A method for the infectivity discrimination of enveloped DNA viruses using palladium compounds pre-treatment followed by real-time PCR.

Cultivation-based assays represent the gold standard for the assessment of virus infectivity; however, they are time-consuming and not suitable for every virus type. Pre-treatment with platinum (Pt) compounds followed by real-time PCR has been shown to discriminate between infectious and non-infectious RNA viruses. This study examined the effect of Pt and palladium (Pd) compounds on enveloped DNA viruses, paying attention to two significant pathogens of livestock - bovine herpesvirus-1 (BoHV-1) and African swine fever virus (ASFV). Native or heat-treated BoHV-1 suspension was incubated with the spectrum of Pt/Pd compounds. Bis(benzonitrile)palladium(II) dichloride (BB-PdCl 2) and dichloro(1,5-cyclooctadiene) palladium(II) (PdCl 2-COD) produced the highest differences found between native and heat- -treated viruses. Optimized pre-treatment conditions (1 mM of Pd compound, 15 min, 4°C) were applied on both virus genera and the heat inactivation profiles were assessed. A significant decrease in the detected quantity of BoHV-1 DNA and ASFV DNA after heat-treatment (60°C and 95°C) and consequent incubation with Pd compounds was observed. BB-PdCl 2 and PdCl 2-COD could help to distinguish between infectious and non-infectious enveloped DNA viruses such as BoHV-1 or ASFV.

CD34+ enriched cell products intended for autologous transendocardial CD34+ cell transplantation release significant amounts of angiopoietin-1.

OBJECTIVES: Cell-based therapy has emerged as a promising strategy for the treatment of patients with heart failure. Increasing evidence supports the hypothesis that paracrine mechanisms mediated by soluble factors released by the cells play a predominate role in reparative processes. The aim of our study was to analyze which cytokines are released by CD34+ enriched cell products intended for autologous transendocardial CD34+ cell transplantation in patients with cardiomyopathy. MATERIAL AND METHODS: The peripheral blood CD34+ cells from 12 patients were mobilized with granulocyte colony-stimulating factor, collected via apheresis and enriched by immunoselection. RESULTS: In CD34+ enriched cell population, hematopoietic, but not mesenchymal or endothelial, progenitors were detected. Except for angiopoietin-1, other measured cytokines (FGF1, FGF2, VEGF, PDGF, IL-6, HGH, SDF-1α/CXCL12, NRG1) were not released by CD34+ cells. The average concentration of angiopoietin-1 released by 5×106 CD34+ cells grown in neutral DMEM medium was 213.6±130.0pg/mL (range: 74-448pg/mL). Angiopoietin-1 secretion correlated well with CD34+ cell's capacity for generating colonies derived from hematopoietic progenitors (Pearson's correlation=0.964; P<0.001). CONCLUSION: Our study presents angiopoietin-1 as an interesting candidate and suggests future studies to explore how its release by CD34+ cells might impact the success of autologous CD34+ cell transplantation.

Functional analysis of long-term outcome after Heller's myotomy for achalasia.

Treatment of achalasia aims at reducing the pressure of the lower esophageal sphincter (LES) and palliate symptoms. Our objective in this study was to investigate functional changes of the esophagus after Heller myotomy and evaluate their influence on postoperative gastroesophageal reflux and esophageal morphologic changes. Between 1980 and 2003, 216 patients with achalasia underwent Heller myotomy, associated with anterior partial fundoplication (Dor fundoplication). Preoperative and long-term outcome data were collected from these patients at our hospital. The objective was to analyze esophageal functional results after Heller myotomy in the long term. Results were classified as excellent, good, fair, or poor, according to Vantrappen and Hellemans' modified classification. One-year, 2-year, 5-year, 10-year, and 20-year postoperative follow-up information was available in 100% of all patients, 91.7%, 85.1%, 60%, 52.6%, and 45.9%, respectively. There were no perioperative deaths. One year after the surgery, all patients had a significant reduction in symptoms of dysphagia and regurgitation. Five years, 10 years, 15 years, and 20 years after surgery, there were 77.2% of patients (142 in 184), 68.1%, 57.1%, and 54.5%, respectively, who were satisfied (excellent to good) with surgery. No esophageal peristalsis was demonstrated in patients during follow-up. Contractile waves in the body of the esophagus were simultaneous. The difference in the distal esophageal amplitude, the LES relaxation rate, and LES pressures in the anterior wall and/ or two sides was significant (P < 0.05) when compared before and after operation. However, there was no significant difference in the LES length and LES pressure in the posterior side. The change of direction of the LES pressure and the relaxation of LES correlate with long-term outcomes. Postoperative gastroesophageal reflux rates, including nocturnal reflux, increased with time. The percentage of patients whose esophageal diameter became normal or remained mildly increased with time in the first 10 years after surgery changed significantly. Myotomy is an effective way to palliate symptoms in patients with achalasia. Adequate myotomy can lead to reduction of LES pressure in two or three directions, which may facilitate esophageal emptying by gravity. Surgical intervention does not lead to the return of esophageal peristalsis. Functional damage of LES in patients with achalasia is irreversible.

