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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.

We report pulmonary resections for lung cancers in 2 patients with partial anomalous pulmonary venous connection (PAPVC) identified preoperatively. In case 1, right upper lobectomy was performed as the definitive operation for both lung cancer and PAPVC in the same lobe. In case 2, because lung cancer and PAPVC existed in different lobes, cardiac catheterization was performed to evaluate the need for correction of the PAPVC. Then, left lower lobectomy was safely performed without correcting the PAPVC located in the left upper lobe. The treatment plan for patients with PAPVC who require pulmonary resection should be carefully considered.

The patient was a 64-year-old woman with no history of laryngeal disorders. She underwent video-assisted right lower lobectomy and node dissection for lung cancer. Using a stylet while the patient was under general anesthesia, tracheal intubation with a 35-French gauge left-sided double-lumen endobronchial tube was successfully performed on the first attempt. The patient developed slight hoarseness on postoperative day 1, and we initially suspected recurrent laryngeal nerve paralysis caused by the surgery, which we elected to treat conservatively. However, because her hoarseness had not improved 4 months after surgery, we evaluated her vocal cords using laryngoscopy. This revealed severe dysfunction of the right vocal cord and arytenoid dislocation, which we treated through reduction using a balloon catheter. By 6 months, the patient's vocal cord mobility had improved. Arytenoid dislocation is a rare complication, but should be suspected when patients have right vocal fold paralysis after lung cancer surgery.

We aimed to determine whether neuropsychological deficits and brain atrophy could predict the efficacy of non-pharmacological interventions. Forty-six participants with mild-to-moderate dementia were monitored for 6 months; 25 underwent an intervention involving physical exercise with music, and 21 performed cognitive stimulation tasks. Participants were categorized into improvement (IMP) and no-IMP subgroups. In the exercise-with-music group, the no-IMP subgroup performed worse than the IMP subgroup on the Rivermead Behavioural Memory Test at baseline. In the cognitive-stimulation group, the no-IMP subgroup performed worse than the IMP subgroup on Raven's Colored Progressive Matrices and the cognitive functional independence measure at baseline. In the no-IMP subgroup, voxel-based morphometric analysis at baseline revealed more extensive gray matter loss in the anterior cingulate gyrus and left middle frontal gyrus in the exercise-with-music and cognitive-stimulation groups, respectively. Participants with mild-to-moderate dementia with cognitive decline and extensive cortical atrophy are less likely to show improved cognitive function after non-pharmaceutical therapy.

Findings from previous studies suggest that physical exercise combined with cognitive training produces more positive effects on cognitive function in elderly people than physical exercise alone. However, the brain plasticity associated with these proposed benefits of combined therapy has not yet been investigated in elderly subjects. We hypothesized that the dual task group would experience greater benefits than the physical exercise alone and non-exercise control groups with regard to both cognitive function and brain plasticity. This study investigated the effect of physical exercise with musical accompaniment on structural brain changes in healthy elderly people. Fifty-one participants performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM), 61 participants performed the same exercise without music (Ex), and 32 participants made up the non-exercise group (Cont). After the 1-year intervention, visuospatial functioning of the ExM but not the Ex group was significantly better than that of the Cont group. Voxel-based morphometry analyses revealed that the ExM group showed greater right superior frontal gyrus volume and preserved volumes of the right anterior cingulate gyrus, left superior temporal gyrus, and insula. These results indicate that compared with exercise alone, physical exercise with music induces greater positive effects on cognitive function and leads to subtle neuroanatomical changes in the brains of elderly people. Therefore, physical exercise with music may be a beneficial intervention to delay age-related cognitive decline.

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.

