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Sample records for advanced epidermoid carcinoma

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

    SciTech Connect

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

    1985-07-01

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

  2. [Initial pretherapeutic assessment of anal epidermoid carcinoma].

    PubMed

    de Parades, Vincent; Bauer, Pierre; Benbunan, Jean-Louis; Bouillet, Thierry; Cottu, Paul-Henri; Cuenod, Charles-André; Durdux, Catherine; Fléjou, Jean-François; Atienza, Patrick

    2007-02-01

    Anal epidermoid carcinoma is a rare malignant tumor, comprising less than 5% of all carcinomas of the colon, rectum, and anus. The primary therapy now includes radiotherapy, often in combination with chemotherapy. Radical surgery is now rarely indicated. Therapeutic indications are based on locoregional staging, the presence of visceral metastases and an evaluation of the medical history. Anorectal endosonography is helpful in evaluating locoregional extension. In addition, magnetic resonance imaging, positron emission tomography scanning and inguinal sentinel lymph node procedure should play a role in a more selective approach in patients with anal carcinoma.

  3. Epidermoid carcinoma of the skin mimicking breast cancer.

    PubMed

    Melo Neto, Baltasar; Oliveira, Giuliano da Paz; Vieira, Sabas Carlos; Leal, Livio Rodrigues; Melo Junior, José Andrade de Carvalho; Vieira, Cyro Franklin

    2013-01-01

    Nonmelanoma skin cancer is the most frequent cancer in the world. Squamous cell cancer often occurs in sun-exposed areas, such as the head and neck. When it involves the breast and ulce-rates, invading the glandular parenchyma, it may mimic breast cancer. Confirmation by means of histopathological examination, combined with clinical examination, is a critical instrument for the accuracy of the diagnosis. We report a case of an epidermoid carcinoma located on the breast skin, initially diagnosed as breast cancer.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Kang, Hoe-Jin; Jang, Young-Joo

    2012-06-01

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

  6. Comparative study of cell alterations in oral lichen planus and epidermoid carcinoma of the mouth mucosa.

    PubMed

    Sousa, Fernando Augusto Cervantes Garcia de; Paradella, Thaís Cachuté; Brandão, Adriana Aigotti Haberbeck; Rosa, Luiz Eduardo Blumer

    2009-01-01

    Currently, much is discussed regarding the pre-malignant nature of mouth mucosa lichen planus. The present study aims at analyzing the alterations found in the epithelial cells present in the oral cavity lichen planus, comparing them to those found in epidermoid carcinoma. Histological cross-sections of oral lichen planus and epidermoid carcinoma, dyed by hematoxylineosin, were analyzed through light microscopy. The most frequently found alterations in oral lichen planus were: an increase in the nucleus/cytoplasm relation (93.33%), nucleus membrane thickness (86.67%) and bi-nucleus or multinucleous (86.67%). The Student t test (alpha=5%) revealed a statistically significant difference between the average number of cell alterations in oral lichen planus (5.87+/-1.57) and in epidermoid carcinoma (7.60+/-1.81). As to the types of alterations, the chi-squared test also revealed statistically significant differences among the lesions assessed in relation to the following cell alterations: nuclear excess chromatism, atypical mitoses, cellular pleomorphism and abnormal cell differentiation (p<0.05). Despite the fact that in some cases, some pathologists may make mistakes in the histopathological diagnosis of oral lichen planus, the results obtained in this study show that the alterations present in oral lichen planus differ considerably from those seen in epidermoid carcinoma, thus showing how distinct these two diseases are.

  7. Radiation therapy for epidermoid carcinoma of the anal canal, clinical and treatment factors associated with outcome.

    PubMed

    Myerson, R J; Kong, F; Birnbaum, E H; Fleshman, J W; Kodner, I J; Picus, J; Ratkin, G A; Read, T E; Walz, B J

    2001-10-01

    In recent years, treatment with combined chemotherapy and radiation has become the standard of care for epidermoid carcinoma of the anus. However, optimal radiotherapy techniques and doses are not well established. During the period 1975-1997, 106 patients with epidermoid carcinoma of the anal canal underwent radiation therapy. Treatment policies evolved from radiation therapy alone or with surgery, to combined chemotherapy and radiation followed by surgery, to combined chemotherapy and radiation. Overall 74% of patients were NED (no evidence of disease) at last follow-up. The most important clinical correlate with ultimate freedom from disease (includes the contribution of salvage surgery) was extent of disease. The 5-year ultimate freedom from disease was 87+/-5% for T1/T2N0, 78+/-10% for T3N0 (15% salvaged by surgery), and 43+/-10% for either T4N0 or any N+ lesions (P<0.001, Tarone-Ware). There was no difference between planned vs. expectant surgery (5-year ultimate NED: 67+/-11% planned surgery vs. 73+/-5% expectant surgery). The most important correlate with late toxicity was a history of major pelvic surgery (surgical vs. non-surgical group: P=0.013, Fisher's exact test, two-tailed summation). Thirty-three additional malignancies have been seen in 26 patients. The most common additional malignancies were gynecologic (nine cases), head and neck (six cases), and lung cancer (five cases). For T1/T2N0 disease, moderate doses of radiation combined with chemotherapy provided adequate treatment. T4N0 and N+ lesions are the most appropriate candidates for investigational protocols evaluating dose intensification. T3N0 tumors may also be appropriate for investigation; however, dose intensification may ultimately prove counterproductive if the cure rate is not improved and salvage surgery is rendered more difficult. The volume of irradiated small bowel should be minimized for patients who have a past history of major pelvic surgery or who (because of locally advanced

  8. Treatment of oral and oropharyngeal epidermoid carcinomas by means of CO2 laser.

    PubMed

    Villarreal Renedo, Pedro M; Monje Gil, Florencio; Junquera Gutiérrez, Luis M; De Vicente Rodríguez, Juan C; Morillo Sánchez, Antonio J

    2004-01-01

    The effect of the wide long-wave CO2 laser is the thermal vaporization of the tissues, getting a maximum energy concentration with a minimum of tissue penetration. In oral surgery, it is generally used for the treatment of oral and oropharyngeal small mucous tumors, due to the scarce morbidity that takes place and the absence of reconstructive necessity. To analyze the postoperative evolution, in the patients treated by oral and oropharyngeal epidermoid carcinomas, after CO2 laser resection. To compare it with that of the patients treated by means of conventional surgical methods, achieving the reconstruction through direct suture or the employment of local, regional or distance flaps. A prospective study was designed including 70 patients treated by oral and oropharyngeal epidermoid carcinomas. Thirty-five patients were treated by means of CO2 laser, in 10 cases direct wound-closure was realized, and in the remaining 25 patients some local, regional or distance flap were used. There were analysed the presence of postoperative pain, the degree of cicatricial retraction, and the speech and swallowing functional results. We obtained a smaller painful degree and postoperative cicatricial retraction by the employment of CO2 laser. It permits minimizing the functional speech sequels (better words articulation) and swallowing (effective and precocious functional recovery). CO2 laser resection has become the elective treatment for small oral and oropharyngeal epidermoid carcinomas. The reasons are the absence of reconstructive surgery necessity, the scarce cicatricial retraction, and the excellent postoperative evolution.

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

    PubMed Central

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

    2017-01-01

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

  10. [Analysis of epidermoid carcinomas using panoramic radiography and computerized tomography].

    PubMed

    Pereira, A C; Cavalcanti, M G; Tossato, P S; Guida, F J; Duaik, M C; Kuroishi, M

    2001-01-01

    The purpose of this work was to compare radiographic findings, such as localization and extension of tumors toward the bone and soft tissues, in panoramic radiography and computed tomography (CT). Four radiologists assessed the radiographic findings of 48 patients with the histopathological diagnosis of squamous cell carcinoma in different sites of the maxillofacial region. Panoramic radiographs and computed tomographs were obtained at the University of Iowa Hospitals and Clinics, at FUNDECTO-USP and at the hospital of the University of São Paulo (USP). We observed a considerable limitation of the panoramic radiography in determining the localization and extension of tumors, since it revealed unclear delimitations. Regarding CT, better results were obtained: it was possible to observe the invasion of the tumor toward adjacent soft tissues, as well as the extension of bone destruction and the depth of the lesion, which were confirmed by surgical findings. We concluded that computed tomography demonstrated to be a sensitive radiographic technique for the detection of the involvement of bone and soft tissues, contributing for a more precise diagnosis, surgical planning and intervention. On the other hand, panoramic radiography was considered less sensitive and less efficient than CT, since it shows only unclear borders of the lesions and is not able to assess the involvement of soft tissues.

  11. Sentinel lymph node procedure in patients with epidermoid carcinoma of the anal canal: early experience.

    PubMed

    Damin, Daniel C; Rosito, Mario A; Gus, Pedro; Spiro, Bernardo L; Amaral, Beatriz B; Meurer, Luise; Cartel, Andre; Schwartsmann, Gilberto

    2003-08-01

    This study was conducted to assess the feasibility of the sentinel lymph node procedure in patients with epidermoid carcinoma of the anal canal. Between February 2001 and November 2002, 14 patients with epidermoid carcinoma of the anal canal and no clinical evidence of inguinal involvement were prospectively enrolled in the study. The sentinel lymph node procedure consisted of a combination of preoperative lymphoscintigraphy with technetium 99m dextran 500 injected around the tumor and intraoperative detection of the sentinel node with a gamma probe. Patent blue V dye was also injected at the periphery of the tumor to facilitate direct identification of the blue-stained lymph node. After removal, the sentinel node was studied by hematoxylin and eosin staining and immunohistochemistry for pancytokeratins (antigen A1 and A3). Detection and removal of sentinel lymph nodes was possible in all patients. There was no correlation between tumor size and pattern of lymphatic drainage to the groin. Tumors located in the midline of the anal canal gave rise to bilateral sentinel nodes in eight of nine cases. In total, 23 sentinel lymph nodes were removed. One patient (7.1 percent) had a node identified as positive for metastatic carcinoma on immunohistochemical staining. Surgical complications were minimal. The standardized technique was safe and highly effective in sampling inguinal sentinel lymph nodes in carcinoma of the anal canal. It also proved to be useful as an instrument to detect micrometastatic deposits in clinically normal nodes. Our early results suggest the sentinel lymph node procedure may have a role in guiding a more selective approach for patients with anal cancer. Additional studies in a larger patient population to determine the sensitivity and specificity of this method are warranted.

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

    SciTech Connect

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

    1988-08-01

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

  13. 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

  14. 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.

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

    PubMed

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

    2017-01-01

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

  16. 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.

  17. Blue light activates phase 2 response proteins and slows growth of a431 epidermoid carcinoma xenografts.

    PubMed

    Patel, Alpesh D; Rotenberg, Shaun; Messer, Regina L W; Wataha, John C; Ogbureke, Kalu U E; McCloud, Veronica V; Lockwood, Petra; Hsu, Stephen; Lewis, Jill B

    2014-11-01

    Recent studies suggest that light in the UVA range (320-400 nm) activates signaling pathways that are anti-inflammatory, antioxidative and play a critical role in protection against cancer. These effects have been attributed to NF-E2-related factor (NRF2)-mediated up-regulation of 'phase 2' genes that neutralize oxidative stress and metabolize electrophiles. We had previously shown that small doses of blue light (400-500 nm) had selective toxicity for cultured oral tumor cells and increased levels of peroxiredoxin phase 2 proteins, which led to our hypothesis that blue light activates NRF2 signaling. A431 epidermoid carcinoma cells were treated in culture and as nude mouse xenografts with doses of blue light. Cell lysates and tumor samples were tested for NRF2 activation, and for markers of proliferation and oxidative stress. Blue light activated the phase 2 response in cultured A431 cells and reduced their viability dose dependently. Light treatment of tumors reduced tumor growth, and levels of proliferating cell nuclear antigen (PCNA), and oxidized proteins. Cellular responses to these light energies are worth further study and may provide therapeutic interventions for inflammation and cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

    PubMed

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

    2010-01-01

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

  19. The new esters derivatives of betulin and betulinic acid in epidermoid squamous carcinoma treatment - In vitro studies.

    PubMed

    Drąg-Zalesińska, Małgorzata; Wysocka, Teresa; Borska, Sylwia; Drąg, Marcin; Poręba, Marcin; Choromańska, Anna; Kulbacka, Julita; Saczko, Jolanta

    2015-05-01

    Betulinic acid and betulin are triterpenes with documented cytotoxic properties toward various cell lines. Unfortunately both betulinic acid and its metabolic precursor, betulin, are very poorly soluble in aqueous buffers, thus their bioavailability and bio-distribution are insufficient in terms of medical applications. To investigate the specific anticancer role of the newly synthesized betulin derivatives in human epidermoid carcinoma cells. In the present study we synthesized five amino acid esters of betulin. For the synthesis we selected alanine (Boc-l-Ala-OH, negative control) and four basic amino acids - natural lysine (Boc-l-Lys(Boc)-OH) and three its unnatural derivatives (Boc-l-Dap(Boc)-OH, Boc-l-Dab(Boc)-OH, and Boc-l-Orn(Boc)-OH). Boc-protected amino acids were most convenient for the synthesis. All new esters have one (betulin-l-Ala-NH2) or two free amino groups which significantly increase their solubility in water and facilitate their transport through the cell membrane. It is worth noting that the biological activity of new esters of betulin is positive correlated with the length of the side chain of l-amino acid. The highest biological activity displayed compound containing lysine side chain (Lys, -CH2-CH2-CH2-CH2-NH2). Considering the biological activity, other derivatives can be set in the following series: Orn (-CH2-CH2-CH2-NH2)>Dab (-CH2-CH2-NH2)>Dap (-CH2-NH2)>Ala (CH3)>betulin. New betulin esters were tested in normal human keratinocytes (HaCaT) and human epidermoid carcinoma cells (A431). To assess cytotoxicity, MTT test was performed after 24, 48 and 72h of incubation with the test compounds at a concentration range of 0.75-100μM. In case of apoptotic activity, a TUNEL method and comet assay were performed. Additionally expression of caspase-3 and PARP1 was evaluated immunocytochemically. The highest cytotoxicity in cells induced skin cancer new compounds, particularly compound containing a lysine side chain (IC50=7μM) and ornithine (IC50

  20. Pineal epidermoid

    PubMed Central

    Senapati, Satya B.; Mishra, Sudhansu S.; Patnaik, Ashis; Patra, Sunil K.

    2012-01-01

    Background: Tumors of pineal region are uncommon, accounting for ≤1% of intracranial tumors in adults and 3–8% of pediatric brain tumors. Epidermoid cysts account for 0.2–1% of all intracranial tumors. The majority occur in and around the cerebellopontine angle and suprasellar area. Getting an epidermoid in pineal region is very rare. Case Description: We report a case of pineal epidermoid, which was diagnosed correctly as epidermoid depending on computed tomography (CT) and magnetic resonance imaging (MRI) findings. Knowing its benign nature, we accordingly planned for its near-total removal. Conclusion: Most cases of pineal tumors present as obstructive hydrocephalus. They either require pre- or postoperative ventriculoperitoneal (VP) shunt. If properly planned, many benign pineal tumors may be successfully excised and, most importantly, postoperative VP shunt could be avoided. PMID:23226611

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

    PubMed

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

    2014-07-18

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

  2. 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.

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

    PubMed Central

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

    1994-01-01

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

  4. 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.

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

    PubMed

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

    2001-12-14

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

  6. [Combined radiochemotherapy in locally advanced nasopharyngeal carcinoma].

    PubMed

    Daniilidis, J; Constantinidis, J; Fountzilas, G

    2001-09-01

    Nasopharyngeal cancer (NPC) is a tumor of epidermoid origin with an entirely different biological behavior than other carcinoma of the head and neck region. A retrospective analysis was performed in 93 cases with locally advanced NPC treated with induction chemotherapy followed by radiation therapy (RT; 79 patients) or concomitant RT and chemotherapy. Totally 66 patients (71%) achieved a complete response (CR), 68% of the patients treated with induction chemotherapy followed by RT, 86% with concomitant chemoradiotherapy. After a median follow-up of 5.5 years 28 out of these 66 relapsed, 25 of them locoregionally. Median time to progression was 22.5 months, median overall survival (OS) 45 months, 5-year actuarial survival was 41.5%. Age, T and N classification, histological type and type of chemotherapy were independent significant factors for OS. Combined chemotherapy and RT in patients with locally advanced NPC result in a high CR rate. The main problem remains the locoregional control. Randomized studies are needed in order to define the optimal use of chemotherapy in combination with RT.

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

    PubMed

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

    1989-05-01

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

  8. Chelidonium majus L. extract induces apoptosis through caspase activity via MAPK-independent NF-κB signaling in human epidermoid carcinoma A431 cells.

    PubMed

    Park, Seung-Won; Kim, Seong Ryul; Kim, Youngchul; Lee, Jang-Hoon; Woo, Hong-Jung; Yoon, Yeo-Kwang; Kim, Young Il

    2015-01-01

    Chelidonium majus L. (C. majus L.) is known to possess certain biological properties such as anti-inflammatory, antimicrobial, antiviral and antitumor activities. We investigated the effects of C. majus L. extract on human epidermoid carcinoma A431 cells through multiple mechanisms, including induction of cell cycle arrest, activation of the caspase-dependent pathway, blocking of nuclear factor-κB (NF-κB) activation and involvement in the mitogen-activated protein kinase (MAPK) pathway. C. majus L. inhibited the proliferation of A431 cells in a dose- and time-dependent manner, increased the percentage of apoptotic cells, significantly decreased the mRNA levels of cyclin D1, Bcl-2, Mcl-1 and survivin and increased p21 and Bax expression. Exposure of A431 cells to C. majus L. extract enhanced the activities of caspase-3 and caspase-9, while co-treatment with C. majus L., the pan-caspase inhibitor Z-VAD-FMK and the caspase-3 inhibitor Z-DEVE-FMK increased the proliferation of A431 cells. C. majus L. extract not only inhibited NF-κB activation, but it also activated p38 MAPK and MEK/ERK signaling. Taken together, these results demonstrate that C. majus L. extract inhibits the proliferation of human epidermoid carcinoma A431 cells by inducing apoptosis through caspase activation and NF-κB inhibition via MAPK-independent pathway.

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

    PubMed

    Ahmad, N; Gupta, S; Mukhtar, H

    1999-03-11

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

  10. Mechanisms underlying the cytotoxic effect of propolis on human laryngeal epidermoid carcinoma cells.

    PubMed

    Frión-Herrera, Yahima; Díaz-García, Alexis; Ruiz-Fuentes, Jenny; Rodríguez-Sánchez, Hermis; Maurício Sforcin, José

    2017-08-08

    Propolis has been used as a traditional remedy for centuries because of its beneficial effects, including anticancer properties. The aim of this study was to compare the cytotoxic mechanism of Cuban red propolis (CP) and Brazilian green propolis (BP) on human laryngeal carcinoma (HEp-2) cells. Cell viability, leakage of lactate dehydrogenase, fluorescence staining, mitochondrial membrane potential (ΔΨm) and the expression of pro/anti-apoptotic genes were assessed. Cell viability and cytotoxic assays suggested a dose-dependent effect of CP and BP extracts with a possible association of intracellular reactive oxygen species production and decreased ΔΨm. Both samples induced apoptosis via activation of TP53, CASP3, BAX, P21 signalling, and downregulation of BCL2 and BCL-XL. CP exerted a higher cytotoxic effect than BP extract. Our findings suggest further investigation of the main components of each propolis sample, what may lead to the development of strategies for the treatment of laryngeal cancer.

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

    PubMed

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

    2013-07-01

    Non-melanoma skin cancers (NMSCs), one of the most common neoplasms, cause serious morbidity and mortality. Therefore, identification of non-toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3',4',7-tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti-oxidant and antiproliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fisetin (5-80 μm) resulted in a significant decrease in cell viability in a dose- and time-dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G₂ /M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti-apoptotic proteins (Bcl2; Bcl-xL and Mcl-1); (ii) increased expression of pro-apoptotic proteins (Bax, Bak and Bad); (iii) disruption of mitochondrial potential; (iv) release of cytochrome c and Smac/DIABLO from mitochondria; (v) activation of caspases; and (vi) cleavage of Poly(ADP-ribose) polymerase (PARP) protein. Pretreatment of A431 cells with the pan-caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed Central

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

    2013-01-01

    Non-melanoma skin cancers (NMSCs) one of the most common neoplasms causes serious morbidity and mortality. Therefore, identification of non-toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3′,4′,7-tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti-oxidant and anti-proliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fistein (5-80 μM) resulted in a significant decrease in cell viability in a dose- and time-dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G2/M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti-apoptotic proteins (Bcl2, Bcl-xL and Mcl-1), (ii) increased expression of pro-apoptotic proteins (Bax, Bak and Bad), (iii) disruption of mitochondrial potential, (iv) release of cytchrome c and Smac/DIABLO from mitochondria, (v) activation of caspases, and (vi) cleavage of PARP protein. Pretreatment of A431 cells with the pan-caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs. PMID:23800058

  13. Giant Earlobe Epidermoid Cyst

    PubMed Central

    Pérez-Guisado, Joaquín; Scilletta, Alessandra; Cabrera-Sánchez, Emilio; Rioja, Luis F; Perrotta, Rosario

    2012-01-01

    Epidermoid cysts represent the most common cutaneous cysts. They are usually small and benign; however, sometimes they can grow to giant epidermoid cists, and occasionally malignancies develop. Giant epidermoid cysts at the earlobe have never been described but in other locations. We describe a case of a giant epidermoid cyst at the earlobe, a location where such a large cyst has never been reported before. The mass was completely resected and the wound of the pedunculated base was sutured with four stitches of nylon 5/0. Histopathology confirmed the presumptive diagnosis of an epidermoid cyst. Six months after the resection, the patient did not have any relapse of the epidermoid cyst. The earlobe is a potential location for giant epidermoid cysts. Although the clinical diagnosis could be enough, due to the possibility of malignancy and to ensure appropriate diagnosis, we consider that all cysts should be sent to the anatomic pathology laboratory for histological evaluation. PMID:22557855

  14. 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.

  15. Extracellular polymeric substance from Aphanizomenon flos-aquae induces apoptosis via the mitochondrial pathway in A431 human epidermoid carcinoma cells.

    PubMed

    Xue, Xing; Lv, Ying; Liu, Qing; Zhang, Xiaolan; Zhao, Youhong; Zhang, Lili; Xu, Shiyuan

    2015-09-01

    Extracellular polymeric substance (EPS) is a substance secreted during algal growth, which has been found to have numerous health-promoting effects. In the present study, A431 human epidermoid carcinoma cells were selected as target cells and cultivated in vitro as an experimental model to investigate the anti-cancer effect of extracellular polymeric substances from Aphanizomenon flos-aquae (EPS-A) and the possible underlying mechanism. Apoptosis- and cell cycle-associated molecules as well as the mitochondrial membrane potential of the cells were quantified using flow cytometry (FCM). FCM showed that EPS-A induced cell cycle arrest, which led to a loss of mitochondrial function of the A431 cells and an increase in necrotic and late apoptotic cells. In order to evaluate the apoptosis and cell viability, acridine orange/ethidium bromide staining was used, morphological changes were observed using fluorescence microscopy and typical apoptotic characteristics were observed. Following treatment with a high dose of EPS-A, transmission electron microscopy showed nuclear fragmentation, chromosome condensation, cell shrinkage and expansion of the endoplasmic reticulum; apoptotic bodies were also observed. In conclusion, EPS-A caused cell cycle arrest, stimulated cell apoptosis via the mitochondrial pathway and exhibited important anti-cancer activity.

  16. Extracellular polymeric substance from Aphanizomenon flos-aquae induces apoptosis via the mitochondrial pathway in A431 human epidermoid carcinoma cells

    PubMed Central

    XUE, XING; LV, YING; LIU, QING; ZHANG, XIAOLAN; ZHAO, YOUHONG; ZHANG, LILI; XU, SHIYUAN

    2015-01-01

    Extracellular polymeric substance (EPS) is a substance secreted during algal growth, which has been found to have numerous health-promoting effects. In the present study, A431 human epidermoid carcinoma cells were selected as target cells and cultivated in vitro as an experimental model to investigate the anti-cancer effect of extracellular polymeric substances from Aphanizomenon flos-aquae (EPS-A) and the possible underlying mechanism. Apoptosis- and cell cycle-associated molecules as well as the mitochondrial membrane potential of the cells were quantified using flow cytometry (FCM). FCM showed that EPS-A induced cell cycle arrest, which led to a loss of mitochondrial function of the A431 cells and an increase in necrotic and late apoptotic cells. In order to evaluate the apoptosis and cell viability, acridine orange/ethidium bromide staining was used, morphological changes were observed using fluorescence microscopy and typical apoptotic characteristics were observed. Following treatment with a high dose of EPS-A, transmission electron microscopy showed nuclear fragmentation, chromosome condensation, cell shrinkage and expansion of the endoplasmic reticulum; apoptotic bodies were also observed. In conclusion, EPS-A caused cell cycle arrest, stimulated cell apoptosis via the mitochondrial pathway and exhibited important anti-cancer activity. PMID:26622416

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

    PubMed

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

    2001-02-01

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

  18. 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.

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

    PubMed

    Bhatia, N; Agarwal, C; Agarwal, R

    2001-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2012-03-01

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

  2. Challenges of advanced hepatocellular carcinoma

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Haemmerli, G; Sträuli, P

    1981-05-15

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

  4. Erlotinib for advanced hepatocellular carcinoma

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2002-04-01

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

  6. Basosquamous Carcinoma: Controversy, Advances, and Future Directions.

    PubMed

    Tan, Caroline Z; Rieger, Kerri E; Sarin, Kavita Y

    2017-01-01

    Basosquamous carcinoma is a rare cutaneous neoplasm that has caused considerable controversy as to its classification, pathogenesis, and management. To review and summarize current literature on the definition, pathogenesis, incidence, and management of basosquamous carcinoma. Through December 2015, an electronic search of the Pubmed database was performed using combinations of basosquamous carcinoma and metatypical basal cell carcinoma as search terms. A selection of 39 publications including case reports and series, retrospective studies, and systematic reviews of the literature were included. Descriptions of the definition of basosquamous carcinoma, clinical behavior, histopathological characteristics, current treatment therapies, and future advances are summarized. This systematic review provides a comprehensive overview of the current understanding of basosquamous carcinoma. Further study is required to elucidate the mechanisms driving the formation of this aggressive tumor.

