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Different concentrations of ionic species across the neuronal membrane and differential perme ability to z pak medications cheap olanzapine generic ionic flow across the membrane are the determinants of the membrane potential medicine to calm nerves quality olanzapine 5mg. Two forces govern ionic flow across channels symptoms gallstones purchase 5 mg olanzapine, a chemical driving force defined by concentra tion gradients medications safe during breastfeeding order genuine olanzapine online, and an electrical driving force determined by the membrane potential. The resting membrane potential is principally influenced by the reversal potential for K+. It has the highest permeability at resting conditions and, therefore, contributes the most in the Goldmann equation to the determination of the resting membrane potential. Ligand-gated and voltage-gated channels represent two mechanisms for controlling the opening of gated channels. The voltage-gated Na+ channel is the principal ionic conductance that underlies the upstroke of the action potential. As neuronal size grows, more current is required to achieve a similar level of depolarization, because the larger neuron has larger membrane surface area, which leads to higher capacitance. A quantitative description of membrane current and its application to conduction and excitation in nerve. The effect of sodium ions on the electrical activity of the giant axon of the squid. Synaptic transmission: a bi-directional and a self-modifiable form of cell-cell communication. Shefner Summary the neuron is uniquely suited for the transmission of electrical impulses. The neuronal membrane itself allows for charge separation; depending on the permeability of the membrane to a given type of ion, that ion will distribute across the membrane, producing a resting membrane potential, described by the Nernst equation. The development of action potentials are dependent on the presence of voltage-gated sodium channels, which open when the membrane itself is partially depolarized through mechanical, electrical, or chemical means. The initiation of an action potential cre ates a spreading area of voltage change, causing additional nearby channels to open, ultimately leading to the propagation of the action potential down the entire length of the axon. Myelin dramatically speeds the process of neuronal depolarization by producing salutatory conduction. Together, with the complex set of processes at the neuromuscular junction, neural transmission is effectively achieved. Key Words: Action potential; ion; myelin; resting membrane potential; sodium–potassium pump; voltage gated. Understanding the underlying neurophysiology governing these electrical signals is very important if one is to correctly identify, record, and interpret the signals. Later, we will see how local changes in the resting membrane potential of excitable cells can initiate propagation of the current to form the basis of communication from nerve to nerve and from nerve to muscle. This chapter repeats some of the information in chapter 2; however, additional information relevant to peripheral nerves is also included. Because the cell membrane is a bilipid layer, it is quite permeable to lipid soluble substances, while acting as an effective barrier against many water-soluble particles. However, the cell membrane also contains specialized protein molecules, which act to selectively transport or allow passage of certain water-soluble particles. It is through these transport and channel proteins that movement of water-soluble ions and molecules occurs in and out of the cell. The mechanisms by which this move ment occurs are passive transport and active transport. Passive Transport Passive transport is defined by movement that does not require the expenditure of energy. Two main forces contribute to passive movement of particles across the membrane—concentration gradient and electrical charge. All other factors being equal, particles will tend to move in such a manner that their concentration is equal throughout a given space. Thus, if a membrane is permeable to a certain particle, and that particle is more highly concentrated on one side of the membrane than the other side, diffusion forces will cause a net movement of particles toward the side with the lower concentration. Physiologically, this movement occurs through the transport proteins in the membrane. If diffusion is the only force determining particle movement, the amount of particle move ment will be determined by the magnitude of the concentration gradient, and by the extent to which the membrane is permeable to that particle. Along the cell membrane, permeability is determined by properties of the transport proteins, with selectivity based on the electrical and mechanical (diameter and shape) properties of the transport protein and the particle to be trans ported. Not all water-soluble ions and molecules move simply down the concentration gradient unaided. Some ions and molecules require a carrier to shuttle them across the cell membrane down the concentration gradient, referred to as facilitated diffusion. The other major force that determines passive movement of particles across the nerve membrane is electrical charge. The particles of interest to us are all charged; potassium, sodium, and calcium are present as positively charged ions, whereas chloride carries a nega tive charge. Therefore, if particles move across the membrane according to concentration gra dients, they carry with them either a net positivity or negativity. Because like charges repel each other, a buildup of either positive or negative charge will tend to inhibit the further trans port of like charges. Active transport