Lymph node involvement is the most important prognostic factor in many solid cancers. Recently, we found that patients with esophageal and lung cancer carrying the C-reactive protein (CRP) 1846T/T genotype, which is associated with lower serum CRP levels, are more likely to have lymph node metastasis. We hypothesized that host CRP directly inhibits lymph node metastasis.We inoculated NR-S1M metastatic cells subcutaneously into the backs of C3H/HeN mice. Concurrently, 1 μg of recombinant mouse CRP or phosphate-buffered saline was injected subcutaneously every 3 days for 5 weeks, after which the mice were killed for evaluation. We evaluated lymph node metastasis and lymphangiogenesis in the implanted tumor by using immunohistochemical analysis with anti-pancytokeratin and antilymphatic vessel endothelial hyaluronan receptor-1 antibodies.There was no substantial difference in tumor size between the 2 groups but the lymph nodes were smaller in the CRP group than the control group (P.044). Immunohistochemical analysis confirmed inguinal lymph node metastasis in 70% (14/20) of control mice, but in only 30% (3/10) of mice in the CRP group. Moreover, the metastatic area within lymph nodes was less in the CRP group (P.042) and tumoral lymphangiogenesis was decreased in the CRP group (P.037).CRP appears to inhibit tumoral lymphangiogenesis and lymph node metastasis in mice. These findings suggest that by inhibiting lymph node metastasis, CPR may have therapeutic potential for use against cancer.

Heat shock protein (Hsp) 90 is a key regulator of various oncogene products and cell-signaling molecules, while Hsp70 protects against heat-induced apoptosis. We previously described a system in which hyperthermia was produced using thermosensitive ferromagnetic particles (FMPs) with a Curie temperature (T c) of 43 °C to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, the antitumor effects of combining Hsp90 inhibitor (17DMAG) and Hsp70 inhibitor (quercetin) with FMP-mediated hyperthermia were examined. Expressions of Hsp90/70 and Akt were evaluated using Western blotting in vitro. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMPs were then injected into the resultant tumors, and the mice were divided into groups treated with quercetin and/or 17DMAG with/without hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMPs increased and stabilized at the T c. The TUNEL method was used to determine whether hyperthermia induced apoptosis within tumors. In the group pretreated with hyperthermia + quercetin + 17DMAG, Akt expression was reduced in vitro, the incidence of apoptosis within tumors was greater, and tumor growth was significantly suppressed 20 days after FMP injection in vivo, compared with other treatment groups. The survival rates among tumor-bearing mice observed for a period of 40 days were significantly higher in the hyperthermia + quercetin + 17DMAG group. Combining Hsp90/70 inhibition with hyperthermia appears to increase their antitumor effects. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90/70 inhibition has important implications for cancer treatment.

Summary Identification of reliable markers of radiosensitivity and the key molecules that donate susceptibility to anticancer treatments to esophageal cancer cells would be highly desirable. We found that the mRNA expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was higher in radioresistant TE-5 and TE-9 cells than in radiosensitive TE-12 cloneA1 cells. Conversely, knocking down expression of IGF2BP3 mRNA in TE-5 and TE-9 cells using small interfering RNA significantly enhanced their radiosensitivity. Furthermore, patients with squamous cell esophageal cancers strongly expressing IGF2BP3 tended to respond poorly to chemoradiation. These data suggest that IGF2BP3 may be a key marker of radiosensitivity that diminishes the susceptibility of squamous cell esophageal cancer cells to radiotherapy. IGF2BP3 may, thus, be a useful target for improving radiotherapy for patients with esophageal squamous cell carcinoma.

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. 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. 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. 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.

