Background: Solid organ transplant (SOT) survival rates have improved with advances in immunosuppressive medications. Chronic immunosuppressive exposure, however, increases the risk of developing malignancies due to the loss of immune surveillance and/or the carcinogenic effects of these medications. Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic lesions that carry malignant potential. The long-term prospective for malignant transformation of IPMN in the setting of chronic immunosuppressive therapy is unclear. In this study, we aim to evaluate the natural history of IPMNs in immunosuppressed transplant patients.

Introduction: COVID-19 has challenged healthcare in an unprecedented manner, requiring quarantines and shutdowns to mitigate virus spread. These restrictions may have inadvertently delayed treatment for oncologic diseases. This study aims to analyze the impact of COVID-19 delays on pancreatic cancer care at a quaternary-referral center. Methods: Fifty-six patients who underwent initial surgical resection of pancreatic neoplasms were retrospectively reviewed. The "COVID" group underwent surgery from March 1 – June 30, 2020, the period of limited hospital operations due to COVID-19. The "pre-COVID" control group included patients from the equivalent period in 2019. Time intervals between important clinical milestones and pathologic stage at resection were compared. Results: During the COVID shutdown, the time interval between almost every step in the care pathway was increased. Despite these clinically relevant differences, the only statistically significant difference was found for the time from presentation to pathological diagnosis with an increase of 14 days (p-value = 0.036). With regards to tumor stage, a 14.7% increase in patients presenting with stage III and IV cancer was found in 2020 compared to 2019, however, this difference did not reach statistical significance, likely related to limited sample size. Conclusion: COVID-19 has caused delays throughout the oncologic care pathway, which may have led to more advanced disease at the time of diagnosis. The impact of these delays on patient outcomes requires ongoing investigation to better characterize the collateral damage of COVID-19. To prevent further harm, healthcare systems need to prioritize oncologic patients while the pandemic persists.Tabled 1EP02D-019 Table 1. Time IntervalsInterval in Oncological Care PathwayTime During "Pre-COVID" (median days [IQR])Time During "COVID" (medians days [IQR])P-ValueSymptom Onset → Presentation12 [4.5 - 30.5]20.5 [1.5 - 74.2 ]0.425Presentation → Imaging Diagnosis1 [0 - 6.2]2.5 [0 - 27.2 ]0.414Presentation → Pathological Diagnosis7 [3 - 22]22 [8.2 - 35.8]0.036Presentation → Tumor Board58 [13 - 124]50 [35.8 - 71.8]0.807Pathological Diagnosis → 1st Treatment (Neoadjuvant + Surgical Resection)16.5 [11 - 39.2]20 [7 - 36.8]0.816Pathological Diagnosis → Neoadjuvant17 [16 - 39]25 [14 - 35.2]0.923Pathological Diagnosis → Surgical Resection49 [14 - 126]28.5 [7 - 107]0.663 Open table in a new tab

Introduction: In Pancreatic Adenocarcinoma (PDAC), CA19-9 is a strong predictor of post-resection survival. However, its use in clinical practice has been limited due to non-specificity, values range, and non-secretor variants. We aimed at exploring relationships between CA19-9 and tumor-size to improve CA19-9-utility to predict post-resection survival of PDAC. Method: Resected PDAC cases were retrospectively-analyzed from 2003-2018. Survival groups were dichotomized into Short (90-days to 1-year) and Prolonged (>2-years). Logistic regression was conducted to predict survival groups based on interaction terms between CA19-9 levels and tumor sizes and adjusted for age, tumor location, and neoadjuvant treatment. Results: One-hundred-eleven patients fitted the survival criteria [27(24.3%) vs. 84(75.7%) in Short and Prolonged groups, respectively] with median follow-ups of 2-years [IQR2-4]. The mean CA19-9 was significantly higher in the Short vs. Prolonged groups 1032±981vs.459±922U/ml, respectively, P<0.001. We then divided the CA19-9 values based on the tumor size (Figure-1). There were significant differences in CA19-9 values between survival groups for small-size (<2cm) tumors (1347±913vs.192±129U/ml, P=0.011) and large-size (>4cm) tumors (1382±1401vs.147±131U/ml, P<0.001), but not for medium-size (2-4cm) tumors (805±854vs.528±1012U/ml, P=0.116). After adjusting for covariates, CA19-9 values for large-tumors were statistically significant in predicting early mortality (OR1.004, P=0.021), overall model-significance of P<0.001. Conclusions: Stratifying CA19-9 by the accompanying tumor size increased post-resection survival predictability. Large-tumor with low CA19-9 values were associated with increased survival compared to equally-sized tumors with high CA19-9 values. Large-tumor is conventionally considered a high-risk; however, those with low CA19-9 values are associated with prolonged survival.

