Prophylactic Octreotide Research Articles

Octreotide and postoperative pancreatic fistula after pancreaticoduodenectomy: What we know so far? A narrative review.

Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used by pancreatic surgeons worldwide after pancreatic resections, often as per surgeon's discretion, to prevent POPF especially in cases at high risk of developing POPF. We herein analyze the data available till date of the subject. A PubMed search with keywords "somatostatin OR octreotide OR somatostatin analogues AND postoperative pancreatic fistula" was made. Further filters were applied in the search "Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Systematic Review, from 1990 - 2021," and the 68 results thus obtained were analyzed and included in this narrative review. There is considerable heterogeneity among the studies assessing the role of octreotide in the prevention of POPF making data comparison difficult, and hence results remain inconclusive. Most of the earlier studies used different definitions of POPF and other complications; included patients with varied pancreatic pathologies such as cancer, chronic pancreatitis, and benign lesions; surgical techniques such as pancreaticoduodenectomy, distal pancreatectomy, and other procedures; use of somatostatin and its analogs such as octreotide, lanreotide, pasireotide, and vapreotide; varied surgeon and institutional volume; and so on. Besides, pancreatic surgery is per se a complex surgical procedure and has its own inherent biases related to patient and the pancreas itself affecting the overall outcome. Data indicate favorable role of newer somatostatin analogs, and further studies are urgently needed. The question about the efficacy of prophylactic octreotide to reduce POPF after pancreaticoduodenectomy remains open to debate.

Perioperative Carcinoid Crisis: A Systematic Review and Meta-Analysis.

Simple SummaryIntraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication for patients with neuroendocrine tumors (NET). Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting the use of perioperative octreotide to prevent CC. The aim of our meta-analysis was to evaluate the existing evidence characterizing CC and the efficacy of prophylactic octreotide. We found that CC occurs frequently in patients having midgut NETs surgery, specifically those with NET liver metastasis, and is associated with worse postoperative outcomes. Our findings did not show a decreased risk in CC with prophylactic octreotide and questioned the advantage of routine prophylactic octreotide.Background: Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide. Methods: A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000–2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models. Results: Eight studies met inclusion criteria (n = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06–0.36]). Liver metastasis (odds ratio 2.85 [1.49–5.47]) and gender (male 0.58 [0.34–0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03–4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32–1.66]). Notably, there was no standard prophylactic octreotide strategy used. Conclusions: Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC.

Prophylactic octreotide for postoperative pancreatic fistula in patients with pancreatoduodenectomy: Risk-stratified analysis.

Background:Postoperative pancreatic fistula is one of the most critical complications following pancreatic surgery. This study aimed to evaluate the utility of selective prophylactic octreotide for patients at high risk of developing postoperative pancreatic fistula.Methods:From June 2019 to July 2020, 263 patients underwent pancreatoduodenectomy with pancreatojejunostomy at Samsung Medical Center. The individual fistula risk scores were calculated using a previously developed nomogram. The clinicopathological data of the patients were retrospectively reviewed.Results:There were 81 patients in the low-risk group and 182 patients in the high-risk group. No statistically significant differences were found in the rates of clinically relevant postoperative pancreatic fistula between octreotide group and the control group in all patients (15.0% vs 14.7%, P = .963) and in the high-risk group (16.1% vs 23.6%, P = .206). In risk factor analysis, postoperative octreotide was not an independent risk factor for clinically relevant pancreatic fistula in all patients and the high-risk group. Drain fluid amylase levels on the first postoperative day were significantly associated with clinically relevant postoperative pancreatic fistula, regardless of the individual risk.Conclusions:The selective use of octreotide, even in high-risk patients, showed no protective effect against pancreatic fistula. Therefore, the routine use of postoperative octreotide is not recommended.