Biologic lung volume reduction therapy for advanced homogeneous emphysema.

This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

Outcome of floppy Nissen fundoplication with intraoperative manometry to treat sliding hiatal hernia.

The aim of this study was to evaluate the effectiveness of floppy Nissen fundoplication with intraoperative esophageal manometry. Between February 1992 and July 2004, there were 102 patients with sliding hiatal hernia undergoing transabdominal Nissen fundoplication. They were divided into three groups: 27 patients were in the Nissen group (CNF), 44 in the floppy Nissen group (FNF, including 5 with laparoscopic Nissen fundoplication), and 31 in the intraoperative-esophageal-manometry group (INF, 13 with laparoscopic Nissen fundoplication). There were no operation-related deaths. Operation-related complications occurred in five patients within 1 month after operation: In CNF, two patients suffered from dysphagia and one from regurgitation; in FNF, one patient had slight dysphagia and two had regurgitation; in INF, there was no one who complained about dysphagia or regurgitation, but pneumothorax occurred in one case. After more than 2 years of follow-up, two patients, in CNF, suffered from severe dysphagia, one recurred and two with abnormal 24 h pH monitoring. In FNF, one patient had dysphagia, one recurred and three had abnormal 24 h pH monitoring; in INF, two patients had acid reflux on 24 h pH monitoring. The postoperative lower esophageal sphincter pressure was in the normal range in 30 of 31 patients (96.5%). The normal rate of postoperative tests in CNF, FNF and INF were 81.5%, 86.4% and 93.5%, respectively. Both the Nissen fundoplication and the floppy Nissen fundoplication are effective approaches to treat patients with sliding hiatal hernia. Intraoperative manometry is useful in standardizing the tightness of the wrap in floppy Nissen fundoplication and may contribute to reducing or avoiding the occurence of postoperative complications.

Platelet gel stimulates proliferation of human dermal fibroblasts in vitro.

BACKGROUND: Platelet gel is a source of many soluble proteins that can modulate tissue regeneration. Dermal fibroblasts play an important role in tissue remodeling and wound healing. OBJECTIVE: The study was performed to investigate the influence of platelet gel and its active ingredients on the proliferation of human dermal fibroblasts in vitro. METHODS: A fibroblast culture was established from a normal human skin biopsy. Platelet gel was prepared from platelet-rich plasma (PRP) following the addition of calcified thrombin solution. Cell proliferation was measured by MTT assay. RESULTS: We showed that platelet gel, PRP, and thrombin stimulate the proliferation of dermal fibroblasts, and that stimulation by PRP is dose dependent. CONCLUSION: Platelet gel can be used to treat chronic skin defects.

Trimodality treatment versus surgery alone for esophageal cancer. A stratified analysis with minimally invasive pretreatment staging.

