Causes of death in patients diagnosed with gastric adenocarcinoma in Sweden, 1970-2014: A population-based study.

The causes of death in patients with gastric adenocarcinoma have not been well characterized. This nationwide population-based cohort study included 56 240 patients diagnosed with gastric adenocarcinoma in 1970-2014 in Sweden. We used competing-risks regression to compare cause-specific risks of death in patients with different characteristics and a multiple-cause approach to assess proportions of deaths attributable to each cause. Among 53 049 deaths, gastric cancer was the main (77.7% of all deaths) underlying cause. Other major underlying causes were nongastric malignancies (8.0%), ischemic heart disease or cerebrovascular disease (6.5%), and respiratory diseases (1.4%). Risk of death from gastric cancer steadily decreased in patients with cardia adenocarcinoma over the study period, but remained relatively stable in patients with noncardia adenocarcinoma since the 1980s. Risk of death from other malignancies increased during later calendar periods (subhazard ratio [SHR] = 2.16, 95% confidence interval [CI] 1.97-2.38, comparing 2001-2014 with 1970-1980). Compared with men, the risk of death in women with cardia adenocarcinoma was higher from gastric cancer (SHR = 1.18, 95% CI 1.10-1.27), but lower from other malignancies (SHR = 0.80, 95% CI 0.71-0.91). In multiple-cause models, 60.4%-71.2% of all deaths were attributable to gastric cancer and 9.5%-12.1% to other malignancies. The temporal trends of cause-specific risks from multiple-cause models were similar to those of underlying causes. Our findings suggest that although most deaths in patients with gastric adenocarcinoma are due to gastric cancer, other causes of death are common. Patients with cardia adenocarcinoma face considerable increasing risk of death from other causes over time, particularly from other malignancies.

Historical Evolution of the Polymorphous Adenocarcinoma.

The 2017 World Health Organization Classification of Head and Neck Tumors introduced for the first time the diagnostic terminology "cribriform variant of polymorphous adenocarcinoma". This nomenclature attempts to reconciliate the ongoing taxonomical controversy related to cribriform adenocarcinoma of tongue. In order to better understand this classification conundrum, it is imperative for pathologist to comprehend the historical evolution of polymorphous adenocarcinoma formerly known as polymorphous "low grade" adenocarcinoma. This review highlights our understanding of these tumors since their origins.

Extensive periosteal new bone formation in a skeleton from post-Medieval Chichester, England: A probable case of metastatic prostatic carcinoma.

An elderly male skeleton from a site in Chichester, UK, was found with a widespread periosteal reaction, principally affecting the axial skeleton and the pelvis. Radiography showed the presence of sclerosing infiltrates, mainly involving the lumbar vertebrae and pelvis. The differential diagnosis is discussed, reaching the conclusion that hypertrophic osteo-arthopathy (HOA) is the only reasonable alternative condition likely to produce such a widespread periosteal reaction as found here. HOA does not produce secondary deposits in the skeleton, however, and we conclude that his is most likely a case of prostatic carcinoma.

What did Sun Yat-sen really die of? A re-assessment of his illness and the cause of his death.

This year is the 150th anniversary of the birth of Sun Yat-sen (November 12, 1866) and the 91st year following his death (March 12, 1925). It generally has been believed that the cause of his death was "liver cancer." However, as indicated in the official autopsy report, dated March 13, 1925, of the Peking Union Medical College Hospital (PUMCH) in Beijing, the cause of his death in reality was an adenocarcinoma of the gallbladder with direct extension to the liver and diaphragm as well as widespread metastases to the peritoneal cavity. This important piece of information seems to have never been reported in the English language literature, and it was only in 2013 that the true cause of his death was stated in a one-line sentence in a non-medical Chinese online source. It had been mistakenly believed that the cause of Dr. Sun's death was liver cancer, based on the observations made following an exploratory laparotomy, which had been performed at PUMCH on January 26, 1925. The purpose of this short report is to provide more details relating to his terminal illness and to correct the historical record for a medical audience as to the cause of the death of Sun Yat-sen, a very important figure in the history of 20th century China.

