Effect of fenfluramine-induced increases in serotonin release on [18F]MPPF binding: a continuous infusion PET study in conscious monkeys

[(18)F]MPPF is a selective and reversible antagonist to the serotonin-1A (5-HT(1A)) receptor. The aim of the present study was to investigate whether the binding of [(18)F]MPPF is sensitive to increases in 5-HT levels. We used the 5-HT releasing agent and reuptake inhibitor fenfluramine (FEN) to increase the concentration of 5-HT. [(18)F]MPPF binding was assessed using positron emission tomography (PET) in conscious monkeys. Possible effects of blood flow on ligand binding were excluded by using a bolus-infusion paradigm. Control scans were obtained to assess the state of ligand equilibrium. FEN (5 or 10 mg/kg, i.v.) was administered between 90 and 130 min after the start of the [(18)F]MPPF infusion. The binding potential (BP) was calculated for an early interval (30 min preceding FEN administration) and late interval (20-50 min after administration of FEN). Microdialyses results showed a 20- and 35-fold increase in extracellular 5-HT levels in the prefrontal cortex after injection of FEN at a dose of 5 mg/kg and 10 mg/kg respectively. However, despite these large increases in 5-HT levels, no differences in BP were found between the control and FEN scans. These results may imply that the majority of 5-HT(1A) receptors is in the low affinity state in the living brain.     

Repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes in a rabbit model

BACKGROUND: Recently, tissue-engineered chondrocyte transplantation has been tried to treat full-thickness cartilage defects. We developed an injectable type II collagen gel scaffold by chemically reacting type II collagen with polyethylene glycol crosslinker. This type II collagen was prepared from the nasal septa of cattle. In the present study, chondrocytes embedded in type II collagen gel were injected into rabbit full-thickness cartilage defects without a periosteal graft, and the feasibility for clinical application of the gel was evaluated. METHODS: Chondrocytes were isolated from 1-kg New Zealand white rabbits. A full-thickness articular cartilage defect (5 mm diameter, 4 mm depth) was created on the patellar groove of the femur of 16 male 3-kg New Zealand white rabbits. A type II collagen solution of mixed chondrocytes at a density of 1 x 10(7) cells/ml was injected and transplanted into the defect in the right knee. The controls were the defect only in the left knee. At 4, 8, 12, and 24 weeks after operation, four cases from each group were evaluated macroscopically and histologically. RESULTS: After injection into the cartilage defect, the gel bonded to the adjacent cartilage and bone within several minutes. Macroscopic examination revealed that the surface of the transplanted area was smooth and exhibited similar coloration and good integration with the surrounding cartilage at 12 and 24 weeks after transplantation. Histological examination at 8 weeks revealed favorable hyaline cartilage regeneration with good chondrocyte morphology. At 12 and 24 weeks, reparative cartilage remained rich in type II collagen. According to O'Driscoll histological scores, significant differences between the transplanted and control groups were apparent at 12 and 24 weeks. Immunohistochemical staining indicated sufficient type II collagen synthesis in regenerated cartilage 8 weeks after transplantation, and it was maintained until 24 weeks. CONCLUSIONS: These results indicate that type II collagen gel is suitable for injection into cartilage defects without any covering of a graft and offers a useful scaffold during chondrocyte transplantation.     

Radiofrequency ablation with hand-assisted laparoscopic surgery for the treatment of hepatocellular carcinoma in the caudate lobe

