Paolo Magistri

Duodenopancreatectomy: open or minimally invasive approach?

BACKGROUND Minimally invasive pancreaticoduodenectomy (MIPD) is a complex procedure, offered to selected patients at institutions highly experienced with the procedure. It is still not clear if this approach may enhance patient recovery and reduce postoperative complications comparing to open pancreaticoduodenectomy (OPD), as demonstrated for other abdominal procedures. METHODS A systematic literature review was conducted to identify studies comparing MIPD and OPD. Perioperative outcomes (e.g., morbidity and mortality, pancreatic fistula rates, blood loss) constituted the study end points. Metaanalyses were performed using a random-effects model. RESULTS For the metaanalysis, 8 studies including 204 patients undergoing MIPD and 419 patients undergoing OPD were considered suitable. The patients in the two groups were similar with respect to age, sex and histological diagnosis, and different with respect to tumor size, rate of pylorus preservation, and type of pancreatic anastomosis. There were no statistically significant differences between MIPD and OPD regarding development of delayed gastric emptying (DGE), pancreatic fistula, wound infection, or rates of reoperation and overall mortality. MIDP resulted in lower post-operative complication rates, less intra-operative blood loss, shorter hospital stays, lower blood transfusion rates, higher numbers of harvested lymph nodes, and improved negative margin status rates. However, MIPD was associated with longer operating times when compared to OPD. CONCLUSIONS The MIPD procedure is feasible, safe, and effective in selected patients. MIPD may have some potential advantages over OPD, and should be performed and further developed by use in selected patients at highly experienced medical centers.

Log Odds of Positive Lymph Nodes (LODDS): What Are Their Role in the Prognostic Assessment of Gastric Adenocarcinoma?

BackgroundNodal status is an important prognostic factor for patients with gastric cancer. Log odds of positive nodes (LODDS) (log of the ratio between the number of positive nodes and the number of negative nodes) are a new effective indicator of prognosis. The aim of the study is to evaluate if LODDS are superior to N stage and lymph nodal ratio (LNR).MethodsPrognostic efficacy of pN, nodal ratio, and LODDS was analyzed and compared in a group of 177 patients with gastric adenocarcinoma who underwent curative gastrectomy.ResultspT, pN, LNR, and LODDS were all significantly correlated with 5-year survival. Multivariate analyses showed significant values as prognostic factor for pN, LNR, and LODDS. A Pearson test demonstrated no significant correlation between LODDS and retrieved nodes. In patients with less than 15 examined nodes, LODDS classification and pN were significantly correlated with survival, whereas LNR classification was not significantly related.ConclusionsLODDS are not correlated with the extension of the lymphadenectomy and are able to predict survival even if less than 15 nodes are examined. They permit an effective prognostic stratification of patients with a nodal ratio approaching 0 and 1. Further studies are needed to clarify their role and if they are capable of guaranteeing some advantages over pN and LNR.

Robotic right colectomy: A worthwhile procedure? Results of a meta-analysis of trials comparing robotic versus laparoscopic right colectomy

Background: Robotic right colectomy (RRC) is a complex procedure, offered to selected patients at institutions highly experienced with the procedure. It is still not clear if this approach is worthwhile in enhancing patient recovery and reducing post-operative complications, compared with laparoscopic right colectomy (LRC). Literature is still fragmented and no meta-analyses have been conducted to compare the two procedures. This work aims at reducing this gap in literature, in order to draw some preliminary conclusions on the differences and similarities between RRC and LRC, focusing on short-term outcomes. Materials and Methods: A systematic literature review was conducted to identify studies comparing RRC and LRC, and meta-analysis was performed using a random-effects model. Peri-operative outcomes (e.g., morbidity, mortality, anastomotic leakage rates, blood loss, operative time) constituted the study end points. Results: Six studies, including 168 patients undergoing RRC and 348 patients undergoing LRC were considered as suitable. The patients in the two groups were similar with respect to sex, body mass index, presence of malignant disease, previous abdominal surgery, and different with respect to age and American Society of Anesthesiologists score. There were no statistically significant differences between RRC and LRC regarding estimated blood loss, rate of conversion to open surgery, number of retrieved lymph nodes, development of anastomotic leakage and other complications, overall morbidity, rates of reoperation, overall mortality, hospital stays. RRC resulted in significantly longer operative time. Conclusions: The RRC procedure is feasible, safe, and effective in selected patients. However, operative times are longer comparing to LRC and no advantages in peri-operative and post-operative outcomes are demonstrated with the use of the robotic surgical system.

