Background
Surgical resection is currently the only treatment with the potential for long‐term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for ...cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on other organs, laparoscopic surgery has been shown to reduce complications and length of hospital stay as compared with open surgery. However, concerns remain about the safety of laparoscopic distal pancreatectomy compared with open distal pancreatectomy in terms of postoperative complications and oncological clearance.
Objectives
To assess the benefits and harms of laparoscopic distal pancreatectomy versus open distal pancreatectomy for people undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma of the body or tail of the pancreas, or both.
Search methods
We used search strategies to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and trials registers until June 2015 to identify randomised controlled trials (RCTs) and non‐randomised studies. We also searched the reference lists of included trials to identify additional studies.
Selection criteria
We considered for inclusion in the review RCTs and non‐randomised studies comparing laparoscopic versus open distal pancreatectomy in patients with resectable pancreatic cancer, irrespective of language, blinding or publication status..
Data collection and analysis
Two review authors independently identified trials and independently extracted data. We calculated odds ratios (ORs), mean differences (MDs) or hazard ratios (HRs) along with 95% confidence intervals (CIs) using both fixed‐effect and random‐effects models with RevMan 5 on the basis of intention‐to‐treat analysis when possible.
Main results
We found no RCTs on this topic. We included in this review 12 non‐randomised studies that compared laparoscopic versus open distal pancreatectomy (1576 participants: 394 underwent laparoscopic distal pancreatectomy and 1182 underwent open distal pancreatectomy); 11 studies (1506 participants: 353 undergoing laparoscopic distal pancreatectomy and 1153 undergoing open distal pancreatectomy) provided information for one or more outcomes. All of these studies were retrospective cohort‐like studies or case‐control studies. Most were at unclear or high risk of bias, and the overall quality of evidence was very low for all reported outcomes.
Differences in short‐term mortality (laparoscopic group: 1/329 (adjusted proportion based on meta‐analysis estimate: 0.5%) vs open group: 11/1122 (1%); OR 0.48, 95% CI 0.11 to 2.17; 1451 participants; nine studies; I2 = 0%), long‐term mortality (HR 0.96, 95% CI 0.82 to 1.12; 277 participants; three studies; I2 = 0%), proportion of people with serious adverse events (laparoscopic group: 7/89 (adjusted proportion: 8.8%) vs open group: 6/117 (5.1%); OR 1.79, 95% CI 0.53 to 6.06; 206 participants; three studies; I2 = 0%), proportion of people with a clinically significant pancreatic fistula (laparoscopic group: 9/109 (adjusted proportion: 7.7%) vs open group: 9/137 (6.6%); OR 1.19, 95% CI 0.47 to 3.02; 246 participants; four studies; I2 = 61%) were imprecise. Differences in recurrence at maximal follow‐up (laparoscopic group: 37/81 (adjusted proportion based on meta‐analysis estimate: 36.3%) vs open group: 59/103 (49.5%); OR 0.58, 95% CI 0.32 to 1.05; 184 participants; two studies; I2 = 13%), adverse events of any severity (laparoscopic group: 33/109 (adjusted proportion: 31.7%) vs open group: 45/137 (32.8%); OR 0.95, 95% CI 0.54 to 1.66; 246 participants; four studies; I2 = 18%) and proportion of participants with positive resection margins (laparoscopic group: 49/333 (adjusted proportion based on meta‐analysis estimate: 14.3%) vs open group: 208/1133 (18.4%); OR 0.74, 95% CI 0.49 to 1.10; 1466 participants; 10 studies; I2 = 6%) were also imprecise. Mean length of hospital stay was shorter by 2.43 days in the laparoscopic group than in the open group (MD ‐2.43 days, 95% CI ‐3.13 to ‐1.73; 1068 participants; five studies; I2 = 0%). None of the included studies reported quality of life at any point in time, recurrence within six months, time to return to normal activity and time to return to work or blood transfusion requirements.
