Development Of Postoperative Pancreatic Fistula Research Articles

The role of acinar content at pancreatic resection margin in the development of postoperative pancreatic fistula and acute pancreatitis after pancreaticoduodenectomy

Purpose: A fatty infiltration of the pancreas has been traditionally regarded as the main histological risk factor for postoperative pancreatic fistula (POPF), whereas the role of the secreting acinar compartment has been poorly investigated. Aim of this study was to evaluate the role of acinar content at pancreatic resection margin in the development of clinically relevant POPF (CR-POPF) and clinically relevant postoperative acute pancreatitis (CR-POAP) after pancreaticoduodenectomy (PD). Method: Data from 388 consecutive patients who underwent PD (2018-2019) were analyzed. Pancreatic section margins were histologically assessed for acinar, fibrosis and fat content. Acinar content was categorized using median and third quartile as cut-offs. Univariate and multivariable analysis of possible predictors of CR-POPF and CR-POAP were performed. Results: Acinar content was <60% in 166 patients (42.8%), ≥60% and ≤80% in 156 patients (40.2%) and >80% in 66 patients (17.0%). The rate of CR-POPF and CR-POAP was significantly higher in patients with acinar content >80% (39.4% and 33.3%, respectively) as well as in those with acinar content ≥60% and ≤80% (36.5% and 35.3%, respectively), compared to patients with acinar content <60% (10.2% and 5.4%, respectively) (P < .001). Acinar content was identified as an independent predictor of CR-POPF [≥60% and ≤80%, odds ratio (OR) 2.51, P = .008; >80%, OR 2.93, P = .010] and CR-POAP (≥60% and ≤80%, OR 9.42, P< .001; >80%, OR 10.16, P < .001). Conclusion: An acinar content at pancreatic resection margin ≥60% is associated to an increased risk of CR-POPF and CR-POAP. Fat content was associated neither with CR-POPF nor with CR-POAP.

Early Drain Removal Regardless of Drain Fluid Amylase Level Might Reduce Risk of Postoperative Pancreatic Fistula.

Drains are frequently placed at the time of distal pancreatectomy (DP) to evacuate pancreatic juice and intra-abdominal exudate and obtain information on abdominal cavity status. However, the timing of drain removal remains debatable. Meanwhile, prolonged drain placement might increase the risk of postoperative pancreatic fistula (POPF), with a prevalence of 5-40%. Therefore, we examined the effect of removing the drain within postoperative day (POD) 3 on the risk of POPF development. A total of 108 consecutive patients who underwent DP between April 2015 and March 2020 were examined and divided into two groups according to the day of drain removal; hence, for some patients, the drain was removed on POD 1 (POD 1 group) and for others on POD 3 (POD 3 group). Furthermore, risk factors, including drain fluid amylase (DFA) levels, for developing POPF were investigated. The overall rate of clinically relevant POPF was 4.6% and did not significantly differ between the POD 1 and POD 3 groups [4.5% and 4.9%, respectively (p=0.924)]. DFA levels on POD 1 did not significantly differ between patients with and without POPF. On POD 3 and POD 5, C-reactive protein (CRP) levels were significantly higher in patients with POPF than in those without (p=0.03 and p<0.001, respectively). Early drain removal regardless of DFA level may reduce the risk of developing POPF. CRP measured on POD 3 and POD 5 appeared to be a useful predictor of clinically relevant POPF.

Postoperative Pancreatic Fistula Following Traumatic Splenectomy: What Techniques Affect Incidence?

Background and Hypothesis: &#x0D; Development of postoperative pancreatic fistula (POPF) in cases of adult splenectomy following trauma occur in 1-3% of cases. Incidence of this complication leads to increased mortality rates, length-of-stays (LOS), and costs for patients. In cases where no previous pancreatic injury was noted, we hypothesized that the use of sutures in splenic hilum ligation instead of staples reduced the rate of incidence. &#x0D; &#x0D; Methods: &#x0D; Adult trauma patients (age ≥17 years) that underwent non-elective splenectomy from 2010-2020 at Indiana University Methodist Hospital were retrospectively evaluated from the hospital’s trauma registry. Due to the low incidence of POPF, our review was not adequately powered to perform statistical analysis with integrity; thus, we report our findings as a case series. &#x0D; &#x0D; Results: &#x0D; 262 adult splenectomies following trauma occurred between 2010 and 2020; 160 passed exclusion criteria and were included in our analysis. Sutures alone across hilar structures were used in 135 cases, 6 of which developed POPF (4.4%). Staples alone across hilar structures were used in 13 cases, 3 of which developed POPF (23%). A combination of staples and sutures was used in 10 cases, none of which developed POPF. In cases of POPF, individuals averaged hospital LOS of 31.6 days, ICU LOS of 15.8 days, and 47.3 days with an abdominal drain in place. These patients averaged 4.78 abdominal CT scans, 1.11 endoscopic retrograde cholangio-pancreatography (ERCP), and 0.78 drain exchanges performed. &#x0D; &#x0D; Conclusion: &#x0D; Though not statistically significant, we noted that POPF are more likely to develop when staples alone are used across hilar structures. In our 10-year retrospective review of POPF, we found the complication to be rare but morbid, with associated prolonged length of hospital and ICU stays and requiring multiple imaging studies and interventions, leading to increased costs. We conclude that further study of optimal technique for emergent splenectomy is warranted.

