at a median of 43 weeks from metastasectomy. Twenty-one patients were alive at a median follow-up of 109 weeks and one patient died of RCC 105 weeks after metastasectomy. Conclusions In a cohort of selected patients with limited tumor burden after treatment with targeted agents, consolidative metastasectomy is feasible with acceptable morbidity. Significant time off targeted therapy and long-term tumor-free status are possible with this approach. PMID:21167518

  14. Survival Benefit of Locoregional Treatment for Hepatocellular Carcinoma with Advanced Liver Cirrhosis

    PubMed Central

    Kitai, Satoshi; Kudo, Masatoshi; Nishida, Naoshi; Izumi, Namiki; Sakamoto, Michiie; Matsuyama, Yutaka; Ichida, Takafumi; Nakashima, Osamu; Matsui, Osamu; Ku, Yonson; Kokudo, Norihiro; Makuuchi, Masatoshi

    2016-01-01

    Background & Aims Hepatocellular carcinoma (HCC) with decompensated liver cirrhosis (LC) is a life-threatening condition, which is amenable to liver transplantation (LT) as the standard first-line treatment. However, the application of LT can be limited due to a shortage of donor livers. This study aimed to clarify the effect of non-surgical therapy on the survival of patients with HCC and decompensated LC. Methods Of the 58,886 patients with HCC registered in the nationwide survey of the Liver Cancer Study Group of Japan (January 2000-December 2005), we included 1,344 patients with primary HCC and Child-Pugh (C-P) grade C for analysis in this retrospective study. Among the patients analyzed, 108 underwent LT, 273 were treated by local ablation therapy (LAT), 370 were treated by transarterial chemoembolization (TACE), and 593 received best supportive care (BSC). The effect of LT, LAT, and TACE on overall survival (OS) was analyzed using multivariate and propensity score analyses. Results Patient characteristics did not differ significantly between each treatment group and the BSC group, after propensity score matching. LAT (hazard ratio [HR]) =0.568; 95% confidence interval [CI], 0.40-0.80) and TACE (HR=0.691; 95% CI, 0.50-0.96) were identified as significant contributors to OS if the C-P score was less than 11 and tumor conditions met the Milan criteria. Conclusions For patients with HCC within the Milan criteria and with a C-P score of 10 or 11, locoregional treatment can be used as a salvage treatment if LT is not feasible. PMID:27493893

  15. A phase II trial of recombinant tumor necrosis factor in patients with advanced colorectal carcinoma.

    PubMed

    Kemeny, N; Childs, B; Larchian, W; Rosado, K; Kelsen, D

    1990-08-15

    Sixteen previously treated (with only one prior regimen) patients with histologically proven metastatic or locally recurrent colorectal carcinoma were treated with recombinant tumor necrosis factor (rTNF) administered by 30-minute i.v. infusions twice daily for 5 consecutive days every other week for 8 weeks. Patients received 100 micrograms/m2 twice daily on day 1 of cycle 1 with escalation to 150 micrograms/m2 twice daily thereafter. Patients were concomitantly treated with indomethacin 25 mg every 6 hours and acetaminophen 650 mg every 4 hours to obviate fever and chills. Toxicities included: nausea/vomiting (69%), headache (25%), chills (69%), pain at tumor sites (63%), hypotension (31%), and hypertension (38%). Hematologic toxicity included leukopenia less than 2000 cells/mm3 (38%) and thrombocytopenia less than 100,000 cells/mm3 (13%). Liver function abnormalities occurred independently of the site or extent of metastatic disease and inconsistently in each treatment cycle. Four patients developed bilirubinemia greater than 2.5 x baseline values (range, 2.5 to 10.3 U/L); five patients had greater than 2.5 x elevations in alkaline phosphatase (range, 624 to 1663 U/L). Two patients developed retinal vein thrombosis in the absence of hemostatic abnormalities. In both instances, this complication occurred several weeks after completion of therapy. No objective responses were noted in 14 evaluable patients (95% confidence interval: 0 to 0.23). Three patients had stable disease for a median duration of 4.5 months. In conclusion, i.v. rTNF at this dose and schedule has no demonstrable antitumor efficacy. Twice-daily i.v. administration of this agent is associated with more hepatotoxicity than previously reported in trials using subcutaneous or once daily i.v. administration. Retinal vein thrombosis may be a late complication of i.v. rTNF at this dose and schedule. PMID:2386895

  16. Prognostic Value of Components of Body Composition in Patients Treated with Targeted Therapy for Advanced Renal Cell Carcinoma: A Retrospective Case Series

    PubMed Central

    Gu, Weijie; Zhu, Yao; Wang, Hongkai; Zhang, Hailiang; Shi, Guohai; Liu, Xiaohang; Ye, Dingwei

    2015-01-01

    Background To evaluate the association between various components of body composition and overall survival of patients treated with targeted therapies for advanced renal cell carcinoma. Methods This retrospective study included 124 Chinese patients with advanced renal cell carcinoma who had been treated with targeted therapy from 2008 to 2012 at Fudan University Cancer Center. The L3 plane from a computed tomography scan was analyzed. Area and density were recorded as quantitative and quality measures. Univariate and multivariate Cox proportion hazard regression models were constructed to calculate the crude and adjusted hazard ratio (HR) of various components of body composition for overall survival. X-tile software was used to search for optimal cutoffs for male and female patients and the concordance index evaluated incremental changes in prognostication. Results After adjusting for age, sex and Heng risk stratification, only visceral adipose tissue index (HR 0.981, p = 0.002) and subcutaneous adipose tissue index (HR 0.987, p = 0.048) were independently associated with overall survival. Visceral adipose tissue remained a significant prognostic factor (HR 0.997, p = 0.005) when the influence of body mass index was included. Using defined cutoffs, patients with low VAT had double the death rate (p = 0.007). Visceral adipose tissue also added significant benefit to Heng risk stratification. Further exploratory analysis revealed that visceral adipose tissue may be an indicator of nutritional status in patients with advanced renal cell carcinoma. Conclusion Radiologic measurement of VAT is an independent prognostic factor for Asian patients treated with targeted therapy for advanced renal cell carcinoma. PMID:25668688

  17. A rare case of verrucous carcinoma of penis in an human immunodeficiency virus- infected patient

    PubMed Central

    Noronha, Tonita Mariola; Girisha, Banavasi S.; Bhat, Shubha P.; Christy, Carol M.; Handattu, Sripathi; Fernandes, Michelle S.

    2015-01-01

    Cancer is a significant cause of morbidity and mortality in human immunodeficiency virus-infected subjects. Verrucous carcinoma is a peculiarly slow evolving, but relentlessly expanding variant of epidermoid carcinoma that is extremely reluctant to metastasize. A 60-year-old unmarried male patient presented with urethral discharge of 3 weeks duration. Dorsal slit of the prepuce revealed an ulceroproliferative growth measuring 3 cm × 3 cm arising from prepuce and involving glans. Biopsy from the growth in the prepuce showed histopathological features of verrucous carcinoma. Partial amputation of the penis was done. Human papillomavirus DNA by polymerase chain reaction was negative. The patient was started on antiretroviral therapy. PMID:26692616

  18. A comparison of patients with hepatitis B- or hepatitis C-based advanced-stage hepatocellular carcinoma.

    PubMed

    Carr, Brian I; Guerra, Vito; Steel, Jennifer L; Lu, Sheng-Nan

    2015-04-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer death and has characteristic causes, epidemiology and clinical features. The leading causes include hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholism, and aflatoxin B1 dietary exposure, as well as combinations of these factors. Few cancers offer the opportunity to study the clinical and cancer phenotype that results from different causes, quite like HCC. Advantage was taken of a large cohort of advanced, unresectable and untransplantable HCCs to compare the phenotypes resulting from HBV-based compared with HCV-based HCC. The main findings were that HBV-based HCC patients were statistically significantly younger, had a higher percent of males, had larger maximum tumor sizes, and had higher blood alpha-fetoprotein (AFP) and albumin levels and platelet counts than HCV-based HCC patients. These differences partly reflect an earlier age of HBV infection and a lesser degree of cirrhosis-associated liver damage, as a result of the different biological consequences of chronic HBV compared with chronic HCV infection. PMID:25843735

  19. 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

  20. 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

  1. 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

  2. Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial

    PubMed Central

    Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

    2015-01-01

    The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival. PMID:26219568

  3. Paneth Cell in Adenomas of the Distal Colorectum Is Inversely Associated with Synchronous Advanced Adenoma and Carcinoma

    PubMed Central

    Mahon, Megan; Xu, Jie; Yi, Xianghua; Liu, Xiuli; Gao, Nan; Zhang, Lanjing

    2016-01-01

    Recent studies have linked appearance of Paneth cells in colorectal adenomas to adenoma burden and male gender. However, the clinical importance of Paneth cells’ associations with synchronous advanced adenoma (AA) and colorectal carcinoma (CRC) is currently unclear. We performed a comprehensive case-control study using 1,900 colorectal adenomas including 785 from females, and 1,115 from males. We prospectively reviewed and recorded Paneth cell status in the colorectal adenomas consecutively collected between February 2014 and June 2015. Multivariable logistic regression analyses revealed that, in contrast to the adenomas without Paneth cells, the Paneth cell-containing adenomas at distal colorectum were inversely associated with presence of a synchronous AA or CRC (odds ratio [OR] 0.39, P = 0.046), whereas no statistical significance was reached for Paneth cell-containing proximal colorectal adenomas (P = 0.33). Synchronous AA and CRC were significantly associated with older age (60 + versus <60 years, OR 1.60, P = 0.002), male gender (OR 1.42, P = 0.021), and a history of AA or CRC (OR 2.31, P < 0.001). However, synchronous CRC was not associated with Paneth cell status, or a history of AA or CRC. Paneth cell presence in the adenomas of distal colorectum may be a negative indicator for synchronous AA and CRC, and seems to warrant further studies. PMID:27188450

  4. 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

  5. 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). PMID:26896963

  6. Comparison of CT and PET-CT based planning of radiation therapy in locally advanced pancreatic carcinoma

    PubMed Central

    Topkan, Erkan; Yavuz, Ali A; Aydin, Mehmet; Onal, Cem; Yapar, Fuat; Yavuz, Melek N

    2008-01-01

    Background To compare computed tomography (CT) with co-registered positron emission tomography-computed tomography (PET-CT) as the basis for delineating gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma (LAPC). Methods Fourteen patients with unresectable LAPC had both CT and PET images acquired. For each patient, two three-dimensional conformal plans were made using the CT and PET-CT fusion data sets. We analyzed differences in treatment plans and doses of radiation to primary tumors and critical organs. Results Changes in GTV delineation were necessary in 5 patients based on PET-CT information. In these patients, the average increase in GTV was 29.7%, due to the incorporation of additional lymph node metastases and extension of the primary tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was 92.5 ± 32.3 cm3 versus 104.5 ± 32.6 cm3 (p = 0.009). Toxicity analysis revealed no clinically significant differences between two plans with regard to doses to critical organs. Conclusion Co-registration of PET and CT information in unresectable LAPC may improve the delineation of GTV and theoretically reduce the likelihood of geographic misses. PMID:18808725

  7. A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy.

    PubMed

    Chao, Tzu-I; Tai, Wei-Tien; Hung, Man-Hsin; Tsai, Ming-Hsien; Chen, Min-Hsuan; Chang, Mao-Ju; Shiau, Chung-Wai; Chen, Kuen-Feng

    2016-02-28

    Sorafenib is the first and currently the only standard treatment for advanced hepatocellular carcinoma (HCC). We previously developed a sorafenib derivative SC-43, which exhibits much more enhanced anti-HCC activity than sorafenib and also promotes apoptosis in sorafenib-resistant HCC cells. Herein, a novel "sorafenib plus" combination therapy was developed by coupling sorafenib treatment with SC-43. Both sorafenib and SC-43 are proven Src homology region 2 domain containing phosphatase 1 (SHP-1) agonists. The combined actions of sorafenib and SC-43 enhanced SHP-1 activity, which was associated with diminished STAT3-related signals and stronger expression of apoptotic genes above that of either drug alone, culminating in increased cell death. Decreased p-STAT3 signaling and tumor size, as well as increased SHP-1 activity were observed in mice receiving the combination therapy in a subcutaneous HCC model. More reduced orthotopic HCC tumor size and prolonged survival were also observed in mice in the combination treatment arm compared to mice in either of the monotherapy arms. These results in the preclinical setting pave the way for further clinical studies to treat unresectable HCC. PMID:26679051

  8. The long-term outcomes of alternating chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multiinstitutional phase II study

    PubMed Central

    Fuwa, Nobukazu; Kodaira, Takeshi; Daimon, Takashi; Yoshizaki, Tomokazu

    2015-01-01

    To examine the long-term outcomes of alternating chemoradiotherapy (ALCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to assess the efficacy of ALCRT for NPC. Patients with stage IIB to IVB, ECOG PS 0–2, 18–70 years-old, and sufficient organ function were eligible for this study. First, chemotherapy, consisting of 5-fluorouracil (800 mg/m2 per 24 h on days 1–5) and cisplatin (100 mg/m2 per 24 h on day 6), was administered, then a wide field of radiotherapy (36 Gy/20 fraction), chemotherapy, a shrinking field of radiotherapy (34 Gy/17 fraction), and chemotherapy were performed alternately. Between December 2003 and March 2006, 90 patients in 25 facilities were enrolled in this study, 87 patients were finally evaluated. A total of 67 patients (76.1%) completed the course of treatment. The overall survival and the progression-free survival rates at 5 years were 78.04% (95% CI: 69.1∼87.0%), and 68.74% (95% CI: 58.8∼78.7%), respectively. The long-term outcomes of ALCRT for NPC were thought to be promising. ALCRT will be considered to be a controlled trial to compare therapeutic results with those of concurrent chemoradiotherapy for NPC. PMID:25991077

  9. Overview of Current Treatment Options and Investigational Targeted Therapies for Locally Advanced Squamous Cell Carcinoma of the Head and Neck.

    PubMed

    Zibelman, Matthew; Mehra, Ranee

    2016-08-01

    Patients with squamous cell carcinoma of the head and neck (SCCHN) typically present with locally advanced (LA) stage III or IV disease and are treated with combined-modality therapy with chemotherapy, radiotherapy, and surgery (if resectable). These aggressive, upfront treatment measures are often associated with substantial morbidity, and about half the patients develop locoregional or distant recurrences. Thus, new therapeutic strategies are needed that offer similar efficacy benefits with less toxicity. Current research is focused on selectively targeting signaling pathways involved in the proliferation and malignant transformation of SCCHN cells and the tumor microenvironment. For example, the ErbB receptor pathway has been implicated in the development and progression of SCCHN, and several agents targeting this pathway and downstream effectors are in various phases of clinical investigation. Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), is the only currently approved targeted therapy for the treatment of LA SCCHN. Additional agents targeting EGFR and other ErbB family members, including monoclonal antibodies (eg, panitumumab, nimotuzumab) and small-molecule tyrosine kinase inhibitors (eg, erlotinib, afatinib, lapatinib) are being studied in LA SCCHN with varying results. Other treatment strategies for LA SCCHN include targeting downstream effectors of signaling and resistance mechanisms to EGFR inhibitors (eg, mammalian target of rapamycin, Src family, and Aurora kinase family). Data from ongoing and future clinical trials will continue to refine current treatment paradigms for LA SCCHN and provide new therapeutic options and potential predictive biomarkers to improve patient efficacy and safety and abrogate resistance. PMID:26967327

  10. Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma

    PubMed Central

    2012-01-01

    We report two cases of gastrointestinal perforation (GIP) after radiotherapy in patients receiving tyrosine kinase inhibitor (TKI) for advanced renal cell carcinoma (RCC). Case 1 was a 61-year-old woman with lung metastases after a radical nephrectomy for a right RCC (cT3aN0M0) treated with interferon-alpha (OIF, 5 MIU, three times per week). She developed lytic metastases of the left femur and the left acetabulum. She was treated with palliative radiotherapy to the metastatic portion (3 Gy × 10 fractions), and 400 mg sorafenib twice per day plus continuing interferon alpha. She experienced sudden left lower abdominal pain after four weeks of treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. Case 2 was a 48-year-old man with lung, lymph node, and bone metastases after a radical nephrectomy for a right RCC (cT2N0M0), and was treated with 400 mg sorafenib twice per day. He developed lytic bone metastases of the lumbar vertebrae, which was treated with palliative radiotherapy to L2-4 (3 Gy × 10 fractions). He experienced sudden abdominal pain after two months of radiation treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. These cases underwent radiotherapy, and therefore this may be related to the radiosensitivity of TKI. PMID:22906119

  11. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy.

