‘Don’t ignore the warning signs’: A message pays off in Nigeria

Memorial Sloan Kettering

EDITOR’S NOTE: This story was reported in collaboration with the Global Health Reporting Center and support from the Pulitzer Center.

The small business owner was diagnosed with appendicitis. The university lecturer and the government clerk, both struggling with stomach pain for more than a year, were told they had ulcers. In each case, the real problem turned out to be colorectal cancer. By the time they were diagnosed, all three required major surgery and nearly a year of debilitating chemotherapy treatments.

These patients live in and around Ile-Ife, a city in southwestern Nigeria, where they shared their stories with CNN. All three were ultimately treated at the Obafemi Awolowo University teaching hospital by Dr. Olusegun Alatise, a professor of surgery.

When he began surgical training in the early 2000s, Alatise was taught that colorectal cancer was rare in sub-Saharan Africa. But it didn’t match what he saw with his own eyes.

“It was supposed to be very rare, but we [the teaching hospital] were seeing a case every week,” he said. “We are talking about an exponential increase in the incidence of colorectal cancer.”

The picture in Nigeria is starkly different from that in the US or western Europe, where 2 in 3 colorectal cancer patients survive at least five years beyond their diagnosis. In Nigeria, it’s just 1 in 5. The biggest reason for the discrepancy, said Alatise, is that patients in Nigeria tend to seek treatment much later in the course of the disease.

“A majority only come to the teaching hospital for treatment when the disease has spread,” he said. “They have symptoms that were neglected. They’d be having rectal bleeding for a year, but everybody would be treating them with other medicines.”

With its aging buildings and visibly worn exam rooms, the OAU hospital doesn’t fit central casting’s idea of a state-of-the-art cancer center, but Alatise has helped build partnerships that are shaping care not just in Nigeria but around the world.

That part of Alatise’s journey started in 2009, when he secured a spot in a program to train international physicians to modernize cancer care in their home countries. It was based at Memorial Sloan Kettering Cancer Center in New York City. Alatise was the first African surgeon to apply.

Laila Johnson-Salami

In the months he spent in New York, Alatise learned new surgical techniques and formed a fast friendship with Dr. Peter Kingham, an American surgeon who had previously worked in Malawi, South Africa, Tanzania and Sierra Leone, and who himself was just finishing a surgical oncology fellowship. In 2011, after returning to Nigeria, Alatise invited Kingham for a visit of several weeks, in what would soon become an annual routine. By then, Kingham had helped establish the Global Cancer Disparities Initiative at Memorial Sloan Kettering. In 2013, the two men founded the African Research Group for Oncology (ARGO), to improve training programs and expand opportunities for Africa-based research.

“The goal is to do clinically meaningful research,” Kingham said. “At MSK, we do a ton of esoteric research, most of which is important, but it’s also a luxury. [In Nigeria] we don’t have the same luxury. Everything we do, we have to ask, ‘Can this really change the course of what happens to a patient?’ ”

The effort has grown to encompass more than two dozen sites in Nigeria, with more than 60 staffers and nearly 10,000 patients taking part in various research programs. At least four grants from the US National Institutes of Health have supported work by ARGO, with colorectal cancer as a major focus.

Globally, as a killer, colorectal cancer ranks second only to lung cancer. What’s more, its incidence is steadily increasing, driven by a surge of cases in young adults. Colorectal cancer rates are higher in the US and Europe than they are in Africa or South Asia, but the gap is shrinking.

Genetics, smoking and alcohol use are risk factors, but Kingham says changing diets are the biggest cause of the global increase. “A Western diet is strongly associated with colorectal cancer, and so are processed foods. That’s the curse of development,” he said.

Alatise says the typical Nigerian diet has shifted dramatically in recent years. “Even people that come from a rural community are mostly eating processed food, because processed food is regarded as the rich man’s food, whereas a high-fiber diet and traditional foods are seen as a poor man’s food,” he said. “Abroad, every rich man is trying to add that fiber to their diet, but in Africa, they’re trying to be more westernized.”

As a practical matter, Alatise saw improving screening as a faster way to improve outcomes for patients, compared with convincing them to change what they eat.

In 2014, he and colleagues at ARGO launched the first of three pilot projects to see whether they could catch cases earlier. In the first study, 362 patients with rectal bleeding were offered free colonoscopies. Nearly 20% had colorectal cancer. Crucially, 74% of the cases were found at a potential curable stage, double the historical rate. The research team also determined that while rectal bleeding alone did not reliably predict colorectal cancer, it did if it appeared along with weight loss and a change in bowel habits.

