Gallbladder cancer – no improvement in survival over time in a Swedish population

Figures & data

Figure 1. Flowchart presenting the variety of treatments over three time periods.

Table 1. Demographics, staging and grading of the patients.

	2000–2004	2005–2009	2010–2014	Total
Total	182	168	196	546
Diagnosed at death	24 (13%)	11 (7%)	4 (2%)	39 (7%)
Article I. Diagnosed in the clinic	158	157	192	507
Invasive/not invasive	153/5	149/8	180/12	482/25
Male/female (%)	27/73	23/77	30/70	26/74
Age, years
<50	1	9	6	16
50–59	14	17	12	43
60–69	35	45	50	129
70–79	68	47	66	181
>80	36	31	45	112
Total diagnosed	154	149	179	482
Clinical only	31 (20%)	26 (17%)	53 (30%)	110 (23%)
Histopathological confirmation	123 (80%)	123 (83%)	126 (70%)	372 (77%)
Staging
T1	5 (3%)	11 (7%)	4 (2%)	20 (4%)
T2	5 (3%)	11 (7%)	19 (11%)	35 (7%)
T?	3 (2%)	1 (1%)	2 (1%)	6 (1%)
T3	16 (10%)	1 (1%)	15 (8%)	32 (7%)
T4	18 (12%)	11 (7%)	7 (4%)	36 (7%)
N1	19 (12%)	13 (9%)	27 (15%)	59 (12%)
M1	65 (42%)	93 (62%)	101 (56%)	259 (54%)
Not staged	23 (15%)	8 (5%)	4 (2%)	35 (7%)
Grading
High differentiated	11 (7%)	13 (8%)	19 (11%)	43 (9%)
Intermediate differentiated	41 (26%)	28 (19%)	37 (21%)	105 (22%)
Low differentiated	40 (26%)	36 (24%)	33 (18%)	109 (23%)
Squamous cell ca	4 (3%)	6 (4%)	1 (6%)	11 (2%)
No grading reported	27 (18%)	40 (29%)	38 (21%)	101 (22%)
Doubtful gallbladder cancer diagnosis	19 (12%)	22 (15%)	25 (14%)	66 (14%)
Differential diagnosis
GBC or IHC	3	6	5	14
GBC or PHC	15	14	20	49
GBC or pancreas ca	1	1		2
GBC or gastric ca	0	1	0	1

Figure 2. (a) Survival for individuals whose diagnosis of GBC was histologically verified or based on clinical findings (p < .0001). (b) Survival over three time periods (p = .28). (c) Survival for individuals with stage M1 cancer. Period A versus Period B (p = .0005).

Table 2. Uni- and multivariable Cox regression analyses on survival.

	Univariable analyses			Multivariable analyses
	N = 482			N = 482
	n	HR (95% CI)	p	n	HR (95% CI)	p
Period	482			482
2000–2004	154	1	–		1	–
2005–2009	149	0.96 (0.76–1.21)	.744		0.91 (0.70–1.18)	.469
2010–2014	179	0.86 (0.68–1.08)	.191		0.78 (0.61–1.01)	.064
Age	482			482
<50	16	0.51 (0.27–0.94)	.032		0.46 (0.24–0.88)	.019
50–59	43	0.65 (0.45–0.94)	.022		0.77 (0.53–1.13)	.185
60–69	129	1	–		1	–
70–79	181	0.93 (0.73–1.17)	.528		1.16 (0.91–1.49)	.236
≥80	112	1.53 (1.18–1.98)	.001		1.83 (1.37–2.44)	<.001
Gender	482			482
Male	129	1	–		1	–
Female	353	0.95 (0.77–1.17)	.640		0.77 (0.61–0.98)	.030
Grade	482			482
High grade	43	1	–		1	–
Intermediate	105	1.82 (1.20–2.75) 0:30	.005		1.13 (0.73–1.76)	.571
Low	109	3.32 (2.21–5.01)	<.001		1.99 (1.29–3.08)	.002
Squamous cell ca	11	5.03 (2.50–10.1)	<.001		2.06 (1.00–4.25)	.051
No grading reported	101	3.38 (2.23–5.12)	<.001		1.85 (1.19–2.86)	.010
Clinical diagnosis	109	5.31 (3.51–8.04)	<.001		2.22 (1.42–3.49)	.001
Stage	482			482
T1–T2 + T?	61	1	–		1	–
T3	32	2.64 (1.59–4.37)	.011		1.00 (1.15–3.235	.013
T4	36	3.99 (2.47–6.46)	<.001		3.17 (1.84–5.15)	<.001
N1	59	3.74 (2.40–5.82)	<.001		3.66 (2.29–5.80)	<.001
M1	259	8.18 (5.56–12.0)	<.001		7.25 (4.90–11.3)	<.001
Not staged	35	7.56 (4.63–12.3)	<.001		5.60 (3.27–9.58)	<.001
Doubtful	482			482
No	416	1	–		1	–
IHC	14	1.03 (0.59–1.80)	.904		1.16 (0.65–2.06)	.618
PHC	49	1.33 (0.99–1.80)	.059		0.93 (0.68–1.26)	.637
Pancreas	2	8.79 (2.14–36.0)	.003		11.5 (2.75–47.8)	.001
Gastric	1	1.94 (0.27–13.8)	.510		0.79 (0.11–5.80)	.820

