Development and external validation of the DOAT and DOATS scores: simple decision support tools to identify disease progression among nonelderly patients with mild/moderate COVID-19.

BACKGROUND: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration. METHODS: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission. RESULTS: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort. CONCLUSIONS: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old.

Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic.

It is unclear whether molnupiravir has a beneficial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the efficacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan. We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 230) and non-users (n = 690) after 1:3 propensity score matching. Additionally, we performed forward stepwise multivariate logistic regression analysis to evaluate the association between clinical deterioration after admission and molnupiravir treatment in the 1:3 propensity score-matched subjects. The characteristics of participants in both groups were balanced as indicated by covariates with a standardized mean difference of < 0.1. Regarding comorbidities, there was no imbalance between the two groups, except for the presence of hypertension, dyslipidemia, diabetes mellitus, and cardiac disease. The clinical deterioration rate was significantly lower in the molnupiravir users compared to the non-users (3.90% vs 8.40%; P = 0.034). Multivariate logistic regression analysis demonstrated that receiving molnupiravir was a factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.206-0.973; P = 0.042), independent of other covariates. This real-world study demonstrates that molnupiravir contributes to the prevention of deterioration in COVID-19 patients after hospitalization during the Omicron variant phase.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic.

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

Delta-like 1 homolog (DLK1) as a possible therapeutic target and its application to radioimmunotherapy using 125I-labelled anti-DLK1 antibody in lung cancer models (HOT1801 and FIGHT004).

OBJECTIVES: Delta-like 1 homolog (DLK1) is a non-canonical Notch ligand known to be expressed in several cancers but whose role in lung cancer is not yet fully understood. We sought to confirm DLK1 expression in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), and to examine DLK1's clinical significance. Furthermore, we examined the possible utility of DLK1 as a novel target in radioimmunotherapy (RIT). METHODS: We retrospectively assessed the correlation between clinical features and DLK1 expression by immunohistochemistry in resected specimens from 112 patients with SCLC and 101 patients with NSCLC. Moreover, we performed cell and animal experiments, and examined the possibility of RIT targeting DLK1 in SCLC using iodine-125 (125I) -labeled anti-DLK1 antibody, knowing that 125I can be replaced with the alpha-particle-emitter astatine-211 (211At). RESULTS: In SCLC and NSCLC, 20.5 % (23/112) and 16.8 % (17/101) of patients (respectively) had DLK1-positive tumors. In NSCLC, DLK1 expression was associated with recurrence-free survival (P < 0.01) but not with overall survival. In SCLC, there was no association between DLK1 expression and survival. In addition, 125I-labeled anti-DLK1 antibody specifically targeted DLK1 on human SCLC tumor cell lines. Furthermore, 125I-labeled anti-DLK1 antibody was incorporated into tumor tissue in a mouse model. CONCLUSION: A proportion of SCLC and NSCLC exhibits DLK1 expression. As a clinical feature, DLK1 expression could be a promising prognostic factor for recurrence in patients with resected NSCLC. In addition, DLK1 could serve as a new therapeutic target, including RIT, as suggested by our pilot study using a radiolabeled anti-DLK1 antibody in SCLC.

A Case of Paraneoplastic Limbic Encephalitis in a Patient with Invasive Thymoma with Anti-Glutamate Receptor Antibody-Positive Cerebrospinal Fluid: A Case Report.

BACKGROUND: Thymoma is known to cause autoimmune neuromuscular disease. However, anti-glutamate receptor antibody limbic encephalitis (LE) with thymoma is relatively rare. CASE PRESENTATION: A 68-year-old woman was admitted with progressive memory impairment and personality change. Brain magnetic resonance imaging (MRI) revealed high intensity in the bilateral limbic areas on T2-weighted fluid-attenuation inversion recovery (FLAIR) images. Chest computed tomography revealed a mass in the anterior mediastinum. Surgical resection of the tumor, which was consistent with a type B3 thymoma, resulted in clinical improvement. After surgery, the cerebrospinal fluid (CSF) was found to be positive for anti-N-methyl-D-aspartate (NMDA) type glutamate receptor antibodies. These findings led to the diagnosis of paraneoplastic LE (PLE) associated with thymoma. CONCLUSION: When a patient presents with neurologic symptoms of unknown origin, the possibility of LE accompanied by thymoma should be considered. Rapid treatment is desirable before the symptoms become irreversible.

Efficacy and tolerability of nanoparticle albumin-bound paclitaxel in combination with carboplatin as a late-phase chemotherapy for recurrent and advanced non-small-cell lung cancer: A multi-center study of the Fukushima lung cancer association group of surgeons.