Background Cytomegalovirus (CMV) infection is endemic worldwide. Although CMV reactivation often becomes a serious problem in immunocompromised patients, the prevalence of CMV reactivation caused by methylprednisolone therapy for ARDS after esophagectomy has yet to be determined. Method Among 175 consecutive patients with thoracic squamous cell esophageal cancer who underwent esophagectomy with extensive lymph node dissection at Akita University Hospital between 2007 and 2010, 11 patients (6.3 %) diagnosed with ARDS during the acute phase of esophagectomy were enrolled and treated with steroid pulse therapy, high-dose (15–20 mg/kg/day) administration and tapering in this retrospective study. Results Seven of the 11 patients (63.6 %) were diagnosed with CMV reactivation based on CMV antigenemia assayed 19.1 days after the start of methylprednisolone administration and were treated with ganciclovir for 39.6 days. Six of the 7 patients (85.7 %) diagnosed with CMV reactivation were administered a total methylprednisolone dose of more than 4,000 mg. Though there was no significant difference between patients with and without CMV reactivation, there was a tendency that patients with CMV reactivation showed a lower minimum number of lymphocytes during the acute phase of esophagectomy (p = 0.051, Student’s t test, average 223.3 and 298.0/μl, respectively). Conclusion Though the number of study patients is small, the prevalence of CMV reactivation caused by high-dose methylprednisolone therapy for ARDS after esophagectomy is remarkably high. This result strikes a note of warning concerning the management of these patients and suggests the importance of screenings for CMV reactivation so as to make an accurate diagnosis and initiate treatment in a timely manner.

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.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.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.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.

症例は58歳男性．検診で，両側胸部異常陰影を指摘された．CTガイド下生検で左S1+2に径27 mm，扁平上皮癌，右S1に径45 mm，腺癌と診断され，両側同時多発肺癌と考えられた．左扁平上皮癌に対し左肺部分切除術施行．術後鎮痛としてフェンタニル 1.25 mg＋ドロペリドール5mgでの経静脈的自己調節鎮痛法を行った．続いて第8病日に右腺癌に対し右上葉切除術を施行．麻酔法，術後鎮痛は同様であるが，閉創時に0.75％ロピバカイン10 mlを創部に滴下する創部浸潤麻酔を追加した．術後12時間まで，Numeric Pain Rating Scaleを用いた評価では創部浸潤麻酔を追加した右側手術が優れ，患者の満足度が高かった．

Bronchial stump fistula after resection of lung cancer is an extremely difficult to treat postoperative complication. Endoscopic fistula closure is a favorable alternative, potentially avoiding major surgical intervention. an 80-year-old man underwent curative resection of squamous cell carcinoma by left upper lobectomy of the lung. The patient suddenly developed massive subcutaneous emphysema on postoperative day 10. Bronchoscopy revealed a fistula about 3 mm in diameter at the lateral edge of the bronchial stump. Concentrated fibrinogen 0.5 ml (fluid A) was sprinkled on the bronchial fistula initially, and then pieces of polyglycolic acid mesh presoaked in fluid A or fluid B (thrombin) of the fibrin glue were pushed with biopsy forceps into the fistula in an alternating fashion (A→B→A→B) under endotracheal local anesthesia. Air leakage was stopped, and the patient did not develop empyema. Particularly for patients in poor general condition, our noninvasive technique seems to serve as a therapy of first choice.

Patients who have received subtotal esophagectomy for thoracic esophageal cancer must be closely monitored for second primary malignancies. The purpose of this study is to review and assess patients who developed a second primary esophageal cancer in the residual cervical esophagus. Between 1996 and 2010, 10 patients were diagnosed in our hospital with esophageal squamous cell cancer in the residual cervical esophagus after undergoing thoracic esophagectomy and were treated with endoscopic or surgical resection. Data from these patients were reviewed retrospectively. Seven of the 10 patients (70%) had multiple primary carcinoma lesions at the time of their esophagectomy. A second primary cancer in the residual cervical esophagus was detected in eight patients during follow-up endoscopic examinations while the patients were still asymptomatic. Seven of the patients underwent endoscopic resection for a superficial cancer. None of those patients experienced any complications, and all are currently alive and cancer-free. The remaining three patients underwent resection of the cervical esophagus with regional lymph node dissection. Two of those patients experienced severe complications; one subsequently died (hospital death) from pneumonia, 12 months after surgery, while the other died from recurrence of his cancer. The third patient is alive and cancer-free. Early detection of a second primary malignancy in the residual cervical esophagus followed by endoscopic resection is the best treatment strategy for patients who previously received subtotal esophagectomy for thoracic esophageal cancer. Surgical resection puts patients at high risk of mortality or morbidity.

