Raul N. Uppot

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

Background Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2. Methods We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas. Results 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). Conclusions 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. Trial Registration Clinicaltrials.gov NCT00126672

Vascular and Biliary Variants in the Liver : Implications for Liver Surgery

Accurate preoperative assessment of the hepatic vascular and biliary anatomy is essential to ensure safe and successful hepatic surgery. Such surgical procedures range from the more complex, like tumor resection and partial hepatectomy for living donor liver transplantation, to others performed more routinely, like laparoscopic cholecystectomy. Modern noninvasive diagnostic imaging techniques, such as multidetector computed tomography (CT) and magnetic resonance (MR) imaging performed with liver-specific contrast agents with biliary excretion, have replaced conventional angiography and endoscopic cholangiography for evaluation of the hepatic vascular and biliary anatomy. These techniques help determine the best hepatectomy plane and help identify patients in whom additional surgical steps will be required. Preoperative knowledge of hepatic vascular and biliary anatomic variants is mandatory for surgical planning and to help reduce postoperative complications. Multidetector CT and MR imaging, with the added value of image postprocessing, allow accurate identification of areas at risk for venous congestion or devascularization. This information may influence surgical planning with regard to the extent of hepatic resection or the need for vascular reconstruction.

Impact of Obesity on Medical Imaging and Image-Guided Intervention

OBJECTIVE The purpose of this article is to discuss the impact of obesity on medical imaging and provide some solutions that are currently available to tackle the challenges of imaging obese patients. CONCLUSION Increasingly, radiologists are asked to image morbidly obese patients. The challenges facing radiology departments include difficulties in transporting patients to the department, inability to accommodate large patients on currently designed imaging equipment, and difficulties in acquiring desired image quality.

Protecting the Ureter during Radiofrequency Ablation of Renal Cell Cancer: A Pilot Study of Retrograde Pyeloperfusion with Cooled Dextrose 5% in Water

PURPOSE To describe early experience with cooled dextrose 5% in water (D5W) solution retrograde pyeloperfusion during radiofrequency (RF) ablation of renal cell carcinoma (RCC) within 1.5 cm of the ureter with respect to feasibility, safety, and incidence of residual/recurrent tumor in proximity to the cooled collecting system. MATERIALS AND METHODS Between November 2004 and April 2007, 17 patients underwent 19 RF ablation sessions of RCCs within 1.5 cm of the ureter during cooled D5W pyeloperfusion (nine men, eight women; mean tumor size, 3.5 cm; mean age, 73 y; mean distance to ureter, 7 mm). RF ablation was performed with pulsed impedance control current. The records and imaging studies of patients treated with this technique were reviewed for demographics, indication, technique, complications, and tumor recurrence. RESULTS All 19 RF ablation and ureteral catheter placement procedures were technically successful. No patient developed a ureteral stricture or hydronephrosis during a mean of 14 months of follow-up (range, 4-32 months). Three patients had residual tumor on the first follow-up imaging study, but all three tumors were completely ablated after a second RF ablation session. No complications or deaths occurred. No recurrent tumor was seen anywhere in the treated tumors, and there was complete ablation of the tumor margin in proximity to the collecting system. CONCLUSIONS RF ablation of RCC within 1.5 cm of the ureter is feasible with cooled D5W retrograde pyeloperfusion and is not associated with reduced efficacy, ureteral injury, or early recurrence.

Postoperative Imaging in Liver Transplantation: What Radiologists Should Know

Liver transplantation is now frequently used in the treatment of end-stage liver disease. Therefore, it is important that radiologists be aware of common anastomotic techniques and expected postoperative imaging findings. Imaging is most useful in evaluating for posttransplantation complications, which are broadly classified into vascular, biliary, and other complications. Hepatic artery thrombosis is the most significant complication and is often associated with graft failure. Radiologists have multiple modalities at their disposal for optimal evaluation. Doppler ultrasonography (US) is the preliminary imaging modality for gross evaluation of the liver parenchyma, biliary tree, and vasculature for abnormalities. When US findings are indeterminate or there is persistent clinical suspicion for an abnormality, computed tomography (CT) is often performed. The major indications for CT are detection of bile leak, hemorrhage, and abscess, but CT is also useful in the assessment of the vasculature. T-tube cholangiography and magnetic resonance cholangiopancreatography are the best noninvasive imaging tools for evaluating for biliary stricture. Some investigators would argue that endoscopic retrograde cholangiopancreatography (ERCP) is a better diagnostic imaging modality; however, ERCP is invasive. Hepatobiliary scintigraphy is optimal for the evaluation of biliary leakage. Early detection of posttransplantation complications will help lower morbidity rates and will likely allow graft salvage in selected cases.

Percutaneous Hepatic Abscess Drainage: Do Multiple Abscesses or Multiloculated Abscesses Preclude Drainage or Affect Outcome?

PURPOSE To compare the effectiveness of percutaneous abscess drainage in patients with pyogenic liver abscesses of the following types: single, single multiloculated, multiple, and multiple multiloculated. MATERIALS AND METHODS One hundred nine patients with 149 liver abscesses who underwent percutaneous drainage during an 11-year period were divided into a single abscess group and a multiple abscess group. Of the 109 patients, 54 had multiloculated abscesses and were divided into single and multiple multiloculated abscess groups. Technical success was defined as the ability to place the catheter within the abscess cavity and clinical success was defined as improvement in the patients symptoms. Clinical findings, management strategy, complication rate, and success rate were analyzed. RESULTS Technical success rates were 96% (82 of 85) for a single abscess and 96% (23 of 24) for multiple abscesses (P = 1.0). Clinical success was achieved in 74 of 85 patients (87%) with a single abscess and 22 of 24 patients (92%) with multiple abscesses (P = .729). Technical success rates were 94% (32 of 34) for a single multiloculated abscess and 95% (19 of 20) for multiple multiloculated abscesses (P = 1.0). Clinical success was achieved in 30 of 34 patients (88%) with a single multiloculated abscess and 18 of 20 patients (90%) with multiple multiloculated abscesses (P = 1). No significant difference in hospital stay was seen between single and multiple abscess groups (P = .373) or between single multiloculated and multiple multiloculated abscess groups (P = .180). There were no major complications or mortality related to the procedure. CONCLUSIONS Percutaneous drainage is a safe and effective procedure in the treatment of pyogenic liver abscess, regardless of abscess complexity and/or multiplicity.

