5 year oncological outcomes of the HIGHLOW randomized clinical trial.

INTRODUCTION: The oncological outcomes of low ligation (LL) compared to high ligation (HL) of the inferior mesenteric artery (IMA) during low-anterior rectal resection (LAR) with total mesorectal excision are still debated. The aim of this study is to report the 5 year oncologic outcomes of patients undergoing laparoscopic LAR with either HL vs. LL of the IMA MATERIALS AND METHODS: Between June 2014 and December 2016, patients who underwent elective laparoscopic LAR + TME in 6 Italian non-academic hospitals were randomized to HL or LL of IMA after meeting the inclusion criteria (HighLow trial; ClinicalTrials.gov Identifier NCT02153801). We analyzed the rate of local recurrence, distant metastasis, overall survival, disease-specific survival, and disease-free survival at 5 years of patients previously enrolled. RESULTS: Five-year follow up data were available for 196 patients. Recurrence happened in 42 (21.4%) of patients. There was no statistically significant difference in the distant recurrence rate (15.8% HL vs. 18.9% LL; P = 0.970) and pelvic recurrence rate (4,9% HL vs 3,2% LL; P = 0.843). No statistically significant difference was found in 5-year OS (p = 0.545), DSS (p = 0.732) or DFS (p = 0.985) between HL and LL. Low vs medium and upper rectum site of tumor, conversion rate, Clavien-Dindo post-operative grade ≥3 complications and tumor stage were found statistically significantly associated to poor oncological outcomes in univariate analysis; in multivariate analysis, however, only conversion rate and stage 3 cancer were found to be independent risk factors for poor DFS at 5 years. CONCLUSION: We confirmed the results found in the previous 3-year survival analysis, the level of inferior mesenteric artery ligation does not affect OS, DSS and DFS at 5-year follow-up.

Video-assisted thoracoscopic resection of lung nodules localized with a hydrogel plug.

OBJECTIVES: Computed tomography (CT)-guided hydrogel plug deployment was recently proposed for lung nodule preoperative localization and simultaneous prevention of pneumothorax. We analysed our initial experience with CT-guided hydrogel plug localization of lung nodules in patients undergoing video-assisted thoracoscopic (VATS) resection. METHODS: We retrospectively evaluated the medical notes from 27 consecutive patients (mean age 68 ± 11 SD years; men 74%) undergoing VATS lung wedge resection for biopsy or definitive treatment of 28 small pulmonary nodules (malignant 82%) at a single institution between October 2017 and July 2018. Difficult intraoperative nodule localization was anticipated with a lesion <10 mm, a depth from pleura:size ratio >1, ground-glass opacity or the judgement of the operating surgeon. All lesions were preoperatively marked by deployment of a CT-guided hydrogel plug. Study end points were frequency of postlocalization pneumothorax; feasibility of delayed surgery; rate of localization of intraoperative nodule and rate of successful VATS resection. RESULTS: The mean sizes of the solid nodules (n = 24) and of the ground-glass opacities (n = 4) were, respectively, 10.4 ± 3.4 mm and 16.0 ± 6.2 mm. One (4%) hydrogel plug marking procedure caused a clinically relevant pneumothorax. Nodule resection was scheduled flexibly as required by patient management/operating room scheduling: same day (11 nodules) or delayed [median 6 days (range 1-60 days)]; (17 nodules). All nodules were localized intraoperatively: 25 (89%) by hydrogel plug; 3 (11%) by palpation and pleural puncture hole visible after plug displacement. All nodules were completely excised by VATS, without complications. CONCLUSIONS: CT-guided hydrogel plug marking was valuable for VATS localization and resection of challenging lung nodules. The plug minimized clinically relevant pneumothoraxes and allowed flexible surgical schedules.

Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization.

Natural killer (NK) cells are crucial in tumor recognition and eradication, but their activity is impaired in cancer patients, becoming poorly cytotoxic. A particular type of NK cells, from the decidua, has low cytotoxicity and shows proangiogenic functions. We investigated whether NK cells from peripheral blood (PB) and pleural effusions of patients develop decidual-like NK phenotype and whether exposure to IL-2 can restore their killing ability in the presence of pleural fluids. NK cells from pleural effusion of patients with inflammatory conditions (iPE, n = 18), primary tumor (ptPE, n = 18), and metastatic tumor (tmPE, n = 27) acquired the CD56brightCD16- phenotype. NK cells from both ptPE and tmPE showed increased expression for the CD49a and CD69 decidual-like (dNK) markers and decreased levels of the CD57 maturation marker. NK from all the PE analyzed showed impaired degranulation capability and reduced perforin release. PE-NK cells efficiently responded to IL-2 stimulation in vitro. Addition of TGFß or cell-free pleural fluid to IL-2 in the culture medium abrogated NK cell CD107a and IFNγ expression even in healthy donors (n = 14) NK. We found that tmPE-NK cells produce VEGF and support the formation of capillary-like structures in endothelial cells. Our results suggest that the PE tumor microenvironment can shape NK cell polarization towards a low cytotoxic, decidual-like, highly proangiogenic phenotype and that IL-2 treatment is not sufficient to limit this process.

