Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer.

BACKGROUND: As more therapeutic options for pancreatic cancer are becoming available, there is a need to improve outcome prediction to support shared decision-making. A systematic evaluation of prediction models in resectable pancreatic cancer is lacking. METHODS: This systematic review followed the CHARMS and PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched up to 11 October 2017. Studies reporting development or validation of models predicting survival in resectable pancreatic cancer were included. Models without performance measures, reviews, abstracts or more than 10 per cent of patients not undergoing resection in postoperative models were excluded. Studies were appraised critically. RESULTS: After screening 4403 studies, 22 (44 319 patients) were included. There were 19 model development/update studies and three validation studies, altogether concerning 21 individual models. Two studies were deemed at low risk of bias. Eight models were developed for the preoperative setting and 13 for the postoperative setting. Most frequently included parameters were differentiation grade (11 of 21 models), nodal status (8 of 21) and serum albumin (7 of 21). Treatment-related variables were included in three models. The C-statistic/area under the curve values ranged from 0·57 to 0·90. Based on study design, validation methods and the availability of web-based calculators, two models were identified as the most promising. CONCLUSION: Although a large number of prediction models for resectable pancreatic cancer have been reported, most are at high risk of bias and have not been validated externally. This overview of prognostic factors provided practical recommendations that could help in designing easily applicable prediction models to support shared decision-making.

The role of abdominal drainage in pancreatic resection - A multicenter validation study for early drain removal.

BACKGROUND: Abdominal drainage and the timing of drain removal in patients undergoing pancreatic resection are under debate. Early drain removal after pancreatic resection has been reported to be safe with a low risk for clinical relevant postoperative pancreatic fistula (CR-POPF) when drain amylase on POD1 is < 5000U/L. The aim of this study was to validate this algorithm in a large national cohort. METHODS: Patients registered in the Dutch Pancreatic Cancer Audit (2014-2016) who underwent pancreatoduodenectomy, distal pancreatectomy or enucleation were analysed. Data on post-operative drain amylase levels, drain removal, postoperative pancreatic fistulae were collected. Univariate and multivariate analysis using a logistic regression model were performed. The primary outcome measure was grade B/C pancreatic fistula (CR-POPF). RESULTS: Among 1402 included patients, 433 patients with a drain fluid amylase level of <5000U/L on POD1, 7% developed a CR-POPF. For patients with an amylase level >5000U/L the CR-POPF rate was 28%. When using a cut-off point of 2000U/L or 1000U/L during POD1-3, the CR-POPF rates were 6% and 5% respectively. For patients with an amylase level of >2000U/L and >1000UL during POD 1-3 the CR-POPF rates were 26% and 22% respectively (n = 223). Drain removal on POD4 or thereafter was associated with more complications (p = 0.004). Drain amylase level was shown to be the most statistically significant predicting factor for CR-POPF (Wald = 49.7; p < 0.001). CONCLUSION: Our data support early drain removal after pancreatic resection. However, a cut-off of 5000U/L drain amylase on POD1 was associated with a relatively high CR-POPF rate of 7%. A cut-off point of 1000U/L during POD1-3 resulted in 5% CR-POPF and might be a safer alternative.

Randomized clinical trial and meta-analysis of the impact of a fibrin sealant patch on pancreatic fistula after distal pancreatectomy: CPR trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the main cause of morbidity in patients after distal pancreatectomy. The objective of this study was to investigate whether an absorbable fibrin sealant patch could prevent POPF after distal pancreatectomy. METHODS: A multicentre, patient-blinded, parallel-group randomized superiority trial was performed in seven Dutch hospitals. Allocation was done using a computer-generated randomization list with a 1 : 1 allocation ratio and concealed varying permuted block sizes. Pancreatic stump closure with a fibrin patch was compared with standard treatment in patients undergoing distal pancreatectomy. The primary endpoint was the development of grade B/C POPF. A systematic review and meta-analysis was performed which combined the present findings with all available evidence. RESULTS: Between October 2010 and August 2017, 247 patients were enrolled. Fifty-four patients (22.2 per cent) developed a POPF, 25 of 125 patients in the patch group versus 29 of 122 in the control group (20.0 versus 23.8 per cent; P = 0·539). No related adverse effects were observed. In the meta-analysis, no significant difference was seen between the patch and control groups (19.7 versus 22.0 per cent; odds ratio 0.89, 95 per cent c.i. 0.60 to 1.32; P = 0·556). CONCLUSION: Application of a fibrin patch to the pancreatic stump does not reduce the incidence of POPF in distal pancreatectomy. Future studies should focus on alternative fistula mitigation strategies, considering pancreatic neck thickness and duct size as risk factors. Trial registration number NL5876 (Netherlands Trial Registry).

Meta-analysis of epidural analgesia in patients undergoing pancreatoduodenectomy.

