Venous Thromboembolism and Risk of Cancer in Patients with Diverticular Disease: A Danish Population-Based Cohort Study

Figures & data

Figure 1 Study flow diagram (*Venous thromboembolism, **Any cancers, ***Fractures/trauma, pregnancy, or surgery, ****According to Charlson Comorbidity Index).

Table 1 Characteristics of Patients Having Venous Thromboembolism (VTE) and Diverticular Disease (DD). Denmark 1996–2016

Variable	Patients with DD and VTE	Patients with DD and PE	Patients with DD and DVT
Total number	3406	1696 (49.8)	1710 (50.2)
Median follow-up time (IQR), years	3.0 (1.0–6.0)	2.1 (0.3–4.7)	3.9 (1.7–7.2)
Median age at VTE diagnosis, years	77.2 (68.4–83.7)	77.8 (69.7–83.9)	76.5 (66.7–90.7)
0–69	981 (28.8)	437 (12.8)	544 (16.0)
70–84	1720 (50.5)	895 (26.3)	825 (24.2)
85+	705 (20.7)	364 (10.7)	341 (10.0)
Sex
Female	2148 (63.1)	1056 (31.0)	1092 (32.1)
Male	1258 (36.9)	640 (18.8)	618 (18.1)
Year of VTE diagnosis
1996–1999	293 (8.6)	110 (3.2)	183 (5.4)
2000–2004	590 (17.3)	260 (7.6)	330 (9.7)
2005–2009	796 (23.4)	353 (10.4)	443 (13.0)
2010–2014	1157 (34.0)	608 (17.9)	549 (16.1)
2015–2016	570 (16.7)	365 (10.7)	205 (6.0)
Type of DD^a
Diverticulitis	213 (6.3)	94 (5.5)	119 (7.0)
Perforated diverticulitis	300 (8.8)	162 (9.6)	138 (8.1)
Type of treatment^b
DD surgically treated	50 (1.7)	22 (0.7)	28 (0.9)
DD conservatively treated	2402 (81.0)	1322 (44.6)	1080 (36.4)
Other cases of diverticular disease	512 (17.3)	164 (5.5)	348 (11.7)
Charlson Comorbidity Index (CCI)
CCI: Low	1227 (36.0)	549 (16.1)	678 (19.9)
CCI: Medium	1501 (44.1)	751 (22.1)	750 (22.0)
CCI: High	678 (19.9)	396 (11.6)	282 (8.3)
Provoking factor^c
Absent	2570 (75.5)	1264 (37.1)	1306 (38.3)
Present	836 (24.5)	432 (12.7)	404 (11.8)

Notes: ^aType of diverticular disease classified according to ICD-10: overall: DK572-9, diverticulitis: 562.11(ICD-8), perforated diverticulitis: 562.12, DK572, DK574, DK578. ^bType of DD treatment classified according to ICD-10: Surgically treated: DK572-9 and KJF, KJG, or KJAH01, conservatively treated: inpatient diagnoses of DK572-9, other: outpatient diagnoses of DK572-9. ^cVTE provoking factors were classified as fracture/trauma, pregnancy, or surgery recorded in the DNPR within three months prior to the VTE event (admission date). Patients without these were considered to have no previous presence of provoking factors.

Abbreviations: PE, pulmonary embolism; DVT, deep venous thrombosis; IQR, interquartile rage.

Figure 2 Cumulative incidence proportion of cancer patients with diverticular disease and venous thromboembolism.

Table 2 One-Year Absolute Risks of Cancer and 95% Confidence Intervals (CI’s) Among Patients with Venous Thromboembolism (VTE) and Diverticular Disease (DD). Denmark 1996–2017

