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W Roy Smythe

Publications and source records attributed to W Roy Smythe.

At least 19 recordsLinked to original sources
PubMed2004

2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma.

BACKGROUND: The current study was performed to assess the value of 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in predicting the pathologic response and survival of patients with esophageal carcinoma treated with preoperative chemoradiation (CRT) and tumor resection. Preliminary reports suggest that FDG-PET may be predictive of the response of esophageal carcinoma patients to preoperative CRT. METHODS: Eighty-three patients with resectable esophageal carcinoma who underwent preoperative CRT and FDG-PET and tumor resection were evaluated for pathologic response to CRT, percent residual tumor, and survival. RESULTS: The majority of patients in the current study were men (74 of 83 patients; 89%). Most tumors were adenocarcinomas (73 of 83 tumors; 88%) and clinical (EUS)T3/4 (69 tumors; 83%) or N1 (46 tumors; 55%). FDG-PET after preoperative CRT identified pathologic responders but failed to rule out microscopic residual tumor in 13 of 73 cases (18%). Pathologic response was found to correlate with the post-CRT FDG-PET standardized uptake value (SUV) (P = 0.03) and a post-CRT FDG-PET SUV of or 4 was found to be the only preoperative factor to correlate with decreased survival (2-year survival rate of 33% vs. 60%; P = 0.01). On univariate Cox regression analysis, only post-CRT FDG-PET was found to be correlated with post-CRT survival (P = 0.04). CONCLUSIONS: Post-CRT FDG-PET was found to be predictive of pathologic response and survival in patients with esophageal carcinoma who undergo preoperative CRT. Esophagectomy should still be considered even if the post-CRT FDG-PET scan is normal because microscopic residual disease cannot be ruled out.

Adenocarcinoma↗
PubMed2004

Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection.

BACKGROUND: To evaluate the safety and effectiveness of a new biodegradable polymeric sealant to close intraoperative air leaks after pulmonary resection. METHODS: In a multicenter prospective randomized trial, 161 patients with a median age of 67 years old (range 18-85 years old), were randomized in a 2:1 ratio to receive sealant or control for at least one significant air leak (> or = 2.0 mm in size) after pulmonary resection. In the sealant group, all significant air leaks underwent attempted repair by standard methods (sutures, staples, or cautery) prior to the application of sealant. The control group underwent only standard methods. Blood was analyzed for immunologic response. Patients were followed up 1 month after surgery. RESULTS: Intraoperative air leaks were sealed in 77% of the sealant group compared with 16% in the control group (p < 0.001). The sealant group had significantly fewer patients with postoperative air leaks compared with the control group (65% vs 86%, p = 0.005). Median length of hospitalization was 6 days (range, 3-23 days) for the sealant group compared with 7 days (range 4-38 days) for controls (p = 0.028). There was no difference in mortality, morbidity, duration of chest tubes, or immune responses between the two groups. CONCLUSIONS: This study demonstrates the effectiveness of a biodegradable polymer when used as an adjunct to standard closure methods for sealing significant intraoperative air leaks that develop from pulmonary surgery. Use of the sealant led to a reduction in postoperative air leaks, which may have decreased the length of hospitalization.

Adolescent↗
PubMed2004

Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer.

BACKGROUND: This study evaluates the utility of positron emission tomography (PET), endoscopic ultrasonography (EUS), and computed tomographic (CT) scans to predict pathologic response and survival following preoperative chemoradiation (CRT) in esophageal cancer. METHODS: One hundred three sequential patients with locoregionally advanced esophageal cancer, who were treated with CRT and esophageal resection between May 2001 and November 2003 at the University of Texas M.D. Anderson Cancer Center, were retrospectively reviewed. PET, EUS, and CT were performed before (pre) or after (post) CRT and before surgical resection. PET standardized uptake value (SUV) was defined as maximal uptake in primary tumor. RESULTS: Most patients were male (91 [88%]) with adenocarcinoma (90 [87%]). Pretreatment clinical stages were: IIA (42 [41%]), IIB (5 [5%]), III (50 [49%]), and IVA (6 [6%]). At the time of surgery, 58 patients (56%) had a pathologic response to CRT (< or =10% viable cells). Post-CRT measurements that correlated with pathologic response were: CT esophageal wall thickness (13.3 vs 15.3 mm, p = 0.04), EUS mass size (0.7 vs 1.7 cm, p = 0.01) and PET SUV (3.1 vs 5.8, p = 0.01). Post-CRT PET SUV equal to or greater than 4 had the highest accuracy for pathologic response (76%). Univariate and multivariate Cox regression analysis demonstrated that a post-CRT PET SUV equal to or greater than 4 was an independent predictor of survival (HR, 3.5, p = 0.04). CONCLUSIONS: The FDG-PET SUV is the most accurate noninvasive test to predict long-term survival after preoperative CRT and before surgical resection. Post-CRT FDG-PET cannot, however, rule out residual microscopic disease so esophagectomy should remain a therapeutic option even if the post-CRT imaging modalities are normal.