The present retrospective multi-center study aimed to evaluate the efficacy and feasibility of nanoparticle albumin-bound (nab)-paclitaxel plus carboplatin as a second or late-phase chemotherapy in patients with non-small cell lung cancer (NSCLC). A total of 25 patients with recurrent or advanced NSCLC who had received previous chemotherapy were treated with nab-paclitaxel (70-100 mg/m2, intravenously) on days 1, 8 and 15 every 28 days with a carboplatin area under the concentration-time curve of 4-6 on day 1. The overall response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicities were statistically evaluated. Of the 25 patients, there were 9 cases of recurrent disease following surgery, 16 cases of advanced disease, 13 cases of adenocarcinoma, 11 cases of squamous cell carcinoma and 1 case of large cell carcinoma. A total of 13 patients received second-line chemotherapy and 12 received fourth-line or later chemotherapy. One patient exhibited a complete response, 7 had a partial response, 10 exhibited stable disease and 7 had progressive disease. The overall response rate was 32.0% and the disease control rate was 72.0%. The median PFS and median OS following nab-paclitaxel treatment were 4.0 and 14.0 months, respectively. Frequent treatment-associated adverse events were myelosuppression, peripheral neuropathy, gastrointestinal symptoms and baldness, the majority of which were grade 1-2. Grade 3-4 neutropenia, thrombocytopenia and anemia occurred in 7 (28.0%), 3 (12.0%) and 2 (8.0%) patients, respectively. No patients experienced grade 3-4 sensory neuropathy and no grade 5 adverse effects were observed. Nab-paclitaxel plus carboplatin as second-phase or later chemotherapy provided a small but significant survival benefit for patients with recurrent or advanced NSCLC, with tolerable adverse effects. To the best of our knowledge, the results of the present study demonstrated for the first time that nab-paclitaxel plus carboplatin is a promising and feasible late-phase chemotherapeutic agent for NSCLC.

Recurrent Intrapulmonary Solitary Fibrous Tumor With Malignant Transformation.

Intrapulmonary solitary fibrous tumor (SFT) of the pleura; the so-called inverted pattern, which appears to grow into the lung parenchyma, is extremely rare. We experienced a 66-year-old woman with an intrapulmonary SFT that recurred locally with malignant transformation 2 years after wedge resection of the left upper lobe for the primary tumor. Subsequently, she underwent a lobectomy of the residual left upper lobe. Six years after the second operation she was well, without rerecurrence. Complete excision and long-term follow-up of intrapulmonary SFTs of the pleura are important, even when the primary tumor displays benign histopathologic features.

Concomitant metastatic lung tumor and hamartoma.

A 65-year-old woman who had undergone surgery for rectal cancer was referred to our hospital with an abnormal shadow on chest X-ray. Chest computed tomography (CT) revealed a 3-cm-diameter mass with ill-defined margins in the left lower lobe and a well-defined, 1-cm-diameter, round nodule in the right upper lobe. Transbronchial lung biopsy (TBLB) of the left lung tumor revealed metastatic adenocarcinoma originating from the rectal cancer. The patient underwent synchronous partial resection of the right upper lobe and left lower lobectomy under video-assisted thoracoscopic surgery (VATS). The pathological diagnosis of the right lung tumor was chondromatous hamartoma, and the left lung tumor was metastasis originating from the rectal cancer. The patient's postoperative course was uneventful, and she was well and free of disease 4 years after pulmonary metastasectomy.

Long-term outcomes after video-assisted thoracic surgery (VATS) lobectomy versus lobectomy via open thoracotomy for clinical stage IA non-small cell lung cancer.

BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy is a standard treatment for lung cancer. This study retrospectively compared long-term outcomes after VATS lobectomy versus lobectomy via open thoracotomy for clinical stage IA non-small cell lung cancer (NSCLC). METHODS: From July 2002 to June 2012, 160 patients were diagnosed with clinical stage IA NSCLC and underwent lobectomy. Of these, 114 underwent VATS lobectomy and 46 underwent lobectomy via open thoracotomy. RESULTS: The 5-year disease-free survival (DFS) rate was 88.0% in the VATS group and 77.1% in the thoracotomy group for clinical stage IA NSCLC (p = 0.1504), and 91.5% in the VATS group and 93.8% in the thoracotomy group for pathological stage IA NSCLC (p = 0.2662). The 5-year overall survival (OS) rate was 94.1% in the VATS group and 81.8% in the thoracotomy group for clinical stage IA NSCLC (p = 0.0268), and 94.8% in the VATS group and 96.2% in the thoracotomy group for pathological stage IA NSCLC (p = 0.5545). The rate of accurate preoperative staging was 71.9% in the VATS group and 56.5% in the thoracotomy group (p = 0.2611). Inconsistencies between the clinical and pathological stages were mainly related to tumor size, nodal status, and pleural invasion. Local recurrence occurred for one lesion in the VATS group and six lesions (five patients) in the thoracotomy group (p = 0.0495). CONCLUSIONS: The DFS and OS were not inferior after VATS compared with thoracotomy. Local control was significantly better after VATS than after thoracotomy. Preoperative staging lacked sufficient accuracy.