We report two cases of rare benign esophageal schwannoma showing high uptake of radiotracer on [18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET). Case 1 was a 78-year-old woman with a tumor (50 × 30 × 30 mm) located on the right side of the upper thoracic esophagus. Case 2 was a 70-year-old woman with a tumor (40 × 35 × 27 mm) located in the left anterior wall of the thoracic-to-cervical esophagus. Both tumors were enucleated and histologically diagnosed as benign esophageal schwannoma with nuclear palisading and lymphoid cuffing (Antoni A type). Immunohistochemical staining showed positivity for S-100 protein. There have been five reported cases of esophageal schwannoma with FDG-PET findings, including the present two cases. All five tumors were FDG-PET positive and presented histologically as benign esophageal schwannoma. There was no association between histological malignancy and FDG uptake. We therefore propose that the malignant potential of esophageal schwannomas cannot be evaluated using FDG-PET.

Chylothorax is a relatively rare complication of thoracic surgery. Most instances of chylothorax after pulmonary resection are diagnosed within 3 days after surgery. Hence, late-onset chylothorax is rare. A 68-year-old woman underwent right lower lobectomy and mediastinal dissection for lung cancer. After discharge, the patient developed a dry cough, and chest radiography more than 3 months after surgery revealed a right-sided pleural effusion occupying more than half of the right hemithorax, which we diagnosed as late-onset chylothorax. Treatment comprised chest drainage, subcutaneous octreotide, and pleurodesis by injecting a preparation of OK-432. Follow-up chest radiography confirmed no reaccumulation of fluid. Three months later no recurrence of pleural effusion was detected. We report a rare case of postoperative late-onset chylothorax that proved difficult to treat.

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.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-12β), and Th2 cytokines (IL-4, IL-10).IL-2 -330TG 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 -330TG polymorphism was not associated with preoperative serum IL-2 levels. Moreover, interferon-γ, IL-12β, IL-4, and IL-10 genetic polymorphisms were not associated with prognosis after esophagectomy for thoracic esophageal squamous cell cancer.It is suggested that IL-2 -330TG genetic polymorphism may be a predictive factor for prognosis in patients receiving esophagectomy for thoracic esophageal squamous cell cancer.

Inhibition of histone deacetylases (HDACs) is a promising new approach to the treatment of lung cancer therapy. The relation between HDAC3 expression and the clinicopathological characteristics of lung cancer is not well understood, however. We therefore addressed this issue in patients with adenocarcinoma of the lung. We used semi-quantitative real-time reverse transcription polymerase chain reaction and immunohistochemical analysis to assess expression of HDAC3 in tumor samples from 94 patients with adenocarcinoma of the lung. We then correlated levels of HDAC3 expression with known clinicopathological factors. The 5-year disease-free survival (5-DFS) rate among patients expressing high levels of HDAC3 was significantly poorer than among those expressing lower levels (P = 0.005; log-rank test). Multivariate Cox proportional hazard analyses revealed male (hazard ratio, 3.88; 95% CI, 1.70-9.39; P = 0.001), nodal metastasis N1 (hazard ratio, 6.39; 95% CI, 1.54-22.7; P = 0.013), N2 (hazard ratio, 6.36; 95% CI, 1.55-33.6; P = 0.009), and HDAC3 (hazard ratio, 3.06; 95% CI, 1.07-7.55; P = 0.037) to be independent factors affecting the 5-DFS rate. Strong tumoral expression of HDAC3 is an independent predictor of a poor prognosis in patients with adenocarcinoma of the lung.

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. 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 (C(4h)). There were significant differences in the C(4h) 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 C(4h) of (R)- and (S)-lansoprazole were associated with CYP2C19 PMs (p = 0.0005 and0.0001 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). 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 C(4h) could be possible.