    PubMed

    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

  12. 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

  13. Paneth Cell in Adenomas of the Distal Colorectum Is Inversely Associated with Synchronous Advanced Adenoma and Carcinoma.

    PubMed

    Mahon, Megan; Xu, Jie; Yi, Xianghua; Liu, Xiuli; Gao, Nan; Zhang, Lanjing

    2016-01-01

    Recent studies have linked appearance of Paneth cells in colorectal adenomas to adenoma burden and male gender. However, the clinical importance of Paneth cells' associations with synchronous advanced adenoma (AA) and colorectal carcinoma (CRC) is currently unclear. We performed a comprehensive case-control study using 1,900 colorectal adenomas including 785 from females, and 1,115 from males. We prospectively reviewed and recorded Paneth cell status in the colorectal adenomas consecutively collected between February 2014 and June 2015. Multivariable logistic regression analyses revealed that, in contrast to the adenomas without Paneth cells, the Paneth cell-containing adenomas at distal colorectum were inversely associated with presence of a synchronous AA or CRC (odds ratio [OR] 0.39, P = 0.046), whereas no statistical significance was reached for Paneth cell-containing proximal colorectal adenomas (P = 0.33). Synchronous AA and CRC were significantly associated with older age (60 + versus <60 years, OR 1.60, P = 0.002), male gender (OR 1.42, P = 0.021), and a history of AA or CRC (OR 2.31, P < 0.001). However, synchronous CRC was not associated with Paneth cell status, or a history of AA or CRC. Paneth cell presence in the adenomas of distal colorectum may be a negative indicator for synchronous AA and CRC, and seems to warrant further studies. PMID:27188450

  14. 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. PMID:25149290

  15. Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with multiple tumor thrombi and pulmonary metastases: A case report

    PubMed Central

    Huang, De-Jia; Li, Yan-Hao; Luo, Yao-Chang; Huang, Jun-Zhen; He, Hai-Yuan

    2016-01-01

    Advanced hepatocellular carcinoma (HCC) with tumor thrombi invading the portal vein and extending into the right atrium (RA) through the hepatic vein is regarded as a terminal-stage condition. Intracardiac tumor thrombus and treatment via liver resection has been reported in the current literature, but results from this therapeutic approach remain unsatisfactory. The present study describes a rare case of HCC with metastatic portal vein, middle hepatic vein, inferior vena cava (IVC) and RA tumor thrombi, and pulmonary metastases. A 29-year-old woman was admitted to The First Affiliated Hospital of Guangxi Traditional Chinese Medical University (Nanning, China) subsequent to experiencing right upper quadrant abdominal pain. Following diagnosis, based on computed tomography analysis and laboratory data, the patient underwent an initial transcatheter arterial chemoembolization (TACE) treatment using fluorouracil (5-FU), pirarubicin, mitomycin C, Lipiodol and sodium alginate microball (KMG). At 1 month post-treatment, serum α-fetoprotein levels remained at >1,000 ng/ml. Subsequently, the patient underwent a second TACE treatment. At 1 month after the second treatment, the abdominal pain had been alleviated and the serum α-fetoprotein levels were reduced to <20 ng/ml. Imaging analysis indicated a marked reduction in tumor burden in the liver and the hepatic vein and IVC tumor thrombi. Furthermore, the portal vein and RA tumor thrombi, and the pulmonary metastases had disappeared. At 40 months after the second TACE therapy, the patient remains alive without any signs of recurrence. The present case demonstrates that the administration of TACE, using 5-FU, pirarubicin, mitomycin C, Lipiodol and KMG, functions as an effective treatment in cases of unresectable advanced HCC presenting with pulmonary metastases and extensive tumor thrombi in the IVC, the RA and one branch of the portal vein. PMID:27602147

  16. [A case of advanced hepatocellular carcinoma successfully treated by liver resection after complete response induced by sorafenib administration].

    PubMed

    Kim, Yongkook; Hosoda, Yohei; Kakita, Naruyasu; Yamada, Yukinori; Yamasaki, Masaru; Nishino, Masaya; Okano, Miho; Nagai, Kenichi; Yasui, Masayoshi; Tsujinaka, Toshimasa

    2014-11-01

    A 50-year-old man presented to our hospital with the chief complaint of right hypochondriac pain and a palpable tumor. Advanced hepatocellular carcinoma (HCC) and chronic hepatitis B infection were diagnosed and treated by twice-repeated transcatheterarterial chemoembolization (TACE) followed by administration of entecavir. Two months after the last TACE, alpha-fetoprotein(AFP)and protein induced by vitamin K absence or antagonistII (PIVKA-II) levels had elevated, and multiple small early enhancing nodules were detected on computed tomography(CT)scan. Based on his age and liver function (Child-Pugh score A5), a full dose of sorafenib (800 mg/day) was administered. The sorafenib dose was decreased after one month to 400mg/day because of hand-foot syndrome. Following sorafenib administration, the lesions shrank markedly, and complete response (CR) according to modified Response Evaluation Criteria In Solid Tumors(mRECIST)was achieved within 4 months. Six months after sorafenib treatment was begun, recurrent HCC was detected in segment 6, near the previously treated lesion. The decreased size of the main tumor and normalization of AFP levels allowed curative surgical resection. The patient was discharged 5 days after surgery and is currently treated with a half dose of sorafenib. Thirteen months after surgery, a small early enhancing lesion is visible on postoperative CT scan, but AFP and PIVKA-II levels are still keeping in a normal range. This case demonstrates that if sorafenib treatment is effective, then subsequent surgical treatment can be reconsidered in patients with advanced HCC responding to this combined therapy. PMID:25731444

  17. 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

  18. Current management and future directions in the treatment of advanced renal cell carcinoma-a latin american perspective: 10 years in review.

    PubMed

    Smaletz, Oren

    2015-01-01

    The worldwide incidence of kidney cancer is estimated at 337,860 new cases per year in the International Agency for Research on Cancer's GLOBOCAN 2012 update, with an estimated 143,369 deaths annually. Over the past 10 years, there have been significant advances in the treatment of advanced/metastatic renal cell carcinoma, including the development of targeted therapies. Currently recommended first-line treatments include sunitinib, temsirolimus, bevacizumab plus interferon, and pazopanib, or high-dose interleukin-2 or sorafenib for selected patients. Recommended second-line treatments include all of the above agents, as well as everolimus and axitinib. Unfortunately, combination therapies have generally resulted in increased toxicity and little improvement in efficacy. Recent studies focused on identification of predictive biomarkers for responses to specific targeted therapies and have not been successful to date. Despite recent advances in targeted treatment for metastatic renal cell carcinoma, important questions regarding biomarkers of efficacy, and optimal combination and sequencing of agents remain to be answered. This paper reviews literature concerned with first-and second-line treatment of metastatic renal cell carcinoma and will discuss key issues in Latin America. PMID:26689508

  19. Recent Advances in Image-Guided Radiotherapy for Head and Neck Carcinoma

    PubMed Central

    Nath, Sameer K.; Simpson, Daniel R.; Rose, Brent S.; Sandhu, Ajay P.

    2009-01-01

    Radiotherapy has a well-established role in the management of head and neck cancers. Over the past decade, a variety of new imaging modalities have been incorporated into the radiotherapy planning and delivery process. These technologies are collectively referred to as image-guided radiotherapy and may lead to significant gains in tumor control and radiation side effect profiles. In the following review, these techniques as they are applied to head and neck cancer patients are described, and clinical studies analyzing their use in target delineation, patient positioning, and adaptive radiotherapy are highlighted. Finally, we conclude with a brief discussion of potential areas of further radiotherapy advancement. PMID:19644564

  20. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-04-05

    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

  1. 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.

  2. Could preoperative short-course radiotherapy be the treatment of choice for localized advanced rectal carcinoma?

    PubMed

    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

    2015-01-01

    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

  3. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010

    PubMed Central

    Sharma, Chakshu; Eltawil, Karim M; Renfrew, Paul D; Walsh, Mark J; Molinari, Michele

    2011-01-01

    Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic. PMID:21412497

  4. [Phase II studies of interferon alpha-2 Sch 30500 in advanced gastrointestinal carcinoma].

    PubMed

    Furue, H

    1985-08-01

    Eighteen patients with advanced metastatic gastrointestinal cancer (stomach cancer 7, liver cancer 9, pancreas cancer 2) were treated with human recombinant interferon alpha-2 at doses of 3.0 X 10(6)-10.0 X 10(6) IU/body i.m. daily or every second day, 30 X 10(6) IU/body for five consecutive days every four weeks, or 30 X 10(6) IU/body once weekly. No tumor response was demonstrated in any of our cases. Among fifteen evaluable cases, nine had stabilization of evaluable disease at four weeks, but six showed progressive disease. On the other hand, fever, chills, fatigue, anorexia, nausea and vomiting were pronounced. In two cases, CNS toxicities developed. In some instances, leukopenia, thrombocytopenia, decrease of hemoglobin content and elevation of transaminase were observed. According to these findings, single use of recombinant interferon alpha-2 at the dose schedule outlined above does not seem to be of use for the treatment of advanced gastrointestinal cancer. PMID:3896154

  5. Prospective randomized study comparing concomitant chemoradiotherapy using weekly cisplatin & paclitaxel versus weekly cisplatin in locally advanced carcinoma cervix

    PubMed Central

    Seam, Rajeev; Gupta, Manoj; Gupta, Manish

    2016-01-01

    Background To evaluate the benefit with the addition of paclitaxel to cisplatin-based concurrent chemoradiotherapy (C-CRT) for the treatment of locally advanced carcinoma of the uterine cervix in terms of local control, disease free survival (DFS) and overall survival (OS). Methods From 1/7/2011 to 31/5/2012, 81 women (median age of 50 years) with newly diagnosed, histopathologically proven carcinoma cervix with FIGO stages IIA to IIIB were randomized to two arms—cisplatin 40 mg/m2/week for 5 weeks was given in single agent cisplatin (control arm), while cisplatin 30 mg/m2/week and paclitaxel 50 mg/m2/week for 5 weeks were given in cisplatin and paclitaxel (study arm). External beam radiotherapy (EBRT) was delivered to a total dose of 50 Gray (Gy) in 25 fractions (#) followed by intracavitary (I/C) brachytherapy or supplement EBRT at 20 Gy/10# with 2 cycles of respective chemotherapy. This prospective trial was registered with clinicaltrials.gov (NCT01593306). Results Patients (n=81) had a maximum follow up of 36 months with a median follow up of 29 months. At first follow up study arm showed complete response in 84% vs. 75.6% in control arm (P=0.4095). An increase in toxicities was observed in the study arm in comparison to the control arm in terms of haematological grade II (35% vs. 12.2%), gastrointestinal (GI) grade III (20% vs. 7.4%) and GI grade IV (12.5% vs. 2.4%) toxicities. At median follow-up, the study arm demonstrated enhanced outcomes over the control arm in terms of DFS (79.5% vs. 64.3%; P=0.07) and OS (87.2% vs. 78.6%; P=0.27). Conclusions Despite the expected increase in manageable toxicities, these early results reveal promise with the inclusion of paclitaxel into the standard cisplatin based chemoradiation regime. Larger multi-institutional studies are justified to confirm a potential for the enhancement of response rates and survival. PMID:26904570

  6. 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

  7. 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

  8. 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

  9. Mixed gastric carcinoma with intestinal and cribriform patterns: a distinctive pathologic appearance associated with poor prognosis in advanced stages and a potential mimicker of metastatic breast carcinoma.

    PubMed

    Lino-Silva, Leonardo Saúl; Salcedo Hernández, Rosa Angélica; Molina-Frías, Ernesto

    2013-02-01

    Gastric adenocarcinoma is characterized by marked heterogeneity at cytological and architectural level and frequently shows overlap between microscopic patterns. This article describes a peculiar pattern of gastric adenocarcinoma, previously unreported, that combines intestinal type adenocarcinoma with areas of cribriform pattern that resembles both architectural and cytological in situ ductal carcinoma of the breast and to the best of the authors' knowledge, there are no earlier reports of this pattern in the stomach, which has been named "gastric carcinoma with cribriform component (CGA). The authors analyzed 12 cases of intestinal type adenocarcinoma with areas at least 20% of cribriform pattern (range from 20% to 90%) that was present in 9% of intestinal type gastric adenocarcinomas in their institution. There is slight predilection for male sex, and the median age of presentation is 55.8 years. The phenotype by immunohistochemistry is the same as with conventional (non-CGA) carcinomas. CGA shows more frequent lymphovascular invasion (P = .039), perineural invasion (P = .027) and resembles both in situ and invasive cribriform carcinoma of the breast. In clinical stage III the overall 3-year survival of CGA was worse than those with non-CGA component (38.6% vs 25%; 3-year survival, P = .010) and proves to be an independent adverse factor for overall survival in a multivariate analysis. Compared with conventional gastric carcinomas, CGA is deep infiltrating, has more nodal metastases, more lymphovascular and perineural invasion, and has decreased overall survival. Thus, proper recognition and report is important, even in small biopsies or small foci. PMID:22744963

  10. Differentiating bronchioloalveolar carcinoma from adenocarcinoma.

    PubMed

    Schraufnagel, D; Peloquin, A; Paré, J A; Wang, N S

    1982-01-01

    The recognition of bronchioloalveolar carcinoma (BAC) as distinct from adenocarcinoma of the lung, is controversial. Using strict pathologic criteria, 43 consecutive patients with BAC were matched by year of diagnosis and compared with a similar number of patients with adenocarcinoma, and for contrast, with those with squamous and oat cell carcinoma of the lung. We demonstrated that BAC is not sex related, and is not as smoking related as the other neoplasms. Unlike epidermoid carcinoma, BAC does not show a predilection for those occupations requiring manual labor. Also, BAC is frequently distinguishable radiologically from the other three by being smaller and peripheral. A pleural tag and an air bronchogram in a mass are rather specific, and BAC is less likely to have large airway involvement and adenopathy. The percentage of patients who were free of tumor after 2 yr was greater in the BAC group than in the others, but the overall survival rate between the BAC group and the adenocarcinoma group was not. Based on inter-observer variability, there is some overlap pathologically between these 2 groups. However, when the overlap between the adenocarcinoma and the BAC groups is compared with that between the adenocarcinoma and the squamous cell carcinoma groups, the difference is not significant. We conclude that BAC should be considered a distinct clinical entity. PMID:6278997

  11. Malnutrition Identified by the Nutritional Risk Index and Poor Prognosis in Advanced Epithelial Ovarian Carcinoma.

    PubMed

    Yim, Ga Won; Eoh, Kyung Jin; Kim, Sang Wun; Nam, Eun Ji; Kim, Young Tae

    2016-07-01

    Ovarian cancer is a chronic disease with a risk of malnutrition. Nutritional Risk Index (NRI) has been reported as a simple and accurate tool to assess the nutritional status. We sought to explore the prevalence of malnutrition and its association with survival in ovarian cancer. A retrospective study was conducted in 213 advanced ovarian cancer patients. NRI was calculated before and at the end of treatment using patients' body weight and serum albumin level. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method, and associations were assessed using a Cox proportional hazards analysis adjusted for known prognostic variables. Moderate to severely malnourished patients had lower 5-yr OS (45.3%) compared to normal to mild group (64.0%), respectively (P = 0.024). Adjusted for covariates, the relative risk of death was 5.8 times higher in moderate/severely malnourished group identified at the last course of chemotherapy (HR = 5.896, 95% CI = 2.723-12.764, P < 0.001). Similarly, this cohort had shorter PFS compared with normal to mild risk group (median 15 vs. 28 months, P = 0.011). Malnutrition is prevalent among ovarian cancer patients and is found to be a significant predictor for mortality. PMID:27044606

  12. 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

  13. 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.

