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Introduction: Recent advances in artificial intelligence (AI) have been substantial. We investigated the effectiveness of an online meeting in which normal older adults (otokai) used a music‐generative AI that transforms text to music (Music Trinity Generative Algorithm‐Human Refined [MusicTGA‐HR]). Methods: One hundred eighteen community‐dwelling, cognitively normal older adults were recruited through the internet (64 men, 54 women; mean age: 69.4 ± 4.4 years). Using MusicTGA‐HR, the participants chose music that they thought was the most suitable to a given theme. We established 11 classes of 7–10 members and one instructor each. Each class held an online meeting once a week, and each participant presented the music they chose. The other participants and the instructor then commented on the music. Neuropsychological assessments were performed before and after the intervention for 6 months, and the results before and after the intervention were statistically analyzed. Results: The category and letter word fluencies (WFs) were significantly improved (category WF: p =.003; letter WF: p =.036), and the time of the Trail‐Making Test‐B was also significantly shortened (p =.039). The Brain Assessment, an online cognitive test we developed, showed significant improvement in the memory of numbers (p <.001). Conclusion: The online meeting of the otokai, which used music‐generative AI, improved the frontal lobe function and memory of independent normal older adults. [ABSTRACT FROM AUTHOR]

Background: We previously reported the enhanced effects of physical exercise when combined with music (ExM) on cognitive function in community-dwelling normal elderly people compared to exercise alone. Following that study, participants voluntarily continued the ExM classes for 5 years.Objective: To identify the effects of a 5-year ExM intervention on cognitive function in normal elderly people.Methods: Fifty-four subjects continued the ExM classes once a week for 5 years (ExM group). Thirty-three subjects retired from the ExM class during the 5 years (Retired group). Twenty-one subjects never participated in any intervention over the 5 years (No-exercise group). Cognitive function and ADLs were assessed using neuropsychological batteries and the functional independence measure (FIM), respectively. The voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) was used to investigate medial temporal lobe atrophy.Results: Analyses of the raw scores after the 5-year intervention showed significant differences between the ExM and No-exercise groups in their MMSE scores, Raven's colored progressive matrices (RCPM) time, logical memory (LM)-I, as well as the total and physical exercise sub-scores of the FIM. Analysis of subjects aged 70- 79 years at the beginning of this project showed significantly quicker performance on the RCPM in the ExM compared to No-exercise groups. The correlation coefficients between the total number of ExM sessions attended and the degree of changes in physical, neuropsychological, and VSRAD scores were significant for RCPM performance time and LM-I scores.Conclusion: Long-term ExM intervention reinforces multifaceted cognitive function in normal elderly people, and is especially beneficial for psychomotor speed. [ABSTRACT FROM AUTHOR]

Background: Physical exercise has positive effects on cognitive function in elderly people. It is unknown, however, if combinations of non-pharmaceutical interventions can produce more benefits than single ones. This study aimed to identify if physical exercise combined with music improves cognitive function in normal elderly people more than exercise alone. Methods: We enrolled 119 subjects (age 65–84 years old). Forty subjects performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM group), developed by YAMAHA Music Foundation; 40 subjects performed the same exercise without music (Ex group); 39 subjects were the control group (Cont group). Before and after the year-long intervention, each patient was assessed by neuropsychological batteries. MRIs were performed before and after intervention; the Voxel-based Specific Regional analysis system for Alzheimer's Disease (VSRAD) was used to assess medial temporal lobe atrophy. Results: Analysis of variance (ANOVA) was significant only in visuospatial function. The multiple comparison (ExM vs. Ex, ExM vs. Cont, Ex vs. Cont) was significant between the ExM and Cont group. Intra-group analyses before and after intervention revealed significant improvement in visuospatial function in the ExM group, and significant improvements in other batteries in all three groups. The VSRAD score significantly worsened in the ExM and Ex groups. Conclusions: Physical exercise combined with music produced more positive effects on cognitive function in elderly people than exercise alone. We attributed this improvement to the multifaceted nature of combining physical exercise with music, which can act simultaneously as both cognitive and physical training. Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000012148 [ABSTRACT FROM AUTHOR]

