Use of technetium-99m tin colloid for sentinel lymph node identification in non-small cell lung cancer

BACKGROUND: To test the reliability of sentinel lymph node identification in non-small cell lung cancer, sentinel nodes were localized with a radioactive colloid in patients undergoing surgery. METHODS: Forty-six patients with non-small cell lung cancer undergoing curative resection with mediastinal lymph node dissection were examined. The day before surgery, technetium-99m ((99m)Tc) tin colloid was injected into the peritumoral region. At operation, the radioactivity of the lymph nodes was counted with a handheld gamma counter before (in vivo) and after (ex vivo) dissection. Lymph nodes with an ex vivo radioactive count more than 10 times the background value were identified as sentinel nodes. The correlation between the in vivo and ex vivo results was examined. RESULTS: Lymphoscintigraphy revealed that it took longer than 6 hours for sufficient (99m)Tc tin colloid to reach the sentinel nodes. Sentinel nodes could be identified in 40 patients (87%). Patients whose sentinel nodes could not be identified had a significantly lower ratio of forced expiratory volume in 1 second to forced vital capacity than did those with identifiable sentinel nodes (P =.03). No false-negative sentinel nodes were detected in 14 patients with N1 or N2 disease (0%). In the hilar lymph node stations, the lobar lymph nodes were most frequently identified as sentinel nodes (as often as 85% of the time). Fourteen patients (35%) had sentinel nodes in the mediastinum, the distribution of which depended on the lobe. In vivo and ex vivo counting showed 88% concurrence for the identification of sentinel nodes in mediastinal lymph node stations. CONCLUSION: The identification of sentinel nodes with (99m)Tc tin colloid is a reliable method of establishing the first site of nodal metastasis in non- small cell lung cancer. Sentinel nodes could be hardly identified in patients with a low ratio of forced expiratory volume in 1 second to forced vital capacity because of such conditions as chronic obstructive pulmonary disease. In vivo identification of sentinel nodes in the mediastinum could be useful approach to guide mediastinal lymph node sampling or dissection.     

Small-volume image-guided radiotherapy using hypofractionated,coplanar, and noncoplanar multiple fields for patients with inoperable Stage I nonsmall cell lung carcinomas

BACKGROUND: Occasionally, medically compromised and/or elderly patients with nonsmall cell lung carcinomas (NSCLCs) cannot be treated surgically. We investigated small-volume hypofractionated image-guided radiotherapy (IGRT) without the need for breath control in patients with inoperable Stage I NSCLCs. METHODS: Between September 1996 and September 1999, 22 patients with Stage I NSCLCs, including 19 males and 3 females, were treated with IGRT. Among these patients, there were 13 Stage IA and 9 Stage IB tumors. The tumors ranged in size from 14.2 to 58.5 mm, with a median size of 26.7 mm. Of the 22 patients, 19 were unfit for surgical treatment due to poor pulmonary function, complications, and/or advanced age and 3 refused surgery. Computed tomographic scans (CT) of the primary tumor were taken during three respiratory phases and they were analyzed to determine the planning target volume, which included only the primary tumor with allowances for respiratory movement. The radiation doses administered at the edge of the moving tumor during normal breathing were 80% of the prescribed dose, either 48 or 60 Gy given in eight fractions over 2 weeks. Clinical evaluation, chest CT scan, and pulmonary function tests were performed before irradiation and at regular intervals for the post-IGRT follow-up. The median follow-up period was 24 months (range, 2-44 months; mean, 21.8 months) (at least 24 months for survivors). RESULTS: Of 17 tumors assessed at the initial follow-up 2-6 months after treatment (5 complete responses, 11 partial responses, and 1 progressive disease), 16 (94%) were controlled locally. One local recurrence was observed during the follow-up. The lung carcinoma-specific survival rate at 1 year was 94% and the 1-year actuarial recurrence-free survival rate was 71%. The lung carcinoma-specific survival rate at 2 years was 73% and the 2-year actuarial recurrence-free survival rate was 67%. The treatment was well tolerated and no major side effects were observed. Localized radiation pneumonitis was observed in all patients who were examined by CT scan, but the patients were asymptomatic. Parameters of pulmonary function, including vital capacity, total lung capacity, and diffusion capacity for carbon monoxide, decreased very little or not at all, indicating that IGRT rarely deteriorated pulmonary functions. CONCLUSIONS: Small-volume hypofractionated IGRT without breath control is a feasible and beneficial method for the curative treatment of patients with Stage I NSCLCs. It has the potential of a high local tumor control rate and low morbidity.     

