Competency, Proficiency, and Mastery: Learning Curves for Robotic Distal Pancreatectomy at 16 International Expert Centers.

Objective: The aim of this study was to evaluate the different phases of the learning curve for robotic distal pancreatectomy (RDP) in international expert centers.

Summary Background Data: RDP is an emerging minimally invasive approach; however, only limited, mostly single center data are available on its safe implementation, including the learning curve.

Methods: Consecutive patients undergoing elective RDP from 16 expert centers across three continents were included to assess the learning curve.

Reclassification of Appendiceal Mucinous Neoplasms and Associated Pseudomyxoma Peritonei According to the Peritoneal Surface Oncology Group International Consensus: Clinicopathological Reflections of a Two-Center Cohort Study.

Background: International consensus on classifications of appendiceal mucinous neoplasms (AMNs) and associated pseudomyxoma peritonei (PMP) have been carefully made but clinicopathological associations supporting decision making remain scarce.

Objective: This study aimed to assess interdependence between AMNs and PMP and provide directions for clinical management.

Methods: This two-center retrospective cohort study reviewed patients with PMP treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy between 2005 and 2021.

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.

Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer.

Colorectal cancer metastasizes predominantly to the liver but also to the lungs and the peritoneum. The presence of extra-hepatic metastases limits curative (surgical) treatment options and is associated with very poor survival. The mechanisms governing multi-organ metastasis formation are incompletely understood.

Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites.

Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs and derive PDTOs from an understudied subtype of NEC, large cell neuroendocrine carcinoma (LCNEC), arising from multiple body sites.

Stromal localization of inactive CD8 T cells in metastatic mismatch repair deficient colorectal cancer.

Background: The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC.

Methods: We profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of fibroblasts and immune cells in primary CRC tumors with or without metastatic capacity.

Sentinel lymph node detection in thyroid carcinoma using [Ga]Ga-tilmanocept PET/CT: a proof-of-concept study.

Purpose: Sentinel lymph node (SLN) biopsy is rarely used for thyroid carcinoma staging. This is due to challenges associated with conventional Tc-99m-labeled tracers, often producing a large hotspot at the injection site, potentially hiding nearby SLNs (shine-through effect). The aim of this study was to demonstrate the feasibility and effectiveness of SLN visualization using the new PET tracer [Ga]Ga-tilmanocept.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

Objective: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities.

Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures.

Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020).

The Feasibility, Proficiency, and Mastery Learning Curves in 635 Robotic Pancreatoduodenectomies Following a Multicenter Training Program: "Standing on the Shoulders of Giants".

Objective: To assess the feasibility, proficiency, and mastery learning curves for robotic pancreatoduodenectomy (RPD) in "second-generation" RPD centers following a multicenter training program adhering to the IDEAL framework.

Background: The long learning curves for RPD reported from "pioneering" expert centers may discourage centers interested in starting an RPD program. However, the feasibility, proficiency, and mastery learning curves may be shorter in "second-generation" centers that participated in dedicated RPD training programs, although data are lacking.

Lymphatic Invasion of Plakoglobin-Dependent Tumor Cell Clusters Drives Formation of Polyclonal Lung Metastases in Colon Cancer.

Background & Aims: Patients with colon cancer with liver metastases may be cured with surgery, but the presence of additional lung metastases often precludes curative treatment. Little is known about the processes driving lung metastasis. This study aimed to elucidate the mechanisms governing lung vs liver metastasis formation.

Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases.

Background: Patients who develop early extrahepatic recurrence (EHR) may not benefit from local treatment of colorectal liver metastases (CRLMs). This study aimed to develop a prediction model for early EHR after local treatment of CRLMs using a national data set.

Methods: A Cox regression prediction model for EHR was developed and validated internally using data on patients who had local treatment for CRLMs with curative intent.

Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice.

