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The purpose of the present study was to define the overexpression of cyclin D1 in superficial and advanced esophageal carcinomas and to investigate whether the expression of this molecule indicates a poor prognosis. This study included 41 patients with superficial esophageal carcinomas (Tis and T1) and 48 patients with advanced esophageal carcinomas (T2, T3, and T4). The expression of cyclin D1 in surgically resected specimens was evaluated immunohistochemically with a monoclonal antibody. Positive immunoreactivity was found in 31 of 89 cases (35%). Overexpression of cyclin D1 did not correlate with TNM classification or histologic type. Of the 48 patients with advanced esophageal carcinomas, 32 patients with cyclin D1-negative tumors survived longer than did 16 patients with cyclin D1-positive tumors (P = 0.0017). In contrast, we observed no survival difference between patients with cyclin D1-positive and -negative superficial esophageal carcinoma. These results suggest that cyclin D1 indicates a poor prognosis in cases of advanced esophageal carcinoma but not in cases of superficial esophageal carcinoma. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the tumor immune microenvironment (TIME) will facilitate the development of prognostic biomarkers and more effective therapeutic strategies in patients with lung cancer. However, little has been reported on the comprehensive evaluation of complex interactions among cancer cells, immune cells, and local immunosuppressive elements in the TIME., Methods: Whole-exome sequencing and RNA sequencing were carried out on 113 lung cancers. We performed single sample gene set enrichment analysis on TIME-related gene sets to develop a new scoring system (TIME score), consisting of T-score ( t umor proliferation), I-score (antitumor i mmunity) and S-score (immuno s uppression). Lung cancers were classified according to a combination of high or low T-score, I-score, and S-scores (eight groups; G1-8). Clinical and genomic features, and immune landscape were investigated among eight groups. The external data sets of 990 lung cancers from The Cancer Genome Atlas and 76 melanomas treated with immune checkpoint inhibitors (ICI) were utilized to evaluate TIME scoring and explore prognostic and predictive accuracy., Results: The representative histological type including adenocarcinoma and squamous cell carcinoma, and driver mutations such as epidermal growth factor receptor and TP53 mutations were different according to the T-score. The numbers of somatic mutations and predicted neoantigens were higher in T hi (G5-8) than T lo (G1-4) tumors. Immune selection pressure against neoantigen expression occurred only in T hi and was dampened in T hi /I lo (G5-6), possibly due to a reduced number of T cells with a high proportion of tumor specific but exhausted cells. T hi /I lo /S hi (G5) displayed the lowest immune responses by additional immune suppressive mechanisms. The T-score, I-score and S-scores were independent prognostic factors, with survival curves well separated into eight groups with G5 displaying the worst overall survival, while the opposite group T lo /I hi /S lo (G4) had the best prognosis. Several oncogenic signaling pathways influenced on T-score and I-scores but not S-score, and PI3K pathway alteration correlated with poor prognosis in accordance with higher T-score and lower I-score. Moreover, the TIME score predicted the efficacy of ICI in patients with melanoma., Conclusion: The TIME score capturing complex interactions among tumor proliferation, antitumor immunity and immunosuppression could be useful for prognostic predictions or selection of treatment strategies in patients with lung cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We report the first case of empyema necessitatis (EN) with pleural fistula and septic arthritis caused by Streptococcus agalactiae following blunt trauma., Presentation of the Case: A 46-year-old man with diabetes mellitus and a history of recent right rib fracture and right knee bruising presented with dyspnea and right knee pain. He was diagnosed with EN and underwent chest drainage, followed by open-window thoracotomy. Septic arthritis occurred on day 8 after thoracotomy. The chest wall wound healed after 3 months., Discussion: EN is a rare complication of empyema. In this patient, infection was invasive, causing necrotizing pneumonia with a pleural fistula. To our knowledge, there are no reports of group B streptococcal EN with a pleural fistula resulting from blunt chest trauma., Conclusion: Group B streptococcal infection might become invasive in immunocompromised patients, so careful follow-up for those patients is important., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We describe a case of resection of a solitary fibrous tumour of the pleura using video-assisted thoracic surgery and removal of the giant tumour using a subxiphoid incision without the need for minithoracotomy. Use of the subxiphoid approach as a retrieval port is simple and feasible., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The impact of coffee and green tea consumption on upper aerodigestive tract (UADT) cancer risk has not been established. Evaluation of the possible anticarcinogenic properties of their ingredients is confounded by the potential increase in risk owing to the high temperatures at which these beverages are generally consumed. We conducted a case-control study to evaluate the association between coffee and tea consumption and the risk of UADT cancer. The study enrolled 961 patients with UADT cancer and 2,883 noncancer outpatients who visited Aichi Cancer Center between 2001 and 2005. Information on coffee and green tea consumption and other lifestyle factors was collected via a self-administered questionnaire. Consumption of three or more cups of coffee per day had a significant inverse association with UADT cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55-0.96]. In contrast, consumption of three or more cups of green tea per day had a significant positive association with UADT cancer (OR 1.39, 95% CI 1.13-1.70). These associations were evident for head and neck cancer but not for esophageal cancer. The association of coffee consumption with head and neck cancer was observed only among never smokers and alcohol drinkers. Similarly, the association of green tea consumption was observed among never smokers and never alcohol drinkers. No change in these associations was seen on stratification by each confounding factors. These findings suggest that consumption of coffee might be associated with a decreased risk of UADT cancer, whereas that of green tea might be associated with an increased risk., (© 2013 UICC.)

