Prognostic impact of circumferential resection margin in esophageal cancer with or without neoadjuvant chemoradiotherapy.

The prognostic impact of circumferential resection margin (CRM) in surgically resected esophageal squamous cell carcinoma (ESCC) has been controversial. This investigation assessed the prognostic impact of CRM in surgically resected pathologic T3 ESCC patients with or without neoadjuvant chemoradiotherapy (nCRT). We reviewed consecutive p/yp T3 ESCC patients undergoing esophagectomy from two medical centers between January 2009 and December 2016. The cohort was divided into two groups: upfront esophagectomy (upfront surgery) and nCRT followed by esophagectomy (nCRT + surgery). CRM status was assessed and divided into CRM > 1 mm, 0 < CRM < 1 mm, and tumor at CRM. A total of 217 p/yp T3 ESCC patients undergoing esophagectomy (138 patients in the upfront surgery group and 79 in the nCRT + surgery group) were enrolled. In the upfront surgery group, patients with 0 < CRM < 1 mm showed equivalent overall survival to those with CRM > 1 mm (log-rank P = 0.817) and significantly outlived those with tumor at CRM (log-rank P < 0.001). However, in the nCRT + surgery group, CRM > 1 mm failed to show survival superiority to CRM between 0 and 1 mm or involved by cancer (log-rank P = 0.390). In conclusion, a negative CRM, even though being <1 mm, is adequate for pT3 ESCC patients undergoing upfront esophagectomy. In contrast, the CRM status is less prognostic in ypT3 ESCC patients undergoing nCRT followed by esophagectomy.

Requirement for signal peptide cleavage of Escherichia coli prolipoprotein.

Oligonucleotide-directed site-specific mutagenesis was applied to alter the cleavage site in the signal peptide of the major outer membrane lipoprotein of Escherichia coli. Replacing the glycine residue at the cleavage site with an alanine residue did not affect the processing of the signal peptide. However, when the same cleavage site was constructed by the deletion of the glycine residue, the signal peptide was no longer cleaved. These results indicate that stringent structural integrity at the cleavage site in the lipoprotein signal sequence is required for correct processing of prolipoprotein.

Thrombotic Ringed Polytetrafluoroethylene Graft With Infection After Living-Donor Liver Transplantation.

BACKGROUND: The safety of the living donor in living-donor liver transplantation (LDLT) is always the first priority, meanwhile, the graft-to-recipient weight ratio (GRWR) and the anatomy of the liver allograft must also not be compromised in order to warrant tranplatation success. When it comes to the allograft of the right lobe of the liver without the middle hepatic vein (R-M), the outflow and adequate drainage for the territory of middle hepatic vein (MHV) is one critical concern. Despite publications in some high-volume transplant centers on the positive results of using expanded polytetrafluoroethylene (ePTFE) grafts to substitute those of autologous veins, complications related to the ePTFE graft have not been well discussed. METHODS: From July 2012 to June 2016, 129 adult patients who underwent living donor liver transplantation in Taipei Veterans General Hospital were analyzed. There were 3 cases of adjacent organ erosion with gas bubbles in the lumen of an ePTFE graft, including gastrointestinal (GI) tract penetration in 2 out of the first 15 cases that used the venous graft of ringed expanded polytetrafluoroethylene (rPTFE). The patient survival rate during this period was compared and radiological findings of rPTFE function and clinical signs of erosion with infection were also examined to raise the concerns of safety as well as early detection of complications of rPTFE. RESULTS: The overall 1-year patient survival rate was 90%, of which the right lobe wih MHV (R+M) group was 93.5% and the R-M group was 91.9%. For the mean of GRWR, the R+M group was 1.05 ± 0.19 and R-M group was 1.19 ± 0.27, while those who needed reconstruction with vein grafts was 0.96 ± 0.11. Among the R-M group, 24 out of 88 cases (27.3%) needed reconstruction of MHV tributaries. Of the 24 cases, 15 cases were done with rPTFE and the 1-year patient survival rate of the rPTFE group was 73%, which is significantly worse (P = .008) than the non-rPTFE (89%) and non-reconstructed (97%) groups. The mean GRWR is significantly higher (P = .001) in the non-reconstructed group (1.19 ± 0.27) than in the rPTFE (0.99 ± 0.11) and non-rPTFE (0.94 ± 0.11) groups. The venous grafts patency rate between the different graft types is no different, and there is also significance in warm ischemic time (P = .009) between the non-reconstructed (49 ± 15), rPTFE (81 ± 51), and non-rPTFE (56 ± 18) groups in the mean minutes. CONCLUSION: In cases of fever of unknown cause in patients receiving LDLT with rPTFE graft, a regular computed tomography (CT) scan with contrast and gas bubbles within the graft lumen is the best way for early detection of graft related infection and suspicious GI tract penetration. To decrease the risks of tissue reaction induced by ePTFE graft in LDLT, omentum patches or other inert agents can be introduced as a buffer between the graft and adjacent organs, especially the GI tracts. However, research in material science shall be explored to solve the problem in the future.

