Clinical outcome and survival after palliative surgery for spinal metastases: palliative surgery in spinal metastases

BACKGROUND: The authors sought to identify treatment-related factors that influenced survival after surgical treatment for metastatic spinal tumors and to evaluate the relationship between survival and postoperative ambulation time as a factor related to quality of life. METHODS: The medical records of 81 patients with metastatic spinal tumors who underwent palliative surgery at the study institution were assessed. Univariate analysis for factors influencing survival used the Kaplan-Meier log rank statistic and multivariate analysis used the Cox proportional hazards model. The Spearman correlation test was used to analyze the relationship between postoperative ambulation and survival time. RESULTS: The patients had a median age of 59.9 years and a median survival of 10.6 months after surgery. For patients, postoperative ambulatory median survival was 16.5 months and median ambulation time was 13.8 months. By univariate analysis, anatomic site of the primary tumor, postoperative ambulation, and combined adjuvant therapy (chemotherapy plus radiotherapy) were associated with prolonged survival (P < 0.05). Multivariate analysis identified primary site and postoperative ambulatory function as independent predictors of prolonged survival (P < 0.0001). Significant correlations were found between ambulation time and survival time of patients who were able to walk after surgery (P < 0.0001), even in patients with liver (P < 0.05) or lung carcinoma (P < 0.05). CONCLUSIONS: The anatomic site of primary carcinoma and postoperative ambulation were associated with longer survival after palliative surgery for metastatic spinal tumor. When ambulation is attained after surgery, it can be preserved until late in remaining life even when the primary tumor is unfavorable. Palliative surgery for spinal metastasis can improve the quality and quantity of life.     

Pain processing within the primary somatosensory cortex in humans

To investigate the processing of noxious stimuli within the primary somatosensory cortex (SI), we recorded magnetoencephalography following noxious epidermal electrical stimulation (ES) and innocuous transcutaneous electrical stimulation (TS) applied to the dorsum of the left hand. TS activated two sources sequentially within SI: one in the posterior bank of the central sulcus and another in the crown of the postcentral gyrus, corresponding to Brodmann's areas 3b and 1, respectively. Activities from area 3b consisted of 20- and 30-ms responses. Activities from area 1 consisted of three components peaking at 26, 36 and 49 ms. ES activated one source within SI whose location and orientation were similar to those of the TS-activated area 1 source. Activities from this source consisted of three components peaking at 88, 98 and 109 ms, later by 60 ms than the corresponding TS responses. ES and TS subsequently activated a similar region in the upper bank of the sylvian fissure, corresponding to the secondary somatosensory cortex (SII). The onset latency of the SII activity following ES (109 ms) was later by 29 ms than that of the first SI response (80 ms). Likewise, the onset latency of SII activity following TS (52 ms) was later by 35 ms than that of area 1 of SI (17 ms). Therefore, our results showed that the processing of noxious and innocuous stimuli is similar with respect to the source locations and activation timings within SI and SII except that there were no detectable activations within area 3b following noxious stimulation.     

Effects of the CYP2C19 genotype and cigarette smoking on the single oral dose pharmacokinetics and pharmacodynamics of estazolam

The effects of the cytochrome P450 (CYP)2C19 genotype and cigarette smoking on the single oral dose pharmacokinetics and pharmacodynamics of estazolam were studied in 16 healthy male volunteers. The two mutated alleles (CYP2C19*2 and CYP2C19*3) causing absent CYP2C19 activity were identified by PCR-based restriction enzyme analysis. Five subjects had no mutated allele, five had one mutated allele, and six had two mutated alleles. Seven subjects were smokers, and nine were nonsmokers. The subjects received a single oral 4-mg dose of estazolam, and blood samplings and evaluation of psychomotor function were conducted up to 72 h after dosing. There was no significant difference among the groups with no, one, and two mutated alleles for the peak plasma concentration (145.2+/-36.5 vs. 142.1+/-33.6 vs. 113.2+/-29.7 ng/ml), area under the plasma concentration-time curve (0- infinity ) (4916.0+/-1276.4 vs. 4389.6+/-736.1 vs. 4047.3+/-613.8 ng x h/ml), apparent oral clearance (0.22+/-0.05 vs. 0.25+/-0.03 vs. 0.25+/-0.03 ml/min/kg), and elimination half-life (24.4+/-4.6 vs. 29.6+/-8.5 vs. 30.7+/-3.9 h). Similarly, none of the pharmacokinetic parameters was significantly different between the nonsmoker and smoker groups. Neither the number of mutated allele nor cigarette smoking affected the psychomotor function parameters significantly. The present study suggests that neither the CYP2C19 genotype nor cigarette smoking affects the single oral dose pharmacokinetics and pharmacodynamics of estazolam.     

