A Non-inferiority Trial: Safety and Efficacy of Topical 1:1000 versus 1:10 000 Epinephrine in Sino-nasal Surgeries.

OBJECTIVE: This study aimed to test the non-inferiority of topical 1:1000 epinephrine compared to topical 1:10 000 with regard to intraoperative hemodynamic stability, and to determine whether it produced superior visibility conditions. METHODS: A single-blinded, prospective, cross-over non-inferiority trial was performed. Topical 1:1000 or topical 1:10 000 was placed in 1 nasal passage. Hemodynamic parameters (heart rate, systolic and diastolic blood pressures, and mean arterial pressure) were measured prior to insertion then every minute for 10 minutes. This was repeated in the contralateral nasal passage of the same patient with the alternate concentration. The surgeon graded the visualization of each passage using the Boezaart Scale. The medians of the greatest absolute change in parameters were compared using a Wilcoxon Rank-Signed test and confidence intervals were calculated using a Hodges-Lehman test. The non-inferiority margin was pre-determined at 10 bpm for heart rate and 10 mmHg for blood pressures. A Wilcoxon Rank-Signed test was used to assess superiority in visualization. RESULTS: Thirty-two patients were enrolled and after exclusions, nineteen were assessed (mean age = 35.63 ± 12.49). Differences in means of greatest absolute change between the 2 concentrations were calculated (heart rate = 2.49 ± 1.20; systolic = -1.51 ± 2.16; diastolic = 2.47 ± 1.47; mean arterial pressure = 0.07 ± 1.83). In analyses of medians, 1:1000 was non-inferior to the 1:10 000. There was a significant difference (-0.58 ± 0.84; P = .012) in visualization in favor of topical 1:1000. CONCLUSION: Topical 1:1000 epinephrine provides no worse intraoperative hemodynamic stability compared to topical 1:10 000 but affords superior visualization and should be used to optimize surgical conditions.

Safety and Efficacy of Isolated Limb Infusion Chemotherapy for Advanced Locoregional Melanoma in Elderly Patients: An Australian Multicenter Study.

BACKGROUND: Isolated limb infusion (ILI) offers a minimally invasive treatment option for locally advanced extremity melanoma. OBJECTIVE: The aim of the current study was to evaluate the safety and efficacy of ILI in elderly patients in an Australian multicenter setting. METHODS: The results of 316 first ILI procedures, performed between 1992 and 2008 in five Australian institutions, were identified and analyzed, with the main focus on elderly patients (≥75 years of age). All institutions used the same protocol: melphalan was circulated in the isolated limb for 20-30 min (±actinomycin D), and toxicity, responses, and survival were recorded. RESULTS: Characteristics of patients aged ≥75 years (n = 148) were similar to those aged <75 years (n = 168), except that older patients had more melanoma deposits (median 4 vs. 5; p = 0.035) and lower limb volumes (5.4 vs. 6.5 L; p = 0.001). Median drug circulation times were lower in the older group (21 vs. 24 min; p = 0.04), and older patients experienced less limb toxicity (grade III/IV in 22 and 37% of patients, respectively; p = 0.003). A complete response (CR) was seen in 27% of patients aged ≥75 years and in 38% of patients aged <75 years (p = 0.06), while overall response rates were 72 and 77%, respectively (p = 0.30). No difference in survival was seen (p = 0.69). CONCLUSIONS: The ILI technique proved safe and effective in elderly patients. When present, toxicity was localized, and lower compared with younger patients, possibly due to shorter drug circulation times. CR rates were higher in younger patients, although not significantly, while overall response and survival were equal. Optimization of perioperative factors in elderly patients may allow response rates to be raised further, while maintaining low toxicity.

Australian Multicenter Study of Isolated Limb Infusion for Melanoma.

