Development of a New Magnetometer for Sentinel Lymph Node Mapping Designed for Video-Assisted Thoracic Surgery in Non-Small Cell Lung Cancer.

BACKGROUND: We previously developed a method for sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC), based on the magnetic force produced by a magnetite tracer already approved for use as a contrast material for magnetic resonance imaging. However, it is difficult to use that technique with video-assisted thoracic surgery (VATS) because the sensing element of the magnetometer is large and thick. The purpose of the present study was to develop a smaller, thinner VATS-compatible magnetometer. METHODS: The tracer employed was Ferucarbotran, a colloidal solution of superparamagnetic iron oxide coated with carbodextran. Fifteen patients with clinical stage I NSCLC were enrolled, and each received 1.6 mL of Ferucarbotran, injected intraoperatively at 5 points around the tumor. The magnetic force within the sampling lymph nodes was measured using the new VATS-compatible magnetometer. RESULTS: SLNs were detected in 11 (73.3%) of the 15 patients using the VATS-compatible magnetometer. The average number of SLNs identified per patient was 1.8 (range 0-4). No complications related to the SLN detection method were observed. CONCLUSIONS: The new VATS-compatible magnetometer appears to have substantial advantages over techniques using a radioisotope and our earlier magnetometer, as it can be inserted through the small VATS port site.

Diagnostic imaging in the preoperative management of lung cancer.

Surgical resection is the accepted standard of care for patients with non-small cell lung cancer (NSCLC). Several imaging modalities play central roles in the detection and staging of the disease. The aim of this review is to evaluate the utility of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and PET/CT for NSCLC staging. Radiographic staging refers to the use of CT as a non-invasive diagnostic technique. However, while the vast majority of patients undergo only CT, CT is a notoriously inaccurate means of tumor and nodal staging in many situations. PET/CT clearly improves the staging, particularly nodal staging, compared to CT or PET alone. In addition, as a result of the increased soft-tissue contrast, MRI is superior to CT for distinguishing between tissue characteristics. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which is a minimally invasive technique, also has pathological diagnostic potential. Extensive research and the resultant improvements in the understanding of genetics, histology, molecular biology and oncology are transforming our understanding of lung cancer, and it is clear that imaging modalities such as CT, MRI, PET and PET/CT will have an important role in its preoperative management. However, thoracic surgeons should also be aware of the limitations of these techniques.

Use of CT to evaluate pleural invasion in non-small cell lung cancer: measurement of the ratio of the interface between tumor and neighboring structures to maximum tumor diameter.

PURPOSE: To develop a simple noninvasive technique for evaluating pleural invasion by using routine preoperative computed tomography (CT). MATERIALS AND METHODS: The institutional review board approved this retrospective study, and written informed consent was obtained for performing the initial and follow-up CT studies. Preoperative CT findings (169 patients with possible pleural invasion) and pathologic diagnoses after surgical resection were evaluated. The length of the interface between the primary tumor and neighboring structures (arch distance) and the maximum tumor diameter were measured on CT images, after which arch distance-to-maximum tumor diameter ratios were calculated. Receiver operating characteristic (ROC) curves were used to analyze the ratios. RESULTS: Median arch distance-to-maximum tumor diameter ratios for pleural invasion categories (pl1, pl2, pl3) assessed by using the Union Internationale Contre le Cancer TNM staging system were as follows: pl1, 0.206 (25th-75th percentile, 0-0.486); pl2, 0.638 (25th-75th percentile, 0.385-0.830); and pl3, 1.092 (25th-75th percentile, 1.045-1.214) (P < .001 between groups). On the basis of the ROC curves, the cut-off value for invasion was an arch distance-to-maximum tumor diameter ratio of 0.9. When the ratio was greater than 0.9, the sensitivity and specificity for thoracic invasion and area under the ROC curve were 89.7%, 96.0%, and 0.976, respectively, which represents an improvement over values obtained by using conventional criteria (radiologists A and B: 46.7% and 74.2% and 91.3% and 84.8%, respectively). CONCLUSION: When diagnosing T3 or T4 lung cancer based on arch distance-to-maximum tumor diameter ratios, a higher performance level was achieved than that with use of conventional criteria. Measurement of the ratios is a simple noninvasive technique for evaluating pleural invasion at CT.

