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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. [ABSTRACT FROM AUTHOR]

Introduction: Cryoablation (CA) has been broadly used mostly in the treatment of small renal masses (SRMs). The present review aims to define the current role of CA in the treatment of SRMs by assessing clinical indications and outcomes.Method: A comprehensive review on patient selection, procedural details, perioperative complications, and short/long-term oncological and functional outcomes was conducted. For each section, a take-home message was formulated with level of evidence (LoE) according to Cochrane collaboration.Results: Age and comorbidity drive the choice of ablation in SRMs, although hospital setting also influences the decision. Technically in adequate CA or first post-CA control occurs in 3-5% of laparoscopic cryoablation (LCA) or percutaneous cryoablation (PCA) series. Meta-analysis does not evidence differences in the rate of residual tumor per person-year between the approaches (0.033 LCA vs. 0.046 PCA, p = 0.25). Perioperative complications (8-25%) are erratically reported. LCA has significantly lower likelihood of complications than minimally invasive partial nephrectomy (MIPN). Systematic reviews indicate 30-month local tumor progression rate of 8.5% for LCA in renal cell carcinoma but low metastatic progression (1-4.4%). Few LCA long-term follow-up series (mean/media 48-98 months) report recurrence-free survival (RFS) and cancer-specific survival (CSS) ranges of 80-100%. For PCA, Kaplan-Meier local disease-free survival (DFS) of 95.6% at 3-5 years [32] and 5-year overall survival and local RFS of 86.3% were reported. The decrease in renal function after CA is minimal, and the only risk factor associated is the basal estimated glomerular filtration rate (eGFR).Conclusion: LoE 3a/b confirms lower CA perioperative complication rate and higher local progression rate than those for MIPN. CA preserves postoperative renal functional, without any evidence of differences in mid-/long-term follow-up compared to nephron sparing surgery. [ABSTRACT FROM AUTHOR]

Introduction: Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation. Methods: A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted. Results: Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1–2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days. Conclusions: Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1–2 hours, this took 24 hours in blood vessels and 7 days in nerves. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of diagnostic work-up and treatment of bodypackers. Identification of predictive factors for surgical treatment. Design: Retrospective descriptive study. Setting: Teaching hospital, The Netherlands. Patients: All 40 consecutive patients, admitted during the period 1995-99 inclusive to the surgical department with the diagnosis of "bodypacker". Main outcome measures: Age, sex, medical history, additional diagnostic investigation, treatment, morbidity, and mortality. Results: There were 36 men and 4 women, the reason for whose visit to the emergency department was the persistence of cocaine packages in the body. 24 had abdominal pain and 15 patients were vomiting. In all cases packages were identified on an abdominal radiograph taken supine. The cocaine concentration in the urine was raised in 8/13 patients. During admission 18/40 patients (45%) were operated on, and in 9 patients (23%) a previously unsuspected lesion was found, which was causing the obstruction. Factors predictive of the need for surgical treatment were: abdominal history (p = 0.01), abdominal pain while in the emergency department (p = 0.001), location of the packages of cocaine in the stomach and small intestine on the abdominal radiograph (p = 0.05), and a high concentration of cocaine in the urine (p = 0.03). 9 of the patients operated on developed complications; no patient died. Conclusion: The number of bodypackers admitted to the surgical department increases. More than half the patients could be treated conservatively. Factors predictive of the need for surgery are: abdominal history, pain, high obstruction, and cocaine in the urine. In 9 of the patients operated on an unsuspected disease was found that was causing the obstruction. [ABSTRACT FROM AUTHOR]

BACKGROUND Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS We included 373 episodes of CVC placement involving 338 patients in the perprotocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. [ABSTRACT FROM AUTHOR]

Background: RECIST may not be optimal for assessing treatment response with current systemic regimens. We evaluated RECIST, morphologic, and pathologically documented response (pathological response) in patients with initially unresectable colorectal cancer liver-only metastases (CRLM)., Patients and Methods: Four hundred and eighty-nine patients from the phase III CAIRO5 trial were included who were treated with FOLFOX/FOLFIRI/FOLFOXIRI and bevacizumab or panitumumab. The association of the different response tools with overall survival (OS) was evaluated for all patients, and with early recurrence (<6 months) for patients after complete local treatment., Results: In the overall population, suboptimal [hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.83-1.47] and optimal (HR 0.95, 95% CI 0.74-1.22) morphologic response were not associated with OS compared with no response. RECIST partial response (HR 0.61, 95% CI 0.49-0.76) and progressive disease (HR 5.77, 95% CI 3.97-8.39) were associated with OS compared with stable disease. In 242 patients who underwent local treatment, suboptimal (HR 1.22, 95% CI 0.76-1.96) and optimal (HR 1.28, 95% CI 0.89-1.86) morphologic response were not associated with OS compared with no response. RECIST partial response was not significantly associated with OS (HR 0.73, 95% CI 0.52-1.01), whereas progressive disease was (HR 19.74, 95% CI 5.75-67.78), compared with stable disease. While major pathological response (HR 0.66, 95% CI 0.44-0.99) was associated with OS, partial pathological response (HR 0.82, 95% CI 0.57-1.19) was not, compared with no pathological response. Pathological response, but not morphologic response and RECIST, was significantly associated with early recurrence (P < 0.001) which occurred in 13/58 (22%) patients with major response, 29/61 (48%) patients with partial response, and 51/88 (58%) patients with no response., Conclusions: Our results show that RECIST but not morphologic response was prognostic for OS. In patients eligible for local treatment, neither RECIST nor morphologic response were associated with early recurrence. Pathological response was associated with early recurrence but is only available post-operatively. Hence, novel preoperative parameters are warranted to predict early recurrence and prevent potentially futile liver surgery., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 E th,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 E th,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., Competing Interests: Declaration of competing interest Author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: K.P.v.L. and T.M.v.G. are paid consultants for Angio-Dynamics. Angio-Dynamics had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.