  7. 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

  8. 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.

  9. Submental epidermoid cysts in children

    PubMed Central

    Zakrzewska, Anna

    2015-01-01

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

  10. 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.

  11. 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

  12. 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

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

    PubMed Central

    Murakami, Y; Mizuno, S; Uehara, Y

    1994-01-01

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

  14. Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations.

    PubMed

    Mohan, Shalini V; Chang, Anne Lynn S

    2014-01-01

    Advanced basal cell carcinomas are a subset of basal cell carcinomas that can be difficult to treat either due to their local invasiveness, proximity to vital structures, or metastasis. The incidence of all basal cell carcinoma is increasing in the United States, although it is not known whether advanced basal cell carcinomas (aBCCs) are also increasing. Recently, highly targeted therapy based on knowledge of the basal cell carcinoma pathogenesis has become available either commercially or through human clinical trials. These orally available drugs inhibit the Hedgehog signaling pathway, and lead to advanced basal cell carcinoma shrinkage that can enable preservation of adjacent vital organs. In this review, we outline the role of Hedgehog pathway inhibitors as well as other treatment modalities such as excision, radiotherapy and more traditional chemotherapy in treating advanced basal cell carcinomas. We also highlight current gaps in knowledge regarding the use and side effects of this targeted therapy.

  15. Antiangiogenic Therapies for Advanced Hepatocellular Carcinoma

    PubMed Central

    Sampat, Keeran R.

    2013-01-01

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

  16. Advanced treatment for basal cell carcinomas.

    PubMed

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

    2014-07-01

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

  17. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

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

    2014-01-01

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

  18. Designed Synthesis of Nanostructured Magnetic Hydroxyapatite Based Drug Nanocarrier for Anti-Cancer Drug Delivery toward the Treatment of Human Epidermoid Carcinoma

    PubMed Central

    Govindan, Bharath; Swarna Latha, Beeseti; Nagamony, Ponpandian; Ahmed, Faheem; Saifi, Muheet Alam; Harrath, Abdel Halim; Alwasel, Saleh; Mansour, Lamjed; Alsharaeh, Edreese H.

    2017-01-01

    Superparamagnetic Fe3O4 nanoparticles on hydroxyapatite nanorod based nanostructures (Fe3O4/HAp) were synthesized using hydrothermal techniques at 180 °C for 12 h and were used as drug delivery nanocarriers for cancer cell therapeutic applications. The synthesized Fe3O4/HAp nanocomposites were characterized by X-ray diffraction analysis (XRD), Field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET)-analysis, and vibrating sample magnetometry (VSM). The morphologies of the Fe3O4/HAp nanocomposites show 15 nm Fe3O4 nanoparticles dispersed in the form of rods. The BET result shows that the synthesized samples have a high specific surface area of 80 m2 g−1 with mesoporous structures. Magnetic measurements revealed that the sample has high saturation magnetization of 18 emu/g with low coercivity. The Fe3O4/HAp nanocomposites had a large specific surface area (SSA), high mesoporous volume, and good magnetic property, which made it a suitable nanocarrier for targeted drug delivery systems. The chemotherapeutic agent, andrographolide, was used to investigate the drug delivery behavior of the Fe3O4/HAp nanocomposites. The human epidermoid skin cancer cells (A431) were used as the model targeting cell lines by treating with andrographolide loaded Fe3O4/HAp nanosystems and were further evaluated for their antiproliferative activities and the induction of apoptosis. Also, the present nanocomposite shows better biocompatibility, therefore it can be used as suitable drug vehicle for cancer therapy applications. PMID:28587317

  19. Combination chemotherapy for advanced bilharzial bladder carcinoma.

    PubMed

    Khaled, H M; Gad el-Mawla, N; el-Said, A; Hamza, M R; Gaafar, R; el-Attar, I; Abu Rabia, A; Magrath, I

    1996-09-01

    Carcinoma of the bilharzial bladder, the most common cancer in Egyptian patients has been, until recently, largely treated by surgery. We have studied the activity of a series of single agents in phase II trials and identified a number of active agents. Here we report the results of a trial in which therapeutic combinations of the most active agents were administered in alternating cycles to patients who had never received chemotherapy. The study included 30 patients with histologically proven inoperable (20), recurrent (5, 2 of whom subsequently developed metastases), or metastatic disease (5). There were 27 males and 3 females, with a median age of 48.5 years (range 29-65 years). Fourteen patients had squamous cell carcinoma, 12 had transitional cell carcinoma, 2 had adenocarcinoma, and the remaining 2 had undifferentiated carcinoma. Chemotherapy consisted of epidoxorubicin (120 mg/sqm i.v. d1) and vincristine (1.4 mg/sqm i.v., days 1 and 8) alternating with etoposide (100 mg/sqm i.v. infusion over 1 hour, days 1 to 5) and ifosfamide (1800 mg/sqm i.v. infusion over 2 hours, days 1 to 5). Mesna was given as a uroprotector at 40% of the ifosfamide dose at 0, 4, and 8 hours after the ifosfamide infusion. Courses were repeated every 3-4 weeks. Among the 22 evaluable patients, 8 (36.5%) had a partial and one (4.5%), a complete response, giving a response rate of 46%. Three more patients had responses that were less than a partial remission, and 6 patients showed disease stabilisation on chemotherapy. Toxicities were tolerable and consisted mainly of myelosuppression. Results were further analysed in relation to pathologic subtype, disease status at the start of chemotherapy, and the delivered dose intensity. No relationship was found between any of these parameters and response to therapy. Advanced bilharzial bladder cancer is relatively sensitive to combination chemotherapy, but complete remission and prolonged survival is rare in this subgroup of patients with

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

    PubMed

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

    1993-04-01

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

  1. 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

  2. Modern management of locally advanced cervical carcinoma.

    PubMed

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

    2003-10-01

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

  3. Definitive Chemoradiotherapy for Advanced Pulmonary Sarcomatoid Carcinoma

    PubMed Central

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

    2016-01-01

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

  4. Advances in the management of cutaneous squamous cell carcinoma

    PubMed Central

    Parikh, Sonal A.

    2014-01-01

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

  5. Carcinoma of the anal canal: small steps in treatment advances.

    PubMed

    Eng, Cathy

    2011-09-01

    For locally advanced squamous cell carcinoma of the anal canal, efforts to discover effective treatments that would protect sphincter preservation led to the development of combined chemoradiotherapy, which, when administered appropriately, is curative. While the standard of combined modality chemoradiotherapy has minimally changed over the past 30 years, various chemotherapeutic and biologic agents, as well as novel methods for delivering radiation, have enhanced the treatment of anal carcinoma and are continuously being explored. This review examines the risk factors associated with anal carcinoma, and subsequently discusses the current standard of care from diagnosis through surveillance, paying attention to the pivotal trials that have shaped modern treatment paradigms.

  6. Advances in the pathology of penile carcinomas.

    PubMed

    Chaux, Alcides; Cubilla, Antonio L

    2012-06-01

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

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

    PubMed

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

    2015-10-01

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

  8. Nursing Management of Advanced Merkel Cell Carcinoma.

    PubMed

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

    2016-11-01

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

  9. [Epidermoid cyst of the mouth floor].

    PubMed

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

    2003-07-01

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

  10. CMV chemotherapy for advanced transitional cell carcinoma.

    PubMed Central

    Jeffery, G. M.; Mead, G. M.

    1992-01-01

    Between May 1986 and September 1990 a total of 43 patients with metastatic transitional cell carcinoma (TCC) of the urinary tract have been treated at our institution with combination chemotherapy (CMV) consisting of cisplatin 100 mg m-2 i.v. day 2; methotrexate 30 mg m-2 i.v. days 1.8; and vinblastine 4 mg m-2 i.v. days 1.8. Chemotherapy was recycled on day 22 and continued for a maximum of six cycles in responding patients. Of 33 patients with measurable disease 8 (24%) achieved a complete remission (CR). The median survival for patients achieving a CR was 13 months (range 5-29+) whilst the median survival for all 43 patients was 7 months (range 1-29+). Only three patients are still alive--two are disease free. More effective and/or less toxic chemotherapy regimens are needed for the treatment of patients with metastatic TCC. PMID:1520591

  11. Adenoid cystic carcinoma of breast: Recent advances

    PubMed Central

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

    2014-01-01

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

  12. 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.

  13. Combination treatment including targeted therapy for advanced hepatocellular carcinoma

    PubMed Central

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

    2016-01-01

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

  14. Extensive Epidermoid Cyst and Breathing Difficulty

    PubMed Central

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

    2015-01-01

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

  15. Cyclical Combination Chemotherapy for Advanced Breast Carcinoma

    PubMed Central

    Canellos, George P.; Devita, Vincent T.; Gold, G. Lennard; Chabner, Bruce A.; Schein, Philip S.; Young, Robert C.

    1974-01-01

    Twenty-five patients with advanced metastatic breast cancer were treated with the combination of methotrexate 60 mg/M2 and 5-fluorouracil 700 mg/M2 intravenously on the first and eighth days, and cyclophosphamide 100 mg/M2 and prednisone 40 mg/M2 by mouth daily for the first 14 days of a 28-day cycle. The patients had had no previous chemotherapy or extensive radiotherapy and all but two had not responded to hormonal therapy or endocrine ablation. The major metastatic lesions were: lung (12 patients), liver (four patients), bone (four patients), soft tissue (three patients), nodes (two patients). Seventeen of the 25 patients (68%) responded to treatment with seven complete remissions; these included patients suffering metastatic lesions in the lung, nodes, and soft tissue. The overall median duration of response was nine months (range 6-26 months). Toxicity was primarily haematological, but the group received an average of at least 75% of their calculated dose for each monthly cycle. Haematological toxicity was most pronounced in patients with liver dysfunction and bone marrow involvement. Out of eight nonresponders seven died, with a median survival of six months. Only six of 17 responders died, and the median survival in this group will exceed thirteen months. There was no correlation between the length of the metastasis-free interval after previous treatment and subsequent response to chemotherapy. PMID:4818162

  16. 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

  17. Sublingual epidermoid cyst in a neonate

    PubMed Central

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

    2014-01-01

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

  18. Epidermoid cyst of the pineal region

    PubMed Central

    Sambasivan, M.; Nayar, Ammu

    1974-01-01

    An epidermoid cyst in the pineal region is reported to underscore the feasibility of successful surgical excision of such lesions and the need to review the management of posterior third ventricular lesions. An interesting, but unexplained, feature in this patient was renal glycosuria which cleared after excision of the tumour. Images PMID:4448997

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

    PubMed

    Keating, Gillian M

    2012-07-30

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

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

    PubMed

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

    2014-01-25

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

  1. Biological targeted therapies in patients with advanced enteropancreatic neuroendocrine carcinomas.

    PubMed

    Fazio, Nicola; Cinieri, Saverio; Lorizzo, Katia; Squadroni, Michela; Orlando, Laura; Spada, Francesca; Maiello, Evaristo; Bodei, Lisa; Paganelli, Giovanni; Delle Fave, Gianfranco; de Braud, Filippo

    2010-11-01

    Enteropancreatic (EP) neuroendocrine carcinomas (NECs) represent relatively rare and heterogeneous malignancies. They are the most common group among neuroendocrine tumors (NETs). In most cases they are advanced at diagnosis and slow-growing, therefore conditioning a better prognosis compared with non neuroendocrine carcinomas from the same sites. No standard medical therapy exists, except for somatostatin analogs in functioning tumors, and octreotide LAR in functioning or non functioning well differentiated NECs from small bowel. Several systemic therapeutic options exist, including chemotherapy, somatostatin analog, interferon, peptide receptor radionuclide therapy (PRRT), and molecular targeted drugs. Among them some therapies have specific biological tumor targets and can be defined as "biological targeted therapies". This review focuses on the status of EP NECs targeted therapies in the light of recent advances. Somatostatin receptors (SSTRs) are the first therapeutic target detected in EP NECs. Through them SS analogs and PRRT act, producing symptomatic, biochemical, and, to a lesser extent, antiproliferative effects. New SS analogs, covering a higher number of SSTR subtypes, were developed, including pasireotide (SOM230), which controls 25% of carcinoid syndromes resistant to full dose octreotide LAR. Chimeric analogs, which bind SSTR2/SSTR5 and dopamine-2 receptor subtype (D2), are in preclinical phase of development. Among the numerous molecular targeted agents investigated in NETs, mTOR inhibitors and VEGF/VEGFR/PDGFR inhibitors are in most advanced clinical phase of investigation. In particular, everolimus, sunitinib, and bevacizumab are all studied in phase III trials. Both everolimus and sunitinib produced significant survival benefit versus placebo in advanced progressing well-differentiated pancreatic NECs. Sunitinib data have been presented at the last ASCO in June 2010, and everolimus data will be presented at next ESMO in September 2010. Copyright

  2. Concurrent chemoradiation in locally advanced carcinoma cervix patients.

    PubMed

    Negi, R R; Gupta, Manish; Kumar, Muninder; Gupta, M K; Seam, R; Rastogi, Madhup

    2010-01-01

    To investigate the feasibility of concurrent chemo radiation in locally advanced carcinoma cervix patients in our clinical setting. From Sept. 1st 2005 to Aug. 31st 2006, 102 patients of carcinoma cervix belonging to stage IIA to IV A were enrolled in the study. External beam radiation therapy was administered using Cobalt 60 teletherapy machine. Cisplatinum (40 mg/m 2) and 5 Fluorouracil (500 mg/m 2 ) continuous infusions with radiotherapy on D2-D5 in first and last 5 # of radiation therapy were administered. Response to treatment and toxicities were monitored and analyzed in 102 patients (50 study group and 52 control group). All 102 patients completed treatment. Out of 50 patients in the study group, 30, 10 and 4 patients had complete, partial and progressive disease, respectively. While out of 52 patients in the control group, 26 had complete and 12 showed partial response. No difference in overall renal, hematological and cutaneous toxicity was seen between two groups. This study did not show any benefit of concurrent chemo radiation as compared to radiotherapy alone in locally advanced cervical cancer patients. This could be due to more bulk of tumor stage per stage, poor nutritional status, less number of patients in both arms, not enough to pick up statistically significant small difference in outcome.

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

    PubMed Central

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

    2014-01-01

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

  4. 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

  5. Extensive epidermoid cyst of the submental region

    PubMed Central

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

    2016-01-01

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

  6. Isolated giant molluscum contagiosum mimicking epidermoid cyst

    PubMed Central

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

    2016-01-01

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

  7. Epidermoid Cyst Arising in the Submandibular Region

    PubMed Central

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

    2013-01-01

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

  8. Giant sublingual epidermoid cyst resembling plunging ranula

    PubMed Central

    Verma, Sandeep; Kushwaha, Jitendra Kumar; Sonkar, A A; Kumar, Rahul; Gupta, Rajni

    2012-01-01

    Epidermoid and dermoid cysts represent less than 0.01% of all oral cavity cysts. We describe a rare case of large epidermoid cyst in floor of mouth, with an oral as well as submental component resembling plunging ranula reported in the literature from India. We present a case of a 16-year-old girl with complaints of a mass in sublingual region, difficulty chewing, and dysphagia for about 5 months. Fine-needle aspiration cytology showed keratin flakes and proteinaceous material. Contrast-enhanced CT oral cavity was done and showed 7.0 × 5 × 4.5 cm well-circumscribed non-enhancing cystic mass extending into the floor of the mouth. On examination, a firm swelling was noticed in the submental area, extending down to the thyroid notch. The patient underwent surgical removal of the mass. On histopathology, acidophilic stratum corneum and basophilic dot like staining of stratum granulosum, which is the hallmark of an epidermoid cyst, were seen. PMID:23833501

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

    PubMed Central

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

    2008-01-01

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

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

    SciTech Connect

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

    1981-11-01

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

  11. 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

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

    PubMed Central

    Ow, Thomas J.

    2011-01-01

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

  13. Advances in the management of basal cell carcinoma

    PubMed Central

    Carucci, John A.

    2015-01-01

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

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

    PubMed

    Oikonomopoulos, Georgios; Aravind, Preetha; Sarker, Debashis

    2016-02-01

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

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

    PubMed Central

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

    2008-01-01

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

  16. Endoscopic Treatment of a Third Ventricular Epidermoid Cyst.

    PubMed

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

    2017-03-01

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

  17. Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma

    PubMed Central

    Sekulic, Aleksandar; Migden, Michael R.; Oro, Anthony E.; Dirix, Luc; Lewis, Karl D.; Hainsworth, John D.; Solomon, James A.; Yoo, Simon; Arron, Sarah T.; Friedlander, Philip A.; Marmur, Ellen; Rudin, Charles M.; Chang, Anne Lynn S.; Low, Jennifer A.; Mackey, Howard M.; Yauch, Robert L.; Graham, Richard A.; Reddy, Josina C.; Hauschild, Axel

    2017-01-01

    BACKGROUND Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma. METHODS In this multicenter, international, two-cohort, nonrandomized study, we enrolled patients with metastatic basal-cell carcinoma and those with locally advanced basal-cell carcinoma who had inoperable disease or for whom surgery was inappropriate (because of multiple recurrences and a low likelihood of surgical cure, or substantial anticipated disfigurement). All patients received 150 mg of oral vismodegib daily. The primary end point was the independently assessed objective response rate; the primary hypotheses were that the response rate would be greater than 20% for patients with locally advanced basal-cell carcinoma and greater than 10% for those with metastatic basal-cell carcinoma. RESULTS In 33 patients with metastatic basal-cell carcinoma, the independently assessed response rate was 30% (95% confidence interval [CI], 16 to 48; P = 0.001). In 63 patients with locally advanced basal-cell carcinoma, the independently assessed response rate was 43% (95% CI, 31 to 56; P<0.001), with complete responses in 13 patients (21%). The median duration of response was 7.6 months in both cohorts. Adverse events occurring in more than 30% of patients were muscle spasms, alopecia, dysgeusia (taste disturbance), weight loss, and fatigue. Serious adverse events were reported in 25% of patients; seven deaths due to adverse events were noted. CONCLUSIONS Vismodegib is associated with tumor responses in patients with locally advanced or metastatic basal-cell carcinoma. (Funded by Genentech; Erivance BCC ClinicalTrials.gov number, NCT00833417

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

    PubMed

    Porta, C; Paglino, C; Grünwald, V

    2014-09-09

    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.

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

    PubMed

    Bodzin, Adam S; Busuttil, Ronald W

    2015-05-28

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

  20. 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

  1. Defining and recognising locally advanced basal cell carcinoma.

    PubMed

    Amici, Jean Michel; Battistella, Maxime; Beylot-Barry, Marie; Chatellier, Anne; Dalac-Ra, Sophie; Dreno, Brigitte; Falandry, Claire; Froget, Nicolas; Giacchero, Damien; Grob, Jean Jacques; Guerreschir, Pierre; Leccia, Marie-Thérèse; Malard, Olivier; Mortier, Laurent; Routier, Emilie; Stefan, Andreea; Stefan, Dinu; Stoebner, Pierre-Emmanuel; Basset-Seguin, Nicole

    2015-01-01

    Rarely, basal cell carcinomas (BCCs) have the potential to become extensively invasive and destructive, a phenomenon that has led to the term "locally advanced BCC" (laBCC). We identified and described the diverse settings that could be considered "locally advanced". The panel of experts included oncodermatologists, dermatological and maxillofacial surgeons, pathologists, radiotherapists and geriatricians. During a 1-day workshop session, an interactive flow/sequence of questions and inputs was debated. Discussion of nine cases permitted us to approach consensus concerning what constitutes laBCC. The expert panel retained three major components for the complete assessment of laBCC cases: factors of complexity related to the tumour itself, factors related to the operability and the technical procedure, and factors related to the patient. Competing risks of death should be precisely identified. To ensure homogeneous multidisciplinary team (MDT) decisions in different clinical settings, the panel aimed to develop a practical tool based on the three components. The grid presented is not a definitive tool, but rather, it is a method for analysing the complexity of laBCC.

  2. Epidermoid cyst of the uvula in a child

    PubMed Central

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

    2016-01-01

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

  3. 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

  4. Nuclear DNA content and p53 overexpression in stage I squamous cell carcinoma of the tongue compared with advanced tongue carcinomas.

    PubMed Central

    Högmo, A; Kuylenstierna, R; Lindholm, J; Nathansson, A; Auer, G; Munck-Wikland, E

    1998-01-01

    AIMS: To evaluate the predictive value of the nuclear DNA content (image cytometry) and p53 overexpression (immuno-histochemistry using antibody CM-1) in uniformly treated stage I carcinomas of the mobile tongue. Also, to compare stage I carcinomas with advanced tongue carcinomas (stages II-IV). METHODS: Archival formalin fixed, paraffin wax embedded tumour specimens from 54 patients with stage I squamous cell carcinoma and 37 patients with advanced squamous cell carcinoma were analysed. Mean follow up time of the stage I carcinomas was 71 months (median, 62.5; range, 6-175). RESULTS: Twenty three patients (stage I) had recurring disease: 10 had local recurrence (in the tongue) and 13 had regional recurrence (cervical metastases). Locally recurring stage I carcinomas had a more pronounced DNA deviation than the other stage I carcinomas and this degree of deviation was comparable with the DNA content of advanced carcinomas. Stage I carcinomas that developed regional recurrences overexpressed p53 more frequently. In Cox multivariate regression analysis of time to recurrence, DNA deviation was a significant parameter in tumours that recurred locally (p = 0.032). p53 overexpression was the only parameter close to significance for regional recurrence (p = 0.065). CONCLUSIONS: Nuclear DNA content and p53 immunostaining are of value for the prediction of recurrence of stage I squamous cell carcinomas of the mobile tongue. Stage I tongue carcinomas that are prone to local recurrence show the same DNA content as do advanced tongue carcinomas. PMID:10193521

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

    PubMed

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

    2003-10-01

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

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

    PubMed

    Yeung, Kay T; Cohen, Ezra E W

    2015-12-15

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

  7. 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

  8. Acquired dorsal intraspinal epidermoid cyst in an adult female

    PubMed Central

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

    2016-01-01

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

  9. 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

  10. 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

  11. 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.

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

    PubMed Central

    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

  13. Epidermoid Cyst of the Sole - A Case Report

    PubMed Central

    Rajput, Santosh Singh; Gopinathan, Nayar Sajeeth

    2016-01-01

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

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

    ClinicalTrials.gov

    2017-02-08

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

  15. Splenic epidermoid cyst - a rare entity.

    PubMed

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

    2014-02-01

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

  16. Epidermoid cyst: Report of two cases

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

  18. Epidermoid cyst in quadrigeminal cistern presenting with mutism

    PubMed Central

    Kawal, Priyanka; Kumar, Raj

    2010-01-01

    Epidermoid cyst of the quadrigeminal cistern is uncommon, and its presentation as mutism as the main clinical finding with no other neurological finding is very rare. We report a case where the epidermoid cyst presented with progressive symptoms of absolute mutism, which improved significantly following surgery. The possible causes and pathophysiological mechanism of mutism in the lesions of this region are discussed in this paper. PMID:21559169

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

    PubMed

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

    2000-01-01

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

  20. 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

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

    PubMed

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

    2008-10-01

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

  2. Two different scenarios of squamous cell carcinoma within advanced Basal cell carcinomas: cases illustrating the importance of serial biopsy during vismodegib usage.

    PubMed

    Zhu, Gefei A; Sundram, Uma; Chang, Anne Lynn S

    2014-09-01

    Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment. The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected. These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.

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

    PubMed

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

    2017-01-21

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

  4. An Unusual Case of Locally Advanced Glycogen-Rich Clear Cell Carcinoma of the Breast

    PubMed Central

    Martín-Martín, Beatriz; Berná-Serna, Juan D.; Sánchez-Henarejos, Pilar; López-Poveda, María J.; Berná-Mestre, Juan D.; Rodríguez-García, José R.

    2011-01-01

    Glycogen-rich clear cell (GRCC) is a rare subtype of breast carcinoma characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. We present the case of a 55-year-old woman with a palpable mass in the right breast and clinical signs of locally advanced breast cancer (LABC). The diagnosis of GRCC carcinoma was based on certain histopathological characteristics of the tumor and immunohistochemical analysis. To our knowledge, this is the first case of GRCC LABC with intratumoral calcifications. There is no evidence of recurrence or metastatic disease after 14 months’ follow-up. PMID:22087097

  5. 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

  6. 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.

  7. 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

  8. Coexistence of intracranial epidermoid tumor and multiple cerebral aneurysms

    PubMed Central

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

    2017-01-01

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

  9. Nontraumatic Intradiploic Epidermoid Cyst and Older Age: Association or Causality?

    PubMed

    Turk, Okan; Ozdemir, Nuriye Guzin; Demirel, Nail; Atci, Ibrahim Burak; Kanat, Ayhan; Yolas, Coskun

    2017-09-25

    Intradiploic epidermoid cysts (IEC) are rare, benign lesions derived from ectodermal remnants during neural tube closure. Their origin is still debated or unknown. Analyzing of the patients with intradiploic epidermoid cysts operated in the authors' department. The patients with IEC who were operated in the authors' department between January 2014 and December 2015 were investigated from data file. Six patients with IEC were found, reviewed the literature, and noted that these cysts usually occur in adults. There are only 3 young cases that occurred after head injury. It was shown that the nontraumatic IEC are more frequent in older ages. In youngs, it can generally be embryologic or rarely of mechanical origin following trauma. Cranial trauma may be important for developing of IEC. Trauma may lead to inclusion of epidermal cells into the diploe of the skull and may be a reason of intradiploic epidermoid cyst in older age. The effect of older age, and gender difference on occurrence should be investigated.

