Biomedical subjects

D J Sugarbaker

Publications and source records attributed to D J Sugarbaker.

At least 91 records · Page 5Linked to original sources

PubMed1995

A neoadjuvant approach to esophageal cancer.

Patients with symptomatic esophageal cancer represent a significant challenge to the thoracic clinician, whether medical oncologist, surgeon, or radiation therapist. Historically, cure has been rare and palliation has been a more realistic goal. Surgery was often viewed as radical or risky as limited long-term survival was weighed against expected operative morbidity and mortality. Epidermoid tumors were minimally responsive to available chemotherapy. Primary radiotherapy achieved similar overall survival; however, recurrent dysphagia limited its palliative benefit.

Adenocarcinoma↗

PubMed1995

Thoracoscopic staging and surgical therapy for esophageal cancer.

Esophageal cancer continues to be a major health problem with an associated poor prognosis. New technology is being applied to the staging of this cancer. The new staging system requires assessment of depth of wall penetration and lymph node status prior to resection. To determine penetration and node status with a high degree of accuracy generally requires some combination of chemotherapy, magnetic resonance imaging, endoesophageal ultrasound, and/or surgical staging. Several variables need to be considered in planning the surgical approach to the patient with esophageal cancer: the intent of the surgeon to either cure or palliate, the anatomic location of the tumor, and the method of reconstruction. Surgery is optimal for localized esophageal cancer. Neoadjuvant chemoradiation has increased survival in specific subgroups. Phase 2 trials have shown the safety and efficacy of chemoradiation. Randomized multi-institutional trials are needed to verify the encouraging results of recent phase 2 trials.

Chemotherapy, Adjuvant↗

PubMed1995

Chest X-ray screening improves outcome in lung cancer. A reappraisal of randomized trials on lung cancer screening.

It is believed that population-based screening for cancer should be advocated only when screening reduces disease-specific mortality. Four randomized controlled studies on lung cancer screening have been conducted in male cigarette smokers, and none has demonstrated reduced mortality. Accordingly, no organization that formulates screening policy advocates any specific early detection strategies for lung cancer. Yet, despite this public policy against screening, there is considerable evidence that chest x-ray screening is associated with earlier detection and improved survival. Two randomized trials, the Memorial Sloan-Kettering and Johns Hopkins Lung Projects, were specifically designed to evaluate the effectiveness of sputum cytologic study. Both evaluated the efficacy of the addition of sputum cytologic studies to annual chest radiographs, and both demonstrated that cytologic study did not favorably influence outcome. All individuals in experimental and control groups in both studies had annual chest radiographs. Because survival rates observed in both studies were about three times higher than predicted, based either on the National Cancer Institute's Surveillance Epidemiology and End Results database or based on the American Cancer Society's annual Cancer Statistics, raises the possibility that the periodic chest radiographs performed in all patients in both studies contributed to an improved outcome. In the Mayo Lung Project and in the Czechoslovak study on lung cancer screening, the experimental groups underwent a program of relatively intensive and regular rescreening with chest radiographs and sputum cytologic study, while the control groups underwent either less-frequent rescreening or no rescreening. In both studies, the screened groups achieved meaningful improvements in stage distribution, resectability, and survival. However, increases in cumulative incidence of lung cancer in the experimental group in both studies (which in the Mayo Lung Project reached statistical significance) prevented significant improvements in survival from translating into corresponding reductions in mortality. The possibility that screening may be associated with lung cancer "overdiagnosis" has been widely postulated to account for higher survival and incidence rates and equivalent mortality rates. However, analysis of autopsy information and of disease outcome in individuals with screen-detected early stage lung cancer who do not undergo surgical resection strongly supports the conclusion that screening does not lead to overdiagnosis of lung cancer. Similarly, lead-time and length bias do not adequately account for the differences in cumulative incidence observed in the Mayo and Czech studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Bias↗

PubMed1995

Thoracoscopy and video-assisted thoracic surgery in the treatment of lung cancer.

