Selection of optimal molecular targets for tumor-specific imaging in pancreatic ductal adenocarcinoma

Discrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this discrimination and to help select and stratify patients for resection. We evaluated various biomarkers for the specific identification of PDAC and associated lymph node metastases. Using immunohistochemistry (IHC), expression levels and patterns were investigated of integrin avβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), Cathepsin E (Cath E), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-MET), thymocyte differentiation antigen 1 (Thy1), and urokinase-type plasminogen activator receptor (uPAR). In a first cohort, multiple types of pancreatic tissue were evaluated (n=62); normal pancreatic tissue (n=8), CP (n=7), PDAC (n=9), tumor associated lymph nodes (n=32), and PDAC after neoadjuvant radiochemotherapy (n=6). In a second cohort, tissues were investigated (n=55) with IHC and immunofluorescence (IF) for concordance of biomarker expression in all tissue types, obtained from an individual patient. Integrin avβ6 and CEACAM5 showed significantly higher expression levels in PDAC versus normal pancreatic tissue (P=0.001 and P < 0.001, respectively) and CP (P=0.003 and P < 0.001, respectively). Avβ6 and CEACAM5 expression identified tumor-positive lymph nodes correctly in 84% and 68%, respectively, and in 100% of tumor-negative nodes for both biomarkers. In conclusion, avβ6 and CEACAM5 are excellent biomarkers to differentiate PDAC from surrounding tissue and to identify lymph node metastases. Individually or combined, these biomarkers are promising targets for tumor-specific molecular imaging of PDAC

Indocyanine green fluorescence perfusion testing in robot-assisted hepatic arterial infusion pump placement

Background: Hepatic arterial infusion pump (HAIP) treatment is a technique used to treat liver localized malignancy with intra-arterial chemotherapy. Methylene blue is generally administered to verify hepatic perfusion and exclude inadvertent extrahepatic perfusion. The use of indocyanine green dye (ICG) combined with near-infrared (NIR) fluorescence imaging during robot-assisted HAIP placement may be an attractive alternative by providing high contrast without blue discoloration of the operative field. Methods: Data was collected retrospectively from 2 centers in the Netherlands. Intraoperative perfusion of the liver segments and extrahepatic perfusion were assessed using ICG/NIR as well as methylene blue on video imaging and correlated to postoperative 99 m-Tc perfusion scintigraphy. Results: 13 patients underwent robot-assisted surgery for HAIP placement; median length of stay was 4 days, complications occurred in 4 patients. Hepatic perfusion showed identical patterns when ICG was compared with methylene blue. In 1 patient, additional extrahepatic perfusion was found using ICG, leading to further vessel ligation. Intraoperative ICG perfusion was concordant with 99 m-Tc perfusion scintigraphy. Discussion: Liver and extrahepatic perfusion determined by ICG fluorescence imaging is concordant with blue dye perfusion and 99 m-Tc perfusion scintigraphy. Therefore, ICG fluorescence imaging is deemed a safe and reliable technique for perfusion testing during robot-assisted HAIP placement. Graphical abstract: (Figure presented.)</p

Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases Following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial

Contains fulltext : 242627.pdf (Publisher’s version ) (Open Access

Added Value of Liver MRI in Patients Eligible for Surgical Resection or Ablation of Colorectal Liver Metastases Based on CT:A Systematic Review and Meta-Analysis

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging modality for detection and staging in patients with colorectal liver metastases (CRLM). Although liver magnetic resonance imaging (MRI) is superior to CT in detecting small lesions, guidelines are ambiguous regarding the added value of an additional liver MRI in the surgical workup of patients with CRLM. Therefore, this systematic review and meta-analysis aimed to evaluate the clinical added value of liver MRI in patients eligible for resection or ablation of CRLM based on CT.METHODS: A systematic search was performed in the PubMed, Embase, and Cochrane Library databases through June 23, 2023. Studies investigating the impact of additional MRI on local treatment plan following CT in patients with CRLM were included. Risk of bias was assessed using the QUADAS-2 tool. The pooled weighted proportions for the primary outcome were calculated using random effect meta-analysis.RESULTS: Overall, 11 studies with 1440 patients were included, of whom 468 patients (32.5%) were assessed for change in local treatment plan. Contrast-enhanced liver MRI was used in 10 studies, including gadoxetic acid in 9 studies. Liver MRI with diffusion-weighted imaging was used in 8 studies. Pooling of data found a 24.12% (95% confidence interval, 15.58%-32.65%) change in the local treatment plan based on the added findings of liver MRI following CT. Sensitivity analysis including 5 studies (268 patients) focusing on monophasic portal venous CT followed by gadoxetic acid-enhanced liver MRI with diffusion-weighted imaging showed a change of local treatment plan of 17.88% (95% confidence interval, 5.14%-30.62%).CONCLUSIONS: This systematic review and meta-analysis found that liver MRI changed the preinterventional local treatment plan in approximately one-fifth of patients eligible for surgical resection or ablation of CRLM based on CT. These findings suggest a clinically relevant added value of routine liver MRI in the preinterventional workup of CRLM, which should be confirmed by large prospective studies.</p