Postoperative pancreatic fistulas decrease the survival of pancreatic cancer patients treated with surgery after neoadjuvant chemoradiotherapy: A retrospective analysis

Background and objectivesA postoperative pancreatic fistula (POPF) is a critical complication after surgery for pancreatic cancer. Whether a POPF affects the long-term prognosis of pancreatic cancer cases remains controversial. This study aimed to clarify the effect of a POPF on the long-term prognosis of pancreatic cancer patients, especially after neoadjuvant chemoradiotherapy (NACRT). MethodsPatients who underwent curative pancreatectomy for pancreatic cancer between January 2012 and June 2019 at Kyoto University Hospital were retrospectively investigated. A fistula ≥ Grade B was considered a POPF. ResultsDuring the study period, 148 patients underwent upfront surgery (Upfront group), and 52 patients underwent surgery after NACRT (NACRT group). A POPF developed in 16% of patients in the Upfront group and 13% in the NACRT group (p = 0.824). In the Upfront group, development of a POPF did not have a significant effect on recurrence-free survival (p = 0.766) or overall survival (p = 0.863). However, in the NACRT group, development of a POPF significantly decreased recurrence-free survival (HR 5.856, p = 0.002) and overall survival (HR 7.097, p = 0.020) on multivariate analysis. ConclusionsThe development of a POPF decreases the survival of pancreatic cancer patients treated by surgery after NACRT.

Investigation of intraoperative factors associated with postoperative pancreatic fistula following laparoscopic left pancreatectomy with stapled closure: a video review-based analysis

Postoperative pancreatic fistula (POPF) following distal pancreatectomy (DP) remains the most frequent complication, potential precursor of more serious events, and mechanisms behind POPF development are not clear. Primary aim of the current study is to investigate correlations between patients' characteristics, including technical intraoperative data assessed by retrospective video review of laparoscopic DP (L-PD), and development of clinically relevant (CR-)POPF and major complication. Patients undergoing L-DP whose surgery video was available for review were included in this study. Retrospective video review, performed by two surgeons blinded for postoperative outcomes, was focused on pancreatic neck transection and identification of pancreatic capsule disruption (PCD)/staple line bleeding (SLB). Correlation between clinical, demographic, and intraoperative factors and CR-POPF/major complications and assessment of factors associated with PCD and SLB were investigated. Of 41 L-DP performed at our institution (June 2015-June 2020) using a triple-row stapler (EndoGIA™ Reloads with Tri-Staple™), surgery video was available for 38 patients [men/women, 13/25; median age (range) 62 (25-84) years; median BMI (range) 24 (17-42)]. PCD and SLB occurred in 15(39%) and 19(50%) patients and were concomitant in 9(24%). CR-POPF and major complications occurred in 8(21%) and 12(31%) patients, respectively. PCD, SLB, and PCD + SLB rates were significantly higher among patients with CR-POPF, compared to patients without (all p < 0.05). Among patients with PCD, pancreatic thickness at pancreatic transection site was higher (19mm), compared to non-PCD patients (13mm, p < 0.001). A directly proportional relation between PCD, CR-POPF, and major complication rate and pancreatic thickness was confirmed by ROC analysis (AUC = 0.949, 0.798, and 0.740, respectively). PCD and SLB close to the staple line detected by retrospective video-review are intraoperatively detectable indicators of severe pancreatic traumatism and a potential precursors of CR-POPF following L-PD. Given the strict correlation between PCD and pancreatic thickness, alternative techniques to stapled closure for pancreatic transection may be recommended for patients with a thick pancreas and modification in postoperative care may be considered in patients with PCD/SLB.

Pancreatic Configuration Index in Predicting Postoperative Pancreatic Fistula in a Tertiary Care Center in Nepal.