Risk factor analysis for involvement of resection margins in gastric and esophagogastric junction cancer: an Italian multicenter study.

BACKGROUND: Resection margin (RM) involvement is associated with negative prognosis after gastrectomy. Intraoperative frozen section (IFS) analysis allows radical resection to be achieved in a single operation but is time-consuming and resource-consuming. The aim of this study was to assess risk factors associated with RM involvement to identify patients who would benefit from IFS analysis. METHODS: We retrospectively analyzed patients who underwent gastrectomy with curative intent for gastric or esophagogastric junction (EGJ) cancer from 2000 to 2014 in six Italian hospitals. RM status was assessed by IFS analysis and/or definitive histopathology examination. A set of 21 potential risk factors were compared in a multivariate analysis between patients with positive RMs on IFS analysis or definitive histopathology examination and a control cohort of similar patients with negative RMs, with the samples stratified into three subgroups (T1, T2-T4 Lauren intestinal pattern, T2-T4 Lauren diffuse/mixed pattern). RESULTS: One hundred forty-five patients had positive RMs. Survival was significantly worse in positive RM patients than in negative RM patients (89.5 months vs 28.9 months). Multivariate analysis showed that in T1 cancers a margin distance of less than 2 cm is a risk factor for RM involvement (odds ratio 15.7), in T2-T4 intestinal pattern cancers, serosa invasion (odds ratio 6.0), EGJ location (odds ratio 4.1), and a margin distance of less than 3 cm (odds ratio 4.0) are independent risk factors, and in T2-T4 diffuse/mixed pattern cancers, lymphatic infiltration (odds ratio 4.2), tumor diameter greater than 4 cm (odds ratio 3.5), EGJ location (odds ratio 2.8), and serosa invasion (odds ratio 2.2) are independent risk factors. CONCLUSIONS: Survival after gastrectomy is negatively affected by positive RMs. IFS analysis should be routinely used in patients with a high risk of positive RMs, especially in diffuse pattern cancers.

Antecolic or Retrocolic Alimentary Limb in Laparoscopic Roux-en-Y Gastric Bypass? A Meta-Analysis.

Internal hernia (IH) is a severe complication after laparoscopic Roux-en-Y gastric bypass. The orientation of the alimentary limb has advocated to affect IH. Available data regarding the incidence of IH, gastro-jejunostomy leakage, obstructive symptoms, anastomotic obstruction, adhesion, incisional hernia, total complications, and recurrent IH were meta-analyzed according to the orientation of the alimentary limb. Fourteen studies (13,660 patients) were included. Antecolic orientation resulted associated with a lower incidence of IH and obstructive symptoms, while the route of the alimentary limb did not show to affect the other outcomes. Antecolic orientation decreases the IH. However, the role and the technique of the closure of mesenteric defects cannot be stated due to the lack of adequate data to date. Well-designed randomized controlled trials (RCTs) are needed.

Intra-abdominal drainage after pancreatic resection: is it really necessary? A meta-analysis of short-term outcomes.

INTRODUCTION: Pancreatic fistula (PF) is the most dreadful complication of patients after pancreatic resection. The use of operative site drains is considered routine all along in pancreatic surgery in order to remove any collections and to act as a warning of hemorrhage or anastomotic leakage. To date few studies investigated the potential benefit and safety of routine drainage compared with no drainage after pancreatic resection and the evidence by literature is not clear. METHODS: A systematic review of the literature was carried out performing an unrestricted search in MEDLINE, EMBASE and Cochrane Library up to 28th February 2014. Reference lists of retrieved articles and review articles were manually searched for other relevant studies. The currently available data regarding the incidence of post-operative short-term outcomes after pancreatic resection were meta-analyzed according to the presence or absence of the intra-abdominal drainage. RESULTS: Overall 7 studies were included in the meta-analysis, that is 2 randomized controlled trials (RCTs) and 5 non-RCTs resulting in 2704 patients totally. Intra-abdominal drainage showed to increase the PF (OR 2.31, 95% CI 1.52-3.51), the total post-operative complications (OR 1.52, 95% CI 1.30-1.78) and the re-admission (OR 1.30, 95% CI 1.06-1.61) rates. A non-significant correlation was found with the presence/absence of the drainage about biliary and enteric fistula, post-operative hemorrhage, intra-abdominal infected collection, wound infection and overall mortality rates. CONCLUSION: The meta-analysis shows that the presence of an intra-abdominal drainage does not improve the post-operative outcome after pancreatic resection.