Lung cancer incidence trends by gender, race and histology in the United States, 1973-2010.

BACKGROUND: Lung cancer (LC) incidence in the United States (US) continues to decrease but with significant differences by histology, gender and race. Whereas squamous, large and small cell carcinoma rates have been decreasing since the mid-80s, adenocarcinoma rates remain stable in males and continue to increase in females, with large racial disparities. We analyzed LC incidence trends by histology in the US with an emphasis on gender and racial differences. METHODS: LC incidence rates from 1973-2010 were obtained from the SEER cancer registry. Age-adjusted incidence trends of five major histological types by gender and race were evaluated using joinpoint regression. Trends of LC histology and stage distributions from 2005-2010 were analyzed. RESULTS: US LC incidence varies by histology. Squamous, large and small cell carcinoma rates continue to decrease for all gender/race combinations, whereas adenocarcinoma rates remain relatively constant in males and increasing in females. An apparent recent increase in the incidence of squamous cell carcinoma and adenocarcinoma since 2005 can be explained by a concomitant decrease in the number of cases classified as other non-small cell carcinoma. Black males continue to be disproportionally affected by squamous LCs, and blacks continue to be diagnosed with more advanced cancers than whites. CONCLUSIONS: LC incidence by histology continues to change over time. Additional variations are expected as screening becomes disseminated. It is important to continue to monitor LC rates to evaluate the impact of screening on current trends, assess the continuing benefits of tobacco control, and focus efforts on reducing racial disparities.

Neoadjuvant therapy for pancreas cancer: past lessons and future therapies.

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgery-first strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

Ever-changing endoscopic treatment for early gastric cancer: yesterday-today-tomorrow.

Endoscopic resection has been an optimal treatment for selected patients with early gastric cancer (EGC) based on advances in endoscopic instruments and techniques. As endoscopic submucosal dissection (ESD) has been widely used for treatment of EGC along with expanding ESD indication, concerns have been asked to achieve curative resection for EGC while guaranteeing precise prediction of lymph node metastasis (LNM). Recently, new techniques including ESD or endoscopic full-thickness resection combined with sentinel node navigation enable minimal tumor resection and a laparoscopic lymphadenectomy in cases of EGC with high risk of LNM. This review covers the development and challenges of endoscopic treatment for EGC. Moreover, a new microscopic imaging and endoscopic techniques for precise endoscopic diagnosis and minimally invasive treatment of EGC are introduced.

[The road to modern esophageal surgery - from maximally invasive to minimally invasive]. / Der Weg zur modernen Speiseröhrenchirurgie - von maximal invasiv zu minimal invasiv.

520 new cases of esophageal carcinoma are diagnosed in Switzerland per year. 80% of these patients eventually die from their disease despite recent advances in surgical technique and systemic treatment. The first successful thoracic esophageal resection for carcinoma was performed in 1913, but only the introduction of modern anesthesia with oral intubation and positive pressure ventilation made thoracic operations routinely feasible. Esophageal resection can be performed open or minimally invasive. The minimally invasive esophageal resection has been proven to be safe with comparable mortality to open resection. Also, there is no difference in terms of radicality of the operation. Overall survival seems to be equal in published series, but results of prospective trials are still pending.

En Suisse chaque année sont diagnostiqués 520 nouveaux cas de cancer de l'oesophage. 80% des patients décèdent malgré les avancées notables des traitements chirurgicaux et médicaux dans ce domaine. La résection chirurgicale est le traitement de choix pour les cancers éligibles. En 1913 a eu lieu avec succès la première résection transthoracique d'un cancer de l'oesophage, mais ces interventions transthoraciques n'ont pu être réalisées dans la pratique courante qu'à compter du développement des techniques anesthésiologiques modernes incluant l'intubation orale et la ventilation par pression positive. L'intervention peut de nos jours être réalisée à ciel ouvert ou par technique mini-invasive. Cette dernière est une technique sûre, ayant un taux de mortalité comparable aux techniques à ciel ouvert dans les centres spécialisés. Aussi, il n'existe aucune différence quant à la radicalité de l'opération. Les résultats oncologiques sont comparables dans les séries publiées, toutefois les résultats d'études standardisées sont encore à venir.

