Identification of insulin-like growth factor 2 mRNA-binding protein 3 as a radioresistance factor in squamous esophageal cancer cells.

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.

Outcomes of endoscopic and surgical resection for a second primary cancer in the residual cervical esophagus after thoracic esophagectomy.

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.

[Thoracic surgery when the patients have cerebrovascular disease].

In cancer patients, cerebrovascular disease is recognized as the 2nd most common complication involving the central nervous system. Once cancer occurs in stroke patients, or vice versa, neurological outcomes significantly worsen and prognosis tends to be poor. Perioperative stroke after noncardiac, nonneurosurgical procedures is more common than generally acknowledged. It is reported to have an incidence of 0.05~7.4% of patients. "The analysis of lung cancer registry for resected cases in 1994", jointly established by the Japan Lung Cancer Society and the Japanese Association for Chest Surgery, reported a 2.4% frequency of cerebrovascular disease. Cerebrovascular disease is an unavoidable comorbidity for thoracic surgeons. Most are thrombotic in origin and are noted after discharge from the postanesthetic care unit. The mortality is more than 2 times greater than in strokes occurring outside the hospital. Delayed diagnosis and a synergistic interaction between the inflammatory changes normally associated with stroke, and those normally occurring after surgery, may explain this increase. Emergency non-contrast scanning of the brain is the primary diagnostic brain imaging study for evaluation of patients with suspected stroke, and the goal is to complete the computer tomography examination within 25 min of the provisional diagnosis being made.

Therapeutic strategy for the treatment of postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy of radiotherapy.

We investigated the effectiveness of chemoradiotherapy for the treatment of lymph node recurrence and hematogenous metastasis after esophagectomy for esophageal squamous cell carcinoma. Between 2001 and 2006, 216 patients with thoracic esophageal squamous cell carcinoma had curative esophagectomy. Of those, 23 with lymph node recurrence received chemoradiotherapy (50.0-68.8 Gy). In addition, five patients had isolated recurrences in a distant organ and received chemoradiotherapy (50.0-60.0 Gy). We analyzed outcomes from the radiotherapy for recurrent esophageal cancer. The 1-, 2-, and 5-year survival rates after recurrence for the 23 patients whose lymph node recurrence was treated with chemoradiotherapy were 52, 31, and 24%, respectively, and the median survival time was 13 months. Among the five patients with recurrent tumors in a distant organ, chemoradiotherapy produced a complete response in two patients, a partial response in one patient, and stable disease in two patients, giving an effectiveness rate of 60% (complete response + partial response). Chemoradiotherapy has a beneficial prognostic effect in patients with lymph node recurrence of esophageal squamous cell carcinoma. Chemoradiotherapy for a metastatic tumor in a distant organ may be the treatment of choice in cases where systemic chemotherapy has proven ineffective.

Small cell carcinoma of the esophagus treated with esophagectomy and following chemotherapy: case report with review of the literature.

We report 2 cases of small cell carcinoma of the esophagus treated with esophagectomy as a primary treatment and following chemotherapy. One patient (pT1N1M0) achieved long-term survival, while the other patient (pT1N1M1-lym) died 18 months after surgery. We used reports on 47 Japanese patients receiving esophagectomy as a primary treatment to determine when esophagectomy for small cell carcinoma of the esophagus is indicated. We conclude that esophagectomy as a local treatment provides relatively good long-term survival only in patients without lymph node involvement.

Preventive wrapping of the fragile tracheobronchial wall using a flap of latissimus dorsi muscle during esophagectomy after chemoradiotherapy.