Objectives: Although 30-day mortality rate is adapted to evaluate perioperative mortality after surgery, whether 90-day mortality rate adequately evaluates perioperative mortality remains unknown. Therefore, we analyzed 30- and 90-day mortality rates after pulmonary resection in patients with primary lung cancer., Methods: A total of 2207 pulmonary resections for primary lung cancer performed between 1996 and 2010 at the Aichi Cancer Center Hospital were analyzed and divided into two groups of almost equal number: the early period group (1070 patients, 1996-2004) and the late period group (1137 patients, 2005-2010). Sixty-six and 34 patients died within a year during the early and late periods, respectively. The causes of death (recurrence, bleeding, sudden death, respiratory failure, and adverse event of chemotherapy), and 30- and 90-day mortality rates were investigated., Results: The 30-/90-day mortality rates in the early and late period groups were 0.56/0.75 and 0.35/0.79 %, respectively. The postoperative survival days of 75 patients who died from recurrence within 1 year after pulmonary resection and 7 patients from bleeding or sudden death were more than 91 days and <30 days, respectively. The median postoperative survival of patients who died from respiratory failure was 67 days (range 20-142 days) in the early period and 100 days (range 47-149 days) in the late period. In the late period, it was difficult to assess perioperative mortality of pulmonary complications with 30-day mortality., Conclusions: A risk assessment of perioperative mortality after pulmonary resection should be performed using the 30- and 90-day mortality.

Purpose: Pulmonary metastases from gastric cancer are rare, and the role of surgery is unclear. The purpose of this study was to determine which patients with metachronous metastatic gastric cancer (MGC) might benefit from pulmonary resection., Methods: Between 1998 and 2011, 12 patients underwent 14 pulmonary resections for MGC. We reviewed their clinical courses and evaluated their radiological findings., Results: Solitary pulmonary lesions were identified for 11 metastases, and the remaining three showed multiple pulmonary lesions. Six patients received treatment for the metastases before pulmonary resection. Lobectomy was performed for five lesions and wedge resection was performed for the remaining nine lesions. At the median follow-up time of 23.0 months, four patients were alive without disease, and the median DFS following pulmonary resection was 6.6 months. The overall 5-year survival rate following pulmonary resection was 58.4 %. In a univariate analysis, the number of lesions and the tumor doubling time (TDT) were significant predictors of the DFS, although prior treatment was not a significant predictor of the DFS., Conclusion: Pulmonary resection for MGC might be an effective therapeutic option when there is a solitary metastatic lesion that has a long TDT, even if the patient has been previously treated for metastases.