OBJECTIVE: To assess the feasibility and safety of radiofrequency ablation (RFA) with hand-assisted laparoscopic surgery (HALS) for hepatocellular carcinoma (HCC) in the caudate lobe with severe liver dysfunction. SUMMARY BACKGROUND DATA: HCC in the caudate lobe remains one of the most difficult locations where various treatments tend to pose problems regarding the optimal surgical approach. The technique of HALS has thus been proposed as a useful method for performing a safe RFA therapy. For this study, we assessed the feasibility and safety of RFA with HALS for the treatment of HCC in the caudate lobe with liver dysfunction. PATIENTS AND METHODS: Between July 1999 and February 2005, 5 patients who suffered from HCC in the caudate lobe were indicated for RFA. The percutaneous puncture was difficult and all patients have severe liver dysfunction with viral chronic hepatitis. Therefore, RFA was assisted by an inserted hand through a minimal skin incision under laparoscopic inspection. An intraoperative endoscopic ultrasound examination was performed before RFA to determine the tumor region. The hand-assisted minimal dissection around the caudate lobe was required to detect tumor and avoid injuries of other tissues. RFA for HCC was performed using a cooled-tip (Radionics Inc, Burligton, MA) connected to a RF generator under the programmed cyclic impedance. RESULTS: The surgical procedures consisted of 5 RFA to tumors in the caudate lobe with HALS, which was performed safely, and a postoperative computed tomography scan revealed a sufficient ablation in all patients. There was no operative mortality but 1 patient had minor bile leakage, which was treated conservatively, and all patients recovered and thus were eventually discharged. One patient had local recurrence after 3 months, 3 patients had tumor recurrences in another segment after 6 months. At a mean follow-up 32.2 months, all patients were still alive. CONCLUSIONS: RFA with HALS is considered to be a safe and feasible technique for HCC in the caudate lobe with liver dysfunction.     

Prevalence of Synchronous Colorectal Neoplasms Detected by Colonoscopy in Patients with Gastric Cancer

Purpose Our purpose was to study the characteristics of colorectal neoplasms in patients with gastric cancer (GC). Methods The study group comprised GC patients who underwent colonoscopy before resection of their GC. We examined the prevalence, site, and histology of colorectal neoplasms, as well as the clinicopathological features and treatment of the patients who had synchronous colorectal cancers (CRC). The logistic regression model was applied to investigate the features of the GC patients with concurrent CRC. Results We studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of whom had a family history of gastrointestinal cancer. Synchronous colorectal adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively. Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were resected endoscopically. The other eight required simultaneous open radical surgery. All the GC patients with synchronous CRC were older than 50 years. Statistical analysis did not show a significant difference between the features of the patients with and those without concurrent CRC. Conclusions The possibility of synchronous colorectal neoplasms in GC patients cannot be disregarded in clinical practice; however, screening of the large bowel may not be necessary in GC patients younger than 50 years.     

Pancreatic schwannoma: Report of a case

Among pancreatic neoplasms, pancreatic schwannoma is quite rare. We report a case of solitary pancreatic schwannoma, plus a literature review of this tumor. A 71-year-old woman was diagnosed by abdominal ultrasonography as having a pancreatic tumor and was hospitalized in our department at Kumamoto University Hospital on January 26, 2006. Abdominal computed tomography, magnetic resonance imaging, and endoscopic ultrasonography all showed this tumor, which was located in the body of the pancreas, to have cystic and solid components, and with a septum in the cystic part of the lesion. The tumor, preoperatively identified as a mucinous cystic neoplasm, was clearly separated from the normal pancreatic parenchyma. We performed a spleen-preserving distal pancreatectomy with a lymph node dissection on February 7, 2006. A histopathological examination of the resected specimen by means of hematoxylin and eosin revealed the tumor to consist of two parts: one with a compact spindle cell pattern (Antoni type A), and the other showing degeneration of fat (Antoni type B). We also found positive results for immunohistochemical staining for S-100 and vimentin. These findings confirmed the tumor’s classification as a pancreatic schwannoma.     

Tracheal chondrosarcoma

Tracheal chondrosarcomas are rare, with only 14 cases previously documented. We report a case of chondrosarcoma of the trachea and review other published cases. Our patient was a 34-year-old man who began to feel shortness of breath 8 months after initial hemoptysis. Transverse and coronal computed tomography demonstrated a tumor that was obstructing nearly 80% of the tracheal lumen at the thoracic inlet. A bronchoscopic biopsy specimen led to an initial diagnosis of chondroma. Five tracheal rings from the third to the seventh including the tumor were completely resected, and an end-to-end anastomosis was performed. The histological diagnosis of the surgical specimen showed it to be a chondrosarcoma. The patient was alive without recurrence at 6 years 4 months after surgery. Because recurrence after incomplete resection and malignant transformation can occur with chondromas, radical resection of the trachea is recommended for all cartilaginous tumors of the trachea.     