Evaluation of the risk of lymph node metastasis using CRP 1846C>T genetic polymorphism in submucosal thoracic esophageal squamous cell carcinoma.

BACKGROUND: More than 40 % of patients with submucosal esophageal squamous cell carcinoma (ESCC) have lymph node metastasis. Furthermore, the potential presence of undetectable metastasis before treatment prompts surgeons to be aggressive with respect to lymph node dissection. Extending the indication for endoscopic resection, a minimally invasive treatment, to superficial ESCCs will require more accurate and individualized evaluation of lymph node metastasis. METHODS: The study participants were 121 esophageal cancer patients who underwent curative surgery for thoracic submucosal ESCC at three Japanese hospitals. DNA was extracted from blood samples, and the C-reactive protein (CRP) 1846C>T genetic polymorphism (rs1205) was investigated using polymerase chain reaction-restriction fragment length polymorphism. We then evaluated the value of CRP 1846C>T polymorphism for diagnosis of lymph node metastasis. RESULTS: Forty-nine (40 %) patients had lymph node metastasis. The CRP 1846 C/T genotype was C/C in 19 patients, C/T in 57 patients, and T/T in 45 patients. Fisher's exact analysis of the CRP 1846C>T polymorphism showed a significantly higher frequency of lymph node involvement with the T/T genotype. Univariate and multivariate logistic regression models revealed that patients carrying the 1846 T/T genotype had a significantly greater likelihood of developing lymph node metastasis (odds ratio >2.6). Combining the CRP 1846 C/T genotype with clinical diagnosis, mainly using CT, brought a negative predictive value of 80 % to diagnosing lymph node involvement. CONCLUSIONS: CRP genetic polymorphism may be a novel predictor of risk of lymph node metastasis in ESCC, which could enable better evaluation of the necessity for lymph node dissection.

REG1A expression status suggests chemosensitivity among advanced thoracic esophageal squamous cell carcinoma patients treated with esophagectomy followed by adjuvant chemotherapy.

BACKGROUND: Regenerating gene 1A (REG1A) plays an important role in tissue regeneration and in cell proliferation in the mucous membrane of the gastrointestinal tract. We previously reported that the positive expression status of REG1A was predictive of chemoradiosensitivity in patients treated with preoperative chemoradiotherapy before esophagectomy or with definitive chemoradiotherapy. To further confirm the utility of REG1A as a chemosensitivity marker, we carried out an additional retrospective clinical study aimed at determining whether REG1A is a reliable chemosensitivity marker in patients treated with esophagectomy followed by adjuvant chemotherapy. METHOD: A total of 177 patients with T2-4 thoracic esophageal squamous cell carcinoma received curative surgery without preoperative treatment at Akita University Hospital between 2001 and 2011. A tissue microarray was constructed, and REG1A expression status was analyzed immunohistochemically. We then statistically analyzed the relationships between REG1A expression status and 5-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS: In the adjuvant group (n=105), REG1A-positive patients showed significantly better prognoses than REG1A-negative patients. (5-year OS, p=.0022; DSS, p=.0004; and DFS, p=.0040). However, there were no significant differences between REG1A-positive and REG1A-negative patients in the surgery group (n=72). Univariate and multivariate analyses showed REG1A expression status to be a significant prognostic factor affecting 5-year DSS, comparable to lymph node metastatic status. CONCLUSION: The present study suggests REG1A expression status has the potential to be a highly reliable and clinically useful chemosensitivity marker in patients treated with advanced thoracic esophageal squamous cell carcinoma. REG1A expression status will provide a good indication of treatment strategy and enable more individualized treatment for patients.

Bronchioloalveolar invasion in non-small cell lung cancer is associated with expression of transforming growth factor-ß1.

