Proposal of set-up standardization for general surgery procedures with the CMR Versius system, a new robotic platform: our initial experience.

BACKGROUND: The article describes our initial experience using CMR Versius platform for several procedures in general surgery. METHODS: Between September 2022 and April 2023, seventy patients underwent robotic surgery in a multi-robotic referral center (San Paolo University Hospital, Milan, Italy). Three surgeons with only laparoscopic experience performed 24 cholecystectomies, 13 inguinal hernia repairs, 9 ventral hernia repairs, 7 right hemicolectomies, 11 left hemicolectomies, 1 sigmoidectomy, 1 ileocecal resection, 1 ventral rectopexy, 1 Nissen fundoplication, 1 total splenectomy, and 1 exploration with multiple biopsies. RESULTS: All surgeries were full-robotic, with only one conversion to laparoscopy. The short length of stay and low rate of severe morbidity are promising findings. Although operative time was lengthened, clinical outcomes were not affected. CONCLUSIONS: Our experience demonstrates that the adoption of Versius system is safe and feasible in general surgery. The standardization of port placement and BSU set-up can certainly reduce the operative time.

Prior Robotic Console Expertise May Improve Basic Skills at the New Hugo RAS Simulator: Results from a Cohort Trial and Implications for Skill Transference Across Platforms.

Background: Robot-assisted surgery ensures minimal invasiveness; since the expiry of the Da Vinci patent, new robotic systems have entered the market. Recently, the Hugo RAS received CE approval for several surgical procedures. However, more is needed to know about skill acquisition at the new simulator. Objective: This study aims to analyse the factors impacting basic surgical skills at the Hugo RAS simulator. Design setting and participants: We present a cross-sectional study involving 71 participants of different backgrounds invited to a hands-on session with the Hugo RAS simulator voluntarily. All of them had no prior expertise with the system. Participants were recruited among medical/nurse students, residents, and laparoscopic and robotic surgeons. Intervention: All participants underwent a hands-on "pick and place" exercise at the Hugo RAS simulator; the metrics of a second-round pick and place exercise were recorded. Outcome measurements and statistical analysis: Metrics were analysed with regard to the following variables: demographics, videogame use, and prior surgical experience (no surgical expertise, experience with laparoscopy, and experience with robotic console). Results and limitations: All participants completed the test. Of them, 77.5% were naïve to surgery, 8.5% had prior laparoscopic expertise, and 14.1% had prior robotic console experience. The time to complete the pick and place exercise was significantly lower (p < 0.001) among prior robotic surgeons (38 s, interquartile range [IQR] 34-45) compared with both naïve participants (61 s, IQR 53-71) and laparoscopists (93 s, IQR 53-162). The overall score of the exercise decreased with age (p = 0.046); however, the overall scores were significantly and steadily higher among surgeons experienced in robotic consoles across all age groups (p = 0.006). Neither gender (p = 0.7) nor videogame use (p = 0.9) correlated significantly with the metrics. Conclusions: This is the first study analysing factors impacting basic skill acquisition at a new robotic simulator. Experience with robotic consoles may represent a major factor, raising the hypothesis of the transferability of basic robotic skills across different robotic systems. Further studies are required to explore this issue. Patient summary: In the present study, we analysed which characteristics may affect the basic surgical skills at a novel robotic platform.

Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression.

Regulatory T (Treg) cells are a barrier for tumor immunity and a target for immunotherapy. Using single-cell transcriptomics, we found that CD4+ T cells infiltrating primary and metastatic colorectal cancer and non-small-cell lung cancer are highly enriched for two subsets of comparable size and suppressor function comprising forkhead box protein P3+ Treg and eomesodermin homolog (EOMES)+ type 1 regulatory T (Tr1)-like cells also expressing granzyme K and chitinase-3-like protein 2. EOMES+ Tr1-like cells, but not Treg cells, were clonally related to effector T cells and were clonally expanded in primary and metastatic tumors, which is consistent with their proliferation and differentiation in situ. Using chitinase-3-like protein 2 as a subset signature, we found that the EOMES+ Tr1-like subset correlates with disease progression but is also associated with response to programmed cell death protein 1-targeted immunotherapy. Collectively, these findings highlight the heterogeneity of Treg cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy.

COVID-19 outbreak and acute cholecystitis in a Hub Hospital in Milan: wider indications for percutaneous cholecystostomy.