Authors' conclusions
Currently, no randomised controlled trials have compared laparoscopic distal pancreatectomy versus open distal pancreatectomy for patients with pancreatic cancers. In observational studies, laparoscopic distal pancreatectomy has been associated with shorter hospital stay as compared with open distal pancreatectomy. Currently, no information is available to determine a causal association in the differences between laparoscopic versus open distal pancreatectomy. Observed differences may be a result of confounding due to laparoscopic operation on less extensive cancer and open surgery on more extensive cancer. In addition, differences in length of hospital stay are relevant only if laparoscopic and open surgery procedures are equivalent oncologically. This information is not available currently. Thus, randomised controlled trials are needed to compare laparoscopic distal pancreatectomy versus open distal pancreatectomy with at least two to three years of follow‐up. Such studies should include patient‐oriented outcomes such as short‐term mortality and long‐term mortality (at least two to three years); health‐related quality of life; complications and the sequelae of complications; resection margins; measures of earlier postoperative recovery such as length of hospital stay, time to return to normal activity and time to return to work (in those who are employed); and recurrence of cancer.
Publishing protocols of randomized controlled trials (RCT) facilitates a more detailed description of study rational, design, and related ethical and safety issues, which should promote transparency. ...Little is known about how the practice of publishing protocols developed over time. Therefore, this study describes the worldwide trends in volume and methodological quality of published RCT protocols.
A systematic search was performed in PubMed and EMBASE, identifying RCT protocols published over a decade from 1 September 2001. Data were extracted on quality characteristics of RCT protocols. The primary outcome, methodological quality, was assessed by individual methodological characteristics (adequate generation of allocation, concealment of allocation and intention-to-treat analysis). A comparison was made by publication period (First, September 2001- December 2004; Second, January 2005-May 2008; Third, June 2008-September 2011), geographical region and medical specialty.
The number of published RCT protocols increased from 69 in the first, to 390 in the third period (p<0.0001). Internal medicine and paediatrics were the most common specialty topics. Whereas most published RCT protocols in the first period originated from North America (n = 30, 44%), in the second and third period this was Europe (respectively, n = 65, 47% and n = 190, 48%, p = 0.02). Quality of RCT protocols was higher in Europe and Australasia, compared to North America (OR = 0.63, CI = 0.40-0.99, p = 0.04). Adequate generation of allocation improved with time (44%, 58%, 67%, p = 0.001), as did concealment of allocation (38%, 53%, 55%, p = 0.03). Surgical protocols had the highest quality among the three specialty topics used in this study (OR = 1.94, CI = 1.09-3.45, p = 0.02).
Publishing RCT protocols has become popular, with a five-fold increase in the past decade. The quality of published RCT protocols also improved, although variation between geographical regions and across medical specialties was seen. This emphasizes the importance of international standards of comprehensive training in RCT methodology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but ...convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis. Methods In this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation APACHE II score ≥8, Imrie score ≥3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications—ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites—during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949. Findings One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1·06, 95% CI 0·75–1·51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2·53, 95% CI 1·22–5·25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0·004). Interpretation In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Irreversible electroporation (IRE) uses short duration, high-voltage electrical pulses to induce cell death via nanoscale defects resulting from altered transmembrane potential. The technique is ...gaining interest for ablations in unresectable pancreatic and hepatobiliary cancer. Metal stents are often used for palliative biliary drainage in these patients, but are currently seen as an absolute contraindication for IRE due to the perceived risk of direct heating of the metal and its surroundings. This study investigates the thermal and tissue viability changes due to a metal stent during IRE.
IRE was performed in a homogeneous tissue model (polyacrylamide gel), without and with a metal stent placed perpendicular and parallel to the electrodes, delivering 90 and 270 pulses (15-35 A, 90 μsec, 1.5 cm active tip exposure, 1.5 cm interelectrode distance, 1000-1500 V/cm, 90 pulses/min), and in-vivo in a porcine liver (4 ablations). Temperature changes were measured with an infrared thermal camera and with fiber-optic probes. Tissue viability after in-vivo IRE was investigated macroscopically using 5-triphenyltetrazolium chloride (TTC) vitality staining.
In the gel, direct stent-heating was not observed. Contrarily, the presence of a stent between the electrodes caused a higher increase in median temperature near the electrodes (23.2 vs 13.3°C 90 pulses; p = 0.021, and 33.1 vs 24.8°C 270 pulses; p = 0.242). In-vivo, no temperature difference was observed for ablations with and without a stent. Tissue examination showed white coagulation 1mm around the electrodes only. A rim of vital tissue remained around the stent, whereas ablation without stent resulted in complete tissue avitality.
