Gastro- or Duodenojejunostomy Leaks After Pancreatoduodenectomy: Single Center Experience and Narrative Literature Review

Background and Methods - Gastro- or duodenojejunostomy leaks after pancreatoduodenectomy is rare. This study aims to analyze the incidence, management, and outcome of gastro- or duodenojejunostomy leaks after pancreatoduodenectomy based on a single center experience from 2004 to 2020 with a narrative literature review. Results - Of a total of 1494 pancreatoduodenectomies, eight patients with gastrojejunostomy (n=1) or duodenojejunostomy (n=7) leak were identified from the institutional pancreatic database. All leaks were treated operatively. In two patients dismantling of the duodenojejunostomy, distal gastrectomy, and closure of the pyloric and jejunal side, a percutaneous endoscopic gastrostomy and a feeding jejunostomy ultimately had to be performed after an unsuccessful attempt of gastrojejunostomy and suture of the duodenojejunostomy, respectively. The literature search revealed three more studies specifically addressing this complication after pancreatoduodenectomy (36 patients of a total of 4739 pancreatoduodenectomies). Based on an analysis of the current study and the literature review, the overall incidence of gastro- or duodenojejunostomy leaks after pancreatoduodenectomy was 0.71 % (44/6233 pancreatoduodenectomies). The occurrence of a gastro- or duodenojejunostomy leak was associated with a concomitant postoperative pancreatic fistula in 50 % of the cases, an increased length of hospital stay, and a mortality rate of 15.9 %. Surgical treatment was performed in 84 % of the cases. Conclusion - Gastro- or duodenojejunostomy leak is a rare complication after pancreatoduodenectomy. Prompt diagnosis and early repair is important. In most cases, a surgical intervention is necessary for a good outcome. Under salvage conditions, a bailout strategy may be to temporarily dismantle the gastro- or duodenojejunal anastomosis

Survival, Complications and Patient Reported Outcomes after Pancreatic Surgery

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Centralizing a national pancreatoduodenectomy service: striking the right balance

Background - Centralization of pancreatic surgery is currently called for owing to superior outcomes in higher‐volume centres. Conversely, organizational and patient concerns speak for a moderation in centralization. Consensus on the optimal balance has not yet been reached. This observational study presents a volume–outcome analysis of a complete national cohort in a health system with long‐standing centralization. Methods - Data for all pancreatoduodenectomies in Norway in 2015 and 2016 were identified through a national quality registry and completed through electronic patient journals. Hospitals were dichotomized (high‐volume (40 or more procedures/year) or medium–low‐volume). Results - Some 394 procedures were performed (201 in high‐volume and 193 in medium–low‐volume units). Major postoperative complications occurred in 125 patients (31·7 per cent). A clinically relevant postoperative pancreatic fistula occurred in 66 patients (16·8 per cent). Some 17 patients (4·3 per cent) died within 90 days, and the failure‐to‐rescue rate was 13·6 per cent (17 of 125 patients). In multivariable comparison with the high‐volume centre, medium–low‐volume units had similar overall complication rates, lower 90‐day mortality (odds ratio 0·24, 95 per cent c.i. 0·07 to 0·82) and no tendency for a higher failure‐to‐rescue rate. Conclusion - Centralization beyond medium volume will probably not improve on 90‐day mortality or failure‐to‐rescue rates after pancreatoduodenectomy

Early detection of anastomotic leakage after pancreatoduodenectomy with microdialysis catheters: an observational Study

Background Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. Methods Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2–4 h thereafter. Results Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P 400 μmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. Conclusion High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559).publishedVersio

Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives

Neoadjuvant therapy improves overall survival compared with a surgery-first approach in patients with borderline resectable pancreatic cancer (BRPC). Evidence of higher quality is required to determine whether neoadjuvant therapy has potential benefits and improves survival for patients with resectable pancreatic cancer (RPC). Most randomized controlled trials (RCTs) have explored short-course neoadjuvant chemotherapy (SNT), but total neoadjuvant chemotherapy (TNT) is now the experimental arm of ongoing RCTs. This article reviews the current status of SNT and TNT in RPC and BRPC, and provides perspectives of future challenges and research directions in this field

Risk factors and preventive strategies for post-operative pancreatic fistula after pancreatic surgery: a comprehensive review

Background: Pancreas surgery has developed into a fairly safe procedure in terms of mortality, but is still hampered by considerable morbidity. Among the most frequent and dreaded complications are the development of a post-operative pancreatic fistula (POPF). The prediction and prevention of POPF remains an area of debate with several questions yet to be firmly addressed with solid answers. Methods: A systematic review of systematic reviews/meta-analyses and randomized trials in the English literature (PubMed/MEDLINE, Cochrane library, EMBASE) covering January 2005 to December 2015 on risk factors and preventive strategies for POPF. Results: A total of 49 systematic reviews and meta-analyses over the past decade discussed patient, surgeon, pancreatic disease and intraoperative related factors of POPF. Non-modifiable factors (age, BMI, comorbidity) and pathology (histotype, gland texture, duct size) that indicates surgery are associated with POPF risk. Consideration of anastomotic technique and use of somatostatin-analogs may slightly modify the risk of fistula. Sealant products appear to have no effect. Perioperative bleeding and transfusion enhance risk, but is modifiable by focus on technique and training. Drains may not prevent fistulae, but may help in early detection. Early drain-amylase may aid in detection. Predictive scores lack uniform validation, but may have a role in patient information if reliable pre-operative risk factors can be obtained. Conclusions: Development of POPF occurs through several demonstrated risk factors. Anastomotic technique and use of somatostatin-analogs may slightly decrease risk. Drains may aid in early detection of leaks, but do not prevent POPF

