Somatostatin and its analogs in the management of postoperative pancreatic fistulas: A comprehensive review

Table 1 Comparative summary of somatostatin and its analogs in the prevention of postoperative pancreatic fistula

Agent	Mechanism	Evidence level	Effect on POPF	Limited factors
Somatostatin (IV infusion)	Pancreatic enzyme suppression (SSTR1-5)	High	Decrease POPF (strong, consistent)	Requires IV infusion
Pasireotide	Broad SSTR1-5 affinity	High (RCT + meta-analyses)	Decrease CR-POPF (56% RRR)	Cost, hyperglycemia
Octreotide	SSTR2, SSTR5 selective	Moderate	Decrease biochemical leaks; inconsistent CR-POPF	Dosing variability
Lanreotide	Long-acting SSTR2, SSTR5	Moderate	Modest POPF reduction	Limited data
Combined protocols (SSA + drainage)	Synergistic mechanical and pharmacologic control	Moderate-high	Decrease POPF and severity	Implementation complexity

SSA: Somatostatin analog; POPF: Postoperative pancreatic fistula; SSTR: Somatostatin receptor; RCT: Randomized controlled trial; CR-POPF: Clinically relevant postoperative pancreatic fistula; RRR: Relative risk reduction.

Table 2 Studies associated with the effect of somatostatin and its analogs on postoperative pancreatic fistula occurrence

Ref.	Study group	Intervention	Outcome
Pillarisetty et al[15]	98 patients undergoing either PD or DP	A single dose of preoperative lanreotide (120 mg)	CR-POPF or intraabdominal abscess was observed in 8 (8%) patients in the total cohort: 7 (11.2%) in the PD group and 1 (2.7%) in the DP group. Biochemical leak was detected in 12 (12.2%) patients
Vuorela et al[11]	A total of 258 patients who underwent DP between 2000 and 2016 at Helsinki University Hospital	900-μg pasireotide administered subcutaneously twice daily for a maximum of 7 days or octreotide administrated through a 200-μg infusion twice daily for 3 days	40 CR-POPF grade B and C (16%; P = 0.739). CR-POPF in the pasireotide group was 7 (15%), 3 (10%) in the octreotide group and 28 (17%) in the control group (P = 0.630)
Yoon et al[8]	Patients who underwent PD at Samsung Medical Center from June 2019 to July 2020 (totally 263 patients, 81 patients in the low-risk group and 182 patients in the high-risk group). CR-POPF was calculated using the nomogram-based web calculator (http://popf.smchbp.org)	Postoperative octreotide for more than three days	No statistically significant differences of CR-POPF between octreotide group and the control group in all patients (15.0% vs 14.7%, P = 0.963) and in the high-risk group (16.1% vs 23.6%, P = 0.206)
Herzberg et al[3]	Patients undergoing pancreatic surgery (PD and rescue pancreatectomy) for pancreatic cancer at Reinbek Hospital St. Adolf-Stift, Germany, from January 2013 till December 2022	Fail-safe protocol included 0.2 mg of octreotide intravenously before the start of the pancreatic resection, in order to block the exocrine pancreatic secretion. Continued by 0.1 mg octreotide every 8 hours subcutaneously for the first 5 postoperative days	Fail-safe protocol in oncologic pancreatic head surgery can lower the rates of overall POPF grade B/C rate of 4.2% vs 18.8% (P = 0.012) before implementation of the fail-safe protocol
Potter et al[10]	A total of 100 patients undergoing elective PD or DP between January 2013 and April 2020 who received perioperative pasireotide therapy	Full course of pasireotide: Either a preoperative dose plus 7 days of postoperative therapy, or pasireotide continued until day of surgical drain removal in the setting of low drain amylase or partial course: A single preoperative dose and early discontinuation due to side effects	Relative to patients receiving full-course pasireotide, a single preprocedure dose was not associated with higher odds of any POPF (OR = 0.90, 95%CI: 0.31-2.61, P = 0.85)
Bootsma et al[7]	1992 patients who underwent elective, open pancreatoduodenectomy between 2014 and 2017 at all 16 Dutch centers for pancreatic surgery	6 protocols based on the hospital the operation took place: (1) No SA administered; (2) Octreotide 100 mg subcutaneous injection three times a day for seven days, starting the day before surgery; (3) Lanreotide 120 mg subcutaneous injection at home a few days before surgery; (4) Pasireotideo 900 μg of subcutaneous pasireotide twice daily beginning preoperatively and continuing for 7 days (14 doses). Administered in patients deemed as high-risk; (5) Octreotide HR 100 mg subcutaneous injection three times a day for five-seven days, starting the day before surgery or on the first postoperative day; and (6) Lanreotide HR 120 mg subcutaneous injection at home a few days before surgery or on the first postoperative day	POPF occurred less often in patients treated according to lanreotide protocol (n = 75, 10.0%) and octreotide-HR (n = 15, 9.4%) and no SA protocol (n = 30, 12.7%), compared to a higher incidence in hospitals with lanreotide-HR (n = 52, 15.1%), octreotide (n = 54, 17.8%) and pasireotide protocol (n = 35, 19.1%). The rate of grade C POPF did not differ significantly (P = 0.358) between hospitals with octreotide-HR protocol (n = 4, 2.5%), lanreotide-HR protocol (n = 23, 2.9%), no protocol (n = 7, 3.0%), lanreotide (n = 23, 3.1%), octreotide (n = 12, 4.0%), and pasireotide protocol (n = 12, 6.0%)
Gaujoux et al[1]	Adult patients (≥ 18 years) who were scheduled to undergo either PD or DP with or without splenectomy	Continuous intravenous somatostatin 6 mg per day for 6 days and 3 mg on POD 7 or subcutaneous octreotide 100 μg subcutaneously 3 times per day until POD 6 and then 100 μg 2 times on POD 7. Treatment initiation starting intraoperatively just after surgical exploration	No statistically significant difference in the incidence of grade B or C POPF between patients treated with somatostatin (24.1%) and patients treated with octreotide (22.9%) (P = 0.73). Comparing all grades of POPF in the ISGPS classification (A/B/C) there was no difference between the two groups (51.9% in the somatostatin arm vs 48.3% in the octreotide arm, P = 0.37)

PD: Pancreaticoduodenectomy; DP: Distal pancreatectomy; CR-POPF: Clinically relevant postoperative pancreatic fistula; SA: Somatostatin analogues; HR: High-risk; POD: Postoperative day; POPF: Postoperative pancreatic fistula; OR: Odds ratio; CI: Canfidence interval; ISGPS: International Study Group on Pancreatic Surgery.