Prophylactic octreotide according to individual risks for postoperative pancreatic fistula after pancreatoduodenectomy

Postoperative pancreatic fistula (POPF) is one of the most critical complications following pancreatic surgery. The aim of this study was to evaluate selective use of prophylactic octreotide for patients stratified by their individual risks of POPF. From June 2019 to July 2020, a total of 243 patients underwent pancreatoduodenectomy with pancreatojejunostomy in Samsung Medical Center. Individual POPF risk scores were calculated with previously developed nomogram and clinicopathological data of the patients were retrospectively reviewed. There were 81 patients in low-risk group and 182 patients in high-risk group. No statistically significant differences were found in clinically relevant POPF (CR-POPF) rates between the control group and the octreotide group in both low- (3.0% vs. 7.1%, p = 0.439) and high- (23.6% vs. 16.1%, p = 0.206) risk groups. In risk factor analyses, postoperative use of octreotide was not an independent risk factor for CR-POPF in all (p = 0.897) patients, low- (p = 0.436), and high- (p = 0.614) risk group. Drain fluid amylase on the first postoperative day was significantly correlated with CR-POPF, regardless of individual risks. Selective use of octreotide, even in high risk patients, showed no protective effect against POPF. Routine use of postoperative octreotide would not be recommended.

The effect of high intraoperative blood loss on pancreatic fistula development after pancreatoduodenectomy: An international, multi-institutional propensity score matched analysis

BackgroundThe association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored. MethodsIn total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003–2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated blood loss and clinically relevant pancreatic fistula occurrence. The study was powered to detect a 33% clinically relevant pancreatic fistula increase in the high estimated blood loss group, with α = 0.05 and β = 0.2. ResultsThe propensity score model included 966 patients with high estimated blood loss and 966 patients with lower estimated blood loss; all covariate imbalantces were solved. Patients with high estimated blood loss patients experienced higher clinically relevant pancreatic fistula rates (19.4 vs 12.6%, odds ratio 1.66; P < .001), as well as higher severe complication rates (27.8 vs 15.6%), transfusions (50.1 vs 14.3%), reoperations (9.2 vs 4.0%), intensive care unit transfers (9.9 vs 4.8%) and 90-day mortality (4.7 vs 2.0%, all P < .001). High estimated blood loss was an independent predictor for clinically relevant pancreatic fistula (odds ratio 1.78, 95% confidence interval 1.37–2.32), as were prophylactic Octreotide administration (odds ratio 1.95, 95% confidence interval 1.46–2.61) and soft pancreatic texture (odds ratio 5.32, 95% confidence interval 3.74–5.57; all P < .001). Moreover, a second model including 1,126 pancreatoduodenectomies was derived including vascular resections as additional confounder (14.0% vascular resections performed in each group). On multivariable regression, high estimated blood loss was confirmed an independent predictor for clinically relevant pancreatic fistula reduction (odds ratio 1.80, 95% confidence interval 1.32–2.44; P < .001), whereas vascular resection was not (odds ratio 0.64, 95% confidence interval 0.34–1.88; P = .156). ConclusionThis study better establishes the relationship between estimated blood loss and outcomes after pancreatoduodenectomy. Despite inherent contributions to blood loss, its minimization is an actionable opportunity for clinically relevant pancreatic fistula reduction and performance optimization in pancreatoduodenectomy. Accordingly, practical insights are offered to achieve this goal.

Percutaneous Image-Guided Core Needle Biopsy of Neuroendocrine Tumors: How Common Is Intraprocedural Carcinoid Crisis?

