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PubMed | University of Gezira, Gezira Center for endoscopy & laparoscopic surgery and National cancer Institute NCI
Type: | Journal: The Pan African medical journal | Year: 2014

The pharyngeal pouch (Zenkers diverticulum) is a diverticulum of the mucosa of the pharynx, just above the cricopharyngeal muscle (i.e. above the upper sphincter of the oesophagus). It occurs commonly in elderly patients (over 70 year) and the typical symptoms include dysphagia, regurgitation, chronic cough, aspiration and weight loss. We are reporting a case of an oropharyngeal dysphagia due to a Zenkers diverticulum in 75 years old Sudanese man with a chronic history of dysphagia for solids. The pathophysiology of Zenkers diverticulum, clinical presentation, and management are reviewed.


PubMed | National Center for Advancing Translational science, U.S. National Institute on Aging, National Center for Advancing Translational Science, National Cancer Institute NCI and 9 more.
Type: | Journal: Journal of extracellular vesicles | Year: 2015

The Extracellular RNA (exRNA) Communication Consortium, funded as an initiative of the NIH Common Fund, represents a consortium of investigators assembled to address the critical issues in the exRNA research arena. The overarching goal is to generate a multi-component community resource for sharing fundamental scientific discoveries, protocols, and innovative tools and technologies. The key initiatives include (a) generating a reference catalogue of exRNAs present in body fluids of normal healthy individuals that would facilitate disease diagnosis and therapies, (b) defining the fundamental principles of exRNA biogenesis, distribution, uptake, and function, as well as development of molecular tools, technologies, and imaging modalities to enable these studies,