The pathogenesis of reexpansion pulmonary edema is not yet fully understood. We therefore studied its mechanism in a rat model in which the left lung was collapsed by bronchial occlusion for 1 h and then reexpanded and ventilated for an additional 3 h. We then evaluated the production of reactive oxygen species in the lungs using fluorescent imaging and cerium deposition electron microscopic techniques and the incidence of apoptosis using the TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. We found that pulmonary reexpansion induced production of reactive oxygen species and then apoptosis, mainly in endothelial and alveolar type II epithelial cells. Endothelial cells and alveolar type I and II epithelial cells in the reexpanded lung were positive for TUNEL and cleaved caspase-3. DNA fragmentation was also observed in the reexpanded lung. In addition, wet-dry ratios obtained with reexpanded lungs were significantly higher than those obtained with control lungs, indicating increased fluid content. All of these effects were attenuated by pretreating rats with a specific xanthine oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one. It thus appears that pulmonary reexpansion activates xanthine oxidase in both endothelial and alveolar type II epithelial cells and that the reactive oxygen species produced by the enzyme induce apoptosis among the endothelial and alveolar type I and II epithelial cells that make up the pulmonary water-air barrier, leading to reexpansion pulmonary edema. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that combined non-pharmacological interventions are more beneficial than single interventions for primary and secondary prevention of dementia. We previously reported enhanced effects of physical exercise with music (ExM) on cognitive function in normal elderly people compared to exercise alone.Objective: To identify if ExM improves cognitive function and activities of daily livings (ADLs) in dementia patients over cognitive stimulation (CS).Methods: We enrolled 85 patients with mild to moderate dementia. Forty-three subjects performed ExM developed by the Yamaha Music Foundation, and 42 subjects performed cognitive stimulation using portable game consoles and drills involving easy calculations, mazes, and mistake-searching in pictures. Interventions were performed once a week for 40 minutes. Before and after the six-month intervention, patients were assessed using neuropsychological batteries, and ADLs were assessed by patients' caregivers using the functional independence measure (FIM). Voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) was used to assess medial temporal lobe atrophy.Results: Twenty-three subjects dropped out during the intervention. Thirty-one patients from each group were analyzed. Post-intervention, both groups showed significantly improved visuospatial function. Significant benefits were observed in psychomotor speed or memory in the ExM or CS groups, respectively. FIM scores, reflecting ADLs, and VSRAD scores were significantly preserved in the ExM group, but significantly worsened in the CS group.Conclusions: ExM produced greater positive effects on cognitive function and ADLs in patients with mild to moderate dementia than CS, excluding memory. Optimal interventions for dementia will likely be achieved by combining ExMand CS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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)-β is known to be produced by progressor tumors, and excessive TGF-β contributes to a pathological excess of tissue fibrosis. TGF-β1 is the most abundant isoform, and its expression is a key event fostering tumor invasion and metastasis. We therefore analyzed the relationship between TGF-β1 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-β1 antibody. The TGF-β1 status was assessed immunohistochemically using the Allred 8-unit system. Results: The rates of TGF-β1 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-β1 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents a surgical procedure using the omental and rectus abdominis muscular flaps to close an esophago-bronchial fistula. Utilising a stapler and inserted omental and left rectus abdominis muscular flaps, primary closure on both sides of the esophagus and lung was performed. Result of the procedure showed that the use of omental and rectus abdominis muscular flaps completely isolated the lower esophagus from the bronchus.