Presenter: Breanna Perlmutter MD | Cleveland Clinic Foundation Background: Despite expert guidelines recommending definitive surgery for T2 disease, there is inconsistent surgical management. This study aims to evaluate the role of radical resection with portal lymphadenectomy on survival in patients with T2 gallbladder cancer. Methods: A retrospective review was conducted at a large academic multi-center institution. All patients with a diagnosis of gallbladder cancer from 2001-2017 were identified. Patients with T2 cancers diagnosed on final pathology were included. Patients with metastatic disease were excluded. Data regarding demographics and operative details were collected. Patients were classified into two groups based on surgical management. “Definitive surgery” was defined as those patients undergoing a radical resection with portal lymphadenectomy whereas “non-definitive surgery” was defined as those patients only undergoing cholecystectomy with no further surgical management. Patients who underwent an en bloc radical cholecystectomy with portal lymphadenectomy at the initial surgery were included in the definitive surgery group. Kaplan-Meier estimates were used to calculate overall median survival. Results: Forty-seven patients met study criteria with 24 (51%) undergoing definitive surgery. Patients who underwent definitive surgery were younger than those who did not (mean age 64.8 v. 74.7 years, p=0.004). The majority of patients were Caucasian (n=36, 76.6%) and female (n=30, 63.8%), with no significant difference in gender distribution or race between the two groups. Eleven patients (23.4%) had gallbladder polyps or masses noted prior to initial surgery, eight of whom underwent definitive surgery. Sixteen patients (69%) in the non-definitive surgery group as opposed to 18 (75%) in the definitive surgery group underwent laparoscopic cholecystectomy at initial operation (p 0.61). The majority of patients (91%) in the definitive surgery group had a cholecystectomy as the initial operation followed by radical resection with portal lymphadenectomy a median delay of 30 days (IQR 22-52 days) later. Overall pathologic TNM staging was comparable between the two groups and was predominantly stage II disease (82% in the non-definitive group vs. 79% in the definitive group). The grade of differentiation was also comparable between the two groups with the majority of patients being moderately differentiated. Final margins were considered after the last surgery the patient underwent. Overall 31.8% of patients in the non-definitive surgery group had a positive margin at the cystic duct. The final margin was positive in one patient (4.2%) undergoing definitive surgery (p=0.02). Median overall survival was significantly better in patients undergoing definitive surgery (4.3 v. 1.9 years, p=0.02). Conclusion: In this study, half of patients with T2 gallbladder disease underwent definitive surgical resection, which was associated with a significantly improved survival. The importance of radical resection with portal lymphadenectomy for T2 gallbladder cancer must continue to be emphasized to improve outcomes in patients who are otherwise candidates for surgery.