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

    PubMed

    Lyseng-Williamson, Katherine A; Keating, Gillian M

    2013-02-01

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

  11. 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

  12. Clinical results with megestrol acetate in patients with advanced carcinoma of the breast.

    PubMed

    Ansfield, F J; Kallas, G J; Singson, J P

    1982-12-01

    Since it has been clearly established that multiple drug chemotherapy is more effective than the use of a single drug for advanced carcinoma of the breast, the latter is not commonly used today. However, upon failure of one of two combinations of drugs, if any of these drugs are then tried singly they are rarely useful, and valuable time is lost. It is at this point that megestrol acetate, a potent progestin, was found to be effective in 30 per cent of a series of 161 patients with advanced carcinoma of the breast. This drug was given orally, 40 milligrams, after each meal and at bedtime, without any toxicity or any undesirable reactions, except a weight gain--not fluid retention--in patients less than 55 years of age. The average duration of response was 8.1 months from onset of megestrol acetate therapy and for the group classified as unchanged, 5.2 months. This drug is at least as effective as any steroid or cytotoxic compound but has the advantage of not producing toxicity and, with the exception of weight gain in patients less than 55 years, no undesirable reactions of any kind, such as bone marrow depression, alopecia, nausea, vomiting or diarrhea. Hence, it can be properly administered by the patient's physician or surgeon. Since oncologists known that medroxyprogesterone therapy had not shown promising use for advanced carcinoma of the breast, it was assumed that megestrol acetate also had little activity, and hence, it was not used. However, those who did give it a trial found it a valuable compound in the management of advanced carcinoma of the breast, even after failure of all hormonal or cytotoxic combination trials. It proved to serve as an important addition to our armamentarium in the management of advanced carcinoma of the breast.

  13. Remarkable response in 2 cases of Advanced Poorly Differentiated Thyroid Carcinoma with liposomal doxorubicin plus cisplatin.

    PubMed

    Yang, Haiyan; Chen, Zhongjian; Wu, Meijuan; Lei, Tao; Yu, Haifeng; Ge, Minghua

    2016-06-02

    Poorly Differentiated Thyroid Carcinoma (PDTC), especially advanced PDTC, is an aggressive disease and displays a much poorer prognosis compared with well differentiated thyroid carcinoma. Surgery is the recommended treatment in the early stage of PDTC, however, no effective treatment modalities are currently available for advanced PDTCMethods: Two advanced PDTC patients with no radioiodine uptake adopted a cytotoxic chemotherapy with liposomal doxorubicin (35 mg/m(2), day 1) plus cisplatin (75 mg/m(2), day1-3) every 3 weeks. Computer tomography (CT) was performed after 6 cycles (case 1) or 5 cycles (case 2) of chemotherapy Our patients achieved remarkable response with one a Complete Remission (CR) and the other a very good Partial Remission (PR)Conclusion: Our findings indicate that liposomal doxorubicin-based chemotherapy regimens might produce response in PDTC patients, and improve their overall survival and quality of life. Hence we believe this result is very important for oncologists in treating PDTC.

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

    PubMed

    Hull, Diana; Armstrong, Ceri

    2010-05-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. [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.

  2. Lateral intraventricular epidermoid in a child with hydrocephalus

    PubMed Central

    Aher, Rajendra B.; Singh, Daljit; Singh, Hukum; Saran, R. K.

    2012-01-01

    Lateral intraventricular tumors are uncommon. They grow linearly rather than exponentially and hence are slow-growing lesions without causing mass effects and hydrocephalus. We report a rare case of large bulky right intraventricular epidermoid tumor in a child. This tumor was associated with mass effect on the surrounding structures and hydrocephalus. PMID:23560010

  3. Subconjunctival epidermoid cysts in Gorlin-Goltz syndrome.

    PubMed

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

    2014-08-01

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

  4. 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.

  5. Liver transplantation for hepatocellular carcinoma: recent advances in China.

    PubMed

    Lu, Tian Fei; Hua, Xiang Wei; Cui, Xiao Lan; Xia, Qiang

    2014-02-01

    Orthotopic liver transplantation is currently the best treatment option for selected patients with hepatocellular carcinoma (HCC). From 1980 to 2011, 8874 patients with HCC in China underwent liver transplantation. The organ donation classification criteria of China (China criteria), which are established by the Government of China, are divided into three parts: China criteria I, donation after brain death; China criteria II, donation after cardiac death and China criteria III, donation after dual brain-cardiac death. Data from the China Liver Transplant Registry(CLTR) System shows that patients within the Milan criteria have higher survival rates than those who are beyond these criteria. Based on CLTR data, altogether 416 patients received living-donor liver transplantation(LDLT) in China. Their 1-year and 3-year survival rates were significantly higher than those of the non-LDLT recipients. The most common early stage(<30 days after liver transplantation) complications include pleural effusion, diabetes, peritoneal effusion or abscess, postoperative infection, hypertension and intraperitoneal hemorrhage; while the most common late stage (≥ 30 days after liver transplantation) complications were diabetes, hypertension, biliary complications,postoperative infection, tacrolimus toxicity and chronic graft rejection. The incidence of vascular complication, which is the main reason for acute graft failure and re-transplantation, was 2.4%. Liver transplantation is an effective treatment for patients with HCC in China.

  6. Multimodality treatment of patients with advanced ovarian carcinoma

    SciTech Connect

    Torres, J.L.P.; Bross, D.S.; Hernandez, E.; Rosenshein, N.; Klein, J.L.; Ettinger, D.S.; Leichner, P.K.; Order, S.E.

    1982-10-01

    A multimodality treatment program has been applied to ovarian carcinoma at the Johns Hopkins Hospital since August 1975. Forty-nine patients were subdivided into 23 patients with maximally resected Stage III micrometastatic, and 26 patients with significant retained disease, 20 with Stage III macrometastatic and 6 with Stage IV. After initial pilot studies, those patients with minimally retained disease entered a randomized prospective study. Antiovarian antiserum was used in one arm of the study; in both study arms colloidal P-32, delayed split whole abdominal irradiation, and maintenance melphalan were used. For the 23 patients with micrometastatic disease the cumulative survival and survival without evidence of disease at four years is 78 and 34% respectively. Twenty-six patients with macrometastatic disease were treated with or without intraperitoneal antiserum and multiagent chemotherapy; their cumulative one year survival is 50%. The lack of significant toxicity of intraperitoneal antiovarian antiserum and the results of multimodality therapy indicate the feasibility of this therapeutic approach to further improve ovarian cancer therapy.

  7. Multimodality treatment of patients with advanced ovarian carcinoma

    SciTech Connect

    Pino y Torres, J.L.; Bross, D.S.; Hernandez, E.; Rosenshein, N.; Klein, J.L.; Ettinger, D.S.; Leichner, P.K.; Order, S.E.

    1982-10-01

    A multimodality treatment program has been applied to ovarian carcinoma at the Johns Hopkins Hospital since August 1975. Forty-nine patients were subdivided into 23 patients with maximally respected Stage III micrometastatic, and 26 patients with significant retained disease, 20 with Stage III macrometastic and 6 with STage IV. After initial pilot studies, those patients with minimally retained disease entered a randomized prospective study. Antiovarian antiserum was used in one arm of the study; in both study arms colloidal P-32, delayed split whole abdominal irradiation, and maintenance melphalan were used. For the 23 patients with micrometastiatic disease the cumulative survival and survival without evidence of disease at four years is 78 and 34% respectively. Twenty-six patients with macrometastatic disease were treated with or witout intraperitoneal antiserum and multiagent chemotherapy; their cummulative one year survival is 50%. The lack of significant toxicity of intraperitoneal antiovarian antiserum and the results of multimodality therapy indicate the feasibility of this therapeutic approach to further improve ovarian cancer therapy.

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

    PubMed

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

    2009-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  10. Superselective embolization as palliative treatment of recurrent hemorrhage in advanced carcinoma of the head and neck.

    PubMed

    Sittel, C; Gossmann, A; Jungehülsing, M; Zähringer, M

    2001-12-01

    We report a case of recurrent major hemorrhage in a patient with advanced head and neck squamous cell carcinoma. Before and between the bleeding episodes, the functional level of the patient was remarkably high. Therefore, an attempt at bleeding control with superselective embolization with Ethibloc was made. Because of its specific characteristics, this substance is almost ideal for the purpose of palliative embolization. The material used and the technique of application are described in detail. After the procedure, no hemorrhage occurred for more than 4 months. We recommend superselective embolization, preferably with Ethibloc, for minimally invasive control of recurrent bleeding as palliative treatment in selected patients with advanced head and neck carcinoma, since significant benefit in terms of the quality of life may result.

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

    PubMed

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

    2014-11-01

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

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

    SciTech Connect

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

    1987-12-01

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

  13. Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Molvar, Christopher; Lewandowski, Robert

    2015-12-01

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

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

    PubMed Central

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

    2001-01-01

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

  16. Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma.

    PubMed

    Leung, Henry W C; Liu, Chung-Feng; Chan, Agnes L F

    2016-05-18

    Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO's guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan.

  17. Targeted therapy in advanced gastric carcinoma: the future is beginning.

    PubMed

    Schinzari, G; Cassano, A; Orlandi, A; Basso, M; Barone, C

    2014-01-01

    Gastric cancer represents one of the most common cancer worldwide. Unfortunately, the majority of patients present in advanced stage and outcome still remains poor with high mortality rate despite decreasing incidence and new diagnostic and therapeutic strategies. Although utility of classical chemotherapy agents has been widely explored, advances have been slow and the efficacy of these agents has reached a plateau of median overall survival not higher than 12 months. Therefore, researchers focused their attention on better understanding molecular biology of carcinogenesis and deeper knowledge of the cancer cell phenotype, as well on development of rationally designed drugs that would target specific molecular aberrancies in signal transduction pathways. These targets include cell surface receptors, circulating growth and angiogenic factors and other molecules involved in downstream intracellular signaling pathways, including receptor tyrosine kinases. However, therapeutic advances in gastric cancer are not so encouraging when compared to other solid organ malignancies such as breast and colorectal cancer. This article reviews the role of targeted agents in gastric cancer as single-agent therapy or in combination regimens, including their rational and emerging mechanism of action, current and emerging data. We focused our attention mainly on published phase III studies, therefore cornerstone clinical trials with trastuzumab and bevacizumab have been largely discussed. Phase III studies presented in important international meetings are also reviewed as well phase II published studies and promising new therapies investigated in preclinical or phase I studies. Today, in first-line treatment only trastuzumab has shown significantly increased survival in combination with chemotherapy, whereas ramucirumab as single agent resulted effective in progressing patients, but - despite several disappointing results - these are the proof of principle that targeting the proper

  18. 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.

  19. 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

  20. Phase 1 study of erlotinib plus radiation therapy in patients with advanced cutaneous squamous cell carcinoma.

    PubMed

    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

    To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. 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. 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%. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Efficacy of nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen in treatment of advanced oral carcinoma.

    PubMed

    Meng, Jian; Gu, Qian-ping; Meng, Qing-fei; Zhang, Jie; Li, Zhi-ping; Si, Ya-meng; Guo, Wei; Zhuang, Qian-wei

    2014-01-01

    The present study aimed to evaluate efficacy and adverse effects of Nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen in the treatment of advanced oral carcinoma. Nine patients with advanced oral carcinoma were treated with Nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen (test group). The treatment was given as follows: Nimotuzumab 200 mg, given as intravenous infusion once a week for 6 weeks; docetaxel and cisplatin, 75 mg/m(2) each, on day 1 only; 5-fluorouracil, 750 mg/m(2) infused continually for 8 h, used from day 1 to 5; the total cycle was for 21 days. Another eight patients comprised control group (docetaxel-cisplatin-fluorouracil regimen alone). Study patients from both groups were evaluated for objective response. The response rate was significantly (p = 0.044) higher in test group (88.9 vs. 37.5 % in control group). The disease control rate also tended to be higher in test group (100 vs. 62.5 % in control group; p = 0.083). The major adverse effects were bone marrow suppression, nausea, vomiting, and alopecia. The incidence of adverse effects was similar between both study groups. In conclusion, Nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen is effective and safe in the treatment of advanced oral carcinoma.

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

    SciTech Connect

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

    2010-12-01

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

  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. Advanced gastroesophageal carcinoma: an update on the current therapeutic landscape.

    PubMed

    Hayashi, Yuki; Blum, Mariela A; Ajani, Jaffer A

    2012-01-01

    Gastroesophageal cancers are usually diagnosed in an advanced stage, and effective treatment options remain limited. The discovery of new drugs to treat these diseases has been slow for decades. An occasional favorable outcome, trastuzumab, in patients with HER2 protein-overexpressing tumors, is welcome but not sufficient. For advanced gastroesophageal adenocarcinoma (AGC), fluoropyrimidines (given orally or intravenously) plus a platinum compound (usually cisplatin) have been accepted as a global reference to streamline new drug development. The addition of a third cytotoxic (docetaxel or epirubicin) can produce modest prolongation of overall survival. In some European countries, the irinotecanbased regimen is considered as an alternative to platinum-based first-line therapy. Selecting a safe, effective, and convenient regimen is desirable and is the focus of current research. Additionally, it appears that survival differences by regions (e.g., Asians survive longer compared to Western and South American patients) are likely due to second- and third-line therapies, differences in tumor biology, or unknown reasons. Future progress could come from 1 of 2 approaches: (1) conducting many empiric phase III trials in unselected patients or (2) through detailed studies of molecular biology to develop rational therapies. We provide a brief update on the treatment of AGC. Copyright © 2012 S. Karger AG, Basel.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    1976-05-01

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

  8. 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.

  9. Could tumor characteristics identified by colonoscopy predict the locally advanced rectal carcinoma?

    PubMed

    Wang, Hao; Cao, Fu-ao; Gong, Hai-feng; Zheng, Jian-ming; Fu, Chuan-gang

    2010-09-01

    Neoadjuvant chemoradiation is now considered the standard care for locally advanced rectal carcinoma (T3-4 or/and N1-2 lesions), but the accuracy of staging examinations including endorectal ultrasonography (ERUS) and MRI is far from excellent. In addition, the above staging equipment or professionals who perform the examinations may not be available in some hospitals, while preoperative colonoscopy and biopsy are usually obtainable in most hospitals. The objective of the present study was to investigate the clinical and pathological characteristics of locally advanced rectal carcinoma and identify candidates for neoadjuvant chemoradiation. This was a retrospective study. Patients who were treated for rectal cancer at Changhai Hospital from January 1999 to July 2008 were identified from our prospectively collected database. Statistical analysis was performed using SPSS Software System (version 15.0). The Mann-Whitney test, chi-square test and multivariate Logistic regression analysis were performed. A total of 1005 cases were included in this research, of which 761 cases were identified as locally advanced rectal carcinoma depending on postoperative TNM staging. The results of multivariate Logistic regression analysis indicated seven independent risk factors that could be used to predict a locally advanced rectal carcinoma independently: a high grade (including poor differentiation and undifferentiation) (OR: 3.856; 95% CI: 2.064 to 7.204; P = 0.000); large tumor size (OR: 2.455; 95% CI: 1.755 to 3.436; P = 0.000); elevated preoperative serum CEA level (OR: 1.823; 95% CI: 1.309 to 2.537; P = 0.000); non-polypoid tumor type (OR: 1.758; 95% CI: 1.273 to 2.427; P = 0.001); the absence of synchronous polyps (OR: 1.602; 95% CI: 1.103 to 2.327; P = 0.013); the absence of blood in stool (OR: 1.659; 95% CI: 1.049 to 2.624; P = 0.030); and a greater circumferential tumor extent (OR: 1.813; 95% CI: 1.055 to 3.113; P = 0.031). Based on these findings, a Logistic equation was

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    1990-01-01

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

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

    PubMed

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

    2015-10-01

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

  15. 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

  16. Craniopharyngioma and epidermoid tumour in same child: a rare association

    PubMed Central

    Singh, Deepak Kumar; Singh, Neha; Parihar, Anit; Singh, Ragini

    2013-01-01

    Simultaneous occurrence of histologically different primary brain tumours is rare, and its preoperative diagnosis is still challenging. The explanations for the simultaneous occurrence of different primary intracranial tumours in the absence of phacomatoses or prior radiation exposure are at present hypothetical, and these tumours could be simply coincidental. Herein, we report a case of a boy presenting with features of raised intracranial pressure and right-sided sensorineural hearing loss. Brain MRI revealed two different neoplastic pathologies at different sites: an intrasellar and suprasellar craniopharyngioma and a right cerebello-pontine angle epidermoid. To the best of our knowledge, this is the first report in literature of a craniopharyngioma coexisting with an epidermoid, in the same individual. PMID:23737578

  17. 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

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

    PubMed

    Bukowski, Ronald M

    2012-01-01

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

  19. Third Generation Tyrosine Kinase Inhibitors and Their Development in Advanced Renal Cell Carcinoma

    PubMed Central

    Bukowski, Ronald M.

    2012-01-01

    Angiogenesis in general and the vascular endothelial growth factor (VEGF) signaling axis in particular is a validated target in renal cell carcinoma (RCC). Clear-cell carcinoma of the kidney is now recognized as a malignancy that is sensitive to inhibitors of the VEGF pathway. Treatment options for patients with metastatic renal cell carcinoma have evolved in dramatic fashion over the past 6 years, and a new paradigm has developed. The cytokines interferon-α and interleukin-2 were previously utilized for therapy, but since December 2005, six new agents have been approved in the United States for the treatment of advanced RCC. Two are tyrosine kinase inhibitors (TKI’s) including sunitinib and recently pazopanib, and the multikinase inhibitor sorafenib. The current review examines the evolving data with the next generation of TKI’s, axitinib and tivozanib being developed for the treatment of advanced RCC. These agents were synthesized to provide increased target specificity and enhanced target inhibition. The preclinical and clinical data are examined, an overview of the development of these TKI’s is provided, and discussion plus speculation concerning their potential roles as RCC therapy is provided. PMID:22655261

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

    PubMed Central

    Yoshida, Naohiro; Kodama, Kozue; Iino, Yukiko

    2014-01-01

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

  1. 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.

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

    PubMed

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

    2013-01-01

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

  3. Thyroid gland invasion in advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Mangussi-Gomes, João; Danelon-Leonhardt, Fernando; Moussalem, Guilherme Figner; Ahumada, Nicolas Galat; Oliveira, Cleydson Lucena; Hojaij, Flávio Carneiro

    Squamous cell carcinoma of the larynx and hypopharynx has the potential to invade the thyroid gland. Despite this risk, the proposition of either partial or total thyroidectomy as part of the surgical treatment of all such cases remains controversial. To evaluate the frequency of invasion of the thyroid gland in patients with advanced laryngeal or hypopharyngeal squamous cell carcinoma submitted to total laryngectomy or pharyngolaryngectomy and thyroidectomy; to determine whether clinic-pathological characteristics can predict glandular involvement. A retrospective case series with chart review, from January 1998 to July 2013, was undertaken in a tertiary care university medical center. An inception cohort of 83 patients with larynx/hypopharynx squamous cell carcinoma was considered. All patients had advanced stage disease (clinically T3-T4) and underwent total laryngectomy or total pharyngolaryngectomy in association with thyroidectomy. Adjuvant therapy was indicated when tumor or neck conditions required. Frequency of thyroid cartilage invasion was calculated; univariate and multivariate analysis of demographic, clinical and pathological characteristics associated with cartilage invasion were performed. The overall frequency of invasion of the thyroid gland was 18.1%. Glandular involvement was associated with invasion of the following structures: anterior commissure (odds ratio=5.13; 95% confidence interval 1.07-24.5), subglottis (odds ratio=12.44; 95% confidence interval 1.55-100.00) and cricoid cartilage (odds ratio=15.95; 95% confidence interval 4.23-60.11). Invasion of the thyroid gland is uncommon in the context of laryngopharyngeal squamous cell carcinoma. Clinical and pathological features such as invasion of the anterior commissure, subglottis and cricoid cartilage are more associated with glandular invasion. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights

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

    PubMed Central

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

    2013-01-01

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

  5. Tubulopapillary mammary carcinoma in a brown bear (Ursus arctos).

    PubMed

    Nak, Deniz; Cangul, I Taci; Nak, Yavuz; Cihan, Huseyin; Celimli, Nureddin

    2008-04-01

    A 28-yr-old, nulliparous female brown bear (Ursus arctos) at the Karacabey Ovakurusu Bear Sanctuary presented with an enlargement of the mammary gland. Three other nodules were also noted in the proximity of the mammary gland and over the vulva. Clinical, hematologic, ultrasonographic, and radiologic examinations were performed; the enlarged mammary gland was removed and the other masses were also excised. Histopathologic examination revealed tubulopapillary carcinoma of the mammary gland, and the other masses were diagnosed as epidermoid cysts. This is the first reported case of tubulopapillary mammary carcinoma accompanied by epidermoid cysts in a bear.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. 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

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

    PubMed Central

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

    2016-01-01

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

  10. Hepatocellular carcinoma in patients without advanced fibrosis after HCV eradication antiviral treatment.

    PubMed

    Sánchez-Torrijos, Yolanda; Ternero Vega, Jara Eloísa; Cepeda Franco, Carmen

    2017-10-01

    From the last few years, hepatitis C virus and the new direct antiviral treatments are being more and more important. In consequence, case studies like the one we present, the appearance of hepatocelullar carcinoma after its eradication with fibrosis grade 2, are getting special interest. In 2007, our patient was treated with pegylated interferon α-2a and ribavirin, having a sustained virological response after it. In this way, liver fibrosis grade 2 was confirmed by a biopsy. Finally, after corroborating a good liver functioning, the patient was discharged (as, according to the guidebooks, an ultrasound scan of screeing every 6 months was not required). In 2014, the patient came to hospital because of a pain at right hypochondrium and he was diagnosed with hepatocelullar carcinoma. A hepatectomy was done objectifying the surgical piece, liver fibrosis grade 2, one more time. Subsequently, a tumour relapse through an abdominal CT scan, a tumour relapse was found and despite the Sorafenib treatment, the patient died on January 2015. This case study provokes curiosity and uncertainty about the attitude which should be taken respect to the monitoring, and hepatocelullar carcinoma screening overall, in patients with a sustained virological response after eradicator treatment and without advanced fibrosis. Nowadays, with the benefits of the new treatments, the amount of patients in this situation is increasing significantly.

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

    PubMed

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

    2009-01-01

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

  12. Clinical Characteristics of Idiopathic Epidermoid and Dermoid Cysts of the Ear

    PubMed Central

    Cho, Yesun; Lee, Dong-Hee

    2017-01-01

    Background and Objectives Epidermoid and dermoid cysts are benign cystic lesions, lined by ectodermal squamous epithelium. They are not common in the head and neck areas, which constitute ~7% of all cases of epidermoid and dermoid cysts. The aim of this study was to investigate the clinical characteristics of epidermoid and dermoid cysts that developed around the ear. Subjects and Methods The clinical records were retrospectively reviewed for patients confirmed histologically as idiopathic epidermoid and dermoid cysts of the ear from January 2011 to December 2015. Results Total 15 cases consisted of 14 epidermoid cysts and only 1 dermoid cyst. There were 11 males and 4 females (mean age of 37.8±16.8 years old). Right side was 7 cases and left was 8. The cyst was located at the lobule in 4 cases, at the ear canal in 4 cases, at the preauricular area in 4 cases, and at the postauricular area in 3 cases. In cases of epidermoid cysts, there was no significant difference in age, sex, and size according to the location. Patients with cysts on helix were younger than others. Conclusions This study demonstrated that most cutaneous cysts developing around the ear were epidermoid cysts and there was no site preference for occurrence of epidermoid cysts. PMID:28704893

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

    PubMed

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

    2012-03-01

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

  14. 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

  15. Mood Disorder as an Early Presentation of Epidermoid of Quadrigeminal Cistern.

    PubMed

    Kar, Sujita Kumar; Das, Kuntal Kanti; Jaiswal, Awadhesh Kumar; Jaiswal, Sushila

    2017-01-01

    Intracranial epidermoids are space-occupying lesions of rare variant. Although cerebropontine angle and parasellar region are common sites of occurrence, it has been reported in various other parts of the intracranial cavity. Headache and features of increased intracranial tension are the common clinical manifestation. Report of psychiatric symptoms as the initial presentation of epidermoid is not known in literature except a single case report, which describes mutism to be the manifestation of intracranial epidermoid. We present here the case of a young male, who presented with long depressive episode persisting for 3 years with subsequent switch to mania, which persisted for more than 3 years. An episode of unconsciousness warranted neuroimaging, which revealed a large epidermoid of the quadrigeminal cistern. Surgical resection of the epidermoid was done. Persisting mood symptoms had responded to mood stabilizer and antipsychotic treatment.

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

    PubMed Central

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

    2015-01-01

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

  17. 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.

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

    PubMed Central

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

    2017-01-01

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

  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. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  4. 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.

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

    PubMed

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

    2014-12-01

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

  6. [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.

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

    SciTech Connect

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

    1990-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-01-01

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

  10. 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.