Elective affinities: a Tudor–Aubergine tale of germline partnership

In Drosophila melanogaster and many other metazoans, the specification of germ cells requires cytoplasmic inheritance of maternally synthesized RNA and protein determinants, which are assembled in electron-dense cytoplasmic structures known as germ or polar granules, found at the posterior end of the oocytes. Recent studies have shown that the formation of germ granules is dependent on the interaction of proteins containing tudor domains with the piwi-interacting RNA (piRNA)-binding Piwi proteins, and such interactions are dependent on symmetrically dimethylated arginines (sDMAs) of Piwi proteins. Tudor–Piwi interactions are crucial and are conserved in the germ cells of sexually reproducing animals, including mammals. In the September 1, 2010, issue of Genes & Development, Liu and colleagues (pp. 1876–1881) use a combination of genetics, biochemistry, and crystallography to uncover the molecular and structural details of how Tudor recognizes and binds the sDMAs of the Piwi protein Aubergine.     

Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules.

The salient histopathologic features of low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA) include complex glandular structures and morules with biotin-rich optically clear nuclei. Interestingly, these characteristic features are shared by the cribriform-morular variant of papillary thyroid carcinoma, whose morphology is identical to that of familial adenomatous polyposis (FAP)-associated thyroid carcinoma. Furthermore, the single reported case of lung cancer associated with FAP was L-FLAC/WDFA. These observations lead us to hypothesize that up-regulation of the Wnt signaling pathway underlies the development of L-FLAC/WDFA. To verify this hypothesis, 11 cases of L-FLAC/WDFA, including the one FAP-associated case, eight cases of high-grade adenocarcinoma of the fetal lung type (H-FLAC), 24 cases of conventional pulmonary adenocarcinoma (CAC), and 13 fetal lungs were immunostained for beta-catenin. All cases of L-FLAC/WDFA showed predominantly aberrant nuclear/cytoplasmic expression, especially in budding glands and morules, whereas six of eight cases (75%) of H-FLAC and all but one case (96%) of CAC showed predominantly membranous expression. Fetal lungs showed nuclear/cytoplasmic expression restricted to the distal branching airway epithelium. Mutational analysis of exon 3 of the beta-catenin gene in five sporadic cases of L-FLAC/WDFA showed a point mutation at codon 34 and codon 37 in two cases, respectively. The present study indicates that up-regulating disturbances in the Wnt signaling pathway, including mutation of the beta-catenin gene, underlie tumorigenesis of L-FLAC/WDFA. The expression pattern of beta-catenin in L-FLAC/WDFA resembles that of the developing fetal lung airway. With the expression pattern of beta-catenin as a marker, most cases of H-FLAC as well as CAC appear to have different oncogenic pathways from cases of L-FLAC/WDFA. The present study together with other available data also suggests that abnormal up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors with morular formation from a variety of anatomic sites.     

Perspectives on phantom boarder symptom

Phantom boarder symptom (PBS) is a hallucinatory and delusional syndrome that tends to occur in the elderly, in which the patient imagines that someone uninvited is living in their home. This article provides an overview of the historical background that has led to the current focus on PBS as a single symptom, from its classification as late paraphrenia to its being recognized as a type of misidentification, and discusses classification problems and PBS subclassifications. In addition, the results of our own investigation of PBS, which focused on PBS in senile dementia, support the findings of previous studies, such as the absence of a relationship between dementia severity and the occurrence of delusion. The discussion therefore focuses on the psychosocial factors that serve as the mechanism of PBS onset, and directions and possibilities for therapy are suggested.     

A case of endocrine carcinoma of the sigmoid colon]

We report a case of endocrine carcinoma of the sigmoid colon. A 71-year-old man was admitted to our hospital because of constipation and bloody stool. Colonoscopy showed a mass lesion with irregular ulceration in the sigmoid colon. He was given a diagnosis of the poorly differentiated adenocarcinoma of the colon, and underwent sigmoidectomy with dissection of the lymph nodes. Histological and immunohistochemical examinations of the resected specimen revealed endocrine carcinoma. Endocrine carcinoma of the colon is rare, and the prognosis is very poor. We discuss this case with references.