PurposeTo retrospectively evaluate the incidence of carcinoid crisis, other complications, and physiologic disturbances during percutaneous image-guided core needle biopsy of neuroendocrine tumors (NETs) in the lung and the liver. Materials and MethodsBetween January 2010 and January 2020, 106 computed tomography (CT) or ultrasound (US)-guided core needle biopsies of lung and liver NETs were performed in 95 consecutive adult patients. The mean age was 64 ± 13 years, and 48% were female. The small bowel was the most common primary site (33%, 31/95), and 32 (34%) patients had pre-existing symptoms of carcinoid syndrome. The mean tumor size was 3.2 ± 2.6 cm, and mean number of passes was 3.4 ± 1.6. A 17/18-gauge needle was used in 91% (96/106) of the biopsies. Thirteen (12%) patients received either outpatient or prophylactic octreotide. ResultsNo patients experienced carcinoid crisis or needed octreotide, inotropes, vasopressors, or resuscitation. A single biopsy procedure (0.9%, 1/106) was complicated by bleeding that required angiographic hepatic artery embolization. Changes in pre-biopsy- versus post-biopsy systolic blood pressure and heart rate were -1.6 mm Hg (P = .390) and 0.6 beat/min (P = .431), respectively. Tumor functional status, overall tumor burden, and the elevation of neuroendocrine markers were not associated with intraprocedural physiologic disturbances. There were 4 minor complications (0.4%, 4/106) associated with the biopsy procedure that were not attributed to hormone excretion from tumor manipulation. ConclusionsPercutaneous image-guided core biopsy of NETs is safe, with low complication rate and no definite carcinoid crisis in the current cohort.

Surgeon experience contributes to improved outcomes in pancreatoduodenectomies at high risk for fistula development

BackgroundPancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood. MethodsThe fistula risk score was applied to identify high-risk patients (fistula risk score 7–10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003–2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models. ResultsEight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (–49.7%) and career length (–41.2%; both P < .001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35–0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22–0.74). ConclusionSurgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss.

The development and initial evaluation of the Diarrhoea Management Diary (DMD) in patients with metastatic breast cancer

PurposeChemotherapy-induced diarrhoea (CID) is a common, but often underreported problem in patients with breast cancer that has a profound effect on quality of life. It is best measured from a patient’s perspective, but tools are limited. The aim of this study was to develop and evaluate the Diarrhoea Management Diary (DMD), a self-report measure to assess CID, use of self-management strategies and treatment adherence.MethodsThe DMD was constructed using an iterative process of instrument development: concept elicitation (literature review), item generation and reduction (cognitive debriefing), and pilot testing in the target population. After translation into eight languages, the DMD was used in an international randomised trial for women receiving lapatinib and capecitabine for metastatic breast cancer with or without prophylactic octreotide. Patterns of missing data and sensitivity to change were examined.ResultsThe understandability and completeness of the 8-item DMD was confirmed in cognitive interviews and pilot testing. Practicability of the DMD was evaluated in 62 women with metastatic breast cancer (median age 57). Up to 68% reported CID at any given time-point, and 19% had diarrhoea at each time-point. Patients also described efficacy of different strategies for diarrhoea management. Missing data were associated with study discontinuation. DMD missing item response was 0.9%. Sensitivity to change was good at most assessment points.ConclusionsAlthough further psychometric testing is recommended, initial evaluation of the DMD showed good content validity and practicability in international research with cancer patients.

The Fistula Risk Score Catalog: Toward Precision Medicine for Pancreatic Fistula After Pancreatoduodenectomy.

This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter. The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes. FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003-2019). The FRS was used to derive 80 unique combinations of patient "scenarios." Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches. The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) - the only negligible-risk scenario (CR-POPF rate = 0.7%). The moderate-risk zone had the most scenarios (50), patients (N = 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12-0.33). Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF.

Prophylactic octreotide does not reduce the incidence of postoperative chylothorax following lobectomy: Results from a retrospective study.

