Impact of surgery for chronic pancreatitis on the risk of pancreatic cancer: Untying the Gordian knot

Table 1 Systematic reviews and meta-analyses evaluating the association between chronic pancreatitis and pancreatic cancer

Ref.	Number of studies	Number of patients	Risk estimate	Remarks
Raimondi et al[6]	22 (12 case-control, 10 cohort)	16124	RR, 11.8 (95%CI: for 1-yr lag period; RR, 5.8 (95%CI: 2.1-15.9) for 2-yr lag period; RR, 69.0 (95%CI: 56.4-84.4) for hereditary pancreatitis; RR, 100 (95%CI: 37.0-218.0) for tropical pancreatitis	Details of seven studies included for risk estimate calculation not mentioned; Details of number of patients with pancreatic cancer in included studies not mentioned; High relative risk reported for tropical pancreatitis based on a single study
Tong et al[7]	17 (14 case-control, 3 cohort)	14667 pancreatic cancer, 17587 pancreatitis	Pooled OR, 10.35 (95%CI: 9.13-11.75) for chronic pancreatitis; Pooled OR, 6.41 (95%CI: 4.93-8.34) for unspecified type of pancreatitis -	Inclusion of studies with both acute and chronic pancreatitis limits generalizability; Inclusion of acute, chronic and unspecified pancreatitis to calculate the temporality of the association might underestimate the relative risk
Kirkegård et al[8]	13 (4 case-control, 9 cohort)	674 pancreatic cancer, 25,329 chronic pancreatitis	EE, 16.16 (95%CI:12.59-20.73) for 2-yr lag period; EE, 7.90 (95%CI: 4.26-14.66) for 5-yr lag period; EE, 3.53 (95%CI: 1.69-7.38) for 9-yr lag period	Some of the included studies had a smaller number of patients with pancreatic cancer or chronic pancreatitis which might inflate the estimated risk; In some of the included studies more than one-third of patients were lost to follow-up

CI: Confidence interval; EE: Effect estimate; OR: Odds ratio; RR: Relative risk.

Table 2 Risk factors for pancreatic cancer in chronic pancreatitis

Ref.	Number of patients	Etiological subtype, n (%)	Pancreatic cancer risk	Specific risk group
Agarwal et al[22]	1415	ACP, 540 (38.1); IJCP, 668 (47.2); ISCP, 207 (14.6)	5-yr risk of pancreatic cancer: ACP, 0.5%; IJCP, 0.2%; ISCP, 3.7%. 10-yr risk of pancreatic cancer: ACP, 0.9%; IJCP, 0.2%; ISCP, 5.2%	Age of onset > 35 yr (HR 12.1; CI: 4.7-31.2; P < 0.001). Smoking (HR 6.48; CI: 2.2-19.0; P < 0.001). Nonalcoholic etiology (HR for alcohol use 0.14; CI: 0.04-0.42; P < 0.001); Absence of steatorrhea (HR for steatorrhea 0.19; 95%CI: 0.04-0.80; P < 0.023)
Hao et al[23]	2037	ACP, 404 (19.8); ICP, 1633 (80.2)	5-yr risk of pancreatic cancer: ACP, 0.2%; ICP, 0.7%. 10-yr risk of pancreatic cancer: ACP, 0.9%; ICP, 1.1%	No significant difference in pancreatic cancer development between ACP and ICP patients
Vujasinovic et al[25]	581	Idiopathic, 47 (8.1); Alcohol and nicotine, 220 (37.9); Nicotine, 81 (13.9); Alcohol, 49 (8.4); Hereditary, 38 (6.5) Immunological, 59 (10.2) Efferent duct 62 (10.7) Miscellaneous/other, 25 (4.3)	Rate per 100 yr; Idiopathic, 0.00; Alcohol and nicotine, 0.07; Nicotine, 0.44; Alcohol, 0.32; Hereditary, 0.00; Immunological, 0.00; Efferent duct, 0.28; Miscellaneous/other, 0.81	Low BMI and pancreatic exocrine insufficiency. Patients with diabetes mellitus and high BMI
Müllhaupt et al[24]	332	ACP, 265; IJCP, 21; ISCP, 46	ACP, 1.5% over 16 yr; IJCP, 4.8% over 22 yr; ISCP, 2.2% over 14 yr	Early onset and prolonged duration of CP (rather than the specific type of CP)

ACP: Alcoholic pancreatitis; BMI: Body mass index; ICP: Idiopathic chronic pancreatitis; IJCP: Idiopathic juvenile chronic pancreatitis; ISCP: Idiopathic senile chronic pancreatitis.

Table 3 Studies evaluating the impact of surgery for chronic pancreatitis on the risk of pancreatic cancer

Ref.	Number of patients	Etiological subtype, n (%)	Type of surgery, n (%)	Pancreatic cancer risk
Ueda et al[12]	506	Alcoholic pancreatitis, 345 (68.0); Idiopathic pancreatitis, 109 (22.0); Autoimmune pancreatitis, 16 (3); Hereditary pancreatitis, 9 (2); Miscellaneous, 27 (5)	Drainage operation, 60 (40.8); Pancreatic resection, 87 (59.2)	Surgery, 1/147 (0.7%); No surgery, 18/352 (5.1%)
Zheng et al[11]	650	Alcoholic pancreatitis, 361 (55.5); Idiopathic pancreatitis, 227 (34.9); Hereditary pancreatitis, 62 (9.5)	Drainage operation, 189 (29.1); Pancreatic resection, 461 (70.9)	Surgery, 12/650 (1.8%); Time interval to surgery, HR, 1.005 (95%CI: 1.002-1.008); De novo endocrine insufficiency, HR, 10.672 (95%CI: 2.567-44.372)