Purpose: A paravertebral block (PVB) given via the surgical field can be safer and technically simpler than an epidural block (EP) for postoperative pain control. We conducted this clinical trial to confirm the effectiveness of PVB after thoracotomy., Methods: In this non-inferiority trial, patients were randomly assigned to receive PVB (n = 35) or EP (n = 35). The primary endpoint was the pain assessed using the visual analog scale (VAS) at rest, 2, 24, and 48 h after thoracotomy, with the non-inferiority margin set at 15 mm. The secondary end points were the pain assessed using the VAS on exercising and on coughing, 2, 24, and 48 h after surgery, respectively, and the complications and need for additional analgesic agents., Results: This trial revealed that PVB was not inferior to EP with respect to the primary end point: The mean VAS scores at rest, 2, 24, and 48 h after thoracotomy were 26.3, 10.8, and 8.3 mm in the PVB group and 23.6, 12.4, and 12.6 mm in the EP group, respectively (P < 0.01 for non-inferiority at all points). There were no significant differences between the groups in the incidence of complications or the need for additional analgesic agents., Conclusion: PVB may replace EP for postoperative pain control because of its technical simplicity and safety.

It is often difficult to differentiate metachronous primary lung cancers from local pulmonary recurrences when the histopathological findings are similar. A 43-year-old man underwent right upper lobectomy with lymph node dissection for primary lung adenocarcinoma (p-T2aN0M0, stage IB). Fifteen years later, he developed a lung nodule in his right middle lobe. The tumor was preoperatively thought to be a metachronous second primary lung adenocarcinoma, and was surgically resected. Histopathological findings for both tumors were of poorly differentiated adenocarcinoma with mucus production. Both tumors also harbored the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene (variant 3a+b). Based on this molecular finding, the pulmonary nodule was considered to be a recurrence after very long latent period., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Pulmonary ground-glass nodules are frequently encountered. The purpose of this study was to evaluate the natural history of them and to gain some insights on how to follow them up., Methods: We retrospectively studied patients with pulmonary nodules that met the following criteria: (1) tumor diameter of 3 cm or less, (2) ground-glass opacity proportion of 50% or more, and (3) observation without treatment for 6 months or more. Between 1999 and 2012, 108 pulmonary lesions in 61 patients fulfilled these criteria. We reevaluated their computed tomography images and analyzed changes in their size., Results: The tumors were 1 cm or lesser in size in 69 lesions, 1.1 cm to 2 cm in 34, and 2.1 cm to 3 cm in five. The proportion of solid lesions was 0% for 82 lesions, 1% to 25% for 19, and 26% to 50 % for seven. At the median observation period of 4.2 years, 29 lesions had become larger, whereas the remaining 79 had persisted without changing in size (±1 mm). The median size change in the nodules that grew was 7 mm (range, 2-32 mm). All 29 tumors began to grow within 3 years of their first observation: 1 year or lesser in 13 lesions, after 1.1 years to 2 years in 12, and after 2.1 years to 3 years in four., Conclusions: Some small lung lesions exhibiting ground-glass opacity persisted without changes in size, whereas others grew gradually. The tendency to grow was clear within the first 3 years in all cases. Therefore, we conclude that these lesions should be followed for at least 3 years.

Background: Cigarette smoking is the major cause for upper aerodigestive tract (UADT) cancers. The time to first cigarette (TTFC) of the day is a distinct indicator of nicotine dependence, but scanty information is available on its possible relation with UADT cancers (oral, oropharyngeal, hypopharyngeal, laryngeal, nasopharyngeal, and esophageal cancers)., Methods: This case-control study includes a total of 1,009 incident UADT cancer cases and 3,027 age- and sex-matched noncancer controls admitted to the Aichi Cancer Center (Nagoya, Japan) between 2001 and 2005. We estimated OR and 95% confidence intervals (CI) for TTFC using logistic regression models after adjustment for several potential confounders., Results: TTFC was inversely related to the risk of UADT cancer, and this association was consistent across subtypes of head and neck cancer and esophageal cancer. For all UADT cancers considered among ever smokers and after accurate allowance for smoking quantity and duration, besides other relevant covariates, compared with TTFC more than 60 minutes, the adjusted ORs were 1.40 (95% CI: 0.93-2.11) for 31 to 60 minutes, 1.76 (95% CI: 1.20-2.58) for 6 to 30 minutes, and 2.43 (95% CI: 1.64-3.61) for within 5 minutes. No significant heterogeneity was found in strata of sex, age, alcohol consumption, fruit and vegetable intake, and occupation for overall and site-specific analysis., Conclusion: Nicotine dependence, as indicated by the TTFC, is associated with increased risk of UADT cancers and is therefore an independent marker of exposure to smoking., Impact: Our result indicates more detailed risk evaluation of UADT cancers that is enabled by the TTFC., (©2012 AACR.)

