Beri M. Ridgeway, MD

• Staff, Center of Urogynecology and Reconstructive Surgery, Department of
• Obstetrics and Gynecology, Obstetrics, Gynecology, and Women? Health
• Institute, Cleveland Clinic, Cleveland, Ohio

In contrast menstrual cycle day 1-4 buy duphaston australia, once the decision is made to treat with sipuleucel-T 6272 menopause generic 10mg duphaston mastercard, a multi-step process is used to produce sipuleucel-T zithromax menstrual cycle 10mg duphaston with amex. Sipuleucel-This made individually for each patient with his own white blood cells menstruation 10 days order duphaston once a day. General Stem cell transplantation is a process in which stem cells are harvested from either a patients (autologous) or donors (allogeneic) bone marrow or peripheral blood for intravenous infusion womens health center 90042 cheap duphaston online. Hematopoietic stem cells are multi-potent stem cells that give rise to all the blood cell types; these stem cells form blood and immune cells menopause increased libido cheap duphaston 10 mg on-line. A hematopoietic stem cell is a cell isolated from blood or bone marrow that can renew itself, differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosis a process by which cells that are unneeded or detrimental will self-destruct. When bone marrow or peripheral blood stem cell transplantation is covered, all necessary steps are included in coverage. When bone marrow or peripheral blood stem cell transplantation is non-covered, none of the steps are covered. These disorders are varied with regard to clinical characteristics, cytologic and pathologic features, and cytogenetics. In addition, the clinical study must adhere to the following standards of scientific integrity and relevance to the Medicare population: a. The principal purpose of the research study is to test whether a particular intervention potentially improves the participants health outcomes. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However a full report of the outcomes must be made public no later than 3 years after the end of data collection. The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria effect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility. The principal purpose of the study is to test whether the item or service meaningfully improves health outcomes of affected beneficiaries who are represented by the enrolled subjects. The study results are not anticipated to unjustifiably duplicate existing knowledge. The research study protocol specifies the method and timing of public release of all prespecified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must include number started/completed, summary results for primary and secondary outcome measures, statistical analyses, and adverse events. Final results must be reported in a publicly accessibly manner; either in a peer-reviewed scientific journal (in print or on-line), in an on-line publicly accessible registry dedicated to the dissemination of clinical trial information such as ClinicalTrials. Other All other indications for stem cell transplantation not otherwise noted above as covered or non-covered remain at local Medicare Administrative Contractor discretion. Inpatient Hospital Stay for Alcohol Detoxification Many hospitals provide detoxification services during the more acute stages of alcoholism or alcohol withdrawal. Generally, detoxification can be accomplished within two to three days with an occasional need for up to five days where the patients condition dictates. This limit (five days) may be extended in an individual case where there is a need for a longer period for detoxification for a particular patient. In such cases, however, there should be documentation by a physician which substantiates that a longer period of detoxification was reasonable and necessary. Following detoxification a patient may be transferred to an inpatient rehabilitation unit or discharged to a residential treatment program or outpatient treatment setting. Inpatient Hospital Stay for Alcohol Rehabilitation Hospitals may also provide structured inpatient alcohol rehabilitation programs to the chronic alcoholic. These programs are composed primarily of coordinated educational and psychotherapeutic services provided on a group basis. Depending on the subject matter, a series of lectures, discussions, films, and group therapy sessions are led by either physicians, psychologists, or alcoholism counselors from the hospital or various outside organizations. Patients may directly enter an inpatient hospital rehabilitation program after having undergone detoxification in the same hospital or in another hospital or may enter an inpatient hospital rehabilitation program without prior hospitalization for detoxification. Alcohol rehabilitation can be provided in a variety of settings other than the hospital setting. In order for an inpatient hospital stay for alcohol rehabilitation to be covered under Medicare it must be medically necessary for the care to be provided in the inpatient hospital setting rather than in a less costly facility or on an outpatient basis. Inpatient hospital care for receipt of an alcohol rehabilitation program would generally be medically necessary where either (l) there is documentation by the physician that recent alcohol rehabilitation services in a less intensive setting or on an outpatient basis have proven unsuccessful and, as a consequence, the patient requires the supervision and intensity of services which can only be found in the controlled environment of the hospital, or (2) only the hospital environment can assure the medical management or control of the patients concomitant conditions during the course of alcohol rehabilitation. Since alcoholism is classifiable as a psychiatric condition the "active treatment" criteria must also be met in order for alcohol rehabilitation services to be covered under Medicare. An inpatient hospital stay for alcohol rehabilitation may be extended beyond this limit in an individual case where a longer period of alcohol rehabilitation is medically necessary. In such cases, however, there should be documentation by a physician which substantiates the need for such care. Subsequent admissions to the inpatient hospital setting for alcohol rehabilitation follow-up, reinforcement, or "recap" treatments are considered to be readmissions (rather than an extension of the original stay) and must meet the requirements of this section for coverage under Medicare. Prior admissions to the inpatient hospital setting either in the same hospital or in a different hospital may be an indication that the "active treatment" requirements are not met. Accordingly, there should be documentation to establish that "readmission" to the hospital setting for alcohol rehabilitation services can reasonably be expected to result in improvement of the patients condition. For example, the documentation should indicate what changes in the patients medical condition, social or emotional status, or treatment plan make improvement likely, or why the patients initial hospital treatment was not sufficient. Not all patients who require the inpatient hospital setting for detoxification also need the inpatient hospital setting for rehabilitation. These services may include, for example, drug therapy, psychotherapy, and patient education and may be furnished by physicians, psychologists, nurses, and alcoholism counselors to individuals who have been discharged from an inpatient hospital stay for treatment of alcoholism and require continued treatment or to individuals from the community who require treatment but do not require the inpatient hospital setting. Thus, educational services and family counseling would only be covered where they are directly related to treatment of the patients condition. Chemical aversion therapy facilitates alcohol abstinence through the development of conditioned aversions to the taste, smell, and sight of alcohol beverages. While a number of drugs have been