PURPOSE: Isolated limb infusion (ILI) offers a less invasive alternative to isolated limb perfusion (ILP) for the treatment of locally advanced extremity melanoma. In Australia, ILI has essentially completely replaced ILP. The aim of this study was to collect and evaluate the results of ILI in an Australian multicenter setting. PATIENTS AND METHODS: The results of 316 first ILI procedures, performed between 1992 and 2008 in five Australian institutions, were collectively analyzed, with all five institutions using the same protocol. Melphalan was circulated in the isolated limb for 20-30 min (±actinomycin D). Response was determined using the World Health Organization criteria, and limb toxicity was assessed using the Wieberdink scale. RESULTS: The median patient age was 74 years (range 28-100) and 59 % of patients were female. Overall response rate was 75 % (complete response [CR] 33 %; partial response 42 %). Stable disease was seen in 18 % of patients and progressive disease in 7 %. Wieberdink grade III or higher was seen in 30 % of the cases. No toxicity-related amputations occurred, and median survival was 44 months. In patients with a CR, median survival was 80 months (p = 0.014). On multivariate analysis, Breslow thickness, lower-limb ILI, and a procedure performed at the Melanoma Institute Australia remained significant predictors for response, although not for survival. CONCLUSIONS: This Australian multicenter study of ILI is the largest reported to date. ILI is a useful technique that can be safely and effectively performed across tertiary referral centers for the successful management of advanced extremity melanoma. Increased optimization of perioperative factors might allow response rates to be raised further, while maintaining acceptable toxicity.

Australian multi-center experience outside of the Sydney Melanoma Unit of isolated limb infusion chemotherapy for melanoma.

INTRODUCTION: Isolated limb infusion (ILI) is a minimally invasive alternative to isolated limb perfusion (ILP) for delivering high-dose regional chemotherapy to treat locally advanced limb melanoma. The current study aimed to evaluate the applicability of ILI in four Australian tertiary referral centers outside of its originating institution, the Sydney Melanoma Unit (SMU; currently known as the Melanoma Institute Australia). METHODS: Data of 131 patients, treated between 1992 and 2008 were collectively analyzed. The ILI procedures were based on the Sydney Melanoma Unit protocol using melphalan. Response was determined using the WHO criteria and toxicity was assessed using the Wieberdink scale. RESULTS: The median patient age was 74 years (range 28-100). Fifty-six percent were female. Overall response (OR) rate to ILI was 63% (CR 27%; PR 36%). Wieberdink toxicity grade III or higher was seen in 13%. No toxicity-related amputations occurred. Median follow-up was 24 months; median survival was 58 months. In patients with a complete response (CR), median survival was 101 months; in patients with a partial response (PR) this was 41 months (P = 0.026). On univariate analysis a younger age, lower-limb procedures and a lower Breslow thickness of the primary melanoma were associated with a favorable response. On multivariate analysis Breslow thickness and lower-limb ILI remained significant predictors for response. CONCLUSION: In this, to date, largest multi-center study of ILI for melanoma the results are comparable to other reports and demonstrate that ILI can be widely implemented and safely applied across tertiary referral centers.

Isolated limb infusion chemotherapy for melanoma: an overview of early experience at the Adelaide Melanoma Unit.

BACKGROUND: Isolated limb infusion (ILI) using cytotoxic agents has been demonstrated to be an effective and less invasive alternative modality than isolated limb perfusion for the treatment of melanoma localized to a limb. Percutaneous catheters were inserted into the axial artery and vein of the affected limb while using a pneumatic cuff to restrict limb vascular flow proximally to "isolate" the limb from the body and enable delivery of high-dose intra-arterial chemotherapy selectively to the limb. The ILI technique was developed at the Sydney Melanoma Unit (now renamed the Melanoma Institute Australia), and only a few other centers have reported separate results. We report our early results using the ILI technique for management of locally recurrent surgically nonresectable melanoma. METHODS AND RESULTS: Twenty-eight ILI procedures were performed in 20 patients treated with one or more procedures between 1997 and 2007. Patient parameters and clinical responses were evaluated. The median follow-up duration was 15.9 months after the first ILI, with an overall response rate after one or more infusions of 70%, of which 35% were complete responders and 35% were partial responders, with a further 20% showing stable disease, giving a "clinically significant" response rate of 90%. After one ILI (n = 20), the overall response rate was 70%, with 20% complete responders and 50% partial responders, and 20% with stable disease. Low limb toxicities were generally observed, and no amputations were required. CONCLUSION: ILI chemotherapy is a useful technique, which can be readily repeated for control of melanoma in the limb. It is generally well tolerated, and is capable of achieving a cure, delayed progression, or effective palliation in selected cases. The longest survivors in this series were 8 and 10 years from the last ILI.