IRE in the vicinity of a metal stent does not cause notable direct heating of the metal, but results in higher temperatures around the electrodes and remnant viable tissue. Future studies should determine for which clinical indications IRE in the presence of metal stents is safe and effective.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Volume–outcome relationships in pancreatic surgery are well established, but an optimal volume remains to be determined. Studies analyzing outcomes in volume categories exceeding ...20 procedures annually are lacking. Study design A consecutive 3420 patients underwent PD for primary pancreatic or periampullary carcinoma (2005–2013) and were registered in the Netherlands Cancer Registry. Relationships between hospital volume (<5, 5–19, 20–39 and ≥40 PDs/year) and mortality and survival were explored. Results There was a non-significant decrease in 90-day mortality from 8.1 to 6.7% during the study period (p = 0.23). Ninety-day mortality was 9.7% in centers performing <5 PDs/year (n = 185 patients), 8.9% for 5–19 PDs/year (n = 1432), 7.3% for 20–39 PDs/year (n = 240) and 4.3% for ≥40 PDs/year (n = 562, p = 0.004). Within volume categories, 90-day mortality did not change over time. After adjustment for confounding factors, significantly lower mortality was found in the ≥40 category compared to 20–39 PDs/year (OR = 1.72 (1.08–2.74)). Overall survival adjusted for confounding factors was better in the ≥40 category compared to categories under 20 PDs/year: HR (≥40 vs 5–19/year) = 1.24 (1.09–1.42). In the ≥40 category significantly more patients received adjuvant chemotherapy and had >10 lymph nodes retrieved compared to lower volume categories. Conclusions Volume–outcome relationships in pancreatic surgery persist in centers performing ≥40 PDs annually, regarding both mortality and survival. The volume plateau for pancreatic surgery has yet to be determined.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose To (a) investigate the safety of percutaneous irreversible electroporation (IRE) for locally advanced pancreatic cancer and (b) evaluate the quality of life (QOL), pain perception, and ...efficacy in terms of time to local progression, event-free survival, and overall survival (OS). Materials and Methods The study was approved by the local review board (NL42888.029.13). All patients provided written informed consent for study participation, the ablation procedure, and data usage. Between January 2014 and June 2015, 25 patients with histologically proved locally advanced pancreatic cancer 5 cm or smaller (13 women, 12 men; median age, 61 years; age range, 41-78 years) were prospectively included to undergo percutaneous computed tomographic-guided IRE. Patients with a metallic biliary Wallstent, epilepsy, or ventricular arrhythmias were excluded. Kaplan-Meier estimates were used to investigate time to local progression, event-free survival, and OS. Safety was assessed on the basis of adverse events, which were graded according to the Common Terminology Criteria for Adverse Events. Pain perception and QOL were evaluated by using specific questionnaires. Results All patients underwent IRE. The median largest tumor diameter was 4.0 cm (range, 3.3-5.0 cm). After a median follow-up of 12 months (interquartile range: 7-16 months), median event-free survival after IRE was 8 months (95% confidence interval CI: 4 months, 12 months); the median time to local progression after IRE was 12 months (95% CI: 8 months, 16 months). The median OS was 11 months from IRE (95% CI: 9 months, 13 months) and 17 months from diagnosis (95% CI: 10 months, 24 months). There were 12 minor complications (grade I or II) and 11 major complications (nine grade III, two grade IV) in 10 patients. There were no deaths within 90 days after IRE. Conclusion Percutaneous IRE for locally advanced pancreatic cancer is generally well tolerated, although major adverse events can occur. Preliminary survival data are encouraging and support the setup of larger phase II and III clinical trials to assess the efficacy of IRE plus chemotherapy in the neoadjuvant and adjuvant or second-line setting compared with more widely adopted regimens such as chemotherapy and/or radiation therapy.
RSNA, 2016 Online supplemental material is available for this article.
