Impact of shifting from laparoscopic to robotic surgery during 600 minimally invasive pancreatic and liver resections.

BACKGROUND: Many centers worldwide are shifting from laparoscopic to robotic minimally invasive hepato-pancreato-biliary resections (MIS-HPB) but large single center series assessing this process are lacking. We hypothesized that the introduction of robot-assisted surgery was safe and feasible in a high-volume center. METHODS: Single center, post-hoc assessment of prospectively collected data including all consecutive MIS-HPB resections (January 2010-February 2022). As of December 2018, all MIS pancreatoduodenectomy and liver resections were robot-assisted. All surgeons had participated in dedicated training programs for laparoscopic and robotic MIS-HPB. Primary outcomes were in-hospital/30-day mortality and Clavien-Dindo ≥ 3 complications. RESULTS: Among 1875 pancreatic and liver resections, 600 (32%) were MIS-HPB resections. The overall rate of conversion was 4.3%, Clavien-Dindo ≥ 3 complications 25.7%, and in-hospital/30-day mortality 1.8% (n = 11). When comparing the period before and after the introduction of robotic MIS-HPB (Dec 2018), the overall use of MIS-HPB increased from 25.3 to 43.8% (P < 0.001) and blood loss decreased from 250 ml [IQR 100-500] to 150 ml [IQR 50-300] (P < 0.001). The 291 MIS pancreatic resections included 163 MIS pancreatoduodenectomies (52 laparoscopic, 111 robotic) with 4.3% conversion rate. The implementation of robotic pancreatoduodenectomy was associated with reduced operation time (450 vs 361 min; P < 0.001), reduced blood loss (350 vs 200 ml; P < 0.001), and a decreased rate of delayed gastric emptying (28.8% vs 9.9%; P = 0.009). The 309 MIS liver resections included 198 laparoscopic and 111 robotic procedures with a 3.6% conversion rate. The implementation of robotic liver resection was associated with less overall complications (24.7% vs 10.8%; P = 0.003) and shorter hospital stay (4 vs 3 days; P < 0.001). CONCLUSION: The introduction of robotic surgery was associated with greater implementation of MIS-HPB in up to nearly half of all pancreatic and liver resections. Although mortality and major morbidity were not affected, robotic surgery was associated with improvements in some selected outcomes. Ultimately, randomized studies and high-quality registries should determine its added value.

Quantitative analysis of contribution of mild and moderate hyperthermia to thermal ablation and sensitization of irreversible electroporation of pancreatic cancer cells.

INTRODUCTION: Irreversible electroporation (IRE) is an ablation modality that applies short, high-voltage electric pulses to unresectable cancers. Although considered a non-thermal technique, temperatures do increase during IRE. This temperature rise sensitizes tumor cells for electroporation as well as inducing partial direct thermal ablation. AIM: To evaluate the extent to which mild and moderate hyperthermia enhance electroporation effects, and to establish and validate in a pilot study cell viability models (CVM) as function of both electroporation parameters and temperature in a relevant pancreatic cancer cell line. METHODS: Several IRE-protocols were applied at different well-controlled temperature levels (37 °C ≤ T ≤ 46 °C) to evaluate temperature dependent cell viability at enhanced temperatures in comparison to cell viability at T = 37 °C. A realistic sigmoid CVM function was used based on thermal damage probability with Arrhenius Equation and cumulative equivalent minutes at 43 °C (CEM43°C) as arguments, and fitted to the experimental data using "Non-linear-least-squares"-analysis. RESULTS: Mild (40 °C) and moderate (46 °C) hyperthermic temperatures boosted cell ablation with up to 30% and 95%, respectively, mainly around the IRE threshold Eth,50% electric-field strength that results in 50% cell viability. The CVM was successfully fitted to the experimental data. CONCLUSION: Both mild- and moderate hyperthermia significantly boost the electroporation effect at electric-field strengths neighboring Eth,50%. Inclusion of temperature in the newly developed CVM correctly predicted both temperature-dependent cell viability and thermal ablation for pancreatic cancer cells exposed to a relevant range of electric-field strengths/pulse parameters and mild moderate hyperthermic temperatures.