Post-operative pancreatic fistula is the single most common and most significant cause of post-operative morbidity and perioperative mortality. Identification of at risk patient preoperatively help to take policy of extra vigilance to act on time. This study evaluated the predictive role and cut-off value of pancreatic configuration index to predict post-operative pancreatic fistula. This was a prospective observational study in patients who had undergone pancreaticoduodenectomy from March 2017 to June 2018 at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. The patients with age <16 years, those who underwent re-exploration or mortality before 3rd postoperative day, additional surgery besides pancreaticoduodenectomy were excluded from the study. Pancreatic configuration index was calculated as a ratio of pancreatic parenchymal thickness and pancreatic duct diameter. Predictive value of pancreatic configuration index in predicting post-operative pancreatic fistula was evaluated. Among 58 patients, 9 were excluded from study and 49 patients were included in the study. The mean age of the patients was 56.6 ± 13.9 years (21 to 79 years) and male to female ratio was 1.1:1 (26 vs 23). Post-operative pancreatic fistula developed in 13/49 (26.5%) patients. On both univariate and multivariate analysis, pancreatic texture (p = 0.022), main pancreatic duct diameter at neck (p = 0.002) and pancreatic configuration index (p = 0.001) were significantly associated with development of post-operative pancreatic fistula. The sensitivity and specificity of pancreatic configuration index to predict post-operative pancreatic fistula are 92.3% and 91.7% with positive predictive value of 80% and negative predictive value of 97.1%. Pancreatic configuration index is a useful preoperative predictor of post-operative pancreatic fistula after pancreaticoduodenectomy.

Microbiome Patterns in Matched Bile, Duodenal, Pancreatic Tumor Tissue, Drainage, and Stool Samples: Association with Preoperative Stenting and Postoperative Pancreatic Fistula Development.

Postoperative complications after pancreatic surgery are still a significant problem in clinical practice. The aim of this study was to characterize and compare the microbiomes of different body compartments (bile duct, duodenal mucosa, pancreatic tumor lesion, postoperative drainage fluid, and stool samples; preoperative and postoperative) in patients undergoing pancreatic surgery for suspected pancreatic cancer, and their association with relevant clinical factors (stent placement, pancreatic fistula, and gland texture). For this, solid (duodenal mucosa, pancreatic tumor tissue, stool) and liquid (bile, drainage fluid) biopsy samples of 10 patients were analyzed using 16s rRNA gene next-generation sequencing. Our analysis revealed: (i) a distinct microbiome in the different compartments, (ii) markedly higher abundance of Enterococcus in patients undergoing preoperative stent placement in the common bile duct, (iii) significant differences in the beta diversity between patients who developed a postoperative pancreatic fistula (POPF B/C), (iv) patients with POPF B/C were more likely to have bacteria belonging to the genus Enterococcus, and (v) differences in microbiome composition with regard to the pancreatic gland texture. The structure of the microbiome is distinctive in different compartments, and can be associated with the development of a postoperative pancreatic fistula.

Pancreatic Inflammation and Proenzyme Activation Are Associated With Clinically Relevant Postoperative Pancreatic Fistulas After Pancreas Resection.

We investigated the activation of pancreatic proenzymes and signs of peripancreatic inflammation in patients with clinically relevant postoperative pancreatic fistulas (POPFs). An increase of systemic amylase concentration was associated with POPFs. This suggested parallels in the pathomechanisms between the development of POPFs and pancreatitis. Trypsinogen, procathepsin B, and IL-6 concentrations as well as cathepsin B, myeloperoxidase and trypsin activities were determined throughout the first 7 postoperative days in drain fluids of 128 consecutive patients after pancreas resection. Histology and immunohistochemistry were performed in pancreatic specimens after total pancreatectomy due to complications and after placing experimental pancreatic sutures in the pancreatic tail of C57/Bl6 mice. Trypsin activity, cathepsin B activity and myeloperoxidase activity on the first postoperative day were elevated and predictive for clinically relevant pancreatic fistulas. Drain fluid stabilized trypsin activity and prevented the activation of the cascade of digestive enzymes. Leukocytes were the source of cathepsin B in drain fluid. Findings differed between fistulas after distal pancreatectomy and pancreatoduodenectomy. Immunohistochemistry of the pancreatic remnant revealed an inflammatory infiltrate expressing cathepsin B, independent of the presence of pancreatic fistulas. The infiltrate could be reproduced experimentally by sutures placed in the pancreatic tail of C57/Bl6 mice. Trypsinogen activation, increased cathepsin B activity and inflammation around the pancreato-enteric anastomosis on post operative day 1 are associated with subsequent clinically relevant POPFs after pancreatoduodenectomy. The parenchymal damage seems to be induced by placing sutures in the pancreatic parenchyma during pancreatic surgery.

