Mind the tributary of the canal: Are stents necessary for insulinoma enucleation in proximity to a prominent Duct of Santorini: A case report and literature review.

RATIONALE: We describe a case of insulinoma located extremely close to the accessory pancreatic duct (APD), but away from the main pancreatic duct (MPD). Previous studies showed insulinoma enucleation is a safe procedure for small benign tumors >3 mm distant from the MPD. However, in this case enucleation of the tumor led to unanticipated APD injury and grade B post-operative pancreatic fistula (POPF). We provide detailed records of clinical management and argue that enucleation of tumors near APD needs to be carefully weighed. PATIENT CONCERNS: The patient experienced a sudden increase of abdominal drain fluid and prolonged drainage time after a regular insulinoma enucleation surgery. DIAGNOSIS: APD damage during the enucleation. INTERVENTIONS: Drain fluid amylase concentration were regularly recorded and prolonged somatostatin analogs were administered. OUTCOMES: Amount of abdominal drain gradually decreased and the drain tube was removed on postoperative 37. LESSONS: Benign pancreatic tumor close to the APD need to be evaluated carefully and clinical evidence is warranted to affirm the necessity of placing a pancreatic duct stent before the surgery.

Perioperative and oncologic outcome of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy: based on pancreatic fistula risk score and cancer/staging matched comparison with open pancreatoduodenectomy.

BACKGROUND: Robotic surgery is a novel approach that scores over conventional minimally invasive approaches, even in pancreatic surgery. We investigated clinical outcomes of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy (RA-MIPD). METHODS: Total 150 patients who underwent RA-MIPD between 2015 and 2018 were compared with 710 patients who underwent open pancreatoduodenectomy (PD) during the same period. Demographics and surgical outcomes were analyzed, and propensity score-matched (PSM) analysis was performed to evaluate complications including clinically relevant postoperative pancreatic fistula (CR-POPF) and oncologic outcomes in patients with malignancy. RESULTS: PSM analysis was performed based on the pancreatic fistula risk. Patients undergoing RA-MIPD were younger (RA-MIPD vs. open PD: 61.2 vs. 65.5 years, P < 0.001); however, no significant intergroup difference was observed in sex (P = 0.091) and body mass index (P = 0.281). Operation time was longer in the RA-MIPD group (361.2 vs. 305.7 min, P < 0.001); however, estimated blood loss did not significantly differ (515.6 vs. 478.0 mL, P = 0.318). Overall complication (24.7% vs. 30.9%, P = 0.178) and CR-POPF rates (6.7% vs. 6.9%, P > 0.999) were similar. The RA-MIPD group showed lower pain scores and shorter length of postoperative hospitalization (11.5 vs. 17.2 days, P < 0.001). After PSM analysis for cancer and staging among patients with malignancies, no significant intergroup difference was observed in the R0 resection rate (96.7% vs. 93.3%, P = 0.527), tumor size (2.59 vs. 2.60 cm, P = 0.954), total number of retrieved lymph nodes (17.0 vs. 16.6, P = 0.793), and 2-year survival rates (84.4% vs. 77.8%, P = 0.898). CONCLUSIONS: Compared with open PD, RA-MIPD is associated with better or at least similar early perioperative and equivalent midterm survival outcomes. RA-MIPD is safe and feasible and enables early postoperative recovery. RA-MIPD is expected to play a key role in near future.

Laser Treatment of Pancreatic Cancer with Immunostimulating Interstitial Laser Thermotherapy Protocol: Safety and Feasibility Results From Two Phase 2a Studies.

PURPOSE: Ablative techniques have emerged as new potential therapeutic options for patients with locally advanced pancreatic cancer (LAPC). We explored the safety and feasibility of using TRANBERG|Thermal Therapy System (Clinical Laserthermia Systems AB, Lund, Sweden) in feedback mode for immunostimulating Interstitial Laser Thermotherapy (imILT) protocol, the newest ablative technique introduced for the treatment of LAPC. METHODS: The safety and feasibility results after the use of imILT protocol treatment in 15 patients of a prospective series of postsystemic therapy LAPC in two high-volume European institutions, the General and Pancreatic Unit of the Pancreas Institute, of the University of Verona, Italy, and the Department of Surgical Oncology of the Institut Paoli-Calmettes of Marseille, France, were assessed. RESULTS: The mean age was 66 ± 5 years, with a mean tumor size of 34.6 (±8) mm. The median number of cycles of pre-imILT chemotherapy was 6 (6-12). The procedure was performed in 13 of 15 (86.6%) cases; indeed, in two cases, the procedure was not performed; in one, the procedure was considered technically demanding; in the other, liver metastases were found intraoperatively. In all treated cases, the procedure was completed. Three late pancreatic fistulas developed over four overall adverse events (26.6%) and were attributed to imILT. Mortality was nil. A learning curve is necessary to interpret and manage the laser parameters. CONCLUSIONS: Safety, feasibility, and device handling outcomes of using TRANBERG|Thermal Therapy System with temperature probes in feedback mode and imILT protocol on LAPC were not satisfactory. The metastatic setting may be appropriate to evaluate the hypothetic abscopal effect.#NCT02702986 and #NCT02973217.

