Global Cancer Surgery—The Lancet Commission

Introduction

Since 1991, the global burden of disease has shifted from communicable to noncommunicable disease (NCDs), primarily due to prevention, mitigation, and treatment of infectious disease in low- and middle-income countries (LMICs). This epidemiological shift has impacted global mortality rates and other important health indicators, and there has been a simultaneous increase in disability and death primarily due to cancer. The increase in cancer has especially impacted low-income countries (LICs), specifically those in sub-Saharan Africa. Economic progress and the westernization of lifestyle have led to increased exposure to cancer risk factors, including tobacco use, sedentary lifestyle, and diet changes to include more processed foods. Overall, Asia and Africa have a 50% higher cancer incidence and higher mortality in relation to the number of new cancer cases. This trend is likely due to a triad of causes: higher frequency of cancer types associated with poorer prognosis, limited access to diagnosis, and limited access to treatment. ^, Globocan cancer statistics for 2018 estimated that there are 8.8 million global cancer-related deaths annually—approximately 17% of all global deaths—with 70% of these cancer deaths occurring in LICs. Without investment in early diagnosis and access to treatment, including surgery, the number of cancer-related deaths might rise to 13.2 million by 2030. ^,

Cancer is a diverse group of diseases, impacting every anatomic and physiologic system during every stage of life. To positively impact cancer and its effect on disability and mortality, health care systems must focus on early diagnosis and access to treatment. Effective cancer mitigation and cure has been accomplished in most high-income countries (HICs) but is rare in LICs. The inflection point for cancer diagnosis often includes surgical intervention in the form of biopsy or resection. The treatment of many cancers is also surgical, and so the increase in cancer burden in LICs has emphasized the role of surgery and safe anesthesia in LICs. The critical lack of access to surgery and safe anesthesia in LICs has negatively impacted cancer diagnosis and treatment, and continues to hinder the progress in LMICs. There is an urgent need for timely access to surgical services, the implementation of screening programs, and a focus on the risk factors.

The World Health Organization (WHO)’s adoption of the global surgery agenda proposed by the Lancet , with commitments by national Ministries of Health (MOH) and local health care systems, will improve access to timely, effective, and safe surgical and anesthesia care, and cancer diagnosis and management programs, thereby socially and economically impacting individuals, families, communities, and countries alike. This agenda aims to achieve a 25% reduction in premature mortality from cancer-related deaths by the year 2025.

The global surgery initiative comprises four essential pillars of cancer treatment and care to engage cancer services worldwide that best fit specific national needs:

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Improve cancer data for public health use
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Improve patient early access and detection—frequently surgical
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Provide timely and accurate treatment—often surgical
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Provide primary and supportive palliative care—may also have a surgical component

The Global Surgical and Anesthesia Crisis

The contribution of communicable disease to the global burden of disease mandated the focus on this disease group in LMICs during much of the last century. ^, This mandate resulted in a neglect of surgery, except for emergency surgery, and played down the importance of safe anesthesia. However, the shift in epidemiology from communicable to NCDs that began in the 1990s led to a greater surgical disease burden. In most, if not all LICs, surgical systems had atrophied due to the necessary focus on communicable disease, and there were limited efforts to train future anesthesiologists and surgeons. Consistent with the focus on infectious disease were the global public health perceptions that surgery is a “luxury” that is too complicated for the limited health care systems in LICs, and “too expensive.” During the important shift in opinion toward the greater burden of NCD, little infrastructure and few resources ^, were available for the growing need for surgery and safe anesthesia.

This reality was recognized by a few internationally focused surgeons and anesthesiologists and their local counterparts, but was not acknowledged by the global public health community until 2015.