involves the transport of ions in a direction not determined by concentration or electrical gradients. For example, positively charged sodium ions passively tend to move into the cell along both electrical and concentration gradients. However, active transport supports the movement of such ions in the opposite direction, against the passive forces. Both sodium and potassium ions are transported Ions, Membrane Potentials, and Myelin 37 actively across the membrane, via a single mechanism called the sodium–potassium (Na–K) pump. Because the role of Na–K pump is to move ions against a concentration gradient, the sodium receptor sites for this pump are located inside the cell membrane (where the sodium concentration is lower), whereas the potassium receptor sites on the pump are located outside the cell membrane (where the potassium concentration is lower). There are three sodium-binding sites and two potassium-binding sites in any Na–K pump. Thus, for every three sodium ions sent out of the cell, two potassium ions are brought inside. If a membrane were completely and equally permeable to all particles, diffusion would be allowed to proceed unchecked, and the various concentration differences across the cell membrane would eventually become equalized. However, in biological systems, both active transport and selective membrane permeability prevent such equalization. The resting membrane potential for a cell membrane is a product of the gradients that exist for single ion species, in combination with energy-requiring processes, such as active transport. The Nernst Potential In a hypothetical situation, let us assume that the cell membrane is permeable to only one single ion, which then tends to diffuse through the cell membrane along its gradient. With ion movement, there will be an accumulation of charge; this charge will tend to oppose further diffusion of like-charged particles with the force of opposition increasing as more ions travel across the membrane. At some point, the diffusion force responsible for ion movement along the concentration gradient will exactly equal the electrical opposing force. The potential difference at which this equalization of forces occurs is called the Nernst potential for that ion. For singly charged ions at 37°C, the formula to calculate this potential (in millivolts) is: 61 fi log10 (concentration of the ion outside divided by the concentration of the ion inside). Because the concentration of different ions is different across the cell membrane, one can see that the Nerst potential will be different for each ion. Using this formula, we can calculate the potential difference across the cell membrane for potassium and sodium ions as examples. For potassium, the Nernst potential is approximately –94 mV, with the negativity inside the cell membrane, whereas it is +61 mV for sodium. The effect that each ion species will have in determining the global resting membrane potential for a membrane is determined by the membrane permeability to than ion. Thus, if a membrane is completely impermeable to an ion, it will have no effect on the membrane potential of the cell, no matter what its Nernst potential might be. Goldman–Hodgkin–Katz Equation this equation objectifies the point made in the preceding paragraph, and suggests that the overall resting membrane potential for a biological membrane is a combination of the Nernst potentials for all permeable ion species inhabiting the perimembrane area, scaled by their respective permeabilities.

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Palpation and visual evaluation of retroperitoneal lymph nodes should not be considered diagnostic treatment for gout order olanzapine on line. Additionally symptoms kennel cough discount olanzapine amex, gross examination of myometrial invasion should not be utilized to medications54583 discount olanzapine online american express P medications for bipolar disorder buy olanzapine 10 mg overnight delivery. Multiple recent series from different institutions have shown the feasibility and accuracy of laparoscopic and robotic staging for endometrial cancer. Minimally invasive surgical staging is generally well tolerated and results in equivalent overall survival and recurrence rates. A survey of the members of the Society of Gynecologic Oncology showed that >50% of its members utilize some form of laparoscopic-assisted staging. A recent meta-analysis including 331 patients demonstrated fewer postoperative complications, less blood loss, longer operating time, shorter hospital stay, and no significant difference between overall survival and recurrence when minimally invasive surgical techniques were utilized versus open surgery for endometrial cancer. Pelvic Lymph Nodes (%) Grade No Invasion Inner 1/3 Mid 1/3 Outer 1/3 1 0 3 0 11 2 3 5 9 19 3 0 9 4 34 Para-aortic Lymph Nodes (%) 1 0 1 5 6 2 3 4 0 14 3 0 4 0 23 From Creasman W, et al. In this new staging system, positive cytology no longer changes the stage, but is still reported. Histopathologic Factors for Endometrial Cancer Type I endometrial cancers are estrogen dependent, arise in a background of hyperplasia, and are of endometrioid histology. Tumor grade affects the risk of spread and recurrence and is therefore important in determining the need for adjuvant therapy. Prognostic Factors for Endometrial Cancer the most significant prognostic factors for recurrence and survival are stage, grade, and depth of myometrial invasion. While positive peritoneal cytology is associated with adverse features such as extrauterine disease, therapy for this finding as an isolated result does not improve survival. Patients with low-risk endometrial cancer of endometrioid type require no further therapy beyond surgery. Management of High Risk