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Cancer is an important cause of morbidity and mortality after liver transplantation and can occur through three mechanisms: recurrence of a recipient's pre-transplant malignancy, donor-related transmission and de novo development. Currently, the decision to list a patient with a history of malignancy is an individual one. Screening guidelines for potential donors and for recipients after transplant are still widely based on general population guidelines, while the role of chronic immunosuppression remains controversial. These shortcomings mean that patients present at diagnosis with advanced stages of the disease, often precluding curative treatments. The present review summarizes current recommendations for the screening of recipients and donors for pre- and post-transplant malignancies, and current management of recipients who develop cancer after a liver transplant., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Tumor dormancy is considered one of the major unsolved questions in cancer biology. Understanding the mechanisms responsible for maintaining and interrupting dormancy would be a major step towards preventing overt metastatic disease. Increasing evidence points to tissue trauma and subsequent wound healing as contributing events in escape from dormancy. In this review, we outline relevant aspects of the wound healing process, and relate this to mechanisms of tumor dormancy and metastatic progression. In addition to important findings in epidemiological and experimental studies, more direct evidence of such a link has recently been presented. These results can have major implications for treatment and prevention of cancer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Spine metastases affect a significant number of cancer patients each year, with the spine being the third most common location for cancer spread. As patients live longer with improved treatments, the opportunity for recurrence at previously treated sites increases. Here, we describe seven patients with recurrent, compressive, metastatic spine tumors at previously surgically treated sites that required additional surgical intervention with manipulation of at least one rod. Five of the patients had recurrence including adjacent levels while two had recurrence solely at the previously decompressed level. The patients remained ambulatory for an average of 31.2 months after the initial surgery. We also discuss the role of adjuvant treatment in these patients and review the literature.

Purpose: Many cancer survivors report experiencing somatic symptoms as well as elevated stress. Theoretical models have suggested that physical symptoms generate subjective stress via fears of recurrence or progression. To date, this indirect effect has not been established empirically. This study aimed to provide preliminary evidence as to whether fear of recurrence or progression is an intermediary between somatic symptom severity and perceived stress among heterogeneous cancer survivors., Methods: Adult cancer survivors (N = 67; median 2.4 years since diagnosis; 34% male) presenting at a hospital survivorship clinic completed measures assessing somatic symptom severity (Patient Health Questionnaire-15 (PHQ-15)), perceived stress (four-item Perceived Stress Scale (PSS-4)), and fear of recurrence or progression (Assessment of Survivor Concerns (ASC)). Interrelatedness among variables was assessed using Pearson correlations. Indirect effects were modeled using 5000-iteration bootstrapping., Results: Survivors endorsed a range of somatic symptom severity (29% minimal, 39% low, 18% medium, and 14% high). Somatic symptoms, perceived stress, and fear of recurrence or progression were all significantly positively correlated (rs 0.29 to 0.47). Controlling for time since diagnosis, there was a significant indirect effect of somatic symptom severity on stress via fear of recurrence or progression [B = 0.06, SE = 0.04 (95% CI 0.01-0.16)]. The model accounted for more than one third of the variance in perceived stress [R 2  = 0.35, F(3,54) = 9.59, p < 0.001]., Conclusions: Survivors with greater somatic symptoms tended to report higher levels of stress, due in part to elevated fears of recurrence or progression. Our findings support concerns about recurrence or progression as a mechanism underlying stress states in cancer survivors. Efforts to assist survivors with stress management should teach strategies for managing cancer-related uncertainties stemming from somatic symptoms.

Cancer stem cells (CSCs) are a class of pluripotent cells that have been observed in most types of solid and hematologic cancers. CSCs have been shown in numerous cancer models to be involved in tumor development, cell proliferation, and metastatic dissemination, while possessing a capacity for sustained self-renewal. CSCs, which typically represent a small proportion of total cells of a given tumor, also exhibit resistance to chemotherapy and radiotherapy. Indeed, exposure to these treatments may promote "stemness" in nonstem cancer cells, which may explain why successful therapeutic reduction of tumor bulk will often fail to produce clinical improvement. Acquisition of stemness involves epithelial-mesenchymal transition (EMT), in which epithelial cells are transformed into a mesenchymal phenotype characterized by increased capacities for migration, invasiveness, and resistance to apoptosis. EMT may also contribute to metastasis by driving dissemination of mesenchymal CSCs to distant locations, whereupon the CSCs revert to an epithelial phenotype to support metastatic tumor growth. Several different approaches to treatment aimed at overcoming the intrinsic resistance of CSCs to conventional therapies are currently being developed. These include agents targeting tumorigenic pathways, such as JAK2/STAT3 and PI3K/mTOR, and immunotherapies, including vaccines and natural killer cells employed to induce a T cell response.