BACKGROUND: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with fibrous stromal invasion are newly introduced subtypes of small lung adenocarcinoma. AIS is a small localized adenocarcinoma in which growth is restricted to neoplastic cells along preexisting alveolar structures without fibrous stromal invasion. In MIA, by contrast, tumor cells have infiltrated the myofibroblastic stroma. Transforming growth factor (TGF)-ß is known to be produced by progressor tumors, and excessive TGF-ß contributes to a pathological excess of tissue fibrosis. TGF-ß1 is the most abundant isoform, and its expression is a key event fostering tumor invasion and metastasis. We therefore analyzed the relationship between TGF-ß1 expression and clinicopathological microinvasion in patients with small lung adenocarcinoma. METHODS: The study participants were 45 patients who underwent curative surgery for AIS and MIA 3 cm or less in size. Those tumors were assessed based on immunohistochemical staining using anti-TGF-ß1 antibody. The TGF-ß1 status was assessed immunohistochemically using the Allred 8-unit system. RESULTS: The rates of TGF-ß1 positivity in the AIS and MIA groups were 27.3% and 65.2%, respectively (P <0.05). The median of Allred score was 0.5 (range 0-5) in the AIS group and 3.0 (range 0-6) in the MIA group (P = 0.0017). CONCLUSIONS: We suggest that TGF-ß1 expression is likely to be significantly stronger in patients with MIA than in those with AIS, and the increased expression may be associated with minimal invasion and infiltration of the myofibroblastic stroma.

A CRP genetic polymorphism associated with the tumoral expression of CRP in esophageal cancer.

C-reactive protein (CRP) produced locally within esophageal cancer is associated with the prognosis and the rate of recurrence. CRP genetic polymorphisms reportedly affect serum CRP concentrations; however, there are no reports of an association between genetic polymorphisms and tumoral CRP expression. This study enrolled 73 Japanese patients classified with Stage IIA-IV thoracic esophageal squamous cell cancer, and also investigated their CRP genetic polymorphisms using DNA extracted from their peripheral blood. The study then assessed the association between CRP genetic polymorphisms and tumoral CRP expression. The results revealed a significant association between the CRP 1846C>T genetic polymorphism and tumoral CRP expression. This finding suggests that tumoral CRP production controlled by CRP genetics significantly influences tumor behavior.

Novel technique for relieving anastomotic tension using halo-vest immobilization after tracheal sleeve resection.

We describe a novel technique of using halo-vest-enforced immobilization to relieve anastomotic tension after tracheal sleeve resection. Immediately after the tracheal sleeve resection, four halo titanium pins were inserted in the skulls of the patients to secure the halo-vest. All patients fitted with halo-vests were able to eat and drink and their clinical course was good. Bronchoscopy confirmed the absence of anastomotic leaks and stenoses, and there were no complications associated with the halo-vest. We believe that ensuring neck flexion using a halo-vest after tracheal sleeve resection is an excellent way of relieving anastomotic tension that would predispose the wound to dehiscence.

Detection of pleural lymph flow using indocyanine green fluorescence imaging in non-small cell lung cancer surgery: a preliminary study.

PURPOSE: Lymphatic spread of lung carcinoma to the mediastinum is a key determinant of prognosis. The lymph flow often carries metastases from the pulmonary segment directly into the mediastinal lymph nodes, without passing through the hilar nodes. This phenomenon is termed as "skip metastasis." This study investigated the subpleural lymphatic flow to the mediastinum using indocyanine green (ICG) with a near-infrared fluorescence imaging system. METHODS: Seventeen patients with lung cancer were enrolled in this study. A 0.3 ml sample of solution containing the fluorescent dye ICG (5 mg/ml) was injected into subpleural sites near the primary tumor. Fluorescence imaging was used to monitor the flow of ICG-containing lymph from the injection site for 5 min. The relationship between the anatomical segment of the primary tumor and the lymphatic flow was assessed. RESULTS: The lymphatic vessels draining from the injection site were revealed by the bright ICG fluorescence in 14 of the patients (82.4 %). A direct lymphatic flow to the mediastinum was confirmed in 3 of those 14 (21.4 %). CONCLUSIONS: These findings confirm the direct flow of lymph to the mediastinum without passage through the hilum pulmonis intraoperatively. These preliminary results may provide a valuable clue for further investigations of the mechanisms underlying skip metastasis.