Zinc Finger Homeobox 3 (ZFHX3) was first identified as a suppressor of alpha-fetoprotein gene and is a good candidate for the 16q22 tumor suppressor. In this study we investigated the relationship between tumoral ZFHX3 mRNA expression and the clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). We used semi-quantitative real time reverse transcription polymerase chain reaction to assess expression of ZFHX3 mRNA in tumor samples from 140 patients with NSCLC. We found that the 5-year overall survival rate among patients weakly expressing ZFHX3 was significantly poorer than among those expressing higher levels of ZFHX3 (P< 0.0001 by log-rank test). Multivariate logistic regression analysis revealed being lower ZFHX3 expression are independent predictors of lymph node metastasis. With low-ZFHX3 tumors, there was a significantly (P=0.009) greater (7.39-fold higher) risk of lymph node metastasis. Multivariate Cox proportional hazard analyses revealed that being lower ZFHX3 expression (Hazard ratio, 4.42; 95% CI, 2.09-8.92; p=0.0002) were independent factors affecting 5-year overall survival. Ratio of ZFHX3 mRNA in tumor against normal lung in low-ZFHX3 tumor was lower than in high-ZFHX3 tumor. In conclusion, suppression of ZFHX3 expression in tumor cells decreases the survival rate among patients with NSCLC. [ABSTRACT FROM AUTHOR]

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. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Benign esophageal strictures are generally treated with medication and balloon dilation; however, when repeated dilations fail, surgery is the only option. When performing surgery for benign esophageal stricture in young patients, it is important to consider not only the surgical stress and likelihood of complications but also digestive function after reconstruction, the durability of the reconstruction, and the potential for cancerous change in the reconstructed organs. We describe how we treated a 14-year-old boy with benign esophageal stricture by performing transhiatal esophagectomy assisted by mediastinoscopy, preserving the whole stomach and vagus nerve, and interposing pedicled jejunum between the cervical esophagus and stomach through a posterior mediastinal route, with good long-term results. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Post-surgical interstitial pneumonia (IP) is a part of postoperative acute respiratory distress syndrome (ARDS). Some cases of ARDS may be an acute exacerbation of idiopathic pulmonary fibrosis (IPF) that is generally not recognised as IPF prior to surgery. In this study, we evaluated IP on preoperative computed tomography (CT) and histopathological findings in patients who underwent thoracic surgery, and attempted to identify high-risk patients who might develop postoperative ARDS. Methods: A retrospective review of preoperative CT and histopathological examination was performed in 487 patients who underwent lobectomy for primary lung cancer at our institute. Results: The incidence of ARDS was 2.05%, and histopathological finding of IP was the only predictor of ARDS (P =0.038, odds ratio (OR)=6.89). The incidence of IP on histopathological examination was 9.7% for all cases of lung cancer; and the incidence of ARDS in the IP-positive group (31.8%) was significantly different from that in the IP-negative group (1.5%) (P <0.05). However, in 85.7% of patients with ARDS, who were histologically IP-positive, IP was masked by emphysematous findings and thus not detected on preoperative CT. Conclusions: In this study, histopathological finding of IP was the only predictor of ARDS; however, it was difficult to identify preoperatively because emphysematous change was also present in the majority of cases, which masks the findings of IP on CT. If identification of the high-risk case of ARDS is insisted upon, screening the presence or absence of IP (e.g., just in the patients with emphysema or IP finding on CT) by histopathological examination, as the need arises, after surgery using resected lung might be one of the additional methods of identifying those at high risk of ARDS. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

1. An intraoral annihilation enteric-coated preparation of lansoprazole is often administered via intestinal fistula. The purpose of this study was to determine the plasma concentrations of lansoprazole enantiomers after enteral administration in subjects with cytochrome P4502C19 (CYP2C19) and ABCB1 C3435T genotypes. 2. Fifty-one patients who underwent a curative oesophagectomy for oesophageal cancer were enrolled in this study. After a single enteral dose of racemic lansoprazole (30 mg), plasma concentrations of lansoprazole enantiomers were measured 4 h post-dose (C4h). 3. There were significant differences in the C4h of (R)- and (S)-lansoprazole and the R/S-enantiomer ratio for three CYP2C19 genotype groups (*1/*1, *1/*2 ± *1/*3, and *2/*2 ± *2/*3 ± *3/*3 (poor metabolizers (PMs)), but not the ABCB1 C3435T genotypes. In a stepwise forward selection multiple regression analysis, the C4h of (R)- and (S)-lansoprazole were associated with CYP2C19 PMs (p = 0.0005 and < 0.0001 respectively) and age (p = 0.0040 and 0.0121 respectively), while the R/S-enantiomer ratio was associated with CYP2C19*1/*1 (p = 0.0191) and CYP2C19 PMs (p = 0.0426). 4. Direct administration to the jejunum is unaffected by residence time in the stomach and the gastric emptying rate. With enteral administration, CYP2C19 phenotyping of patients using the lansoprazole R/S enantiomer index at C4h could be possible. [ABSTRACT FROM AUTHOR]