BACKGROUND: Accurate pretreatment staging of esophageal cancer (EC) is important in the evaluation and comparison of results of different treatment modalities. Few studies using minimally invasive staging techniques for this purpose have been reported. We previously demonstrated the usefulness of the thoracoscopic/laparoscopic (Ts/Ls) technique in pretreatment staging of EC. This study was conducted to evaluate the impact of trimodality based on pretreatment Ts/Ls staging diagnosis on EC. METHODS: A retrospective study was performed on 2 groups of EC patients. Group A (44 patients) underwent pretreatment Ts/Ls staging and had trimodality treatment. Preoperative therapy consisted of concurrent chemotherapy (5-FU + cisplatinum) and radiotherapy. Group B (33 patients) underwent surgery alone. The study focused on stratified comparison of patterns of recurrence and survival in different pretreatment surgical T, N, and TNM stage categories. RESULTS: The 3-year disease free survival of Group A was 40.8% with a median survival of 32.0 months, it was 43.6% with a median survival of 23.6 months in Group B. The difference was not significant (p=0.87). There was no difference in recurrence pattern between the 2 groups. Patients with squamous cell carcinoma in Group A had no local recurrence during the follow-up period while those in Group B had a high local recurrence rate of 40% (p<0.005). When stratified by T factor, patients with locally advanced T stage (T3-4) in Group A had a lower distant recurrence rate than their counterpart patients in Group B (9.1 vs 38.5%, p=0.03), they had a better survival but the difference was not significant (3-year disease free survival: 41.7 vs 17.9%, p=0.14). There were no significant differences in recurrence pattern and survival in different N categories and TNM stages between 2 groups. Multivariate analysis showed that only pretreatment surgical N status was an independent prognostic factor for the whole group (p=0.02). CONCLUSIONS: Pretreatment Ts/Ls staging can provide accurate staging information for EC patients. Trimodality treatment was successful in local control for patients with squamous cell carcinoma. It was effective in reducing distant recurrence and might prolong survival in patients with advanced T stages. Pretreatment lymph node status was the most important prognosticator regardless of treatment modality. Pretreatment pathological staging should be included in the future clinical trials on multimodality treatments in EC patients.

Global gene expression profiling in Barrett's esophagus and esophageal cancer: a comparative analysis using cDNA microarrays.

In order to identify and contrast global gene expression profiles defining the premalignant syndrome, Barrett's esophagus, as well as frank esophageal cancer, we utilized cDNA microarray technology in conjunction with bioinformatics tools. We hybridized microarrays, each containing 8000 cDNA clones, to RNAs extracted from 13 esophageal surgical or endoscopic biopsy specimens (seven Barrett's metaplasias and six esophageal carcinomas). Hierarchical cluster analysis was performed on these results and displayed using a color-coded graphic representation (Treeview). The esophageal samples clustered naturally into two principal groups, each possessing unique global gene expression profiles. After retrieving histologic reports for these tissues, we found that one main cluster contained all seven Barrett's samples, while the remaining principal cluster comprised the six esophageal cancers. The cancers also clustered according to histopathological subtype. Thus, squamous cell carcinomas (SCCAs) constituted one group, adenocarcinomas (ADCAs) clustered separately, and one signet-ring carcinoma was in its own cluster, distinct from the ADCA cluster. We conclude that cDNA microarrays and bioinformatics show promise in the classification of esophageal malignant and premalignant diseases, and that these methods can be applied to small biopsy samples.

Pretreatment surgical lymph node staging predicts results of trimodality therapy in esophageal cancer.

OBJECTIVE: Prediction of responders to induction therapy in esophageal cancer (EC) patients is important. In this study, we evaluated the role of thoracoscopic/laparoscopic (Ts/Ls) staging in prediction of treatment response and survival in EC patients with trimodality treatment. METHODS: Retrospective study of EC patients who had undergone Ts/Ls staging and received trimodality treatment at the University of Maryland Medical Center and the Baltimore Veterans Administration Hospitals from July, 1991 to December, 1999. Preoperative therapy consisted of concurrent chemotherapy (5-FU + cisplatinum) and radiotherapy. RESULTS: Forty-four EC patients who underwent pretreatment Ts/Ls staging during the study period were able to complete concurrent chemoradiotherapy followed by surgical resection. There were 36 men and 8 women aged 40 to 77 (median age 62). Twenty-seven (61.4%) patients were found to have lymph node metastasis by surgical staging. Fourteen patients (31.8%) had a pathologic complete response. Patients with positive lymph nodes had a lower response rate than those with negative lymph nodes (14.8% vs. 58.8%, P=0.006). Other clinicopathologic features including gender, weight loss, clinical TNM stage, surgical T stage, and histology did not correlate with treatment response. Univariate analysis showed that weight loss and treatment response were important prognostic factors for disease-free survival (P=0.01 and P=0.02, respectively). Histology, surgical N stage and surgical TNM stage appeared to be associated with prognosis (P=0.067-0.097). Multivariate analysis revealed that only surgical N status and weight loss were significant prognostic factors (P=0.05, and P=0.006, respectively). CONCLUSIONS: Surgical Ts/Ls staging provides accurate evaluation of tumor spread in EC patients. Pretreatment N status was the single most important predictor of response to induction treatment as well as a reliable prognosticator of survival.