How to divide the pancreatic parenchyma in patients with a portal annular pancreas: laparoscopic spleen-preserving distal pancreatectomy for serous cystic neoplasms

BackgroundPortal annular pancreas (PAP) is a rare pancreatic anomaly in which the uncinate process wraps annularly around the portal vein and fuses to the body of the pancreas. PAP is highly relevant to the development of postoperative pancreatic fistula (POPF) in pancreatic surgery. Here, we describe our experience and surgical technique of laparoscopic spleen-preserving distal pancreatectomy using Warshaw’s procedure for patients with the PAP.Case presentationA 49-year-old woman with PAP was referred to our hospital for a suspicious mucinous cystic neoplasms 1.5 cm in diameter in the pancreatic tail. Laparoscopic spleen-preserving distal pancreatectomy using Warshaw’s procedure was performed. Mobilization of the pancreatic tail was first performed, and then, the splenic artery was cut. After dividing the pancreatic tail from the splenic hilum, the ventral pancreatic parenchyma was divided using a stapler. After cutting the splenic vein, complete mobilization of the pancreatic body and tail enabled easy division of the PAP. Finally, the PAP was also divided using the stapler. Although grade B POPF occurred, she was discharged on the 9th postoperative day.ConclusionsSurgeons should understand the anatomical characteristics of PAP and be aware of the possibility of POPF.

Albumin difference as a new predictor of pancreatic fistula following distal pancreatectomy: a retrospective study of 211 consecutive patients.

The level of albumin declines after surgery, and whether the difference between preoperative and postoperative albumin levels on postoperative day 1 has an effect on the development of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) is unclear. Our aim was to evaluate the effect of albumin difference on POPF. A retrospective analysis of consecutive patients who had undergone DP between January 2016 and October 2018 at a single institution was conducted. Patient demographic data and perioperative data were analysed using univariate and multivariate models. Pancreatic fistula was defined by the 2016 International Study Group of Pancreatic Surgery criteria. All patients were followed for up to 90days. A total of 211 consecutive patients were identified. The POPF rate was 15.64%, and no 90-day mortality was observed. Five predictors were independently associated with POPF: albumin difference (OR 6.60, 95% CI 2.36-18.45, P < 0.001), pancreatic texture (OR 4.15, 95% CI 1.62-10.63, P = 0.003), operative time (OR 3.13, 95% CI 1.19-8.24, P = 0.021), intraoperative fluid transfusion (OR 4.85, 95% CI 1.70-13.79, P = 0.003), and cardiovascular disease (OR 5.38, 95% CI 1.99-14.55, P = 0.001). Although DP can be performed with a low rate of mortality, POPF remains a common complication. Albumin difference is a new, accessible predictor for POPF following DP.

Use of radiation therapy in neoadjuvany treatment for pancreatic adenocarcinoma decreases risk of postoperative pancreatic fistula: A nsqip analysis

Presenter: Christopher Mangieri MD | Wake Forest University Background: Neoadjuvant therapy for pancreatic cancer decreases the risk of post-operative pancreatic fistula (POPF). However, there is a paucity of published data specifying which neoadjuvant regimen is most protective against POPF development. We evaluated the differences between neoadjuvant chemotherapy (CT), radiation therapy (RT), and chemotherapy/radiation therapy (CRT) in regard to effect on POPF rates. We hypothesize combined therapy decreases POPF. Methods: The main and targeted pancreatectomy National Surgical Quality Improvement (NSQIP) registries for 2014-2016 were retrospectively reviewed. Cases that did not contain information on the use of neoadjuvant therapy or POPF development were excluded. Additionally, cases that did not identify a malignant etiology were excluded. Linear regression analysis of NSQIP factors that have previously been shown to be associated with or suspected to be associated with POPF was performed. Factors included neoadjuvant therapy, sex, age, BMI, diabetes, smoking, steroid therapy, preoperative weight loss, preoperative albumin level, perioperative blood transfusions, wound classification, ASA classification, duct size (6mm), gland texture (soft, intermediate, hard), and anastomotic technique. Factors identified to be statistically significant with the development of POPF were then compared between cases that received neoadjuvant CT, RT, and CRT. Results: 10,117 cases were analyzed. Development of POPF was significantly associated with lack of neoadjuvant therapy, male sex, higher BMI, non-diabetic status, post-operative blood transfusion, decreased duct size, and soft gland texture. Neoadjuvant therapy, BMI, duct size, and gland texture had the strongest associations with development of POPF (all p values < 0.0001). Overall 1,765 cases (17.45%) underwent neoadjuvant therapy. 1,031 cases underwent CT, 62 cases underwent RT, and 672 cases underwent CRT. The POPF rates were 20.1%, 11.15%, 4.84%, and 8.18% for cases that received no neoadjuvant therapy, CT, RT, and CRT respectively (p value < 0.0001). Comparison of POPF rates between groups receiving only neoadjuvant therapy demonstrated persistent significant differences with the inclusion of radiation therapy (p value 0.039). Decreasing POPF rates correlated significantly with firmer gland texture with the hard gland rates being 54.84%, 54.17%, 42.48%, and 29.01% in the RT, CRT, CT, and no therapy groups respectively (p value < 0.001). Comparison of the neoadjuvant treatment groups revealed no statistically significant differences between duct size, diabetic status, post-operative transfusions, and BMI. Conclusion: To our knowledge this is the largest analysis of specific neoadjuvant regimens in regard to the development of POPF following pancreaticoduodenectomy. The addition of radiation therapy to neoadjuvant regimens provides the strongest protective effect. This is potentially due to increased fibrosis in the pancreatic parenchyma from the radiation therapy resulting in a firmer gland. These findings provide additional support to alleviate concerns the use of neoadjuvant therapy with radiation will increase adverse outcomes after pancreaticoduodenectomy.

