False positive accumulation in 18F fluorodeoxyglucose positron emission tomography scan due to sarcoid reaction following induction chemotherapy for lung cancer.

We present a case of lung cancer that showed false positive accumulation in an 18F fluorodeoxyglucose positron emission tomography (FDG-PET) scan following induction chemotherapy for suspected metastasis and progression of malignancy. A 66-year-old man was diagnosed with squamous cell carcinoma in the lung, classified as clinical stage IIIA (T2N2M0), and underwent induction chemotherapy. An FDG-PET scan prior to chemotherapy demonstrated accumulation only in the tumor, whereas following treatment it revealed a strong accumulation not only in the tumor, but also in the supraclavicular lymph nodes, which indicated lymph node metastasis. The patient underwent a biopsy of the right supraclavicular lymph node and mediastinoscopy, after which all dissected lymph nodes showed sarcoid reactions and no tumor cells were found pathologically. We concluded that when evaluating the effect of induction chemotherapy for malignancy, a sarcoid reaction might lead to the false positive accumulation of FDG.

Long-term graft patency after replacement of the brachiocephalic veins combined with resection of mediastinal tumors.

OBJECTIVE: We sought to investigate the correlation between type of vascular reconstruction and long-term graft patency after replacement of brachiocephalic veins combined with resection of mediastinal malignancies. METHODS: Eighteen patients underwent surgical resection of tumors and the superior vena cava with concomitant vascular reconstruction using ringed polytetrafluoroethylene grafts. Graft patency was verified by means of venography or contrast-enhanced computed tomography at time points ranging from 3 to 77 months (median, 33 months) postoperatively. RESULTS: Seven patients underwent sole reconstruction of the right brachiocephalic vein, with occlusion observed in only 1 patient. In 6 patients who underwent reconstruction of the bilateral brachiocephalic veins with 2 separate grafts, the grafts remained patent in 2, whereas 4 patients experienced occlusion of one of the two grafts yet remained asymptomatic. Both patients who underwent reconstruction with a Y graft experienced left brachiocephalic vein graft occlusion. In the 3 patients who underwent reconstruction of a left brachiocephalic vein, the graft became occluded, and superior vena cava syndrome developed in 2 of these patients. CONCLUSION: When replacing the superior vena cava, reconstruction of a left brachiocephalic vein alone results in a significant rate of occlusion and development of superior vena cava syndrome. Thus we advocate sole right brachiocephalic vein reconstruction or bilateral brachiocephalic vein reconstruction in this setting, and separate reconstruction of the veins is preferable to use of a Y graft.

Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in tumor tissues and the efficacy of 5-fluorouracil in patients with non-small-cell lung cancer.

We examined 116 stage I-IIIA non-small-cell lung cancer (NSCLC) patients for intra-tumoral expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) using TaqMan reverse transcription polymerase chain reaction (RT-PCR) assay to clarify the correlation between gene expression and the efficacy of 5-fluorouracil (5-FU) in patients with NSCLC. Patients who were administered 5-FU alone after surgery comprised the 5-FU group (n = 30), and those who underwent only surgery comprised the control group (n = 86). When dichotomized at the mean TS and DPD mRNA level, patients with low-DPD tumors who were administered 5-FU had a significantly better prognosis than those who did not receive adjuvant treatment (p = 0.041). In addition, in the 5-FU group, 10 patients with both low-TS and low-DPD tumors have not had any relapse, whereas 8 of the 20 patients with either high-TS or high-DPD tumors developed distant metastasis after surgery. Based on these results, the quantitation of TS and DPD mRNA levels may predict the efficacy of 5-FU after surgery for patient with NSCLC.

Benefits of home parenteral nutrition before lung transplantation: report of a case.

A 54-year-old woman, who was severely malnourished and awaiting lung transplantation for chronic respiratory failure, was given nutritional support by home parenteral nutrition (HPN). The patient's emaciated state was further compromised by the fact that she had undergone a distal gastrectomy 4 years earlier. We decided that HPN was indicated because her oral intake was so poor and drinking enteral formula reduced her appetite. After 1 year of HPN, her body weight increased and her nutritional, anthropometric, and biochemical values were well maintained by the time of transplantation. Moreover, her progress after lung transplantation was remarkably good, indicating the effectiveness of nutritional support by HPN during the protracted waiting period.

Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis.

The "a disintegrin and metalloprotease" (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9, -10, -12, -15, and -17 in sublines of an EBC-1 lung cancer cell line that were highly metastatic to either brain or bone. ADAM9 mRNA levels were significantly higher in highly brain-metastatic sublines than in the parent or highly bone-metastatic sublines. To elucidate the role of ADAM9 in brain metastasis, we stably transfected A549 and EBC-1 cells with a full-length ADAM9 expression vector. Compared with mock-transfectants, ADAM9 overexpression resulted in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha 3 and beta 1 subunits. Administration of the anti-beta 1 monoclonal antibody attenuated this increase in invasive and adhesive activity. Intravenous administration of ADAM9-overexpressing A549 cells to mice resulted in micrometastatic foci in the brain and multiple metastatic colonies in the lungs. In contrast, administration of parent and mock-transfected A549 cells to mice resulted in lung tumors without brain metastasis. These results suggest that ADAM9 overexpression enhances cell adhesion and invasion of non-small cell lung cancer cells via modulation of other adhesion molecules and changes in sensitivity to growth factors, thereby promoting metastatic capacity to the brain.

New prognostic indicator for non-small-cell lung cancer, quantitation of thymidylate synthase by real-time reverse transcription polymerase chain reaction.

