Predictive factors associated with carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors

doi:10.3748/wjg.v23.i40.7283

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World Journal of Gastroenterology

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1007-9327

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Retrospective Study

World J Gastroenterol. Oct 28, 2017; 23(40): 7283-7291
Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7283

Table 1 Patient demographics n (%)

	Development Database				Validation Database
	CS Cohort	Non-CS Cohort	All	P value	CS Cohort	Non-CS Cohort	All	P value
n	251	753	1,004		181	543	724
Age (yr) 18-44	52.77 ± 10.88	54.37 ± 13.28	53.97 ± 12.74	0.058	51.76 ± 9.33	51.67 ± 10.03	51.69 ± 9.85	0.913
Age (yr) 18-44	52 (20.7)	143 (19.0)	195 (19.4)	0.034	33 (18.2)	100 (18.4)	133 (18.4)	0.637
45-54	80 (31.9)	219 (29.1)	299 (29.8)		64 (35.4)	203 (37.4)	267 (36.9)
55-64	94 (37.5)	257 (34.1)	351 (35.0)		83 (45.9)	231 (42.5)	314 (43.4)
65+	25 (10.0)	134 (17.8)	159 (15.8)		1 (0.6)	9 (1.7)	10 (1.4)
Female	133 (53.0)	407 (54.1)	540 (53.8)	0.770	109 (60.2)	297 (54.7)	406 (56.1)	0.195
Region				0.306				0.667
Midwest	67 (26.7)	219 (29.1)	286 (28.5)		37 (20.4)	118 (21.7)	155 (21.4)
Northeast	57 (22.7)	200 (26.6)	257 (25.6)		41 (22.7)	100 (18.4)	141 (19.5)
South	106 (42.2)	269 (35.7)	375 (37.4)		80 (44.2)	254 (46.8)	334 (46.1)
West	21 (8.4)	65 (8.6)	86 (8.6)		23 (12.7)	71 (13.1)	94 (13.0)

Table 2 Patients with gastrointestinal neuroendocrine tumors: Most frequent diagnoses1 in carcinoid syndrome patients, ordered by prevalence in carcinoid syndrome cohort n (%)

Diagnosis description	No. of patients		Difference in Rate(CS-Non-CS)	Relative Risk(CS vs Non-CS)
Diagnosis description	CS cohortn = 251	Non-CS cohortn = 753	Difference in Rate(CS-Non-CS)	Relative Risk(CS vs Non-CS)
Abdominal pain²	166 (66.14)	388 (51.53)	14.61%	1.28
Hypertension²	127 (50.60)	393 (52.19)	-1.59%	0.97
Dyslipidemia²	124 (49.40)	347 (46.08)	3.32%	1.07
Benign neoplasm large bowel	79 (31.47)	241 (32.01)	-0.53%	0.98
Esophageal reflux	74 (29.48)	190 (25.23)	4.25%	1.17
Diverticulosis of colon (without mention of hemorrhage)	68 (27.09)	159 (21.12)	5.98%	1.28
Liver disorder²	56 (22.31)	79 (10.49)	11.82%	2.13
Chest pain, unspecified	53 (21.12)	147 (19.52)	1.59%	1.08
Anemia, unspecified	51 (20.32)	141 (18.73)	1.59%	1.09
Pain in limb	41 (16.33)	117 (15.54)	0.80%	1.05
Internal hemorrhoids without mention of complication	41 (16.33)	87 (11.55)	4.78%	1.41
Neoplasm of uncertain behavior of stomach, intestine, and rectum	39 (15.54)	95 (12.62)	2.92%	1.23
Nonspecific (abnormal) findings on radiological and other examination of gastrointestinal tract	38 (15.14)	66 (8.76)	6.37%	1.73
Lumbago	38 (15.14)	79 (10.49)	4.65%	1.44
Enlargement of lymph nodes	36 (14.34)	40 (5.31)	9.03%	2.70
Malignant neoplasm of colon, unspecified site	35 (13.94)	114 (15.14)	-1.20%	0.92
Hypothyroidism, unspecified	34 (13.55)	106 (14.08)	-0.53%	0.96
Abdominal or pelvic swelling, mass, or lump, unspecified site (begin 1994)	34 (13.55)	60 (7.97)	5.58%	1.70
Other and unspecified noninfectious gastroenteritis and colitis	32 (12.75)	73 (9.69)	3.05%	1.32
Type 2 diabetes mellitus²	32 (12.75)	158 (20.98)	-8.23%	0.61
Other specified disorders of intestine	29 (11.55)	70 (9.30)	2.26%	1.24
Obesity, unspecified	28 (11.16)	82 (10.89)	0.27%	1.02
Diaphragmatic hernia	28 (11.16)	65 (8.63)	2.52%	1.29
Headache	28 (11.16)	74 (9.83)	1.33%	1.14
Anxiety state, unspecified	27 (10.76)	71 (9.43)	1.33%	1.14
Acute appendicitis, unspecified	26 (10.36)	91 (12.08)	-1.73%	0.86
Reflux esophagitis	26 (10.36)	41 (5.44)	4.91%	1.90
Abdominal or pelvic swelling, mass, or lump, other specified site	26 (10.36)	35 (4.65)	5.71%	2.23
Dyspepsia and other specified disorders of function of stomach	26 (10.36)	26 (3.45)	6.91%	3.00
Urinary tract infection, unspecified	26 (10.36)	96 (12.75)	-2.39%	0.81
Pre-operative cardiovascular examination	25 (9.96)	102 (13.55)	-3.59%	0.74
Tobacco use disorder	24 (9.56)	77 (10.23)	-0.66%	0.94
Constipation, unspecified	24 (9.56)	79 (10.49)	-0.93%	0.91

