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Mark J Krasna

Publications and source records attributed to Mark J Krasna.

At least 19 recordsLinked to original sources
PubMed2006

Nodal downstaging predicts survival following induction chemotherapy for stage IIIA (N2) non-small cell lung cancer in CALGB protocol #8935.

BACKGROUND AND OBJECTIVES: CALGB 8935 was a phase II protocol for mediastinoscopically staged IIIA (N2) non-small cell lung cancer. Induction cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of pathologic nodes. METHODS: Failure-free survival was calculated from a landmark 3 months after resection to account for heterogeneity in adjuvant therapy. RESULTS: Nine of 42 (21%) resected patients had no residual N2 disease. This subset of 9 had a median failure-free interval of 47.8 months from landmark, whereas the 33 patients (79%) with persistent N2 disease had a median failure-free survival of 8.2 months from landmark (P=0.01). Although 21/42 (50%) had an incomplete resection (positive highest resected node and/or margin), completeness of resection did not influence failure-free survival. There were 3 distant and no local recurrences among the N2 negative group, and 12 local recurrences among patients with residual N2 disease (P=0.041). CONCLUSIONS: These data suggest: (1) persistent N2 disease following induction chemotherapy is unfavorable; (2) patients downstaged to N2 negative may benefit from surgical resection; however, (3) 33% of N2 negative patients suffered disease relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Promoter methylation and response to chemotherapy and radiation in esophageal cancer.

BACKGROUND & AIMS: Multiple studies have shown that promoter methylation of tumor suppressor genes underlies esophageal carcinogenesis. Hypothetically, methylation resulting in tumor suppressor gene inactivation might result in tumors that are unresponsive to chemotherapy and radiation. Accordingly, our aim was to find methylation markers that could be used to predict response to chemoradiation. METHODS: Tumor specimens were obtained before treatment from 35 patients enrolled in a uniform chemoradiation treatment protocol. Methylation-specific quantitative polymerase chain reaction was performed on all samples. Pathology reports from esophagectomy specimens were used to define response to treatment. RESULTS: Thirteen (37%) of 35 patients were responders, and 22 (63%) of 35 patients were nonresponders. The number of methylated genes per patient was significantly lower in responders than in nonresponders (1.4 vs 2.4 genes per patient; Student t test, P = .026). The combined mean level of promoter methylation of p16, Reprimo, p57, p73, RUNX-3, CHFR, MGMT, TIMP-3, and HPP1 was also lower in responders than in nonresponders (Student t test, P = .003; Mann-Whitney test, P = .001). The frequency (15% of responders vs 64% of nonresponders; Fisher exact test, P = .01) and level (0.078 in responders vs 0.313 in nonresponders; Mann-Whitney test, P = .037) of Reprimo methylation was significantly lower in responders than in nonresponders. CONCLUSIONS: Reprimo methylation occurred at significantly lower levels and less frequently in chemoradioresponsive than in nonresponsive esophageal cancer patients, suggesting potential clinical application of this single-gene biomarker in defining prognosis and management. In addition, increased methylation of a 9-gene panel correlated significantly with poor responsiveness to chemoradiation.

Adenocarcinoma↗
PubMed2006

Patient and surgical factors influencing air leak after lung volume reduction surgery: lessons learned from the National Emphysema Treatment Trial.

BACKGROUND: Although staple line buttressing is advocated to reduce air leak after lung volume reduction surgery (LVRS), its effectiveness is unknown. We sought to identify risk factors for air leak and its duration and to estimate its medical consequences for selecting optimal perioperative technique(s), such as buttressing technique, to preempt or treat post-LVRS air leak. METHODS: Detailed air leak data were available for 552 of 580 patients receiving bilateral stapled LVRS in the National Emphysema Treatment Trial. Risk factors for prevalence and duration of air leak were identified by logistic and hazard function analyses. Medical consequences were estimated in propensity-matched pairs with and without air leak. RESULTS: Within 30 days of LVRS, 90% of patients developed air leak (median duration = 7 days). Its occurrence was more common and duration prolonged in patients with lower diffusing capacity (p = 0.06), upper lobe disease (p = 0.04), and important pleural adhesions (p = 0.007). Duration was also protracted in Caucasians (p < 0.0001), patients using inhaled steroids (p = 0.004), and those with lower 1-second forced expiratory volume (p = 0.0003). Surgical approach, buttressing, stapler brand, and intraoperative adjunctive procedures were not associated with fewer or less prolonged air leaks (p >/= 0.2). Postoperative complications occurred more often in matched patients experiencing air leak (57% vs 30%, p = 0.0004), and postoperative stay was longer (11.8 +/- 6.5 days vs 7.6 +/- 4.4 days, p = 0.0005). CONCLUSIONS: Air leak accompanies LVRS in 90% of patients, is often prolonged, and is associated with a more complicated and protracted hospital course. Its occurrence and duration are associated with characteristics of patients and their disease, not with a specific surgical technique.