Adenocarcinoma↗
PubMed2004

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Academic Medical Centers↗
PubMed2004

The role of Bcl-2 family members in non-small cell lung cancer.

The treatment of advanced nonsmall cell lung cancer (NSCLC) continues to pose great challenges for the thoracic surgeon. Current therapeutic strategies with chemotherapy and radiation are often ineffective adjuncts to surgery. Accordingly, preclinical research concentration has turned to molecular targets that may prove to be more effective. The Bcl-2 family consists of a homologous network of genes that regulate apoptosis or programmed cell death. Altered expression of members in this family leads to aberrant cell proliferation and malignant growth. This review will discuss the expression and significance of Bcl-2 family members in NSCLC and consider potential methods of intervention that are currently being tested and may have clinical applicability. In addition, the current experience with clinical trials involving Bcl-2 down-regulation in solid organ tumors will be summarized.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Endoscopic ultrasound after preoperative chemoradiation can help identify patients who benefit maximally after surgical esophageal resection.

BACKGROUND: We investigated whether differences in postoperative survival exist based on the presence and site of residual tumor (esophagus vs regional lymph nodes) after preoperative chemoXRT in patients with esophageal cancer. Based on these data, we reevaluated the role of EUS in identifying patients who maximally benefit from surgical esophageal resection after preoperative chemoXRT. METHODS: We studied 97 consecutive esophageal cancer patients treated with preoperative chemoXRT and a potentially curative surgical procedure between 1998 to 2001. All patients had EUS examination prior to chemoXRT and 53 had a repeat EUS examination after chemoXRT but prior to surgery. Surgical resection specimens were analyzed for absence or presence of residual tumor and its location. RESULTS: Patients with residual tumor in the esophagus (pathT1-3N0) and patients without residual tumor (pathT0N0) had similar cumulative survival (p= 0.92). Patients with residual cancer in lymph nodes showed a trend toward shorter cumulative survival compared to patients without residual tumor in lymph nodes (p= 0.086). The actuarial survival in pathN1 group was lower than pathN0 group at 1, 2, and 3 yr. Patients with significant residual lymphadenopathy detected by EUS after therapy had significantly worse postoperative survival compared to patients with no residual lymphadenopathy (p= 0.028). In eight patients, we found that reliable cytologic identification of residual malignancy was technically feasible by EUS-FNA after chemoradiation therapy. CONCLUSIONS: Following preoperative chemoXRT and surgery, patients with residual tumor in the regional lymph nodes have lower actuarial survival at 1, 2, and 3 yr after surgery, compared to patients with path CR or with residual tumor only in the esophagus. EUS and EUS-guided FNA can be helpful in identifying residual tumor in the lymph nodes after preoperative chemoXRT to select patients who benefit maximally from surgery.

Adenocarcinoma↗
PubMed2004

Antisense oligonucleotides directed at the bcl-xl gene product augment chemotherapy response in mesothelioma.

OBJECTIVE: Malignant pleural mesothelioma (MPM) is resistant to both conventional chemotherapy and apoptosis. The bcl-2 family proteins are major determinants of apoptotic homeostasis. MPM lines and tumors routinely overexpress the anti-apoptotic protein BCL-XL. We have previously shown that antisense inhibition of BCL-XL in MPM cells leads to apoptosis. We sought to determine whether antisense oligonucleotides directed at the bcl-xl gene product would augment response to a conventional chemotherapeutic agent in human mesothelioma cell lines. METHODS: The human MPM cell lines REN and I-45 were exposed to two bcl-xl antisense oligonucleotides (15999, 16009) and one sense oligonucleotide (113529) construct at varying doses, followed by IC(50) cisplatin. Cellular viability was assessed by a calorimetric assay, and apoptosis was evaluated by Hoechst staining, Annexin V staining, and sub-G(1) fluorescence-activated cell sorter analysis. Western blot analysis of BCL-2 family proteins was performed following single agent and combined treatment. Isobologram mathematical analysis was used to determine whether or not combination therapies were additive or synergistic. RESULTS: Cell viability was most affected with the 15999 antisense oligonucleotides plus IC(50) cisplatin combination (70% of I-45 and 90% of REN cells killed), and apoptosis was markedly increased with this combination by all measures. Western blot demonstrated 15999 antisense oligonucleotides construct down-regulation of BCL-XL, but no further effect on expression of BCL-2 proteins with cisplatin. Isobologram analysis demonstrated 15999 + cisplatin synergistic effect. CONCLUSIONS: Exposure of human MPM cells to bcl-xl antisense oligonucleotides sensitizes human mesothelioma cells to the conventional chemotherapeutic agent cisplatin. Similar approaches using a combination of molecular and conventional treatment may have clinical utility for this tumor.