Presenter: Robert Naples DO | Cleveland Clinic Foundation Background: Gallbladder cancer is the most common biliary tract malignancy and has a poor prognosis. The clinical significance of the pathologic pattern for gallbladder cancer, focal versus diffuse, remains unclear. We hypothesized that diffuse gallbladder cancer will have a worse survival than focal gallbladder cancer. Methods: A retrospective review was conducted on all patients with gallbladder cancer where pattern (focal including both visceral and liver sides, versus diffuse) was reported in pathology reports. Patient with metastatic disease were excluded. Demographics and operative details were collected. Pathology was reviewed, and gallbladder pattern was defined as “diffuse” if the tumor was multicentric or “focal” if the tumor was only in a single location. TNM staging was assessed in patients with definitive resection. Patients undergoing liver resection and portal lymphadenectomy were considered to have definitive surgery. The primary outcome was overall survival. Results: Thirty-seven patients met study criteria with 19 (51%) having diffuse cancer. Of the 37 patients, the majority were female (n=28, 75.7%). Those patients with diffuse cancer were older in comparison to patients with focal cancer (70.3 vs 66.4 years, p=0.04). There was no difference in gender distribution or ethnicity among the groups. No difference was observed in utilization of definitive surgery between the groups (11 [61%] with focal cancer and 10 [56%] with diffuse cancer, p 0.73). Patients with diffuse gallbladder cancer were noted to have a higher T, N, and overall pathologic stage although not statistically significant. Additionally, poorly differentiated adenocarcinoma was significantly more common in patients with diffuse cancer (53% vs 18%, p=0.005). Six patients (33%) with diffuse disease had a positive cystic duct margin following initial cholecystectomy, while none with focal cancer had the margin positive (p=0.01). After definitive surgery there was no statistically significant difference in positive margin between the two groups. Overall median survival was significantly improved in those with focal cancer (6.93 vs 1.92 years, p=0.04). Although this difference persisted in patients who underwent definitive surgery (overall median survival of 6.9 years in patients with focal vs. 2.3 years in diffuse cancer) it was not statistically significant. Conclusion: Patients with diffuse gallbladder cancer likely represent a subset with aggressive biology and worse overall survival compared to focal disease. When suspected on imaging, these patients may be considered for upfront neoadjuvant and/or aggressive adjuvant modalities.

When we think of "climate change," we think of man-made global warming, caused by greenhouse gas emissions. But natural climate change has occurred throughout human history, and populations have had to adapt to the climate's vicissitudes. Anthony J. McMichael, a renowned epidemiologist and a pioneer in the field of how human health relates to climate change, is the ideal person to tell this story. Climate Change and the Health of Nations shows how the natural environment has vast direct and indirect repercussions for human health and welfare. McMichael takes us on a tour of human history through the lens of major transformations in climate. From the very beginning of our species some five million years ago, human biology has evolved in response to cooling temperatures, new food sources, and changing geography. As societies began to form, they too adapted in relation to their environments, most notably with the development of agriculture eleven thousand years ago. Agricultural civilization was a Faustian bargain, however: the prosperity and comfort that an agrarian society provides relies on the assumption that the environment will largely remain stable. Indeed, for agriculture to succeed, environmental conditions must be just right, which McMichael refers to as the "Goldilocks phenomenon." Global warming is disrupting this balance, just as other climate-related upheavals have tested human societies throughout history. As McMichael shows, the break-up of the Roman Empire, the bubonic Plague of Justinian, and the mysterious collapse of Mayan civilization all have roots in climate change. Why devote so much analysis to the past, when the daunting future of climate change is already here? Because the story of mankindâs previous survival in the face of an unpredictable and unstable climate, and of the terrible toll that climate change can take, could not be more important as we face the realities of a warming planet. This sweeping magnum opus is not only a rigorous, innovative, and fascinating exploration of how the climate affects the human condition, but also an urgent call to recognize our species' utter reliance on the earth as it is.

Instructions Accompanying New Domestic devices are tedious. So, uninstructed, we plunge into assembling the device … and the likely result is all too familiar. By analogy, a basic understanding of the cli­mate system and the forces influencing it will shed more light on later chapters. The climate system has many interacting parts, encompassing the linkages between atmosphere, oceans, land, and ice surfaces. The atmosphere and oceans are the prime global distributors of that part of incoming solar energy that Earth retains in the form of heat, much of which is then re- expressed as water vapor, wind, and ocean currents. As part of the Earth system, the world’s climate is always changing. The internal dynamics of the climate system are complex and region­ally distinctive, and include, on shorter time scales, chaotic behavior. Meanwhile, larger forces are at work. As continents coalesce and then drift apart; as massive mountain ranges get pressed skyward; as Earth’s elliptical orbit around the sun alternates between greater and lesser ro­tundity; as both the tilt and wobble of the planet’s axis vary; as solar sunspots come and go; as fluctuations occur in the great ocean- based regional climatic cycles (the Pacific’s El Niño Southern Oscillation, the Indian Ocean Dipole Oscillation, the North Atlantic Inter- Decadal Oscillation, and others); and as volcanic eruptions enshroud the lower atmosphere— so the world’s climate varies on time- scales ranging from tens of millions of years to just several years. The main engine of the climate system, the atmosphere, is made up of many local circulation subsystems, often interacting with (or “coupled” with) the oceans. At a regional scale, different combinations of local circulation systems account for changes in climate, such as the decline in rainfall in Mesopotamia during the third millennium B.C.E., or the southward encroachment of the Arctic polar vortex that imposed the Big Freeze on much of the north eastern USA in the 2013– 2014 winter.