An extremely elderly patient with lung cancer who underwent surgery.

We report the case of an extremely elderly patient with long-term survival after surgical resection for lung cancer. A 93-year-old man was evaluated for an abnormal density on chest radiography. Chest computed tomography (CT) showed a nodular density of 2.5 × 2.5 cm in the left S4b segment. Lung cancer was diagnosed by bronchoscopy, and left posterolateral thoracotomy and S4 segmentectomy were performed. Group 1 lymph node dissection and sampling of the 6th lymph node were also performed. Pathological examination revealed poorly differentiated squamous cell carcinoma without any lymph node metastases. The tumor was staged as p-T1aN0M0 stage IA. No complications were encountered postoperatively, and the patient was discharged. He remains alive as of 5 years postoperatively without any recurrence.

Well-differentiated fetal adenocarcinoma of the lung in a 20-year-old woman.

A 20-year-old woman was found to have a tumor shadow on chest X-ray examination during mass screening and was admitted to our hospital. The chest radiograph revealed a round tumor in the right upper lung field. Chest computed tomography (CT) showed a well-defined, 3-cm-diameter mass in the right upper lobe. The patient underwent a right upper lobectomy under video-assisted thoracoscopic surgery. The postoperative pathological diagnosis was well-differentiated fetal adenocarcinoma (WDFA), stage IA (pT1bN0M0). The patient was well and free of disease four years after surgery. WDFA is a rare pulmonary neoplasm resembling fetal lung and classified as a variant of adenocarcinoma. WDFA occurs in younger people more often than the other histological types of primary lung cancer. An additional young case of WDFA is reported, along with a review of the relevant literature.

Incidental early lung adenocarcinoma after surgery for catamenial pneumothorax.

A 40-year-old female patient underwent surgery at our hospital for recurrent pneumothorax. A defect on the right diaphragm was diagnosed as ectopic endometriosis. However, air leakage continued 2 days after surgery. Chest computed tomography identified a 5-mm ground glass opacity in the right S3 field, suggestive of lung cancer. Ten days after the initial surgery, she underwent curative surgery for both pneumothorax and the lung tumor. The tumor was diagnosed as bronchioloalveolar carcinoma, but no other endometriosis was identified. The patient has remained well with no recurrence of lung cancer or pneumothorax since the second surgery.

Traffic of infused bone marrow cells after genetically-labeled syngeneic bone marrow transplantation following lethal irradiation in mice.

UNLABELLED: Bone marrow (BM) cells are considered the source of stem cells for various organs. However, how quickly BM cells can penetrate and constitute lymphoid organs remains elusive. In the present study, we addressed this issue in a model using genetically-labeled syngeneic BM transplantation (BMT). METHODS: Donor BM cells were obtained from "green mice", transgenic mice with enhanced GFP. Lethally irradiated C57BL/6 mice were infused with 1 x 10(6) BM cells from the green mice through the tail vein. BM chimerism was analyzed by FACS and the presence of donor BM cells in thoracoabdominal organs was assessed by fluorescence microscopy. The commitment of BM cells was examined by immunohistochemical staining using epithelium-, macrophage-, B and T-lymphocyte, and endothelium-specific antibodies. RESULTS: BM chimerism reached 40+/- 18.5%, 82.6 +/- 23.4%, and 72 +/- 18% (mean +/- SD) at 1, 4, and 12 wks after BMT, respectively. GFP-positive cells were detected in all organs in the course of chimeric formation. Most GFP-positive cells were T and B lymphocytes in lymphoid systems including spleen, thymus, mesenteric lymph nodes and microvilli, and some were positive for macrophage and endothelial cell markers. CONCLUSIONS: Our results indicate that BM-derived cells migrate rapidly into various thoracoabdominal organs after BMT, and that lymphoid tissues are predominantly replaced with infused BM in lethally-irradiated mice. This confirmed the previous finding by others and suggests high interest of this model for further studies to characterize kinetics and roles of infused cells.