Lymph nodes (LNs) are highly organized structures where specific immune responses are initiated by dendritic cells (DCs). We investigated the frequency and distribution of human myeloid (mDCs) and plasmacytoid (pDCs) in LNs and blood during the earliest phases of rheumatoid arthritis (RA). We included 22 RA-risk individuals positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies, 16 biological-naïve RA patients and 8 healthy controls (HCs). DC subsets (CD1c + mDCs and CD304 + pDCs) in LN tissue and paired peripheral blood were analyzed using flow cytometry and confocal microscopy. In blood of RA patients a significant decreased frequency of pDCs was found, with a similar trend for mDCs. In contrast, mDC frequencies were higher in RA compared with HCs and RA-risk individuals, especially in LN. Frequency of mDCs seemed higher in LNs compared to paired blood samples in all donors, while pDCs were higher in LNs only in RA patients. As expected, both mDCs and pDCs localized mainly in T-cell areas of LN tissue. In conclusion, compared with RA-risk individuals, mDCs and pDCs were enriched in the LN tissue of early-RA patients, while their frequency in RA-risk individuals was comparable to HCs. This may suggest that other antigen-presenting cells are responsible for initial breaks of tolerance, while mDCs and pDCs are involved in sustaining inflammation.

Aim: To compare the objective and subjective image quality of non-contrast three-dimensional (3D) navigator-gated balanced steady state free precession magnetic resonance angiography (NC-MRA) and contrast-enhanced magnetic resonance angiography (CE-MRA) along the entire thoracic aorta., Materials and Methods: Fifty consecutive patients with thoracic aortic disease underwent NC-MRA and CE-MRA using a 1.5 T MRI system. Vessel sharpness was assessed using signal intensity profiles at five predefined levels of the thoracic aorta. Two readers scored subjective quality. Manual diameter measurements of both readers were used for calculation of interobserver variation., Results: NC-MRA resulted in significantly sharper delineation of the aortic root, ascending aorta, and distal descending aorta compared to CE-MRA. Sharpness was comparable at the level of the arch and proximal descending aorta. NC-MRA resulted in significantly better subjective image quality. Interobserver agreement for diameter measurements was excellent for both techniques., Conclusion: NC-MRA resulted in superior image quality for assessment of the thoracic aorta and in better vessel sharpness for assessment of the aortic root and ascending aorta, when compared to CE-MRA. NC-MRA can be considered the MRA technique of choice for the assessment of the thoracic aorta diameters in clinical practice., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Correction of coagulopathy prior to central venous catheter (CVC) placement is advocated by guidelines, while retrospective studies support restrictive use of transfusion products., Study Design and Methods: We conducted a mixed vignette and questionnaire web survey to investigate current practice and preferences for CVC placement. Clinical vignettes were used to quantify the tendency to administer platelet concentrate. A positive ß-coefficient is in favour of administering platelet concentrate., Results: Ninety-seven physicians answered the survey questions (36 critical care physicians, 14 haematologists, 20 radiologists and 27 anaesthesiologist). Eighty-six physicians subsequently completed the clinical vignettes (response rate 71%). Preferences in favour of correcting thrombocytopenia prior CVC placement were platelet counts of 10 × 10 9 /L and 20 × 10 9 /L (ß = 3·9; ß = 3·2, respectively), the subclavian insertion site (ß = 0·8). An elevated INR (INR = 3; ß = 0·6) and an elevated aPTT (aPTT = 60 s; ß = 0·4) showed a positive trend towards platelet transfusion. Platelet transfusion was less likely in an emergency setting (ß = -0·4). Reported transfusion thresholds for CVC placement varied from <10 × 10 9 /L to 80 × 10 9 /L for platelet count, from 1·0 to 10·0 for INR and from 25 s to 150 s for aPTT. Implementation of ultrasound guidance as standard practice was limited., Conclusion: Current transfusion practice prior to CVC placement is highly variable. Physicians adjust the decision to correct coagulopathy prior CVC placement based on clinical parameters, insertion site and technique applied., (© 2017 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Introduction: We present a novel approach to the treatment of membranous duodenal stenosis (MDS). To our knowledge this is the first paper to describe balloon dilatation for this entity., Material and Methods: Four children, 2 boys and 2 girls, aged between 8 and 28 days, underwent duodenal balloon dilatation. Balloon dilatation was performed under general anaesthesia using standard angiography balloons per os. Balloon diameters ranged from 6 to 14 mm., Results: All balloon dilatations were successful. None of the procedures showed procedural or post-procedural complications. None of the patients subsequently required surgical intervention. To date all children are doing well., Discussion: The initial experience with balloon dilation of MDS showed a 100% success rate, without procedural or post-procedural complications. The results obtained in this small group of patients suggest that the use of balloon dilatation in cases of MDS may be a safe technique that can be readily performed by an experienced interventional radiologist.