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

    ClinicalTrials.gov

    2017-09-15

    Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage III Major Salivary Gland Cancer AJCC v7; Stage III Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Tongue Carcinoma

  12. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2017-03-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-10-01

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

  17. 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

  18. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

    Kang, Ha Yan; Moon, Sung Hoon; Song, Il Han

    2014-02-26

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

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

    PubMed

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

    1997-10-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-11-15

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

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

    PubMed Central

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

    2016-01-01

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

  9. 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

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

    PubMed Central

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

    2015-01-01

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

  11. Practical Effect of Sorafenib Monotherapy on Advanced Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis

    PubMed Central

    Jeong, Soung Won; Shim, Kwang Yeun; Lee, Sae Hwan; Kim, Sang Gyune; Cha, Sang-Woo; Kim, Young Seok; Cho, Young Deok; Kim, Hong Soo; Kim, Boo Sung; Kim, Kyoung Ha; Kim, Jung Hoon

    2013-01-01

    Background/Aims We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. Methods In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. Results All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. Conclusions A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted. PMID:24312711

  12. Radiomic machine-learning classifiers for prognostic biomarkers of advanced nasopharyngeal carcinoma.

    PubMed

    Zhang, Bin; He, Xin; Ouyang, Fusheng; Gu, Dongsheng; Dong, Yuhao; Zhang, Lu; Mo, Xiaokai; Huang, Wenhui; Tian, Jie; Zhang, Shuixing

    2017-09-10

    We aimed to identify optimal machine-learning methods for radiomics-based prediction of local failure and distant failure in advanced nasopharyngeal carcinoma (NPC). We enrolled 110 patients with advanced NPC. A total of 970 radiomic features were extracted from MRI images for each patient. Six feature selection methods and nine classification methods were evaluated in terms of their performance. We applied the 10-fold cross-validation as the criterion for feature selection and classification. We repeated each combination for 50 times to obtain the mean area under the curve (AUC) and test error. We observed that the combination methods Random Forest (RF) + RF (AUC, 0.8464 ± 0.0069; test error, 0.3135 ± 0.0088) had the highest prognostic performance, followed by RF + Adaptive Boosting (AdaBoost) (AUC, 0.8204 ± 0.0095; test error, 0.3384 ± 0.0097), and Sure Independence Screening (SIS) + Linear Support Vector Machines (LSVM) (AUC, 0.7883 ± 0.0096; test error, 0.3985 ± 0.0100). Our radiomics study identified optimal machine-learning methods for the radiomics-based prediction of local failure and distant failure in advanced NPC, which could enhance the applications of radiomics in precision oncology and clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

    Biró, Krisztina; Küronya, Zsófia

    2010-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. Assessment of improved organ at risk sparing for advanced cervix carcinoma utilizing precision radiotherapy techniques.

    PubMed

    Georg, Dietmar; Georg, Petra; Hillbrand, Martin; Pötter, Richard; Mock, Ulrike

    2008-11-01

    To evaluate the potential benefit of proton therapy and photon based intensity-modulated radiotherapy in comparison to 3-D conformal photon radiotherapy (3D-CRT) in locally advanced cervix cancer. In five patients with advanced cervix cancer 3D-CRT (four-field box) was compared with intensity modulated photon (IMXT) and proton therapy (IMPT) as well as proton beam therapy (PT) based on passive scattering. Planning target volumes (PTVs) included primary tumor and pelvic and para-aortic lymph nodes. Dose-volume histograms (DVHs) were analyzed for the PTV and various organs at risk (OARs) (rectal wall, bladder, small bowel, colon, femoral heads, and kidneys). In addition dose conformity, dose inhomogeneity and overall volumes of 50% isodoses were assessed. All plans were comparable concerning PTV parameters. Large differences between photon and proton techniques were seen in volumes of the 50% isodoses and conformity indices. DVH for colon and small bowel were significantly improved with PT and IMPT compared to IMXT, with D(mean) reductions of 50-80%. Doses to kidneys and femoral heads could also be substantially reduced with PT and IMPT. Sparing of rectum and bladder was superior with protons as well but less pronounced. Proton beam RT has significant potential to improve treatment related side effects in the bowel compared to photon beam RT in patients with advanced cervix carcinoma.

  16. 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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2015-12-01

    Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression-free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child-Pugh class, baseline serum des-gamma-carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long-term treatment for advanced HCC patients regardless of their extrahepatic metastasis status. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2007-08-01

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

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

    PubMed

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

    1981-01-01

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

  3. Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

    PubMed

    De Paz, Dante; Kao, Huang-Kai; Huang, Yenlin; Chang, Kai-Ping

    2017-08-10

    Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients. In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy. Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

  4. 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

  5. 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

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

    PubMed

    Glen, Hilary

    2016-10-01

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

  7. 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

  8. The safety and efficacy of sonidegib for the treatment of locally advanced basal cell carcinoma.

    PubMed

    Collier, Nicholas J; Ali, Faisal R; Lear, John T

    2016-10-01

    Basal cell carcinomas (BCCs) are the commonest malignancy in the Western world. Locally advanced BCCs (laBCCs) represent tumours that have developed in difficult-to-treat facial sites, aggressively recurrent tumours, large neglected tumours and those in which current treatment options are excluded by clinical or patient-driven criteria. It is estimated laBCCs represent 1% of BCCs. Sonidegib is an oral hedgehog pathway inhibitor with a novel structure. It has recently been licensed for the treatment of laBCC. This article provides a comprehensive review of the literature regarding sonidegib, detailing the pharmacology of the compound, clinical trial data, competitor compounds and a future perspective. Expert commentary: Sonidegib is a novel smoothened (SMO) inhibitor with comparable efficacy to vismodegib, with patient response rates of 44% (sonidegib) and 43% (vismodegib). The adverse effect profile of these two treatments is similar with the main effects being considered to be class effects of SMO inhibitors.

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

    Jiang, Wenpeng; Wang, Zhou; Jia, Yang

    2017-01-01

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

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

    PubMed

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

    1990-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Prescription Patterns of Sorafenib and Outcomes of Patients with Advanced Hepatocellular Carcinoma: A National Population Study.

    PubMed

    Lu, Li-Chun; Chen, Pei-Jer; Yeh, Yi-Chun; Hsu, Chih-Hung; Chen, Ho-Min; Lai, Mei-Shu; Shao, Yu-Yun; Cheng, Ann-Lii

    2017-05-01

    Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC). We analyzed national prescription patterns and treatment outcomes of patients who received sorafenib for advanced HCC. We established a nation-wide cohort of patients who started receiving treatment with sorafenib for advanced HCC between August 2012 and July 2013 from the National Health Insurance Research Database of Taiwan and also retrieved demographic and prescription data. The databases of National Death Registry and Taiwan Cancer Registry were used for survival outcomes and cancer diagnosis information, respectively. A total of 3,293 patients were enrolled. The median overall survival (OS) and time to treatment discontinuation (TTD) of all patients were 6.8 and 2.6 months, respectively. Upon the first prescription of sorafenib, 58.4% of patients received the standard dose (800 mg/day). Among them, 61.9% had subsequent dose reduction. A total of 41.6% of patients initially received lower than standard doses; 36.1% of them had subsequent dose escalation to 800 mg/day. Being male (odds ratio=1.41; p<0.001) and treatment year of 2012 (odds ratio=1.28; p=0.002) were associated with the standard initial dose. Patients who received standard initial dose of sorafenib, compared to patients who received lower initial doses, exhibited longer OS (median of 7.8 vs. 6.6 months, p<0.001) but similar TTD (median of 2.6 vs. 2.9 months, p=0.840). A considerable number of patients with advanced HCC received less than the standard dose of sorafenib. The treatment outcomes in the general population were consistent with those reported in clinical trials. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

    PubMed

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

    2005-04-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

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

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

    PubMed

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

    2015-08-01

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

  18. Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis.

    PubMed

    Liu, Zhi-Gang; Zhao, Yu; Tang, Jiao; Zhou, Yu-Juan; Yang, Wen-Juan; Qiu, Yan-Fang; Wang, Hui

    2016-04-26

    Nimotuzumab is a blocking monoclonal antibody against epidermal growth factor receptor (EGFR). However, little is known about the safety and preliminary efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NPC patients. A total of 42 patients diagnosed between 2011 and 2013 were enrolled. Our results demonstrated 38 patients had a complete response (90.5%), 4 patients had a partial response (9.5%). And no patients had progressive disease at early treatment response evaluation, giving an ORR of 100%. The 2-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.4%, 93.1% and 96.6% respectively. The most common adverse events were mucositis (19 patients), hematology toxicity (14 patients) with 6 and 3 cases of grade 3/4 toxicity respectively. Skin rash was not developed in our 43 patients. Thus, nimotuzumab combined with concurrent chemoradiotherapy showed encouraging outcomes in the treatment of locally advanced nasopharyngeal carcinoma, without accumulation of toxicity and well-tolerated.

  19. Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis

    PubMed Central

    Zhou, Yu-juan; Yang, Wen-juan; Qiu, Yan-fang; Wang, Hui

    2016-01-01

    Nimotuzumab is a blocking monoclonal antibody against epidermal growth factor receptor (EGFR). However, little is known about the safety and preliminary efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NPC patients. A total of 42 patients diagnosed between 2011 and 2013 were enrolled. Our results demonstrated 38 patients had a complete response (90.5%), 4 patients had a partial response (9.5%). And no patients had progressive disease at early treatment response evaluation, giving an ORR of 100%. The 2-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.4%, 93.1% and 96.6% respectively. The most common adverse events were mucositis (19 patients), hematology toxicity (14 patients) with 6 and 3 cases of grade 3/4 toxicity respectively. Skin rash was not developed in our 43 patients. Thus, nimotuzumab combined with concurrent chemoradiotherapy showed encouraging outcomes in the treatment of locally advanced nasopharyngeal carcinoma, without accumulation of toxicity and well-tolerated. PMID:27016412

  20. A Phase II Randomized Dose Escalation Trial of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

    PubMed Central

    Pressiani, Tiziana; Boni, Corrado; Carnaghi, Carlo; Rota Caremoli, Elena; Fagiuoli, Stefano; Foa, Paolo; Salvagni, Stefania; Cortesi, Enrico; Chiara Tronconi, Maria; Personeni, Nicola; Bozzarelli, Silvia; Chiara Banzi, Maria; Fanello, Silvia; Romano Lutman, Fabio; Giordano, Laura; Santoro, Armando

    2013-01-01

    Background. Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated. Methods. Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52). The primary end point was progression-free survival (PFS). Time to progression, overall survival, and safety were also evaluated. Results. The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1–2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand-foot-skin reaction (49%), abdominal pain (37%), and stomatitis (26%). Conclusions. Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second-line treatment still remains an open issue to be explored in appropriate clinical trials. PMID:23580239

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2015-07-01

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

  3. Epidermoid cysts: an exclusive palatal presentation and a case series.

    PubMed

    Ravindranath, Abhilash Pasare; Ramalingam, Karthikeyan; Natesan, Anuja; Ramani, Pratibha; Premkumar, Priya; Thiruvengadam, Chandrasekar

    2009-04-01

    Epidermoid cysts (EC) can occur anywhere in the body. In the head and neck region, they more often present in the midline between the submental region and the supra sternal notch. EC in the oral cavity are extremely rare and present as benign, slow growing lesions. Records from College of Dental Surgery, Saveetha University, from 2002 to 2006 were searched for cases coded as EC. The study included 13 cases within the oral and maxillofacial region. Of the 13 cases, 11 occurred in male patients and 2 in female patients. Specific anatomic locations included posterior auricular region (n = 2), forehead region (n = 2), lateral side of the face (n = 3), chin (n = 1), gingiva (n = 3), intraosseous within the anterior maxilla (n = 1), and hard palate (n = 1). Besides the previously reported locations, we present the first case occurring in the hard palate, measuring 5 x 3 cm in size along with melanin pigmentation.

  4. Phase 2 Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)

    ClinicalTrials.gov

    2016-12-09

    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

  5. The Level of Squamous Cell Carcinoma Antigen and Lymph Node Metastasis in Locally Advanced Cervical Cancer.

    PubMed

    Lekskul, Navamol; Charakorn, Chuenkamon; Lertkhachonsuk, Arb-Aroon; Rattanasiri, Sasivimol; Israngura Na Ayudhya, Nathpong

    2015-01-01

    This study aimed to determine the utility and a cut-off level of serum squamous cell carcinoma antigen (SCC-Ag) to predict lymph node metastasis in locally advanced cervical cancer cases. We also investigated the correlation between SCC-Ag level and lymph node status. From June 2009 to June 2014, 232 patients with cervical cancer stage IB2-IVA, who were treated at Ramathibodi Hospital, were recruited. Receiver operating characteristic (ROC) curves were used to identify the best cut-off point of SCC-Ag level to predict lymph node metastasis. Quantile regression was performed to evaluate the correlation between SCC-Ag levels and pelvic lymph node metastasis, paraaortic lymph node metastasis, and parametrial involvement as well as tumor size. Pelvic lymph node metastasis and paraaortic lymph node metastasis were diagnosed in 46.6% and 20.1% of the patients, respectively. The median SCC-Ag level was 6 ng/mL (range, 0.5 to 464.6 ng/ mL). The areas under ROC curves between SCC-Ag level and pelvic lymph node metastasis, paraaotic lymph node metastasis, parametrial involvements were low. SCC-Ag level was significantly correlated with paraaortic lymph node status (p=0.045) but not with pelvic lymph node status and parametrial involvement. SCC-Ag level was also related to the tumor diameter (p<0.05). SCC-Ag level is not a good predictor for pelvic and paraaortic lymph node metastasis. However, it is still beneficial to assess the tumor burden of squamous cell carcinoma of the cervix.

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

    PubMed Central

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

    2001-01-01

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

  7. 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.

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

    PubMed

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

    2015-09-01

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

  9. 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).

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  12. Systemic cytotoxic chemotherapy of patients with advanced hepatocellular carcinoma in the era of sorafenib nonavailability.

    PubMed

    Yoon, Eileen L; Yeon, Jong Eun; Lee, Hyun Jung; Suh, Sang Jun; Lee, Sun Jae; Kang, Seong Hee; Kang, Keunhee; Yoo, Yang Jae; Kim, Ji Hoon; Yim, Hyung Joon; Byun, Kwan Soo

    2014-03-01

    The goal of the study was to compare the efficacy and safety of sorafenib with those of systemic cytotoxic chemotherapy. Sorafenib treatment has shown to improve the survival in patients with advanced hepatocellular carcinoma (HCC) when compared with placebo. However, whether sorafenib controls advanced-stage HCC better than systemic cytotoxic chemotherapy has not been elucidated. We retrospectively reviewed the medical records of 220 patients with measurable advanced HCC who had not received systemic treatment previously between January 2007 and April 2012. Among these patients, 78 had been treated with sorafenib. Another 14 patients who were treated with a 4-weekly regimen of adriamycin, cisplatin, and capecitabine were included as the historical control group for comparison. The median overall survival, the progression-free survival, response rates, and safety profiles were evaluated. Baseline characteristics were similar between the treatment groups. The median overall survival was 7.2 months [95% confidence interval (CI), 5.6-8.8] in the sorafenib group and 11.2 months (95% CI, 8.1-14.2) in the cytotoxic chemotherapy group (P=0.10). The median progression-free survival was 3.2 months (95% CI, 2.2-4.3) in the sorafenib group and 5.9 months (95% CI, 3.6-8.2) in the cytotoxic chemotherapy group (P=0.07). The deterioration of liver function and neutropenia were the most frequent serious adverse events in the sorafenib and the systemic chemotherapy group. Although a direct head-to-head comparison could not be done, there were some patients who showed a good response to systemic cytotoxic chemotherapy. Further assessment is necessary to study the role of chemotherapy in patients who are intolerant or intractable to sorafenib.

  13. Relationships between pazopanib exposure and clinical safety and efficacy in patients with advanced renal cell carcinoma

    PubMed Central

    Suttle, A B; Ball, H A; Molimard, M; Hutson, T E; Carpenter, C; Rajagopalan, D; Lin, Y; Swann, S; Amado, R; Pandite, L

    2014-01-01

    Background: Pazopanib, an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-Kit, is approved in locally advanced/metastatic renal cell carcinoma (RCC). Methods: Data from trials in advanced solid tumours and advanced/metastatic RCC were used to explore the relationships between plasma pazopanib concentrations and biomarker changes, safety, and efficacy. Initially, the relationships between pharmacokinetic parameters and increased blood pressure were investigated, followed by analysis of steady-state trough concentration (Cτ) and sVEGFR2, safety, progression-free survival (PFS), response rate, and tumour shrinkage. Efficacy/safety end points were compared at Cτ decile boundaries. Results: Strong correlation between increased blood pressure and Cτ was observed (r2=0.91), whereas weak correlation was observed between Cτ and decline from baseline in sVEGFR2 (r2=0.27). Cτ threshold of >20.5 μg ml−1 was associated with improved efficacy (PFS, P<0.004; tumour shrinkage, P<0.001), but there was no appreciable benefit in absolute PFS or tumour shrinkage from Cτ >20.5 μg ml−1. However, the association of Cτ with certain adverse events, particularly hand–foot syndrome, was continuous over the entire Cτ range. Conclusions: The threshold concentration for efficacy overlaps with concentrations at which toxicity occurs, although some toxicities increase over the entire Cτ range. Monitoring Cτ may optimise systemic exposure to improve clinical benefit and decrease the risk of certain adverse events. PMID:25349968

  14. Clinical effectiveness of 125I-seed implantation in combination with nimotuzumab therapy for the advanced oral carcinoma: preliminary results.

    PubMed

    Meng, J; Wang, X; Zhuang, Q-W; Gu, Q-P; Zhang, J; Li, Z-P

    2014-01-01

    This study determines the short-term efficacy and toxicity of combined 125I-seed implantation and nimotuzumab in treating the advanced oral carcinoma. 125I-seed implantation is safe and has shown good short-term efficacy in clinical practice. Nimotuzumab is a useful biological agent for targeted therapy. Effect of 125I-seed implantation with nimotuzumab in treating oral carcinomas remains unclear. From November 2011 to December 2012, 11 patients with advanced oral carcinoma (pathologic types: 7 cases of squamous cell carcinoma and 4 cases of poorly differentiated adenocarcinoma) were enrolled in our hospital. The patients did not receive surgery due to systemic disease or locally advanced cancer. All of them underwent 125I-seed implantation with the matched peripheral doses (MPD) ranging from 90-100 Gy. The apparent activity per seed ranged from 0.6 mCi (2.22 MBq) to 0.7 mCi (2.59 MBq). Later, all patients were given nimotuzumab (200 mg, intravenous drip, weekly, for 6 weeks). The patients were then followed up and the response rate, acute/chronic radiation-induced injury, and safety of the induction treatment were analyzed. Three patients achieved complete while 6 patients had partial response; yielding a response rate of 81.8%. Major adverse events included radiation-induced oral mucositis, local hemorrhage, bone marrow suppression, nausea/vomiting, and alopecia. Adverse reaction was not significantly different between the group of patients under 65 years of age and over 65 years of age (p > 0.05). Nimotuzumab enhanced the tumor sensitivity to brachytherapy without increasing AEs and improved the patients' life quality. 125I-seed implantation combined with nimotuzumab is effective and safe for patients with unresectable oral carcinoma.

  15. Multiple field hyperthermia combined with radiotherapy in advanced carcinoma of the breast.

    PubMed

    Engin, K; Tupchong, L; Waterman, F M; Komarnicky, L; Mansfield, C M; Hussain, N; Hoh, L L; McFarlane, J D; Leeper, D B

    1994-01-01

    Extensive recurrences on the chest wall of advanced carcinoma of the breast in 20 patients were treated with multiple field patchwork hyperthermia combined with radiation therapy between 1987-1991. The objective of the study was to evaluate the feasibility, tumour response and complications of treating extensive lesions with multiple, overlapping fields of hyperthermia. All lesions were diffuse encompassing up to 2900 cm2 in area with or without multiple nodules < or = 3 cm deep. All lesions had failed previous therapy with all but three failing previous radiotherapy. Hyperthermia consisted of 282 hyperthermia applicator fields and 357 hyperthermia treatments with external 915 MHz microwaves using commercially available applicators. Hyperthermia applicator fields were defined by the surface 50% SAR distribution of a particular applicator, and hyperthermia fields were abutted to cover the entire tumour bearing area. Radiation therapy consisted of 81 fields to a mean dose of 40 +/- 1 Gy (SE), 88% of fields received between 30 and 50 Gy. The equivalent dose was 42 +/- 1 Gy, based on the linear-quadratic model and alpha/beta = 25 (Fowler 1989). Overlapping hyperthermia fields were separated by an interval of at least three days. Up to four heat sessions per week were required to cover the entire tumour in a rotating fashion. The hyperthermia treatment time was 60 min. Hyperthermia treatments were continued for the duration of radiation therapy. Each hyperthermia applicator field was heated at least once. Patients were exposed to a mean of 14 +/- 3 hyperthermia applicator fields (range of 3-46 fields) and a mean of 18 +/- 3 hyperthermia treatments (range of 6-61) delivered over a mean of 7.5 +/- 0.9 weeks (range of 3-17 weeks). Each field was heated an average of 1.3 times. The tumour complete response rate was 95% with a recurrence rate of 5%. Nevertheless, the mean survival of patients with a complete response was only 10.8 +/- 1.7 months (range of 2-28 months

  16. Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma.

    PubMed

    Mabed, M; El-Helw, L; Shamaa, S

    2004-01-12

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although a wide range of therapeutic options is available, the efficacy of these methods and the prognosis of patients with HCC remain very poor. This study was conducted to evaluate the efficacy and safety of viscum fraxini-2 in patients with chemotherapy-naïve, advanced hepatocellular carcinoma. 23 patients with unrespectable HCC who had received no prior systemic chemotherapy with objectively measurable tumors were enrolled on this study. The mistletoe preparation for the study is an aqueous injectable solution. It contains one milliliter of viscum fraxini in dilution stage-2 (15 mg extract of 20 mg mistletoe herb from ash tree, diluted in di-natrium-mono-hydrogen phosphate, ascorbic acid and water) which is equivalent to 10 000 ng/ml injection ampoules. 2 ampoules of viscum fraxini-2 were administered subcutaneously once weekly. As assessed by conventional imaging criteria, 3 (13.1%) patients have achieved complete response, 2 (8.1%) patients have achieved a partial response. 9 (39.1%) had progressive disease while 9 (39.1%) patients didn't have evaluation of response due to early death. The median overall survival time for all patients was 5 months (range 2-38 months), for those who achieved a CR was 29 months (range 12-38 months) and, for those who achieved a PR was 6.5 months (range 6-7 months). The median progression free survival for all patients was 2 months (range 1-38 months), for those who achieved a CR, it was 29 months (range 8-38 months) and for those who achieved a partial response, it was 5 months (range 4-6 months). No hematologic toxicity has been encountered. The spectrum of non-hematologic toxicity was mild. The WHO toxicity criteria grade 3-4 were 34.8% drug related fever, 13.1% erthyma at injection site and 17.4% pain at the site of injection. No drug related discontinuation or toxic deaths have occurred. Viscum fraxini-2 seems to be particularly promising in

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

    PubMed

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

    2005-03-01

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

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

    PubMed

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

    2016-04-01

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

  19. 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.

  20. The implication of tumor biomarker CA19-9 in the diagnosis of intracranial epidermoid cyst.

    PubMed

    Wang, Yongjie; Yan, Wei; Wu, Qun; Chen, Gao; Zhang, Jianmin

    2017-01-10

    The diagnosis of intracranial epidermoid cyst (IEC) relies solely on MRI, which is time and money consuming. The application of tumor biomarkers in IEC has never been systematically studied. Here we screened a group of commonly used tumor biomarkers to assess their diagnostic value in IEC. Serum tumor biomarkers were assessed in 42 IECs and 42 paired healthy controls. Only serum CA19-9 level was significantly higher in the IEC group (median 20.3U/ml vs. 6.5U/ml, p < 0.001). Area under curve for CA19-9 was 0.806 (95% CI 0.700-0.912), with cutoff value of 13.15 U/ml (sensitivity 71.4%, specificity 97.6%). Tumor size was significantly different between CA19-9 positive and CA19-9 negative groups(64.14 ± 67.91cm3 vs. 19.43 ± 13.76 cm3, p = 0.04) and linear regression analysis revealed a positive correlation. Neither the extent of resection nor recurrence rate showed any significant difference between the two groups. This is a retrospective study of IEC patients treated between 2009 and 2014. We analyzed the expression of common serum tumor biomarkers, including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, carbohydrate antigen125 and squamous cell carcinoma in both IEC and healthy control group. Receiver operating characterisitics curves were constructed to evaluate the diagnostic accuracy. Our data indicated that for serum CA19-9 level higher than 13.15U/ml, after excluding the possibility of gastrointestinal system tumor, lung cancer, inflammation and other related diseases, the existence of IEC should be considered. Further prospective study is needed to gain more understanding of the value of CA19- 9 in postoperative evaluation and surveillance.