Stress hyperglycemia refers to the transient hyperglycemia seen during illness and is usually restricted to patients without previous evidence of diabetes. The influence of genetics on surgery-induced hyperglycemia remains only partially understood. The study participants were Japanese patients treated for thoracic esophageal cancer with curative esophagectomy at Akita University Hospital between 2003 and 2007. We determined the associations between esophagectomy-induced stress hyperglycemia (≥30 mg/dl increases in blood glucose during surgery) and genetic polymorphisms for C-reactive protein (CRP), tumor necrosis factor (TNF)-α, -β, interferon-γ, transforming growth factor-β1, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-6 receptors, IL-10, IL-12β, adiponectin, and peroxisome proliferator-activated receptor-γ. In 28 (46%) patients, blood glucose levels increased more than 30 mg/dl during surgery. Among the genetic polymorphisms tested, CRP − 717C> T was significantly associated with stress hyperglycemia during esophagectomy. Multivariate logistic regression revealed that patients with the CRP − 717T/T genotype had a significantly greater risk of developing surgery-induced hyperglycemia than those with the CRP − 717C/T genotype. Stress hyperglycemia was also significantly associated with postoperative infectious complications and duration of intensive care unit stay. It is suggested that CRP − 717 C> T genetic polymorphism may be a predictive factor for stress hyperglycemia in patients receiving esophagectomy for thoracic esophageal cancer. [ABSTRACT FROM AUTHOR]

Abstract: Regenerating gene (REG) I plays important roles in cancer cell biology. The purpose of this study was to determine whether REG I affects cytokine production in cancer cells. We transfected TE-5 and TE-9 squamous esophageal cancer cells with REG Iα and Iβ and examined its effects on cytokine expression. We found that transfecting TE-5 and TE-9 cells with REG I Iα and Iβ led to significantly increased expression of interleukin (IL)-6 mRNA and protein, but it had little or no effect on expression of IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17A, interferon-γ, tumor necrosis factor-α, granulocyte-colony stimulating factor or transforming growth factor-β1. The elevated IL-6 expression seen in REG Iα transfectants was silenced by small interfering RNA-mediated knockdown. These finding suggest that REG I may act through IL-6 to exert effects on squamous esophageal cancer cell biology. [Copyright &y& Elsevier]

Background: Little is known about how C-reactive protein (CRP) genetic polymorphisms influence the rise in serum CRP levels seen after surgery. The purpose of this study was to assess the association between CRP polymorphisms and acute-phase serum CRP levels after esophagectomy for thoracic esophageal cancer. Study Design: We enrolled 110 patients who underwent curative esophagectomy without neoadjuvant treatment between 2003 and 2008. Using peripheral blood samples collected from the patients, polymorphisms for CRP, tumor necrosis factor, interferon-γ, tumor growth factor-β1, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12β were all investigated to determine which, if any, affect postoperative serum CRP levels and clinical outcomes. Results: Although preoperative serum CRP levels did not differ, 12 hours after esophagectomy, serum CRP levels were significantly higher in patients carrying the CRP 1059G/G genotype than in those with the 1059G/C genotype (111 ± 35 mg/L versus 78 ± 17 mg/L; p = 0.0266), and after 36 hours CRP levels remained higher in those with the 1059G/G genotype (217 ± 63 mg/L versus 140 ± 51 mg/L; p = 0.0020). Logistic regression models revealed that patients carrying the CRP 1059G/G genotype had a significantly higher likelihood of a postesophagectomy increase in serum CRP, although the CRP 1059G>C genetic polymorphism had no effect on clinical outcomes. None of the other cytokine genetic polymorphisms influenced postoperative serum CRP levels. Conclusions: Our findings suggest that the CRP 1059G>C genetic polymorphism is 1 determinant of serum CRP levels after major surgery. [Copyright &y& Elsevier]

