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The Stanford V regimen is effective in patients with good risk Hodgkin lymphoma but radiotherapy is a necessary component. Multivariate normal tissue complication probability modeling of heart valve dysfunction in Hodgkin lymphoma survivors. Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors: a retrospective cohort study. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Long-term outcomes in patients with early stage nodular lymphocyte-predominant Hodgkin’s lymphoma treated with radiotherapy. Radiation is not medically necessary in the definitive or adjuvant treatment of renal cell cancer Fractionation I. A partial nephrectomy can be used in the treatment of early stage renal cell cancer while an open radical nephrectomy is used with locally advanced disease. There is no benefit with radiotherapy in the adjuvant or neo-adjuvant setting in the treatment of renal cell cancer (Escudier, 2014). In an individual with unresectable disease or recurrent disease, radiation can be utilized to improve local control (Mourad, 2014). However, there are no prospective studies examining this issue, and current standard of care for patients with inoperable localized renal cell cancer include radiofrequency or cryo-ablative therapies (Mourad, 2014). Page 151 of 311 Adrenal cancers include adrenocortical carcinoma and malignant pheochromocytoma. For nonmetastatic adrenocortical cancer, adjuvant radiation can be considered for an individual with high risk of recurrence including one with positive margins, ruptured capsule, large size (> 7 cm), or high grade (Sabolch, 2015). Adjuvant radiation therapy improves local control after surgical resection in patients with localized adrenocortical carcinoma. Solitary Plasmacytoma these lesions are diagnosed by a complete multiple myeloma evaluation to rule out the presence of other lesions or systemic disease. Solitary plasmacytomas of the bone generally involve the axial skeleton and account for almost seventy percent of clinical Page 153 of 311 presentations. The remaining are extramedullary lesions generally presenting in the upper aerodigestive tract. The optimal radiation dose for the treatment of these lesions is not well known, with doses ranging from 30 Gy to 60 Gy in the published literature. The largest series, with 258 patients, reported is the European Multicenter Rare Cancer Network study (Ozsahin et al. Thirty-three were treated with a combination of radiation therapy and chemotherapy. Sixty percent of the patients who did not receive radiation therapy relapsed locally, while only 12% of the radiation therapy group experienced local relapse. A 10-year probability of disease progression to multiple myeloma was 36% for extramedullary plasmacytoma and 72% for solitary plasmacytoma of bone. Considerable care must be taken in the workup of a suspected solitary plasmacytoma to ensure that other lesions and hence, a diagnosis of multiple myeloma, are not present. Following a positive biopsy of the lesion, a full multiple myeloma evaluation should be performed. Bone marrow aspirate and biopsy are mandatory to document the lack of clonal cells for a diagnosis of solitary plasmacytoma. A variant of solitary plasmacytoma, when there are fewer than 10% of clonal plasma cells is termed solitary plasmacytoma with minimal bone marrow involvement. In addition to the previous workup, diagnostic imaging plays an important role in securing the diagnosis. Following confirmation of the diagnosis, surgery may play a role in certain definitive clinical presentations or is performed for clinical presentations requiring neurologic decompression or stabilization of a weight-bearing bone prior to the performance of Page 154 of 311 radiation therapy. Lesions excised with positive margins or small, well-defined lesions may be treated with 40 Gy. Anatomic location, tumor size, surgical resection, older age at diagnosis and persistence of myeloma protein for one year post radiation treatment have all been postulated to be of prognostic significance but none have been definitely proven due to contrasting studies. Multiple Myeloma the role of radiation therapy in multiple myeloma is largely palliative with use of radiation dose regimens as listed in the Policy section of this guideline. Multiple Myeloma and Other Plasma Cell Neoplasms (Chapter 78) in Gunderson L, Tepper J, editors. Plasma Cell Neoplasms (Chapter 112) in Devita, Hellman, and Rosenberg’s Cancer Principles & Practice of Oncology, 10th edition. Outcomes and patterns of failure in solitary plamacytoma: a multicenter rare cancer network study of 258 patients. Radiation therapy for solitary plasmacytoma and multiple myeloma: guidelines from the International Lymphoma Radiation Oncology Group. Respiratory gating techniques and image guidance techniques may be appropriate to minimize the amount of critical tissue (such as lung) that is exposed to the full doses of radiation C. The treatment of lymphomas with radiation is generally done using relatively low doses in the range of 15 to 36 Gy at standard fractionation, sometimes with doses as low as 4 Gy in 2 fractions F. Doses of 36 Gy, to the original extent of disease for the following histologies: a. Sequential chemotherapy carries a high toxicity burden and requires substantial supportive care and the expertise of an experienced multidisciplinary team V. In an individual with advanced or recurrent disease that is felt not to be curative and who is experiencing symptomatic local disease, photon and/or electron techniques are indicated for symptom control 1. Treatment decisions are preceded by workup and staging and planned in conjunction with the appropriate members of the multidisciplinary team. Initial management requires chemotherapy as the cornerstone of therapy (in a variety of different acceptable regimens), followed by assessment of response leading to an appropriate choice of radiation therapy technique, dose, and use of radioimmunotherapy as clinically indicated. Radiation treatment may be given after initial chemotherapy to the original extent of disease i. Omitting sites that had no clear involvement in an effort to minimize toxicity ii. Generally encompassable in a single site setup, requiring the use of Complex or 3D techniques with image guidance iv. Radiation may be considered for an individual with a sub-optimal response to therapy 4. Consolidative radiation therapy after initial chemotherapy to a dose of 36 Gy to the original extent of disease for the following histologies: a. Long-term outcomes for patients with limited stage follicular lymphoma: involved regional radiotherapy versus involved node radiotherapy. Long-term outcome in localized extranodal mucosa-associated lymphoid tissue lymphomas treated with radiotherapy Cancer. High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas. Radiation therapy is considered medically necessary for the following noNon malignant disorders for which radiation therapy is medically necessary when criteria are met: A. Basalioma (see separate Guideline, Radiation Therapy of thefor Skin: Basal Cell, Squamous Cell, and Malignant Melanoma Cancers of the Skin) Cancer) H. Chemodectoma (carotid, glomus jugulare, aortic body, glomus vagale, glomus tympanicum [chromaffin negative]) K. Choroidal hemangioma (also see separate Guideline, Proton Beam Radiation Therapy) M. Total body irradiation used as preparation of patients for bone marrow or stem cell transplant I. Radiation Therapy is medically necessary for the following non-malignant disorders when there is failure, intolerance, or contraindication to established medical therapy and surgical treatments: Non-malignant disorders for which radiation therapy may be medically necessary when criteria are met (Note that all requests require review by an eviCore radiation oncologist): Angiomatosis retinae (von Hippel Lindau syndrome) D. Angofibroma of nasopharynx (juvenile nasopharyngeal angiofibroma) with extension into the orbital apex or base of skull C. Inflammatory (acute/chronic) disorders not responsive to antibiotics (furuncles, carbuncles, sweat gland abscesses) R. Vernal catarrh For specific details, including criteria needed to meet medical necessity and typical treatment regimen(s), please refer to the comprehensive list in the Key Clinical Points section of this Guideline.