Basel, November 14, 2016 - Novartis today announced that the US Food and Drug Administration (FDA) granted Priority Review to the PKC412 (midostaurin) new drug application (NDA) for the treatment of acute myeloid leukemia (AML) in newly-diagnosed adults with an FMS-like tyrosine kinase-3 (FLT3) mutation, as well as for the treatment of advanced systemic mastocytosis (SM). The premarket approval application (PMA) for the PKC412 (midostaurin) FLT3 companion diagnostic, developed in collaboration with Invivoscribe Technologies, Inc. (IVS)* has also been accepted for review by the FDA. Outside the US, the marketing authorization application for PKC412 (midostaurin) in these indications has already been accepted by the European Medicines Agency (EMA). "FLT3-mutated AML and advanced SM are devastating and rare diseases, with significant unmet needs due to limited existing treatment options," said Bruno Strigini, CEO, Novartis Oncology. "This regulatory designation signifies the importance of midostaurin as a potential therapy for these patients who haven't had the benefit of targeted medicines." The NDA submission for PKC412 (midostaurin) includes data from the largest clinical trials conducted to date in each indication. In the Phase III RATIFY trial (CALGB 10603), which investigated PKC412 (midostaurin) plus standard chemotherapy versus placebo plus standard chemotherapy in adult patients less than 60 years of age with FLT3-mutated AML, those in the PKC412 (midostaurin) arm experienced a statistically significant improvement in overall survival (OS) with a 23% reduction in risk of death compared to the placebo arm (hazard ratio [HR] = 0.77, P = 0.0074)[1]. Based on these data, PKC412 (midostaurin) was also granted Breakthrough Therapy designation by the FDA earlier this year for newly-diagnosed FLT3-mutated AML. In the RATIFY trial, no statistically significant differences were observed in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events (AEs) in the PKC412 (midostaurin) treatment group versus the placebo group[5]. The most frequent all grade AEs were febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae (small red skin spots) and pyrexia[5]. A total of 36 deaths occurring within 30 days of the last dose of study drug were reported, with no difference in treatment-related deaths observed between groups[5]. Data from the Phase II single-arm study (CPKC412D2201) evaluating the efficacy of PKC412 (midostaurin) in patients with advanced SM were also published in the New England Journal of Medicine in June 2016. The study showed that treatment with PKC412 (midostaurin) resulted in an overall response rate of 60% (defined as complete or partial resolution of organ damage) with a median duration of response of 24.1 months (95% CI, 10.8-not estimated [NE]) and a median OS of 28.7 months (95% CI, 18.1-NE)[2]. The most frequent AEs were low-grade nausea, vomiting and diarrhea. New or worsening grade 3 or 4 neutropenia, anemia and thrombocytopenia occurred mostly in patients with pre-existing cytopenias[2]. A Priority Review designation is granted by the FDA to therapies that may provide significant improvements in the treatment, diagnosis or prevention of serious conditions[3]. According to the FDA, the goal is to take action on a Priority Review application within six months, compared to 10 months under the standard review process[3]. Novartis has been granted a growing number of Priority Review designations by the FDA, underscoring the company's ongoing commitment to developing innovative therapies for rare diseases or underserved cancer patients. Since PKC412 (midostaurin) remains investigational at this time, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and in the US, an Expanded Treatment Protocol, to enable access to eligible patients with newly-diagnosed AML and advanced SM. Physicians who wish to request PKC412 (midostaurin) for eligible patients should contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information. About AML and the FLT3 mutation AML is a rare and aggressive cancer of the blood and bone marrow[6]. It is the most common acute leukemia in adults[7]. Of the approximately 350,000 people with leukemias worldwide[8], about 25% have AML[7]. AML has a low survival rate, with around 25% of patients surviving at 5 years[9]. AML is associated with the accumulation of blood cells that are unable to mature properly, causing a buildup of immature "blast" cells that do not allow room for normal blood cell development[6]. Mutations in specific genes are found in many cases of AML, and molecular testing is recommended for newly-diagnosed patients to help determine prognosis and best possible treatment[4]. FLT3 is a receptor tyrosine kinase, a type of cell-surface receptor, which plays a role in the proliferation, or increase, in the number of certain blood cells. The FLT3 gene mutation is one of the most common in AML, occurring in about one-third of patients, and commonly results in faster disease progression, a higher relapse rate and shorter survival[10]-[12]. About the FLT3 companion diagnostic In order to help identify patients who may have a FLT3 mutation and potentially benefit from treatment with PKC412 (midostaurin), Novartis is collaborating with IVS for the development and FDA approval of the FLT3 companion diagnostic. The same test is being CE marked in Europe. Regulatory submissions for the companion diagnostic are being led by IVS. About advanced SM Systemic mastocytosis (SM) comprises a group of rare diseases, affecting between 1 in 20,000 to 40,000 people worldwide[13]. The disease is characterized by uncontrolled growth and accumulation of mast cells - or mediators of allergic responses - in one or more organs[14]. In advanced SM, mast cells accumulate in such high quantities that they begin to cause organ damage[15]. Patients also suffer from debilitating systemic symptoms such as pruritus (severe itching of the skin), among other symptoms, caused by mast cells releasing inflammatory mediators such as histamine into the blood[15]. Median OS is currently between 3.5 years to less than six months depending on subtype[14]. The uncontrolled proliferation of mast cells is caused in many people by a KIT gene mutation - the most common mutation, encoding the D816V substitution, occurs in approximately 90% of patients[16]. The KIT gene mutation results in activation of the KIT enzyme, which triggers the abnormal proliferation and survival of mast cells[15]. About PKC412 (midostaurin) PKC412 (midostaurin) is an investigational, oral, multi-targeted kinase inhibitor in development for the treatment of patients with AML with a FLT3 mutation and for patients with advanced SM. The safety and efficacy profile has not been fully established, and it is not approved for any indication in any market at this time. There is no guarantee that PKC412 (midostaurin) will become commercially available. Disclaimer The foregoing release contains forward-looking statements that can be identified by words such as "Priority Review," "will," "expected," "may," "potential," "Breakthrough Therapy designation," "goal," "growing," "commitment," "investigational," "potentially," "currently," "in development," "at this time," or similar terms, or by express or implied discussions regarding potential marketing approvals for PKC412, or regarding potential future revenues from PKC412. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that PKC412 will be submitted or approved for sale in any market, or at any particular time. Nor can there be any guarantee that PKC412 will be commercially successful in the future. In particular, management's expectations regarding PKC412 could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2015, the Group achieved net sales of USD 49.4 billion, while R&D throughout the Group amounted to approximately USD 8.9 billion (USD 8.7 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are available in approximately 180 countries around the world. For more information, please visit http://www.novartis.com. Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis and @NovartisCancer at http://twitter.com/novartiscancer  For Novartis multimedia content, please visit www.novartis.com/news/media-library For questions about the site or required registration, please contact media.relations@novartis.com * FLT3 detection is conducted by the Laboratory of Personalized Molecular Medicine pursuant to patents licensed by Invivoscribe technologies, Inc. from Takara Bio of Otsu, Japan. References [1] Stone RM, et al. The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]). Presented at the 57th Annual Meeting of the American Society of Hematology. [2] Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016;374(26):2530-2541. [3] US Food and Drug Administration (FDA). Priority Review. http://www.fda.gov/forpatients/approvals/fast/ucm405405.htm. Accessed November 1, 2016. [4] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Version 1.2016 Acute Myeloid Leukemia. http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed November1, 2016. [5] Novartis data on file. [6] National Institute of Health (NIH) National Cancer Institute NCI. Adult Acute Myeloid Leukemia Treatment (PDQ®) http://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq. Accessed November 1, 2016. [7] Deschler B, Lübbert M. Acute myeloid leukemia: epidemiology and etiology. Cancer. 2006;107(9):2009-2107. [8] Union for International Cancer Control. 2014. Acute Myelogenous Leukemia and Acute Promyelocytic Leukemia. http://www.who.int/selection_medicines/committees/expert/20/applications/AML_APL.pdf?ua=1ble. Accessed November 1, 2016. [9] NIH National Cancer Institute (NCI). SEER Stat Fact Sheets: Acute Myeloid Leukemia (AML). http://seer.cancer.gov/statfacts/html/amyl.html Accessed November 1, 2016. [10] Yanada M, Matsuo K, Suzuki T, et al. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia. 2005;19(8):1345-1349. [11] Patel JP, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012; 22;366(12):1079-89. [12] Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology Am Soc Hematol Educ Program. 2013;2013:220-6. [13] Orpha.net. Systemic Mastocytosis. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=2467.  Accessed November 1, 2016. [14] Lim KH, Tefferi A, Lasho T, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113:5727-5736. [15] Verstovsek S. Advanced systemic mastocytosis: the impact of KIT mutations in diagnosis, treatment, and progression. Eur J Haematology. 2013;90(2):89-98. [16] Garcia-Montero AC, Jara-Acevedo M, Teodosi C, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108(7):2366-2372.