Administration, Inhalation↗
PubMed2006

Nerve injury: injury to the recurrent laryngeal, phrenic, vagus, long thoracic, and sympathetic nerves during thoracic surgery.

Nerve injury occurs in about 1% of patients undergoing thoracic surgery. Most commonly, it is the result of surgical trauma specific to the area of operation. Alternatively, it may be due to retraction on adjacent structures during the exposure of complex surgical procedures. This article reviews the most common types of nerve injury and discusses the pathophysiology, etiology, diagnosis, and treatment of each.

Diagnostic Imaging↗
PubMed2005

Predictors of operative mortality and cardiopulmonary morbidity in the National Emphysema Treatment Trial.

OBJECTIVE: We sought to identify predictors of operative mortality, pulmonary morbidity, and cardiovascular morbidity after lung volume reduction surgery. METHODS: Univariate and multivariate logistic regression analyses were performed. Candidate predictors included demographic characteristics, physical condition characteristics, pulmonary function measures, measures of the distribution of emphysema as determined by radiologists and by means of computerized analysis of chest computed tomographic scans, and measures of exercise capacity, dyspnea, and quality of life. End points analyzed were operative mortality (death within 90 days of the operation), major pulmonary morbidities (tracheostomy, failure to wean, reintubation, pneumonia, and ventilator for > or =3 days), and cardiovascular morbidities (infarction, pulmonary embolus, or arrhythmia requiring treatment). RESULTS: Five hundred eleven patients in the non-high-risk group of the National Emphysema Treatment Trial underwent lung volume reduction. The incidence of operative mortality was 5.5%, major pulmonary morbidity occurred in 29.8% of patients, and cardiovascular morbidity occurred in 20.0% of patients. Predictors for these end points are as follows: [table: see text]. CONCLUSIONS: Although lung volume reduction can be performed in selected patients with acceptable mortality, the incidence of major cardiopulmonary morbidity remains high. The lone predictor for operative mortality of lung volume reduction was the presence of non-upper-lobe-predominant emphysema, as assessed by the radiologist. Pulmonary morbidity can be expected in elderly patients who have a low diffusing capacity for carbon monoxide and forced expiratory volume in 1 second. When assessing morbidity, the computer-assisted chest computed tomographic analysis proved useful only in predicting cardiovascular complications.

Aged↗
PubMed2005

Less efficient g2-m checkpoint is associated with an increased risk of lung cancer in African Americans.

Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non-small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of gamma-radiation-induced G2-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 Gy gamma-radiation, and harvested at 3 hours after gamma-radiation treatment. gamma-Radiation-induced G2-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in gamma-radiation-treated cultures from the same subject. The mean percentage of gamma-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44, P < 0.01) and hospital controls (1.18 versus 1.40, P = 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of gamma-radiation-induced G2-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97-5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G2-M arrest was observed (P(trend) = 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% CI, 0.98-14.3). This trend was most apparent among African American females (P(trend) < 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% CI, 1.47-94.04). The results suggest that a less-efficient DNA damage-induced G2-M checkpoint is associated with an increased risk of lung cancer among African Americans. Interestingly, we observed a stronger association of DNA damage-induced G2-M arrest and lung cancer among African Americans when compared with Caucasians. If replicated, these results may provide clues to the exceedingly high lung cancer incidence experienced by African Americans.

Black or African American↗
PubMed2005

Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk.

Patients with Barrett's esophagus (BE) are at increased risk of developing esophageal adenocarcinoma (EAC). Clinical neoplastic progression risk factors, such as age and the length of the esophageal BE segment, have been identified. However, improved molecular biomarkers predicting increased progression risk are needed for improved risk assessment and stratification. Using real-time quantitative methylation-specific PCR, we screened 10 genes (HPP1, RUNX3, RIZ1, CRBP1, 3-OST-2, APC, TIMP3, p16, MGMT, p14) for promoter hypermethylation in 77 EAC, 93 BE, and 64 normal esophagus (NE) specimens. A subset of genes manifesting significant differences in methylation frequencies between BE and EAC was then analysed in 20 dysplastic specimens. All 10 genes except p14 were frequently methylated in EACs, with RUNX3, HPP1, CRBP1, RIZ1, and OST-2 representing novel methylation targets in EAC and/or BE. p16, RUNX3, and HPP1 displayed increasing methylation frequencies in BE vs EAC. Furthermore, these increases in methylation occurred early, at the interface between BE and low-grade dysplasia (LGD). To demonstrate the silencing effect of hypermethylation, we selected the EAC cells BIC1, in which the HPP1 promoter is natively methylated, and subjected them to 5-aza-2'-deoxycytidine (Aza-C) treatment. Real-time RT-PCR indicated increased HPP1 mRNA levels after 3 days of Aza-C treatment, as well as decreased levels of methylated HPP1 DNA. Hypermethylation of a subset of six genes (APC, TIMP3, CRBP1, p16, RUNX3, and HPP1) was then tested in a retrospective longitudinal study of 99 BE and nine LGD specimens obtained from 53 BE patients undergoing surveillance endoscopy. Only high-grade dysplasia (HGD) or EAC were defined as progression end points. Two patient groups were compared: eight progressors (P) and 45 nonprogressors (NP), using Cox proportional hazards models to determine the relative progression risks of age, BE segment length, and methylation events. Multivariate analyses revealed that only hypermethylation of p16 (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.33-2.20), RUNX3 (OR 1.80, 95% CI 1.08-2.81), and HPP1 (OR 1.77, 95% CI 1.06-2.81) were independently associated with an increased risk of progression, whereas age, BE segment length, and hypermethylation of TIMP3, APC, or CRBP1 were not independent risk factors. In combined analyses, risk was detectable up to, but not earlier than, 2 years preceding neoplastic progression. Hypermethylation of p16, RUNX3, and HPP1 in BE or LGD may represent independent risk factors for the progression of BE to HGD or EAC. These findings have implications regarding risk stratification, early EAC detection, and the appropriate endoscopic surveillance interval for patients with BE.

Adenocarcinoma↗
PubMed2005

Outcome results of the 1996-1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus.

PURPOSE: A Patterns of Care Study of patients treated from 1996 to 1999 evaluated the national practice for patients receiving radiation therapy for carcinoma of the esophagus in the United States. METHODS: A national survey was conducted at 59 institutions in a stratified random sample selected from a master list of radiation therapy facilities throughout the United States. Patient, tumor, and treatment characteristics were evaluated. Multivariate comparisons of survival times were made using the Cox proportional hazards model. RESULTS: Adenocarcinoma was diagnosed in 51% of patients and squamous cell carcinoma in 49% of patients. Sixteen percent of patients were clinical stage (CS) I (using the 1983 American Joint Committee on Cancer system), 39% were CS II, and 33% were CS III. Significant variables in the multivariate analysis of survival times included clinical stage, treatment approach, and facility size. Patients with CS III disease had a higher hazard risk of death as compared with CS I patients (hazard ratio [HR], 2.01; P = .001), whereas those treated with chemoradiotherapy followed by surgery (HR, 0.32; P < .0001) had a decreased risk of death compared with chemoradiotherapy-only patients. Patients at small centers had a higher risk of death (HR, 1.32; P = .03) compared with patients treated at larger facilities. CONCLUSION: Concurrent chemoradiotherapy continued to be the most commonly utilized treatment approach during the time period studied. The observation that patients undergoing surgical resection following chemoradiation have a decreased HR or chance of death compared with other treatment schemes supports the need for a randomized trial comparing these strategies.

Adenocarcinoma↗
PubMed2005

Clinical experience in 397 consecutive thoracoscopic sympathectomies.

BACKGROUND: The purpose of this study is to evaluate the safety and efficacy of thoracoscopic sympathectomy for the treatment of hyperhidrosis, blushing, reflex sympathetic dystrophy, and digital ischemia. METHODS: We conducted a retrospective review of 202 patients who underwent thoracoscopic sympathectomy at the University of Maryland from March 1992 to April 2003. RESULTS: Three hundred ninety-seven procedures were performed on 202 patients (105 women, 97 men). Mean age was 29 years (range, 9 to 65). Indications for surgery included hyperhidrosis, facial blushing, digital ischemia, and reflex sympathetic dystrophy. Synchronous bilateral sympathectomies were performed in 194 patients; right side alone (n = 6); left side alone (n = 1); 1 patient had staged bilateral sympathectomies. Single incision with lung isolation technique was used. There was no mortality. Preoperative symptoms resolved completely or significantly improved in greater than 90% of patients. One patient with reflex sympathetic dystrophy recurred and 1 patient with hyperhidrosis complained of significant compensatory sweating. Compensatory sweating to a lesser degree occurred in approximately one third of patients. Complications included asymptomatic pleural effusion (n = 1), pneumothorax (n = 1), and reoperation for chylothorax that was identified early (n = 1). In 2 patients treated for facial blushing, Horner's syndrome developed postoperatively; 1 of them subsequently underwent blepharoplasty. In 3 patients, hyperesthesias developed at the incision. CONCLUSIONS: Thoracoscopic sympathectomy can be performed safely and with excellent results. Compensatory sweating is the main side effect, although significant complaints from this are rare. Horner's syndrome remains an extremely uncommon complication as a result of thoracoscopic sympathectomy at our institution.

Adolescent↗
PubMed2005

High-dose radiotherapy in trimodality treatment of Pancoast tumors results in high pathologic complete response rates and excellent long-term survival.

OBJECTIVE: We sought to study the clinical characteristics and outcomes of patients treated with a surgery-inclusive multimodality approach for Pancoast tumors. METHODS: Clinical records of patients with Pancoast lung cancer who were enrolled for multimodality treatment between 1993 and 2003 at our institution were reviewed retrospectively. RESULTS: Thirty-six patients completed neodjuvant chemoradiation followed by en bloc surgical resection, whereas one patient received high-dose radiation alone followed by surgical intervention. There were 22 men and 15 women. Thirty-four lobectomies and 3 pneumonectomies were performed. Pretreatment non-small cell lung cancer stages were IIB, IIIA, IIIB, and IV (presenting with solitary brain metastasis) in 18, 8, 6, and 5 cases, respectively. R0 resection was achieved in 36 (97.3%) patients. Operative mortality was 2.7% (n = 1). High-dose radiotherapy was successfully tolerated in all but 1 patient. Mean total radiation dose was 56.9 Gy. Pathologic complete response was found in 40.5% (n = 15) of patients. Recurrences were found in 50% (n = 18) of patients. Brain metastasis was the most common recurrence (n = 9), followed by other distant recurrences (n = 4) and local recurrences (n = 5). Median survival time for the group is 2.6 years, and median survival time (pathologic complete response) is 7.8 years. It is noteworthy that median survival time of patients with positive pretreatment lymph nodes (12 patients) was not reached. CONCLUSIONS: Surgical resection of Pancoast tumors after neoadjuvant high-dose radiation and chemotherapy can be safely performed. High-dose radiation in trimodality treatment is well tolerated and might be beneficial. Similar to other studies, late central nervous system relapse is problematic and indicates a need for assessing the role of prophylactic cranial irradiation in this disease.

Adult↗
PubMed2005

Multimodality treatment of esophageal cancer.

Stage specific management of non-small cell lung cancer is widely accepted. The use of pretreatment disease stage to guide therapy for esophageal cancer is an intellectually appealing concept. To date, there isa relative lack of data upon which one may base stage specific treatment decisions for esophageal carcinoma. This is because thorough pretreatment TNM staging is not universally practiced. As a result, stage-specific treatment varies widely. Based upon the available data, surgery alone may be appropriate for resectable, node-negative disease. In the case of clearly un-resectable disease, definitive chemoradiation is indicated.The value of neoadjuvant or adjuvant treatment modalities in the case of clearly resectable node-negative disease (TlN0 or T2N0) is questionable;however, in the presence of lymph node involvement (N1), or in the case of a marginally resectable primary tumor (T3 or T4), neoadjuvant chemoradiation is probably indicated. Although the achievement ofa complete pathologic response following chemoradiation may obviate surgical resection, even microscopic residual cancer can result in local recurrence. To date, there is no reliable method of ascertaining a complete pathologic response before surgical resection. Therefore, when feasible, the addition of surgical resection following chemoradiation is warranted. Future treatment trials for esophageal cancer should include rigorous pretreatment staging protocols to elucidate stage-specific results of therapy.

Combined Modality Therapy↗
PubMed2005

The effects of pulmonary rehabilitation in the national emphysema treatment trial.

STUDY OBJECTIVES: Pulmonary rehabilitation is an established treatment in patients with chronic lung disease but is not widely utilized. Most trials have been conducted in single centers. The National Emphysema Treatment Trial (NETT) provided an opportunity to evaluate pulmonary rehabilitation in a large cohort of patients who were treated in centers throughout the United States. DESIGN: Prospective observational study of cohort prior to randomization in a multicenter clinical trial. SETTING: University-based clinical centers and community-based satellite pulmonary rehabilitation programs. PATIENTS AND INTERVENTION: A total of 1,218 patients with severe emphysema underwent pulmonary rehabilitation before and after randomization to lung volume reduction surgery (LVRS) or continued medical management. Rehabilitation was conducted at 17 NETT centers supplemented by 539 satellite centers. MEASUREMENTS AND RESULTS: Lung function, exercise tolerance, dyspnea, and quality of life were evaluated at regular intervals. Significant (p < 0.001) improvements were observed consistently in exercise (cycle ergometry, 3.1 W; 6-min walk test distance, 76 feet), dyspnea (University of California, San Diego Shortness of Breath Questionnaire score, -3.2; Borg breathlessness score: breathing cycle, -0.8; 6-min walk, -0.5) and quality of life (St. George Respiratory Questionnaire score, -3.5; Quality of Well-Being Scale score, +0.035; Medical Outcomes Study 36-item short form score: physical health summary, +1.3; mental health summary, + 2.0). Patients who had not undergone prior rehabilitation improved more than those who had. In multivariate models, only prior rehabilitation status predicted changes after rehabilitation. In 20% of patients, exercise level changed sufficiently after rehabilitation to alter the NETT subgroup predictive of outcome. Overall, changes after rehabilitation did not predict differential mortality or improvement in exercise (primary outcomes) by treatment group. CONCLUSIONS: The NETT experience demonstrates the effectiveness of pulmonary rehabilitation in patients with severe emphysema who were treated in a national cross-section of programs. Pulmonary rehabilitation plays an important role in preparing and selecting patients for surgical interventions such as LVRS.

Aged↗
PubMed2004

Predictors of acute esophagitis in patients with non-small-cell lung carcinoma treated with concurrent chemotherapy and hyperfractionated radiotherapy followed by surgery.

PURPOSE: To evaluate possible clinical and dosimetric predictors of acute esophagitis in patients with locally advanced non-small-cell lung carcinoma treated in a prospective Phase I-II trimodality protocol. METHODS AND MATERIALS: The data from 36 patients with Stage III non-small-cell lung carcinoma treated in a Phase I-II high-dose concurrent chemoradiotherapy protocol were analyzed for possible predictors of acute esophagitis. The median age was 58 years (range, 38-77 years). Patients included in this study had either Stage IIIA (n = 24) or IIIB (n = 12) disease. All patients were treated with induction concurrent carboplatin (area under the plasma concentration-time curve 1), vinorelbine (5-15 mg/m(2)), and hyperfractionated radiotherapy (69.6 Gy) followed by consolidation chemotherapy (carboplatin area under the plasma concentration-time curve 6, vinorelbine 25 mg/m(2), docetaxel 75 mg/m(2)) or surgery (n = 19) plus consolidation chemotherapy. Acute toxicities were graded using the Radiation Therapy Oncology Group criteria. The following clinical and dosimetric parameters were analyzed: age, gender, race, T stage, N stage, pretreatment body mass index, percentage of weight lost during therapy, pretherapy serum albumin, tumor location, length of esophagus in treatment field, percentage of esophagus volume treated to >40, >45, >50, >55, >60, and >65 Gy. These parameters were coded and analyzed against Grade 2 and worse esophagitis using univariate and multivariate regression analyses. RESULTS: Of the 36 patients, Grade 1, 2, and 3 acute esophagitis was observed in 16 (44%), 12 (33%), and 2 (5.5%) patients, respectively. Grade 4 or 5 toxicity was not observed in this patient cohort. Only the pretreatment body mass index (rho = -0.431, p = 0.004) and percentage of esophagus volume treated to >50 Gy (rho = 0.297, p = 0.040) demonstrated a statistically significant correlation with the incidence of Grade 2 or worse esophagitis on univariate analysis. These parameters retained their statistical significance on multivariate regression analysis (p = 0.029 and 0.049, respectively). CONCLUSION: In patients undergoing concurrent high-dose chemotherapy and hyperfractionated radiotherapy, a low pretherapy body mass index and percentage of esophagus volume treated to >50 Gy were significantly associated with acute Grade 2 or worse esophagitis.

Adult↗
PubMed2003

Leukotriene A4 hydrolase in rat and human esophageal adenocarcinomas and inhibitory effects of bestatin.

BACKGROUND: Esophageal adenocarcinoma (EAC) is increasing at the most rapid rate of any cancer in the United States. An esophagogastroduodenal anastomosis (EGDA) surgical model in rats mimics human gastroesophageal reflux and results in EAC. Leukotriene A4 hydrolase (LTA4H), a protein overexpressed in EAC in this model, is a rate-limiting enzyme in the biosynthesis of leukotriene B4 (LTB4), a potent inflammatory mediator. We used this model and human EAC and non-tumor tissues to elucidate the expression pattern of LTA4H and to evaluate it as a target for chemoprevention. METHODS: LTA4H expression was examined by western blotting and immunohistochemistry. The functional role of LTA4H in carcinogenesis was investigated by use of an LTA4H inhibitor, bestatin, in the rat EGDA model. All statistical tests were two-sided. RESULTS: LTA4H was overexpressed in all 10 rat EACs examined, compared with its level in normal rat tissue; it was also overexpressed in four of six human EAC tumor samples, compared with its level in adjacent non-tumor tissue. In tissue sections from 20 EGDA rats and 92 patients (86 with EAC, one with dysplasia, and five with columnar-lined esophagus), LTA4H was expressed in infiltrating inflammatory cells and overexpressed in the columnar cells of preinvasive lesions and cancers, especially in well-differentiated EACs, as compared with the basal cells of the normal esophageal squamous epithelium. Bestatin statistically significantly inhibited LTB4 biosynthesis in the esophageal tissues of EGDA rats (without bestatin = 8.28 ng/mg of protein; with bestatin = 4.68 ng/mg of protein; difference = 3.60, 95% CI = 1.59 to 5.61; P = .002) and reduced the incidence of EAC in the EGDA rats from 57.7% (15 of 26 rats) to 26.1% (6 of 23 rats) (difference = 31.6%, 95% CI = 0.3% to 56.2%; P = .042). CONCLUSION: LTA4H overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the chemoprevention of EAC.

Adenocarcinoma↗
PubMed2003

The national practice for patients receiving radiation therapy for carcinoma of the esophagus: results of the 1996-1999 Patterns of Care Study.