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Effect of an uptake inhibi beta signaling in fbroblasts modulates the oncogenic poten tor on serotonin metabolism in rat brain: studies with 3-(p tial of adjacent epithelia. Inhibitory effect of fluoxetine on vasion and lymph node metastasis of carcinogen-induced lymphoma growth through the modulation of antitumor colorectal tumors. The role of ceramide in major de tion, clonality, and epithelial stem cells: the spread of mutat pressive disorder. Effect of antidepressants on body antioxidant action of selective serotonin re-uptake inhibitors. Antioxidant potential of fluoxetine in tal cancer risk in relation to antidepressant medication comparison to Curcuma longa in restraint-stressed rats. Antioxidant activity of fluoxetine: studies in fects against colon cancer development in epithelial and mice melanoma model. Dif 70 Yang Z, Li C, Wang X, Zhai C, Yi Z, Wang L, Liu B, Du B, ferential induction of apoptosis by antidepressants in glioma Wu H, Guo X, Liu M, Li D, Luo J. Dauricine induces apop and neuroblastoma cell lines: evidence for p-c-Jun, cyto tosis, inhibits proliferation and invasion through inhibiting chrome c, and caspase-3 involvement. Stimula catenin/p65 downstream signaling pathway and colon car tion of malignant growth in rodents by antidepressant drugs cinogenesis in rats. How cancer metabolism is tuned for lism: mitochondria are the powerhouse and Achilles’ heel of proliferation and vulnerable to disruption. Antide cancer metastasis: visualizing tumor cell mitochondria and pressants inhibit proton currents and tumor necrosis factor-α the “reverse Warburg effect” in positive lymph node tissue. Systematic analysis of cell cycle effects of common drugs standing the aging and cancer connection. Con to emerge, and by combining the efforts from all re ventional treatment approaches such as surgery, radiation, searchers in this area, a fnal panel of ideal markers can be chemotherapy, or a combination thereof have had little [26-28] developed to combat this dreadful disease. Therefore, these studies em frmed, and also validated for their diagnostic potential in phasize that the hope for better control of this disease is an independent cohort of eleven early stage pancreatic through diagnosis at its earlier stages when surgical resec cancer patients. Written informed late stage disease, or in determining operability or moni consent was obtained from all study participants. The toring patients for recurrence, these markers have gener pancreatic cancer patient group included stage ⅡA/Ⅱ ally inadequate specificity and unreliable sensitivity to B patients whose stage was confirmed post-operatively pancreatic cancer and are not recommended for screen by pathologists from the Valley Hospital. The high risk group included eleven healthy par event and play important roles in tumorigenesis, cancer ticipants who had a strong family history of pancreatic [12] development, migration and metastasis. The log2 transformed spot intensities for all 8816 features were degree relatives” having a pancreatic cancer diagnosis. The mean probe intensities for each of the prior pancreatic cancer surgery, had other concomitant 1209 human probes on each of the 20 arrays were then cancers other than non-melanoma basal cell skin cancer, determined by averaging the triplicate spot intensities. Spots fagged as poor quality during data extraction were omitted prior to averaging. The microarrays were produced ibility of the arrays was determined by monitoring the by Microarrays Inc. Differential expression analysis: For statistical analysis, Sample processing: Samples were isolated from 0. Genes were median-centered Data pre-processing: Spot intensities were obtained prior to hierarchical clustering. Remarkably, as depicted in the hierarchical dendrogram, the clustering pattern clearly separates the pancreatic cancer from most healthy con B trols. The dendrogram on top consistent signals (data not shown) and therefore were indicates the hierarchical clustering relationship between pancreatic cancer pa chosen for the subsequent confrmation study. Validation study with 11 stage ⅡA/ⅡB pancreatic cancer patients and 11 healthy controls. However, Carlsen et al used chronic of the let-7 family (especially let-7d) and miR-146a to pancreatitis patients as controls instead of normal healthy [26] be signifcantly lower in cancer. Also, the gene expression profile should resemble early stage [26] Liu et al screened for pancreatic cancer patients from pancreatic cancer more closely than advanced stage can all stages (13. Functionally, miR-885-5p is found to be located in the Our plan is to study an expanded sample of patients to 3p25. The authors are grateful for the generous support from MiR-22 has been proposed as a potential serum marker [52] the community of the Valley Hospital, including the De for non-small cell lung cancer, esophageal squamous [53] [54] partment of Oncology Clinical Trials for patient follow cell carcinoma, and nasopharyngeal carcinoma. The authors also Our experimental strategy in this study focused on want to thank Dr. Lawrence Harrison of the Valley Hos using hybridization-based microarray technology as the pital for enrolling patients, and Drs. Gastroenterology sessment and prognostic panels eventually developing into clinical tests. If it is effective, pancreatic cancer detection can be per ers in gastrointestinal cancer. J Clin Oncol 2006; 24: 5313-5327 formed by a simple non-invasive blood draw instead of an invasive procedure. Furthermore, the authors have 13 Navon R, Wang H, Steinfeld I, Tsalenko A, Ben-Dor A, Yakhi included a group of high risk individuals as controls. Minute carcinoma of the pancreas tumor suppressor gene expression in pancreatic cancer measuring 1 cm or less in diameter-collective review of cells. Tumor suppres 35 Lubezky N, Loewenstein S, Ben-Haim M, Brazowski E, sor miR-22 suppresses lung cancer cell progression through Marmor S, Pasmanik-Chor M, Oron-Karni V, Rechavi G, post-transcriptional regulation of ErbB3. Molecular genetics of ductal pancreatic escence by suppressing the interferon response and cell-cycle neoplasia. Hot topic articles refer to papers that are included improve diagnostic and therapeutic skills of clinicians. These commentary articles should nutritional support, molecular mechanisms, and therapy of benign focus on the status quo of research, the most important research and malignant tumors of the digestive tract. Basic information about medical ethics, original articles, case report, clinical case conference the article to be commented (including authors, article title, journal (Clinicopathological conference), and autobiography. Priority pub name, year, volume, and inclusive page numbers); (6) Minireviews: lication will be given to articles concerning diagnosis and treatment the editorial board members are invited to write short reviews on of gastrointestinal oncology diseases. The following aspects are cov recent advances and trends in research of molecular biology, genom ered: Clinical diagnosis, laboratory diagnosis, differential diagnosis, ics, and related cutting-edge technologies to provide readers with the imaging tests, pathological diagnosis, molecular biological diagnosis, latest knowledge and help improve their diagnostic and therapeutic immunological diagnosis, genetic diagnosis, functional diagnostics, skills; (7) Review: To make a systematic review to focus on the status and physical diagnosis; and comprehensive therapy, drug therapy, quo of research, the most important research topics, the problems surgical therapy, interventional treatment, minimally invasive thera that have now been resolved and remain to be resolved, and future py, and robot-assisted therapy. The topic covers general biography: the editorial board members are invited to write their clinical diagnosis, differential diagnosis, pathological diagnosis, lab autobiography to provide readers with stories of success or failure in oratory diagnosis, imaging diagnosis, endoscopic diagnosis, biotech their scientifc research career. The topic covers their basic personal nological diagnosis, functional diagnosis, and physical diagnosis; (4) information and information about when they started doing re Therapeutics Advances: the editorial board members are invited search work, where and how they did research work, what they have to write high-quality therapeutic advances in their feld to help im achieved, and their lessons from success or failure. Standard deviations are preferred to of Gastroenterology, Gastrointestinal Oncology, School of Medicine, standard errors. Referees are also asked to indi Jin-Lei Wang, Director cate any potential conflict they might have reviewing a particular Xiu-Xia Song, Vice Director paper. Before submitting, authors are suggested to read “Uniform World Journal of Gastrointestinal Oncology Requirements for Manuscripts Submitted to Biomedical Journals: Room 903, Building D, Ocean International Center, Ethical Considerations in the Conduct and Reporting of Research: No. Fax: +86-10-85381893 Sample wording: [Name of individual] has received fees for serv E-mail: bpgoffce@wjgnet. Wanchai, Hong Kong, China Telephone: +852-65557188 Statement of informed consent Fax: +852-31779906 Manuscripts should contain a statement to the effect that all human E-mail: bpgoffce@wjgnet. Details that might disclose Production center the identity of the subjects under study should be omitted. Generally, we suggest authors follow the lead investigator’s na Telephone: +1-925-2238242 tional standard. If doubt exists whether the research was conducted Fax: +1-925-2238243 in accordance with the above standards, the authors must explain the rationale for their approach and demonstrate that the institutional Instructions to authors review body explicitly approved the doubtful aspects of the study. If human participants were involved, manuscripts must be ac Indexed and Abstracted in companied by a statement that the experiments were undertaken with PubMed Central, PubMed, Digital Object Identifer, and Direc the understanding and appropriate informed consent of each. For the Correspondence to: Only one corresponding address should be sake of transparency in regard to the performance and reporting of provided. The only register now avail A space interval should be inserted between country name and email able, to our knowledge, is. Tele Authors should retain one copy of the text, tables, photographs phone: +86-10-85381891 Fax: +86-10-85381893 and illustrations because rejected manuscripts will not be returned to the author(s) and the editors will not be responsible for loss or Peer reviewers: All articles received are subject to peer review. Decision on accept ance is made only when at least two experts recommend publication Online submissions of an article. All peer-reviewers are acknowledged on Express Sub Manuscripts should be submitted through the Online Submission mission and Peer-review System website. The specifc requirements for structured abstracts tering problems with the Online Submission System may send an are as follows: email describing the problem to bpgoffce@wjgnet. Abstracts of original contributions should be struc not make a postal contribution.

