New Insights in the Setting of Transplant Oncology.

Background and Objectives: Liver transplantation (LT) is the best strategy for curing several primary and secondary hepatic malignancies. In recent years, growing interest has been observed in the enlargement of the transplant oncology indications. This paper aims to review the most recent developments in the setting of LT oncology, with particular attention to LT for unresectable colorectal liver metastases (CRLM) and cholangiocellular carcinoma (CCA). Materials and Methods: A review of the recently published literature was conducted. Results: Growing evidence exists on the efficacy of LT in curing CRLM and peri-hilar and intrahepatic CCA in well-selected patients when integrating this strategy with (neo)-adjuvant chemotherapy, radiotherapy, or locoregional treatments. Conclusion: For unresectable CCA and CRLM management, several prospective protocols are forthcoming to elucidate LT's impact relative to alternative therapies. Advances in diagnosis, treatment protocols, and donor-to-recipient matching are needed to better define the oncological indications for transplantation. Prospective, multicenter trials studying these advances and their impact on outcomes are still required.

Uniportal video-assisted thoracic surgery approach for simultaneous lung cancer and thymic carcinoma: Case report and literature review.

Thymic carcinoma is an epithelial tumor derived from thymic epithelial cells. Thymic tumors may be associated with other simultaneous and/or metachronous extra-thymic tumors (e.g., lung cancer). Here, we report a case of simultaneous surgical management of lung and mediastinal neoplasm together with a review of the literature. During radiological follow-up for prostate and colorectal cancer, an 82-year-old man was diagnosed with lung cancer with simultaneous mediastinal suspected neoplasm. Both were surgically removed with a single intervention performed via a uniportal video-assisted thoracic surgery (uni-VATS) approach. The literature emphasizes how extra-thymic cancer can be diagnosed before, concurrently and consecutively with thymic neoplasia. The surgical treatment of such simultaneous cancer is challenging. We succeeded in the excision of both neoplasia with a mini-invasive surgical technique. This report highlights the feasibility of uniportal VATS in a patient with very unusual clinical and oncological history.

DCLK1, a Putative Stem Cell Marker in Human Cholangiocarcinoma.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a very aggressive cancer showing the presence of high cancer stem cells (CSCs). Doublecortin-like kinase1 (DCLK1) has been demonstrated as a CSC marker in different gastroenterological solid tumors. Our aim was to evaluate in vitro the expression and the biological function of DCLK1 in intrahepatic CCA (iCCA) and perihilar CCA (pCCA). APPROACH AND RESULTS: Specimens surgically resected of human CCA were enzymatically digested, submitted to immunosorting for specific CSC markers (LGR5 [leucine-rich repeat-containing G protein-coupled receptor], CD [clusters of differentiation] 90, EpCAM [epithelial cell adhesion molecule], CD133, and CD13), and primary cell cultures were prepared. DCLK1 expression was analyzed in CCA cell cultures by real-time quantitative PCR, western blot, and immunofluorescence. Functional studies have been performed by evaluating the effects of selective DCLK1 inhibitor (LRRK2-IN-1) on cell proliferation (MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, cell population doubling time), apoptosis, and colony formation capacity. DCLK1 was investigated in situ by immunohistochemistry and real-time quantitative PCR. DCLK1 serum concentration was analyzed by enzyme-linked immunosorbent assay. We describe DCLK1 in CCA with an increased gene and protein DCLK1 expression in pCCALGR5+ and in iCCACD133+ cells compared with unsorted cells. LRRK2-IN-1 showed an anti-proliferative effect in a dose-dependent manner. LRRK2-IN-1 markedly impaired cell proliferation, induced apoptosis, and decreased colony formation capacity and colony size in both iCCA and pCCA compared with the untreated cells. In situ analysis confirmed that DCLK1 is present only in tumors, and not in healthy tissue. Interestingly, DCLK1 was detected in the human serum samples of patients with iCCA (high), pCCA (high), HCC (low), and cirrhosis (low), but it was almost undetectable in healthy controls. CONCLUSIONS: DCLK1 characterizes a specific CSC subpopulation of iCCACD133+ and pCCALGR5+ , and its inhibition exerts anti-neoplastic effects in primary CCA cell cultures. Human DCLK1 serum might represent a serum biomarker for the early CCA diagnosis.

Laparoscopic Liver Surgery: What Are the Advantages in Patients with Cirrhosis and Portal Hypertension? Systematic Review and Meta-Analysis with Personal Experience.

