Cutaneous effects of BRAF inhibitor therapy: a case series.

BACKGROUND: The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors. PATIENTS AND METHODS: To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4-92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded. RESULTS: Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%). CONCLUSIONS: Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects.

The influence of new technologies on laparoscopic adrenalectomy: our personal experience with 91 patients.

BACKGROUND: Laparoscopic adrenalectomy has proved to be the technique of choice for managing benign pathologies of the adrenals and isolated adrenal metastases, especially those arising from lung tumor, but the procedure should not be performed for primitive adrenal carcinoma. The Authors wanted to test the advantages of the Harmonic Scalpel in laparoscopic adrenalectomy. METHODS: From April 1995 to April 2001, the authors investigated their series of laparoscopic adrenalectomies performed at the Careggi General Hospital, Division of General and Vascular Surgery, Florence, Italy. This study enrolled 91 patients with various adrenal pathologies. The transperitoneal approach was used, with the patient in a lateral position, as suggested by Gagner. Special care was taken to improve the surgical approach to the adrenals by the use of new technological devices such as the Harmonic Scalpel. The operative time required by the surgical procedure was computed by dividing the study into three periods: 1995-1997, 1998-1999, 2000-2001. The first period was necessary to complete the learning curve. In the second period, a steady state in surgical time was reached. During the third period, the Harmonic Scalpel was introduced. The differences between the three periods were tested using a nonparametric analysis (Mann-Whitney U test or Kruskal-Wallis test) as appropriate. A two-tailed p value of 0.05 or less was considered statistically significant. The authors investigated the cost of the operation performed in each of the two groups using, respectively, the conventional laparoscopic device (1998-1999) and the Harmonic Scalpel (2000-2001). The following expenses were considered: Harmonic Scalpel impulse generator and disposable shears, operating room cost per hour, and endoclip applier. RESULTS: The 91 laparoscopic adrenalectomies were performed with these indications: 31 incidentalomas (26 adenomas and 5 cysts), 25 cases of Conn's disease, 18 cases of Cushing's disease, 9 pheochromocytomas, 2 myelolipomas, 5 metastases (from lung, kidney, and breast) and 1 primitive carcinoma diagnosed preoperatively. Considering the whole series (1995-2001), there was a significant trend of reduction in operative time (p = 0.0001). Moreover looking at the first period (1995-1997), in which the learning curve was completed, the mean surgical time was 148 min, as compared with 125 mm. For the second period (1998-1999) (p = 0.0002). This represents a significant reduction in operative time. The authors noted a further reduction in the operative time when surgery was performed with the Harmonic Scalpel (2000-2001) (92 min; p = 0.001). The reduction in operative time attributable to the Harmonic Scalpel was confirmed also by a multivariate analysis of covariance general linear models procedure (GLM), which accounts for several confounders: age, gender, site and size of tumors, and histology (p = 0.0001). The rate was 3.3% for morbidity, 1.1% for mortality, and 2.2% for conversion. There was no difference in complications between patients treated with conventional devices and those treated with the Harmonic Scalpel. CONCLUSIONS: The laparoscopic approach has proved to be an extremely reliable procedure for benign pathologies and isolated metastases. There may yet be doubts about its use for the treatment of adrenal carcinomas preoperatively diagnosed. When surgery is performed using Harmonic Scalpel, operative time is significantly reduced and surgery is easier and less expensive. Infact use of the Harmonic Scalpel allowed the cost per operation to be reduced $70. Moreover, if surgery is performed using the nondisposable clip applier, the expenses are reduced $105.