Pleural perfusion thermo-chemotherapy under VATS: a new less invasive modality for advanced lung cancer with pleural spread

BACKGROUND: We conducted a trial of a new less invasive, locoregional modality for lung cancer with pleural spread. This study was planned to investigate the feasibility, safety, and pharmacokinetics of pleural perfusion thermochemotherapy (PPTC) under video-assisted thoracoscopic surgery (VATS) and its modified method with a short perfusion time for preventing heat damage to the lung during the procedure. METHODS: Seventeen patients, 59 to 79 years old, underwent surgical resection of the primary lesions and PPTC under VATS without thoracotomy. All had pleural spread with malignant effusion due to lung cancer proven before the treatment. PPTC consists of irrigating the pleural space with 42 degrees C saline solution containing cisplatin (200 mg/m(2)) using a devised circuit. The time for perfusion was two hours in 10 patients (group L), and one hour in 7 patients (group S). RESULTS: All patients successfully completed this treatment with acceptable toxicities. The pharmacokinetic analysis showed that high platinum levels for the regional pleural exposure, which was 20- to 40-fold greater than those for the plasma in both groups. These values were equivalent between the groups, although the levels for the plasma were higher in group L than in group S. Postoperative lung damage was seen in 4 patients with no serious conditions in group L, and none in group S. The median survival for the L and S groups was 17 and 19 months, respectively. CONCLUSIONS: This less invasive modality seems to offer a safe, feasible, and pharmacokinetically advantageous procedure to have excellent local control for lung cancer with pleural spread.     

Spinal anesthesia for 12 patients receiving home oxygen therapy

From Jan 2001 to Nov 2003, 12 patients receiving home oxygen therapy (HOT) underwent surgery under spinal anesthesia at Okayama Rosai Hospital. The basic diseases for HOT were emphysema (n=8), interstitial pneumonia (n=1), asthma (n=1) and lung cancer (n=1). Mean FEV1.0 and FVC were 0.85 l and 1.97 l, respectively. Mean PaO2 and PaCO2 were 76.5 mmHg and 45.5 mmHg, respectively, under nasal oxygen of 1.67 l x min(-1). Perioperative complications occured in 3 cases. In case 5, postoperative heart failure occured and was easily treated with diuretics. In case 8, intraoperative hypotension (systemic blood pressure less than 80 mmHg) occured. In case 12, the patient developed dyspnea because of high spinal anesthetic level of T1. She was not intubated because PaO2, PaCO2 and pH were not deteriorated. Perioperative PaO2, PaCO2 and pH were stable and there were no pulmonary or morbid complications in all cases. It is important to assess not only pulmonary function but also cardiovascular status by echocardiography and general physical status by Hugh-Jones classification in order to avoid severe complications.     

Quantitative analysis of radioisotope cisternography in the diagnosis of intracranial hypotension

OBJECT: The authors attempted a quantitative analysis of conventional radioisotope cisternography for the purpose of more accurate diagnosis of intracranial hypotension. METHODS: Fifty-seven patients suspected of having intracranial hypotension underwent radioisotope cisternography. Whole-body images were obtained 2.5, 6, and 24 hours after intrathecal injection of 111In-diethylenetriamine pentaacetic acid. Radioactivity in the cerebrospinal fluid (CSF) space was counted during scanning, and radioisotope clearance was studied. Direct signs of radioisotope leakage into the spinal epidural space were found in 25 patients. Most leaks were located in the lumbosacral region. Analysis of the radioisotope clearance curve revealed two different patterns. In patients without a radiographically demonstrated radioisotope leak, absolutely exponential curves were observed (R2 > 0.99). The activity of the radioisotope decreased at a rate of e(-003) to e(-0.107) (mean +/- standard deviation, e(-0.056 +/- 0.018); 32 patients). Clearance in patients with an overt radioisotope leak was not a simple exponential curve; it could be divided into an early rapid phase and a late slow phase. The clearance rate during the first 6 hours was e(-0.219 +/- 0.127) (25 patients) and e(-0.076 +/- 0.021) thereafter. The authors speculated that the early escape of undiluted radioisotope solution through an aberrant CSF outlet, such as a traumatic spinal dural tear, was responsible for this phenomenon. CONCLUSIONS: The quantitative analysis featured in this study seems to be useful in the diagnosis of intracranial hypotension. A small CSF leak below the limit of radioisotope cisternography resolution might be detected using this technique.     