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

BACKGROUND AND OBJECTIVES: A 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). METHODS: Patients 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. RESULTS: During 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. CONCLUSIONS: The development of a POPF decreases the survival of pancreatic cancer patients treated by surgery after NACRT.

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 2.07 mg/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.

Stapler sizes optimized for pancreatic thickness can reduce pancreatic fistula incidence after distal pancreatectomy.

PURPOSE: The purpose of this paper was to identify the optimum-sized stapler cartridges for reducing the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). METHODS: The authors retrospectively analyzed 101 patients who underwent DP with a triple-row stapler to identify the clinicopathological factors that strongly influence POPF after DP. The height difference (HD) was defined as the difference between the pancreatic thickness and the height of the closed stapler. RESULTS: POPF occurred in 58 (57%) patients. A multivariate analysis identified HD and pancreatic thickness as independent risk factors for the occurrence of POPF after DP. Akaike's information criterion for identifying the risk factors was more favorable for HD (115.18) than for pancreatic thickness (118.02). The incidence of POPF was significantly lower (29%) in patients with an HD between 6 and 12 mm than in the other two groups (< 6-mm group: 100%, P = 0.008; ≥ 12-mm group: 84%, P < 0.001). CONCLUSIONS: A too-thick or too-narrow pancreas carries a risk of developing POPF after DP when using a triple-row stapler. Selecting staplers to achieve an HD of 6-12 mm may reduce the incidence of POPF following DP.

Natural course of low output external pancreatic fistula in patients with disconnected pancreatic duct syndrome following acute necrotising pancreatitis.

BACKGROUND: External pancreatic fistulae (EPF) associated with complete pancreatic duct (PD) disruption leading on to disconnected pancreatic duct syndrome (DPDS) is a therapeutic nightmare usually requiring surgery. However, spontaneous closure also has been reported. There is paucity of data on the natural history of EPF associated with DPDS. OBJECTIVE: To retrospectively study outcome of conservative treatment in patients with low output (<200 ml/day) EPF with DPDS following percutaneous or surgical intervention in acute necrotising pancreatitis (ANP). METHODS: The data of patients of low output EPF with DPDS treated conservatively in our unit over last 5 years was retrospectively analysed. Their clinical course, complications as well as time taken for fistula closure was retrieved. RESULTS: 33 patients (27 males; mean age: 40.5 ± 9.3 years) of low output EPF and DPDS were studied. 31 patients developed EPF following percutaneous drainage (PCD) and 2 patients developed fistula following surgery. The drain fluid amylase ranged from 1600 to 32,000 IU/l and site of disruption was neck, proximal body and distal body in 4, 16 and 13 patients respectively. EPF closed spontaneously in all patients within 88.2 ± 63.46 days. PCD slipped out in 2 patients and led to formation of pseudocyst in 1 patient that was treated endoscopically. There has been no recurrence in any patient over follow up of 32.5 ± 21.9 months. CONCLUSION: Low output EPF developing post PCD or surgery in patients with DPDS following ANP closely spontaneously in majority of patients within 3 months with good long term outcome.

A score model based on pancreatic steatosis and fibrosis and pancreatic duct diameter to predict postoperative pancreatic fistula after Pancreatoduodenectomy.

