Overexpression of glucose transporter 1 in esophageal squamous cell carcinomas: a marker for poor prognosis

SUMMARY: Recently, Glut1 (human erythrocyte glucose transporter) expression has been demonstrated in various tumors. The aim of this study is to evaluate the prognostic utility of Glut1 expression in esophageal carcinomas. We studied Glut1 expression by immunohistochemistry of paraffin sections from 63 esophageal squamous cell carcinomas. All 63 carcinomas expressed Glut1. The mean percentage of positively stained tumor cells was 77.8% (median, 84.7%). There were two staining patterns in positive cells: 'strongly positive' and 'weakly positive'. The percentage of 'strongly positive' cells (%Glut1-SP) ranged from 0% to 95.6% (mean, 32.3%; median, 27.4%). The 5-year survival rate for patients with a high %Glut1-SP (> 30%) was significantly lower than that for patients with a low %Glut1-SP (< 30%) (P < 0.01). Statistical analysis revealed that the relative risk of death for patients with high %Glut1-SP was 2.02 times that for patients with low %Glut1-SP (P = 0.064), suggesting a possible independent predictive value for %Glut1-SP.     

Spindle cell oncocytoma of the adenohypophysis with marked hypervascularity

A 68-year-old male presented with a very rare case of spindle cell oncocytoma (SCO), a recently identified very rare neoplasm of the anterior pituitary, manifesting as panhypopituitarism and visual field defect. The pituitary tumor with suprasellar extension was only partially resected via transsphenoidal surgery because of the tumor consistency and bleeding. Histological diagnosis was consistent with schwannoma. The tumor regrew and angiography revealed hypervascularity, so a transcranial approach was employed for the re-operation which only achieved partial resection because of intraoperative extensive bleeding. The tumor cells showed similar histological and immunohistochemical profiles to the previous specimen, but electron microscopy demonstrated that cytoplasm abundantly filled with mitochondria. The final diagnosis of SCO was established and the patient received postoperative conventional radiation therapy of 50 Gy. Only 15 cases of SCO have been reported, and the diagnosis was mistaken in many cases as schwannoma, oncocytic pituitary adenoma, or craniopharyngioma, and multiple surgeries followed by radiation therapy were required.     

Latent psychological distress existing behind a set of assessment measures is comparable to or more important than symptoms or disability in the association with quality of life and working status of patients with rheumatoid arthritis

Abstract

Objectives: To identify the determinant of patients’ perspectives of quality of life (QOL) and working status out of analysis-derived components underlying a set of assessment measures of the status of patients with rheumatoid arthritis (RA).

Methods: From the NinJa database in Japan (2012–2014), 1455 RA patients with DAS28?>?3.2 were recruited. Components explaining RA status were derived from principal component analysis of 15 assessment measures. Multivariate regression was used to examine the relative contribution of each identified component to the EuroQOL-5 Dimension Questionnaire score and working status.

Results: Among the identified components (patient symptoms, physical disability, evaluated symptoms, patient distress, inflammatory marker, and serological marker), patient distress showed highest contribution to EuroQOL for both male (44.6%) and female patients (39.3%). Physical disability was associated with significantly less participation in paid work in male (odds ratio [OR]; 0.63) and both household and paid work in female (OR; 0.82 and 0.54, respectively), though patient distress showed the strongest association with less participation in both household and paid work in female (OR; 0.64 and 0.45, respectively).

Conclusion: The approach to latent patient distress using psychological screening tools, concurrently with the treatment to control the activity of arthritis, can be help to improve health-related QOL (HRQOL) including work participation.     

PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population

Objective

Systemic sclerosis (SSc) is an autoimmune disease for which multiple susceptibility genes have been reported. Genome‐wide association studies have shown that large numbers of susceptibility genes are shared among autoimmune diseases. Recently, our group identified 9 novel susceptibility genes associated with rheumatoid arthritis (RA) in a Japanese population. The aim of this study was to elucidate whether the 18 genes that displayed associations or suggestive associations for RA in our previous study are associated with SSc in Japanese.

Methods

We performed an association study that included 415 patients with SSc and 16,891 control subjects, followed by a replication study that included 315 patients and 21,054 control subjects. The 18 markers reported to display association with RA were analyzed for their associations with SSc in the first study, and 5 markers were further analyzed in the replication study. The inverse variance method was used to evaluate the associations of these markers with SSc in a combined study.

Results

In the phospholipase D4 gene (PLD4), rs2841277 displayed a significant association with SSc in Japanese patients (P = 0.00017). We observed that rs2841280 in exon 2 of PLD4 was in strong linkage disequilibrium with rs2841277 and introduced an amino acid alteration. We also observed associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 (P = 0.0000095 and P = 0.0030, respectively), both of which displayed associations with SSc in a European population.

Conclusion

We determined that PLD4 is a novel susceptibility gene for SSc in Japanese, thus confirming the involvement of PLD4 in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected in our Japanese population. SSc and RA appear to share relatively large proportions of their genetic backgrounds.

     

Direct synaptic contacts of catecholamine axons on the preganglionic sympathetic neurons in the rat thoracic spinal cord

Preganglionic sympathetic neurons were labelled by retrograde transport of horseradish peroxidase, while catecholamine axon varicosities were marked by the uptake of 5-hydroxydopamine in the intermediolateral nucleus of the rat. The direct synaptic contacts from the catecholamine axons to the preganglionic sympathetic neurons were demonstrated. Catecholamine axons formed symmetric synapses.     