employed in chemical aversion therapy, the three most commonly used are emetine, apomorphine, and lithium. None of the drugs being used, however, have yet been approved by the Food and Drug Administration specifically for use in chemical aversion therapy for alcoholism. Accordingly, when these drugs are being employed in conjunction with this therapy, patients undergoing this treatment need to be kept under medical observation. Available evidence indicates that chemical aversion therapy may be an effective component of certain alcoholism treatment programs, particularly as part of multi-modality treatment programs which include other behavioral techniques and therapies, such as psychotherapy. Based on this evidence, the Centers for Medicare & Medicaid Services medical consultants have recommended that chemical aversion therapy be covered under Medicare. However, since chemical aversion therapy is a demanding therapy which may not be appropriate for all Medicare beneficiaries needing treatment for alcoholism, a physician should certify to the appropriateness of chemical aversion therapy in the individual case. Therefore, if chemical aversion therapy for treatment of alcoholism is determined to be reasonable and necessary for an individual patient, it is covered under Medicare. When it is medically necessary for a patient to receive chemical aversion therapy as a hospital inpatient, coverage for care in that setting is available. Thus, where a patient is admitted as an inpatient for receipt of chemical aversion therapy, there must be documentation by the physician of the need in the individual case for the inpatient hospital admission. Electrical aversion therapy is a behavior modification technique to foster abstinence from ingestion of alcoholic beverages by developing in a patient conditioned aversions to their taste, smell and sight through electric stimulation. Electrical aversion therapy has not been shown to be safe and effective and therefore is excluded from coverage. The coverage available for these services is subject to the same rules generally applicable to the coverage of clinic services. Of course, the services also must be reasonable and necessary for the diagnosis or treatment of the individuals alcoholism or drug abuse. However, the intensity and duration of treatment for drug abuse may vary (depending on the particular substance(s) of abuse, duration of use, and the patients medical and emotional condition) from the duration of treatment or intensity needed to treat alcoholism. Accordingly, when it is medically necessary for a patient to receive detoxification and/or rehabilitation for drug substance abuse as a hospital inpatient, coverage for care in that setting is available. Coverage is also available for treatment services that are provided in the outpatient department of a hospital to patients who, for example, have been discharged from an inpatient stay for the treatment of drug substance abuse or who require treatment but do not require the availability and intensity of services found only in the inpatient hospital setting. The coverage available for these services is subject to the same rules generally applicable to the coverage of outpatient hospital services. Drugs that the physician provides in connection with this treatment are also covered if they cannot be self administered and meet all other statutory requirements. In the case where a woman suffers from a physical disorder, physical injury, or physical illness, including a life-endangering physical condition caused by or arising from the pregnancy itself, that would, as certified by a physician, place the woman in danger of death unless an abortion is performed. While extirpation of the disease remains of primary importance, the quality of life following initial treatment is increasingly recognized as of great concern. Reconstruction of the affected and the contralateral unaffected breast following a medically necessary mastectomy is considered a relatively safe and effective noncosmetic procedure. Accordingly, program payment may be made for breast reconstruction surgery following removal of a breast for any medical reason. The condition giving rise to the patients preoperative appearance is generally not a consideration. The only exception to the exclusion is surgery for the prompt repair of an accidental injury or for the improvement of a malformed body member which coincidentally serves some cosmetic purpose. Procedures performed with lasers are sometimes used in place of more conventional techniques. The determination of coverage for a procedure performed using a laser is made on the basis that the use of lasers to alter, revise, or destroy tissue is a surgical procedure. Therefore, coverage of laser procedures is restricted to practitioners with training in the surgical management of the disease or condition being treated. Among surgical events on the list is "Wrong surgical procedure performed on a patient. A surgical or other invasive procedure is considered to be the wrong procedure if it is not consistent with the correctly documented informed consent for that patient. Emergent situations that occur in the course of surgery and/or whose exigency precludes obtaining informed consent are not considered erroneous under this decision. Also, the event is not intended to capture changes in the plan upon surgical entry into the 1. Invasive procedures include a range of procedures from minimally invasive dermatological procedures (biopsy, excision, and deep cryotherapy for malignant lesions) to extensive multi-organ transplantation. A surgical or other invasive procedure is considered to have been performed on the wrong body part if it is not consistent with the correctly documented informed consent for that patient including surgery on the right body part, but on the wrong location of the body; for example, left versus right (appendages and/or organs), or at the wrong level (spine). Emergent situations that occur in the course of surgery and/or whose exigency 2. Also, the event is not intended to capture changes in the plan upon surgical entry into the patient due to the discovery of pathology in close proximity to the intended site when the risk of a second surgery outweighs the benefit of patient consultation; or the discovery of an unusual physical configuration. Surgical and other invasive procedures are defined as operative procedures in which skin or mucous membranes and connective tissue are incised or an instrument is introduced through a natural body orifice. They do not include use of instruments such as otoscopes for examinations or very minor procedures such as drawing blood. Among surgical events on the list is "Surgical procedure performed on the wrong patient. A surgical or other invasive procedure is considered to have been performed on the wrong patient if that procedure is not consistent with the correctly documented informed consent for that patient. They include minimally invasive procedures involving biopsies or placement of probes or catheters requiring the entry into a body cavity through a needle or trocar. General Gender reassignment surgery is a general term to describe a surgery or surgeries that affirm a persons gender identity. Manipulation of the Rib Cage Manual manipulation of the rib cage contributes to the treatment of respiratory conditions such as bronchitis, emphysema, and asthma as part of a regimen that includes other elements of therapy, and is covered only under such circumstances. Manipulation of the Head Manipulation of the occipitocervical or temporomandibular regions of the head when indicated for conditions affecting those portions of the head and neck is a covered service. General Electrical stimulation to augment bone repair can be attained either invasively or non-invasively. Invasive devices provide electrical stimulation directly at the fracture site either through percutaneously placed cathodes or by implantation of a coiled cathode wire into the fracture site.