Nassar M.Y.,Benha University | El-Shahat M.F.,Ain Shams University | Khalile S.M.,National Organization for Drug Control and Research NODCAR | El-Desawy M.,Nuclear Research Center - Negev | Mohamed E.A.,National Cancer Institute NCI
Journal of Thermal Analysis and Calorimetry | Year: 2014

Mesalazine (MZ) drug has been used for several decades as a primary treatment for inflammatory bowel diseases. The drug was investigated using thermal analysis (TA) measurements and electron impact mass spectral fragmentation at 70 and 15 eV of electron energy. The optimum molecular geometry and the total energy of the neutral and the positively charged MZ molecules were calculated by density functional theory method with 6-311++G(d,p) basis sets. Stability of the molecules arising from hyperconjugative interactions, charge delocalization, and the natural atomic charges has been analyzed using natural bond orbital analysis. In electron ionization mass spectrometry, the primary rupture is due to successive loss of H2O (OH from carboxyl and H from phenolic OH of the ring) and CO of the acetyl group. Thermogravimetric results have revealed two stages of mass loss at 75.3 and 25.3 % in ranges 225-350 and 350-650°C, respectively. The first one may be due to successive losses of different groups or molecules with fast rate of decomposition. A comparison between MS and TA helped in selection the proper pathway representing the fragmentation mechanism of this drug. © 2014 Akadémiai Kiadó, Budapest, Hungary.