Endometrial Cancer Treatment for women with higher risk disease is more controversial. These women were then randomized to receive or not receive pelvic radiation with 4,600 cGy. However, the rate of death from cancer was not statistically different between the two groups (9. Additionally, radiation therapy for vaginal recurrence in the nonradiated group was successful in inducing a complete response in 89%, and 5-year survival of this salvage radiation group was 65%. Therefore, postoperative radiation can significantly increase local control but does not appear to impact survival. A multicenter retrospective trial demonstrated an 81% response rate to salvage radiation for isolated vaginal recurrences in surgical Stage I patients who did not initially receive adjuvant radiation. If cervical involvement is known preoperatively, a radical hysterectomy should be considered, which has been shown to result in a 75% 5-year survival rate. A combination of extrafascial hysterectomy followed by radiation is associated with a 5-year survival rate of 70%. Adjuvant therapy after cytoreduction is advised; however, the optimal mode of adjuvant therapy is unclear. Complete salvage cytoreduction for recurrent disease has been associated with a prolonged postrecurrence survival (39 months) versus patients with gross residual disease (13. There was a significantly higher rate of peripheral neuropathy in the group treated with paclitaxel. Neither Megace combined with cyclophosphamide, doxorubicin, and fluorouracil nor Megace combined with fluorouracil and melphalan has proven to be superior to single-agent regimens. Patients who fail first-line chemotherapy generally have a very poor prognosis with a response rate to second and third-line agents of <10% and overall survival of <9 months. Posttreatment Surveillance After treatment, surveillance for recurrence should include an examination every 3 to 6 months for 2 years and then annually. Vaginal cytology should be performed every 6 months for 2 years and then each year. Endometrial Cancer these are often treated with adjuvant therapy regardless of stage. The overall 5-year disease-free survival for clear cell endometrial cancers is only 40%. As in ovarian cancer, chemotherapy regimens with carboplatinum and taxol have been the most successful. Fertility Preservation Women with very early endometrial cancer who wish to preserve their fertility have been treated with progesterone rather than surgery. Of those who responded, 24% recurred, and median time to recurrence was 19 months. A multicenter prospective study examined 28 women with endometrial carcinoma and 17 women with atypical hyperplasia who were treated with progesterone. Complete response was noted in 55% of the patients with carcinoma and 82% of those with atypical hyperplasia. The patients were followed for 3 years during which there were 12 pregnancies and a 47% recurrence rate. A recent prospective trial followed 105 women with endometrial hyperplasia treated with a levonorgestrel-releasing intrauterine device and showed a 90% regression rate after 2 years. Grade 1 or 2 tumors with <50% myometrial invasion have a <10% risk of having positive lymph nodes and >90% 5-year survival without any further treatment. However, any grade 3 cancer or grade 1 and 2 cancers with more than 50% invasion pose a >10% risk of positive pelvic lymph nodes, and 5-year survival is decreased to 70% to 85% without further treatment. Laparoscopic node dissection can be used for patients who were incompletely staged at their initial surgery. Medical Contraindications to Surgery Women who are medically unable to undergo surgery can be treated with pelvic radiation alone. However, 5-year survival for clinical stage I disease is decreased to 69% with this approach versus 87% for surgery alone. In these cases, vaginal hysterectomy is a therapeutic option for those women unable to undergo a more extensive operation. In a small series of patients with a well-differentiated endometrial adenocarcinoma, a progestin-secreting intrauterine device has been shown to be effective therapy. They usually present with postmenopausal bleeding, and often on exam the woman will be found to have a fungating mass protruding from her cervix. Mixed Mullerian Mesodermal Tumors Mixed mullerian mesodermal tumors are carcinosarcomas and the most aggressive of. Thus, carcinosarcoma should be studied separately from high-risk endometrial cancers given the difference in behavior. In a series of 1,432 patients who underwent a hysterectomy for a fibroid uterus, only 0. Another series of 1,332 patients who underwent hysterectomy for fibroids had a subset of patients with “rapidly growing fibroids” and only 0. These tumors appear like leiomyomas but have >10 mitoses per 10 high power fields and diffuse nuclear atypia. Chemotherapy has not been shown to be beneficial; however, with metastatic disease, doxorubicin and ifosfamide have been used. Prognosis for Uterine Sarcoma A retrospective study including women with all forms of sarcoma showed a 3-year survival rate of 82%, 60%, and 20% for sarcomas with low-, medium-, and highgrade histology, respectively. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Laparoscopically assisted versus open surgery for endometrial cancer—a meta analysis of randomized controlled trials. Role of systematic lymphadenectomy and adjuvant therapy in stage I uterine papillary serous carcinoma. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Treatment effects, disease recurrence, and survival in obese women with early endometrial carcinoma: a Gynecologic Oncology Group study. Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Ovarian cancer is the second most common gynecologic cancer, following cancer of the uterine corpus.

