Chemokine Receptor Redundancy and Specificity Are Context Dependent.

Currently, we lack an understanding of the individual and combinatorial roles for chemokine receptors in the inflammatory process. We report studies on mice with a compound deletion of Ccr1, Ccr2, Ccr3, and Ccr5, which together control monocytic and eosinophilic recruitment to resting and inflamed sites. Analysis of resting tissues from these mice, and mice deficient in each individual receptor, provides clear evidence for redundant use of these receptors in establishing tissue-resident monocytic cell populations. In contrast, analysis of cellular recruitment to inflamed sites provides evidence of specificity of receptor use for distinct leukocyte subtypes and no indication of comprehensive redundancy. We find no evidence of involvement of any of these receptors in the recruitment of neutrophils or lymphocytes to resting or acutely inflamed tissues. Our data shed important light on combinatorial inflammatory chemokine receptor function and highlight Ccr2 as the primary driver of myelomonocytic cell recruitment in acutely inflamed contexts.

Comparison of clinical outcome between laparoscopic and open hepatectomy of high difficulty score for hepatocellular carcinoma: a propensity score analysis.

BACKGROUND: Laparoscopic liver resection (LLR) of high difficulty score is technically challenging. There is a lack of clinical evidence to support its applicability in terms of the long-term survival benefits. This study aims to compare clinical outcomes between LLR and the open liver resection of high difficulty score for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From 2010 to 2020, using Iwate criteria, 424 patients underwent liver resection of high difficulty score by the laparoscopic (n = 65) or open (n = 359) approach. Propensity score (PS) matching was performed between the two groups. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. RESULTS: The laparoscopic group had significantly fewer severe complications (3% vs. 10.8%), and shorter median hospital stays (6 days vs. 8 days) than the open group. Meanwhile, the long-term oncological outcomes were comparable between the two groups, in terms of the tumor recurrence rate (40% vs. 46.1%), the 5-year overall survival rate (75.4% vs. 76.2%), and the 5-year recurrence-free survival rate (50.3% vs. 53.5%). The high preoperative serum alpha-fetoprotein level, multiple tumors, and severe postoperative complications were the independent poor prognostic factors associated with worse overall survival. The surgical approach (Laparoscopic vs. Open) did not influence the survival. CONCLUSION: LLR of high difficulty score for selected patients with HCC has better short-term outcomes than the open approach. More importantly, it can achieve similar long-term survival outcomes as the open approach.

Comparison of post-hepatectomy long-term survival outcome between non-colorectal non-neuroendocrine and colorectal liver metastases: A population-based propensity-score matching analysis.

BACKGROUND: Hepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort. METHODS: From 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n â€‹= â€‹133) or CLM (n â€‹= â€‹831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. RESULTS: There were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 â€‹% vs 1.5 â€‹%) and morbidity (19.5 â€‹% vs 20.3 â€‹%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 â€‹% vs 39.8 â€‹%) and recurrence-free (25.1 â€‹% vs 23.4 â€‹%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival. CONCLUSION: Hepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival.

Propensity-score Matched and Coarsened-exact Matched Analysis Comparing Robotic and Laparoscopic Major Hepatectomies: An International Multicenter Study of 4822 Cases.