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Sets are stored at room temperature B6778-6 1235-305 Tri-level serum control 1/ea and have a long shelf life Set 1430-050 provides results in 3 minutes with urine; set 1440-050 gives results in 3 minutes with urine and 5 minutes with serum Suitable for 50 tests Cat. For more information or to order, contact your Cardinal Health sales representative or call 800. Alberto Gimeno, Ingeniero Industrial Quimico, trabajo como Director Tecnico (en varias Empresas de Espana y Portugal) especialista en el control de calidad de materias primas y alimentos compuestos para animales con especial incidencia en el area de las micotoxinas y en las pruebas de campo sobre el efecto toxicologico de las mismas y relacionado con la nutricion animal. Durante 5 anos fue Asesor Tecnico de la Comision para Normalizacion de Metodos de Analisis del Ministerio de Agricultura Espanol en Madrid. Durante 14 anos colaboro con International Agency for Research on Cancer (World Health Organization) en Mycotoxin Check Sample Survey. Realizo un total de 146 conferencias sobre micotoxinas,entre los paises de Espana, Portugal, Egipto, Tailandia, Malasia, Indonesia, Austria, Brasil, Chile, Peru, Italia, Republica Checa, Cuba, Mexico, Ecuador, Costa Rica, Guatemala, Republica Dominicana y Estados Unidos de America. Realizo un total de 15 cursos sobre el control de calidad de alimentos para animales y micotoxicologia alimentar y 11 conferencias sobre nutricion animal, entre los paises de Espana y Portugal. Publico 73 articulos sobre el control analitico de micotoxinas y micotoxicologia alimentar en varias revistas cientifcas, tecnicas, libros de Simposio, libros y paginas web, tales como: J. Publico un manual en portugues con el titulo "Micotoxicoses en Avicultura Controlo e Prevencao". Publico en espanol y en ingles un manual titulado "Micotoxinas y Micotoxicosis en Animales y Humanos" (1 Edicion) y "Mycotoxins and Mycotoxicosis in Animals and Humans". Consultor Tecnico de varias empresas en el area de micotoxinas y micotoxicologia alimentaria. Especializada en el control de calidad de hongos y micotoxinas en la alimentacion animal y humana. Trabajo 30 anos en el Laboratorio Nacional de Investigacao Veterinaria de Lisboa, Portugal. Oriento 15 cursos de practicas sobre el analisis de hongos y micotoxinas en la alimentacion animal y humana. Participo con la presentacion de 42 trabajos y conferencias sobre micologia, micotoxicologia y analisis de hongos y micotoxinas en Congresos Internacionales, entre los paises de Portugal, Espana, Republica Checa, Hungria, Polonia, Italia, Alemania, Inglaterra, Finlandia y Noruega. Realizo un total de 17 cursos de Pos-Graduacion en micologia medica y "Master" en produccion animal en Portugal. Publico 61 articulos sobre micologia, micotoxicosis y analisis de hongos y micotoxinas en varias revista cientifcas, tecnicas, libros de Simposio, libro y paginas web, tales como: J. Micotoxinas y Micotoxicosis en Animales y Humanos 5 Alberto Gimeno Ingeniero Industrial Quimico Consultoria Tecnica en Micotoxinas y Micotoxicologia Alimentaria. Micosis es el nombre con el que se conocen a las enfermedades ocasionadas por los hongos en el hombre y en los animales. Micotoxicosis es el nombre que se da al grupo de enfermedades y trastornos originados en el hombre y en los animales, por unos metabolitos secundarios toxicos llamados micotoxinas y que son producidos por cepas toxicogenicas de especies de algunos generos de mohos. Los hongos son vegetales carentes de clorofla pertenecientes al grupo de las taloftas. Esta carencia de clorofla no es solo una caracteristica que distingue a los hongos de los otros vegetales, si no que tambien es un condicionante importante en la actividad biologica de estos vegetales. El hecho de carecer de clorofla provoca el que ellos no son capaces de sintetizar materia organica utilizando la luz solar como fuente energetica, por este motivo deben desarrollarse sobre un sustrato que contenga materia organica. Asi pues cada producto alimentario es un sistema ecologico especial en el que la interaccion de factores quimicos, fisicos y biologicos tienen un papel fundamental en el deterioro del alimento debido a un crecimiento y proliferacion fungica. Clasifcaciones mas modernas incluyen a los hongos en el reino protista (intermedio entre plantas y animales), sin embargo y visto que los hongos se alimentan por via de absorcion se considera que los hongos no son ni plantas ni animales pero si un dominio diferente llamado reino "Fungi". Los hongos tienen gran capacidad para infectar tejidos vegetales vivos, con un gran poder de invasion, diseminacion y deterioro de productos almacenados. A todo esto debemos anadir los problemas de micosis que pueden ocasionar y la capacidad genetica que algunos de ellos tienen para producir metabolitos secundarios toxicos denominados micotoxinas con la consecuente posibilidad de producir micotoxicosis en los animales y en los humanos que consumen el alimento contaminado. Este conjunto de factores hace que los hongos formen un grupo importante dentro de la microbiologia alimentar. Las micotoxinas son compuestos policetonicos resultantes de las reacciones de condensacion que tienen lugar cuando en determinadas condiciones fisicas, quimicas y biologicas se interrumpe la reduccion de los grupos cetonicos en la biosintesis de los acidos grasos realizada por los mohos. Estos acidos grasos son metabolitos primarios utilizados por los mohos como fuente de energia. Las micotoxinas se suelen formar al fnal de la fase exponencial o al principio de la fase estacionaria del crecimiento del moho. Se han identifcado hasta ahora mas de 200 Micotoxinas, sin embargo las que se pueden encontrar de una forma mas frecuente como contaminantes naturales en los alimentos para animales y para humanos, son: afatoxinas, ocratoxinas, zearalenona, fumonisinas, toxinas tricotecenas (toxina T-2, diacetoxiscirpenol, deoxinivalenol o vomitoxina, nivalenol, monoacetoxiscirpenol, triacetoxiscirpenol, escirpentriol), citrinina, patulina, acido penicilico, sterigmatocistina, toxinas de alternaria (alternariol, alternariol monometil eter, altenuene, altenuisol, etc. Todas ellas reportan en mayor o menor grado una serie de cuadros clinicos patologicos, trastornos y efectos toxicos en los animales y en los humanos de forma a ocupar un lugar muy importante en el mundo de los alimentos. Para el crecimiento de los hongos y la produccion de micotoxinas existen tres factores fundamentales que son condicionantes, a saber: a. Una descripcion detallada de esos tres factores puede ser consultada en (Gimeno, 1999; Gimeno, 2000). Sin embargo nos gustaria brevemente dejar bien claro el concepto de actividad de agua (aw), llamada tambien algunas veces, agua disponible, o sea: La cantidad de agua existente en el ambiente y en los sustratos es uno de los factores importantes para el desarrollo de los hongos y para la produccion de micotoxinas. Sin embargo no solo infuye la cantidad de agua sino tambien la forma de presentacion de la misma, asi pues, el agua se encuentra en forma libre y en forma combinada. El agua libre existe dentro y alrededor de los tejidos vegetales o de las celulas y puede ser eliminada sin interferir seriamente con los procesos vitales. La forma combinada esta presente en los tejidos vegetales y animales, formando parte integrante de las celulas que los componen y en union con las proteinas y glucidos. Para la germinacion de las esporas de hongos, es necesario que el agua se encuentre en forma libre. Existen dos grandes unidades Micotoxinas y Micotoxicosis