Search

Background Major bile duct injury (BDI) after cholecystectomy generally requires surgical reconstruction by means of hepaticojejunostomy. However, there is controversy regarding the optimal timing of surgical reconstruction. Methods A systematic review was performed by searching PubMed, Embase and Cochrane databases for studies published between 1990 and 2018 reporting on the timing of hepaticojejunostomy for BDI (PROSPERO registration CRD42018106611). The main outcomes were postoperative morbidity, postoperative mortality and anastomotic stricture. When individual patient data were available, time intervals of these studies were attuned to render these comparable with other studies. Data for comparable time intervals were pooled using a random‐effects model. In addition, data for all included studies were pooled using a generalized linear model. Results Some 21 studies were included, representing 2484 patients. In these studies, 15 different time intervals were used. Eight studies used the time intervals of less than 14 days (early), 14 days to 6 weeks (intermediate) and more than 6 weeks (delayed). Meta‐analysis revealed a higher risk of postoperative morbidity in the intermediate interval (early versus intermediate: risk ratio (RR) 0·73, 95 per cent c.i. 0·54 to 0·98; intermediate versus delayed: RR 1·50, 1·16 to 1·93). Stricture rate was lowest in the delayed interval group (intermediate versus delayed: RR 1·53, 1·07 to 2·20). Postoperative mortality did not differ within time intervals. The additional analysis demonstrated increased odds of postoperative morbidity for reconstruction between 2 and 6 weeks, and decreased odds of anastomotic stricture for delayed reconstruction. Conclusion This meta‐analysis found that surgical reconstruction of BDI between 2 and 6 weeks should be avoided as this was associated with higher risk of postoperative morbidity and hepaticojejunostomy stricture., This meta‐analysis addressed the timing of surgical reconstruction with hepaticojejunostomy for bile duct injury. Reconstruction between 2 and 6 weeks after injury was associated with an increased risk of postoperative morbidity as well as anastomotic stricture formation. Both early (less than 2 weeks) and delayed (more than 6 weeks) reconstruction showed lower postoperative morbidity, as well as a lower risk of anastomotic stricture. Avoid repair between 2 and 6 weeks from injury

Background Portal vein embolization (PVE) is performed to reduce the risk of liver failure and subsequent mortality after major liver resection. Although a cut‐off value of 2·7 per cent per min per m2 has been used with hepatobiliary scintigraphy (HBS) for future remnant liver function (FRLF), patients with perihilar cholangiocarcinoma (PHC) potentially benefit from an additional cut‐off of 8·5 per cent/min (not corrected for body surface area). Since January 2016 a more liberal approach to PVE has been adopted, including this additional cut‐off for HBS of 8·5 per cent/min. The aim of this study was to assess the effect of this approach on liver failure and mortality. Methods This was a single‐centre retrospective study in which consecutive patients undergoing liver resection under suspicion of PHC in 2000–2015 were compared with patients treated in 2016–2019, after implementation of the more liberal approach. Primary outcomes were postoperative liver failure (International Study Group of Liver Surgery grade B/C) and 90‐day mortality. Results Some 191 patients with PHC underwent liver resection. PVE was performed in 6·4 per cent (9 of 141) of the patients treated in 2000–2015 and in 32 per cent (16 of 50) of those treated in 2016–2019. The 90‐day mortality rate decreased from 16·3 per cent (23 of 141) to 2 per cent (1 of 50) (P = 0·009), together with a decrease in the rate of liver failure from 19·9 per cent (28 of 141) to 4 per cent (2 of 50) (P = 0·008). In 2016–2019, 24 patients had a FRLF greater than 8·5 per cent/min and no liver failure or death occurred, suggesting that 8·5 per cent/min is a reliable cut‐off for patients with suspected PHC. Conclusion The major decrease in liver failure and mortality rates in recent years and the simultaneous increased use of PVE suggests an important role for PVE in reducing adverse outcomes after surgery for PHC., The use of portal vein embolization (PVE) in patients undergoing major liver resection for perihilar cholangiocarcinoma at the authors' centre increased from 6·4 per cent in 2000–2015 to 32 per cent in 2016–2019. This increased use of PVE coincided with a major decrease in the postoperative liver failure rate, from 19·9 to 4 per cent, and a decrease in the 90‐day mortality rate, from 16·3 to 2 per cent. Using hepatobiliary scintigraphy, an additional cut‐off for future remnant liver function of 8·5 per cent/min (not corrected for body surface area) correlated with safe liver resection in patients with suspected perihilar cholangiocarcinoma. Portal vein embolization decreases rates of liver failure and mortality