CALGB 9380: a prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer.

BACKGROUND: The staging of esophageal cancer is imprecise. Thoracoscopic/laparoscopic (TS/LS) staging has been proposed as a more accurate lymph node (LN) staging method. We report the experience of an Intergroup NCI trial (CALGB 9380) evaluating the feasibility and accuracy of this staging modality. PATIENTS AND METHODS: From February 1995 to September 1999, 134 patients were entered in the study. This study represents the analysis of final data on 113 patients. TS/LS was considered feasible if TS and 1 LN sampled at least 3 LN by LS; a confirmed positive node was found; or T4 or M1 disease was documented. If this was accomplished in more than 70% of patients, TS/LS was believed to be feasible. RESULTS: The LN stations most frequently sampled in the thorax (134 patients) were levels 2 (33%), 3 (38%), 4 (40%), 7 (76%), 8 (69%), 9 (55%), and 10 (43%) and in the abdomen levels 17 (70%) and 20 (55%). The frequency of positive LN by level were as follows: 2 (10%), 3 (8%), 4 (10%), 7 (10%), 8 (25%), 9 (10%), 10 (10%), 17 (34%), and 20 (27%). Noninvasive tests (computed tomographic scan, magnetic resonance imaging, esophageal ultrasound scan) each incorrectly identified TN staging as noted by missed positive or false-negative LN or metastatic disease found at TS/LS staging in 50%, 40%, and 30% of patients, respectively. Median operating time was 210 minutes (range, 40 to 865 minutes). Median postoperative hospital stay was 3 days (range, 1 to 35 days). There were no deaths or major complications. Seventy-three percent of patients met the definition for feasibility. In 30 patients TS was not feasible. Positive LN disease was found in 43 patients; 32 were deemed N0. Ten patients had T4/M1 disease. Of the 32 potentially resectable N0 patients, 14 patients had preoperative induction therapy; 13 patients went directly to operation with N0 confirmed in 9 patients, NX in 1 and N1 in 3. Three patients were unresectable, 1 patient died, and 1 was lost to follow-up. CONCLUSIONS: In summary, the feasibility of TS/LS was confirmed. It doubled the number of positive LNs identified by conventional, noninvasive staging. The overall accuracy remains to be defined by analysis of the LN negative group in follow-up. Although the positive predictive value was high, further study is warranted to confirm the role of TS/LS in the staging algorithm of esophageal cancer.

Accurate lymph node assessment prior to trimodality therapy for esophageal carcinoma.

