Capsule Endoscopy for Management of Small Bowel Melanoma—Is It Time Yet?

The global burden of melanoma is increasing. Currently, 132,000 cases of melanoma are diagnosed each year worldwide.¹ In Australia, which has the highest incidence of melanoma in the world, more than 11,000 new cases are diagnosed every year.² The number of cases doubled in the 20 years from 1986 to 2006.² In 2007, a total of 1,279 Australians died from melanoma, making this cancer responsible for 3.2% of all cancer deaths.² Overall, 1 in 19 Australians will be diagnosed with melanoma before the age of 85 years. The risk of melanoma is higher among men than women (1 in 15 vs 1 in 24, respectively).² Melanoma is now the third most common form of cancer in both Australian men (behind prostate cancer and colon cancer) and Australian women (behind breast cancer and colon cancer), and melanoma comprises 10% of all cancers.² It is the most common cancer in young Australians (aged 15—44 years), and it kills more young Australians than any other single cancer.² Although melanoma makes up only 2.3% of all skin cancers, it is responsible for 75% of skin cancer deaths.²

In the United States, the incidence of melanoma is about one third as high as in Australia, but this incidence has also been increasing over the past 30 years.^3,4 Between 1992 and 2004, the rate of diagnosis rose by 3.1% annually.⁵ An estimated 123,590 new cases of melanoma were diagnosed in the United States in 2011, resulting in 8,790 deaths.³ As in Australia, melanoma is the most common form of cancer for young adults in the United States.⁶ Of particular concern is the rise seen among women aged 15—29 years, in whom the torso is the most common location of the tumor. This finding has been attributed to high-risk tanning behaviors.⁷ Melanoma is 10 times more common in whites than in African Americans, Latinos, and Asians, but it is frequently fatal in these ethnic groups.^3,5 One American dies of melanoma almost every hour (every 62 minutes).³

European figures also show an increasing incidence of melanoma.^8,9 The highest rates have been reported in Scandinavia, where 15 patients are diagnosed per 100,000 individuals per year. This finding is due to the high-risk skin type of this population.

The rates of melanoma in Mediterranean countries are lower, at 5—7 cases per 100,000 individuals per year.¹⁰ Data from Asia, the Middle East, and Africa are limited but indicate low rates of melanoma in these areas.⁸

The risk of developing melanoma depends on a combination of genetic and environmental factors. A personal or family history of melanoma increases this risk significantly, as does the presence of atypical or numerous moles (more than 50), immunosuppression, and/or a history of other skin cancers.³ Other factors that make melanoma more likely include sun sensitivity (characterized by sunburning easily, difficulty tanning, and natural blond or red hair color), excessive sun exposure, and use of tanning booths; this recreational sun exposure is the main reason for the rising incidence of melanoma, particularly among patients with fair skin, who have a higher risk overall.¹ Depletion of the ozone layer, with its protective function as a filter for ultraviolet radiation, may also be contributing to the rising rates of melanoma. Estimates suggest that a 10% decrease in ozone levels will result in an additional 4,500 cases of melanoma.¹

Clinicians have long recognized that melanoma is more likely than other skin tumors to spread to other parts of the body, and melanoma is the most common tumor to metastasize to the gastrointestinal (GI) tract. When it does metastasize to the GI tract, the small bowel (SB) is involved more frequently than the stomach or the colon.^11-15 Primary SB melanoma is extremely rare.¹⁶ The case report by Atiq and coauthors adds to previous reports of SB involvement by melanoma.¹⁷ Importantly, this case illustrates that not all patients are symptomatic, not all melanoma lesions are pigmented, and the most common lesion is polypoid in nature.^18-20 In this particular case, the pretest probability of finding an abnormality was high since the patient had one of the most common indicators of possible SB melanoma, namely iron-deficiency anemia due to occult bleeding.^16,21-23

Albert and colleagues recently proposed an algorithm for the detection of SB melanoma.²⁴ In their open, mul-ticenter, prospective study, 390 patients with melanoma of all stages were screened for GI bleeding using fecal occult blood testing (FOBT). Those patients who were positive by FOBT underwent panendoscopy, including capsule endoscopy (CE). In addition, all patients with stage IV disease (distant metastases) were offered pan-endoscopy. Forty-nine of the 390 patients (12.6%) were positive by FOBT or had other evidence of GI bleeding. Thirty-eight of these patients (77.6%) agreed to undergo endoscopic evaluation. The detection rate of SB melanoma was 28.6% in patients with stage IV disease but then dropped significantly: 1.7% in patients with stage III disease (nodal involvement) and 0% in patients with stage I/II disease. In patients who were FOBT-positive alone, SB melanoma detection rates were higher: 72.7% in patients with stage IV disease and 14.3% in patients with stage III disease. In 10 patients, SB melanoma was detected by CE. Albert and colleagues also found that a positive FOBT result was an independent, negative prognostic factor for survival in patients with stage III or IV disease.²⁴

The question that always arises is whether there is any clinical benefit to the detection of SB involvement by melanoma. Approximately 84% of melanomas are diagnosed when they are still localized. Treatment at this early stage is generally successful, with a 5-year survival rate of 98%.³ This rate falls to 62% and 16% for patients with regional and distant spread, respectively. Patients with advanced disease are more likely to have SB involvement.²⁴ Similarly, those with secondary tumors in the SB will often have metastases elsewhere.²⁵ While the prognosis in this group is generally poor, studies have shown that complete resection of metastatic melanoma can significantly improve survival and provide effective palliation.^{14,15,22,23,26-28} This reasoning also applies to resection of GI disease, which is safe and can achieve prolonged remission.²⁹ It is therefore recommended that clinicians attempt to identify SB secondary tumors in symptomatic patients who are undergoing treatment with “curative” intent.

It is reasonable to hypothesize that finding SB melanoma at an earlier stage could improve survival. As mentioned by Atiq and coauthors in their literature review, CE is superior to other modalities for detecting SB tumors.¹⁷ Given that the SB is the most common location for GI melanoma metastases, CE would seem to be an ideal diagnostic tool.^11-15 We have previously reported that CE is more sensitive than SB follow-through and abdominal computed tomography (CT) for detecting SB melanoma.¹⁹ CE can also identify SB involvement that is not seen on fludeoxyglucose positron emission tomography—CT scanning, although the converse may also apply.¹⁸

In the case report by Atiq and colleagues, the capsule was retained.¹⁷ However, the case report does not document whether it was found at surgery. Capsule retention is a possibility in any patient with a tumor. However, in our series, the capsule passed spontaneously in all patients.¹⁸ Nevertheless, the possibility of capsule retention is not a contraindication to the procedure, provided the patient does not have a history of small bowel obstruction.

At present, we recommend that melanoma patients be investigated by CE for possible SB disease if they have either iron-deficiency anemia or unexplained GI symptoms or signs, provided they do not have end-stage disease that would preclude further treatment if metastases are found.

Likewise, any patient with increased uptake in the abdomen on a PET-CT scan should also undergo CE. These 2 investigations should be regarded as complementary.