Expression and alteration of ras and p53 proteins in patients with lung carcinoma accompanied by idiopathic pulmonary fibrosis

BACKGROUND: The ras oncogene and the p53 tumor suppressor gene play important roles in the carcinogenic process of lung carcinoma. The authors evaluated whether alterations of the ras and p53 proteins may contribute to the development of lung carcinoma in patients with idiopathic pulmonary fibrosis (IPF) and whether such alterations may explain the high incidence of lung carcinoma among patients with IPF. METHODS: Lung tissues were obtained from 35 patients who had IPF without complications of lung carcinoma and from 36 patients who had IPF with complications of lung carcinoma. Altered expression of ras and p53 proteins was evaluated by immunohistochemistry, and mutations of both genes were evaluated by polymerase chain reaction-single strand conformation polymorphism and sequencing analyses. RESULTS: The frequency of expression of ras protein in type II alveolar pneumocytes was significantly greater in lung tissues from patients with IPF who had lung carcinoma compared with lung tissues from patients with IPF who did not have lung carcinoma (75% vs. 40%, respectively; P < 0.01). K-ras point mutation in codon 12 (GGT to GTT transversion) was detected in lung tissue with interstitial pneumonia, in which ras protein was overexpressed in type II alveolar pneumocytes obtained from 2 of 41 patients with IPF complicated by lung carcinoma, causing amino acid substitution (Gly to Val) in both patients. A p53 mutation was detected in three of six lung tissue samples from patients who had IPF lung with positive p53 immunoreactivity, and multiple mutations were detected in two samples. CONCLUSIONS: Expression of ras protein in type II alveolar pneumocytes and mutation in the codon 12 of K-ras gene in lung tissue may contribute to the induction of lung carcinoma in patients with IPF. Furthermore, the presence of multiple mutations in the p53 gene may explain the high incidence lung carcinoma in patients with IPF.     

Increased expression of beta-catenin predicts better prognosis in nonsmall cell lung carcinomas

BACKGROUND: beta-Catenin has been shown to function as a Wnt signaling molecule to stimulate cyclin D1 expression and cell growth in several kinds of tumors. METHODS: The authors immunohistochemically examined specimens of 217 surgically resected primary nonsmall cell lung carcinomas (NSCLCs) for beta-catenin expression and classified them semiquantitatively into three categories, including those with high, moderate, and low scores of expression. RESULTS: High, moderate, and low scores of expression were found in 37 (17.1%), 145 (66.8%), and 35 (16.1%) tumors, respectively. beta-Catenin expression was not correlated with cyclin D1 expression, but was positively correlated with the Ki-67 cell growth fraction (P = 0.04). The direct sequencing analysis for the beta-catenin gene mutation of 13 specimens of 217 tumors for the current study revealed no mutations. The relation between survival and beta-catenin expression was evaluated in 148 potentially curatively resected tumors with pathologic Stages I-IIIA. A trend toward better survival was found in patients with tumors having higher scores. In multivariate analysis, high beta-catenin expression was a significant and independent favorable prognostic factor (hazards ratio, 0.31; P = 0.007) as was pathologic stage. Analyzed by cell type, in nonsquamous cell carcinomas, patients with tumors having high scores survived a significantly longer time than those with tumors having moderate or low scores (5-year survival rates, 84%, 55%, and 32%, respectively; P = 0.02), and high beta-catenin expression tended to be a favorable prognostic factor (hazards ratio, 0.32; P = 0.052). CONCLUSIONS: These results indicate that, in NSCLCs, increased expression of beta-catenin can predict favorable prognosis of patients with resected tumors, suggesting that accumulation of beta-catenin has no or little oncogenic effect via activation of the Wnt pathway, unlike in colon carcinomas or hepatomas.     

