Luca Morelli

In recent years, a growing number of studies have evaluated the role of exosomes in pancreatic ductal adenocarcinoma cancer (PDAC) demonstrating their involvement in a multitude of pathways, including the induction of chemoresistance. The aim of this review is to present an overview of the current knowledge on the role of exosomes in the resistance to gemcitabine and nab-paclitaxel, which are two of the most commonly used drugs for the treatment of PDAC patients. Exosomes are vesicular cargos that transport multiple miRNAs, mRNAs and proteins from one cell to another cell and some of these factors can influence specific determinants of gemcitabine activity, such as the nucleoside transporter hENT1, or multidrug resistance proteins involved in the resistance to paclitaxel. Additional mechanisms underlying exosome-mediated resistance include the modulation of apoptotic pathways, cellular metabolism, or the modulation of oncogenic miRNA, such as miR-21 and miR-155. The current status o...

Background Few studies have reported a structured cost analysis of robotic distal pancreatectomy (RDP), and none have compared the relative costs between the robotic-assisted surgery (RAS) and the direct manual laparoscopy (DML) in this setting. The aim of the present study is to address this issue by comparing surgical outcomes and costs of RDP and laparoscopic distal pancreatectomies (LDP). Methods Eighty-eight RDP and 47 LDP performed between January 2008 and January 2020 were retrospectively analyzed. Three comparable groups of 35 patients each (Si-RDP-group, Xi-RDP group, LDP-group) were obtained matching 1:1 the RDP-groups with the LDP-group. Overall costs, including overall variable costs (OVC) and fixed costs were compared using generalized linear regression model adjusting for covariates. Results The conversion rate was significantly lower in the Si-RDP-group and Xi-RDP-group: 2.9% and 0%, respectively, versus 14.3% in the LDP-group (p = 0.045). Although not statistically s...

Wearable Video See-Through (VST) devices for Augmented Reality (AR) and for obtaining a Magnified View are taking hold in the medical and surgical fields. However, these devices are not yet usable in daily clinical practice, due to focusing problems and a limited depth of field. This study investigates the use of liquid-lens optics to create an autofocus system for wearable VST visors. The autofocus system is based on a Time of Flight (TOF) distance sensor and an active autofocus control system. The integrated autofocus system in the wearable VST viewers showed good potential in terms of providing rapid focus at various distances and a magnified view.

Background: SDF-1/CXCL12 is a chemokine with pleiotropic functions in hematopoietic stem cell niche homeostasis, germinal center architecture, B cell maturation, neoangiogenesis, and fibrosis. Recently, the CXCL12/CXCR4/CXCR7 axis was associated with cancer metastasis and autoimmune diseases. The IgG4-related disease (IgG4-RD) is a pathological condition characterized by IgG4+ plasma cells infiltrating fibrotic lesions. The aim of this research is to investigate the relevance of SDF-1/CXCL12 in IgG4-RD.Materials and Methods: Peripheral blood samples were collected before therapy from a single-center cohort of 28 IgG4-RD patients, fulfilling the ACR-EULAR classification criteria. Clinical and serological data were obtained for each patient. In total, 14 healthy donors (NHS), 9 patients with pancreatic ductal adenocarcinoma (PDAC), and 9 with Sjogren syndrome (SSj) were recruited as controls and screened for circulating SDF-1/CXCL12 by ELISA. Moreover, paraffin-embedded pancreatic bio...

