Preoperative chemotherapy in upfront resectable colorectal liver metastases: New elements for an old dilemma?

The use of preoperative or "neoadjuvant" chemotherapy (NAC) has long been controversial for resectable colorectal liver metastases (CRLM). The European Society of Medical Oncology (ESMO) 2023 guidelines on metastatic colorectal cancer (CRC) indicate a combination of surgical/technical and oncologic/prognostic criteria as the two determinants for allocating patients to NAC or upfront hepatectomy. However, surgical and technical criteria have evolved, and oncologic prognostic criteria date from the pre-modern chemotherapy era and lack prospective validation. The traditional literature is interpreted as not supporting the use of NAC because several studies fail to demonstrate a benefit in overall survival (OS) compared to upfront surgery; however, OS may not be the most appropriate endpoint to consider. Moreover, the commonly quoted studies against NAC contain many limitations that may explain why NAC failed to demonstrate its value. The query of the recent literature focused primarily on other aspects than OS, such as surgical technique, the impact of side effects of chemotherapy, the histological growth pattern of metastases, or the detection of circulating tumor DNA, shows data that support a more widespread use of NAC. These should prompt a critical reappraisal of the use of NAC, leading to a more precise selection of patients who could benefit from it.

Concomitant training in robotic and laparoscopic liver resections of low-to-intermediate difficulty score: a retrospective analysis of the learning curve.

In the setting of minimally invasive liver surgery (MILS), training in robotic liver resections (RLR) usually follows previous experience in laparoscopic liver resections (LLR). The aim of our study was to assess the learning curve of RLR in case of concomitant training with LLR. We analyzed consecutive RLRs and LLRs by a surgeon trained simultaneously in both techniques (Surg1); while a second surgeon trained only in LLRs was used as control (Surg2). A regression model was used to adjust for confounders and a Cumulative Sum (CUSUM) analysis was carried out to assess the learning phases according to operative time and difficulty of the procedures (IWATE score). Two-hundred-forty-five procedures were identified (RobSurg1, n = 75, LapSurg1, n = 102, LapSurg2, n = 68). Mean IWATE was 4.0, 4.3 and 5.8 (p < 0.001) in each group. The CUSUM analysis of the adjusted operative times estimated the learning phase in 40 cases (RobSurg1), 40 cases (LapSurg1), 48 cases (LapSurg2); for IWATE score it was 38 cases (RobSurg1), 33 cases (LapSurg1), 38 cases (LapSurg2) respectively. Our preliminary experience showed a similar learning curve of 40 cases for low and intermediate difficulty RLR and LLR. Concomitant training in both techniques was safe and may be a practical option for starting a MILS program.

Neo-Adjuvant Treatment in Primary Resectable Pancreatic Cancer: A Systematic Review and PRISMA-Compliant Updated Metanalysis of Oncological Outcomes.

BACKGROUND: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. METHODS: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. RESULTS: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72-0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56-0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32-0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23-2.36) were also found in patients treated with NAT, despite high heterogeneity. CONCLUSIONS: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required.

Robotic versus laparoscopic liver resections: propensity-matched comparison of two-center experience.

BACKGROUND: The advantages of the robotic approach in minimally invasive liver surgery (MILS) are still debated. This study compares the short-term outcomes between laparoscopic (LLR) and robotic (RLR) liver resections in propensity score matched cohorts. METHODS: Data regarding minimally invasive liver resections in two liver surgery units were retrospectively reviewed. A propensity score matched analysis (1:1 ratio) identified two groups of patients with similar characteristics. Intra- and post-operative outcomes were then compared. The difficulty of MILS was based on the IWATE criteria. RESULTS: Two hundred sixty-nine patients underwent MILS between January 2014 and December 2021 (LLR = 192; RLR = 77). Propensity score matching identified 148 cases (LLR = 74; RLR = 74) consisting of compensated cirrhotic patients (100%) underwent non-anatomic resection of IWATE 1-2 class (90.5%) for a solitary tumor < 5 cm in diameter (93.2%). In such patients, RLRs had shorter operative time (227 vs. 250 min, p = 0.002), shorter Pringle's cumulative time (12 vs. 28 min, p < 0.0001), and less blood loss (137 vs. 209 cc, p = 0.006) vs. LLRs. Conversion rate was nihil (both groups). In RLRs compared to LLRs, R0 rate (93 vs. 96%, p > 0.71) and major morbidity (4.1 vs. 5.4%, p > 0.999) were similar, without post-operative mortality. Hospital stay was shorter in the robotic group (6.2 vs. 6.6, p = 0.0001). CONCLUSION: This study supports the non-inferiority of RLR over LLR. In compensated cirrhotic patients underwent resection of low-to-intermediate difficulty for a solitary nodule < 5 cm, RLR was faster, with less blood loss despite the shorter hilar clamping, and required shorter hospitalization compared to LLR.

Minimally-invasive versus open pancreatic enucleation: systematic review and metanalysis of short-term outcomes.