  14. Subtotal resection and omentoplasty of the epidermoid splenic cyst: a case report

    PubMed Central

    Spahija, Gazmend S; Hashani, Shemsedin I; Osmani, Eshref A; Hoxha, Sejdullah A; Hamza, Astrit H; Gashi-Luci, Lumturije H

    2009-01-01

    Introduction Nonparasitic splenic cysts are uncommon clinical entity and because of it, there is no information regarding their optimal surgical treatment. Case presentation A 41-years-old female with incidentally diagnosed nonparasitic splenic cyst which initially was asymptomatic. After two years of follow up, the patient underwent surgery; subtotal cystectomy and omentoplasty as an additional procedure. Postoperative course was uneventful. Conclusion Short and mid term results showed that near total cystectomy with omentoplasty was a safe successful procedure for treatment of epidermoid splenic cyst. PMID:19829799

  15. MR imaging of intracranial epidermoid tumors: specific diagnosis with Turbo-FLAIR pulse sequence.

    PubMed

    Karantanas, A H

    2001-01-01

    The purpose of this study is to present the imaging findings with particular reference to the FLAIR magnetic resonance (MR) pulse sequence, of four patients with epidermoid cysts. In all cases CT showed hypodense lesions with stippled peripheral calcifications and no enhancement. The MR showed low signal intensity lesions in T1-weighted images, high signal intensity in T2-weighted lesions, no or minor enhancement after gadolinium administration and characteristic heterogeneous appearance in FLAIR images. Including the FLAIR sequence in MR imaging, a specific diagnosis can be suggested. PMID:11179701

  16. Computed tomography and magnetic resonance imaging features of a rare case of a primary epidermoid tumor of the jugular foramen

    PubMed Central

    Mahajan, Parag Suresh; Mahajan, Anuradha Parag; Al Moosawi, Nawal M.

    2015-01-01

    We present computed tomography (CT) and magnetic resonance imaging (MRI) features of a very rare case of a primary epidermoid tumor of the jugular foramen (JF). A 45-year-old male patient presented with gradually progressive vertigo and tinnitus. CT and MRI scans revealed a 3.5 cm right-sided JF tumor with characteristic bright signal (restricted diffusion) on diffusion-weighted MRI (DWI). DWI may be useful in accurately differentiating the lesion from other cystic neoplasms of the JF. We describe the imaging features of intracranial epidermoid and JF tumors and discuss its differential diagnosis. PMID:25810672

  17. Real-world cost-effectiveness of cetuximab in locally advanced squamous cell carcinoma of the head and neck.

    PubMed

    van der Linden, N; van Gils, C W M; Pescott, C P; Buter, J; Vergeer, M R; Groot, C A Uyl-de

    2015-08-01

    Clinical trial EMR 62202-006 demonstrates prolonged median locoregional control (24.4 vs. 14.9 months), progression-free survival (17.1 vs. 12.4 months) and overall survival (49.0 vs. 29.3 months) for patients who receive cetuximab added to the comparator radiotherapy for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). In the Netherlands, hospitals receive reimbursement for cetuximab conditional on cost-effectiveness in daily practice. To estimate the real-world incremental cost per quality adjusted life-year (QALY) gained for radiotherapy + cetuximab over radiotherapy alone in first line treatment of LA SCCHN, a Markov model is constructed with health states "alive without progression", "alive following progression" and "death". Transition probabilities per month are estimated from clinical trial data and retrospectively collected real-world data from two Dutch head and neck cancer treatment centres (2007-2010, n = 141). 5-year, 10-year and lifetime horizons are used, without and with discounting (4 % costs, 1.5 % effects) to calculate incremental cost-effectiveness ratios. Two scenarios explore different assumptions on prognosis of real-world versus trial patients. Adding cetuximab to radiotherapy results in increased costs and health gains in both scenarios and across each of the time horizons. Incremental costs per QALY gained range between 14,624 and 38,543 in the base-case. For a willingness to pay of 80,000 per QALY, the acceptability curves for the different scenarios show probabilities between 0.76 and 0.87 of radiotherapy + cetuximab being cost-effective compared to radiotherapy alone. Current results show the combined treatment of radiotherapy + cetuximab to be a cost-effective treatment option for patients with LA SCCHN. PMID:24943191

  18. 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.

  19. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-06-20

    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

  20. Feasibility and efficacy of chemoradiotherapy for elderly patients with locoregionally advanced nasopharyngeal carcinoma: results from a matched cohort analysis

    PubMed Central

    2013-01-01

    Background To clarify the feasibility and efficacy of chemoradiotherapy (CRT) in elderly (age≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods From January 2000 to December 2006, 101 newly diagnosed elderly non-metastatic NPC patients (age≥65 years) who received cisplatin 3-weekly or weekly concurrent CRT with/without sequential chemotherapy were recruited. Each patient from the CRT group was matched to another patient treated with radiotherapy (RT) alone based on age, gender, pathological type, performance status, overall stage, stage method, Adult Comorbidity Evaluation-27 (ACE-27) score and RT technique, from the same institute and time period. We also recruited 101 young patients (age<65 years) as the referent group, which had been matched to the CRT group based on patient characteristics and treatment parameters. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared among groups. Results CRT was feasible in elderly NPC patients, while a concurrent regimen of weekly cisplatin was more tolerable. Grade≥3 acute toxicity in CRT group was similar with referent group, although it was significantly higher than the RT alone group (65.3% vs. 43.6%, P=0.002). Furthermore, patients with ACE-27 score≥2 in the CRT group had significantly higher severe acute toxicity and dose reduction. Survival was poorer in elderly patients than the referent group. Compared to RT alone, CRT significantly improved the 5-year overall survival (OS: 54.6% vs. 39.3%, P=0.009), cancer-specific survival (CSS: 56.6% vs. 42.7%, P=0.022), disease-free survival (DFS: 51.6% vs. 30.2%, P=0.028) and locoregional relapse-free survival (LRRFS: 78.4% vs. 52.2%, P=0.003), but not distant metastasis-free survival (DMFS: 69.6% vs. 63.6%, P=0.669). However, CRT did not significantly improve 5-year OS (43.6% vs. 27.3%, P=0.893) or CSS (43.6% vs. 34.1%, P=0.971) in elderly NPC patients with ACE-27 score≥2

  1. Phase II Trial Of Neoadjuvant Axitinib In Patients With Locally Advanced Non-Metastatic Clear Cell Renal Cell Carcinoma

    PubMed Central

    Karam, Jose A.; Devine, Catherine E.; Urbauer, Diana L.; Lozano, Marisa; Maity, Tapati; Ahrar, Kamran; Tamboli, Pheroze; Tannir, Nizar M.; Wood, Christopher G.

    2015-01-01

    Background Previous studies have shown modest impact of tyrosine kinase inhibitors on primary renal tumors. These studies were mostly retrospective and heterogeneous in their eligibility criteria with regards to histology, disease stage, duration of therapy, and time off therapy prior to surgery. Objective To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with non-metastatic biopsy-proven clear cell renal cell carcinoma (ccRCC). Design, Setting, and Participants This is a single-institutional, single-arm phase 2 clinical trial. Patients with locally-advanced non-metastatic biopsy-proven ccRCC were eligible. This trial was registered with clinicaltrials.gov(NCT01263769). Intervention Patients received axitinib 5mg for up to 12 weeks. Axitinib was continued until 36 hours prior to surgery. Patient underwent partial or radical nephrectomy after axitinib therapy. Outcome Measurements and Statistical Analysis The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all CT scans to evaluate for response using RECIST. Results and Limitations Twenty-four patients were treated. 22 patients continued axitinib for 12 weeks, while 1 patient continued axitinib for 11 weeks, and underwent surgery as planned. One patient stopped treatment at 7 weeks due to adverse events. Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response by RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. FKSI (Functional Assessment of Cancer Therapy-Kidney Specific Index-15) changed over time, with quality of life worsening while on therapy

  2. 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. PMID:22700002

  3. The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    2016-01-01

    Background Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC. Methods We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled. Results Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510). Conclusion Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients. PMID:26745625

  4. Parathyroid carcinoma.

    PubMed

    Butt, Waqas Tariq; Azim, Asad; Abbas, Ansab; Gauhar, Tooba Mahmud; Afzal, Ameer; Azim, Khawaja Muhammad

    2012-09-01

    Parathyroid carcinoma is a rare endocrine malignancy accounting for less than 1% of all cases of hyperparathyroidism. We present a case of a middle-aged woman who was undiagnosed for 3 years before presenting with renal stones and advanced musculoskeletal disease. Investigations revealed primary hyperparathyroidism. Focused cervical exploration and left inferior parathyroidectomy was carried out based on the pre-operative localization studies. Parathyroid carcinoma was diagnosed on histopathology postoperatively. Subsequent en bloc resection was not performed and the patient is being monitored with serial parathyroid hormone levels which have not shown any increase in 6 months of follow-up. Only two previous cases of parathyroid carcinoma have been reported from Pakistan. PMID:22980615

  5. Intradiploic epidermoid cyst with intracranial hypertension syndrome: Report of two cases and literature review

    PubMed Central

    Moreira-Holguin, J.C.; Medélez-Borbonio, R.; Quintero-Lopez, E.; García-González, U.; Gómez-Amador, J.L.

    2015-01-01

    Introduction Intradiploic epidermoid intracranial cysts (IEIC) derive from ectodermal cells and are covered with stratified squamous epithelium. They are extremely rare, and most common locations are in the occipital, frontal and parietal bones. They have a very slow growth and can be asymptomatic until becoming evident by the deformation produced. The treatment is based on the removal of the lesion, and subsequent histopathological confirmation. Presentation of case Two cases are reported, with intracranial hypertension syndrome, which is very uncommon because of the slow growth of this type of pathology; however, decompensations occurring in the space-occupying lesions at intracranial level explain this type of clinical presentation. Discussion The most common presentation of intracranial intradiploic epidermoid cysts (IEIC) is asymptomatically, which is made evident by the prominence at the level of the soft tissues and then presenting less frequently local pain and cephalea; rarely the size of the lesion can cause focal neurological signs. Conclusion These benign lesions, although they are of low incidence, are seen very rarely in intradiploic locations and above all, of significant size, may produce significant mass effect in patients, which was initially tolerated because of its slow growth, however, they may become decompensate and cause intracranial hypertension syndrome. PMID:26433925

  6. Unusual case of spinal epidermoid cyst and a concomitant spinal arachnoid cyst.

    PubMed

    Celik, Ahmet Orhan; Baris, Mustafa Mahmut; Demirtas, Hakan; Umul, Ayşe

    2016-01-01

    A 38-year-old woman presented with a 12-month history of subjective weakness and pain in her legs. Thoracolumbar MRI revealed two spinal intradural cystic lesions at T5-6 and T11 levels, respectively. The lesion located at the T5-6 level was heterogeneously hyperintense on T2-weighted images and heterogeneously hypointense on T1-weighted images. This lesion showed high signal intensity on diffusion weighted MRI (DWI) and low signal intensity on apparent diffusion coefficient images (ADC). According to the MRI findings, we reported this tumour as a spinal epidermoid cyst. The pathology result suggested that the lesion was an epidermoid cyst. The second intradural lesion, at the T11 level, showed a hypointense signal on T1 and hyperintense signal on T2 images. However, in contrast to the superior lesion, this lesion was hypointense on DWI and hyperintense on ADC. We evaluated the second lesion as an arachnoid cyst according to the MRI findings. PMID:26907820

  7. 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

  8. Laparoscopic resection of epidermoid cyst arising from an intrapancreatic accessory spleen: a case report with a review of the literature.

    PubMed

    Iwasaki, Yoshimi; Tagaya, Nobumi; Nakagawa, Aya; Kita, Junji; Imura, Johji; Fujimori, Takahiro; Kubota, Keiichi

    2011-10-01

    We describe a rare case of epidermoid cyst arising in an intrapancreatic accessory spleen that presented as a cystic mass in the tail of the pancreas, and for which laparoscopic distal pancreatectomy was performed successfully. A 36-year-old woman with a cystic mass in the tail of the pancreas, which had been discovered incidentally at a medical checkup, was referred to our department for further examination. Endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography and positron emission tomography demonstrated a multilocular cyst in the tail of the pancreas without any evidence of malignancy, although differential diagnosis was extremely difficult because of the neoplasm-like appearance of the lesion. Therefore, we performed laparoscopic distal pancreatectomy under a preoperative diagnosis of mucinous cystic neoplasm. Postoperative pathologic examination demonstrated an epidermoid cyst arising from a heterotopic spleen within the pancreas. This is the first report of successful laparoscopic distal pancreatectomy for an epidermoid cyst arising in an intrapancreatic accessory spleen. One virtually has no chance to diagnose an epidermoid cyst in an accessory spleen on the basis of preoperative diagnostic workup, and consequently the type of surgical resection (open vs. laparoscopic) would be conditioned by factors other than the clinical entity suspected at the preoperative period. PMID:22002295

  9. 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

  10. 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

  11. The Importance of Lamivudine Therapy in Liver Cirrhosis Patients Related HBV with Advanced Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy

    PubMed Central

    Momiyama, Koichi; Nagai, Hidenari; Ogino, Yu; Mukouzu, Takanori; Matsui, Daigo; Kogame, Michio; Matsui, Teppei; Wakui, Noritaka; Shinohara, Mie; Igarashi, Yoshinori; Sumino, Yasukiyo

    2015-01-01

    Purpose: We have previously reported that continuous hepatic arterial infusion chemotherapy (HAIC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with liver cirrhosis (LC) related to HCV infection (C-LC) or alcohol abuse (A-LC) than in patients who had LC related to HBV infection (B-LC). The aim of the present study was to retrospectively assess the efficacy of lamivudine therapy for B-LC patients with aHCC undergoing HAIC. Methods: Seventeen adult Japanese B-LC patients with aHCC were treated by HAIC with or without lamivudine (100 mg/day) between 2002 and 2008 at our hospital. Their tumors were inoperable according to computed tomography findings. HAIC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was given via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. Results: Nine of the 17 patients received lamivudine at a dose of 100 mg/day together with HAIC (LAM group), while 8 patients did not receive lamivudine and only had HAIC (non-LAM group). The response rate was 12.5 in the non-LAM group and 0.0% in the LAM group. However, the survival of the LAM group was better than that of the non-LAM group, although there was no significant difference between them. The median survival time of the LAM and non-LAM groups was 310 and 157 days, respectively. HBV-DNA levels were significantly lower after chemotherapy compared with that before chemotherapy in the LAM group. In the non-LAM group, the percentage of Th2 cells before HAIC and after HAIC was significantly higher than in the control group. However, the percentage of Th2 cells in the LAM group after HAIC was not different from that in the control group, although it was significantly higher in the LAM group than in the control group before chemotherapy. Conclusions: These results indicate that lamivudine therapy may prolong the survival of B-LC patients receiving HAIC for aHCC by reducing HBV

  12. Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma and Child-Pugh A or B cirrhosis

    PubMed Central

    FEDERICO, ALESSANDRO; ORDITURA, MICHELE; COTTICELLI, GAETANO; DE SIO, ILARIO; ROMANO, MARCO; GRAVINA, ANTONIETTA GERARDA; DALLIO, MARCELLO; FABOZZI, ALESSIO; CIARDIELLO, FORTUNATO; LOGUERCIO, CARMELA; DE VITA, FERDINANDO

    2015-01-01

    Sorafenib confers a survival benefit for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) A liver cirrhosis. At present, limited data exists with regard to the safety and efficacy of sorafenib in treating CP-B HCC patients. The present study describes the use of sorafenib in patients with HCC and CP-A or -B cirrhosis. Clinical data was obtained from patients with HCC who were treated with sorafenib at the Department of Clinical and Experimental Medicine, Second University of Naples (Naples, Italy) and were analyzed retrospectively in terms of tumor response, tolerance and survival. The treatment outcomes were analyzed according to the respective CP status. The adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events, version 3.0, and the tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.2. In total, 26 patients received sorafenib at 400 mg twice daily. The median age was 69 years (range, 58–81 years) and the ratio of males to females was 18:8. Overall, 15 patients were infected with the hepatitis C virus (HCV), eight with HBV and three were co-infected with HCV/HBV. In total, 20 (77%) patients presented with an underlying CP-A (CP-A5 and CP-A6) cirrhosis and six (23%) with CP-B (CP-B7). Previous treatments included surgery (n=4), transarterial chemoembolization (n=5) and percutaneous ethanol injection or radiofrequency interstitial thermal ablation (n=12). A partial response was observed in three patients (12%), a stable disease lasting at least 12 weeks in 13 patients (50%) and a progression of disease in 10 patients (38%). The median overall survival (OS) time was 7.4 months [95% confidence interval (CI), 3.2–11.6) and the median progression-free survival (PFS) time was 3.7 months (95% CI, 1.9–5.5). The median OS and PFS times differed between patients with CP-A and CP-B, with a trend (P=0.06) toward a worse outcome in those with CP-B, although this