Background: Drain use in pancreatic surgery remains controversial. This survey sought to evaluate habits, experiences, and opinions of experts in the field on the use of drains to provide interesting insights for pancreatic surgeons worldwide. Methods: An online survey designed via Google Forms was sent in December 2020 to experienced surgeons of the International Study Group for Pancreatic Surgery. Results: Forty-two surgeons (42/63, 67%) completed the survey. During their career, 74% (31/42) performed personally >500 pancreatic resections; of these, 9 (21%) >1,500. Sixty-nine percent of the respondents (29/42) declared to always use drains during pancreatic resections and 17% (7/42) in >50% of the operations. For these participants, the use of drains does not increase but reduces the risk of pancreatic fistula and other complications, and more importantly, helps to detect them earlier and manage them better. By contrast, 2 surgeons (5%) declared to never apply drains, whereas other 4 (10%) use drains only in selective cases, deeming that drains increase the risk of infection and other complications. When applied, drains are managed very heterogeneously as for the type of drains, enzyme testing, and removal schedules. Four participants declared to practice continuous irrigation. Twenty-two surgeons (55%) remove drains routinely within the third postoperative day, other 11 (27.5%) only in selected cases, whereas 7 (17.5%) normally keep drains longer. Conclusion: Despite plenty of publications on this topic, drain management in pancreatic surgery remains very heterogeneous. Safety and the surgeon´s personal experience seem to play a determining role.

Item does not contain fulltext BACKGROUND: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC. METHODS: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval. RESULTS: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP. CONCLUSION: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.

Central pancreatectomy is a parenchyma-sparing alternative to distal pancreatectomy in patients with a benign or low-grade malignant tumor in the body of the pancreas. The aim of central pancreatectomy is to prevent postoperative life-long endocrine and exocrine insufficiency. The downside of central pancreatectomy is the high rate of postoperative pancreatic fistula, which is the main reason that many surgeons do not routinely use central pancreatectomy in eligible patients. Most studies report open or laparoscopic central pancreatectomy with a pancreatico-gastrostomy anastomosis in adults. This is the first description of a standardized approach to robotic central pancreatectomy with Roux-en-Y pancreaticojejunostomy reconstruction in an adolescent (16-year-old boy) with a pseudopapillary tumor in the body of the pancreas. The operation time was 248 min with 20 mL of blood loss. The postoperative course was uneventful except for the short-term medical treatment for a grade B pancreatic fistula. Robotic central pancreatectomy can be safely applied in selected patients in experienced centers.

Background: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking. Methods: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3. Results: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98). Conclusion: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms.

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)., Postoperative pancreatic fistula (POPF) remain a major concern in patients after distal pancreatectomy. Although stump closure with a fibrin sealant patch has shown promising results, in this multicenter, patient-blinded randomized controlled trial, patch application did not reduce the incidence of POPF.

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 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 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 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. (C) 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Item does not contain fulltext BACKGROUND: The aim of this study is to collect the best available evidence for diagnostic modalities, frequency, and duration of surveillance after resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: PDAC guidelines published after 2015 were collected. Furthermore, a systematic search of the literature on postoperative surveillance was performed in PubMed and Embase from 2000 to 2019. Articles comparing different diagnostic modalities and frequencies of postoperative surveillance in PDAC patients with regard to survival, quality of life, morbidity and cost-effectiveness were selected. RESULTS: The literature search resulted in 570 articles. A total of seven guidelines and twelve original clinical studies were eventually evaluated. PDAC guidelines increasingly recommend a combination of tumor marker testing and computed tomography (CT) imaging every three to six months during the first two years after resection. These guidelines are, however, based on expert opinion and other low-level evidence. Prospective studies comparing different surveillance strategies are lacking. According to recent studies, surveillance with tumor markers and imaging at regular intervals results in the detection of PDAC recurrence before the onset of symptoms and more frequent administration of further therapy, such as chemotherapy or radiotherapy. CONCLUSION: Current evidence for recurrence-focused surveillance after PDAC resection is limited and contradictory. Consequently, recommendations on surveillance are conflicting. To define the clinical merit of recurrence-focused surveillance, patients who are most likely to benefit from early detection and treatment of PDAC recurrence need to be identified. To this purpose, well-designed prospective studies are needed, accounting for both economical and psychosocial implications of surveillance.