Apoptosis↗
PubMed2003

Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters.

PURPOSE: To clarify the relationship between the percentage of lung receiving low radiation doses with concurrent chemotherapy and the occurrence of postoperative pulmonary complications in the treatment of esophageal carcinoma. METHODS: From 117 patients who underwent preoperative chemoradiation for esophageal cancer at our institution between 1998 and 2002, we selected 61 patients for whom complete pulmonary dose-volume histogram (DVH) data were available and analyzed the incidence of pneumonia and acute respiratory distress syndrome (ARDS) in this group. All patients received concurrent chemoradiation therapy, and 39 patients also received induction chemotherapy before concurrent chemoradiation. The median age was 62 years, and the median radiotherapy dose was 45 Gy. The percentage of lung volume receiving at least 10 Gy (V10), 15 Gy (V15), and 20 Gy (V20) were recorded from each pulmonary DVH. RESULTS: Eleven (18%) of the 61 patients had pulmonary complications, 2 of whom died after progression of pneumonia. Pulmonary complications were noted more often (35% vs. 8%, p = 0.014) when the pulmonary V10 was > or =40% vs. <40% and when the V15 was > or /=30% vs. < 30% (33% vs. 10%, p = 0.036). An apparent increase in pulmonary complication rate when V20 was > or =20% vs. <20% (32% vs. 10%, p = 0.079) was not significant. None of the other factors analyzed (surgical procedure, tumor location, use of induction chemotherapy, use of concurrent taxane-based chemoradiation, or smoking history) was associated with the occurrence of pulmonary complications. The median hospital stay was 17 days for patients who had pulmonary complications vs. 12 days for patients who did not (p = 0.08). CONCLUSIONS: The use of multimodality therapy may require minimization of lung volume irradiation to levels lower than previously expected. Radiotherapy techniques that decrease the volume of lung receiving low radiation doses may significantly reduce the risk of this potentially life-threatening complication.

Adenocarcinoma↗
PubMed2003

Long-term outcome of phase II trial evaluating chemotherapy, chemoradiotherapy, and surgery for locoregionally advanced esophageal cancer.

PURPOSE: To evaluate the long-term outcome of chemotherapy, chemoradiotherapy, and surgery for patients with locoregionally advanced esophageal cancer. METHODS AND MATERIALS: Thirty-eight patients with locoregionally advanced esophageal cancer were entered into a Phase II study between November 1996 and October 1998 at the University of Texas M. D. Anderson Cancer Center. Patients initially received two cycles of chemotherapy with paclitaxel (200 mg/m(2)), 5-fluorouracil (750 mg/m(2)/d for 5 days), and cisplatin (15 mg/m(2)/d for 5 days), followed by chemoradiotherapy, consisting of radiation (45 Gy during 5 weeks) with 5-fluorouracil (300 mg/m(2)/d during radiation) and cisplatin (15 mg/m(2)/d for 5 days). Surgical resection was performed 4-6 weeks after the completion of the chemoradiotherapy. RESULTS: Most patients had adenocarcinoma (n = 32; 84%). Pretreatment endoscopic ultrasonography revealed T3 tumors in 33 patients (87%) and N1 disease in 25 patients (66%). Thirty-seven patients (97%) completed the planned chemotherapy and chemoradiotherapy, and 35 patients (92%) underwent surgery, with a 30-day mortality rate of 6% (2 of 35 patients). A pathologic complete response or microscopic residual carcinoma (<10% viable) was found in 25 (71%) of 35 patients and was associated with a disease-free survival rate of 72% at 3 years and 51% at 5 years. On the basis of an intention-to-treat analysis and a median potential follow-up of 58 months, the 3- and 5-year overall survival rate for all 38 patients was 63% and 39%, respectively. CONCLUSION: The long-term results of this study suggest that the strategy of induction chemotherapy followed by chemoradiotherapy and surgery is safe and warrants further evaluation in the treatment of patients with locoregionally advanced esophageal cancer.

Adenocarcinoma↗
PubMed2003

Intensity-modulated radiotherapy following extrapleural pneumonectomy for the treatment of malignant mesothelioma: clinical implementation.

