Biomedical subjects

C D Wright

Publications and source records attributed to C D Wright.

At least 37 records · Page 2Linked to original sources

PubMed1999

Induction immunosuppression for lung transplantation with OKT3.

BACKGROUND: The use of OKT3, an anti-CD3 monoclonal antibody, for immunosuppressive therapy for lung transplantation has been restricted because of concerns regarding infectious risk and cardiopulmonary instability after its administration. METHODS: Fifty-two patients received OKT3 (5 mg/d intravenously for 10 days) for induction of immunosuppressive therapy, along with azathioprine (1.5 mg x kg(-1) x d(-1) intravenously) and enteral cyclosporine (12 mg x kg(-1) x d(-1)). Maintenance steroid therapy was begun on postoperative day 8. Prophylactic antifungal therapy (fluconazole or amphotericin B) and ganciclovir was used in all patients. Serial transbronchial biopsy and measurements of pulmonary function were used to assess patients for evidence of infection or rejection. Cytomegalovirus infection was diagnosed by biopsy or the presence of cytomegalovirus antigenemia. RESULTS: The 30-day mortality rate was 4%; the in-hospital mortality rate was 8%. Acute graft failure was seen in 6 patients. The median length of intubation was 5 days, and the median hospital stay was 30 days. Systemic and pulmonary artery systolic pressures, cardiac index, and ratio of arterial partial oxygen pressure to fraction of inspired oxygen showed no significant alteration after OKT3 dosage. Gram-negative pulmonary infections were identified in 12 patients. Aspergillus infection was seen in 7 patients. Cytomegalovirus infection in 8 patients responded to ganciclovir and did not affect mortality. Respiratory syncytial viral infection was seen in 7 patients. Acute rejection was never seen during OKT3 administration. No episodes of acute rejection were identified in 14 patients at any time postoperatively. In the remainder, episodes of acute rejection responded to steroid or antithymocyte globulin therapy. At a median length of follow-up of 31 months, freedom from obliterative bronchiolitis was 69%+/-9% at 36 months. The overall survival rate was 88%+/-5% at 12 months, 82%+/-6% at 24 months, and 74%+/-7% at 36 months after transplantation. CONCLUSIONS: OKT3 is a safe and effective agent for induction immunosuppressive therapy in lung transplant recipients that limits the incidence of acute rejection and may decrease the incidence of obliterative bronchiolitis.

Adolescent↗

PubMed1999

Long-segment colon interposition for acquired esophageal disease.

BACKGROUND: Long-segment colon interposition has been used for esophageal replacement for acquired esophageal disease. The indications for use, morbidity, and functional results of these conduits have been debated. METHODS: We reviewed the medical records, office visits, and operative reports of patients undergoing long colon interposition for acquired esophageal disease at our institution from 1956 to 1997. RESULTS: Long colon interposition was performed in 52 patients for caustic injury (n = 20), gastroesophageal disease (n = 16), previous irradiation (n = 8), primary motility disorders (n = 4), and acquired absence of the esophagus (n = 4). From 1976 to 1997, acquired diseases accounted for 62% of long colon interposition. The left colon was used in 46 patients and the right colon in 6. The in-hospital mortality rate was 4%. Early complications included graft ischemia in 5 patients, anastomotic leak in 3, and small bowel obstruction in 1. Late complications included anastomotic stenosis requiring dilation in 26 patients, with 2 requiring surgical revision, and bile reflux requiring surgical diversion in 1 patient. Swallowing function was excellent in 24% of patients, good in 66%, and poor in 10%. CONCLUSIONS: Long colon interposition can be performed safely, with acceptable long-term functional results in patients with acquired esophageal disease.

Adult↗

PubMed1999

Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival.