We read with great interest the article by Pugliese et al. entitled “The clinical use of 3D printing in surgery” recently published by Updates in Surgery [1]. In the past years, 3D printing has seen an almost exponential growth in several fields, including medicine and surgery, as testified by the increasing number of published articles. This success was fostered by technological progresses on manufacturing processes allowing to build layer by layer 3D objects at higher resolution. In surgery, knowledge of patient anatomy has traditionally been based on analysis of 2D radiological images. The advent of computer-assisted surgery has improved the understanding of patients’ anatomy in the preoperative phase, including complex cases, enabling reconstruction of virtual 3D models starting from radiological datasets, which can be viewed on computer screens. 3D printing pushes further comprehension of anatomy allowing surgeons to touch and feel a physical model, complementing visual with tactile feedback. The authors present the role of 3D printing for preoperative planning and intraoperative navigation in several surgical specialties, particularly in general and transplantation surgery, neurosurgery, and maxillofacial surgery [1]. Authors also comment how the most recent advances in the manufacturing process enable 3D printing of deformable and hollow structures such as vessels, allowing physical simulation of vessels clamping, stapling, and anastomosis, thus extending the use of this technology to vascular surgery. In this regard, we think that this technology could have a great impact in (endo)vascular surgeons’ training for two main reasons. First, 3D printing could be particularly important for endovascular procedures which represent a radically new way to operate for vascular surgeons, in comparison with the open air or laparoscopic approach. Indeed, during endovascular procedures, e.g., endovascular aneurysm repair (EVAR), the surgeon deals with a closed abdomen, with limited information of vascular anatomy obtained by preoperative angiogram imaging (CTA) and intraoperative angiographic images visualized on the monitors [2]. Thus, the surgeon has no direct contact with the aorta, its branches, the aneurysm, and surrounding structures. Therefore, for these procedures the capacity to mentally reconstruct the vascular anatomy starting from CTA images is of paramount importance. In this scenario, the use of 3D models could lead to a revolution for planning, and probably, above all, for training young surgeons approaching endovascular procedures. In fact, thanks to the physical reproduction of a patient-specific model, it is possible to better understand the patient’s anatomy in the preoperative stage; to accurately identify the location of key elements, such as the aortic landing zones and the side of a penetrating ulcer or intimal tear; and to define type, length, and oversizing of the endograft, thus reducing the risk of periprocedural complications [3]. Last but not least, the surgeon can rehearse the endovascular procedure before performing it on real patient to reduce the time of the procedure and the use of radiopaque contrast, thus decreasing the renal function insult, especially in patients with kidney failure; and the use of radiation, shortening the exposure of patient and staff to its hazardous effect [3]. However, because of the exponential adoption of the endovascular surgery, we are concerned that young vascular surgeons may become less familiar with treatment of open aortic aneurysm repair. This might eventually lead to the paradox that in the future only the most complex cases of aneurysm repair, such as ruptured aneurysms or those including multi-visceral vessels origins, may be treated with open surgery by non-experienced surgeons [4]. For these * Andrea Moglia andrea.moglia@endocas.org

The growing waiting lists for pancreas transplantation for the United States and Eurotransplant countries reflect the critical need for new strategies for the management of patients affected by type 1 diabetes mellitus. As with solid organs, the extension of the donor selection criteria for pancreas transplantation was proposed in the last decades, but only few studies have been published about this issue to date. Initially, donor age of 45 years or more was considered a relative contraindication for pancreas transplantation; however, a study in 2005 was one of the first studies reporting extended donor criteria using donors with a mean age >45 year. The 1and 5-year survival rates of patients (87.5% at both time points) and grafts (81.2% and 67.7%, respectively), were comparable to the current literature data, underlining the importance of an appropriate general donor assessment evaluation more than the age alone. A local allocation policy to reduce the ischemia time continues to play a pivotal role in this context. After more than 10 years, the prospective EXPAND study by Proneth et al confirmed these results, achieving a 1-year graft survival rate of 83.3% after transplants using extended donor criteria on age (between 50 and 60), which was equal to the rate attained using standard criteria (83.5%) with donor age averaging 31.7 years. These results can give a new impulse to the application of donor extension criteria for pancreas transplantation. Due to the delicate nature of diabetic patients and pancreas graft, which are prone to complications and long-term high failure rate, it is important to obtain the 5-year results. We think that these data would be crucial to establish if an extended pancreas deceased donors’ program could represent the best option to increase life expectancy and improve the quality of life for many patients with juvenile diabetes. Although the level of evidence of data reported in this work is stronger in respect to previous ones because it is the first prospective multicenter study on this issue, the clinical outcomes are not different from the past. This is in contrast to what we would have expected, considering the progress of surgical technique and of immunosuppressant therapies in the last years. Other strategies such as islet transplantation and living donor pancreas transplantation have been recently improved, amplifying the question of which option really represents the best way to shorten the waiting lists for pancreas transplantation The continuously growing demand of pancreas transplantation and the concomitant lack of ideal donors induce surgeons and clinicians to make more and more efforts to find new strategies to shorten the waiting lists. The question of whether the extension of the donor criteria for solid organ transplantations represents the best option to follow today remains an unsolved question.

Among the several new targets for the comprehension of the biology of pancreatic ductal adenocarcinoma (PDAC), Prion proteins (PrPc) deserve particular mention, since they share a marked neurotropism. Actually, PrPc could have also a role in tumorigenesis, as recently demonstrated. However, only few in vitro studies in cell cultures showed the occurrence of PrPc in PDAC cells. We aim to evaluate the presence of PrPc in vivo in PDAC tissues as a potential new biomarker. Samples from tumors of 23 patients undergone pancreatic resections from July 2018 to May 2020 at our institution were collected and analyzed. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrPc and of CD155, a tumoral stem-cell marker. All cases were moderately differentiated PDAC, with perineural invasion (PNI) in 19/23 cases (83%). According to western-blot analysis, PrPc was markedly expressed in PDAC tissues (273.5 ± 44.63 OD) respect to controls (100 ± 28.35 OD, p = 0.0018). Immunohistochemistry confirmed these findings, with higher linear staining of PrPc in PDAC ducts (127.145 ± 7.56 μm vs 75.21 ± 5.01 μm, p < 0.0001). PrPc and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrPc with cancer stemness. Finally, PrPc expression related with cancer stage and there was a potential correspondence with PNI. Our work provides evidence for increased levels of PrPc in PDAC. This might contribute to cancer aggressiveness and provides a potentially new biomarker. Work is in progress to decipher clinical implications.

