Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Clinicaltrials.gov NCT00126672

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

Dünndarmruptur nach stumpfem Abdominaltrauma bei vorbestehender Inguinalhernie

BACKGROUND: Intestinal perforation following blunt trauma to the abdomen is a rare but life-threatening complication in patients with pre-existing inguinal hernia. MATERIAL AND METHODS: We examined retrospective case series of patients with intestinal perforation following blunt abdominal trauma. RESULTS: Within 2 years, three patients with pre-existing inguinal hernia were referred to our clinic following simple falls while cross-country skiing. Upon signs of abdominal tenderness and radiographic evidence of free air, explorative laparotomy with revision of the affected bowel segments was performed. The postoperative course was uneventful in two patients. One developed adhesive ileus and incisional hernia within 1 year. CONCLUSIONS: Intestinal perforation must be suspected in patients with inguinal hernia and signs of diffuse abdominal tenderness following blunt trauma. Urgent explorative laparotomy with revision of the affected bowel segments is mandatory in patients with free abdominal air. Secondary hernia repair may represent the safest and most reliable approach and should be delayed until full recovery from the initial surgery

Challenges in the surgical management of spine trauma in the morbidly obese patient: A case series

Object: The treatment of morbidly obese individuals with spine trauma presents unique challenges to spine surgeons and trauma staff. This study aims to increase awareness of current limitations in the surgical management of spine trauma in morbidly obese individuals, and to illustrate practical solutions. Methods: Six morbidly obese patients were treated surgically for spine trauma over a 2-year period at a single trauma center in Australia. All patients were involved in high-speed motor vehicle accidents and had multisystem injuries. All weighed in excess of 265 pounds (120 kg) with a body mass index ≥ 40 (range 47.8–67.1). Cases were selected according to the considerable challenges they presented in all aspects of their management. Results: Best medical and surgical care may be compromised and outcome adversely affected in morbidly obese patients with spine trauma. The time taken to perform all aspects of care is usually extended, often by many hours. Customized orthotics may be required. Imaging quality is often compromised and patients may not fit into scanners. Surgical challenges include patient positioning, surgical access, confirmation of the anatomical level, and obtaining adequate instrument length. Postoperative nursing care, wound healing, and venous thromboembolism prophylaxis are also significant issues. Conclusions: Management pathways and hospital guidelines should be developed to optimize the treatment of morbidly obese patients, but innovative solutions may be required for individual cases.Hannah E. Rosenfeld, Rebecca Limb, Patrick Chan, Mark Fitzgerald, William Pierre Litherland Bradley, and Jeffrey V. Rosenfel