Variable	Absolute First Year-Risk (95% CI)
All	6.2 (5.5–7.1)
Median age at VTE diagnosis, years
0–69	4.9 (3.7–6.4)
70–84	7.7 (6.5–9.0)
85+	4.5 (3.2–6.3)
Sex
Female	5.5 (4.5–6.5)
Male	7.6 (6.2–9.1)
Year of VTE diagnosis
1996–1999	5.5 (3.3–8.5)
2000–2004	4.6 (3.1–6.5)
2005–2009	6.3 (4.7–8.1)
2010–2014	6.6 (5.2–8.1)
2015–2016	7.5 (5.6–9.9)
VTE Type^a
PE	7.3 (6.1–8.6)
DVT	5.2 (4.2–6.3)
Charlson Comorbidity Index (CCI)
CCI: Low	6.8 (5.5–8.3)
CCI: Medium	5.8 (4.7–7.1)
CCI: High	6.2 (4.6–8.2)
Provoking factors^b
Absent	6.5 (5.6–7.5)
Present	5.3 (3.9–6.9)

Notes: ^aICD-10: pulmonary embolism (PE) DI26, deep venous thromboembolism (DVT) DI80.1–3. ^bVTE provoking factors were classified as fracture/trauma, pregnancy, or surgery recorded in the Danish National Patient Registry (DNPR) within three months prior to the VTE event (admission date). Patients without these were considered to have no previous presence of provoking factors.

Table 3 Age, Sex, and Calendar Period Standardized Incidence Ratios (SIRs) of Cancer and 95% Confidence Intervals (CI’s) Among Patients with Diverticular Disease (DD) and Venous Thromboembolism (VTE). Denmark 1996–2017

Variable	First Year After VTE		>1 Year After VTE
	O/E	SIR (95% CI)	O/E	SIR (95% CI)
Total	212/72.7	2.9 (2.5–3.3)	337/300.7	1.1 (1.0–1.3)
Sex
Female	117/41.5	2.8 (2.3–3.4)	199/176.0	1.1 (1.0–1.3)
Male	95/31.2	3.0 (2.5–3.7)	138/124.6	1.1 (0.9–1.3)
Age at having VTE diagnosis
0–69 years	48/14.2	3.4 (2.5–4.5)	120/100.6	1.2 (1.0–1.4)
70–84 years	132/43.0	3.1 (2.6–3.6)	178/163.2	1.1 (0.9–1.3)
85+ years	32/15.4	2.1 (1.4–2.9)	39/36.8	1.1 (0.8–1.5)
Year of VTE diagnosis
1996–1999	16/4.9	3.3 (1.9–5.3)	33/36.3	0.9 (0.6–1.3)
2000–2004	27/10.6	2.5 (1.7–3.7)	96/74.1	1.3 (1.1–1.6)
2005–2009	50/16.7	3.0 (2.2–4.0)	99/93.5	1.1 (0.9–1.3)
2010–2014	76/27.2	2.8 (2.2–3.5)	97/85.1	1.1 (0.9–1.4)
2015–2016	43/13.3	3.2 (2.3–4.4)	12/11.6	1.0 (0.5–1.8)
Type of VTE^a
PE	123/33.9	3.6 (3.0–4.3)	126/114.0	1.1 (0.9–1.3)
DVT	89/38.8	2.3 (1.8–2.8)	221/186.7	1.1 (1.0–1.3)
Charlson Comorbidity Index
CCI: Low	83/25.6	3.2 (2.6–4.0)	150/136.4	1.1 (0.9–1.3)
CCI: Medium	87/33.1	2.6 (2.1–3.2)	132/130.1	1.0 (0.9–1.2)
CCI: High	42/14.0	3.0 (2.2–4.1)	55/34.1	1.6 (1.2–2.1)
Provoking factor^b
Absent	168/56.1	3.0 (2.6–3.5)	265/231.0	1.1 (1.0–1.3)
Present	44/16.5	2.7 (1.9–3.6)	72/69.7	1.0 (0.8–1.3)

Notes: ^aICD-10: pulmonary embolism (PE) DI26, deep venous thromboembolism (DVT) DI80.1–3. ^bVTE provoking factors were classified as fracture/trauma, pregnancy, or surgery recorded in the Danish National Patient Registry (DNPR) within three months prior to the VTE event (admission date). Patients without these were considered to have no previous presence of provoking factors.

Abbreviations: CCI, Charlson Comorbidity Index; O, observed; E, expected.

