Robot-assisted one-stage resection of rectal cancer with liver and lung metastases

The Da Vinci Surgical System may help to overcome some of the difficulties of laparoscopy for complicated abdominal surgery.The authors of this article present a case of robot-assisted, one-stage radical resection of three tumors, including robotic anterior resection for rectal cancer, segmental hepatectomy for liver metastasis, and wedge-shaped excision for lung metastasis.A 59-year-old man with primary rectal cancer and liver and lung metastases was operated upon with a one-stage radical resection approach using the Da Vinci Surgical System.Resection and anastomosis of rectal cancer were performed extracorporeally afterundocking the robot.The procedure was successfully completed in 500 min.No surgical complications occurred during the intervention and postoperative period, and no conversion to laparotomy or additional trocars were required.To the best of our knowledge, this is the first case of simultaneous resection for rectal cancer with liver and lung metastases using the Da Vinci Surgery System to be reported.The procedure is feasible and safe and its main advantages for patient are avoiding repeated operation, reducing surgical trauma, shortening recovery time, and early implementation of postoperative adjuvant therapy.

Anti-EGFR and anti-VEGF agents:Important targeted therapies of colorectal liver metastases

Colorectal liver metastasis(CLM)is common worldwide.Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials,and are now becoming standards for patients with CLM.Thedevelopment and application of anti-epidermal growth factor receptor(anti-EGFR)and anti-vascular endothelial growth factor(anti-VEGF)antibodies represents significant advances in the treatment of this disease.However,new findings continue to emerge casting doubt on the efficacy of this approach.The Kirsten ratsarcoma viral oncogene(KRAS)has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM.Whereas a recent study summarizedseveral randomized controlled trials,and showed thatpatients with the KRAS G13D mutation significantlybenefited from the addition of cetuximab in terms of progress-free survival(PFS,4.0 mo vs 1.9 mo,HR=0.51,P=0.004)and overall survival(OS,7.6 mo vs5.7 mo,HR=0.50,P=0.005).Some other studiesalso reported that the KRAS G13D mutation might notbe absolutely predictive of non-responsiveness to antiEGFR therapy.At the same time,"new"RAS mutations,including mutations in neuroblastoma RAS viral(vras)oncogene homolog(NRAS)and exons 3 and 4 of KRAS,have been suggested to be predictors of a poor treatment response.This finding was first reported by the update of the PRIME trial.The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations,panitumumab-fluorouracil,leucovorin,and oxaliplatin(FOLFOX)4 treatment led to inferior PFS(HR=1.28,95%CI:0.79-2.07)and OS(HR=1.29,95%CI:0.79-2.10),which was consistent with the findings in patients with KRAS mutations in exon 2.Then,the update of the PEAK trial and the FIRE-Ⅲtrial also supported this finding,which would reduce candidates for anti-EGFR therapy but enhance the efficacy.In firstline targeted combination therapy,the regimens of cetuximab plus FOLFOX was called into question because of the inferior prognosis in the COIN trial and the NORDIC-Ⅶtrial.Also,bevacizumab plus oxaliplatin-based chemotherapy was questioned because of the NO16966trial.By the update and further analysis of the COIN trial and the NORDIC-Ⅶtrial,cetuximab plus FOLFOX was reported to be reliable again.But bevacizumab plus oxaliplatin-based chemotherapy was still controversial.In addition,some trials have reported that bevacizumab is not suitable for conversion therapy.The results of the FIRE-Ⅲtrial showed that cetuximab led to a significant advantage over bevacizumab in response rate(72%vs 63%,P=0.017)for evaluable population.With the balanced allocation of second-line treatment,the FIRE-Ⅲtrial was expected to provide evidence for selecting following regimens after first-line progression.There is still no strong evidence for the efficacy of targeted therapy as a preoperative treatment for resectable CLM or postoperative treatment for resected CLM,although the combined regimen is often administered based on experience.Combination therapy with more than one targeted agent has been proven to provide no benefit,and even was reported to be harmful as first-line treatment by four large clinical trials.However,recent studies reported positive results of erlotinib plus bevacizumab for maintenance treatment.The mechanism of antagonism between different targeted agents deserves further study,and may also provide greater understanding of the development of resistance to targeted agents.

Early activated hepatic stellate cell-derived molecules reverse acute hepatic injury

AIM: To test whether hepatic stellate cells(HSCs) at different activation stages play different roles in acetaminophen(APAP)-induced acute liver injury(ALI).METHODS: HSCs were isolated from mouse liver and cultured in vitro.Morphological changes of initiation HSCs [HSCs(5d)] and perpetuation HSCs [HSCs(p3)] were observed by immunofluorescence and transmission electron microscopy.The protective effects of HSCderived molecules, cell lysates and HSC-conditioned medium(HSC-CM) were tested in vivo by survival and histopathological analyses.Liver injury was determined by measuring aminotransferase levels in the serum and by histologic examination of tissue sections under a light microscope.Additionally, to determine the molecular mediators of the observed protective effects of initiation HSCs, we examined HSC-CM using a highdensity protein array.RESULTS: HSCs(5d) and HSCs(p3) had different morphological and phenotypic traits.HSCs(5d) presented a star-shaped appearance with expressing α-SMA at non-uniform levels between cells.However, HSCs(p3) evolved into myofibroblast-like cells without lipid droplets and expressed a uniform and higher level of α-SMA.HSC-CM(5d), but not HSC-CM(p3), provided a significant survival benefit and showed a dramatic reduction of hepatocellular necrosis and panlobular leukocyte infiltrates in mice exposed to APAP.However, this protective effect was abrogated at higher cell masses, indicating a therapeutic window of effectiveness.Furthermore, the protein array screenrevealed that HSC-CM(5d) was composed of many chemokines and growth factors that correlated with inflammatory inhibition and therapeutic activity.When compared with HSC-CM(p3), higher levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1γ, hepatocyte growth factor, interleukin-10, and matrix metalloproteinase-2, but lower levels of stem cell factor and Fas-Ligand were observed in HSCCM(5d).CONCLUSION: These data indicated that initiation HSCs and perpetuation HSCs were different in morphology and protein expression, and provided the first experimental evidence of the potential medical value of initiation HSC-derived molecules in the treatment of ALI.