Background: The optimal analgesic technique after pancreatoduodenectomy remains under debate. This study aimed to see whether epidural analgesia (EA) has superior clinical outcomes compared with non-epidural alternatives (N-EA) in patients undergoing pancreatoduodenectomy. Methods: A systematic review with meta-analysis was performed according to PRISMA guidelines. On 28 August 2018, relevant literature databases were searched. Primary outcomes were pain scores. Secondary outcomes were treatment failure of initial analgesia, complications, duration of hospital stay and mortality. Results: Three RCTs and eight cohort studies (25 089 patients) were included. N-EA treatments studied were: intravenous morphine, continuous wound infiltration, bilateral paravertebral thoracic catheters and intrathecal morphine. Patients receiving EA had a marginally lower pain score on days 0-3 after surgery than those receiving intravenous morphine (mean difference (MD) -0·50, 95 per cent c.i. -0·80 to -0·21; P < 0·001) and similar pain scores to patients who had continuous wound infiltration. Treatment failure occurred in 28·5 per cent of patients receiving EA, mainly for haemodynamic instability or inadequate pain control. EA was associated with fewer complications (odds ratio (OR) 0·69, 95 per cent c.i. 0·06 to 0·79; P < 0·001), shorter duration of hospital stay (MD -2·69 (95 per cent c.i. -2·76 to -2·62) days; P < 0·001) and lower mortality (OR 0·69, 0·51 to 0 93; P = 0·02) compared with intravenous morphine. Conclusion: EA provides marginally lower pain scores in the first postoperative days than intravenous morphine, and appears to be associated with fewer complications, shorter duration of hospital stay and less mortality.

Antecedentes: La técnica analgésica óptima tras una duodenopancreatectomía permanece en debate. El objetivo de este estudio fue analizar si la analgesia epidural (epidural analgesia, EA) presenta resultados clínicos superiores en comparación con las alternativas no epidurales (non­epidural alternatives, N­EA) en pacientes que se someten a una duodenopancreatectomía. Métodos: Se realizó una revisión sistemática con metaanálisis de acuerdo con las recomendaciones PRISMA. El 28 de agosto de 2018, se realizó una búsqueda en las bases de datos relevantes de la literatura. El objetivo primario fueron las puntuaciones de dolor. Los objetivos secundarios fueron el fracaso del tratamiento de la analgesia inicial, las complicaciones, la duración de la estancia hospitalaria y la mortalidad. Resultados: Se incluyeron tres ensayos aleatorizados y controlados y ocho estudios de cohortes (25.089 pacientes). Las N­EA estudiadas fueron: morfina intravenosa (iv), infiltración continua de la herida, catéteres torácicos paravertebrales bilaterales y morfina intratecal. Los pacientes con EA tuvieron una puntuación de dolor marginalmente más baja en los días postoperatorios 0 a 3 en comparación con la morfina iv (diferencia de medias (MD) = ­ 0,50, i.c. del 95% ­0,80 a ­0,21; P < 0,001) y puntuaciones de dolor similares en comparación con la infiltración continua de la herida. El fallo del tratamiento ocurrió en el 28,5% de los pacientes con EA, principalmente por inestabilidad hemodinámica o control inadecuado del dolor. La EA se asoció con menos complicaciones (razón de oportunidades, odds ratio, OR = 0,69, i.c. del 95% 0,061 a 0,79; P < 0,001), menor duración de la estancia hospitalaria (MD = ­2,69 días, i.c. del 95% ­2,76 a ­2,62; P < 0,001) y menor mortalidad en comparación con la morfina iv (OR = 0,69, i.c. del 95% 0,51 a 0,93; P = 0,01). Conclusión: La EA proporciona puntuaciones de dolor ligeramente más bajas en los primeros días postoperatorios en comparación con la morfina iv y parece asociarse con menos complicaciones, menor duración de la estancia hospitalaria y menor mortalidad.

[Placement of nasoenteral feeding tubes by nurses]. / Plaatsing van naso-enterale voedingssondes door verpleegkundigen.

Electromagnetic-guided placement of nasoenteral feeding tubes by nurses is an alternative to endoscopic placement by gastroenterologists. During placement, the electromagnetic signal that is emitted by the tip of the guidewire enables visualisation of the position of the tube on a portable monitor. The procedure can be performed by a trained endoscopy nurse at the bedside of the patient. This could have logistic advantages, as the patient transport is not necessary and confirmation of the position of the tube by an abdominal X-ray is not required. Other possible advantages of the new technique are no preprocedural fasting and no need for sedation. If the tube coils in the stomach, it can be repositioned without the need for a repeat procedure. A randomised multicentre trial found electromagnetic nasoenteral placement of feeding tubes to be non-inferior on comparison with endoscopic placement by gastroenterologists, and it can be considered as the preferred technique.

FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre Cohort Study.

Introduction: FOLFIRINOX is emerging as new standard of care for fit patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to high toxicity rates reported in earlier studies. We reviewed our experience with FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy. Methods: We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our institution between April 2011 and December 2015. Unresectability (stage III and IV) was determined by the institution's multidisciplinary team for pancreatic cancer. Results: Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was given as first-line treatment in 82% of patients. Dose modifications were applied in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade 3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was 25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC, respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and 5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative therapy and 1 patient (6%) a resection, leading to a median survival of 21.8 months. Conclusion: FOLFIRINOX treatment with nearly routine dose modification was associated with acceptable toxicity rates, relatively high response rates and an encouraging overall survival.