  13. 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

  14. Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Kuzuya, Teiji; Ishigami, Masatoshi; Ishizu, Yoji; Honda, Takashi; Hayashi, Kazuhiko; Katano, Yoshiaki; Hirooka, Yoshiki; Ishikawa, Tetsuya; Nakano, Isao; Goto, Hidemi

    2015-01-01

    Background & Aims We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma. Methods Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated. Results After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively). Conclusions Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma. PMID:26421430

  15. Evaluation of Spatially Fractionated Radiotherapy (GRID) and Definitive Chemoradiotherapy With Curative Intent for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Initial Response Rates and Toxicity

    SciTech Connect

    Penagaricano, Jose A.; Moros, Eduardo G.; Ratanatharathorn, Vaneerat; Yan Yulong; Corry, Peter

    2010-04-15

    Purpose: To present results and acute toxicity in 14 patients with bulky (>=6 cm) tumors from locally advanced squamous cell carcinoma of the head and neck who received spatially fractionated radiotherapy (GRID) therapy to the bulky mass followed by concomitant chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT). Methods and Materials: GRID therapy to the GTV was delivered by creating one treatment field with a checkerboard pattern composed of open-closed areas using a multileaf collimator. The GRID prescription was 20 Gy in one fraction. Chemotherapy started the day of GRID therapy and continued throughout the course of SIB-IMRT. The SIB-IMRT prescription was 66, 60, and 54 Gy to the planning target volume (PTV), intermediate-risk PTV, and low-risk PTV, respectively, in 30 fractions. Results: With a median follow-up of 19.5 months (range, 2-38 months), the overall control rate of the GRID gross tumor volume was 79% (11 of 14). The most common acute skin and mucosal toxicities were Grade 3 and 2, respectively. Conclusion: For the treatment of locally advanced neck squamous cell carcinoma of the head and neck, GRID followed by chemotherapy and SIB-IMRT is well tolerated and yields encouraging clinical and pathologic responses, with similar acute toxicity profiles as in patients receiving chemoradiotherapy without GRID.

  16. A prospective, randomized trial of pancreatectomy combined with isolated hepatic perfusion via a dual route or conventional postoperative adjuvant therapy in patients with advanced pancreatic head carcinoma.

    PubMed

    He, Xiaojun; Kong, Yalin; Wen, Dongqing; Liu, Chengli; Xiao, Mei; Zhao, Gang; Zhen, Yuying; Zhang, Hongyi

    2015-01-01

    Prognosis of locally advanced pancreatic head carcinoma after Whipple remains poor. This study is to investigate the efficacy and safety of regional lymphadenectomy and chemotherapy of isolated hypoxic perfusion (IHP) via dual-route, and to analyze the effect for survival period. Consecutive patients subjected to our department from January 1, 2006 to December 31 2011 for locally advanced pancreatic head carcinoma were prospectively divided into two groups according to therapeutic modality, and clinical and follow-up data was recorded. In study group, operation duration and postoperative stay time were shorter, blood loss and blood transfusion were less, and incidence of complications was lower. The mean and median survival time was 17.4 ± 0.76 months and 18.0 months in study group, longer than control group of 14.1 ± 0.85 months and 17.6 months. Regional lymphadenectomy can be performed with low mortality and morbidity, and combined postoperative IHP via dual-route can improve survival time. PMID:26131274

  17. Mucoepidermoid carcinoma of eyelid: A usual tumor at an unusual site.

    PubMed

    Singh, Lavleen; Singh, Shuchita; Jain, Deepali; Sharma, Suresh C

    2015-01-01

    Mucoepidermoid carcinoma is a malignant epithelial neoplasm comprising mucous, intermediate and epidermoid cells, arising mainly in salivary gland. It is extremely uncommon in ocular region, where it can arise in conjunctiva, lacrimal gland or lacrimal sac. The index case is being presented for its rarity and for highlighting the importance of meticulous sampling for correct diagnosis. A 68-year-old female presented with complaints of ulceration over right lower eyelid for 3 years. She underwent a local surgical excision 2 years ago after which she was asymptomatic for the following 1 year. Histopathological examination of excised specimen showed features of mucoepidermoid carcinoma. Mucoepidermoid carcinoma in ocular adnexa may be difficult to differentiate from its close mimickers like basal, squamous, sebaceous cell carcinoma and apocrine carcinoma. Meticulous sampling, judicious use of special stains and immunohistochemistry are pivotal in establishing the diagnosis. PMID:26881601

  18. Surgical strategy for intracranial dermoid and epidermoid tumors: An experience with 33 Patients

    PubMed Central

    Lynch, Jose Carlos; Aversa, Antônio; Pereira, Celestino; Nogueira, Jânio; Gonçalves, Mariangela; Lopes, Hélio

    2014-01-01

    Background: The aim of this paper is to report on our surgical strategy and technique and to identify the best management for intracranial dermoids and epidermoids tumors (IDETs). Methods: We retrospectively reviewed 33 consecutive patients (14 males and 19 females; mean age at surgery, 37.9 years) with pathologically confirmed IDETs who underwent surgical resection, with mean follow-up of 7.2 years. Results: Gross total tumor removal was achieved in 24 cases (72.7%) with zero surgical mortality and a recurrence rate of 9%. Conclusions: The surgical strategies used in this group of patients enabled total removal of most tumors without surgical mortality and with low morbidity and recurrence rates, proving to be safe and effective. PMID:25558422

  19. 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

  20. Epidermoid Cyst

    MedlinePlus

    ... epidermis) grows into the middle layer of the skin (dermis). This may occur due to injury or blocked hair follicles. The lesion may be ... the cyst. However, this is a temporary measure. After this treatment, a cyst will refill with the cheesy contents because the lining of the cyst has not been removed. ... Jean L., ed. Dermatology , pp. ...

  1. 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

  2. [Results of complex treatment of patients with squamous cell carcinoma of the anal canal using advanced radiotherapy technologies].

    PubMed

    Glebovskaya, V V; Tkachev, S I; Rasulov, A O; Tsaryuk, V F; Gordeev, S S; Fedyanin, M Yu; Aliev, V A; Mamedly, Z Z; Kuzmichev, D V; Trofimova, O P; Borisova, T N; Yazhgunovich, I P

    2015-01-01

    During recent decades radiotherapy is the basis, on which it is built a medical complex that is the first-line treatment of patients with squamous cell carcinoma of the anal canal. An increase of overall and disease-free survival and quality of life of patients with squamous cell carcinoma of the anal canal at the present stage of development of a comprehensive medical treatment is largely due to the improvement of technical equipment of radiotherapy departments of oncology clinics. The use of modem linear electron accelerators and systems of computer dosimetric planning to create a 3D program of isodose distribution, diagnostic devices (computed tomography and magnetic resonance imaging) as well as a number of other conditions permit accurate summarizing of proposed dose, reducing of absorbed dose to critical structures, diminishing unplanned interruptions in chemoradiotherapy course by means of modern technologies of conformal radiotherapy (3D CRT, IMRT, VMAT). The paper presents the preliminary results of a comprehensive medical treatment of 14 patients with squamous cell carcinoma of the anal canal. PMID:26571840

  3. 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

  4. 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.

  5. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    ClinicalTrials.gov

    2016-08-10

    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

  6. Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma.

    PubMed

    Ajani, J A; Rios, A A; Ende, K; Abbruzzese, J L; Edwards, C; Faintuch, J S; Saks, S; Gutterman, J U; Levin, B

    1989-04-01

    Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied. The dose levels constituting the MTD were as follows: 5-fluorouracil (500 g/m2/day) and recombinant gamma-interferon (0.5 mg/m2/day). Four patients achieved a partial response in the phase I study. In the phase II study, 30 patients received therapy at the MTD. Among 29 evaluable patients in the phase II study, two patients achieved a partial response. Common toxicities included malaise, fever, anorexia, nausea and vomiting, and diarrhea. Transient severe myelosuppression was common but did not result in significant morbidity. Our data suggest that the combination of 5-fluorouracil and recombinant gamma-interferon did not have the same antitumor effect in patients as it had in the preclinical experiments. PMID:2499663

  7. Nasopharyngeal mucoepidermoid carcinoma - a common entity at an uncommon location.

    PubMed

    Hemalatha, A L; Kumar H K, Sharath; S, Geetanjali; M, Giripunja; S D, Shashikumar

    2014-01-01

    Mucoepidermoid carcinomas mostly occur in the major salivary glands, the minor salivary glands of oral cavity and in the lacrimal glands. These tumours rarely occur in the sino-nasal tract. When they occur in the sino-nasal tract, the most frequent site is the maxillary antrum, followed by the nasal cavity, the nasopharynx and the ethmoidal sinuses. As per review of literature, nasopharyngeal mucoepidermoid carcinomas account for 0.6% of salivary gland tumours and 4.8% of mucoepidermoid carcinomas. Extensive literature search revealed 21 cases of nasopharyngeal mucoepidermoid carcinomas reported till date. These cases showed an age incidence ranging from 20 to 60 years with a female preponderance. In contrast to nasopharyngeal carcinomas, these tumours show low positivity rates for Ebstein-Barr virus serological test. Histochemical positivity for mucin may be demonstrated in the glandular and mucinous components of these tumours. High grade mucoepidermoid carcinoma of nasopharynx is treated with surgical excision combined with radiotherapy and is associated with poor survival. Therefore, early diagnosis and prompt treatment are of utmost importance. This case report highlights the rare occurrence of a high grade nasopharyngeal muco-epidermoid carcinoma in a 70-year-old male and is presented for its unusual occurrence in the nasopharynx which is the most infrequent location for this lesion. PMID:24596757

  8. Preoperative Neutrophil-to-lymphocyte Ratio Predicts Long-term Survival in Patients Undergoing Total Laryngectomy With Advanced Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Fu, Yan; Liu, Weiwei; OuYang, Dian; Yang, Ankui; Zhang, Quan

    2016-01-01

    Abstract There is increasing evidence that the neutrophil-to-lymphocyte ratio (NLR) is a stage-independent predictor of poor outcome in patients with cancer. The purpose of this study was to investigate the association between cancer-specific survival (CSS), overall survival (OS), and the preoperative NLR in patients with advanced laryngeal squamous cell carcinoma (LSCC) undergoing total laryngectomy (TL). All patients with a new diagnosis of advanced laryngeal cancer (stages III and IV) presenting at the Department of Head and Neck Oncology, Sun Yat-sen University Cancer Center between January 1990 and July 2010 (n = 420) were included. To evaluate the independent prognostic relevance of the NLR, univariate and multivariate Cox regression models were used. CSS and OS were estimated using the Kaplan-Meier method. Four-hundred twenty patients were enrolled in this study. Patients with an NLR ≥2.59 showed a significantly lower CSS (P = .014) and OS (P = .032) than patients with an NLR <2.59. The Cox proportional multivariate hazard model showed that a higher preoperative NLR was independently correlated with a poor CSS and OS, with hazard ratios of 1.42 (95% confidence interval [CI] 1.06–1.91, P = .018) and 1.31 (95% CI 1.00–1.71, P = .046), respectively. The NLR may be an independent prognostic marker for CSS and OS in patients with advanced LSCC undergoing TL. PMID:26871799

  9. 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.

  10. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

    PubMed

    Cebon, J; Findlay, M; Hargreaves, C; Stockler, M; Thompson, P; Boyer, M; Roberts, S; Poon, A; Scott, A M; Kalff, V; Garas, G; Dowling, A; Crawford, D; Ring, J; Basser, R; Strickland, A; Macdonald, G; Green, M; Nowak, A; Dickman, B; Dhillon, H; Gebski, V

    2006-10-01

    Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways. PMID:16953241

  11. Induction chemotherapy with TPF (Docetaxel, Carboplatin and Fluorouracil) in the treatment of locally advanced squamous cell carcinoma of the head and neck.

    PubMed

    Schultz, J D; Bran, G; Anders, C; Sadick, H; Faber, A; Hörmann, K; Sauter, A

    2010-11-01

    Squamous cell carcinoma of the head and neck (SCCHN) presents at a locally advanced (LA) stage in many patients. Chemotherapy, which is one fundamental therapy mode for local disease control of inoperable disease or if organ preservation is desired, has become an important factor of first line treatment regimens either during or prior to radiotherapy (RT). Patients with locoregionally advanced inoperable, recurrent or metastatic disease still have a poor prognosis, which enforces the need for new treatment approaches and new drug therapies, adjusted to the different settings of the disease. One innovative progress for this collective of patients with locally advanced tumor was the implementation of Docetaxel in chemotherapeutic regimes in optimal combination with concurrent chemoradiotherapy or in neoadjuvant setting of induction phase treatment. Docetaxel combined with the conventional chemotherapy regimen, containing Cisplatin and 5-Fluorouracil (TPF), is now acknowledged as being the gold standard of induction treatment. Various studies suggest survival advantage due to the induction chemotherapy (ICT) followed by chemoradiotherapy, which is known as sequential therapy, over chemoradiotherapy alone. In contrast to prevailing studies we administered Docetaxel, Carboplatin and 5-FU within the frame-work of induction chemotherapy instead of conventional use of Cisplatin for five patients with locoregionally advanced HNSCC. The clinical progress was evaluated through cross section imaging (computer tomography/MRI) prior and after ICT and classified following the RECIST criteria. Due to a very small collective of patient and the administration of Carboplatin instead of Cisplatin in this study, it was not possible to document the the efficacy of ICT (TPF) concerning survival advantage in patient with locoregionally advanced head and neck tumors. Further studies with an extended collective of patients are neccessary. PMID:20878112

  12. 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.

  13. 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.

  14. Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study.

    PubMed

    Wadler, S; Lembersky, B; Atkins, M; Kirkwood, J; Petrelli, N

    1991-10-01

    In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable. PMID:1919631

  15. Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma

    PubMed Central

    Agarwal, Neeraj; Bellmunt, Joaquim; Maughan, Benjamin L.; Boucher, Kenneth M.; Choueiri, Toni K.; Qu, Angela Q.; Vogelzang, Nicholas J.; Fougeray, Ronan; Niegisch, Guenter; Albers, Peter; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S.; Tantravahi, Srinivas K.; Galsky, Matthew D.; Petrylak, Daniel P.; Vaishampayan, Ulka N.; Mehta, Amitkumar N.; Beer, Tomasz M.; Sternberg, Cora. N.; Rosenberg, Jonathan E.; Sonpavde, Guru

    2014-01-01

    This study examined the association of progression-free survival at 6 months with overall survival in the context of second-line therapy of advanced urothelial carcinoma in pooled patient-level data from 10 phase II trials and then externally validated in a large phase III trial. Progression-free survival at 6 months was significantly correlated with overall survival and is an innovative primary endpoint to evaluate new agents in this setting. Objective Second-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents. Methods Ten second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction. Results In the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R2 = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R2 = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared PMID:24220220

  16. A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party.

    PubMed Central

    Mead, G. M.; Russell, M.; Clark, P.; Harland, S. J.; Harper, P. G.; Cowan, R.; Roberts, J. T.; Uscinska, B. M.; Griffiths, G. O.; Parmar, M. K.