BACKGROUND: The principal feature of bronchoalveolar carcinoma is that it spreads along airways or aerogenously with multifocality, but many issues are unresolved. METHODS: We studied 119 patients with pathologically confirmed bronchoalveolar carcinoma. Symptoms, smoking status, radiologic findings, the size of tumor, operative procedures, and complications were reviewed. We studied the pathologic features: presence or absence of aerogenous spread, patterns of growth, cell type, nuclear grade, mitosis, rate of bronchoalveolar carcinoma in adenocarcinoma, and lymphocyte infiltration. The correlation among clinical, radiologic, and pathologic findings was examined, and the factors affecting survival were analyzed. RESULTS: Symptomatic patients had more infiltrative radiographic features, and asymptomatic patients tended to have more mass-like features (P <.0001). Tumors with radiographically infiltrating lesions tended to have mucinous histologic features (P =.006). Tumors with mass lesions by radiograph tended to have nonmucinous and sclerosing histologic features (P =.003). Aerogenous spread was seen in 94% of specimens. The presence of a variety of cell types suggested multiple clonal origin. The overall survival in those patients undergoing resection was 69.1% at 5 years and 56.5% at 10 years. The significant factors affecting survival were radiologic presence of a mass or infiltrate, pathologic findings of the presence of sclerosis, association with a scar, the rate of bronchoalveolar carcinoma in adenocarcinoma, lymphocyte infiltration grade, nodal involvement, and status of complete resection. Mitosis or nuclear grade of tumor cells did not correlate with survival. CONCLUSIONS: Bronchoalveolar carcinoma showed good overall survival with appropriate surgical procedures. Certain radiologic or pathologic findings correlated with survival. These findings may enhance the ability to predict long-term survival.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1999

Superior sulcus lung tumors: impact of local control on survival.

OBJECTIVES: Our goal was to assess patient survival and response to treatment for superior sulcus tumors treated with combined radiation therapy and surgery when possible, or with radiation alone when surgery was not possible. METHODS: Seventy-three patients were treated for primary non-small cell carcinoma of the superior pulmonary sulcus. Thirty-four patients received combined resection and irradiation. Thirty-nine patients who had extensive primary disease, distant metastases, or who were medically unfit for surgery were treated with radiation alone. Thirty-one patients (91%) assigned to the resection/irradiation group completed treatment. Combined therapy patients routinely received 40 Gy before the operation, with additional postoperative irradiation based on the surgical findings. RESULTS: Overall survival at 5 years was 19% and disease-specific survival was 20% for all patients. Overall survival and disease-specific survival at 5 years for the resection/irradiation group were 33% and 38%, respectively. Significant indicators of poor prognosis included unresected primary disease, low performance score, T4 stage, or positive node status. Eighty-two percent of the patients who received irradiation alone were treated with palliative intent. Freedom from local-regional progression, achieved initially in 66% of these patients, was associated with a median survival of 8 months. Median survival for 7 patients considered for definitive irradiation was 25 months. During the first 18 months, distant failures occurred in approximately 35% of patients in each treatment group. CONCLUSIONS: Selection of medically fit patients with resectable disease for combined surgery and aggressive radiation therapy resulted in a high likelihood of local control. Overall survival for the resection/irradiation group was significantly poorer for patients with T4 stage, nodal disease, or Horner's syndrome. Distant metastases eventually developed in 56% of patients undergoing resection. Median survival in the resection/irradiation group was significantly prolonged for those patients who could tolerate high-dose radiation treatment.

Carcinoma, Non-Small-Cell Lung↗

PubMed1999

Clinical experience with carinal resection.

