[Surgically treated pleomorphic carcinoma of the lung].

We experienced 3 resected cases of pleomorphic carcinoma of the lung. Each cases were 74-year-old man (case 1), 74-year-old woman (case 2) and 69-year-old man (case 3). Two patients (case 1 and 2) were histologically diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with giant cell carcinoma. One patient (case 3) was similarly diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with adenocarcinoma and squamous cell carcinoma. Although lymph nodes metastasis were not recognized in all patients, invasion to vessels were recognized in 2 patients (case 1 and 3). In one patient (case 1), recurrence was recognized at contralateral side 1 month after surgery and he died of other disease 2 months after surgery. The other 2 patients were alive without recurrence 24 and 5 months after surgery. Recently it is reported that recurrence is recognized at early phase after surgery and prognosis is poor in a case with vessel invasions in spite of pathological NO state. Since one patient (case 3) had nonmetastatic lymph nodes with vessel invasions, careful observation is considered to be necessary.

[Clinical analysis of tracheoplasty and bronchoplasty in primary lung cancer].

In our department, there were 482 thoracic surgeries for primary lung cancer between 1994 and 2007. We clinically reviewed cases that underwent tracheoplasty or bronchoplasty (n = 22, 4.6%). The patients consisted of 21 males and 1 female (66.5 +/- 12.0 years-old). All patients were smokers. The tissue forms were 19 squamous cell carcinomas, 2 adenocarcinomas, 1 large cell carcinoma, 1 adenoid cystic carcinoma and 1 carcinoid, including 2 multiple carcinomas. Sleeve resections involved the trachea in 1, upper lobes in 13, lower lobes in 3, upper-middle lobes in 2 and intermediate bronchus in 1. Wedge resections were performed in the upper lobes in 2. Fourteen reconstructions were performed. We ordinarily sutured the trachea and bronchus in any case, using a single outside knot. There was no leakage at the anastomosis. There were 2 hospital deaths. There were 4 cancer deaths, including 2 local recurrences. There were 4 patients demonstrating stenosis post operatively. There were 3 stenoses among 4 preoperative radiation therapies. We considered that radiation therapy disturbed the repair of the anastomosis. There were 8 pneumonia patients who developed post operatively. There were 2 operative hospital deaths among 3 angio-bronchoplasties without coverage. Recently, we have routinely covered the anastomosis at the reconstruction site and have not experienced any major complications.

[Approach by clamshell incision for bilateral pulmonary metastasis].

In recent years thoracotomy by "clamshell incision" has frequently been chosen for heart-lung transplantation, bilateral lung tumors and mediastinal tumor merging into lung tumor because this approach provides very good visibility to access the whole bilateral lung including the lower lobe and mediastinal organs. In our hospital, 4 patients underwent bilateral thoracotomy by clamshell incision for pulmonary metastasectomy between 2001 and 2005. All cases had bilateral pulmonary metastases, and multiple wedge resection was performed. All lesions that were planned for resection on preoperative computed tomography (CT) could be resected. Regarding the surgical approach to bilateral pulmonary metastases that did not need lobectomy, clamshell incision is one of the useful approaches that can allow wedge resection anywhere in the whole lung. In cases that are expected multiple procedures, bilateral thoracotomy by clamshell incision is recommended because it allows another route for thoracotomy at reoperation.

[Clinical experience with 16 cases of mediastinal lymphoma].

Sixteen cases of mediastinal lymphoma in our hospital were reviewed clinically. There were 7 men and 9 women, whose mean age is 35 years old. The histological types were non-Hodgkins' disease in 12 (B-cell type in 6 and T-cell type in 6), Hodgkins' disease in 2, mucosa-associated lymphoid tissue (MALT) lymphoma in 2. All cases except 1 in which percutaneous needle biopsy was performed were diagnosed histologically. Even small specimens by percutaneous needle biopsy can be helpful in diagnosing histological type and subtype with immunohistlogy, recommending percutaneous needle biopsy as an mitial step for diagnosis. When histological diagnosis can not be made by needle biopsy, open biopsy should be done.

The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer.