International trends in lung cancer incidence by histological subtype: adenocarcinoma stabilizing in men but still increasing in women.

OBJECTIVES: Trends in overall lung cancer incidence in different countries reflect the maturity of the smoking epidemic. Further understanding of the underlying causes for trends over time can be gained by assessing the trends by sex and histological subtype. We provide a temporal analysis of lung cancer incidence in 12 populations (11 countries), with a focus on cohort-specific trends for the main histological subtypes (squamous cell carcinomas (SCC), adenocarcinomas (AdC), and small cell carcinoma). MATERIAL AND METHODS: We restrict the analysis to population-based registry data of sufficient quality to provide meaningful interpretation, using data in Europe, North America and Oceania, extracted from successive Cancer Incidence in Five Continents Volumes. Poorly specified morphologies were reallocated to a specified grouping on a population, 5-year period and age group basis. RESULTS: In men, lung cancer rates have been declining overall and by subtype, since the beginning of the study period, except for AdC. AdC incidence rates have risen and surpassed those of SCC (historically the most frequent subtype) in the majority of these populations, but started to stabilize during the mid-1980s in North America, Australia and Iceland. In women, AdC has been historically the most frequent subtype and rates continue to increase in most populations studied. Early signs of a decline in AdC can however be observed in Canada, Denmark and Australia among very recent female cohorts, born after 1950. CONCLUSIONS: The continuing rise in lung cancer among women in many countries reinforces the need for targeted smoking cessation efforts alongside preventive actions.

Whence lepidic?: the history of a Canadian neologism.

The term lepidic is used prominently in the recently published multidisciplinary classification of adenocarcinoma. The lack of use in common (nonmedical) English has led to some confusion over the proper definition of this term. This historical perspective traces the history of the term lepidic from its origins at McGill University in Montreal, Canada, through its uses in English pathologic descriptions, to its current state in pulmonary pathology.

Barrett's esophagus: A historical perspective, an update on core practicalities and predictions on future evolutions of management.

Interpretation of exploding knowledge about Barrett's esophagus is impaired by use of several conflicting definitions. Because any histological type of esophageal columnar metaplasia carries risk for esophageal adenocarcinoma, the diagnosis of Barrett's esophagus should no longer require demonstration of intestinal-type metaplasia. Endoscopic recognition and grading of Barrett's esophagus remains a significant source of ambiguity. Reflux disease is a key factor for development of Barrett's esophagus, but other factors must underlie its development, since it occurs in only a minority of reflux disease patients. Neither antireflux surgery nor proton pump inhibitor (PPI) therapy has major impacts on cancer risk. Within a year, a major trial should indicate whether low-dose aspirin usefully reduces cancer risk. The best referral centers have transformed the accuracy of screening and surveillance for early curable esophageal adenocarcinoma by use of enhanced and novel endoscopic imaging, visually-guided, rather than blind biopsies and by partnership with expert pathologists. General endoscopists now need to upgrade their skills and equipment so that they can rely mainly on visual targeting of biopsies on mucosal areas of concern in their surveillance practice. General pathologists need to greatly improve their interpretation of biopsies. Endoscopic therapy now achieves very high rates of cure of high-grade dysplasia and esophageal adenocarcinoma with minimal morbidity and risk. Such results will only be achieved by skilled interventional endoscopists. Esophagectomy should now be mainly restricted to patients whose cancer has extended into and beyond the submucosa. Weighing risks and benefits in the management of Barrett's esophagus is difficult, as is the process of adequately informing patients about their specific cancer risk.