Chylothorax after lobectomy is common, lacking reliable preventive measures. Octreotide is widely used for treatment of chyle leakage, but its role in preventing chylothorax has not been estimated. The aim of this study was to evaluate whether prophylactic octreotide could reduce the incidence of postoperative chylothorax.Patients who underwent lobectomy for lung cancer from January 2016 to September 2018 were retrospectively reviewed. The cases in prophylactic group received octreotide 1 day before the surgery until removal of chest tubes, while those in the control group did not use it unless the diagnosis of chylothorax.A total of 379 patients were enrolled, with 190 patients in control and 189 cases in prophylactic group. Octreotide was well tolerated in patients who received this agent. No 30-day mortality was indicated. Seven cases in control (3.7%, 7/190) and 3 cases in prophylactic group (1.6%, 3/189) with chylothorax were observed (P = .337). The patients in prophylactic group showed shorter duration of chest drainage ([3.6 ± 1.6] days vs [4.1 ± 2.0] days, P = .006) and reduced drainage volume ([441.8 ± 271.1] mL vs [638.7 ± 463.3] mL, P < .001). In addition, they showed similar stations and numbers of dissected lymph nodes, surgery-related complications, and postoperative hospital stay. Besides, 11 (5.8%, 11/190) patients in control and 6 (3.2%, 6/189) cases in the prophylactic group were readmitted for pleural effusion needing reinsertion of chest tubes (P = .321). Moreover, multivariable logistic analysis showed that induction therapy (odds ratio [OR] =12.03; 95% confidence interval [CI] 3.15–46.03, P < .001) was a risk factor, while high-volume experience of the surgeon (OR = 0.23; 95% CI 0.06–0.97, P = .045) was a preventive factor of surgery-related chylothorax. Additionally, prophylactic octreotide (OR = 0.18; 95% CI 0.11–0.28, P < .001) and perioperative low-fat diet (OR = 0.46; 95% CI 0.29–0.73, P = .001) were negatively associated with the drainage volume of pleural effusion. Furthermore, high-volume experience of the surgeon (OR = 6.03; 95% CI 1.30–27.85, P = .021) and induction therapy (OR = 8.87; 95% CI 2.97–26.48, P < .001) were risk factors of unplanned readmission.Prophylactic octreotide does not reduce the incidence of postoperative chylothorax or unplanned readmission following anatomic lobectomy. The routine application of octreotide should not be recommended. High-quality trials are required to validate these findings.

Risk Factors and Mitigation Strategies for Pancreatic Fistula After Distal Pancreatectomy: Analysis of 2026 Resections From the International, Multi-institutional Distal Pancreatectomy Study Group.

To identify a clinical fistula risk score following distal pancreatectomy. Clinically relevant pancreatic fistula (CR-POPF) following distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive. This multinational, retrospective study of 2026 DPs involved 52 surgeons at 10 institutions (2001-2016). CR-POPFs were defined by 2016 International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution. CR-POPF occurred following 306 (15.1%) DPs. Risk factors independently associated with CR-POPF included: age (<60 yrs: OR 1.42, 95% CI 1.05-1.82), obesity (OR 1.54, 95% CI 1.19-2.12), hypoalbuminenia (OR 1.63, 95% CI 1.06-2.51), the absence of epidural anesthesia (OR 1.59, 95% CI 1.17-2.16), neuroendocrine or nonmalignant pathology (OR 1.56, 95% CI 1.18-2.06), concomitant splenectomy (OR 1.99, 95% CI 1.25-3.17), and vascular resection (OR 2.29, 95% CI 1.25-3.17). After adjusting for inherent risk between cases by multivariable regression, the following were not independently associated with CR-POPF: method of transection, suture ligation of the pancreatic duct, staple size, the use of staple line reinforcement, tissue patches, biologic sealants, or prophylactic octreotide. Intraoperative drainage was associated with a greater fistula rate (OR 2.09, 95% CI 1.51-3.78) but reduced fistula severity (P < 0.001). From this large analysis of pancreatic fistula following DP, CR-POPF occurrence cannot be reliably predicted. Opportunities for developing a risk score model are limited for performing risk-adjusted analyses of mitigation strategies and surgeon performance.