A review and development of sentinel node navigation surgery for lung cancer

Sentinel node navigation surgery (SNNS) for lung caner has not yet been established. Sentinel node (SN) identification using dye or radioisotope has been developed; however, the SN identification rate was less than 50% in the dye method and use of radioisotopes is strongly restricted in Japan. The novel method using a CT or MRI contrast medium are expected. A study of local immune reaction for lung cancer in SN is also a very interesting issue.     

Inhibition of metastasis of tumor cells overexpressing thymidine phosphorylase by 2-deoxy-L-ribose

Thymidine phosphorylase (TP) catalyzes the reversible conversion of thymidine to thymine, thereby generating 2-deoxy-D-ribose-1-phosphate, which upon dephosphorylation forms 2-deoxy-D-ribose (D-dRib), a degradation product of thymidine. We have previously shown that D-dRib promotes angiogenesis and chemotaxis of endothelial cells and also confers resistance to hypoxia-induced apoptosis in some cancer cell lines. 2-Deoxy-L-ribose (L-dRib), a stereoisomer of D-dRib, can inhibit D-dRib anti-apoptotic effects and suppressed the growth of KB cells overexpressing TP (KB/TP cells) transplanted into nude mice. In this study, we examined the ability of L-dRib to suppress metastasis of KB/TP cells using two different models of metastasis. The antimetastatic effect of L-dRib was first investigated in a liver-metastasis model in nude mice inoculated with KB/TP cells. Oral administration of L-dRib for 28 days at a dose of 20 mg/kg/day significantly reduced the number of metastatic nodules in the liver and suppressed angiogenesis and enhanced apoptosis in KB/TP metastatic nodules. Next, we compared the ability of L-dRib and tegafur alone or in combination to decrease the number of metastatic nodules in organs in the abdominal cavity in nude mice receiving s.c. of KB/TP cells into their backs. L-dRib (20 mg/kg/day) was significantly (P < 0.05) more efficient than tegafur (100 mg/kg/day) in decreasing the number of metastatic nodules in organs in the abdominal cavity. By in vitro invasion assay, L-dRib also reduced the number of invading KB/TP cells. L-dRib anti-invasive activity may be mediated by its ability to suppress the enhancing effect of TP and D-dRib on both mRNA and protein expression of vascular endothelial growth factor and interleukin-8 in cultured KB cells. These findings suggest that L-dRib may be useful in a clinical setting for the suppression of metastasis of tumor cells expressing TP.     

Eosinophilic myelitis associated with atopic diathesis: a combined neuroimaging and histopathological study

Histologically proven eosinophilic myelitis has rarely been reported except in connection with parasitism. To clarify its clinicopathological features, we conducted a nationwide survey of biopsy-proven eosinophilic myelitis of unknown cause throughout Japan. Six such cases were collected and studied immunologically and pathologically. All were young to middle-aged men. All showed a protracted and fluctuating course with mild disability for 3-25 (mean 12.5) months before biopsy. Magnetic resonance imaging revealed localized lesions of T2-high and T1-iso signal intensity with a partial gadolinium enhancement in all cases. Cerebrospinal fluid (CSF) examinations were completely normal except for modest pleocytosis in two cases. Eosinophilia was present in the peripheral blood in two cases but was absent from the CSF of all cases. In spite of the chronic nature of the disease, spinal cord pathology revealed very active lesions with marked cell infiltration consisting mainly of CD8(+) T cells and varying numbers of eosinophils in the perivascular areas and the parenchyma. Both the myelin and axons were severely disrupted in all cases. Moreover, eosinophil cationic protein (ECP), an activated eosinophil product, was heavily deposited in the tissues. All but one case had hyperIgEemia and mite antigen-specific IgE in the sera, and two had accompanying atopic disorders. The present study thus revealed idiopathic eosinophilic myelitis to be a localized and persistent inflammation of the spinal cord, with distinct clinicopathological features, that has a possible link to atopic diathesis.     