Although the combination of tobacco smoking and alcohol drinking account for approximately 80% of upper aerodigestive tract (UADT) cancer risk, the role of dietary factors, including dairy products, in the risk of these cancers remains controversial. We aimed to evaluate the association between dairy product intake and UADT cancer risk in a Japanese population. We conducted a case-control study in 959 patients with UADT cancer and 2877 sex- and age-matched noncancer control subjects who visited the Aichi Cancer Center in Nagoya, Japan. Data on lifestyle factors, including diet, were obtained by self-administered questionnaire. Associations were assessed by multivariate logistic regression models that considered potential confounders. We found a significant inverse association between yoghurt intake and UADT cancer risk with multivariate-adjusted odds ratios and 95% confidence intervals for <1 time/week, ≥ 1 time/week and <1 time/day, and ≥ 1 time/day consumption of yoghurt of 0.70 (95% confidence interval: 0.54-0.91), 0.67 (0.54-0.84), and 0.73 (0.55-0.95) relative to nonconsumers (P trend=0.005). When stratified by primary tumor site, this association was significant among patients with hypopharyngeal, laryngeal, and esophageal cancer. However, we saw no significant association between milk or butter intake and UADT cancer risk. In this study, we found that a high intake of yoghurt may lower the risk of developing UADT cancer in a Japanese population. Further investigation of this association is warranted.

Introduction: The fusion oncogene of echinoderm microtubule-associated protein like 4 (EML4) and anaplastic lymphoma kinase (ALK) defines a new molecular subset of non-small-cell lung cancer. We explored the EML4-ALK gene in a relatively large cohort and reviewed the clinicoradiologic background of the patients., Methods: We studied 720 patients with lung adenocarcinoma. The clinicopathological characteristics of each patient were compared among the subgroups stratified by the EML4-ALK gene status. For radiographic evaluation, we scored the proportion of the ground-glass opacity (GGO) component and calculated the tumor disappearance rate (TDR) in each tumor in the cohort of 168 patients that were extracted by using a case-matching procedure., Results: Twenty-eight (3.9%) patients harbored the EML4-ALK gene. Younger age (p=0.001), no or light history of smoking (p=0.05) and normal serum carcinoembryonic antigen (CEA) level (p=0.04) were characteristics of the patients with EML4-ALK. No significant difference was observed for overall and disease free survival between the two groups. All but one tumor in the EML4-ALK-positive group exhibited no GGO, whereas half of the tumors (69/140 patients) in the EML4-ALK-negative group exhibited some GGO (p=0.0004). The mean TDRs were 0.33 and 0.54, respectively, which was significantly lower in the positive group (p=0.0006)., Conclusions: We identified younger age, no or light history of smoking, and normal serum CEA as clinical features of patients with EML4-ALK-positive lung adenocarcinoma. In addition, EML4-ALK-positive tumors exhibited a solid pattern on CT. These features may be of value in predicting for patient selection for ALK inhibition therapy in the absence of genetic screening., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT., Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of the 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition., Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage., Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Oral hygiene is attracting increasing attention as a potential risk factor for cancers. To investigate the association between toothbrushing frequency and upper aerodigestive tract (UADT) cancer, the authors conducted a large-scale case-control study., Methods: A total of 856 UADT cancer case participants and 2696 age- and sex-matched control subjects without cancer were included. Edentulous or participants with unknown frequency of toothbrushing or number of remaining teeth were excluded. Associations were assessed by odds ratios and 95% confidence intervals in logistic regression models with adjustment for potential confounders., Results: Compared with toothbrushing once per day, the adjusted odds ratio for brushing twice or more was 0.82 (95% confidence interval: 0.68, 0.99) whereas that for not brushing was 1.79 (0.79, 4.05). This association was observed especially in subjects who had a history of heavy smoking or drinking., Conclusions: The authors suggest that toothbrushing could have a protective effect for UADT cancer., (Copyright © 2010 Wiley Periodicals, Inc.)

