Search

Aim: To assess the added value of Near InfraRed Fluorescence (NIRF) imaging during laparoscopic cholecystectomy. Methods: This international multicentre randomized controlled trial included participants with an indication for elective laparoscopic cholecystectomy. Participants were randomised into a NIRF imaging assisted laparoscopic cholecystectomy (NIRF-LC) group and a conventional laparoscopic cholecystectomy (CLC) group. Primary end point was time to ‘Critical View of Safety’ (CVS). The follow-up period of this study was 90 postoperative days. An expert panel analysed the video recordings after surgery to confirm designated surgical time points. Results: A total of 294 patients were included, of which 143 were randomized in the NIRF-LC and 151 in the CLC group. Baseline characteristics were equally distributed. Time to CVS was on average 19 min and 14 s for the NIRF-LC group and 23 min and 9 s for the CLC group (p 0.032). Time to identification of the CD was 6 min and 47 s and 13 min for NIRF-LC and CLC respectively (p < 0.001). Transition of the CD in the gallbladder was identified after an average of 9 min and 39 s with NIRF-LC, compared to 18 min and 7 s with CLC (p < 0.001). No difference in postoperative length of hospital stay nor occurrence of postoperative complications was found. ICG related complications were limited to one patient who developed a rash after injection of ICG. Conclusion: Use of NIRF imaging in laparoscopic cholecystectomy provides earlier identification of relevant extrahepatic biliary anatomy: earlier achievement of CVS, cystic duct visualisation and visualisation of both cystic duct and cystic artery transition into the gallbladder.

Objective Lymph node ratio (LNR, positive lymph nodes/collected lymph nodes during surgery) was identified as an important prognostic factor of survival in resected pancreatic cancer. Several nomograms based on LNR were recently proposed to predict survival after pancreatoduodenectomy (PD). The present study aimed to externally validate 3 published nomograms using an international cohort. Methods Consecutive patients with ductal adenocarcinoma of the pancreatic head who underwent PD without neoadjuvant treatment from 6 tertiary centers in Europe and the USA were retrospectively collected from 2000 to 2017. Patients with metastases at diagnosis, R2 resection, missing data regarding LNR, and who died within 90 postoperative days were excluded. The 3 selected nomograms were the updated Amsterdam nomogram (including LNR, adjuvant therapy, margin status, and tumor grade), the nomogram by Pu et al. (including LNR, age, tumor grade, and T stage) and the nomogram by Li et al. (including LNR, age, tumor location, grade, size, and TNM stage). Overall survivals (OS) were calculated using Kaplan-Meier method. For the validation, calibration (Hosmer-Lemeshow test), discrimination capacity (ROC curves for 3-year OS), and clinical utility (sensitivity and specificity at the value of Youden index) were assessed. Results After exclusion of 95 patients with metastases, R2 resection, and who died within 90 postoperative days, 1167 patients were included. Median OS of the entire cohort was 23 months (95% confidence interval: 21-24). For the 3 nomograms, Kaplan-Meier curves showed significant diminution of OS with increasing scores (p Conclusion The 3 selected nomograms were validated using an external international cohort and displayed interesting and comparable predictive values. Those nomograms may be used in clinical practice to estimate survival after PD for ductal adenocarcinoma.

Background Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. Method An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. Results A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P Conclusion High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

Neoadjuvant systemic treatment is increasingly being integrated in the standard treatment of pancreatic ductal adenocarcinoma (PDAC) patients to improve oncological outcomes. Current available imaging techniques remain unreliable in assessing response to therapies, as they cannot distinguish between (vital) tumor tissue and therapy induced fibrosis (TIF). Consequently, resections with tumor positive margins and subsequent early post-operative recurrences occur and patients eligible for potential radical resection could be missed. To optimize patient selection and monitor results of neoadjuvant treatment, PDAC-specific diagnostic and intraoperative molecular imaging methods are required. This study aims to evaluate molecular imaging targets for PDAC after neoadjuvant FOLFIRINOX treatment. Expression of integrin α

