Can Regional Anesthesia and Analgesia Prolong Cancer Survival After Orthopaedic Oncologic Surgery?

Background

The perioperative period of major oncologic surgery is characterized by immunosuppression, angiogenesis, and an increased load of circulating malignant cells. It is a window period in which cancer cells may seed, invade, and proliferate. Thus, it has been hypothesized that the use of regional anesthesia with the goal of reducing surgical stress and opioid and volatile anesthetic consumption would avoid perioperative immune suppression and angiogenesis and ultimately cancer recurrence.

Questions/purposes

We performed a systematic review of the literature on the use of regional anesthesia and postoperative analgesia to improve cancer-related survival after oncologic surgery. Our primary topic of interest is survival after orthopaedic oncologic surgery, but because that literature is limited, we also have systematically reviewed the question of survival after breast, gastrointestinal, and genitourologic cancers.

Methods

We searched the PubMed and Embase databases with the search terms: “anesthesia and analgesia”, “local neoplasm recurrence”, “cancer recurrence”, “loco-regional neoplasm recurrence”, “disease-free survival”, and “cumulative survival rates”. Our initial search of the two databases provided 836 studies of which 693 were rejected. Of the remaining 143 studies, only 13 articles qualified for inclusion in this systematic review, based on defined inclusion criteria. All these studies had retrospective design. Due to the high heterogeneity among the identified studies and the complete absence of randomized controlled trials from the literature on this topic, the results of a meta-analysis would be heavily confounded; hence, we instead performed a systematic review of the literature.

Results

No eligible studies addressed the question of whether regional anesthesia and analgesia have an impact on survival after musculoskeletal cancer surgery. Only one relevant clinical study was identified on regional breast cancer survival; it suggested a benefit. The literature on gastrointestinal and genitourinary surgery was larger but mixed, although some preliminary studies do suggest a benefit of regional anesthesia on survival after oncologic surgery in those patient populations.

Conclusions

Although basic science studies suggest a potential benefit of regional anesthesia and stress response reduction in cancer formation, we found little clinical evidence to support the theory that regional anesthesia and analgesia improve overall patient survival after oncologic surgery.     

Alvimopan Accelerates Gastrointestinal Recovery After Radical Cystectomy: A Multicenter Randomized Placebo-Controlled Trial

Background

Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS).

Objective

To assess the efficacy of alvimopan to accelerate GI recovery after RC.

Design, setting, and participants

We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics.

Intervention

Oral alvimopan 12 mg (maximum: 15 inpatient doses) versus placebo.

Outcome measurements and statistical analysis

The two-component primary end point was time to upper (first tolerance of solid food) and lower (first bowel movement) GI recovery (GI-2). Time to discharge order written, postoperative LOS, postoperative ileus (POI)-related morbidity, opioid consumption, and adverse events (AEs) were evaluated. An independent adjudication of cardiovascular AEs was performed.

Results and limitations

Patients were randomized to alvimopan (n = 143) or placebo (n = 137); 277 patients were included in the modified intention-to-treat population. The alvimopan cohort experienced quicker GI-2 recovery (5.5 vs 6.8 d; hazard ratio: 1.8; p < 0.0001), shorter mean LOS (7.4 vs 10.1 d; p = 0.0051), and fewer episodes of POI-related morbidity (8.4% vs 29.1%; p < 0.001). The incidence of opioid consumption and AEs or serious AEs (SAEs) was comparable except for POI, which was lower in the alvimopan group (AEs: 7% vs 26%; SAEs: 5% vs 20%, respectively). Cardiovascular AEs occurred in 8.4% (alvimopan) and 15.3% (placebo) of patients (p = 0.09). Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy.

Conclusions

Alvimopan is a useful addition to a standardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS, with a safety profile similar to placebo.

Patient summary

This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer. Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety.