The contemporary surgical repertoire for the evaluation and treatment of patients with lung cancer includes the bronchoscope, mediastinoscope, thoracoscope, and standard surgical instrumentation. The recent advances in video optics and the development of endoscopic instruments have significantly expanded the surgical options for patients with lung cancer. Thoracoscopy, or the more inclusive term of video-assisted thoracic surgery (VATS), has been characterized as "minimally invasive" surgery. Thoracoscopy and VATS have decreased operative trauma and facilitated surgical staging prior to neoadjuvant therapy. An ancillary benefit to diminished surgical morbidity is shorter hospital stays with a concomitant reduction in costs to the patient and health-care system. These advantages make VATS ideal for elderly patients or patients with significant comorbidity.

Humans↗

PubMed1995

Mesothelioma and radical multimodality therapy: who benefits?

The incidence of malignant pleural mesothelioma is increasing. Untreated, patients with this disease experience a rapid and horrendous clinical decline. Surgery plays a role in the diagnosis, staging, and treatment of this malignancy. Surgery, chemotherapy, and radiotherapy alone have been unable to achieve major improvements in survival for most patients. More recent phase II trials suggest that surgery, at one time a purely palliative approach, may have a potentially curative role when used in combination with chemotherapy and radiotherapy.

Antineoplastic Agents↗

PubMed1995

A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer.

A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.

Adult↗

PubMed1995

The safety and versatility of video-thoracoscopy: a prospective analysis of 895 consecutive cases.

BACKGROUND: The application of video-endoscopy to general thoracic surgery is radically changing the approach to many benign and malignant diseases of the chest. Since July 1991, we have performed 794 purely thoracoscopic and 101 video-assisted thoracic surgical (VATS) procedures on 860 patients. STUDY DESIGN: Comprehensive, prospectively acquired data examining the specific indications for and outcomes of this new technique were prospectively entered into a thoracic surgical database. Preoperative, intraoperative, postoperative, and outcome variables were studied for the entire group as well as three high-risk cohorts: age over 70 years (n = 198), forced expiratory volume in one second (FEV1) of less than 1 L (n = 46), and Karnofsky performance index of less than 8 (n = 61). RESULTS: The 895 cases involved 449 men and 446 women of ages 15 to 89 years (mean 56 +/- 16 years standard deviation). The indications for surgery were diagnostic in 501 cases (56 percent), therapeutic in 244 cases (27 percent), and both diagnostic and therapeutic in an additional 150 cases (17 percent). The specific procedures performed were operations on the lung (569 cases), pleura (196 cases), esophagus (42 cases), mediastinum (51 cases), and pericardium (37 cases). Fifty-seven percent of the procedures were for a malignant process and 43 percent were for benign or infectious pathology. There were nine deaths for a series operative mortality rate of 1.0 percent. Thirteen patients (1.4 percent) required conversion to a limited thoracotomy for technical reasons. There were 127 complications in 121 patients yielding a morbidity rate in all patients of 14 percent. Mortality rates in the elderly, poor lung function, and depressed performance index cohorts were 1.5, 2.1, and 9.8 percent, respectively. Morbidity rates in these high-risk populations were 19, 30, and 18 percent, respectively. The median postoperative length of stay was three days after closed thoracoscopy and five days after VATS resection. CONCLUSIONS: These data underscore the flexibility, safety, efficacy, and potential for cost savings of videoscopic surgery in patients with thoracic diseases. The ability to perform excisional biopsy improves diagnostic specificity and sensitivity to nearly 100 percent. Video-assisted thoracic surgical techniques also offer a minimally invasive procedure with acceptable risk to patients heretofore inoperable by standard thoracotomy.

Adolescent↗

PubMed1995

Neuronal control of esophageal function.

Esophageal peristalsis and sphincter function are controlled by the autonomic nervous system, with contributions from parasympathetic, sympathetic, and enteric divisions. Proximal regions, including the upper esophageal sphincter, are composed of striated muscle and are under direct (cholinergic) control of vagal motoneurons located in the nucleus ambiguus. Sequential peristaltic contraction is coordinated by a brainstem pattern generator circuit involving the nucleus of the solitary tract and modulated by vagal afferents. Distal esophageal regions including the lower sphincter are controlled by intramural enteric circuitry, with a poorly characterized contribution from vagal preganglionic fibers arising in the dorsal motor nucleus of the vagus. Peristaltic contraction depends on cholinergic (muscarinic) excitation and NO-mediated inhibition. Neurally-produced lower esophageal sphincter relaxation is mediated by NO, vasoactive intestinal polypeptide, or both.

