Border between N1 and N2 stations in lung carcinoma: lessons from lymph node metastatic patterns of lower lobe tumors

OBJECTIVE: Distinction of lymph node stations is one of the most crucial topics still not entirely resolved by many lung cancer surgeons. The nodes around the junction of the hilum and mediastinum are key points at issue. We examined the spread pattern of lymph node metastases, investigated the prognosis according to the level of the involved nodes, and conclusively analyzed the border between N1 and N2 stations. METHODS: We reviewed the records of 604 consecutive patients who underwent complete resection for non-small cell lung carcinoma of the lower lobe. RESULTS: There were 390 patients (64.6%) with N0 disease, 127 (21.0%) with N1, and 87 (14.4%) with N2. Whereas 11.3% of patients with right N2 disease had skip metastases limited to the subcarinal nodes, 32.6% of patients with left N2 disease had skip metastases, of which 64.2% had involvement of N2 station nodes, except the subcarinal ones. The overall 5-year survivals of patients with N0, N1, and N2 disease were 71.0%, 50.8%, and 16.7%, respectively (N0 vs N1 P = .0001, N1 vs N2, P < .0001). Although there were no significant differences in survival according to the side of the tumor among patients with N0 or N1 disease, patients with a left N2 tumor had a worse prognosis than those with a right N2 tumor (P = .0387). The overall 5-year survivals of patients with N0, intralobar N1, hilar N1, lower mediastinal N2, and upper mediastinal N2 disease were 71.0%, 60.1%, 38.8%, 24.8%, and 0%, respectively. Significant differences were observed between intralobar N1 and hilar N1 disease ( P = .0489), hilar N1 and lower mediastinal N2 disease (P = .0158), and lower and upper mediastinal N2 disease (P = .0446). Also, the 5-year survivals of patients with involvement up to station 11, up to station 10, and up to station 7 were 41.4%, 37.9% and 37.7%, respectively (difference not significant). CONCLUSIONS: N1 and N2 diseases appeared as a combination of subgroups: intralobar N1 disease, hilar N1 disease, lower mediastinal N2 disease, and upper mediastinal N2 disease. Interestingly, the survivals of patients with involvement up to interlobar nodes (station 11), main bronchus nodes (station 10), and subcarinal nodes (station 7) were identical. These data constitute the basis for a larger investigation to develop a lymph node map in lung cancer.     

Nasal resistance for determinant factor of nasal surgery in CPAP failure patients with obstructive sleep apnea syndrome

OBJECTIVES: Given that criteria for nasal surgery in individuals with obstructive sleep apnea syndrome (OSAS) have not been proposed, we investigated the effectiveness of nasal surgery for CPAP failure in patients with both severe OSAS and nasal obstruction. PATIENTS AND METHODS: Conventional nasal surgery was performed in 12 patients who were refractory to treatment by CPAP. The subject group consisted of 12 males (mean age, 54.2 +/- 9.2 years; range 39-66 years). The effect of nasal surgery was evaluated with data from preoperative and postoperative polysomunography. The nasal resistance value was first deduced to determine which OSAS patients with CPAP failure should undergo nasal surgery, compared to control values. RESULTS: Nasal surgery resulted in a significant decrease in nasal resistance, as measured by rhinomanometry, from 0.57 +/- 0.31 Pa/cm3 /sec to 0.16 +/- 0.03 Pa/cm3/sec and rendered all patients tolerant to CPAP. In addition, the lowest nocturnal oxygen saturation significantly increased from 68.3 +/- 12.1% to 75.3 +/- 7.1% after surgery. Subjectively, Epworth sleepiness scale (ESS) significantly decreased from 11.7 +/- 4.1 to 3.3 +/- 1.3 after surgery, but the number of apnea and hypopnea episodes per hour did not change significantly. In five patients, for whom it was possible to perform a CPAP titration before nasal surgery, the value decreased significantly from 16.8 +/- 1.1 to 12.0 +/- 1.9 cmH2O. The bilateral nasal resistance of the 410SAS patients with CPAP therapy (control group) was 0.24 +/- 0.11 Pa/cm3/sec. The cut off value for differentiation between CPAP failure patients and control group was determined as 0.38 Pa/cm3 /sec. CONCLUSION: Increased nasal resistance is a determinant of CPAP failure, and the surgical correction of severe nasal obstruction should thus be considered to facilitate treatment of OSAS patients with CPAP.     

Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines

AIM: To ascertain whether vitreous and plasma levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and fundus findings could predict the outcome of vitreous surgery in patients with proliferative diabetic retinopathy (PDR). METHODS: Vitreous fluid samples were obtained during vitreoretinal surgery from 73 consecutive eyes with PDR. The levels of VEGF and IL-6 in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay. Patients were prospectively followed for 6 months and the postoperative outcome was analysed by logistic regression analysis. RESULTS: No improvement and/or progression of PDR occurred in 23 (32%) of the 73 eyes (progression group). The vitreous levels of VEGF and IL-6 were significantly higher in eyes from the progression group than in eyes with regression of PDR (regression group) (P=0.0032 and 0.0088, respectively). Multivariate logistic regression analysis showed that higher vitreous levels of VEGF were associated with the progression of PDR after vitreous surgery (odds ratio 2.72, P=0.0003). CONCLUSIONS: High vitreous levels of VEGF identified as a significant risk factor for the outcome of vitreous surgery in patients with PDR. A model was developed to predict the probability of PDR progression and measurement of the vitreous level of VEGF may be useful for predicting the outcome of surgery.     

Ciliochoroidal Effusion Syndrome Associated with Posterior Scleritis

Background

To determine the cause of angle-closure glaucoma in a case of posterior scleritis.

Case

The patient was a 65-year-old woman with unilateral acute angle-closure glaucoma who did not respond to laser iridotomy.

Observations

Slit-lamp examination demonstrated a shallow anterior chamber in the left eye. Intraocular pressure was 22?mmHg even after application of two antiglaucoma eye-drop preparations. B-scan ultrasonography demonstrated scleral thickening and choroidal detachment in the left eye. Ultrasound biomicroscopy showed a shallow anterior chamber with angle closure, annular ciliochoroidal effusion with ciliary body edema, and an anterior rotation of the ciliary body. After instillation of cycloplegics, the ciliary body and ciliary processes rotated posteriorly, resulting in the release of the pressure on the iris. These changes led to the opening of the angle and subsequent normalization of intraocular pressure. A diagnosis was made of ciliochoroidal effusion syndrome associated with posterior scleritis.

Conclusions

Patients with posterior scleritis can develop ciliochoroidal effusion syndrome, which can lead to angle-closure glaucoma. The therapeutic strategy for acute angle-closure glaucoma induced by ciliochoroidal effusion syndrome differs completely from that for acute angle-closure glaucoma with pupillary block. In the case of ciliochoroidal effusion syndrome, it is important to relieve the compression of the angle by the iris by displacing the lens–iris diaphragm posteriorly by cycloplegics.?Jpn J Ophthalmol 2007;51:49–52 © Japanese Ophthalmological Society 2007

     

Adenomatous goiter with hyperthyroidism

Adenomatous goiter with hyperthyroidism is a rare disease entity in Japan. Over a five-year period, we operated on 20 patients with this disease. Pre-operatively, basal thyrotropin was not necessarily suppressed and the thyrotropin-binding inhibiting immunoglobulin activity, which had been recently measured in five patients, showed normal values. Uneven patches of cold areas were noted on¹³¹I thyroidal scintigrams. Thyroid function tests carried out three years after surgery in one lobectomy case and in eleven subtotal thyroidectomy cases revealed hypothyroidism in seven, hyperthyroidism in two and euthyroidism in only three cases. These results suggest that the pathogenesis and clinical features of adenomatous goiter with hyperthyroidism are quite different from those of Graves’ disease, and that routinely performing near-total thyroidectomy may be considered as the treatment of choice.     

Effects of diisopropylamine dichloroacetate on proliferation and differentiation of normal human keratinocytes in vitro.

We found that diisopropylamine dichloroacetate (DADA), known as a vasodilator, enhanced growth of keratinocytes in 4 days culture at 1-30 microg/ml, and such promoting effects of cell proliferation were reconfirmed by measuring DNA synthesis using [(3)H]thymidine incorporation. On the other hand, this substance enhanced synthesis of keratin K1, a potent marker of differentiation in keratinocytes, at 1-100 microg/ml in low calcium (0.1 mM) or high calcium medium (1. 25 mM). Moreover, the formation of cornified envelope, another potent marker of differentiation in keratinocytes, was also promoted by DADA at a concentration of 0.1-10 mM which includes valid concentration of DADA for the enhancement of keratin K1 formation (1-100 microg/ml: 0.05-0.5 mM DADA). These results indicate that DADA has a double function, enhancement of both proliferation and differentiation of cells, which could be linked to the turnover of skin epidermis. Furthermore, in order to analyze the effect of DADA on keratinocytes, we examined the effects of each component of this substance, diisopropylamine (DIA) and dichloroacetate (DCA), on keratinocytes. As the result of these investigations, evidence was found that DCA was effective on enhancement of cell growth, but DIA was ineffective. Moreover, we found that DCA was effective on keratinocyte differentiation by evaluating the enhancement of a differentiation marker, formation of cornified envelopes, within 10 mM, while DIA was not effective. Therefore, we concluded that only DCA was an active component of the DADA molecule for the proliferation and the differentiation of keratinocytes in vitro.     