BACKGROUND Gray scale ultrasound (US), Doppler and Contrast Enhanced Ultrasound (CEUS) represent important surveillance tools in the early post-operative period after pancreas transplantation (PTx), when complications are more common. This review summarizes the available evidence on their clinical application in this setting. METHODS We searched the Pub-Med database from inception to October 2018 for English literature on the clinical use of US, Doppler and CEUS in the post-PTx surveillance. Article selection was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria (PRISMA). RESULTS Twenty-nine articles concerning the clinical applications of US, Doppler and CEUS were identified, 13 of which, involving 264 patients, were focused on the sonographic findings in immunologic rejection, whereas 11 studies reporting on 887 patients were focused on post-PTx vascular complications. The remaining five articles, involving a total of 196 patients, described US or CEUS applied in the study of pancreatic morphology and texture to diagnose peri-graft fluids collections or to obtain experimental data on allograft endocrine function. CONCLUSIONS US, Doppler and CEUS have proven to be valuable assets in post-PTx follow up, thanks to the combination of their non-invasiveness with a high accuracy in the detection of early abnormalities, in particular regarding vascular complications. Preliminary experiences are directing towards functional research; however, future prospective trials are necessary to precisely correlate organ perfusion, early abnormalities and allograft function.

The treatment of pancreatic stump is a critical step of pancreatoduodenectomy (PD) because leaks from this anastomosis incur major morbidity and mortality. We describe the technical details of a modified end-to-side pancreatojejunostomy (mPJ), and report on the outcome of the first 100 patients. From October 2008 to June 2017, 424 pancreatic resections were performed, of which 203 were PD. The mPJ was introduced in November 2010 and used in 100 consecutive patients, by a single surgeon. Data were retrieved from a prospectively collected Institutional database, and used for the present retrospective evaluation. Post-operative pancreatic fistulas (POPF) were stratified with the Fistula Risk Score (FRS), based on the 2005-International Study Group of Pancreatic Fistula classification (ISGPFc) and on the subsequent 2016-revised version (ISGPSc). ISGPFc POPF occurred in 17/100 (17%): grade A in 10/100 (10%), grade B in 6/100 (6%) and grade C in 1/100 (1%). On the ISGPSc, POPF rate averaged 7%: grade B in 6/100 (6%) and grade C in 1/100 (1%). POPF rate associated with high FRS was 18.8%/6.3% (ISGPFc/ISGPSc). With low and intermediate FRS, POPFs were 5.3%/0% (ISGPFc/ISGPSc) and 21.3%/9.8% (ISGPFc/ISGPSc) respectively. Re-operation rate was 3%. In-hospital mortality rate was 2% and specific mortality rate for POPF was 1%. The mPJ technique is associated with a POPF rate which was less than expected, especially for "difficult" pancreas with high FRS (soft gland texture and small duct). A larger prospective series is needed in addition to comparative studies with other techniques for robust assessment.

The aim of this study is to compare surgical parameters and the costs of robotic surgery with those of laparoscopic approach in rectal cancer based on a single surgeon's early robotic experience. Data from 25 laparoscopic (LapTME) and the first 50 robotic (RobTME) rectal resections performed at our institution by an experienced laparoscopic surgeon (>100 procedures) between 2009 and 2014 were retrospectively analyzed and compared. Patient demographic, procedure, and outcome data were gathered. Costs of the two procedures were collected, differentiated into fixed and variable costs, and analyzed against the robotic learning curve according to the cumulative sum (CUSUM) method. Based on CUSUM analysis, RobTME group was divided into three phases (Rob1: 1-19; Rob2: 20-40; Rob3: 41-50). Overall median operative time (OT) was significantly lower in LapTME than in RobTME (270 vs 312.5 min, p = 0.006). A statistically significant change in OT by phase of robotic experience was detected in the RobTME group (p = 0.010). Overall mean costs associated with LapTME procedures were significantly lower than with RobTME (p < 0.001). Statistically significant reductions in variable and overall costs were found between robotic phases (p < 0.009 for both). With fixed costs excluded, the difference between laparoscopic and Rob3 was no longer statistically significant. Our results suggest a significant optimization of robotic rectal surgery's costs with experience. Efforts to reduce the dominant fixed cost are recommended to maintain the sustainability of the system and benefit from the technical advantages offered by the robot.

