Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models.

PURPOSE: Early identification of esophageal cancer patients who are responding or resistant to combined chemoradiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemoradiotherapy in experimental models of esophageal carcinoma. EXPERIMENTAL DESIGN: The in vitro and ex vivo tumor uptake of [(3)H]FLT in SEG-1 human esophageal adenocarcinoma cells were studied at various early time points after docetaxel plus irradiation and validated with conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67] and [(18)F]FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [(18)F]FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments. RESULTS: In vitro [(3)H]FLT and [(3)H]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [(3)H]FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared with baseline (P < 0.005) by 2 days after chemoradiotherapy, despite the lack of change in tumor size. In contrast, the decline of [(3)H]FDG uptake was gradual and less pronounced. Tumor uptake of [(3)H]FLT was more closely correlated with Ki-67 expression (r = 0.89, P < 0.001) than was [(3)H]FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [(18)F]FLT and [(18)F]FDG tumor uptake. Autoradiographs displayed spatial correlations between [(18)F]FLT uptake and histologic Ki-67 distribution in preliminary studies. CONCLUSIONS: FLT-PET is suitable and more specific than FDG-PET for depicting early reductions in tumor proliferation that precede tumor size changes after chemoradiotherapy.     

Laparoscopic nephron sparing surgery: evolution in a decade

OBJECTIVE: To present our experience with laparoscopic nephron sparing surgery (NSS) over a decade. METHODS: Seventy-eight patients underwent NSS since 1994. Two techniques were used-partial nephrectomy without ischemia (group 1) in 29 patients, and with ischemia (group 2) which was in cold or warm ischemia in 24 and 25 patients respectively. The mean tumour size was 1.97 and 2.2 cm in groups 1 and 2 respectively. Renal reconstruction evolved in our hands during this period. We changed many technical details and now we depend more on clips for securing the sutures rather than free hand knotting. RESULTS: The mean operative time was 162 and 216 minutes in groups 1 and 2 respectively. Mean ischemia time for patients with cold and warm ischemia was 44.9 and 33.8 minutes respectively. 3 patients in group 2 were converted to open surgery. Mean blood loss was 254 and 212 ml for group 1 and 2 respectively with two major bleedings in group 2. Minor intra-operative complication occurred in 3 patients, and major and minor postoperative complication in 15 patients. At a mean follow-up of 23.9 and 12.2 months for groups 1 and 2 respectively there was no recurrence. CONCLUSION: Warm and cold ischemia have widened the indications for laparoscopic NSS to more complex tumours and allow renal reconstruction with acceptable complication rate.     

Prolonged allogeneic islet graft survival by protoporphyrins

Transplantation of islets of Langerhans in patients with type 1 diabetes allows for improved metabolic control and insulin independence. The need for chronic immunosuppression limits this procedure to selected patients with brittle diabetes. Definition of therapeutic strategies allowing permanent engraftment without the need for chronic immunosuppression could overcome such limitations. We tested the effect of the use of protoporphyrins (CoPP and FePP), powerful inducers of the cytoprotective protein heme-oxygenase 1 (HO-1), on allogeneic islet graft survival. Chemically induced diabetic C57BL/6 mice received DBA/2 islets. Treatment consisted in peritransplant administration of CoPP or saline. Islets were either cultured in the presence of FePP or vehicle before implant. Short-course administration of CoPP led to long-term islet allograft survival in a sizable proportion of recipients. Long-term graft-bearing animals rejected third-party islets while accepting a second set donor-specific graft permanently, without additional treatment. Preconditioning of islets with FePP by itself led to improved graft survival in untreated recipients, and provided additional advantage in CoPP-treated recipients, resulting in an increased proportion of long-term surviving grafts. Preconditioning of the graft with protoporphyrins prior to implant resulted in reduction of class II expression. Administration of protoporphyrins to the recipients of allogeneic islets also resulted in transient powerful immunosuppression with reduced lymphocyte proliferative responses, increased proportion of regulatory cells (CD4+CD25+), decreased mononuclear cell infiltrating the graft, paralleled by a systemic upregulation of HO-1 expression. All these mechanisms may have contributed to the induction of donor-specific hyporesponsiveness in a proportion of the protoporphyrin-treated animals.     