PURPOSE: New insight into the extent of the target volume for the postoperative irradiation of malignant pleural mesothelioma as determined during surgery has indicated that standard conformal radiotherapy (IMRT) is not sufficient for curative treatment. We describe a novel technique for implementing intensity-modulated radiotherapy (IMRT) to deliver higher doses to treat the full extent of these complex target volumes. METHODS AND MATERIALS: After extrapleural pneumonectomy, 7 patients underwent simulation, treatment planning, and treatment with IMRT to the involved hemithorax and adjacent abdomen. The target volumes encompassed the entire operative bed, including the ipsilateral mediastinum, anterior pleural reflection, and ipsilateral pericardium and the insertion of the diaphragm and crura. These were extensively marked during surgery with radiopaque markers to facilitate target delineation. RESULTS: Setup uncertainty and respiratory-dependent motion were found to be small. Coverage of the planning target volume was very good, with the crus of the diaphragm the most difficult volume to irradiate. The radiation doses to normal structures were acceptable. CONCLUSION: IMRT for treatment of malignant mesothelioma after extrapleural pneumonectomy results in more potentially curative doses to large, complex target volumes with acceptable doses to normal tissues.

Humans↗
PubMed2003

Intensity-modulated radiation therapy: a novel approach to the management of malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) causes symptoms and death mainly due to local progression, even after combined modality treatment. Poor local control after conventional radiotherapy may be due to the low dose of radiation that has been administered or to restriction of the target volume to avoid critical organs. Intensity-modulated radiation therapy (IMRT) has the potential to overcome these geometric/dosimetric constraints. METHODS AND MATERIALS: Seven patients with MPM who had an extrapleural pneumonectomy (EPP) were treated with adjuvant IMRT. The clinical target volume (CTV) included the surgically violated area inside the chest wall with particular attention to the insertion of the diaphragm, pleural reflections, and the deep margin of the thoracotomy incision. Treatment was delivered by intensity-modulated 6-MV photon beams using dynamic multileaf collimation. RESULTS: The CTV ranged from 2667 to 7286 mL. The average CTV covered to 50 Gy was 94% (range, 92% to 98%). Respiratory motion was minimal. The average volume of the boost areas covered by 60 Gy was 92% (range, 82% to 99%). Dose-volume constraints for normal tissue were met in almost all cases. Acute toxicity was mild to moderate. The most severe side effects were anorexia, nausea or vomiting, and dyspnea. Esophagitis was absent or mild. After a minimum of 13 months follow-up care there were no cases of disease recurrence within the ipsilateral hemithorax. CONCLUSION: Treatment of the extensive operative area after an EPP is feasible using IMRT. Input from the radiologist and from the surgeon in the planning process facilitates definition of the high dose volumes. In light of patients' tolerance to post-EPP IMRT, it may be feasible to incorporate systemic therapy, including novel biologic therapies into the treatment regimen.

Aged↗
PubMed2003

Gene therapy of lung cancer.

It is estimated that there will be 157,200 deaths from lung cancer in 2003. Current regimens of surgery, chemotherapy and radiation have not significantly changed overall 5-year survival rates for this disease. Thanks to intensive molecular studies over the last three decades, new targets for treatment have been identified, including replacement of tumor suppressor genes, prevention of angiogenesis and tumor growth, and regulation of programmed cell death. Promising advances have been made but obstacles still abound before effective use of these strategies at the patient bedside can occur. One area of concentration lies in developing more accurate and complete delivery of the therapeutic constructs. In the evolution of gene therapy approaches, from beginning theory to translational research, investigators in thoracic malignancies have played a leading role, utilizing a number of methods and delivery vehicles. The objective of this review is to discuss some of the major molecular targets available for manipulation in lung cancer, describe vectors and techniques currently used by thoracic researchers to deliver therapy, and provide the p53 model as an example of progression from bench research to clinical treatment.

Genes, Tumor Suppressor↗
PubMed2003

Primary lymphoepithelioma of the esophagus.

A case of primary lymphoepithelioma of the esophagus is presented in an Arabic female patient. This very rare Epstein-Barr virus infection-related malignancy has previously been reported only in patients from Japan. The tumor exhibited classic histologic and immunohistochemical features of lymphoepithelioma, and was successfully treated with neoadjuvant chemotherapy and irradiation followed by surgical resection.

Biopsy, Needle↗
PubMed2003

The risk of second primary tumors after resection of stage I nonsmall cell lung cancer.

