Cancer control in the Caribbean island countries and territories: some progress but the journey continues.

Cancer causes a fifth of deaths in the Caribbean region and its incidence is increasing. Incidence and mortality patterns of cancer in the Caribbean reflect globally widespread epidemiological transitions, and show cancer profiles that are unique to the region. Providing comprehensive and locally responsive cancer care is particularly challenging in the Caribbean because of the geographical spread of the islands, the frequently under-resourced health-care systems, and the absence of a cohesive approach to cancer control. In many Caribbean countries and territories, cancer surveillance systems are poorly developed, advanced disease presentations are commonplace, and access to cancer screening, diagnostics, and treatment is often suboptimal, with many patients with cancer seeking treatment abroad. Capacity building across the cancer-control continuum in the region is urgently needed and can be accomplished through collaborative efforts and increased investment in health care and cancer control.

Cancer management in the Pacific region: a report on innovation and good practice.

Pacific island countries and territories (PICTs) face the challenge of a growing cancer burden. In response to these challenges, examples of innovative practice in cancer planning, prevention, and treatment in the region are emerging, including regionalisation and coalition building in the US-affiliated Pacific nations, a point-of-care test and treat programme for cervical cancer control in Papua New Guinea, improving the management of children with cancer in the Pacific, and surgical workforce development in the region. For each innovation, key factors leading to its success have been identified that could allow the implementation of these new developments in other PICTs or regions outside of the Pacific islands. These factors include the strengthening of partnerships within and between countries, regional collaboration within the Pacific islands (eg, the US-affiliated Pacific nations) and with other regional groupings of small island nations (eg, the Caribbean islands), a local commitment to the idea of change, and the development of PICT-specific programmes.

Cancer control in small island nations: from local challenges to global action.

Cancer is a leading cause of death in small island nations and is forecast to increase substantially over the coming years. Governments, regional agencies, and health services of these nations face daunting challenges, including small and fragile economies, unequal distribution of resources, weak or fragmented health services, small population sizes that make sustainable workforce and service development problematic, and the unavailability of specialised cancer services to large parts of the population. Action is required to prevent large human and economic costs relating to cancer. This final Series paper highlights the challenges and opportunities for small island nations, and identifies ways in which the international community can support efforts to improve cancer control in these settings. Our recommendations focus on funding and investment opportunities to strengthen cancer-related health systems to improve sharing of technical assistance for research, surveillance, workforce, and service development, and to support small island nations with policy changes to reduce the consumption of commodities (eg, tobacco and unhealthy food products) that increase cancer risk.

Cancer control in the Pacific: big challenges facing small island states.

This Series paper describes the current state of cancer control in Pacific island countries and territories (PICTs). PICTs are diverse but face common challenges of having small, geographically dispersed, isolated populations, with restricted resources, fragile ecological and economic systems, and overburdened health services. PICTs face a triple burden of infection-related cancers, rapid transition to lifestyle-related diseases, and ageing populations; additionally, PICTs are increasingly having to respond to natural disasters associated with climate change. In the Pacific region, cancer surveillance systems are generally weaker than those in high-income countries, and patients often present at advanced cancer stage. Many PICTs are unable to provide comprehensive cancer services, with some patients receiving cancer care in other countries where resources allow. Many PICTs do not have, or have poorly developed, cancer screening, pathology, oncology, surgical, and palliative care services, although some examples of innovative cancer planning, prevention, and treatment approaches have been developed in the region. To improve cancer outcomes, we recommend prioritising regional collaborative approaches, enhancing cervical cancer prevention, improving cancer surveillance and palliative care services, and developing targeted treatment capacity in the region.

Metabolite profiling and pharmacokinetic evaluation of hydrocortisone in a perfused three-dimensional human liver bioreactor.

Endotoxin lipopolysaccharide (LPS) is known to cause liver injury primarily involving inflammatory cells such as Kupffer cells, but few in vitro culture models are applicable for investigation of inflammatory effects on drug metabolism. We have developed a three-dimensional human microphysiological hepatocyte-Kupffer cell coculture system and evaluated the anti-inflammatory effect of glucocorticoids on liver cultures. LPS was introduced to the cultures to elicit an inflammatory response and was assessed by the release of proinflammatory cytokines, interleukin 6 and tumor necrosis factor α. A sensitive and specific reversed-phase-ultra high-performance liquid chromatography-quadrupole time of flight-mass spectrometry method was used to evaluate hydrocortisone disappearance and metabolism at near physiologic levels. For this, the systems were dosed with 100 nM hydrocortisone and circulated for 2 days; hydrocortisone was depleted to approximately 30 nM, with first-order kinetics. Phase I metabolites, including tetrahydrocortisone and dihydrocortisol, accounted for 8-10% of the loss, and 45-52% consisted of phase II metabolites, including glucuronides of tetrahydrocortisol and tetrahydrocortisone. Pharmacokinetic parameters, i.e., half-life, rate of elimination, clearance, and area under the curve, were 23.03 hours, 0.03 hour(-1), 6.6 × 10(-5) l⋅hour(-1), and 1.03 (mg/l)*h, respectively. The ability of the bioreactor to predict the in vivo clearance of hydrocortisone was characterized, and the obtained intrinsic clearance values correlated with human data. This system offers a physiologically relevant tool for investigating hepatic function in an inflamed liver.