    1998-01-01

    Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity. PMID:9792152

  17. Adrenocortical carcinoma.

    PubMed

    Baudin, Eric

    2015-06-01

    Recent developments in the treatment of adrenocortical carcinoma (ACC) include diagnostic and prognostic risk stratification algorithms, increasing evidence of the impact of historical therapies on overall survival, and emerging targets from integrated epigenomic and genomic analyses. Advances include proper clinical and molecular characterization of all patients with ACC, standardization of proliferative index analyses, referral of these patients to large cancer referral centers at the time of first surgery, and development of new trials in patients with well-characterized ACC. Networking and progress in the molecular characterization of ACC constitute the basis for significant future therapeutic breakthroughs. PMID:26038209

  18. 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

  19. Adenoviral p53 gene transfer and gemcitabine in three patients with liver metastases due to advanced pancreatic carcinoma

    PubMed Central

    Thiede, Christian; Fischer, Rainer; Ehninger, Gerhard; Haag, Cornelie

    2007-01-01

    Background. Current therapies for adenocarcinoma of the pancreas do not improve the life expectancy of patients. Methods. In a non-randomized pilot trail we tested whether a local therapy based upon an adenoviral gene transfer of wild type p53 in combination with gemcitabine administration would be safe in patients with liver metastases due to pancreatic carcinoma. We report on the clinical course of three patients with respect to safety, tolerability and tumor response. Results. Transient grade III toxicities occurred with fever, leucopenia, elevation of AP, ALT, AST, GGT, while grade IV toxicity occurred for bilirubin only. Laboratory tests suggested disseminated intravascular coagulation in all three patients, but fine needle biopsies of liver did not show any histological evidence of thrombus or clot formation. Progression of liver metastases was documented in one and stable disease in another patient two months after treatment. However, a major improvement with regression of the indexed lesion by 80% occurred in a third patient after a single administration of 7.5×1012 viral particles, and time to progression was extended to six months. Conclusion. The combination therapy of viral gene transfer and chemotherapy temporarily controls and diminishes tumor burden. Improvement of the toxicity profile is necessary. Further trials are warranted to improve treatment and life expectancy of patients suffering from fatal diseases such as pancreatic carcinoma. PMID:18333108

  20. A Broadly Adaptive Array of Dose-Constraint Templates for Planning of Intensity-Modulated Radiation Therapy for Advanced T-Stage Nasopharyngeal Carcinoma

    SciTech Connect

    Chau, R.M.-C. Leung, S.-F.; Kam, M.K.-M.; Cheung, K.-Y.; Kwan, W.-H.; Yu, K.-H.; Chiu, K.-W.; Cheung, M.L.-M.; Chan, A.T.-C.

    2009-05-01

    Purpose: To develop and validate adaptive dose-constraint templates in intensity-modulated radiotherapy (IMRT) planning for advanced T-stage nasopharyngeal carcinoma (NPC). Method and Materials: Dose-volume histograms of clinically approved plans for 20 patients with advanced T-stage NPC were analyzed, and the pattern of distribution in relation to the degree of overlap between targets and organs at risk (OARs) was explored. An adaptive dose constraint template (ADCT) was developed based on the degree of overlap. Another set of 10 patients with advanced T-stage NPC was selected for validation. Results of the manual arm optimization protocol and the ADCT optimization protocol were compared with respect to dose optimization time, conformity indices, multiple-dose end points, tumor control probability, and normal tissue complication probability. Results: For the ADCT protocol, average time required to achieve an acceptable plan was 9 minutes, with one optimization compared with 94 minutes with more than two optimizations of the manual arm protocol. Target coverage was similar between the manual arm and ADCT plans. A more desirable dose distribution in the region of overlap between planning target volume and OARs was achieved in the ADCT plan. Dose end points of OARs were similar between the manual arm and ADCT plans. Conclusions: With the developed ADCT, IMRT treatment planning becomes more efficient and less dependent on the planner's experience on dose optimization. The developed ADCT is applicable to a wide range of advanced T-stage NPC treatment and has the potential to be applied in a broader context to IMRT planning for other cancer sites.

  1. Maintenance monotherapy with Gemcitabine following cisplatin-based primary combination chemotherapy in surgically treated advanced urothelial carcinoma: A matched-pair single institution analysis

    PubMed Central

    KALOGIROU, CHARIS; SVISTUNOV, ANDREY; KREBS, MARKUS; LAUSENMEYER, EVA MARIA; VERGHO, DANIEL; RIEDMILLER, HUBERTUS; KOCOT, ARKADIUS

    2016-01-01

    The role of maintenance therapy with Gemcitabine (GEM) following cisplatin-based combination chemotherapy (CBCC) in patients with surgically treated advanced urothelial carcinoma (UC) remains to be fully elucidated. In the present case control study, a retrospective analysis was performed to evaluate the role of GEM monotherapy following surgical intervention for advanced UC. Between 1999 and 2013, 38 patients were identified with surgically treated advanced UC after having completed CBCC, who were additionally treated quarterly with two consecutive GEM (1,250 mg/m2) infusions as maintenance therapy. This collective was matched by propensity score matching to a control collective (n=38) that received primary CBCC alone, and the overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) rates were determined for the two collectives using Kaplan-Meier estimates and the log-rank test. Regression analysis was performed using the Cox proportional hazards model. The median follow-up time was 37 months (interquartile range: 9–148). Interestingly, patients treated with GEM following primary chemotherapy had a significantly improved outcome with respect to the 5-year OS (46.2 vs. 26.4%, P=0.0314) and 5-year CSS (61.3 vs. 33.4%, P=0.0386) rates. Notably, the 5-year PFS rate did not differ between the two groups (10.3 vs. 16.1%, P=0.134). It is proposed that additional GEM maintenance monotherapy is able to improve survival rates following primary CBCC in surgically treated patients with advanced UC, suggesting a possible treatment option for patients with, e.g., unclear disease status, or those who would require an active maintenance therapy in the future. Prospective studies should further determine the impact of GEM monotherapy with respect to PFS rates in groups comprising larger numbers of patients. PMID:27073682

  2. Final Results of Sequential Doxorubicin Plus Gemcitabine and Ifosfamide, Paclitaxel, and Cisplatin Chemotherapy in Patients With Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium

    PubMed Central

    Milowsky, Matthew I.; Nanus, David M.; Maluf, Fernando C.; Mironov, Svetlana; Shi, Weiji; Iasonos, Alexia; Riches, Jamie; Regazzi, Ashley; Bajorin, Dean F.

    2009-01-01

    Purpose Sequential chemotherapy with doxorubicin and gemcitabine (AG) followed by ifosfamide, paclitaxel, and cisplatin (ITP) was previously demonstrated to be well tolerated in patients with advanced transitional cell carcinoma (TCC). This study sought to evaluate the efficacy and to additionally define toxicity. Patients and Methods Sixty patients with advanced TCC received AG every 2 weeks for five or six cycles followed by ITP every 21 days for four cycles. Granulocyte colony-stimulating factor was given between cycles. Results Myelosuppression was seen with 68% of patients who experienced grades 3 to 4 neutropenia and with 25% who experienced febrile neutropenia. Grade 3 or greater nonhematologic toxicities were infrequent. Forty (73%) of 55 evaluable patients (95% CI, 59% to 84%) demonstrated a major response (complete, n = 19; partial, n = 21) and had a median response duration of 11.3 months (range, 1.7 to ≥ 105.6 months). Twenty-seven (79%) of 34 patients with locally advanced disease (ie, T4, N0, M0) or with regional lymph node involvement (ie, T3-4, N1, M0) and 10 (56%) of 18 patients with distant metastases achieved a major response. The median progression-free survival was 12.1 months (95% CI, 9.0 to 14.8 months), and the median overall survival was 16.4 months (95% CI, 14.0 to 22.5 months). At a median follow-up of 76.4 months, seven (11.7%) patients remain alive, and all were disease free. Conclusion AG plus ITP is an active regimen in previously untreated patients with advanced TCC; however, it is associated with toxicity and does not clearly offer a benefit compared with other nonsequential, cisplatin-based regimens. PMID:19636012

  3. 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

  4. [Advances in the research of BRAF(V600E) gene mutation correlated with papillary thyroid carcinoma].

    PubMed

    Xu, X Q; Wang, X H; Jing, J X

    2016-08-01

    The increase in the incidence of papillary thyroid carcinoma (PTC) is a serious threat to public health. V-raf murine sarcoma viral oncogene homolog B(BRAF)(V600E) gene mutation is not only the common genetics factors, but also is the early event in process of thyroid carcinogenesis. We mainly illustrate the mechanism of BRAF(V600E) gene in genesis and development of PTC and the correlation of BRAF(V600E) gene mutation and the clinicopathological characteristics of PTC. Finally, we briefly summarize some scientific achievements about tyrosine kinase inhibitors targeted for BRAF(V600E) gene and their clinical prospect in terms of translation medicine concept. In summary, BRAF(V600E) gene is expected to be a new molecular marker of PTC, which will take a new hope for individualized precise treatment for patients with PTC. PMID:27625138

  5. Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From a Phase II Trial

    PubMed Central

    Bilen, Mehmet Asim; Zurita, Amado J.; Ilias-Khan, Nasreen A.; Chen, Hsiang-Chun; Wang, Xuemei; Kearney, Alper Y.; Hodges, Sherie; Jonasch, Eric; Huang, Shixia; Khakoo, Aarif Yusuf

    2015-01-01

    Background. We evaluated the significance of hypertension developing during vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (VEGFR-TKI) treatment and a group of cytokines and angiogenic factors (CAFs) in advanced non-clear cell renal cell carcinoma (nccRCC) patients treated with sunitinib in a phase II study. Materials and Methods. Using multiplex assays, we analyzed the levels of 38 CAFs in plasma at baseline and after 4 weeks of sunitinib therapy. Sunitinib benefit was defined as a partial response or stable disease using the Response Evaluation Criteria in Solid Tumors lasting ≥4 months. Cox proportional hazards regression models were used to assess the associations among hypertension, CAFs, and progression-free (PFS) and overall survival (OS). Results. Fifty-seven patients were evaluable; 53 had baseline CAF levels available. The median PFS and OS were 2.9 months (95% confidence interval [CI], 1.4–5.5) and 16.8 months (95% CI, 10.7–27.4), respectively. Sunitinib benefit was observed in 21 patients (37%). However, 33 patients (60%) developed hypertension during treatment, although no association was found with survival or response. Elevated baseline soluble tumor necrosis factor (TNF) receptor I, interleukin-8, growth-regulated oncogene, transforming growth factor-α, and VEGFR-2 levels were associated with an increased risk of death on multivariate analysis. Conclusion. We found no association between the development of hypertension and survival or sunitinib benefit in advanced nccRCC. TNF and angiogenic/immunomodulatory mediators were identified for evaluation as markers of prognosis and VEGFR-TKI benefit in future studies. Implications for Practice: The present study describes the first analysis of hypertension and a relatively large set of circulating cytokines and angiogenic factors in patients with advanced non-clear cell renal cell carcinoma (nccRCC) treated with sunitinib. No association was found between hypertension

  6. Efficacy of the Additional Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: a Bayesian Network Meta-analysis of Randomized Controlled Trials

    PubMed Central

    Chen, Yu-Pei; Guo, Rui; Liu, Na; Liu, Xu; Mao, Yan-Ping; Tang, Ling-Long; Zhou, Guan-Qun; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2015-01-01

    Background: Due to the lack of studies, it remains unclear whether the additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locoregionally advanced nasopharyngeal carcinoma (NPC). The main objective of this Bayesian network meta-analysis was to determine the efficacy of NACT+CCRT as compared with CCRT alone. Methods: We comprehensively searched databases and extracted data from randomized controlled trials involving NPC patients who received NACT+CCRT, CCRT, NACT+radiotherapy (RT), or RT. Overall survival (OS) with hazard ratio (HR), and locoregional recurrence rate (LRR) and distant metastasis rate (DMR) with relative risks (RRs), were concerned. Results: Nine trials involving 1988 patients were analyzed. In the network meta-analysis, there was significant benefit of NACT+CCRT over CCRT for DMR (RR=0.54, 95% credible interval [CrI]=0.27-0.94). However, NACT+CCRT had a tendency to worsen locoregional control significantly as compared with CCRT (RR =1.71, 95%CrI =0.94-2.84), and no significant improvement in OS was found (HR =0.73, 95%CrI=0.40-1.23). Conclusions: NACT+CCRT is associated with reduced distant failure as compared with CCRT alone, and whether the additional NACT can improve survival for locoregionally advanced NPC should be further explored. Optimizing regimens and identifying patients at high risk of metastasis may enhance the efficacy of NACT+CCRT. PMID:26284140

  7. 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.

  8. A Multi-institutional Investigation of the Prognostic Value of Lymph Nodal Yield in Advanced Stage Oral Cavity Squamous Cell Carcinoma (OCSCC)

    PubMed Central

    Jaber, James J.; Zender, Chad A.; Mehta, Vikas; Davis, Kara; Ferris, Robert L.; Lavertu, Pierre; Rezaee, Rod; Feustel, Paul J.

    2014-01-01

    Background Although existing literature provides surgical recommendations for treating occult disease (cN0) in early stage oral cavity squamous cell carcinoma, a focus on late stage OCSCC is less pervasive. Methods The records of 162 late stage OCSCC pN0 individuals that underwent primary neck dissections were reviewed. Lymph node yield (LNY) as a prognosticator was examined. Results Despite being staged pN0, patients that had a higher LNY had an improved regional/distant control rates, DFS, DSS, and OS. LNY consistently outperformed all other standard variables as being the single best prognostic factor with a tight risk ratio range (RR = 0.95–0.98) even when correcting for the number of lymph nodes examined. Conclusion The results of this study showed that lower regional recurrence rates and improved survival outcomes were seen as lymph node yield increased for advanced T-stage OCSCC pN0. This suggests that increasing lymph node yield with an extended cervical lymphadenectomy may result in lower recurrence rates and improved survival outcomes for this advanced stage group. PMID:24038739

  9. 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

  10. Presence of tumour high-endothelial venules is an independent positive prognostic factor and stratifies patients with advanced-stage oral squamous cell carcinoma.

    PubMed

    Wirsing, Anna M; Rikardsen, Oddveig G; Steigen, Sonja E; Uhlin-Hansen, Lars; Hadler-Olsen, Elin

    2016-02-01

    Staging of oral squamous cell carcinoma is based on the tumour-node-metastasis (TNM) system, which has been deemed insufficient for prognostic purposes. Hence, better prognostic tools are needed to reflect the biological diversity of these cancers. Previously, high numbers of specialized blood vessels called high-endothelial venules have been reported to be associated with prolonged survival in patients with breast cancer. In this study, we analysed the prognostic value and morphological characteristics of tumour-associated high-endothelial venules in oral cancer. The presence of tumour-associated high-endothelial venules was evaluated by immunohistochemistry in 75 patients with oral squamous cell carcinoma and analysed with correlation to clinicopathological parameters, patients' survival and vessel morphology. Ten of the samples were analysed at multiple levels to evaluate intratumoural heterogeneity. The presence of tumour-associated high-endothelial venules was found to be associated with lower disease-specific death in multivariate regression analyses (P = 0.002). High-endothelial venules were present in all (n = 53) T1-T2 tumours, but only in two thirds (n = 14) of the T3-T4 tumours. The morphology of high-endothelial venules was heterogeneous and correlated with lymphocyte density. High-endothelial venules were found to be distributed homogeneously within the tumours. We found the presence of tumour-associated high-endothelial venules to be an easy-to-use, robust, and independent positive prognostic factor for patients with oral cancer. Absence of these vessels in advanced-stage tumours might identify patients with more aggressive disease. Evaluating the presence of tumour-associated high-endothelial venules might help to tailor the treatment of oral cancer patients to their individual needs. PMID:26383526

  11. 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.