Background Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. Methods This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien–Dindo grade IIIA or higher) and 30‐day or in‐hospital mortality. Results A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non‐CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher‐volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. Conclusion Hospital volume and postoperative outcomes were not associated., This study analysed the association between hospital volume and postoperative outcomes in the nationwide Dutch Hepato Biliary Audit. A total of 5590 resections was performed across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. No association was found between hospital and postoperative outcomes. Cut‐off about right

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.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.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;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.La técnica analgésica óptima tras una duodenopancreatectomía permanece en debate. El objetivo de este estudio fue analizar si la analgesia epidural (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.Se incluyeron tres ensayos aleatorizados y controlados y ocho estudios de cohortes (25.089 pacientes). Las N‐EA 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;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.

Background The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is poor and selection of patients for surgery is challenging. This study examined the impact of a positive resection margin (R1) on locoregional recurrence (LRR) and overall survival (OS); and also aimed to identified tumour characteristics and/or technical factors associated with a positive resection margin in patients with PDAC. Methods Patients scheduled for pancreatic resection for PDAC between 2006 and 2016 were identified from an institutional database. The effect of resection margin status, patient characteristics and tumour characteristics on LRR, distant metastasis and OS was assessed. Results A total of 322 patients underwent pancreatectomy for PDAC. A positive resection (R1) margin was found in 129 patients (40·1 per cent); this was associated with decreased OS compared with that in patients with an R0 margin (median 15 (95 per cent c.i. 13 to 17) versus 22 months; P < 0·001). R1 status was associated with reduced time to LRR (median 16 versus 36 (not estimated, n.e.) months; P = 0·002). Disease recurrence patterns were similar in the R1 and R0 groups. Risk factors for early recurrence were tumour stage, positive lymph nodes (N1) and perineural invasion. Among 100 patients with N0 disease, R1 status was associated with shorter OS compared with R0 resection (median 17 (10 to 24) versus 45 (n.e.) months; P = 0·002), whereas R status was not related to OS in 222 patients with N1 disease (median 14 (12 to 16) versus 17 (15 to 19) months after R1 and R0 resection respectively; P = 0·068). Conclusion Although pancreatic resection with a positive margin was associated with poor survival and early recurrence, particularly in patients with N1 disease, disease recurrence patterns were similar between R1 and R0 groups.

Background Postpancreatectomy haemorrhage (PPH) and venous thromboembolism (VTE) are serious complications following pancreatic surgery. The aim was to assess the timing, occurrence and predictors of PPH and VTE. Methods Elective pancreatic resections undertaken in a single university hospital between November 2013 and September 2017 were assessed. Three intervals were reviewed, each with a different routine regimen of nadroparin: 2850 units once daily (single dose) administered in hospital only, or 5700 units once daily (double dose) or 2850 units twice daily (split dose) administered in hospital and continued for 6 weeks after surgery. Clinically relevant PPH (CR-PPH) was classified according to International Study Group of Pancreatic Surgery criteria. VTE was defined according to a number of key diagnostic criteria within 6 weeks of surgery. Cox regression analyses were performed to test the hypotheses that the double-dose group would experience more PPH than the other two groups, the single-dose group would experience more VTE than the other two groups, and the split-dose group would experience the fewest adverse events (PPH or VTE). Results In total, 240 patients were included, 80 per group. The double-dose group experienced significantly more CR-PPH (hazard ratio (HR) 2·14, 95 per cent c.i. 1·16 to 3·94; P = 0·015). More relaparotomies due to CR-PPH were performed in the double-dose group (16 versus 3·8 per cent; P = 0·002). The single-dose group did not experience more VTE (HR 1·41, 0·43 to 4·62; P = 0·570). The split dose was not associated with fewer adverse events (HR 0·77, 0·41 to 1·46; P = 0·422). Double-dose low molecular weight heparin (LMWH), high BMI and pancreatic fistula were independent predictors of CR-PPH. Conclusion A double dose of LMWH prophylaxis continued for 6 weeks after pancreatic resection was associated with a twofold higher rate of CR-PPH, resulting in four times more relaparotomies. Patients receiving a single daily dose of LMWH in hospital only did not experience a higher rate of VTE.