  1. Relationship of Th17/Treg Cells and Radiation Pneumonia in Locally Advanced Esophageal Carcinoma.

    PubMed

    Wang, Yan; Xu, Gang; Wang, Jie; Li, Xin-Hua; Sun, Ping; Zhang, Wei; Li, Jun-Xia; Wu, Chao-Yang

    2017-08-01

    Radiation pneumonia is a main side-effect that has limited the clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in inflammatory diseases. The balance between Treg and Th17 cells is a key factor in the progression of many inflammatory and autoimmune diseases. Whether Tregs and Th17 cells are predictive factors of radiation pneumonia has not yet been reported. In this study, we investigated the relationships of Treg/Th17 cells and radiation pneumonia in patients with locally advanced esophageal cancer who received radiotherapy. One hundred and forty-eight patients with locally advanced esophageal cancer who received radical and palliative radiotherapy were enrolled. The levels of Th17 and Treg cells in the blood of patients were detected using flow cytometry at the time point of pre-radiotherapy, 1st, 2nd, 3rd, 4th, 5th and 6th week from the start of radiation and 4 weeks after completion of radiotherapy. Radiation pneumonia was evaluated according to Radiation Therapy Oncology Group's acute radiation pneumonia standards, with the endpoint being grade 2 or above radiation pneumonia. There were 24 cases of radiation pneumonia in 148 cases of locally advanced esophageal cancer patients who underwent radiotherapy. Th17 cells increased and, in contrast, Treg cells decreased in the radiation pneumonia group. The change in the ratio of Th17/Treg was more pronounced and the difference was statistically significant from the 5th week after irradiation compared to patients with no radiation pneumonia (p<0.05). There was no significant difference in dosimetric parameters, including V5, V20, V30 and mean lung dose (MLD) and clinical factors, such as gender, age, smoking history, history of surgery and chemotherapy. The ratio of Th17/Treg cells may be an effective predictive factor of radiation pneumonia. Copyright© 2017, International Institute of Anticancer Research (Dr

  2. 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

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

    PubMed Central

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

    2014-01-01

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

  4. Pulmonary atelectasis and survival in advanced non-small cell lung carcinoma

    PubMed Central

    2010-01-01

    Atelectasis was reported as a favorable prognostic sign of pulmonary carcinoma; however, the underlying mechanism in those patients is not known. In this study, we aimed to investigate prospectively the potential impact of atelectasis and/or obstructive pneumonitis (AO) on survival and the relation between atelectasis and some laboratory blood parameters. The study was conducted on 87 advanced stage non-small cell lung cancer (NSCLC) patients. Clinical and laboratory parameters of patients at first presentation were recorded, and patients were divided into two groups according to the presence of AO in thorax computed tomography (CT). Survival was calculated using Kaplan-Meier and univariate Cox's regression analyses. Laboratory parameters that might be related with prolonged survival in atelectasis were compared using chi-square, Student's t, and Mann-Whitney U tests. Of the patients, 54% had stage IV disease, and AO was detected in 48.3% of all cases. Overall median survival was 13.2 months for all cases, 10.9 months for patients without AO, and 13.9 months for patients with AO (P = 0.067). Survival was significantly longer in stage III patients with AO (14.5 months versus 9.2 months, P = 0.032), but not in stage IV patients. Patients with AO in stage III had significantly lower platelet counts (P = 0.032) and blood sedimentation rates than did those with no AO (P = 0.045). We concluded that atelectasis and/or obstructive pneumonitis was associated with prolonged survival in locally advanced NSCLC. There was also a clear association between atelectasis and/or obstructive pneumonitis and platelets and blood sedimentation rate. PMID:20636252

  5. Pulmonary atelectasis and survival in advanced non-small cell lung carcinoma.

    PubMed

    Bulbul, Yilmaz; Eris, Bulent; Orem, Asim; Gulsoy, Ayhan; Oztuna, Funda; Ozlu, Tevfik; Ozsu, Savas

    2010-08-01

    Atelectasis was reported as a favorable prognostic sign of pulmonary carcinoma; however, the underlying mechanism in those patients is not known. In this study, we aimed to investigate prospectively the potential impact of atelectasis and/or obstructive pneumonitis (AO) on survival and the relation between atelectasis and some laboratory blood parameters. The study was conducted on 87 advanced stage non-small cell lung cancer (NSCLC) patients. Clinical and laboratory parameters of patients at first presentation were recorded, and patients were divided into two groups according to the presence of AO in thorax computed tomography (CT). Survival was calculated using Kaplan-Meier and univariate Cox's regression analyses. Laboratory parameters that might be related with prolonged survival in atelectasis were compared using chi-square, Student's t, and Mann-Whitney U tests. Of the patients, 54% had stage IV disease, and AO was detected in 48.3% of all cases. Overall median survival was 13.2 months for all cases, 10.9 months for patients without AO, and 13.9 months for patients with AO (P=0.067). Survival was significantly longer in stage III patients with AO (14.5 months versus 9.2 months, P=0.032), but not in stage IV patients. Patients with AO in stage III had significantly lower platelet counts (P=0.032) and blood sedimentation rates than did those with no AO (P=0.045). We concluded that atelectasis and/or obstructive pneumonitis was associated with prolonged survival in locally advanced NSCLC. There was also a clear association between atelectasis and/or obstructive pneumonitis and platelets and blood sedimentation rate.

  6. 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.

  7. 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.

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  11. 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.

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

    PubMed

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

    2015-05-18

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2001-01-01

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

  15. 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.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  18. Hepatocellular Carcinoma in Alcoholic Liver Disease: Current Management and Recent Advances.

    PubMed

    Galati, Giovanni; Dell'Unto, Chiara; Vespasiani-Gentilucci, Umberto; Vincentis, Antonio De; Gallo, Paolo; Guidi, Alessandro; Picardi, Antonio

    2016-01-01

    Hepatocellular Carcinoma (HCC) is a major healthcare problem. Almost ninety percent of HCCs develops on cirrhosis due to chronic viral hepatitis, Non-Alcoholic Steatohepatitis (NASH) and alcohol abuse. Alcohol itself is defined a strong human carcinogenic agent. Some genetic polymorphisms in alcohol-metabolizing systems and more recently, some sequence variations within the genes coding for patatin-like phospholipase encoding 3 (PNPLA3) and Transmembrane 6 superfamily 2 (TM6SF2), have been found to promote liver fibrosis in alcohol abuse, until HCC development. The current management of HCC is related to tumor burden and liver function and it does not differ in alcoholics, although in alcoholics the surveillance for HCC could be less effective because socioeconomic context, such as the recall policy, the stage at the diagnosis and the prognosis are not different compared to viral HCCs. On regards of loco-regional treatment options, there have not been significant advances in the last few years, though an increasing role will be probably reserved to radio embolization and irreversible electroporation in the next future. Sorafenib (SOR) is still the only drug approved as systemic therapy in patients with HCC, whereas immunotherapy represents a promising approach for the treatment of HCC.

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

    PubMed Central

    Jain, Sachin; Song, Ruolan; Xie, Jingwu

    2017-01-01

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

  20. [Analysis of the nutritional status and nosocomial infection during chemoradiotherapy in advanced nasopharyngeal carcinoma patients].

    PubMed

    Liu, Jie; Liao, Jianxuan; Yang, Qiao

    2014-02-01

    To analyze the nutritional status and nosocomial infection of nasopharyngeal carcinoma patients before and after the chemoradiotherapy treatment. An analysis was made for the nutritional and nosocomial infection status of 82 cases before and after chemoradiotherapy treatment. Statistically significant differences were revealed between indexes related with nutritional status such as body mass, hemoglobin, serum albumin before and after the treatment. Sixty-three patients occurred nosocomial infection. The infection rate was 76.83%. The main risk factor was oropharynx mucosal lesion and the rate is 92.68%. Isolates of 39 bacteria were found, of which Gram-negative organisms were 58.97%, Fungi were 30.77%, Gram-positive ones were 7.69%, Herpes zoster were 2.56%. Chemoradiotherapy has negative influence on nutritional status of patients. Medical personnel should pay attention to patients' nutritional status and do a good job of nutritional status monitoring, nutrition support, dieting guidance, reducing side effects, in order to improve the patient's tolerability and quality of life. The nosocomial infection rate of Gram-negative bacteria of oropharyngeal mucosal is the highest in patients with advanced nasopharyngeal cancer during chemoradiotherapy. It is very important for us to prevent and control nosocomial infection.

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

    PubMed

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

    2008-09-01

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

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

    PubMed

    Bukowski, Ronald M

    2010-05-01

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

  3. 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

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

    SciTech Connect

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

    2006-02-01

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

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

    PubMed

    Goldenberg, Gary; Hamid, Omid

    2013-12-01

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

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

    PubMed Central

    Kimura, Yasunori

    2015-01-01

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

  7. Phase II Study of First‐Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Blanc, Jean‐Frederic; Miles, Steven; Ganten, Tom; Trojan, Jörg; Cebon, Jonathan; Liem, Andre K.; Lipton, Lara; Gupta, Charu; Wu, Benjamin; Bass, Michael; Hollywood, Ellen; Ma, Jennifer; Bradley, Margaret; Litten, Jason; Saltz, Leonard B.

    2017-01-01

    Abstract Lessons Learned. Trebananib leveraging anti‐angiogenic mechanism that is distinct from the classic sorafenib anti‐vascular endothelial growth factor inhibition did not demonstrate improved progression‐free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang‐2 levels’ association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang‐2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang‐2. Background. Ang‐1 and Ang‐2 are angiopoietins thought to promote neovascularization via activation of the Tie‐2 angiopoietin receptor. Trebananib sequesters Ang‐1 and Ang‐2, preventing interaction with the Tie‐2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang‐2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC). Methods. Patients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs‐Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression‐free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang‐2. Results. Thirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar‐plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One

  8. Phase II Study of First-Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma.

    PubMed

    Abou-Alfa, Ghassan K; Blanc, Jean-Frederic; Miles, Steven; Ganten, Tom; Trojan, Jörg; Cebon, Jonathan; Liem, Andre K; Lipton, Lara; Gupta, Charu; Wu, Benjamin; Bass, Michael; Hollywood, Ellen; Ma, Jennifer; Bradley, Margaret; Litten, Jason; Saltz, Leonard B

    2017-07-01

    Trebananib leveraging anti-angiogenic mechanism that is distinct from the classic sorafenib anti-vascular endothelial growth factor inhibition did not demonstrate improved progression-free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang-2 levels' association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang-2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang-2. Ang-1 and Ang-2 are angiopoietins thought to promote neovascularization via activation of the Tie-2 angiopoietin receptor. Trebananib sequesters Ang-1 and Ang-2, preventing interaction with the Tie-2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang-2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC). Patients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs-Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression-free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang-2. Thirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar-plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One death was due to hepatic failure. Serum Ang-2 dichotomized at the median was associated with

  9. Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

    PubMed

    Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.

    2000-11-01

    Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

  10. 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.

  11. 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

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

    PubMed

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

    2016-01-01

    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 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. 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.

  13. 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.

  14. 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.

  15. Induction chemotherapy followed by concurrent chemoradiotherapy for advanced stage oropharyngeal squamous cell carcinoma with HPV and P16 testing.

    PubMed

    Flavill, Eric; Fang, Yisheng V; Miles, Brett; Truelson, John; Perkins, Steve

    2014-05-01

    The objective was to report our experience with advanced stage oropharyngeal squamous cell carcinoma treated sequentially with induction chemotherapy followed by concurrent chemoradiotherapy. Retrospective chart review identified 49 eligible patients with advanced stage oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiotherapy. HPV and p16(INK4A) testing was performed on pathology specimens. Follow-up of over 11 months was required unless a death or treatment failure occurred before that time. Treatment with induction chemotherapy followed by concurrent chemoradiotherapy resulted in 44/48 (90%) complete durable response. One death occurred from pulmonary embolism. Toxicity profiles were comparable to other published data. Average follow-up was 3.9 years. Oncologic failure rates among subgroups showed 5.7% failure for HPV+/p16+ cancer, 9.1% failure for HPV-/p16+ cancer, 100% failure for HPV-/p16- cancer, 0% failure for nonsmokers, and 17.9% failure for smokers. This study showed favorable outcomes in terms of durable oncologic response and acceptable toxicity profiles. It is notable that 36/49 patients were HPV+/p16+ and 11/49 were HPV-/p16+. Only 2 patients were HPV-/p16-, and both died as a result of oncologic failures. This highlights the importance of obtaining HPV and p16 testing in studies evaluating the efficacy of treatments for oropharyngeal squamous cell carcinoma.

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

    PubMed

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

    2013-05-01

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

  17. 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

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

    PubMed

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

    2013-03-01

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

  19. Phase II study of paclitaxel plus the protein kinase C inhibitor bryostatin-1 in advanced pancreatic carcinoma.

    PubMed

    Lam, Anthony P; Sparano, Joseph A; Vinciguerra, Vincent; Ocean, Allyson J; Christos, Paul; Hochster, Howard; Camacho, Fernando; Goel, Sanjay; Mani, Sridhar; Kaubisch, Andreas

    2010-04-01

    To determine the efficacy and toxicity of the protein kinase C inhibitor bryostatin-1 plus paclitaxel in patients with advanced pancreatic carcinoma. Each treatment cycle consisted of paclitaxel 90 mg/m by intravenous infusion over 1 hour on days 1, 8, and 16, plus bryostatin 25 mcg/m as a 1-hour intravenous infusion on days 2, 9, and 15, given every 28 days. Patients were evaluated for response after every 2 treatment cycles, and continued therapy until disease progression or prohibitive toxicity. The primary objective was to determine whether the combination produced a response rate of at least 30%. Nineteen patients with locally advanced or metastatic pancreatic adenocarcinoma received a total of 52 cycles of therapy (range: 1-10). Patients received the combination as first-line therapy for advanced disease (N = 5) or after prior chemotherapy used alone or in combination with local therapy. No patients had a confirmed objective response. The median time to treatment failure was 1.9 months (95% confidence intervals: 1.2, 2.6 months). Reasons for discontinuing therapy included progressive disease or death in 14 patients (74%) or because of adverse events or patient choice in 5 patients (26%). The most common grade 3 to 4 toxicities included leukopenia in 26%, anemia in 11%, myalgias in 11%, gastrointestinal bleeding in 11%, infection in 10%, and thrombosis in 10%. The combination of weekly paclitaxel and bryostatin-1 is not an effective therapy for patients with advanced pancreatic carcinoma.

  20. Common questions regarding clinical use of axitinib in advanced renal cell carcinoma.

    PubMed

    Borst, Diane L; Arruda, Lillian S; MacLean, Elizabeth; Pithavala, Yazdi K; Morgado, James E

    2014-07-01

    An overview of the responses to some of the most frequently asked questions regarding axitinib administration and dosage modifications used in clinical practice are presented. Axitinib was approved for second-line treatment of advanced renal cell carcinoma by the Food and Drug Administration on January 27, 2012. Inquiries received over the first six months after the approval date were reviewed. A large number of questions were related to administration of axitinib in different patient populations or in patients with various comorbidities, such as its (1) use in patients unable to swallow oral medication or administration of axitinib via a nasogastric tube, (2) use in patients with renal or hepatic impairment, (3) central nervous system penetration and use in patients with brain metastases, (4) drug interactions, particularly with anticoagulants, and (5) dosage modifications. Responses to these inquiries were provided based on the published literature or from data on file from the manufacturer. The dosage of axitinib can be adjusted for use in patients with hepatic impairment or in patients who cannot otherwise tolerate the usual regimen. Patients taking concomitant warfarin can also take axitinib, and patients who cannot swallow oral medications can receive a liquid formulation of the drug, though its efficacy and comparability to the tablet formulation has not been tested. Based on the published literature and company data on file, the axitinib dosage may be modified to accommodate patients with renal or hepatic impairment, who cannot swallow oral medication, are receiving concomitant warfarin, or who cannot otherwise tolerate the standard dosage regimen. For patients who cannot swallow, an oral suspension can be prepared because crushing axitinib is not recommended. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  1. Cost-effectiveness of sorafenib for second-line treatment of advanced renal cell carcinoma.

    PubMed

    Hoyle, Martin; Green, Colin; Thompson-Coon, Jo; Liu, Zulian; Welch, Karen; Moxham, Tiffany; Stein, Ken

    2010-01-01

    To estimate the cost-effectiveness of sorafenib (Nexavar, Bayer, Leverkusen, Germany) versus best supportive care (BSC) for second-line treatment of advanced renal cell carcinoma from the perspective of the UK National Health Service. A decision analytic model was developed to estimate the cost-effectiveness of sorafenib. The clinical effectiveness of sorafenib versus BSC was taken from a recent randomized phase III trial. Utility values were taken from a phase II trial of sunitinib, using EQ-5D tariffs. Cost data were obtained from published literature and were based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses. Compared to BSC, sorafenib treatment resulted in an incremental cost per quality-adjusted life year (QALY) gained of pound75,398, based on an estimated mean gain of 0.27 QALYs per patient, at a mean additional cost of pound20,063 (inflated to 2007/2008). The probability that sorafenib is cost-effective compared to BSC at a willingness to pay threshold of pound30,000 per QALY is 0.0%. In sensitivity analysis, estimates of cost per QALY were sensitive to changes in the clinical effectiveness parameters, and to health state utilities and drug costs. Sorafenib has been shown to be clinically effective compared to BSC, offering additional health benefits; however, with a cost per QALY in excess of pound70,000, it may not be regarded as a cost-effective use of resources in some health-care settings.

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

    SciTech Connect

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

    2010-08-01

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

  3. The effect of treatment on survival in patients with advanced laryngeal carcinoma.

    PubMed

    Gourin, Christine G; Conger, Bryant T; Sheils, W Chris; Bilodeau, Paul A; Coleman, Teresa A; Porubsky, Edward S

    2009-07-01

    Over the last 2 decades, survival from laryngeal cancer has decreased. We sought to identify factors associated with decreased survival in laryngeal cancer. Patients diagnosed with laryngeal squamous cell carcinoma from 1985 to 2002 were retrospectively reviewed. A total of 451 patients met study criteria. Five-year survival rates were 85% for stage I, 77% for stage II, 51% for stage III, and 35% for stage IV disease. Survival for patients with stage I-III disease was similar for patients treated operatively or nonoperatively (P = .4). However, patients with stage III disease treated nonoperatively had worse survival with radiation alone (XRT) compared to chemoradiation (CR) (P = .006). Patients with stage IV disease had significantly better survival with surgery (49%) than CR (21%) or XRT alone (14%) (P < .0001). Analysis by primary tumor stage demonstrated that survival for T1-T3 disease was independent of treatment modality (P = .2); however, for T4 patients, operative treatment was associated with significantly better survival (55%) than CR (25%) or XRT (0%) (P < .0001). Proportional hazards models confirmed significantly worse survival for stage IV, T4, N2 or N3 disease, and nonoperative treatment. For T4 disease, after controlling for nodal status, nonoperative treatment was the only significant predictor of worse survival. Primary surgical treatment is associated with improved survival for patients with stage IV disease and specifically T4 primary tumors. These data suggest that the observed national decrease in survival from laryngeal cancer may be due to a shift toward nonoperative treatment in that subset of patients with advanced primary disease.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Bukowski, Ronald M

    2011-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor’s underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients. PMID:21931501

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Shi, Yaoping; Zhai, Bo

    2016-01-01

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

  10. Prognostic value of hypoxia-associated markers in advanced larynx and hypopharynx squamous cell carcinoma.

    PubMed

    Bernstein, Jonathan M; Andrews, Timothy D; Slevin, Nick J; West, Catharine M L; Homer, Jarrod J

    2015-01-01

    To determine the prognostic value of hypoxia-associated markers carbonic anhydrase-9 (CA-9) and hypoxia-inducible factor-1α (HIF-1α) in advanced larynx and hypopharynx squamous cell carcinoma (SCCa) treated by organ preservation strategies. Retrospective cohort study. Pretreatment CA-9 and HIF-1α expression, clinicopathologic data, and tumor volume were analyzed in a series of 114 patients with T3-4 SCCa larynx or hypopharynx treated by (chemo)radiation. Adverse prognostic factors for locoregional control were T4 classification (P = 0.008), and for disease-specific survival were CA-9 positivity (P = 0.039), T4 classification (P = 0.001), larger tumor volume (P = 0.004), N1-3 classification (P = 0.002), and pretreatment hemoglobin < 13.0 g/dl (P = 0.014). With increasing CA-9 expression, there was a trend to increasing tumor recurrence (P trend = 0.009) and decreasing survival (P trend = 0.002). On multivariate analysis, independent variables were T4 classification (hazard ratio [HR] 13.54, P = 0.01) for locoregional failure, and CA-9 positivity (HR = 8.02, P = 0.042) and higher tumor volume (HR = 3.33, P = 0.007) for disease-specific mortality. This is the first study to look specifically at T3 and T4 SCCa larynx and hypopharynx for a relationship between hypoxia-associated marker expression and clinical outcome. Pretreatment immunohistochemical CA-9 expression is an adverse prognostic factor for disease-specific survival, indicating that CA-9 expression may confer a more aggressive tumor phenotype. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2017-09-15

    Advanced Adult Hepatocellular Carcinoma; Child-Pugh Class A; Stage III Hepatocellular Carcinoma; Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IV Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

  12. Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system.

    PubMed

    Yamaguchi, Tomohiro; Machida, Nozomu; Morizane, Chigusa; Kasuga, Akiyoshi; Takahashi, Hideaki; Sudo, Kentaro; Nishina, Tomohiro; Tobimatsu, Kazutoshi; Ishido, Kenji; Furuse, Junji; Boku, Narikazu; Okusaka, Takuji

    2014-09-01

    This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46-0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48-1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. 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

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

    ClinicalTrials.gov

    2017-01-19

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

  17. Unusual Intraparenchymal Pontomedullary Epidermoid Cyst in a 2-Year-Old Child: A Case Report and Review of the Literature.

    PubMed

    Shtaya, Anan; Dabbous, Bassam; Fanou, Evgenia; Bridges, Leslie; Hettige, Samantha

    2017-08-01

    Intrinsic brainstem epidermoid cysts are rare, benign, slow-growing lesions. Their eloquence precludes complete excision; however, subtotal resection often will result in prolonged or sometimes permanent relief of presenting symptoms and signs. We describe an unusual case and review the literature of this pathology in the pediatric population. We report an intra-axial pontine epidermoid cyst in a 2-year-old girl who presented with developmental delay, multiple cranial nerve palsies, and pneumonia. Magnetic resonance imaging demonstrated an intrinsic pontine lesion with partial restricted diffusion and an enhancing plaque, the latter not typically seen in congenital lesions like epidermoid. However, gross surgical inspection and histopathology confirmed an epidermoid. Our case, supported by the literature, shows that brain stem epidermoid cysts may have atypical radiologic characteristics and that near-total resection remains safe and can improve outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. [Primary thymic carcinomas. Three cases and a review of the literature].

    PubMed

    Ayadi-Kaddour, A; Bacha, D; Smati, B; Kilani, T; El Mezni, F

    2009-04-01

    Thymic carcinoma is a very rare malignancy. In 1999, a World Health Organization committee published histologic criteria for distinct thymoma entities (labelled as type A, AB, B1, B2, B3 thymomas) and for the heterogeneous group of thymic carcinomas, collectively called type C tumour. Thymic carcinoma differs from thymoma in that it displays cytologically malignant features, extensive local invasion, and a substantial potential for metastasis. It constitutes a heterogeneous group of tumours that display different biological behaviours and prognoses. The majority of thymic carcinomas are either squamous carcinomas or lymphoepithelioma-like carcinomas. This study included three male patients aged 20, 46 and 19years respectively with histologically proven thymic carcinoma diagnosed at the author's institution. All of the patients presented a large mass of the anterior mediastinum. Histological examination of the different tumours revealed three distinct variants of thymic carcinoma, namely: epidermoid carcinoma, clear cell carcinoma and lymphoepithelioma-like carcinoma.

  2. Leech therapy for epidermoid cysts and review of the literature

    PubMed Central

    Rasi, Abbas; Faghihi, Alireza; Jalali, Mirhadi Aziz; Zamanian, Abbas; Ghaffarpour, Gholamhossein

    2014-01-01

    Hirudo medicinalis sucks blood directly through the external mammalian skin. We recently observed a healthy 64-year-old Iranian man, who presented with numerous asymptomatic multilobular oval-to-round well-defined 0.5 to 1.5 cm cystic lesions with central umbilication (central black eschar) over the upper portion of his chest. We made the diagnosis of epidermoid cyst, giant comedone and leech bite on the basis of the constellation of clinical features. The patient was treated with oral ciprofloxacin at a dose of 2 g daily, and 2% topical erythromycin solution. Despite improvement, the evidence of cystic lesions persisted. There was no history of similar lesions in any other family member. There was no history of trauma. The patient was not using any topical or systemic medication. Two weeks before his visit, he had a history of leech therapy under the supervision of a general practitioner. His medical history was significant for leech therapy of the lesions, five days previously. He was followed up for another two weeks and after disappearance of the inflammation, with the patient under local anesthesia, the well-circumscribed mass was completely evacuated with a sharp curette and comedone extractor. The patient was subsequently lost to follow-up. Conclusion: Considering the efficacy of leeches, it would be favorable to breed a germ-free leech. In Iran, the use of the leeches in surgery, in recent years, has been infrequent. It appears that the positive effects of this ancient remedy may now be explained through scientific methods, promising potentially even more uses of this admirable creature in medicine. PMID:24804186

  3. FOLFOX4 or sorafenib as the first-line treatments for advanced hepatocellular carcinoma: A cost-effectiveness analysis.

    PubMed

    Zhang, Pengfei; Wen, Feng; Li, Qiu

    2016-12-01

    This study aimed to investigate the pharmaco-economic implications of FOLFOX4 or sorafenib for advanced hepatocellular carcinoma in China. To conduct the analysis, we performed a Markov model to simulate the process of advanced HCC treated with sorafenib or FOLFOX4. Clinical data were obtained from the ORIENTAL trial and the EACH trial. Incremental cost-effectiveness ratio was regarded as the primary outcome in the analysis. One-way sensitivity analysis as well as probabilistic sensitivity analysis was performed to explore the impact of essential variables on the results of the analysis. Treatment with sorafenib provided an effectiveness gain of 0.3935 quality-adjusted life year at an average cost of $18,748.00, whereas chemotherapy of FOLFOX4 brought 0.3808 quality-adjusted life year at a cost of $6876.02. The incremental cost-effectiveness ratio of FOLFOX4 versus sorafenib was $934,801.57/QALY. In a probabilistic sensitivity analysis based on a Monte Carlo simulation of 1000 items, the probabilities of FOLFOX4 and sorafenib being cost-effective were 100% and 0% using a willingness-to-pay threshold of $20,301.00 per quality-adjusted life year. FOLFOX4 chemotherapy is likely to be a cost-effective option compared with sorafenib in the treatment of advanced hepatocellular carcinoma in China. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  4. Clinically advanced and metastatic pure mucinous carcinoma of the breast: a comprehensive genomic profiling study.

    PubMed

    Ross, Jeffrey S; Gay, Laurie M; Nozad, Sahar; Wang, Kai; Ali, Siraj M; Boguniewicz, Ann; Khaira, Depinder; Johnson, Adrienne; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Miller, Vincent A; Stephens, Philip J

    2016-01-01

    Pure mucinous breast carcinoma (pmucBC) is a distinctive variant of breast cancer (BC) featuring an excellent overall prognosis. However, on rare occasions, pmucBC pursues an aggressive clinical course. We queried whether comprehensive genomic profiling (CGP) would uncover clinically relevant genomic alterations (CRGA) that could lead to targeted therapy treatment for patients with an advanced and metastatic form of pmucBC. From a series of 51,238 total cancer samples, which included 5605 cases of clinically advanced BC and 22 cases of stage IV pmucBC, DNA was extracted from 40 microns of FFPE sections. Comprehensive genomic profiling was performed using a hybrid-capture, adaptor ligation-based next generation sequencing assay to a mean coverage depth of 564X. The results were analyzed for all classes of genomic alterations (GA) including base substitutions, insertions and deletions, select rearrangements, and copy number changes. Clinically relevant genomic alterations were defined as those indicating possible treatment with anti-cancer drugs on the market or in registered clinical trials. Samples were obtained from breast (11), lymph nodes (3), chest wall (2), liver (2), soft tissue (2), bone (1), and pleura (1). The median age of the 22 pmucBC patients was 57 years (range 32-79 years). Three pmucBCs were grade 1, 17 were grade 2, and 2 were grade 3. Twenty-one (95 %) pmucBC were ER+, 18 (82 %) were PR+, and 3 (14 %) were HER2+ by IHC and/or FISH. A total of 132 GA were identified (6.0 GA per tumor), including 53 CRGA, for a mean of 2.4 GA per tumor. Amplification of FGFR1 or ZNF703, located within the same amplicon, was found in 8 of 22 cases (36 %). This enrichment of FGFR1 amplification in 36 % of pmucBC versus 11 % of non-mucinous ER+ BC (601 cases) was significant (p < 0.005). Other frequently altered genes of interest in pmucBC were CCND1 and the FGF3/FGF4/FGF19 amplicon (27 %), often co-amplified together. ERBB2/HER2 alterations were identified in 5 pmuc

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

    ClinicalTrials.gov

    2017-03-08

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

  6. Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC.

    PubMed

    Sekulic, Aleksandar; Migden, Michael R; Lewis, Karl; Hainsworth, John D; Solomon, James A; Yoo, Simon; Arron, Sarah T; Friedlander, Philip A; Marmur, Ellen; Rudin, Charles M; Chang, Anne Lynn S; Dirix, Luc; Hou, Jeannie; Yue, Huibin; Hauschild, Axel

    2015-06-01

    Primary analysis from the pivotal ERIVANCE BCC study resulted in approval of vismodegib, a Hedgehog pathway inhibitor indicated for treatment of adults with metastatic or locally advanced basal cell carcinoma (BCC) that has recurred after surgery or for patients who are not candidates for surgery or radiation. An efficacy and safety analysis was conducted 12 months after primary analysis. This was a multinational, multicenter, nonrandomized, 2-cohort study in patients with measurable and histologically confirmed locally advanced or metastatic BCC taking oral vismodegib (150 mg/d). Primary outcome measure was objective response rate (complete and partial responses) assessed by independent review facility. After 12 months of additional follow-up, median duration of exposure to vismodegib was 12.9 months. Objective response rate increased from 30.3% to 33.3% in patients with metastatic disease, and from 42.9% to 47.6% in patients with the locally advanced form. Median duration of response in patients with locally advanced BCC increased from 7.6 to 9.5 months. No new safety signals emerged with extended treatment duration. Limitations include low prevalence of advanced BCC and challenges of designing a study with heterogenous manifestations. The 12-month update of the study confirms the efficacy and safety of vismodegib in management of advanced BCC. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?

    PubMed

    Bradley, A J; MacDonald, L; Whiteside, S; Johnson, R J; Ramani, V A C

    2015-08-01

    To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7(th) edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2-5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88% PPV, respectively, for the presence of tumour stage for pT stage >T3a

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-09-05

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

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

    PubMed Central

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

    2016-01-01

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

  13. Definitive radiotherapy for locally advanced squamous cell carcinoma of the vulva and technical issues: a case report

    NASA Astrophysics Data System (ADS)

    Kumar, Gokula; Norhafizah, I.; Shazril, I.; Nursyatina, AR; Aziz, MZ Abdul; Zin, Hafiz M.; Zakir, MK; Norjayadi; Norliza, AS; Ismail, A.; Khairun, N.

    2017-05-01

    This case report describes a complex radical 3D-Conformal Radiotherapy treatment planning, dosimetric issues and outcome of definitive treatment of un-resectable carcinoma of the vulvar in a 42-year old lady. The patient presented with large fungating mass of the vulva which was biopsy confirmed as Keratinizing Squamous Cell Carcinoma. Further staging investigation revealed locally advanced disease (T4), with bilateral inguinal lymph nodes involvement. There is no systemic metastasis or intra-pelvic nodes. The patient was seen by Gynae-Oncology team and the disease was deemed un-resectable without significant morbidity. She was treated to a total dose of 64.8Gy in 36 fractions over 7 weeks with concurrent weekly Cisplatinum in 2 phases. 3D-Conformal radiotherapy technique using the modified segmental boost technique (MSBT, large PA and small AP photon fields with inguinal electron matching) was used. TLD chips were used for in-vivo dose verification in phase 1 and 2 of the treatment. At completion of planned radiotherapy, patient had a complete clinical response, grade 2-3 skin toxicity, grade 2 rectal toxicity, and grade 2 dysuria Vulval Squamous Cell Carcinomas are very radiosensitive tumours and the skills of the treating Radiation Oncologist, Dosimetrists, Physicist, Radiation Therapist and also nurses is of foremost importance is ensuring good clinical outcomes.

  14. Endoscopic diagnosis of extrahepatic bile duct carcinoma: Advances and current limitations

    PubMed Central

    Tamada, Kiichi; Ushio, Jun; Sugano, Kentaro

    2011-01-01

    The accurate diagnosis of extrahepatic bile duct carcinoma is difficult, even now. When ultrasonography (US) shows dilatation of the bile duct, magnetic resonance cholangiopancreatography followed by endoscopic US (EUS) is the next step. When US or EUS shows localized bile duct wall thickening, endoscopic retrograde cholangiopancreatography should be conducted with intraductal US (IDUS) and forceps biopsy. Fluorescence in situ hybridization increases the sensitivity of brush cytology with similar specificity. In patients with papillary type bile duct carcinoma, three biopsies are sufficient. In patients with nodular or infiltrating-type bile duct carcinoma, multiple biopsies are warranted, and IDUS can compensate for the limitations of biopsies. In preoperative staging, the combination of dynamic multi-detector low computed tomography (MDCT) and IDUS is useful for evaluating vascular invasion and cancer depth infiltration. However, assessment of lymph nodes metastases is difficult. In resectable cases, assessment of longitudinal cancer spread is important. The combination of IDUS and MDCT is useful for revealing submucosal cancer extension, which is common in hilar cholangiocarcinoma. To estimate the mucosal extension, which is common in extrahepatic bile duct carcinoma, the combination of IDUS and cholangioscopy is required. The utility of current peroral cholangioscopy is limited by the maneuverability of the “baby scope”. A new baby scope (10 Fr), called “SpyGlass” has potential, if the image quality can be improved. Since extrahepatic bile duct carcinoma is common in the Far East, many researchers in Japan and Korea contributed these studies, especially, in the evaluation of longitudinal cancer extension. PMID:21611097

  15. Comprehensive Genomic Profiling of Advanced Esophageal Squamous Cell Carcinomas and Esophageal Adenocarcinomas Reveals Similarities and Differences.

    PubMed

    Wang, Kai; Johnson, Adrienne; Ali, Siraj M; Klempner, Samuel J; Bekaii-Saab, Tanios; Vacirca, Jeffrey L; Khaira, Depinder; Yelensky, Roman; Chmielecki, Juliann; Elvin, Julia A; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S

    2015-10-01

    Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations. Next-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of >650× for all coding exons of 315 cancer-related genes plus selected introns from 28 genes frequently rearranged in cancer. Results from a single sample were evaluated for all classes of genomic alterations (GAs) including point mutations, short insertions and deletions, gene amplifications, homozygous deletions, and fusions/rearrangements. Clinically relevant genomic alterations (CRGAs) were defined as alterations linked to approved drugs and those under evaluation in mechanism-driven clinical trials. There were no significant differences by sex for either tumor type, and the median age for all patients was 63 years. All ESCCs and EACs were at an advanced stage at the time of sequencing. All 71 ESCCs and 231 EACs featured GAs on profiling, with 522 GAs in ESCC (7.4 per sample) and 1,303 GAs in EAC (5.6 per sample). The frequency of clinically relevant GAs in ESCC was 94% (2.6 per sample) and 93% in EAC (2.7 per sample). CRGAs occurring more frequently in EAC included KRAS (23% EAC vs. 6% ESCC) and ERBB2 (23% EAC vs. 3% ESCC). ESCC samples were enriched for CRGA in PIK3CA (24% ESCC vs. 10% EAC), PTEN (11% ESCC vs. 4% EAC), and NOTCH1 (17% ESCC vs. 3% EAC). Other GAs that differed significantly between histologic tumor types included SMAD4 (14% EAC

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

    PubMed Central

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

    2016-01-01

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

  17. Response evaluation after chemoradiotherapy for advanced staged oropharyngeal squamous cell carcinoma: a nationwide survey in the Netherlands.

    PubMed

    Schouten, Charlotte S; Hoekstra, Otto S; Leemans, C René; Castelijns, Jonas A; de Bree, Remco

    2015-11-01

    Following failure of chemoradiotherapy (CRT) for advanced staged oropharyngeal squamous cell carcinomas (OPSCC), residual tumor can often be treated successfully with salvage surgery, if detected early. Current clinical practice in the VU University Medical Center is to perform routine response evaluation, i.e., examination under general anesthesia (EUA), 12 weeks after treatment. However, in the Netherlands there is no consensus on response evaluation in patients with advanced oropharyngeal cancer. Questionnaire on current clinical practice concerning response evaluation after CRT for advanced OPSCC in all eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group. The response rate was 100%. Response evaluation was routinely performed with various methods in five institutions (62.5%) and in one institute (12.5%) only if clinical evaluation was difficult. Two centers (25%) did not perform response evaluation. In case of suspicion of residual disease during follow-up, six centers (75%) performed imaging prior to EUA and two centers (25%) only if clinical evaluation was difficult. Diagnostic techniques used prior to EUA were MRI (87.5%), diffusion-weighted MRI (37.5%), 18F-FDG-PET-CT (75-87.5%) and CT (37.5%). This survey shows a substantial variation in the diagnostic policy concerning response evaluation after CRT for advanced OPSCC in the Netherlands. There is a need for guidelines for response evaluation in patients with advanced oropharyngeal cancer.

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

    PubMed Central

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

    2017-01-01

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

  19. Challenges and advances in the diagnosis, biology, and treatment of urothelial upper tract and bladder carcinomas.

    PubMed

    Aragon-Ching, Jeanny B

    2017-07-01

    Urothelial carcinomas span the bladder, ureter, and renal pelvis, and while there had been stagnation in the field of drug approval for the past two decades, there is now accelerated and regular US FDA approval of 5 immunotherapy agents. However, patients who inherently do not respond or progress on such therapies still represent an area of increased unmet need. In this special Seminars issue, we explore varying aspects of bladder urothelial carcinoma treatment with targeted therapies, the unique presentation and challenges in the treatment of upper tract and renal pelvis tumors, as well as new and emerging diagnostic imaging tools for varying genitourinary cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2014-01-01

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

  1. The radionuclide scintigraphic appearance in a rare case of epidermoid cyst of the testis.

    PubMed

    Garty, I; Chaimovitch, G; Wajsman, S; Sudarsky, M

    1984-10-01

    A rare case of epidermoid cyst of the testis, represented scintigraphically by an area of avascularity in the affected testicle, is described. The differential diagnosis from epididymitis and torsion of testis, and the diagnostic value fo the scintigraphic method to rule out malignant (vascular) testicular tumors, is emphasized.

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

    PubMed Central

    Yu, Alice; Capolicchio, John-Paul

    2017-01-01

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

  3. 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

  4. 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

  5. A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas.

    PubMed

    Medina, José Antonio; Rueda, Antonio; de Pasos, Antonio Sacchetti; Contreras, Jorge; Cobo, Manuel; Moreno, Paloma; Benavides, Manuel; Villanueva, Asunción; Alba, Emilio

    2006-04-01

    This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.

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

    SciTech Connect

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

    1985-10-01

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

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

    PubMed Central

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

    2017-01-01

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

  8. Transoral laser microsurgery for locally advanced (T3-T4a) supraglottic squamous cell carcinoma: Sixteen years of experience.

    PubMed

    Vilaseca, Isabel; Blanch, José Luis; Berenguer, Joan; Grau, Juan José; Verger, Eugenia; Muxí, África; Bernal-Sprekelsen, Manuel

    2016-07-01

    Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function-preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy-free survival with preserved function was 74.5%. TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1050-1057, 2016. © 2016 Wiley Periodicals, Inc.

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

    PubMed

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

    2012-07-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1989-01-01

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

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

    PubMed

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

    2017-01-01

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

  13. 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.

  14. 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.

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

    PubMed

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

    2017-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Wang, C.C.

    1985-12-01

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

  18. Concomitant oral tyrosine kinase inhibitors and bisphosphonates in advanced renal cell carcinoma with bone metastases

    PubMed Central

    Beuselinck, B; Wolter, P; Karadimou, A; Elaidi, R; Dumez, H; Rogiers, A; Van Cann, T; Willems, L; Body, J-J; Berkers, J; Van Poppel, H; Lerut, E; Debruyne, P; Paridaens, R; Schöffski, P

    2012-01-01

    Background: The presence of bone metastases in patients with metastatic renal cell carcinoma treated with oral tyrosine kinase inhibitors (TKIs) is associated with poorer outcome as compared with patients without bone involvement. Concomitant bisphosphonates could probably improve outcomes but also induce osteonecrosis of the jaw (ONJ). Methods: Retrospective study on all the renal cell carcinoma patients with bone metastases treated with sunitinib or sorafenib between November 2005 and June 2012 at the University Hospitals Leuven and AZ Groeninge in Kortrijk. Results: Seventy-six patients were included in the outcome analysis: 49 treated with concomitant bisphosphonates, 27 with TKI alone. Both groups were well balanced in terms of prognostic and predictive markers. Response rate (38% vs 16% partial responses, P=0.028), median progression-free survival (7.0 vs 4.0 months, P=0.0011) and median overall survival (17.0 vs 7.0 months, P=0.022) were significantly better in patients receiving bisphosphonates. The incidence of ONJ was 10% in patients treated with TKI and bisphosphonates. Conclusion: Concomitant use of bisphosphonates and TKI in renal cell carcinoma patients with bone involvement probably improves treatment efficacy, to be confirmed by prospective studies, but is associated with a high incidence of ONJ. PMID:23132391

  19. [Metachronous cancers after treatment for undifferentiated nasopharyngeal carcinoma].

    PubMed

    Boussen, H; Kochbati, L; Oueslati, Z; Gritli, S; Daoud, J; Gammoudi, A; Besbes, M; Bouaouina, N; Benna, F; Ladgham, A; Maalej, M

    2004-11-01

    To collect second cancers occurring in the head and neck area after treatment by chemotherapy and/or radiotherapy for undifferentiated nasopharyngeal carcinoma in Tunisia. This is a retrospective study of patients developing second cancers after treatment for nasopharyngeal UCNT by radiotherapy and/or chemotherapy. To be retained in this study, second tumour had to be histologically different from the initial UCNT, localised in the irradiated area and occurring after a minimal delay of 3 years. We collect 11 cases of second cancers occurring among 2346 patients treated from 1984 to 2001 in Tunisia (0.46%). Patients have been treated for nasopharyngeal UCNT mainly advanced T3-T4 (72%) or N2-N3 (63%). Median age was 20 years (11 to 48) with a sex-ratio of 0.3 (3 M/8 F). Treatment protocol included primary chemotherapy in 4 cases (adriamycin-cisplatin) or adjuvant (in 4) associated to the loco-regional irradiation at a mean dose of 72 Gy (70 to 75). Median delay of second cancer occurrence was 9 years (3 to 17). Tumors were epidermoid carcinomas in 4 cases, fibrosarcomas (2), osteosarcomas (2), glioblastoma (1) and basocellular carcinomas in 2. Second tumors have been treated by surgery alone in 4 cases and chemotherapy alone in 7 patients. No patient have been reirradiated. Median survival was 17 months, 4 patients died and 7 are still alive including 4 in complete remission (24+, 36, 36 and 48+ months) and 3 with progressing disease (8, 16 and 18 months). Even very rare, second cancers after treatment for UCNT need to be detected and have a poor prognosis.

  20. 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

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

    PubMed

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

    2014-01-01

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

  2. Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial.

    PubMed

    Basset-Seguin, Nicole; Hauschild, Axel; Grob, Jean-Jacques; Kunstfeld, Rainer; Dréno, Brigitte; Mortier, Laurent; Ascierto, Paolo A; Licitra, Lisa; Dutriaux, Caroline; Thomas, Luc; Jouary, Thomas; Meyer, Nicolas; Guillot, Bernard; Dummer, Reinhard; Fife, Kate; Ernst, D Scott; Williams, Sarah; Fittipaldo, Alberto; Xynos, Ioannis; Hansson, Johan

    2015-06-01

    The Hedgehog pathway inhibitor vismodegib has shown clinical benefit in patients with advanced basal cell carcinoma and is approved for treatment of patients with advanced basal cell carcinoma for whom surgery is inappropriate. STEVIE was designed to assess the safety of vismodegib in a situation similar to routine practice, with a long follow-up. In this multicentre, open-label trial, adult patients with histologically confirmed locally advanced basal cell carcinoma or metastatic basal cell carcinoma were recruited from regional referral centres or specialist clinics. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and adequate organ function. Patients with locally advanced basal cell carcinoma had to have been deemed ineligible for surgery. All patients received 150 mg oral vismodegib capsules once a day on a continuous basis in 28-day cycles. The primary objective was safety (incidence of adverse events until disease progression or unacceptable toxic effects), with assessments on day 1 of each treatment cycle (28 days) by principal investigator and coinvestigators at the site. Efficacy variables were assessed as secondary endpoints. The safety evaluable population included all patients who received at least one dose of study drug. Patients with histologically confirmed basal cell carcinoma who received at least one dose of study drug were included in the efficacy analysis. An interim analysis was pre-planned after 500 patients achieved 1 year of follow-up. This trial is registered with ClinicalTrials.gov, number NCT01367665. The study is still ongoing. Between June 30, 2011, and Nov 6, 2014, we enrolled 1227 patients. At clinical cutoff (Nov 6, 2013), 499 patients (468 with locally advanced basal cell carcinoma and 31 with metastatic basal cell carcinoma) had received study drug and had the potential to be followed up for 12 months or longer. Treatment was discontinued in 400 (80

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

    PubMed

    Zhai, Rui-Ping; Ying, Hong-Mei; Kong, Fang-Fang; Du, Cheng-Run; Huang, Shuang; Zhou, Jun-Jun; Hu, Chao-Su

    2015-01-01

    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. 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. 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. Nimotuzumab plus IMRT showed promising outcomes in terms of locoregional control and survival, without increasing the incidence of radiation-related toxicities for patients.

  4. [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.

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

    PubMed Central

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

    2016-01-01

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

  6. 125I brachytherapy alone for recurrent or locally advanced adenoid cystic carcinoma of the oral and maxillofacial region.

    PubMed

    Huang, M-W; Zheng, L; Liu, S-M; Shi, Y; Zhang, J; Yu, G-Y; Zhang, J-G

    2013-06-01

    This retrospective study was to evaluate the local control and survival of (125)I brachytherapy for recurrent and/or locally advanced adenoid cystic carcinoma (ACC) of the oral and maxillofacial region. A total of 38 patients with recurrent and/or locally advanced ACC of the oral and maxillofacial region received (125)I brachytherapy alone from 2001-2010. Twenty-nine were recurrent cases following previous surgery and radiation therapy. The other 9 cases involved primary tumors. Overall, 12 tumors were located in the major salivary glands, 12 in the minor salivary glands, and 14 in the paranasal region, the nasal cavity or the skull base. The prescribed dose was 100-160 Gy. Patients were followed for 12-122 months (median 51 months). The 2-, 5-, and 10-year local tumor control rates were 86.3, 59, and 31.5 %, respectively. The 2-, 5-, and 10-year overall survival rates were 92.1, 65 and 34.1 %, respectively. Tumors > 6 cm had significantly lower local control and survival rates. No severe complications were observed during follow-up. (125)I brachytherapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent ACC.

  7. Impact of lymph node invasion and sarcomatoid differentiation on the survival of patients with locally advanced renal cell carcinoma.

    PubMed

    Rodríguez-Covarrubias, Francisco; Castillejos-Molina, Ricardo; Sotomayor, Mariano; Méndez-Probst, Carlos E; Gómez-Alvarado, Martha Olivia; Uribe-Uribe, Norma; Gabilondo, Fernando; Feria-Bernal, Guillermo

    2010-01-01

    The application of current prognosticators in locally advanced nonmetastatic renal cell carcinoma (RCC) is controversial. We analyzed the impact of clinical and pathological variables on the survival of this subset of patients. We studied patients with RCC in stages III and IV without metastases, treated surgically between 1980 and 2009. We calculated disease-free (DFS) and cancer-specific survival (CSS), and the relation of clinical and pathological variables with these end-points. We identified 126 patients with locally advanced RCC; 8.7% had sarcomatoid differentiation. Tumor stage was pT3a in 48% and pT3b in 42%; 11.9% had lymph node invasion (N+). Patients with N- and N+ had a 10-year DFS of 49.0 and 23.4%, respectively (p = 0.0001). In multivariate analysis N+ (p = 0.0002) was the strongest predictor of DFS. The 10-year CSS of patients without sarcomatoid differentiation was 53.1% while those with sarcomatoid differentiation did not reach the median time to death (p < 0.0001). In multivariate analysis, sarcomatoid differentiation (p = 0.01) was the strongest predictor of CSS. Locally advanced RCC portends poor prognosis. Preoperatively, weight loss and Eastern Cooperative Oncology Group performance status are predictors of recurrence and mortality, respectively. However, the most powerful predictors of DFS and CSS in our cohort were lymph node status and sarcomatoid differentiation. Copyright (c) 2010 S. Karger AG, Basel.

  8. Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: Seven cases

    PubMed Central

    Uka, Kiminori; Aikata, Hiroshi; Takaki, Shintaro; Kawaoka, Tomokazu; Saneto, Hiromi; Miki, Daiki; Takahashi, Shoichi; Toyota, Naoyuki; Ito, Katsuhide; Chayama, Kazuaki

    2008-01-01

    The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC). Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP). Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients), and progressive disease (no patients). The median survival period was 8 mo (range, 5-55). With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%), seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non-resectable advanced HCC, but it has severe hematologic toxicity. PMID:18442216

  9. Ultra-deep targeted sequencing of advanced oral squamous cell carcinoma identifies a mutation-based prognostic gene signature

    PubMed Central

    Huang, Po-Jung; Huang, Yi; Hsu, An; Tang, Petrus; Chang, Yu-Sun; Chen, Hua-Chien; Yen, Tzu-Chen

    2015-01-01

    Background Patients with advanced oral squamous cell carcinoma (OSCC) have heterogeneous outcomes that limit the implementation of tailored treatment options. Genetic markers for improved prognostic stratification are eagerly awaited. Methods Herein, next-generation sequencing (NGS) was performed in 345 formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC patients. Genetic mutations on the hotspot regions of 45 cancer-related genes were detected using an ultra-deep (>1000×) sequencing approach. Kaplan-Meier plots and Cox regression analyses were used to investigate the associations between the mutation status and disease-free survival (DFS). Results We identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA, CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14 genes were found to predict DFS. A mutation-based signature affecting ten genes (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was devised to predict DFS. Two different resampling methods were used to validate the prognostic value of the identified gene signature. Multivariate analysis demonstrated that presence of a mutated gene signature was an independent predictor of poorer DFS (P = 0.005). Conclusions Genetic variants identified by NGS technology in FFPE samples are clinically useful to predict prognosis in advanced OSCC patients. PMID:25980437

  10. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab

    PubMed Central

    McDermott, David F.; Drake, Charles G.; Sznol, Mario; Choueiri, Toni K.; Powderly, John D.; Smith, David C.; Brahmer, Julie R.; Carvajal, Richard D.; Hammers, Hans J.; Puzanov, Igor; Hodi, F. Stephen; Kluger, Harriet M.; Topalian, Suzanne L.; Pardoll, Drew M.; Wigginton, Jon M.; Kollia, Georgia D.; Gupta, Ashok; McDonald, Dan; Sankar, Vindira; Sosman, Jeffrey A.; Atkins, Michael B.

    2015-01-01

    Purpose Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Results Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Conclusion Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC. PMID:25800770

  11. Efficacy of radioembolization according to tumor morphology and portal vein thrombosis in intermediate-advanced hepatocellular carcinoma.

    PubMed

    Golfieri, Rita; Mosconi, Cristina; Cappelli, Alberta; Giampalma, Emanuela; Galaverni, Maria Cristina; Pettinato, Cinzia; Renzulli, Matteo; Monari, Fabio; Angelelli, Bruna; Pini, Patrizia; Terzi, Eleonora; Ascanio, Salvatore; Garzillo, Giorgio; Piscaglia, Fabio; Bolondi, Luigi; Trevisani, Franco

    2015-01-01

    We analyzed overall survival (OS) following radioembolization according to macroscopic growth pattern (nodular vs infiltrative) and vascular invasion in intermediate-advanced hepatocellular carcinoma (HCC). Between September 2005 and November 2013, 104 patients (50.0% portal vein thrombosis [PVT], 29.8% infiltrative morphology) were treated. Median OS differed significantly between patients with segmental and lobar or main PVT (p = 0.031), but was 17 months in both those with patent vessels and segmental PVT. Median OS did not differ for infiltrative and nodular HCC. Median OS was prolonged in patients with a treatment response at 3 months (p = 0.023). Prior TACE was also a significant predictor of improved OS. A further indication for radioembolization might be infiltrative HCC, since OS was similar to nodular types.