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Although there is high correlation for the anterior 2/3 from 1 nostril are not reliably representative of the total cell distri 242 of the nasal cavity 10 medications effective olanzapine 7.5 mg, the posterior nasal cavity shows more vari bution in both nostrils medicine you can give dogs purchase olanzapine us. Samples collected by blowing mucus 222-225 into transparent wrap contain less cellular material than when a cy ance medicine expiration dates buy olanzapine 5 mg cheap. Acoustic rhinometry are used symptoms intestinal blockage order olanzapine 20mg without prescription, but are adequate for detecting eosinophils and neutro 231 853-855 and rhinomanometry have similar reproducibility and compare phils. Once collected, the nasal secretions are transferred 232 to a slide, fixed, and then treated with Hansel stain, which high favorably in challenge studies but measure different changes 233-235 856 and are best viewed as complementary. Although nasal smears rhinometry is used to help diagnose rhinitis, evaluate nasal pha are generally adequate for assessment of nasal eosinophilia, there ryngeal surgical outcome, and monitor response and adherence is some evidence that nasal biopsy for eosinophils is more accu 226,227 857 to medical therapy such as intranasal corticosteroids. Many studies have shown a high correlation of nasal eo a logical choice for the objective measurement of area and volume sinophilia and allergic rhinitis; however, it is questionable how in diseases of the nose. A number of factors lead to measurement much this benefits the clinician in making the diagnosis of allergic 87-89 variation when the procedure is used. In a study of adolescents and adults, adding nasal surement inaccuracy are an air leak between the nosepiece and the smears for eosinophils to an expert’s clinical evaluation in estab 228 nose and the presence of nasal secretions. Studies have shown lishing a diagnosis of allergic rhinitis contributed very little to the 90 that patient perception of nasal obstruction does not correlate with final diagnosis and was considered clinically irrelevant. In clinical trials, nasal eosinophils have been used to eval allergen usually can be based on a history of symptoms of allergic uate anti-infiammatory effects of intranasal corticosteroids and rhinitis provoked by exposure to the allergen and confirmed by 376,380 may be associated with improved nasal symptom scores. For example, nasal provocation 91 and a positive nasal smear for eosinophils, and may have nasal testing with allergen may be required for confirmation of sensi 241 91,241 specific IgE, supporting the diagnosis of allergic rhinitis. Single-dose allergen provocation measures nasal wish to conduct a nasal or conjunctival challenge test. Because nasal reactions to hand, as many as 6% of patients with a similar history suggestive of instillation of placebo materials may occur, response to diluent allergy will have negative prick skin test and nasal challenge but must be measured before provocation with allergens. Although this measurement may be a marker for these response to medical therapy can be anticipated. However, these provocation tests may be eosinophilia was found to predict prolonged or subsequent useful during clinical trials to determine the efficacy of drugs 858 allergic rhinitis symptoms. In addition, the nasal eosinophil and allergen immunotherapy in reducing nasal irritability. Recognizing that many patients Nasal cytology, ciliary functional studies, and biopsy with allergic rhinitis have increased airway reactivity and will 43. Nasal smears for eosinophils are not necessary for routine subsequently develop asthma, the nasal smear for eosinophils use in diagnosing allergic rhinitis when the diagnosis is may help predict the progression of disease; in adult patients clearly supported by the history, physical examination, and with allergic rhinitis as the only allergic diagnosis, it has been specific IgE diagnostic studies but may be a useful adjunct shown that the number of nasal eosinophils correlates with the 89,860 when the diagnosis of allergic rhinitis is in question. Although the saccharin test for mucociliary clearance has the absence of eosinophils and the presence of large numbers been relied on as a clinical screening test, it cannot be relied of polymorphonuclear neutrophils especially when intracellular 92 on for a definitive diagnosis of mucociliary dysfunction. A viral infection is usually associated with fewer when they are suspected to have comorbid conditions such 243 polymorphonuclear cells than a bacterial process. C the mere presence of neutrophilia cannot be diagnostic of an infec tious process because as many as 79% of school children and 97% In children with rhinitis, select tests that may be indicated on an 88 individual basis include quantitative immunoglobulins, comple of infants have neutrophils in their nasal secretions. The saccharin test (with saccharine or a substitute dye marker) ment studies, ciliary functional and morphologic studies (as may be used by the clinician as a screening test for primary or described in Summary Statements 44, 45), and the sweat test secondary ciliary dysfunction. The subject then sits ‘‘Practice Parameter for the Diagnosis and Management of 864 with the head bent forward and the test is completed