The dual puncture is one of the diseaseful complications at the induction of the epidural anesthesia, which causes severe symptoms of intracranial hypotension such as headache and nausea. The clinical courses of 3 patients with the dual puncture symptoms after pulmonary resections were retrospectively reviewed, and the effect of the continuous epidural saline infusion treatment (CESI) for the dual puncture was evaluated. Pneumococcal empyema developed in 1 patient who had been treated with conservative management. In contrast, the symptoms of the others who were treated with the CESI were quickly recovered or were effectively prevented. This report strongly suggested that the CESI was convenient and effective treatment for dual punctune symptoms by suppressing the cerebrospinal fluid leakage by elevation of the fluid pressure in the extradural space.

Background: This study aimed to evaluate the efficacy of docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer., Patients and Methods: We retrospectively analyzed data regarding thirty patients with borderline-resectable T4 tumor who received either DCF or cisplatin plus 5-fluorouracil (FP) as induction chemotherapy., Results: The overall response rate was significantly better for the DCF group than the FP group. In the DCF group, 6/16 patients achieved a grade 2 histological post-chemotherapeutic effect after treatment, compared to 1/14 in FP group. Except for myelotoxicity, no other significant differences in toxicity were observed during induction chemotherapy between groups. The DCF regimen did not result in increased postoperative complications compared to the FP regimen. Postoperative recurrence or distant metastasis was observed in 7/10 of FP patients and 5/12 of DCF patients., Conclusion: DCF induction chemotherapy may be an option for conversion therapy of initially unresectable, locally advanced esophageal cancer.

Purpose: Carcinoembryonic antigen (CEA) is a tumor marker widely used for nonsmall cell lung cancer (NSCLC). The aim of this study was to evaluate changes in serum CEA levels as a surrogate marker for tumor response to chemotherapy in NSCLC., Methods: From 1995 through 2005, we retrospectively analyzed 24 NSCLC patients who had high serum CEA levels (>5 ng/ml) and who received chemotherapy followed by surgery. We compared serum CEA levels with tumor response, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) or World Health Organization (WHO) criteria, as well as with histological response., Results: Serum CEA levels after chemotherapy significantly decreased in patients who achieved partial response, defined by RECIST or WHO criteria (p = 0.004 and p = 0.008, respectively), when compared with the CEA levels before chemotherapy. In contrast, there was no significant difference in CEA levels in patients with either stable disease or no response to chemotherapy. They decreased significantly, however, in patients in whom less than one-third of tumor cells was viable by pathological examination, but not in patients in whom more than a third was viable (p = 0.008). Using the receiver-operating characteristic (ROC) curve analysis, we found that a 60% reduction of CEA levels was an appropriate cutoff value in predicting a good response to chemotherapy. When the value was set at that level, the sensitivity of CEA for RECIST was 82%, and the specificity was 69%., Conclusion: Serum CEA concentration was a useful surrogate marker for the evaluation of tumor response to chemotherapy and seemed to be comparable with RECIST in NSCLC patients who had elevated CEA levels prior to treatment.

Some Japanese exhibit facial flushing after drinking alcohol. Facial flushing was considered to be caused by acetaldehydemia. The concentration of blood acetaldehyde was concerned with the catalytic activity of acetaldehyde dehydrogenase (ALDH). Acetaldehyde dehydrogenase (ALDH)-2 polymorphism (rs671, Glu504Lys) was known to be associated with upper aerodigestive tract (UAT) cancer due to modulation of ALDH2 enzyme activity. It remains controversial whether facial flushing is useful in predicting UAT cancer risk as a surrogate marker of ALDH2 polymorphism. We conducted a case-control study to assess the risk of UAT cancer and facial flushing and ALDH2 polymorphism. Cases and controls were 585 UAT cancer patients and matched 1170 noncancer outpatients of Aichi Cancer Center Hospital. Information on facial flushing and other lifestyle factors was collected via a self-administered questionnaire. Association between facial flushing, polymorphism, and UAT cancer was assessed by odds ratios and 95% confidence intervals by using conditional logistic regression models. The facial flushing had no significant association with UAT cancer, although ALDH2 Lys allele was significantly associated with UAT cancer. No significant interaction between facial flushing and alcohol consumption was observed in this study, whereas ALDH2 Lys allele had significant association with UAT cancer. The misclassification between facial flushing and ALDH2 genotype was observed in 18% of controls with ALDH2 Glu/Glu genotype and in 16% of controls with ALDH2 Glu/Lys genotype. Facial flushing was less useful to predict UAT cancer risk than genotyping ALDH2 polymorphism.