Outcomes of patients receiving additional esophagectomy after endoscopic resection for clinically mucosal, but pathologically submucosal, squamous cell carcinoma of the esophagus.

PURPOSE: This study investigated the actual rate or extent of lymph node metastasis or the survival outcomes among patients that underwent esophagectomy with lymph node dissection after ESD for clinical mucosal, but pathological submucosal, esophageal cancer. METHODS: Seventeen patients that received esophagectomy with two- or three-field lymph node dissection as additional treatment after ESD for clinical mucosal, but pathological submucosal, esophageal cancer between 2006 and 2010 were analyzed. The rate and extent of lymph node metastasis and the patient outcomes were determined. RESULTS: The tumor depths were diagnosed as SM1 in 8 (47 %) patients and SM2 in 9 (53 %), based on the analyses of resected specimens. Lymphatic invasion was evident in 13 (76 %) patients, while venous invasion was detected in 5 (29 %). Five (29 %) patients had pathologically detected lymph node involvement. Seven (0.8 %) of the 890 dissected nodes showed cancer involvement. Three patients had one involved node in the mediastinum or abdomen, and 2 patients had 2 involved nodes in the abdomen. The patients were followed up for 11-71 months (median 23 months), and all were alive without recurrence at the final follow-up. CONCLUSION: Twenty-nine percent of the patients diagnosed with clinically mucosal, but pathologically submucosal, thoracic squamous cell esophageal cancer after ESD had 1-2 cancer-involved lymph nodes in the lower mediastinum and abdomen. Esophagectomy with lymph node dissection is therefore considered to be a necessary and effective additional treatment for these patients.

Online physical exercise program with music improves working memory.

Objective: The spread of coronavirus disease (COVID-19) has limited the implementation of face-to-face non-pharmacological treatment for the prevention of dementia. As a result, online non-pharmacological treatment has become increasingly important. In this study, we used an online conferencing system to implement an online version of a physical exercise program with music, and examined its effect on cognitive function. Methods: The participants were 114 healthy older adults [63 men and 51 women; mean age of 70.7 years (standard deviation = 4.6)]. Seventy-five participants were allocated to the physical exercise with music group (60 min, once a week, total 20 sessions), while the remaining 39 participants were assigned to the control group, and only underwent the examinations. In the physical exercise with music group, we performed neuropsychological examinations and brain tests both before and after the exercise program. Neuropsychological tests included the Mini-Mental State Examination, Raven's Colored Progressive Matrices (RCPM), the Rivermead Behavioral Memory Test, graphic imitation, word fluency (WF) (animal names and initial sounds), and the Trail Making Test-A/B. As an assessment of brain function, we developed an online examination of subtle cognitive decline, including tests of number and word memory, spatial grasp, the N-back task, and change inference. Results: In the N-back task, the physical exercise with music group improved significantly relative to the control group (p = 0.008). Discussion: The present findings suggest that the online version of the physical exercise with music program improved working memory, which mainly involves the frontal lobe.

An Online Version of Physical Exercise with Musical Accompaniment Might Facilitate Participation by Subjects Who Cannot Participate in Person: A Questionnaire-Based Study.

Introduction: Due to the ongoing outbreak of the coronavirus disease 2019 (COVID-19), it is currently difficult to conduct in-person exercise classes. We thus started the program of an online physical exercise with musical accompaniment. Several interesting differences were found in the characteristics of the online participants compared with our previous in-person interventions. Participants and Methods: The total number of subjects was 88 (71.2 ± 4.9 years old; male 42, female 46). The questionnaire included the attributes of the participants, the perceived advantages of the exercise classes, and the presence or absence of noticeable changes in cognitive and physical function after participating in the classes. Results: The personal computers used to attend the online classes were operated by the participants themselves. About 42% of the participants felt that their sense of day of the week and volition were improved by attending the exercise classes for 3 months. The most frequent answer to the reason for participation was because it was free (81.8%). The second most frequent answer was because the classes were held online (75.0%). Almost half of the participants answered that they would not participate if it was held in person because of the risk of COVID-19 infection (75.0%) and the difficulty getting to the site where the exercise classes were held (59.1%). Conclusion: Online physical exercise with musical accompaniment improved the perceived orientation, volition, activity, exercise habits, and health condition in 30-40% of the participants and also stimulated greater participation by males compared to classes held in person.

