Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.

Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested; many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to help us address disease relapse, which is a substantial and longstanding problem, so a proposed agenda for future research is offered.

Gastrointestinal healing is a topic rarely reviewed in the literature, yet it is of paramount importance to the surgeon. Failure of anastomotic healing may lead to life-threatening complications, additional surgical procedures, increased length of stay, increased cost, long-term disability, and reduced quality of life for the patient. The goal of this article is to review the biological response to wounded tissue, to outline discrete differences between skin and gastrointestinal healing, to discuss local and systemic factors important to gastrointestinal healing, and to compare methods of measuring collagen content and strength of the newly formed anastomosis. Part II of this review will focus on techniques and therapies available to optimize anastomotic healing.

Hiatus hernia, Mesh repair, Laparoscopy, Randomized controlled trial. Trial registration -This trial is registered with the Australia and New Zealand ClinicalTrials Registry ACTRN12605000725662 Determine whether absorbable or non-absorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared to suture repair. Summary Background Data:Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short term recurrence with mesh, but adverse outcomes limit mesh use. Methods:Multicentre prospective double blind randomized controlled trial of 3 methods of repair; sutures vs. absorbable mesh vs. non-absorbable mesh. Primary outcome -hernia recurrence assessed by barium meal X-ray and endoscopy at 6 months. Secondary outcomes -clinical symptom scores at 1, 3, 6 and 12 months. Results:126 patients enrolled -43 sutures, 41 absorbable mesh and 42 non-absorbable mesh. 96.0%were followed to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% following suture repair, 30.8% -absorbable mesh, and 12.8%

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