  12. Electrochemotherapy in combination with chemoradiotherapy in the treatment of oral carcinomas in advanced stages of disease: efficacy, safety, and clinical outcomes in a small number of selected cases

    PubMed Central

    Domanico, Rossana; Trapasso, Serena; Santoro, Mariaquila; Pingitore, Domenico; Allegra, Eugenia

    2015-01-01

    Introduction Electrochemotherapy (ECT) is a new therapeutic method that is used in oncology as palliative treatment in patients with recurrent head and neck tumors and who are not candidates for standard therapeutic options. The aim of our study was to evaluate the cytoreductive effect of ECT in patients subjected to chemoradiotherapy for squamous cell carcinoma of the oral cavity. The primary endpoint of the study was to verify tumor debulking after ECT treatment as neoadjuvant, before conventional chemoradiotherapy. The secondary endpoint was to assess the safety and tolerability of ECT treatment. Materials and methods This experimental study was conducted at the Division of Otolaryngology, University of Catanzaro, Italy. From February 2013 to February 2014, four patients were enrolled, two males and two females, with a mean age of 56 years (range: 47–65 years), and with squamous cell carcinoma of the oral cavity in advanced stages of disease (T3–T4). All patients, with their informed consent, received ECT treatment in accordance with the Standard Operating Procedures defined in the European Standard Operating Procedures on Electrochemotherapy (ESOPE) study, followed by conventional chemoradiotherapy. Their response to ECT treatment was assessed after 30 days. For each patient, the following parameters were evaluated with the appropriate forms: local tumor control, control of pain (analgesia postsurgery scale [APS]), and quality of life (Short Form [36] Health Survey [SF-36]; v1). Results Three of four patients (75%) showed a partial response, whereas in one patient (25%), the disease remained stable. The treatment was well-tolerated by all patients, according to the APS and SF-36 results. Conclusion Although the study was conducted on a small number of cases, data from this study show that ECT represents a safe and effective treatment in terms of tumor cytoreduction and locoregional control of the disease. It also allows good control of postoperative pain

  13. Difference in distant failure site between locally advanced squamous cell carcinoma and adenocarcinoma of the uterine cervix after C-ion RT

    PubMed Central

    Wakatsuki, Masaru; Kato, Shingo; Ohno, Tatsuya; Kiyohara, Hiroki; Karasawa, Kumiko; Tamaki, Tomoaki; Ando, Ken; Irie, Daisuke; Shiba, Shintaro; Tsujii, Hirohiko; Nakano, Takashi; Kamada, Tadashi; Shozu, Makio

    2015-01-01

    We investigated the first site of distant failure after carbon ion radiotherapy (C-ion RT) for locally advanced cervical cancer in three clinical trials. A total of 91 cases were enrolled in the three trials (Protocol 9702, 9704 and 9902). Histologically, 36 cases had squamous cell carcinoma (SqCC) and 55 cases had adenocarcinoma (AC), including 13 with adenosquamous cell carcinoma. The number of cases with Stage IIB, IIIB and IVA disease was 21, 59 and 11, respectively. Of the 91 cases, 42 had positive pelvic lymph nodes (PLNs). The median tumor size was 6.0 cm (range, 3.0–12.0 cm). The median follow-up duration for all cases was 40 months (range, 7–181 months). A total of 40 cases developed distant failure as the first site of failure: 13 of 36 (36.1%) SqCC cases had distant failure, with 9 of them with para-aortic lymph node (PALN) failure; 27 of 55 (44.0%) AC cases had distant failure, and 23 of them had distant failure excluding PALN metastasis. Distant failure rates of SqCC cases who had positive and negative PLNs before C-ion RT were 61.1% and 11.1%, respectively (P = 0.0045). Those of AC cases were 54.2% and 45.2%, respectively (P = 0.507). In conclusion, there were high rates of distant failure after C-ion RT in AC cases regardless of PLN status, and there were high rates of distant failure after C-ion RT, especially PALN failure, in SqCC cases with positive PLNs. PMID:25589503

  14. 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

  15. 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

  16. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Impact of Early Response to 4 Weeks of Treatment

    PubMed Central

    Lin, Chen-Chun; Hung, Chien-Fu; Chen, Wei-Ting; Lin, Shi-Ming

    2015-01-01

    Aim The aim of the study was to investigate the impact of early response (ER) to hepatic arterial infusion chemotherapy (HAIC) on outcomes of patients with advanced hepatocellular carcinoma (HCC) complicated with major portal vein tumor thrombosis (PVTT). Methods Thirty-nine patients receiving HAIC with low-dose cisplatin, 5-fluorouracil (5FU), and leucovorin were enrolled. One course of HAIC consisted of 5 days of treatment and 2 days rest per week for 4 consecutive weeks. ER was categorized as complete response, partial response, or minor response and was determined by World Health Organization criteria with dynamic computed tomography findings performed within 1 week after the first course of HAIC. Results Thirteen (33%) patients achieved an ER. Twelve (92.3%) of these 13 ER patients achieved a higher overall response than all but one (3.8%) of the 26 non-early responders (NERs) (p<0.001). ER was the exclusive independent favorable factor for survival (p=0.003). Downstaging of tumors was noted in 76.9% of ERs, and these patients could proceed to locoregional therapies. ER patients subsequently had a higher 1-year survival (76.9% vs. 3.8%, p<0.001) and 6-month progression-free survival (PFS) (84.6% vs. 15.4%, p<0.001) than those for NERs. Only 8% of patients experienced grade 3 or higher toxicity during the first 4-week course of HAIC. Conclusions HAIC can yield a satisfactory ER for advanced HCC with PVTT. Moreover, achievement of ER after HAIC in advanced HCC with PVTT is strongly associated with better overall survival and PFS. PMID:26734578

  17. Prognostic Value of Neoadjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma with Low Pre-treatment Epstein-Barr Virus DNA: a Propensity-matched Analysis

    PubMed Central

    Peng, Hao; Chen, Lei; Li, Wen-Fei; Guo, Rui; Zhang, Yuan; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Background: The aim of this study is to investigate the prognostic value of neoadjuvant chemotherapy (NCT) in locoregionally advanced nasopharyngeal carcinoma (NPC) with low pre-treatment Epstein-Barr virus (EBV) DNA in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 1099 locoregionally advanced NPC patients treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of covariates. Patient survival between NCT and non-NCT groups were compared. Results: The cut-off value of pre-treatment Epstein-Barr virus DNA (pre-DNA) was 1550 copies/ml for DMFS (area under curve [AUC], 0.655; sensitivity, 0.819; specificity, 0.445). For the 145 pairs selected by PSM, the 3-year distant metastasis-free survival (DMFS), overall survival (OS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates were 98.6% vs. 93.7% (P = 0.101), 95.8% vs. 94.4% (P = 0.881), 91.7% vs. 87.5% (P = 0.309) and 94.4% vs. 95.0% (P = 0.667), respectively. Multivariate analysis did not identify NCT as an independent prognostic factor (P > 0.05 for all rates), and stratified analysis based on overall stage (III and IV) and N category (N0-1 and N2-3) also got the same results. Conclusion: NCT was not established as an independent prognostic factor, and it should not be used in locoregionally advanced NPC with low pre-DNA. PMID:27471562

  18. Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method

    PubMed Central

    Fukubayashi, Kotaro; Tanaka, Motohiko; Izumi, Kazuhiro; Watanabe, Takehisa; Fujie, Satomi; Kawasaki, Takeshi; Yoshimaru, Yoko; Tateyama, Masakuni; Setoyama, Hiroko; Naoe, Hideaki; Kikuchi, Ken; Sasaki, Yutaka

    2015-01-01

    While sorafenib (SFN) is the established worldwide standard therapeutic agent for advanced hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) is also considered a favorable treatment for some advanced HCCs. This study aimed to evaluate each treatment and provide an optimal therapeutic choice for advanced HCCs. We analyzed 72 patients treated with SFN and 128 patients receiving HAIC. Both treatment groups were analyzed for prognostic and disease progression factors, and matched pair analysis was performed using the propensity score matching method. The preferable status of intrahepatic lesions, that is, no lesions or only a single (<3 cm) intrahepetic lesion, was positively associated with good prognosis and negatively associated with disease progression in the SFN group. Maximum tumor size (>5 cm) and low albumin (≤3.4 g/dL) were poor prognostic and disease progression factors in the HAIC group. Analysis of 53 patients selected from each of the SFN and HAIC groups based on the propensity score matching method showed no significant differences in survival or disease progression between the two matched subgroups. On the other hand, progression-free survival (PFS) in the HAIC-matched subgroup was significantly longer than in the SFN-matched subgroup, particularly in patients with portal vein invasion (PVI) and/or without extrahepatic spread (EHS). The treatment efficacy of HAIC is similar to that of SFN regarding survival and disease progression. Longer PFS might be expected for HAIC compared with SFN, particularly in patients with PVI and/or without EHS. PMID:26044168

  19. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

    PubMed Central

    2009-01-01

    Background Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC). Methods Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Results Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. Conclusion The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Trial registration Current Controlled Trials RPCEC00000052. PMID:19643007

  20. 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.

  1. 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

  2. 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.

  3. Resection of large epidermoid tumors ventral to the brainstem: techniques to expand the operative corridor across the basilar artery.

    PubMed

    Cohen-Gadol, Aaron A

    2014-01-01

    Epidermoid tumors comprise about 1% of all intracranial tumors. They are congenital lesions that arise from paramedian cisterns within the posterior fossa. These tumors present as heterogeneous hyperintense lesions on FLAIR and homogenous hyperintense lesions on DWI. Surgical resection remains the most accepted form of therapy, but epidermoid tumors may recur. These tumors are well exposed through a traditional retrosigmoid approach. The tumor can be removed relatively easily as it is avascular. However, the propensity of this tumor type to fill the small spaces within basal cisterns and attach to cranial nerves may make its complete resection challenging. Tumors resection has to preserve the surrounding arachnoid membranes encasing the cranial nerves. The author presents the case of a 42-year-old woman with a 1-year history of imbalance and nystagmus. An MRI revealed a large right-sided CP angle epidermoid tumor filling the ventral brainstem cistern and extending to the contralateral side, compressing the brainstem. The accompanying video illustrates resection of this mass through an extended (exposing the sigmoid sinus) retrosigmoid approach. The author removed the tumor piecemeal while protecting the cranial nerves. Small pieces of affected arachnoid covering the cranial nerves were not significantly manipulated. To excise the tumor along the contralateral paramedian cistern, the author used the space between the V and VII/VII cranial nerves to expose the space contralateral to the basilar artery and remove additional tumor. This maneuver allowed gross total resection of the tumor without a need to employ a more elaborate skull base approach such as petrosectomy. At 3-month follow-up visit after surgery, the patient's neurological exam returned to normal. The video can be found here: http://youtu.be/CzRb-GUvhog . PMID:24380510

  4. Phase I study of tivantinib in Japanese patients with advanced hepatocellular carcinoma: Distinctive pharmacokinetic profiles from other solid tumors.

    PubMed

    Okusaka, Takuji; Aramaki, Takeshi; Inaba, Yoshitaka; Nakamura, Shinichiro; Morimoto, Manabu; Moriguchi, Michihisa; Sato, Takashi; Ikawa, Yuta; Ikeda, Masafumi; Furuse, Junji

    2015-05-01

    A c-Met inhibitor tivantinib is a candidate anticancer agent for patients with hepatocellular carcinoma (HCC), and CYP2C19 is the key metabolic enzyme for tivantinib. Previous Japanese phase I studies in patients with solid tumors (except HCC) recommend 360 mg twice daily (BID) and 240 mg BID for CYP2C19 extensive metabolizers (EM) and poor metabolizers (PM), respectively. In this study, Japanese patients with HCC in whom sorafenib treatment has failed were enrolled to evaluate the safety, tolerability and pharmacokinetics of oral tivantinib as a single agent. The dose was escalated separately in EM and PM, from 120 mg BID to 240 mg BID, in both capsule and tablet formulations. A total of 28 patients (EM: 21, PM: 7) received tivantinib. At a dose of 120 mg BID, dose-limiting toxicities (DLT) did not develop in 12 EM (capsule: 6, tablet: 6) and 7 PM (capsule: 4, tablet: 3) during the DLT-observation period (for 29 days after first dosing). At this dose, the pharmacokinetic profiles of tivantinib (AUC0-12 and Cmax ) did not remarkably differ between EM and PM. When treated with 240 mg BID, 5 of 9 EM (capsule: 4 of 6, tablet: 1 of 3) developed neutropenia-related DLT accompanying plasma tivantinib concentration higher than expected from the previous studies. Consequently, PM did not receive 240 mg BID. In conclusion, 120 mg BID of tivantinib is recommended among Japanese patients with HCC regardless of CYP2C19 phenotype. PMID:25711511

  5. Establishment of a Cell Line (CNUH-HNSCC-1) Derived from an Advanced Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Lee, Dong-Hoon

    2011-01-01

    Cancer cell lines are the basic material for various lines of cancer research. Diverse cancer cell lines derived from tissues of various head and neck regions are needed for biological research on head and neck cancer. However, cell lines derived from cancer of the head and neck are not common. Recently, we established and characterized a novel human squamous carcinoma cell line, CNUH-HNSCC-1. From six cases of head and neck cancer, we established one specimen that was maintained for over 50 passages. We characterized the cell line as follows: growth patterns and curve, morphology by use of phase-contrast microscopy, and tumorigenicity by implanting the cell line into nude mice and making morphological comparisons. CNUH-HNSCC-1 cells grew well in vitro even after passage 50. However, the cells failed to form tumors in nude mice. CNUH-HNSCC-1 cells could be used as a control cell line for studying the biology of head and neck cancer. PMID:22111066

  6. 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. PMID:22727410

  7. Concomitant chemoradiotherapy using low-dose weekly gemcitabine versus low-dose weekly paclitaxel in locally advanced head and neck squamous cell carcinoma: a phase III study.

    PubMed

    Halim, Amal Ahmed-Fouad; Wahba, Hanan Ahmed; El-Hadaad, Hend Ahmed; Abo-Elyazeed, Ahmed

    2012-03-01

    The objective of this study was to compare concomitant chemoradiotherapy based on weekly low-dose gemcitabine versus weekly low-dose paclitaxel in locally advanced head and neck squamous cell carcinoma. Previously, untreated patients with locally advanced squamous cell carcinoma of the head and neck were randomly assigned to one of the two concomitant chemoradiation regimens: (1) weekly gemcitabine at a dose of 100 mg/m(2) over 30 min 1-2 h before radiotherapy and (2) weekly paclitaxal at a dose of 20 mg/m(2) over 60 min 4-6 h before radiotherapy. The planned radiotherapy dose was 65 Gy over 6.5 weeks in 32 settings. Two hundred and sixteen patients were randomly divided into 2 groups: group A (110 patients) and group B (106 patients) who received concomitant weekly low-dose gemcitabine and low-dose paclitaxal, respectively, with the radiotherapy protocol. The hematological toxicity was generally mild. On the contrary, non-hematologic toxicities were severe. Grade III mucositis occurred in 36% in group A and in 24% in group B (P = 0.04). Moreover, grade III dermatitis were encountered in 24% in group A and 13% in group B (P = 0.049). Thirty-two (29%) of group A and 18(17%) of group B patients required enteral or parenteral feeding (P = 0.01). Sixteen (15%) of group A and 6 (6%) of group B required enteral or parenteral feeding that lasted for 6 months (P = 0.03). Regarding the late effect on swallowing, 8% of patients in group A and 2% of patients in group B required enteral or parenteral feeding for more than 6 months (P = 0.035). Response rates were 78 and 89% in groups A and B, respectively (P = 0.038). The 2-year progression-free survival figures were 54 and 64% of groups A and B, respectively; however, the 2-year overall survival figures were 56 and 67%, respectively. On the other hand, the 3-year progression-free survival figures were 39 and 48% for groups A and B, respectively, while the 3-year overall survival figures were 45 and 49%, respectively (P = 0

  8. A randomized prospective study of comparison of reservoir ports versus conventional vascular access in advanced-stage ovarian carcinoma cases treated with chemotherapy.