Chemotherapy for advanced and recurrent cancer patients--the effect of combination chemotherapy using cisplatin, peplomycin, mitomycin C, adriamycin, and 5-fluorouracil]

According to the data obtained from the fundamental investigations using flow cytometry we designed the schedule of combination chemotherapy for solid cancer patients and we tried this therapy on 25 patients with non-curative, unresectable and recurrent cancers: 9 gastric, 5 colo-rectal, 3 esophageal, 3 pancreatic, 2 gall bladder, 2 lung and 1 breast cancer. The treatment was performed every 3 or 4 weeks as follows: CDDP 70 mg/m2 (d.i.), PEP 4 mg/m2 (i.v.) and MMC 4 mg/m2 (i.v.) on day 1, ADM 15 mg/m2 (i.v.) on day 4, and 5-Fu 250 mg/body (d.i.) every day. Among 22 patients evaluated completely, 1 complete response, 9 partial responses, 11 no changes, 1 progressive disease were obtained. The overall response rate was 45%. From the comparison of survival curves, survival rate was significantly better in patients responded to this therapy than in patients who did not respond to it (p less than 0.05). As for side effects, myelosuppression occurred in 19 patients (86%), increase of BUN and/or creatinine were observed in 3 patients (14%), increase of GOT and/or GPT were seen in 10 patients (45%), gastrointestinal symptoms and alopecia were observed in almost all patients, but all of these toxicity were transient and did not impede the continuous treatment.     

Reevaluation of the toxicity of chlorinated water and the usefulness of MX as an index

Changes in the toxicity in chlorinated water after chlorine addition were examined. For toxicity evaluation, the chromosomal aberration test and the transformation test were conducted as indexes of initiation activity and promotion activity, respectively, in the carcinogenesis process. Activity inducing chromosomal aberrations in chlorinated Lake Biwa water gradually decreased over time after chlorination. In contrast, activity inducing transformations determined by the two-stage assay gradually increased. Thus, toxicity that decreases or increases is present in chlorinated water. Furthermore, activity inducing transformations determined by the non-two-stage assay gradually decreased over time. This direction of change is opposite to that of activity inducing transformations determined by the two-stage assay and is consistent with that of activity inducing chromosomal aberrations. The drastic decrease in initiation activity detected as activity inducing chromosomal aberrations could be the main cause for the decrease in activity inducing transformations determined by the non-two-stage assay (an index of the sum of initiation and promotion activity). MX change was quantitatively consistent with those of activity inducing chromosomal aberrations and transformations determined by the non-two-stage assay. On the other hand, directions of changes in concentrations of typical by-products such as chloroform were consistent only with that of activity inducing transformations determined by the two-stage assay. Findings of this study suggest that MX is appropriate as an index for comparing the carcinogenicity of tap water near and far from a water purification plant.     

Bactericidal effects of acidic electrolyzed water on the dental unit waterline

Many studies have been conducted in the United States regarding the microbial contamination of dental unit waterline, but not in Japan. Recently, acidic electrolyzed water has been used in the medical and dental fields. In this study, we investigated the bactericidal effects of the temporary inflow of acidic electrolyzed water on microbial contamination of the dental unit waterline. First, in order to observe the daily bacterial contamination of the dental unit waterline, water samples were collected at the end of handpieces and three-way syringes before the inflow of acidic electrolyzed water. They were cultured to detect viable bacteria. Later, the inflow of acidic electrolyzed water was conducted through the piping box of the dental unit. Before starting operation on next day, water samples were collected and cultured, as described above. The mean viable bacteria count was 910 -/+ 190 CFU/ml at the end of handpieces, and 521 -/+ 116 CFU/ml at the end of three-way syringes before the inflow of acidic electrolyzed water. However, bacteria were detected in only small numbers at the end of handpieces and three-way syringes on the next day. These results indicated that acidic electrolyzed water could be applied as an appropriate measure against bacterial contamination of the dental unit waterline.     

Central nervous system primitive neuroectodermal tumor of spinal cord developing 20 years after curative treatment of pineal tumor

A 65-year-old male who had previously received curative treatment for a pineal tumor presented with an extremely rare case of primary central nervous system (CNS) primitive neuroectodermal tumor (PNET) of the spinal cord manifesting as progressive tetraparesis. Although the histology was not verified, highly radiosensitive tumor was suspected because of the benign clinical course for over 20 years after only radiation therapy. Magnetic resonance imaging demonstrated an intramedullary tumor extending from C5 to T1. He underwent partial resection and histological examination revealed blue tumor with undifferentiated small round cells. Immunohistochemically, c-kit was negative but CD99 was strongly and diffusely positive. Therefore, rearrangement of the Ewing sarcoma gene was examined to determine the presence of peripheral type of PNET. The results were negative and systemic workup revealed no other disease. These findings led to the diagnosis of primary intramedullary CNS PNET of the spinal cord, and suggested that the spinal cord tumor occurred independently of the prior pineal disease. The residual tumor was controlled by postoperative local radiation therapy.