Minimally invasive palliative procedures in oncology: a review of a multidisciplinary collaboration.

INTRODUCTION: Minimally invasive palliative procedures (MIPPs) are sometimes considered step 4 of the World Health Organization's three-step ladder. A case conference has been created at the BC Cancer Agency to facilitate access to MIPPs for advanced cancer patients with severe pain not responding to conventional analgesics. The twice monthly conference discusses referrals for pain control procedures and reviews imaging, with palliative care, musculoskeletal interventional radiology, radiation oncology, medical oncology, and anesthesia experts in attendance. STUDY OBJECTIVES: The aims of this study are: first, to determine the benefit to patients from the procedures recommended by the case conference, and second, to explore the impact of the case conference on clinical decision-making. METHODS: A retrospective review of electronic charts of all cancer patients referred to the MIPP case conference between December 20, 2011 and June 25, 2013. RESULTS: There were 103 referrals, resulting in 69 procedures performed among 63 patients. Over 80 % of procedures provided analgesic benefit. Pain scores fell across all categories post-procedure. Mean worst pain scores fell from 8.1 ± 1.4 to 4.6 ± 2.8 (P < 0.001). Patient function, mobility, and symptoms measured by the Edmonton Symptom Assessment System also improved post-procedure. At time of abstract submission, 37/63 (58.7 %) patients had died, and the mean survival post-procedure was 200 days. The documented rate of major adverse events attributable to MIPPs was 2/69 (2.9 %). CONCLUSIONS: MIPPs are valuable treatment options in patients with severe cancer pain despite use of appropriate step 3 WHO ladder medications. The case conference facilitates excellent communication and sharing of expertise, ensuring optimal patient care.

Meta-Analysis of Treatment for Primary Sjögren's Syndrome.

OBJECTIVE: The current focus of treatment in primary Sjögren's syndrome (SS) is symptom management. Since SS is an autoimmune disease with multisystem involvement, systemic immunosuppression may have a role in improving signs and symptoms and preventing progression. We undertook this review to assess the efficacy and safety of immunomodulation on primary SS from randomized clinical trials (RCTs). METHODS: Five electronic databases (Medline, Embase, Central, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform) were searched to include RCTs for the treatment of SS. Primary outcome measures included ocular dryness, oral dryness, tear production, and salivary function. Serious adverse events (AEs) and withdrawals due to AEs were also assessed. RESULTS: The search yielded 32 trials evaluating 19 different medications. The average duration of diagnosis was long (up to 9.2 years). Twenty-two trials examined ocular and oral dryness, for which only 2 and 4 trials showed statistically significant improvements, respectively. No studies found a benefit for tear production; few studies found improvements for unstimulated salivary flow (3 of 16 RCTs) and stimulated salivary flow (2 of 14 RCTs). Meta-analysis at 6 months found improvements as compared to placebo for unstimulated salivary flow (P = 0.003) and a decrease in the erythrocyte sedimentation rate (P = 0.007). No differences were seen for serious AEs, but there were increased withdrawals from AEs (risk ratio 2.33; P = 0.03). CONCLUSION: Reducing inflammation potentially improves salivary gland function. No individual immunomodulatory drug demonstrated a consistent benefit in xerostomia and xerophthalmia. Further work is needed to identify SS patients with an ability to improve and with outcomes that are valid and sensitive to change within clinical trials. Tradeoffs in the future between benefit and safety may also be important, because more withdrawals occurred with active treatment.

Testosterone reinforcement: intravenous and intracerebroventricular self-administration in male rats and hamsters.

RATIONALE: Anabolic steroids are drugs of abuse. However, the potential for addiction remains unclear. Testosterone induces conditioned place preference in rats and oral self-administration in hamsters. OBJECTIVES: To determine if male rats and hamsters consume testosterone by intravenous (IV) or intracerebroventricular (ICV) self-administration. METHODS: With each nose-poke in the active hole during daily 4-h tests in an operant conditioning chamber, gonad-intact adult rats and hamsters received 50 microg testosterone in an aqueous solution of beta-cyclodextrin via jugular cannula. The inactive nose-poke hole served as a control. Additional hamsters received vehicle infusions. RESULTS: Rats ( n=7) expressed a significant preference for the active nose-poke hole (10.0+/-2.8 responses/4 h) over the inactive hole (4.7+/-1.2 responses/4 h). Similarly, during 16 days of testosterone self-administration IV, hamsters ( n=9) averaged 11.7+/-2.9 responses/4 h and 6.3+/-1.1 responses/4 h in the active and inactive nose-poke holes, respectively. By contrast, vehicle controls ( n=8) failed to develop a preference for the active nose-poke hole (6.5+/-0.5 and 6.4+/-0.3 responses/4 h). Hamsters ( n=8) also self-administered 1 microg testosterone ICV (active hole:39.8+/-6.0 nose-pokes/4 h; inactive hole: 22.6+/-7.1 nose-pokes/4 h). When testosterone was replaced with vehicle, nose-poking in the active hole declined from 31.1+/-7.6 to 11.9+/-3.2 responses/4 h within 6 days. Likewise, reversing active and inactive holes increased nose-poking in the previously inactive hole from 9.1+/-1.9 to 25.6+/-5.4 responses/4 h. However, reducing the testosterone dose from 1 microg to 0.2 microg per 1 microl injection did not change nose-poking. CONCLUSIONS: Compared with other drugs of abuse, testosterone reinforcement is modest. Nonetheless, these data support the hypothesis that testosterone is reinforcing.

Castration, dopamine and food choice: a cost/benefit test in male hamsters.

Testosterone is essential for copulation, and contributes to sexual motivation. In addition, castrated males are fatter and less active, suggesting that androgens may play a role in non-sexual behaviors, including food-related responses. To test this hypothesis, male hamsters were trained with a cost/benefit test, which compares operant responding for more-preferred food versus ad libitum consumption of lab chow. Males were tested before and after castration. The effect of the dopamine antagonist, haloperidol, on instrumental responses in intact and castrated males was also determined. Food-deprived hamsters responded vigorously for 45 mg Bio-Serv pellets in daily 30-min tests (665 presses, 6.0+/-0.9 g). When lab chow was available, males continued to respond for pellets (3.6+/-0.6 g) over chow ad libitum (1.2+/-0.3 g). Dopamine is central to this response because haloperidol (1.0 mg/kg i.p.) reversed food intake (pellets: 0.5+/-0.1 g; chow 2.0+/-0.5 g). Castration had no effect on operant responding for pellets alone (6.6+/-0.7 g). When chow was present, castrates consumed an even greater proportion of their total food intake as pellets [6.0+/-0.4 g pellets (92%), 1.6+/-0.5 g chow (8%), vs. 75 and 25%, respectively, for intact males]. This is contrary to our original hypothesis. In addition, castration did not change the effects of haloperidol on food intake: (0.4+/-0.1 g pellets; 1.6+/-0.5 g chow). These results support previous findings in rats that dopamine affects response allocation in a cost/benefit test. However, they do not support the hypothesis that testosterone modifies the allocation of food-related responses.