Nonrecurrent inferior laryngeal nerve without vascular anomaly as a genuine entity.

Inferior laryngeal nerve (ILN), which usually arises from vagus nerve, runs recurrent course and is called recurrent ILN (RILN). Intimate knowledge of normal and anatomic variants of the ILN reduces the risk of nerve injury and vocal cord paralysis in thyroid and parathyroid surgery. The nonrecurrent ILN (NRILN) is a rare nerve anomaly that is associated with a right aberrant subclavian artery. We encountered 2 patients with NRILN during thyroid surgery. Patient 1, a 57-year-old woman, had mediastinal thyroid tumor without vascular anomaly. Patient 2, a 47-year-old woman with a history of esophageal foreign body (fish bone), was suspected to have NRILN with vascular anomaly before surgery, as judged by preoperative enhanced CT. In the patient 1, we verified laryngeal mobility function of the NRILN by nerve stimulation, and confirmed the absence of RILN in usual recurrent course. The findings in the patient 1 indicate that NRILN without subclavian artery anomaly is a genuine entity. In both patients we performed thyroid surgery safely and fast by expectation and identification of NRILN by use of nerve stimulator. In conclusion, we confirm the existence of NRILN without vascular anomaly and show effectiveness of preoperative enhanced CT and valuable use of nerve stimulator for nerve preservation in the patients with NRILN.

Expression of secretoglobin3A2 (SCGB3A2) in primary pulmonary carcinomas.

Secretoglobin (SCGB) 3A2 is a downstream target gene for the thyroid transcription factor-1 (TITF1). SCGB3A2 plays a role as an anti-inflammatory agent, however, its role in primary pulmonary carcinomas has not been examined. We assessed immunohistochemical expression of SCGB3A2 in primary pulmonary carcinomas and evaluated the correlation between the expression and histopathological phenotypes and prognosis. One hundred and fifty-six primary lung cancers undergone for surgical resection were examined. The percentages of SCGB3A2 positive cells were scored and tumors had immunoreactivity in more than 10% of tumor cells were considered positive for SCGB3A2. Overall reactivity for SCGB3A2 was observed in 116 (74.4%) of 156 primary lung cancers. SCGB3A2 was predominantly expressed in adenocarcinomas (86.5%), compared with squamous cell carcinomas (50.0%) and small cell carcinomas (42.9%). The expression in papillary adenocarcinomas was seen at higher frequency than that in tubular adenocarcinomas. There was no significant relationship between SCGB3A2 expression and tumor differentiation, and pathological stage. Positive expression of SCGB3A2 was not associated with better survival rate. SCGB3A2 expression in primary pulmonary carcinomas is high, especially in adenocarcinomas. Our results indicate that SCGB3A2 has a potential to be a specific and useful marker for primary pulmonary adenocarcinomas.

Carbohydrate status detecting by PNA is changeable through cancer prognosis from primary to metastatic nodal site: A possible prognostic factor in patient with node-positive lung adenocarcinoma.

Carbohydrates antigens in cancer cells are considered to be important molecules, which may play a critical role for metastasis. To elucidate the prognostic relevance of the expression of peanut agglutinin (PNA) binding carbohydrates in patients with lung adenocarcinoma, we investigated the PNA binding carbohydrates immunohistochemically in both of primary tumors and involving nodal lesions. A total of 62 patients with node-positive primary lung adenocarcinoma, who had undergone complete resection and regional nodes dissection were subjected to this study. There were no significant correlations between PNA staining rates and clinicopathological variables. The survival rate of patients who had positive PNA staining in both of primary tumor and nodal lesion was significantly higher than those of patients in the other groups. Furthermore, the loss of the staining rate of PNA was an independent prognostic factor beside the lymphatic vessel invasion using multivariate analysis. The expression of PNA binding carbohydrates in tumor tissue and nodal lesion would be a novel significant prognostic factor for patients with node-positive lung adenocarcinomas.

Identification of the decay-accelerating factor CD55 as a peanut agglutinin-binding protein and its alteration in non-small cell lung cancers.