A 71-year-old man who had undergone surgical resection of esophageal gastrointestinal stromal tumors (GISTs) through a right posterolateral thoracotomy 8 years earlier was referred for treatment of an anterior mediastinal mass discovered on a follow-up chest radiograph in October 2007. Computed tomography findings revealed a tumor, 82 x 49 mm, with calcification, in the anterior mediastinum. When we radically resected the tumor via a median sternectomy, we found that it was actually located in the pleural cavity, and there was a small nodule near the main tumor on other pleura. Microscopically, the tumor was comprised of uniform spindle cells with fibrillary eosinophilic cytoplasm. In addition, immunostaining showed that the tumor was positive for CD117 (c-kit). The diagnosis was pleural dissemination of esophageal GISTs 8 years after primary surgery, making this the first report of pleural dissemination of esophageal GISTs after such a prolonged postsurgical interval.

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 (or =30 mg/dl increases in blood glucose during surgery) and genetic polymorphisms for C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, -beta, interferon-gamma, transforming growth factor-beta1, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-6 receptors, IL-10, IL-12beta, adiponectin, and peroxisome proliferator-activated receptor-gamma.In 28 (46%) patients, blood glucose levels increased more than 30 mg/dl during surgery. Among the genetic polymorphisms tested, CRP -717CT 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 CT genetic polymorphism may be a predictive factor for stress hyperglycemia in patients receiving esophagectomy for thoracic esophageal cancer.

フィブリンの析出のためにドレナージが困難となった急性膿胸および肺炎随伴性胸水に対して，胸腔鏡下の手術奏功例が多数報告されているが，全身状態が不良で手術困難な場合も少なくない．このような症例に対してウロキナーゼの胸腔内投与の有用性が報告されている．しかし標準的な投与方法は確立していない．当科でウロキナーゼの投与を行った急性膿胸および肺炎随伴性胸水5例を対象に，ウロキナーゼ投与方法，治療期間，効果を中心にretrospectiveに検討した．全例で多房性胸水を認めていた．4例は発症後1～16日の経過で，ウロキナーゼ投与（1回12万単位，6～9回投与）のみで肺の良好な再膨張が見られた．ウロキナーゼ注入に加えて外科治療を要した1例は，発症から1ヵ月経過した膿胸で，手術後治癒した．出血などの合併症はなかった．ウロキナーゼの胸腔内投与は簡便であり大きな合併症もなく，poor risk症例に対して考慮すべき治療法と思われた．

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 Ialpha and Ibeta and examined its effects on cytokine expression. We found that transfecting TE-5 and TE-9 cells with REG I Ialpha and Ibeta 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-gamma, tumor necrosis factor-alpha, granulocyte-colony stimulating factor or transforming growth factor-beta1. The elevated IL-6 expression seen in REG Ialpha 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.

Background Cytokines play a major role in the organization of orchestrated responses to infections, and there is an emerging consensus that cytokine gene polymorphisms mediate individual variations in cytokine expression. Our aim in this study was to assess whether cytokine polymorphisms were associated with infectious complications following esophagectomy in a Japanese population. Methods The study participants were Japanese patients treated with transthoracic esophagectomy without neoadjuvant treatment. DNA was extracted from blood samples, and genetic polymorphisms for interferon (INF)-γ, tumor necrosis factor-α and -β, transforming growth factor-β1, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-6, IL-6 receptor, IL-10, and IL-12β were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between gene polymorphisms and postoperative infection. Results Of the 110 patients studied, 18 (16%) developed a postoperative infection (pneumonia, 14 patients; pyothorax, 5; intraabdominal abscess, 1; neck abscess, 1; sepsis, 2). Although the characteristics of patients who developed postoperative infections did not differ, analysis of the genotypes using the Fisher exact test revealed a significantly ( P = .0215) greater incidence of postoperative infections among those carrying the INF-γ 874 (rs2430561) A/A and A/T genotypes. Moreover, univariate and multivariate logistic regression models showed patients carrying the INF-γ 874A/T genotype were significantly more likely to develop postoperative infectious complications (odds ratio>3.4). Conclusion Our findings suggest that the IFN-γ 874A>T polymorphism is potentially predictive of the likelihood that patients undergoing esophagectomy for thoracic esophageal cancer will develop postoperative infections. This polymorphism may therefore have important clinical relevance and should be considered when treatment regimens are designed.