Pre-tracheal lymph node metastasis in squamous cell carcinoma of the thoracic esophagus.

AIMS: To clarify the incidence of pre-tracheal lymph node metastasis in squamous cell carcinoma of the esophagus, and their impact on survival. METHODS: A cohort of 101 patients with squamous cell carcinoma of the thoracic esophagus who underwent esophagectomy together with 2-field lymphadenectomy including the pre-tracheal region was analysed, retrospectively. The p-TNM staging included stage I in 9, stage IIa in 33, stage IIb in 4, stage III in 43, and stage IV in 12 cases. RESULTS: Nodal metastases were identified in 56 patients (55.4%). Subcarinal lymph node and pre-tracheal lymph-node metastases were found in 24 patients (23.8%) and 15 patients (14.9%), respectively. The 5-year cumulative survival rates were 26.5 and 2.5% in nodal negative and nodal positive patients, respectively. Patients with pre-tracheal nodal metastasis all died within 2 years. Cox proportional hazards model in patients with nodal involvement revealed T-factor (p=0.0017), pre-tracheal nodal involvement (p=0.0055) and distant metastasis (p=0.0024) as independent prognostic factors. CONCLUSIONS: Our findings suggest that pre-tracheal lymph node metastasis indicates a dismal prognosis. Its occurrence is not unusual, especially in tumour of upper or middle thoracic esophagus. The subcarinal node cannot be regarded as a sentinel node of the pre-tracheal nodal station. Complete lymphadenectomy excluding the pre-tracheal lymph nodes in treating esophageal cancers is only a myth.

Development and characterization of an immobilized human organic cation transporter based liquid chromatographic stationary phase.

Membranes from a stably transfected cell line that expresses the human organic cation 1 transporter (hOCT1) have been immobilized on the immobilized artificial membrane (IAM) liquid chromatographic stationary phase to form the hOCT1(+)-IAM stationary phase. Membranes from the parent cell line that does not express the hOCT1 were also immobilized to create the hOCT1(-)-IAM stationary phase. Columns were created using both stationary phases, and frontal displacement chromatography experiments were conducted using [(3)H]-methyl phenyl pyridinium ([(3)H]-MPP(+)) as the marker ligand and MPP(+), verapamil, quinidine, quinine, nicotine, dopamine and vinblastin as the displacers. The K(d) values calculated from the chromatographic studies correlated with previously reported K(i) values (r(2)=0.9987; p<0.001). The data indicate that the hOCT1(+)-IAM column can be used for the on-line determination of binding affinities to the hOCT1 and that these affinities are comparable to those obtained using cellular uptake studies. In addition, the chromatographic method was able to identify a previously undetected high affinity binding site for MPP(+) and to determine that hOCT1 bound (R)-verapamil to a greater extent than (S)-verapamil.

Antisense suppression of proline-directed protein kinase FA enhances chemosensitivity in human prostate cancer cells.

Initial clinic studies revealed that proline-directed protein kinase FA (PDPK FA) is overexpressed manyfold in various human cancerous tissues relative to the normal control. However, the role of overexpressed PDPK FA in cancers remains unknown and needs to be established. To determine whether PDPK FA is associated with drug sensitivity, we investigated the effects of partial inhibition of this kinase on the human prostate carcinoma cell line (PC-3). PDPK FA antisense expression vector and its specific antibody were successfully developed. Two stable transfected antisense clones (PA7 and PA3) of human prostate carcinoma cell were subcloned, and they expressed approximately 75% and approximately 35% of the total PDPK FA existing in the control-transfected clone as determined by both immunoprecipitate activity assay and immunoblot analysis. In sharp contrast, the PDPK FA antisense clones expressed no significant suppression of any other related proline-directed protein kinase member expression, demonstrating the specificity of these two antisense clones. When compared with parental or control-transfected cells, the low-PDPK FA-expressing antisense clones displayed an enhanced sensitivity to carboplatin, 5-fluorouracil, paclitaxel, and hydroxyurea. Estimation of the IC50 index further revealed that the antisense clones displayed up to > 100-fold drug sensitivity, and there was a correlation between suppressed levels of PDPK FA and drug sensitivity. Taken together, the results demonstrate that specific antisense suppression of overexpressed PDPK FA in human prostate cancer cells is sufficient to enhance various drug sensitivity, indicating that PDPK FA is an important regulator in controlling multiple drug resistance of human prostate cancer cells.