when either Primary Immunodeficiency’’). If the time is radiography in children for the diagnosis of acute bacterial 77,865,866 beyond 1 hour or the subject is unable to taste the saccharin or de sinusitis. Although the diagnosis of acute bacterial sinus tect the dye, mucociliary clearance is considered impaired. When itis in children can usually be made by clinical assessment, plain an abnormal study is obtained, additional studies are required be radiography may be considered for confirmation in children 6 166 years and older with persistent symptoms and for all children (re fore a firm diagnosis can be established, because the saccharin 867,868 test has too many false-positives and false-negatives. Biopsies to determine ciliary structure and function complications of acute bacterial sinusitis, such as orbital or can be obtained endoscopically from bronchi or the nasopharynx intracranial complications, for patients who fail to improve with and by curette or brush from the inferior concha. The cilia can be appropriate medical therapy, or for the diagnosis of chronic sinus 866,869 viewed by video or examined in cross-section by electron itis. A lateral nasopharyngeal radiograph may help to ex 244,245 clude adenoid hypertrophy in children with mouth breathing, microscopy for specific defects or usual ultrastructure. Combining electron microscopy with computer-based image pro snoring, sleep apneic episodes, and nasal obstruction. When cessing algorithms can improve the visualization of ultrastructural available, dynamic video rhinoscopy is more accurate at assessing 165,167-169,862 adenoid hypertrophy and percent airway occlusion than lateral defects. Depending on the results of the nasal biopsy 216 evaluation of ciliary function, a tracheal biopsy may be required neck radiography. The measurement of total IgE and IgG subclasses for the di sidered in children and adults presenting with chronic rhini agnosis of allergic rhinitis has limited value and should not this and other risk factors associated with sleep-disordered be routinely performed. The presence of b-2-transferrin in the nasal secretions is a 257 Atopy has been associated with habitual snoring in infants. Children who are African American, have upper respi Measurement of total IgE in cord blood or in children has been ratory disease, and have a family history of sleep apnea are at en 259 proposed as means of predicting the risk of allergic disease; hanced risk for sleep-disordered breathing. The total serum IgE has low sensi with chronic rhinitis and other risk factors associated with tivity (43. Obstructive sleep apnea episodes deter responses of the IgG subclasses has been suggested to be a risk mined by polysomnography were more frequent in patients with 863 factor for allergic disease. Furthermore, measurement of nonspe ragweed allergy during symptomatic periods when nasal resis 871 cific and specific IgG4 and/or of other subclasses has been advo tance was increased than during asymptomatic periods. The routine measurement of IgG4 should not be part may be of benefit in the management of some patients with 261 of the diagnosis evaluation of patients with allergic nasal disease. Pulmonary function tests should be considered in patients many trees, grasses, and weeds, although exposure to pollen from with rhinitis to assess the possibility that asthma might be insect-pollinated (entomophilous) plants may produce symptoms 872 present. Allergens are quickly eluted from pollen grains on contact with ocular or respi Rhinitis and asthma are linked by common epidemiologic, ratory mucosa. In addition, similar allergens may be found on physiologic, and pathologic mechanisms, as well as common fragments derived from other portions of the plant. Pollen aller comorbidities and therapeutic approaches, leading to the concept 262-265 gens, forming an allergenic bio aerosol, can be detected in the of ‘‘one airway, one disease. The dose of pollen ence of asthma may not be apparent because such patients (1) allergen that is able to elicit symptoms depends on the degree of may have difficulty in recognizing their symptoms, (2) may allergic sensitization and on nasal mucosal infiammation that have variable symptoms throughout the day, (3) may have a 721,876,877 already is present, often referred to as ‘‘priming. Therefore, to reduce Furthermore, the physical examination of the lower respiratory indoor exposure, windows and doors should be kept closed. If air systems may be normal during the medical evaluation of conditioning is used to keep the home or vehicle comfortable, any rhinitis. It may be helpful to take a Unproven tests shower or bath following outdoor activity, thereby reducing in door pollen contamination. There is no evidence that the following procedures have diagnostic validity for allergic rhinitis: cytotoxic tests, pollen intrusion, it may be beneficial to wash furry animals after provocation-neutralization, electrodermal testing, applied they have been outdoors. Although it is not practical to remain in doors all of the time, it is helpful to limit outdoor exposure during kinesiology, iridology, and hair analysis. For example, because ragweed Diagnostic Testing: An Updated Practice Parameter’’) pollen concentrations tend to peak at noon or in the early after noon, it may help to plan outdoor activities for the early morning 880 Management of