Retroperitoneal schwannomas: advantages of laparoscopic resection. Review of the literature and case presentation of a large paracaval benign schwannoma (with video)

Retroperitoneal schwannomas represent 0.5%–3% of all retroperitoneal tumors. Complete surgical removal is the treatment of choice because it permits a correct histological diagnosis and prevents eventual degeneration. Laparoscopic surgery has been reported as safe and effective by several authors. We present a comprehensive review of the literature regarding the role of laparoscopy in surgical resection of retroperitoneal schwannomas, and we present a case showing the technique (with video). Laparoscopic resection in experienced hands is safe and effective, and guarantees excellent postoperative results in terms of patient recovery.

Robotic liver surgery is the optimal approach as bridge to transplantation

The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas (HCC) is not merely a technical or technological issue. Nowadays, the epidemiology of HCC is evolving due to the increasing role of non-alcoholic fatty-liver-disease, and the emerging concerns on direct-acting antivirals against hepatitis C virus in terms of HCC incidence. Therefore, a fully multidisciplinary study of the cirrhotic patient is currently more important than ever before, and the management of those patients should be reserved to tertiary referral hepatobiliary centers. In particular, minimally invasive approach to the liver showed several advantages compared to the classical open procedure, in terms of: (1) the small impact on abdominal wall; (2) the gentle manipulation on the liver; (3) the limited surgical trauma; and (4) the respect of venous shunts. Therefore, more direct indications should be outlined also in the Barcelona Clinic Liver Cancer model. We believe that treatment of HCC in cirrhotic patients should be reserved to tertiary referral hepatobiliary centers, that should offer patient-tailored approaches to the liver disease, in order to provide the best care for each case, according to the individual comorbidities, risk factors, and personal quality of life expectations.

Liver transplantation and combined hepatocellular-cholangiocarcinoma: Feasibility and outcomes

INTRODUCTION Combined hepatocellular-cholangiocarcinoma (CHC or cHCC-CC) is a rare primary liver tumor displaying histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Most patients are not suitable for surgery because of the advanced stage of the disease at the moment of diagnosis. We decided to review the literature in order to identify the outcomes after liver transplantation for CHC and to clarify which is the most appropriate treatment. MATERIAL AND METHODS A systematic literature search was performed. Studies reporting outcomes of liver transplantation (LT) for CHC and studies comparing oncologic outcomes after LT versus liver resection (LR) for CHC were included in this review. RESULTS The mean 5-y Disease Free Survival (DFS) reported in literature is 45.4%, while the mean 5-y overall survival (OS) is 41.8%, analyzing a cohort of 418 cases. The mean DSF in our series after LT was 7.97 months, while the mean OS was 11.7 months. CONCLUSIONS LT should be avoided for the treatment of CHC, in order to allocate organs for more appropriate diseases. Moreover, surgical resections, and in particular major hepatectomies, seem to be associated with acceptable outcomes. An accurate preoperative management is needed, and the use of PET-CT when differential diagnosis is difficult should be considered.

Transthoracically or transabdominally: how to approach adenocarcinoma of the distal esophagus and cardia. A meta-analysis

Esophageal carcinoma is the eighth most frequent cancer worldwide and the sixth cancer-related cause of death. Here we propose a new meta-analysis to identify the most appropriate approach for resectable adenocarcinoma of the distal esophagus and cardia (Siewert 1-2). A systematic literature search was performed independently by 2 of the manuscripts authors using PubMed, EMBASE, Scopus and the Cochrane Library Central. The following criteria were set for inclusion in this meta-analysis: 1) studies comparing transthoracic esophagectomy and transhiatal esophagectomy for adenocarcinoma of the esophagus; 2) studies reporting at least 1 perioperative outcome; and 3) if more than 1 study was reported by the same institute, only the most recent or the highest quality study was included. A total of 6 articles dated between 1996 and 2012 fulfilled the selection criteria and were therefore included in this meta-analysis; this pool of articles consisted of 2 prospective and 4 retrospective studies. A statistically significant difference favoring the transthoracic procedure was noted regarding the number of retrieved lymph nodes, 5-year disease-free survival rate and 5-year overall survival rate (p = 0.001, p = 0.05 and p = 0.03, respectively). In conclusion, transthoracic esophagectomy for adenocarcinoma of the distal esophagus and esophagogastric junction (Siewert 1-2) appears to be superior to the transhiatal approach in terms of oncological outcomes.

Oncological Impact of M-Tor Inhibitor Immunosuppressive Therapy after Liver Transplantation for Hepatocellular Carcinoma: Review of the Literature

Background: Hepatocellular Carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Hepatitis B (HBV) and C (HCV) viral infections and alcohol abuse are the principal etiological factors for HCC. Liver transplantation (LT) is oncologically the preferable approach to HCC, as it can remove all the intrahepatic tumor foci, and also the oncogenic cirrhotic liver. The use of mTOR inhibitors (mTORi) for immunosuppression after LT for HCC has been proposed due to rapamycin antitumor activity. We decided to review the literature to clarify the oncological role of mTORi after liver transplantation for HCC, analyzing both present condition and future perspectives. Material and Methods: A systematic literature search was performed using PubMed, EMBASE, Scopus, and the Cochrane Library Central. The search was limited to studies in humans and to those reported in the English language in the period of time between January 2005 and December 2015. Results: The literature search yielded 93 articles; after duplicates were removed, 77 titles and abstracts were reviewed. Most relevant data and papers are herein reported and discussed. Conclusions: So far, the use of mTORi is encouraging in terms of oncological outcomes for patients underwent LT for HCC, both for prevention and treatment of HCC recurrence although definitive data are still awaited.