This was a valuable insight, to better allocate scarce resources in a country where the standard cost of a colonoscopy is half the average monthly income. Other ARGO-led studies concluded that less expensive screening tests, which are widely used in the US and look for blood in stool, are too costly to implement at scale in Nigeria due to the number of follow-up colonoscopies that would be required for people who test positive.

More recently, Alatise and colleagues took on the problem that had so frustrated him since his days as a young surgeon: patients whose symptoms are missed or ignored. Initially, the group aired jingles on the radio and distributed flyers around Ife, stressing the importance of early detection. Then they trained providers at a network of local clinics where patients receive basic medical care.

The information was simple: reminding providers about the combination of symptoms - bleeding and weight loss - that were so telling in the first study. “They were told more about how to identify these symptoms and how to get a history from the patient,” and how to quickly refer the person for further screening at a hospital if needed, explained Dr. Tajudeen Mohammed, a surgeon who helped with the project.

Simple as the messages were, conversations could be difficult. The patients who met with CNN all said their previous doctors treated cancer as taboo. Two said doctors never even told them they had cancer, even after their diagnoses; both learned the news from family members. Mayowa Ajayi, a government clerk, says he had never even heard of colorectal cancer before he landed in the hospital. And a university lecturer, 44, who was given anti-ulcer medication for months even as she endured intense pain and trouble with bowel movements, asked to remain anonymous because revealing her illness would cause too much trouble with colleagues and friends.

Chris Bamidele, a research associate who coordinates studies on colorectal cancer for ARGO, says many patients are reluctant to seek help. “For some people, I think it’s fear, and for others, there’s a religious ideology around things like [cancer],” he said. Others lack transportation or can’t afford the cost of a doctor’s visit and turn to herbal remedies instead, Bamidele said.

Despite such hurdles, the nurses and doctors behind the pilot program say it shows that their messages worked. More than 300 people were referred for colonoscopies - which were offered free in the pilot program - which identified four cases of early-stage cancer and another 13 cases of high-risk precancerous polyps that were easily removed. Alatise says that included two senior colleagues who signed up for screenings out of curiosity. “They could have ended up dead from colorectal cancer, but we removed the polyps, and now those guys are doing very well,” he said.

But there are hurdles to broader implementation, starting with cost. Alatise says the research group is trying to expand education for health providers while working in tandem with Memorial Sloan Kettering and the University of Alberta to develop a screening test that could diagnose colorectal cancer by looking for metabolites in urine.

The research isn’t limited to screening. Earlier this year, Alatise’s group launched a trial to treat colorectal cancer patients with tislelizumab, a type of drug known as an immune checkpoint inhibitor, which helps the body’s own immune system recognize and fight cancer cells. It’s one of just a handful of immunotherapy trials ever conducted in sub-Saharan Africa. Based on prior studies, Kingham says, tislelizumab appears to be most effective in patients with a specific genetic signature - a signature that is three times more prevalent in Nigeria than in the US. “That means it’s three times more likely to benefit patients there,” he said.

Along with improving care for patients in Nigeria, Kingham says the partnership with ARGO is a clear opportunity to help patients everywhere. One reason: While the cost of many medical procedures - like colonoscopies - can be a stretch for ordinary Nigerians, they can be offered in clinical trials for a fraction of what it costs in higher-income countrie s. That means research dollars go further.

But such calculations were only in the background on the summer day where the university lecturer recounted her health struggles over the past five years. She beat the odds, despite her late diagnosis. Today she’s cancer-free but urges others not to wait as long as she did. “Getting screened isn’t comfortable, but the discomfort is way less than the problem of becoming a cancer patient,” she said. “I encourage people to embrace it.”