Long-term results of coronary artery bypass grafting in patients with dialysis-dependent renal failure.

AIM: Coronary artery disease is the main cause of mortality and morbidity in dialysis-dependent renal failure patients. Both the prevalence and incidence of renal failure are high in Taiwan. However, there were few reports exploring the outcome of coronary aortic bypass grafting (CABG) in these patients. The aim of this study was to determine the survival outcome and risk factors for mortality from CABG in this population. METHODS: The operative, early postoperative and late results of 170 dialysis patients undergoing isolated coronary artery bypass grafting from January, 2000 to January, 2012 were retrospectively reviewed. Operative mortality, long-term survival, and risk factors were analyzed. RESULTS: One hundred and seventeen patients (68.8%) were male, and the mean age was 61.5±10.3 years (range, 34-86 years). Follow-up was 40.3±32.1 months. Operative mortality was 8.2%. Actuarial survival, including operative mortality, was 81±3% at 1 year, 68±4% at 3 years, 58±5% at 5 years and 49±6% at 10 years, better than the natural course of dialysis-dependent renal failure patients. Age, emergent operation, postoperative ventricular tachycardia or fibrillation, postoperative intra-aortic balloon pump insertion, gastrointestinal bleeding, and left internal mammary artery graft were significant predictors of operative or long term mortality. Most causes of late death were due to infection or cardiac events. CONCLUSION: CABG in dialysis patients is associated with a higher incidence of complications, but has acceptable mortality. CABG is beneficial in this population. Internal mammary artery grafting may provide more favorable long term outcomes.

Bronchioloalveolar carcinoma.

Bronchioloalveolar carcinoma is a subtype of adenocarcinoma of the lung with a relatively better prognosis. We reviewed the cases of 50 consecutive patients with bronchioloalveolar carcinoma treated during a 10-year period and attempted to analyze factors related to prognosis. During the 10-year study period, the prevalence of bronchioloalveolar carcinoma relative to adenocarcinoma of the lung remained steady. The subjects included 32 male and 18 female patients with mean ages of 64.7 years and 55.1 years, respectively (p = 0.0030). The preoperative radiographic findings included 40 cases of localized and 10 cases of diffuse bronchioloalveolar carcinoma. The clinicopathologic TNM staging included 20 patients with stage I cancer, 4 with stage II cancer, 11 with stage IIIa cancer, 3 with stage IIIb cancer, and 12 with stage IV cancer. Forty patients with clinical stage I, II, or III disease underwent operation (operability 80%). The resectability rate was 90% (36 of 40). Thirty-four procedures were considered as curative. The overall cumulative survival at 5 years was 22.2% (46.4% for stage I). Different TNM stages showed significant differences in survival time (p = 0.0001). The median survival times were 64.6 months for stage I, 48.0 months for stage II, 24.7 months for stage IIIa, 9.0 months for stage IIIb, and 4.5 months for stage IV disease. The median survival time for localized bronchioloalveolar carcinoma was 27.5 months, and the median survival time for diffuse bronchioloalveolar carcinoma was 4.3 months (p = 0.0002). The median survival time for the curative resection group was 30.6 months, and the median survival time for the noncurative resection or nonresection group was 5.8 months (p = 0.0001). On the basis of this study we conclude that (1) the prevalence of bronchioloalveolar carcinoma is quite steady, (2) bronchioloalveolar carcinoma presents at an earlier age in women, (3) bronchioloalveolar carcinoma frequently presents with lymphatic spread or systemic metastasis at diagnosis, (4) most localized bronchioloalveolar carcinomas are resectable and the prognosis with this type is better than that of the diffuse type, and (5) long-term survival correlates closely with initial roentgenographic appearance, TNM stage, and completeness of surgical resection.

