In recent years, a growing number of studies have evaluated the role of exosomes in pancreatic du... more 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 ... more 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... more 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 nic... more 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...
e15511Background: In the last years, availability of active upfront systemic regimens, developmen... more e15511Background: In the last years, availability of active upfront systemic regimens, development of surgical techniques and diffusion of locoregional treatments (LrTx) increased the therapeutic o...
We read with great interest the article by Pugliese et al. entitled “The clinical use of 3D print... more 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 c... more 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 adenocarc... more 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 ... more 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 ... more 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 &amp;amp;quot;difficult&amp;amp;quot; 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 tho... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;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 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Statistically significant reductions in variable and overall costs were found between robotic phases (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;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 Surgica... more 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 lap... more 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-deri... more 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...
In recent years, a growing number of studies have evaluated the role of exosomes in pancreatic du... more 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 ... more 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... more 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 nic... more 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...
e15511Background: In the last years, availability of active upfront systemic regimens, developmen... more e15511Background: In the last years, availability of active upfront systemic regimens, development of surgical techniques and diffusion of locoregional treatments (LrTx) increased the therapeutic o...
We read with great interest the article by Pugliese et al. entitled “The clinical use of 3D print... more 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 c... more 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 adenocarc... more 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 ... more 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 ... more 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 &amp;amp;quot;difficult&amp;amp;quot; 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 tho... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;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 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Statistically significant reductions in variable and overall costs were found between robotic phases (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;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 Surgica... more 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 lap... more 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-deri... more 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...
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