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Death Rates and 5-Year Relative Survival (Percent) By Primary Cancer Site, Sex and Time Period. Source 7 b: Seabury, “Quantifying Gains in the War on Cancer Due to Improved Treatment and Earlier Detection,” Forum for Health Economics and Policy 2016; 19(1): 141–156 that states. The Rising Cost of Medical Care: Understanding the Problem and Exploring Solutions. The International Myeloma Foundation Says New Studies Show Longer Survival for Myeloma Patients and Improved Response to Treatments. Longer treatment duration and better adherence may improve outcomes for the patient. The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Lower pain symptoms in breast cancer survivors compared with the general population were reported in one prior study. Table 22: Life expectancy at birth, at age 65, and at age 75, by sex, race, and Hispanic origin: United States, selected years 1900-2010. The value of increasing the quality and length of life is substantial; longer life and greater well-being lead to greater productivity and economic growth. National Health Expenditures; Aggregate and Per Capita Amounts, Annual Percent Change and Percent Distribution: Selected Calendar Years 1960-2012. Biopharmaceutical companies invest approximately more than 12 times the amount of R&D dollars per employee than manufacturing industries overall. R&D Expenditures per Employee by Manufacturing Industry, 2000‐2013 Biopharmaceuticals* 147,281 Semiconductors* 57,755 Chemicals 55,717 Computers and electronics 47,084 Celgene’s 2016 R&D expenditure per employee is Aerospace* 23,231 ~$626,573 Medical equipment 20,098 Transportation equipment 16,986 Petroleum & coal 10,994 *Manufacturing subsectors Source 5: Celgene data on file. Investment in the •••••••••••••• jobs and added $67 billion to Human Genome Project the U. Note: Represents all clinical trials Phase 2 through Phase 4 that registered with clinicaltrials. Also excluded are nonclinical R&D such as basic and preclinical research and the significant economic contribution from non-R&D activities of the industry such as manufacturing and distribution. National Health Expenditures; Aggregate and Per Capita Amounts, Annual Percent Change and Percent Distribution: Selected Calendar Years 1960 2012. Celgene Annual Reports 2015 reflect average research and development investment of 32. Medical innovation is transforming certain types of cancer from leading causes of death to long-term, manageable diseases while also reducing the overall strain on healthcare systems. By improving health, medicines can reduce hospital admissions and reduce the use of costly medical services. These advancements coupled with improved access to medicines can result in a decrease of overall healthcare costs. Medical innovation has allowed for significant changes in the treatment for cancer care. Increasingly, cancer will be managed by preventing and controlling cancer through genetic biomarkers and precision medicine with the hope of stopping the cancer as quickly as possible. And while new cancer therapies may have a positive impact for patients, it cannot be sustained without a balance in the virtuous cycle of medical innovation. New medicines continue to be a major contributor to improvements in life expectancy. The impact of new drug launches on longevity: evidence from longitudinal disease-level data from 52 countries, 1982-2001. Countries include Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Japan, Korea, Luxembourg, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States. Reductions in mortality among Medicare beneficiaries following the implementation of Medicare Part D. The interviews were conducted online and the data were weighted to approximate a target sample of seniors based on age, race/ethnicity and gender. Results from the full survey have a margin of error of plus or minus 2 percentage points. Actual Growth in Specialty Medication Spending From a Major Pharmacy Benefits Management Company* 24% 27% 17% 27% 17% 18% 19% 18% 14% 2011 2012 2013 Forecasted 2 years prior Forecasted 1 year prior As reported for year * As reported in annual Drug Trend Reports from Express Scripts. Table L1: National Cancer Treatment Expenditures in Billions of Dollars (1963-2004). Of First Full 2 3 4 5 6 7 8 9 10 11 12 Before Generic Month Generic Entry Entry Number of Months After First Generic Entry * Average monthly generic share of total standardized units of unique molecule/form combination Source 20: Pharmaceutical Research and Manufacturers of America. Prescription Drug Prices Fall Significantly Over Time Once Generic, Promoting Innovation and Affordability Daily Cost of Top-10* Therapeutic Classes Most Commonly Used by Part D Enrollees Has Declined Brand Generic % 1. Department of Health and Human Services, Agency for Healthcare Research and Quality, Medical Expenditure Panel Survey, 2014. Analysis includes individuals with any source of health care coverage, public or private; this includes individuals who had health coverage without coverage for prescription drugs, which can be expected to account for less than 2% of those with health coverage. Source 27 a: Kaiser Family Foundation/Health Research & Educational Trust, Employer Health Benefits: 2015 Annual Survey. Coinsurance can make a patient’s out-of-pocket costs Coinsurance 74% difficult to predict – and potentially much higher – than fixed-dollar copays. Plans subject different medicines to different levels of cost sharing, or “tiers”. Medicines assigned to a “specialty tier” typically require the highest level of cost sharing. Avalere Health Release Majority of Drugs Now Subject to Coinsurance in Medicare Part D Plans. France United Australia Scotland Sweden Gerrmany Italy Canada Spain Kingdom Reimbursed Not Reimbursed Note: the categorization of “not reimbursed” does not mean that there is no patient access to these medicines, and there may be non-standard means for obtaining access to new medicines through special funds and submission of applications for approval outside of standard guidelines. Impact of cost sharing on specialty drug utilization and outcomes: a review of the evidence and future directions. Higher patient cost sharing is associated with prescription abandonment and delay in fills of novel oral oncolytic prescriptions. Pharmaceutical innovation and longevity growth in 30 developing and high-income countries, 2000-2009. Implementation of Medicare Part D and Nondrug Medical Spending for Elderly Adults With Limited Prior Drug Coverage. Implementation of Medicare Part D and nondrug medical spending for elderly adults with limited prior drug coverage. Table 111 Gross domestic product, national health expenditures, per capita amounts, percent distribution, and average annual percent change: United States, selected years 1960–2011. This section will highlight the importance of sustaining and spreading innovation throughout the world. The alternative would create the negative impact of halting medical progress and advancements in cancer, including its effect on survival, death, prosperity and progress. The cost and commitment necessary to keep our promise of a world free from cancers is increasing – and the investment required is not keeping up. Impeding innovation and interrupting the virtuous cycle of medical progress will cost both lives and economic growth. Fortunately, we know what is needed to sustain the incentives for investment in innovation to continue medical progress in the 21st century. Emerging combinations of medicines hold particular promise for controlling and killing cancer cells. Louis Weiner help target and kill cancer cells by Director of the Georgetown “releasing the breaks” on the Lombardi Comprehensive Immunotherapies ” immune system Cancer Center Source 3: World Medical innovation Forum: Cancer. Public and private sector contributions to the research & development of the most transformational drugs of the last 25 years. Time Between Approval of First and Second Medicines in a Pharmacologic Class 12 10 of second medicines in a class were approved within 2. However, ongoing research revealed that patients with a specific mutation demonstrated significant survival gains. Accelerated Indication limited Approved for “Gefitinib is a textbook example approval as to those currently first-line use in of how much oncology has second– or third– benefiting from patients with changed over the past decade.

