Debate on appropriate triggers for transfusion of allogeneic blood products and their effects on short- and long-term survival in surgical and critically ill patients continue with no definitive evidence or decisive resolution. Although transfusion-related immune modulation (TRIM) is well established, its influence on immune competence in the recipient and its effects on cancer recurrence after a curative resection remains controversial. An association between perioperative transfusion of allogeneic blood products and risk for recurrence has been shown in colorectal cancer in randomized trials; whether the same is true for other types of cancer remains to be determined. This article focuses on the laboratory, animal, and clinical evidence to date on the mechanistic understanding of inflammatory and immune-modulatory effects of blood products and their significance for recurrence in the cancer surgical patient.

Background. The therapeutic resistance of pancreatic ductal adenocarcinoma (PDAC) is partly ascribed to ineffective delivery of chemotherapy to cancer cells. We hypothesized that physical properties at vascular, extracellular, and cellular scales influence delivery of and response to gemcitabine-based therapy.Methods. We developed a method to measure mass transport properties during routine contrast-enhanced CT scans of individual human PDAC tumors. Additionally, we evaluated gemcitabine infusion during PDAC resection in 12 patients, measuring gemcitabine incorporation into tumor DNA and correlating its uptake with human equilibrative nucleoside transporter (hENT1) levels, stromal reaction, and CT-derived mass transport properties. We also studied associations between CT-derived transport properties and clinical outcomes in patients who received preoperative gemcitabine-based chemoradiotherapy for resectable PDAC.Results. Transport modeling of 176 CT scans illustrated striking differences in transport properties between normal pancreas and tumor, with a wide array of enhancement profiles. Reflecting the interpatient differences in contrast enhancement, resected tumors exhibited dramatic differences in gemcitabine DNA incorporation, despite similar intravascular pharmacokinetics. Gemcitabine incorporation into tumor DNA was inversely related to CT-derived transport parameters and PDAC stromal score, after accounting for hENT1 levels. Moreover, stromal score directly correlated with CT-derived parameters. Among 110 patients who received preoperative gemcitabine-based chemoradiotherapy, CT-derived parameters correlated with pathological response and survival.Conclusion. Gemcitabine incorporation into tumor DNA is highly variable and correlates with multiscale transport properties that can be derived from routine CT scans. Furthermore, pretherapy CT-derived properties correlate with clinically relevant endpoints.Trial registration. Clinicaltrials.gov NCT01276613.

:  The hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a novel hypnotic‐anesthetic agent. Sublingually or orally administered melatonin is an effective premedicant in adults and children. Melatonin premedication like midazolam is associated with sedation and preoperative anxiolysis, however, unlike midazolam these effects are not associated with impaired psychomotor skills or the quality of recovery. Melatonin administration also is associated with a tendency toward faster recovery and a lower incidence of postoperative excitement than midazolam. Oral premedication with 0.2 mg/kg melatonin significantly reduces the propofol and thiopental doses required for loss of responses to verbal commands and eyelash stimulation. In rats, melatonin and the more potent melatonin analogs 2‐bromomelatonin and phenylmelatonin have been found to have anesthetic properties similar to those of thiopental and propofol, with the added advantage of providing potent antinociceptive effects. The exact mechanism(s) by which structurally diverse intravenous and volatile anesthetics produce general anesthesia is still largely unknown, but positive modulation of γ‐aminobutyric acid type A (GABAA) receptor function has been recognized as an important and common pathway underlying the depressant effects of many of these agents. Accumulating evidence indicates that there is interplay between the melatonergic and GABAergic systems, and it has been demonstrated that melatonin administration produces significant, dose‐dependent increases in GABA concentrations in the central nervous system. Additional in vitro data suggest that melatonin alters GABAergic transmission by modulating GABAA receptor function. Of greater importance, data from in vivo studies suggest that the central anesthetic effects of melatonin are mediated, at least in part, via GABAergic system activation, as they can be blocked or reversed by GABAA receptor antagonists. Further work is needed to better understand the general anesthetic properties of melatonin at the molecular, cellular, and systems levels.

Enhanced recovery after surgery (ERAS) programs aim to hasten functional recovery and improve postoperative outcomes. However, there is a paucity of data on ERAS programs in gynecologic surgery. We reviewed the published literature on ERAS programs in colorectal surgery, general gynecologic surgery, and gynecologic oncology surgery to evaluate the impact of such programs on outcomes, and to identify key elements in establishing a successful ERAS program. ERAS programs are associated with shorter length of hospital stay, a reduction in overall health care costs, and improvements in patient satisfaction. We suggest an ERAS program for gynecologic oncology practice involving preoperative, intraoperative, and postoperative strategies including; preadmission counseling, avoidance of preoperative bowel preparation, use of opioid-sparing multimodal perioperative analgesia (including loco-regional analgesia), intraoperative goal-directed fluid therapy (GDT), and use of minimally invasive surgical techniques with avoidance of routine use of nasogastric tube, drains and/or catheters. Postoperatively, it is important to encourage early feeding, early mobilization, timely removal of tubes and drains, if present, and function oriented multimodal analgesia regimens. Successful implementation of an ERAS program requires a multidisciplinary team effort and active participation of the patient in their goal-oriented functional recovery program. However, future outcome studies should evaluate the efficacy of an intervention within the pathway, include objective measures of symptom burden and control, study measures of functional recovery, and quantify outcomes of the program in relation to the rates of adherence to the key elements of care in gynecologic oncology such as oncologic outcomes and return to intended oncologic therapy (RIOT).

Preclinical studies have demonstrated that opioid receptor agonists increase the rate of non-small cell lung cancer (NSCLC) growth and metastasis. Following institutional review board approval, we retrieved data on 901 patients who underwent surgery for NSCLC at MD Anderson Cancer Center. Comprehensive demographics, intraoperative data, and recurrence-free survival (RFS) and overall survival (OS) at 3 and 5 years were obtained. Cox proportional analyses were conducted to assess the association between intraoperative opioid exposure and RFS and OS. The median intraoperative fentanyl equivalents dosage was 10.15 μg/kg. The multivariate analysis by stage indicated that a trend toward significance for opioid consumption as a risk factor in stage I patients (P = 0.053). No effect was found on RFS for stage II or III patients. Alternatively, opioid consumption was a risk factor for OS for stage I patients (P = 0.036), whereas no effect was noted for stage II or III patients. Intraoperative opioid use is associated with decreased OS in stage I but not stage II–III NSCLC patients. Until randomized controlled studies explore this association further, opioids should continue to be a key component of balanced anesthesia.