The Benefit of Prophylactic Octreotide for Pancreatectomy

The Benefit of Prophylactic Octreotide for Pancreatectomy

The Role of Prophylactic Octreotide Following Pancreaticoduodenectomy to Prevent Postoperative Pancreatic Fistula: A Meta-Analysis of the Randomized Controlled Trials

Introduction A postoperative pancreatic fistula (POPF) is a major cause of morbidity and mortality following pancreaticoduodenectomy (PD). A pharmacologic approach using perioperative octreotide, a long-acting somatostatin analog having an inhibitory action on pancreatic exocrine secretion, was proposed to reduce the incidence of the POPF. Despite contradictory results in various randomized controlled trials (RCTs), the prophylactic octreotide has been widely used in the last two decades to reduce the POPF. The present meta-analysis aims to assess the effectiveness of the prophylactic octreotide in preventing the POPF following PD. Methods A literature search was performed in the PubMed for the RCTs that compared the prophylactic octreotide with the placebo following PD published prior to October 2016. Review manager (Cochrane Collaboration's software) version RevMan 5.2 was used for analysis. Those RCTs which had compared the prophylactic Octreotide with placebo to reduce the POPF following PD were considered eligible for the meta-analysis. The low quality (Jadad score of two or less) RCTs or those including mixed pancreatic resections without reporting specific pancreaticoduodenectomy outcomes were excluded. The effect size for the dichotomous and the continuous data was displayed as the odds ratio (OR) and the weighted mean difference (WMD), respectively, with their corresponding 95% confidence intervals (CI). A fixed effect or random effects model was used to pool the data according to the result of a statistical heterogeneity test. The heterogeneity between the studies was evaluated using the Cochran Q statistic and the I 2 test, with p < 0.05 indicating significant heterogeneity. Results There were eight RCTs available for the analysis. A total of 959 patients were included in the meta-analysis–492 received the prophylactic octreotide and 467 patients received the placebo. The prophylactic octreotide was not found to significantly decrease the total number of the POPF (OR, 1.03'; 95% CI: 0.73–1.45; p -value 0.85) or the clinically significant POPF (OR, 0.76; 95% CI: 0.35–1.65; p -value 0.49) compared with the placebo. There was also no difference in the duration of hospital stay (WMD, 1.19; 95% CI:1.84–4.23; p -value 0.44) or the postoperative mortality (OR, 2.04; 95% CI: 0.87–4.78; p -value 0.10) between the two groups. The prophylactic octreotide was also not found to significantly delay the gastric emptying (OR, 0.76; 95% CI: 0.41–1.40; p -value 0.38). Conclusion The present meta-analysis does not support the role of the prophylactic octreotide to prevent the POPF following PD.

319P - A randomized, open label, phase II study of prophylactic octreotide (OCT) to prevent/reduce the frequency and severity of diarrhea in patients (pts) receiving lapatinib (LAP) with capecitabine (CAP) for the treatment of metastatic breast cancer (mBC)

319P - A randomized, open label, phase II study of prophylactic octreotide (OCT) to prevent/reduce the frequency and severity of diarrhea in patients (pts) receiving lapatinib (LAP) with capecitabine (CAP) for the treatment of metastatic breast cancer (mBC)

Randomized controlled study of the effect of octreotide on pancreatic exocrine secretion and pancreatic fistula after pancreatoduodenectomy

Octreotide is known to decrease the rate of postoperative complication after pancreatic resection by diminishing exocrine function of the pancreas. The aim of this study was to evaluate the effect of octreotide in decreasing exocrine excretion of pancreas and preventing pancreatic fistula. Prospective randomized trial was conducted involving 59 patients undergoing pancreaticoduodenectomy for either malignant or benign tumor, 29 patients were randomized to receive octreotide; 30 patients allotted to placebo. All pancreaticojejunal anastomosis was performed with external stent of negative-pressured drainage and the amount of pancreatic juice through the external stent was measured until postoperative 7th day. Pancreatic fistula was recorded. There were no differences in demographics, pancreatic texture and pancreatic duct diameter between the octreotide and placebo group. The median output of pancreatic juice was not significantly different between both groups during 7 days after surgery. When the patients were stratified according to the diameter of pancreatic duct (duct ≤5mm, > 5mm), there were no significant differences in daily amount of pancreatic juice, however, when stratified according to pancreatic texture, median output of pancreatic juice was significantly lower in patients with hard pancreas compared with those with soft pancreas from 5 day to 7 day after surgery (p<0.05). No significant differences in pancreatic fistula and postoperative complications were found between the octreotide and placebo groups. Prophylactic octreotide is not effective to inhibit the exocrine secretion of the remnant pancreas and does not decrease the incidence of pancreatic fistula after pancreaticoduodenectomy.

