Impact of mediastinal lymph node dissection on octogenarians with non-small cell lung cancer

Objective: Impacts of mediastinal lymph node dissection on a patient’s course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. Methods: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. Results: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. Conclusion: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.     

Angiotensinogen gene polymorphism as a risk factor for ischemic stroke.

While gene polymorphism for angiotensinogen (AGT) is reported to contribute to the regulation of blood pressure and salt sensitivity, its effect on the risk of ischemic stroke remains controversial. We hypothesized that polymorphism of the AGT gene could be a risk factor for ischemic stroke. Major clinical risk factors and the AGT gene M235T polymorphism were examined in 147 consecutive stroke patients and 133 healthy age-matched controls. All patients were categorized into four stroke types (single lacuna, multiple lacunae, large-artery atherosclerosis and branch atheromatous disease in brainstem) and two vascular groups (large and perforating arterial lesions). The AGT gene M allele significantly increased the risk of single lacuna, multiple lacunae and small arterial lesions, in male patients (p=0.029, 0.031 and 0.026, respectively). Synergistic effects of the AGT gene polymorphism and clinical risks were not observed. In conclusion, AGT M allele may present a risk of lacunar infarctions in Japanese men, independent of hypertension.     

Self-expandable metallic stent for unresectable malignant strictures in the esophagus and cardia

Objective Self-expandable metallic stent (EMS) placement has been the first choice for dysphagia because of the certainty over its safety, low invasiveness, and immediate efficacy. However, there still remain some problems in relation to the EMS placement site and anticancer therapies before and after EMS placement. Methods: Consecutive 78 patients in whom EMS was placed due to the unresectable malignant stricture in the esophagus or cardia from July 1995 to August 2003 in our department were studied. Results: Gastroesophageal reflux was found in 5 of 8 patients after placement of conventional EMS for the stricture in the gastroesophageal junction. Meanwhile, acid and bile reflux into the esophagus were not detected by pH and bilirubin monitoring, respectively, in 6 patients after placement of the EMS with an anti-reflux mechanism for the stricture in the gastroesophageal junction. The median survival period of all patients after EMS placement was 123 days. The median survival period of 7 patients with radiotherapy only after EMS placement was 138 days and that of 17 patients with radiotherapy before EMS placement was 60 days, which was shorter than that of the former (p<0.05). On the other hand, the median survival period after hospital admission due to dysphagia of these 7 patients was longer than that of 17 patients with radiotherapy only before EMS placement, although, the difference was not significant. Conclusion: EMS with an antireflux mechanism is not commercially available in Japan and approval is urgently required. The indication of radiotherapy associated with EMS placement is to be studied further.     

Hypoxia‐inducible factor 1α may be a marker for vasculitic neuropathy

Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia‐inducible factor 1α (HIF‐1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty‐one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF‐1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF‐1α‐positive nuclei was significant. Two patients with possible vasculitis who showed HIF‐1α‐positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF‐1α‐IR. HIF‐1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions.     

Serum thymidine kinase,a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase

We measured serum thymidine kinase (TK) activity with a radioenzyme assay system employing [I-125]-iododeoxyuridine as the tracer on serial specimens from five bone marrow transplant (BMT) patients before and after transplantation. The serum level of TK activity in the 4 patients with effective BMT treatment ranged from 3.0 to 16.9 U/L (mean, 7.80 U/L) before transplantation and from 27.3 to 236.1 U/L (mean, 82.95 U/L) after the BMT treatment. Mean serum TK activity increased 13.17-fold (range, 1.68 to 29.14-fold). In contrast, the activity in the patient with ineffective BMT treatment was not significantly different during, before, or after BMT treatment. In addition, serum TK activity in BMT patients was well correlated with the change in the number of leukocytes before and after BMT treatment [r = +0.709 (p less than 0.01), y = 0.012 x +0.87]. We conclude that the determination of serum TK activity in BMT patients is very useful in monitoring the course of bone marrow transplantation in the early recovery phase.     

Changes in thrombomodulin level in plasma of endotoxin-infused rabbits.

Changes in the plasma thrombomodulin (TM) level were examined in endotoxin-infused rabbits. The plasma TM level in normal rabbits was 143.8 +/- 8.4 ng/ml (n = 67) and the molecular weight of the major TM was about 55 kd. Endotoxin (lipopolysaccharide, LPS, E. Coli B8:0127) was intravenously infused. LPS infusion increased the plasma TM level dose-dependently between 0.2 mg/kg and 5 mg/kg. When 5 mg/kg LPS was infused, the plasma TM level started to increase immediately and was 2.3 times higher than the control value within 1 hr. The molecular weight of the major TM was about 75 kd. This rapid increase in TM occurred before the decrease in fibrinogen content and the prolongation of prothrombin time. To examine the effect of circulating leukocytes on the TM increase in endotoxin-infused rabbits, 5 mg/kg LPS was infused into rabbits with leukocytopenia induced by X-ray irradiation. The maximum plasma level of TM was significantly lower than in the untreated rabbits given LPS. These data suggest that the increase in plasma TM is caused by LPS-stimulated leukocyte's prior to hemostaseological changes. It is well known that endothelial cells can be injured by stimulated leukocytes, so this increase in plasma TM probably reflects the deterioration of endothelial cells. This deterioration decreases the ability of endothelial cells to inhibit thrombosis, which would, in turn, contribute to the development of disseminated intravascular coagulation in endotoxin-infused rabbits.     

Late massive hemoptysis after transbronchial biopsy of hamartoma: an involvement of pulmonary artery and vein.

Pulmonary hamartoma is a common benign neoplasm that is usually asymptomatic and that arises in the periphery of the lung. However, when the tumor is growing without showing characteristic findings of hamartoma, such as involving calcification, fat density, and chondromatous contents in chest X-rays or computed tomography, the diagnosis is sometimes that problematic and definitive histological diagnosis should be established. We herein report a case with a massive hemoptysis 10 days after a successful transbronchial biopsy. A 69-year-old man who underwent mitral valve plasty 6 years earlier presented a left lung shadow during a routine chest X-ray. The shadow was seen to be growing by a series of chest X-rays. A week after warfarin had been stopped, a bronchoscopic biopsy was performed. No bronchial hemorrhage was observed during the procedure, and warfarin was not restarted. The patient began noticing bloody sputa once or twice a day, and 10 days after the biopsy, 400 mL of hemoptysis was suddenly disgorged. An emergency left upper lobectomy of the lung was performed, and the hemoptysis soon disappeared postoperatively. The patient is well without respiratory symptoms 36 months after the surgery.