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M J Krasna

Publications and source records attributed to M J Krasna.

At least 19 recordsLinked to original sources
PubMed2002

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.

Barrett Esophagus↗
PubMed2002

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.

Adenocarcinoma↗
PubMed2001

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.

Adenocarcinoma↗
PubMed2001

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.

Aged↗
PubMed2000

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.

Adenocarcinoma↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Biopsy↗
PubMed2000

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.

Endosonography↗
PubMed2000

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.

Chemotherapy, Adjuvant↗
PubMed2000

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.

Abdominal Pain↗
PubMed1999

Combined modality therapy for esophageal cancer.

Whereas many patients with esophageal carcinoma present with what appears to be localized disease, cure rates with surgical resection alone remain low. Although surgical resection, where feasible, affords patients the best chance of cure, the primary tumor has often invaded local tissues or structures, and occult micrometastases often exist at the time of presentation. In an effort to improve treatment results, various combinations of surgery, radiotherapy, and chemotherapy have been used. The results of combined modality therapy are reviewed in this article. The importance of accurate pretreatment staging is discussed, and ongoing prospective randomized trials are reviewed.

Antineoplastic Agents↗
PubMed1999

Lung cancer staging and treatment in multidisciplinary trials: Cancer and Leukemia Group B cooperative group approach. Thoracic Surgeons of CALGB.

BACKGROUND: Aggressive routine surgical staging is necessary to evaluate patients to be treated on cooperative oncology protocols. Less than 1% of lung cancer patients in the United States are currently being treated in a clinical trial. Only with results from large, prospective trials can the questions of neoadjuvant and adjuvant therapy be answered. METHODS: An outline describing the schema of preoperative patient evaluation, surgical staging, and the definition of surgical staging and resection procedures appropriate for patients considered for cooperative group protocol is presented. Current Cancer and Leukemia Group B (CALGB) protocols are used in the discussion as examples of this systematic approach. CONCLUSIONS: Over the next few years, it will be important to enter the maximum number of patients into combined modality studies to identify the role of neoadjuvant treatment in lung cancer. Entry of patients into protocols will also make their pathological specimens and clinical information available for basic science research related to treatment results. Adherence to a logical sequence of patient evaluation as outlined above will optimize patient care, as well as accrual to cooperative group studies.

Clinical Trials as Topic↗
PubMed1999

Safe pulmonary resection after chemotherapy and high-dose thoracic radiation.

BACKGROUND: Pulmonary resection after high-dose thoracic irradiation is reported to be associated with a high morbidity and mortality, and has been considered to be prohibitive. METHODS: We report safe pulmonary resection in 19 consecutive patients receiving neoadjuvant therapy that included greater than 59 Gy thoracic radiation. The mean thoracic radiation dose was 61.8 Gy (range 59.5-66.5) and mean age was 52 years (range 36-72 years). Cell type was adenocarcinoma (6), squamous (7), and other non-small cell lung cancer (NSCLC) (6). Sixteen of 19 patients received concurrent chemotherapy. Median time from end of treatment to surgical resection was 89 days (range 22-258 days). Surgical resection included 13 lobectomies and six pneumonectomies (four right, two left). RESULTS: A complete pathologic response was seen in 8 of 19 (42%) patients. Three patients required intraoperative transfusion of blood. Mean intensive care unit stay was 2.0 days (range 1-8 days), and mean length of stay (LOS) was 8.0 days (range 3-18 days). There were four postoperative complications; one bronchopulmonary fistula, one subarachnoid-pleural fistula, and 2 patients with prolonged atelectasis. There was no incidence of acute respiratory distress syndrome (ARDS) or operative mortality. CONCLUSIONS: Pulmonary resection, including pneumonectomy, after chemotherapy and high-dose thoracic radiation may be performed safely with a low rate of intraoperative and postoperative complications.

Adenocarcinoma↗
PubMed1999

P53 gene protein overexpression predicts results of trimodality therapy in esophageal cancer patients.