纪念斯隆-凯特琳癌症中心

编者按：本文由全球健康报道中心合作撰写，并得到普利策中心的支持。

这位小企业主被诊断出患有阑尾炎。那位大学讲师和那位政府职员，两人都饱受胃痛折磨一年多，却被告知患有溃疡。然而，最终确诊的都是结直肠癌。等到确诊时，三人都已接受了大型手术，并经历了近一年痛苦不堪的化疗。

这些患者居住在尼日利亚西南部城市伊莱伊费及其周边地区，他们向CNN讲述了自己的经历。最终，这三名患者都在奥巴费米·阿沃洛沃大学教学医院接受了外科教授奥卢塞贡·阿拉蒂斯博士的治疗。

2000 年代初，阿拉蒂斯开始接受外科培训时，他被告知结直肠癌在撒哈拉以南非洲地区很少见。但这与他亲眼所见的情况并不相符。

“原本以为这种病非常罕见，但我们（这家教学医院）每周都会接诊一例，”他说。“我们现在说的是结直肠癌发病率呈指数级增长。”

尼日利亚的情况与美国或西欧截然不同。在美国或西欧，三分之二的结直肠癌患者在确诊后至少能存活五年。而在尼日利亚，这一比例仅为五分之一。阿拉蒂斯指出，造成这种差异的最大原因是尼日利亚的患者往往在疾病发展到晚期才寻求治疗。

他说：“大多数患者只有在病情扩散后才会到教学医院就诊。他们的症状都被忽视了。他们可能已经直肠出血一年之久，但所有人都用其他药物治疗他们。”

由于建筑老旧、检查室明显破旧，OAU 医院并不符合人们对一流癌症中心的普遍印象，但 Alatise 帮助建立了合作伙伴关系，这些合作伙伴关系不仅正在塑造尼日利亚的医疗护理，而且正在塑造全世界的医疗护理。

阿莱蒂斯的这段旅程始于2009年，当时他获得了一个培训国际医生以改善其本国癌症治疗水平的项目名额。该项目设在纽约市的纪念斯隆-凯特琳癌症中心。阿莱蒂斯是第一位申请该项目的非洲外科医生。

莱拉·约翰逊-萨拉米

在纽约的几个月里，阿拉蒂斯学习了新的外科手术技巧，并与彼得·金厄姆医生迅速结下了深厚的友谊。金厄姆医生是一位美国外科医生，曾在马拉维、南非、坦桑尼亚和塞拉利昂工作，当时他刚刚完成外科肿瘤学专科培训。2011年，阿拉蒂斯回到尼日利亚后，邀请金厄姆医生来访数周，此后这很快成为每年的例行活动。那时，金厄姆医生已协助在纪念斯隆-凯特琳癌症中心建立了全球癌症差异倡议。2013年，两人共同创立了非洲肿瘤研究小组（ARGO），旨在改进培训项目，并拓展非洲的研究机会。

“我们的目标是开展具有临床意义的研究，”金厄姆说。“在纪念斯隆-凯特琳癌症中心，我们做了很多深奥的研究，其中大部分都很重要，但这也是一种奢侈。[在尼日利亚]我们没有同样的条件。我们做的每一件事，都必须问自己：‘这真的能改变患者的命运吗？’”

该项目已发展到覆盖尼日利亚二十多个研究中心，拥有六十多名工作人员和近万名患者参与各项研究项目。美国国立卫生研究院至少四项拨款支持了ARGO的研究工作，其中结直肠癌是重点研究领域。

在全球范围内，结直肠癌的致死率仅次于肺癌。更令人担忧的是，其发病率正在稳步上升，这主要是由于年轻人群病例激增所致。美国和欧洲的结直肠癌发病率高于非洲和南亚，但差距正在缩小。

遗传、吸烟和饮酒都是风险因素，但金厄姆表示，饮食习惯的改变才是全球结直肠癌发病率上升的最大原因。“西式饮食与结直肠癌密切相关，加工食品也是如此。这就是发展的弊端，”他说道。

阿拉蒂斯表示，近年来尼日利亚人的典型饮食习惯发生了巨大变化。“即使是来自农村地区的人们，也大多吃加工食品，因为加工食品被认为是富人的食物，而高纤维饮食和传统食物则被视为穷人的食物，”他说。“在国外，每个富人都在努力增加膳食纤维的摄入量，但在非洲，人们却试图变得更加西化。”

从实际角度来看，阿拉蒂斯认为，与说服患者改变饮食习惯相比，改进筛查是改善患者预后的更快方法。

2014年，他和ARGO的同事启动了三个试点项目中的第一个，旨在探索能否更早地发现病例。在第一项研究中，362名直肠出血患者接受了免费的结肠镜检查。其中近20%的患者患有结直肠癌。至关重要的是，74%的病例在潜在可治愈阶段被发现，是历史数据的两倍。研究团队还发现，虽然单纯的直肠出血并不能可靠地预测结直肠癌，但如果伴有体重减轻和排便习惯改变，则可以有效预测。

