Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.     

Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation

Background

Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy.

Methods

Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m² at day ?14 and day ?1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant.

Results

Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year.

Conclusion

Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

     

Cervical ossification of the posterior longitudinal ligament: factors affecting the effect of posterior decompression

Objective: Decompression procedures for cervical myelopathy of ossification of the posterior longitudinal ligament (OPLL) are anterior decompression with fusion, laminoplasty, and posterior decompression with fusion. Preoperative and postoperative stress analyses were performed for compression from hill-shaped cervical OPLL using 3-dimensional finite element method (FEM) spinal cord models.

Methods: Three FEM models of vertebral arch, OPLL, and spinal cord were used to develop preoperative compression models of the spinal cord to which 10%, 20%, and 30% compression was applied; a posterior compression with fusion model of the posteriorly shifted vertebral arch; an advanced kyphosis model following posterior decompression with the spinal cord stretched in the kyphotic direction; and a combined model of advanced kyphosis following posterior decompression and intervertebral mobility. The combined model had discontinuity in the middle of OPLL, assuming the presence of residual intervertebral mobility at the level of maximum cord compression, and the spinal cord was mobile according to flexion of vertebral bodies by 5°, 10°, and 15°.

Results: In the preoperative compression model, intraspinal stress increased as compression increased. In the posterior decompression with fusion model, intraspinal stress decreased, but partially persisted under 30% compression. In the advanced kyphosis model, intraspinal stress increased again. As anterior compression was higher, the stress increased more. In the advanced kyphosis +?intervertebral mobility model, intraspinal stress increased more than in the only advanced kyphosis model following decompression. Intraspinal stress increased more as intervertebral mobility increased.

Conclusion: In high residual compression or instability after posterior decompression, anterior decompression with fusion or posterior decompression with instrumented fusion should be considered.     

A novel method of cryopreservation of rat and human hepatocytes by using encapsulation technique and possible use for cell transplantation

Encapsulated hepatocyte transplantation is a promising approach to cell transplantation without immunosuppression as an alternative to whole organ liver transplantation. However, the shortage of donor cells for hepatocyte transplantation has not been resolved, and at this critical point, it seems necessary to establish a method of hepatocyte cryopreservation to allow clinical application of hepatocyte transplantation and the development of a bioartificial liver system in the near future. In this study we demonstrated that cryopreserved microencapsulated rat and human hepatocytes can retain their hepatic function and that cryopreserved microencapsulated human hepatocytes transplanted into rat spleen remain viable without immunosuppression. Rat and human hepatocytes were isolated by a collagenase digestion method, and they were microencapsulated with poly-L-lysine. The microencapsulated rat hepatocytes were transferred to culture medium (DMEM containing 10% FBS and 10% DMSO) and immediately frozen in liquid nitrogen. A warm water bath (37 degrees C) was used to thaw the microencapsulated hepatocytes. Hepatic function, drug metabolism, and cell morphology were assessed after 90 days of cryopreservation. After 1 week of cryopreservation, microencapsulated hepatocytes were cultured for up to 2 weeks to assess their hepatic function and morphology. The morphology of human hepatocytes was assessed after 30 days of cryopreservation. Cryopreserved human hepatocytes were transplanted into rat spleen to assess their morphology. Cryopreserved microencapsulated hepatocytes retained their viability and were strongly positive for expression of albumin, OAT2, CYP3A2, and CYP3A9. Two weeks after cultivation, the cryopreserved microencapsulated rat hepatocytes had retained their hepatic function (urea synthesis). Cryopreserved microencapsulated human hepatocytes also mainly survived and retained their hepatic function for at least 30 days after cryopreservation. Moreover, entrapped cryopreserved human hepatocytes also survived and expressed albumin in rat spleen after transplantation. We demonstrated a novel method of long-term cryopreservation of rat and human hepatocytes by using an encapsulation technique, with retention of biological activity and excellent survival of the cryopreserved microencapsulated human hepatocytes transplanted into rat spleen. We believe that this novel approach to hepatocytes cryopreservation provides a new direction in encapsulated cell therapy with the goal of clinical application in the near future.     

Flexion Model Simulating Spinal Cord Injury Without Radiographic Abnormality in Patients With Ossification of the Longitudinal Ligament: The Influence of Flexion Speed on the Cervical Spine

Background/Objective:

It is suspected that the speed of the motion of the spinal cord under static compression may be the cause of spinal cord injury (SCI). However, little is known about the relationship between the speed of the motion of the spinal cord and its stress distributions. The objective was to carry out a biomechanical study of SCI in patients with ossification of the longitudinal ligament without radiologic evidence of injury.

Methods:

A 3-dimensional finite element spinal cord model was established. After the application of static compression, the model underwent anterior flexion to simulate SCI in ossification of the longitudinal ligament patients without radiologic abnormality. Flexion of the spine was assumed to occur at 1 motor segment. Flexion angle was 5°, and flexion speeds were 0.5°/s, 5°/s, and 50°/s. Stress distributions inside of the spinal cord were evaluated.

Results:

Stresses on the spinal cord increased slightly after the application of 5° of flexion at a speed of 0.5°/s. Stresses became much higher at a speed of 5°/s and increased further at 50°s.

Conclusions:

The stress distribution of the spinal cord under static compression increased with faster flexion speed of the spinal cord. High-speed motion of the spinal cord under static compression may be one of the causes of SCI in the absence of radiologic abnormality.     

