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Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: A cohort study

['Annie Herbert', 'Mrc Integrative Epidemiology Unit At University Of Bristol', 'Bristol', 'United Kingdom', 'Population Health Sciences', 'University Of Bristol', 'Epidemiology Of Cancer Healthcare', 'Outcomes', 'Echo', 'Research Group']

Date: None

Table 1 describes the composition of the 6 symptom cohorts by patient characteristic. Except for rectal bleeding, there was a preponderance of women across the cohorts, ranging from 118,371 (50%) for rectal bleeding to 73,583 (73%) for abdominal bloating/distension. The median age at the time of the index consultation ranged from 52 years in the abdominal pain cohort to 63 years in the change in bowel habit and dysphagia cohorts. For abdominal pain, change in bowel habit, dyspepsia, dysphagia, and rectal bleeding, a large majority (87% to 99%) of patients had a single abdominal symptom recorded at their index consultation, and, typically (75% to 92%), without any previous consultations for the other studied abdominal symptoms in the previous year. A contrasting pattern was observed for abdominal bloating/distension, where 66% of all patients had at least another abdominal symptom recorded at their index consultation, while 75% had at least another abdominal symptom recorded either at the index consultation or in the previous year (most frequently for dyspepsia).

During 2000 to 2017, 16,421,201 patients consulted at least once (for any reason) in the 742 general practices included in THIN ( S1 Diagram ). After exclusions, the number of patients with at least 1 consultation with a relevant symptom during 2001 to 2016 was 102,785 for abdominal bloating/distension, 909,451 for abdominal pain, 108,698 for change in bowel habit, 528,428 for dyspepsia, 87,971 for dysphagia, and 240,253 for rectal bleeding ( S1 Diagram ). Across the 6 symptom cohorts, between 86,193 and 890,490 patients had at least 1 consultation for the relevant symptom, which was not preceded by consultations for the same symptom, cancer, or IBD in the previous year.

Positive predictive values of the studied abdominal symptoms

The number of new diagnoses of cancer and new diagnoses of IBD observed in each cohort, together with PPVs for cancer, are presented in Table 2. Overall, the number of patients diagnosed with any cancer and those diagnosed with IBD was of similar order of magnitude, although in men, PPVs for cancer were higher than those for IBD for all abdominal symptoms (e.g., abdominal pain: 1.77% versus 1.17%; Table 2). In contrast, in women, the risk of cancer and IBD tended to be similar; further, for change in bowel habit and for rectal bleeding, the risk of IBD exceeded that for cancer.

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larger image TIFF original image Download: Table 2. Number of incident cases and PPVs (95% CIs) for cancer and for IBD in the year following each abdominal symptom, considering each symptom regardless of other symptoms, or in 2-way combinations with the other examined symptoms * . https://doi.org/10.1371/journal.pmed.1003708.t002

Across the 6 symptom cohorts, 1.41% (95% CI: 1.36% to 1.46%) to 4.64% (4.45% to 4.84%) of men and 1.03% (0.99% to 1.07%) to 2.46% (2.37% to 2.55%) of women were diagnosed with cancer in the year following their index presentation. For each studied abdominal symptom, PPVs for cancer were higher in men than in women. Change in bowel habit, dysphagia, and rectal bleeding were the 3 symptoms with relatively higher PPVs for cancer (men: 4.68%, 4.28%, and 3.20%, respectively, and women: 2.57%, 2.13%, and 2.46%, respectively).

Risks (for both cancer and IBD) were influenced by whether a symptom was recorded “in combination” with other abdominal symptoms (either at the same consultation or during another consultation in the preceding 12 months; Table 2). For example, abdominal bloating/distension in men had a PPV for cancer of 1.65% (95% CI: 1.50% to 1.80%), increasing to 2.53% (2.06% to 2.99%) when combined with abdominal pain. In both sexes, PPVs increased notably if the index symptom was combined with change in bowel habit (among those presenting with any of the other 5 symptoms) or if combined with rectal bleeding (among those presenting with abdominal bloating/distension and change in bowel habit). Consequently, the highest PPVs were seen among those presenting with change in bowel habit combined with rectal bleeding or vice versa; in these strata, the risk of cancer or IBD ranged between 5% and 8% in the year following the index consultation. Among the patients subsequently diagnosed with cancer, the percentage of those with more than 1 symptom recorded in the same consultation or the following year was greatest for abdominal bloating/distension (56%) and dyspepsia (13%), with smaller respective percentages for change in bowel habit (5%) and rectal bleeding, dysphagia, and abdominal pain (2% for all 3).