Dear Editor: Integrated Table Motion (ITM) for the da Vinci Xi surgical system (Intuitive Surgical Inc., Sunnyvale, CA, USA) is a new feature comprising a unique operating table by Trumpf Medical Systems that communicates wirelessly with the da Vinci Xi. The ITM feature allows surgical staff to reposition the patient without undocking the robot and without removing instruments from inside the abdomen. The da Vinci Xi surgical system and the TruSystem 7000dV operating table (TS7000dV, TRUMPF Medizin Systeme GmbH & Co. KG, Saalfeld, Germany) have been specifically developed to address some technical limitations of the da Vinci Si surgical system, and to improve multiquadrant robotic surgery. An important drawback during robotic procedures with the previous da Vinci Si system is the inability to move the table position with the robotic arms docked. This problem may be particularly amplified in multiquadrant operations, such as colorectal surgery, in which the patient and the robot itself need to be rearranged several times to optimally achieve different surgical targets or provide patient relief. Herein, we present the first study on human use of this device in colorectal surgery. The purpose of this study was to evaluate the efficacy, feasibility, and safety of ITM for the da Vinci Xi system in performing robotic colorectal resections. Between May and October 2015, the first human use of ITMwas carried out in a post-market study in the EU in which 40 cases from different specialties (general surgery, urology, or gynecology) were prospectively enrolled. The Ethics Committee of our institution approved this study. Patients who planned to undergo minimally invasive surgery within the specialties of general surgery, urology, or gynecology with the commercially available da Vinci Xi surgical system and who were eligible based on the inclusion and exclusion criteria of this study were offered enrolment. Study-specific informed consent was obtained in writing from each patient before any procedure specific to the clinical investigation was performed. Inclusion criteria were as follows: bodymass index ≤45 kg/ m; age 18 years or older; suitable for minimally invasive surgery; undergoing a surgical procedure in urology, gynecology, or general surgery; ability to tolerate the Trendelenburg position; willingness to participate as demonstrated by giving written informed consent. Exclusion criteria were as follows: American Society of Anesthesiologists (ASA) IV patients; pregnancy; lack of cooperation due to psychological or severe systemic illness; comorbid medical conditions contraindicating general anesthesia or standard surgical approaches; vulnerable population (such as prisoners, mentally disabled); anatomy unsuitable for endoscopic visualization or minimally invasive surgery; extensive previous abdominal surgery; patient not Study supported by the ARPA foundation, www.fondazionearpa.it

The STAR System (Ekymed SpA) is a novel multipurpose sponge developed for conventional manual laparoscopic surgery. Between December 2012 and December 2014, we successfully used the sponge in ten robot-assisted and ten direct manual laparoscopic operations to achieve haemostasis, for blunt dissections, for atraumatic lifting of solid organs, to check for bile leaks, for cleaning the surgical field thus avoiding frequent use of suction or the application of haemostatic agents. The reason of the insertion (RI), the main use (MU) and any further use (FU), once inserted, were registered for each operation and compared between the two groups. The principal RI was haemostasis for minor bleeding, without differences between the two groups (P = not significant). Regard to MU, in the robotic group cleaning the surgical field was utilised more than laparoscopic group (100% vs. 60%; P = 0.03). About FU, atraumatic solid organs lifting was more frequent during robotically assisted surgery than with laparoscopy (50% vs. 0%; P = 0.01). A statistically more frequent use of the sponge was registered during standard laparoscopy for the blunt dissection (30% vs. 80%; P = 0.03). The STAR System was beneficial in both approaches, but it imparts added benefit during robotically-assisted laparoscopic surgery organs because of the lack of tactile feedback and because the operating surgeon is remote from the patient, and has to rely on the assisting surgeon in the sterile field for dealing with bleeding episodes, cleansing/mopping the operative field when necessary, who may not be experienced or completely proficient.

Simple Summary Treating the PDAC (pancreatic ductal adenocarcinoma) zPDXs (zebrafish patient-derived xenografts) with chemotherapy regimens commonly used, we performed a co-clinical trial testing the predictiveness of the model. We found that zPDX may predict patient outcomes, classifying them into responders (R) and non-responders (NR), reporting a statistically significant higher cancer recurrence rate at 1 year after surgery in the NR group: 66.7 versus 14.3%. Our zPDX model seems to be a promising tool for the stratification of PDAC patients. This is a crucial starting point for future study involving more patients to obtain a method to really personalize the oncological treatment of PDAC patients. Abstract It is increasingly evident the necessity of new predictive tools for the treatment of pancreatic ductal adenocarcinoma in a personalized manner. We present a co-clinical trial testing the predictiveness of zPDX (zebrafish patient-derived xenograft) for assessing if patients c...