Elevation of serum thrombopoietin precedes thrombocytosis in acute infections

To clarify the mechanisms underlying thrombocytosis secondary to infections, we longitudinally studied serum levels of thrombopoietin (TPO) and interleukin (IL)-6 in 15 infants and young children with prominent thrombocytosis (platelets >700 x 10(9)/l) following acute infections and 116 age-matched controls using an enzyme-linked immunosorbent assay. The subjects included nine patients with bacterial infections, three with viral infections and three with non-determined pathogens. TPO values in the controls were 2.24 +/- 0.87 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85-4.47 fmol/ml. In the first week of infection, platelet counts were normal, but TPO values increased (approximately 10.73 fmol/ml). TPO levels peaked on day 4 +/- 2 at 6.44 +/- 2.37 fmol/ml and then fell gradually. When platelet counts peaked in the second and third weeks, TPO levels were similar to the controls. IL-6 levels in the first week rose and dropped more rapidly than TPO. Serum TPO values were significantly correlated with C-reactive protein levels (r = 0.688, P < 0.001) and IL-6 levels (r = 0.481, P = 0.027). These results suggest that TPO contributes to thrombocytosis following infections in conjunction with IL-6, arguing for additional regulatory mechanisms of blood TPO levels.     

Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann–Pick C1-deficient cells

We investigated intracellular trafficking of GM1 ganglioside in Niemann-Pick C1 (NPC1)-deficient Chinese hamster ovary cells [NPC1(-) cells] by using cholera toxin (CT) as a probe. Both the holotoxin and the B subunit (CTB) accumulated in GM1-enriched intracellular vesicles of NPC1(-) cells. CTB-labeled vesicles contained the early endosome marker Rab5 but not lysosome-associated membrane protein 2 and were not labeled with either Texas red-transferrin or Lysotracker, indicating that they represent early endosomes. Similarly, CT accumulated in intracellular vesicles of human NPC fibroblasts that contained both Rab5 and early endosomal antigen 1. CTB accumulation in NPC1(-) cells was abolished by expression of wild-type NPC1 but not by mutant proteins with a mutation either in the NPC domain or the sterol-sensing domain. A part of these mutant NPC1 proteins expressed in NPC1(-) cells was localized on CTB-labeled vesicles. U18666A treatment of "knock in" cells [NPC1(-) cells that stably expressed wild-type NPC1] caused CTB accumulation similar to that in NPC1(-) cells, and a part of wild-type NPC1was localized on CTB-labeled vesicles in drug-treated cells. Finally, CT tracer experiments in NPC1(-) cells revealed retarded excretion of internalized toxin into the culture medium and an increase in the intracellular release of A subunits. In accordance with the latter result, CT was more effective in stimulating cAMP formation in NPC1(-) than in wild-type cells. These results suggest that transport of CT/GM1 complexes from the early endosome to the plasma membrane depends on the function of NPC1, whereas transport to the Golgi apparatus/endoplasmic reticulum does not.     

Vascularity of advanced gastric carcinoma: evaluation by using power Doppler imaging

BACKGROUND: We investigated the vascularity of advanced gastric adenocarcinomas by using percutaneous power Doppler imaging. METHODS: Seventeen patients with gastric cancer and 10 without a gastric tumor, but with a slightly thick gastric wall in the B-mode ultrasound, were investigated with the use of power Doppler imaging. The color signals of the gastric lesion were graded as follows: 1, no color signals or the same as the surroundings; 2, color signals were slightly increasing; and 3, color signals were obviously increasing. RESULTS: The color signals of three patients were graded 1, those of eight patients were graded 2 and those of six patients were graded 3 in the gastric cancer group. The color signals of all 10 patients without a gastric tumor were grade 1. This difference was statistically significant (P = 0.0002). CONCLUSIONS: Power Doppler imaging showed vascularity of gastric cancer increasing in the majority of patients (14 of 17: 82%). Thus, power Doppler imaging might be a good screening examination method for gastric cancer.