The role of postoperative radiotherapy in non-small cell lung cancer; a retrospective analysis of our experience

Sixty-one patients with completely resected non-small cell lung cancer followed by postoperative radiotherapy were retrospectively reviewed. Forty-six patients were male and 15 were female. Ages ranged 34-79 (median 64) years. Squamous cell carcinoma (scc) in 28, adenoca. in 31, large cell ca in 1 and adenoid cystic ca. in 1. Pathological stage was IIA in 1, IIB in 9, IIIA in 41 and IIIB in 10. Over-all 5-year survival rate (OS) was 56.0%, and 5-year disease-free survival rate (DFS) was 39.7%. For IIB, IIIA, IIIB patients, OS were 77.8%, 55.4%, 24.0% respectively. According to purpose of radiotherapy, patients divided into 3 types as local invasion (LI) group (T3-4N0-1, n = 12), lymphnode metastases (LN) group (T1-2N2-3, n = 38) and both advanced (BA) group (T3-4N2-3, n = 8). OS were 71.6%, 50.7%, 46.9% and DFS were 68.6%, 31.0%, 42.9% respectively. In LN group, half of patients with scc had no relapse, but about half of non-scc had distant metastases. All N2 patients divided 2 types as single-station N2 and multi-station N2. OS were 71.8%, 40.0% and DFS were 53.5%, 21.1% respectively. DFS was significantly different (p = 0.04). The advantage was remarkable in patients with scc-single-station N2 (OS was 88.9%, DFS was 77.8%). The effectiveness of postoperative radiotherapy is not showed, but our results suggest the possibility for existence of subgroup benefited from postoperative radiotherapy.     

The effects of arginine and selective inducible nitric oxide synthase inhibitor on pathophysiology of sepsis in a CLP model

BACKGROUND: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. METHOD: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. RESULTS: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. CONCLUSION: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.     

Intradural extramedullary ganglioneuroma associated with multiple hamartoma syndrome

A 51-year-old woman presented with a rare completely intradural and extramedullary spinal ganglioneuroma associated with multiple hamartoma syndrome and manifesting as complaints of neck pain and dizziness persisting for 8 months. Magnetic resonance imaging of the spinal cord revealed an intradural extramedullary lesion at the C1 level. She underwent right suboccipital craniectomy and C1-2 hemilaminectomy to remove the tumor. Histological examination confirmed ganglioneuroma. She also suffered from multiple facial trichilemmomas, thyroid goiter, multiple polyposis of the gastrointestinal tract, and pulmonary hamartoma indicating multiple hamartoma syndrome. These benign neoplasms were treated conservatively.     

Prospective analysis of depression and psychological distress before and after surgical resection of lung cancer

Objectives The psychological effects of surgery have received little attention in patients with lung cancer, so it is unclear how much psychological support is required by these patients. This study was done to assess the mental state of patients with lung cancer before and after surgery and to determine their need for psychological care. Methods A group of 165 patients with lung cancer scheduled for surgical treatment were included in this study. They were asked to complete the Profile of Mood States questionnaire before surgery and on discharge after completion of treatment. The data on mood from the questionnaires were analyzed. Results Tension-anxiety improved significantly after surgery, whereas the fatigue score increased significantly. The scores for depression-dejection and confusion were elevated before surgery and were unchanged afterward. Conclusions Patients with lung cancer were depressed before surgery and remained depressed after their operations, although postoperative tension-anxiety diminished. These results indicate that lung cancer patients need psychological support to alleviate depression during the perioperative period.     

Dikkopf-1 as a novel serologic and prognostic biomarker for lung and esophageal carcinomas

Gene expression profile analysis of lung and esophageal carcinomas revealed that Dikkopf-1 (DKK1) was highly transactivated in the great majority of lung cancers and esophageal squamous cell carcinomas (ESCC). Immunohistochemical staining using tumor tissue microarrays consisting of 279 archived non-small cell lung cancers (NSCLC) and 280 ESCC specimens showed that a high level of DKK1 expression was associated with poor prognosis of patients with NSCLC as well as ESCC, and multivariate analysis confirmed its independent prognostic value for NSCLC. In addition, we identified that exogenous expression of DKK1 increased the migratory activity of mammalian cells, suggesting that DKK1 may play a significant role in progression of human cancer. We established an ELISA system to measure serum levels of DKK1 and found that serum DKK1 levels were significantly higher in lung and esophageal cancer patients than in healthy controls. The proportion of the DKK1-positive cases was 126 of 180 (70.0%) NSCLC, 59 of 85 (69.4%) SCLC, and 51 of 81 (63.0%) ESCC patients, whereas only 10 of 207 (4.8%) healthy volunteers were falsely diagnosed as positive. A combined ELISA assays for both DKK1 and carcinoembryonic antigen increased sensitivity and classified 82.2% of the NSCLC patients as positive whereas only 7.7% of healthy volunteers were falsely diagnosed to be positive. The use of both DKK1 and ProGRP increased sensitivity to detect SCLCs up to 89.4%, whereas false-positive rate in healthy donors was only 6.3%. Our data imply that DKK1 should be useful as a novel diagnostic/prognostic biomarker in clinic and probably as a therapeutic target for lung and esophageal cancer.     

A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are known to modulate carcinogenesis. In this study, we investigated whether a lipophilic HMG-CoA reductase inhibitor pitavastatin suppresses inflammation-related mouse colon carcinogenesis. Male CD-1 (ICR) mice were initiated with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and promoted by 2% (w/v) dextran sodium sulfate (DSS) in drinking water for 7 days. The experimental diets containing pitavastatin at 2 dose levels (1 and 10 ppm) were fed to male CD-1 (ICR) mice for 17 weeks, staring 1 week after the cessation of DSS exposure. The effects of dietary pitavastatin on colonic tumor development were assessed at Weeks 5, 10 and 20. Feeding with pitavastatin at both doses significantly inhibited the multiplicity of colonic adenocarcinoma at Week 20. Furthermore, the treatment significantly lowered the positive rates of proliferating cell nuclear antigen and increased the apoptotic index in the colonic epithelial malignancies. The treatment also reduced nitrotyrosine-positivity in the colonic mucosa. Our findings thus show that pitavastatin is effective in inhibiting colitis-related colon carcinogenesis through modulation of mucosal inflammation, oxidative/nitrosative stress, and cell proliferation.