Table 4 Age, Sex, and Calendar Period Standardized Incidence Ratios (SIRs) of Cancer and 95% Confidence Intervals (CI’s) Among Patients with Venous Thromboembolism (VTE) and Diverticular Disease. Denmark 1996–2017. Numbers and SIRs Below Five are Marked with <5 to Secure Anonymity According to Danish Legislation

Cancer Groups	First Year After VTE		>1 Year After VTE
	O/E	SIR (95% CI)	O/E	SIR (95% CI)
All	212/72.7	2.9 (2.5–3.3)	337/300	1.1 (1.0–1.3)
Stomach	9/1.0	9.2 (4.2–17.4)	6/3.9	1.5 (0.6–3.3)
Large intestine incl. Colon rectosigmoid	24/6.1	3.9 (2.5–5.9)	35/24.9	1.4 (1.0–2.0)
Rectum	<5	NA	9/10.3	0.9 (0.4–1.7)
Pancreas	12/1.8	6.8 (3.5–12.0)	9/7.2	1.3 (0.6–2.4)
Lung, bronchi and trachea	25/7.1	3.5 (2.3–5.2)	48/28.2	1.7 (1.3–2.3)
Malignant melanoma	<5	NA	7/7.3	1.0 (0.4–2.0)
Other skin cancer (excl. Basal cell carcinoma)	5/4.4	1.1 (0.4–2.7)	33/20.5	1.6 (1.1–2.3)
Breast	7/6.8	1.0 (0.4–2.1)	19/28.1	0.7 (0.4–1.1)
Uterus	<5	NA	7/5.7	1.2 (0.5–2.5)
Ovary	11/1.0	11.5 (5.7–20.5)	<5	NA
Prostate	21/6.1	3.5 (2.1–5.3)	22/24.1	0.9 (0.6–1.4)
Kidney	8/1.0	8.2 (3.6–16.2)	<5	NA
Urinary bladder	7/3.3	2.1 (0.8–4.3)	12/13.2	0.9 (0.5–1.6)
Non-Hodgkin malignant lymphoma	10/2.4	4.2 (2.0–7.7)	7/9.9	0.7 (0.3–1.5)
Metastases and non-specified cancer in lymph nodes	20/1.6	12.8 (7.8–19.8)	5/6.2	0.8 (0.3–1.9)
Basal cell carcinoma	16/15.8	1.0 (0.6–1.6)	71/68.1	1.0 (0.8–1.3)

Abbreviations: O, observed; E, expected.

Table 5 One-Year Absolute Risks and Age, Sex, and Calendar Period Standardized Incidence Ratios (SIRs) of Cancer and 95% Confidence Intervals (CI’s) Among Patients with Venous Thromboembolism (VTE) and Diverticular Disease (DD) According to Type and Treatment of DD. Denmark 1996–2017. Numbers and SIRs Below Five are Marked with <5 to Secure Anonymity According to Danish Legislation

Variable	Absolute First Year-Risk (95% CI)	First Year After VTE		>1 Year After VTE
		O/E	SIR (95% CI)	O/E	SIR (95% CI)
Type of DD^a
Diverticulitis	7.5 (4.5–11.6)	16/4.2	3.8 (2.2–6.3)	27/24.1	1.1 (0.7–1.6)
Perforated diverticulitis	9.3 (6.4–13.0)	28/5.3	5.3 (3.5–7.7)	32/24.3	1.3 (0.9–1.9)
Type of treatment^b
DD surgically treated	2.0 (0.2–9.4)	<5	NA	9/5.6	1.6 (0.7–3.1)
DD conservatively treated	6.8 (5.8–7.8)	163/50.5	3.2 (2.8–3.8)	210/197.8	1.1 (0.9–1.2)
Other cases of DD	4.1 (2.6–6.1)	21/12.5	1.7 (1.0–2.6)	59/48.2	1.2 (0.9–1.6)

Notes: ^aType of diverticular disease classified according to ICD-10: overall: DK572-9, diverticulitis: 562.11(ICD-8), perforated diverticulitis: 562.12, DK572, DK574, DK578. ^bType of diverticular disease treatment classified according to ICD-10: Surgically treated: DK572-9 and KJF, KJG, or KJAH01, conservatively treated: inpatient diagnoses of DK572-9, other: Outpatient diagnoses of DK572-9.