Clinical experience in radical lymphadenectomy for adenocarcinoma of the gastric cardia.

OBJECTIVES: We evaluated the pattern of nodal metastasis and its prognosis after radical lymphadenectomy in adenocarcinoma of the gastric cardia. METHODS: We conducted a retrospective cohort study of 70 patients (52 men and 18 women; mean age 63.6 years) with adenocarcinomas of the gastric cardia who underwent extended gastrectomy (65 total gastrectomies and 5 proximal gastrectomies) and radical lymphadenectomy (D2 to D4) at Taichung Veterans General Hospital between 1989 and 1995. RESULTS: Twenty-four complications developed in 22 (31.4%) patients, and seven (10.0%) hospital deaths occurred. An overall 5-year cumulative survival of 37.6% was obtained. Lymph node metastases were identified in 53 (75.7%) patients. Nodal involvement was closely related to the depth of tumor invasion (p = 0.005). When the gastric wall invasion was limited to the subserosal layer (T1 and T2, n = 15), no patient had N4 group nodal metastasis. Once the serosal layer had been involved (beyond T3), N4 group nodal metastasis was frequently seen (30.9%, 17 of 55 patients). A multivariable analysis revealed that the level of nodal involvement, the depth of tumor invasion, and the presence of complications were independent prognostic factors. Cumulative 5-year survivals of curability A (n = 12), B (n = 19), and C (n = 32) resections were 100%, 21.2%, and 27.5%, respectively (p = 0.0001). The long-term survival of the patients after resection was also closely related to their pTNM stages (p = 0.0004). CONCLUSIONS: We conclude that gastrectomy accompanied by radical lymphadenectomy provides a reasonable long-term survival expectancy that is closely related to the stage of the disease and the curability of resection.

Thymic carcinoma. Ten years' experience in twenty patients.

Thymic carcinoma is a rare neoplasm with extremely poor prognosis. To evaluate the outcome of treatment in thymic carcinoma, we reviewed a 10-year (1982 to 1992) experience with 20 consecutive patients in Taichung Veterans General Hospital. There were 9 men and 11 women: ages ranged from 34 to 70 years old (mean 51.4 years). None of these patients had concomitant myasthenia gravis. All of the patients received surgical intervention, and the diagnosis was made by pathologic study. Postoperative staging was made according to the modified Masaoka staging system. None of our patients were in stage I. One patient (5%) had stage II disease, 12 (60%) stage III, and 7 (35%) stage IV. The pathologic subtypes of thymic carcinoma included eight squamous cell carcinomas, seven undifferentiated carcinomas, one lymphoepithelioma-like carcinoma, one clear-cell carcinoma, 1 mucoepidermoid carcinoma, and two carcinoid tumors. Curative resection could be done in seven patients (35%). The overall cumulative survival was 45.9% at 3 years and 34.4% at 5 years. The median survival times for patients with complete and incomplete resection were 39.0 months and 14.3 months, respectively (p = 0.1752). The median survival times of patients with postoperative radiotherapy and without postoperative radiotherapy were 39.3 months and 15.0 months, respectively (p = 0.0738). The median survival times of patients with squamous cell carcinoma and undifferentiated carcinoma were 25.4 months and 11.3 months, respectively (p = 0.1464). Our data show that complete resection, postoperative radiotherapy, and squamous cell carcinoma do not indicate a significantly favorable result, even though they result in longer median survival times. Yet a positive trend of favorable outcome in patients who received postoperative radiotherapy is ambiguously shown.

Serotonin-6 receptor variant (C267T) and clinical response to clozapine.

Clozapine is an effective atypical antipsychotic that has high affinity for serotonin type 6 receptors (5HT6). We tested the hypothesis that clinical response to clozapine in patients refractory to typical antipsychotic treatment is related to the genetic variant (C267T) of the 5HT6 receptors. Ninety-nine schizophrenic patients with a history of non-response to typical antipsychotics were included in the study. The results demonstrated a modest but significant relationship between presence of the variant of the 5HT6 receptors and the response to clozapine in these patients. Patients with homogenous 267T/T genotype had a better response than other patients. Although replication is required, these results suggest that the 5HT6 receptor C267T polymorphism may be involved in clozapine response, especially in patients with anxious or depressed symptoms.