Animals↗

PubMed1995

Localized adenocarcinoma of the lung: oncogene expression of erbB-2 and p53 in 150 patients.

Historical information and pathological material from 150 consecutive patients with localized adenocarcinoma of the lung was collected to evaluate oncogene expression of erbB-2 and p53, and erbB-2 gene amplification. Pathological material after resection was reviewed to verify histological staging, and patient follow-up was complete in all cases for at least 68 months. Immunohistochemistry of erbB-2 (HER-2/neu) and p53 oncogene expression was performed on two separate paraffin tumor blocks for each patient with normal lung as control. Gene amplification of erbB-2 was measured after DNA extraction from 20-micrometer sections of erbB-2-positive and -negative tumors. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Two adequate blocks of tumor and normal lung were available for 138 (92%) patients. Immunohistochemical identification of expression of p53 was observed in 49 (37%) patients and erbB-2 in 17 (13%) patients. DNA dot blot analyses were performed on 17 erbB-2-positive and 13 randomly selected erbB-2-negative tumors. There was 1 (6%) of 17 erbB-2-positve tumors with 4-fold erbB-2 gene amplification. Actual 5-year survival was 63% and actuarial 10-year survival was 59% for the entire population of 150 patients. Significant univariate predictors (P < 0.05) of cancer death were the presence of symptoms, tumor size >3 cm, poor differentiation, visceral pleural invasion, and p53 expression. Multivariate analysis associated symptoms and p53 expression as independent factors with decreased survival. Thus, this project examined p53 and erbB-2 expression in patients with localized adenocarcinoma and associated p53 status with survival. Multicenter collection of data should allow the development of a model of cancer recurrence in this most common lung cancer.

Adult↗

PubMed1994

A clinical prediction rule for delirium after elective noncardiac surgery.

OBJECTIVE: To develop and validate a clinical prediction rule for postoperative delirium using data available to clinicians preoperatively. DESIGN: Prospective cohort study. SETTING: General surgery, orthopedic surgery, and gynecology services at Brigham and Women's Hospital, Boston, Mass. PATIENTS: Consenting patients older than 50 years admitted for major elective noncardiac surgery between November 1, 1990, and March 15, 1992 (N = 1341). MEASUREMENTS: All patients underwent preoperative evaluations, including a medical history, physical examination, laboratory tests, and assessments of physical and cognitive function using the Specific Activity Scale and the Telephone Interview for Cognitive Status. Postoperative delirium was diagnosed using the Confusion Assessment Method or using data from the medical record and the hospital's nursing intensity index. Patients were followed up for the duration of hospitalization to determine major complication rates, length of stay, and discharge disposition. RESULTS: Postoperative delirium occurred in 117 (9%) of the 1341 patients studied. Independent correlates included age 70 years or older; self-reported alcohol abuse; poor cognitive status; poor functional status; markedly abnormal preoperative serum sodium, potassium, or glucose level; noncardiac thoracic surgery; and aortic aneurysm surgery. Using these seven preoperative factors, a simple predictive rule was developed. In an independent population, the rule stratified patients into groups with low (2%), medium (8%, 13%), and high (50%) rates of postoperative delirium. Patients who developed delirium had higher rates of major complications, longer lengths of stay, and higher rates of discharge to long-term care or rehabilitative facilities. CONCLUSIONS: Using data available preoperatively, clinicians can stratify patients into risk groups for the development of delirium. Since delirium is associated with a variety of adverse outcomes, patients with substantial risk for this complication could be candidates for interventions to reduce the incidence of postoperative delirium and potentially improve overall surgical outcomes.

Aged↗

PubMed1994

Single-lung transplantation in situs inversus.

Situs inversus totalis is a rare anatomic condition characterized by the mirror-imaged arrangement of asymmetric thoracic and abdominal organs. Although associated cardiopulmonary disease is uncommon, end-stage lung disease can develop in patients with situs inversus, necessitating transplantation. In this report, we describe a 30-year-old patient with situs inversus totalis and end-stage pulmonary hypertension who underwent successful orthotopic left lung transplantation.