Objective: Lobectomy with systematic complete mediastinal lymph node dissection is standard surgical treatment for localized non-small cell lung cancer. However, selective mediastinal lymph node dissection based on lobe-specific metastases (selective dissection) has often been performed. This study was designed to evaluate the validity of the selective lymph node dissection., Methods: From 1995 through 2003, 625 patients in our hospital had surgery for complete mediastinal lymph node dissection and 147 for selective dissection. We evaluated whether selective dissection adversely affected overall survival. To minimize possible biases due to confounding by treatment indication, we performed a retrospective cohort analysis by applying a propensity score. The propensity score was calculated by logistic regression based on 15 factors available that were potentially associated with treatment indication. Patients were divided into 4 groups according to quartile, and comparison between selective dissection and complete mediastinal lymph node dissection was made using propensity score quartile-stratified Cox proportional hazard models., Results: Comparison of baseline characteristics between patients having selective dissection and patients having complete mediastinal lymph node dissection according to propensity score quartile supported comparability of the 2 groups. The 5-year overall survival rates were 76.0% for selective dissection versus 71.9% for complete mediastinal lymph node dissection. The 5-year survival probabilities stratified by propensity score quartile consistently showed no marked difference. In multivariate models, there was no significant difference between the 2 groups (hazard ratio = 1.17, P = .500) as also seen in the analysis without propensity score (hazard ratio = 1.06; 95% confidence interval, 0.68-1.64; P = .810). Therefore, selective dissection showed no significant impact on poor survival compared with complete mediastinal lymph node dissection., Conclusions: Selective lymph node dissection did not worsen the survival of patients with non-small cell lung cancer., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Smoking is a well-known risk factor for esophageal cancer. However, there are few reports that directly evaluate smoking as a prognostic factor for esophageal cancer. Moreover, scarce evidence is available on whether smoking interacts with major treatment modalities of esophageal cancer. In this study we retrospectively analyzed 364 patients with esophageal squamous cell cancer who were treated between 2001 and 2005 at our institution. Background characteristics, including smoking history, were analyzed as potential prognostic factors. Of the 363 patients, 76 patients (20.9%) were non-smokers or light smokers (non-heavy), whereas 287 patients (79.1%) were heavy smokers. The 5-year survival rate for non-heavy smokers and heavy smokers was 61.8% (95% confidence interval [CI]: 49.1-72.2) vs 44.6% (95% CI: 38.2-50.9), respectively. In a multivariate Cox model (adjusted for age, gender, performance status, alcohol consumption, histology, tumor length, International Union Against Cancer [UICC] stage, and treatment), the hazard ratio for heavy smokers in comparison with non-heavy smokers was 1.73 (95% CI: 1.12-2.68; P = 0.013). When we stratified by treatment method, heavy smoking was significantly associated with poor survival only in patients treated by chemoradiotherapy (hazard ratio, 2.43; 95% CI: 1.38-4.27; P = 0.002). More importantly, a statistically significant interaction between heavy smoking history and treatment modality was observed (P = 0.041). Our results indicated that smoking history is strongly associated with poor prognosis in patients with esophageal cancer, especially those treated by chemoradiotherapy. Further investigation is warranted to explain this different prognosis.