OBJECTIVE: To compare the outcomes between robotic major hepatectomy (R-MH) and laparoscopic major hepatectomy (L-MH). BACKGROUND: Robotic techniques may overcome the limitations of laparoscopic liver resection. However, it is unknown whether R-MH is superior to L-MH. METHODS: This is a post hoc analysis of a multicenter database of patients undergoing R-MH or L-MH at 59 international centers from 2008 to 2021. Data on patient demographics, center experience volume, perioperative outcomes, and tumor characteristics were collected and analyzed. Both 1:1 propensity-score matched (PSM) and coarsened-exact matched (CEM) analyses were performed to minimize selection bias between both groups. RESULTS: A total of 4822 cases met the study criteria, of which 892 underwent R-MH and 3930 underwent L-MH. Both 1:1 PSM (841 R-MH vs. 841 L-MH) and CEM (237 R-MH vs. 356 L-MH) were performed. R-MH was associated with significantly less blood loss {PSM:200.0 [interquartile range (IQR):100.0, 450.0] vs 300.0 (IQR:150.0, 500.0) mL; P = 0.012; CEM:170.0 (IQR: 90.0, 400.0) vs 200.0 (IQR:100.0, 400.0) mL; P = 0.006}, lower rates of Pringle maneuver application (PSM: 47.1% vs 63.0%; P < 0.001; CEM: 54.0% vs 65.0%; P = 0.007) and open conversion (PSM: 5.1% vs 11.9%; P < 0.001; CEM: 5.5% vs 10.4%, P = 0.04) compared with L-MH. On subset analysis of 1273 patients with cirrhosis, R-MH was associated with a lower postoperative morbidity rate (PSM: 19.5% vs 29.9%; P = 0.02; CEM 10.4% vs 25.5%; P = 0.02) and shorter postoperative stay [PSM: 6.9 (IQR: 5.0, 9.0) days vs 8.0 (IQR: 6.0 11.3) days; P < 0.001; CEM 7.0 (IQR: 5.0, 9.0) days vs 7.0 (IQR: 6.0, 10.0) days; P = 0.047]. CONCLUSIONS: This international multicenter study demonstrated that R-MH was comparable to L-MH in safety and was associated with reduced blood loss, lower rates of Pringle maneuver application, and conversion to open surgery.

Baveno VII criteria identify varices needing treatment in patients with hepatocellular carcinoma of different Barcelona Clinic Liver Cancer stages.

BACKGROUND: Baveno VII criteria for predicting varices needing treatment (VNT) have not been tested in hepatocellular carcinoma (HCC) population. We evaluated Baveno VII consensus for VNT in HCC patients of different stages according to Barcelona Clinic Liver Cancer (BCLC) stages undergoing curative hepatectomy. METHODS: This was a prospective cohort study of patients with HCC. Patients underwent transient elastography examination before HCC treatment and received at least one upper endoscopic examination afterwards. Patients were prospectively followed for clinical events including VNT. RESULTS: Six hundred and seventy-three patients (83.1% male, median age 62 years) with HCC of BCLC stage 0 (10%), A (57%), B (17%) and C (15%) were recruited and followed for 47 months. The median (range) LSM was 10.5 (6.9-20.4) kPa; 74% had LSM ≤ 20 kPa and 58% had platelet count ≥150 × 10/L, respectively. VNT occurred in 51 (7.6%) patients. In patients who fulfilled Baveno VII criteria, that is, LSM ≤ 20 kPa and platelet count above 150 × 10/L, only 11 (1.6%) patients had VNT. In all BCLC stages of HCC, the proportion of patients with VNT was below 5%, which support the validity and applicability of Baveno VII criteria in all BCLC stages of HCC. CONCLUSIONS: The Baveno VII criteria are valid and applicable in HCC patients undergoing curative hepatectomy for selecting patients to undergo screening endoscopy for VNT. The validity was consistent across different BCLC stages of HCC.

An international multicentre propensity score matched analysis comparing between robotic versus laparoscopic left lateral sectionectomy.

BACKGROUND: Left lateral sectionectomy (LLS) is one of the most commonly performed minimally invasive liver resections. While laparoscopic (L)-LLS is a well-established technique, over traditional open resection, it remains controversial if robotic (R)-LLS provides any advantages of L-LLS. METHODS: A post hoc analysis of 997 patients from 21 international centres undergoing L-LLS or R-LLS from 2006 to 2020 was conducted. A total of 886 cases (214 R-LLS, 672 L-LLS) met study criteria. 1:1 and 1:2 propensity score matched (PSM) comparison was performed between R-LLS & L-LLS. Further subset analysis by Iwate difficulty was also performed. Outcomes measured include operating time, blood loss, open conversion, readmission rates, morbidity and mortality. RESULTS: Comparison between R-LLS and L-LLS after PSM 1:2 demonstrated statistically significantly lower open conversion rate in R-LLS than L-LLS (0.6% versus 5%, p = 0.009) and median blood loss was also statistically significantly lower in R-LLS at 50 (80) versus 100 (170) in L-LLS (p = 0.011) after PSM 1:1 although there was no difference in the blood transfusion rate. Pringle manoeuvre was also found to be used more frequently in R-LLS, with 53(24.8%) cases versus to 84(12.5%) L-LLS cases (p < 0.001). There was no significant difference in the other key perioperative outcomes such as operating time, length of stay, postoperative morbidity, major morbidity and 90-day mortality between both groups. CONCLUSION: R-LLS was associated with similar key perioperative outcomes compared to L-LLS. It was also associated with significantly lower blood loss and open conversion rates compared to L-LLS.