Extended Resections for Advanced Gallbladder Cancer: Results from a Nationwide Cohort Study.

BACKGROUND: Extended resections (i.e., major hepatectomy and/or pancreatoduodenectomy) are rarely performed for gallbladder cancer (GBC) because outcomes remain inconclusive. Data regarding extended resections from Western centers are sparse. This Dutch, multicenter cohort study analyzed the outcomes of patients who underwent extended resections for locally advanced GBC. METHODS: Patients with GBC who underwent extended resection with curative intent between January 2000 and September 2018 were identified from the Netherlands Cancer Registry. Extended resection was defined as a major hepatectomy (resection of ≥ 3 liver segments), a pancreatoduodenectomy, or both. Treatment and survival data were obtained. Postoperative morbidity, mortality, survival, and characteristics of short- and long-term survivors were assessed. RESULTS: The study included 33 patients. For 16 of the patients, R0 resection margins were achieved. Major postoperative complications (Clavien Dindo ≥ 3A) occurred for 19 patients, and 4 patients experienced postoperative mortality within 90 days. Recurrence occurred for 24 patients. The median overall survival (OS) was 12.8 months (95% confidence interval, 6.5-19.0 months). A 2-year survival period was achieved for 10 patients (30%) and a 5-year survival period for 5 patients (15%). Common bile duct, liver, perineural and perivascular invasion and jaundice were associated with reduced survival. All three recurrence-free patients had R0 resection margins and no liver invasion. CONCLUSION: The median OS after extended resections for advanced GBC was 12.8 months in this cohort. Although postoperative morbidity and mortality were significant, long-term survival (≥ 2 years) was achieved in a subset of patients. Therefore, GBC requiring major surgery does not preclude long-term survival, and a subgroup of patients benefit from surgery.

Safe, selective histopathological examination of gallbladder specimens: a systematic review.

BACKGROUND: Routine histopathological examination after cholecystectomy is costly, but the prevalence of unsuspected gallbladder cancer (incidental GBC) is low. This study determined whether selective histopathological examination is safe. METHODS: A comprehensive search of PubMed, Embase, Web of Science and the Cochrane Library was performed. Pooled incidences of incidental and truly incidental GBC (GBC detected during histopathological examination without preoperative or intraoperative suspicion) were estimated using a random-effects model. The clinical consequences of truly incidental GBC were assessed. RESULTS: Seventy-three studies (232 155 patients) were included. In low-incidence countries, the pooled incidence was 0·32 (95 per cent c.i. 0·25 to 0·42) per cent for incidental GBC and 0·18 (0·10 to 0·35) per cent for truly incidental GBC. Subgroup analysis of studies in which surgeons systematically examined the gallbladder revealed a pooled incidence of 0·04 (0·01 to 0·14) per cent. In high-incidence countries, corresponding pooled incidences were 0·83 (0·58 to 1·18), 0·44 (0·21 to 0·91) and 0·08 (0·02 to 0·39) per cent respectively. Clinical consequences were reported for 176 (39·3 per cent) of 448 patients with truly incidental GBC. Thirty-three patients (18·8 per cent) underwent secondary surgery. Subgroup analysis showed that at least half of GBC not detected during the surgeon's systematic examination of the gallbladder was early stage (T1a status or below) and of no clinical consequence. CONCLUSION: Selective histopathological examination of the gallbladder after initial macroscopic assessment by the surgeon seems safe and could reduce costs.