BACKGROUND Recent evidences have shown a relationship between prion protein (PrPc) expression and pancreatic ductal adenocarcinoma (PDAC). Indeed, PrPc could be one of the markers explaining the aggressiveness of this tumor. However, studies investigating the specific compartmentalization of increased PrPc expression within PDAC cells are lacking, as well as a correlation between ultrastructural evidence, ultrastructural morphometry of PrPc protein and clinical data. These data, as well as the quantitative stoichiometry of this protein detected by immuno-gold, provide a significant advancement in understanding the biology of disease and the outcome of surgical resection. AIM To analyze quantitative stoichiometry and compartmentalization of PrPc in PDAC cells and to correlate its presence with prognostic data METHODS Between June 2018 and December 2020, samples from pancreatic tissues of 45 patients treated with pancreatic resection for a preoperative suspicion of PDAC at our Institution were collected. When the frozen section excluded a PDAC diagnosis, or the nodules were too small for adequate sampling, patients were ruled out from the present study. Western blotting was used to detect, quantify and compare the expression of PrPc in PDAC and control tissues, such as those of non-affected neighboring pancreatic tissue of the same patient. To quantify the increase of PrPc and to detect the subcellular compartmentalization of PrPc within PDAC cells, immuno-gold stoichiometry within specific cell compartments was analyzed with electron microscopy. Finally, an analysis of quantitative PrPc expression according to prognostic data, such as cancer stage, recurrence of the disease at 12 mo after surgery and recurrence during adjuvant chemotherapy was made. RESULTS The amount of PrPc within specimen from 38 out of 45 patients was determined by semi-quantitative analysis by using Western blotting, which indicates that PrPc increases almost three-fold in tumor pancreatic tissue compared with healthy pancreatic regions [242.41 ± 28.36 optical density (OD) vs 95 ± 17.40 OD, P < 0.0001]. Quantitative morphometry carried out by using immuno-gold detection at transmission electron microscopy confirms an increased PrPc expression in PDAC ductal cells of all patients and allows to detect a specific compartmentalization of PrPc within tumor cells. In particular, the number of immuno-gold particles of PrPc was significantly higher in PDAC cells respect to controls, when considering the whole cell (19.8 ± 0.79 particles vs 9.44 ± 0.45, P < 0.0001). Remarkably, considering PDAC cells, the increase of PrPc was higher in the nucleus than cytosol of tumor cells, which indicates a shift in PrPc compartmentalization within tumor cells. In fact, the increase of immuno-gold within nuclear compartment exceeds at large the augment of PrPc which was detected in the cytosol (nucleus: 12.88 ± 0.59 particles vs 5.12 ± 0.32, P < 0.0001; cytosol: 7.74. ± 0.44 particles vs 4.3 ± 0.24, P < 0.0001). In order to analyze the prognostic impact of PrPc, we found a correlation between PrPc expression and cancer stage according to pathology results, with a significantly higher expression of PrPc for advanced stages. Moreover, 24 patients with a mean follow-up of 16.8 mo were considered. Immuno-blot analysis revealed a significantly higher expression of PrPc in patients with disease recurrence at 12 mo after radical surgery (360.71 ± 69.01 OD vs 170.23 ± 23.06 OD, P = 0.023), also in the subgroup of patients treated with adjuvant CT (368.36 ± 79.26 OD in the recurrence group vs 162.86 ± 24.16 OD, P = 0.028), which indicates a correlation with a higher chemo-resistance. CONCLUSION Expression of PrPc is significantly higher in PDAC cells compared with control, with the protein mainly placed in the nucleus. Preliminary clinical data confirm the correlation with a poorer prognosis.

Background: Pancreatic metastases from renal-cell carcinoma (RCC-PMs) are rare. Surgery may play a role in improving overall (OS) and disease-free survival (DFS). Methods: Clinical-pathological features, surgery and follow-up data of patients with RCC-PMs operated on in three pancreatic surgical centers (2000–2019) were retrospectively evaluated. Results: Thirty-nine patients (21 male/18 female, averaging 65 years) were enrolled. RCC-PMs were metachronous in 36 patients (mean 94 months, up to 24 years after nephrectomy), multiple in 21 patients, and with a median size of 2.5 (range, 0.7–7.5) cm. All the patients underwent pancreatic surgery (33 standard resections, 6 limited resections). Fifteen patients had post-operative complications (morbidity 38.5%). The median DFS was 63 months, and 19 out of 36 patients showed a disease recurrence. The median OS was 134 months, and 13 out of 36 patients were alive with no evidence of disease. At univariate analysis, lymph node positivity (HR ...