BACKGROUND: COVID-19 pandemic has impacted the Italian National Health Care system at many different levels, causing a complete reorganization of surgical wards. In this context, our study retrospectively analysed the management strategy for patients with acute cholecystitis. METHODS: We analysed all patients admitted to our Emergency Department for acute cholecystitis between February and April 2020 and we graded each case according to 2018 Tokyo Guidelines. All patients were tested for positivity to SARS-CoV-2 and received an initial conservative treatment. We focused on patients submitted to cholecystostomy during the acute phase of pandemic and their subsequent disease evolution. RESULTS: Thirty-seven patients were admitted for acute cholecystitis (13 grade I, 16 grade II, 8 grade III). According to Tokyo Guidelines (2018), patients were successfully treated with antibiotic only, bedside percutaneous transhepatic gallbladder drainage (PC) and laparoscopic cholecystectomy (LC) in 29.7%, 21.6% and 48.7% of cases respectively. Therapeutic strategy of three out of 8 cases, otherwise fit for surgery, submitted to bedside percutaneous transhepatic gallbladder drainage (37.5%), were directly modified by COVID-19 pandemic: one due to the SARS-CoV-2 positivity, while two others due to unavailability of operating room and intensive care unit for post-operative monitoring respectively. Overall success rate of percutaneous cholecystostomy was of 87.5%. The mean post-procedural hospitalization length was 9 days, and no related adverse events were observed apart from transient parietal bleeding, conservatively treated. Once discharged, two patients required readmission because of acute biliary symptoms. Median time of drainage removal was 43 days and only 50% patients thereafter underwent cholecystectomy. CONCLUSIONS: Percutaneous cholecystostomy has shown to be an effective and safe treatment thus acquiring an increased relevance in the first phase of the pandemic. Nowadays, considering we are forced to live with the SARS-CoV-2 virus, PC should be considered as a virtuous, alternative tool for potentially all COVID-19 positive patients and selectively for negative cases unresponsive to conservative therapy and unfit for surgery.

Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ.

Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human tumors, highlighting a pan-cancer epigenetic rewiring which at single-cell level distinguishes malignant from normal cell populations. YAP/TAZ inhibition in established tumor organoids causes extensive cell death unveiling their essential role in tumor maintenance. This work indicates a common layer of YAP/TAZ-fueled enhancer reprogramming that is key for the cancer cell state and can be exploited for the development of improved therapeutic avenues.

LI-RADS to categorize liver nodules in patients at risk of HCC: tool or a gadget in daily practice?

PURPOSE: To determine the effectiveness of liver reporting and data system (LI-RADS) to diagnose hepatocellular carcinoma (HCC) and to retrospectively evaluate its impact on the adopted therapeutic strategy. MATERIALS AND METHODS: Preoperative imaging of 40 of 350 patients (median age 66, 31 M/9 F) submitted to liver resection for suspected HCC, between January 2008 and August 2019, has been retrospectively analyzed by two radiologists with different expertise, according to CT/MRI LI-RADS® v2018, both blinded to clinical and pathological results and untrained to using aforementioned scoring system. RESULTS: The perfect agreement between the readers was about 62.5% (25/40) (Cohen k: 0.41), better for LR-5 category (16/25) and higher in magnetic resonance imaging (MRI) investigations (68%; 13/19), which has been demonstrated the modality of choice for diagnosis of high probable and certain HCC, with arterial phase hyperenhancement as the most sensitive and accurate major feature. Compared to final histology, LR4 and LR5 scores assigned by senior radiologist reached sensitivity, specificity, positive and negative predictive values (PPV, PNV) and diagnostic accuracy of 90,9%, 29,0%, 93,8%, 62,5% and 87,5%, respectively, slightly higher than junior's ones. Misdiagnosis of HCC was done by both radiologists in the same two patients: 1 primary hepatic lymphoma (PHL) and 1 regenerative liver nodule (RLN). If LI-RADS would have been applied at the time of pre-surgical imaging, treatment planning would be modified in 10% of patients (4/40); the patient scheduled as LR-3 and finally resulted a focal nodular hyperplasia would have avoided liver resection. CONCLUSIONS: Application of LI-RADS, especially on MRI, may provide a more accurate evaluation of suspected HCC. PHL and RLN are the Achille's heels according to our experience.

Safety and effectiveness of biosimilar enoxaparin (Inhixa) for the prevention of thromboembolism in medical and surgical inpatients.

In 2016, biosimilar enoxaparin (Inhixa®, Techdow) was introduced in European markets with the same indications as branded enoxaparin (Clexane®, Sanofi). Its use is constantly increasing in clinical practice, however, little information from post-marketing clinical trials is available on its safety and effectiveness. We conducted an observational, retrospective study to assess the safety and effectiveness of Inhixa in preventing venous thromboembolism (VTE) in medically ill patients and in patients undergoing major abdominal surgery. We then compared our results with the incidence of symptomatic VTE and bleeding events during treatment with Clexane by pooling the results of clinical studies carried out in the same settings. We enrolled 381 patients, 189 admitted to a Medical Department and 192 to a Surgical Department from two single institutions. The incidence of major bleeding events was 1.8% globally (95% IC 0.7-3.8), 1.6% in medical patients (95% IC 0.3-4.6) and 2.1% in surgical patients (95% IC 0.6-5.3). VTE rate was 0.5% in the whole population (95% IC 0.1-1.9) and 0.5% (95% IC 0.01-2.9) in each group, respectively. The pooled estimate of the incidence of major bleeding with Clexane was 0.5% (IC 95%: 0.2-1.1) in medical patients and 2.6% (IC 95% 1.3-5.1) in surgical patients. The incidence of thrombotic events was 0.6% (IC 95%: 0.2-1.8) and 0.7% (CI95% 0.3-1.6), respectively. The incidence of bleeding and thrombosis in medical and surgical patients receiving Inhixa was low suggesting biosimilar enoxaparin is a valid alternative to branded enoxaparin.