ANTECEDENTES: El examen histopatológico rutinario después de la colecistectomía es caro y la prevalencia de cáncer de vesícula biliar (gallbladder cancer, GBC) no sospechado o incidental es baja. Este estudio determinó si el examen histológico selectivo es seguro. MÉTODOS: Se realizó una búsqueda exhaustiva en PubMed, Embase, Web of Science y en la Biblioteca Cochrane. Se estimaron las incidencias agrupadas de GBC incidental y realmente incidental (GBC detectado durante el examen histopatológico sin sospecha previa o intraoperatoria) utilizando un modelo de efectos aleatorios. Además, se evaluaron las consecuencias clínicas del GBC realmente incidental. RESULTADOS: Se incluyeron 73 estudios (n = 232.155). En los países de baja incidencia, la incidencia agrupada fue de 0,32% para el GBC incidental (i.c. del 95% 0,25 a 0,42) y de 0,18% (0,10 a 0,35) para GBC realmente incidental. El análisis de subgrupos que incluye estudios en los que los cirujanos examinaron sistemáticamente la vesícula biliar reveló una incidencia agrupada de 0,04% (0,01 a 0,14). En los países de alta incidencia, las incidencias agrupadas correspondientes fueron 0,83% (0,58 a 1,18), 0,44% (0.2 a 0.91) y 0,08% (0,02 a 0,39), respectivamente. Se describieron consecuencias clínicas en 176 (39,3%) de 448 pacientes con GBC realmente incidental. Treinta y tres pacientes (18,6%) se sometieron a cirugía secundaria. El análisis por subgrupos mostró que al menos la mitad de los GBC no detectados durante el examen sistemático de la vesícula biliar por parte del cirujano eran tumores de estadio precoz (≤ T1a) y sin consecuencias clínicas. CONCLUSIÓN: El examen histológico selectivo de vesículas biliares después de la evaluación macroscópica inicial realizada por el cirujano parece seguro y podría reducir los costes.

Effect of preoperative biliary drainage on cholestasis-associated inflammatory and fibrotic gene signatures in perihilar cholangiocarcinoma.

Preoperative biliary drainage (PBD) is used routinely in the evaluation of patients with potentially resectable perihilar cholangiocarcinoma to relieve cholestasis and improve the liver's resilience to surgery. Little preclinical or translatational data are, however, currently available to guide the use of PBD in this patient group. The effect of PBD on hepatic gene expression profiles was therefore studied by microarray analysis. Drainage affects inflammatory and fibrotic gene signatures.

Safety and efficacy of transarterial embolization of hepatocellular adenomas.

BACKGROUND: Hepatocellular adenoma (HCA) larger than 5 cm in diameter has an increased risk of haemorrhage and malignant transformation, and is considered an indication for resection. As an alternative to resection, transarterial embolization (TAE) may play a role in prevention of complications of HCA, but its safety and efficacy are largely unknown. The aim of this study was to assess outcomes and postembolization effects of selective TAE in the management of HCA. METHODS: This retrospective, multicentre cohort study included patients aged at least 18 years, diagnosed with HCA and treated with TAE. Patient characteristics, 30-day complications, tumour size before and after TAE, symptoms before and after TAE, and need for secondary interventions were analysed. RESULTS: Overall, 59 patients with a median age of 33.5 years were included from six centres; 57 of the 59 patients were women. Median tumour size at time of TAE was 76 mm. Six of 59 patients (10 per cent) had a major complication (cyst formation or sepsis), which could be resolved with minimal therapy, but prolonged hospital stay. Thirty-four patients (58 per cent) were symptomatic at presentation. There were no significant differences in symptoms before TAE and symptoms evaluated in the short term (within 3 months) after TAE (P = 0·134). First follow-up imaging was performed a median of 5·5 months after TAE and showed a reduction in size to a median of 48 mm (P < 0·001). CONCLUSION: TAE is safe, can lead to adequate size reduction of HCA and, offers an alternative to resection in selected patients.

Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial.

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.

ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.

Comparison between dynamic gadoxetate-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT for quantitative assessment of liver function.

