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International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: 1) To improve concordance and to align with practical consequences, a two-tiered system (low vs. high-grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low-grade. Thus, “high-grade dysplasia” is to be reserved for only the uppermost end of the spectrum (“carcinoma in situ” type lesions). 2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. 3) Intraductal lesions 0.5–1 cm can be either large PanINs or small IPMNs. The term “incipient IPMN” should be reserved for lesions in this size with intestinal- or oncocytic-papillae or GNAS mutations. 4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the “associated” group) ought to be genetically distinct from an IPMN elsewhere in the gland. 5) “Intraductal spread of invasive carcinoma” (aka, “colonization”) is recommended to describe lesions of invasive carcinoma invading back into and extending along the duct system, which may morphologically mimic high-grade PanIN or even IPMN. 6) “Simple mucinous cyst” is recommended to describe cysts > 1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN. 7) Human lesions resembling the acinar-to-ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist and may reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study. These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas.
PMCID: PMC4646710  PMID: 26559377
Pancreatic intraepithelial neoplasia (PanIN); intraductal papillary mucinous neoplasm (IPMN); mucinous cystic neoplasm (MCN); precursor; adenocarcinoma; atypical flat lesions (AFL)
2.  Modeling Scenarios for the End of AIDS 
At the end of 2012, 3 decades after the human immunodeficiency virus (HIV) was first identified, neither a cure nor a fully preventive vaccine was available. Despite multiple efforts, the epidemic remains an exceptional public health challenge. At the end of 2012, it was estimated that, globally, 35 million people were living with HIV, 2.3 million had become newly infected, and 1.6 million had died from AIDS-related causes. Despite substantial prevention efforts and increases in the number of individuals on highly active antiretroviral therapy (HAART), the epidemic burden continues to be high. Here, we provide a brief overview of the epidemiology of HIV transmission, the work that has been done to date regarding HIV modeling in different settings around the world, and how to finance the response to the HIV epidemic. In addition, we suggest discussion topics on how to move forward with the prevention agenda and highlight the role of treatment as prevention (TasP) in curbing the epidemic.
PMCID: PMC4141492  PMID: 24926027
HIV epidemic; mathematical models; prevention; treatment as prevention; TasP
3.  Comorbidity of dementia: a cross-sectional study of primary care older patients 
BMC Psychiatry  2014;14:84.
The epidemiologic study of comorbidities of an index health problem represents a methodological challenge. This study cross-sectionally describes and analyzes the comorbidities associated with dementia in older patients and reviews the existing similarities and differences between identified comorbid diseases using the statistical methods most frequently applied in current research.
Cross-sectional study of 72,815 patients over 64 seen in 19 Spanish primary care centers during 2008. Chronic diseases were extracted from electronic health records and grouped into Expanded Diagnostic Clusters®. Three different statistical methods were applied (i.e., analysis of prevalence data, multiple regression and factor analysis), stratifying by sex.
The two most frequent comorbidities both for men and women with dementia were hypertension and diabetes. Yet, logistic regression and factor analysis demonstrated that the comorbidities significantly associated with dementia were Parkinson’s disease, congestive heart failure, cerebrovascular disease, anemia, cardiac arrhythmia, chronic skin ulcers, osteoporosis, thyroid disease, retinal disorders, prostatic hypertrophy, insomnia and anxiety and neurosis.
The analysis of the comorbidities associated with an index disease (e.g., dementia) must not be exclusively based on prevalence rates, but rather on methodologies that allow the discovery of non-random associations between diseases. A deep and reliable knowledge about how different diseases are grouped and associated around an index disease such as dementia may orient future longitudinal studies aimed at unraveling causal associations.
PMCID: PMC3994526  PMID: 24645776
Dementia; Comorbidity; Factor analysis; Primary care; Electronic health records
4.  Multiple Determinants, Common Vulnerabilities, and Creative Responses: Addressing the AIDS Pandemic in Diverse Populations Globally 
The AIDS epidemic has been fueled by global inequities. Ranging from gender inequality and underdevelopment to homophobia impeding health care access for men who have sex with men (MSM), imbalanced resource allocations and social biases have potentiated the epidemic’s spread. However, recognition of culturally specific aspects of each microepidemic has yielded development of community-based organizations, which have resulted in locally effective responses to AIDS. This effective approach to HIV prevention, care and treatment is illustrated through examples of community-based responses in Haiti, the United States, Africa, and other impoverished settings.