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The endocervical canal and the underlying crypts are covered by mucin-secreting columnar epithelium. The visualisation of the portio and the localisation of the transformation zone are essential for the collection of an adequate smear. A: Squamous cells B: Metaplastic cells C: Columnar cells An exo and endocervical smear give the best guarantee to find cytological abnormalities. Microscope slide, pencil, gloves, sampling devices, fixative, slide holder and request form. After insertion of the vaginal speculum the cervix is visualised and the position of the transformation zone is checked. Specimen collection using Cervex-Brush R the rubber bristles of the Cervex-Brush are flexible and adapt themselves to most of the cervixes. The central bristles of the Cervex-BrushR are inserted with gentle pressure in the endocervical canal until the lateral bristles bend against the exocervix. The broom is then turned five times 360° by rolling the handle clockwise between thumb and index finger. Transferring the sample to the slide using Cervex-Brush the sample is spread onto the slide with a painting action, using both sides of the brush. An exocervical smear should be taken using the end of the spatula which corresponds best with the anatomy of the cervix (the Aylesbury pole in nullipara and the Ayre pole in multipara). The whole circumference of the exocervix is sampled under gentle pressure with the broad end of the spatula. Collection of an endocervical smear with the Cytobrush the brush is inserted for two thirds in the endocervical canal and gently rotated 90° to 180°. The material on the spatula is spread in a thin layer in one movement over the middle third of the slide. Standard request form the fixed specimen is left to air dry and subsequently packed in the holder. Three categories are distinguished: satisfactory (synonyms: adequate, optimal) satisfactory for evaluation but limited by (qualify with reason) (synonym: suboptimal) unsatisfactory (qualify with reason), (synonym: inadequate or poor) Four kinds of criteria are used for the quality evaluation of the smear: identity details of the woman and specimen, availability of adequate and pertinent clinical data, cellular composition and technical interpretability. The quality of the smear to a great extent determines the accuracy of the cytological interpretation. Below is the definition of the three categories of quality evaluation: Satisfactory Satisfactory labelling of the specimen matching the identification details on the request form. The requirement for the presence of a transformation zone/endocervical component does not change with age and applies equally for pre and post menopausal women. The presence of metaplastic squamous cells and/or columnar cells as well as squamous cells or mucus indicate that the transformation zone has been sampled. On the basis of the cellular composition alone, the cytologist cannot guarantee that the entire circumference of the transformation zone has been sampled. Satisfactory for evaluation but limited by Between 50% and 75% of the specimen cannot be read because of interfering elements (blood, inflammation, aggregation of cells, defective fixation, drying artefacts, cytolysis, contamination etc. Unsatisfactory Too few squamousl cells: well-preserved and recognisable squamous cells covering less than 10% of the area of the smear. Smears in which abnormalities of the epithelial cells are discovered are not labelled “unsatisfactory”. With the specification of “satisfactory for evaluation but limited by” and ”unsatisfactory” the reason is given (see Table 2). Quality evaluation 0 Satisfactory 0 Satisfactory but limited by 0 Unsatisfactory Reasons:  exclusively endocervical cells  too much blood, pus  no endocervical cells  extensive cytolysis  poor or unsatisfactory fixation  poor smear technique  too little cellular material  other. Thompson [1989] considers the finding of squamous metaplasia to be a strong indication that a sample has been taken from the target zone. The presence of endocervical columnar cells proves that cellular material from beyond the transformation zone has been included in the specimen. The presence of squamous metaplastic and/or columnar cells as well as pavement cells, however, does not prove that the entire transformation zone was sampled. Many observations support the thesis that the presence of endocervical or metaplastic squamous cells increase the likelihood of finding cytological lesions. A few recent longitudinal studies do not support this contention [Kivlahan, 1986; Mitchell, 1991]. Mitchell [1992] was able to confirm this correlation only for the presence of metaplastic, but not for columnar endocervical cells. Boon [1993] stands by the contention that the presence of immature metaplastic cells and/or columnar cells is associated with the detection of high-grade intra-epithelial lesions. If low grade lesions are also included in the definition of a positive smear, this connection disappears. Boon [1993] also reports that the progressive nature of squamous cell lesions increases the closer they are to the metasquamo-columnar junction and therefore also pleads for double endocervical/exocervical sampling. Histological examination of conisation material and colposcopic observations confirm this latest thesis [Burghardt, 1998]. The exclusive presence of columnar cells (with no squamous cells) indicates a non-representative smear. Oorsprong staal £ cervix £ vagina Gynaecologische status Vorig uitstrijkje Datum laatste menses. Afname-instrument Gevolgde therapie £ Gecombineerde spatel £ Chemotherapie £ Pelvische radiotherapie £ Spatel en Cytobrush £ Anti-oestrogenen £ Cervex-Brush £ Andere:(preciseer) Andere relevante inlichtingen uit de anamnese of het klinisch onderzoek. A smear taken unsatisfactorily is a significant cause of false negative and false positive results. Below is a concise summary of “A technical guideline: collection of adequate Pap smears of the uterine cervix” compiled by the technical Sampling Working Group. The aim is to propagate the consensus amongst all general practitioners, gynaecologists, pathologists and other healthcare workers involved in the detection of cervical cancer in Flanders. Therefore, it is important that cell material be sampled primarily from this zone. An optimum smear contains metaplastic and columnar endocervical cells as well as squamous cells. The presence of significant quantities of blood cells or inflammatory cells can reduce the quality of the smear. Quality evaluation of the smear (satisfactory, satisfactory but limited and unsatisfactory) is an essential component of the cytology report. Contra-indications for screening smears Total hysterectomy, cervical amputation, and the presence of a suspect, macroscopically visible lesion in the area of the cervix are contra-indications for screening. In the latter case, the woman must be referred for colposcopic examination and/or biopsy. Factors adversely affecting the quality of a smear the quality of a smear is adversely affected by. Information to the woman the woman is informed of the aim of the smear and its procedure. She is informed that sometimes the examination has to be repeated within 3 to 6 months, if the smear was not of satisfactory quality. The doctor makes a clear arrangement how the woman will be notified of the laboratory result. If there is extreme retro or anteversion of the uterus, the cervix can be manipulated into a good position with a pair of closed atraumatic forceps. Excessive mucus, discharge or blood can be removed carefully with a swab (not wiped away). Sampling devices Cervical screening always requires an endocervical and an exocervical sample, taken with the appropriate instruments. The wooden spatula (Figure 1a) with an Ayre end and Aylesbury end (with elongated tip) is best. The combination method is best if the squamocolumnar junction is high (often post menopausal), after cervical surgery or if there is extensive ectropion of the columnar epithelium. Cervex-Brush Endocervical cells and exocervical cells are sampled simultaneously the long bristles pick up endocervical cells while the short bristles collect exocervical cells. If closer, the cells are blown away or frozen, if on a slant, the material is blown into aggregates. A very fast fixation, within a few seconds, is essential to prevent drying artefacts.