Following esophagectomy, tracheobronchial lesions (TBLs) can occur as a result of ischemia caused by extensive dissection around the tracheobronchus. In this study we assessed the causes and clinical features of these complications, paying particular attention to lymph node (LN)-related factors. Between January 2000 and March 2007, 305 consecutive patients underwent subtotal esophagectomy using a transthoracic approach with LN dissection for thoracic esophageal cancer. TBLs, including erosions, ulcers, and fistulae, without traumatic injury during the operation, were detected during bronchoscopic examinations performed twice daily after the operation. The correlation between TBLs and tumor or surgical factors were analyzed. TBLs were observed in 14 patients, accounting for an overall incidence of 5%; these included 6 fistulae, 5 ulcers, and 3 erosions. Cases with TBLs significantly more often involved three-field LN dissections (3FLD) than those without TBLs. Six (43%) patients with TBLs had more than four metastatic lymph nodes, while 9 (64%) had cervical and upper-mediastinal LN metastasis ( p = 0.034 and 0.041, respectively). More than 60 LNs were dissected from 10 (71%) patients with TBLs ( p = 0.021), and logistic regression analysis revealed that dissection of more than 60 lymph nodes and 3FLD were independent predictors of TBLs. Esophageal cancer patients requiring extensive LN dissection of more than 60 nodes and/or 3FLD have an increased risk of developing a TBL during their postoperative course. [ABSTRACT FROM AUTHOR]

Three-field lymph node dissection for thoracic esophageal cancer is associated with high morbidity and reduced quality of life after surgery. Consequently, minimized lymphadenectomy would be desirable, if appropriate. In the present study, we retrospectively analyzed the status of involved nodes and the direction of metastatic lymphatic flow from tumors into involved nodes to determine whether submucosal squamous cell esophageal cancers are potential candidates for minimized lymphadenectomy. We enrolled 199 patients who received esophagectomy with extensive lymph node dissection between 1989 and 2005 and retrospectively analyzed their prognoses, distribution of solitary metastatic lymph nodes, and the direction of metastatic lymphatic flow from the tumor, taking into consideration tumor location and depth. Of these patients with submucosal cancers, 83% had 1 or 2 involved nodes, and their esophageal cancer-specific 5-year survival rate was 66%. Solitary lymph node metastasis did not occur in neck lymph nodes in lower thoracic submucosal esophageal cancers, and the direction of metastatic lymphatic flow from the tumor was almost always in one direction. By contrast, T2–4 cancers with 2–4 involved nodes had bidirectional metastatic lymphatic flow from the tumor. There was a difference in the status of lymph node metastasis and the direction of metastatic lymphatic flow from tumors into involved nodes between submucosal and T2–4 thoracic squamous cell esophageal cancers. This analysis may be useful for developing an approach to minimized lymphadenectomy for thoracic esophageal cancers. [ABSTRACT FROM AUTHOR]

Purpose: The criteria for the diagnosis of lymph node metastasis (LNM) in non-small cell lung cancer were investigated using helical computed tomography (hCT). The conventional criterion (1-cm short axis threshold) is generally accepted; however, this criterion is based on conventional CT. New criteria for LNM were investigated because the resolution of hCT is better than that of conventional CT. Methods: Ninety-seven NSCLC patients examined with hCT were enrolled. Both the long axis (LA) and short axis (SA) of the nodes were measured using hCT. Results: Based on the receiver operating characteristic curves, the thresholds that gave optimal sensitivity and specificity for LNM were 13 mm for LA and 9 mm for SA. The LNM diagnosis was re-evaluated using the combination of cutoff values. When the LA was ≥13 mm and the SA was ≥9 mm, the sensitivity, specificity, and accuracy were 56.3%, 92.1%, and 88.1%, respectively. When the LA was ≥13 mm or SA was ≥9 mm, sensitivity, specificity, and accuracy were 75.0%, 74.7%, and 74.7%, respectively. These values were not so different from the conventional criterion recalculated from these data. Conclusion: The new criteria are considered to be useful for making a LNM diagnosis. The conventional criteria for the LNM diagnosis might therefore be applicable even for hCT. [ABSTRACT FROM AUTHOR]