rhinitis or late evening. Highly sensitive patients whose symptoms are Environmental control measures triggered by very low pollen levels may need to limit their outdoor 277 Environmental triggers for rhinitis can be divided into 2 general activities. Having such individuals wear a facemask during out 277 categories: allergens and irritants. Activities involving ex rhinitis includes identification of these triggers when possible and tended time outdoors, such as camping trips, may need to be implementation of avoidance measures when practical. Because pollen counts tend to be higher on sunny, windy days with low humidity, it 52. The most common allergic triggers for rhinitis include pol may help to limit outdoor activities when those weather conditions lens, fungi, dust mites, furry animals, and insect emanations. In contrast, outdoor activities may be well tolerated B after a gentle, sustained rain when pollen counts tend to be low. Allergens are substances that trigger rhinitis through an IgE Because the interplay of different weather factors (eg, wind, tem dependent mechanism. The most common allergic triggers for perature, rain, humidity) is complex, it is not reliably possible to rhinitis include pollens, fungi, dust mites, furry animals, and insect predict levels of outdoor aeroallergens on the basis of the infiu 270-272 emanations. The ideal way for patients to manage allergic rhinitis ence of a single weather factor.

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Determinants of successful the effectiveness of population-based improve communication medicine 2 times a day purchase genuine olanzapine, organiza implementation of population-based cancer screening is predominantly tion medications for high blood pressure cheap olanzapine 7.5 mg with mastercard, professional performance symptoms vitamin d deficiency cheap olanzapine 20 mg with amex, and cancer screening programmes have available from programmes in high equipment premonitory symptoms discount olanzapine 2.5 mg. To fully evaluate the impact of a lation substantially limits the effec Insights into the implementation of screening programme, the potential tiveness and the cost-effectiveness such programmes are provided in harms mentioned above must also of any programme. Since the full impact of a aware of this and other constraints livery of multidisciplinary screening screening programme will not be that may limit the achievable impact services at all resource levels. Of prime importance is is a common goal in all attempts to ties in the screening process from the availability and sustainability of improve cancer control through early the outset, i. European Colorectal Cancer Screening European Commission, Publications Offce European guidelines for quality assur Guidelines Working Group (2013). Worldwide trends in cervi int/cancer/publications/cancer control ity assurance in breast cancer screening cal cancer incidence: Impact of screen detection/en/index. International Cancer Screening Network Swedish two-county trial: impact of mam Are breast cancer screening pro (2013). National Cancer mographic screening on breast cancer grammes increasing rates of mastecto Institute. Sankaranarayanan R, Ramadas K, screening – comprehensive, population Somanathan T et al. Cancer Screening in the European Union: Report on the Implementation of Screening Group, Section of Early Detection 19. Dean Nada Al Alwan Rengaswamy Sankaranarayanan • Programmes should be imple patients outside the programme. Summary mented gradually, tailoring ex these factors, in combination, lead pansion of the screening service to an overall improvement in the level • Global implementation of popu to the capacity of the health-care of cancer care [1]. Successful implementation of pop ulation-based cancer screening • In many high-income countries Implementation of quality-assured programmes requires expertise in and some middle-income coun population-based cancer screen areas relevant to other prevention tries, population-based screen ing programmes affects very large activities, such as motivation, com ing programmes for breast and numbers of people in the eligible age munication, and reinforcement of cervical cancer have been estab range (see Chapter 4. The pro efforts designed to prevent cancer lished for decades, or shorter pe cess requires many years, beginning [2]. The ability to mobilize large num riods, and some have achieved with the development and testing of bers of health-care professionals, signifcant reductions in cancer a comprehensive quality assurance other stakeholders, and the target specifc mortality. Colorectal system to ensure the provision of population itself in collective actions cancer screening programmes cost-effective, affordable, and ac focused on a common goal is cru have been introduced more ceptable services for the entire target cial to the success of any screening recently. Screening can stim screening conducted as planned political commitment, engage ulate health systems development fulfls the key performance targets ment of civil society, competent and raises the level of awareness and is likely to be cost-effective. It oversight, and adequate, sus of cancer symptoms among health may take several years to collect suf tainable resources. A quality-assured population be drawn about routine implementa have the authority to coordinate based