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While non-serious adverse events were frequent, the majority of these events resolved. Compliance with device usage was quite high suggesting that patients regarded therapy as beneficial despite the minor discomforts and need for multiple stimulation adjustments. Any adverse events will be summarized by seriousness, severity, relatedness to the device and temporal relationship to the procedure. Data will be analyzed in a descriptive fashion using 95% confidence limits for the estimates. New Enrollment Study: this study will be conducted as per protocol dated March 19, 2014, Version 1. This is a multi-center, prospective, single arm cohort study to evaluate long-term device safety and effectiveness. The study will also evaluate effectiveness of physicians’ training program in a postmarket setting. Safety endpoints will be collected to evaluate: long-term device-related serious adverse events, therapy-specific adverse events. Physician training measures of post-operative safety outcomes must include surgical times, post-operative pain recovery, procedure related adverse events, and post operative comments. Subjects must be evaluated at baseline, during implant, at 1-, 2-, 6-, and 12-months post-implant, and every six months thereafter through 5 years of post-implant follow-up. A one-sided binomial exact test will be used to test if long term device related serious adverse events is less than a performance goal of 24% at 5 years. For therapy specific adverse events non-inferiority test with a margin of 5% using the Bayes Factor at 12 months post implant will be used. All therapy and procedure-related adverse events will be described and summarized by seriousness, severity, relatedness, and temporal relationship to the device and/or procedure. Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, Precautions, and Adverse Events in the device labeling. Papanikolaou" General Hospital, Aristotle a1111111111 University of Thessaloniki, Thessaloniki, Greece a1111111111 * gtrakada@hotmail. We conclude that sleepiness, anxiety and depression were similar in both groups, Funding: the authors received no specific funding whereas fatigue was more prominent in patients with overlap syndrome than in sleep apneic for this work. The prevalence of overlap syndrome in adults aged 40 years and over is estimated about 0. Both diseases are characterized by severe clinical symptoms and are associated with signifi cant morbidity and mortality. Thus, one could anticipate that patients with overlap syndrome may have a worse symptomatology and prognosis than patients with only one of either disease. Moreover, a strong association exists between anxiety and depression and sleep apnea [9]. Written informed consent was obtained from all individual participants included in the study and the study protocol was approved by the Ethical Committee of the “Alexandra” University hospital, before the initiation of the study. Any patient who had dyspnea, chronic cough or sputum production, and / or history of exposure to risk factors for the disease underwent spirometry and static lung volumes measurement to confirm the presence of persistent airflow limitation. At baseline, each patient underwent clinical examination, oximetry (model 8800, Nonin Medical, Inc. Grading ranges from 1 (strong disagreement) to 7 (strong agreement) where the final score is the mean value of the nine items, and a score! Sleep records were scored according to standard criteria and manually revised by an expert [17]. At the end of the 3 months period of therapy, the patients were reassessed using the same protocol. Normality of the parameters’ distribution was assessed with the Wilks-Shapiro test. The parameters which were not normally distributed were compared with the Kruskall Wallis test. No statistically significant difference was observed in the number and the type of comorbidities between the two groups. The control subjects had higher anxiety and margin ally higher depression scores than both patient groups [F(2, 70) = 4. Sleepiness express a subjective difficulty in maintaining an awake state, and an increase ease of falling asleep when a person is sedentary. Moderate to severe excessive daytime sleepiness is observed in about 10% of the general population accord ing to a large epidemiological study [19]. In sleep clinics, sleepiness is a cardinal symptom, mainly due to sleep fragmentation, as a result of apnea or due to sleep deprivation, as a result of socioeconomics conditions (work, life style etc. In a previous study, fatigue, tiredness, and lack of energy were more often reported when compared to sleepiness (57%, 61%, and 62% vs 47%, respectively) and the one most significant symptom was lack of energy (about 40%) than any other problem, including sleepiness (about 22%) [25]. Psychiatric comorbidities, like depression and / or anxiety, are often observed in patients suffering from chronic somatic diseases. In general popu lation, the prevalence of anxiety disorders is 14% and of depressive disorders 7. These symptoms affect the quality of life and the prognosis of the patients, and are independently associated with poorer adherence to therapy [31]. Finally, we did not record sleep habits (time in bed, naps) and dura tion that can act as confounding factors in symptoms. Our control subjects had higher anxiety and marginally higher depression scores despite better lung function and better sleep. Possibly this finding reflects a lurking somatoform disorder in some of them, taking into account the fact that their workup results were normal despite their reported complaints. Fatigue should be evaluated whenever there is clinical suspicion of overlap syndrome. Data curation: Nicholas-Tiberio Economou, Ioannis Ilias, Lemonia Velentza, Yiannis Papa chatzakis, Anastasios Kallianos, Georgia Trakada. Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical Guideline for the Evaluation, Management and Long-term Care of Obstructive Sleep Apnea in Adults J Clin Sleep Med. Clinical guideline for the eval uation, management and long-term care of obstructive sleep apnea in adults. Mermigkis C, Kopanakis A, Foldvary-Schaefer N, Golish J, Polychronopoulos V, Schiza S, et al. Health related quality of life in patients with obstructive sleep apnoea and chronic obstructive pulmonary dis ease (overlap syndrome). Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression. Prevalence of reported sleep disturbances in a general adult population and their relationship to obstructive airways diseases. Excessive Daytime Sleepiness in Sleep Apnea: It’s Not Just Apnea Hypopnea Index, Sleep Med. Fatigue and multidimensional disease severity in chronic obstructive pulmonary disease. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Christodoulou C, Michopoulos J, Tournikioti K, Douzenis A, Bouras G, Seretis D, et al. The effect of treating obstructive sleep apnea with positive airway pressure on depression and other subjective symptoms: A systematic review and meta-analysis. Uncited references: References that occur in the reference list but are not cited in the text. N/A Missing references: References listed below were noted in the text but are missing from the reference list. Anthropologists have understood for decades that dies such as dental caries, periodontal disease and malocclu human craniofacial volume has been steadily diminishing sion. Similar to what is now understood about why might yield warning signs that a child might be suffering from diabetes and periodontal disease often coexist in the same impaired ability to breathe properly during sleep. Per the various comorbidi now have a higher frequency of patient encounters than do ties associated with various surgical interventions, wherever most other allied health professionals.