BACKGROUND: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed.DISCUSSION: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

BACKGROUND:Between 2010 and 2012, the World Health Organization Division of Pacific Technical Support led a regional climate change and health vulnerability assessment and adaptation planning project, in collaboration with health sector partners, in 13 Pacific island countries-Cook Islands, Federated States of Micronesia, Fiji, Kiribati, Marshall Islands, Nauru, Niue, Palau, Samoa, Solomon Islands, Tonga, Tuvalu, and Vanuatu. OBJECTIVE:We assessed the vulnerabilities of Pacific island countries to the health impacts of climate change and planned adaptation strategies to minimize such threats to health. METHODS:This assessment involved a combination of quantitative and qualitative techniques. The former included descriptive epidemiology, time series analyses, Poisson regression, and spatial modeling of climate and climate-sensitive disease data, in the few instances where this was possible; the latter included wide stakeholder consultations, iterative consensus building, and expert opinion. Vulnerabilities were ranked using a "likelihood versus impact" matrix, and adaptation strategies were prioritized and planned accordingly. RESULTS:The highest-priority climate-sensitive health risks in Pacific island countries included trauma from extreme weather events, heat-related illnesses, compromised safety and security of water and food, vector-borne diseases, zoonoses, respiratory illnesses, psychosocial ill-health, non-communicable diseases, population pressures, and health system deficiencies. Adaptation strategies relating to these climate change and health risks could be clustered according to categories common to many countries in the Pacific region. CONCLUSION:Pacific island countries are among the most vulnerable in the world to the health impacts of climate change. This vulnerability is a function of their unique geographic, demographic, and socioeconomic characteristics combined with their exposure to changing weather patterns associated with climate change, the health risks entailed, and the limited capacity of the countries to manage and adapt in the face of such risks. Citation: McIver L, Kim R, Woodward A, Hales S, Spickett J, Katscherian D, Hashizume M, Honda Y, Kim H, Iddings S, Naicker J, Bambrick H, McMichael AJ, Ebi KL. 2016. Health impacts of climate change in Pacific island countries: a regional assessment of vulnerabilities and adaptation priorities. Environ Health Perspect 124:1707-1714; http://dx.doi.org/10.1289/ehp.1509756.

Human-driven climatic changes will fundamentally influence patterns of human health, including infectious disease clusters and epidemics following extreme weather events. Extreme weather events are projected to increase further with the advance of human-driven climate change. Both recent and historical experiences indicate that infectious disease outbreaks very often follow extreme weather events, as microbes, vectors and reservoir animal hosts exploit the disrupted social and environmental conditions of extreme weather events. This review article examines infectious disease risks associated with extreme weather events; it draws on recent experiences including Hurricane Katrina in 2005 and the 2010 Pakistan mega-floods, and historical examples from previous centuries of epidemics and ‘pestilence’ associated with extreme weather disasters and climatic changes. A fuller understanding of climatic change, the precursors and triggers of extreme weather events and health consequences is needed in order to anticipate and respond to the infectious disease risks associated with human-driven climate change. Post-event risks to human health can be constrained, nonetheless, by reducing background rates of persistent infection, preparatory action such as coordinated disease surveillance and vaccination coverage, and strengthened disaster response. In the face of changing climate and weather conditions, it is critically important to think in ecological terms about the determinants of health, disease and death in human populations.

Previous articleNext article No AccessBook ReviewsAlison Bashford. Global Population: History, Geopolitics, and Life on Earth. (Columbia Studies in International and Global History.) xii + 466 pp., illus., maps, bibl., index. New York: Columbia University Press, 2014. $50 (cloth).Anthony McMichaelAnthony McMichael Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Isis Volume 106, Number 3September 2015 Publication of the History of Science Society Article DOIhttps://doi.org/10.1086/683419 Views: 79Total views on this site Citations: 1Citations are reported from Crossref © 2015 by The History of Science Society. All rights reserved.PDF download Crossref reports the following articles citing this article: Current Bibliography of the History of Science and Its Cultural Influences, 2016, Isis 107, no.S1S1 (Jun 2017): i–240.https://doi.org/10.1086/692972