OBJECTIVES: To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. METHODS: Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. RESULTS: A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p < 0.001 respectively). There was a strong agreement between the functional share determined with both modalities (ICC = 0.944, 95% CI 0.863-0.978, n = 20). There was a significant negative correlation between liver aminotransferases and bilirubin for both MUR and Ki. CONCLUSIONS: Assessment of liver function with DHCE-MRI is comparable with that of 99mTc-mebrofenin HBS and has the potential to be combined with diagnostic MRI imaging. This can therefore provide a one-stop-shop modality for the preoperative assessment of patients undergoing liver surgery. KEY POINTS: • Quantitative assessment of liver function using hepatobiliary scintigraphy is performed in the preoperative assessment of patients undergoing liver surgery in order to prevent posthepatectomy liver failure. • Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) is an emerging method to quantify liver function and can serve as a potential alternative to hepatobiliary scintigraphy. • Assessment of liver function with dynamic gadoxetate-enhanced MRI is comparable with that of hepatobiliary scintigraphy and has the potential to be combined with diagnostic MRI imaging.

Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin.

BACKGROUND: Biliary tract cancer (BTC) is an uncommon cancer with an unfavorable prognosis. Since 2010, the standard of care for patients with unresectable BTC is palliative treatment with gemcitabine plus cisplatin, based on the landmark phase III ABC-02 trial. This current study aims to evaluate the efficacy and safety of gemcitabine and cisplatin in patients with unresectable cholangiocarcinoma and gallbladder cancer in daily practice that meet the criteria for the ABC-02 trial in comparison to patients who did not. METHODS: Patients diagnosed with unresectable BTC between 2010 and 2015 with an indication for gemcitabine and cisplatin were included. We divided these patients into three groups: (I) patients who received chemotherapy and met the criteria of the ABC-02 trial, (II) patients who received chemotherapy and did not meet these criteria and (III) patients who had an indication for chemotherapy, but received best supportive care without chemotherapy. Primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS). RESULTS: We collected data of 208 patients, of which 138 (66.3%) patients received first line chemotherapy with gemcitabine and cisplatin. Median OS of 69 patients in group I, 63 patients in group II and 65 patients in group III was 9.6 months (95%CI = 6.7-12.5), 9.5 months (95%CI = 7.7-11.3) and 7.6 months (95%CI = 5.0-10.2), respectively. Median PFS was 6.0 months (95%CI = 4.4-7.6) in group I and 5.1 months (95%CI = 3.7-6.5) in group II. Toxicity and number of dose reductions (p = .974) were comparable between the two chemotherapy groups. CONCLUSION: First-line gemcitabine and cisplatin is an effective and safe treatment for patients with unresectable BTC who do not meet the eligibility criteria for the ABC-02 trial. Median OS, PFS and treatment side effects were comparable between the patients who received chemotherapy (group I vs. group II).

Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC experience.

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.

Systematic review of transarterial embolization for hepatocellular adenomas.

BACKGROUND: Hepatocellular adenoma (HCA) larger than 5 cm in diameter is considered an indication for elective surgery, because of the risk of haemorrhage and malignant transformation. Transarterial embolization (TAE) is used to manage bleeding HCA and occasionally to reduce tumour size. TAE might have potential as an elective therapy, but its current role in this context is uncertain. This systematic review provides an overview of clinical outcomes after TAE, in bleeding and non-bleeding HCA. METHODS: Two independent reviewers performed a systematic search of literature in PubMed and Embase. Outcomes were change in tumour size, avoidance of surgery, complications and malignant transformation after TAE in bleeding and non-bleeding HCA. The Critical Appraisal Skills Programme tool for cohort studies was used for quality assessment of included studies. RESULTS: From 320 potential articles, 20 cohort studies and 20 case reports including 851 patients met the inclusion criteria. TAE was performed in 151 of 851 patients (17·7 per cent), involving 196 tumours, of which 95 (48·5 per cent) were non-bleeding. Surgical treatment was avoided in 68 of 151 patients (45·0 per cent). Elective TAE was performed in 49 patients involving 66 HCAs, with 41 of these patients (84 per cent) not requiring surgery. Major complications occurred in eight of 151 patients (5·3 per cent); no death was reported. Among cohort studies, complete tumour disappearance was observed in 10 per cent of patients, and regression in 75 per cent. CONCLUSION: Acute or elective TAE in the management of HCA is safe. In the elective setting, TAE provides a potential alternative to surgery.

Effect of obeticholic acid on liver regeneration following portal vein embolization in an experimental model.