Cellular prion protein (PrPC) is seminal to modulate a variety of baseline cell functions to grant homeostasis. The classic role of such a protein was defined as a chaperone-like molecule being able to rescue cell survival. Nonetheless, PrPC also represents the precursor of the deleterious misfolded variant known as scrapie prion protein (PrPSc). This variant is detrimental in a variety of prion disorders. This multi-faceted role of PrP is greatly increased by recent findings showing how PrPC in its folded conformation may foster tumor progression by acting at multiple levels. The present review focuses on such a cancer-promoting effect. The manuscript analyzes recent findings on the occurrence of PrPC in various cancers and discusses the multiple effects, which sustain cancer progression. Within this frame, the effects of PrPC on stemness and differentiation are discussed. A special emphasis is provided on the spreading of PrPC and the epigenetic effects, which are induced in neigh...

Pancreatic ductal adenocarcinoma (PDAC) is traditionally associated with thrombocytosis/hypercoagulation and novel insights on platelet-PDAC “dangerous liaisons” are warranted. Here we performed an integrative omics study investigating the biological processes of mRNAs and expressed miRNAs, as well as proteins in PDAC blood platelets, using benign disease as a reference for inflammatory noise. Gene ontology mining revealed enrichment of RNA splicing, mRNA processing and translation initiation in miRNAs and proteins but depletion in RNA transcripts. Remarkably, correlation analyses revealed a negative regulation on SPARC transcription by isomiRs involved in cancer signaling, suggesting a specific ”education” in PDAC platelets. Platelets of benign patients were enriched for non-templated additions of G nucleotides (#ntaG) miRNAs, while PDAC presented length variation on 3′ (lv3p) as the most frequent modification on miRNAs. Additionally, we provided an actionable repertoire of PDAC an...

Purpose Robotic assistance could increase the rate of ileo-colic intra-corporeal anastomosis (ICA) during robotic right colectomy (RRC). However, although robotic ICA can be accomplished with several different technical variants, it is not clear whether some of these technical details should be preferred. An evaluation of the possible advantage of one respect to another would be useful. Methods We conducted a systematic review of literature on technical details of robotic ileo-colic ICA, from which we performed a meta-analysis of clinical outcomes. The extracted data allowed a comparative analysis regarding the outcome of overall complication (OC), bleeding rate (BR) and leakage rate (LR), between (1) mechanical anastomosis with robotic stapler, versus laparoscopic stapler, versus totally hand-sewn anastomosis and (2) closure of enterocolotomy with manual double layer, versus single layer, versus stapled. Results A total of 30 studies including 2066 patients were selected. Globally,...

Background The treatment of the pancreatic stump is a critical step of pancreatoduodenectomy (PD). Robot-assisted surgery (RAS) can facilitate minimally invasive challenging abdominal procedures, including pancreatojejunostomy. However, one of the major limitations of RAS stems from its lack of tactile feedback that can lead to pancreatic parenchyma laceration during knot tying or during traction on the suture. Moreover, a Wirsung-jejunostomy is not always easy to execute, especially in cases with small diameter duct. Herein, we describe and video-report the technical details of a robotic modified end-to-side invaginated robotic pancreatojejunostomy (RmPJ) with the use of barbed suture instead of the “classical” Wirsung-jejunostomy. Methods The RmPJ technique consists of a double layer of absorbable monofilament running barbed suture (3–0 V-Loc), the outer layer is used to invaginate the pancreatic stump. Thereafter, a small enterotomy is made in the jejunum exactly opposite to the ...

Total pancreatectomy (TP) is a highly invasive procedure often performed in patients affected by anorexia, malabsorption, cachexia, and malnutrition, which are risk factors for bad surgical outcome and even may cause enhanced toxicity to chemo-radiotherapy. The role of nutritional therapies and the association between nutritional aspects and the outcome of patients who have undergone TP is described in some studies. The aim of this comprehensive review is to summarize the available recent evidence about the influence of nutritional factors in TP. Preoperative nutritional and metabolic assessment, but also intra-operative and post-operative nutritional therapies and their consequences, are analyzed in order to identify the aspects that can influence the outcome of patients undergoing TP. The results of this review show that preoperative nutritional status, sarcopenia, BMI and serum albumin are prognostic factors both in TP for pancreatic cancer to support chemotherapy, prevent recurr...

