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Hepatic metastases are amenable to ablation; however, many patients are not suitable candidates for such therapy and recurrence is common. The tumor microenvironment is known to be essential for metastatic growth, yet identification of plausible targets for cancer therapy in the microenvironment has proven elusive. We found that human colorectal cancer liver metastases and murine gastrointestinal experimental liver metastases are infiltrated by neutrophils. Plasticity in neutrophils has recently been shown to lead to both protumor and antitumor effects. Here, neutrophils promoted the growth of hepatic metastases, given that depletion of neutrophils in already established, experimental, murine liver metastases led to diminished metastatic growth. Decreased growth was associated with reductions in vascular density and branching suggestive of vessel normalization. Metastasis-associated neutrophils expressed substantially more fibroblast growth factor 2 (FGF2) than naive neutrophils, indicating neutrophil polarization by the tumor microenvironment. Administration of FGF2 neutralizing antibody to mice bearing experimental liver metastases phenocopied neutrophil depletion by reducing liver metastatic colony growth, vascular density, and branching. Conclusion Here, we show, using FGF2 as an example, that identification of factors responsible for the protumoral effects of infiltrating myeloid cells can be used to target established liver metastases. Such therapies could be utilized to limit disease progression and potentiate the effects of standard ablative therapies. (Hepatology 2017;65:1920-1935).

To systematically review studies reporting clinicopathological features of intraductal papillary neoplasm of the bile duct (IPNB) to provide evidence-based guidance for management.IPNB is a rare tumor type. Management decisions are currently based upon anecdotal evidence and small case series. To data, there has been no systematic review of IPNB literature.MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched and data were extracted from relevant studies. Meta-analysis was used to pool study estimates. Evidence of association was determined by comparing pooled crude odds ratios (OR) derived from abstracted data.Fifty-seven retrospective case series were included. At least 43% of 476 specimens contained invasive disease. Invasive tumors were found at significantly higher frequency in pancreaticobiliary than intestinal, gastric or oncocytic-type IPNB [pooled OR 2.5, 95% confidence interval (CI) 1.5-4.2, P0.001]. A significantly higher proportion of pancreaticobiliary tumors compared with intestinal tumors expressed MUC-1 [86.4% (95% CI 75.1%-94.7%) vs 13.2% (95% CI 4.6%-25.2%), respectively P0.001]. IPNB identified in centers from Asia were more likely to be intrahepatic and were less frequently invasive compared with those from Western centers. Pooled estimates of absolute survival after IPNB resection were 96% (95% CI 93%-99%) at 1 year, 79% (95% CI 69%-88%) at 3 years, and 65% (95% CI 46%-76%) at 5 years.Early surgery is advisable for radiologically suspected IPNB as it is frequently invasive. The pathobiology of IPNB demonstrates geographic variation. Pancreaticobiliary IPNB expresses MUC1 and is more frequently associated with invasive disease than other IPNB subtypes.

Myeloid cells are known to mediate metastatic progression. Here, we attempted to elucidate the mechanisms underlying these effects by identifying gene expression alterations in cancer cells forming hepatic metastases after myeloid cell depletion. Hepatic metastases are heavily infiltrated by CD11b+ myeloid cells. We established hepatic metastases in transgenic CD11b-diphtheria toxin receptor mice by intrasplenic injection of MC38 colon and Lewis lung carcinoma cells before depleting myeloid cells with diphtheria toxin. Myeloid cell depletion inhibited metastatic growth with a marked diminishment of tumor vasculature. Expression of ANGPTL7 (angiopoietin-like 7), a protein not previously linked to metastasis, was highly up-regulated in cancer cells after myeloid cell depletion. This effect was duplicated in tissue culture, where coculture of cancer cells with tumor-conditioned myeloid cells from liver metastases or myeloid cell conditioned media down-regulated ANGPTL7 expression. Analogous to myeloid cell depletion, overexpression of ANGPTL7 in cancer cells significantly reduced hepatic metastasis formation and angiogenesis. We found that ANGPTL7 itself has strong antiangiogenic effects in vitro. Furthermore, analysis of The Cancer Genome Atlas colorectal and breast cancer data sets revealed striking ANGPTL7 underexpression in cancerous compared to normal tissues. Also, ANGPTL7 was down-regulated in metastatic liver colonies of colorectal cancer patients compared to their adjacent liver tissue. Conclusion: Myeloid cells promote liver metastasis by down-regulating ANGPTL7 expression in cancer cells; our findings implicate ANGPTL7 as a mediator of metastatic progression and a potential target for interference with liver metastases. (Hepatology 2015;62:521–533

OBJECTIVES: Sigmoid volvulus accounts for 5% of cases of large-bowel obstruction. Here, we present the development of a new minimally invasive treatment method that aims to reduce the complication rate of standard percutaneous endoscopic colostomy tube insertion and negate the need for prolonged anesthesia or colectomy. METHODS: Six patients underwent laparoscopic-assisted endoscopic sigmoidopexy for recurrent sigmoid volvulus at a mean age of 80.5 years (range, 76-83). The volvulus was decompressed endoscopically before laparoscopic adhesiolysis and detorsion of the sigmoid. Finally, the sigmoid was approximated with the anterior abdominal wall, and 2 endoscopically placed percutaneous endoscopic colostomy tubes were inserted. Later, the external component of the percutaneous endoscopic colostomy tubes was removed, and the internal parts were passed by way of the rectum. RESULTS: Each operation was completed successfully in a mean time of 69 minutes and with no intraoperative complication. The mean postoperative stay was 20 days (range, 4-54). At median follow-up of 10.8 months, all patients were tube free with no incidence of recurrent volvulus, inadvertent tube traction, or leak. CONCLUSIONS: This preliminary report shows laparoscopic-assisted endoscopic sigmoidopexy to be a safe treatment modality for recurrent sigmoid volvulus. As such, it is particularly useful for elderly patients, for whom colectomy is a high-risk procedure.