No evidence for association of serotonin-2A receptor variant (102T/C) with schizophrenia or clozapine response in a Chinese population.

The serotonin hypothesis in schizophrenia had regained interest with the superior efficacy of clozapine in the refractory schizophrenic patients. Among the serotonin receptors, the serotonin 2A (5HT2A) receptor subtype is the most widely studied. Previous studies on the association between a silent mutation polymorphism of the 5HT2A gene (102T/C) and schizophrenia or clozapine response have yielded conflicting findings. Therefore, we investigated whether these genetic variants of the 5HT2A receptor are associated with schizophrenia or with response to clozapine treatment in a Chinese population. Ninety-seven schizophrenic patients and 101 control subjects were included in the study. The receptor variants were found at similar frequencies in schizophrenic patients and healthy control subjects. Also, we did not find the variants to influence the response to clozapine in schizophrenic patients. We suggest that the assessment method of clozapine response and the ethnicity may influence the result.

Experiences in thoracoscopic sympathectomy for axillary hyperhidrosis and osmidrosis: focusing on the extent of sympathectomy.

HYPOTHESIS: A more selective sympathectomy can improve the outcome of axillary hyperhidrosis and osmidrosis and minimize the potential sequelae. DESIGN: Retrospective cohort. SETTING: Tertiary care center. PATIENTS: Between July 1, 1996, and May 30, 2000, 171 patients with axillary hyperhidrosis and osmidrosis were studied. INTERVENTIONS: T3-4 sympathectomies were performed in 40 patients (group 1), T4 sympathectomies were performed in 56 patients (group 2), and T4-5 sympathectomies were performed in 75 patients (group 3). MAIN OUTCOME MEASURES: The surgical outcomes were evaluated by direct patient interview in the outpatient clinic or by telephone or mail questionnaires. The results were categorized as excellent (significant or complete disappearance of symptoms), good (>/=50% improvement), or poor (<50% improvement). RESULTS: There were no surgical mortalities in this study. Twenty-eight group 1 patients (70%), 16 group 2 patients (29%), and 22 group 3 patients (29%) developed compensatory perspiration (P<.001). Six group 1 patients (15%), 1 group 2 patient (2%), and 1 group 3 patient (1%) developed dry hands (P =.02). In the group 1 patients, the surgical outcomes were excellent in 21 (52%), good in 6 (15%), and poor in 13 (32%). In the group 2 patients, the surgical outcomes were excellent in 29 (52%), good in 10 (18%), and poor in 17 (30%). In the group 3 patients, the surgical outcomes were excellent in 53 (71%), good in 11 (15%), and poor in 11(15%) (P =.04). (Percentages may not sum to 100 because of rounding.) CONCLUSION: T4-5 sympathectomies provide higher patient satisfaction rates in treating axillary hyperhidrosis and osmidrosis, with fewer sequelae.

Outpatient thoracoscopic limited sympathectomy for hyperhidrosis palmaris.

Thoracoscopic sympathectomy is considered the most effective treatment for hyperhidrosis palmaris. We have treated 1,043 cases of this disease by this method. We have developed an outpatient technique of thoracoscopic sympathectomy using electrocautery. This procedure has been used in 47 patients with hyperhidrosis palmaris. The early results have been favorable. We describe this fast, safe, economic, and effective method for the treatment of hyperhidrosis palmaris.

Video-assisted thoracoscopic T2 sympathectomy for hyperhidrosis palmaris.

BACKGROUND: Hyperhidrosis palmaris is a functionally and socially disabling problem. Thoracic sympathectomy of the T2 ganglion has proved to be the time-honored treatment modality. STUDY DESIGN: The results of this study demonstrate the effectiveness of video-assisted thoracoscope for treatment of hyperhidrosis palmaris. The possibility to apply different anesthetic techniques and to measure surface temperature change of the hand were documented as well. RESULTS: Eighty consecutive cases (159 procedures) of essential hyperhidrosis palmaris were treated by video-assisted thoracoscopic T2 sympathectomy between January 1991 and December 1992. The surgical results were classified as excellent (much improved, very dry) in 88.1 percent, good (improved, minimal wet) in 9.4 percent, and fair (slightly improved, still wet) in 2.5 percent of the patients. The postoperative complications included one prolonged air leakage, one hemothorax, two wound infections, and 15 cases of facial anhidrosis. There were no recurrent cases (mean follow-up, 14.5 months). Fifty-six patients had concomitant hyperhidrosis pedum. Interestingly enough, through unknown mechanism, 64.3 percent of the patients with concomitant hyperhidrosis pedum were cured after this procedure. CONCLUSIONS: Video-assisted thoracoscopy provides magnified surgical fields, which make thoracoscopic sympathectomy for hyperhidrosis palmaris an effective, safe, easy to use, and time-saving procedure. This technique is also excellent for teaching purposes and allows the assistant to participate in the operation.