这项发现极具价值，有助于在结肠镜检查费用相当于平均月收入一半的国家更好地分配稀缺资源。其他由ARGO牵头的研究也得出结论：在美国广泛使用的、价格较低的粪便隐血筛查方法，由于阳性患者需要进行多次后续结肠镜检查，因此在尼日利亚大规模推广成本过高。

最近，阿拉蒂斯和他的同事们着手解决一个自他年轻时做外科医生以来就一直困扰着他的难题：患者的症状常常被漏诊或忽视。起初，他们通过电台播放宣传歌曲，并在伊费市各处散发传单，强调早期发现的重要性。随后，他们为当地诊所网络的医护人员提供培训，这些诊所为患者提供基础医疗服务。

信息很简单：提醒医护人员注意出血和体重减轻这两种症状的组合——这些症状在第一项研究中表现得尤为明显。“他们被告知要更多地了解如何识别这些症状，如何询问患者病史，”参与该项目的外科医生塔朱丁·穆罕默德博士解释说，“以及如果需要，如何迅速将患者转诊至医院进行进一步筛查。”

尽管信息很简单，但对话却可能很艰难。接受CNN采访的患者都表示，他们之前的医生对癌症视而不见。其中两位患者说，即使在确诊之后，医生也从未告诉过他们患有癌症；她们都是从家人那里得知这一消息的。政府职员马约瓦·阿贾伊说，在住院之前，他甚至从未听说过结直肠癌。一位44岁的大学讲师，在忍受着剧烈疼痛和排便困难的情况下，仍然服用抗溃疡药物数月之久。她要求匿名，因为公开病情会给同事和朋友带来太多麻烦。

ARGO 负责协调结直肠癌研究的研究员克里斯·班米德勒表示，许多患者不愿寻求帮助。“我认为有些人是因为恐惧，而另一些人则是因为对癌症之类的疾病抱有宗教信仰，”他说。班米德勒还提到，还有一些人缺乏交通工具或负担不起看医生的费用，于是转而求助于草药疗法。

尽管面临诸多挑战，试点项目的医护人员表示，这表明他们的宣传信息发挥了作用。试点项目为300多人提供免费的结肠镜检查，结果发现4例早期癌症和13例高风险癌前息肉，这些息肉均被轻松切除。阿拉蒂斯表示，这其中还包括两位出于好奇而报名参加筛查的资深同事。“他们原本可能死于结直肠癌，但我们切除了息肉，现在他们恢复得很好，”他说道。

但要更广泛地推广应用这项技术，首先面临成本方面的挑战。阿拉蒂斯表示，研究小组正努力扩大对医护人员的教育，同时与纪念斯隆-凯特琳癌症中心和阿尔伯塔大学合作，开发一种通过检测尿液中的代谢物来诊断结直肠癌的筛查测试。

这项研究并不局限于筛查。今年早些时候，阿拉蒂斯的研究团队启动了一项试验，使用替雷利珠单抗（一种免疫检查点抑制剂）治疗结直肠癌患者。这种药物能够帮助人体自身的免疫系统识别并对抗癌细胞。这是撒哈拉以南非洲地区开展的为数不多的免疫疗法试验之一。金厄姆表示，根据之前的研究，替雷利珠单抗似乎对具有特定基因特征的患者最为有效——这种基因特征在尼日利亚的出现频率是美国的三倍。“这意味着，在尼日利亚，这种疗法更有可能使患者获益，”他说道。

金厄姆表示，与ARGO的合作不仅能改善尼日利亚患者的医疗护理，更是一个惠及全球患者的绝佳机会。原因之一是：许多医疗程序（例如结肠镜检查）对普通尼日利亚人来说费用高昂，但在临床试验中，这些程序的费用仅为高收入国家的几分之一。这意味着研究经费能发挥更大的作用。

但在那年夏天的一个下午，这位大学讲师讲述自己过去五年与病魔抗争的经历时，这些考量都只是背景。尽管确诊较晚，她还是战胜了病魔。如今她已摆脱癌症，但她告诫其他人不要像她一样拖延。“筛查虽然不舒服，但这种不适远不及罹患癌症的痛苦，”她说，“我鼓励大家积极接受筛查。”