Summary: Regenerating gene I alpha (REG1A) is a known growth factor affecting pancreatic islet beta cells. Although REG1A expression also has been observed in various tumors, the correlation between REG1A expression and the clinicopathological characteristics of non-small cell lung cancer (NSCLC) and patient prognosis has not been evaluated. Methods: We used real-time semi-quantitative reverse transcription polymerase chain reaction to assess REG1A mRNA expression in tumor samples from 86 NSCLC patients. We then correlated REG1A mRNA expression with known clinicopathological factors. We also used immunohistochemical staining to determine the source of REG1A. Results: Within samples of tumor tissue, the cytosol of tumor cells was stained with anti-REG1A antibody. Cells from normal tissue were not stained. The 5-year over-all survival rate among patients expressing lower levels of REG1A was significantly better than among those expressing higher levels of REG1A (P =0.0031 by log-rank test). Multivariate Cox proportional hazard analyses revealed REG1A (hazard ratio, 2.34; 95% CI, 1.25–5.90; P =0.0055) and pathological stage III (hazard ratio, 3.46; 95% CI, 1.52–14.82; P =0.0012) to be independent factors affecting the 5-year over-all survival rate. Conclusion: High levels of REG1A expression by tumor cells are an independent predictor of a poor prognosis in patients with NSCLC. [Copyright &y& Elsevier]

Denervated stomach used as an esophageal substitute after esophagectomy often retains or spontaneously recovers acid production. The aims of the present study were to assess the relationship between esophageal acid exposure or gastric acidity and reflux-related symptoms after esophagectomy, and to assess the ability of proton pump inhibitors (PPIs) to relieve gastroesophageal reflux-related symptoms. Forty-four patients underwent esophageal and gastric 24-h pH monitoring early after esophagectomy with gastric reconstruction. Initially, patients with both gastric acidity and reflux symptoms were treated with PPIs (Treatment group), then all patients with gastric acidity, whether symptomatic or not, were treated (Prevention group). Reflux-related symptoms were correlated with esophageal acid exposure and postoperative gastric acidity. Gastric acidity was then correlated with serum anti- Helicobacter pylori immunoglobulin G (IgG) titers and preoperative endoscopic findings Sixteen patients (36.4%) reporting reflux and showing gastric acid production were treated with PPIs, which provided relief to 13 (81.3%). Although symptoms did not correlate with the esophageal acid exposure, postoperative gastric acidity was significantly greater among patients who were symptomatic than among those who were not. Overall, acid production was lower in older patients (> 64 years of age), although older patients who were H. pylori-negative and without chronic atrophic gastritis also showed high levels of gastric acidity. Proton pump inhibitors should be administered prophylactically early after esophagectomy to relieve and prevent reflux-related symptoms. Candidates for preventive therapy include those less than 64 years of age or older patients who are H. pylori-negative and without chronic atrophic gastritis. [ABSTRACT FROM AUTHOR]

Summary: Objective: The presence of a small solitary pulmonary nodule (SSPN) is a common finding on chest computed tomography (CT); however, preoperative diagnosis of SSPN is often difficult. We measured the extent of ground-glass opacity (GGO) and our own original method of circumference difference (CD) as an additional approach in classifying SSPN revealed on CT, and evaluated the likelihood of malignancy. Method: In total, 214 single SSPN with diameter <15mm were studied. All SSPN were histologically examined with surgical resection; preoperative CT findings and pathological diagnosis were evaluated retrospectively. The extent of the ratio of GGO and CD was evaluated using NIH image, where CD is defined as the ratio of the nodule margin distance to the circumference of the predicted circle with an area equal to that of the nodule. Results: The thresholds for differentiating SSPN are 70% of GGO and 68% of the CD ratio. Differentiation of malignancy from benign tumor using our algorithm had sensitivity of 96.6%, specificity of 86.1%, and positive predictive value of 94.1%. Conclusion: Combined with other malignant likelihood parameters such as extent of GGO, CD ratio is a useful additional factor for estimating the likelihood of malignancy of SSPN on CT. [Copyright &y& Elsevier]