BACKGROUND: P53 protein overexpression in esophageal cancer and its correlation with response and survival after chemoradiation was retrospectively investigated. METHODS: Pretreatment and resection specimens were stained by automatic p53 immunohistochemical staining technique. RESULTS: P53 was expressed in 84.0% of esophagoscopy (EGD) biopsies; 71.4% of patients with metastasis of thoracoscopy/laparoscopy lymph nodes (TS/LS LN) identified by hematoxylin/eosin (H/E) were p53 (+); 14.2% of patients with negative TS/LS LN by H/E were p53 (+). Eleven out of 18 patients with p53 (+) in pretreatment EGD remained p53 (+) after chemoradiation; 38.8% of these patients had a pathological complete response (pCR). The median survival of this group was 15 months. Of 4 patients with p53 (-) pretreatment EGD, all of those were still p53 (-) after chemoradiation; 75% of these patients had pCR. The median survival was 30 months. In patients with p53 (+) TS/LS LN, 23% had a pCR after chemoradiation with a median survival of 16 months. In patients with p53 (-) TS/LS LN, 50.0% had a pCR with a median survival of 31.5 months. CONCLUSIONS: P53 protein overexpression in pretreatment EGD and TS/LS LN may predict response to chemoradiation and survival in esophageal cancer patients.

Adenocarcinoma↗
PubMed1999

The role of thoracoscopic staging of esophageal cancer patients.

INTRODUCTION: This study was designed to compare thoracoscopy/laparoscopy (TS/LS) staging with non-invasive clinical staging by CT and EUS for patients with esophageal carcinoma. METHODS AND RESULTS: CT and EUS followed by TS/LS were used to stage 88 patients with EGD proven esophageal carcinoma. Thoracoscopic staging was done in 82 patients and found N1 in 11 patients. Fifty-four patients had laparoscopy which detected N1 in 21 patients. Thirty-four cases had chemoradiation followed by surgery. Esophagectomy was performed in 47 patients after thoracoscopic staging and 33 with laparoscopic staging. Of these 47 resected patients, thoracoscopic staging showed N0 in 42 patients and N1 in five patients with an accuracy of 93.6%. Laparoscopic staging detected normal celiac lymph nodes in 20 patients and diseased LN in 11 patients with an accuracy of 93.9%. Comparing with final resection pathology, the sensitivity, specificity and positive predictive value of staging for N1 disease in the chest was 62.5, 100.0 and 100.0% by TS; 75.0, 75.6, and 23.1% by CT and 0.0, 51.4 and 5.5% by EUS, respectively. For N1 disease in the abdomen it was 84.6, 100.0 and 100.0% by Ls; 0.0, 97.1 and 0.0% by CT and 22.2, 81.5 and 28.6% by EUS, respectively. CONCLUSION: TS/LS staging of esophageal cancer patients with or without preoperative chemoradiation has a higher specificity and accuracy than CT and EUS, especially for N1 disease in the chest. It also allows individualization of preoperative radiotherapy fields.

Adult↗
PubMed1999

Accuracy of CT for the detection of pleural adhesions: correlation with video-assisted thoracoscopic surgery.

STUDY OBJECTIVE: The presence of pleural adhesions may render video-assisted thoracoscopic surgery (VATS) difficult or impossible. The aim of this study was to assess the value of chest CT in the detection of pleural adhesions prior to VATS. DESIGN: Prospective study of the accuracy of chest CT in detecting pleural adhesions prior to VATS. SETTING: Tertiary-referra; teaching hospital and Veterans Administration hospital. PATIENTS: Between July 1994 and March 1995, 63 consecutive patients undergoing 64 VATS procedures were evaluated with chest CT prior to surgery. MEASUREMENTS AND RESULTS: Preoperative scans were interpreted by consensus of two pulmonary radiologists prior to surgery. Suspected pleural adhesions and other findings related to the pleura were recorded on a form given to the surgeon prior to VATS. The surgeon confirmed or excluded each suspected adhesion during VATS, and documented any other lesions not identified preoperatively. Patient-by-patient and lesion-by-lesion analyses were performed. Pleural adhesions were correctly identified by CT in 28 of 39 cases (sensitivity, 71%) and excluded in 18 of 25 cases (specificity, 72%). On a lesion-by-lesion basis, 73 adhesions were identified during VATS, of which only 28 were identified prospectively at CT. There were 45 missed adhesions and 20 adhesions that were suggested falsely (sensitivity, 38%; specificity, 46%). Eighteen pleural spaces were correctly identified as being free of pleural adhesions. CONCLUSIONS: CT is moderately sensitive and specific for preoperative identification of pleural adhesions in patients undergoing VATS but its accuracy is poorer for individual lesions.

Adult↗