Introduction: In clinical practice, peripheral small-sized lung cancers with positive mediastinal lymph nodes are sometimes detected. To understand the characteristics of these aggressive tumors, we reviewed the clinicopathological features of small-sized non-small cell lung cancer patients with mediastinal lymph node metastasis resected in our institution., Methods: We studied 360 patients with small-sized lung lesions with a maximum diameter of 2 cm or less. The clinicopathological characteristics of each patient were reviewed and compared among the subgroups, which were stratified according to pathological nodal status., Results: 21 patients (5.8%) had a positive mediastinal lymph node. Among them, 17 patients had lung lesions larger than 1.5 cm. No mediastinal nodal involvement was found in patients with squamous cell carcinomas. In contrast, mediastinal nodal involvement was significantly common in patients with poorly differentiated carcinoma (P=0.004) and high serum carcinoembryonic antigen levels detected during preoperative evaluation (P=0.006). None of the 14 patients with upper lobe tumor had a positive subcarinal lymph node. Lower lobe tumors frequently developed extensive multiple-level involvement, which included the upper mediastinum. Radiographic evaluation of pN2 patients using computed tomography revealed a total absence of ground-glass opacity, or the presence of a small area of ground-glass opacity., Conclusions: Most small-sized non-small cell lung cancer cases with mediastinal lymph node metastasis were invasive adenocarcinoma with poor differentiation, which usually showed a solid shadow without ground-glass opacity on computed tomography.

Alcohol intake is positively associated with the risk of upper aerodigestive tract (UAT) cancer. The genes that encode alcohol-metabolizing enzymes, primarily alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH), are polymorphic. In Caucasians, significant associations between polymorphisms in ADH1B (rs1229984) and ADH1C (rs698 and rs1693482), and UAT cancer have been observed, despite strong linkage disequilibrium among them. Moreover, UAT cancer was significantly associated with rs1573496 in ADH7, and not with rs1984362 in ADH4. However, little evidence is available concerning ADH4 or ADH7 polymorphisms in Asian populations. We conducted a matched case-control study to clarify the role of ADH polymorphisms in a Japanese population. Cases and controls were 585 patients with UAT cancer and 1,170 noncancer outpatients. Genotyping for ADHs and ALDH2 was done using TaqMan assays. Associations between polymorphisms and UAT cancer were assessed by odds ratios and 95% confidence intervals using conditional logistic regression models that adjusted for age, sex, smoking, drinking, and ALDH2. Adjusted odds ratios were significant for rs4148887 and rs3805322 in ADH4, rs1229984 in ADH1B, rs698 and rs1693482 in ADH1C, and rs284787, rs1154460, and rs3737482 in ADH7. We also observed that ADH7 rs3737482 and ADH4 rs4148887 had independently and statistically significant effects on UAT cancer. The magnitude of effect of these ADH polymorphisms was greater in subjects who were heavy drinkers, heavy smokers, and had esophageal cancer. These findings show that multiple ADH gene polymorphisms were associated with UAT cancer in this Japanese population. Further studies in various ethnicities are required.

Introduction: The efficacy of high-dose (1250 mg/d) gefitinib for the treatment of leptomeningeal metastasis in a patient with lung cancer harboring a mutation in the epidermal growth factor receptor (EGFR) gene was previously reported. We speculate that erlotinib, instead of high dose of gefitinib, may be also effective for the treatment of central nervous system (CNS) lesions, as trough serum concentration of erlotinib is nine times higher than that of gefitinib., Patients and Methods: Patients with lung cancer in whom CNS lesions developed after an initial good response to gefitinib for extra CNS lesions were enrolled in the study. Tumor response, performance status, neurologic symptoms, and survival were retrospectively evaluated., Results: All seven patients had EGFR mutations in their primary tumors except one patient. The median interval between gefitinib withdrawal and erlotinib administration was 5 days. Three patients showed partial response, three had stable disease, and one had progressive disease. Performance status and symptoms improved in five patients. The overall survival from the initiation of erlotinib treatment ranged from 15 to 530 days (median, 88 days)., Conclusions: Erlotinib was a reasonable option for the treatment of CNS diseases that appeared after a good initial response of extra CNS disease to gefitinib.

We have been using a silastic drain [Blake drain (BD)] after pulmonary resection by different placement methods and reviewed the daily amount of drainage in each patient. A 19-Fr BD was placed for each of 110 patients. First, a drain was inserted from the anterior chest wall and the tip reached the dorsal part of the diaphragm [anterior-to-posterior (AP)]. For the others [posterior-to-anterior (PA); n=37], we inserted a drain from the lower intercostal space, turned it around the apex and placed its tip in the lower front. Patients in the AP group included those placed under a water seal (AP-WS; n=43) or suction (AP-SC; n=30). The reference group consisted of 68 patients with a 32-Fr plastic drain during the same period [conventional drains (CD)]. The amount of drainage on the day of surgery in the PA group was significantly higher than that in the AP-WS group (P<0.0001) and similar to that in the CD group (P=0.54). The mean amount of drainage on postoperative day 1 and total amounts accumulating during drain placement showed no significant differences between the four groups. A BD placed using a PA approach with suction might be efficient for drainage.