BACKGROUND: The incidence of second primary lung cancers (SPLC) after resection of nonsmall cell lung cancer (NSCLC) is estimated to be 1% to 4% per patient year. The overall effect of SPLC on survival after resection of stage I NSCLC is unknown. Here we report the incidence, management, and outcome of SPLC in a large prospective cohort of patients who underwent careful follow-up. METHODS: National Cancer Institute Intergroup Trial NCI #I91-0001 examined the effectiveness of isotretinoin A for chemoprevention of second primary tumors, the primary endpoint in that trial. Prospective data from patients randomly assigned to the placebo arm were analyzed. RESULTS: Five hundred sixty-nine patients underwent complete resection of pathologic stage I NSCLC. The median follow-up was 5.9 years. Second primary tumors developed in 88 (15%) patients. Of these, 49 (56%) were SPLC (incidence = 1.99/100 patient-years), with a median interval from initial surgery of 4.2 years. Second primary lung cancer never developed in patients who had never smoked (n = 44, p = 0.046; never versus ever smokers). Current smokers had a higher incidence of SPLC than former smokers (hazard ratio = 1.91, p = 0.03). Age, sex, stage, histology, tumor location and initial surgery had no effect on SPLC development. Despite semiannual follow-up with chest radiographs, 12 (24%) patients had metastatic disease at the time of diagnosis of SPLC. Surgical resection was performed in 31 (63%) SPLC patients. Median survival was 4.1 years in those who underwent surgery and 1.4 years in those who did not (p = 0.003). Overall SPLC-related mortality in the original cohort was 3.7%. CONCLUSIONS: Patients who undergo surgery for SPLC can achieve prolonged survival. Despite close follow-up however many patients with SPLC present with advanced disease. That indicates a need for continued lifelong postoperative surveillance.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Suramin inhibits the growth of malignant mesothelioma in vitro, and in vivo, in murine flank and intraperitoneal models.

Surgical debulking of malignant mesothelioma (MM) ultimately fails due to local recurrence. Suramin, an inhibitor of extracellular growth factors (ECGFs), has demonstrated efficacy in the treatment of malignant mesothelioma in a small case series. Our goal was to study survival benefits and disease progression in several MM animal models treated with suramin as a potential agent for adjuvant therapy. In vitro growth of human (REN, I-45), rat (II-45) and murine (AB12) mesothelioma cell lines were measured with or without suramin exposure. Human and murine MM tumors were implanted subcutaneously into murine flanks or injected intraperitoneally (i.p.) into murine abdominal cavities. Dose and treatment schedules were optimized to reduce the rate of tumor progression and to improve survival curves. Suramin inhibited the in vitro growth of all cell lines, reaching statistical significance (P<0.01) three doubling cycles after suramin administration, with a maximum inhibition of 10-25% of control growth. A significant time- and dose-dependent effect was observed. In vivo, suramin inhibited the growth of MM in the xenogeneic model (55% of control growth, P<0.01), and in the syngeneic model at both the low and high loading doses (46 and 36% of control growth, respectively, P<0.01). Suramin treatment inhibited in vivo growth in the REN intraperitoneal model shown grossly by necropsy of same day deaths comparing treatment and control animals. Tumor inhibition with the higher dose was also reflected by the lower mean tumor burden scores (control: 4.0 and high dose: 3.4). Suramin inhibits the growth of human, murine, and rat MM in vitro, in a time- and dose-dependent manner. Suramin also inhibits the growth of human MM flank and intraperitoneal xenografts in vivo in an immunodeficient host, as well as the growth of syngeneic murine flank tumors in an immunocompetent host. These studies demonstrate that suramin may have the potential to provide effective therapy for MM, and that further studies are necessary to elucidate the survival advantage of suramin mediated MM growth inhibition.

Animals↗
PubMed2003

The first American textbook of surgery.

The first systematic textbook of surgery written in the United States, The Elements of Surgery, was completed in 1813 by John Syng Dorsey, a University of Pennsylvania surgeon. The work thoroughly covered all major clinical areas of surgery of that time in a two-volume, 797-page text. Subsequent editions were published in 1818, 1823, and 1831. It became the standard surgical textbook in this country during that era and was the first American medical text exported abroad for use at the more established European centers of medical education. The reasons for writing the text included a desire to put into print the teachings of Philip Syng Physick (first Chair of the Department of Surgery at the University of Pennsylvania, and Dorsey's uncle), the new American nationalism, and socioeconomic pressures forced on the American publishing industry by the War of 1812 and preceding trade embargoes. In addition to extensive exposure to Physick, Dorsey was also uniquely qualified to write and illustrate this text, as he exhibited an unusually succinct style and was a remarkable medical artist. The book was the forerunner to William Gibson's The Institutes and Practice of Surgery and all American surgical textbooks to follow.

General Surgery↗