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Mesothelioma: Scientific clues for prevention, diagnosis, and therapy
Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high‐resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1‐asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.
Journal Article
Kwèadٌay Dèan Ts'لinchٌi : Teachings From Long Ago Person Found
\"On a late summer day, many years ago, a young man set out on voyage through the mountains. He never reached his destination. When his remains were discovered by three BC hunters, perhaps three hundred years after he left the northern coast and vanished into a storm, his name had faded from even the long memory of the coastal people. They decided to call him Kwèadٌay Dèan Ts'لinchٌi--the Long Ago Person Found. The discovery of the Kwèadٌay Dèan Ts'لinchٌi man raised many questions. Where had he come from? Where was he going, and for what purpose? What did his world look like? But his remains, preserved in glacial ice for centuries, offered answers, too--as did the traditional knowledge and experience of the Indigenous peoples in whose territories he lived and died. In this comprehensive and collaborative account, scientific analysis and cultural knowledge interweave to describe a life that ended almost precisely as Europeans began to arrive in the northwest. What emerges is not only a portrait of an individual and his world, but also a model for how diverse ways of knowing, in both scholarly and oral traditions, can complement each other to provide a new understanding of our complex histories.\"-- Provided by publisher.
Book
The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future
Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy-specifically hyperthermic intraperitoneal chemotherapy-with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development.
Journal Article
Thresholds of lake and reservoir connectivity in river networks control nitrogen removal
Lakes, reservoirs, and other ponded waters are ubiquitous features of the aquatic landscape, yet their cumulative role in nitrogen removal in large river basins is often unclear. Here we use predictive modeling, together with comprehensive river water quality, land use, and hydrography datasets, to examine and explain the influences of more than 18,000 ponded waters on nitrogen removal through river networks of the Northeastern United States. Thresholds in pond density where ponded waters become important features to regional nitrogen removal are identified and shown to vary according to a ponded waters’ relative size, network position, and degree of connectivity to the river network, which suggests worldwide importance of these new metrics. Consideration of the interacting physical and biological factors, along with thresholds in connectivity, reveal where, why, and how much ponded waters function differently than streams in removing nitrogen, what regional water quality outcomes may result, and in what capacity management strategies could most effectively achieve desired nitrogen loading reduction.
Lakes, reservoirs, and other ponded waters are common in large river basins yet their influence on nitrogen budgets is often indistinct. Here, the authors show how a ponded waters’ relative size, shape, and degree of connectivity to the river network control nitrogen removal.
Journal Article
Empirical approaches to the phonological structure of words
\"One of the basic grammatical categories in linguistics is the phonological word. But how are words made up in terms of their sounds? And how is the information on the sound structure of words used in the processing of words? This volume brings together scholars interested in the complex relations of the phonological word, applying different empirical approaches.\"-- Back cover.
BOOK
Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases
Purpose
There is no consensus for the treatment of melanoma metastatic to the liver. Percutaneous hepatic perfusion with melphalan (PHP-Mel) is a method of delivering regional chemotherapy selectively to the liver. In this study, we report the results of a multicenter, randomized controlled trial comparing PHP-Mel with best alternative care (BAC) for patients with ocular or cutaneous melanoma metastatic to the liver.
Patients and Methods
A total of 93 patients were randomized to PHP-Mel (
n
= 44) or BAC (
n
= 49). On the PHP-Mel arm, melphalan was delivered via the hepatic artery, and the hepatic effluent captured and filtered extracorporeally prior to return to the systemic circulation via a venovenous bypass circuit. PHP-Mel was repeatable every 4–8 weeks. The primary endpoint was hepatic progression-free survival (hPFS), and secondary endpoints included overall PFS (oPFS), overall survival (OS), hepatic objective response (hOR), and safety.
Results
hPFS was 7.0 months for PHP-Mel and 1.6 months for BAC (
p
< 0.0001), while oPFS was 5.4 months for PHP-Mel and 1.6 months for BAC (
p
< 0.0001). Median OS was not significantly different (PHP-Mel 10.6 months vs. BAC 10.0 months), likely due to crossover to PHP-Mel treatment (57.1 %) from the BAC arm, and the hOR was 36.4 % for PHP-Mel and 2.0 % for BAC (
p
< 0.001). The majority of adverse events were related to bone marrow suppression. Four deaths were attributed to PHP-Mel, three in the primary PHP-Mel group, and one post-crossover to PHP-Mel from BAC.
Conclusion
This randomized, phase III study demonstrated the efficacy of the PHP-Mel procedure. hPFS, oPFS, and hOR were significantly improved with PHP-Mel. PHP with melphalan should provide a new treatment option for unresectable metastatic melanoma in the liver.
Journal Article