SMO Inhibition Modulates Cellular Plasticity and Invasiveness in Colorectal Cancer

HIGHLIGHTS Preliminary results of this work were presented at the 2016 Academic Surgical Congress, Jacksonville (FL), February 2–4 2016 (Original title: Selective Smo-Inhibition Interferes With Cellular Energetic Metabolism In Colorectal Cancer) This study was funded by “Sapienza—University of Rome” (Funds for young researchers) and “AIRC” (Italian Association for Cancer Research) Hedgehog inhibitor was kindly provided by Genentech, Inc.®. Colon Cancer (CC) is the fourth most frequently diagnosed tumor and the second leading cause of death in the USA. Abnormalities of Hedgehog pathway have been demonstrated in several types of human cancers, however the role of Hedgehog (Hh) in CC remain controversial. In this study, we analyzed the association between increased mRNA expression of GLI1 and GLI2, two Hh target genes, and CC survival and recurrence by gene expression microarray from a cohort of 382 CC patients. We found that patients with increased expression of GLI1 showed a statistically significant reduction in survival. In order to demonstrate a causal role of Hh pathway activation in the pathogenesis of CC, we treated HCT 116, SW480 and SW620 CC cells lines with GDC-0449, a pharmacological inhibitor of Smoothened (SMO). Treatment with GDC-0449 markedly reduced expression of Hh target genes GLI1, PTCH1, HIP1, MUC5AC, thus indicating that this pathway is constitutively active in CC cell lines. Moreover, GDC-0449 partially reduced cell proliferation, which was associated with upregulation of p21 and downregulation of CycD1. Finally, treatment with the same drug reduced migration and three-dimensional invasion, which were associated with downregulation of Snail1, the EMT master gene, and with induction of the epithelial markers Cytokeratin-18 and E-cadherin. These results were confirmed by SMO genetic silencing. Notably, treatment with 5E1, a Sonic Hedgehog-specific mAb, markedly reduced the expression of Hedgehog target genes, as well as inhibited cell proliferation and mediated reversion toward an epithelial phenotype. This suggests the existence of a Hedgehog autocrine signaling loop affecting cell plasticity and fostering cell proliferation and migration/invasion in CC cell lines. These discoveries encourage future investigations to better characterize the role of Hedgehog in cellular plasticity and invasion during the different steps of CC pathogenesis.

Living donor liver transplantation: Are we ready for full robotic harvesting?

We read with great interest the article by Chen et al. recently published in Liver Transplantation. We compliment the authors for their valuable contribution to the development of a minimally invasive approach to living donor liver transplantation (LDLT). In fact, although safety and feasibility of robotic surgery for liver resections have been described in the literature, the role of the robotic platform in liver transplantation is still a pioneering one. In particular, we strongly support their cautiousness for the diffusion of this technique that is so well described in their manuscript. First of all, we should notice that the robotic platform is currently lacking liverspecific tools for hepatic dissection. Therefore, the complex anatomy of the liver, together with the absence of inflow control and the need for a short ischemia time, may result in a higher risk for both donor and graft safety. The wider success of robotic kidney procurement and transplantation seems in fact mainly related to the more favorable anatomy of the kidney, compared with the complex vascular reconstruction needed in liver transplantation. Clear benefits of the robotic approach for LDLT are yet to be demonstrated, and given the significant risk of morbidity and mortality associated with this procedure, only experienced surgical centers should perform it. One of the most interesting perspectives is the possibility to integrate the robotic platform with intraoperative imaging guidance and augmented reality. However, as is well depicted by Iuppa et al. in their editorial, it seems not possible to navigate the replacement of an open approach with a minimally invasive one without taking risks. It is mandatory to preserve donor safety but also to identify a favorable milieu for such a transition, with an effort from institutions and local authorities to lead this development. We need formal indications by surgical societies to prevent reckless attempts by inexperienced surgeons, rigorous guidelines to guarantee that adverse events will not stop this process, and the development of robotic-friendly liver dissection tools to preserve donor safety. In conclusion, we believe that the development of robotic surgery for complex operations has been ignited and should not be discouraged. However, while developing new technologies, we should guarantee high quality standards and an ethics-driven surgical growth.