PURPOSE: The diagnosis of esophageal carcinoma has historically been associated with a poor prognosis. Recently, investigators have reported improved outcomes for this patient population with the use of trimodality therapy. These results have fueled the debate regarding which patients may benefit from this aggressive treatment course. This retrospective analysis was conducted in order to evaluate the importance of regional lymph node involvement, determined by surgical staging before the initiation of therapy. PATIENTS AND MATERIALS: Between July 1991 and June 1999, 45 patients underwent surgical staging with thoracoscopy and/or laparoscopy followed by induction chemoradiation and surgical resection. All patients underwent consultation in our thoracic multidisciplinary clinic. Thoracoscopy included nodal sampling from American Thoracic Society levels 5, 6, 8, and 9 within the mediastinum. Laparoscopy included inspection of the liver and nodal sampling from the lesser curvature and the celiac axis. Preoperative chemoradiation consisted of two cycles of 5-fluorouracil (1000 mg/M2) and cisplatin (100 mg/M2) weeks 1 and 4 with 50.4 Gy. Radiotherapy was delivered at 1.8 Gy/fraction with 39.6 Gy being delivered to the large-field and 10.8 Gy to a small-field boost. The routine surgical procedure was an Ivor-Lewis esophagectomy performed 4 to 6 weeks after completion of induction therapy. RESULTS: The median follow up was 24 months for all patients. The median overall survival was 23 months, with 1-, 2-, and 3-year survivals of 64%, 42%, and 34%, respectively. Thirty patients had pathological evidence of lymph node disease before therapy. The pathological complete response rate for the entire group was 51%. Node-positive patients had a path complete response rate of 14%, as compared with 59% for those who were NO. The median survival for these two groups was 15 months versus 35 months. Patients whose nodes were cleared by chemoradiation had a 3-year survival of 40%, whereas all patients with persistent nodal disease were dead by 2 years. Twenty-one patients have experienced recurrence of their disease. Thirteen patients had evidence of distant metastasis only, three local only, and five with both. CONCLUSION: Trimodality therapy offers patients with esophageal cancer an opportunity for long-term survival. Our experience has shown that minimally invasive pretreatment surgical staging provides useful information that can predict complete response and can help in the selection of appropriate patients for aggressive therapy.

The use of concurrent chemotherapy with high-dose radiation before surgical resection in patients presenting with apical sulcus tumors.

PURPOSE: Patients presenting with apical sulcus tumors have historically been treated with preoperative radiotherapy followed by surgical resection. Since 1991, we have delivered an induction regimen consisting of combination chemotherapy and high-dose radiation in an attempt to improve tumor responses and increase survival for this patient population. PATIENTS AND MATERIALS: This retrospective analysis consisted of 23 (13 men and 10 women) consecutive patients who completed trimodality therapy. The median age was 53 years. Histologies included adenocarcinoma (nine patients), squamous cell (five patients), large cell (three patients), and undifferentiated non-small cell lung carcinoma (six patients). Pretreatment stages were T3NO (14 patients), T3N2 (two patients), T3N3 (one patient), T4NO (five patients), and T4N2 (one patient). Preoperative therapy consisted of daily radiotherapy (median dose, 59.4 Gy) delivered at 1.8 Gy/day and concurrent combination chemotherapy consisting of either two cycles of cisplatin and etoposide or weekly carboplatin and paclitaxel. Surgical resection typically included lobectomy with chest wall resection. RESULTS: All 23 patients were available for analysis of response and survival. The median follow-up was 53 months. The median number of days between completion of induction therapy and surgery was 56 days. Postoperative complications included prolonged atelectasis (two patients), pulmonary embolism (one patient), subarachnoid-pleural fistula (one patient), and deep vein thrombosis in the subclavian vein (one patient). The pathological complete response rate to induction therapy was 46% for the entire group. An additional 38% had evidence of tumor regression at the time of surgery. The 5-year disease-free and overall survivals were 36% and 49%, respectively. The median overall survival was 33 months. The median overall survival for those who achieved a pathological complete response has not been reached. Analysis of factors including age, sex, histology, differentiation, stage of disease, and radiation dose failed to identify any predictors of response or survival. CONCLUSION Concurrent chemotherapy and high-dose radiation can be safely delivered before surgery in patients presentingwith apical sulcus tumors. Our results compare favorably to other institutional series and support the further investigation of this approach in prospective trials.

Thoracoscopic sympathectomy.

The objective was to evaluate the safety and effectiveness of endoscopic thoracic sympathectomy (ETS) for treatment of a variety of sympathetic disorders, including hyperhidrosis, splanchnic pain, reflex sympathetic dystrophy, and Raynaud upper extremity ischemia. Sixty-three ETS procedures were performed in 34 patients at the University of Maryland Medical System between March 1992 and August 1999 (14 male patients, 20 female patients; mean age 22 years). The indications for surgery were hyperhidrosis in 26 patients, upper extremity ischemia in 3 patients, splanchnic pain and reflex sympathetic dystrophy in 2 patients each, and facial blushing in 1 patient. Preoperative symptoms resolved completely or improved significantly in 97.1% (33/34) of patients. One patient with left reflex sympathetic dystrophy had symptoms that recurred shortly after surgery. There were no major complications; one patient with hyperhidrosis reported significant compensatory hyperhidrosis. These findings suggest that ETS is a safe and effective procedure for treatment of a variety of sympathetic disorders. Its application for hyperhidrosis is very effective, and its treatment of splanchnic pain, reflex sympathetic dystrophy, and Raynaud syndrome are rewarding. With increasing experience, ETS should become established in the repertoire of the thoracic surgeon.

Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma.

BACKGROUND: The adenomatous polyposis coli (APC) locus on chromosome 5q21-22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter regions is known to affect several other tumor suppressor genes, we investigated whether the APC promoter region is hypermethylated in esophageal cancer patients and whether this abnormality could serve as a prognostic plasma biomarker. METHODS: We assayed DNA from tumor tissue and matched plasma from esophageal cancer patients for hypermethylation of the promoter region of the APC gene. We used the maximal chi-square statistic to identify a discriminatory cutoff value for hypermethylated APC DNA levels in plasma and used bootstrap-like simulations to determine the P: value to test for the strength of this association. This cutoff value was used to generate Kaplan-Meier survival curves. All P values were based on two-sided tests. RESULTS: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues. Hypermethylated APC DNA was observed in the plasma of 13 (25%) of 52 adenocarcinoma patients and in two (6.3%) of 32 squamous carcinoma patients. High plasma levels of methylated APC DNA were statistically significantly associated with reduced patient survival (P =.016). CONCLUSION: The APC promoter region was hypermethylated in tumors of the majority of patients with primary esophageal adenocarcinomas. Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.

Thoracoscopic and laparoscopic staging for esophageal cancer.

Accurate pretreatment staging for patients with esophageal cancer (EC) is becoming increasingly important in the evaluation and comparison of different treatment modalities. Noninvasive staging methods are imperfect in detecting lymph node metastasis in patients with EC. Surgical staging with the thoracoscopic/laparoscopic (Ts/Ls) technique may provide accurate staging information that is useful for evaluating and comparing the results of clinical trials of preoperative chemotherapy and radiotherapy. It can be used to confirm or exclude suspicious distant metastasis found by other staging methods. Pretreatment (lymph node) biopsies obtained by Ts/Ls staging allow further molecular biologic analysis to detect occult lymph node metastasis for more accurate lymph node staging. Since 1992, we have used Ts/Ls staging for EC in 111 patients. We found that Ts/Ls is a promising method for staging lymph nodes in EC patients. A recent study showed that pretreatment surgical lymph node staging can predict response and survival for EC patients receiving trimodality treatment (ie, radiation, chemotherapy, and surgery). The information obtained with surgical staging now offers us the opportunity to optimize therapy to specific patient groups based on the extent of disease at the time of initial presentation. Nevertheless, unlike the practice of mediastinoscopy in lung cancer patients, Ts/Ls staging in EC patients remains an academic interest rather than a clinical practice. The concept of accurate pretreatment staging of EC remains to be realized and accepted in the clinical community.

The role of multimodality therapy for esophageal cancer.

One trial has suggested improved survival with preoperative chemotherapy and radiation therapy with acceptable morbidity and mortality. Other studies have not demonstrated apparent improvement in survival, although the protocols are somewhat different. Longer follow-up is needed in these preliminary studies, and well-designed, prospective, multicenter randomized trials are necessary in the future. These studies should compare identical CRT and surgery regimens and identify a group of esophageal patients that might benefit from preoperative chemotherapy or radiation therapy. In order to evaluate the results of future trials without bias and to determine which group of esophageal patients will benefit from preoperative CRT, pretreatment, accurate TNM staging by CT and EUS combined with pathologic LN staging when possible will be crucial in future trimodality therapy trials for esophageal cancer. The investigation of biologic molecular markers to predict chemoradiation sensitivity and prognosis deserves careful exploration. Unfortunately, those patients without a response do not benefit from the preoperative chemotherapy but still may suffer the associated toxicity. These patients may have a much higher risk of postoperative fatal complications including respiratory failure, bone marrow suppression, and sepsis. It has been shown that CR patients in the chemotherapy/surgery group survive longer than nonresponders; it would be helpful to find useful molecular biomarkers to identify chemotherapy-sensitive patients before the preoperative chemotherapy is employed. Several pilot trials are underway using chemotherapy sensitivity testing on the endoscopic biopsy specimen before the chemotherapy is applied.