screening programme raises tion and to make any necessary ad all activities essential for provi the standards of cancer diagnosis justments to the screening protocol sion of screening services, in and treatment throughout the medi warranted by the pilot results. Professionals trained studies are also needed to provide monitoring, and other aspects of to meet the standards of the screen information on the cost-effective quality assurance. Immunochemical faecal occult blood testing kit used in the Lampang Province national or regional programmes for colorectal cancer screening programme in Thailand. In most high-income countries, the burden of cancer has resulted in coordinated efforts to implement population-based screening for all of the tumour types for which evi dence-based methods are currently established (breast, cervical, and colorectal cancer). In other coun tries, due to the comparatively long period required to successfully es tablish population-based screening programmes, time trends in cancer incidence and mortality should be taken into account when prioritizing potential target cancers for screen ing [1]. On this basis, cancers cur rently suitable for screening in low and middle-income countries include, for example, cervical can cer in sub-Saharan Africa, India, and Latin America; breast cancer in Latin America, the Middle East, and some countries in Asia; and colorec tal cancer in countries in transition, an individual country. Before ful pilot studies, gradual, quality In a fully established programme, a commitment is made to the roll controlled roll-out of the programme the proportion of the expenditure out of a screening programme, the across the country begins, with the devoted to quality assurance in a potential cost-effectiveness of the health-care system controlling the high-resource setting should be no programme in the country should be pace of programme expansion, with less than 10–20% [7]. If pilot studies particular reference to specialized proportion of these resources are indicate that the cost per year of life training of staff and investment in in required for well-organized informa saved by a given intervention is less frastructure. The entire process of tion systems, such as those used than the per capita gross national programme implementation rarely by cancer and screening registries, product, a screening programme can takes less than 10 years [1]. Programme tation of population-based cancer for example through training of com resources include a dedicated screening programmes, efforts to petent staff. When access to prompt budget and staff, computerized in improve early detection of cancer diagnosis and treatment is available, formation systems, and registries should be integrated into national alternative strategies of early detec for cancer, population, and screen comprehensive cancer control plans tion can be considered in countries ing, all based on individual data that establish overall priorities in the where low incidence rates do not [5]. Successful implementation of health-care agenda and take into ac yet justify population-based screen effective screening programmes count all relevant activities, such as ing programmes for asymptomatic Chapter 4. Estimates of the impact of ser vice screening in Europe have re cently been obtained from a review of all available observational studies from which suffcient longitudinal in dividual data were available, directly linking a woman’s screening history to her cause of death. The authors considered that the most reliable es timates of reduction in breast cancer mortality were 25–31% for women invited for screening and 38–48% for women actually screened [21]. Population-based colo and the performance of breast self cervical cancer in the medium and rectal cancer screening programmes examination, suggesting a potential long term [14,15]. Morocco is currently establish mammography were initiated in of performance have recently been ing universal access to comprehen Europe, Canada, and Australia in developed for the population-based sive cancer diagnosis, treatment, the late 1980s after randomized programmes in Europe based on re and palliative care according to the controlled trials showed the eff sults achieved in randomized trials 2010–2019 national cancer control cacy of screening [16,17]. This includes a nationwide population-based breast screening early detection programme for clini programmes were running or be Fig. Now that cer screening programmes were screening has been performed for launched in middle and high-income more than two decades in several countries in the 1960s to 1980s, for population-based programmes in cervical cancer screening. These Europe, methodologies used to programmes were based on con estimate the impact of screening ventional cytology, and many led to and the level of overdiagnosis have reductions of 50–80% in cervical been evaluated using data from ser cancer mortality within two to three vice screening programmes [19]. In Registry studies analysing popula recent years, primary cervical cancer tion breast cancer mortality rates 332 and routine programmes [23]. Screening programmes in upper-middle-income countries Opportunistic, large-scale cervical cancer screening has been conduct ed in some upper-middle-income countries for several years. The resulting impact on cervical cancer incidence and