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.

Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis.The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and -beta, interferon (IFN)-gamma, transforming growth factor (TGF)- beta, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis.For CRP 1846CT polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846CT polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively.These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.

Background 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. Methods 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. Results 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. Conclusions 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.

両側自然気胸は片側自然気胸よりも術後再発率が高いとされているが，その詳細は十分に検討されていない．今回，過去11年間に経験した原発性自然気胸手術症例を対象に，両側自然気胸の術後再発率や臨床的特徴について検討した．両側自然気胸は片側自然気胸と比較して，術後再発率が高く（31.6％（6/19例）vs 7.1％（12/169例），p＜0.001），若年（p＜0.001）で非喫煙者（p＜0.01）の男性が多く認められた．手術術式と術後再発率は関連せず，初回手術所見で肺尖部ブラと胸壁との間に線維性癒着を認めた全症例で術後再発を認めた（p＜0.01）．両側自然気胸は片側自然気胸と異なった臨床的特徴を有しており，現行の手術術式では術後再発率が高いため，新しい再発予防法について検討する必要があると考えられた．

食道癌術後再建胃管に生じたGastrointestinal stromal tumor（GIST）症例に対し腫瘍核出術を行った．文献上，再建胃管GIST症例の報告はなく，術式を中心に考察を加え報告する．症例は78歳男性．15年前，胸部食道癌（p-StageI）に対し前医で非開胸食道切除，胸骨後経路食道胃管吻合術を受けた．嚥下困難を訴え受診，精査の結果，再建胃管に粘膜下腫瘍を認めた．超音波下針生検にて胃管GISTと診断され，イマチニブ400mg/日が投与された．しかし腫瘍は増大，また重度の副作用が出現したため，手術目的で当院紹介となった．手術は患者背景，根治度および手術侵襲から腫瘍核出術とした．切除した腫瘍は組織学的にc-kit陽性，CD34陽性，Ki-67陽性率5％，核分裂像0～1個/10HPFで，総合的に中リスク群に群別された．術後経過は良好で，術後1年経過した現在，再発を認めていない．

Perforation of the esophagus during endoscopic therapy is a severe complicati1on. Nonetheless, almost all perforations made during endoscopic submucosal dissection can be treated conservatively because their early diagnosis, the good condition of the patient, and their small size enables them to be closed with endoscopic clips. If inflammation around the esophagus progresses to mediastinitis, however, surgical management such as debridement and drainage should be applied without delay. Here we report three cases of esophageal perforation during endoscopic submucosal dissection that were successfully treated: in case 1, by drainage of the mediastinal abscess under thoracoscopy; in case 2, by mediastinal drainage from the cervix; and in case 3, by application of endoscopic clips. These techniques are effective and less invasive than other surgical approaches.

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.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.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 wasor =13 mm and the SA wasor =9 mm, the sensitivity, specificity, and accuracy were 56.3%, 92.1%, and 88.1%, respectively. When the LA wasor =13 mm or SA wasor =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.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.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign breast disease. Pseudoangiomatous stromal hyperplasia is characterized by a collagenous proliferation of mammary stroma, associated with capillary-like spaces. We herein report the case of a 48-year-old woman who presented with a huge mass in her right breast. Physical examination revealed a 20 x 23-cm mass, which was surgically excised. Histopathologically, the tumor was composed of abundant fibrous stroma containing non-vascular slit-like spaces and scattered ducts and lobules. Neither stromal nor epithelial cells showed atypia. We therefore diagnosed the tumor to be PASH.

A reliable marker of chemoradiosensitivity that would enable appropriate and individualized treatment of thoracic squamous cell esophageal cancer has long been sought. We investigated whether regenerating gene (REG) Ialpha is such a marker.We assessed expression of REG Ialpha in untreated endoscopic biopsy specimens and examined the correlation between REG Ialpha expression and the clinical responses to definitive chemoradiotherapy and prognosis. We also examined the relationship between REG Ialpha expression in the resected tumor and the prognosis of patients who received esophagectomy for thoracic squamous cell esophageal cancer.Among the 42 patients treated with definitive chemoradiotherapy, 8 of the 23 REG I-positive patients (35%) showed complete responses to chemoradiotherapy, while only one of the 19 REG I-negative patients did so. The survival rate among the REG I-positive patients was significantly better than among the REG I-negative patients. For the 76 patients treated surgically, there was no significant difference in the survival rates among the REG I-positive and REG I-negative patients.REG Ialpha expression in squamous cell esophageal carcinoma may be a reliable marker of chemoradiosensitivity. We anticipate that it will enable us to provide more appropriate and individualized treatment to patients of advanced esophageal squamous cell carcinoma.

症例は20代の男性，統合失調症．2006年末，自殺企図でサンポール（トイレ用洗浄剤，9.5％塩酸）およびハミング（衣類用柔軟仕上げ剤，界面活性剤）を内服し近医に救急搬送された．入院時に嘔吐と嗄声を認めた．上部消化管内視鏡検査にてGrade2bの所見を咽頭喉頭，食道，胃に認めたが，ICU入室し保存的治療で急性期を乗り切った．希死念慮が強く，精神科転科し精神面の治療を行った後，空腸瘻を造設，全身状態の改善と精神状態の安定を待って，両親の住む地元に転院し，経腸栄養管理を継続した．幸い食道狭窄は軽度であり，徐々に改善したため拡張術や手術は必要としなかった．経口摂取と経腸栄養により十分な栄養摂取が可能であったが統合失調症の治療に時間を費やし第154病日に退院した．受傷後15カ月では消化器症状を認めていない．空腸瘻造設は低侵襲手術であり，受傷後早期から有用と考えられた．

Summary Background The sentinel lymph node (SLN) concept is that lymphatic flux from a primary tumor initially flows into a SLN. The mechanism mediating tumor metastasis within SLNs remains largely unknown; however, primary tumors overexpressing vascular endothelial growth factor (VEGF)-A appear to induce SLN lymphangiogenesis prior to metastasis in animal model. Our aim was to further investigate the capacity of VEGFs to induce lymphangiogenesis within SLNs and to assess their role in SLN metastasis in non-small cell lung carcinoma (NSCLC). Methods Real-time quantitative RT-PCR was used to assess expression of mRNAs encoding several VEGFs (VEGF121, VEGF165, VEGFR1, VEGFR2, VEGFR3, VEGF-C and VEGF-D) in resected lymph node specimens from 35 NSCLC patients, after which we compared their expression SLNs and non-SLNs. In addition, expression of the lymphatic endothelium-specific hyaluronan receptor (LYVE)-1 was used to assess lymphangiogenesis in SLNs and non-SLNs. Results Immunohistochemical staining revealed substantial expression of LYVE-1 in SLNs. Moreover, levels LYVE-1 mRNA were significantly higher in SLNs than non-SLNs ( P P P = 0.02, respectively). In addition metastasis-positive SLNs showed significantly higher levels of VEGF121, VEGF-C and VEGF-D mRNA than metastasis-negative SLNs ( P P = 0.01 and P = 0.01, respectively), and VEGF121 induced the proliferation of lymphatic endothelial cells ( P Conclusions Our findings suggest that active lymphangiogenesis is ongoing within SLNs from NSCLC patients, even before metastasis. This lymphangiogenesis may be promoted by upregulation of VEGF121, which may in turn act in part via induction of VEGF-C.

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.In total, 214 single SSPN with diameter15mm 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.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%.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.