Effectiveness of continuous hyperthermic peritoneal perfusion for the peritoneal dissemination of gastric cancer

We investigated the effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for the peritoneal dissemination of gastric cancer. A total 124 patients with advanced gastric cancer were enrolled in this study. Prophylactic CHPP (P-CHPP) was performed in 45 patients who had macroscopic serosal invasion without peritoneal dissemination, and 79 patients without CHPP were a control group. Therapeutic CHPP (T-CHPP) was performed in 21 patients with peritoneal dissemination, and 52 patients without CHPP were a control group. There was no significant difference in 5 year survival between patients treated and not treated with P-CHPP. Univariate analysis showed that location of tumor, tumor diameter, and lymph node metastasis influenced prognosis, but there was no prognostic factor in the Cox proportional regression hazard model. There was no significant difference in 5-year survival between patients treated and not treated with T-CHPP. Univariate analysis showed that degree of peritoneal dissemination and adjuvant chemotherapy influenced prognosis, and the Cox proportional regression hazard model showed that the macroscopic types and degree of peritoneal dissemination affected prognosis. In the patients with CHPP, the incidences of respiratory failure and renal failure were each statistically greater than in the patients undergoing CHPP.     

Experience of Aozora Medical Clinic in EMInet

We present here the EMInet (Electronic Medical Information network), a closed information network established by the City government and the Medical Association in Matsudo City, Chiba, Japan. In this network, medical information is shared by multiple certified medical facilities under the informed consent of the patients. The medical record is written only by the physician in charge of the patient and reserved in the server computer. The medical record cannot be rewritten or modified by anyone except the physician in charge of the patient. Other medical professionals can only have access to the record. In the emergency room of certified hospitals, a physician can open the patient's record by using the IC card carried by the patient.     

Oxidative ability and toxicity of n-hexane insoluble fraction of diesel exhaust particles.

Diesel exhaust particles (DEP) are known to induce adverse biological responses such as inflammation of the airway. However, the relationship between the chemical characteristics of organic compounds adsorbed on DEP and their biological effects is not yet fully understood. In this study, the dichloromethane-soluble fraction (DMSF) from DEP was fractionated into its n-hexane-soluble fraction (n-HSF) and n-hexane-insoluble fraction (n-HISF). Using these DEP fractions, we designed the present studies to elucidate (1) chemical characteristics, (2) biological characteristics, and (3) the relationship between the chemical and the biological characteristics of these DEP fractions. Dithiothreitol (DTT) assay, Fourier transform-infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H-NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS) were used to characterize their chemical properties. Heme oxygenase-1 (HO-1) protein expression, viability of rat alveolar type II epithelial cell line (SV40T2), and inflammatory cell infiltration into the peritoneal cavity of BALB/c mice were evaluated as markers of oxidative stress, cytotoxicity, and inflammatory response, respectively. The oxidative ability of the DEP fractions was n-HISF > DMSF > n-HSF. IR, 1H-NMR, and GC-MS spectra showed that n-HISF was mainly composed of compounds having many functional groups related to oxygenation, such as hydroxyl and carbonyl groups. The relative strength of HO-1 protein expression, cytotoxicity, and inflammatory responses was also n-HISF > DMSF > n-HSF. All of the n-HISF-induced biological activities were decreased by reduction with N-acetyl-L-cysteine (NAC). These results suggest that n-HISF has high oxidative ability and many functional groups related to oxygenation and that this ability strongly contributes to the induction of oxidative stress, cytotoxicity, and inflammatory response.     

Polyurethane-covered wallstents to recanalize wallstents obstructed by tumor ingrowth from malignant common bile duct obstruction

Four patients with malignant obstruction of the common bile duct had been treated with uncovered Wallstents and suffered from a reobstruction after 2-13 months (mean 5.3 months). Repeat cholangiography revealed severe stenosis of the stent lumen caused by tumor ingrowth through the mesh. A Wallstent with a self-made polyurethane-cover was inserted through the uncovered stent in these patients. The four patients were followed for 3-13 months (mean 6.3 months) until death. There was good drainage with no evidence of recurrent obstruction in all patients. We conclude that a covered Wallstent may extend patency of stented bile ducts, preventing tumor ingrowth in patients with neoplastic obstruction. Further observations are needed.     