en Animales y Humanos 15 relacionadas con el agua libre (humedad), a saber: a. La aw nos indica cual es la cantidad de agua disponible para el desarrollo de los microorganismos una vez se ha alcanzado el equilibrio hidrico en el sistema alimento/medio ambiente. Las oleaginosas son mas dificiles de conservar mismo con valores de humedad (agua libre) relativamente bajos ya que el medio lipidico facilita la evaporacion del agua y su paso a la atmosfera que rodea las particulas del alimento. En general, con una actividad de agua a 25 C del 0,85 que aproximadamente puede corresponder a un 15-16% de humedad o agua libre en el sustrato, las esporas fungicas germinan en 5 a 12 dias. En cambio con una actividad de agua de 0,75 (que corresponderia aproximadamente al 13-14% de humedad en el sustrato) a la misma temperatura, las esporas fungicas tardan en germinar de 4 a 12 semanas. Sin embargo, las cosas pueden variar signifcativamente a depender del tipo de sustrato (amilaceo o bien oleaginoso) y tal como hemos visto anteriormente. Cuando se trata de silos horizontales al aire libre el problema es el mismo, solo que este ocurre esencialmente dentro de la masa alimentar visto que el aire que rodea las particulas de sustrato queda encerrado en el interior de esa masa, de aqui las recomendaciones que muchas veces se dan de intentar remover la masa alimentar para efectuar una liberacion y renovacion del aire que rodea las particulas de sustrato, o bien las de introducir aire frio y seco (de abajo hacia arriba) en los silos verticales de cara a los mismos fnes, ademas de reducir la temperatura del alimento. A pesar de todas las micotoxinas anteriormente mencionadas, seleccionaremos aqui las que mas signifcativamente pueden representar riesgos de micotoxicosis en algunas especies animales (pollos, gallinas, patos, pavos, cerdos, vacas lecheras y conejos) y en humanos, asi pues, nos referiremos a micotoxinas de Aspergillus (afatoxinas y ocratoxina A), de Fusarium (zearalenona, vomitoxina o deoxinivalenol, fumonisinas, toxina T-2, diacetoxiscirpenol, monoacetoxiscirpenol, triacetoxiscirpenol y escirpentriol) y de Penicillium (patulina). En general, la temperatura minima necesaria para desarrollarse y producir micotoxinas es de 10 12 C. La actividad de agua (aw) necesaria para iniciar su desarrollo y para producir micotoxinas es, a partir de 0,75 y de 0,83, respectivamente. Aspergillus crece y puede producir micotoxinas de una forma optima a 25 C, con una actividad de agua de 0,95. Sin embargo, existen cepas de Aspergillus favus que en sustratos tales como el arroz, crecen entre 6 y 45 C con un optimo a 37 C y la produccion de micotoxinas se efectua entre 11 y 36 C con un maximo de produccion a 30 C (Hesseltine, 1976). En cambio la produccion de afatoxinas en soja es baja, del orden de 19 y 2,8 mg/kg, respectivamente. Dentro de unas condiciones de temperatura y actividad de agua (aw) optimas, podemos ver que la cepa y la composicion del sustrato estan muy ligados a la produccion de la micotoxina. Las principales micotoxinas producidas por Aspergillus son las afatoxinas y las ocratoxinas. Otras micotoxinas como la patulina y el acido penicilico tambien pueden ser producidas por algunos Aspergillus. Sin embargo las que vamos a tratar y que deben tenerse en cuenta para los riesgos de micotoxicosis en especies animales tales como: pollos, gallinas, patos, pavos, cerdos, vacas lecheras, conejos y en la especie humana, son las dos primeras. Las afatoxinas se pueden encontrar como contaminantes naturales en los cereales (esencialmente en el maiz, trigo, sorgo y arroz) y subproductos de cereales, turtos de oleaginosas (algodon, cacahuete, colza, coco, girasol y otros), mandioca y toda una serie de alimentos para humana de los que destacamos productos de cereales, frutos secos, productos de salchicheria, especias, vinos, leguminosas, frutas, leche y derivados. Los principales organos afectados son: el higado, rinon y cerebro (Hesseltine, 1976; Edds, 1979). La absorcion de los aminoacidos se ve alterada y la retencion hepatica de estos aumenta. El efecto inmunosupresivo predispone al organismo animal para que sea invadido por microorganismos patogenos, algunos de los cuales pueden dar lugar a problemas de mamitis, agalactia y metritis. Parece ser que estas micotoxinas pueden producir alteraciones espermaticas en verracos, con una disminucion en la concentracion y supervivencia de los espermatozoides y un aumento de estos anormales (Picha et al. La ocratoxina A puede encontrase como contaminante natural en los cereales (esencialmente la cebada y arroz), subproductos de cereales, harina y turto de cacahuete y en una serie de alimentos para humanos como son, granos de cafe crudo, legumbres, quesos, carnes ahumadas (jamon, tocino, embutidos), vinos y otros generos alimenticios. Los organos afectados son: el higado y el rinon (Carlton, 1979; Gimeno y Martins, 1982). En cerdos, la ocratoxina A puede afectar la calidad del semen del verraco y la produccion espermatica. Durante la espermatogenesis, la micotoxina altera la estabilidad de la membrana del espermatozoide debido a su potente accion inhibidora de la sintesis proteica (Solti et al. Es aerobio y necesita en general de una actividad de agua (aw) superior a 0,88 para crecer y proliferar y superior a 0,91 para producir micotoxinas. En lo que se refere a la temperatura hay casos como el Fusarium roseum que necesita de un minimo de 15 C para desarrollarse con un optimo entre 24 y 27 C y que en cambio, una de las micotoxinas que puede producir como es el caso de zearalenona, solo la producira a temperaturas entre 10-14 C. No obstante hay variedades de Fusarium roseum como es el caso de Fusarium roseum "gibbosum" y Fusarium roseum "semitectum" que son capaces de producir en un sustrato de sorgo a 25 C, cantidades de zearalenona equivalentes a las producidas a una temperatura de 10 C. El Fusarium es uno de los grupos de mohos con mas capacidad genetica para producir micotoxinas cuando se tienen las condiciones fisicas, quimicas y biologicas adecuadas para ello. El Fusarium contamina el cereal en el campo y posteriormente cuando este cereal es sometido a procesos de secado y otros, el moho puede morir y no obstante la micotoxina permanecer en el sustrato. Asi pues, no es de extranar que en los analisis micologicos y de micotoxinas que se realicen posteriormente al cereal almacenado, se encuentre la micotoxina y no el Fusarium. Por otro lado tambien no es extrano que se encuentre Fusarium en ese cereal almacenado, o bien porque el tratamiento del cereal fue insufciente para matar totalmente a ese moho o bien como consecuencia de recontaminaciones posteriores debidas por ejemplo, a vectores trasportadores como son el aire y los insectos. En lo que se refere a los humanos, la vomitoxina o deoxinivalenol y la fumonisina B1 son micotoxinas muy importantes a tener en consideracion por los riesgos de micotoxicosis que se pueden presentar con el consumo de alimentos contaminados con estas. Existen unos 16 derivados de la zearalenona de los cuales el mas importante es la zearalenona y despues el alfa y beta-zearalenol. La zearalenona puede encontrase como contaminante natural en maiz y subproductos, cebada, trigo, avena, sorgo, semilla de sesamo, heno y ensilados. El principal sindrome de la zearalenona es el estrogenico dando lugar a casos muy signifcativos de hiperestrogenismo con vulvas dilatadas y enrojecidas (vulvovaginitis y edemas de vulva) (Mirocha y Christensen, 1974; Mirocha, 1977; Christensen, 1979). Micotoxinas y Micotoxicosis en Animales y Humanos 25 El mecanismo de accion de la