Efficacy and safety of the perclose closer s device after neurointerventional procedures: prospective study and literature review

BACKGROUND AND PURPOSE: The purpose of this study was to examine the efficacy and safety of the 6F Closer S device (Perclose; Redwood City, CA) versus manual compression to close arteriotomy sites after neurointerventional procedures in both virgin vessels and those previously treated with the device. METHODS: This single-center, multiple-operator, controlled, prospective study included 475 procedures (337 patients) with the device and 79 procedures (79 patients) with manual compression. A substantial number of patients receiving anticoagulation and/or antiplatelet medications were included. Efficacy and safety were evaluated on the basis of the rate of hemostatic success and the incidence of clinically significant complications. The literature was reviewed by using MEDLINE. RESULTS: Overall success rates were 95% in the device group versus 96% in the manual-compression group (P = 0.78), and clinically relevant complication rates were 0.6% versus 2.5%, respectively (P = 0.15). Success rates significantly declined in vessels previously treated with the device three or more times. However, complication rates did not significantly change. Literature review yielded 12 articles reporting complication rates of 3.2-35% for the device and 2.3%-33.3% for manual compression. CONCLUSION: The device was safe and effective for closing arteriotomy sites in patients undergoing neurointerventional procedures, including those receiving anticoagulation/antiplatelet therapy or those previously treated with the device one or two times.     

Revision surgery for residual or recurrent vestibular schwannoma.

OBJECTIVE: Assess the requirement for and describe the complication rates of revision surgery for vestibular schwannoma. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Patients undergoing surgery for vestibular schwannoma by the Manchester Neurotology Service between 1978 and 2004. INTERVENTION: Surgery. MAIN OUTCOME MEASURE(S): The presence of recurrent or residual tumor; necessity for further treatment; complications from revision surgery. RESULTS: Primary surgery was undertaken on 1,037 tumors, with 866 total (19 recurred), 128 near-total, and 43 subtotal removals. Further treatment was performed for 4 recurrent, 2 near-total, and 11 subtotal excised tumors. Thirty-five revision operations resulted in 14 total (1 recurred), 8 near-total, and 13 subtotal removals. Further treatment was required for 3 near-total and 6 subtotal excisions. Poor preoperative facial function (House-Brackmann Grades 4-6) was present in 9 of the 35 patients. A further 10 deteriorated by at least 3 grades by 1 year postoperatively. Other complications of revision surgery included 3 patients with cerebrospinal fluid leaks, a postoperative hematoma requiring evacuation, 2 cerebrovascular accidents, and 2 patients with new cranial nerve deficits. CONCLUSION: Most residual tumors after primary surgery are successfully managed with watch and rescan. Tumor fragment size is the greatest determinant of revision treatment. After revision surgery, tumor regrowth is much less predictable. Revision surgery is usually considerably more difficult than primary surgery, with a higher complication rate, particularly with regard to the facial nerve. Changing the approach for revision surgery may confer an advantage to facial nerve function.     

The effect of education and written material on compliance of pediatric clients

One hundred and fifty babies and their mothers, presenting to the Well Baby Clinic of the Pediatric Outpatient Department were studied for compliance. They were divided randomly into three groups, one serving as a control (n = 55) and two as experimental groups (n = 48 and 47). The latter were exposed to two different intervention methods; teaching and written material respectively, in addition to the routine care given to the control group. The three groups were compared in terms of compliance and improvement in knowledge. The results showed that reinforcement of the doctor's advice by a nurse, or written instructions to the patients, did not improve knowledge or compliance. Possible explanations for such results are given and suggestions for other modes of intervention are made.