Emergence of Global Surgery

In 2015, three important initiatives came to fruition. The Disease Control Priorities in Developing Countries 3rd Edition (DCP3), a publication of the World Bank that is published approximately every 5 years with the intention of setting health priorities in LMICs, focused on Essential Surgery for the first time in the history of the publication. The first volume of DCP3 , Essential Surgery, focused on the global burden of surgical disease, estimating that more than 30% of the global disease burden could be averted with appropriate surgical intervention and safe anesthesia. Further, the authors and editors proposed a list of 44 cost-effective and essential surgical interventions, inclusive of appropriate anesthesia techniques, to address the global burden of surgical disease in district hospitals in all LMICs. A month after the DCP3 publication in March 2016, the Lancet Commission on Global Surgery (LCoGS) was published. This landmark publication built on the foundations of DCP3 and furthered the global surgery agenda through modeling, suggesting that 5 billion people lacked access to surgery and safe anesthesia when needed. The key Lancet indicators include access to essential surgery and safe anesthesia within 2 h, an increase in overall surgical volume in LMICs, an increase in surgical, anesthesia, and obstetrical providers per 100,000 population, tracking of the perioperative mortality rate (POMR), and a focus on decreasing impoverishing and catastrophic expenditures related to emergency and essential surgery. These two pivotal publications were followed in May 2015 by the annual World Health Assembly, which unanimously resolved to support and improve access to safe, timely, and affordable surgical, obstetric, and anesthesia care, to optimize health outcomes through the World Health Assembly Resolution #68.15. ^, ^, In summary, these documents and the resolution concluded with a moral and economic imperative to include emergency and essential surgery and safe anesthesia in primary health care in LMICs. They paved the way to improving surgical care for the 5 billion citizens without access to this basic health care need.

The events of 2015 and the initiatives that have followed, including the National Surgical, Obstetric, and Anesthesia Plans (NSOAPs), have led to more generous support for surgery and anesthesia and ongoing plans to scale up and provide 44 essential surgeries in all district hospitals in LMICs. The plan focuses on access to surgery and safe anesthesia, previously unprioritized in most national health care plans. A surgical assessment tool (SAT) is used to evaluate critical components of a surgical system—infrastructure, service delivery, workforce, information management, and financing—and to inform the NSOAP ( Fig. 2.1 ).

The NSOAP process is a framework for the planning, delivery, and management of quality surgical, obstetric, and anesthesia services at all levels of health delivery systems by incorporating three steps:

1.

Expansion of the workforce and infrastructure at the district level
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Increase health management information systems
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Develop financing mechanisms and strong leadership.

The NSOAP is an ambitious plan and to date has only been implemented in a few countries. Zambia was the first to report success. The plan aligns with current health care policies and has seen a modest 3% increase in health care costs. The development of the plan in Zambia can serve as a model to other countries that wish to develop similar surgical services and research strategies for better perioperative outcomes.

Perioperative Management

The perioperative period, from preoperative evaluation to postoperative management and outcomes, is a relatively new commitment in HICs. As such, and because of the related resource requirement, it has not become a commitment in LMICs. In fact, many LMICs are struggling to adequately provide comprehensive preoperative evaluation and related testing.

While this phase of surgical care has yet to be realized in low-resource settings, where the scale-up to safe anesthesia and surgery has just begun, it is important to the future of anesthesia and surgical outcomes in LMICs. Pain management is an important part of the perioperative process. Uncontrollable postoperative pain increases the incidence of chronic pain. ^, Pain medications are often unavailable, even though they are on the WHO list of essential medications. Deficits in the perioperative workforce have shifted the tasks of health care workers to those less qualified. This task shifting is a controversial subject among health care professionals as concerns regarding training and patient safety exist. ^, The level of professional care in the perioperative period is unknown in LICs, and family members are often the direct caregivers in the immediate postoperative period. This contributes to higher-than-expected perioperative morbidity and mortality.

Few studies have addressed the issue of postoperative mortality in LICs. The high rates of postoperative mortality reported are commonly due to unrecognized hypoxia and hypovolemia. Inadequate equipment, especially pulse oximetry, lack of trained anesthesia and perioperative personnel, and inadequate supervision contribute to this high mortality rate. There is also a lack of postoperative follow up once the patient is discharged home. This results in mortality rates 100–1000 times higher in LICs compared with those in HICs. ^, Improvement in surgical and anesthesia resources will lead to a reduction in POMRs in LICs. The POMR will be shifted toward patients with increased comorbidities and greater acuity of illnesses.

Perioperative patient management is one focus of the NSOAP process. For example, in Uganda, implementation of the NSOAP process has resulted in a better understanding of surgical services, partnerships within different levels of care to improve access to safe surgery and the first country-wide quality metrics. An example would be a retrospective analysis of surgical volume and perioperative mortality as recorded in a simple logbook. POMR is a good indicator of a healthy surgical service. Surgical societies, regional organizations, professional societies, and MOH engage and work together at every level from local to national to provide essential surgical services. These coordinated efforts strengthen the health care system and contribute to overall social and economic well being and lead to the meaningful exchange of ideas and resources.