Background: The Blake drain (BD) has recently begun to be used as a chest tube after pulmonary resection; however, its fluid drainage and air evacuation characteristics remain unclear. We compared the performance of the 19F BD with that of the 32F conventional drain (CD)., Methods: We studied 148 consecutive patients (74 with BD; 74 with CD) who underwent pulmonary resection. Postoperative drainage rates (daily drainage and total drainage) were analyzed to assess fluid drainage. Air evacuation was evaluated to determine whether subcutaneous emphysema or insufficient residual lung expansion developed when air leakage occurred. The BD group was initially managed with water seal or suction, whereas the CD group was managed with water seal. Furthermore, we experimentally measured the evacuation pressure required to expel a constant volume of air through various chest tubes to determine basic air evaluation performance of the tubes., Results: Drainage rates on the operative day were significantly lower in the BD group than in the CD group, but were similar in both groups on the following day with greater variation in the water-sealed BD group. Among cases with air leakage, air evacuation insufficiency was more frequent in the BD group (16 of 22, 73%) than in the CD group (4 of 17, 24%; p = 0.004). The experiment revealed that air evacuation performance of the 19F BD was equivalent to that of the 12F CD, indicating that the BD requires higher intrathoracic pressure for air evacuation., Conclusions: Suction is required for the BD to obtain fluid drainage performance comparable to that of the water-sealed CD. When air leakage occurs, air evacuation by the BD tends to be insufficient, irrespective of suction conditions.

Objective: In patients with thoracic/abdominal esophageal cancer with no clinical evidence of lymph node metastasis, there is no consensus about whether the irradiation field should include regional lymph nodes. In this study, the extent of the irradiation field for clinical stage T1-3N0M0 esophageal cancer was determined based on the postoperative pathological results., Methods: From July 1989 to June 2008, 103 patients diagnosed with clinical stage T1-3N0M0 thoracic/abdominal esophageal cancer underwent standard esophagectomy and regional lymph node dissection at the Aichi Cancer Center Hospital. Of these 103 patients, the pathological results of the resected specimens could be confirmed in 95 (92%) patients. The pathological lymphatic spread was reviewed retrospectively, and the extent of the irradiation field was determined based on the postoperative pathological results., Results: Of 95 patients with clinical stage T1-3N0M0 esophageal cancer, 40 (42.1%) had pathological lymph node metastases, and the frequency of nodal metastases was studied by tumor location. The rates of lymph node metastases for the upper, middle, lower and abdominal esophagus were 37.5%, 32.5%, 46% and 70%, respectively., Conclusions: Pathological lymph nodes metastases are often seen after operation in clinical stage T1-3N0M0 esophageal cancer. In the present study, the optimal lymph nodes to be included in the irradiation field were determined according to the primary site in the esophagus.

Background: In advanced non-small cell lung cancer(NSCLC), the standard treatment is chemotherapy with platinum doublet. Gemcitabine (GEM)is one of the major drugs administered in combination with platinum. We studied the feasibility and response of GEM and Carboplatin(CBDCA)biweekly combination chemotherapy for patients with / postoperative recurrence NSCLC., Method: Patients received GEM(1,000 mg/m(2))over 30 minutes and CBDCA(AUC =3)over 60 minutes intravenously on day 1 biweekly. Response was evaluated with RECIST., Result: Between April 2005 and December 2006 thirteen patients with PS 0 or 1 were entered in the study. All patients received 4 or more cycles. Eight patients received 8 cycles. Of them, only two patients required dose-reduction for hematologic toxicity. / Grade 3/4 hematologic or non-hematologic toxicities and more than grade 2 thrombocytopenia did not occur in any patients. The overall response rate was 20%. SD was seen in 6 patients., Conclusion: GEM and CBDCA biweekly combination chemotherapy is a well-tolerated regimen with promising activity against NSCLC.