Background: Laparoscopic surgery is a choice of treatment for liver diseases; it can decrease postoperative morbidity and length of hospital stay (LOS). Hepatocellular carcinoma (HCC) in patients with cirrhosis and portal hypertension may benefit from minimally invasive liver resections (MILRs) instead of open liver resections (OLRs). Whether minimally invasive approaches are superior to conventional ones is still a matter of debate. We thus aimed to gather the available literature on this specific topic to achieve greater clarity. Materials and Methods: PubMed, EMBASE and Web of Sciences databases were assessed for studies comparing OLRs versus MILRs for HCC in cirrhotic patients up to February 2020. Data from our surgical experience from June 2010 to February 2020 were also included. Demographic characteristics, liver function, the presence of portal hypertension, tumor number, and tumor size and location were assessed; operative time, need for Pringle maneuver, estimated blood loss (EBL), major or minor hepatectomy performance, and conversion rate were evaluated for operative findings. Postoperative outcomes and liver-related complications, surgical site infection (SSI) rate, blood transfusion (BT) rate, need for reintervention, LOS, in-hospital or 30-day mortality, and radicality of resection were also considered. Meta-analysis was performed employing Review Manager 5.3 software. Results: One thousand three hundred twenty-one patients from 13 studies and our own series were considered in the meta-analysis. At preoperative settings, the OLR and MILR groups differed significantly only by tumor size (4.4 versus 3.0, P = .006). Laparoscopic procedures resulted significantly faster (120.32-330 minutes versus 146.8-342.75 minutes, P = .002) and with lower EBL than open ones (88-483 mL versus 200-580 mL, P < .00001), thus requiring less BTs (7.9% versus 13.2%, P = .02). In terms of overall morbidity, minimally invasive surgeries resulted significantly favorable (19.32% versus 38.04%, P < .00001), as well as for ascites (2.7% versus 12.9% P < .00001), postoperative liver failure (7.51% versus 13.61% P = .009), and SSI (1.8% versus 5.42%, P = .002). Accordingly, patients who had undergone MILRs had significantly shorter postoperative hospitalization than patients who underwent conventional open surgery (2.4-36 days versus 4.2-19 days P < .00001). Both groups did not differ in terms of mortality rate and radicality of resection (OLR 93.8% versus 96.1% laparoscopic liver resection, P = .12). Conclusions: Based on the available evidence in the literature, laparoscopic resections rather than open liver ones for HCC surgery in cirrhotic patients seem to reduce postoperative overall morbidity, liver-specific complications, and LOS. The lack of randomized studies on this topic precludes the possibility of achieving defining statements.

Robotic Liver Resections: Application of Difficulty Score Systems to an Initial Experience. Is a Specific Robotic Difficulty Score Necessary?

Background: Recently, the minimally invasive surgical approach has been available for performing liver resections (LRs) with laparoscopic and robotic techniques. The robotic approach for LRs seems to overcome several laparoscopic limitations, which is a valid alternative when performed in high volume and specialized centers. Laparoscopic difficulty score systems (DSSs) should serve to guide the surgeon's choice in the best surgical approach to adopt for every single patient, giving the possibility to switch to the open approach when needed. To this day, no specific robotic difficulty scores exist. The aim of our study was to verify the feasibility of applying these scores and related updates on robotic LRs performed in our Institute. Materials and Methods: Out of a total of 683 LRs performed from June 2010 to July 2019, 60 were performed through using a mini invasive approach and of these 18 were performed robotically. The Ban DSS and subsequently the modified Iwate DSS were applied to our cases. Results: Based on our findings, applying the DSS we divided our series into two groups: a low difficulty level group (1-3) made up of 5 patients, and an intermediate difficulty level group (4-6) consisting of 13 patients. Average Ban DSS and subsequently updated score system results were 4.6 ± 1.5 points (range 2-6) for both scores. Conclusions: Difficulties were encountered in applying the score when simultaneous multiple wedge resections were performed. The laparoscopic DSS is applicable to robotic LRs with some limitations due to the peculiarity of the two different minimally invasive approaches. A specific robotic difficulty rating score could be necessary to include these elements.

Organ-saving surgery for rectal cancer after neoadjuvant chemoradiation: Analysis of failures and long-term results.

BACKGROUND: To analyze long-term results and risk of relapse in the clinical TNM stages II and III, mid-low rectal cancer patients (RC pts), treated with transanal local excision (LE) after major response to neoadjuvant chemoradiation (n-CRT). METHODS: Thirty-two out of 345 extraperitoneal cT3-4 or N+ RC pts (9.3%) underwent LE. INCLUSION CRITERIA: extraperitoneal RC, adenocarcinoma, ECOG Performance Status ≤2. Pts with distant metastases were excluded. RESULTS: All pts showed histologically clear margins of resection and 81.2% were restaged ypT0/mic/1. Nine out of 32 (28.1%) pts relapsed: 7 (21.8%) showed a local recurrence, of which 5 (15.6%) at the endorectal suture, 1 (3.1%) pelvic and 1 (3.1%) mesorectal. Two pts (6.2%) relapsed distantly. Among the pT0/1, 11.5% relapsed vs 100% of the pT2 and pT4 ones. The six pts relapsing locally or in the mesorectal fat underwent a salvage total mesorectal excision surgery. The old patient with pelvic recurrence relapsed after 108 months and underwent a re-irradiation; the two pts with distant metastases were treated with chemotherapy followed by radical surgery. CONCLUSIONS: Presently combined approach seems a valid option in major responders, confirming its potential curative impact in the ypT0/mic/1 pts. A strict selection of pts is basic to obtain favourable results.