zearalenona es semejante al de los estrogenos. Como alteraciones microscopicas destacamos que el miometrio y el endometrio sufren una hiperplasia e hipertrofa dando lugar a aun engrosamiento y edema del utero. En las hembras ciclicas, se producen fallos en la concepcion, pseudogestacion y aborto, la funcion del cuerpo luteo se ve alterada y el intervalo entre celos consecutivos se prolonga (Roy et al. En las cerdas gestantes, uno de los signos clinicos mas signifcativos es la mortalidad embrionaria. El anestro y pseudogestacion son signos clinicos observados en cerdas no gestantes (Roy et al. En los verracos jovenes puede haber una reduccion de la produccion de espermatozoides, peso de los testiculos y la libido (McEvoy et al. Existen 6 tipos de fumonisinas, la B1, B2, B3, B4, A1 y A2 (Marasas, 1995; Visconti et al. Los principales sindromes que producen son: neurotoxicos (leucoencefalomelacia), nefrotoxicos, edema pulmonar y cerebral, hepatotoxicos y lesiones cardiacas. Estas micotoxinas inhiben la biosintesis de los esfngolipidos e interferen con el metabolismo de la esfngosina y esfnganina dando lugar a una perturbacion en el metabolismo de los esfngolipidos, estos son constituyentes del higado y de las lipoproteinas (Prelusky et al, 1974; Marasas, 1995; Visconti et al. Los esfngolipidos tienen una gran importancia en la regulacion de las celulas y en el control de proteinas a nivel de membrana celular visto que estan presentes en esta, ellos son los mediadores del crecimiento celular y la diferenciacion y muerte de las celulas. En los mamiferos, la concentracion de esfngosina es, por lo general, de 3 a 5 veces mas elevada 26 Micotoxinas y Micotoxicosis en Animales y Humanos que la de esfnganina.

They are oxidized aerobically by a limited range of bac teria women's health center farmville va purchase 10mg duphaston visa, a process known as nitri cation menstruation food cheap duphaston 10 mg amex. Nitri cation is therefore an un Light desirable process in agriculture breast cancer jordans 2014 generic duphaston 10mg without prescription, especially in areas with high rainfall menopause urinary incontinence discount 10mg duphaston with amex. Run-off of nitrate produced in this way Photosystem I and from added agricultural fertilizer women's health center fremont ca purchase 10mg duphaston overnight delivery, into reservoirs women's health clinic enterprise al order duphaston 10 mg on-line, Fig. Nitri cation occurs in well-drained soils Inorganic electron donor, Reverse electron transport. Such bacteria tend to be facultative chemoau phide (H S), elemental sulphur (S0) and thiosulphate totrophs, capable of chemoheterotrophic growth, al 2 (S O 2-). Bacteria such as sul One genus able to obtain energy in this way is phate reducers and methanogens use hydrogen as an Thiobacillus. They are Gram-negative rods approxi electron donor and all are obligate anaerobes. Finally, mately 2mm in length, some of which are acidophiles some phototrophic purple sulphur bacteria can grow that can considerably lower the pH of their environ as hydrogen oxidizers, under aerobic conditions in ment. Once inside, the protons need to be removed, Calvin cycle to keep the internal pH near neutral. The cells process a large quantity of iron for chemolithotrophic bacteria, and autotrophic methylo very small yields of energy, which can be seen as an trophs (see p. Initial carboxylation involves the addition of 2 4 long as coal is unmined no pyrite oxidation can occur. The resulting C6 tions, oxygen becomes available, and they quickly product is immediately split into two C3 units, forming become contaminated with T. Methylotrophs are found within bacte Filamentous fungi ria, yeasts and lamentous fungi. They may be aerobic Gliocladium deliquescens or anaerobic and can be divided into three categories Paecilomyces variotii (examples shown in Table 3. Trichoderma lignorum 1 Heterotrophic methylotrophs, which can also grow Obligate methylotrophic bacteria heterotrophically on polycarbon compounds. The regulation is imposed at two levels, the modi cation of enzyme activity and the control of enzyme synthesis. Metabolic regulation Microorganisms naturally have tight control over their Modi cation of enzyme activity metabolism, but this often needs to be overcome when they are used in industrial fermentations. Conse enzymes to rapidly change the ow of carbon within a quently, the study of metabolic regulation is of special pathway. This may be achieved through initial strain selection, strain develop the simplest mechanism for the regulation of enzyme ment and the optimization of fermentation conditions activity merely involves controlling the concentration of (see Chapter 4). The most obvious Most metabolic pathways are controlled by a combi mechanism is the control of substrate entry into a cell nation of several different systems organized to con across the cytoplasmic membrane. Prokaryotes and off by their reversible covalent modi cation, such lack organelles, but development of concentration gra as phosphorylation and dephosphorylation. This is usually the rst step or rst unique step of the pathway and it is often irreversible. If levels of the end-products become too high, the for ne tuning the ux of carbon through a pathway. End-products of 66 Chapter 3 each branch often inhibit both the enzyme at the start of the ne tuning provided by regulatory enzymes, and is their respective branch and the pacemaker enzyme at the more difficult to reverse. In some branched path Some enzymes are constantly synthesized and are ways, several isoenzymes (isozymes) may control the constitutive components of the cell, whereas others are rst step, rather than having a single initial pacemaker synthesized only when required. This provides a more subtle means enzymes are produced at different concentrations, as of control for the ow of carbon, as each isozyme can some genes are more highly expressed than others. Alternatively, expression is controlled by the strength of their gene when there is just one enzyme, it may be regulated by all promoter, which lies upstream from the structural gene end-products of the branches. Strong promoters are very useful in products must be present at elevated levels to complete genetic engineering. First, the in Many catabolic enzymes are regulated by induction, termediate at the branch point accumulates, due to end as it is efficient for them to be synthesized only product inhibition of the enzymes responsible for its when their substrates are present, whereas synthesis of onward metabolism, whereupon it inhibits the enzyme anabolic enzymes is mostly controlled through repres at the beginning of the pathway. When a cell accumulates excess end-product of an anabolic pathway, such as an amino acid, or if a supply of that compound is encountered in the environment, Control of enzyme synthesis it responds by slowing or stopping the synthesis of the concentration of any enzyme is determined by its enzymes in the biosynthetic pathway for this product. However, thus preventing needless further carbon ux through the it is enzyme synthesis that generally plays the most im pathway. Con considered as a coarse tuning mechanism, as opposed to trol of enzyme synthesis in prokaryotes is normally at (a) Isozymes (b) Concerted (c) Cumulative (d) Sequential feedback feedback feedback I1 1 1 1 e1a e1b e1 e1 e1 I2 2 I2 I2 e2 e2 e2 e2 I3 3 3 I3 e3 e5 e3 e5 e3 e5 e3 e5 I4 I5 4 5 4 5 4 5 e4 e6 e4 e6 e4 e6 e4 e6 Fig. Studies on Mechanisms of general regulation the induction of b-galactosidase in E. In the ab Aerobic respiration and fermentation