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Other promising tar cervix, and corpus uteri; they show fallopian tube, and peritoneum has gets currently being studied based sheets or tubules of malignant cells been proposed by the International on ovarian cancer biology include with clear cytoplasm (Fig. Factors affecting transmission of terminology standardization project for velopments in vulvovaginal pathology. Human papillomavirus and cervical adenocarcinomas and squamous cell car Oncol Hematol, 68:131–156. Population-level impact of the biva the molecular biology of endometrial can cers and the implications for pathogene tibility loci for ovarian cancer at 2q31 and lent, quadrivalent, and nonavalent human 8q24. Sankaranarayanan R, Gaffkin L, Jacob in patients with recurrent endometrial carci N Engl J Med, 363:1532–1543. Uterine Cancer: cancer and hormone-replacement ther tation frequencies and cancer penetrances. Individuals who do not fulfl have been related to normal coun any of these criteria but who have. Subsequently, incidence rates have stabilized, while mortal ity rates have declined in some settings. There are no There is great interest in prognostica in only up to about 10–15% of cases. The hope is that Genome-wide association studies sequencing studies have demonstrat this new knowledge may lead to more have revealed multiple susceptibility ed numerous recurrent mutations in targeted and effective therapies. Estimated global number of new cases and deaths with proportions by major world regions, for lymphoma in both sexes combined, 2012. Age-standardized (World) mortality rates per 100 000 by year in selected populations, for lymphoma in 100 000 by year in selected populations, for lymphoma in men, circa 1975–2012. The disease ranks as the 11th most frequent in terms of cancer incidence and the 10th most common cause of cancer death. Mortality rates have fallen for certain subtypes in higher-income countries due to improving therapeutics. Hairy cell with other malignancies such as vide another therapeutic target with Chapter 5. Estimated global number of new cases and deaths with proportions by major world regions, for leukaemia in both sexes combined, 2012. Age-standardized (World) mortality rates per 100 000 by year in selected populations, for leukaemia in 100 000 by year in selected populations, for leukaemia in men, circa 1975–2012. Most B cells are activated within the germinal centre, but T-cell independent activation can take place outside the germinal centre. The disease is more renal insuffciency, anaemia, bone common in African Americans than Plasma cell myeloma lesions). Plasma cell myeloma, sometimes referred to as multiple myeloma, is ing) myeloma requires a serum a bone marrow-based, disseminated paraprotein level of more than 30 g/l Genetics neoplasm composed of monoclonal and/or at least 10% clonal bone mar Upregulation of one of the cyclin post-germinal centre long-lived row plasma cells and no myeloma D genes due to hyperdiploidy or plasma cells, which must be distin associated end-organ damage or translocations involving the immuno guished from monoclonal gammop myeloma-associated symptoms. Symptomatic plasma cell myelo are more than 2 × 109 circulating Other important early events seen ma requires a serum and/or urine peripheral blood plasma cells/l or in a signifcant minority of patients monoclonal paraprotein, clonal they make up more than 20% of all include monosomy 13 or 13q14 Chapter 5. Mature T cells include αβ and γδ T cells, both of which mature in the thymus gland. Primary duodenal genetic and epigenetic events and on the number of centroblasts pres follicular lymphoma is also distinc pathways are implicated in disease ent. Etiology, pathology, and molecular differences [8], and from genetics in situ follicular lymphoma/intrafol Etiology and pathology Follicular lymphoma is diagnosed licular neoplasia/follicular lympho the etiology of mantle cell lympho based on its morphological features, ma-like B cells of uncertain/unde ma is unknown. Known gene alterations leading to constitutive pathway activity are shown in colour. The other variant that may not rep resent an overt malignancy is in situ mantle cell lymphoma/mantle cell lymphoma-like B cells of undeter mined/uncertain signifcance. These cases lack architectural destruction and show partially infltrated follicu lar mantle zones, often at the mantle zone/germinal centre interface. Historically, it had been dif Marginal zone lymphoma lymphomas) are relatively common; fcult to distinguish lymphoplasma and lymphoplasmacytic they have been reported in nearly cytic lymphoma from marginal zone lymphoma every anatomical site but are most lymphomas as both show evidence of these diseases are post-germinal frequent in the stomach, lung, and plasmacytoid differentiation. A boy with Burkitt lymphoma receives treatment at Banso Baptist Hospital Burkitt lymphoma in Cameroon. Endemic Burkitt lymphoma is prevalent in equatorial Africa, corresponding in distribution to the malaria belt. Recent studies using genomic sequencing have identifed recurrent somatic mutations that provide new insights into the pathogenesis of Burkitt lymphoma (reviewed in [19]). Mutations in rarely encountered in marginal zone B-cell-like group, and primary me this pathway were seen in sporadic lymphomas, facilitating distinction of diastinal (thymic) large B-cell lym and immunodefciency-associated these groups. The third group shares many features with classic Hodgkin lym what lesser proportion of endemic Diffuse large B-cell phoma, showing activation of the cases of this disease. The capacity of our immune patients include the stratifcation of low levels, allowing immediate inter systems to recognize millions of patients into treatment risk groups vention to treat molecular disease. Epigenetic alterations may be lecular pathogenesis of most periph Hodgkin lymphoma. Both are de responsible in part for loss of the eral T-cell lymphomas remains to be rived from B cells, but the B-cell B-cell programme [22]. Currently, karyotype and age are the most powerful predictors of prog nosis [26,27]. However, not terized by increased blasts (usually methyltransferases in normal and all cytogenetic abnormalities are ≥ 20% myeloblasts, monoblasts plus malignant haematopoiesis”) [29]. Serial Haematopoietic stem cell-spe in regulating gene expression during stem cell transplantation augments cifc Dnmt3b knockout mice and development and is known to be dis this effect, such that phenotypically Dnmt3a-Dnmt3b double-knockout turbed in a variety of malignancies. The differentiated progeny of to malignant transformation com pared with the oncogene or Dnmt3a Murine haematopoietic stem Dnmt3a knockout haematopoietic knockout alone. Using con genes that are normally repressed methyltransferases found in human ditional knockout mice, the role of during differentiation. Nat Genet, haematopoietic stem cell self-re observed in the mice within the time 44:23–31. These locytosis, followed by an accelerated cessive production of differentiated additional abnormalities may ac phase and/or a myeloid or lymphoid myeloid cells, which are sometimes count for the only modest success blast phase. The development of diffcult to distinguish from reactive to date using tyrosine kinase inhibi tyrosine kinase inhibitors has dra marrow proliferations. Genome-wide association study of B cell predictors of outcome in acute lympho dx. Leuk Lymphoma, Follicular lymphomas in children and young nisms in Burkitt lymphoma. Mihm Jr Massimo Tommasino (reviewer) tanning devices, particularly in In addition to genetic factors, ul Summary young people, is the most effec traviolet radiation from sun exposure tive way to prevent melanoma also contributes to melanoma devel-. Most melanomas (80%) are gressive human cancer; over the caused by ultraviolet damage to sen past few decades, its incidence sitive skin, i. Most damage melanoma is a malignant prolifera nant melanoma varies mark caused by sunlight occurs in child tion of melanocytes, the pigment edly according to racial back hood and adolescence. Etiology posure, especially during childhood Ultraviolet-emitting tanning de Environmental factors play impor and early adolescence, for example vices increase the risk of malig tant roles in melanoma development through indoor tanning; children and nant melanoma. Only 20–30% of Melanoma may occur anywhere adequate surgical excision; melanomas arise in association with on the skin, but in men most mela metastatic melanoma is largely a melanocytic naevus, but the pres nomas occur on the back, whereas resistant to current therapies. Other anatomical sites in fair-skinned pop which are malignant epithelial risk factors include family history of ulations show that melanomas aris neoplasms that often arise on melanoma and prior melanoma. In ing on intermittently exposed body sun-exposed areas of the skin addition, rarely germline mutations sites are signifcantly more common in fair-skinned populations. Rates are highest in countries with predominantly Caucasian populations, and more than 80% of the estimated new cases and close to 65% of the cancer deaths occurred in Oceania, Europe, and North America. Incidence rates tend to be rather low in most African, Asian, and Latin American countries. Of note is the (cohort-specifc) sta bilization and/or recent decline in incidence in certain high-risk populations. In low-risk populations (Asia, Africa, and to some extent Latin America), incidence rates have remained low and stable over time. Moreover, melanoma can occur in melanocytes are also present in the factors, is recommended [6]. The areas of the body without sun expo conjunctiva, the retina, and the menin most robust independent prognos sure as well as in any ethnic group. Melanoma can be subtyped his tic factor in melanoma is tumour tologically into superfcial spreading thickness (Breslow depth), found by Pathology melanoma, nodular melanoma, acral measuring the vertical depth from the Melanomas occur primarily in the skin – lentiginous melanoma, and lentigo granular cell layer of the epidermis more than 95% of cases – but are maligna melanoma. A staging sys to the deepest detectable melanoma also found in the mucous membranes tem based on the histopathological cell.