Figure 3. Survival after curatively aiming operative procedures over three time periods (p = .02).

Table 3. Surgery with curative intent, by type of surgery.

	2000–2004	2005–2009	2010–2014	Total
Initial surgery
Open cholecystectomy	26 (39%)	31 (56%)	15 (27%)	72 (41%)
Laparoscopic cholecystectomy	10 (15%)	4 (7.4%)	7 (13%)	21 (12%)
Cholecystectomy and bile duct resection	9 (14%)	0	0	9
Cholecystectomy and liver bed resection	8 (12%)	9 (17%)	14 (26%)	31 (18%)
Cholecystectomy and liver bed and bile duct resection	1 (2%)	3 (6%)	2 (4%)	6 (3%)
Total	54 (81%)	47 (85%)	38 (69%)	139 (78%)
Complementary surgery
Complementary liver bed resection	10 (15%)	5 (9.3%)	11 (21%)	26 (15%)
Complementary liver bed and bile duct resection	3 (5%)	3 (5%)	6 (11%)	12 (7%)
Total	13 (20%)	8 (15%)	17 (32%)	38 (22%)
Liver bed resection	22 (33%)	20 (36%)	33 (60%)	75 (42%)
No liver bed resection	45 (67%)	35 (64%)	22 (40%)	102 (58%)
All curatively aiming surgery	67	55	55	177

In patients subjected to complementary liver bed surgery the preceding cholecystectomy is excluded.

Table 4. Uni- and multivariable Cox regression analyses on survival of patients undergoing surgery with curative intent (n = 177).

	Univariable analyses			Multivariable analyses
	N = 177			N = 177
	n	HR (95% CI)	p		HR (95% CI)	p
Period	177
2000–2004	67	1	–		1	–
2005–2009	55	0.74 (0.49–1.13)	.163		1.02 (0.60–1.72)	.955
2010–2014	55	0.59 (0.38–0.91)	.016		0.87 (0.53–1.44)	.581
Age	177
<50	9	0.47 (0.17–1.32)	.149		0.66 (0.22–1.96)	.455
50–59	25	0.76 (0.43–1.36)	.363		0.90 (0.48–1.69)	.748
60–69	45	1	–		1	–
70–79	68	0.72 (0.46–1.13)	.157		1.09 (0.67–1.76)	.726
≥80	30	1.82 (1.10–2.99)	.019		2.40 (1.29–4.48)	.006
Gender	177
Male	41	1	–		–	–
Female	136	0.98 (0.64–1.47)	.911		–	–
Grade	177
High grade	38	1	–		–	–
Intermediate	62	1.52 (0.88–2.53)	.117		0.93 (0.52–1.68)	.708
Low	46	2.98 (1.75–5.08)	<.001		1.95 (1.09–3.51)	.032
Squamous cell ca	2	9.22 (2.11–40.4)	.003		2.26 (0.42–12.1)	.391
No grading reported	29	2.16 (1.17–3.95)	.013		1.58 (0.80–3.11)	.184
Stage	177
T1–T2 + T?	53	1	–		1	–
T3	21	3.38 (1.70–6.72)	.001		3.45 (1.62–7.38)	.001
T4	15	5.16 (2.47–10.8)	<.001		6.30 (2.64–15.0)	<.001
N1	32	3.72 (2.02–6.83)	<.001		5.28 (2.63–10.6)	<.001
M1	47	8.00 (4.53–14.1)	<.001		7.08 (3.67–13.7)	<.001
Not staged	9	8.45(3.77–18.9)	<.001		6.66 (2.61–17.0)	<.001

Figure 4. Survival after palliative chemotherapy over time and compared with patients given COX-2 (p = .40 and p = .74, respectively).