BACKGROUND: The bile salt-activated transcription factor farnesoid X receptor (FXR) is a key mediator of proliferative bile salt signalling, which is assumed to play a role in the early phase of compensatory liver growth. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic acid, OCA) on liver growth following portal vein embolization (PVE). METHODS: Rabbits were allocated to receive daily oral gavage with OCA (10 mg/kg) or vehicle (control group) starting 7 days before PVE (n = 18 per group), and continued until 7 days after PVE. PVE of the cranial liver lobes was performed using polyvinyl alcohol particles and coils on day 0. Caudal liver volume (CLV) was analysed by CT volumetry on days -7, -1, +3 and +7. Liver function was determined by measuring mebrofenin uptake using hepatobiliary scintigraphy. Additional parameters analysed were plasma aminotransferase levels, and histological scoring of haematoxylin and eosin- and Ki-67-stained liver sections. RESULTS: Three days after PVE of the cranial lobes, the increase in CLV was 2·2-fold greater in the OCA group than in controls (mean(s.d.) 56·1(20·3) versus 26·1(15·4) per cent respectively; P < 0·001). This increase remained greater 7 days after PVE (+1·5-fold; P = 0·020). The increase in caudal liver function at day +3 was greater in OCA-treated animals (+1·2-fold; P = 0·017). The number of Ki-67-positive hepatocytes was 1·6-fold higher in OCA-treated animals 3 days after PVE (P = 0·045). Plasma aminotransferase levels and histology did not differ significantly between groups. CONCLUSION: OCA accelerated liver regeneration after PVE in a rabbit model. OCA treatment might increase the efficacy of PVE and, thereby, resectability. Surgical relevance Liver failure is the most feared complication after liver surgery, with no effective treatment options. Liver regeneration is essential to avoid liver failure, and recently bile acid signalling was implicated in the initiation of liver regeneration through the nuclear bile acid receptor farnesoid X receptor (FXR). In this study, the potent FXR agonist obeticholic acid accelerated liver regeneration following portal vein embolization in a rabbit model, in terms of liver volume, liver function and proliferation. Obeticholic acid treatment could enhance the efficacy of portal vein embolization, thereby increasing resectability, and could reduce the interval to surgery. In addition, obeticholic acid might have a place in the prevention of liver failure after liver surgery.

Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer.

INTRODUCTION: In pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk. METHODS: A prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT's plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed. RESULTS: 53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients' characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%. CONCLUSIONS: For PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated. TRIAL REGISTRATION NUMBER: Dutch Trial Registry (NTR3142).

Systematic review of outcomes after distal pancreatectomy with coeliac axis resection for locally advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer involving the coeliac axis is considered unresectable by most guidelines, with a median survival of 6-11 months. A subgroup of these patients can undergo distal pancreatectomy with coeliac axis resection, but consensus on the value of this procedure is lacking. The evidence for this procedure, including the impact of preoperative hepatic artery embolization and (neo)adjuvant therapy, was evaluated. METHODS: A systematic review was performed according to the PRISMA guidelines until 27 May 2015. The primary endpoint was overall survival; secondary endpoints included morbidity and radical resection rates. RESULTS: A total of 19 retrospective studies, involving 240 patients, were included. The methodological quality of the studies ranged from poor to moderate. A radical resection was reported in 74·5 per cent (152 of 204), major morbidity in 27 per cent (26 of 96), ischaemic morbidity in 9·0 per cent (21 of 223) and 90-day mortality in 3·5 per cent (4 of 113). Overall, 35·5 per cent of patients (55 of 155) underwent preoperative hepatic artery embolization without an apparent beneficial impact on ischaemic morbidity. Overall, 15·7 per cent (29 of 185) had neoadjuvant and 51·0 per cent (75 of 147) had adjuvant therapy. There was a difference in survival between patient series where less than half of patients had (neo)adjuvant chemotherapy and series where more than half were receiving this treatment: case-weighted median overall survival was 16 (range 9-48) versus 18 (10-26) months respectively (P = 0·002). Overall median survival for the whole study population was 14·4 (range 9-48) months. CONCLUSION: Distal pancreatectomy with coeliac axis resection seems a valuable option for selected patients with pancreatic cancer involving the coeliac axis with acceptable morbidity and mortality, and a median survival of 18 months when combined with (neo)adjuvant therapy.