can be regulated sence of lactose, a repressor protein, produced under the by environmental conditions, which include the avail direction of regulatory genes, binds to the operator re ability of oxygen and sugars. The change of conforma rylation is considerably more efficient than fermenta tion prevents them from binding to the operator region tion. For enzyme synthesis controlled by repression, which is apparent only at low sugar concentrations (less the opposite occurs. The ux through in the presence of a corepressor, enabling them to bind to glycolysis appears to be primarily controlled by the the operator region thereby inhibiting transcription. Crabtree effect, where at high sugar concentrations, When a metabolite is catabolized or synthesized by even in the presence of oxygen, fermentation overrides a series of enzymes, it is usually advantageous for all respiration. This may more easily achieved as the genes for these enzymes are be explained by the saturation of the limited respiratory often located together as a cluster on the chromosome capacity of Crabtree-positive organisms. In eukaryotes the situa must usually be produced for the catabolism of any tion is much more complex, as genes for related activi other carbon and energy source. If glucose is present in ties tend to be scattered, rather than clustered together the medium, along with other sugars, it is always the rst as an operon. The result is sequential utilization that pro Enzyme synthesis may also be controlled by a mecha duces a diauxic (biphasic) growth pattern. In some cases, it is due to glucose-induced Tryptophan biosynthesis, which involves an operon of inactivation of key enzymes; for others, repression re ve enzymes, is coordinated through both repression, sults from rapid glucose uptake, which causes the intra as mentioned above, and attenuation. This important compound is involved in the positive control of many catabolic enzymes. Secondary metabolism and its control Time (h) Secondary metabolism is performed by many lamen Key: Glucose Lactose Growth tous fungi, but is rather less widespread amongst bacteria. Trophophase is the growth phase of a culture and idiophase is the fol lowing period when the secondary metabolites are lac operon. Although glucose has been the that are not essential for growth of the microorganism. These pathways Carbon catabolite regulation of primary metabolism are often not as well characterized as those for primary provides a selective advantage for the organism, as it en metabolism. It also Although secondary metabolism can be easily plays a role in controlling secondary metabolism. For demonstrated in batch culture, it can be studied in con example, glucose has a repressive effect on the produc tinuous systems, as it occurs at low dilution (growth) tion of many secondary metabolites, including antibi rates. Here, secondary metabolism can be demonstrated otics (b-lactams and tetracylines) and some alkaloids. Those that perform speci c roles for their pro collectively have important control functions within the ducer organism include sideramines (ferrichromes and cell. Some compounds may inhibit competing or Additional control of secondary metabolism is ganisms and others such as gramicidins are associated provided by the following. However, several small the synthesis of secondary metabolites is usually peptides, such as some antibiotics, are formed via an tightly regulated by the cell. Carbon sources that support high committed enzymes, produced at the end of exponential growth rates tend to be repressive; for example, glucose growth. S, produced by Bacillus brevis, is composed of two 70 Chapter 3 pentapeptide dimers, and each dimer is formed from level of 1mmol/L phosphate is necessary to ensure that four activated amino acids (amino-acyl derivatives). Cyclosporin is exploited as an immunosup particularly repression and feedback inhibition, must be pressant that is extensively used in the treatment of avoided. If potentially suppressive nutrients are used, autoimmune diseases and in transplant surgery. This may involve small mole Further reading cules, such as factor A (2 (S)-isocapryloyl-3-(S) hydroxymethyl-g-butyrolactone), which is produced Papers and reviews by Streptomyces species. They appear to function as hormone-like autoregulatory compounds that stimu Maden, B. The alkaloid ergoline, which is produced by Claviceps purpurea, is stimulated Books by the addition of l-tryptophan or tryptophan ana Berry, D. Black logues to the culture media during the exponential phase well Scienti c Publications, Oxford. Part 2 Bioprocessing 4 Industrial microorganisms Microoorganisms are used extensively to provide a vast new microorganism are more stringent and associated range of products and services (Table 4. Their ability to readily un employed and it may be possible to use modi ed (crip dergo genetic manipulation has also opened up almost pled) strains that cannot exist outside the fermenter en limitless further possibilities for new products and vironment (see Chapter 8). Traditional fermentations were originally performed Isolation of suitable microorganisms from (and still are in some cases) by a mixture of wild the environment microorganisms emanating from the raw materials or the local environment. Initial attempts to improve industrial microorganism from the environment the microorganisms involved occurred little more can be divided into two types, shotgun and objective than 120 years ago, when they were rst isolated from approaches. In the shotgun approach, samples of free these processes as pure cultures from which the most living microorganisms, bio lms or other microbial com useful strains were then selected. Those fermentation munities are collected from animal and plant material, processes developed during the rst 80 years of the 20th soil, sewage, water and waste streams, and particularly century have mostly used monocultures. These microorganisms employed were often isolated from the isolates are then screened for desirable traits. The alter natural environment, which involved the random native is to take a more objective approach by sampling screening of a large number of isolates. Alternatively, from speci c sites where organisms with the desired suitable microorganisms were acquired from culture characteristics are considered to be likely components collections (see p. For example, when attempt irrespective of their origins, were subsequently modi ed ing to isolate an organism that can degrade or detoxify a by conventional strain improvement strategies, using speci c target compound, sites may be sampled that are mutagenesis or breeding programmes, to improve known to be contaminated by this material. Several processes ronmental conditions may select for microorganisms developed in the last 20 years have involved recombi able to metabolize this compound. An initial step is often to kill or repress major importance when choosing microorganisms the proliferation of common organisms and encourage for industrial use. This is because of those organisms with the desired traits and increases requirements for process and product approval using a the quantity of these target organisms, prior to isolation 75 Table 4. Others, notably national collections, publish catalogues listing the organisms Bacteria held and provide extensive services for industrial Bacillus subtilis and academic organizations (Table 4. Aspergillus oryzae the prime functions of a culture collection are to Mucor javanicus (Mucor circinelloides f. Problems of culture mainte Note: Normally, these microorganisms require no