mortality has been limited, due to poor coverage and lack of quality assurance in cytol ogy screening, suboptimal adher ence by screen-positive women to further diagnosis and treatment, and lack of information systems to moni tor progress and assess impact. Implementation of ed and shows potential to increase vices currently preclude introducing acetic acid-based screening may cervical screening effectiveness by screening programmes in most of improve development of screening increasing participation, especially these countries. In recent positive women, as well as the lim fordable viral tests become widely years, many of these programmes ited impact of Pap smear screening available. Improving breast spread, but population-based breast with acetic acid have been evalu awareness may facilitate earlier clin cancer screening programmes have ated as alternative methods, and ical diagnosis among symptomatic yet to evolve in many upper-middle single-visit approaches, involving women in such settings, but these income countries. Colorectal cancer diagnosis and treatment of screen efforts may be counterproductive if screening is less widespread; a na positive women in the same sitting the women cannot obtain timely di tional programme exists in Uruguay. For the same reason, systematic ap Screening programmes in Recent results from such studies proaches to early detection based lower-middle-income and have prompted the introduction of on breast examination and imaging low-income countries visual inspection of the cervix with methods are required in countries Cancer screening programmes are acetic acid screening programmes that have an increasing burden of operational in very few lower-middle in Bangladesh [27], Tamil Nadu state breast cancer but that currently lack income and low-income countries in in India, Thailand [28], and Zambia adequate diagnostic and therapeu Africa, Asia, Central America, and [29], as well as demonstration tic services [30,31]. Population the Caribbean, despite the high risk programmes in 43 counties of 31 based colorectal cancer screening Chapter 4. A woman being screened for stomach cancer at the Osaka Cancer Prevention lower-middle-income country, with and Detection Center, in Japan, in research directed towards the development of a the exception of Thailand, where population-based protocol for this tumour type. Outlook Breast, cervical, and colorectal cancer screening programmes have been improved globally through re search in terms of quality inputs, effciency, and effectiveness. New research fndings have catalysed the planning and organization of new screening programmes in some countries [32]. Research has indicat ed the effcacy of mammography and faecal occult blood screening and paved the way for population-based screening programmes. Screening approaches for other tumour types, such as lung, ovarian, oesophageal, stomach, and prostate cancer, are low and middle-income countries, and appropriate diagnostic and ther currently being investigated in re where cancers are mainly detected apeutic services universally avail search settings (Fig. Recent Provision of adequate resources will cancer screening programme in research may lead to new approach be decisive. Unless es to early detection and treatment International cooperation can these initiatives prove their effcacy, using improved awareness of symp enable countries to avoid common feasibility, and cost-effectiveness tomatic disease and population pitfalls in the implementation of in those settings, population-based based screening of asymptomatic screening programmes and other programmes are unlikely to be es people. Success in decreasing the bur share knowledge about successful Population-based screening den of cancer will depend on the methods and approaches. Sharing programmes for breast, cervical, acceptance by the population of a of expertise may enable a country and colorectal cancer have been screening programme that is an to implement programmes more suc introduced as part of cancer con chored in a comprehensive and cessfully and to avoid unnecessary trol in many high-income countries. Population-based cancer screening gramme, and on the capacity of the programmes do not exist in most health-care system to make effcient 334 References 1. Pract Res Clin Gastroenterol, 24:381– tice regarding breast cancer and breast the impact of mammographic screening on 396. Cuzick J, Bergeron C, von Knebel Doeberitz dicators on an international level: the the European experience. New technologies and pro International Colorectal Cancer Screening Mex, 55:318–328. Latin Dublin, Ireland: National Cancer Screening Periodic breast cancer screening in reduc America Special Issue, 27:2. Control Assessment and Advice Requested Cancer Screening Working Group of the Available at Clinical trials Overview of the national cancer screen breast and cervix cancer screening in of cancer screening in the developing ing programme and the cancer screening Mumbai, India: methodology and interim world and their impact on cancer health status in Korea.

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Early talks on the foundation of the SGA. The meeting was held in Professor Amstutz's office at the University of Heidelberg on 19./20. June 1965. Sitting (from left) A. Maucher, Lombard, P. Routhier, P. Ramdohr, G.L. Krol; standing: A. Bernard and C. Amstutz.