BACKGROUND: Thanks to significant recent progress in the application of chemoradiotherapy (CRT) in the treatment of esophageal cancer, the numbers of operations on patients who have undergone preoperative CRT are increasing. In these patients, preoperative CRT often leads to formation of an unstable, scleroid layer comprised of what appears to be scar tissue around the tracheobronchial wall. This scleroid layer must be removed with the tumor, thereby weakening the wall. METHOD: We performed preventive intrathoracic transposition of a pedicled latissimus dorsi muscle flap on 6 patients with clinically T4 esophageal cancer (6 males; age: 63-75 years). All 6 patients had undergone preoperative CRT (median, 43.0 Gy; range, 32.0-60.0 Gy; with cisplatin + 5-fluorouracil infusion) to relieve direct invasion of the airway. RESULTS: In 6 patients, preventive use of a pedicled latissimus dorsi muscle flap resulted in uneventful recovery from the tracheobronchial wall weakness. Anastomotic leakage, recurrent nerve paralysis and pneumonia occurred in 2 patients each (33.3%); there were no life-threatening complications or operation-related deaths, however. CONCLUSIONS: When performing an esophagectomy for thoracic esophageal squamous-cell cancer in patients who have received preoperative CRT, the weakened tracheobronchial wall can potentially be reinforced using a pedicled latissimus dorsi muscle flap.

[Experience of twenty-one cases of tracheo-bronchoplasty].

Twenty-one cases of tracheo-bronchoplasty were performed in Akita University Hospital from 1997 to 2007. There are 14 cases of squamous cell carcinoma, 3 cases of adenocarcinoma, 2 cases of adenoid cystic carcinoma, 1 case of inflammatory tracheal stenosis, and 1 case of inflammatory bronchial stenosis. We performed 12 cases of right upper sleeve lobectomy, 4 cases of left upper sleeve lobectomy, 2 cases of left lower sleeve lobectomy, 1 case of right sleeve pneumonectomy, and 2 cases of tracheoplasty. Of 3 cases, we added sleeve resection of pulmonary artery. The ends of the bronchus are anastomosed end-to-end. The bronchial anastomotic suture was carried out peri-cartilaginously through all layers using an interrupted suture technique except for membranous portion. Membranous portion was sutured a continuous anastomotic technique. We use monofilament, absorbable suture material.

LPP inhibits collective cell migration during lung cancer dissemination.

Lipoma preferred partner (LPP) is a LIM domain protein, which has multiple functions as an actin-binding protein and a transcriptional coactivator, and it has been suggested that LPP has some roles in cell migration or invasion, however, its role in cancer cells remains to be elucidated. Here, we showed that LPP degraded N-cadherin in lung cancer, PC14PE6 cells via regulating the expression of matrix metalloproteinase 15 (MMP-15), and loss-of-LPP increases collective cell migration (CCM) and dissemination consequently. Knockdown of LPP and its functional partner, Etv5, markedly restores the full-length N-cadherin and increases cell-cell adhesion. We investigated the common target of LPP and Etv5, and found that MMP-15 is transcribed as their direct transcriptional target. Furthermore, MMP-15 could directly digest the N-cadherin extracellular domain. LPP knockdown in PC14PE6 cells increases N-cadherin-dependent CCM in the three-dimensional collagen gel invasion assays, and promoted the dissemination of cancer cells when they were orthotopically implanted in nude mice. Immunohistochemistry of lung adenocarcinoma specimens revealed the heterogeneity of LPP intensity and complementary expression of LPP and N-cadherin in the primary tumors. These findings suggest that loss-of-LPP, Etv5 or MMP-15 can be a prognostic marker of increasing malignancy.

[Thymolipoma in association with myasthenia gravis; report of a case].

An 18-year-old man was admitted with easy fatigue and muscle weakness. A diagnosis of myasthenia gravis was made. Chest X-ray showed no mediastinal abnormality, however, chest computed tomography (CT) showed a soft tissue mass in the thymus. The patient underwent extended thymectomy and small tumor (2 x 2 x 2 cm) was resected. On histological examination the tumor proved to be a thymolipoma composed of mature adipose elements containing cords and nests of thymic tissue. Symptoms of myasthenia gravis were dramatically improved after the operation. This case is the 12th in the world literature in which a thymolipoma is associated with symptoms of myasthenia gravis.

[An analysis of the mechanism of postoperative hyperbilirubinemia following resection of thoracic esophageal cancer in terms of hepatic venous oxygen saturation and excessive systemic reactions].