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Tarsal tunnel syndrome caused by an gluteal artery caused by non-typhi salmonella in a man anomalous muscle. Medial plantar digital proper nerve patient: anatomical considerations, aetiology and review of syndrome (Joplin’s neuroma): typical presentation. Joplin’s neuroma or compression pregnancy and after childbirth: an unusual case not to miss. Med caused by a huge iliopectineal synovitis extending to the iliac Sci Sports Exerc. The practice has evolved continually since Albee and Hibbs independently reported the frst cases in 1913, and advancements in both technique and patient selection continue through the present day. Clinical and radiological indications for surgery have been tested in trials, and other diagnostic modalities have developed and been studied. Fusion practices have also advanced; instrumentation, surgical approaches, biologics, and more recently, operative planning, have undergone stark changes at a seemingly increasing pace over the last decade. As the general population ages, treatment of degenera tive lumbar disease will become a more prevalent—and costlier—issue for surgeons as well as the healthcare system overall. This review will cover the evolution of indications and techniques for fusion in degenerative lumbar disease, with emphasis on the evidence for current practices. Justifcation for spinal stabilization has bilitating ailment, causing pain and disability in changed as our understanding of lumbar instability and L patients and burdening our healthcare system and spinal alignment has grown, and outcomes research has economy with high and ever-increasing costs. The preva more precisely defned those patients who do well with, lence of low-back pain due to lumbar spondylosis is esti or without, fusion procedures. However, fusion procedures have not been effective for all this paper will review and update modern indications patients, and as rates of both disease and treatments have and techniques in lumbar fusion for degenerative disease, risen, the number of patients undergoing unsuccessful fu including the best evidence to support current practices. Studies of fusion for low-back pain modern fxation, including interbody implants, and recent Authors & Evidence Description advances in operative planning and navigation. Aside from offering guidance in diagnosing degenera tive disease—importantly, ruling out more malignant con ditions such as infection or neoplasm—a careful history and physical examination will often offer clues as to which were statistically superior to conservative management. Ultimately, patients with severe disability from back pain the hallmark of mechanical back pain, due to degenera can improve with surgery, but the clinical examination is tion of the lumbar disc–joint complex, has classically been an imprecise tool for selecting these patients. Two studies have shown studies have demonstrated that this aspect of the patient improvement in chronic back pain (Table 1). Low-back pain may be re leave” from work for at least 1 year, had back pain greater ferred from sources other than the lumbar vertebrae, such than leg pain, and had high scores on validated, functional as the hip or the sacroiliac joint. Trochanteric bursitis is another common extra patients had failed a trial of conservative management. Radiculopathy and psychiatric fndings may be more useful in selecting candidates for disease were again among the exclusion criteria. Radiculopathy and/or back pain resulting from a her They enrolled only patients with high levels of disability niated disc is common. Patients undergoing fusion had better re 2009 surgery vs conservative management sults for low-back pain and recurrence, but overall clinical for low-back pain and lumbar spondy outcome scores were not signifcantly different. Patients update for the performance of fusion procedures for degenerative disease of undergoing fusion surgery had lower rates of revision and the lumbar spine. J Neurosurg Spine lower low-back pain scores than those undergoing only 21:2–6, 2014. Recurrent disc herniations following ini tial discectomy are more widely considered an indication for fusion, but again, supporting evidence is spare. Radiological signs spective study in which patients with recurrent herniation of instability can be inconsistent, and interpretations vary. Both prospective and retrospective tri cant difference in overall outcomes and high satisfaction als have indicated that patients with stenosis due to spon rates in both groups. Improved outcomes were main bar nerves, either in the canal or the neural foramen, is tained through 4 and 8-year follow-up. While these patients though large, was complicated by heterogeneity in both regularly do well with decompression procedures, in part patient characteristics and surgical technique. Multiple due to the greater specifcity in identifying the location smaller trials have also demonstrated beneft for fusion of symptom generation, lumbar fusion for spinal stenosis surgery in patients with spondylolisthesis. Studies of discoblock as diagnostic tool that for spondylolisthesis, and deformity surgery spe Authors & Evidence cifcally will be covered by other reviews in this series. Year Class* Description Patients with moderate symptoms and signifcant or pro gressive sagittal or coronal deformities are generally con Ohtori et al. J Neurosurg Spine tal balance to outcomes and progression of spinal disease, 21:2–6, 2014. Modic the challenges of executing a randomized controlled endplate changes—demonstrating increased signal in the study for lumbar surgery are many. Trials are lengthy and vertebral body endplate—often correlate with overall de expensive, and patient enrollment is diffcult. Although previously widespread use of electronic record keeping, the volume of reported as a factor in the surgical decision-making pro data available for clinical research has rapidly increased. Frailty indices have been used to quantify the joint is considered to be a pain generator in 15%–45% preoperative physiological reserve in patients and predict of patients with low-back pain. Injections of steroids and lo dex has been applied to patients undergoing lumbar fusion cal anesthetics have resulted in temporary pain relief for to predict complications, length of stay, readmission, reop properly selected patients. These pre Discography has been used as a diagnostic test to eval dictive tools are dependent on the quality of data available uate potentially pathologic intervertebral discs as pain to them. While some trials have shown an association Improvement Program, International Spine Study Group, between concordant pain on discography and improve and National Inpatient Sample provide varying sizes and ment following lumbar fusion, several have shown no as granularity. As more data become available, more uni sociation, and there is no high-quality evidence in favor form, and more organized, predictive analytics will pro of discography as a predictive tool for patient selection. Soon thereafter, a multi been consistently, but not universally, demonstrated over center trial confrmed statistically signifcantly improved 8,4 0,4 2,61,7 9,8 7,16 3 98 noninstrumented fusion. Current posterolateral fusion poor outcomes associated with a pseudarthrosis, although techniques include several options. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2015–2109. Defnitive conclu sions regarding superiority cannot be made given variable and limited follow-up of less than a year. Freehand trajectories have not been adequately characterized and there may be some increased risk of medial breach into the central canal at the proximal insertion site of the screw in examination of cadaveric models. It was described in the middle of the last century and has been more recently studied in conjunction with anteriorly or laterally placed interbody devices. A wide dissection is therefore is more common in higher lumbar levels such as L1 and required, with a medialized trajectory toward the preverte L2, and may make this technique diffcult. Although there may be a trend toward and are used for trauma, tumors, deformity, and degenera a slightly increased risk of pseudarthrosis with the com tive processes. New navigation, robotic, and through the ipsilateral lamina and through the facet joint. Demonstrated are the various surgical approaches to the inter vertebral disc space. Despite a tendency toward improved functional Mechanical studies have confrmed the excessive strain outcomes as well, this has not been shown to be statistical placed at the base of long constructs and most agree that ly signifcant. Most modern reports tions for interbody fusion have been described and no de of degenerative, idiopathic, and neuromuscular deformity fnitive superior technique has been demonstrated (Fig. Additionally, ante as the S2–alar iliac screw, has been described as an option rior fxation with fusion combined with posterior fusion with excellent success, and possibly lower rates of screw is likely equivalent in outcomes compared to cases that fracture and reoperation when compared with iliac wing also had a posterolateral fusion performed, with the latter screw fxation in the adult degenerative population. The threaded cages Developments in Lateral Lumbar Interbody Fusion were useful in achieving fusion but were superseded by the Laterally placed interbody devices have been used tapered, wider construction cages that allowed for more safely in the degenerative spine, with most complications robust angular correction. Most hip-fexion weakness, lumbosacral plexopathy and neuro commonly, screws or blades are placed into the endplate logical injury, and vascular injury. Well-designed clinical trials and compari provide similar reductions in range of motion. Some mod sons of the rapidly developing new designs have not yet 112 els have demonstrated lateral plating concomitant with been performed. Anterior plating has not proven to clinical studies revealed that old age and central placement restore suffcient stability to the construct. Despite the intended design for “kidney” or “banana”-type cages to be placed anteriorly, Conceptualization of the “Oblique” Antepsoas Approach most were indeed inadequately placed in the ventral com ponent and tended to be placed in the central portion of A new option that allows for lateral or anterior access the endplate.