PMCID: PMC3740592  PMID: 22772387
Disparities; Inequity; Health Care Access; Homophobia; Gender Inequality
5.  Learning Curve in a Western Training Center of the Circumferential En Bloc Esophageal Endoscopic Submucosal Dissection in an In Vivo Animal Model 
Aim. Evaluate the feasibility to overcome the learning curve in a western training center of the en bloc circumferential esophageal (ECE-) ESD in an in vivo animal model. Methods. ECE-ESD was performed on ten canine models under general anesthesia on artificial lesions at the esophagus marked with coagulation points. After the ESD each canine model was euthanized and surgical resection of the esophagus and stomach was carried out according to “the Principles of Humane Experimental Technique, Russel and Burch.” The specimen was fixed with needles on cork submerged in formalin with the esophagus and stomach then delivered to the pathology department to be analyzed. Results. ECE-ESD was completed without complications in the last 3/10 animal models. Mean duration for the procedures was 192 ± 35 minutes (range 140–235 minutes). All the procedures were done at the animal lab surgery room with cardio pulmonary monitoring and artificial ventilation by staff surgery members and a staff member of the Gastroenterology department trained during 1999–2001 at the Fujigaoka hospital of the Showa U. in Yokohama, Japan, length (range 15–18 mm) and 51 ± 6.99 width (range 40–60 mm). Conclusion. ECE-ESD training is feasible in canine models for postgraduate endoscopy fellows.
PMCID: PMC3185270  PMID: 21976950
6.  Endoscopic submucosal dissection in dogs in a World Gastroenterology Organisation training center 
AIM: To evaluate if canine models are appropriate for teaching endoscopy fellows the techniques of endoscopic submucosal dissection (ESD).
METHODS: ESD was performed in 10 canine models under general anesthesia, on artificial lesions of the esophagus or stomach marked with coagulation points. After ESD, each canine model was euthanized and surgical resection of the esophagus or stomach was carried out according to “The Principles of Humane Experimental Technique, Russel and Burch”. The ESD specimens were fixed with needles on cork submerged in a formol solution with the esophagus or stomach, and delivered to the pathology department to be analyzed.
RESULTS: ESD was completed without complications using the Hook-knife in five esophageal areas, with a procedural duration of 124 ± 19 min, a length of 27.4 ± 2.6 mm and a width of 21 ± 2.4 mm. ESD was also completed without complications using the IT-knife2 in five gastric areas, with a procedural duration of 92.6 ± 19 min, a length of 32 ± 2.5 mm and a width of 18 ± 3.7 mm.
CONCLUSION: ESD is feasible in the normal esophagus and stomach of canine models, which are appropriate for teaching this technique.
PMCID: PMC2852825  PMID: 20380009
Endoscopic mucosal resection; Endoscopic submucosal dissection; Stomach neoplasms; Training
7.  Sex between men in the context of HIV: The AIDS 2008 Jonathan Mann Memorial Lecture in health and human rights 
Gay, bisexual, and other men who have sex with men (MSM) have been among the most affected populations by HIV since the AIDS pandemic was first identified in the 1980s. Evidence from a wide range of studies show that these men remain at the highest risk for HIV acquisition in both developed and developing countries, and that despite three decades of evidence of their vulnerability to HIV, they remain under-served and under-studied. Prevention strategies targeted to MSM are markedly under-funded in most countries, leading to limited access to health services including prevention, treatment, and care. We explore the global epidemic among MSM in 2008, the limited funding available globally to respond to these epidemics, and the human rights contexts and factors which drive HIV spread and limit HIV responses for these men.
What do we mean by the term MSM? MSM is a construct from the 1990s that tries to capture behavior and not identity. It was crafted to avoid stigmatizing and culturally laden terms such as gay or bisexual, which do not capture the wide diversity of orientations, sexual practices, cultures, and contextual settings in which male same-sex behaviors occur, and where HIV transmission and acquisition risks are centered. MSM includes both gay and non-gay identified men, bisexual men, and MSM who identify themselves as heterosexuals. It also includes men engaging in "situational" sex between men, such as can occur in prisons, schools, militaries or other environments; and it includes male sex workers who may be of any orientation but are often at very high risk for HIV. MSM may include some biologically male transgender persons, though some do not identify as male. And MSM includes a wide array of traditional and local terms worldwide–with enormous cultural diversity in Asia, Africa, Latin America and elsewhere. We use the term MSM here at its most inclusive.
PMCID: PMC2631526  PMID: 19108725

Results 1-7 (7)