Achieving an R0-resection is a prerequisite for long-term survival in pancreatic cancer. Preoperative therapy may downstage locally advanced and borderline pancreatic cancer and thereby increase the chance of an R0 resection. Promising results of this approach have been reported, with survival rates of 30–34 months following chemotherapy and subsequent resection. Recently, two randomized trials in patients with borderline resectable pancreatic cancer have reported promising outcomes of preoperative chemoradiotherapy. For locally advanced pancreatic cancer randomized trials are thus far lacking.

Background Surgical factors, including resection of Gerota’s fascia, R0-resection, and lymph node yield, may be associated with survival after distal pancreatectomy (DP) for pancreatic ductal adenocarcinoma (PDAC), but evidence from large multicenter studies is lacking. This study aimed to identify predictors for overall survival after DP for PDAC, especially those related to surgical technique. Patients and Methods Data from an international retrospective cohort including patients from 11 European countries and the USA who underwent DP for PDAC (2007–2015) were analyzed. Cox proportional hazard analyses were performed and included Gerota’s fascia resection, R0 resection, lymph node ratio, extended resection, and a minimally invasive approach. Results Overall, 1200 patients from 34 centers with median follow-up of 15 months [interquartile range (IQR) 5–31 months] and median survival period of 30 months [95% confidence interval (CI), 27–33 months] were included. Gerota’s fascia resection [hazard ratio (HR) 0.74; p = 0.019], R0 resection (HR 0.70; p = 0.006), and decreased lymph node ratio (HR 0.28; p p p = 0.350). Adjuvant chemotherapy (HR 0.67; p = 0.003) was also associated with improved overall survival. Conclusions This international cohort identified Gerota’s fascia resection, R0 resection, and decreased lymph node ratio as factors associated with improved overall survival during DP for PDAC. Surgeons should strive for R0 resection and adequate lymphadenectomy and could also consider Gerota’s fascia resection in their routine surgical approach.

Background Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26–34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. Methods The “Pancreatic Locally Advanced Unresectable Cancer Ablation” (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. Discussion The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. Trial registration Dutch Trial RegistryNL4997. Registered on December 29, 2015. ClinicalTrials.govNCT03690323. Retrospectively registered on October 1, 2018

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 αvβ6, carcinoembryonic antigen cell adhesion molecule 5 (CEACAM5), mesothelin, prostate-specific membrane antigen (PSMA), urokinase-type plasminogen activator receptor, fibroblast activating receptor, integrin α5 subunit and epidermal growth factor receptor was evaluated using immunohistochemistry. Immunoreactivity was determined using the semiquantitative H-score. Resection specimens from patients after neoadjuvant FOLFIRINOX treatment containing PDAC (n = 32), tumor associated pancreatitis (TAP) and TIF (n = 15), normal pancreas parenchyma (NPP) (n = 32) and tumor positive (n = 24) and negative (n = 56) lymph nodes were included. Integrin αvβ6, CEACAM5, mesothelin and PSMA stainings showed significantly higher expression in PDAC compared to TAP and NPP. No expression of αvβ6, CEACAM5 and mesothelin was observed in TIF. Integrin αvβ6 and CEACAM5 allow for accurate metastatic lymph node detection. Targeting integrin αvβ6, CEA, mesothelin and PSMA has the potential to distinguish vital PDAC from fibrotic tissue after neoadjuvant FOLFIRINOX treatment. Integrin αvβ6 and CEACAM5 detect primary tumors and tumor positive lymph nodes.

Background Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

Pancreatic parenchyma sparing surgery for insulinomas avoids the risk of endocrine and exocrine insufficiency, and potential high-risk anastomoses associated with pancreatic resection. Robotic surgery may be used as an alternative for open pancreatic enucleation without compromising dexterity and 3D-vision. We present the case of a 42-year old woman who presented with sweating, tremor and episodes of hypoglycemia. A fasting test confirmed endogenic insulin overproduction. After inconclusive CT- and MRI imaging, endoscopic ultrasonography showed a hypoechoic lesion, which was fully within the pancreatic head. Although consent was obtained for pancreatoduodenectomy, robotic enucleation seemed feasible. After mobilization, intraoperative ultrasonography was used to identify the lesion and its relation with the pancreatic duct. Dissection was performed using a traction suture, hot shears and bipolar diathermia. A sealant patch was applied for hemostasis and a drain placed. The patient developed a grade B pancreatic fistula for which endoscopic sphincterotomy was performed; the surgical drain could be removed in the outpatient clinic after 20 days. Prospective studies should confirm the short- and long-term benefits of robotic enucleation of insulinomas.