Studies in temperate countries have shown that both hot weather in summer and cold weather in winter increase short-term (daily) mortality. The gradual warming, decade on decade, that Australia has experienced since the 1960s, might therefore be expected to have differentially affected mortality in the two seasons, and thus indicate an early impact of climate change on human health. Failure to detect such a signal would challenge the widespread assumption that the effect of weather on mortality implies a similar effect of a change from the present to projected future climate. We examine the ratio of summer to winter deaths against a background of rising average annual temperatures over four decades: the ratio has increased from 0.71 to 0.86 since 1968. The same trend, albeit of varying strength, is evident in all states of Australia, in four age groups (aged 55 years and above) and in both sexes. Analysis of cause-specific mortality suggests that the change has so far been driven more by reduced winter mortality than by increased summer mortality. Furthermore, comparisons of this seasonal mortality ratio calculated in the warmest subsets of seasons in each decade, with that calculated in the coldest seasons, show that particularly warm annual conditions, which mimic the expected temperatures of future climate change, increase the likelihood of higher ratios (approaching 1:1). Overall, our results indicate that gradual climate change, as well as short-term weather variations, affect patterns of mortality.

1. Caldecott B, Tilbury J, Ma Y. Stranded Down Under? Environment-related Factors Changing China’s Demand for Coal and What this means for Australian Coal Assets. Oxford (UK): University of Oxford Smith School of Enterprise and the Environment; 2013 Dec. p. 1–78. 2. Swan J. Tony Abbott’s business adviser says Australia taken ‘hostage’ by ‘climate change madness’. The Age. 2013 Dec 31. 3. Chen Y, Ebenstein A, Greenstone M, Li H. Evidence on the impact of sustained exposure to air pollution on life expectancy from China’s Huai River policy. Proc Natl Acad Sci. 2013;110(32):12936–41. 4. Deaton A. The Great Escape: Health, Wealth, and the Origins of Inequality. Princeton (NJ): Princeton University Press; 2013. 5. Niu S, Jia Y, Wang W, He R, Hu L, Liu Y. Electricity consumption and human development level: A comparative analysis based on panel data for 50 countries. Int J Electrical Power Energy System. 2013;53: 338–47. 6. Gohlke JM, Thomas R, Woodward A, CampbellLendrum D, Prüss-Ustün A, Hales S, et al. Estimating the global public health implications of electricity and coal consumption. Environ Health Perspect. 2011;119(6):821–6. 7. Peters GP, Andrew RM, Boden T, Canadell JG, Ciais P, Le Quéré C, et al. The challenge to keep global warming below 2°C. Nature Climate Change. 2013;3(1):4–6. 8. Carbon Tracker. Unburnable Carbon 2013: Wasted Capital and stranded Assets. London (UK): Carbon Tracker Initiative in Collaboration with Grantham Research Institute on Climate Change and the Environment, LSE; 2013 Apr. p. 1–40. 9. Juniper T. What has Nature Ever Done for Us? London (UK): Profile Books; 2013.

In 2008 the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) commissioned ten think-tanks to work on disease-specific and thematic reference groups to identify top research priorities that would advance the research agenda on infectious diseases of poverty, thus contributing to improvements in human health. The first of the thematic reference group reports - on environment, agriculture and infectious diseases of poverty - was recently released. In this article we review, from an insider perspective, the strengths and weaknesses of this thematic reference group report and highlight key messages for policy-makers, funders and researchers.

Human-induced climate change, with such rapid and continuing global-scale warming, is historically unprecedented and signifies that human pressures on Earth's life-supporting natural systems now exceed the planet's bio-geo-capacity. The risks from climate change to health and survival in populations are diverse, as are the social and political ramifications. Although attributing observed health changes in a population to the recent climatic change is difficult, a coherent pattern of climate- and weather-associated changes is now evident in many regions of the world. The risks impinge unevenly, especially on poorer and vulnerable regions, and are amplified by pre-existing high rates of climate-sensitive diseases and conditions. If, as now appears likely, the world warms by 3-5oC by 2100, the health consequences, directly and via massive social and economic disruption, will be severe. The health sector has an important message to convey, comparing the health risks and benefits of enlightened action to avert climate change and to achieve sustainable ways of living versus the self-interested or complacent inaction.