Impact of prophylactic octreotide to pancreatic exocrine secretion and pancreatic fistula after pancreatoduodenectomy: RCT

Impact of prophylactic octreotide to pancreatic exocrine secretion and pancreatic fistula after pancreatoduodenectomy: RCT

Taking Theory to Practice: Quality Improvement for Pancreaticoduodenectomy and Development and Integration of the Fistula Risk Score

Improvements in surgical outcomes are predicated on recognizing effective practices with subsequent adaptation. It is unknown whether risk assessment for pancreatic fistula (clinically relevant postoperative pancreatic fistula [CR-POPF]) after pancreaticoduodenectomy (PD) translates to improved patient outcomes at the practice level. A prospectively collected, single-surgeon career experience (2003 to 2018) of 455 consecutive pancreatectomies (303 PDs and 152 distal pancreatectomies) was examined. Analysis occurred during 4 eras of practice: learning curve for PD (n= 50); development of the Fistula Risk Score (n= 48); reactive, data-driven adjustments of anastomotic stent use (n= 94); and omission of prophylactic octreotide with adoption of selective drainage (n= 111). Observed to expected ratios of CR-POPF were calculated using a multi-institutional derivation set (5,379 PDs). After adjustment for increasing fistula risk across the 4 eras (p= 0.016), the risk-adjusted CR-POPF rate declined significantly (observed to expected ratio 1.42→1.28→1.01→0.30; p < 0.001). Literature-driven changes in fistula mitigation strategies likewise led to reductions in the overall complication burden (Postoperative Morbidity Index: 0.20→0.24→0.25→0.15; p= 0.015) and resource use (therapeutic antibiotics: p= 0.019; hospital readmission: p= 0.006; postoperative transfusion: p= 0.007). In contrast, the CR-POPF rate after distal pancreatectomy, for which no validated risk-adjustment process exists, did not vary (approximately 12%; p= 0.878). Patient outcomes for PD can be optimized by risk-adjusted evaluation and deliberate modification of practice.

Prophylactic octreotide in the prevention of pancreatic fistula and its related complications after pancreatic resection: a Meta-analysis

Objective To study the clinical impact of prophylactic octreotide on patients who underwent pancreatic resection using evidence-based medicine. Methods Electronic databases which included the Cochrane library, Pubmed and Embase were searched. A Meta-analysis of all randomized controlled trials (RCTs) on the clinical impact of prophylactic octreotide on pancreatic resection was performed. The evaluation of the literature quality and the effective of the data were based on the Cochrane Handbook for systematic reviews. The Review Manager 5.3 was used for the meta-analysis. Results 13 studies which involved 2 108 patients were included into this study, with 1 057 patients in the octreotide group and 1 051 patients in the control group. Meta-analysis revealed that the rates of pancreatic fistula (PF), including Class A, B and C and the total postoperative complication rate were lower in patients treated with prophylactic octreotide than those without octreotide (14.7% vs. 21.6%, RR=0.67, 95%CI: 0.56-0.81, P 0.05). Conclusion Octreotide reduced PF including Class A, B and C and decreased the total complication rate, but did not reduce the clinically relevant fistulas and perioperative mortality. Key words: Pancreatic fistula; Pancreatic resection; Octreotide; Complications; Meta-analysis

Postoperative narcotic use is associated with development of clinically relevant pancreatic fistulas after distal pancreatectomy