Okasha H.H.,Cairo University | Naga M.I.,Cairo University | Esmat S.,Cairo University | Naguib M.,Cairo University | And 7 more authors.
Endoscopic Ultrasound | Year: 2013

Objective: Pancreatic carcinoma is one of the leading cancer morbidity and mortality world-wide. Controversy has arisen about whether the percutaneous approach with computed tomography/ultrasonography-guidance fine needle aspiration (US-FNA) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the preferred method to obtain diagnostic tissue. Our purpose of this study is to compare between the diagnostic accuracy of EUS-FNA and percutaneous US-FNA in diagnosis of pancreatic cancer. Patients and Methods: A total of 197 patients with pancreatic masses were included in the study, 125 patients underwent US-FNA (Group 1) and 72 patients underwent EUS-FNA (Group 2). Results: EUS-FNA has nearly the same accuracy (88.9%) as US-FNA (87.2%) in diagnosis of pancreatic cancer. The sensitivity, specificity, positive predictive value and negative predictive value for EUS-FNA was 84%, 100%, 100%, 73.3% respectively. It was 85.5%, 90.4%, 94.7%, 76% respectively for US-FNA. EUS-FNA had a lower complication rate (1.38%) than US-FNA (5.6%). Conclusion: EUS-FNA has nearly the same accuracy as US-FNA of pancreatic masses with a lower complication rate.


PubMed | National Cancer Institute NCI, Assiut University, Institute of Tropical Medicine and Cairo University
Type: Journal Article | Journal: Endoscopic ultrasound | Year: 2014

Pancreatic carcinoma is one of the leading cancer morbidity and mortality world-wide. Controversy has arisen about whether the percutaneous approach with computed tomography/ultrasonography-guidance fine needle aspiration (US-FNA) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the preferred method to obtain diagnostic tissue. Our purpose of this study is to compare between the diagnostic accuracy of EUS-FNA and percutaneous US-FNA in diagnosis of pancreatic cancer.A total of 197 patients with pancreatic masses were included in the study, 125 patients underwent US-FNA (Group 1) and 72 patients underwent EUS-FNA (Group 2).EUS-FNA has nearly the same accuracy (88.9%) as US-FNA (87.2%) in diagnosis of pancreatic cancer. The sensitivity, specificity, positive predictive value and negative predictive value for EUS-FNA was 84%, 100%, 100%, 73.3% respectively. It was 85.5%, 90.4%, 94.7%, 76% respectively for US-FNA. EUS-FNA had a lower complication rate (1.38%) than US-FNA (5.6%).EUS-FNA has nearly the same accuracy as US-FNA of pancreatic masses with a lower complication rate.


Abdel-Gawad W.,National Cancer Institute NCI | Zaghloul A.,National Cancer Institute NCI | Fakhr I.,National Cancer Institute NCI | Sakr M.,National Cancer Institute NCI | And 3 more authors.
Journal of the Egyptian National Cancer Institute | Year: 2014

Introduction: Abdomino-perineal resection has been the standard treatment for rectal tumors located ≤5. cm from the anal verge. Recently, intersphincteric resection became a valid option which preserves the bowel continuity with better functional outcome. Aim: Is to evaluate the oncological and functional outcome alongside the associated surgical morbidity in patients with T1-3 rectal cancer, who underwent intersphincteric resection (ISR). Patients & methods: Between the years 2006 and 2011, 55 patients with invasive rectal adenocarcinoma, T1-3 lesions, located 2-5. cm from the anal verge underwent ISR with total mesorectal excision. When inevitable, complete. ISR was performed, otherwise partial ISR was done. All T3 patients underwent total meso-rectal excision (TME) while some had lateral lymph node dissection (LND) with concomitant pelvic autonomic nerve preservation (PANP). Results: Among the 55 patients, 21 (38.1%) patients were T1-2 and 34 (61.9%) patients were T3. The tumor location range was 0-5. cm from the anal verge (median 2.3. cm). Partial or complete ISR was done for 35 (63.6%) and 20 (36.4%), respectively. Patients were followed for a median of 1.5. years (range 1-4.6. years). The 3. year local recurrence and distant metastasis free rates were 85.2% and 85.6%, respectively. All the 3 local recurrences occurred in T3 patients group, and had positive circumferential resection margins. Overall 3-year disease-free survival was 82.6%; while the overall 3-year survival was 88.7%. Conclusion: Intersphincteric resection with TME does not affect the local recurrence or overall survival rate in early rectal cancer T1-2 & 3, with preservation of bowel continuity and better life quality. © 2014.