OBJECTIVE: Pathologic processes that involve the carina pose a tremendous challenge to thoracic surgeons. Although techniques have been developed to allow primary resection and reconstruction, few institutions have accumulated sufficient experience to allow meaningful conclusions about the indications and the morbidity and mortality rates for this type of surgery. METHODS: Since 1962, 135 patients have undergone 143 carinal resections (134 primary resection, 9 re-resection) at our institution. Indications for carinal resection included bronchogenic cancer (58 patients), other airway neoplasms (60 patients), and benign or inflammatory strictures (16 patients). Thirty-seven patients (28%) had a history of prior lung or airway surgery not involving the carina. Carinal resection without pulmonary resection was accomplished in 52 patients; 57 patients had carinal pneumonectomy (44 right, 13 left); 14 patients had carinal plus lobar resection, and 11 patients had carinal resection after pneumonectomy (9 left, 2 right). There were 15 different modes of reconstruction, based on the type and extent of resection. Techniques were used to reduce anastomotic tension. RESULTS: The operative mortality rate in the 134 patients after primary carinal resection was 12.7%. Adult respiratory distress syndrome was responsible for 9 early deaths. Predominant predictors of operative death included postoperative mechanical ventilation (P =.001), length of resected airway (P =.03), and development of anastomotic complications (P =.04). Mortality rates varied by the type of procedure and the indication for resection. Left carinal pneumonectomy was associated with a high operative mortality rate (31%). Complications were noted in 52 patients (39%), including atrial arrhythmias (20 patients) and pneumonia (11 patients). Anastomotic complications, both early and late, were seen in a total of 23 patients (17%) and resulted in death or surgical reintervention in 21 patients (91%). The operative mortality rate for carinal re-resection was 11.1%. CONCLUSIONS: Carinal resection with primary reconstruction may be accomplished with acceptable mortality rates, but the underlying pathologic process and chance for long-term survival must be carefully considered before the operation is recommended, especially in the case of left carinal pneumonectomy. Anastomotic complications exact a heavy toll on involved patients. Careful patient selection and meticulous anesthetic and surgical technique remain the key to minimizing morbidity and mortality rates.

Adolescent↗

PubMed1999

Surgical treatment of primary pulmonary sarcomas.

OBJECTIVE: We sought to identify the long-term prognosis after surgical treatment for primary pulmonary sarcoma. METHODS: Twenty-three patients were retrospectively identified as having been treated surgically for primary pulmonary sarcoma between 1981 and 1996. The records of all patients were reviewed, and the histopathology reexamined by a pathologist. RESULTS: Fifteen patients were male and eight female; their ages ranged from 20 to 78 (mean 51) years. Tumors measured between 0.9 and 12.0 (mean 5.2) cm across the greatest diameter. The histologic diagnoses were malignant fibrous histiocytoma (8, three grade 1 or 2, two grade 3), synovial sarcoma (4), malignant schwannoma (3), leiomyosarcoma (3), and one case each of angiosarcoma, intimal sarcoma, epitheloid hemangioendothelioma, fibrosarcoma and primitive neuroectodermal tumor. Three patients were found to be unresectable. All three underwent radiation and chemotherapy. Lobectomies or bilobectomies were performed in 13 patients including two sleeve resections, one carinal resection, and one chest wall resection. Four patients underwent radical pneumonectomies. Three patients with invasion of the pulmonary artery, pulmonary veins or atrial wall underwent extended resections with the use of cardiopulmonary bypass. In two, a homograft was used to reconstruct the right ventricular outflow tract. Of the resected patients, six had a positive resection margin, and four had at least one positive lymph node in the specimen. Three patients underwent repeat pulmonary resections for recurrences. Eleven patients received postoperative chemotherapy and eight had radiation therapy. Follow-up was available on 22 patients, and ranged from 2 to 183 (mean 48) months; 14 patients are disease free, six died of disease, one died of surgical complications (operative mortality 5%), and two are alive with disease. Actuarial 3- and 5-year survival of the resected patients was 69%. Size and grade were not found to be correlated with significantly increased survival, but completeness of resection was (P<0.05). CONCLUSIONS: Resection of primary pulmonary sarcomas can produce an acceptable survival rate if the resection is complete. Cardiopulmonary bypass can be a useful adjunct when tumors involve a resectable area of the heart or great vessels.

Adult↗

PubMed1999

Thymoma: state of the art.

Thymoma is the most common tumor of the anterior mediastinum. This tumor is associated with unique paraneoplastic syndromes, such as myasthenia gravis, hypogammaglobulinemia, and pure red cell aplasia. The rarity of this tumor, however, has somewhat obscured the optimal treatment for this disease. For the majority of patients who present with localized tumor, surgical extirpation remains the standard of choice. Adjuvant radiotherapy seems to improve local control and survival. In more advanced disease, systemic therapy has been demonstrated to produce a 50% to 80% objective response rate. These observations have led to the development of multimodality therapy for the treatment of patients with advanced thymoma. In this article, we will review the current perspectives on the management of early stage and advanced thymoma.

Antineoplastic Agents↗

PubMed1999

Multimodality therapy of esophageal cancer.