Time trends of mortality from gastric cancer in Europe.

BACKGROUND: The time trends of gastric and duodenal ulcer disease are shaped by a birth-cohort phenomenon. AIMS: The aim of this study was to assess the extent by which a birth-cohort phenomenon also affected the long-term time trends of gastric cancer among different European countries. METHODS: Mortality data from France, Germany, Netherlands, Scotland, Spain, and Sweden of the past 56-85 years were analyzed. The age-specific death rates were plotted against the period of death as period-age contours and against the period of birth as cohort-age contours. RESULTS: The long-term time trends of gastric cancer mortality were found to have risen among generations born during the 18th century until the mid-19th century and then to have declined in all subsequent generations. The rise and fall of gastric cancer preceded similar birth-cohort patterns of gastric and duodenal ulcer by about 10-30 years. With the exception of gastric cancer in Germany, similar birth-cohort phenomena were found in all countries, as well as in men and women. CONCLUSIONS: The time trends of mortality from gastric cancer and peptic are shaped by birth-cohort patterns that have affected all countries of Europe. It remains an enigma why mortality associated with gastric cancer and peptic ulcer suddenly started to rise within a short time period during the 19th century.

Gene-environment interactions in the pre-Industrial Era: the cancer of King Ferrante I of Aragon (1431-1494).

King Ferrante I of Aragon, leading figure of the Italian Renaissance, died in 1494. The autopsy of his mummy revealed a tumor infiltrating the small pelvis. We examined the histologic and molecular features of this ancient tumor to investigate its primary origin. Hematoxylin-eosin, Van Gieson, and Alcian Blue staining showed neoplastic cells infiltrating muscular fibers and forming pseudo-glandular lumina disseminated in fibrous stroma with scarce mucus. A strong immunoreactivity of the neoplastic cells was shown for pancytokeratins and proliferating cell nuclear antigen. Molecular fingerprints were investigated by examining K-ras, BRAF, and microsatellite instability in ancient tumor DNA. Sequencing analysis showed G-to-A transition in codon 12 of K-ras. BRAF mutations and microsatellite instability were not observed. Because the presence of K-ras codon 12 mutation could be associated with exposure to chemical carcinogens, possibly present in some food items, paleodietary reconstruction of the King Ferrante I was carried out by carbon (δ(13)C ) and nitrogen (δ(15)N) stable isotopes analysis. δ(13)C and δ(15)N values found in bone collagen of the King were consistent with a massive intake of animal proteins. Overall, our data show that the tumor of Ferrante I was a mucinous adenocarcinoma with molecular fingerprints characteristic of colorectal carcinogenesis linked to K-ras pathway. Paleodietary reconstruction and historical chronicles indicate a strong consumption of meat by the King. The possible abundance of dietary carcinogens, related to meat consumption, could explain the K-ras mutation causing the colorectal tumor that killed Ferrante I more than 5 centuries ago.

[Requiem for Henrietta]. / Requiem pour Henrietta.

Fifty years after Henrietta Lacks died of aggressive glandular cervical cancer, the first cell line - HeLa cell line - is the workhorse of laboratories everywhere. It helped to produce drugs for numerous diseases, including poliomyelitis, Parkinson's, leukemias. But they are so outrageously robust that they contaminated hundred of other cell lines, as far away as Russia. For decades, biologists worked with contaminated cell lines and today, the problem is not yet solved. But the story of HeLa cells is also a moving reflection of racial and ethical issues in medicine in the late half-twentieth century in the USA.

Esme Hadfield (1921-92) and the Wycombe woodworkers.

This paper reflects on the life and work of Esme Hadfield, an otolaryngologist based at Wycombe General Hospital and, in particular, on her discovery of the link between adenocarcinoma of the paranasal sinuses and wood dust exposure from those in the furniture industry. The paper also explores the woodworking industry that forms the backdrop to her discovery.