Purpose This study evaluated the controversial role of somatostatin after pancreatoduodenectomy (PD), stratifying patients for the main risk factors using the most recent postoperative pancreatic fistula (POPF) classification and including only patients who had undergone PD with the same technique of pancreatojejunostomy. Methods Between November 2010 and February 2020, 218 PD procedures were carried out via personal modified pancreatojejunostomy (mPJ-PD). Somatostatin was routinely administered between 2010 and 2016, while from 2017, 97 mPJ-PD procedures without somatostatin (WS) were performed. The WS group was retrospectively compared with a control (C) group obtained with one-to-one case–control matching according to the body mass index, American Society of Anesthesiologists’ score, and Fistula Risk Score (FRS). Results A total of 144 patients (72 WS group versus 72 C group) were compared. In the WS group. 6 patients (8.3%) developed clinically relevant POPF, compared with 8 pat...

Animal “avatars” and co-clinical trials are being developed for possible use in personalized medicine in oncology. In a co-clinical trial, the cancer cells of the patient’s tumor are xenotransplanted into the animal avatar for drug efficacy studies, and the data collected in the animal trial are used to plan the best drug treatment in the patient trial. Zebrafish have recently been proposed for implementing avatar models, however the lack of a general criterion for the chemotherapy dose conversion from humans to fish is a limitation in terms of conducting co-clinical trials. Here, we validate a simple, reliant and cost-effective avatar model based on the use of zebrafish embryos. By crossing data from safety and efficacy studies, we found a basic formula for estimating the equivalent dose for use in co-clinical trials which we validated in a clinical study enrolling 24 adult patients with solid cancers (XenoZ, NCT03668418).

Purpose. To investigate the oncological outcome and survival of patients following a conservative approach on the portal-mesenteric axis, in an intraoperative ultrasound-selected group of pancreatoduodenectomy (PD), performed on patients with primary resectable with vascular contact (prVC) pancreatic ductal adenocarcinoma (PDAC). Methods. A consecutive series of patients who underwent PD for PDAC at our tertiary care center, between 2008 and 2017, were reviewed. A total of 156 PDs and 88 total pancreatectomies were performed during the study period, including 35 vascular resections. We identified a group of 40 (25.6%) patients with prVC-PDAC in whom after checking the feasibility with intraoperative ultrasound, we were able to perform PD by separation of the tumor from the portomesenteric axis avoiding vascular resection, without residual macroscopic disease (no vascular resection, nvrPD), and compared this group, using case-matched methodology, with the standard PD (sPD) group of p...

Robotic-assisted surgery by the da Vinci Si appears to benefit rectal cancer surgery in selected patients, but still has some limitations, one of which is its high costs. Preliminary studies have indicated that the use of the new da Vinci Xi provides some added advantages, but their impact on cost is unknown. The aim of the present study is to compare surgical outcomes and costs of rectal cancer resection by the two platforms, in a single surgeon's experience. From April 2010 to April 2017, 90 robotic rectal resections were performed, with either the da Vinci Si (Si-RobTME) or the da Vinci Xi (Xi-RobTME). Based on CUSUM analysis, two comparable groups of 40 consecutive Si-RobTME and 40 consecutive Xi-RobTME were obtained from the prospectively collected database and used for the present retrospective comparative study. Data costs were analysed based on the level of experience on the proficiency-gain curve (p-g curve) by the surgeon with each platform. In both groups, two homogen...

Cystic pancreatic lesions (CPLs) are being identified increasingly, and some benefit from surgical treatment. With the increasing use of robotic-assisted surgery (RAS) for neoplasms of the pancreas, the aim of the present comparative study is to establish whether the RAS offered any advantages over conventional open surgery (OS) in the management of CPLs. Twenty-seven out of 37 robot-assisted left-sided pancreatectomy (LSP) performed between January 2010 and April 2017 were carried out for CPLs. The surgical outcome and histopathology were compared retrospectively with a control group of 27 patients who had undergone open LSP for CPLs, selected using a one-to-one case-matched methodology (OS-Group) from the prospectively collected institutional database. The spleen was preserved in a significantly higher percentage of patients in the RAS-group (63% vs. 33.3%, P< 0.05). There was no difference in the post-operative course (pancreatic fistula and morbidity) between the two groups. ...

Proficiency-based training has become essential in the training of surgeons such that on completion they can execute complex operations with novel surgical approaches including direct manual laparoscopic surgery (DMLS) and robotically assisted laparoscopic surgery (RALS). To this effect, several virtual reality (VR) simulators have been developed. The objective of the present study was to assess and establish proficiency gain curves for medical students on VR simulators for DMLS and RALS. Five medical students participated in training course consisting of didactic teaching and practical hands-on training with VR simulators for DMLS and RALS. Evaluation of didactic component was by questionnaire completed by participating students, who also were required to undertake selected exercises to reach proficiency at each VR simulator: (1) 12 tasks on LapSim VR (Surgical Science, Gothenburg, Sweden) for DMLS, and (2) six selected exercises on the dV-Trainer Mimic (Seattle, WA, United States)...