A positive association between vascular endothelial growth factor-C (VEGF-C) expression and lymph node metastasis has been reported in several cancers. However, the relationship of VEGF-C and lymph node metastasis in some cancers, including non-small cell lung cancer (NSCLC), is controversial. We evaluated the VEGF-C and vascular endothelial growth factor receptor-3 (VEGFR-3) expression in NSCLC samples from patients who had undergone surgery between 1998 and 2002 using real-time quantitative RT-PCR and immunohistochemical staining. We failed to find a positive association between VEGF-C and VEGFR-3 mRNA expression and lymph node metastasis in NSCLC. An immunohistological study demonstrated that VEGF-C was expressed not only in cancer cells, but also in macrophages in NSCLC, and that VEGFR-3 was expressed in cancer cells, macrophages, type II pneumocytes and lymph vessels. The VEGF-C/VEGFR-3 ratio of the node-positive group was significantly higher than that of the node-negative group. Immunohistochemical staining showed that VEGFR-3 was mainly expressed in cancer cells. The immunoreactivity of VEGF-C and VEGFR-3 was roughly correlated to the mRNA levels of VEGF-C and VEGFR-3 in real-time PCR. VEGF-C mRNA alone has no positive association with lymph node metastasis in NSCLC. The VEGF-C/VEGFR-3 ratio was positively associated with lymph node metastasis in NSCLC. This suggests that VEGF-C promotes lymph node metastasis while being influenced by the strength of the VEGF-C autocrine loop, and the VEGF-C/VEGFR-3 ratio can be a useful predictor of lymph node metastasis in NSCLC.

[Clinical analysis of operative and hospital deaths in primary lung cancer].

In our department, there were 313 thoracic surgeries for primary lung cancer from January 1994 to December 2003. We clinically reviewed for the operative and hospital death (n=18, 5.8%). The patients were 16 males and 2 females (70.6 +/- 5.6 years old). The surgical procedures were 4 pneumonectomies, 13 lobectomies (3 bronchoplasties) and 1 partial resection. The mean interval until postoperative death was 122.5 +/- 156.1 days. There were 5 direct operative deaths within 30 days (1.6%). There were 4 cancer deaths, 2 hemoptyses, 2 operative bleeding, 2 thromboses, 2 cerebral hemorrhages, 1 pyothorax, 1 pneumonia, 1 respiratory failure, 1 multiple organ failure after chemotherapy and 2 unexplained deaths. The patients with pneumonectomy or aged significantly had high mortality. For postoperative complications such as hemoptysis or bleeding, perioperative management that takes these issues into consideration is needed. Furthermore, we must carefully review the preoperative evaluation and combined treatment, because there were many cancer deaths among cases showing early recurrence and metastasis.

Spatial resolution in the electrical impedance tomography for the local tissue.

Electrical impedance tomography (EIT) is one of the medical tissue diagnosis devices and it creates a two- or three-dimensional image of electrical impedance distribution in a living tissue. It is used for imaging the information of tissue structures, and physiological functions and states of the tissue. However, there are several problems to achieve the practical use of EIT, which are an inverse algorithm for estimating parameters and electrode structure and so on. EIT is calculated from impedance data, which is measured non-invasively by surface electrodes. Therefore, it is important to choose a proper electrode structure to realize a practical EIT measurement system. In this study, we used a electrode structure, called "divided electrode", which is proposed for a short time measurement of bio-impedance in a cross section of the local tissue. Its capability is examined by computer simulations, where a distributed equivalent circuit is used as a model for the cross section tissue. Estimation of impedance parameters is carried out by use of the Newton method. The objective of this study is to examine the spatial resolution on the circuit model. Moreover, the current flowing in the circuit model is examined.

Mediastinoscope-assisted transhiatal esophagectomy for esophageal cancer.

BACKGROUND: Transthoracic esophagectomy (TTE) is a radical strategy for treatment of esophageal cancer, and the morbidity and mortality are high. Transhiatal esophagectomy (THE) is advantageous because it avoids thoracotomy and has a shorter surgical time, but risk of intraoperative morbidity stresses the surgeon and lymph node sampling is not possible. METHODS: Mediastinoscope-assisted transhiatal esophagectomy (MATHE) was performed in 42 patients with esophageal cancer. Patients with superficial esophageal cancer and medical risk were included. Feasibility and efficacy of this procedure are discussed by examining short- and long-term morbidity, mortality, and survival. RESULTS: With the mediastinoscope, esophagectomy was performed safely under direct vision. There was only a small amount of bleeding, and surgical time was short. Little morbidity and no deaths were recorded. CONCLUSION: MATHE is a safe and minimally invasive technique that allows direct visualization of mediastinal structures Lymph node sampling was feasible because of clear visualization of the mediastinum.

Comparison of interleukin-6, interleukin-8, and granulocyte colony-stimulating factor production by the peritoneum in laparoscopic and open surgery.