further nance have been aided by the development and use of testing if used under acceptable cultivation conditions. However, this mode of selection is suit glass beads (2mm diameter) that may be placed in able only for cases where the desired trait provides a frozen storage, from which individual beads may be competitive advantage for the organisms. Subsequent isolation as pure cultures on solid growth Use of microorganisms selected from a culture collec media involves choosing or developing the appropriate tion obviously provides signi cant cost savings selective media and growth conditions. Once isolated as compared with environmental isolation and has the pure cultures, each must be screened for the desired advantage that some characterization of the microor property; production of a speci c enzyme, inhibitory ganism will have already been performed. However, at this stage the level of activ disadvantage is that competitors have access to the same ity or concentration of the target product per se is not of microorganism. Selected iso Industrial strains and strain improvement lates must also be screened for other important features, such as stability and, where necessary, non-toxicity. Irrespective of the origins of an industrial microorgan these isolation and screening procedures are more ism, it should ideally exhibit: easily applied to the search for a single microorganism. There are almost 500 culture collections 8 ready breakage, if the target product is intracellular; around the world; most of these are small, specialized and Industrial microorganisms 79 Table4. Consequently, they should not tion, which bring together genetic elements from two be shear sensitive, or generate excessive foam, nor be different genomes into one unit to form new genotypes. Those recom binants and mutants are then subjected to screening and selection to obtain strains whose characteristics are Strain improvement more speci cally suited to the industrial fermentation Further strain improvement is a vital part of process de process. Also, they must the genes picked up from their previous host, into the then be maintained on speci c media that select for, and new hosts chromosome. However, they able to exchange some genetic material via the processes are capable of entering and thus transforming only of conjugation, transduction and transformation. The bacteriophage attaches to a bacte homologous chromosomes to form new combinations. This is promoted Industrial microorganisms 81 when two genetically different haploid strains are tions caused by chrysogenin, a yellow pigment pro grown together, allowing fusion of their hyphae. Mutagenesis pro events result in the formation of a heterokaryon, com grammes have also been highly effective in increasing posed of mycelium containing nuclei derived from each the yield of penicillin in industrial strains of the same strain. Other notable examples of impairment of performed in vitro by fusing protoplasts, which are cells control processes, resulting in greater product yields, that have had their walls removed. Also, certain eukary are seen in several microorganisms used for amino acid otes, including some yeasts and lamentous fungi, pos production. As mutants can arise bridoma formation for monoclonal antibody produc naturally or be induced, they are considered to be the tion (Chapter 17), have had a major impact on product of natural events.

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Prostate 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history women's health clinic lincoln ne order duphaston once a day, physical examination breast cancer ultrasound imaging generic duphaston 10mg otc, and staging evaluation women's health clinic at darnall order 10mg duphaston with amex, or for documenting treatment plans or follow-up womens health yahoo answers buy generic duphaston line. Note: Positive surgical margin should be indicated by an R1 descriptor menstrual gas remedies buy cheap duphaston 10 mg, indicating residual microscopic disease menstruation every two weeks order duphaston cheap. Needle core biopsies positive: in one side in both sides beyond prostate 12. Testis 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Testis 7 Registry Data Collection Variables See chapter for more details on these variables. Kidney 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Adrenal gland involvement by direct extension (T4) or as a separate nodule (M1): 8. Histologic tumor necrosis: 7 Histologic Grade (G) the Fuhrman grading system, published in 1982, has been widely utilized. It is a four-tier system based on nuclear size, nuclear shape, and nucleolar prominence. Despite the widespread usage of Fuhrman grading, serious problems are associated with its implementation, reproducibility, and outcome prediction. As a result, a modified grading system has been proposed to be based on nucleolar prominence for the first three grading categories, while grade 4 is based on the presence of marked nuclear pleomorphism, which may include tumor giant cells or sarcomatoid and/or rhabdoid differentiation. Renal Pelvis and Ureter Urothelial Carcinomas, Squamous Cell Carcinoma and Adenocarcinoma arising in the Renal Pelvis and Ureter have distinct Histologic Grade (G) sections. Intratubular spread of this urothelial carcinoma (involvement of renal collecting tubules without stromal invasion): 7 Histologic Grade (G) For squamous cell carcinoma and adenocarcinoma, the following grading schema is recommended. Urinary Bladder Urothelial Carcinomas, Squamous Cell Carcinoma and Adenocarcinoma arising in the Urinary Bladder have distinct Histologic Grade (G) sections. Urinary Bladder: Urothelial Carcinomas 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Urinary Bladder: Squamous Cell Carcinoma and Adenocarcinoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Urethra Urothelial Carcinomas, Squamous Cell Carcinoma and Adenocarcinoma arising in the Urethra have distinct Histologic Grade (G) sections. Additionally, there are different Definitions of Primary Tumor (T) for Male Penile and Female Urethra, and Prostatic Urethra. Please choose the appropriate staging form based on primary site and histologic type. Male Penile Urethra and Female Urethra: Urothelial Carcinomas 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Male Penile and Female Urethra: Squamous Cell Carcinoma and Adenocarcinoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Definition of primary tumor (T) for Ta, Tis, T1, and T2 with depth of invasion ranging from the epithelium to the urogenital diaphragm. Definition of primary tumor (T) for Ta, Tis, T1, T2, and T3 with depth of invasion ranging from the epithelium to the urogenital diaphragm. Prostatic Urethra: Urothelial Carcinomas 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. This form may be used by physicians to record data on T, N, and M categories; prognostic stage groups; additional prognostic factors; cancer grade; and other important information. Prostatic Urethra: Squamous Cell Carcinoma and Adenocarcinoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Eyelid Carcinoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Conjunctival Carcinoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Conjunctival Carcinoma 6 Registry Data Collection Variables See chapter for more details on these variables. The map displays the entire conjunctiva as a flat surface, with the central point located at the center of the cornea and concentric regions, such as the limbus, bulbar conjunctiva, fornix, palpebral conjunctiva, and eyelid, considered progressively