Sakkary M.A.,National Cancer Institute NCI
World Journal of Surgical Oncology | Year: 2012

Background: Prolonged and excessive drainage of serous fluid and seroma formation constitute the most common complications after mastectomy for breast carcinoma. Seroma formation delays wound healing, increases susceptibility to infection, skin flap necrosis, persistent pain and prolongs convalescence. For this, several techniques have been investigated to improve primary healing and minimize seroma formation.Materials and methods: Between June 2009 and July 2010 forty patients with breast carcinoma, scheduled for modified radical mastectomy, were randomly divided into 2 groups, the study group (20) and the control group (20). In the study group; the mastectomy flaps were fixed to the underlying muscles in raws, at various parts of the flap and at the wound edge using fine absorbable sutures. In the control group; the wound was closed in the conventional method at the edges. Closed suction drains were used in both groups. Patients, tumor characteristics and operative related factors were recorded. The amount and color of drained fluid were recorded daily. The drains were removed when the amount become less than 50 cc. The total amount and duration of drained fluid and the formation of seroma were recorded and the results were compared between the two groups.Results: In the flap fixation group, the drain was removed in significantly shorter time compared to the control group (p < 0.001). Also, the total amount of fluid drained was significantly lower in the flap fixation group (p < 0.001). The flap fixation group showed a significantly lower frequency of seroma formation compared to the control group, both clinically (p = 0.028) and ultrasonographically (p = 0.047).Conclusions: The mastectomy flap fixation technique is a valuable procedure that significantly decreases the incidence of seroma formation, and reduces the duration and amount of drained fluid. However, it should be tried on a much wider scale to prove its validity. © 2012 Sakkary; licensee BioMed Central Ltd.


Amin A.A.,National Cancer Institute NCI | Sakkary M.A.,National Cancer Institute NCI | Khalil A.A.,Cairo University | Rifaat M.A.,National Cancer Institute NCI | Zayed S.B.,National Cancer Institute NCI
Head and Neck Oncology | Year: 2011

Background and purpose. The submental flap is gaining popularity as a simple technique for reconstruction of small to moderate size defects of the oral cavity. However, its role in composite defects involving the jaw is not clearly defined. Indeed, controversy exists about the flap's interference with an oncologically sound neck dissection. Patients and Methods. A total of 21 patients with oral cavity cancers over a three year period were included. All patients underwent surgical resection and immediate reconstruction with submental flap except one patient who had delayed reconstruction with reversed flap. The flap was used for reconstruction of intra-oral soft tissue defect in 13 patients and composite defects in 8 patients. Results: Of 21 patients 12 were males and 9 were females, age ranged from 32 to 83 years. The primary tumor sites included buccal mucosa (7), tongue (4), alveolar margin (3), floor of mouth (5) and lip (2). Eventually in this study, we adopted completing the neck dissection first before flap harvest. Complete flap loss occurred in 2 whereas 3 patients had partial flap loss. Follow up ranged from 3 to 44 months, one patient died from metastatic disease. Four patients developed neck recurrences. Conclusion: The submental flap is a valid option for reconstruction of intra-oral soft tissue as well as composite oral defects particularly in elderly patients. However, oncologically sound neck dissection should be assured. © 2011 Amin et al; licensee BioMed Central Ltd.


PubMed | National Cancer Institute NCI
Type: Clinical Trial | Journal: American journal of hematology | Year: 2015

There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity, or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (P<0.0001), IgG (P<0.0001), and IgA (P=0.001), elevated uric acid (P=0.008) and total protein (P=0.0004), and higher numbers of CD3+ (P=0.002), CD4+ (P=0.001), CD8+ (P=0.023) T cells, and CD19+ B cells (P<0.0001). Multiple antibodies were detected in 35% of patients. Prior rituximab therapy (n=66) was associated with reduced presence of autoantibodies (48 vs. 66% P=0.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (P=0.028). No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD.

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