Effects of intravenous adenosine 5′-triphosphate on intraoperative hemodynamics and postoperative pain in patients undergoing major orofacial surgery: a double-blind placebo-controlled study

Purpose  We conducted a double-blind placebo-controlled study to investigate the effects of the intraoperative intravenous infusion of adenosine 5′-triphosphate (ATP) on intraoperative hemodynamics and postoperative pain in patients undergoing major orofacial surgery. Methods  Thirty patients (age, 16–42 years; 16 males/14 females) scheduled for sagittal split ramus osteotomy were assigned in a double-blind fashion to receive intraoperative intravenous infusion of ATP (n = 15) or saline (n = 15). Anesthesia was induced and maintained with propofol, fentanyl, and vecuronium. Local anesthesia was added for intraoperative analgesia. In the ATP group, ATP was infused at a rate of 160 μg·kg⁻¹·min⁻¹ throughout surgery. Postoperative pain was managed with intravenous patient-controlled analgesia (PCA) with morphine. The intensity of postoperative pain was assessed with a verbal numeric rating scale (NRS). Morphine consumption was also assessed. Results  There were no differences in demographic, anesthetic, and surgical data between the ATP and placebo groups. Intraoperatively, ATP effectively suppressed responses of blood pressure and heart rate to painful surgical stimuli. There were no differences in postoperative NRS scores between the two groups. However, postoperative morphine consumption was significantly less in the ATP group, compared with the placebo group, throughout the 72-h postoperative observation period. Cumulative morphine consumption for 72 h postoperatively was 47% less with ATP, compared with placebo. No adverse effect of ATP was observed. Conclusion  Our data suggest that intraoperative ATP infusion can blunt hemodynamic responses to surgical stimuli and produce prolonged analgesia in patients undergoing major orofacial surgery.     

Postoperative management using intensive patient-controlled epidural analgesia and early rehabilitation after an esophagectomy

Purpose  Patient-controlled epidural analgesia (PCEA) was developed for use after surgery for thoracic esophageal cancer to relieve wound pain, introduce early rehabilitation, and provide an uneventful postoperative recovery. Methods  This retrospective study investigated 22 patients who underwent esophageal surgery to determine the efficacy of postoperative management with PCEA. In the PCEA group (n = 12), patients had two epidural catheters inserted to cover both the thoracic and abdominal incision with a patient-controlled bolus capability. Results  Postoperative mechanical ventilation was administered in all cases in the control group (n = 10). On the other hand, this was only necessary in two patients in the PCEA group. The amount of time the patients stayed in the intensive care unit and the hospital was significantly shorter in the PCEA group than in the control group (P < 0.001 and P < 0.01, respectively). Respiratory complications occurred in four patients in the control group, and none in the PCEA group. The mean number of supplemental analgesics administered for breakthrough pain until the 7th postoperative day was 5.5 in the control group, and 1.3 in the PCEA group (P < 0.001). Conclusions  Early rehabilitation is facilitated with intensive PCEA, while it also improves postoperative management and reduces hospitalization after esophageal surgery.     

The dynamics and clinical significance of alpha 2 plasmin inhibitor-plasmin complex and thrombin-antithrombin complex in postoperative pleural effusion following a pulmonary lobectomy

Purpose  The overall incidence of postoperative alveolar air leakage (AAL) remains high; however, the mechanism regarding how to adequately heal such postoperative AAL remains to be elucidated. The aim of this study was to determine any correlations between the activity of the fibrinolytic and coagulation system in the postoperative pleural effusion and appearance or disappearance of postoperative AAL. Methods  This study prospectively investigated 25 patients who underwent a pulmonary lobectomy from July 2005 to March 2006. Pleural effusion was collected through the chest tube. Alpha 2 plasmin inhibitor-plasmin complex (PIC), as a fibrinolytic marker, and thrombin-antithrombin complex (TAT), as a coagulation marker, were measured. Results  The activity of the coagulation system was higher than that of the fibrinolytic system. The concentration of TAT tended to increase (3rd vs 4th postoperative day [POD], P = 0.0907). The mean time of appearance and disappearance of postoperative AAL was 1.4 days and 3.2 days, respectively. The patients with postoperative AAL had a TAT level significantly below the average on the 3rd POD in comparison to the patients without postoperative AAL (P = 0.0163). Moreover, the concentration of TAT in patients with postoperative AAL was significantly lower than that in patients without postoperative AAL (1824.0 ± 137.3 ng/ml vs 3444.0 ± 287.6 ng/ml, P = 0.0113) on the 3rd POD. On the 4th POD, the concentration of TAT was almost same and there was no significance (P = 0.6759). Conclusions  This study demonstrated for the first time the course of the fibrinolytic and coagulation activity in the pleural effusion after a pulmonary lobectomy, and showed that the delayed activity of the coagulation system is associated with the appearance of the postoperative AAL.     

Novel retractor for lymph node dissection by video-assisted thoracic surgery

In nonrandomized studies, the video-assisted thoracic surgical (VATS) lobectomy seems to be a safe and effective procedure for treatment of lung cancer. However, there are some difficulties in VATS complete mediastinal lymph node dissection. The presence of the lymph node deep in the mediastinal space necessitates retraction of the surrounding organs. Therefore, we developed a retractor to create enough working space during the VATS procedure. To dissect lymph nodes, we use endoscopic bipolar forceps. These instruments are connected to a special electrosurgical generator to apply bipolar soft coagulation, which enables simultaneous dissection and sealing. Thus, "en bloc" lymph node dissection can be performed during the VATS procedure.