A subclass of soluble HLA-G1 modulates the release of cytokines from mononuclear cells present in the decidua additively to membrane-bound HLA-G1

Problem: Our previous studies have demonstrated that a subclass of soluble human leukocyte antigen-G1 protein (sub-sHLA-G1), that has 1 to 3 extra-cellular portion but lacks C-terminus of authentic soluble HLA-G1 secreted by trophoblasts, fine-tunes the release of cytokines from peripheral blood mononuclear cells (PBMCs) chiefly by counterbalancing membrane-bound HLA-G1 (mHLA-G1), and thereby may play a role in maintaining pregnancy. In this study, we investigated whether the presence of sHLA-G1 protein altered the release of cytokines from decidual mononuclear cells (DMCs) which are localized at the interface of feto–maternal interaction and whose cell population is completely different from PBMCs. Method of study: We cultured peripheral DMCs with either HLA-A and -B lacking B lymphoblast cell line (721.221 cells) or the cells transfected with mHLA-G1 (721.221-G1 cells) with or without sub-sHLA-G1. Cytokines concentrations in the culture media were determined by an enzyme-linked immunosorbent assay. Results: Regardless of the presence of mHLA-G1 expressing cells, the addition of the recombinant sub-sHLA-G1 protein in the DMC culture media decreased the amounts of tumor necrosis factor (TNF)- and interferon (IFN)-γ, with the release of IL-4 from DMCs being unchanged. Conclusion: The sub-sHLA-G1 protein modulates the release of cytokines from DMCs additively to mHLA-G1 expressing cells. In view of the distinct fetomaternal interaction during implantation, it appears that sHLA-G1 might play a role in the establishment of pregnancy by regulating cytokine release in concert with mHLA-G1.     

N-glycosylation sites on the nicotinic ACh receptor subunits regulate receptor channel desensitization and conductance

The present study investigated the effects of N-glycosylation sites on Torpedo acetylcholine (ACh) receptors expressed in Xenopus oocytes by monitoring whole-cell membrane currents and single-channel currents from excised patches. Receptors with the mutant subunit at the asparagine residue on the conserved N-glycosylation site (mbetaN141D, mgammaN141D, or mdeltaN143D) or the serine/threonine residue (mbetaT143A, mgammaS143A, or mdeltaS145A) delayed the rate of current decay as compared with wild-type receptors, and the most striking effect was found with receptors with mbetaT143A or mgammaS143A. For wild-type receptors, the lectin concanavalin A, that binds to glycosylated membrane proteins with high affinity, mimicked this effect. Receptors with mbetaN141D or mdeltaN143D exhibited lower single-channel conductance, but those with mbetaT143A, mgammaS143A, or mdeltaS145A otherwise revealed higher conductance than wild-type receptors. Mean opening time of single-channel currents was little affected by the mutation. N-glycosylation sites, thus, appear to play a role in the regulation of ACh receptor desensitization and ion permeability.     

A comparison of (13)C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-(13)C]glucose

13C-labeled glucose is increasingly used in conjunction with magnetic resonance spectroscopy to measure rates of metabolic pathways in the brain in vivo. Most studies of human subjects have used intravenous infusions to administer the labeled compounds, but the procedure is cumbersome and can be uncomfortable for patients with neurological or psychiatric disorders. It may be possible to improve the practicality of the method by administering the glucose orally instead of intravenously. This report describes the performance and comparison of the oral and intravenous protocols in the same subjects. The conclusion is that oral administration does yield the same result as intravenous administration but with lower precision. That sensitivity of the oral protocol may be improved by several ways that are available today.