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Sharpen existing expertise and enhance the participant’s spectrum of professional competency 2. Identify the spectrum of myoepithelial neoplasms developing in the lacrimal gland 2. Formulate a working differential diagnosis of nerve sheath tumors and associated syndromes affecting the orbit 3. Recognize the histopathologic features of pseudoneoplastic mass lesions that may be encountered in orbital biopsies 4. Defne the usual questions asked in an interview and describe successful interview strategies 3. List the most common genes associated with hereditary cancer predisposition in infants and children 2. Recognize the association between specifc rare tumor types and genetic predisposition to cancer 3. Appreciate recent updates in the diagnosis and classifcation of bone and soft tissue tumors 2. Understand the applications of molecular testing to cytopathology specimens for accurate diagnosis 2. Be cognizant of the limitations of molecular and ancillary testing in certain conditions 3. Provide a differential diagnosis of hematopathology disorders based on select clinical and pathologic fndings 2. Identify the key histopathologic features associated with specifc hematopathology disorders 3. Integrate clinical information and laboratory testing results into their interpretation of liver biopsy injury patterns 2. Have an understanding of the key pathologic features required for a diagnosis of Erdheim Chester disease 2. Know the signifcance of a diagnosis of anti-phospholipid antibodies and how they can affect the cardiovascular system 3. Identify commonly used Immunohistochemical biomarkers that are useful in the daily practice of surgical neuropathology 3. Appreciate which molecular markers in surgical neuropathology are primarily diagnostic. Integrate the imaging and pathology fndings in the appropriate clinical context 3. Identify subtle histologic features that allow one to classify colitis in mucosal biopsy samples 3. Recognize when molecular tests are indicated to further characterize fungal organisms 3. Work up the renal biopsy cases to the highest standard of practice based on clinical presentation of individual patients 2. Demonstrate the ability to identify and explain the etiology, pathogenesis, relevant investigations, and the differential diagnosis of discussed entities 3. Recognize new salivary gland tumors, including high-grade or aggressive variants 3. Sharpen existing expertise in mediastinal pathology to distinguish primary pulmonary from primary mediastinal tumors 2. Identify pitfalls in the diagnosis of lymphoproliferative processes of the mediastinum as distinct from thymic tumors 4. Pathologists, as directors of molecular pathology laboratories, are already playing a leading role in applying genomic technology to patient care. Regardless of your planned specialty, genomic pathology will become an important part of your career as a pathologist. Using a case-based, interactive small-group approach, workshop participants will learn principles related to the development of genomic assays and interpretation of results. The workshop will also include practical hands-on instruction with the use of online genomic pathology tools. Established in 2010, this group made up of experts in molecular pathology, medical education, and genetic counseling was formed to provide genomic pathology educational resources. While there will be short lectures at the beginning and end of each session, the majority of learning will take place in small resident teams with faculty support. This includes general pathologists, subspecialty pathologists, residents, and fellows. The course material and potential benefts will be accessible to all attendees regardless of their level of experience with social media. Beginners will learn the basic features and how to get started on social media and how to gain familiarity with using it. The curriculum will provide an opportunity for participants to undertake a guided exploration of the following areas of study. Both formalin fxed paraffn embedded tissues and blood-based “liquid biopsies” will be considered. The remaining sections of the course will consist of a case by case analysis that includes lung cancer, breast cancer, colorectal cancer, melanoma, brain tumors and cancer of unknown primary origin. However, the increasing burden of clinical care, daily operations, and regulatory compliance have challenged the maintenance of a safe and high quality care environment. In parallel to increasing clinical demands, the health care community has become sharply focused on patient safety, with many major organizations calling on the laboratory to adapt to a culture of reliability, accountability, and transparency. Despite these shifts in the healthcare landscape, little to no specifc tools exist to guide anatomic pathologists on exactly how to investigate medical errors and carry out quality improvement initiatives. This half day course will provide such a tool kit for frontline pathologists and pathologists-in-training. The course will be heavily case based and interactive, utilizing a set of validated tools from the quality and safety literature and practical pathology-specifc applications to facilitate learning. In order to prepare practicing pathologists this course will explain the current and future approach to evaluating patient specimens. Molecular diagnostic and genomic applications are rapidly penetrating the daily practice of the pathologist as the list of actionable genetic alteration in solid and hematologic tumors continues to expand. Similar educational needs are evident among practicing pathologists in the community and academic centers, pathology residents and fellows in institutions that are yet to develop a formal curriculum. The current course proposal intends to build upon and extend the role that the latter course, that is no longer offered, fulflled. They will take you down the tube for a sensational educational experience that is enduring, contemporary and evocative. However, error in diagnosing, grading and reporting prostate cancer has remained a signifcant problem in clinical practice, with diagnostic errors that potentially impact clinical management in 1-15% of prostate biopsies. Gleason grading system has undergone signifcant modifcation and a new grading system has been proposed, yet the adoption of these changes in clinical practice is slow. New entities of important clinical signifcance, such as intraductal carcinoma, have been described. There have been tremendous advances in the understanding of molecular and genetic mechanisms in prostate carcinogenesis and progression which has led to development of multigene genetic and genomic tests. However, there has been a lack of understanding of the new entities and molecular diagnostic tests among practicing pathologists. Review histological criteria for diagnosing prostate cancer and use of immunohistochemistry markers. Past-Presidents of the United States and Canadian Academy of Pathology may have completed their official tenures and leadership contributions, but represent a continuous source of institutional memory, wisdom, and contemporary, imaginative ideas. Through this identity, Past-Presidents may serve as advisors to current leadership, Ambassadors, and Strategic Planning, give courses in the Powers-Sanchez Interactive Center, and engage in media outreach to promote international development of the Academy. Humphrey is a surgical pathologist with expertise in urologic and prostate pathology. In December 1988, he joined the faculty at Duke as Assistant Professor of Pathology and in 1992 left to become Associate Professor at Washington University School of Medicine in St. Louis, where he became Full Professor and in 2006 was named the Ladenson Professor and Director of Anatomic and Molecular Pathology. In 2014 he joined the Yale School of Medicine Department of Pathology as Professor and Director of Genitourinary Pathology. Humphrey has published over 330 papers, reviews, and book chapters, with a dominant focus on genitourinary pathology and diseases of the prostate. He has lectured and given courses throughout the United States and world, including 6 of the 7 continents (with only Antarctica to go). His prostate research includes clinico-pathologic and molecular pathologic studies.

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