Paper Abstract Restoring normal functioning and tissue healing after surgical intervention is, among others, critically dependent on tissue oxygenation and perfusion. Tissue necrosis, caused by inadequate tissue perfusion and/or oxygenation, is a common complication after surgical reconstruction of e.g. bowel anastomoses or skin defects. Currently, several optical techniques, which do not require administration of contrast agents, have been used to evaluate tissue perfusion and oxygenation. An emerging technique is hyperspectral imaging, which is capable to detect the scattering and absorption of light delivered to the tissue, caused by inhomogeneity of biological structures, such as haemoglobin, fat or water. Recently, a snapshot hyperspectral camera was developed to measure tissue oxygenation non-invasively using relevant wavelengths in the VIS-NIR region (450-950 nm). In this study, the effect of occlusion-reperfusion of the brachial artery on cutaneous blood oxygenation is explored in three human volunteers as assessed by a snapshot hyperspectral camera system. Furthermore, measurements of local changes in skin oxygenation and blood flow after applying a local vasodilator (capsaicin-based cream) and a local vasoconstrictor (brimonidine gel) are compared to measurements of an untreated area of the skin. Hyperspectral results are correlated to the haemoglobin oxygen saturation measured by an oximeter. Simultaneously with the hyperspectral measurements, real-time blood perfusion mapping is performed using Laser Speckle Contrast Imaging, which is able to measure cutaneous skin blood flow through analysis of the speckle pattern.

For solid tumors, such as breast cancer, surgery is usually the treatment of choice. For these operations, it is of utmost importance to remove the whole tumor, since tumor-positive resection margins may result in recurrent disease and impaired overall survival. Current optical imaging techniques using endogenous contrast - e.g. diffuse reflectance spectroscopy or optical coherence tomography – for detection of breast cancers are limited to point measurements or long acquisition times. Broadband hyperspectral cameras, which provide a complete spectral fingerprint of the object at pixel level, are needed for two-dimensional imaging of the operative region. An ex vivo study was conducted to evaluate the feasibility of hyperspectral imaging for breast cancer detection. Fresh (

The introduction of optical imaging by using near-infrared (NIR) light shines new light in the field of (oncologic) surgery. The use of non-specific fluorophores, such as Indocyanine Green (ICG) and Methylene Blue (MB) have already shown its value for different applications during image-guided surgery. Both ICG and MB are currently the only fluorophores approved by regulatory agencies for off-label use. ICG improves visibility of several solid tumors, sentinel lymph nodes, biliary ducts and can be used to evaluate tissue perfusion. MB could be used for ureter imaging and neuroendocrine or thyroid tumors detection. Recently, a shift to molecular imaging was made by the introduction of new NIR fluorophores (IRDye-800CW, ZW800-1), which could be conjugated to tumor or structure specific targets, such as proteins, antibodies, antibody fragments or nanoparticles. Several clinical trials showed detection of both tumor and metastases in patients with head-and neck, colorectal, pancreatic, ovarian, and renal tumors. Furthermore, nerve and ureter specific agents are (pre-)clinically evaluated, however more research is necessary to make these agents clinically available. Limitations of using NIR fluorescence imaging during surgery are the lack of quantification of fluorescence signals and limited penetration depth. Further optimization of NIR fluorescence imaging and evaluation of the clinical benefit for the patient are necessary steps to make NIR fluorescence guided surgery general applicable into surgical daily practice.