Multimodality therapy of esophageal cancer has been evaluated in several clinical trials, with positive results in terms of improved survival compared with single-modality therapy. A case report is presented describing the use of paclitaxel in a multimodality regimen for a patient with a bulky esophageal tumor. In addition, results are described of a clinical trial in which patients received a paclitaxel-based regimen as part of multimodality therapy for esophageal cancer.

Adult↗

PubMed1999

Secretory leukocyte protease inhibitor prevents allergen-induced pulmonary responses in animal models of asthma.

Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways that exhibits broad spectrum inhibitory activity against mast cell and leukocyte serine proteases implicated in asthma pathology. To assess the potential therapeutic utility of SLPI in this disorder, its effects on antigen-induced pulmonary responses were evaluated. In Ascaris-sensitized sheep, SLPI (3 mg) administered by aerosol daily for 4 days, with the final dose 0.5 h before antigen challenge, reduced the areas under the curve for early- and late-phase bronchoconstriction (73 and 95%, respectively; p <.05 versus control responses). SLPI also inhibited the development of airway hyperresponsiveness to carbachol (84%, p <. 05 versus control response) measured 24 h after antigen challenge. In ovalbumin-sensitized guinea pigs, intratracheal administration of SLPI daily for 3 days, with the final dose 1 h before antigen challenge, inhibited the development of airway hyperresponsiveness to histamine with an ED50 of <0.05 mg/kg. Prolonged pharmacodynamic activity of SLPI was observed in both species. In a murine model of atopic asthma, SLPI inhibited leukocyte influx into the airways after chronic allergen challenge. SLPI administered to sheep by the predosing protocol described above also prevented the antigen-induced decrease of tracheal mucus velocity (p <.05). In addition, a single aerosol administration of SLPI (30 mg) to sheep 1 h after antigen challenge inhibited the subsequent late-phase bronchoconstriction and development of hyperresponsiveness and reversed the stimulated decrease in tracheal mucus velocity. These results suggest that SLPI may provide therapeutic intervention against the pathophysiology of asthma and its underlying pathology.

Aerosols↗

PubMed1998

Interaction of secretory leukocyte protease inhibitor with heparin inhibits proteases involved in asthma.

Protease inhibition by secretory leukocyte protease inhibitor (SLPI) is accelerated by the sulfated polysaccharides. The nature of the SLPI-polysaccharide interaction, explored with affinity chromatography, indicated that this interaction was sensitive to the charge and type of polysaccharide. Dextran and chondroitin had the lowest affinity for SLPI, followed by dermatan, heparan, and dextran sulfates. While heparin bound SLPI tightly, the highest affinity heparin chains unexpectedly contained a lower level of sulfation than more weakly interacting chains. Heparin oligosaccharides, prepared using heparin lyase I were SLPI-affinity fractionated. Surprisingly, undersulfated heparin oligosaccharides bound SLPI with the highest affinity, suggesting the importance of free hydroxyl groups for high affinity interaction. Isothermal titration calorimetry was used to determine the thermodynamics of SLPI interaction with a low molecular weight heparin, an undersulfated decasaccharide and a tetrasaccharide. The studies showed 12-14 saccharide units, corresponding to molecular weight of approximately 4,800, were required for a 1:1 (SLPI:heparin) binding stoichiometry. Furthermore, an undersulfated decasaccharide was able to bind SLPI tightly (Kd approximately 13 nM), resulting in its activation and the inhibition of neutrophil elastase and pancreatic chymotrypsin. The in vitro assessment of heparin and the decasaccharide and tetrasaccharide using stopped-flow kinetics suggested that heparin was the optimal choice to study SLPI-based in vivo protease inhibition. SLPI and heparin were co-administered by inhalation in therapy against antigen-induced airway hyperresponsiveness in a sheep bronchoprovocation model. Heparin, in combination with SLPI demonstrated in vivo efficacy reducing early and late phase bronchoconstriction. Heparin also increased the therapeutic activity of SLPI against antigen-induced airway hyperresponsiveness.

Animals↗

PubMed1998

Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection.

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.

Administration, Inhalation↗

PubMed1998

Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi.

Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequence, tryptase inhibitors have become the subject of study as potential novel therapeutic agents for asthma. Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways which exhibits anti-tryptase activity. To assess the potential therapeutic utility of SLPI in asthma, its effects were evaluated using in vitro and ex vivo models of airway hyperresponsiveness and compared with the effects of the small molecule tryptase inhibitor APC-366. Our results demonstrate that SLPI inhibits tryptase-mediated hyperresponsiveness in vitro and attenuates the hyperresponsiveness observed in airway smooth muscle from antigen-sensitized animals subjected to antigen exposure. The small molecule tryptase inhibitor APC-366 has a similar inhibitory effect. Thus, tryptase appears to be a significant contributor to the development of hyperresponsiveness in these models. To the extent that tryptase contributes to the development and progression of asthma, SLPI may possess therapeutic potential in this disease setting.

Animals↗

PubMed1998

Respiratory syncytial virus-associated infections in adult recipients of solid organ transplants.

BACKGROUND: Although respiratory syncytial virus (RSV) infection is known to cause severe pulmonary infections in bone marrow transplant recipients, less is known concerning its clinical course, diagnosis, and treatment in solid organ transplant recipients. METHODS: We have conducted a retrospective review of seven cases of RSV infection in adult recipients of solid organ transplants. Four patients received lungs, two received kidneys, and one received a heart. RESULTS: The most common presenting complaints were dyspnea (100%), cough (86%), and purulent sputum (57%). Physical findings included fever (43%), rales (100%), and wheezing (29%). Admission studies were significant for leukocytosis (29%), a left shift in the white blood cell differential (86%), and hypoxemia (mean PaO2 = 64). Chest radiographs were unchanged in 29% and showed infiltrates that were bilateral in 43% and unilateral in 29%. Pulmonary function tests in lung transplant recipients showed a mean fall in forced expiratory volume in 1 second of 26% and a fall in diffusion capacity for carbon monoxide of 24%. Five patients were treated with aerosolized ribavirin. Adverse events associated with treatment included wheezing (80%) and mild dyspnea (20%). The conditions of three of five treated patients were believed by their physicians to have improved 7 days after the initiation of therapy. One of the five treated patients died, and both untreated patients survived. CONCLUSIONS: RSV infection in this population has an extremely variable severity and clinical course, usually dominated by lower respiratory symptoms and obstructive airway disease. Ribavirin therapy is well tolerated, but its efficacy remains unknown.

Adult↗

PubMed1997

The cloning and characterization of a murine secretory leukocyte protease inhibitor cDNA.

Human secretory leukocyte protease inhibitor (hSLPI) is produced by epithelial cells at mucosal surfaces, where it regulates both the neutrophil-mediated inflammation that characterizes inflammatory diseases, and pathogens themselves via both antiprotease and "defensin-like" activities. Additionally, hSLPI may regulate other processes such as cutaneous desquamation and placental invasiveness. To better understand the primary physiologic roles of SLPI, it will be important to establish a genetically tractable animal model, the most attractive candidate being the mouse. In this report, the cloning and characterization of murine (m) SLPI is described. mSLPI is encoded by a single copy gene, and appears structurally highly similar to hSLPI. At the same time, significant differences between mSLPI and hSLPI are presented, notably a difference in expression pattern, and a structural difference in the protease binding site that correlates with a difference in the spectrum of protease inhibiton. Such species-specific evolution of this protease inhibitor is notable given that species-specific structure-function differences have previously been reported for the alpha-1 antitrypsin family.

Amino Acid Sequence↗

PubMed1997

Pulmonary lobectomy patient care pathway: a model to control cost and maintain quality.

BACKGROUND: Cost containment is a reality in thoracic surgery. Patient care pathways have proved effective in cardiac surgery to reduce length of stay and control costs. METHODS: A multidisciplinary team formulated a pulmonary lobectomy patient care pathway to standardize care, reduce length of stay and costs, and maintain quality. Variance codes were developed to collect data prospectively on reasons for prolonged stay. A patient satisfaction survey was instituted to learn patients' responses to their hospitalization. RESULTS: One hundred forty-seven patients underwent lobectomy in 1995 before institution of the pathway with a mean length of stay of 10.6 days and a mean cost of $16,063. The lobectomy pathway was instituted at the beginning of 1996. One hundred thirty patients underwent lobectomy in 1996 with a mean length of stay of 7.5 days (p = 0.03) and a mean cost of $14,792 (p = 0.47). Readmission and mortality rates were unchanged. Eighty-eight of 130 patients (68%) were able to be discharged by the target length of stay of 7 days in 1996 as opposed to 76 of 147 patients (52%) in 1995. The most common reason for delayed discharge was inadequate pain control. The majority of patients felt prepared for discharge by the seventh postoperative day (70 of 96 patients, 73%). CONCLUSIONS: The institution of a lobectomy patient care pathway appeared to reduce length of stay and costs. The pathway provided a framework to begin systematic quality control measures to enhance patient care.

Cost Control↗

PubMed1997

Reoperative tracheal resection and reconstruction for unsuccessful repair of postintubation stenosis.

OBJECTIVE: Our objective was to analyze characteristics and results of redo tracheal resection and reconstruction. METHODS: Seventy-five patients were operated on between 1966 and 1997 after unsuccessful initial repairs for postintubation tracheal stenosis. RESULTS: Sixteen of these patients came from a group of 32 patients with unsuccessful repair among the 450 primary resections and reconstructions performed at our institution. Fifty-nine patients were referred to us after unsuccessful initial repair elsewhere. Initial management was a T-tube or tracheotomy in 39 patients. The length of repeat resection ranged from 1.0 cm to 5.5 cm (mean 3.5 cm). A laryngeal release was used in 19 patients (25%) to reduce anastomotic tension. Complications occurred in 29 patients (39%) and were most frequent in the group requiring laryngeal release (12/19, 63.2%). Overall outcome was good in 59 patients (78.6%) and satisfactory in 10 (13.3%). The repair was unsuccessful in four patients (5.3%), and two patients died (2.6%). CONCLUSIONS: Despite difficulties encountered in reoperative surgery after failed tracheal reconstruction for postintubation stenosis, successful outcome may be achieved in a large number of cases.

Adult↗

PubMed1997

Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study.

OBJECTIVE: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma. We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates. METHODS: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m2) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor). The mean age was 62 years, and 32 patients (80%) had adenocarcinoma. Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater). RESULTS: The average hospitalization for induction treatment was 17 days. Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication. The maximum tolerated dose of paclitaxel was 100 mg/m2. Two patients died during induction treatment. Thirty-six patients (90%) underwent resection. The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response. Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076). The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months. CONCLUSIONS: Paclitaxel at a dose of 100 mg/m2 appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival.

Adenocarcinoma↗

PubMed1997

Bronchopulmonary carcinoid tumors associated with Cushing's syndrome: a more aggressive variant of typical carcinoid.

OBJECTIVES: Our objectives were to delineate the clinicopathologic characteristics of adrenocorticotropin-secreting bronchopulmonary carcinoid tumors causing Cushing's syndrome and to derive from these findings a rational approach to diagnosis and surgical management of this unusual condition. METHODS: We conducted a retrospective, chart-review analysis of seven consecutive patients treated at the Massachusetts General Hospital over a 16-year period. RESULTS: The patients uniformly had symptoms of marked hypercortisolism, and the underlying lung lesions remained clinically occult for a mean of 24 months. Standard endocrine testing was misleading in 83% of patients, reinforcing the need for an alternative diagnostic strategy based on petrosal sinus catheterization and computed tomography of the chest. Although 72% of the tumors were typical carcinoids by standard criteria, 57% demonstrated microscopic evidence of local invasiveness, and 43% were associated with mediastinal lymph node metastases. Eighty-six percent of patients have been cured by pulmonary resection a mean of 59 months after the operation, but 50% of these required a second operation for resection of involved lymph nodes after an initial relapse. CONCLUSIONS: These data suggest that adrenocorticotropin-secreting bronchopulmonary carcinoid tumors represent a distinct, more aggressive subtype of the usual, typical carcinoid. The high rate of lymphatic and local spread demands a surgical approach consisting of anatomic resection and routine mediastinal lymph node dissection.

ACTH Syndrome, Ectopic↗