Significance of transforming growth factor β1 as a new tumor marker for colorectal cancer

Transforming growth factor β1 (TGF‐β1) is thought to be involved in cancer growth and progression. TGF‐β1 changes to its active form after being secreted in its latent form. Our aim was to clarify the significance of plasma concentrations of active and total TGF‐β1 of patients with colorectal cancer. Plasma concentrations of active and total TGF‐β1 in 45 patients with colorectal cancer and 23 healthy volunteers were measured using ELISA and the activation rate (ratio of active to total TGF‐β1) was determined. Plasma concentrations of active TGF‐β1 (21.9 ± 12.8 pg/ml) were significantly higher in patients with colorectal cancer than in healthy volunteers (9.9 ± 5.9 pg/ml; p < 0.001, Welch's t‐test). Concentration of total TGF‐β1 was also significantly higher for patients with colorectal cancer (18.0 ± 13.0 ng/ml vs. 11.1 ± 6.4 ng/ml; p < 0.01, Welch's t‐test). However, there was no significant difference in the TGF‐β1 activation rate between the 2 groups. There was a correlation between Dukes' stage and plasma concentration of active or total TGF‐β1 (p < 0.01, Spearman's rank correlation test) and on day 7 the active TGF‐β1 levels for patients recovering from curative resection were similar to those of the control group of healthy volunteers. These results suggest that active TGF‐β1 might be used as a tumor marker for colorectal cancer. © 2001 Wiley‐Liss, Inc.     

Molecular Analysis of edicinally-Used Chinese and Japanese Curcuma Based on 18S rRNA Gene and trnK Gene Sequences

ＧｅｎｕｓＣｕｒｃｕｍａｏｆｔｈｅｆａｍｉｌｙＺｉｎｇｉｂｅｒａｃｅａｅｃｏｎｓｉｓｔｓｏｆａｂｏｕｔ 70ｓｐｅｃｉｅｓｉｎｔｈｅｗｏｒｌｄ ,ｏｆｗｈｉｃｈｍｏｒｅｔｈａｎｔｅｎａｒｅｄｉｓｔｒｉｂｕｔｅｄｏｒｃｕｌｔｉｖａｔｅｄｉｎＣｈｉｎａ[1] ａｎｄＪａｐａｎ[2 ] .ＳｅｖｅｒａｌｈｅｒｂａｌｄｒｕｇｓｕｓｅｄｆｒｅｑｕｅｎｔｌｙａｒｅｄｅｒｉｖｅｄｆｒｏｍｔｈｅＣｕｒｃｕｍａｓｐｅｃｉｅｓ.ＩｎＣｈｉｎａ ,“Ｊｉａｎｇｈｕａｎｇ”ｆｒｏｍｔｈｅｒｈｉ ｚｏｍｅｏｆＣｕｒｃｕｍａｌｏｎｇａ ,“Ｐｉａｎｊｉａｎｇｈｕａｎｇ”ｆｒｏｍｔｈｅｓｌｉｃｅｄｒｈｉｚｏｍｅｏｆＣ .ｗｅｎｙｕｊｉｎ ,“Ｅｚｈｕ”ｆｒｏｍｔｈｅｒｈｉｚｏｍｅｓｏｆＣ .ｐｈａｅｏｃａｕｌｉｓ,Ｃ .ｗｅｎｙｕｊｉｎｏｒＣ .ｋｗａｎｇｓｉｅｎｓｉｓ,ａｎｄ“Ｙｕｊｉｎ”ｆｒｏｍｔｈｅｔｕｂｅｒｓｏｆＣ .ｗｅｎｙｕｊｉｎ ,Ｃ .ｌｏｎｇａ ,Ｃ .ｋｗａｎｇｓｉｅｎｓｉｓｏｒＣ .ｐｈａｅｏｃａｕｌｉｓａｒｅｉｎｕｓｅ .[3] ＩｎＪａｐａｎ ,“Ｇａｊｕｔｓｕ”ｆｒｏｍｔｈｅｒｈｉｚｏｍｅｏｆＣ .ｚｅｄｏａｒ...