Assessment of fully quantitative and simplified methods for analysis of [⁶⁸Ga]Ga-FAPI-46 uptake in patients with pancreatobiliary cancer using LAFOV PET/CT

Purpose: The aim of this study was to validate simplified methods for quantifying [68Ga]Ga-FAPI-46 uptake against full pharmacokinetic modeling. Methods: Ten patients with pancreatobiliary cancer underwent a 90-min dynamic PET/CT scan using a long axial field of view system. Arterial blood samples were used to establish calibrated plasma-input function from both continuous arterial sampling and image-derived input function (IDIF). Lesional [68Ga]Ga-FAPI-46 kinetics were described using conventional non-linear plasma-input tissue-compartment models. Logan plots using 30–90 min and 30–60 min post-injection (p.i), image-based target-to-whole blood ratio (TBR), mean standardized uptake values (SUVmean) normalized to body weight, lean body mass, and body surface area, at 20–30 min, 60–70 min and 80–90 min p.i were assessed. Results: One patient was excluded due to discontinued scan acquisition and missing arterial sampling. Thirteen tumoral lesions and 11 non-tumoral lesions were included. A reversible 2-tissue-compartment model showed most preferrable fits for all types of [68Ga]Ga-FAPI-46 positive lesions. The distribution volume (VT) results obtained using arterial sampling plasma-input function and those using plasma-IDIF (VT_plasma_IDIF) showed an excellent correlation (Spearman rank correlation coefficient (rs) = 0.949). Logan VT using both time intervals were highly correlated with VT_plasma_IDIF (rs ≥ 0.938). The correlation values with VT_plasma_IDIF for image-based TBR and SUVmean parameters were higher at 80–90 min (rs ≥ 0.839) and at 60–70 min (rs ≥ 0.835) p.i than at 20–30 min p.i (rs ≤ 0.774). Conclusion: Image-based TBR and SUVmean at 60–70 min p.i are suitable for quantifying [68Ga]Ga-FAPI-46 uptake.</p

A European expert consensus surgical technique description for robotic hepatectomy

The robotic platform enables surgeons to operate with a similar level of freedom and control as in open surgery, while still providing the patient with the benefits of a minimally invasive approach. More centres continue to adopt robotic liver surgery however standardized training materials and consensus on the surgical technique are currently lacking. The availability of a standardized surgical protocol could benefit the further dissemination of the robotic approach while promoting safe and effective operating techniques. We present a comprehensive surgical technique description for robotic hepatectomy agreed upon by seven expert robotic liver surgeons in Europe. They contributed insights from their extensive experience with the robot to develop this report, highlighting the key steps and important considerations for performing robotic hepatectomy. We describe the surgical technique for four most common hepatectomy types with varying complexity: partial anterolateral resections, partial posterosuperior resections, left hepatectomy and right hepatectomy. This report encompasses recommendations from the experts, covering the preparatory steps such as patient selection and pre-operative imaging, and extending through to care in the postoperative phase. The step-by-step surgical technique description serves as a compendium of best practice methods presently utilized in robotic liver surgery. Although some variations in technique cannot be eliminated from practice, general recommendations in a structured form will help to homogenize the technique, safeguarding surgical quality. This paper aims to inform and advise surgeons in the process of adopting robotic liver surgery and can act as a starting point for further optimization and refinement of the technique

Robotic Versus Open Hepatic Arterial Infusion Pump Placement for Unresectable Intrahepatic Cholangiocarcinoma