Aim: Perihilar cholangiocarcinoma (PHC) is a challenging disease and requires aggressive surgical treatment in order to achieve curation. The assessment and work-up of patients with presumed PHC is multidisciplinary, complex and requires extensive experience. The aim of this paper is to review current aspects of diagnosis, preoperative work-up and extended resection in patients with PHC from the perspective of our own institutional experience with this complex tumor. Methods: We provided a review of applied modalities in the diagnosis and work-up of PHC according to current literature. All patients with presumed PHC in our center between 2000 and 2016 were identified and described. The types of resection, surgical techniques and outcomes were analyzed. Results and conclusion: Upcoming diagnostic modalities such as Spyglass and combinations of serum biomarkers and molecular markers have potential to decrease the rate of misdiagnosis of benign, inflammatory disease. Assessment of liver function with hepatobiliary scintigraphy provides better information on the future remnant liver (FRL) than volume alone. The selective use of staging laparoscopy is advisable to avoid futile laparotomies. In patients requiring extended resection, selective preoperative biliary drainage is mandatory in cholangitis and when FRL is small (< 50%). Preoperative portal vein embolization (PVE) is used when FRL volume is less than 40% and optionally includes the left portal vein branches to segment 4. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as alternative to PVE is not recommended in PHC. N2 positive lymph nodes preclude long-term survival. The benefit of unconditional en bloc resection of the portal vein bifurcation is uncertain. Along these lines, an aggressive surgical approach encompassing extended liver resection including segment 1, regional lymphadenectomy and conditional portal venous resection translates into favorable long-term survival.

Hepatic vascular inflow occlusion (VIO) can be applied during resection of colorectal liver metastases (CRLM) to control intra-operative blood loss, but has been linked to accelerated growth of micrometastases in experimental models. This study aimed to investigate the effects of hepatic VIO on disease-free and overall survival (DFS and OS) in patients following resection for CRLM. All patients who underwent liver resection for CRLM between January 2006 and September 2015 at our center were analyzed. Hepatic VIO was performed if deemed indicated by the operating surgeon and severe ischemia was defined as ≥20 min continuous or ≥45 min cumulative intermittent VIO. Cox regression analysis was performed to identify predictive factors for DFS and OS. A total of 208 patients underwent liver resection for CRLM. VIO was performed in 64 procedures (31%), and fulfilled the definition of severe ischemia in 40 patients. Patients with severe ischemia had inferior DFS (5-year DFS 32% vs. 11%, P < 0.01), and inferior OS (5-year OS 37% vs. 64%, P < 0.01). At multivariate analysis, a high clinical risk score (Hazard ratio (HR) 1.60 (1.08-2.36)) and severe ischemia (HR 1.89 (1.21-2.97)) were independent predictors of worse DFS. Severe ischemia was not an independent predictor of OS. The present cohort study suggests that prolonged hepatic VIO during liver resection for CRLM was associated with reduced DFS. A patient-tailored approach seems advisable although larger studies should confirm these findings

Minimally invasive surgery (MIS) is quickly becoming mainstream in hepato-pancreato-biliary surgery because of presumed advantages. Surgery for perihilar cholangiocarcinoma (PHC) is highly demanding which may hamper the feasibility and safety of MIS in this setting. This study aimed to systematically review the existing literature on MIS for PHC. A systematic literature review was performed according to the PRISMA statement. The PubMed and EMBASE databases were searched and all studies describing MIS in patients with PHC were included. Data extraction and risk of bias were assessed by two independent researchers. Overall, 21 studies reporting on a total of 142 MIS procedures for PHC were included. These included 82 laparoscopic, 59 robot-assisted and 1 hybrid procedure(s). Risk of bias was deemed substantial. Pooled conversion rate was 7/142 (4.9%), pooled morbidity 30/126 (23.8%), and pooled mortality rate 4/126 (3.2%). The only comparative study, comparing 10 robot-assisted procedures to 32 open procedures, reported a significant increased operative time and higher morbidity rate with MIS. The available evidence on MIS for PHC is limited and generally of poor quality. This systematic review shows that the implementation of MIS for patients with PHC is still in its infancy.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit.