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Biomedical subjects

Virginia R Litle

Publications and source records attributed to Virginia R Litle.

10 recordsLinked to original sources

A combination of molecular markers accurately detects lymph node metastasis in non-small cell lung cancer patients.

Occult lymph node metastasis (micrometastasis) is a good prognostic indicator in non-small cell lung cancer (NSCLC) and could be used to direct adjuvant chemotherapy in stage I patients. This study was designed to evaluate molecular markers for detection of occult lymph node metastasis in NSCLC, define the best marker or marker combination to distinguish positive from benign lymph nodes, and evaluate these markers in lymph nodes from pathologically node-negative (pN(0)) NSCLC patients. Potential markers were identified through literature and database searches and all markers were analyzed by quantitative reverse transcription-PCR in a primary screen of six NSCLC specimens and 10 benign nodes. Selected markers were further evaluated on 21 primary NSCLC specimens, 21 positive nodes, and 21 benign nodes, and the best individual markers and combinations were identified. A combination of three markers was further validated on an independent set of 32 benign lymph nodes, 38 histologically positive lymph nodes, and 462 lymph nodes from 68 pN(0) NSCLC patients. Forty-two markers were evaluated in the primary screen and eight promising markers were selected for further analysis. A combination of three markers (SFTPB, TACSTD1, and PVA) was identified that provided perfect classification of benign and positive nodes in all sample sets. PVA and SFTPB are particularly powerful in tumors of squamous and adenocarcinoma histologies, respectively, whereas TACSTD1 is a good general marker for NSCLC metastasis. The combination of these genes identified 32 of 462 (7%) lymph nodes from 20 of 68 (29%) patients as potentially positive for occult metastasis. Long-term follow-up will determine the clinical relevance of these findings.

Antigens, Neoplasm↗

Postoperative bleeding: coagulopathy, bleeding, hemothorax.

Several issues are involved in determining a patient's risk for postoperative hemorrhage and in managing this potential postoperative complication. The impact of minimally invasive procedures on the incidence of this complication is addressed in this article.

Blood Transfusion↗

Molecular staging of lymph nodes from patients with esophageal adenocarcinoma.

PURPOSE: This study was designed to evaluate molecular markers for the detection of micrometastasis in esophageal adenocarcinoma, define algorithms to distinguish positive from benign lymph nodes and to validate these findings in an independent tissue set and in patients with p(N0) esophageal adenocarcinoma. EXPERIMENTAL DESIGN: Potential markers were identified through literature and database searches. All markers were analyzed by quantitative reverse transcription (QRT)-PCR on a limited set of primary tumors and benign lymph nodes. Selected markers were further evaluated on a larger tissue set and classification algorithms were generated for individual markers and combinations. Algorithms were statistically validated internally as well as externally on an independent set of lymph nodes. Selected markers were then used to identify occult disease in lymph nodes from 34 patients with p(N0) esophageal adenocarcinoma. RESULTS: Thirty-nine markers were evaluated, six underwent further analysis and five were analyzed in the external validation study. Two markers provided perfect classification in both the screening and validation sets, although parametric bootstrap analysis estimated 2% to 3% optimism in the observed classification accuracy. Several marker combinations also gave perfect classification in the observed data sets, and estimates of optimism were lower, implying more robust classification than with individual markers alone. Five of thirty-four patients with esophageal adenocarcinoma had positive nodes by multimarker QRT-PCR analysis and disease-free survival was significantly worse in these patients (P = 0.0023). CONCLUSIONS: We have identified novel QRT-PCR markers for the detection of occult lymph node disease in patients with esophageal adenocarcinoma. The objective nature of QRT-PCR results, and the ability to detect occult metastases, make this an attractive alternative to routine pathology.

Adenocarcinoma↗

Minimally invasive esophagectomy.

Minimally invasive esophagectomy can be safely performed in selected cases in centers specializing in minimally invasive esophageal surgery.Potential benefits include lessened physiologic insult, with decreased hospital stay and a more rapid recovery to full activity. Drawbacks include the cost of the disposable instrumentation and the steep learning curve. As thoracic surgeons continue to acquire expertise with this procedure, improved results may be expected. Prospective trials with longer follow-up will be required to confirm any advantages of MIE over conventional approaches. Open surgical approaches should remain the standard operation for esophagectomy in most institutions.

Anastomosis, Surgical↗

Prognostic significance of micrometastasis in non-small-cell lung cancer.