Hepatic venous oxygen saturation (ShvO2), parameters of systemic circulation and cytokine (Interleukin 6) (IL-6)) level were measured in 21 patients with thoracic esophageal cancer in order to analyze the mechanism of occurrence of postoperative hyperbilirubinemia (PHB). ShvO2 fell during operation, especially during intrathoracic procedures, and a significant correlation was noted between the total time during which ShvO2 was below 60% and the postoperative peak serum bilirubin level (peak-Bil) (r = 0.595, p = 0.0037). Patients with PHB (group H) had worse systemic circulation and a lower oxygen supply postoperatively than patients without PHB (group N). Body weight and water balance recovered earlier in group N. Postoperatively, numbers of peripheral lymphocytes and platelets changed lower in group H, while CRP and IL-6 changed higher in group H. Furthermore, a significant correlation was noted between the IL-6 level just after operation and peak-Bil (r = 0.669, p = 0.0006). These results suggests PHB results from intraoperative liver hypoxia and poor postoperative systemic circulation. Individual severeness of reactions to the operative stress, excessive or adequate, plays a role in the occurrence of PHB as well.

Postoperative lung volume calculated by chest computed tomography in patients with esophageal cancer.

It has been reported that, due to the severe surgical stress of thoracotomy, respiratory function after esophagectomy under thoracotomy worsened as late as a month after surgery. To investigate the mechanism of the reduction of the respiratory function, we utilized chest CT to analyze separately the changes in the lung volume of the thoracotomized side and the other side. Here, we reported the results of our comparative study of lung volume and respiratory function, which was performed by spirogram before esophagectomy and 6 months afterwards. We selected twenty-three patients who had undergone esophagectomy under right thoracotomy. Fourteen of the selectees received standard thoracotomy, while the other nine had the anterior serratus muscle and the latissimus dorsi muscle preserved. Total lung volume was found to have decreased from a preoperative value of 4077 +/- 674 ml (mean +/- SD) to a postoperative value of 3964 +/- 774 ml, and right-lung volume significantly decreased from 2229 +/- 397 to 2023 +/- 397 ml, while left-lung volume tended to increase. While right-lung volume in standard thoracotomy displayed a significant decrease from 2264 +/- 334 to 1949 +/- 424 ml, that in muscle-preserving thoracotomy showed almost no change. Spirogram revealed that vital capacity had decreased from 3574 +/- 601 to 2666 +/- 576 ml, and forced expiratory volume in the first second showed a significant decrease from 2680 +/- 500 to 2249 +/- 485 ml. Comparing the decreasing rate, the correlation coefficients between right-lung volume and %VC was 0.58. These results suggested that a change of lung volume in the thoracotomized side could play a role in the post-operative decrease of vital capacity and that muscle-preserving thoracotomy might induce less surgical stress than standard thoracotomy.

[Surgical treatment for pulmonary metastases from colorectal cancer].

Blalock first reported pulmonary resection for metastatic colorectal cancer in 1944. Since then, surgical resection of pulmonary metastases has been generally accepted as a standard therapeutic procedure in properly selected cases. Recently, the criteria of eligibility have been progressively expanded according to the development of radiological diagnosis using helical computed tomography (CT), widespread of minimum invasive video-assisted thoracic surgery. In this review summarized the surgical treatment of pulmonary metastases from colorectal cancer based on the recent literatures. Major areas of controversy remain with respect to the following aspects: prognostic factors (i.e., number of metastases, size of tumor, disease free interval, preoperative serum carcinoembryonic antigen level), procedure of operation (i.e., role of video-assisted thoracic surgery, lymphonode dissection), indication of surgical treatment on metastases both lung and liver, role of repeat thoracotomy for recurrence. For all above-mentioned points it appeared reasonable to try to the cooperative multicentric clinical prospective study.

[A case of recurrent lung cancer successfully treated with vinorelbine and cisplatin].