BACKGROUND: Minimally Invasive Pancreatic Enucleation, either laparoscopic or robot-assisted, is rarely performed. The aim of this study was to offer the current available evidence about the outcomes of minimally invasive pancreatic enucleations and explore the possible advantage of this approach over traditional surgery. METHODS: PubMed (MEDLINE), Cochrane Library and Embase (ELSEVIER) medical databases were searched for articles published from January 1990 to March 2022. Studies which included more than 10 cases of minimally-invasive pancreatic enucleation were included. Data on the outcomes were synthetized and meta-analyzed when appropriate. RESULTS: Twenty studies published between 2009 and 2022 with a total of 552 patients were included in the systematic review: three hundred fifty-one patients (63.5%) had a laparoscopic intervention, two hundred and one (36.5%) robot-assisted with a cumulative incidence of conversion rate of 5%. Minimally-invasive surgery was performed in 63% of cases on the body/tail of the Pancreas and in 37% of the cases on the head/uncinate process of the Pancreas. The cumulative post-operative 30 days - mortality rate was 0.2% and the major postoperative morbidity (Clavien-Dindo III-IV-V) 35%. Clinically relevant pancreatic fistula was observed in 17% of the patients. Compared with the standardized open approach (n: 366 patients), mean length of hospital stay was significantly reduced in patients undergoing minimally invasive pancreatic enucleation (2.45 days, p = 0.003) with a favorable trend for post-operative major morbidity (Clavien-Dindo III-IV) (- 24% RR, p: 0.13). Operative time, blood loss and clinically relevant pancreatic fistula rate were comparable between the two groups. One hundred and fourteen robot-assisted enucleations entered in a subgroup analysis with comparable results to open surgery. CONCLUSION: Minimally-Invasive approach for pancreatic enucleation is safe, feasible and offers short-term clinical outcomes comparable with open surgery. The potential benefit of robotic surgery will need to be verified in further studies.

Imaging based body composition profiling and outcomes after oncologic liver surgery.

Body composition profiling is gaining attention as a pre-operative factor that can play a role in predicting the short- and long- term outcomes of patients undergoing oncologic liver surgery. Existing evidence is mostly limited to retrospective and single-institution series and in many of these studies, the evaluation of body composition is based on parameters which are derived from CT-scan imaging. Among body composition phenotypes, sarcopenia is the most well studied but this is only one of the possible profiles which can impact the outcomes of oncologic hepatic surgery. Interest has recently grown in studying the effect of sarcopenic obesity, central obesity, or visceral fat amount, myosteatosis, and bone mineral density on -such patients. The objective of this review is to summarize the current evidence on whether imaging-based parameters of body composition have an impact on the outcome of patients undergoing liver surgery for each of the most frequent indications for liver resection in clinical practice: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM).

Implementing a robotic liver resection program does not always require prior laparoscopic experience.

BACKGROUND: Preliminary experience in laparoscopic liver surgery is usually suggested prior to implementation of a robotic liver resection program. METHODS: This was a retrospective cohort analysis of patients undergoing robotic (RLR) versus laparoscopic liver resection (LLR) for hepatocellular carcinoma at a center with concomitant initiation of robotic and laparoscopic programs RESULTS: A total of 92 consecutive patients operated on between May 2014 and February 2019 were included: 40 RLR versus 52 LLR. Median age (69 vs. 67; p = 0.74), male sex (62.5% vs. 59.6%; p = 0.96), incidence of chronic liver disease (97.5% vs.98.1%; p = 0.85), median model for end-stage liver disease (MELD) score (8 vs. 9; p = 0.92), and median largest nodule size (22 vs. 24 mm) were similar between RLR and LLR. In the LLR group, there was a numerically higher incidence of nodules located in segment 4 (20.0% vs. 16.6%; p = 0.79); a numerically higher use of Pringle's maneuver (32.7% vs. 20%; p = 0.23), and a shorter duration of surgery (median of 165.5 vs. 217.5 min; p = 0.04). Incidence of complications (25% vs.32.7%; p = 0.49), blood transfusions (2.5% vs.9.6%; p = 0.21), and median length of stay (6 vs. 5; p = 0.54) were similar between RLR and LLR. The overall (OS) and recurrence-free (RFS) survival rates at 1 and 5 years were 100 and 79 and 95 and 26% for RLR versus 96.2 and 76.9 and 84.6 and 26.9% for LLR (log-rank p = 0.65 for OS and 0.72 for RFS). CONCLUSIONS: Based on our results, concurrent implementation of a robotic and laparoscopic liver resection program appears feasible and safe, and is associated with similar oncologic long-term outcomes.

Real Space Observation of Electronic Coupling between Self-Assembled Quantum Dots.

The control of quantum coupling between nano-objects is essential to quantum technologies. Confined nanostructures, such as cavities, resonators, or quantum dots, are designed to enhance interactions between electrons, photons, or phonons, giving rise to new properties, on which devices are developed. The nature and strength of these interactions are often measured indirectly on an assembly of dissimilar objects. Here, we adopt an innovative point of view by directly mapping the coupling of single nanostructures using scanning tunneling microscopy and spectroscopy (STM and STS). We take advantage of the unique capabilities of STM/STS to map simultaneously the nano-object's morphology and electronic density in order to observe in real space the electronic coupling of pairs of In(Ga)As/GaAs self-assembled quantum dots (QDs), forming quantum dot molecules (QDMs). Differential conductance maps d I/d V ( E, x, y) demonstrate the presence of an effective electronic coupling, leading to bonding and antibonding states, even for dissymmetric QDMs. The experimental results are supported by numerical simulations. The actual geometry of the QDMs is taken into account to determine the strength of the coupling, showing the crucial role of quantum dot size and pair separation for device growth optimization.

Analyzing written communication in AAC contexts: a statistical perspective.

This research note focuses on some of the opportunities provided by the statistical analysis of textual data, by illustrating examples of the use of lexicon-based quantitative measures with texts within a particular context of augmentative and alternative communication. The corpus is composed of 12 essays produced by six individuals with autism and six participants without disabilities in a control group during sessions of facilitated communication. The study raises questions that can be answered thanks to the statistical methods implemented in the text analysis framework and other procedures that may be used to identify the characteristics of texts (and their writers) and compare texts (or subcorpora). The aim is to discuss strengths, weaknesses, opportunities, and threats of the approach and to highlight its connections to qualitative approaches.