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

    PubMed

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

    1999-02-01

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

  13. Hepatocellular carcinoma.

    PubMed

    Macdonald, G A

    1999-05-01

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

  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. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-12-01

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

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

    PubMed Central

    Park, Ha-Na; Kim, Kyoung-A

    2016-01-01

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

  2. Dyke-Davidoff-Masson Syndrome Associated with Epidermoid Tumour and Arachnoid Cyst: A Case Report

    PubMed Central

    Menekşe, Güner; Özsoy, Kerem Mazhar; Ateş, Tuncay; Ökten, Ali İhsan; Güzel, Aslan

    2013-01-01

    Background: Dyke-Davidoff-Masson Syndrome (DDMS) is a rarely seen clinical entity which is characterised by cerebral hemiatrophy, contralateral hemiparesis and epilepsy. Radiological features are typical, such as unilateral atrophy of the cerebral hemisphere and associated compensatory bone changes in the skull, like thickening, enlargement of the paranasal sinuses and mastoid air cells. Case Report: In this article, we report the first case of DDMS associated with epidermoid tumour and arachnoid cyst, who underwent operation for an epidermoid tumour in the inter-hemispheric region. To our knowledge, this is the first report of DDMS associated with multiple intracranial pathologies and this association has not been previously described in the literature. Conclusion: Any patient who receives DDMS in the light of clinical and radiological findings should be investigated for concomitant pathologies. Different sequences of MRI may be useful in the diagnosis of other intracranial lesions. PMID:25207154

  3. Dyke-davidoff-masson syndrome associated with epidermoid tumour and arachnoid cyst: a case report.

    PubMed

    Menekşe, Güner; Ozsoy, Kerem Mazhar; Ateş, Tuncay; Okten, Ali İhsan; Güzel, Aslan

    2013-12-01

    Dyke-Davidoff-Masson Syndrome (DDMS) is a rarely seen clinical entity which is characterised by cerebral hemiatrophy, contralateral hemiparesis and epilepsy. Radiological features are typical, such as unilateral atrophy of the cerebral hemisphere and associated compensatory bone changes in the skull, like thickening, enlargement of the paranasal sinuses and mastoid air cells. In this article, we report the first case of DDMS associated with epidermoid tumour and arachnoid cyst, who underwent operation for an epidermoid tumour in the inter-hemispheric region. To our knowledge, this is the first report of DDMS associated with multiple intracranial pathologies and this association has not been previously described in the literature. Any patient who receives DDMS in the light of clinical and radiological findings should be investigated for concomitant pathologies. Different sequences of MRI may be useful in the diagnosis of other intracranial lesions.

  4. Huge splenic epidermoid cyst with elevation of serum CA19-9 level.

    PubMed

    Matsumoto, Sayo; Mori, Toshifumi; Miyoshi, Jinsei; Imoto, Yoshitaka; Shinomiya, Hirohiko; Wada, Satoshi; Nakao, Toshihiro; Shinohara, Hisamitsu; Yoshida, Sadahiro; Izumi, Keisuke; Okazaki, Jun; Muguruma, Naoki; Takayama, Tetsuji

    2015-01-01

    A 30-year-old female was referred to our hospital for further examination of liver dysfunction. A huge, soft mass was noted in her left upper quadrant on physical examination. Abdominal ultrasonography and computed tomography revealed a huge cystic tumor of 20 cm in the hilus of the spleen. Serum CA19-9 was 491 U/ml, and splenectomy was performed under suspicion of a malignant cystic tumor. The inner surface of the cyst was lined by squamous epithelial cells that were immunohistochemically positive for CA19-9. Serum CA19-9 level was normalized after the surgery. Our case of a very rare, huge epidermoid cyst of the spleen suggests that measurement of the serum CA19-9 level is useful for evaluating therapeutic efficacy of a splenic epidermoid cyst.

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

    PubMed

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

    1989-12-01

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

  6. 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.

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

    PubMed

    Furtado, Sunil V; Hegde, Alangar S

    2009-09-01

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

  8. A case of cerebellopontine angle epidermoid cyst presenting as trigeminal neuropathy.

    PubMed

    Muzammil, Sadat; Leong, King Sun

    2009-05-01

    We present the case of a 35-year-old female who had paraesthesia and numbness on the left side of her face. Initially the ophthalmic division and maxillary divisions on the trigeminal nerve were involved, but later involved the mandibular division as well. On MRI, a cerebellopontine angle (CPA) epidermoid cyst was detected. After 18 months of follow up, her symptoms remain stable and she is being managed conservatively.

  9. Technically accurate intracavitary insertions improve pelvic control and survival among patients with locally advanced carcinoma of the uterine cervix.

    PubMed

    Corn, B W; Hanlon, A L; Pajak, T F; Owen, J; Hanks, G E

    1994-06-01

    The purpose of this study was to document whether the technical qualities of a brachytherapy application impacts on the outcome of patients with locally advanced cervix cancer treated by definitive irradiation. A previous report from the patterns of care study demonstrated the importance of brachytherapy in the treatment of locally advanced cervix cancer. Locally advanced disease was defined as FIGO stages Ib (if tumor diameter was < or = 4 cm), IIb (if disease was bilateral or involved the lateral aspect of either parametrium), and III. Localization films from 128 patients with locally advanced squamous cell carcinoma of the cervix were reviewed by a radiation physicist and a radiation oncologist with expertise in gynecologic radiotherapy. All patients received external beam irradiation followed by one brachytherapy application (median point A dose = 8040 cGy; range, 4083-10,020 cGy). Brachytherapy parameters assessed were (a) the distance between the right colpostat source and the distal tandem source, (b) the distance between the left colpostat source and the distal tandem source, and (c) the symmetry of colpostat placement. Implants were scored as "ideal" (n = 8) when all three parameters were deemed satisfactory, "unacceptable" (n = 17) when none of the parameters was deemed satisfactory, and "adequate" (n = 41) in all other cases. Significantly improved 5-year local control was seen when comparing ideal and adequate placements to unacceptable placements (68% vs 34%, P = 0.02). A strong trend toward improved 5-year survival was also noted among the group with ideal and adequate implants as opposed to unacceptable implants (60% vs 40%). Multivariate analysis showed that the technical adequacy of the brachytherapy implant was the most important prognostic discriminant of local control. In conclusion, these analyses demonstrate the direct influence of competent technical implant performance on tumor control and even survival. While only a small fraction of

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

    PubMed Central

    Prajapati, Hasmukh J.

    2017-01-01

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

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

    PubMed

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

    2016-10-01

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

  12. Sorafenib With and Without Transarterial Chemoembolization for Advanced Hepatocellular Carcinoma With Main Portal Vein Tumor Thrombosis: A Retrospective Analysis.

    PubMed

    Zhang, Yingqiang; Fan, Wenzhe; Wang, Yu; Lu, Ligong; Fu, Sirui; Yang, Jianyong; Huang, Yonghui; Yao, Wang; Li, Jiaping

    2015-12-01

    The survival benefit of combining sorafenib and transarterial chemoembolization (TACE) therapy compared with sorafenib monotherapy for patients with advanced hepatocellular carcinoma (HCC) and main portal vein tumor thrombosis (MPVTT) is unclear. Between January 2009 and June 2013, 183 consecutive patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) and MPVTT were retrospectively reviewed. Of these, 89 patients with advanced HCC and MPVTT were enrolled in this study: 45 were treated with combination therapy (sorafenib-TACE group), and the other 44 treated with sorafenib monotherapy (sorafenib group). The mean number of TACE sessions per patient was 2.6 (range: 1-5). The median duration of sorafenib in the sorafenib-TACE group and sorafenib group was 5.6 months and 5.4 months, respectively. The disease control rate was similar between the two groups. Median time to progression was 3.0 months (95% confidence interval [CI]: 2.2, 3.7) in the sorafenib-TACE group, and 3.0 months (95% CI: 2.1, 3.8) in the sorafenib group (p = .924). Median overall survival was 7.0 months (95% CI: 6.1, 7.8) and 6.0 months (95% CI: 4.7, 7.3) in the sorafenib-TACE group and the sorafenib group, respectively (p = .544). The adverse events related to sorafenib were comparable between the two groups. Twenty-one adverse events of grade 3-4 related to TACE occurred in 12 patients (26.7%), and 2 of them died (4.4%). This study demonstrated no advantage of combination therapy over sorafenib monotherapy. Considering the patients' morbidity after TACE, sorafenib monotherapy is appropriate for managing patients with advanced HCC and MPVTT. ©AlphaMed Press.

  13. HATT: a phase IV, single-arm, open-label study of sorafenib in Taiwanese patients with advanced hepatocellular carcinoma.

    PubMed

    Lin, Shi-Ming; Lu, Sheng-Nan; Chen, Ping-Tsung; Jeng, Long-Bin; Chen, Shinn-Cherng; Hu, Chi-Tan; Yang, Sien-Sing; Le Berre, Marie-Aude; Liu, Xuan; Mitchell, David Y; Prins, Klaas; Grevel, Joachim; Peña, Carol A E; Meinhardt, Gerold

    2017-03-01

    Sorafenib significantly improves survival in patients with advanced hepatocellular carcinoma (HCC). This phase IV study assessed sorafenib efficacy/safety in Taiwanese patients with advanced HCC and Child-Pugh A status. All patients received 400 mg sorafenib BID. Safety, efficacy, sorafenib pharmacokinetics, and Child-Pugh progression were evaluated. A hand-foot skin reaction (HFSR) prevention substudy assessed HFSR incidence and grade/severity and time to HFSR in 29 and 34 patients randomized to corticosteroid and noncorticosteroid ointments, respectively, and in 88 nonrandomized patients. The 151 patients included 120 (80%) male patients and 81 (54%) with stage IV disease. Mean sorafenib dose was 626 mg/day, and median treatment duration was 4.2 months. Median overall survival (OS), progression-free survival, and time to progression (TTP) were 8.6, 2.7, and 3.8 months, respectively. Disease control and response rates (partial responses only) were 48 and 6.6%, respectively. Median TTP from Child-Pugh A to B/C was 88 days. Drug-related adverse events (AEs) occurred in 89.4% of patients; none were new or unexpected. The most frequent grade ≥3 drug-related, treatment-emergent AEs were HFSR (13.2%), diarrhea (11.9%), and hypertension (6.6%). Corticosteroid ointment tended to reduce the severity and incidence of all HFSR-associated parameters. Pharmacokinetic exposure was unaltered by Child-Pugh progression. The final pharmacokinetic model predicted 13.1 and 33.8% reductions in sorafenib exposure over 6 and 12 months, respectively. There was a trend of longer OS and TTP in Taiwanese patients with advanced HCC compared with patients with advanced HCC in the Asia-Pacific trial. Sorafenib exposure did not correlate with liver function. Reduced pharmacokinetic exposure over time was unrelated to reduced or interrupted dosing.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2010-01-01

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

  16. [Treatment of advanced hepatocellular carcinoma : Novel agents and role of local therapy].

    PubMed

    Parisod, Louis; Duran, Rafael; Denys, Alban; Digklia, Antonia

    2017-05-17

    The incidence of hepatocellular carcinoma (HCC) is increasing in Switzerland and its treatment is a challenge. The purpose of this article is to summarize the different therapeutic approaches in the metastatic stage, as well as the perspectives of targeted treatments and immunotherapy. Until recently, the only recognized therapeutic standard for these patients with metastatic CHC was sorafenib, a tyrosine kinase inhibitor. If the patient was to progress under sorafenib, no other recognized therapeutic option was available as second line. We present in this article the recent data on regorafenib, also an inhibitor of tyrosine kinases, the first systemic therapy showing an increase in survival for patients progressing under sorafenib. Then we will discuss promising data and progress made in treatments checkpoints inhibitors and therapies combining local and systematic approaches.

  17. Surgery for retrohepatic caval thrombus in patients with advanced renal cell carcinoma: a case series.

    PubMed

    Polańska-Płachta, Małgorzata; Proczka, Robert; Dudek, Magdalena; Ostrowska, Małgorzata; Polański, Jerzy A

    2016-01-15

    Thrombotic involvement of the inferior vena cava (IVC) occurs in about 10% of all patients with renal cell carcinoma (RCC). It is treated with radical resection of tumor and thrombus. We present the results of a recent case series of 20 patients with retrohepatic IVC thrombus. Our cohort of 20 patients included 16 primary resections (radical nephrectomy and thrombectomy with and without vascular graft), three recurrences primarily operated on elsewhere (thrombectomy and vascular graft), and one recurrence due to a new liver metastasis. All surviving patients were discharged with a patent IVC. The overall mortality rate was 10%, and the overall complication rate was 35%. Both are in keeping with results presented worldwide. Our series provides a corroborating extension to the existing dataset on RCC-related IVC thrombus removal. It confirms that the radical surgical approach can be performed safely and successfully with respect to venous patency.

  18. Recent Advances in Biomarkers and Potential Targeted Therapies in Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Yavrouian, Eric J.; Sinha, Uttam K.

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a devastating tumor of the upper aerodigestive tract with no significant change in treatment modality or improvement in survival over the last several decades. Biomarkers are important biological molecules that can be utilized in tumor detection, prognosis, and as targeted therapies. There are several important biomarkers and potential targets in the forefront, including biomarkers of tumorigenesis, signal transduction molecules, proteins involved in angiogenesis, and oncogenic viruses. The clinical applications of these biomarkers are in various states from in vitro and in vivo models, phase II and III clinical trials, to accepted modes of treatment in patients with HNSCC. Given the potential improvement in prognosis that biomarkers and their targeted therapies may have on the treatment of HNSCC, their investigation is both important and essential. PMID:22523710

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

    PubMed

    Tucker, H M

    1998-05-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

    NEMOTO, TOMOYUKI; MATSUDA, HIDETAKA; NOSAKA, TAKUTO; SAITO, YASUSHI; OZAKI, YOSHIHIKO; HAYAMA, RYOKO; NAITO, TATSUSHI; TAKAHASHI, KAZUTO; OFUJI, KAZUYA; OHTANI, MASAHIRO; HIRAMATSU, KATSUSHI; SUTO, HIROYUKI; NAKAMOTO, YASUNARI

    2014-01-01

    Sorafenib and hepatic arterial infusion chemotherapy (HAIC) are both indicated for unresectable hepatocellular carcinoma (HCC). In this study, we compared the efficacy and safety of HAIC to that of sorafenib in elderly patients with HCC. Eligible patients included those aged ≥70 years, with histologically or clinically confirmed advanced HCC. A total of 12 patients received sorafenib (800 mg per day) and 8 patients received HAIC with 5-fluorouracil (300 mg/m2 on days 1–5 and 8–12) with or without cisplatin (20 mg/m2 on days 1 and 8), with interferon-α (3 times per week for 4 weeks). The response rate was significantly higher in patients treated with HAIC (37.5%) compared to that in patients treated with sorafenib (no response). The median overall survival (18.6 and 11.7 months) and progression-free survival (4.0 and 5.0 months) were similar between the sorafenib and HAIC groups, respectively. In the sorafenib group, 58.3% of the patients discontinued treatment compared to none in the HAIC group. The most frequent adverse event leading to discontinuation of sorafenib was anorexia. Similar to sorafenib, HAIC appears to be a feasible treatment and may also have the advantage of an adequate safety profile for elderly patients with advanced HCC. Further study of HAIC in a larger population of elderly patients is required to assess its potential as an alternative to sorafenib for HCC. PMID:25279193

  3. 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.

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

    PubMed Central

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

    2017-01-01

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

  5. Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma.

    PubMed

    Tsuchiya, Norihiko; Narita, Shintaro; Inoue, Takamitsu; Hasunuma, Naoko; Numakura, Kazuyuki; Horikawa, Yohei; Satoh, Shigeru; Notoya, Takeshi; Fujishima, Naohito; Hatakeyama, Shingo; Ohyama, Chikara; Habuchi, Tomonori

    2013-03-01

    The aim of this study was to evaluate the clinical factors, drug-related genetic polymorphisms, and human leukocyte antigen (HLA) types to determine the association with sorafenib-induced high-grade skin rash (HGSR) in Japanese patients with advanced renal cell carcinoma (RCC). A total of 55 patients with advanced RCC treated with sorafenib were analyzed retrospectively. Of these, 33 patients were subjected to HLA typing and polymorphism analyses of CYP3A5, ABCB1, ABCC2, and UGT1A1, which are involved in the metabolism and membrane transport of sorafenib. Grade 3 or higher SR developed in 12 (22%), and a higher incidence was observed in female patients than in male patients (40 vs. 15%, P=0.046). The initial dose, initial dose per body weight, and initial dose per body surface area in patients with HGSR were significantly higher than those in patients without HGSR. Patients with the ABCC2 -24CC genotype were at a significantly higher risk of SR than those with the CT genotype (35 vs. 0%, P=0.032). HLA-A*24 was significantly associated with the occurrence of HGSR (P=0.049). Our finding suggested that women, higher initial dose per body weight or body surface area, the ABCC2 -24CC genotype, and HLA-A*24 are associated with the risk of sorafenib-induced HGSR in Japanese RCC patients.

  6. 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.

  7. 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

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

    PubMed

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

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

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

    PubMed Central

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

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

  10. Survival after free flap reconstruction in patients with advanced oral squamous cell carcinoma.

    PubMed

    de Vicente, Juan Carlos; Rodríguez-Santamarta, Tania; Rosado, Pablo; Peña, Ignacio; de Villalaín, Lucas

    2012-02-01

    The purpose of the present study was to assess the effect of free-flap reconstruction on the survival of patients treated for oral squamous cell carcinoma. The present study was based on a retrospective cohort of 98 patients. Of the 98 patients, 49 underwent surgical reconstruction with microvascular tissue transfer (test group) and in 49 (control group), only local or regional flaps were used. For the free-flap group, the average follow-up period was 34.6 months. For the control group, the average follow-up was 39.8 months. At the end of the follow-up period, 23 (47%) and 33 (67.3%) patients had died of oral squamous cell carcinoma in the microvascular reconstructive and control group, respectively. The difference in the final status between the 2 groups was statistically significant (P = .03). In the free-flap group, the mean and median survival time was 65 and 60 months. In the locoregional flap group, the mean and median survival time was 54 and 24 months, respectively. No difference was seen in the survival time between the free-flap and local flap groups (P = .2). Univariate Kaplan-Meier analysis revealed that positive surgical margins were significantly associated with shortened survival in the free-flap group and that recurrence was significant in both reconstructive groups. On multivariate Cox regression analysis, the status of the resection margin (P = .07) and tumor recurrence (P < .0005) showed a significant relationship with survival. Patients with free-flap reconstruction of surgically created defects after oral cancer resection showed a trend toward better 5-year survival. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Hepatocellular carcinoma

    SciTech Connect

    Nakashima, T.; Kojiro, M.

    1986-01-01

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

  12. Neoadjuvant treatment intensification or adjuvant chemotherapy for locally advanced carcinoma rectum: The optimum treatment approach remains unresolved.

    PubMed

    Mallick, Supriya; Benson, Rony; Haresh, K P; Rath, G K

    2015-12-01

    Rectal carcinoma [RC] is often managed with preoperative radiotherapy or radio-chemotherapy followed by total mesorectal excision (TME). Efforts are being made to improve outcome by intensifying the preoperative treatment. However, the optimum therapy remains unclear. There is ongoing controversy regarding the optimum radiation dose, chemotherapy regimen and schedule. In addition there exists growing disagreement regarding the role of adjuvant chemotherapy after neoadjuvant radiation or chemoradiation. We reviewed the recent land mark trials to find a road map in the management of locally advanced rectal carcinoma. Preoperative short course radiotherapy has long been proven to improve local disease control. The initial trials with long course chemoradiotherapy, comparing short course radiotherapy have shown to increase local control and pathological complete response rates. Since then treatment intensification of this neoadjuvant schedule has been tried by many researchers. But initial results of these treatment intensification trials, show no significant benefit and are associated with increased toxicity. There is an unmet need to stratify patients depending on risk to assign them to long course chemoradiotherapy or short course radiotherapy. Current evidence does not support the use of adjuvant chemotherapy in patients who were treated with preoperative (chemo)radiotherapy. Preoperative radiotherapy appears to improve disease control with favorable toxicity profile and there is very little to choose between long course chemoradiotherapy and short course radiotherapy. However, long course chemoradiotherapy may be beneficial for patients with high risk features like positive circumferential resection margin [CRM] and extramural spread of >5mm. There is no role for adjuvant chemotherapy in patients who were treated preoperative (chemo)radiotherapy. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. The GNAS1 T393C polymorphism predicts survival in patients with advanced squamous cell carcinoma of the larynx.

    PubMed

    Lehnerdt, Goetz F; Franz, Peter; Winterhoff, Sebastian; Bankfalvi, Agnes; Grehl, Sara; Lang, Stephan; Schmid, Kurt W; Siffert, Winfried; Jahnke, Klaus; Frey, Ulrich H

    2008-12-01

    In previous studies, we have demonstrated that the T-allele of a specific single nucleotide polymorphism (SNP) in the Galphas gene (T393C) correlates with increased Galphas expression and hence apoptosis. The T-allele was associated with a favorable outcome in a variety of human cancers, for example, carcinoma of the urinary bladder, kidney, colorectal, oro- and hypopharynx. The prognostic value of the T393C SNP was retrospectively evaluated in an unselected series of patients treated with curative intent for laryngeal squamous cell carcinomas including all tumor stages with different therapeutic regimens. DNA analysis was performed using DNA from paraffin-embedded tissue samples from 157 patients (142 men, 15 women) with a median follow-up of 68 (3-143) months. The various genotypes were correlated with the overall survival. Survival was significantly dependent on the T393C genotype in advanced American Joint Committee on Cancer (AJCC) stages (III-IV) with an apparent gene-dose effect (P = .0437). Five-year survival rates were 76% for TT, 49% for TC, and 43.5% for CC. In multivariate analysis including age at diagnosis, AJCC stage, grade, gender, and T393C genotypes, patients with CC genotype displayed a higher risk for death with a hazard ratio of 2.59 (95% confidence interval: 1.01-6.64, P = .047) compared with the reference group consisting of T393 homozygous individuals. The T393C SNP is a prognostic marker that could help to identify high risk patients suffering from head and neck cancer.

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

    SciTech Connect

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

    2006-01-01

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

  15. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings.

    PubMed

    Beck, J; Procopio, G; Bajetta, E; Keilholz, U; Negrier, S; Szczylik, C; Bokemeyer, C; Bracarda, S; Richel, D J; Staehler, M; Strauss, U P; Mersmann, S; Burock, K; Escudier, B

    2011-08-01

    The European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study provided sorafenib to advanced renal cell carcinoma (RCC) patients in whom previous systemic therapy had failed. The study assessed the safety and use of sorafenib for the treatment of advanced RCC in a large community-based patient population across 11 countries in Europe. EU-ARCCS was a single-arm, open-label trial of sorafenib in advanced RCC patients. End points included safety, time to progression, progression-free survival (PFS), and disease control rate (DCR). Subgroup analyses included age, Eastern Cooperative Oncology Group performance status, histology, prior therapy, and number and sites of metastases. About 1159 advanced RCC patients were enrolled. Most patients (94%) experienced drug-related adverse events (AEs) of any grade, with the most common grade ≥3 AEs including hand-foot skin reaction (13%), diarrhea (7%), fatigue (7%), hypertension (6%), and rash/desquamation (5%). The incidence of AEs in the subgroups was similar to that in the overall population. Median PFS was 6.6 months; DCR at ≥8 and ≥12 weeks was 85% and 78%, respectively. The sorafenib safety profile in European community-based practice settings was similar to that reported in clinical trials. The heterogeneous advanced RCC patient population in EU-ARCCS permitted assessment of sorafenib in important subpopulations of advanced RCC patients.

  16. Carcinoma of the cervix with extensive endometrial and myometrial involvement.

    PubMed

    de Jesus, M; Tang, W; Sadjadi, M; Belmonte, A H; Poon, T P

    1990-02-01

    Verrucous carcinoma is a rare variant of epidermoid carcinoma with distinct clinical and histopathologic features. To date, 31 cases have been reported in the cervix. They are typically slow-growing, locally invasive tumors with low potential for lymphatic metastasis and appear to be radioresistant. We report a case which is unusual in having endometrial and deep myometrial invasion. Electron microscopy, immunohistochemical stains, and DNA in situ hybridization studies failed to detect human papilloma virus particles but the oncogenic potential of the virus is not excluded.

  17. Integrated Analysis of Long Noncoding RNA and mRNA Expression Profile in Advanced Laryngeal Squamous Cell Carcinoma.

    PubMed

    Feng, Ling; Wang, Ru; Lian, Meng; Ma, Hongzhi; He, Ning; Liu, Honggang; Wang, Haizhou; Fang, Jugao

    2016-01-01

    Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the expression pattern and function of lncRNAs in laryngeal squamous cell carcinoma (LSCC) are still unclear. To investigate the aberrantly expressed lncRNAs and mRNAs in advanced LSCC, we screened lncRNA and mRNA expression profiles in 9 pairs of primary Stage IVA LSCC tissues and adjacent non-neoplastic tissues by lncRNA and mRNA integrated microarrays. Gene Ontology and pathway analysis were performed to find out the significant function and pathway of the differentially expressed mRNAs, gene-gene functional interaction network and ceRNA network were constructed to select core mRNAs, and lncRNA-mRNA expression correlation network was built to identify the interactions between lncRNA and mRNA. qRT-PCR was performed to further validate the expressions of selected lncRNAs and mRNAs in advanced LSCC. We found 1459 differentially expressed lncRNAs and 2381 differentially expressed mRNAs, including 846 up-regulated lncRNAs and 613 down-regulated lncRNAs, 1542 up-regulated mRNAs and 839 down-regulated mRNAs. The mRNAs ITGB1, HIF1A, and DDIT4 were selected as core mRNAs, which are mainly involved in biological processes, such as matrix organization, cell cycle, adhesion, and metabolic pathway. LncRNA-mRNA expression correlation network showed LncRNA NR_027340, MIR31HG were positively correlated with ITGB1, HIF1A respectively. LncRNA SOX2-OT was negatively correlated with DDIT4. qRT-PCR further validated the expression of these lncRNAs and mRNAs. The work provides convincing evidence that the identified lncRNAs and mRNAs are potential biomarkers in advanced LSCC for further future studies.