The type of anastomosis and its outcome can affect postoperative morbidity, mortality, and quality of life after esophagectomy. We compared the outcomes of cervical hand-sewn anastomosis (CHS) and intrathoracic stapled anastomosis (ITS) performed after esophagectomy and gastric reconstruction. Thirty-two patients with middle or lower thoracic esophageal cancer were prospectively randomized to undergo CHS (n = 18) or ITS (n = 14) after esophagectomy. We compared clinical data, postoperative symptoms, and long-term survival in the two groups. The rates of anastomotic leak and stricture in the CHS and ITS groups were 16.7% versus 7.1% and 0% versus 14.2%, respectively, which do not represent significant differences. The respective rates of recurrent laryngeal nerve palsy were 38.8% versus 7.1% (P < 0.05), and proximal esophageal resection was 15 mm longer (P < 0.05) in the CHS group. There were no significant differences in symptoms 6 months after surgery, or in the overall 5-year survival rates (72.2% and 85.7%, respectively). The two methods of anastomosis yielded similar anastomotic outcomes. Although the incidence of recurrent laryngeal nerve injury was higher after CHS, and proximal esophageal resection was longer, this had little impact on postoperative symptoms and long-term survival.

Background For thoracic esophageal cancer patients with a history of gastrectomy, esophageal reconstruction using segments of colon was often accomplished using the anterior mediastinal route to avoid fatal complications related to colon necrosis. Our aim was to review our experience with reconstruction by the posterior mediastinal route and assess the surgical outcomes. Methods Between 1989 and August 2006, 34 esophageal cancer patients at Akita University Hospital underwent esophageal reconstruction accomplished by colon interposition by the posterior mediastinal route. Data from these patients were reviewed. Results Colon conduits consisted of left colon segments in 4 patients and right colon segments in 30. The grafts were supplied with blood by the left colonic artery in 13 patients, the middle colonic artery in 20, and the right colonic artery in 1. The esophagocolic (pharyngocolic) anastomosis was located in the neck in 33 patients (97%) and in the thorax in 1. No patient died during the initial hospital stay. There were no instances of colon necrosis. An anastomotic fistula occurred in 3 patients (9%). Proximal anastomotic strictures occurred in 2 patients (6%). No late graft redundancies resulting in significant dysphagia occurred. Reductions in body weight did not differ from those seen when the gastric tube was used for reconstruction, and alimentary function was good after surgery. The 1-, 2-, 3-, and 5-year survival rates were 66%, 52%, 48%, and 48%, respectively. Conclusions Colon interposition by the posterior mediastinal route provides a good outcome and is considered the route of first choice.

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.

A 55-year-old man underwent subtotal esophagectomy with extended three-field lymph node dissection for squamous cell carcinoma of the middle thoracic esophagus (histological stage pT3N4(3b)M0, pStage IVa). About 9 months later, contrast-enhanced computed tomography showed recurrence in several lymph nodes in the anterior mediastinum and the right side of the neck. We treated the recurrence by dissecting the affected nodes, followed by chemoradiotherapy. At the time of writing, 5 years later, the patient was well, without any further evidence of recurrence. Although the indications for resection of recurrent esophageal cancer are controversial and we cannot generalize about the best treatment for these patients, this case highlights the possibility of using salvage surgical resection to treat recurrent esophageal cancer with anterior mediastinal lymph node involvement in selected patients.

Lymphatic flux from a primary tumor initially flows into a tumor-draining lymph node (LN), the so-called sentinel LN (SLN). Carried by the lymph fluid are a variety of mediators produced by the tumor that can influence immune responses within the SLN, making it a good model with which to investigate tumor-related immunology. For instance, dendritic cell (DC) numbers are reduced in SLNs from melanoma and breast cancer patients. In the present study, we investigated the mechanism by which DC numbers were reduced within SLNs from patients with non-small cell lung cancer. We found that the incidence of apoptosis among DCs was higher in SLNs than in non-SLNs, as were levels of TGFβ-1. In contrast, levels of TGFβ-1 mRNA did not differ between SLNs and non-SLNs, but were 30 times higher in tumors than in either LN type. In vitro, incubation for 2 days with TGFβ-1 induced apoptosis among both cultured DCs and DCs acutely isolated from normal thoracic LNs, effects that were blocked by the TGFβ-1 inhibitor DAN/Fc chimera. Taken together, these results suggest that tumor-derived TGFβ-1 induces immunosuppression within SLNs before the movement of tumor cells into the SLNs, thereby facilitating metastasis within those nodes.

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.