¹Claims in 1 year prior to the index date, excluding those for CS, NET, or symptoms/conditions known to be associated with CS;

²Abdominal Pain (ICD-9-CM 789.0x, 789.6x); Type 2 DM (ICD-9-CM 250.x0, 250.x2); Hypertension (ICD-9-CM 401.xx, 402.xx, 403.xx, 404.xx, 405.xx, 437.2x); Dyslipidemia (ICD-9-CM 272.xx); Liver disorder (ICD-9-CM 573.8x, 573.9x). Variables not shown: Screening (Routine medical examination, Other screening mammogram, Long-term (current) use of other medications, Routine gynecological examination, Vaccination for influenza, Screen for malignant neoplasms of colon, Other specified pre-operative examination; GI cancer (Digestive neoplasm, unspecified); Prevalence < 10% in both CS and non-CS cohort (Screening for malignant neoplasms of prostate, Backache unspecified, Other abnormal blood chemistry, Vitamin D deficiency unspecified, Lumbar or lumbosacral intervertebral disc degeneration, Atrophic gastritis without mention of hemorrhage, Personal history of colonic polyps, Cervicalgia, Iron deficiency anemia unspecified). CS: Carcinoid syndrome; NET: Neuroendocrine tumors.

Table 3 Patients with gastrointestinal neuroendocrine tumors: Selected measures n (%)

	Development database				Validation database
	CS Cohort	Non-CS Cohort	All	P value	CS Cohort	Non-CS Cohort	All	P value
n	251	753	1004		181	543	724
Abdominal pain	166 (66.1)	388 (51.5)	554 (55.2)	< 0.001	104 (57.5)	253 (46.6)	357 (49.3)	0.011
Dyslipidemia	124 (49.4)	347 (46.1)	471 (46.9)	0.361	67 (37.0)	209 (38.5)	276 (38.1)	0.724
Diverticulosis of colon	68 (27.1)	159 (21.1)	227 (22.6)	0.050	37 (20.4)	93 (17.1)	130 (18.0)	0.314
Liver disorder	56 (22.3)	79 (10.5)	135 (13.4)	< 0.001	50 (27.6)	44 (8.1)	94 (13.0)	< 0.001
Enlarged lymph nodes	36 (14.3)	40 (5.3)	76 (7.6)	< 0.001	23 (12.7)	25 (4.6)	48 (6.6)	< 0.001
Type 2 diabetes	32 (12.7)	158 (21.0)	190 (18.9)	0.004	30 (16.6)	91 (16.8)	121 (16.7)	0.954
Abdominal mass	26 (10.4)	35 (4.6)	61 (6.1)	0.010	23 (12.7)	16 (2.9)	39 (5.4)	< 0.001
Dyspepsia and other specified disorders of function of stomach	26 (10.4)	26 (3.5)	52 (5.2)	< 0.001	8 (4.4)	35 (6.4)	43 (5.9)	0.318

CS: Carcinoid syndrome

Table 4 Patients with gastrointestinal neuroendocrine tumors: Results of final model

Independent variable¹	Development database		Validation database
Independent variable¹	OR (95%CI)	P value	OR (95%CI)	P value
Age group
18-44 vs 65+	2.30 (1.26-4.23)	0.007	4.88 (0.56-42.11)	0.150
45-54 vs 65+	1.94 (1.14-3.31)	0.015	3.63 (0.43-30.41)	0.235
55-64 vs 65+	2.01 (1.20-3.38)	0.008	3.85 (0.46-31.93)	0.212
Number of chronic conditions	0.94 (0.87-1.01)	0.093	1.13 (1.02-1.24)	0.014
Abdominal pain	1.50 (1.08-2.09)	0.016	1.22 (0.83-1.77)	0.309
Dyslipidemia	1.52 (1.08-2.15)	0.016	0.83 (0.55-1.25)	0.373
Diverticulosis of colon	1.55 (1.08-2.24)	0.019	1.16 (0.72-1.86)	0.537
Liver disorder²	2.12 (1.40-3.20)	< 0.001	3.38 (2.07-5.51)	< 0.001
Enlarged lymph nodes	2.33 (1.38-3.92)	0.001	2.13 (1.10-4.11)	0.025
Type 2 diabetes	0.59 (0.38-0.92)	0.021	0.89 (0.54-1.48)	0.653
Abdominal mass	1.89 (1.06-3.37)	0.031	3.79 (1.87-7.69)	< 0.001
Dyspepsia and other specified disorders of function of stomach	2.95 (1.60-5.43)	< 0.001	0.54 (0.23-1.26)	0.154

¹Variables found consistently significantly associated with risk of CS are bolded;

²Liver disorder includes other specified disorders of liver (ICD-9-CM 573.8x, 573.9x). CS: Carcinoid syndrome.

Citation: Cai B, Broder MS, Chang E, Yan T, Metz DC. Predictive factors associated with carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors. World J Gastroenterol 2017; 23(40): 7283-7291
URL: https://www.wjgnet.com/1007-9327/full/v23/i40/7283.htm
DOI: https://dx.doi.org/10.3748/wjg.v23.i40.7283