Cancer Anesthesia and Surgery

Surgical Access

Access to surgery and safe anesthesia is essential to the diagnosis and treatment of cancer in LMICs. Limited by workforce, infrastructure, necessary equipment, and medicines in LMIC, the support of the LCoGS and the practical process of NSOAPs are just the beginning. National MOH ultimately must invest in the resources necessary for the success of the NSOAP process, and thereafter in a system-wide commitment to a surgical program that is accessible, scalable, safe, and trusted by the population. The growth of surgical programs will take time; these must be practical and acknowledge local strengths and challenges. Recommendations from the NSOAPs include increasing education and training, task shifting to nonphysician providers, building and equipping surgical facilities, and purchasing equipment for surgery and anesthesia, including safety monitoring equipment.

Safe Anesthesia

Anesthesia must be emphasized as an integral part of every health care system and as essential for surgical programs. This seems obvious, but anesthesia continues to be a challenge, even an afterthought, in many resource-constrained settings. The historical and current underresourcing of anesthesia has resulted in poor anesthesia outcomes in many LICs. While multifactorial, this reality is primarily due to a lack of education and training for nonphysician anesthesia providers, as well as limited access to essential medicines, including oxygen and absent or underutilized safety monitoring equipment. ^,

Patient safety initiatives in HICs have resulted in better patient outcomes ^, ; however, limited emphasis and advances in patient safety in LICs contribute to poor anesthesia outcomes. This has not gone unnoticed by the international community. Efforts to provide training for anesthesia providers, access to essential medicines, guidelines, and support have been ongoing for many years. The global health initiative for safe surgery and anesthesia ^, has prioritized access to safe anesthesia and surgery and emphasized that this is a fundamental human right for proper health care. International standards, developed by the WHO and the World Federation of Societies of Anesthesiologists, provide guidance to MOH and health care systems to improve quality of care and patient safety. However, such guidelines have little impact without investment from governments. It is estimated that 32 million people worldwide receive anesthesia, oxygen, and critical monitoring from unqualified anesthesia providers, and for these patients, it is imperative that basic patient safety practices be embraced. A bare minimum approach is possible, entailing the use of a precordial stethoscope, pulse oximetry, and oxygen, and being vigilant to the clinical signs of color, pupils, and pulse. ^–

Pain Management

Pain management is recognized as a fundamental right in health care as part of the Universal Declaration of Human Rights and is an essential part of anesthetic management. Pain medicines, opioids, and multimodal therapies are often unavailable in LICs, despite their low costs and inclusion on the WHO list of essential medications ( Table 2.1 ). In addition to a lack of available pain medications, there is a shortage of trained personnel in regional anesthesia, outside of spinal anesthesia. Equipment to perform regional procedures is often nonexistent. Currently, pain management in the postoperative period is often left to the family to administer. As the WHO mandates essential surgery availability in LICs, it is important to focus on intraoperative and acute postoperative pain management.

Table 2.1

The World Health Organization’s List of Essential Medicines for Anesthesia and Pain Management 2013

Medication Class	Medication
Inhalational gas	Oxygen, halothane, isoflurane, nitrous oxide
Muscle relaxant	Atracurium, suxamethonium
Sedative/hypnotic	Ketamine, propofol or thiopental, midazolam, diazepam
Narcotic	Morphine, codeine
Local anesthetic	Lidocaine, bupivacaine
Nonsteroidal antiinflammatory	Ibuprofen, paracetamol
Antiemetic	Ondansetron
Chronic pain medication	Amitriptyline
Muscle relaxant reversal	Neostigmine
Narcotic antidote	Naloxone
Adrenergic system modulators	Epinephrine, atropine, ephedrine

In 2012, the first WHO global survey on the availability and barriers to access of opioid analgesics to patients in pain was conducted in 81 countries, in collaboration with 17 leading cancer and palliative organizations worldwide. A majority of the global medical opioid consumption occurs in HICs, and only 7% occurs in LICs. Globally, there are 5.5 million patients with terminal cancer and an estimated 80% experience moderate-to-severe pain due to inadequate access to medicines. ^, The survey identified the following barriers:

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Essential opioids are not available. Of the seven on the WHO mandatory list for cancer pain management, only morphine and codeine are on national lists.
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Legal and regulatory restrictions limit access to health care providers and discourage their ability to prescribe them.
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Administrative overregulation and costs passed on to the patient discourage patients from seeking pain relief, regardless of pain levels.
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Inadequate clinical education, misconceptions, social stigma, and fear of addiction are persistent barriers that most urgently need addressing.