more peripheral. Conjunctival Melanoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Tumor thickness: infiltration depth (measured in millimeters) into the substantia propria from the surface of the conjunctival epithelium: 2. Presence/absence of adjacent conjunctival melanoma in situ, including status within surgical margins: 10. The presence or absence of microscopic satellites/satellite in-transit metastases, which may be considered for future pathologic staging of pN level, as in the case of cutaneous melanoma*: *Satellite in-transit metastasis: discrete micronodule/nodule of melanoma <1 mm to several millimeters in diameter in subepithelial tissue close to but clearly separated from the primary melanoma by at least 1 to 2 mm or more of uninvolved connective tissue. Both these types of metastasis usually are angiotropic and may be solitary or often multiple. Conjunctival Melanoma 7 Histologic Grade (G) In accordance with melanomas at other anatomic sites, grading is not performed for conjunctival melanoma. The map displays the entire conjunctiva as a flat surface, with the central point located at the center of the cornea and concentric regions such as the limbus, bulbar conjunctiva, fornix, palpebral conjunctiva, and eyelid considered progressively more peripheral. Uveal Melanoma the Definitions of Primary Tumor (T) differ between Iris Melanomas and Choroidal and Ciliary Body Melanomas. If less than half the tumor volume is located within the iris, the tumor may have originated in the ciliary body, and consideration should be given to classifying it accordingly. Extravascular matrix patterns (extracellular closed loops and networks, defined as at least three back-to-back closed loops, is associated with death from metastatic disease): 10. Primary ciliary body and choroidal melanomas are classified according to the four tumor size categories defined in Figure 67. Ultrasonography and fundus photography are used to provide more accurate measurements. When histopathologic measurements are recorded after fixation, tumor diameter and thickness may be underestimated because of tissue shrinkage. Retinoblastoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. T Suffix Definition (m) Select if synchronous primary tumors are found in single organ. Lacrimal Gland Carcinoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Ki-67 growth fraction (percentage of tumor cells positive for Ki-67 on immunohistochemistry): 6. For carcinoma ex pleomorphic adenoma, extent of invasion beyond capsule of pleomorphic adenoma: 7. For adenoid cystic carcinoma, approximate percentage of basaloid pattern present on pathological examination: 8. Involvement of periosteum only or periosteum and bone: this form continues on the next page. Orbital Sarcoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Each feature is scored separately, and the three scores are added to obtain the grade. Grade 1 is defined as a total score of 2 or 3, grade 2 as a total score of 4 or 5, and grade 3 as a total score of 6 to 8. To enhance the reproducibility of the system, the parameters are defined as precisely as possible. The main value of the grading is to determine risk of distant metastases and overall survival, rather than local recurrence, which depends more on adequate surgical margins. Necrosis related to previous surgery or to ulceration is not be taken into account, nor is hemorrhage or hyalinization. Necrosis Definition Score 0 No necrosis 1 <50% tumor necrosis 2 50% tumor necrosis 7. Ocular Adnexal Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Brain and Spinal Cord 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Always refer to the specific chapter for rules on clinical and pathological classification of this disease. Size of largest metastatic foci within an involved lymph node: 8 Histologic Grade (G) There is no formal grading system for thyroid cancers. Size of largest metastatic foci within an involved lymph node: 7 Histologic Grade (G) There is no formal grading system for thyroid cancers. The staging form may be used to document cancer stage at different points in the patients care and during the course of therapy, including before therapy begins, after surgery and completion of all staging evaluations, or at the time of recurrence. Whether the patient has medullary thyroid carcinoma that is sporadic or hereditary, if known: 7 Histologic Grade (G) Grade is not used in the staging for medullary thyroid carcinoma. Parathyroid 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. They generally include tumors that have two or more concerning features, such as fibrous bands, mitotic figures, necrosis, trabecular growth, or adherence to surrounding tissues intraoperatively. Atypical parathyroid neoplasms usually have a smaller dimension, weight, and volume than carcinomas and are less likely to have coagulative tumor necrosis. Parathyroid 6 Registry Data Collection Variables See chapter for more details on these variables. Location of primary tumor: left or right and superior (upper) or inferior (lower): 6. Time to recurrence (months): 7 Histologic Grade (G) Cytonuclear grade is defined as low grade or high grade. Adrenal Cortical Carcinoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Adrenal Cortical Carcinoma 6 Registry Data Collection Variables See chapter for more details on these variables. Hormonal function: 24-hour urinary fractionated metanephrines/plasma metanephrines: 6. Plasma methoxytyramine: 7 Histologic Grade (G) There is no recommended histologic grading system at this time. Hodgkin and Non Hodgkin Lymphomas Non Hodgkin Lymphomas have different Prognostic Factors Required for Staging depending on histologic type. Additionally, Non Hodgkin Lymphomas and Hodgkin Lymphomas use different staging classifications. Non-Hodgkin Lymphomas: Unspecified or Other Type 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. Non-Hodgkin Lymphomas: Diffuse Large B Cell Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Non-Hodgkin Lymphomas: Mantle Cell Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Non-Hodgkin Lymphomas: Follicular Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Always refer to the specific chapter for explicit instructions on classification for this disease. Non-Hodgkin Lymphomas: Marginal Zone Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. As a result of improved diagnostic imaging, staging laparotomy and pathological staging generally are no longer performed. Non-Hodgkin Lymphomas: Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Thrombocytopenia (Plt <100,000/ L): yes no this form continues on the next page. Non-Hodgkin Lymphomas: Peripheral T-cell Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Hodgkin Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Unexplained weight loss of more than 10% of the usual body weight in the 6 months prior to diagnosis 6 Registry Data Collection Variables See chapter for more details on these variables. Pediatric Hodgkin and Non Hodgkin Lymphomas Pediatric Non Hodgkin Lymphomas and Hodgkin Lymphomas use different staging classifications. Pediatric Hodgkin Lymphoma 1 Terms of Use the cancer staging form is a specific document in the patient record; it is not a substitute for documentation of history, physical examination, and staging evaluation, or for documenting treatment plans or follow-up. Select one: Designation Definition A Asymptomatic (No B symptoms) B Any B symptom(s): 1. A or B designation for symptoms must be part of the stage: this form continues on the next page. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification.