Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial–mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk.

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

Background: Robotic (RLR) and laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) provide similar short-term outcomes, but data focused on recurrence and survival are still lacking. We hypothesized non-inferior oncologic results of RLR compared to LLR for HCC of stage BCLC 0-A. Methods: RLRs and LLRs on patients with HCC of stage BCLC 0-A and preserved liver function (Child A or B if cirrhosis) were retrospectively reviewed. Propensity score matching (PSM) was used to mitigate selection bias. The primary endpoints were recurrence-free (RFS) and overall survival (OS); secondary endpoints were incidence, pattern, and treatment of recurrences. Results: After 1:1 PSM, two groups (RLR = 68; LLR = 68) of patients with similar characteristics, liver function and HCC features were obtained: median age 71-years, males 73.5%, underlying cirrhosis 91.2% (Child A, 96.8%, MELD ≤ 9, 96.0%), portal hypertension 22.1%, single-HCC 90.4%. Two- and 5-year RFS were 78.0 vs 59.0% and 54.0 vs 53.0% (p = 0.107), while OS was 97.0 vs 90.0% and 87.0 vs 90.0% (p = 0.951) for RLR vs LLR, respectively. Incidence of HCC recurrence was similar (35.3 vs 39.7%; p = 0.723). Recurrences developed mostly within the liver (29.4 vs 30.9%; p = 1.000) and within 2 years after hepatectomy (19.1 vs 32.4%, p = 0.116) in RLR vs LLRs. Curative-intent treatment of recurrences did not differ (liver transplantation 19.6%, redo-resection 15.7%, locoregional treatments 52.9%) except for a tendency toward more redo-resections for recurrences after RLR. Conclusions: Oncologic outcomes of RLR were not inferior to those of LLR in selected HCC patients of stage BCLC 0-A with underlying cirrhosis. Both techniques guaranteed similar salvageability in case of HCC recurrence.

The hepato-pancreato-biliary and transplant surgeons of the Asan Medical Center are highly esteemed by their peers for their technical qualities and their extraordinary experience (>4000 living-donor liver transplantataion). The article in this issue of Annals is a further confirmation of their skill, but it is interesting in some other aspects. The first one is that the solution of resecting and replacing the whole vena cava even in an living-donor liver transplantataion, as the one attributed to Alexander the Great who cut with his sword the reputedly inextricable knot,1 is conceptually simple, provided that the reluctance to use synthetic grafts (either bare or composite, with venous patches) is overcome. It saves undertaking the difficult and dangerous dissection of the retrohepatic vena cava from the hypertrophic and highly collateralized segment 1 that is a constant feature of the Budd-Chiari syndrome. Also, there is a sizeable literature that these grafts are safe in liver transplantation (infection is rare and probably preventable by technical details2–4) even if their use can be reduced in western transplant centers where homografts from deceased donors are generally available. Cryopreserved vein grafts are much more expensive and probably offer no advantages. The second is that the authors share a number of technical points that derive from experience (bad experiences and mistakes, in fact, such as a Satinsky clamp slipping from the right atrium) reminding us that even in the best hands our craft is stressful and dangerous. The transplant surgeons will extract useful advice from the way the cases are reported, even in the more common situation of a transplant with a full cadaveric graft. In particular, the anastomosis on the right atrium is tricky, the wall is much more fragile, and the systematic help of a cardiac surgeon gave additional comfort and safety in our experience. Starting the suture of the polytetrafluoroethylene tube from the anterior wall is an interesting and counterintuitive point, but we have no personal experience of it in our cases in which we could suture to the right atrium the more elastic and forgiving suprahepatic vena cava of a whole graft. The third is the sheer pleasure that the reader has in seeing the degree of refinement to which these colleagues go to have the results for which they are admired in the rest of the world, and that should be an example for us all, seniors and juniors alike.