Acquired xanthine dehydrogenase expression shortens survival in patients with resected adenocarcinoma of lung.

Xanthine dehydrogenase (XDH), also known as xanthine oxidoreductase (XOR), has long been recognized as the key enzyme in the catabolism of purines, oxidizing hypoxanthine into xanthine and then xanthine into uric acid. In addition, levels of XDH expression are reportedly related to the prognosis of patients with malignant tumors, though the relationship between the clinicopathological features of lung cancer and XDH is not fully understood. We therefore used semiquantitative real-time reverse transcription polymerase chain reaction to assess expression of XDH mRNA in tumor samples from 88 patients with adenocarcinoma of the lung. We then correlated XDH mRNA levels with known clinicopathological factors. We found that the 5-year overall survival rate among patients strongly expressing XDH was significantly poorer than among those expressing lower levels of XDH (P < 0.001; log-rank test). Normal lung tissue does not express XDH. Multivariate Cox proportional hazard analyses revealed that being male (hazard ratio, 3.14; 95 % confidence interval (CI), 1.45-7.07; P = 0.004), nodal metastasis positivity (hazard ratio, 5.74; 95 % CI, 1.94-19.3; P = 0.001), and high XDH expression (hazard ratio, 2.33; 95 % CI, 1.11-5.02; P = 0.026) were all independent factors affecting 5-year disease-free survival. In conclusion, high tumoral XDH expression is an independent predictor of a poor prognosis in patients with adenocarcinoma of the lung.

Estimating the need for neck lymphadenectomy in submucosal esophageal cancer using superparamagnetic iron oxide-enhanced magnetic resonance imaging: clinical validation study.

BACKGROUND: In cases of thoracic esophageal cancer, multidirectional lymphatic flow from the tumor means that lymph node metastasis can occur in an area extending from the neck to the abdomen. To validate a method for limiting the performance of three-field lymphadenectomy only to patients who need it, we carried out a prospective study in which superparamagnetic iron oxide (SPIO)-enhanced lymphatic mapping was used to determine whether to perform neck lymph node dissection in patients with submucosal thoracic esophageal cancer. METHODS: A total of 22 patients with clinically submucosal thoracic squamous cell esophageal cancer, without neck lymph node metastasis, were enrolled. SPIO was endoscopically injected into the peritumoral submucosal layer, after which its appearance in lymph nodes in the neck was evaluated using magnetic resonance imaging (MRI). Neck lymph nodes were then dissected based on the SPIO-enhanced MRI lymphatic mapping. RESULTS: Influx of SPIO into lymph nodes was detected in 21 patients (95% detection rate). SPIO flowed to the neck in 8 (36%) patients. Influx of SPIO into neck lymph nodes was unilateral in five patients and bilateral in three patients, and the lymph nodes were dissected accordingly. A cancer-involved node was identified in two of those patients. In 14 patients, we did not dissect neck nodes. Patients were followed up for 6 to 47 months. The neck lymph node recurrence rate was zero, and the overall recurrence rate was 5%. CONCLUSIONS: SPIO-enhanced lymphatic mapping may be useful for estimating the need for three-field lymphadenectomy with neck dissection.

Interleukin-6 -634G>C genetic polymorphism is associated with prognosis following surgery for advanced thoracic esophageal squamous cell carcinoma.