BACKGROUND: Human mesothelial cells secrete a variety of cytokines. The levels of postoperative serum inflammatory cytokines are thought to reflect the magnitude of surgical stress. METHODS: Pieces of peritoneum were obtained immediately upon and 1 h after entry into the abdominal cavity in nine patients undergoing laparoscopic surgery and 11 patients undergoing open surgery. The samples were cultured and interleukin (IL)-6, IL-8, and granylocyte colony-stimulating factor (G-CSF) levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Expression of IL-6, IL-8, and G-CSF mRNAs was examined by RT-PCR. RESULTS: At 1 h after laparotomy, the amounts of IL-6 and G-CSF produced by the peritoneum were significantly greater than those obtained immediately after the procedure, but this difference was not observed with laparoscopic surgery. Reverse transcription-polymerase chain reaction (RT-PCR), which showed an increase in the expression of cytokine mRNAs at 1 h after laparotomy, was compatible with these results. CONCLUSION: The lower levels of cytokine production by the peritoneum suggest that laparoscopic surgery is associated with lower degree of surgical stress.

[Local therapy for stage IV advanced breast cancer with brain metastasis].

A 55-year-old female patient was diagnosed with right breast cancer with brain metastasis of 3 cm in size. Neurological examination revealed paralysis in the left upper and lower extremities. Chemotherapy and hormone therapy were performed. Brachytherapy by Cyberknife was performed for the brain metastatic lesion. As a result, the brain metastatic lesion decreased in size to 1 cm on the CT-scan after 2 months. The paralysis disappeared and the patient's QOL improved. Cyberknife therapy was useful for a brain metastatic lesion that harmed the patient's QOL.

Nm23-H1 gene as a molecular switch between the free-floating and adherent states of gastric cancer cells.

The contribution of the nm23-H1 gene to metastasis in malignant tumors, including gastric cancer, is controversial. In this study, we compared nm23-H1 levels in two cell subtypes with different morphologies (floating and adherent states), but that were derived from the same gastric cancer cell line, KATO-III. A real-time quantitative reverse transcription-polymerase chain reaction showed that the number of nm23-H1 mRNA molecules in floating cells was significantly higher than that in adherent cells (P<0.0001). The average of the copies in floating cells was approximately 2.4-fold higher than that in adherent cells. Consistent with mRNA levels, intracellular levels of nm23-H1 protein were higher in floating cells than in adherent cells. There was no difference in cell cycle characteristics between the two subtypes. In conclusion, our present data indicate that expression of nm23-H1 by a tumor could be altered during the different steps in metastases, suggesting that nm23-H1 may act as a molecular switch between the free-floating and adherent states of cancer cells.

Interleukin-6 production in lung tissue after transthoracic esophagectomy.

BACKGROUND: The mechanisms of the reported high increase in interleukin-6 (IL-6) levels after esophagectomy are unclear. We investigated the influence of an intrathoracic procedure, esophagectomy, on IL-6 production in lung tissue. STUDY DESIGN: Fourteen paired lung tissue samples were obtained from patients before and after they underwent transthoracic esophagectomy for esophageal cancer. IL-6 levels in the lung were measured with enzyme-linked immunosorbent assay, and IL-6 mRNA expression was determined with real-time quantitative reverse transcription-polymerase chain reaction. Immunohistochemical staining was used to localize IL-6, and circulating levels were also measured. RESULTS: IL-6 protein and mRNA were significantly increased in lung tissue after this intrathoracic procedure (p < 0.05). Peak levels of plasma IL-6 after surgery were correlated with IL-6 levels in lung tissues obtained after the procedure (p < 0.05). Immunohistochemical staining revealed IL-6 production from alveolar and bronchial epithelial cells but not from alveolar macrophages. CONCLUSIONS: Transthoracic esophagectomy causes an increase in IL-6 production from airway epithelial cells, secondary to increased expression of IL-6 mRNA. Local response of lung tissue may be one source of increased serum IL-6 after this procedure.

[Significance of reduction surgery for giant hepatocellular carcinoma with diffuse lung metastases and multiple intrahepatic metastases].

Continuous systemic infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (500 mg/body/day) was performed for advanced hepatocellular carcinoma (HCC) after hepatectomy with diffuse lung metastases and multiple intrahepatic metastases. This infusion chemotherapy, cisplatin was continued for five days, and discontinued for two days, whereas 5-fluorouracil was administered every day and repeated four weeks as one course basally. Remnant metastases had almost disappeared after systemic chemotherapy for 10 weeks. In our experience, the response rate in 13 patients who underwent reduction surgery for multiple HCC was 84.6%. Continuous infusion of low-dose CDDP/5-FU may be effective in patients having absolute non-curative resection.

[Hepatocellular carcinoma with tumor thrombus in the portal and hepatic veins treated successfully with hepatectomy and chemotherapy--a case report].