    PubMed

    Sehirali, S; Inal, M M; Ozsezgin, S; Sanci, M; Atli, O; Nayki, C; Yildirim, Y; Tinar, S

    2005-01-01

    Vascular access ports were developed to overcome many of the problems associated with limited peripheral access, combined with the need for frequent venipuncture, in oncology patients receiving long-term intensive therapy. In this study, we compared the effectivity and acceptability of vascular access port with conventional needle application together with complication rates in ovarian cancer patients. Advanced-stage ovarian carcinoma cases under chemotherapy treatment were equally randomized into two groups, implantable vascular access ports applied to one group (22 cases) and conventional vascular access applied to the other (38 cases) as a control group. Anteroposterior thoracic X-rays of implantable port-applied cases were taken before and after the application. Vortex reservoir ports (Horizon Medical Products, Inc., Manchester, GA) were used in the application to the subclavian vein. Classic peripheral venipuncture method (Medikit), Mediflon(trade mark) IV cannula with PTFE radiopaque catheter and injection valve, Eastern Medikit Ltd, Gurgaon, Haryana, India) was used in the control group. Vascular accesses of all cases were controlled just after the application, 12 h after the application, and during each drug or intravenous fluid application. Mean port insertion time was 26.3 min. Total port occlusion was observed in two of the port-applied cases (11.7%) and partial port occlusion was observed in five of the port-applied cases (29%). Heparin and saline combination was used in order to open the port tip, in five cases, two with total occlusion and three with partial occlusion. Infection was observed in only one case (5%) to whom appropriate therapy was given, and the port was taken out. Ports of two cases were also taken out because of skin dehiscence. No change in port tip position was observed in any of the cases. Total occlusion was observed in 16 of the 38 cases (42.1%) with conventional vascular access. In 12 cases (31.5%), a need arose to change the

  9. 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

  10. Volume and dosimetric variations during two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

    PubMed

    Wang, Rui-hao; Zhang, Shu-xu; Zhou, Ling-hong; Zhang, Guo-qian; Yu, Hui; Lin, Xiao-dan; Lin, Shengqu

    2014-01-01

    The aims of this study were to evaluate the volume and dosimetric variations during IMRT for locally advanced NPC and to identify the benefits of a two-phase adaptive IMRT method. Twenty patients with locally advanced NPC having received IMRT treatment were included. Each patient had both an initial planning CT (CT-1) and a repeated CT scan (CT-2) after treatment at a dose of 40 Gy. Three IMRT planning scenarios were compared: (1) the initial plan on the CT-1 (plan-1); (2) the hybrid plan recalculated the initial plan on the CT-2 (plan-2); (3) the replan generated on the CT-2 being used to complete the course of IMRT (plan-3). The mean gross target volume and mean volumes of the positive neck lymph nodes, high-risk clinical target volume, and the left and right parotid glands significantly decreased by 30.2%, 45.1%, 21.1%, 14.7% and 18.2%, respectively on the CT-2. Comparing plan-2 with plan-1, the dose coverage of the targets remained unchanged, whereas the dose delivered to the parotid glands and spinal cord increased significantly. These patients with locally advanced NPC might benefit from replanning because of the sparing of the parotid glands and spinal cord. PMID:24212016

  11. Efficacy of combination treatment modalities for intermediate and advanced hepatocellular carcinoma: intra-arterial therapies, sorafenib and novel small molecules

    PubMed Central

    Gutierrez, Julio A.; Gish, Robert G.

    2015-01-01

    Hepatocellular carcinoma (HCC) is a growing epidemic with a high mortality rate and clear need for improved therapies. In patients with Barcelona-Clinic Liver Cancer (BCLC) B and C, treatment with transarterial chemoembolization (TACE) has been the gold standard in therapy as it delays progression; however, recurrence proves common. In the US, transarterial bead embolization (TABE) has uniformly replaced TACE. With this limited armamentarium, there is need for a shift to novel strategies combining different modalities to further improve patient outcomes. Historically, HCC drug discovery concentrated on common features of HCC including its highly vascular nature and dependence on growth factors (GFs). The multikinase inhibitor sorafenib acts on angiogenesis via modulation of vascular endothelial GF expression and was the first step toward systemic targeted therapy against HCC. Sorafenib has provided clinicians with a tool to modestly improve survival by 2–6 months or longer. Despite the progress in survival provided by TACE, TABE and sorafenib independently, rigorous combination clinical trials do not consistently show significant improvement over TACE/TABE monotherapy. Other novel small molecules targeting angiogenesis such as brivanib, linifanib and everolimus have failed or are in development. Anti-HCV treatment became more feasible with the novel direct-acting antiviral agents; with the much higher and more durable treatment responses that they provide, the risk of HCC progression may be reduced. The most effective strategies in developing combination therapies are hampered by the complexities of FDA testing along with intellectual property and economic issues. To achieve significant progress, more basic science studies are necessary to help understand which novel molecules demonstrate the greatest synergy. Individual patient genomic profiling and biomarkers may help guide therapy and improve the clinician’s ability to tailor treatment and to know when it

  12. 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

  13. 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

  14. 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

  15. Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma.

    PubMed

    Hong, Ying-Fen; Chen, Zhan-Hong; Ma, Xiao-Kun; Li, Xing; Wu, Dong-Hao; Chen, Jie; Dong, Min; Wei, Li; Wang, Tian-Tian; Ruan, Dan-Yun; Lin, Ze-Xiao; Wen, Jing-Yun; Lin, Qu; Jia, Chang-Chang; Wu, Xiang-Yuan

    2016-04-01

    Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients

  16. Identification of potential erythrocyte phospholipid fatty acid biomarkers of advanced lung adenocarcinoma, squamous cell lung carcinoma, and small cell lung cancer.

    PubMed

    Sánchez-Rodríguez, Patricia; Rodríguez, Marina C; Sánchez-Yagüe, Jesús

    2015-07-01

    New biomarkers for lung cancer would be valuable. Our aim was to analyze the fatty acid profiles of the main phospholipid species in erythrocytes from patients with advanced squamous cell lung carcinoma (SCC), lung adenocarcinoma (ADC), and small cell lung cancer (SCLC) and benign lung diseases (chronic obstructive pulmonary disease (COPD) and asthma) to determine the fatty acids that could be use as lung cancer markers. Twenty-eight, 18, 14, 16, and 15 patients with, respectively, SCC, ADC, SCLC, asthma, and COPD and 50 healthy subjects were enrolled in the study. Fatty acid profiles were investigated using gas chromatography/mass spectrometry followed by receiver operating characteristic (ROC) curve analysis. The fatty acid profiles changed significantly in the different pathologies analyzed. Based on the diagnostic yields and operating characteristics, the most significant fatty acids that might be used as biomarkers were as follows: ADC--arachidonic acid (20:4n6) in phosphatidylcholine and oleic acid (18:1n9) in phosphatidylethanolamine (PE); SCC--eicosapentaenoic acid (20:5n3) in PE and palmitic acid (16:0) in phosphatidylserine + phosphatidylinositol (PS+PI); SCLC--eicosadienoic acid (20:2n6) in PS+PI and lignoceric acid (24:0) in sphingomyelin. In conclusion, fatty acids from erythrocyte phospholipid species might serve as biomarkers in the diagnosis, and probably in other aspects related to clinical disease management, of ADC, SCC, and SCLC. PMID:25702090

  17. Prognostic Value of Neutrophil-Related Factors in Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin-Based Concurrent Chemoradiotherapy

    PubMed Central

    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. PMID:27087737

  18. Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy

    PubMed Central

    Chen, Y; Pithavala, YK; Nickens, DJ; Valota, O; Amantea, MA

    2016-01-01

    A mixed effect model describing median overall survival (mOS) in patients with advanced hepatocellular carcinoma (aHCC) treated with antiangiogenic therapy (AAT) was developed from literature data. Data were extracted from 59 studies, representing 4,813 patients. The final model included estimates of mOS after AAT (8.5 months) or placebo (7.1 months) administration. The mOS increased 21% when the AAT was sorafenib (SOR) or 42% when locoregional therapy was coadministered. The mOS decreased when patients received prior systemic therapy (↓7%) or concomitant chemotherapy (↓4%) or the percentage of patients with hepatitis B increased (↓∼0.4%/%). Clinical trial simulations of a phase II comparative trial predicted an mOS ratio (placebo:AAT) of 0.687 or 0.831, with a 65% or 22% probability of demonstrating superiority, for SOR or other AATs, respectively. Additionally, the 95% confidence interval (CI) of the simulated median mOS ratio for non‐SOR AATs was similar to the 95% CI of the hazard ratio (HR) observed in the trial. PMID:27299940

  19. Clinical Trial Simulations From a Model-Based Meta-Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy.

    PubMed

    Zierhut, M L; Chen, Y; Pithavala, Y K; Nickens, D J; Valota, O; Amantea, M A

    2016-05-01

    A mixed effect model describing median overall survival (mOS) in patients with advanced hepatocellular carcinoma (aHCC) treated with antiangiogenic therapy (AAT) was developed from literature data. Data were extracted from 59 studies, representing 4,813 patients. The final model included estimates of mOS after AAT (8.5 months) or placebo (7.1 months) administration. The mOS increased 21% when the AAT was sorafenib (SOR) or 42% when locoregional therapy was coadministered. The mOS decreased when patients received prior systemic therapy (↓7%) or concomitant chemotherapy (↓4%) or the percentage of patients with hepatitis B increased (↓∼0.4%/%). Clinical trial simulations of a phase II comparative trial predicted an mOS ratio (placebo:AAT) of 0.687 or 0.831, with a 65% or 22% probability of demonstrating superiority, for SOR or other AATs, respectively. Additionally, the 95% confidence interval (CI) of the simulated median mOS ratio for non-SOR AATs was similar to the 95% CI of the hazard ratio (HR) observed in the trial. PMID:27299940

  20. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages

    PubMed Central

    Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection. PMID:27454179

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization.

    PubMed

    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

  6. 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

  7. 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

  8. Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma.

    PubMed

    Zhong, Lai-ping; Zhang, Chen-ping; Ren, Guo-xin; Guo, Wei; William, William N; Hong, Christopher S; Sun, Jian; Zhu, Han-guang; Tu, Wen-yong; Li, Jiang; Cai, Yi-li; Yin, Qiu-ming; Wang, Li-zhen; Wang, Zhong-he; Hu, Yong-jie; Ji, Tong; Yang, Wen-jun; Ye, Wei-min; Li, Jun; He, Yue; Wang, Yan-an; Xu, Li-qun; Zhuang, Zhengping; Lee, J Jack; Myers, Jeffrey N; Zhang, Zhi-yuan

    2015-07-30

    Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC. PMID:26124084

  9. 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.

  10. Changes in plasma vascular endothelial growth factor at 8 weeks after sorafenib administration as predictors of survival for advanced hepatocellular carcinoma

    PubMed Central

    Tsuchiya, Kaoru; Asahina, Yasuhiro; Matsuda, Shuya; Muraoka, Masaru; Nakata, Toru; Suzuki, Yuichiro; Tamaki, Nobuharu; Yasui, Yutaka; Suzuki, Shoko; Hosokawa, Takanori; Nishimura, Takashi; Ueda, Ken; Kuzuya, Teiji; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Kurosaki, Masayuki; Enomoto, Nobuyuki; Izumi, Namiki

    2014-01-01

    Background A new predictive biomarker for determining prognosis in patients with hepatocellular carcinoma (HCC) who receive sorafenib is required, because achieving a reduction in tumor size with sorafenib is rare, even in patients who have a favorable prognosis. Vascular endothelial growth factor (VEGF) receptor is a sorafenib target. In the current study, the authors examined changes in plasma VEGF concentrations during sorafenib treatment and determined the clinical significance of VEGF as a prognostic indicator in patients with HCC. Methods Plasma VEGF concentrations were serially measured in 63 patients with advanced HCC before and during sorafenib treatment. A plasma VEGF concentration that decreased >5% from the pretreatment level at 8 weeks was defined as a “VEGF decrease.” An objective tumor response was determined using modified Response Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and every 3 months thereafter. Results Patients who had a VEGF decrease at week 8 (n = 14) had a longer median survival than those who did not have a VEGF decrease (n = 49; 30.9 months vs 14.4 months; P = .038). All patients who had a VEGF decrease survived for >6 months, and the patients who had both a VEGF decrease and an α-fetoprotein response (n = 6) survived during the observation period (median, 19.7 months; range, 6.5-31.0 months). In univariate analyses, a VEGF decrease, radiologic findings classified as progressive disease, and major vascular invasion were associated significantly with 1-year survival; and, in multivariate analysis, a VEGF decrease was identified as an independent factor associated significantly with survival. Conclusions A plasma VEGF concentration decrease at 8 weeks after starting sorafenib treatment may predict favorable overall survival in patients with advanced HCC. PMID:24122122

  11. 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.

  12. SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

    PubMed Central

    Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

    2015-01-01

    Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

  13. A single arm phase 1b study of everolimus and sunitinib in patients with advanced renal cell carcinoma (RCC)

    PubMed Central

    Kanesvaran, R.; Watt, K.; Turnbull, J. D.; Armstrong, A. J.; Cohen-Wolkowiez, M.; George, D. J.

    2016-01-01

    Background Everolimus ,an oral inhibitor of mammalian target of rapamycin (mTOR), and sunitinib, an oral inhibitor of VEGF/PDGF receptor tyrosine kinase signaling, have both been shown to provide clinical benefit in patients with advanced RCC. We sought to determine the safety and efficacy of combination therapy with these agents in patients with advanced RCC. Methods We conducted a phase Ib dose escalation trial of sunitinib and everolimus in patients with advanced metastatic RCC. Prior nephrectomy was required, and prior radiation or chemotherapy other than VEGF/mTOR-based therapies was permitted. The primary endpoint was to determine the MTD/recommended phase 2 dose. Results A total of 4 out of a planned 30 subjects were enrolled in this study (M:F= 2:2; mean age 52 years, 50% with KPS <80). The first three patients were enrolled on a 4+2 dosing schedule of daily sunitinib 50 mg and weekly everolimus 30 mg. Mean time on drug was 99 days. One partial response was seen. Toxicities included mucositis, thrombocytopenia, anemia, fatigue, dehydration and hypoglycemia. Due to multiple grade 3–4 toxicities, the protocol was amended to 2+1 dosing of sunitinib 37.5 mg and daily everolimus 5mg. The first patient on this schedule died from multi-organ failure with septic shock after 1 cycle of treatment. Subsequently, the study was closed. Pharmacokinetics results inconclusively suggest that toxicities could be attributed to the drug exposure. Conclusions Combined use of everolimus and sunitinib in the treatment of mRCC was not well tolerated in this small cohort. PMID:26174223

  14. 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.

  15. 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

  16. Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index

    PubMed Central

    Chen, Jin-Hua; Yen, Yu-Chun; Yang, Hsuan-Chia; Liu, Shing-Hwa; Yuan, Sheng-Po; Wu, Li-Li; Lee, Fei-Peng; Lin, Kuan-Chou; Lai, Ming-Tang; Wu, Chia-Che; Chen, Tsung-Ming; Chang, Chia-Lun; Chow, Jyh-Ming; Ding, Yi-Fang; Wu, Szu-Yuan

    2016-01-01

    Abstract For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival. Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0–148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments). We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31–0.35), 0.34 (0.31–0.36), and 0.37 (0.28–0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82–1.55), 0.67 (0.62–0.73), and 0.49 (0.46–0.53) for CCI scores of ≥10, 5 to 9, and <5, respectively. Aggressive treatments improve survival in elderly (≥65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for

  17. Treatment of Advanced Pancreatic Carcinoma with 90Y-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial

    PubMed Central

    Gulec, Seza A.; Cohen, Steven J.; Pennington, Kenneth L.; Zuckier, Lionel S.; Hauke, Ralph J.; Horne, Heather; Wegener, William A.; Teoh, Nick; Gold, David V.; Sharkey, Robert M.; Goldenberg, David M.

    2014-01-01

    Purpose Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of 90Y-clivatuzumab tetraxetan (90Y-labeled hPAM4) in patients with advanced pancreatic cancer. Experimental Design Twenty-one patients (4 stage III; 17 stage IV) received 111In-hPAM4 for imaging and serum sampling before 90Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). Results 111In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before 90Y-hPAM4; otherwise, 20 patients received 90Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m2 (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with 90Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m2 encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m2 as the maximal tolerated 90Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%–52% tumor diameter shrinkage). Conclusion 90Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated 90Y dose, and is a potential new therapeutic for advanced pancreatic cancer. PMID:21527562

  18. Prospective Study of Transcatheter Arterial Chemoembolization (TACE) with Ginsenoside Rg3 versus TACE Alone for the Treatment of Patients with Advanced Hepatocellular Carcinoma.

    PubMed

    Zhou, Bo; Yan, Zhiping; Liu, Rong; Shi, Peng; Qian, Sheng; Qu, Xudong; Zhu, Liang; Zhang, Wei; Wang, Jianhua

    2016-08-01

    Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age ± standard deviation, 52.4 years ± 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years ± 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may

  19. 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.