The Impact of Involved Resection Margin on Recurrence and Survival After Pancreaticoduodenectomy for Periampullary Carcinoma, with Emphasis on Pancreatic Head Carcinoma.

BACKGROUND: The supposed adverse effect of involved resection margin during pancreaticoduodenectomy (PD) for periampullary carcinoma or pancreatic head carcinoma (CaP) on long-term oncological outcomes is still inconclusive. METHODS: This is a retrospective study on periampullary carcinoma undergoing PD. Patients with R0 (margin clear) resection were compared to patients with R1 (microscopically directly involved margin) resection. Patients with gross involved margin (R2 resection) were excluded. Long-term oncological outcomes measured included incidence and site of recurrent disease, overall survival (OS) and disease-free survival (DFS). A subgroup analysis was made on patients with CaP. RESULTS: Between January 2003 and December 2019, 203 PD were identified for present study. The incidence of R1 resection was common (12% in periampullary carcinoma and 20% in CaP). In periampullary carcinoma, R1 resection had greater proportion of CaP, lesser proportion of carcinoma of ampulla (CaA), more perineural invasion, more lymph node (LN) metastasis. R1 group had a shorter OS and DFS, but no difference in the incidence and site of recurrent disease. In the subgroup of CaP (91 patients), R1 group did not differ from R0 group except for more LN metastasis. There was no difference in incidence and site of recurrent disease, OS and DFS. On multivariable analysis, R1 resection was not an independent factor for OS and DFS for periampullary carcinoma or for CaP only. CONCLUSION: Involved resection margin was not uncommon. It was not associated with higher incidence of recurrent disease including local recurrence, and was not an independent prognosticator for OS and DFS.

Minimally invasive versus open liver resection for hepatocellular carcinoma: a propensity score matching analysis of 224 patients.

PURPOSE: To compare the peri-operative and long-term survival outcomes of minimally invasive liver resection (MILR) (robotic or laparoscopic) with open liver resection (OLR) in patients with hepatocellular carcinoma (HCC). METHODS: Data of patients who underwent liver resection for HCC were reviewed from a prospectively collected database. Outcomes of MILR were compared with those of OLR. A propensity score matching analysis with a ratio of 1:1 was performed to minimise the potential bias in clinical pathological factors. RESULTS: From January 2003 to December 2017, a total of 705 patients underwent liver resection for HCC. Amongst them, 112 patients received MILR and 593 patients received OLR. After propensity score matching, there were 112 patients in each of the MILR and OLR groups. Patients were matched by age, sex, hepatitis status, presence of cirrhosis, platelet count, albumin level, bilirubin level, alkaline phosphatase (ALP) level, alanine transferase (ALT) level, creatinine level, tumour differentiation, tumour size, tumour number, presence of tumour rupture, presence of vascular invasion, extent of liver resection (minor/major) and difficulty score. The 1-, 3- and 5-year overall survival rates were 94.4%, 90.4% and 82.3% in the MILR group vs 95.4%, 80.5% and 71.8% in the open group (p = 0.240). The 1-, 3- and 5-year disease-free survival rates were 81.0%, 63.1% and 55.8% in the MILR group vs 79.1%, 58.1% and 45.7 in the open group (p = 0.449). The MILR group demonstrated significantly less blood loss (p < 0.001), less blood transfusion (p = 0.004), lower post-operative complications (p < 0.001) and shorter hospital stay (p < 0.001) when compared with the OLR group. CONCLUSIONS: Our data shows MILR yielded superior post-operative outcomes to OLR, with comparable survival outcomes.

Psychosocial interventions for teenagers with adolescent idiopathic scoliosis: A systematic literature review.