PURPOSE: A Patterns of Care Study (PCS) was conducted to evaluate the standards of practice for patients receiving radiation therapy for esophageal cancer from 1996 to 1999. This study examined the evaluation and treatment schemes used during this time and compared these results to the PCS data obtained between 1992 and 1994 to identify any fundamental changes in national practice. METHODS: A national survey was conducted using a two-stage cluster sampling technique. Specific information was collected on 414 patients with esophageal cancer who received radiotherapy (RT) as part of definitive or adjuvant management at 59 institutions. Patients were staged according to the 1983 AJCC. Eligibility criteria for case review included RT between 1996 and 1999, no evidence of distant metastasis (including CT evidence of either supraclavicular or celiac nodes >1 cm), squamous cell or adenocarcinoma histology, Karnofsky performance status >60, tumors in the thoracic esophagus with <2 cm extension into the stomach, and no prior malignancies within the last 5 years. Statistical analysis was performed on the database using SUDAAN software to accurately reflect the type of sampling technique used by PCS. For the purpose of this analysis, institutions were stratified as either large or small based on the number of new cases seen each year. For the purposes of comparison, the 1992-1994 PCS esophageal survey results were subjected to the same statistical procedures and tests. RESULTS: The median age of patients was 64 years. Seventy-seven percent were male, and 23% were female. Karnofsky performance status was >or=80% in 85% of patients. The racial profile mirrors the previous survey with 75% Caucasian, 21% African-American, 3% Asian, and <1% Hispanic. A review of the histology revealed a nearly 50:50 split between squamous cell and adenocarcinoma. Sixteen percent were clinical Stage I, 39% clinical Stage II, and 33% clinical Stage III according to the 1983 AJCC system. Workup included endoscopy (96%), CT of the chest (87%), CT of the abdomen (75%), and esophagram (64%). Endoscopic ultrasound (EUS) was used in 18% of cases as compared to <2% in the original survey (p < 0.0001). Patients treated at large centers were more likely to undergo EUS than those treated at small centers (23% vs. 12%, p = 0.047). Fifty-six percent of patients received concurrent chemoradiation as definitive treatment. There was a significant increase in the use of concurrent chemoradiation before planned surgical resection as compared to the original survey (27% vs. 10%, p = 0.007). Other schemes included RT alone (10%), postoperative RT (1%), and postoperative chemoradiation (5%). Forty-six percent of patients with adenocarcinoma underwent trimodality therapy as compared to 19% with squamous cell carcinomas (p = 0.0002). Patients undergoing preoperative chemoradiation were more likely to have had an EUS. The median total dose of external RT was 50.4 Gy, and the median dose per fraction was 1.8 Gy. Brachytherapy was used in 6% of cases. The chemotherapy agents most commonly used included 5-fluorouracil (82%), cisplatin (67%), and paclitaxel (22%). Paclitaxel was more commonly employed as part of a preoperative chemoradiation regimen than in the setting of definitive chemoradiation (46% vs. 12%, p = 0.03). Compared to the original survey, paclitaxel use significantly increased between 1996 and 1999 (0.2% vs. 22%, p = 0.001). CONCLUSIONS: The Patterns of Care Survey confirms the use of concurrent chemoradiation as part of the national standards of practice for the management of esophageal cancer patients. A comparison with the previous study documents the significant rise in the use of EUS, preoperative chemoradiation followed by surgery, and the increasing use of paclitaxel as part of a combined modality regimen.

Adenocarcinoma↗
PubMed2003

The management of the patient undergoing combined modality therapy for locally advanced non-small cell lung cancer.

Multimodality management of locally advanced non-small cell lung cancer is commonplace. Locally advanced disease is defined as patients with stage IIIA, IIIB (without pleural effusions), and Pancoast tumors. Improvements in the median and landmark survival rates of patients have been accomplished by integration of chemotherapy, radiotherapy, and surgery. Although the optimal sequencing and number of modalities remains to be established, the safe treatment of patients requires cooperation of the specialties (joint clinics and tumor boards). The toxicities of chemoradiotherapy are esophagitis, pneumonitis, and myelosuppression. These complications are a function of the dose and fractionation scheme of radiotherapy and the dose, schedule, and specific chemotherapy agents used. The use of modern techniques, including three-dimensional conformal radiotherapy, limitation of field size, and aggressive treatment of symptoms reduces toxicity and the number of treatment breaks, and allows delivery of planned therapy in many patients. In appropriate patients, surgery may be successful after induction chemotherapy or chemoradiotherapy. In addition to exclusion of medically inappropriate patients, patients with persistent mediastinal adenopathy after induction therapy are not likely to benefit from resection. Therefore, mediastinal sampling must be repeated after chemoradiotherapy and before surgery.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Immunohistochemistry analysis of micrometastasis in pretreatment lymph nodes from patients with esophageal cancer.

BACKGROUND: With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology. METHODS: Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53, an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed. RESULTS: 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series. CONCLUSIONS: Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.

Aged↗