Background: The immunogenic nature of metastatic colorectal cancer (CRC) with high microsatellite instability (MSI-H) underlies their responsiveness to immune checkpoint blockade (ICB). However, resistance to ICB is commonly observed, and is associated with the presence of peritoneal-metastases and ascites formation. The mechanisms underlying this site-specific benefit of ICB are unknown.

Diagnosing pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 in daily practice.

Background: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (PanNETs) have a high prevalence and represent the main cause of death. This study aimed to assess the diagnostic accuracy of the currently used conventional pancreatic imaging techniques and the added value of fine needle aspirations (FNAs).

Methods: Patients who had at least one imaging study were included from the population-based MEN1 database of the DutchMEN Study Group from 1990 to 2017.

Consensus molecular subtype 4 (CMS4)-targeted therapy in primary colon cancer: A proof-of-concept study.

Background: Mesenchymal Consensus Molecular Subtype 4 (CMS4) colon cancer is associated with poor prognosis and therapy resistance. In this proof-of-concept study, we assessed whether a rationally chosen drug could mitigate the distinguishing molecular features of primary CMS4 colon cancer.

Methods: In the ImPACCT trial, informed consent was obtained for molecular subtyping at initial diagnosis of colon cancer using a validated RT-qPCR CMS4-test on three biopsies per tumor (Phase-1, n=69 patients), and for neoadjuvant CMS4-targeting therapy with imatinib (Phase-2, n=5).

Early Recurrence After Resection of Locally Advanced Pancreatic Cancer Following Induction Therapy: An International Multicenter Study.

Objective: To establish an evidence-based cutoff and predictors for early recurrence in patients with resected locally advanced pancreatic cancer (LAPC).

Background: It is unclear how many and which patients develop early recurrence after LAPC resection. Surgery in these patients is probably of little benefit.

Sentinel Lymph Node Mapping in Breast Cancer Patients Through Fluorescent Imaging Using Indocyanine Green: The INFLUENCE Trial.

Objective: The aim was to compare the (sentinel) lymph node detection rate of indocyanine green (ICG)-fluorescent imaging versus standard-of-care 99m Tc-nanocoilloid for sentinel lymph node (SLN)-mapping.

Background: The current gold standard for axillary staging in patients with breast cancer is sentinel lymph node biopsy (SLNB) using radio-guided surgery using radioisotope technetium ( 99m Tc), sometimes combined with blue dye. A promising alternative is fluorescent imaging using ICG.

Assessing Outcomes After Adrenalectomy for Primary Aldosteronism - Early is Accurate: Retrospective Cohort Study.

Objective: We aimed to investigate the postoperative trend in blood pressure (BP)-related outcomes [BP and antihypertensive (AHT) drug use] during the year following adrenalectomy for primary aldosteronism (PA) to determine the optimal timing for outcome assessment and to determine the necessary follow-up length.

Background: Since the course of BP-related outcomes after adrenalectomy is unknown, the optimal timing of outcome assessment and follow-up duration are not clear.

Methods: In this retrospective single center cohort study, we used a prospectively collected database with all patients referred for difficult-to-control-hypertension-analysis.

Robotic Distal Pancreatectomy: A Novel Standard of Care? Benchmark Values for Surgical Outcomes From 16 International Expert Centers.

Background And Objective: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve.

External Validation of Two Established Clinical Risk Scores Predicting Outcome after Local Treatment of Colorectal Liver Metastases in a Nationwide Cohort.

Optimized surgical techniques and systemic therapy have increased the number of patients with colorectal liver metastases (CRLM) eligible for local treatment. To increase postoperative survival, we need to stratify patients to customize therapy. Most clinical risk scores (CRSs) which predict prognosis after CRLM resection were based on the outcome of studies in specialized centers, and this may hamper the generalizability of these CRSs in unselected populations and underrepresented subgroups.

Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage.

Unlabelled: Micrometastases of colorectal cancer can remain dormant for years prior to the formation of actively growing, clinically detectable lesions (i.e., colonization).