PURPOSES: To establish a scoring model for the risk of postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD). METHODS: PD Patients from 7 institutions in 2 independent sets: developmental (n = 457) and validation cohort (n = 152) were retrospectively enrolled and analyzed. Pancreatic Fibrosis (PF) and Pancreatic Steatosis (PS) were assessed by pathological examination of the pancreatic stump. RESULTS: Stepwise univariate and multivariate analysis indicated that pancreatic duct diameter ≤ 3 mm, increased PS and decreased PF were independent risk factors for POPF and Clinically Relevant Postoperative Pancreatic Fistula (CR-POPF). Based on the relative weight and odds ratio of each factor in the POPF, a simplified scoring model was developed. And patients were stratified into high-risk group (22~28 points), medium-risk group (15~21 points) and low-risk group (8~14 points). The receiver operating characteristic curve demonstrated that the Area under the curve for the predictive model was 0.868 and 0.887 in the model design group and the external validation group. CONCLUSIONS: This study establishes a simplified scoring model based on accurately and quantitatively measuring the PS, PF and pancreatic duct diameter. The scoring model accurately predicted the risk of POPF.

Surgical management and outcome of grade-C pancreatic fistulas after pancreaticoduodenectomy: A retrospective multicenter cohort study.

BACKGROUND: Management strategies for grade-C postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy (PD) vary. The aim of this study was to evaluate surgical indications, approaches, and outcomes of grade-C POPF following PD. MATERIALS AND METHODS: The clinical data of grade-C POPF patients from 9 high-volume institutions between January 1, 2012 and December 31, 2016 were retrospectively reviewed. The indications and outcomes of different surgical strategies were analyzed. Risk factors for unfavorable outcomes were evaluated by multivariate regression analysis. RESULTS: Out of 5115 patients that underwent PD, 68 were diagnosed as grade-C POPF, and 53 underwent re-laparotomy. Pancreas-preserving surgical strategies were mostly used in this cohort (96.2%). Postoperative hospital stay in the external wirsungostomy group tended to be shorter than the other two major surgical approaches (20 days vs. 38 days and 34.5 days). Mortality and morbidity were comparable among different surgical strategies. Prolonged high drain amylase level prior to the development of grade-C POPF was negatively associated with unfavorable outcomes after re-laparotomy (OR: 0.20, 95% CI: 0.05-0.82). CONCLUSION: Pancreas-preserving approaches were preferred for grade-C POPF in this multicenter database, although the choice of definite procedure differed according to different clinical scenarios. Longstanding high amylase drainage may predict better outcomes after re-laparotomy.

Endoscopic treatment of refractory external pancreatic fistulae with disconnected pancreatic duct syndrome.

BACKGROUND: External pancreatic fistulae (EPF) developing in setting of disconnected pancreatic duct syndrome (DPDS) are associated with significant morbidity and surgery is the only effective treatment. AIM: To describe safety and efficacy of various endoscopic including endoscopic ultrasound (EUS) guided drainage techniques for resolving EPF in DPDS. METHODS: Retrospective analysis of data base of 18 patients (15 males; mean age: 37.6 ±â€¯7.1years) with EPF and DPDS who were treated with various endoscopic techniques including EUS guided transmural drainage. RESULTS: EPF developed post percutaneous drainage (PCD) (n = 15) or post-surgical necrosectomy (n = 3) of acute necrotic collections. All patients had refractory EPF with daily output of >50 ml/day with mean duration being 19.2 ±â€¯6.1 weeks. One patient had failed surgical fistulo-jejunostomy. Various endoscopic techniques used were: transmural placement of pigtail stent through gastric opening of trans-gastric PCD (n = 5), EUS guided transmural puncture of fluid collection created by clamping PCD (n = 5) or by instillation of water though PCD (n = 3), direct EUS-guided puncture of fistula tract (n = 1) and EUS guided pancreaticogastrostomy (n = 4). EPF healed in 17/18 (94%) patients within 5-21 days and there has been no recurrence over follow up of 16.7 ±â€¯12.8 weeks. Asymptomatic spontaneous external migration of stents was observed in 5/18 (29.4%) patients. CONCLUSION: Management of refractory EPFs in setting of DPDS is challenging. In our experience, combination of various endoscopic techniques including EUS guided transmural drainage appears to be safe and effective treatment modality for treating these complex EPF's. However, further studies to identify patient selection and best treatment approaches are needed.

Risk Factors for Life-threatening Grade C Postoperative Pancreatic Fistula After Pancreatoduodenectomy Compared to Grade B.