  18. 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

  19. Genetic Variations in Radiation and Chemotherapy Drug Action Pathways and Survival in locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy

    PubMed Central

    Guo, Xiang; Tang, Lin-Quan; Chen, Qiu-Yan; Zhang, Lu; Guo, Ling; Luo, Dong-Hua; Huang, Pei-Yu; Mo, Hao-Yuan; Xiang, Yan-Qun; Qiu, Fang; Sun, Rui; Zhang, Ying; Chen, Ming-Yuan; Hua, Yi-Jun; Lv, Xing; Wang, Lin; Zhao, Chong; Cao, Ka-Jia; Qian, Chao-Nan; Hong, Ming-Huang; Mai, Hai-Qiang

    2013-01-01

    Background and Purpose Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Material and Methods Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction. Results After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms. Conclusions Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk. PMID:24340057

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

    PubMed Central

    2011-01-01

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

  1. Combined nimotuzumab with chemoradiotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma: A retrospective study.

    PubMed

    Lai, Xiaojing; Gu, Qing; Zheng, Xiao; Liu, Guan; Feng, Wei; Lin, Xiao; Mao, Weimin

    2016-10-01

    To observe the efficacy and toxicities of combined nimotuzumab with chemoradiotherapy as the first-line treatment to advanced esophageal squamous cell carcinoma (ESCC). The clinical data of 43 patients with local advanced or metastatic ESCC treated with nimotuzumab combined with chemoradiotherapy in our hospital were included in this retrospective study. The overall response, adverse events, overall survival (OS), and progressive-free survival (PFS) were analyzed. At 1 month after the treatment, objective response rate (complete response [CR] + partial response [PR]) was 65.12%, and disease control rate (CR + PR + stable disease [SD]) was 86.05%, with one patient (2.33%) showing CR, 27 (62.79%) patients with PR, 9 (20.93%) with SD, and 6 (13.95%) with progressive disease, respectively. The median OS was 15.5 months, and the median PFS was 8.83 months. Multivariate analysis showed that the patients with more cycles (>6 times) of nimotuzumab treatment had better PFS and OS than those with fewer cycles (≤6 times). Patients received high-dose radiation (>55 Gy) had a better PFS than those patients received low-dose radiation (≤55 Gy). Three patients suffered severe esophageal fistula, and three patients showed superficial skin erosion. Chemoradiotherapy in combination with more than 6 weekly doses of nimotuzumab (>1400 mg) had a survival benefit to the patients with advanced ESCC. High-dose radiation therapy for primary tumor has been confirmed to improve PFS in these patients. Patients treated with nimotuzumab showed no increased risk of adverse events.

  2. A cross-sectional investigation of fatigue in advanced renal cell carcinoma treatment: results from the FAMOUS study.

    PubMed

    P J, Goebell; A, Münch; L, Müller; H J, Hurtz; M, Koska; S, Busies; N, Marschner

    2014-04-01

    With an increasing choice of new treatment options, the management of side effects to maintain a chosen treatment if likely to be effective on the tumor remains important. The perception of side effects however varies between the physician and the patient, leading to possible wrong assumptions on tolerability that result in dose modifications, which may ultimately affect effectiveness. The aim was to assess fatigue in patients with advanced or metastatic renal cell carcinoma (RCC) by comparing the evaluation of the physician to the one provided by their respective patient. In addition, we aimed to assess possible influences of fatigue on parameters of quality of life. Patients receiving systemic treatment for advanced RCC and their physicians were questioned independently regarding incidence and severity of fatigue and its effect on quality of life. Both physicians and patients completed 98 matching questionnaires. Patients were treated with sunitinib, sorafenib, bevacizumab combined with interferon alpha, temsirolimus, everolimus, or interferon alpha alone. Incidence and severity of fatigue was differently assessed by patients and physicians, with fatigue being more severe when reported by the patient. The severity of fatigue increased with progressing treatment lines. Quality of life was significantly lower in patients experiencing fatigue compared with patients without fatigue. Emotional, functional, and physical well-being were all affected by fatigue, the latter being the most affected subscale. Social well-being was least affected. Fatigue is a complex and cumulative condition of patients treated for advanced RCC, and it considerably affects patient's quality of life. As many of its underlying causes may be treated, the divergent perception of occurrence and severity of fatigue should be integrated in treatment concepts. The active role of the patient in helping to manage ailments through assessment should be implemented when optimizing treatment of RCC.

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

    PubMed Central

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

    2016-01-01

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

  4. Correlation of skin toxicity and hypertension with clinical benefit in advanced hepatocellular carcinoma patients treated with sorafenib.

    PubMed

    Shin, Sun Young; Lee, Yu Jeung

    2013-11-01

    The purpose of this study was to identify the correlation of skin toxicity and hypertension with clinical benefit in advanced hepatocellular carcinoma (HCC) patients treated with sorafenib by analyzing medical records retrospectively. Data from medical records was statistically analyzed to identify a correlation of skin toxicity and hypertension with treatment response and prognosis in advanced HCC patients who had received sorafenib at the Asan Medical Center from July 2010 to June 2012. This study investigated prognostic factors for overall survival and the correlation between the development of skin toxicities and hypertension. A total of 99 patients receiving sorafenib were included in this study. 29 patients who developed skin toxicities Grade 2 or higher showed significantly longer survival than the 70 patients who developed skin toxicities less than Grade 2 or those without skin toxicity (p = 0.024). However, development of hypertension was not related to survival (p = 0.262). In a multivariate analysis, skin toxicities were found to be good prognostic factors for overall survival (hazard ratio, 0.320; 95% CI, 0.119 - 0.861; p = 0.024) as well as low α-fetoprotein level (hazard ratio, 0.195; 95% CI, 0.076 - 0.500; p = 0.001). On the other hand, no correlation was found between the development of skin toxicities and hypertension (p = 0.109). Skin toxicities that are common adverse reactions in advanced HCC patients treated with sorafenib may be used as surrogate markers for clinical benefit. Therefore, early detection and proper management of these toxicities is crucial for continuing treatment with sorafenib.

  5. Therapies for Advanced Stage Hepatocellular Carcinoma with Macrovascular invasion or Metastatic Disease: a Systematic Review and Meta-analysis.

    PubMed

    Finn, Richard S; Zhu, Andrew X; Wigdan, Farah; Almasri, Jehad; Zaiem, Feras; Prokop, Larry J; Hassan Murad, Mohammad; Mohammed, Khaled

    2017-09-07

    Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors such as macrovascular invasion and extrahepatic spread. We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics including patients with both Child-Pugh scores of A and B. A comprehensive search of several databases from each database inception to February 15th 2016, any language was conducted.We included 14 studies (3 randomized controlled studies (RCTs) and 11 observational studies).We included studies that compared sorafenib, transarterial bland embolisation/transarterial chemoembolization, yttrium-90/radiation therapy, ablation (or combination) and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in OS for patients with advanced HCC and MVI and/or EHS and Child Pugh-A liver disease (HR 0.66 (95% CI 0.51-0.87), I(2) = 0%). Several observational studies evaluated loco-regional therapies alone or in combination with other treatments and were limited by very low quality of evidence. This was true for both patients with EHS and MVI. In patients with advanced HCC and Child-Pugh A liver function, sorafenib is the only treatment that has been shown to improve overall survival in randomized studies. High quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease is lacking. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  6. Chemotherapy with gemcitabine plus cisplatin in patients with advanced biliary tract carcinoma at Chang Gung Memorial Hospital: a retrospective analysis.

    PubMed

    Wu, Chiao-En; Hsu, Hung-Chih; Shen, Wen-Chi; Lin, Yang-Chung; Wang, Hung-Ming; Chang, John Wen-Chen; Chen, Jen-Shi

    2012-01-01

    A gemcitabine-cisplatin combination is a standard treatment option for patients with advanced biliary tract carcinoma (BTC). We assessed the efficacy and safety of this regimen at Chang Gung Memorial Hospital. Between April 2009 and December 2010, 30 chemotherapy-naïve patients (13 men and 17 women; median age: 61.5 years) with advanced BTC were retrospectively analyzed. Treatment consisted of gemcitabine (Gemmis(®); TTY, Taipei, Taiwan) 1000 mg/m(2), followed by cisplatin 30 mg/m(2) on days 1 and 8 every 3 weeks. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 2-3 cycles. The toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3. At the end of July, 2011, 27 patients were evaluated using the RECIST criteria. According to the intent to treat analysis of response, 5 patients (16.7%) had a partial response, 10 patients (33.3%) had stable disease and 12 patients (40.0%) had progressive disease. The median time to progression (TTP) and median overall survival (OS) of the 30 patients were 4.8 months and 13.4 months, respectively. The patients with biliary obstruction requiring drainage before treatment had a significantly shorter OS than those without biliary obstruction (p = 0.02) even though the TTP showed no statistically significant difference (p = 0.69) between groups. The major grade III/IV adverse events in the 30 patients included infection (n = 8, 26.7%), anemia (n = 5, 16.7%), neutropenia (n = 4, 13.3%), and elevated alanine aminotransferase (n = 2, 6.7%). There were no treatment-related deaths. Gemcitabine plus cisplatin is a feasible chemotherapy regimen with manageable toxicity in patients with advanced BTC. Maintaining good biliary drainage is essential for these patients.

  7. 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

  8. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial.

    PubMed

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas; Tannir, Nizar M; Mainwaring, Paul N; Rini, Brian I; Hammers, Hans J; Donskov, Frede; Roth, Bruce J; Peltola, Katriina; Lee, Jae Lyun; Heng, Daniel Y C; Schmidinger, Manuela; Agarwal, Neeraj; Sternberg, Cora N; McDermott, David F; Aftab, Dana T; Hessel, Colin; Scheffold, Christian; Schwab, Gisela; Hutson, Thomas E; Pal, Sumanta; Motzer, Robert J

    2016-07-01

    Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment. Here, we report the final overall survival results from this study based on an unplanned second interim analysis. In this open-label, randomised phase 3 trial, we randomly assigned (1:1) patients aged 18 years and older with advanced or metastatic clear-cell renal cell carcinoma, measurable disease, and previous treatment with one or more VEGFR tyrosine-kinase inhibitors to receive 60 mg cabozantinib once a day or 10 mg everolimus once a day. Randomisation was done with an interactive voice and web response system. Stratification factors were Memorial Sloan Kettering Cancer Center risk group and the number of previous treatments with VEGFR tyrosine-kinase inhibitors. The primary endpoint was progression-free survival as assessed by an independent radiology review committee in the first 375 randomly assigned patients and has been previously reported. Secondary endpoints were overall survival and objective response in all randomly assigned patients assessed by intention-to-treat. Safety was assessed per protocol in all patients who received at least one dose of study drug. The study is closed for enrolment but treatment and follow-up of patients is ongoing for long-term safety evaluation. This trial is registered with ClinicalTrials.gov, number NCT01865747. Between Aug 8, 2013, and Nov 24, 2014, 658 patients were randomly assigned to receive cabozantinib (n=330) or everolimus (n=328). The median duration of follow-up for overall survival and safety was 18·7 months (IQR 16·1-21·1) in the cabozantinib group and 18·8 months (16·0-21·2) in the everolimus group. Median overall survival was 21·4 months (95% CI 18·7-not estimable) with

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

    PubMed

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

    2017-05-01

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

  10. Survival and cost-effectiveness of sorafenib therapy in advanced hepatocellular carcinoma: An analysis of the SEER-Medicare database.

    PubMed

    Parikh, Neehar D; Marshall, Vincent D; Singal, Amit G; Nathan, Hari; Lok, Anna S; Balkrishnan, Rajesh; Shahinian, Vahakn

    2017-01-01

    Sorafenib is the only chemotherapeutic approved for treatment of advanced hepatocellular carcinoma (HCC). However, its effectiveness in patients with Child-Pugh class B cirrhosis and any moderating effects of health system characteristics are unclear. We examined the survival and cost-effectiveness associated with sorafenib in elderly patients with advanced HCC. We performed an analysis of Medicare beneficiaries with HCC diagnoses from 2007 to 2009. We compared advanced stage patients with HCC (American Joint Committee on Cancer stage III/IV) who received sorafenib within 6 months of diagnosis (and were otherwise untreated) to advanced stage patients with HCC who received no therapy (control). We performed univariate and multivariate analyses to identify predictors of survival. Incremental cost-effectiveness ratios (ICERs) were calculated for sorafenib-treated and control patients. We included 228 sorafenib-treated patients and 870 control patients. The median survival of the sorafenib-treated patients was 150.5 days versus 62 days for control patients. On multivariate analysis, significant predictors of improved survival were treatment with sorafenib (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.57-0.77), being seen at a National Cancer Institute-designated cancer center (HR, 0.77; 95% CI, 0.62-0.97), and being seen at a transplantation center (HR, 0.77; 95% CI, 0.65-0.93). Predictors of worse survival included stage IV disease (HR, 1.40; 95% CI, 1.24-1.58), decompensated cirrhosis (HR, 1.49; 95% CI, 1.30-1.70), and treatment in an urban setting (HR, 1.45; 95% CI, 1.21-1.73.) Although sorafenib use was associated with a survival benefit (HR, 0.61; 95% CI, 0.47-0.79) among patients with decompensated cirrhosis, the median survival benefit was 31 days, and it was not cost-effective (ICER, $224,914 per life year gained). Sorafenib is associated with improved survival in elderly patients with advanced HCC; however, it is not cost-effective among those with

  11. Advances of Salivary Proteomics in Oral Squamous Cell Carcinoma (OSCC) Detection: An Update

    PubMed Central

    Sannam Khan, Rabia; Khurshid, Zohaib; Akhbar, Shazia; Faraz Moin, Syed

    2016-01-01

    Oral cancer refers to malignancies that have higher morbidity and mortality rates due to the late stage diagnosis and no early detection of a reliable diagnostic marker, while oral squamous cell carcinoma (OSCC) is amongst the world’s top ten most common cancers. Diagnosis of cancer requires highly sensitive and specific diagnostic tools which can support untraceable hidden sites of OSCC, yet to be unleashed, for which plenty of biomarkers are identified; the most recommended biomarker detection medium for OSCC includes biological fluids, such as blood and saliva. Saliva holds a promising future in the search for new clinical biomarkers that are easily accessible, less complex, accurate, and cost effective as well as being a non-invasive technique to follow, by analysing the malignant cells’ molecular pathology obtained from saliva through proteomic, genomic and transcriptomic approaches. However, protein biomarkers provide an immense potential for developing novel marker-based assays for oral cancer, hence this current review offers an overall focus on the discovery of a panel of candidates as salivary protein biomarkers, as well as the proteomic tools used for their identification and their significance in early oral cancer detection. PMID:28248250

  12. Advances in computed tomography and magnetic resonance imaging of hepatocellular carcinoma.

    PubMed

    Hennedige, Tiffany; Venkatesh, Sudhakar K

    2016-01-07

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Imaging is important for establishing a diagnosis of HCC and early diagnosis is imperative as several potentially curative treatments are available when HCC is small. Hepatocarcinogenesis occurs in a stepwise manner on a background of chronic liver disease or cirrhosis wherein multiple genes are altered resulting in a range of cirrhosis-associated nodules. This progression is related to increased cellularity, neovascularity and size of the nodule. An understanding of the stepwise progression may aid in early diagnosis. Dynamic and multiphase contrast-enhanced computed tomography and magnetic resonance imaging still form the cornerstone in the diagnosis of HCC. An overview of the current diagnostic standards of HCC in accordance to the more common practicing guidelines and their differences will be reviewed. Ancillary features contribute to diagnostic confidence and has been incorporated into the more recent Liver Imaging Reporting and Data System. The use of hepatocyte-specific contrast agents is increasing and gradually changing the standard of diagnosis of HCC; the most significant benefit being the lack of uptake in the hepatocyte phase in the earlier stages of HCC progression. An outline of supplementary techniques in the imaging of HCC will also be reviewed.

  13. 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

  14. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract.

    PubMed

    Thar, Yu Yu; Patel, Poras; Huang, Tiangui; Guevara, Elizabeth

    2016-01-01

    Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck.

  15. 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

  16. Radiotherapy plus razoxane for advanced limited extent carcinoma of the lung

    SciTech Connect

    Corder, M.P.; Tewfik, H.H.; Clamon, G.H.; Platz, C.E.; Leimert, J.T.; Herbst, K.D.; Byfield, J.E.

    1984-05-01

    Forty-four patients with limited extent American Joint Committee on Cancer Stage II-III non-small cell carcinoma of the lung were randomly assigned to potentially curative radiation therapy plus one of two schedules of razoxane. The weekly schedule was 1 gram per square meter body surface area (BSA) every 8 hours for two doses per week, and the daily schedule was a fixed dose of 250 mg per day. The 50% Kaplan-Meier survival estimate for both groups combined was 9 months. There was no survival difference between the two dose-schedules. Toxicity was formidable with an 82% incidence of esophagitis, and a 20% incidence of grade III-IV esophagitis. Fifty-nine percent of patients developed hematologic toxicity. This was greater with the weekly dose-schedule (P . 0.01). Forty-one percent of patients developed radiographic or symptomatic pneumonitis. One patient developed a fatal myelitis. This program is no more effective than irradiation alone, and has substantial morbidity.

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

    PubMed Central

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

    2016-01-01

    Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α). Strategies of tumor immune evasion include T-cell suppression by negative signals deriving from the interaction between programmed death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells. Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus reversing T-cell suppression and activating antitumor responses. The aim of this review is to summarize the safety and efficacy data of nivolumab in mRCC. Objective responses and safety profile of single-agent nivolumab are favorable in both previously treated and treatment-naïve mRCC patients. Despite toxic effects, combination therapies with nivolumab have shown promising results, indicating a potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to-patient basis represents a major challenge for the future. PMID:27695530

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

    PubMed Central

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

    2010-01-01

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

  19. Multimodality therapy including surgical resection and intraoperative electron radiotherapy for recurrent or advanced primary carcinoma of the urinary bladder or ureter.

    PubMed

    Hallemeier, Christopher L; Karnes, Robert J; Pisansky, Thomas M; Davis, Brian J; Gunderson, Leonard L; Leibovich, Bradley C; Haddock, Michael G; Choo, Richard

    2013-12-01

    To report outcomes of multimodality therapy incorporating surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent or advanced primary urothelial carcinoma. From 1983 to 2009, 17 patients, consisting of 11 with LR recurrence after cystectomy for bladder carcinoma, 4 with LR recurrence after nephroureterectomy for ureteral carcinoma, and 2 with advanced primary bladder carcinoma were treated with multimodality therapy. In 8 patients with LR recurrence, the multimodality treatment was a second salvage attempt. Sixteen patients received perioperative external beam radiotherapy (median dose, 50.4 Gy; range, 21.6 to 60 Gy). Extent of resection was R0 (n=7), R1 (n=1), and R2 (n=9). The median IOERT dose was 12.5 Gy (range, 10 to 20 Gy). Overall survival (OS) and relapse patterns were determined from the date of resection and IOERT using the Kaplan-Meier method. The median follow-up for surviving patients was 3.6 years (range, 1.1 to 10 y). OS at 1, 2, and 5 years was 53%, 31%, and 16%, respectively. Central (within the IOERT field), LR (tumor bed or regional lymph nodes), and distant relapses at 2 years were 15%, 49%, and 67%, respectively. On univariate analysis, resection of all gross disease (R0-1) was associated with improved OS (P=0.03). Mortality within 30 days was 0%. Two patients (12%) experienced NCI-CTCAE grades 4 and 5 late adverse events. In patients with recurrent or advanced urothelial carcinoma, this multimodality approach yielded a low rate of recurrence within the IOERT field with acceptable toxicity. However, LR and distant relapse were common, indicating a need for better patient selection, LR therapy, and systemic therapy.

  20. Surrogate End Points for Overall Survival in Loco-Regionally Advanced Nasopharyngeal Carcinoma: An Individual Patient Data Meta-analysis.

    PubMed

    Rotolo, Federico; Pignon, Jean-Pierre; Bourhis, Jean; Marguet, Sophie; Leclercq, Julie; Tong Ng, Wai; Ma, Jun; Chan, Anthony T C; Huang, Pei-Yu; Zhu, Guopei; Chua, Daniel T T; Chen, Yong; Mai, Hai-Qiang; Kwong, Dora L W; Soong, Yoke Lim; Moon, James; Tung, Yuk; Chi, Kwan-Hwa; Fountzilas, George; Zhang, Li; Hui, Edwin Pun; Lee, Anne W M; Blanchard, Pierre; Michiels, Stefan

    2017-04-01

    Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs). Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R(2) between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS. PFS was strongly correlated with OS at the individual level (ρ = 0.93, 95% confidence interval [CI] = 0.93 to 0.94) and at the trial level (R(2) = 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (ρ = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R(2) = 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (ρ = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R(2) = 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (ρ = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R(2) = 0.78, 95% CI = 0.33 to 1.00). PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. 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.

  2. 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

  3. 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.

  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. Two Concurrent Large Epidermoid Cysts in Sublingual and Submental Region Resembling Plunging Ranula: Report of a Rare Case

    PubMed Central

    Sahoo, Ranjan Kumar; Sahoo, Pradyumna Kumar; Mohapatra, Debahuti; Subudhi, Santosh

    2017-01-01

    An elderly female patient presented to surgical outpatient clinic with complaint of gradual onset of painless submental and sublingual midline swellings for 6 months of duration. The swellings were noncompressible, nontranslucent, nonpulsatile, and nontender on palpation. Clinical diagnosis was plunging ranula or dermoid cysts. Ultrasound examination of sublingual swelling showed cystic lesion with particulate content. Submental swelling showed cystic swelling with few echogenic floating lobules inside suggesting possibility of epidermoid/dermoid cyst. Magnetic resonance imaging of the face showed homogeneous fluid content within the sublingual cystic lesion and heterogeneous fluid content with few floating nodules within submental swelling. Both cystic lesions were noncommunicative and were showing diffusion restriction and no fat signal. Radiological diagnosis was sublingual and submental epidermoid cysts. She was operated under general anesthesia, and two separate cystic masses were excised with intact capsule. Histopathological diagnosis of masses confirms epidermoid cyst. Several literature have reported isolated sublingual or submandibular epidermoid cyst. However, concurrent sublingual and submental epidermoid cysts with different imaging appearance are rarely reported. PMID:28713758

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

    PubMed

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

    2017-01-01

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

  7. NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma

    ClinicalTrials.gov

    2017-10-12

    Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Carcinoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer

  8. Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma.

    PubMed

    Brose, Marcia S; Smit, Johannes; Capdevila, Jaume; Elisei, Rossella; Nutting, Christopher; Pitoia, Fabian; Robinson, Bruce; Schlumberger, Martin; Shong, Young Kee; Takami, Hiroshi

    2012-09-01

    For patients with advanced, radioactive iodine-refractory differentiated thyroid cancer, current treatment guidelines recommend clinical trial enrollment or small-molecule kinase inhibitor therapy. However, details of patient management vary between countries depending on trial availability and national regulatory policies. Insufficient clinical trial data and variable disease characteristics challenge the creation of universal guidelines, and treatment plans often reflect regional influences. A multidisciplinary, multiregional panel of experts met to discuss regional approaches to managing patients with advanced, radioactive iodine-refractory differentiated thyroid cancer and the potential impact of emerging therapies on current treatment strategies. Despite process-oriented regional differences, the decision-making strategies were similar. Multidisciplinary teams used to manage high-risk patients varied in composition across regions, particularly regarding the responsible physician's specialty. Cytotoxic chemotherapy was viewed as limited in clinical benefit, and targeted agents as attractive, based on promising data. Panel members support clinical trial enrollment as the preferred treatment strategy for managing these patients.

  9. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    SciTech Connect

    Du, Zhongli; Zhang, Wencheng; Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen; Xiao, Zefen; Tan, Wen; and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  10. 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

  11. The Treatment Responses in Cases of Radiation Therapy to Portal Vein Thrombosis in Advanced Hepatocellular Carcinoma

    SciTech Connect

    Huang, Y.-J.; Hsu, H.-C.; Wang, C.-Y.; Wang, C.-J.; Chen, H.-C.; Huang, E.-Y.; Fang, F.-M.; Lu, S.-N.

    2009-03-15

    Purpose: To review the response to radiation therapy for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) and determine the factors favoring its efficacy. Methods and Materials: Patients with HCC and PVT referred for radiation therapy between 1997 and 2005 were retrospectively reviewed. Patients who had undergone treatment to primary HCC before radiation or had extrahepatic metastasis were excluded. A radiation dose of 60 Gy with 2 to 3Gy per fraction was prescribed. Clinical features before therapy were investigated, and the most significant imaging change after radiotherapy was regarded as the treatment response. Survival times were compared and the hazard ratios of independent variables were determined. Results: The treatment response rate of the 326 patients included in the study was 25.2% (n = 82). The median survival times were 13.3, 11.6, 9.0, 4.5, and 2.1 months for complete response, partial response, vascular transformation, no response, a