Range of motion during the perioperative period in total knee arthroplasty

INTRODUCTION: This study focused on the change in the range of motion (ROM) during the perioperative period, i.e., the preoperative and intraoperative ROM, and that on discharge, and compared the difference between posterior cruciate ligament-retaining (PCLR) and -sacrificing (PCLS) prostheses. MATERIALS AND METHODS: In this prospectively randomized study, we compared the changes in the ROM in PCLR (n = 50) and PCLS (n = 50) total knee arthroplasties. RESULTS: The mean flexion in PCLR prostheses was 130.0 degrees preoperatively, 120.0 degrees intraoperatively, and 105.0 degrees at discharge, and 125.0 degrees , 120.0 degrees , and 100.0 degrees , respectively, in PCLS. The designs did not differ statistically in each period (P > 0.05). Both designs showed significant correlations between the preoperative and intraoperative ROM, and between the preoperative and discharge ROM. Only the PCLS showed a significant correlation between the intraoperative and discharge ROM, and a significant difference was observed in correlation of rank coefficient between the two prostheses (P < 0.001). CONCLUSIONS: The PCLS design has an advantage in rehabilitation planning because of the predictable changes in the ROM during the perioperative period, although the acquired average ROM at discharge did not differ statistically.     

Carotid artery stenting via a transbrachial artery: techniques and problems

Recently, carotid artery stenting (CAS) has been reported to be an alternative of carotid endarterectomy (CEA) for internal carotid artery (ICA) stenosis due to the improvement of protection devices. In general, the transfemoral approach has been chosen for CAS because of the sizes of the devices. However, the transfemoral route seems to be unavailable or at high risk, in cases of severe atherosclerotic changes or aneurysm of the femoral, iliac artery or aorta, or after bypass graft placement. In this report, we presented 5 patients who underwent CAS using the transbrachial approach. The mean stenotic rate of 84% before treatment was reduced to 14% after the procedures. The 30-day morbidity and mortality were both 0%. Major local complications at the puncture site were not encountered. There has been no stroke nor death during a mean follow-up period of 6 months. We suggest that CAS via transbrachial route is an effective and safe treatment for ICA stenosis, by use of low-profile devices and bi-plane DSA equipment, especially in patients who are not eligible for the transfemoral access.     

Implications of MYCN amplification in patients with stage 4 neuroblastoma who undergo intensive chemotherapy

Background/Purpose

This study aims to clarify the implications of MYCN amplification in patients with high-risk neuroblastomas treated with 2 different regimens of induction chemotherapy established by the Japan Study Group for Advanced Neuroblastoma.

Methods

Between 1985 and 2003 in Japan, 392 patients with stage 4 neuroblastomas who were older than 12 months were treated with 2 regimens of induction chemotherapy (the combination of cyclophosphamide [CTX], cisplatin [CDDP], pirarubicin, and vincristine or etoposide). Regimen 91A3 or 98A3 (A3) (CTX 2400 mg/m², CDDP 125 mg/m²) was a higher dose combination of CTX and CDDP than regimen 85A1 or 91A1 (A1) (CTX 1200 mg/m², CDDP 90 mg/m²). The 392 cases were classified into 3 groups (A, 1 copy; B, 2-9 copies; C, more than 10 copies) based on the MYCN amplification status by a Southern blot analysis.

Results

The 5-year overall survival rate (5-YS) was 41.1% for all 392 cases. Regarding the MYCN amplification status, the 5-YS was 46.6% for A group (n = 227), 22.7% for B group (n = 26), and 36.0% for C group (n = 139). A flouresence in situ hybridization analysis showed the presence of the cells with more than 10 copies in cases with 2 to 9 copies based on the Southern blot findings. Of the 227 patients in a group, the 5-YS was 46.7% for the 70 cases treated by A3 and 47.0% for 154 cases treated by A1 (nonsignificant). The 5-YS of the 210 patients with stem cell transplantation (SCT) (51.%) was significantly better than that of the 127 patients without SCT (41.1%) (P < .05).

Conclusions

Regarding the MYCN amplification status, the tumor aggressiveness might thus be different between 2 and 9 copies and a single copy of MYCN. In neuroblastomas with 2 and 9 copies of MYCN based on a Southern blot analysis, the MYCN amplification status should be analyzed using the flouresence in situ hybridization method. Induction chemotherapy followed by SCT according to the Japan Study Group for Advanced Neuroblastoma protocol improved the outcome of neuroblastomas with MYCN amplification; however, obtaining a further improvement in the long-term survival of stage 4 neuroblastomas may therefore require the development of an even more effective treatment modality.