Purpose of Review: With the majority of deaths from cancer because of their metastases, strategies to reduce this from occurring are at the forefront of treatment. It has been hypothesized that morphine may result in an increase in cancer metastases, following many in-vitro and animal studies, but the evidence from human retrospective data is inconclusive. This article will explore the possible mechanisms by which opioids can impact on the natural history of the cancer cell and whether they are likely to be harmful in individuals with cancer., Recent Findings: Although there have been trials demonstrating benefits with regional anaesthesia techniques (opioid sparing) in the surgical population, it is not clear whether the source of the benefit arises directly from the avoidance of opioids or an added benefit afforded by regional anaesthesia. Research has shown that in particular cancer cell types, morphine may actually be beneficial and that the μ-opioid receptor (MOR) plays a role in cancer disease. With the crystal structure of the MOR having recently been elucidated, this may offer new opportunities for treatments aimed at reducing cancer metastasis., Summary: The role opioids play in the development of cancer metastasis and recurrence is far from clear and appears to differ depending on the cancer cell type in question. Prospective randomized controlled trials are currently underway in humans to help clarify the situation further and there results are awaited with anticipation. The negative impact of pain on the immune system is well documented and it appears that appropriate analgesia is paramount in minimizing this. Opioids still constitute a central role in the management of moderate-to-severe cancer pain.

Many of the most common anesthetics are used in surgical oncology, yet effects on cancer cells are still not known. Anesthesia technique could differentially affect cancer recurrence in oncologic patients undergoing surgery, due to immunosuppression, stimulation of angiogenesis, and dissemination of residual cancer cells. Data support the use of intravenous anesthetics, such as propofol anesthesia, thanks to antitumoral protective effects inhibiting cyclooxygenase 2 and prostaglandins E2 in cancer cells, and stimulation of immunity response; a restriction in the use of volatile anesthetics; restriction in the use of opioids as they suppress humoral and cellular immunity, and their chronic use favors angiogenesis and development of metastases; use of locoregional anesthesia compared with general anesthesia, as locoregional appears to reduce cancer recurrence after surgery. However, these findings must be interpreted cautiously as there is no evidence that simple changes in the practice of anesthesia can have a positive impact on postsurgical survival of cancer patients.

Diagnosis of cancer is an emotionally traumatic event that significantly impacts the quality of life (QoL) of the patients. Progression to metastasis or recurrence of cancer after first diagnosis poses a greater threat to life that further increases this emotional trauma and can worsen the QoL. In this research we sought to explore the differences in QoL (symptom severity and physical functioning) experienced by primary non-metastatic (PNM), primary metastatic (PM) and recurrent (RC) cancer patients. Cancer patients recruited in two cognitive intervention trials formed the sample for this analysis. Data were analysed using longitudinal mixed models, with two interaction terms. Least square means were calculated and compared. Over the period of study RC patients reported the worst symptom severity and physical function followed by PM and PNM patients. Primary non-metastatic patients showed a steady decline in severity whereas PM and RC showed slight gains after the first follow-up. Primary non-metastatic patients displayed best physical functioning followed by PM and RC patients, and remained stable over time. Breast cancer patients displayed most variation in symptom severity among the three progression groups, whereas significant variation in physical function among the three groups was observed within all cancer sites.

Patients with cancer can develop recurrent metastatic disease with latency periods that range from years even to decades. This pause can be explained by cancer dormancy, a stage in cancer progression in which residual disease is present but remains asymptomatic. Cancer dormancy is poorly understood, resulting in major shortcomings in our understanding of the full complexity of the disease. Here, I review experimental and clinical evidence that supports the existence of various mechanisms of cancer dormancy including angiogenic dormancy, cellular dormancy (G0-G1 arrest) and immunosurveillance. The advances in this field provide an emerging picture of how cancer dormancy can ensue and how it could be therapeutically targeted.