BackgroundVarious strategies to decrease postoperative pancreatic fistula after a distal pancreatectomy have proved unsuccessful. Because narcotics can cause spasm of the sphincter of Oddi and thereby increase pressure within the pancreatic duct stump, we hypothesized that increased narcotic use would be associated with increased occurrence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. MethodsRetrospective analysis of consecutive distal pancreatectomies (2011–2016) was performed. Postoperative narcotic use was calculated in morphine equivalents. Postoperative pancreatic fistula was graded according to the International Study Group on Pancreatic Surgery. Perioperative variables were evaluated using multivariate logistic regression with clinically relevant postoperative pancreatic fistula as the dependent outcome. ResultsIn the study, 310 distal pancreatectomies were analyzed (61% robotic, 20% open, 19% laparoscopic). Average age was 62 (53% female), and median total dose of morphine equivalents was 424 mg (interquartile range 242–768). Clinically relevant postoperative pancreatic fistula occurred in 21.6%. Clinically relevant postoperative pancreatic fistula and not clinically relevant postoperative pancreatic fistula cohorts were similar in most demographics and operative variables, but clinically relevant postoperative pancreatic fistula patients had fewer stapled transections (80 vs 90%, P = .025), less pancreatic cancers (11 vs 35%, P < .001), and greater median total morphine equivalents (577 vs 403 mg, P < .009). On univariate analysis, clinically relevant postoperative pancreatic fistula was associated with body mass index, nonstapled transection, suture ligation of the PD, a nonpancreatic cancer pathology, prophylactic octreotide, and total morphine equivalents >424 (cohort median). On multivariate analysis, only pancreatic cancer pathology was protective against a clinically relevant postoperative pancreatic fistula (odds ratio 0.24, confidence interval, 0.10–0.50, P = .001), while increasing total morphine equivalents were predictive of a clinically relevant postoperative pancreatic fistula (odds ratio 1.13, confidence interval, 1.01–1.27, P = .035) with a 13% increased risk for every approximate ≈100 mg increase in total morphine equivalents. ConclusionIn this retrospective analysis, postoperative narcotic use was associated with the development of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. Limiting narcotic use may be one of the few available mitigating strategies against the development of a clinically relevant postoperative pancreatic fistula after distal pancreatectomy.

Risk Factors and Mitigation Strategies for Pancreatic Fistula after Distal Pancreatectomy: Analysis of 2,026 Resections from the International, Multi-Institution Distal Pancreatectomy Study Group

Clinically relevant pancreatic fistula (CR-POPF) after distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive. This multinational, retrospective study of 2,026 DPs involved 52 surgeons at 10 institutions (2001 to 2016). CR-POPFs were defined by International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution. CR-POPF occurred in 306 (15.1%) DPs. Risk factors independently associated with fistula included: BMI 25–30 kg/m2: odds ratio (OR) 1.38, 95% CI 1.01–1.87; ≥30 kg/m2: OR 1.52, 95% CI 1.11–2.09, hypoalbuminenia (OR 1.56, 95% CI 1.03–2.44), high-risk pathology (neuroendocrine or benign: OR 1.62, 95% CI 1.23–2.14), concomitant splenectomy (OR 2.02, 95% CI 1.27–3.21), and vascular resection (OR 2.25, 95% CI 1.23–4.11). However, the model had poor predictive discrimination (c-statistic 0.635). Intraoperative drainage was more frequently utilized in cases of increased fistula risk (OR 2.11, p = 0.013). CR-POPF rates varied by method of transection (stapled: 12.7% vs handsewn: 19.1% vs energy device: 24.2%, p < 0.001); however, in a multivariable model, method of transection, suture ligation of the pancreatic duct, staple size, and the use of mesh reinforcement, tissue patches, biologic sealants, or prophylactic octreotide were not independently associated with CR-POPF. From this multi-institutional analysis of pancreatic fistula after DP, CR-POPF cannot be reliably predicted, prohibiting risk score development and effective risk-adjusted analysis of mitigation strategies or surgeon performance.