OBJECTIVES: Psychosocial interventions can improve teenagers' self-esteem, mental health and bracing compliance. There is a need to compile available evidence of psychosocial care in adolescent idiopathic scoliosis. This systematic review aimed to identify and evaluate the effects of existing interventional studies of psychosocial care for the adolescent idiopathic scoliosis population. METHODS: A comprehensive search of relevant literature published from the inception to March 2023 was conducted using nine databases. A google scholar search was performed on 1 July 2023, to update the searching results. Two reviewers independently assessed the methodological quality and extracted details of the included studies. Given the heterogeneity of the selected articles, the findings were synthesized narratively without conducting a meta-analysis. RESULTS: Four randomized controlled trials reported in six articles involving 385 teenagers were included. The interventions appeared acceptable with high recruitment rates and low dropout rates reported. Psychosocial interventions had shown significant positive effects on postoperative pain, engagement in daily and social activities as well as brace use, coping abilities and anxiety. CONCLUSION: Psychosocial interventions are generally feasible and acceptable among the adolescent idiopathic scoliosis population and have produced positive effects on a variety of physical and psychosocial outcomes. Study findings need to be interpreted with caution due to the limited number of available articles and the methodological concerns of the reviewed articles. PRACTICAL IMPLICATIONS: Well-designed clinical trials are warranted in people from cultural backgrounds to develop and implement effective psychosocial interventions for teenagers with adolescent idiopathic scoliosis, not only for those at the post-surgery stage but also for those receiving conservative treatment.

Placental chemokine compartmentalisation: A novel mammalian molecular control mechanism.

Atypical chemokine receptor 2 (ACKR2) is a chemokine-scavenging receptor. ACKR2-/-embryos display a reduction in size of a novel, to our knowledge, embryonic skin macrophage population referred to as 'intermediate' cells. CC chemokine receptor 2 (CCR2)-/-embryos display an identical phenotype, indicating that these cells require CCR2 to enable them to populate embryonic skin. Further analysis revealed that ACKR2-/-embryos have higher circulating concentrations of the CCR2 ligand, CC ligand 2 (CCL2); thus, ACKR2 regulates intraembryonic CCL2 levels. We show that ACKR2 is strongly expressed by trophoblasts and that it blocks movement of inflammatory chemokines, such as CCL2, from the maternal decidua into the embryonic circulation. We propose that trophoblastic ACKR2 is responsible for ensuring chemokine compartmentalisation on the maternal decidua, without which chemokines enter the embryonic circulation, disrupting gradients essential for directed intraembryonic cell migration. Overall, therefore, we describe a novel, to our knowledge, molecular mechanism whereby maternal decidual chemokines can function in a compartmentalised fashion without interfering with intraembryonic leukocyte migration. These data suggest similar functions for other atypical chemokine receptors in the placenta and indicate that defects in such receptors may have unanticipated developmental consequences.

Yoga as an adjunct activity for medical students learning anatomy.

BACKGROUND: Medical students experience high levels of stress during training due to demanding course loads which often leaves less time for self-care. This study combines the self-care technique of yoga with learning anatomical locations, innervations, actions, and functions of the muscles and organs to determine if anatomy tests scores are improved and whether students' stress levels attenuate from participating in yoga. METHODS: In this randomized controlled study, 64 student volunteers were randomized into either a yoga intervention group or wait list control group throughout the M1 anatomy course. The yoga group (n = 32) participated in 8 yoga sessions synced with the anatomy topics they were learning in lecture. The wait list group (n = 32) went through their normal anatomy curriculum but had an option to participate in the same yoga sessions after the anatomy course. The primary research purpose was to determine whether yoga improved anatomy exam performance by comparing four anatomy exam scores between the two groups. The secondary research purposes included the following: to determine whether yoga classes including anatomy teaching still conferred acute and long-lasting stress relief by, respectively, comparing a students' own pre- and post-yoga stress level and self-perceived stress levels between the two groups; and to determine if a student's confidence in anatomy was improved after a yoga session. RESULTS: There was no significant difference in anatomy exam performance between students who received yoga and those on the waitlist (all p > 0.05). For students who received yoga, their average self-reported stress levels decreased after each yoga session, their average DASS (Depression, Anxiety and Stress Scale) score decreased after a yoga session, but they were not significantly less stressed than their waitlist peers prior to an exam, and their self-reported confidence in anatomy material related to the back, upper extremity, head and neck, and abdomen/pelvis increased. CONCLUSION: With this sample, there was no evidence that yoga sessions paired with anatomy lecture material improved overall anatomy exam performance, as opposed to only the musculoskeletal portion which other studies have looked at. However, yoga acutely reduced stress levels, and subjective feelings of knowledge improvement were noted by participants. Both of these can provide benefits to medical students.