Accurate staging of non-small-cell lung cancer (NSCLC) determines prognosis and facilitates decisions regarding treatment options. Unfortunately, even after an apparently complete resection in patients with stage I disease, the recurrence rates range from 25% to 50%, and overall survival is not encouraging. One possible reason for this may be that those patients with a poor outcome actually have more extensive disease, with occult locoregional and/or distant metastasis than originally identified by routine pathologic staging techniques. There is now a sizable body of literature on the detection and possible prognostic role of occult disease in lung cancer. The majority of these studies are based on immunohistochemical analysis of lymph nodes and/or bone marrow, but a handful of studies use molecular approaches. The purpose of this review is to summarize and critique the current literature on occult tumor cell spread to lymph nodes and bone marrow in patients with NSCLC. Based on this literature, we believe that the prognostic significance of bone marrow micrometastasis remains unclear. However, the majority of studies indicate that occult lymph node disease is associated with a poor outcome. Thus, our ability to detect individual tumor cells could result in more accurate staging of NSCLC in patients and would potentially lead to the development of novel therapies, as well as influence decisions regarding the use of appropriate multimodality treatment strategies, the choice of surgical technique, and extent of dissection. As data accumulate, the presence or absence of occult nodal involvement should probably be considered at the next revision of the staging system for NSCLC.

Bone Marrow↗

Photodynamic therapy for endobronchial metastases from nonbronchogenic primaries.

BACKGROUND: Endobronchial metastases (EBM) occur in 2% of nonbronchogenic malignancies and frequently present with hemoptysis or dyspnea. This report summarizes our recent experience with photodynamic therapy (PDT) for EBM. METHODS: All patients who have undergone PDT for the treatment of symptomatic EBM from nonbronchogenic primaries were identified in the Division of Thoracic Surgery database to determine number of treatments, frequency of symptom relief, and patient survival. RESULTS: Endobronchial PDT was administered to 27 patients from April 1997 through December 2000. The predominant primary tumor was renal cell (44%). Endobronchial metastases presented metachronously in 74% of patients. Patients underwent a median of two PDT treatments. Local anesthesia with sedation was used in 76% of treatments. Four patients (15%) developed immediate postoperative respiratory distress. Follow-up bronchoscopy 24 to 48 hours after initial treatment demonstrated tumor necrosis in all cases. Acute relief of hemoptysis and dyspnea was achieved in 85% of patients. Seven patients died within 6 weeks of treatment. Median survival time after PDT was 4 months (range 0.2 to 30 months). CONCLUSIONS: Patients with EBM treated with PDT had a median survival of 4 months and patients with limited metastatic disease survived up to 30 months. Photodynamic therapy was effective in palliating hemoptysis or dyspnea from EBM with an acceptable morbidity, although the 30-day mortality was 22%.

Adult↗

Photodynamic therapy as palliation for esophageal cancer: experience in 215 patients.

BACKGROUND: Photodynamic therapy (PDT) utilizes a photosensitizing agent, light, and oxygen to endoscopically ablate cancer cells. This review summarizes our experience with PDT for the palliation of bleeding or obstructing esophageal cancer (EC). METHODS: All patients with bleeding or obstructing EC treated with PDT from November 1996 through June 2002, were reviewed. After Photofrin II injection, nonthermal light treatment was delivered endoscopically. Dysphagia scores, duration of palliation, reinterventions, complications, and survival after treatment were reviewed. RESULTS: A total of 215 patients underwent 318 courses of PDT for bleeding (n = 15), obstruction (n = 277), bleeding and obstruction (n = 18), or other indications (n = 8). Tumor histology included 179 adenocarcinomas, 33 squamous cell carcinomas, and 3 undifferentiated. Seventy-five percent of EC were in the distal esophagus. In 85% of courses for obstruction, mean dysphagia scores improved pre- and post-PDT. The mean dysphagia-free interval was 66 days. Supplemental nutrition was discontinued after PDT in 8 of 27 patients (30%). Thirty-five patients required stent placement after PDT with a mean interval to reintervention of 58.5 days. PDT complications included perforation (2% of treatment courses), stricture (2%), Candida esophagitis (2%), pleural effusions (4%), and sunburn (6%). The procedure-related mortality rate was 1.8%, and median survival was 4.8 months. CONCLUSIONS: PDT offers effective palliation for patients with obstructing EC in 85% of treatment courses. The ideal EC patient for PDT palliation has an obstructing endoluminal cancer. Patients living more than 2 months may require reintervention to maintain palliation of malignant dysphagia, and a multimodality treatment approach is common.

Adult↗

Minimally invasive esophagectomy: outcomes in 222 patients.

OBJECTIVE: To assess our outcomes after minimally invasive esophagectomy (MIE). SUMMARY BACKGROUND DATA: Esophagectomy has traditionally been performed by open methods. Results from most series include mortality rates in excess of 5% and hospital stays frequently greater than 10 days. MIE has the potential to improve these results, but only a few small series have been reported. This report summarizes our experience of 222 cases. METHODS: From 1996 to 2002, MIE was performed in 222 patients. Indications for operation included high-grade dysplasia (n = 47) and cancer (n = 175). Neoadjuvant chemotherapy was used in 78 (35.1%) and radiation in 36 (16.2%). Initially, a laparoscopic transhiatal approach was used (n = 8), but subsequently our approach evolved to include thoracoscopic mobilization (n = 214). RESULTS: There were 186 men and 36 women. Median age was 66.5 years (range, 39-89). Nonemergent conversion to open procedure was required in 16 patients (7.2%). MIE was successfully completed in 206 (92.8%) patients. The median intensive care unit stay was 1 day (range, 1-30); hospital stay was 7 days (range, 3-75). Operative mortality was 1.4% (n = 3). Anastomotic leak rate was 11.7% (n = 26). At a mean follow-up of 19 months (range, 1-68), quality of life scores were similar to preoperative values and population norms. Stage specific survival was similar to open series. CONCLUSIONS: MIE offers results as good as or better than open operation in our center with extensive minimally invasive and open experience. In this single institution experience, we observed a lower mortality rate (1.4%) and shorter hospital stay (7 days) than most open series. Given these results, we are now developing an intergroup trial (ECOG 2202) to assess MIE in a multicenter setting.

Adult↗

Results of laparoscopic repair of giant paraesophageal hernias: 200 consecutive patients.

BACKGROUND: Giant paraesophageal hernias (GPEH) have traditionally required open operations. Increasingly, a laparoscopic approach is being applied to more complex esophageal surgery. Our objective was to update our growing experience with laparoscopic repair of GPEH. METHODS: We performed a retrospective review at our institution of patients undergoing laparoscopic repair of GPEH from July 1995 to July 2001. The GPEH was defined as greater than one-third of the stomach in the chest. RESULTS: Elective laparoscopic repair of a GPEH was attempted in 203 patients. Mean age was 67 years. The most common symptoms included heartburn (96 patients), dysphagia (72), epigastric pain (56), and vomiting (47 patients). Laparoscopic procedures included 69 Nissens, 112 Collis-Nissens, and 19 other procedures. There were three open conversions due to adhesions, but no intraoperative emergencies. Median length of stay was 3 days (range, 1 to 120 days). Minor or major complications occurred in 57 patients (28%). There were six postoperative esophageal leaks (3%), and 1 death. Median follow-up was 18 months. Five patients required reoperation for recurrent hiatal hernia. Excellent results were reported in 128 (84%) patients, 12 (8%) had a good result, 7 (5%) fair, and 5 (3%) poor (based on postoperative follow-up and GERD questionnaire). The mean postoperative GERD Health-related Quality of Life Score was 2.4 (scale 0 to 45; 0 = no symptoms, 45 = worst). CONCLUSIONS: Laparoscopic repair of GPEH is possible in the majority of patients with acceptable morbidity, a median length of hospital stay of 3 days and excellent intermediate-term results in an experienced center.

Adult↗

Minimally invasive resection for esophageal cancer.

MIE is technically demanding with a steep learning curve. Operative times decrease from 7 to 8 hours to 4.5 to 5 hours after the surgeons and assistants in the authors' center had performed 20 operations. In the authors' experience the operation was performed safely in the context of the authors' extensive experience with open esophageal surgery and advanced minimally invasive procedures. In the authors' first 77 cases, the 30-day operative mortality was zero, with a median hospital stay of 7 days, which compares favorably to many open series. Prospective studies will be required to determine whether postoperative pain, recovery time, and cost are improved. The optimal surgical approach for each patient should be decided based on surgical experience, tumor characteristics, and patient preference. A multi-institutional prospective trial is planned to evaluate the clinical and oncologic results of MIE for cancer compared with traditional open surgery.

Esophageal Neoplasms↗