A 39-year-old woman was admitted to our hospital because of advanced hepatocellular carcinoma. She had good liver function with clinical Stage I. Abdominal ultrasonographic study and CT scan revealed a huge tumor of 12 cm in diameter in the left lobe of the liver, with tumor thrombi in the portal and hepatic veins. A chest CT scan demonstrated multiple bilateral lung metastases from 5 to 10 mm in size. An extended left hemihepatectomy with extirpation of the portal and hepatic venous tumor thrombi was performed. On postoperative day 7, low-dose cisplatin (10 mg/day-5 days/week) and 5-fluorouracil (250 mg/day-continuous for 7 days/week) were administered intravenously. Four weeks after chemotherapy, CT scan revealed no recurrence in the liver and no change in the lung metastases. The patient is now being treated on an outpatient basis with no change in the metastatic tumors.

Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells: possible association with Na(+), K(+)-ATPase.

Previously, we showed that expression of nm23-H1 is associated inversely with sensitivity to cisplatin in human oesophageal squamous cell carcinoma (OSCC). The present study was undertaken to investigate the association of nm23-H1 expression with cisplatin-induced DNA damage in OSCC using antisense nm23-H1 transfectants. YES-2/AS-12, an antisense nm23-H1-transfected OSCC cell line, showed significantly reduced expression of intracellular nm23-H1 protein compared with that in parental YES-2 cells and YES-2/Neo transfectants. Surface expression of nm23-H1 protein was not observed in any of the three cell lines. PCR analysis for DNA damage demonstrated that YES-2/AS-12 cells were more resistant to nuclear and mitochondrial DNA damage by cisplatin than were YES-2/Neo cells. In addition, mitochondrial membrane potentials and DNA fragmentation assays confirmed that YES-2/AS-12 was more resistant than YES-2/Neo to apoptosis induced by cisplatin. In contrast, YES-2/AS-12 was more sensitive to ouabain, a selective inhibitor of Na(+), K(+)-ATPase, than YES-2 and YES-2/Neo. Pre-treatment with ouabain resulted in no differences in cisplatin sensitivity between the three cell lines examined. Intracellular platinum level in YES-2/AS-12 was significantly lower than that in YES-2 and YES-2/Neo following incubation with cisplatin, whereas ouabain pre-treatment resulted in no differences in intracellular platinum accumulations between the three cell lines. Our data support the conclusion that reduced expression of intracellular nm23-H1 in OSCC cells is associated with cisplatin resistance via the prevention of both nuclear and mitochondrial DNA damage and suggest that it may be related to Na(+), K(+)-ATPase activity, which is responsible for intracellular cisplatin accumulation.

Detection of telomerase activity in peritoneal lavage fluid from patients with gastric cancer using immunomagnetic beads.

Cytologic examination of peritoneal lavage fluid is a useful predictor of peritoneal recurrence in gastric cancer. However, this technique is not overly sensitive and requires special abilities in the cytologist. In this study, telomerase activity was used to detect free cancer cells in peritoneal lavage fluid from patients with gastric cancer. In the first part, 12 lavage-fluid samples obtained from 12 patients with gastric cancer were analysed using the conventional telomeric repeat amplification protocol (TRAP) assay. Three of five patients with early gastric cancer had positive telomerase activity. These false-positive results may have been due to lymphocyte contamination. Furthermore, polymerase chain reaction inhibitors were also detected in the lavage-fluid samples. Therefore, we developed a novel method for elimination of haematopoietic cell and Taq polymerase inhibitors to increase the accuracy of the TRAP assay using immunomagnetic beads, which bind to most normal and neoplastic human epithelial cells. Telomerase activity was found in 10 of 20 (50%) lavage-fluid samples from patients with serosal or subserosal invasion. Cytologic examination was positive in nine of 20 (45%) samples. Both the telomerase activity and cytology were negative in all 14 patients without serosal or subserosal invasion. These results suggest that the TRAP assay combined with immunomagnetic beads might be useful for detection of free cancer cells in the peritoneal space in gastric cancer without the aid of an experienced cytologist.

Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6.

Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.

[Esophageal dilation therapy for achalasia of the esophagus].

Esophageal dilation therapy for esophageal achalasia has a 300-year history and remains the first-line therapy because of its low cost, progressively decreasing morbidity and mortality, and possibility of surgery for patients who do not improve. Another advantage is the feasibility of repeated trial even after surgery. The aim of this procedure is to produce a controlled tear in the lower esophageal sphincter muscle. Precise esophagographic, endoscopic, and manometric diagnosis is necessary for successful esophageal dilation therapy. In addition, the exclusion of pseudoachalasia using echogram or CT scan is important. The procedure should be carried out accurately to prevent complications. If perforation occurs, appropriate, timely management is required.