Abstract: Background: The advantages and disadvantages of various tracer injection protocols for sentinel lymph node (SLN) mapping have been extensively discussed in relation to breast and gastric cancer. But no such discussion has taken place in relation to SLN mapping in non-small cell lung cancer. We therefore studied the effect of two tracer injection protocols on SLN mapping in patients with non-small cell lung cancer; of particular interest was the relationship between subpleural tracer injection and identification of mediastinal SLNs. Methods: A quadrant injection group (n =49) received 1.6ml of ferucarbotran by peritumoral quadrant injection after thoracotomy. In the subpleural injection group, the same amount of ferucarbotran was injected into the peritumoral quadrants plus the subpleural region (n =27). SLNs were then detected intraoperatively by measuring the magnetic force within lymph nodes using a hand-held magnetometer. After completing the SLN mapping, lobectomy and hilar and mediastinal lymph node dissection was performed. Results: The incidence of mediastinal SLNs was significantly higher in the subpleural injection group (45.4%) than in the quadrant injection group (14.6%) (p =0.007). Moreover, nominal logistic regression analysis revealed subpleural injection to be a significant independent factor contributing to detection of mediastinal SLNs (p =0.024, odds ratio 5.26). In the quadrant injection group, mediastinal lymph node metastasis was detected in two patients thought to have nonmetastatic parenchymal SLNs. By contrast, there were no false-negative cases in the subpleural injection group. Conclusion: Subpleural tracer injection significantly improves detection of mediastinal SLNs in non-small cell lung cancer. [Copyright &y& Elsevier]

The aim of the present study was to assess the outcome of treatment for patients with recurrent mid- and lower-thoracic esophageal cancers in whom recurrence was localized to the lymph nodes of the neck, and to determine the best strategy for further treatment. Between 1989 and 2001, 270 patients with mid- and lower-thoracic esophageal cancer underwent curative esophagectomy; 90 of those patients had a cancer recurrence. Our focus was on lymph node recurrence, especially when the recurrent cancers were localized to the lymph nodes in the neck. The outcomes of those patients and the efficacy of the strategies used to treat the recurrent cancers were determined. In 43 patients (48%), recurrent cancer initially appeared in the lymph nodes. Among the 43 patients, 15 (35%) had localized neck recurrence. The time between tumor recurrence and death among the 15 patients with localized neck recurrence was significantly longer than among the 28 patients with other recurrence patterns. In addition, 15 patients underwent lymph node resection, while 28 patients were treated non-surgically. The time between tumor recurrence and death was significantly longer in patients treated surgically. Of the 15 patients in whom recurrence affected the neck lymph nodes only, 10 (67%) were treated surgically; their 2-year survival rate after recurrence was 45%. The outcomes of recurrent esophageal cancers localized to the lymph nodes of the neck were better than those seen with other recurrence patterns, and salvage resection followed by chemoradiation therapy would seem to be indicated for those patients. [ABSTRACT FROM AUTHOR]