There has been an international effort by the WHO to address cancer pain treatment. Morphine was included on the WHO essential medicine list back in 1977, and the three-step analgesic ladder for cancer pain in 1986 incorporated multimodal therapies, all of which are on the WHO list of essential medications ( Table 2.1 ).

In 2008, the Global Year Against Cancer Pain Initiative implemented an educational program based on local needs with a detailed budget at minimal social cost for LMICs. This initiative created a system of pain centers to act as regional hubs for education and training in pain management. They also coordinate with local governments for the expansion of programs. Several reviews have led to significant improvement in clinical management and pain education.

Palliative Pain Management

As the burden of cancer increases in the developing world, a high number of cases will be incurable at the time of diagnosis. Furthermore, it is estimated that 80% of cancer patients will experience moderate-to-severe pain in their cancer journey. In many LMICs, cultural norms, societal attitudes, and personal beliefs accept pain as part of the disease process. In addition, in many of these countries, few doctors and nurses have adequate knowledge of the pain management and treatment options available. Lack of adequate and timely assessment provides little information about the actual incidence and prevalence of acute postoperative pain or chronic pain conditions. ^, The WHO Essential Medications List for pain management includes lidocaine, bupivacaine, morphine, codeine, ketamine, ibuprofen, paracetamol, and amitriptyline. This list informs the MOH about what should be available to treat acute and chronic pain, but in many LMICs, these medications are only sporadically available or not available at all. The basic treatment of postoperative pain, as well as chronic pain and palliative care, will need to be the focus of all medical personnel, including anesthesia providers and general practitioners, for the adequate treatment of cancer in LMICs. To date, there is limited literature on the incidence and prevalence of postoperative and chronic pain in LMICs. Cancer pain and postoperative pain may lead to disability from chronic pain, which is known to have economic consequences in LMICs. ^, ^,

Implementing policies on evidence-based measures and monitoring progress toward alleviating the burden of pain must use a rigorous research agenda. This endeavor would primarily be supported through nongovernmental and international funding agencies and societies.

Future Advances for the Surgical and Anesthesia Management of Cancer Patients in Low-Income Countries

Advancing surgery and safe anesthesia in LMICs will improve cancer care in these settings. The qualities of a successful surgical program are inherent to health care systems in general, and improving surgical and anesthesia care results in improvements elsewhere in the health care system, including critical care and pain management.

Advancing the surgical agenda and adding modern paradigms to the perioperative care process is likely to provide additional improvements to comprehensive cancer care in these settings. In addition, applying the Enhanced Recovery After Surgery (ERAS) principles of care is likely to benefit cancer patients and surgical outcomes in LMICs. Discussions regarding ERAS for LICs are underway, and it is recognized that applying ERAS standardization may improve overall cost-effectiveness and outcomes as LIC surgical systems scale up. ^,

Factors, such as nutritional status, comorbidities, prevalence of HIV, and the burden of disease, should be taken into account when developing an ERAS protocol.

A modified approach to ERAS has shown to provide some benefit in limited resource health care systems ( Fig. 2.2 ). However, more piloting and outcomes analysis are necessary in the short term. Standardization, guidelines, and protocols that are inherent in ERAS success in HICs must be embraced by all health system stakeholders for success and impact on perioperative care and surgical and anesthesia outcomes. Protocols should focus on all elements of ERAS: preoperative evaluation and optimization, cost-effective antibiotics, regional anesthesia, multimodal pain therapy, early removal of drains, and early mobilization. Implementation of modified ERAS protocols is possible at district-level hospitals for all 44 essential surgical procedures and is likely to prove cost-effective and efficient, and improve perioperative outcomes. ^, ^,