Thymidylate synthase (TS) is an enzyme that catalyzes an important DNA biosynthesis process. The gene expression of TS has not been reported in non-small-cell lung cancer (NSCLC) patients. To clarify the correlation between TS mRNA levels and clinicopathological features of NSCLC, we examined 70 Stage I and II NSCLC patients for intra-tumoral expression of TS using TaqMan reverse transcription polymerase chain reaction (RT-PCR) assay and immunohistochemistry methods. We also investigated the TS promoter 28 bp polymorphism in 48 cancer tissues using PCR amplification of genomic DNA. Lung cancer tissue showed higher TS mRNA levels than normal lung tissue (Mann-Whitney U-tests; p = 0.0020). Further, TS mRNA expression was correlated with immunohistochemical TS expression (p = 0.029). We obtained 2 different DNA fragments, which indicated triple-repeat (3R) and double-repeat (2R) type alleles. Cancer tissues with the 3R/3R genotype showed significantly higher TS mRNA levels as compared to those with other genotypes (p = 0.0019). The TS genotype was also correlated with immunohistochemical TS expression (chi(2) test; p = 0.0079). The disease-free survival of the low TS mRNA level group was significantly better than those with high TS mRNA levels (log-rank test; p = 0.010), however, there were no significant differences found by immunohistochemical evaluation (p = 0.34) or TS genotype analysis (p = 0.11). A multivariate analysis revealed that high TS mRNA levels independently contributed to disease-free survival. The quantitation of TS mRNA levels is clinically more sensitive and useful for determining the prognosis of Stage I and II NSCLC patients than an immunohistochemical evaluation.

Prognostic significance of p27KIP1 expression in resected non-small cell lung cancers: analysis in combination with expressions of p16INK4A, pRB, and p53.

BACKGROUND AND OBJECTIVES: Whether a prognostic role for expression of the tumor suppressor gene (TSG) products exists in resected non-small call lung cancers (NSCLCs) remains controversial. Our study was performed to determine the value of TSGs expressions for patients survival in NSCLCs. METHODS: We examined 108 resected NSCLCs for the expression of TSG products, p27(KIP1), p16(INK4A), pRB, and p53 that govern cell cycle transition by immunohistochemistry and compared them with patient clinical characteristics and prognoses. RESULTS: Abnormal expressions of p27(KIP1), p16(INK4A), pRB, and p53 were found in 61 (57%), 53 (49%), 42 (39%), and 48 (44%), respectively, of the 108 NSCLCs. Univariate analysis showed abnormal expression of p27(KIP1) to be a strong indicator for poor patient survival, not only in the total cohort (P = 0.0024), but also in subgroups with T1-T2 (P = 0.016), N0 (P = 0.047), and squamous cell carcinomas (P = 0.026), but not according to the expression of p16(INK4A), pRB, or p53. In the Cox regression analysis, p27(KIP1) expression was found to be an independent prognostic factor (P = 0.0148) and associated with pathological stage (P = 0.0278). CONCLUSIONS: Our results suggest that abnormal p27(KIP1) expression may be a useful indicator to predict postoperative prognosis, especially in patients with early stage NSCLCs, as compared to other TSG products examined.

Appearance of thymoma 15 years after extended thymectomy for myasthenia gravis without thymoma.

Several cases of thymoma recurrence after resection have been reported. However, thymoma appearance following an extended thymectomy for non-thymomatous myasthenia gravis is very rare. We report a case of thymoma in a 48-year-old woman, 15 years after an extended thymectomy for non-thymomatous myasthenia gravis. The importance of a complete dissection of mediastinal adipose tissue during the extended thymectomy as well as careful follow-up for such patients is also noted.

Overexpression of the Wilms' tumor gene WT1 in de novo lung cancers.

Expression of the Wilms' tumor gene WT1 in de novo lung cancer was examined using quantitative real-time RT-PCR and immunohistochemistry. Overexpression of the WT1 gene was detected by RT-PCR in 54/56 (96%) de novo non-small cell lung cancers examined and confirmed by detection of WT1 protein with an anti-WT1 antibody. Overexpression of the WT1 gene was also demonstrated in 5/6 (83%) de novo small cell lung cancers by immunohistochemistry. Furthermore, when the WT1 gene was examined for mutations by direct sequencing of genomic DNA in 7 lung cancers, no mutations were found. These results suggest that the nonmutated, wild-type WT1 gene plays an important role in tumorigenesis of de novo lung cancers and may provide us with the rationale for new therapeutic strategies for lung cancer targeting the WT1 gene and its products.

Bilateral cervicomediastinal neurofibroma originating from the vagal nerve in a patient with von Recklinghausen's disease: report of a case.

A 19-year-old woman with von Recklinghausen's disease was admitted with symptoms of hoarseness. A computed tomography scan showed a bilateral cervicomediastinal tumor. An extirpation of the left cervicomediastinal tumor was performed for the purpose of diagnosis and treatment. On thoracotomy, the tumor, which measured 9 x 8 x 4 cm in size, arose from the intrathoracic vagal nerve and the left tumor was resected with a segment of the vagal nerve and recurrent nerve. The pathological diagnosis of the tumor was a neurofibroma. The tumor on the right side was left untreated due to concerns about possibly causing palsy of the bilateral recurrent nerve and also because of the asymptomatic state of the right tumor. Mediastinal neurofibroma in a patient with von Recklinghausen's disease often arises from the intrathoracic vagal nerve. To our knowledge, this is the first report of bilateral cervicomediastinal neurofibroma originating from the vagal nerves.