A retrospective comparative study of robotic distal pancreatectomy with or without splenic vessel and spleen preservation.

BACKGROUND: Robotic distal pancreatectomy has been accepted to be safe and effective for pancreatic tail lesion. Whether spleen preservation by preserving the splenic vessels with robot assistance is feasible and beneficial remains controversial. Here we would like to compare the operative outcomes of robotic distal pancreatectomy and splenectomy (DPS) with robotic spleen preserving distal pancreatectomy by means of splenic vessel preservation (SVP). METHODS: Between March 2011 and September 2019, 56 consecutive patients undergoing robotic distal pancreatectomy were identified, with 28 patients in each group. Patient demographics, histopathology findings and operative outcomes were prospectively collected and compared between the two groups. A subgroup analysis was made after excluding malignant and pancreatic lesions >6 cm in the DPS group. RESULTS: The two groups had similar conversion rate, blood loss, morbidity and pancreatic fistula rate. There was no operative mortality. The SVP group had shorter median operative time (245 vs 303.5 min, P = 0.019) and shorter median hospital stay (5 vs 6 days, P = 0.019) than the DPS group. However, all malignant lesions occurred in the DPS group and lesion size in DPS group was significantly larger. After matching, there were 28 SVP and 15 DPS. The histopathology findings and lesion size became comparable. The SVP group still had shorter operative time (245 vs 290 min, P = 0.022) and shorter hospital stay (5 vs 7 days, P = 0.014) than the DPS group. CONCLUSION: Apart from avoiding risk of overwhelming postsplenectomy sepsis, robotic SVP had additional advantage of shorter operative time and shorter hospital stay than robotic DPS.

Liver stiffness measurement predicts short-term and long-term outcomes in patients with hepatocellular carcinoma after curative liver resection.

BACKGROUND AND AIM: Hepatocellular carcinoma is one of the commonest cancer in the world. Despite curative resection, recurrence remains the largest challenge. Many risk factors were identified for predicting recurrence, including liver fibrosis and cirrhosis. Transient elastography (Fibroscan) is an accurate tool in measuring liver fibrosis. This study aimed to evaluate the use of preoperative liver stiffness measurement (LSM), with Fibroscan in predicting long-term recurrence of hepatocellular carcinoma (HCC) after curative resection. METHOD: A prospective cohort study was conducted from February 2010 - June 2017 in Prince of Wales hospital. All consecutive patients with HCC undergone hepatectomy were included. Demographic factors, preoperative LSM, tumor characteristics and operative details were assessed. Primary outcome and secondary outcome were overall survival and disease free survival at 1 year, 3 year and 5 year respectively. RESULTS: A total of 401 cases were included. Patients with LSM ≥12kPa had significantly lower 5-year overall survival rate (75.1% vs 57.3%, p < 0.001) and disease free survival rate (45.8% vs. 26.7%, p < 0.001). On multivariate analysis, pre-operative creatinine and vascular invasion of tumor were significant factors in predicting early recurrence (p = 0.012 and p = 0.004). LSM ≥12kPa were the only significant factor in predicting late recurrence (p = 0.048). CONCLUSION: Pre-operative liver stiffness measurement could predict the late recurrence of hepatocellular carcinoma after curative resection.

Robotic versus open hemihepatectomy: a propensity score-matched study.