Use of an absorbable embolization material for reversible portal vein embolization in an experimental model.

BACKGROUND: Portal vein embolization (PVE) is used to increase future remnant liver size in patients requiring major hepatic resection. PVE using permanent embolization, however, predisposes to complications and excludes the use of PVE in living donor liver transplantation. In the present study, an absorbable embolization material containing fibrin glue and different concentrations of the fibrinolysis inhibitor aprotinin was used in an experimental animal model. METHODS: PVE of the cranial liver lobes was performed in 30 New Zealand White rabbits, which were divided into five groups, fibrin glue + 1000, 700, 500, 300 or 150 kunits/ml aprotinin, and were compared with a previous series of permanent embolization using the same experimental set-up. Caudal liver lobe hypertrophy was determined by CT volumetry, and portal recanalization was identified on contrast-enhanced CT images. Animals were killed after 7 or 42 days, and the results were compared with those of permanent embolization. RESULTS: PVE using fibrin glue with aprotinin as embolic material was effective, with 500 kunits/ml providing the optimal hypertrophic response. Lower concentrations of aprotinin (150 and 300 kunits/ml) led to reduced hypertrophy owing to early recanalization of the embolized segments. The regeneration rate over the first 3 days was higher in the group with 500 kunits/ml aprotinin than in the groups with 300 or 150 kunits/ml or permanent embolization. In the 500-kunits/ml group, four of five animals showed recanalization 42 days after embolization, with minimal histological changes in the cranial lobes following recanalization. CONCLUSION: Fibrin glue combined with 500 kunits/ml aprotinin resulted in reversible PVE in 80 per cent of animals, with a hypertrophy response comparable to that achieved with permanent embolization material. Surgical relevance Portal vein embolization (PVE) is used to increase future remnant liver volume in patients scheduled for major liver resection who have insufficient future remnant liver size to perform a safe resection. The current standard is PVE with permanent embolization materials, which renders patients found to have unresectable disease prone to complications owing to the permanently deportalized liver segments. Absorbable embolization might prevent the PVE-associated morbidity and lower the threshold for its application. In this study, PVE using fibrin glue and aprotinin resulted in an adequate hypertrophy response with 80 per cent recanalization after 42 days. Considering the minor histological changes following recanalization of embolized segments and potentially preserved function, reversible PVE might also be applied in living donor liver transplantation.

Survival after resection of perihilar cholangiocarcinoma-development and external validation of a prognostic nomogram.

BACKGROUND: The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS: A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS: For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS: The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.

Gastric emptying and quality of life after pancreatoduodenectomy with retrocolic or antecolic gastroenteric anastomosis.

BACKGROUND: Delayed gastric emptying (DGE) is a major problem after pancreatoduodenectomy (PD). A recent multicentre randomized trial reported no difference in gastric emptying rates between retrocolic and antecolic reconstruction routes. The present study looked at quality of life with these two approaches and the correlation with gastric emptying. METHODS: This was a substudy of patients completing a panel of quality-of-life questionnaires within a randomized trial comparing retrocolic and antecolic gastroenteric reconstruction after PD. Gastric emptying was assessed by scintigraphy 1 week after surgery. Quality of life was measured with the EuroQoL - 5D questionnaire (EQ-5D), the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) with its pancreatic cancer module (PAN26), and the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: There were 38 patients in the retrocolic and 35 in the antecolic group. Baseline characteristics and clinical outcomes were similar in the two groups. Median time to half-emptying of stomach content after surgery was 145 and 64 min in the retrocolic and antecolic group respectively (P = 0.189). Median percentages of residual activity after 2 h were 64 and 28 per cent respectively (P = 0.213). Quality of life did not differ at any time point between the groups. At 2 weeks after surgery, patients with DGE had significantly worse outcomes on two EQ-5D domains, ten QLQ-C30/PAN26 subscales, and two GIQLI subscales and total score. Effect sizes were moderate to large. CONCLUSION: The route of gastroenteric reconstruction after PD does not influence either gastric emptying at scintigraphy or quality of life. The impact of DGE on quality of life is clinically significant. Registration number NTR1697 (www.trialregister.nl).