Pancreatic transection using a reinforced staple to reduce pancreatic fistula rates following distal pancreatectomy

Background: Distal pancreatectomy (DP) is frequently complicated by the development of postoperative pancreatic fistula (POPF). Various Methods to divide the pancreatic neck and reinforce the transected stump have been proposed, yet no single technique has been shown to be superior in the prevention of POPF. The aim of this study was to evaluate the rates of POPF following division of the pancreatic neck with the EndoGIATM stapler using a standard Tri-StapleTM reload compared to a reinforced Tri-StapleTM reload; utilising an integrated absorbable buttress material to reinforce the staple line. Conclusions: Patients undergoing elective DP under a single surgeon in the regional hepatobiliary centre were identified over a two-year period from October 2016 to October 2018. Between October 2016 and October 2017 transection of the pancreatic neck was performed using the standard Tri-StapleTM reload. From October 2017 to October 2018 division was completed using the reinforced Tri-StapleTM reload. Patient and operative details, mortality and morbidity were all collated. POPF was defined in accordance with the revised 2016 International Study Group of Pancreatic Fistula (ISGPF) guidelines. Results: 23 DP were performed over the two-year period; 12 using the standard Tri-StapleTM and 11 with the reinforced reload. The rate of POPF was lower in the reinforced stapler group, however this difference was not statistically significant (Table 1). In keeping with fewer and less severe grades of POPF, the mean length of stay (LOS) in the reinforced staple group was lower compared to the standard stapler (p=0.19). One mortality occurred in the standard stapler group in a patient who developed a Grade C POPF. Conclusion: Preliminary Results using a reinforced stapler are encouraging with a non-significant reduction in POPF in this small cohort; however larger scale, prospective studies are needed to confirm its efficacy in reducing the risk of this common and serious complication. Tabled 1Table 1.

Predictors of prolonged pancreatic fistula in patients undergoing pancreatoduodenectomy (whipple procedure)