OBJECTIVE: Systemic and/or local interleukin-6 (IL-6) reportedly plays an active role in the progression and prognosis of thoracic esophageal squamous cell carcinoma (TESCC). We assessed the associations between IL-6 and IL-6 receptor (IL-6R) genetic polymorphisms, tumoral IL-6 expression and survival rates following surgery. METHODS: The study participants were 63 Japanese patients treated between 2003 and 2008 for T2-T4 advanced TESCC using curative esophagectomy without neoadjuvant treatment. We investigated IL-6 -634G>C (rs1800796) and IL-6R 48892A>C (rs8192284, Asp358Ala) genetic polymorphisms using DNA from peripheral blood samples. In addition, tumoral IL-6 expression was investigated immunohistochemically in resected specimens, and serum IL-6 was measured using a human IL-6 immunoassay. RESULTS: There was a significant difference in survival between patients with the IL-6 -634G/G+G/C genotype and those with the C/C genotype, such that their 5-year overall survival rates were 42 and 72%, respectively. By contrast, the IL-6R 48892A /C genotype and tumoral IL-6 expression had no significant effect on survival among patients. Univariate and multivariate analyses revealed that IL-6 -634G>C polymorphism was an independent prognostic factor with a hazard ratio of 3. CONCLUSIONS: IL-6 -634G>C genetic polymorphism may be a predictive prognostic factor in patients receiving esophagectomy for TESCC.

Tumoral CRP expression in thoracic esophageal squamous cell cancers is associated with poor outcomes.

PURPOSE: Cancer cells reportedly produce C-reactive protein (CRP) locally within tumors. The aim of this study was to determine whether tumoral CRP is associated with clinical outcome and recurrence in thoracic esophageal squamous cell cancer. METHODS: The subjects included 73 Japanese patients with thoracic esophageal squamous cell cancer (pathological Stage IIA-IV) that had not been treated preoperatively with either chemotherapy or radiotherapy. Tumoral CRP expression in resected specimens of tumor tissue was assessed by immunohistochemistry. The survival rate following surgery, the rates and patterns of recurrence, and the serum CRP levels before treatment and at recurrence were analyzed in patients with and without tumoral CRP expression. RESULTS: Fifty-nine percent of the study participants (43/73) were positive for tumoral CRP expression, and the remaining 41% (30/73) were negative. No significant difference in clinicopathological factors was observed between the tumoral CRP-positive and CRP-negative groups; however, patients expressing tumoral CRP showed significantly poorer survival and recurrence rates. A multivariate analysis showed that tumoral CRP expression was an independent factor contributing to the likelihood of a poor outcome. CONCLUSION: Tumoral CRP is associated with a poor outcome in thoracic esophageal squamous cell cancer. Tumoral CRP could therefore be an important target for the treatment of this disease.

[A case of complete resection of non-squamous non-small-cell lung cancer after induction chemotherapy using carboplatin, paclitaxel, and bevacizumab].

Since locally advanced non-small-cell lung cancer(NSCLC)treated by surgical therapy alone has a poor prognosis, the efficacy of preoperative chemotherapy for improving postoperative survival in patients with NSCLC is controversial. A 69-year-old female was referred to our hospital for Stage IIIA(cT3bulkyN2M0)adenocarcinoma of the right lung. Computed tomography(CT)revealed a small nodule, 21mm in diameter, in the right S6, with isolated pulmonary metastasis in the same lobe and bulky subcarinal lymph node swelling. She received two courses of a combination of carboplatin(CBDCA AUC5), paclitaxel(PTX 200mg/m2)and bevacizumab(15mg/kg)as induction therapy, and showed no serious adverse effects. CT after induction therapy revealed a minor radiographic response. She underwent right lower lobectomy with node dissection 2a in 2011. An intercostal muscle flap was used for the bronchial stump. Histopathological examination revealed adenocarcinoma pT1aN0M0 of Stage I A, and showed that the pulmonary metastasis had disappeared even though the effect of induction chemotherapy was Ef2. Induction chemotherapy with carboplatin, paclitaxel and bevacizumab may be useful for treatment of locally advanced lung cancer.

IGFBP3 and BAG1 enhance radiation-induced apoptosis in squamous esophageal cancer cells.