Background Surgery is the cornerstone of treatment for many solid tumours. A wide variety of imaging modalities are available before surgery for staging, although surgeons still rely primarily on visual and haptic cues in the operating environment. Image and molecular guidance might improve the adequacy of resection through enhanced tumour definition and detection of aberrant deposits. Intraoperative modalities available for image- and molecular-guided cancer surgery are reviewed here. Methods Intraoperative cancer detection techniques were identified through a systematic literature search, with selection of peer-reviewed publications from January 2012 to January 2017. Modalities were reviewed, described and compared according to 25 predefined characteristics. To summarize the data in a comparable way, a three-point rating scale was applied to quantitative characteristics. Results The search identified ten image- and molecular-guided surgery techniques, which can be divided into four groups: conventional, optical, nuclear and endogenous reflectance modalities. Conventional techniques are the most well known imaging modalities, but unfortunately have the drawback of a defined resolution and long acquisition time. Optical imaging is a real-time modality; however, the penetration depth is limited. Nuclear modalities have excellent penetration depth, but their intraoperative use is limited by the use of radioactivity. Endogenous reflectance modalities provide high resolution, although with a narrow field of view. Conclusion Each modality has its strengths and weaknesses; no single technique will be suitable for all surgical procedures. Strict selection of modalities per cancer type and surgical requirements is required as well as combining techniques to find the optimal balance.

Background Neoadjuvant chemotherapy for early breast cancer can avoid mastectomy by shrinkage of tumour volume. This review assesses the effectiveness of neoadjuvant chemotherapy on clinical outcome. Methods All randomized trials comparing neoadjuvant and adjuvant chemotherapy for early breast cancer were reviewed systematically and meta-analyses were performed. Results Fourteen studies randomizing 5500 women were eligible for analysis. Overall survival was equivalent in both groups. In the neoadjuvant group, the mastectomy rate was lower (relative risk 0·71 (95 per cent confidence interval (c.i.) 0·67 to 0·75)) without hampering local control (hazard ratio 1·12 (95 per cent c.i. 0·92 to 1·37)). Neoadjuvant chemotherapy was associated fewer adverse effects. Conclusion Neoadjuvant chemotherapy is an established treatment option for early breast cancer.

Background Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer Care, is a platform aiming to harmonize cancer data collection and improve cancer care by feedback. After the prior launch of the projects on colorectal, breast and upper GI cancer, EURECCA's newest project is collecting data on pancreatic cancer in several European countries. Methods National cancer registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between different national registries and will enable data comparison on a larger scale. Additionally, first data was requested from the participating countries. Results Over 24 countries have been approached and 11 confirmed participation: Austria, Belgium, Bulgaria, Denmark, Germany, The Netherlands, Slovenia, Spain, Sweden, Ukraine and United Kingdom. The number of collected data items varied between 16 and 285. This led to a shared items list of 25 variables divided into five categories: patient characteristics, preoperative diagnostics, treatment, staging and survival. Eight countries shared their first data. Conclusions A list of 25 shared items on pancreatic cancer coming from eleven participating registries was created, providing a basis for future prospective data collection in pancreatic cancer treatment internationally.

Neoadjuvant systemic therapy is administered preoperatively in order to provide a better preparation for surgery by down sizing the tumour. A recent meta-analysis comparing neoadjuvant and adjuvant chemotherapy demonstrated a 17% (95% CI: 15.1-18.1) increase in breast-conserving operations with equal survival rates and maintenance of local control providing adequate surgery was performed. Comparable results have been reported with neoadjuvant hormonal therapy. However, in the case of hormonal therapy the tumour-shrinking effects persisted when treatment was sustained. Research has shown that the sentinel lymph node procedure continues to be reliable after neoadjuvant therapy. Therefore, axillary lymph node dissection is not necessary if the lymph node metastases have disappeared as a result of the neoadjuvant therapy: down staging. However, further research is needed to confirm the safety of this treatment approach. Assessment oftumour sensitivity during neoadjuvant therapy facilitates analysis of the prognostic value of tumour markers. The aim of this translational research is to provide better selection criteria to identify patients in which the systemic treatment will be beneficial.