Presenter: May Tee MD, MPH | Mercy Medical Center Background: Postoperative pancreatic fistula (POPF) contributes to substantial morbidity associated with pancreatoduodenectomy (PD). Risk stratification for development of POPF, based on factors such as pancreatic duct size, pancreatic texture, and intraoperative blood loss, may mitigate severity of POPF by treatment with antibiotics, additional drains, or feeding tubes. We aimed to examine predictors of prolonged POPF (POPF at 30 days or greater) in patients undergoing PD to provide further stratification of patients at risk. Methods: The American College of Surgeons National Surgical Quality Improvement Program pancreatectomy procedure targeted participant use file was queried from 2015-2017, when persistent POPF at postoperative day 30 was captured. All PD procedures were extracted with emergent cases excluded. Univariable and multivariable analyses were conducted to examine the association between persistent POPF and 30-day surgical outcomes. Results: N = 12,014 patients undergoing open and minimally invasive PD were evaluated. On univariate analyses, persistent POPF was associated with the following outcomes: surgical site infection (SSI) superficial (11.0% vs. 7.4%, P < 0.001), deep SSI (3.1% vs. 1.2%, P < 0.001), organ space SSI (44.1% vs. 13.1%, P < 0.001), wound dehiscence (2.3% vs. 1.0%, P < 0.001), pneumonia (6.7% vs. 3.5%, P < 0.001), reintubation (9.2% vs. 3.2%, P < 0.001), pulmonary embolus (2.9% vs. 1.1%, P < 0.001), failure to wean off mechanical ventilation (9.2% vs. 2.4%, P < 0.001), renal insufficiency (1.6% vs. 0.6%, P < 0.001), renal failure (2.4% vs. 0.8%, P < 0.001), myocardial infarction (2.3% vs. 1.1%, P=0.001), deep vein thrombosis (6.8% vs. 2.6%, P < 0.001), sepsis (19.2% vs. 8.5%, P < 0.001), septic shock (9.9% vs. 2.4%, P < 0.001), length of stay greater than 12 days (58.9% vs. 23.7%, P < 0.001), discharge to destination other than home (28.9 vs. 12.8%, P < 0.001), return to operating room (13.5% vs. 4.9%, P < 0.001), readmission to hospital (23.8% vs. 15.8%, P < 0.001), delayed gastric emptying (35.2% vs. 15.4%, P < 0.001), percutaneous drain placement (33.3% vs. 10.9%, P < 0.001), and postoperative C. difficile colitis (3.3% vs. 1.8%, P=0.003). On multivariable analyses, independent predictors of prolonged POPF include: male sex (OR=1.6, P < 0.001), obesity (OR=1.5, P < 0.001), operative time greater than 420 minutes (OR=1.2, P=0.03), preoperative chemotherapy (OR=0.6, P=0.002), postoperative blood transfusion (OR=1.7, P < 0.001), pancreatic duct < 3mm (OR=1.7, P=0.002), soft pancreatic texture (OR=2.4, P < 0.001), and drain to suction (OR=1.4, P=0.015). Conclusion: Prolonged POPF is a major source of morbidity following PD but not mortality. Further risk stratification for POPF may be considered for male patients with increased body mass index undergoing prolonged PD procedures. Significant perioperative blood loss requiring transfusion, small pancreatic duct, and soft pancreas remain important predictors of prolonged POPF. Interestingly, drain placed to suction was associated with increased odds of prolonged POPF but neoadjuvant chemotherapy appeared to be protective against prolonged POPF.

HYAL-1-induced autophagy facilitates pancreatic fistula for patients who underwent pancreaticoduodenectomy.

The main mechanism of hyaluronidase 1(HYAL-1) in the development of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) was unknown. In this study, a comprehensive inventory of pre-, intra-, and postoperative clinical and biological data of two cohorts (62 pancreatic cancer [PCa] and 111 pancreatic ductal adenocarcinoma [PDAC]) which could induce POPF were retrospectively analyzed. Then, a total of 7644 genes correlated with HYAL-1 was predicted in PDAC tissues and the enriched pathway, kinase targets and biological process of those correlated genes were evaluated. Finally, a mouse pancreatic fistula (PF) model was first built and in vitro studies were performed to investigate the effects of HYAL-1 on PF progression. Our data indicated that preoperative serum HYAL-1 level, pancreatic fibrosis score, and pancreatic duct size were valuable factors for detecting POPF of Grade B and C. The serum HYAL-1 level of 2.07mg/ml and pancreatic fibrosis score of 2.5 were proposed as the cutoff values for indicating POPF. The bioinformatic analysis and in vitro and in vivo studies demonstrated that HYAL-1 facilitates pancreatic acinar cell autophagy via the dephosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and signal transducers and activators of transcription 3 (STAT3) signaling pathways, which exacerbate pancreatic secretion and inflammation. In summary, the preoperative serum HYAL-1 was a significant predictor for POPF in patients who underwent PD. Tumor-induced HYAL-1 is one of core risk in accelerating PF and then promoting pancreatic secretion and acute inflammation response through the AMPK and STAT3-induced autophagy.

Drain Amylase or Lipase for the Detection of POPF-Adding Evidence to an Ongoing Discussion.