PURPOSE: Peanut agglutinin (PNA) recognizes tumor-associated carbohydrates. In this study, we aimed to identify the core protein harboring PNA-binding sugars in the human lung and to explore the relationship with the pathology of primary non-small cell lung cancers (NSCLC). EXPERIMENTAL DESIGN: PNA lectin blotting was used to detect PNA-binding proteins in the microsomal fraction of lung tissue from 24 patients with NSCLC. The 55- to 65-kDa core peptide PNA-binding protein was characterized by enzymatic treatment and identified by immunoprecipitation and affinity chromatography. The expression level and increase in size of the 55- to 65-kDa PNA-binding protein/decay-accelerating factor (DAF) were compared between normal and tumor regions of the tumor tissue by Western blotting and quantitative PCR. RESULTS: The 55- to 65-kDa PNA-binding protein was observed in human lung. This was a glycosylphosphatidylinositol-anchored membrane protein carrying O-linked carbohydrates. This core protein was identified as DAF, one of the complementary regulatory proteins. DAF was enlarged to 65 to 75 kDa in NSCLC tumor lesions due to sialylation in the sugar moiety. At the transcription level, DAF levels were significantly lower in tumor regions, suggesting its down-regulation in NSCLC cells. CONCLUSIONS: DAF was identified as a new PNA-binding protein in the human lung. The down-regulation and heavy sialylation of DAF was associated with pathology in NSCLC, and these alterations make this protein a potential marker for NSCLC.

Molecular cloning and characterization of novel splicing variants of human decay-accelerating factor.

Decay-accelerating factor (DAF) is one of the complement regulatory proteins. Two isoforms of DAF have been identified in humans. In this study, we isolated novel cDNAs encoding five isoforms of DAF from the human lung, which were generated by insertion of new exonic sequences. RT-PCR revealed that all isoforms were expressed in almost all tissues tested, although the expression patterns and levels differed among the tissues. Transfection of isoform vDAF1, 2, and 3 cDNAs into CHO cells showed that these molecules are soluble forms secreted after glycosylation. Isoform vDAF4 and vDAF5 cDNAs included a part of and the entire intron 7 sequence, respectively, and the transfection of vDAF4 cDNA produced a large, glycosylated, membrane-bound form. These results suggest that more than seven isoforms of human DAF are involved in the regulation of complement activation under physiological conditions through their specific structures and localization.

Prognostic impact of p53 protein overexpression in patients with node-negative lung adenocarcinoma.

Prognostic value of p53 protein expression in node-negative lung adenocarcinoma is still controversy. The expression of p53 protein was examined immunohistochemically in lung adenocarcinoma using monoclonal antibody BP53-12. A total 131 cases of primary lung adenocarcinoma were examined. Relationship between expression of p53 protein and clinicopathologic factors were studied. Overexpression of p53 protein was found in 19 patients (14.5%). Univariate and multivariate analysis showed that overexpression of p53 protein was an independent prognostic factor in node-negative lung adenocarcinoma. p53 alteration could be a valuable predictor for prognosis in node-negative lung adenocarcinoma.

Expression of liver-type fatty-acid-binding protein, fatty acid synthase and vascular endothelial growth factor in human lung carcinoma.

OBJECTIVE: A key enzyme of fatty acid synthesis, fatty acid synthase (FAS), is expressed in human cancers, including squamous-cell carcinoma of the lung, and long-chain fatty acids are intracellularly transported and/or taken up from blood by fatty-acid-binding proteins (FABPs). Since the liver-type (L-) FABP, a member of the FABPs, is detected in a subset of gastric adenocarcinomas, the expression of FAS, L-FABP and vascular endothelial growth factor (VEGF) was investigated in human lung carcinomas to elucidate the mechanisms of production and transportation of fatty acid(s) in cancer. METHODS: Expression of L-FABP, FAS and VEGF in 199 surgically resected lung carcinomas was examined immunohistochemically. Possible associations of the expression of each protein with major clinicopathological factors were analyzed. RESULTS: L-FABP was detected in 60% (120 of 199) of the lung carcinoma cases; detection was increased in large-cell carcinoma (80%) and adenosquamous carcinoma (83%), but low in squamous-cell carcinoma (47%) and in small-cell carcinoma (57%). Overall expression of FAS was 67.3% (134 of 199 cases) and that of VEGF was 86.8% (158 of 199 cases), respectively. Expression of L-FABP was not correlated with the FAS status, but there was a tendency to co-expression of L-FABP and VEGF. There was no association between L-FABP, FAS or VEGF expression and clinicopathological data. CONCLUSIONS: L-FABP, FAS and VEGF are highly expressed in human lung cancer, and expression of L-FABP is associated with that of VEGF but not that of FAS, suggesting that L-FABP might be involved in the uptake of fatty acid(s) from the bloodstream.