Considering the composite outcome of either cancer or IBD across the 6 symptom cohorts, PPVs ranged from 2.29% (2.23% to 2.36%) to 7.41% (7.17% to 7.65%) in men and from 2.02% (95% CI: 1.97% to 2.07%) to 5.18% (5.05% to 5.30%) in women (Table 3). Both men and women presenting with change in bowel habit, dysphagia, or rectal bleeding had PPVs for either cancer or IBD exceeding 3%.

PPVs for cancer by sex–age group are shown in Fig 1 (see S1 Table for exact values). Those increased with age, particularly in men presenting with change in bowel habit, dysphagia, and rectal bleeding. Although PPVs for cancer were similar between men and women in younger age groups, PPVs among those aged 60 years or over were higher in men.

In contrast to PPVs for cancer, those for IBD remained similar across age groups (Fig 2; see S1 Table for exact values) and exceeded PPVs for cancer in younger age groups (30 to 39 and 40 to 49 years; Figs 1 and 2).

Considering the composite outcome of either cancer or IBD, the PPVs of dysphagia and rectal bleeding exceeded 3% across all age groups (Fig 3; see S2 Table for exact values), while those of abdominal pain, change in bowel habit, and dyspepsia exceeded 3% in patients aged 60 years or older.

Table 4 contextualises the number of observed cases of cancer and IBD compared with the number of cases that would have been expected by applying the 12-month general population incidence of these outcomes on the age and sex structure of the population of patients presenting with each symptom in our study.

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larger image TIFF original image Download: Table 4. Illustration of additional cases of cancer and IBD following presentation with each studied symptom above what would be expected by the 12-month general population incidence, as applied to the age and sex composition of our study population. https://doi.org/10.1371/journal.pmed.1003708.t004

Table 5 displays PPVs for specific cancer sites, noting that the sum of PPVs across each row slightly exceeds the all-cancer PPVs reported in Table 2, as among the cohorts between 42 and 274 patients (0.02% to 0.16% of the cohorts or 1.9% to 4.8% of those diagnosed with any cancer) were diagnosed with more than 1 cancer type.

For change in bowel habit and rectal bleeding, the all-cancer PPVs in men (4.64% and 3.20%, respectively) were accounted for principally by colon (1.80% and 1.15%) and rectal cancers (1.84% and 1.24%), with similar patterns in women. Similarly, for dysphagia, the all-cancer PPV (4.28% in men and 2.13% in women) was principally accounted for by esophageal cancer (2.74% and 1.06%, respectively). For abdominal bloating/distension in women (all-cancer PPV: 1.33%), the PPV was highest for ovarian cancer (0.54%). Abdominal pain (all-cancer PPV of 1.77% in men and 1.20% in women) and dyspepsia (all-cancer PPV of 1.41% in men and 1.03% in women) had relatively low PPVs, which was accounted for by a broader range of cancer sites. The number of incident cases of cancer and PPVs for cancer (specific to colon, rectal, esophageal, and other cancers, stratified by age groups) are provided in S3 Table.

Among cancer cases, the relative distribution of different cancer sites by symptom cohort (i.e., the cancer site case mix of each symptom cohort among diagnosed cases) is depicted in S1 Fig. Cancer cases diagnosed after presentation with either change in bowel habit or rectal bleeding were most likely diagnosed with colon and rectal cancer, whereas after presentation with dysphagia, esophageal was the most likely cancer diagnosis, noting, however, that across all 6 symptoms, a substantial minority of patients were diagnosed with “other” cancers. Considering patients diagnosed with either cancer or IBD, IBD contributed between 41% and 48% of all such cases for the 5 studied symptoms other than dysphagia, for which IBD was diagnosed in 21% (S2 Fig).

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