BACKGROUND: Minimally invasive approach has been increasingly applied in liver resection. However, laparoscopic major hepatectomy is technically demanding and is practiced only in expert centers around the world. Conversely, use of robot may help to overcome the difficulty and facilitate major hepatectomy. METHODS: Between September 2010 and March 2019, 151 patients received robotic hepatectomy for various indications in our center. 36 patients received robotic hemihepatectomy: 26 left hepatectomy and 10 right hepatectomy. During the same period, 737 patients received open hepatectomy and out of these, 173 patients received open hemihepatectomy. A propensity score-matched analysis was performed in a 1:1 ratio. RESULTS: After matching, there were 36 patients each in the robotic and open group. The two groups were comparable in demographic data, type of hemihepatectomy, underlying pathology, size of tumor, and background cirrhosis. Conversion was needed in 3 patients (8.3%) in the robotic group. There was no operative mortality. The operative blood loss and resection margin were similar. Though not significantly different, there was a higher rate of complications in the robotic group (36.1% vs. 22.2%) and this difference was mostly driven by higher intra-abdominal collection (16.7% vs. 5.6%) and bile leak (5.6% vs. 2.8%). Operative time was significantly longer (400.8 ± 136.1 min vs 255.4 ± 74.4 min, P < 0.001) but the postoperative hospital stay was significantly shorter (median 5 days vs 6.5 days, P = 0.040) in the robotic group. When right and left hepatectomy were analyzed separately, the advantage of shorter hospital stay remained in left but not right hepatectomy. For patients with hepatocellular carcinoma, there was no difference between the two groups in 5-year overall and disease-free survival. CONCLUSION: Compared with the open approach, robotic hemihepatectomy has longer operation time but shorter hospital stay. Thus, use of robot is feasible and effective in hemihepatectomy with the benefit of shorter hospital stay.

Development and validation of a novel nomogram predicting 10-year actual survival after curative hepatectomy for hepatocellular carcinoma.

INTRODUCTION: Although hepatectomy is a curative treatment modality for hepatocellular carcinoma (HCC), the associated 10-year long-term actual survival are rarely reported. This study aims to develop and validate a predictive nomogram for 10-year actual survivors with HCC. MATERIALS AND METHODS: From 2004 to 2009, 753 patients with curative hepatectomy for HCC (development set, n = 325; validation set, n = 428) were included. In development set, comparison of clinic-pathological data was made between patients surviving ≥10 years and those surviving <10 years. Good independent prognostic factors identified by multivariate analysis were involved in a nomogram development, which was validated internally and externally using validation set. RESULTS: On multivariate analysis, five independent good prognostic factors for 10-year survival were identified, including young age (OR = 0.943), good ASA status (≤2) (OR = 2.794), higher albumin level (OR = 1.116), solitary tumor (OR = 2.531) and absence of microvascular invasion (OR = 3.367). A novel nomogram was constructed with C-index of 0.801 (95% CI 0.762-0.864). A cut-off point of 167.5 had a sensitivity of 0.794 and specificity of 0.730. Internal validation using bootstrap sampling and external validation using validation set revealed C-index of 0.792 (95% CI, 0.741-0.853) and 0.761 (95% CI, 0.718-0.817). CONCLUSION: A novel nomogram for 10-year HCC survivor using age, ASA status, preoperative albumin, tumor number and presence of microvascular tumor invasion was developed and validated with high accuracy.

Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland.

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2-/- mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes.

The Atypical Chemokine Receptor Ackr2 Constrains NK Cell Migratory Activity and Promotes Metastasis.

Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient in the atypical chemokine receptor Ackr2 display impaired development of metastasis in vivo in both cell line and spontaneous models. Further analysis reveals that this relates to increased expression of the chemokine receptor CCR2, specifically by KLRG1+ NK cells from the Ackr2-/- mice. This leads to increased recruitment of KLRG1+ NK cells to CCL2-expressing tumors and enhanced tumor killing. Together, these data indicate that Ackr2 limits the expression of CCR2 on NK cells and restricts their tumoricidal activity. Our data have important implications for our understanding of the roles for chemokines in the metastatic process and highlight Ackr2 and CCR2 as potentially manipulable therapeutic targets in metastasis.

Laparoscopic Hepatectomy (with or without Robotic Assistance) versus Radiofrequency Ablation as a Minimally Invasive Treatment for Very Early-Stage or Early-Stage Hepatocellular Carcinoma.