Identification of reliable markers of radiosensitivity and the key molecules that enhance the susceptibility of esophageal cancer cells to anticancer treatments would be highly desirable. To identify molecules that confer radiosensitivity to esophageal squamous carcinoma cells, we assessed the radiosensitivities of the TE-5, TE-9 and TE-12 cloneA1 cell lines. TE-12 cloneA1 cells showed significantly greater susceptibility to radiotherapy at 5 and 10Gy than either TE-5 or TE-9 cells. Consistent with that finding, 24h after irradiation (5Gy), TE-12 cloneA1 cells showed higher levels of caspase 3/7 activity than TE-5 or TE-9 cells. When we used DNA microarrays to compare the gene expression profiles of TE-5 and TE-12 cloneA1 cells, we found that the mRNA and protein expression of insulin-like growth factor binding protein 3 (IGFBP3) and Bcl-2-associated athanogene 1 (BAG1) was five or more times higher in TE-12 cloneA1 cells than TE-5 cells. Conversely, knocking down expression of IGFBP3 and BAG1 mRNA in TE-12 cloneA1 cells using small interfering RNA (siRNA) significantly reduced radiosensitivity. These data suggest that IGFBP3 and BAG1 may be key markers of radiosensitivity that enhance the susceptibility of squamous cell esophageal cancer to radiotherapy. IGFBP3 and BAG1 may thus be useful targets for improved and more individualized treatments for patients with esophageal squamous cell carcinoma.

Expression of the transient receptor potential channel c3 correlates with a favorable prognosis in patients with adenocarcinoma of the lung.

BACKGROUND: The cation channels of the transient receptor potential (TRP) superfamily are implicated in cancer formation; in particular, TRPC3 has been shown to contribute to the progression of human ovarian cancer. However, the relationship between TRP expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood. Therefore, we investigated the relationship between TRP expression and the prognosis of patients with adenocarcinoma of the lung. METHODS: We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of TRP mRNA in tumor samples from 95 patients with adenocarcinoma of the lung. We then correlated the TRP mRNA levels with clinicopathological factors. We also used immunohistochemical staining to determine the localization of expressed TRP. RESULTS: The 5-year overall and disease-free survival rates among patients expressing higher levels of TRPC3 mRNA were significantly better than the corresponding rates among patients expressing lower levels (P=0.004, P=0.002, respectively, by log-rank test). Multivariate Cox proportional hazard analyses revealed that tumor size (hazard ratio, 2.46; 95% confidence interval [CI], 1.06 to 5.79; P=0.036), n2 (hazard ratio, 3.81; 95% CI, 1.29 to 11.77; P=0.015) and TRPC3 (hazard ratio, 2.71; 95% CI, 1.33 to 5.59; P=0.006) were independent factors affecting the 5-year overall survival rate. Immunohistochemistry showed that the cytoplasm of tumor cells were stained positively for TRPC3. CONCLUSIONS: Higher levels of TRPC3 expression in tumor cells are an independent predictor of a better prognosis in patients with adenocarcinoma of the lung.

Interleukin-2 -330T>G genetic polymorphism associates with prognosis following surgery for thoracic esophageal squamous cell cancer.

BACKGROUND: Key molecules in the T helper (Th)1 and Th2 pathways underlie differential responses to the progression and surgical treatment of cancer. We investigated the relationship between Th1/Th2 cytokine polymorphism and prognosis in patients with thoracic esophageal squamous cell cancer. MATERIALS AND METHODS: The study participants were 159 Japanese patients treated for thoracic esophageal squamous cell cancer with curative esophagectomy at Akita University Hospital. We determined the associations between prognosis following esophagectomy and genetic polymorphisms in Th1 cytokines (interleukin [IL]-2, Interferon-γ, IL-12ß), and Th2 cytokines (IL-4, IL-10). RESULTS: IL-2 -330T>G genetic polymorphism was significantly associated with prognosis after esophagectomy. Univariate and multivariate analyses using a Cox proportional hazards model revealed that patients carrying the IL-2 -330G/G genotype had a significantly poorer prognosis than those carrying the T/G or T/T genotype. However, IL-2 -330T>G polymorphism was not associated with preoperative serum IL-2 levels. Moreover, interferon-γ, IL-12ß, IL-4, and IL-10 genetic polymorphisms were not associated with prognosis after esophagectomy for thoracic esophageal squamous cell cancer. CONCLUSIONS: It is suggested that IL-2 -330T>G genetic polymorphism may be a predictive factor for prognosis in patients receiving esophagectomy for thoracic esophageal squamous cell cancer.