Optimizing Caco-2 cell monolayers to increase throughput in drug intestinal absorption analysis.

INTRODUCTION: The aim of this investigation was to evaluate methods for increasing Caco-2 cell throughput for assessing drug intestinal absorption. The use of 6-, 12-, and 24-well membranes and the effect of membrane size on permeability and the integrity of the Caco-2 cell monolayer were assessed. In an effort to optimize the assessment of drug permeability, increased throughput was investigated by testing compounds singly or as mixtures of analytes. METHOD: The transepithelial electrical resistance (TEER) of cell monolayers was measured on 0.33, 1.0, and 4.7 cm2 polycarbonate membranes using EVOM, over a 25-day period. Absorptive transport was determined on all compounds tested using LC-MS/MS assays, or liquid scintillation spectrometry. RESULTS: The effect of multiple compounds in one well compared to single compounds was assessed with atenolol, nadolol, metoprolol, and propranolol for mixtures of four compounds and with RWJ-53308, atenolol, terbutaline, propranolol, naproxen, piroxicam, topiramate, and furosemide for mixtures of eight compounds. The apparent permeability (Papp) values correlated well between single analytes and mixtures of four and eight analytes in each well. Drug permeability decreased slightly with an increase in well size. The TEER value increased with the number of days in culture for each of the 6-, 12-, and 24-well sizes. DISCUSSION: It was demonstrated that the 24-well format system is ideal for high-throughput assessment. Furthermore, the approach of mixing four or eight analytes in each well to further increase throughput was also demonstrated to be valid.

Surgical experience in treating T4 lung cancer: its resectability, morbidity, mortality and prognosis.

Extensive experience in the treatment of locally advanced lung cancers is rare. The aim of this study is to show the rationality and effectiveness of an aggressive surgical approach in T4 lung cancers. Between 1984 and 1994, 111 consecutive cases of T4 lung cancers were operated on. The patients included 91 males and 20 females, with mean ages of 61.8 years and 55.3 years, respectively. The cell types included 57 squamous cell carcinomas, 42 adenocarcinomas, and 12 miscellaneous malignancies. Fifty-three (47.7%) procedures were non-resectional. The remaining 58 (52.3%) procedures had various extents of pulmonary resection. These surgical procedures included 24 (21.6%) pulmonary resections with gross residual tumour (R2), nine (8.1%) pulmonary resections with microscopic residual tumour (R1), and 25 (22.5%) curative pulmonary resections without residual tumour (R0). Post-operative adjuvant therapy included radiotherapy ( > or = 3000 rads) in 53 patients (47.7%), and cisplatin-based chemotherapy in 15 patients (13.5%). The overall median survival time of these 111 patients was 9.1 months. The overall cumulative survival rates at 1, 2, 3 and 5 years were 38.0%, 20.4%, 15.3%, and 5.5%, respectively. There were 24 (21.6%) complications and eight (7.2%) hospital mortalities. Most of the pleural seedings were caused by adenocarcinomas, while most of the curatively resected tumours were squamous cell carcinomas. Our data demonstrate that: (1) Almost a quarter (22.5%) of T4 lung cancers could be curatively resected, and the cumulative 5-year survival rate was 23.4%; (2) squamous cell carcinoma had a higher curative resection rate (P = 0.0381), while adenocarcinoma showed higher possibility of pleural seeding (P = 0.0000); (3) the prognosis of T4 lung cancers did not relate to their nodal status (P = 0.7978), and cell type (P = 0.4169); (4) complete surgical resection provided the best rates for long-term survival (P = 0.0263); (5) the complication rate was higher in the resectional group (P = 0.0221); (6) post-operative irradiation did not lengthen survival times (P = 0.1720); and (7) post-operative chemotherapy did not improve survival (P = 0.1577). We conclude that surgery to T4 lung cancers should only be performed in highly selected patients due to their poor prognosis, and the associated high complication and mortality rates.