Objectives: A postoperative pancreatic fistula (POPF) is defined as a threefold increase in the amylase concentration in abdominal drains on or after the third postoperative day (POD). However, additional lipase fluid analysis is widely used despite lacking evidence. In this study, drain amylase and lipase levels were compared regarding their value in detecting POPF. Methods: We conducted a retrospective study including all patients who underwent pancreatic resections at our center between 2005 and 2016. Drain fluid analysis was performed from day 2 to 5. Results: 990 patients were included in the analysis. Overall, 333 (34%) patients developed a POPF. The median amylase and lipase concentrations at POD 3 in cases with POPF were 11.55 µmol/(s·L) (≈13 ×-fold increase) and 39 µmol/(s·L) (≈39 ×-fold increase), respectively. Seven patients with subsequent POPF (2%) were missed with amylase analysis on POD 3, but detected using 3-fold lipase analysis. The false-positive rate of lipase was 51/424 = 12%. A cutoff lipase value at POD 3 of > 4.88 yielded a specificity of 94% and a sensitivity of 89% for development of a POPF. Increased body mass index turned out as risk factor for the development of POPF in a multivariable model. Conclusions: Threefold-elevated lipase concentration may be used as an indicator of a POPF. However, the additional detection of POPF using simultaneous lipase analysis is marginal. Therefore, assessment of lipase concentration does not provide added clinical value and only results in extra costs.

Feasibility, Morbidity and Mortality in Two Hundred Consecutive Cases of Pancreaticogastrostomy After Pancreaticoduodenectomy

BackgroundPostoperative mortality associated with pancreaticoduodenectomy (PD) in high-volume hospitals is below 5%, yet morbidity rates range between 45% and 60%. Recent studies show a lower incidence of complications and postoperative pancreatic fistula (POPF) in pancreaticogastrostomy (PG). The primary objective was to assess the incidence and predictive factors for complications: POPF, post-pancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) following the criteria of the ISGPS and Clavien-Dindo classifications. MethodsA prospective observational study that included all patients who underwent PD between 2008 and 2016. PG was the surgical procedure of choice for PD reconstruction. ResultsTwo hundred forty-nine (249) patients underwent surgery with intention of performing a PD. The feasibility of PG was 90.5%. One hundred and six (53%) patients had complications, 36 (18%) were severe (Clavien-Dindo grade ≥ III). Death within 90 postoperative days was 4%. DGE was the most frequent complication (22.5%), followed by PPH (21%). The clinical POPF rate was 15% (6% Clavien-Dindo grade ≥ III). The primary risk factors associated with complications were age >70 years (1.9 [1–3.55]), being male (1.89 (1; 3.6]) and soft pancreatic texture (3.38 [1.5; 7.37]). ConclusionsIn this paper, we report a feasibility study for PG (90.5%). The primary risk factors associated with complications are age >70 years, being male and soft pancreatic texture. Soft pancreatic texture is also associated with the development and severity of POPF.

Analysis of complications after Whippleʼs procedure using ERAS protocols

Background: The administration of perioperative fluids is a controversial issue that can be associated with the development of postoperative pancreatic fistula (POPF) after Whipple procedure. Objective: To evaluate whether intraoperative fluid management along with Enhanced Recovery after Surgery (ERAS) protocols affect outcomes following major pancreatic resection. Methods: A retrospective cohort study was conducted from January 2012 to January 2017, collecting all patients scheduled for duodenopancreatectomy (DP). Patients were divided into 2 groups according to the use of ERAS protocols and the use of a fluid therapy algorithm. Results: A total of 67 patients were analyzed, 49.3% of which were females. The most frequent diagnoses were Pancreatic Cancer n:48 (71.6%), followed by intraductal papillary mucinous neoplasm n:6 (9%). The majority of patients were in the ERAS group n:46 (68.7%); 80.4% and 95.7% of them did not develop pancreatic fistula or delayed gastric emptying (DGE) respectively, and the incidence for both was 11.94%. Fluid therapy was below 5000 mL (P=0.001) with blood loss less 300 mL (P = 0.001) in the ERAS group. The length of stay was shorter in the ERAS group (7 days, interquartilel range 5-12, P < 0.001). No differences in 30 days mortality were found. Conclusion: The implementation of ERAS protocols in DP did show a decrease in intraoperative blood loss, intravenous fluids therapy, need for transfusion, DGE, or total hospital stay. However, intraoperative fluid restriction in DP did not show a reduction in the development of POPF.