Background: Hepatic arterial infusion pump (HAIP) chemotherapy is an effective treatment for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). HAIP chemotherapy requires a catheter inserted in the gastroduodenal artery and a subcutaneous pump. The catheter can be placed using an open or robotic approach. Objective: This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA. Methods: We analyzed patients with unresectable iCCA included in the PUMP-II trial from January 2020 to September 2022 undergoing robotic or open HAIP placement at Amsterdam UMC, Erasmus MC, and UMC Utrecht. The primary outcome was time to functional recovery (TTFR). Results: In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2 days after robotic placement versus 5 days after open HAIP placement (p &lt; 0.001). One patient (4.5%) in the robotic group underwent a conversion to open because of a large bulky tumor leaning on the hilum immobilizing the liver. Postoperative complications were similar—36% (8/22) after robotic placement versus 39% (11/28) after open placement (p = 1.000). The median length of hospital stay was shorter in the robotic group—3 versus 5 days (p &lt; 0.001). All 22 robotic patients initiated HAIP chemotherapy post-surgery, i.e. 93% (26/28) in the open group (p = 0.497). The median time to start HAIP chemotherapy was 14 versus 18 days (p = 0.153). Conclusion: Robotic HAIP placement in patients with unresectable iCCA is a safe and effective procedure and is associated with a significantly shorter TTFR and hospital stay than open HAIP placement.</p

Robotic Versus Open Hepatic Arterial Infusion Pump Placement for Unresectable Intrahepatic Cholangiocarcinoma

Background: Hepatic arterial infusion pump (HAIP) chemotherapy is an effective treatment for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). HAIP chemotherapy requires a catheter inserted in the gastroduodenal artery and a subcutaneous pump. The catheter can be placed using an open or robotic approach. Objective: This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA. Methods: We analyzed patients with unresectable iCCA included in the PUMP-II trial from January 2020 to September 2022 undergoing robotic or open HAIP placement at Amsterdam UMC, Erasmus MC, and UMC Utrecht. The primary outcome was time to functional recovery (TTFR). Results: In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2 days after robotic placement versus 5 days after open HAIP placement (p &lt; 0.001). One patient (4.5%) in the robotic group underwent a conversion to open because of a large bulky tumor leaning on the hilum immobilizing the liver. Postoperative complications were similar—36% (8/22) after robotic placement versus 39% (11/28) after open placement (p = 1.000). The median length of hospital stay was shorter in the robotic group—3 versus 5 days (p &lt; 0.001). All 22 robotic patients initiated HAIP chemotherapy post-surgery, i.e. 93% (26/28) in the open group (p = 0.497). The median time to start HAIP chemotherapy was 14 versus 18 days (p = 0.153). Conclusion: Robotic HAIP placement in patients with unresectable iCCA is a safe and effective procedure and is associated with a significantly shorter TTFR and hospital stay than open HAIP placement.</p

Indocyanine green fluorescence perfusion testing in robot-assisted hepatic arterial infusion pump placement

Background: Hepatic arterial infusion pump (HAIP) treatment is a technique used to treat liver localized malignancy with intra-arterial chemotherapy. Methylene blue is generally administered to verify hepatic perfusion and exclude inadvertent extrahepatic perfusion. The use of indocyanine green dye (ICG) combined with near-infrared (NIR) fluorescence imaging during robot-assisted HAIP placement may be an attractive alternative by providing high contrast without blue discoloration of the operative field. Methods: Data was collected retrospectively from 2 centers in the Netherlands. Intraoperative perfusion of the liver segments and extrahepatic perfusion were assessed using ICG/NIR as well as methylene blue on video imaging and correlated to postoperative 99 m-Tc perfusion scintigraphy. Results: 13 patients underwent robot-assisted surgery for HAIP placement; median length of stay was 4 days, complications occurred in 4 patients. Hepatic perfusion showed identical patterns when ICG was compared with methylene blue. In 1 patient, additional extrahepatic perfusion was found using ICG, leading to further vessel ligation. Intraoperative ICG perfusion was concordant with 99 m-Tc perfusion scintigraphy. Discussion: Liver and extrahepatic perfusion determined by ICG fluorescence imaging is concordant with blue dye perfusion and 99 m-Tc perfusion scintigraphy. Therefore, ICG fluorescence imaging is deemed a safe and reliable technique for perfusion testing during robot-assisted HAIP placement. Graphical abstract: (Figure presented.