A 56-year-old female underwent lobectomy with ND2a lymph node dissection for left lung cancer in April 1999. Histopathological examination demonstrated moderately differentiated adenocarcinoma (pT2N2M0, stage III A). She received one course of a combination of etoposide and cisplatin as adjuvant therapy, followed by oral intake of UFT. In November 1999, a left para-aortic lymph node recurrence was found. She received radiation therapy (total 60 Gy) to the mediastinum. In April 2000, new lung and left supraclavicular lymph node recurrences were found. She received three courses of vinorelbine 20 mg/m2 (days 1, 8) and cisplatin 80 mg/m2 (day 1) followed by radiation therapy (total 50.4 Gy) to the left supraclavicular lesion. After the chemotherapy, a complete response (CR) of all metastatic lesions was achieved. Adverse reactions were grade 1 alopecia, grade 2 nausea/vomiting, grade 3 neutropenia, hypochromia, and injection site reaction. The combination of vinorelbine and cisplatin is a useful regimen in non-small-cell lung cancer.

Estimation of pulmonary oxygen consumption in the early postoperative period after thoracic surgery.

Lung injury, including pneumonia, can occur in the early postoperative period following thoracic surgery. Pulmonary oxygen consumption is thought to increase in patients with pulmonary infection. This study measured oxygen consumption in relationship to lung injury in the early postoperative period after thoracic surgery. Thirty-five patients who underwent thoraco-abdominal oesophagectomy for oesophageal cancer were studied. Measured oxygen-consumption was obtained by indirect calorimetry and calculated oxygen-consumption was simultaneously determined by the reverse Fick method. The difference in oxygen consumption was attributed to pulmonary oxygen consumption. The difference in oxygen consumption increased to 23.1 ml.min(-1).m(-2) on postoperative day 2. In patients with pneumonia the difference in oxygen consumption increased significantly to 39.0 ml.min(-1).m(-2) the day before clinical onset of pneumonia, and it increased further to 65.7 ml.min(-1).m(-2) on the day that pneumonia became clinically apparent. These findings suggest that the difference in oxygen consumption may be useful for estimating the extent of lung injury and for predicting pulmonary complications in the postoperative period.

Mediastinal extraadrenal myelolipoma: report of a case.

We herein report a case of surgically resected mediastinal extraadrenal myelolipoma. Myelolipoma is an uncommon tumor composed of adipose tissue and normal hematopoietic elements, and is most often found in the adrenal glands. We could find only five such cases of mediastinal myelolipoma in the English literature.

Ca2+ waves in lung capillary endothelium.

Although cytosolic Ca2+ importantly regulates organ function, lung microvascular [Ca2+]i regulation remains poorly understood because of the lack of direct in situ quantification. In the present study, we report the first endothelial [Ca2+]i quantification by the fura 2 method in microscopically imaged venular capillaries of the isolated blood-perfused rat lung. Sequential images indicated the presence of intercellular Ca2+ waves that spontaneously originated from pacemaker endothelial cells and then spread for short distances along the capillary wall, inducing synchronous endothelial [Ca2+]i oscillations. Fast Fourier analyses of the oscillations revealed a dominant wave component with an amplitude of 37 nmol/L, frequency of 0.4 min-1, and velocity of 5 microns/s. The intracellular Ca2+ wave was unaffected by blood flow stoppage or by infusions of Ca(2+)-containing or Ca(2+)-free dextran. Inhibition of the wave by thapsigargin in Ca(2+)-free dextran and by the gap junction uncoupler, heptanol, indicated that it was generated by endosomal Ca2+ release in the pacemaker cell and was propagated by gap junctional communication. In the presence of histamine, enhancement of the wave accounted for a significant component of the coordinated [Ca2+]i increase in the capillary segment. No intercellular Ca2+ waves were evident in adjoining alveolar epithelial cells. Our findings indicate a novel mechanism of [Ca2+]i regulation in the lung capillary under both resting and stimulated conditions. Pacemaker-induced Ca2+ waves, generated intracellularly by unknown initiating mechanisms, communicated to adjoining cells to determine [Ca2+]i profiles in short interbranch segments of capillary walls.