Nasogastric Tube on Demand is Rarely Necessary After Pancreatoduodenectomy Within an Enhanced Recovery Pathway

Background - Evidence-based guidelines for enhanced recovery (ERAS) pathways after pancreatoduodenectomy (PD) are available. Routine use of nasogatric tube (NGT) after PD is not recommended. This study aims to evaluate the need for NGT reinsertion after PD performed within an ERAS setting. Methods - It is a prospective observational study of all patients undergoing PD in a tertiary referral hospital within the study period from 2015 throughout 2016. Pre- and postoperative variables were collected. Patients requiring NGT reinsertion were identified. Comparative analysis of patients with and without a NGT reinsertion was performed, as well as multivariate analysis for risk factors for on-demand NGT reinsertion. Results - Two-hundred and one patients were included. In total, 45 (22.4%) patients required NGT reinsertion after PD. A total of 32 (15.9%) patients underwent a relaparotomy. Reinsertion of NGT in patients not undergoing a relaparotomy occurred in 26 (15.4%) patients. The presence of a major postoperative complication was a risk factor for reinsertion of NGT, OR 5.27 (2.54–10.94, p = 0.001). Patients with the need for a NGT reinsertion had a higher frequency of major postoperative complications and relaparotomy compared to patients without the need of a NGT reinsertion, 26 (57.8%) versus 32 (20.5%), p p  Conclusion - Routine use of NGT after PD is not justified within an ERAS setting. Immediate removal of the NGT after the procedure can be performed safely, and reinsertion on demand is rarely necessary in uncomplicated courses

Molecular biology in pancreatic ductal adenocarcinoma: implications for future diagnostics and therapy

Background: Novel technology has enabled researchers to better characterize pancreatic cancers at the molecular level. We wanted to explore some of the emerging discoveries, such as molecular subclassification, use of liquid biopsy and use of organoids in cancer assessment. Methods: A literature review with a search specific to the topic, with recent reviews in major journals and a focus on the last 5 years (until December 2018), was done. Results: Pancreatic ductal adenocarcinoma (PDAC) may now be classified into clinical subgroups based on the predominant genomic profiles, but consensus on one classification system is lacking. Several subtypes have been suggested, including categories such as basal-like, stroma-activated, desmoplastic, pure classical and immune classical types. Further refinement may translate into clinically meaningful groups for therapeutic or prognostic purposes. Liquid biopsies (by means of circulating cancer cells, cell-free DNA, exosomes or other constituents of cancer cells in blood) may aid in earlier diagnosis, define prognostic groups and even predict therapy response and resistance. Organoids are increasingly used for the opportunity to investigate druggable and effective targets ex vivo and should facilitate personalized and precise, targeted therapy in the near future. While immunotherapy has not yet proved to be effective, a better understanding of molecular subgroups and specific immune profiles may help identify candidates for this approach in a more selective approach. Conclusion: Novel molecular techniques have the potential to accelerate the road to improved outcomes in patients with pancreatic cancer

Molecular biology in pancreatic ductal adenocarcinoma: implications for future diagnostics and therapy

Background: Novel technology has enabled researchers to better characterize pancreatic cancers at the molecular level. We wanted to explore some of the emerging discoveries, such as molecular subclassification, use of liquid biopsy and use of organoids in cancer assessment. Methods: A literature review with a search specific to the topic, with recent reviews in major journals and a focus on the last 5 years (until December 2018), was done. Results: Pancreatic ductal adenocarcinoma (PDAC) may now be classified into clinical subgroups based on the predominant genomic profiles, but consensus on one classification system is lacking. Several subtypes have been suggested, including categories such as basal-like, stroma-activated, desmoplastic, pure classical and immune classical types. Further refinement may translate into clinically meaningful groups for therapeutic or prognostic purposes. Liquid biopsies (by means of circulating cancer cells, cell-free DNA, exosomes or other constituents of cancer cells in blood) may aid in earlier diagnosis, define prognostic groups and even predict therapy response and resistance. Organoids are increasingly used for the opportunity to investigate druggable and effective targets ex vivo and should facilitate personalized and precise, targeted therapy in the near future. While immunotherapy has not yet proved to be effective, a better understanding of molecular subgroups and specific immune profiles may help identify candidates for this approach in a more selective approach. Conclusion: Novel molecular techniques have the potential to accelerate the road to improved outcomes in patients with pancreatic cancer