Impact of lymph node ratio on survival in patients with pancreatic and periampullary cancer.

BACKGROUND: According to some studies, the number of lymph nodes with metastases in relation to the total number of removed lymph nodes, the lymph node ratio (LNR), is one of the most powerful predictors of survival after resection in patients with pancreatic cancer. However, contradictory results have been reported, and small sample sizes of the cohorts and different definitions of a microscopic positive resection margin (R1) hamper the interpretation of data. METHODS: The predictive value of LNR for 3-year survival was assessed using a Cox proportional hazards model. From 1992 to 2012, all patients with pancreatic and periampullary cancer operated on with pancreatoduodenectomy were selected from a database. Clinicopathological characteristics were analysed. Microscopic positive resection margin was defined as the microscopic presence of tumour cells within 1 mm of the margins. A nomogram was created. RESULTS: Some 760 patients were included. Predictive factors for death in 350 patients with pancreatic ductal adenocarcinoma included in the nomogram were: R1 resection (hazard ratio (HR) 1·55, 95 per cent c.i. 1·07 to 2·25), poor tumour differentiation (HR 2·78, 1·40 to 5·52), LNR above 0·18 (HR 1·75, 1·13 to 2·70) and no adjuvant therapy (HR 1·54, 1·01 to 2·34). The C statistic was 0·658 (0·632 to 0·698), and calibration was good (Hosmer-Lemeshow χ(2) = 5·67, P =0·773). LNR and poor tumour differentiation (HR 4·51 and 3·30 respectively) were also predictive in patients with distal common bile duct (CBD) cancer. LNR, R1 resection and jaundice were predictors of death in patients with ampullary cancer (HR 7·82, 2·68 and 1·93 respectively). CONCLUSION: LNR is a common predictor of poor survival in pancreatic, distal CBD and ampullary cancer.

Risk factors for bleeding in hepatocellular adenoma.

BACKGROUND: Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding, although the risk of bleeding is ill-defined. The aim of this study was to assess risk factors for bleeding in patients diagnosed with HCA. METHODS: Patients with HCA were included prospectively from January 2008 to July 2012. Patient characteristics were noted. Patients underwent dynamic magnetic resonance imaging (MRI) and/or computed tomography (CT) at presentation and during follow-up. Lesion characteristics on (follow-up) imaging were noted, and bleeding was graded as intratumoral (grade I), intrahepatic (grade II) or extrahepatic (grade III). The standard of reference for diagnosis was histopathology, or dynamic MRI and/or CT findings. Possible risk factors were included if mentioned in literature (lesion size, body mass index), or based on clinical experience (lesion location, visible vessels on imaging). RESULTS: A total of 45 patients (median age 39 (range 22-60) years; 44 women) with 195 lesions (median size 24 (10-250) mm) were evaluated. Bleeding occurred in 29 patients (64 per cent) and in 42 lesions (21.5 per cent) with a median size of 62 (10-160) mm. Size was a risk factor for bleeding (P < 0.001), with an increased number of bleeding events in lesions of 35 mm or more. Exophytic lesions (protruding from liver) had more bleeding (16 of 24, 67 per cent) than intrahepatic (9 of 82, 11 per cent) or subcapsular (17 of 89, 19 per cent) lesions (P < 0.001). Lesions in segments II and III had more bleeds than those in the right liver (11 of 32 versus 31 of 163; P = 0.049), as did lesions in which peripheral or central arteries were visualized on imaging (10 of 13 versus 32 of 182 lesions with no visible vascularization; P < 0.001). CONCLUSION: Risk factors for bleeding of HCA include diameter of 35 mm or more, visualization of lesional arteries, location in the left lateral liver, and exophytic growth.