  20. Brain metastases from ovarian carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2011-01-01

    This paper will focus on knowledge related to brain metastases from ovarian carcinoma. So far, less than 600 cases were documented in the literature with an incidence among ovarian carcinoma patients ranging from 0.29% to 11.6%. The ovarian carcinoma was usually an advanced-stage epithelial serous carcinoma, and the median interval between diagnosis of ovarian carcinoma and brain metastases was 2 years. Most often, brain metastases, affected the cerebrum, were multiple and part of a disseminated disease. Treatment of brain metastasis has evolved over the years from whole brain radiotherapy (WBRT) only to multimodal therapy including surgical resection or stereotactic radiosurgery followed by WBRT and/or chemotherapy. The median survival after diagnosis of brain metastases was 6 months; nevertheless, a significantly better survival was achieved with multimodal therapy compared to WBRT only. It is suggested that brain imaging studies should be included in the followup of patients after treatment for ovarian carcinoma. PMID:22191058

  1. Split hyperfractionated accelerated radiation therapy and concomitant cisplatin for locally advanced head and neck carcinomas: A preliminary report

    SciTech Connect

    Arias, F.; Dominguez, M.A.; Illarramendi, J.J.

    1995-10-15

    The feasibility and activity of an intensive chemoradiotherapeutic scheme for patients with locally advanced squamous cell head and neck cancers were tested in a single institution Phase II pilot study. Between January 1990 and February 1992, 40 patients were entered into this trial. The treatment protocol consisted of split hyperfractionated accelerated radiation therapy (SHART), 1.6 Gy per fraction given twice per day to a total dose of 64-67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin (20 mg/sqm/Days 1 to 5, in continuous perfusion) concomitantly. All of the 40 patients are evaluable for response and survival. Toxicity was significant, but tolerable. A complete tumor response to this treatment was achieved by 37 patients (92.5%). With a minimal follow-up of 22 months (median 30 months) there have been 16 local relapses and 19 patients have died, 2 without tumor. The projected 2- and 3-year overall survival rates are 64% (confidence interval (CI) 95%, 49-79%) and 47%, respectively. The 2-year local control probability has been 56% (CI 95, 39-73%). This treatment obtains a high rate of complete responses with increased acute toxicity but tolerable late effects. Preliminary results are encouraging for laryngeal neoplasms. A longer follow-up is needed to evaluate the impact of this treatment on patient survival. 47 refs., 3 figs., 3 tabs.

  2. 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.

  3. Phase I Trials in Patients with Relapsed, Advanced Upper Gastrointestinal Carcinomas – Experience in a Specialist Unit

    PubMed Central

    Starling, Naureen; Sclafani, Francesco; Shah, Krunal; Judson, Ian; Molife, L Rhoda; Banerji, Udai; de Bono, Johann S; Cunningham, David; Kaye, Stan B

    2016-01-01

    Background Conventional therapeutic options for patients with advanced upper gastrointestinal cancers (UGIC) are limited. Following first-line treatments, some patients are offered experimental therapies, including participation in Phase I trials. This study aims to describe the experience of UGIC patients treated in a dedicated Phase I unit. Methods Patient, tumour and treatment characteristics, and clinical outcomes of UGIC patients treated consecutively at the Drug Development Unit, Royal Marsden Hospital, between 2005 and 2009, were recorded. Results Ninety-six patients who previously received a median of 2 [range 1-4] lines of chemotherapies were treated in 30 Phase I trials. Of 81 evaluable patients, 9 achieved RECIST-objective response (11%) with a 6-month clinical benefit rate of 14%. Overall median progression free and overall survival were 7.0 weeks (95%CI: 5.6-8.4) and 19.0 weeks (95%CI: 17.4-20.6), respectively. Grade 3 or 4 toxicities were observed in 37 patients (39%) and led to trial discontinuation in 9 (9%); no toxicity-related death was recorded. In the multivariate analysis, serum albumin (<35g/dl, HR2.0, p=0.002) and lactate dehydrogenase (>192umol/l, HR1.7, p=0.016) were prognostic of overall survival. Conclusion Phase I clinical trials can be considered a reasonable option in selected patients with relapsed UGIC. The use of objective prognosticators may improve selection and risk/benefit profile of patients. Mini-Abstract There are no published data on the experience of phase I trials in UGIC. We present largest data of treating UGIC in phase I setting confirming the feasibility of this approach. PMID:24445485

  4. Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma : a NICE single technology appraisal.

    PubMed

    Kilonzo, Mary; Hislop, Jenni; Elders, Andrew; Fraser, Cynthia; Bissett, Donald; McClinton, Samuel; Mowatt, Graham; Vale, Luke

    2013-01-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute's single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE's subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies

  5. Adrenocortical carcinoma

    MedlinePlus

    ... JavaScript. Adrenocortical carcinoma is a cancer of the adrenal glands . Causes Adrenocortical carcinoma is most common in children ... tumor. Symptoms Symptoms of increased cortisol or other adrenal gland hormones: Fatty, rounded hump high on the back ...

  6. A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

    PubMed Central

    Rigg, A.; Cunningham, D.; Gore, M.; Hill, M.; O'Brien, M.; Nicolson, M.; Chang, J.; Watson, M.; Norman, A.; Hill, A.; Oates, J.; Moore, H.; Ross, P.

    1997-01-01

    Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5). PMID:9000605

  7. The Clinical Usefulness of 18F-Fluorodeoxyglucose Positron Emission Tomography (PET) to Predict Oncologic Outcomes and PET-Based Radiotherapeutic Considerations in Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Yoon, Hong In; Kim, Kyung Hwan; Lee, Jeongshim; Roh, Yun Ho; Yun, Mijin; Cho, Byoung Chul; Lee, Chang Geol; Keum, Ki Chang

    2016-01-01

    Purpose We investigated 18F-fluorodeoxyglucose positron emission tomography (PET)-derived parameters as prognostic indices for disease progression and survival in locally advanced nasopharyngeal carcinoma (NPC) and the effect of high-dose radiotherapy for a subpopulation with PET-based poor prognoses. Materials and Methods Ninety-seven stage III and Iva-b NPC patients who underwent definitive treatment and PET were reviewed. For each primary, nodal, and whole tumor, maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) were evaluated. Results Based on the C-index (0.666) and incremental area under the curve (0.669), the whole tumor TLGwas the most useful predictorfor progression-free survival (PFS); thewhole tumor TLG cut-off value showing the best predictive performance was 322.7. In multivariate analysis, whole tumor TLG was a significant prognostic factor for PFS (hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.14 to 0.65; p=0.002) and OS (HR, 0.29; 95% CI, 0.11 to 0.79; p=0.02). Patients with low whole tumor TLG showed the higher 5-year PFS in the subgroup for only patients receiving intensity modulated radiotherapy (77.4% vs. 53.0%, p=0.01). In the subgroup of patients with high whole tumor TLG, patients receiving an EQD2 ≥ 70 Gy showed significantly greater complete remission rates (71.4% vs. 33.3%, p=0.03) and higher 5-year OS (74.7% vs. 19.6%, p=0.02). Conclusion Our findings demonstrated that whole tumor TLG could be an independent prognostic factor and high-dose radiotherapy could improve outcomes for NPC showing high whole tumor TLG. PMID:26693913

  8. 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.

  9. 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

  10. A Phase II Clinical Trial of Concurrent Helical Tomotherapy plus Cetuximab Followed by Adjuvant Chemotherapy with Cisplatin and Docetaxel for Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Xinxin; Du, Lei; Zhao, Feifang; Wang, Qiuju; Yang, Shiming; Ma, Lin

    2016-01-01

    Purpose: The present clinical trial was designed to evaluate the efficacy and safety of concurrent helical tomotherapy (HT) with cetuximab followed by adjuvant chemotherapy with docetaxel and cisplatin (TP) in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Materials and Methods: This phase II clinical trial included 43 patients with Stage III/IV LANC (33 Stage III and 10 Stage IV). The treatment consisted of concurrent HT with cetuximab (400 mg/m2 loading dose and weekly 250mg/m2), followed by four cycles of chemotherapy [docetaxel (70 mg/m2 on Day 1) and cisplatin (40 mg/m2 on Days 1 and 2 every 3 weeks). Side effects were evaluated with CTCAE criteria (Common Terminology Criteria for Adverse Events 3.0). Results: The median follow-up duration was 48.0 months [95% confidence interval (CI) 41.7-58.0 months], the 2-year locoregional failure-free rate (LFFR), progression-free survival (PFS), distant failure-free rate (DFFR) and overall survival (OS) were 95.2%, 79.1%, 88.1% and 93.0% respectively; the 3-year LFFR, DFFR, PFS and OS were 92.7%, 85.6%, 72.0% and 85.7% respectively. The most common grade 3 toxicities were oropharyngeal mucositis (81.4%) and RT-related dermatitis (7.0%). No patients had more than grade 3 radiation related toxicities and no patients required nasogastric feeding. One patient experienced grade 3 osteonecrosis at 18 months after treatment. Conclusions: Concurrent HT with cetuximab followed by adjuvant chemotherapy with TP is an effective strategy for the treatment of LANC with encouraging survival rates and minimal side effects. PMID:27019628

  11. 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

  12. Induction of thymidine phosphorylase as a pharmacodynamic end-point in patients with advanced carcinoma treated with 5-fluorouracil, folinic acid and interferon alpha

    PubMed Central

    Braybrooke, J P; Propper, D J; O’Byrne, K J; Koukourakis, M I; Patterson, A V; Houlbrook, S; Love, S D; Varcoe, S; Taylor, M; Ganesan, T S; Talbot, D C; Harris, A L

    2000-01-01

    Thymidine phosphorylase (TP) is an essential enzyme for the biochemical activation of 5-fluorouracil (5-FU). Interferon upregulates TP in vivo, although the dose and schedule of interferon for optimal biomodulation of 5-FU is not known. In this study, TP activity was measured in peripheral blood lymphocytes (PBLs) from patients with advanced carcinoma receiving treatment with 5-FU and folinic acid. Cohorts of patients were treated with interferon alpha (IFNα), immediately prior to 5-FU/folinic acid, at doses of 3 MIU m–2, 9 MIU m–2and 18 MIUm–2. IFNα was administered on day 0 cycle two, day –1 and day 0 cycle three and day –2, day –1 and day 0 cycle four. A fourth cohort was treated with IFNα 9 MIU m–2three times per week from cycle 2 onwards. Twenty-one patients were entered into the study with 19 evaluable for response. Six patients (32%) had stable disease and 13 (68%) progressive disease. There were no grade-IV toxicities. TP activity was detected in PBLs from all patients with wide interpatient variability in constitutive TP activity prior to chemotherapy, and in response to IFNα. 5-FU/folinic acid alone did not induce TP activity but a single dose of IFNα led to upregulation of TP within 2 h of administration with a further increase by 24 h (signed rank test, P = 0.006). TP activity remained elevated for at least 13 days (signed rank test, P = 0.02). There were no significant differences in TP activity between schedules or with additional doses of IFNα. A single dose of IFNα as low as 3 MIU m–2can cause sustained elevation of PBL TP activity in vivo indicating that biochemical markers are important pharmacodynamic endpoints for developing optimal schedules of IFNα for biomodulation of 5-FU. © 2000 Cancer Research Campaign PMID:10901374

  13. Impact of Metronomic UFT/Cyclophosphamide Chemotherapy and Antiangiogenic Drug Assessed in a New Preclinical Model of Locally Advanced Orthotopic Hepatocellular Carcinoma1

    PubMed Central

    Tang, Terence C; Man, Shan; Lee, Christina R; Xu, Ping; Kerbel, Robert S

    2010-01-01

    Hepatocellular carcinoma (HCC) is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce the extensive liver disease associated with HCC or metastasize. To address this deficiency, we developed an orthotopic model. Human HCC cells were transfected with the gene encoding secretable β-subunit human choriogonadotropin (β-hCG), which was used as a surrogate marker of tumor burden. The HCC cells were implanted into the left liver lobe of severe combined immunodeficient (SCID) mice, after which the efficacy of different therapies was evaluated on established, but liver-confined human Hep3B cell line HCC. Treatments included sorafenib or metronomic chemotherapy using cyclophosphamide (CTX), UFT, an oral 5-fluorouracil prodrug, or doxorubicin either alone or in various combinations, with or without an antiangiogenic agent, DC101, an anti-vascular endothelial growth factor receptor-2 antibody. Sorafenib inhibited tumor growth in a dose-dependent manner but caused severe weight loss in SCID mice, thus necessitating use of DC101 in subsequent experiments. Although less toxicity was observed using either single or doublet metronomic chemotherapy without any added antiangiogenic agent, none, provided survival benefit. In contrast, significantly improved overall survival was observed using various combinations of metronomic chemotherapy regimens such as UFT + CTX with DC101. In conclusion, using this model of liver-confined but advanced HCC suggests that the efficacy of a targeted antiangiogenic drug or metronomic chemotherapy can be mutually enhanced by concurrent combination treatment. PMID:20234820

  14. Randomized study of sinusoidal chronomodulated versus flat intermittent induction chemotherapy with cisplatin and 5-fluorouracil followed by traditional radiotherapy for locoregionally advanced nasopharyngeal carcinoma

    PubMed Central

    Lin, Huan-Xin; Hua, Yi-Jun; Chen, Qiu-Yan; Luo, Dong-Hua; Sun, Rui; Qiu, Fang; Mo, Hao-Yuan; Mai, Hai-Qiang; Guo, Xiang; Xian, Li-Jian; Hong, Ming-Huang; Guo, Ling

    2013-01-01

    Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma (NPC). Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear. This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) and 5-fluorouracil (5-FU) followed by radiotherapy in patients with locoregionally advanced NPC. Patients with biopsy-diagnosed untreated stages III and IV NPC (according to the 2002 UICC staging system) were randomized to undergo 2 cycles of sinusoidal chronomodulated infusion (Arm A) or flat intermittent constant rate infusion (Arm B) of DDP and 5-FU followed by radical radiotherapy. Using a “MELODIE” multi-channel programmed pump, the patients were given 12-hour continuous infusions of DDP (20 mg/m2) and 5-FU (750 mg/m2) for 5 days, repeated every 3 weeks for 2 cycles. DDP was administered from 10:00 am to 10:00 pm, and 5-FU was administered from 10:00 pm to 10:00 am each day. Chronomodulated infusion was performed in Arm A, with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm. The patients in Arm B underwent a constant rate of infusion. Radiotherapy was initiated in the fifth week, and both arms were treated with the same radiotherapy techniques and dose fractions. Between June 2004 and June 2006, 125 patients were registered, and 124 were eligible for analysis of response and toxicity. The major toxicity observed during neoadjuvant chemotherapy was neutropenia. The incidence of acute toxicity was similar in both arms. During radiotherapy, the incidence of stomatitis was significantly lower in Arm A than in Arm B (38.1% vs. 59.0%, P = 0.020). No significant differences were observed for other toxicities. The 1-, 3-, and 5-year overall survival rates were 88.9%, 82.4%, and 74.8% for Arm A and 91.8%, 90.2%, and 82.1% for Arm B. The 1-, 3-, and 5-year progression-free survival rates were 91

  15. Details of out-field regional recurrence after involved-field irradiation with concurrent chemotherapy for locally advanced esophageal squamous cell carcinoma

    PubMed Central

    Zhang, Xiaoli; Yu, Jinming; Li, Minghuan; Zhu, Hui

    2016-01-01

    Background The purpose of this study was to describe the patterns of out-field regional recurrence after involved-field irradiation (IFI) in definitive concurrent chemoradiotherapy (CCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) and identify the possible risk factors. Patients and methods Eighty patients with LA-ESCC who received CCRT with IFI between January 2003 and January 2009 at the Shandong Cancer Hospital were recruited and analyzed. Imaging scans demonstrating first sites of failure were compared with original computed tomography-based radiation treatment plans, and failure patterns were defined as in-field, outfield regional (failures in initially uninvolved regional nodes), and distant failures. Results After a median follow-up time of 52.6 months, 24 patients had evidence of out-field regional failure, 43 patients had evidence of in-field failure, and 33 patients had the evidence of distant failure. Multivariate analysis revealed that out-field regional failure was associated with clinical tumor status (T4 vs T1–3, odds ratio [OR] =6.547, P=0.002), tumor length (>8 cm vs ≤8 cm, OR =4.130, P=0.036), response to CCRT (complete response vs no complete response, OR =2.646, P=0.035), and in-field failure (no in-field failure vs in-field failure, OR =1.32, P=0.016). Survival analyses indicated that, compared to in-field failure or distant failure alone group, out-field regional failure alone group tended to have longer overall (P=0.006) and progression-free survival (P=0.164). Conclusion Our data suggested that