Abstract Background The introduction of minimally invasive pancreatic resection (MIPR) into surgical practice has been slow. The worldwide utilization of MIPR and attitude towards future perspectives ...of MIPR remains unknown. Methods An anonymous survey on MIPR was sent to the members of six international associations of Hepato-Pancreato-Biliary (HPB) surgery. Results The survey was completed by 435 surgeons from 50 countries, with each surgeon performing a median of 22 (IQR 12–40) pancreatic resections annually. Minimally invasive distal pancreatectomy (MIDP) was performed by 345 (79%) surgeons and minimally invasive pancreatoduodenectomy (MIPD) by 124 (29%). The median total personal experience was 20 (IQR 10–50) MIDPs and 12 (IQR 4–40) MIPDs. Current superiority for MIDP was claimed by 304 (70%) and for MIPD by 44 (10%) surgeons. The most frequently mentioned reason for not performing MIDP (54/90 (60%)) and MIPD (193/311 (62%)) was lack of specific training. Most surgeons (394/435 (90%)) would consider participating in an international registry on MIPR. Discussion This worldwide survey showed that most participating HPB surgeons value MIPR as a useful development, especially for MIDP, but the role and implementation of MIPD requires further assessment. Most HPB surgeons would welcome specific training in MIPR and the establishment of an international registry.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is ...crucial for clinical implementation.
To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls.
Prospective.
15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age-/sex-matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC.
3-T, spin-echo echo-planar-imaging, turbo spin-echo, and fast field echo gradient-echo.
Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal-to-noise ratio (SNR) was compared between all regimens. MRE repeatability (test-retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions-of-interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability.
Repeated measures analysis of variance, coefficients of variation (CoVs), Bland-Altman analysis, (un)paired t-test, Mann-Whitney U-test, and Wilcoxon signed-rank test. P-value<0.05 was considered statistically significant.
Preparation regimens did not significantly influence MRE-SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy-nontumor (P = 0.094).
The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue-tumor and tumor-nontumor.
2 TECHNICAL EFFICACY STAGE: 2.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment ...option but the current literature does not provide the surgical community with evidence based advice.
The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs.
The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients.
Netherlands Trial Register (NTR): NTR2666.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Series from expert centers suggest that pancreas cancer surgery is safe for elderly patients but nationwide data, taking hospital volume into account, are lacking.
Methods
From the ...Netherlands Cancer Registry, all 3420 patients who underwent pancreatoduodenectomy (PD) for primary pancreatic or periampullary carcinoma in 2005–2013 were selected. Associations between age (<75, ≥75 years), hospital volume (tertiles), and postoperative mortality (30, 90 day) were evaluated by
χ
2
tests and logistic regression analyses. Overall survival was investigated by means of Kaplan–Meier and Cox proportional hazard regression analyses.
Results
The proportion of elderly patients (≥75 years) undergoing PD increased from 15 % in 2005–2007 to 20 % in 2011–2013 (
p
= 0.009). In low (<15 per year), medium (15–28 per year), and high (>28 per year) hospital volume tertiles, the proportion of elderly patients was 16, 20, and 17 %, respectively (
p
= 0.10). With increasing hospital volume, 30-day postoperative mortality was 6.0–4.5–2.9 % (
p
= 0.002) and 90-day mortality 9.3–8.0–5.3 % (
p
= 0.001), respectively. Within each volume tertile, adjusted 30- and 90-day mortality of elderly patients was 1.6–2.5 times higher compared to outcomes of younger patients. Adjusted 30-day mortality in elderly patients was higher in low-volume hospitals (odds ratio = 2.87, 95 % confidence interval 1.15–7.17) compared to high-volume hospitals. Similarly, elderly patients had a worse overall survival in low-volume hospitals (hazard ratio = 1.28, 95 % confidence interval 1.01–1.63). Postoperative mortality of elderly patients in high-volume hospitals was similar to mortality of younger patients in low- and medium-volume hospitals.
Conclusions
Elderly patients benefit from centralization by undergoing PD in high-volume hospitals, both with respect to postoperative mortality and survival. It would seem reasonable to place elderly patients into a high-risk category; they should only undergo surgery in the highest-tertile-volume hospitals.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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