Invasive aspergillosis (IA) represents a major cause of morbidity and mortality in immunocompromised patients. Involvement of the gastrointestinal tract by Aspergillus is mostly reported as part of a disseminated infection from a primary pulmonary site and only rarely as an isolated organ infection. We report a case of small bowel perforation due to IA in a patient with acute leukemia under chemotherapy and pulmonary aspergillosis. We performed a systematic review of the literature as well. A 43-year-old man with acute myeloid leukemia under chemotherapy developed severe neutropenia and pulmonary aspergillosis due to Aspergillus flavus. He developed melena and hemodynamic failure and a contrast-enhanced ultrasound scan suggested active intestinal bleeding. During emergency laparotomy we found multiple intestinal abscesses, several perforations of intestinal loop and Aspergillus flavus was isolated from the abscesses. Resection of the jejunum was performed. The patient received voric...

The da Vinci Table Motion (dVTM) is a new device that enables patients to be repositioned with instruments in place within the abdomen, and without undocking the robot. The present study was designed to compare operative and short-term outcomes of patients undergoing colorectal cancer surgery with the da Vinci Xi system, with or without use of the dVTM. Ten patients underwent robotic colorectal resection for cancer with the use of dVTM (Xi-dVTM group) between May 2015 and October 2015 at our center. The intraoperative and short-term clinical outcome were compared, using a case-control methodology (propensity scores approach to create 1:2 matched pairs), with a similar group of patients who underwent robotic colorectal surgery for cancer without the use of the dVTM device (Xi-only group). Overall robotic operative time was shorter in the Xi-dVTM group ( P = .04). Operations were executed fully robotic in all Xi-dVTM cases, while 2 cases of the Xi-only group required conversion to ope...

The role of minimally invasive surgery of gastrointestinal stromal tumours (GISTs) of the stomach remains uncertain especially for large and/or difficult located tumours. We are hereby presenting a single-centre series of robot-assisted resections using the da Vinci Surgical System (Si or Xi). Data of patients undergoing robot-assisted treatment of gastric GIST were retrieved from the prospectively collected institutional database and a retrospective analysis was performed. Patients were stratified according to size and location of the tumour. Difficult cases (DCs) were considered for size if tumour was> 50 mm and/or for location if the tumour was Type II, III or IV sec. Privette/Al-Thani classification. Between May 2010 and February 2017, 12 consecutive patients underwent robot-assisted treatment of GIST at our institution. DCs were 10/12 cases (83.3%), of which 6/10 (50%) for location, 2/10 (25%) for size and 2/10 (25%) for both. The da Vinci Si was used in 8 patients, of which...

A new robotic stapler for the da Vinci Xi is directly controlled by the surgeon at the console and equipped with EndoWrist technology. We evaluated operative and short-term results of the first patients who underwent anterior rectal resection for cancer with the da Vinci Xi and new staplers, and compared the results with those of a comparable group treated with traditional laparoscopic staplers. From December 2015 to December 2017, 25 patients underwent anterior rectal resection for cancer with robotic EndoWrist staplers (EndoWrist group). Using a case-control method, we compared the results with those of a similar group of patients treated with the same system and a traditional laparoscopic endostapler, controlled by a bedside assistant (Control group). No conversions to laparoscopy or laparotomy were observed, in either group. The mean number of charges was 2.1 ± 0.2 in the EndoWrist group versus 2.7 ± 0.7 in the Control group (P = .0004). The other perioperative results were comp...

There is an increasing interest for a test assessing objectively the innate aptitude for surgery as a craft specialty to complement the current selection process of surgical residents. The aim of this study was to quantify the size of individuals with high, average, and low level of innate psychomotor skills among medical students. A volunteer sample of 155 medical students, without prior experience with surgical simulator, executed five tasks at a virtual simulator for robot-assisted surgery. They had to reach proficiency twice consecutively in each before moving to the next one. A weighting based on time and number of attempts needed to reach proficiency was assigned to each task. Nine students (5.8%) out of 155 significantly outperformed all the others on median (i.q.r.) weighted time [44.7 (42.2-47.3) min vs. 98.5 (70.8-131.8) min, p < 0.001], and number of attempts to reach proficiency [14 (12-15) vs. 23 (19-32.75), p < 0.001). Seventeen students (11.0%) scored significan...

Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs. We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials. Both major histopathologic response (tumour regression grade TRG1-2, 32 vs 14%, p = 0.013) and infarct-like necrosis...