Concordant expression of the telomerase-associated genes in non-small cell lung cancer.

AIMS: h-TERT is the keystone gene in controlling telomerase expression under the modulation of many associated genes. Our study was designed to observe the concordant expression of the telomerase associated genes in NSCLC (non-small cell lung cancer). METHODS: Between January 1999 and December 1999, 78 NSCLC patients were studied. The telomerase activity was measured by TRAP (telomeric repeat amplification protocol) assay, and the associated genes (h-TERT, h-TERC, TP1, c-Myc, TRF1, and TRF2) were detected using RT-PCR method. RESULTS: Positive telomerase activity was identified in 47 (60.3%) patients. Expression of the h-TERT, h-TERC, TP1, c-Myc, TRF1 and TRF2 genes were observed in 66.6, 92.3, 100.0, 91.0, 74.4 and 83.3% of the tumor tissues, respectively. Higher expression of the telomerase activity was found in advanced T-status (p=0.0265), and late TNM stages (p=0.0497) patients. In addition to the tumor tissue itself (p<0.0001), higher telomerase expression rates were observed in positive h-TERT (p<0.0001), and positive TRF1 (p=0.003) tumor tissues compared to their normal counterparts. Furthermore, h-TERT expression was closely related to the TRF1 (p=0.003), TRF2 (p=0.024), and c-Myc (p=0.042) expression. CONCLUSIONS: Our data demonstrate that expression of the telomerase activity can be observed in the majority of NSCLC tumor tissues, and is also closely related to the T-status and TNM stage of the tumor. h-TERT expression and subsequent telomerase activation leads to telomere repair under modulation by the TRF1, TRF2 and c-Myc genes.

CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs.

The present study characterized Chinese hamster ovary cells overexpressing a human intestinal peptide transporter, CHO/hPEPT1 cells, as an in vitro model for peptidomimetic drugs. The kinetic parameters of Gly-Sar uptake were determined in three different cell culture systems such as untransfected CHO cells (CHO-K1), transfected CHO cells (CHO/hPEPT1) and Caco-2 cells. Vmax in CHO/hPEPT1 cells was approximately 3-fold higher than those in Caco-2 cells and CHO-K1 cells, while Km values were similar in all cases. The uptake of beta-lactam antibiotics in CHO/hPEPT1 cells was three to twelve fold higher than that in CHO-K1 cells, indicating that CHO/hPEPT1 cells significantly enhanced the peptide transport activity. However, amino acid drugs also exhibited high cellular uptake in both CHO-K1 and CHO/hPEPT1 cells due to the high background level of amino acid transporters. Thus, cellular uptake study in CHO/hPEPT1 cells is not sensitive enough to distinguish the peptidyl drugs from amino acid drugs. The potential of CHO/hPEPT1 cells as an in vitro model for peptidomimetic drugs was also examined through the inhibition study on Gly-Sar uptake. Peptidomimetic drugs such as beta-lactam antibiotics and enalapril significantly inhibited Gly-Sar uptake whereas the nonpeptidyl compounds, L-dopa and alpha-methyldopa, did not compete with Gly-Sar for cellular uptake within the therapeutic concentrations. In conclusion, the present study demonstrates the further characterization of CHO/hPEPT1 cells as an uptake model as well as inhibition study and suggests their utility as an alternative in vitro model for drug candidates targeting the hPEPT1 transporter.

Subxiphoid approach for thoracoscopic thymectomy.

Avoiding sternotomy, cumulative experience has demonstrated the efficacy and safety of minimally invasive thoracoscopic thymectomy. Previous reports describing the transcervical, left or right thoracic approach, although demonstrating promising results, involve some compromise of the surgical exposure. We designed a new approach through the subxiphoid route to perform extended thymectomy using the standard thoracoscopic technique. We used this approach on two consecutive patients. Additional port sites were created on both sides of the anterior chest wall for introducing instruments. This approach provides an excellent view of the bilateral pleural cavities, which is essential for adequate mediastinal fatty tissue dissection, especially because the surgical plan calls for removal of all the bilateral pericardiophrenic fat pads and the mediastinal fat tissue between the bilateral phrenic nerves. This approach omits the sternotomy while making extended thymectomy possible through the bilateral access. All the possible thymic-bearing mediastinal fat tissues can be removed under direct thoracoscopic view, which may subsequently translate into better results.