Imaging-Guided Percutaneous Ablation of Renal Cell Carcinoma: A Primer of How We Do It

OBJECTIVE This article is a primer in conducting an imaging-guided percutaneous renal ablation program based on the clinical experience of three institutions. CONCLUSION Imaging-guided percutaneous ablation is becoming a viable alternative to surgery for the management of locally confined renal cell carcinoma. Conducting a successful renal tumor ablation program includes understanding the treatment options for early-stage renal cell carcinoma, selecting the appropriate patients, understanding the procedural techniques, and organizing a comprehensive follow-up.

Imaging-Guided Percutaneous Renal Biopsy: Rationale and Approach

OBJECTIVE The purpose of this article is to discuss the history of, indications and rationale for, and approach to imaging-guided percutaneous renal biopsies. CONCLUSION With the progressive increase in the number of incidentally discovered renal masses, increased use of percutaneous ablation as a treatment alternative for the management of renal cell carcinoma and improvements in immunohistochemistry techniques, imaging-guided renal biopsy will continue to serve as a useful tool for the evaluation and management of renal diseases.

Adjunctive Intrapleural Tissue Plasminogen Activator Administered via Chest Tubes Placed with Imaging Guidance: Effectiveness and Risk for Hemorrhage

PURPOSE To retrospectively determine the effectiveness of and risk for hemorrhage with intrapleural adjunctive tissue plasminogen activator (tPA) administered via chest tubes placed with imaging guidance. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board of Massachusetts General Hospital, with informed consent waived. A retrospective review of 66 patients (age range, 1-95 years; mean age, 55 years; 44 male, 22 female) who received intrapleural tPA between 2000 and 2006 was performed. Overall effectiveness of tPA was defined as successful drainage without need for additional decortication or video-assisted thoracoscopic surgery. Primary and secondary effectiveness were defined as effectiveness after one and two cycles of tPA, respectively. Imaging findings and complications were recorded. Hemorrhagic complications were noted, and the Fisher exact test was used to show whether concurrent systemic anticoagulation increased bleeding risk. RESULTS Fifty-seven (86%) of 66 patients underwent complete drainage with tPA without further surgical procedures. Primary effectiveness was seen in 52 (87%) of 60 patients and secondary effectiveness was seen in five (83%) of six. Loculation of fluid was the most common finding in this selected cohort. Number of fluid pockets, pleural heterogeneity, and pleural thickness were not predictors of effectiveness. There were five major pleural hemorrhages in four patients across five tPA cycles. Hemorrhages occurred only in patients receiving therapeutic anticoagulation (four of 12) and in none of the other patients (P < .001). No hemorrhages occurred in the 38 patients receiving prophylactic anticoagulation. CONCLUSION Intrapleural tPA is effective in improving drainage of loculated effusions not drained with catheters alone; prophylactic systemic anticoagulation does not increase bleeding risk with intrapleural tPA, but therapeutic anticoagulation is associated with a significantly increased risk of pleural hemorrhage.

Case 23-2013

Dr. Sara R. Schoenfeld (Medicine): A 54-year-old woman was admitted to this hospital because of abdominal pain, vomiting, and confusion. The patient was in her usual health until approximately 3 days before admission, when she reportedly began to feel unwell, with weakness, chills, and skin that was abnormally warm to the touch. She self-administered aspirin, without improvement. During the next 2 days, her oral intake decreased. Approximately 22 hours before presentation, vomiting occurred. Nine hours before presentation, she began to travel home to Italy from the eastern United States. During the next 2 hours, increasing abdominal pain occurred, associated with vomiting and shortness of breath, and she took additional aspirin for pain. Approximately 2 hours before presentation, while the patient was in flight, abdominal pain markedly worsened, vomiting increased, and she became confused and unresponsive. The flight was diverted to Boston. On examination by emergency medical services personnel, she was nonverbal and was moaning continuously. The blood pressure was 120/70 mm Hg, the pulse 52 beats per minute, and the respiratory rate 26 breaths per minute. The capillary blood glucose level was 116 mg per deciliter (6.4 mmol per liter). She was brought to the emergency department at this hospital by ambulance. The patient’s history was obtained from her husband through an interpreter. She had non–insulin-dependent (type 2) diabetes mellitus, hypertension, nephrolithiasis, and chronic kidney disease. Medications included enalapril, metformin, glimepiride, nimesulide, imipramine, aspirin, and ibuprofen. She had no known allergies. She was married and had children. She lived in Italy and did not speak English. She had vacationed in North America for 10 days, traveling to urban areas. She did not smoke, drink alcohol, or use illicit drugs, and there was no history of unusual ingestions. On examination, the patient was incoherent and appeared agitated and uncomfortable, with frequent groaning. She was oriented to person only and opened her eyes to command. The blood pressure was 120/70 mm Hg, the pulse 52 beats per minute, the temperature 36.7°C, the respiratory rate 18 breaths per minute, and the oxygen saturation 95% while she was breathing ambient air. The pupils were 3 mm