Adult↗

PubMed1994

Nitrinergic and peptidergic innervation of the human oesophagus.

The distribution, colocalisation, and interconnections of nitrinergic and peptidergic neurons and nerves in the human oesophagus were examined. Cryosections of surgically resected tissues from eight subjects were studied with indirect immunofluorescence for the presence of 11 neuropeptides and neuron specific enolase. After immunohistochemistry, nitric oxide synthase was shown on the same sections with the beta nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical reaction. The histochemical findings were verified immunohistochemically on other sections with an antiserum against nitric oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%) received terminations positive for vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase containing fibers seen in the muscle layers, many had closely associated VIP and galanin, but only rarely CGRP and substance P. Thus, despite abundant representation of both peptidergic and nitrinergic systems in oesophageal smooth muscle, only VIP and galanin colocalised to any significant extent with the nitrinergic elements. These findings provide morphological support for the role of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the human oesophagus and for its possible interactive role with the peptidergic system.

Adult↗

PubMed1994

Assessment of operative risk in patients undergoing lung resection. Importance of predicted pulmonary function.

OBJECTIVE: To evaluate the ability of preoperative variables to identify patients at increased risk for complications after lung resection and the usefulness of predicted postoperative FEV1 as a marker of risk for adverse outcomes. DESIGN: Prospective analysis of a cohort of patients undergoing pulmonary resection. Complication rates were analyzed according to preoperative pulmonary variables, demographic variables, procedure performed, and predicted postoperative FEV1. Predicted postoperative FEV1 was calculated using a formula estimating the decline in preoperative FEV1 based on the number of bronchopulmonary segments removed during surgery. SETTING: A major teaching hospital and tertiary referral center. PATIENTS: A consecutive series of patients undergoing pulmonary resection. MEASUREMENTS AND MAIN RESULTS: Medical complications were recorded as part of an ongoing clinical database. The overall complication rate was low (17 percent rate of any complication, 1 percent death rate). Univariate predictors of complications included age > or = 60, male sex, history of smoking, a pneumonectomy procedure, and a low predicted postoperative FEV1. Hypercarbia (> or = 45 mm Hg) on preoperative arterial blood gas analysis, desaturation on exercise oximetry (< or = 90 percent), and a preoperative FEV1 less than 1 L were not predictive of complications. When the effect of these variables was controlled for in a multivariate analysis, a low predicted postoperative FEV1 remained the only significant independent predictor of complications. For each 0.2 L decrease in predicted FEV1, the odds ratio for complications was 1.46 (95 percent confidence interval [CI] 1.2 to 1.8). CONCLUSIONS: A low predicted postoperative FEV1 appears to be the best indicator of patients at high risk for complications, and it was the only significant correlate of complications when the effect of other potential risk factors was controlled for in a multivariate analysis. Pulmonary resection should not be denied on the basis of traditionally cited preoperative pulmonary variables, and a prediction of postoperative pulmonary function by a technique of simple calculation may be useful to identify patients at increased risk for medical complications.

Age Factors↗

PubMed1994

Esophageal physiology.

Esophageal peristalsis and sphincter function involve coordinated neuromuscular processes the nature of which differs according to regional muscular anatomy and, to a degree, according to whether motility is initiated by swallowing or esophageal distension. The physical characteristics of the bolus and the conditions of testing may alter the speed and force of the propulsive contraction. Neural control of these processes and their modulation involves parasympathetic, sympathetic and enteric innervation of the organ. In smooth muscle regions, myogenic mechanisms may also play a role.

Deglutition↗

PubMed1993

Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways.