: BackgroundRecent advances in the treatment of thoracic esophageal cancer have afforded it a better prognosis. As a consequence, increasing attention is being paid to the outcomes with postoperative monitoring for second primary malignancies after esophagectomy, but no recent study has focused on the longterm followup and outcomes in these patients.: Study designIn 1989, we began intensive prospective screening and surveillance designed to detect cancers of the head and neck, lung, stomach, residual esophagus, and colon/rectum after esophagectomy. Between 1989 and 2001, 365 patients underwent esophagectomy for thoracic squamous cell esophageal carcinoma in our department. Of those, 200 were followed up as part of this program. Excluded were patients in whom esophageal cancer recurred, patients with other prior or simultaneous malignancies, and patients who died within a year of operation. Clinicopathologic profiles and treatment outcomes were determined for 33 patients who developed a second primary malignancy after esophagectomy.: ResultsThe interval between the primary esophageal cancer and the secondary carcinoma was 49 ± 40 months (median, 48 months). The second primary malignancies were located in the stomach (30%), head and neck (24%), lung (24%), colon/rectum (9%), liver (6%), pancreas (3%), and blood (6%). Twenty-one patients (64%) were classified as stage 0, I, or II; 10 (30%) were stage III or IV. Overall, the 2-year, 3-year, and 5-year survival rates following diagnosis of a second primary malignancy were 58.0%, 58.0%, and 48.6%, respectively. Of the 19 patients (58%) in whom second primary malignancies were detected before symptoms developed, the 5-year survival rate was 70.7%, which was significantly greater than that among patients whose secondary malignancies were discovered after symptoms developed (17.1%).: ConclusionsGood outcomes in the treatment of second primary malignancies after esophagectomy for thoracic squamous cell esophageal carcinoma can be obtained with longterm, intensive followup and active surgical intervention for detected malignancies. [Copyright &y& Elsevier]

Background. Low-flow hypoxia induces xanthine oxidase-dependent hydrogen peroxide production by hepatocytes in the midzone of blood-perfused rat livers and apoptosis in sinusoidal endothelial cells (SECs). As Bcl-2 is a potent inhibitor of apoptotic cell death and is localized mainly in the inner mitochondrial membrane and crista, the purpose of this study was to determine whether cell-specific changes in mitochondrial Bcl-2 levels could account for the hypoxia-induced apoptosis in SECs.Materials and methods. A low-flow hypoxia model was generated in isolated rat livers by reducing perfusate inflow pressure from 10 to 2.5 cmH2O for 2 h. Apoptosis was then evaluated using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. Mitochondrial Bcl-2 protein levels were determined in hepatocytes and SECs using cryosectioning immunogold labeling electron microscopy.Results. TUNEL-positive nonparenchymal cells, identified as SECs, were observed predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchymal cells were stained. Mitochondrial Bcl-2 levels were higher in SECs than in hepatocytes under control conditions, but they declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. In hepatocytes, by contrast, Bcl-2 levels were unaffected by hypoxia. Pretreatment with a specific xanthine oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate, which blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs.Conclusion. Hydrogen peroxide-dependent declines in Bcl-2 induce apoptosis in SECs in the hypoxic rat liver. [Copyright &y& Elsevier]

Aims/Background: Rat liver perfused with an oxygenated buffered solution alone results in degenerative changes even when the perfusion flow is accelerated to give a sufficient oxygen supply. On the other hand, perfusion media supplemented with red blood cells (RBCs) preserve the viability of the liver. The present study was conducted to clarify how RBCs protect the isolated perfused liver. Methods: The liver was perfused with and without RBCs in a perfusate equilibrated with supra-physiological oxygen tension at regulated inflow pressures, and controlled hepatic oxygen consumption. We examined alanine aminotransferase and purine nucleoside phosphorylase activity in the perfusate as specific markers of liver cells injury. Hydrogen peroxide (H2O2) production and morphological changes were determined using cerium electron microscopy. Apoptosis was detected by measuring CPP 32 protease activity and using TdT-mediated dUTP-digoxigenin nick end-labeling. Results: When the liver was perfused with RBC-free buffer, H2O2 production and consequent injury progressing to apoptosis were initiated in the sinusoidal endothelial cells (SECs). After SECs were injured, H2O2 appeared in the hepatocytes. H2O2 production and associated degenerative changes were attenuated both morphologically and enzymatically by the addition of RBCs, a specific xanthine oxidase (XOD) inhibitor and the H2O2 radical scavenger, catalase. Conclusions: In the liver perfused with RBC-free buffer, H2O2 production and consequent injury were initiated in SECs. RBCs attenuate liver injury by scavenging XOD-dependent H2O2. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a two-stage esophagectomy followed by pancreaticoduodenectomy.

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. [ABSTRACT FROM AUTHOR]