Traumatic pancreatitis

Post-traumatic pancreatitis can develop secondary to blunt or penetrating abdominal trauma, post-endoscopic retrograde cholangiopancreatography, or following pancreatic surgery. Clinical findings are often nonspecific, and imaging findings can be subtle on presentation. Early diagnosis of pancreatic duct injury is critical and informs management strategy; imaging plays important role in diagnosis of ductal injury and identification of delayed complications such as retroperitoneal fluid collections, pancreatic fistula, ductal strictures, and recurrent pancreatitis. Delayed diagnosis of pancreatic injury is associated with high mortality and morbidity, and therefore, heightened clinical suspicion is important in order for the radiologist to effectively impact patient care. There are accepted scoring systems for classification of post-traumatic pancreatic injuries and these should be included in radiology reports. Pancreatitis following ERCP appears similar on imaging to other causes of acute pancreatitis unless concomitant perforation occurs. Postoperative pancreatitis may be difficult to diagnose given associated or overlapping expected postoperative findings. Postoperative pancreatic fistulas typically arise from either a leaking pancreatic resection surface or the pancreatoenteric anastomosis and are more common in patients with a "soft" pancreas. Preoperative imaging biomarkers like duct diameter, pancreatic glandular steatosis and parenchymal fibrosis can help predict risk of development of postoperative pancreatic fistula. This review will illustrate the imaging features and the most important imaging findings in patients with post-traumatic pancreatitis.

Calprotectin and Calgranulin C as Biomarkers of Pancreatic Tumors: Baseline Levels and Level Changes after Surgery.

Pancreatic tumors and their surgical resection are associated with significant morbidity and mortality, and the biomarkers currently used for these conditions have limited sensitivity and specificity. Because calprotectin and calgranulin C serum levels have been demonstrated to be potential biomarkers of certain cancers and complications of major surgery, the levels of both proteins were tested in the current study in patients with benign and malignant pancreatic tumors that were surgically removed. The baseline serum levels and kinetics of calprotectin and calgranulin C during the 7-day postoperative period were evaluated with immunoassays in 98 adult patients who underwent pancreatic surgery. The baseline serum levels of calprotectin and calgranulin C in patients with malignant (n = 84) and benign tumors (n = 14) were significantly higher (p < 0.01) when compared to those in the healthy controls (n = 26). The serum levels of both proteins were also significantly (p < 0.05) higher in patients with benign tumors than in those with malignant tumors. After surgery, the serum levels of calprotectin and calgranulin C were significantly (p < 0.01) higher than their baseline values, and this elevation persisted throughout the seven days of the follow-up period. Interestingly, starting on day 1 of the postoperative period, the serum levels of both proteins were significantly (p < 0.05) higher in the 37 patients who developed postoperative pancreatic fistulas (POPFs) than in the patients who had uneventful recoveries (n = 61). Moreover, the serum levels of calprotectin and calgranulin C demonstrated a significant predictive value for the development of POPF; the predictive values of these two proteins were better than those of the serum level of C-reactive protein and the white blood cell count. Taken together, the results of this study suggest that calprotectin and calgranulin C serum levels are potential biomarkers for pancreatic tumors, surgical injury to the pancreatic tissue and the development of POPFs.

Blame it on the injury: Trauma is a risk factor for pancreatic fistula following distal pancreatectomy compared with elective resection.

Postoperative pancreatic fistula (POPF) remains a significant source of morbidity following distal pancreatectomy (DP). There is a lack of information regarding the impact of trauma on POPF rates when compared with elective resection. We hypothesize that trauma will be a significant risk factor for the development of POPF following DP. A retrospective, single-institution review of all patients undergoing DP from 1999 to 2017 was performed. Outcomes were compared between patients undergoing DP for traumatic injury to those undergoing elective resection. Univariate and multivariable analyses were performed using SAS (version 9.4). Of the 372 patients who underwent DP during the study period, 298 met inclusion criteria: 38 DPs for trauma (TDP), 260 elective DPs (EDP). Clinically significant grade B or C POPFs occurred in 17 (44.7%) of 38 TDPs compared with 41 (15.8%) of 260 EDPs (p < 0.0001). On multivariable analysis, traumatic injury was found to be independently predictive of developing a grade B or C POPF (odds ratio, 4.3; 95% confidence interval, 2.10-8.89). Age, sex, and wound infection were highly correlated with traumatic etiology and therefore were not retained in the multivariable model. When analyzing risk factors for each group (trauma vs. elective) separately, we found that TDP patients who developed POPFs had less sutured closure of their duct, higher infectious complications, and longer hospital stays, while EDP patients that suffered POPFs were more likely to be male, younger in age, and at a greater risk for infectious complications. Lastly, in a subgroup analysis involving only patients with drains left postoperatively, trauma was an independent predictor of any grade of fistula (A, B, or C) compared with elective DP (odds ratio, 8.6; 95% confidence interval, 3.09-24.15), suggesting that traumatic injury is risk factor for pancreatic stump closure disruption following DP. To our knowledge, this study represents the largest cohort of patients comparing pancreatic leak rates in traumatic versus elective DP, and demonstrates that traumatic injury is an independent risk factor for developing an ISGPF grade B or C pancreatic fistula following DP. Prognostic study, Therapeutic, level III.