BACKGROUND: The aim of the present study was to investigate risk factors for the development of grade C compared to grade B cases of postoperative pancreatic fistula (POPF). MATERIALS AND METHODS: Clinicopathological data from 43 patients who developed grade B or C POPF were retrospectively analyzed. The following types of factors were analyzed: Patient-related, surgery-related, and pancreas-related, including the value of the drain amylase and the detection of gram-negative rod bacteria within the first 7 postoperative days (PODs). RESULTS: Univariate analysis showed that male sex (p=0.0492) and detection of gram-negative rods within the first 7 PODs (p=0.0010) were risk factors for development of grade C POPF. Only detection of gram-negative rods within the first 7 PODs was a significant factor after multivariate analysis (p=0.0027). CONCLUSION: Sensitive and specific predictive criteria for early detection of grade C POPF should be developed to allow for a management approach appropriately tailored to this condition.

Pancreatic MRI associated with pancreatic fibrosis and postoperative fistula: comparison between pancreatic cancer and non-pancreatic cancer tissue.

AIM: To evaluate the potential value of magnetic resonance imaging (MRI) for predicting postoperative pancreatic fistula (POPF) in patients with pancreatic cancer (PC) and non-pancreatic cancer (non-PC). MATERIAL AND METHODS: This retrospective study was approved by the institutional review board and written informed consent was waived. Forty patients underwent pancreatoduodenectomy due to PC (n=31) and non-PC (n=9). The pancreas-to-muscle signal intensity ratio (SIR) on three-dimensional (3D)- fast field echo (FFE) T1-, in- and opposed-phase T1-, and T2-weighted images, as well as the apparent diffusion coefficient (ADC) value of the pancreas were measured. The frequency of POPF and MRI measurements were compared between patients with PC and non-PC. The MRI measurements were also compared with the grade of pancreatic fibrosis on pathological findings, fat deposition, and interstitial oedema. RESULTS: The frequency of POPF was significantly higher in patients with non-PC than in those with PC (p=0.0067), with an odds ratio of 10.4. The SIR on 3D-FFE T1-weighted images was significantly higher in patients with non-PC (p=0.0001) and those with POPF (p=0.017) than in those with PC and those without POPF, respectively. Multiple regression analysis demonstrated that the SIR on 3D-FFE T1-weighted image was independently associated with the grade of pancreatic fibrosis (p<0.0001). CONCLUSION: The frequency of POPF was significantly higher in patients with non-PC than in those with PC was inversely related to the grade of pancreatic fibrosis. The SIR on 3D-FFE T1-weighted image might be a potential imaging biomarker for predicting POPF.

Pancreaticopleural and pancreaticomediastinal fistula extending to the cervical region, with dysphagia as initial symptom: A case report.

RATIONALE: Pancreaticopleural and pancreaticomediastinal fistulas are rare complications of pancreatitis. They are often misdiagnosed and there are no strict guidelines of treatment. In this study, we present a brief report of a combined pancreaticopleural and pancreaticomediastinal fistula extending to the cervical region, causing dysphagia and cervical swelling as initial symptoms. PATIENT CONCERNS: A 36-year-old female with history of alcohol abuse and pancreatitis presented progressing dysphagia and mild dyspnea on admission. DIAGNOSIS: Chest X-ray and chest and abdominal computed tomography scan (CT) indicated pancreaticopleural fistula combined with pancreaticomediastinal fistula, a diagnosis confirmed by high amylase levels in pleural fluid. INTERVENTIONS: Conservative treatment was administered and ERCP was performed but pancreatic duct stenting was impossible. The patient presented rapid anterior cervical swelling with progressing dysphagia and dyspnea. CT showed fistula penetration to the cervical region. The patient underwent urgent surgery and pancreaticojejunal anastomosis was performed. OUTCOMES: The surgery led to recovery. Six months later, the patient reported good health and weight gain. LESSONS: Coexistence of pancreaticopleural and pancreaticomediastinal fistula with cervical penetration is an extremely rare pancreatitis complication. It presents with dysphagia and anterior cervical swelling as initial symptoms. It is important to consider this complication in all patients with history of pancreatitis, presenting with dysphagia.

