Background: Regional anesthesia is known to prevent or attenuate the surgical stress response; therefore, inhibiting surgical stress by paravertebral anesthesia might attenuate perioperative factors that enhance tumor growth and spread. The authors hypothesized that breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastases than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia. Methods: In this retrospective study, the authors examined the medical records of 129 consecutive patients undergoing mastectomy and axillary clearance for breast cancer between September 2001 and December 2002. Results: Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia. The follow-up time was 32 +/- 5 months (mean +/- SD). There were no significant differences in patients or surgical details, tumor presentation, or prognostic factors. Recurrence- and metastasis-free survival was 94% (95% confidence interval, 87-100%) and 82% (74-91%) at 24 months and 94% (87-100%) and 77% (68-87%) at 36 months in the paravertebral and general anesthesia patients, respectively (P = 0.012). Conclusions: This retrospective analysis suggests that paravertebral anesthesia and analgesia for breast cancer surgery reduces the risk of recurrence or metastasis during the initial years of follow-up. Prospective trials evaluating the effects of regional analgesia and morphine sparing on cancer recurrence seem warranted.

Background: Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. Methods: In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. Results: After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. Conclusions: Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.

There is increasing evidence that intraoperative fluid therapy decisions may influence postoperative outcomes. In the past, patients undergoing major surgery were often administered large volumes of crystalloid, based on a presumption of preoperative dehydration and nebulous intraoperative 'third space' fluid loss. However, positive perioperative fluid balance, with postoperative fluid-based weight gain, is associated with increased major morbidity. The concept of 'third space' fluid loss has been emphatically refuted, and preoperative dehydration has been almost eliminated by reduced fasting times and use of oral fluids up to 2 h before operation. A 'restrictive' intraoperative fluid regimen, avoiding hypovolaemia but limiting infusion to the minimum necessary, initially reduced major complications after complex surgery, but inconsistencies in defining restrictive vs liberal fluid regimens, the type of fluid infused, and in definitions of adverse outcomes have produced conflicting results in clinical trials. The advent of individualized goal-directed fluid therapy, facilitated by minimally invasive, flow-based cardiovascular monitoring, for example, oesophageal Doppler monitoring, has improved outcomes in colorectal surgery in particular, and this monitor has been approved by clinical guidance authorities. In the contrasting clinical context of relatively low-risk patients undergoing ambulatory surgery, high-volume crystalloid infusion (20-30 ml kg(-1)) reduces postoperative nausea and vomiting, dizziness, and pain. This review revises relevant physiology of body water distribution and capillary-tissue flow dynamics, outlines the rationale behind the fluid regimens mentioned above, and summarizes the current clinical evidence base for them, particularly the increasing use of individualized goal-directed fluid therapy facilitated by oesophageal Doppler monitoring.

Cancer is a leading cause of morbidity and mortality worldwide and the ratio of incidence is increasing. Mortality usually results from recurrence or metastases. Surgical removal of the primary tumour is the mainstay of treatment, but this is associated with inadvertent dispersal of neoplastic cells into the blood and lymphatic systems. The fate of the dispersed cells depends on the balance of perioperative factors promoting tumour survival and growth (including surgery per se, many anaesthetics per se, acute postoperative pain, and opioid analgesics) together with the perioperative immune status of the patient. Available evidence from experimental cell culture and live animal data on these factors are summarized, together with clinical evidence from retrospective studies. Taken together, current data are sufficient only to generate a hypothesis that an anaesthetic technique during primary cancer surgery could affect recurrence or metastases, but a causal link can only be proved by prospective, randomized, clinical trials. Many are ongoing, but definitive results might not emerge for a further 5 yr or longer. Meanwhile, there is no hard evidence to support altering anaesthetic technique in cancer patients, pending the outcome of the ongoing clinical trials.

Introduction Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO₂) in patients with inflammatory arthritis with macroscopic/microscopic inflammation and local levels of proinflammatory mediators. Methods Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO₂ under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor α (TNFα), interleukin 1β (IL1β), interferon γ (IFNγ), IL6, macrophage inflammatory protein 3α (MIP3α) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. Results The tPO₂ was 22.5 (range 3.2–54.1) mm Hg and correlated inversely with macroscopic synovitis (r=−0.421, p=0.02), sublining CD3 cells (−0.611, p<0.01) and sublining CD68 cells (r=−0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO₂ in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor α (TNFα), IL1β, IFNγ and MIP3α in patients with tPO₂ <20 mm Hg (all p values <0.05). Conclusions This is the first study to show a direct in vivo correlation between synovial tPO₂, inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.