Purpose: To describe the frequency distribution for the number of residual subclinical metastatic tumor cells after removal of the primary cancer., Materials and Methods: Previously obtained autopsy, surgical pathological and laboratory data were used to characterize the size and number distributions for hematogenous and lymphatic metastases. Monte Carlo simulations were used to estimate the numbers of residual tumor cells based upon the assumption of a lognormal distribution for the sizes of metastases and Poisson, Poisson negative binomial, or negative binomial distributed numbers of metastases (corresponding to lymphatic metastases within individuals, hematogenous metastases within individuals, and lymphatic metastases within populations, respectively)., Results: In each of the scenarios the resultant distribution for the numbers of subclinical tumor cells was unimodal and positively skewed, with a tail extending to the higher numbers of metastases. When plotted with equal sized counting bins and according the logarithm of the number of tumor cells, the distributions showed deviations from the normal form no greater than several percentage points--a result considered acceptable given the variabilities inherent to metastasis data., Conclusions: The distribution for the number of residual subclinical metastases may be extrapolated from data and models derived from the size and number distributions for metastases. In the absence of a closed form description for this distribution, the lognormal distribution could provide a crude, but practical, approximation for cases limited to occult microscopic residual disease. These analyses will facilitate the definition of the dose-response for the adjuvant therapy of subclinical metastases.

The ability of GH, via its mediator peptide IGF-1, to influence regulation of cellular growth has been the focus of much interest in recent years. In this review, we will explore the association between GH and cancer. Available experimental data support the suggestion that GH/IGF-1 status may influence neoplastic tissue growth. Extensive epidemiological data exist that also support a link between GH/IGF-1 status and cancer risk. Epidemiological studies of patients with acromegaly indicate an increased risk of colorectal cancer, although risk of other cancers is unproven, and a long-term follow-up study of children deficient in GH treated with pituitary-derived GH has indicated an increased risk of colorectal cancer. Conversely, extensive studies of the outcome of GH replacement in childhood cancer survivors show no evidence of an excess of de novo cancers, and more recent surveillance of children and adults treated with GH has revealed no increase in observed cancer risk. However, given the experimental evidence that indicates GH/IGF-1 provides an anti-apoptotic environment that may favour survival of genetically damaged cells, longer-term surveillance is necessary; over many years, even a subtle alteration in the environmental milieu in this direction, although not inducing cancer, could result in acceleration of carcinogenesis. Finally, even if GH/IGF-1 therapy does result in a small increase in cancer risk compared to untreated patients with GH deficiency, it is likely that the eventual risk will be the same as the general population. Such a restoration to normality will need to be balanced against the known morbidity of untreated GH deficiency.

Fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) allows in vivo analysis of tissue metabolic activity. Based on the observation that most malignant tumors display a higher metabolic activity than benign tissues, [18F]FDG-PET offers an interesting option for the diagnosis of primary and recurrent malignant tumors. For the oncological surgeon [18F]FDG-PET is particularly helpful for the diagnosis of tumors of the pancreas, colorectum, lung and esophagus. This short review describes the biological basis of [18F]FDG-PET and gives a critical discussion of its role in oncological surgery.

Seventeen patients with intractable pain due to progressive malignancies were treated by electrical stimulation of the brain after more conventional pain therapies applied in the University of California, Los Angeles Cancer Pain Clinic had failed. Electrodes were stereotactically implanted under local anesthesia in the periaqueductal grey (PAG) or periventricular grey (PVG) in 11 patients. In six patients electrodes were placed in both PAG-PVG targets and in the sensory thalamic nuclei. Thirteen of the 17 patients achieved virtually total pain relief and 2 others achieved partial pain relief. At the hospital discharge only 4 of 17 patients required narcotic analgesics for pain relief. Follow-up periods ranged from 1 to 21 months and 6 patients remain alive. Fourteen patients eventually required narcotics for pain relief, usually in the terminal few weeks of their lives. Pain relief was achieved in spite of the fact that all patients were tolerant to large doses of systematically or intraspinally administered narcotics at the time of electrode placement. No complications related to brain stimulation were identified. Brain stimulation is a safe and effective method for treatment of intractable pain due to malignancy in certain patients.