Risk stratification for postoperative pancreatic fistula using the pancreatic surgery registry StuDoQ|Pancreas of the German Society for General and Visceral Surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a major factor for morbidity and mortality after pancreatic resection. Risk stratification for POPF is important for adjustment of treatment, selection of target groups in trials and quality assessment in pancreatic surgery. In this study, we built a risk-prediction model for POPF based on a large number of predictor variables from the German pancreatic surgery registry StuDoQ|Pancreas. METHODS: StuDoQ|Pancreas was searched for patients, who underwent pancreatoduodenectomy from 2014 to 2016. A multivariable logistic regression model with elastic net regularization was built including 66 preoperative und intraoperative parameters. Cross-validation was used to select the optimal model. The model was assessed via area under the ROC curve (AUC) and calibration slope and intercept. RESULTS: A total of N = 2488 patients were included. In the optimal model the predictors selected were texture of the pancreatic parenchyma (soft versus hard), body mass index, histological diagnosis pancreatic ductal adenocarcinoma and operation time. The AUC was 0.70 (95% CI 0.69-0.70), the calibration slope 1.67 and intercept 1.12. In the validation set the AUC was 0.65 (95% CI 0.64-0.66), calibration slope and intercept were 1.22 and 0.42, respectively. CONCLUSION: The model we present is a valid measurement instrument for POPF risk based on four predictor variables. It can be applied in clinical practice as well as for risk-adjustment in research studies and quality assurance in surgery.

Evaluation of Pancreatic Fibrosis With Acoustic Radiation Force Impulse Imaging and Automated Quantification of Pancreatic Tissue Components.

OBJECTIVES: The aim of this study was to determine whether computer-assisted digital analysis and acoustic radiation force impulse (ARFI) imaging were useful for assessing pancreatic fibrosis, and if ARFI imaging predicted postoperative pancreatic fistula (POPF). METHODS: Seventy-eight patients scheduled to undergo pancreatic resection were enrolled. Shear wave velocity (SWV) at the pancreatic neck was measured preoperatively using ARFI imaging. Pancreatic tissue components on a whole slide image were quantified using an automatic image processing software. The relationship between SWV, fibrotic tissue content, and POPF incidence and clinical severity was analyzed. RESULTS: The median collagen fiber, fatty tissue, and acinar cell contents were 11.6%, 8.5%, and 61.3%, respectively. Unlike fatty tissue, collagen fiber content and acinar cells were correlated with SWV (ρ = 0.440, P < 0.001 and ρ = -0.428, P < 0.001, respectively). Although collagen fiber content and SWV were associated with the overall incidence of POPF (P = 0.004 and 0.001, respectively), collagen fiber content and SWV had no statistical correlation with clinically relevant POPF (P = 0.268 and 0.052, respectively). CONCLUSIONS: We objectively quantified the pancreatic tissue components using an automatic image processing software. Shear wave velocity was significantly related to collagen fiber content and suggests that ARFI imaging can be useful for evaluating pancreatic fibrosis.

A Bi-national Analysis of 252 Pancreatic Resections for Chronic Pancreatitis with Regard to Incidental Carcinoma Sequence and Overall Postoperative Outcome.

BACKGROUND/AIM: Numerous treatment algorithms for patients with chronic pancreatitis are still debated. In particular, surgical therapy is often only considered after long-term conservative treatment. The aim of this study was the bi-national analysis of patients who underwent pancreatic resection for suspected chronic pancreatitis at an Austrian and a German high-volume center with regard to overall postoperative outcome and incidental carcinoma sequence. PATIENTS AND METHODS: Overall, 252 consecutive pancreatic resections for suspected chronic pancreatitis were performed at the two institutions between 2005 and 2015. In a bi-national retrospective analysis, postoperative results as well as histopathological findings were analyzed. RESULTS: Pancreatic resections were performed in 193 male (76.6%) and 59 female patients (23.4%), with a median age of 53.2 years. A total of 175 resections of the pancreatic head (69.4%), 37 distal pancreatectomies (14.7%), 23 total pancreatectomies (9.1%) and 18 other pancreatic resections (7.1%) were performed within our study period. Postoperative complications Clavien-Dindo grade II or greater occurred in 94 patients (37.3%). Twenty-one patients (8.3%) developed clinically relevant postoperative pancreatic fistula (grade B and C), while postoperative mortality occurred in four patients (1.6%). Final histological examination of the operative specimen revealed incidental pancreatic adenocarcinoma in 18 out of the 252 patients (7.1%). CONCLUSION: The results of our study demonstrate that pancreatic resections for chronic pancreatitis may nowadays be considered technically feasible and safe. The high incidence of incidental pancreatic adenocarcinoma especially underlines the necessity for an early surgical therapeutic approach for these patients.