BACKGROUND: The advantages of radiofrequency ablation (RFA) over hepatectomy as a treatment for early-stage hepatocellular carcinoma (HCC) include reduced morbidity and more rapid recovery. Although minimally invasive surgery provides similar benefits, few studies have compared the long-term oncological outcomes of these techniques. This study aimed to compare the outcomes of minimally invasive hepatectomy (MIH) and RFA. METHODS: Patients who underwent MIH or RFA for HCC between January 2005 and January 2015 were included in a propensity score matching analysis. Only patients who underwent minimally invasive procedures for small HCC were included. Baseline clinical and laboratory parameters were retrieved from the hospital database and analyzed. RESULTS: Two hundred and twenty-five patients underwent MIH or RFA for HCC during the study period. Propensity score matching yielded 59 patient-pairs. The complication rates did not differ statistically between the 2 groups (p = 0.309). However, MIH provided significantly better overall (p = 0.005) and disease-free survival outcomes (p < 0.001) than RFA. CONCLUSIONS: Compared with RFA, MIH provided better long-term survival outcomes in patients with early-stage HCC, with no increase in the incidence of complications. When feasible, MIH should be considered a first-line treatment for this patient population.

Prospective double-blinded randomized controlled trial of Microwave versus RadioFrequency Ablation for hepatocellular carcinoma (McRFA trial).

BACKGROUND: Microwave (MWA) and radiofrequency ablation are the commonly used local ablation for hepatocellular carcinoma (HCC). Studies comparing both techniques are scarce. The aim of this study was to compare the efficacy of MWA versus RFA as a treatment for HCC. METHODS: Patients with HCC who were suitable for local ablation were randomized into MWA or RFA. All patients were followed up regularly with contrast-enhanced computed tomography (CT) performed at 1, 3, 6 and 12 months after ablation. Both patients and the radiologists who interpreted the post-procedure CT scans were blinded to the treatment allocation. Treatment-related morbidity, overall and disease-free survivals were analyzed. RESULTS: A total of 93 patients were recruited. Among them, 47 and 46 patients were randomized to MWA and RFA respectively. Patients in two groups were comparable in baseline demographics and tumor characteristics. With a median follow-up of around 30 months, there were no significant difference in the treatment-related morbidity, overall and disease-free survivals. MWA had a significantly shorter overall ablation time when compared with RFA (12 min vs 24 min, p < 0.001). CONCLUSIONS: MWA is no different to RFA with respect to completeness of ablation and survivals. It is, however, as safe and effective as RFA in treating small HCC.

Percutaneous Portal Vein Embolization Using a Simplified Sheathless 18-Gauge Trocar Needle Approach: Review of Efficacy and Safety.

PURPOSE: Portal vein (PV) embolization (PVE) is traditionally performed via a PV sheath with selective embolization of PV branches. Here, the efficacy and safety of PVE with the use of only an 18-gauge needle is reported. MATERIALS AND METHODS: Consecutive patients who underwent PVE from 2009 through 2017 were retrospectively reviewed. Forty-five patients (mean age, 60 y ± 7.6; 38 men) underwent 45 PVE procedures. Hepatocellular carcinoma, cholangiocarcinoma, and metastases accounted for 26 (58%), 13 (29%), and 6 (13%) patients, respectively. PVE was performed by puncturing a branch of right PV with an 18-gauge needle under US guidance. Via the same needle, direct portography was performed, followed by PVE with an N-butyl cyanoacrylate/Lipiodol mixture. Percentage increase of future liver remnant (FLR) volume and increase in ratio of FLR to total liver volume were estimated as measures of efficacy. Complications were reported according to Society of Interventional Radiology classification. Fluoroscopy time, procedure time, and dose-area product (DAP) were recorded. RESULTS: Technical success rate was 100%. The median DAP, fluoroscopy time, and procedure time were 74,387 mGy·cm2 (IQR, 90,349 mGy·cm2), 3.5 min (IQR, 2.10 min), and 24 min (IQR, 10.5 min). Among the 23 patients with complete CT volumetry data, mean increase in the ratio of FLR to total liver volume and percentage increase of FLR volume were 12.5% ± 7.7 and 50% ± 33, respectively. There were 3 minor complications (asymptomatic nonocclusive emboli in FLR) and 3 major complications (1 hepatic vein emboli, 1 subphrenic collection, and 1 hepatic infarct). CONCLUSIONS: PVE via a sheathless 18-gauge needle approach is feasible, with satisfactory FLR hypertrophy.