Use of minimally invasive surgery in staging esophageal cancer.

Noninvasive staging of esophageal cancer (EC) is often inaccurate, and this fact has compromised clinical trials of treatment for EC. Prognostic evaluation might allocate chemotherapy and radiation more appropriately. Thoracoscopy and laparoscopy has recently shown promising results, and molecular analysis of the recovered tissue may further improve staging accuracy.

Pleural lavage cytology in esophageal cancer without pleural effusions: clinicopathologic analysis.

OBJECTIVE: The literature of pleural lavage cytology (PLC) is focused on lung cancer. We conducted this pilot study to determine the incidence of malignant pleural cytologies in patients without pleural effusions who undergo curative resection for esophageal cancer, and to evaluate the clinicopathologic significance of positive cytology. METHODS: Forty-eight patients underwent esophagectomy for thoracic esophageal cancer in our unit from January 1998 to January 1999. After thoracotomy, pleural lavage was performed before any intrathoracic manipulation and cytologically evaluated. RESULTS: There was one patient with stage I, 27 patients with stage II, and 20 patients with stage III cancer of the thoracic esophagus. The mean age was 55 years (range 41-77 years). Fifteen cases (31.3%) were found to have positive lymph nodes (N1). Squamous cell carcinoma was the dominant histopathologic type (91.7%). Positive lavage cytology in the whole group was found in 18.8% (9/48). There was no significant correlation to gender, age, clinical symptoms, histology, T or N status, TNM stage, or tumor location. CONCLUSIONS: The incidence of positive pleural lavage cytology in esophageal cancer is disconcertingly high. Positive cytology might suggest a more aggressive tumor biology. Future studies on its relation to survival and occult lymphatic metastasis are warranted.

Thoracoscopic resection of posterior neurogenic tumors.

Video-assisted thoracic surgery (VATS) may be used for resection of posterior mediastinal tumors to avoid thoracotomy and shorten hospital stay. Between October 1990 and June 1998, 23 patients had VATS resection of posterior neurogenic tumors. The 14 females and 9 males ranged in age from 14 months to 70 years, with a median of 35 years. Operation time ranged from 30 to 120 minutes (median, 83), and intraoperative complications were limited to minor problems as well as conversion to thoracotomy to enhance complete tumor resection in four cases. Tumor pathology included nerve sheath origin (20) and autonomic ganglia (3). There was only one malignant schwannoma. Tumor size ranged from 0.7 to 13 cm in diameter. Median chest tube days was 1 day (range, 1-4), and hospital stay was 2 days (range, 1-9). Postoperative complications included transient paresthesia (three cases), ileus (two cases), pleural effusion (one case), and transient intercostal pain (one case). Posterior neurogenic tumors may be resected safely using video-assisted techniques. Conversion to thoracotomy to enhance complete resection is both possible and encouraged. The use of VATS seems to decrease hospital stay and minimize postoperative complications. In posterior neurogenic tumors without tumor extension to the spinal canal, VATS has become our preferred method for resection.

Surgical staging and surgical treatment in esophageal cancer.

Esophageal cancer is the fastest growing malignancy in the United States. Surgery remains the standard primary treatment but overall survival for all patients undergoing primary surgery is dismal. This is thought to be secondary to the advanced stage in many patients at the time of diagnosis. The presence or absence of metastatic lymph nodes is indeed the single most important prognosticator. Current preoperative staging includes computerized tomography, magnetic resonance imaging, and transesophageal ultrasound. The limitations of each of these techniques are well known. Preoperative thoracoscopy and laparoscopy staging is emerging as a safe, effective, and accurate way of staging patients with esophageal cancer. Moreover, it may become important in allocating treatment, as it may be used to individualize radiation therapy fields, or to allocate bimodality or trimodality therapy to patients in trials, depending on the results of pretreatment lymph node sampling. Future trials in esophageal cancer should consider the results of pretreatment pathologic staging in allocating patients to appropriate modalities of therapy.