Surgical Strategy During the COVID-19 Pandemic in a University Metropolitan Hospital in Milan, Italy.

The COVID-19 pandemic has spread rapidly, forcing some drastic changes not only in our daily lives, but also in our clinical and surgical activities. Given our extensive Italian experience, we hereby describe how our surgical unit activity has changed and how, in some cases, it was necessary to modify surgical strategies. We hope our experience can be shared with our global colleagues who are suffering under similar condition.

Can Surgery for Inflammatory Bowel Disease be Personalized?

BACKGROUND: In the treatment of Inflammatory Bowel Diseases (IBD) despite advances in medical therapies, surgery has maintained a leading role in the management of complications of the disease, as well as in cases of failure of medical therapy. OBJECTIVE: discuss the possible role for a personalization in debated fields of surgical treatment of Crohn's disease and ulcerative colitis. CONCLUSIONS: Surgery has become more and more minimally invasive, struggling for a difficult balance between guidelines and personalized treatment tailored on the single patient's need. There is no room for fixed management for surgery in IBD. A tailored approach is key to better outcome in each specific patient.

Surgical Resection vs. Ablative Therapies Through a Laparoscopic Approach for Hepatocellular Carcinoma: a Comparative Study.

BACKGROUND: When compatible with the liver functional reserve, laparoscopic hepatic resection remains the treatment of choice for hepatocellular carcinoma while laparoscopic ablation therapies appear as a promising less invasive alternative. The aim of the study is to compare two homogeneous groups of patients submitted to either hepatic resection or thermoablation for the treatment of single hepatocellular carcinoma (≤ 3 cm). METHODS: We enrolled 264 cirrhotic patients out of 905 cases consecutively evaluated for hepatocellular carcinoma. We performed 59 hepatic resections and 205 thermoablations through a laparoscopic approach, and they were then followed for similar follow-up (41.7 ± 31.5 months for laparoscopic hepatic resection vs. 38.7±32.3 for laparoscopic ablation therapy). Outcomes included short- and long-term morbidities, tumoral recurrence, and overall survival. RESULTS: Short-term morbidity was significantly higher in the resection group (but the two groups had similar rates for severe complications) while, during follow-up, recurrence was more frequent in patients treated with thermoablation, with a clear disadvantage in terms of survival. At multivariate analysis, only the type of surgical treatment was an independent predictor of disease recurrence, while plasmatic alpha-fetoprotein and Hb values, model for end-stage liver disease score, time to recurrence, and the type of surgical treatment were independent predictors of overall survival. CONCLUSION: Our data ultimately support some therapeutic advantages for hepatic resection in patients with a single nodule and preserved liver function. However, thermoablation is an adequate alternative in patients with nodules that would require complex surgical resections or imply a poor prognosis that might therefore better tolerate a less invasive procedure.

Variations of high frequency parameter of heart rate variability following osteopathic manipulative treatment in healthy subjects compared to control group and sham therapy: randomized controlled trial.

CONTEXT: Heart Rate Variability (HRV) indicates how heart rate changes in response to inner and external stimuli. HRV is linked to health status and it is an indirect marker of the autonomic nervous system (ANS) function. OBJECTIVE: To investigate the influence of osteopathic manipulative treatment (OMT) on cardiac autonomic modulation in healthy subjects, compared with sham therapy and control group. METHODS: Sixty-six healthy subjects, both male and female, were included in the present 3-armed randomized placebo controlled within subject cross-over single blinded study. Participants were asymptomatic adults (26.7 ± 8.4 y, 51% male, BMI 18.5 ± 4.8), both smokers and non-smokers and not on medications. At enrollment subjects were randomized in three groups: A, B, C. Standardized structural evaluation followed by a patient need-based osteopathic treatment was performed in the first session of group A and in the second session of group B. Standardized evaluation followed by a protocoled sham treatment was provided in the second session of group A and in the first session of group B. No intervention was performed in the two sessions of group C, acting as a time-control. The trial was registered on clinicaltrials.gov identifier: NCT01908920. MAIN OUTCOMES MEASURES: HRV was calculated from electrocardiography before, during and after the intervention, for a total amount time of 25 min and considering frequency domain as well as linear and non-linear methods as outcome measures. RESULTS: OMT engendered a statistically significant increase of parasympathetic activity, as shown by High Frequency power (p < 0.001), expressed in normalized and absolute unit, and possibly decrease of sympathetic activity, as revealed by Low Frequency power (p < 0.01); results also showed a reduction of Low Frequency/High Frequency ratio (p < 0.001) and Detrended fluctuation scaling exponent (p < 0.05). CONCLUSIONS: Findings suggested that OMT can influence ANS activity increasing parasympathetic function and decreasing sympathetic activity, compared to sham therapy and control group.