Trial registration

ClinicalTrials.gov identifier NCT00708201     

Predicting effective connectivity from resting‐state networks in healthy elderly and patients with prodromal Alzheimer's disease

Using functional neuroimaging techniques two aspects of functional integration in the human brain have been investigated, functional connectivity and effective connectivity. In this study we examined both connectivity types in parallel within an executive attention network during rest and while performing an attention task. We analyzed the predictive value of resting‐state functional connectivity on task‐induced effective connectivity in patients with prodromal Alzheimer's disease (AD) and healthy elderly. We found that in healthy elderly, functional connectivity was a significant predictor for effective connectivity, however, it was frequency‐specific. Effective top‐down connectivity emerging from prefrontal areas was related with higher frequencies of functional connectivity (e.g., 0.08–0.15 Hz), in contrast to effective bottom‐up connectivity going to prefrontal areas, which was related to lower frequencies of functional connectivity (e.g., 0.001–0.03 Hz). In patients, the prediction of effective connectivity by functional connectivity was disturbed. We conclude that functional connectivity and effective connectivity are interrelated in healthy brains but this relationship is aberrant in very early AD. Hum Brain Mapp 35:954–963, 2014. © 2013 Wiley Periodicals, Inc.     

Prophylactic use of hyperimmunoglobulin for cytomegalovirus infection in heart transplantation

Cytomegalovirus (CMV) infection in solid organ recipients can endanger the immunosuppressed patient and increase vulnerability to secondary infections and the high risk of rejection triggered by the viral disease. The effect of passive immunization against CMV was examined in 69 heart transplant patients. The patients received weekly administrations of 1 ml/kg of CMV hyperimmunoglobulin from the day of transplantation until the 30th postoperative day. Forty-four of the patients were monitored clinically and serologically up to the 120th postoperative day. Nine patients showed clinical and serologic signs of CMV infection; in 15 the only evidence of CMV infection was a rise in antibody titers. The remaining 20 patients showed no clinical or serologic signs of CMV infection. Three patients who were seronegative preoperatively remained seronegative until the end of the observation period. The results indicate a potential therapeutic benefit of hyperimmunoglobulin prophylaxis to prevent infectious complications due to CMV in heart transplant patients.     

Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug.

Hydralazine has been shown to reduce mortality in patients with congestive heart failure when given concomitantly with isosorbide dinitrate. Recently, we demonstrated that nitrate tolerance is in part due to enhanced vascular superoxide .O2- production. We sought to determine mechanisms whereby hydralazine may prevent tolerance. Rabbits either received no treatment, nitroglycerin patches (1.5 micrograms/kg/min x 3 d), hydralazine alone (10 mg/kg/d in drinking water), or hydralazine and nitroglycerin. Aortic segments were studied in organ chambers and relative rates of vascular .O2- production were determined using lucigenin-enhanced chemiluminescence. Nitroglycerin treatment markedly inhibited relaxations to nitroglycerin (maximum relaxations in untreated: 92 +/- 1 vs. 64 +/- 3% in nitroglycerin-treated patients and increased vascular .O2- production by over two-fold (P < 0.05). Treatment with hydralazine in rabbits not receiving nitroglycerin significantly decreased .O2- production in intact rabbit aorta and increased sensitivity to nitroglycerin. When given concomitantly with nitroglycerin, hydralazine completely prevented the development of nitrate tolerance and normalized endogenous rates of vascular .O2- production. Studies of vessel homogenates demonstrated that the major source of .O2- was an NADH-dependent membrane-associated oxidase displaying activities of 67 +/- 12 vs. 28 +/- 2 nmol .O2-.min-1.mg protein-1 in nitroglycerin-treated vs. untreated aortic homogenates. In additional studies, we found that acute addition of hydralazine (10 microM) to nitroglycerin-tolerant vessels immediately inhibited .O2- production and NADH oxidase activity in vascular homogenates. The chemiluminescence signal was inhibited by a recombinant heparin-binding superoxide dismutase (HBSOD) demonstrating the specificity of this assay for .O2-. These observations suggest that a specific membrane-associated oxidase is activated by chronic nitroglycerin treatment, and the activity of this oxidase is inhibited by hydralazine, providing a mechanism whereby hydralazine may prevent tolerance. The ability of hydralazine to inhibit vascular .O2- anion production represents a novel mechanism of action for this drug.     

Editorial

Wiener Medizinische Wochenschrift -