Pancreatic parenchymal injection of ethanol and octreotide to induce focal pancreatic fibrosis in rats: Strategies to eliminate postoperative pancreatic fistula.

BACKGROUND: Postoperative pancreatic fistula (POPF) is more likely to occur in a soft pancreas compared to a hard pancreas in which fibrosis has progressed. There is almost no leakage at the anastomosis site or cut surface of a hard pancreas. The aim of this study was to induce localized fibrosis at the cut surface of the pancreas in a rat model. METHODS: Thirty-six rats were divided into three groups (group S: normal saline group; group E: ethanol group; and group O: octreotide group). Each rat was directly injected with a particular compound at the duodenal lobe of the pancreatic parenchyma. Each group was divided into three subgroups according to the time of post-injection sacrifice (1, 2, or 4 weeks). The hardness, suture holding capacity (SHC), and histological fibrosis grade of each pancreas were measured. RESULTS: The hardness, SHC, and fibrosis grade of groups E and O were increased at week 1, with greater increases in group E (all P < 0.001). In a subgroup comparison, the hardness, SHC, and fibrosis grade of group E tended to decrease gradually over time, with no regular pattern evident in group O. A comparison between the injected site (duodenal lobe) and non-injected site (splenic lobe) of the pancreas revealed increases in the three parameters of group E only in the duodenal lobe, with increases in group O at both the duodenal and splenic lobes. CONCLUSIONS: Parenchymal injection of ethanol and octreotide increased pancreatic fibrosis. Unlike octreotide, ethanol provoked localized fibrosis that was maintained over time. It is expected that ethanol injection could eliminate POPF during pancreatic surgery.

Acinar cell density at the pancreatic resection margin is associated with post-pancreatectomy pancreatitis and the development of postoperative pancreatic fistula.

BACKGROUND: There has been recent evidence supporting post-pancreatectomy pancreatitis as a factor in the development of postoperative pancreatic fistula (POPF). The aims of this study were to evaluate: (i) the correlation of the acinar cell density at the pancreatic resection margin with the intra-operative amylase concentration (IOAC) of peri-pancreatic fluid, postoperative pancreatitis, and POPF; and (ii) the association between postoperative pancreatitis on the first postoperative day and POPF. METHODS: Consecutive patients who underwent pancreatic resection between June 2016 and July 2017 were included for analysis. Fluid for IOAC was collected, and amylase concentration was determined in drain fluid on postoperative days 1, 3, and 5. Serum amylase and lipase and urinary trypsinogen-2 concentrations were determined on the first postoperative day. Histology slides of the pancreatic resection margin were scored for acinar cell density. RESULTS: Sixty-one patients were included in the analysis. Acinar cell density significantly correlated with IOAC (r = 0.566, p < 0.001), and was significantly associated with postoperative pancreatitis (p < 0.001), and POPF (p = 0.003). Postoperative pancreatitis was significantly associated with the development of POPF (OR 17.81, 95%CI 2.17-145.9, p = 0.001). DISCUSSION: The development of POPF may involve a complex interaction between acinar cell density, immediate leakage of pancreatic fluid, and postoperative pancreatitis.

Engineered mesenchymal stem-cell-sheets patches prevents postoperative pancreatic leakage in a rat model.

Post-operative pancreatic fistula (POPF) following pancreatic resection is a life-threatening surgical complication. Cell sheets were prepared and harvested using temperature-responsive culture dishes and transplanted as patches to seal POPF. Two different mesenchymal stem cell (MSC) sheets were compared in terms of the preventative ability for pancreatic leakage in a rat model. Both rat adipose-derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus maintained their cell-cell junctions and adhesion proteins with intact fibronectin on the basal side, as well as characteristics of MSCs. The rats with post-pancreatectomy rADSC- or rBMSC-sheet patches had significantly decreased abdominal fluid leakage compared with the control group, demonstrated by MR image analysis and measurement of the volume of abdominal fluid. Amylase level was significantly lower in the rats with rADSC-sheet and rBMSC-sheet patches compared with the control groups. The rADSC sheet patches had increased adhesive and immune-cytokine profiles (ICAM-1, L-selectin, TIMP-1), and the rBMSC sheets had reduced immune reactions compared to the control. This is first project looking at the feasibility of tissue engineering therapy using MSC-sheets as tissue patches preventing leakage of abdominal fluid caused by POPF.