Recent discoveries suggesting essential bioactivities of nitric oxide (NO.) in the lung are difficult to reconcile with the established pulmonary cytotoxicity of this common air pollutant. These conflicting observations suggest that metabolic intermediaries may exist in the lung to modulate the bioactivity and toxicity of NO.. We report that S-nitrosothiols (RS-NO), predominantly the adduct with glutathione, are present at nano- to micromolar concentrations in the airways of normal subjects and that their levels vary in different human pathophysiologic states. These endogenous RS-NO are long-lived, potent relaxants of human airways under physiological O2 concentrations. Moreover, RS-NO form in high concentrations upon administration of NO. gas. Nitrite (10-20 microM) is found in airway lining fluid in concentrations linearly proportional to leukocyte counts, suggestive of local NO. metabolism. NO. itself was not detected either free in solution or in complexes with transition metals. These observations may provide insight into the means by which NO. is packaged in biological systems to preserve its bioactivity and limit its potential O2-dependent toxicity and suggest an important role for NO. in regulation of airway luminal homeostasis.

Adolescent↗

PubMed1993

Preoperative and postoperative combination chemotherapy for potentially resectable gastric carcinoma.

BACKGROUND: Median survival of patients with local-regional gastric carcinoma is 10 months. Resection of the primary tumor and regional lymph nodes, with tumor-free margins (curative resection), has been the most effective treatment for local-regional gastric carcinoma. However, median survival of patients with curative resection of gastric carcinoma is 24 months, and the 5-year survival rate is about 20%. A single institution pilot study has established the feasibility of administering two courses of chemotherapy preoperatively and three courses postoperatively. In another study, a 15% pathologically documented complete response (pathologic complete response) has been reported in unresectable gastric carcinoma treated with etoposide, doxorubicin, and cisplatin. PURPOSE: Our purpose was to increase the curative resection rate in potentially resectable gastric carcinoma and to delay or eliminate micrometastases and thus improve survival. We also evaluated clinical and pathologic response to chemotherapy. METHODS: Forty-eight previously untreated patients with potentially resectable gastric carcinoma received a chemotherapy regimen (EAP) consisting of etoposide (120 mg/m2 intravenously over a 2-hour period on days 4, 5, and 6), doxorubicin (20 mg/m2 as a 10-minute intravenous infusion on days 1 and 7), and cisplatin (40 mg/m2 as a 1-hour intravenous infusion on days 2 and 8). Patients received three courses of chemotherapy before resection, and responding patients received two courses postoperatively. Clinical and pathologic response rates, toxicity, patterns of treatment failure, and survival times were assessed. RESULTS: A median of three courses (range, 1-5) of preoperative therapy was administered; six (12%) of the 48 patients had clinical complete response, and nine (19%) had partial response. Forty-one (85%) underwent surgery; 37 (90%) of these 41 (77% of the 48 patients) had a curative resection. There were no pathologic complete responses. Median survival for all patients is 15.5 months (range, 2-29+ months). Therapy was discontinued because of the toxic effects in one patient before surgery and in six patients after surgery. Doses were reduced in 37 patients (77%), mainly because of hematologic toxicity. Nineteen (40%) were hospitalized because of toxic effects, including 15 patients who developed fever with neutropenia. Grade 3 or 4 nausea and vomiting occurred in 15 patients and grade 3 or 4 diarrhea in seven patients. One death was directly related to chemotherapy. CONCLUSIONS: These data support that administration of preoperative and postoperative chemotherapy for local-regional gastric carcinoma is feasible in a multi-institutional setting. Our findings demonstrate that this EAP regimen is modestly active but is associated with substantial toxicity. IMPLICATIONS: Use of preoperative chemotherapy in resectable gastric carcinoma merits further evaluation, but more effective drug regimens will be required before a controlled trial is initiated.

Adenocarcinoma↗

PubMed1993

Cisplatin, 5-fluorouracil, and etoposide for advanced non-small cell lung cancer.

BACKGROUND: Cisplatin and etoposide combination chemotherapy is the most commonly used regimen for advanced non-small cell lung cancer (NSCLC). 5-Fluorouracil (5-FU) is an agent with little intrinsic activity against NSCLC: However, there is increasing evidence that 5-FU is synergistic with cisplatin and vice versa. In an effort to improve on the traditional chemotherapeutic approach to NSCLC, a treatment regimen consisting of cisplatin, 5-FU, and etoposide (PFE) was developed. METHODS: Thirty-five patients with advanced NSCLC were treated with the PFE regimen (cisplatin 25/mg/m2/d and 5-FU 1000 mg/m2/d by continuous infusion and etoposide 60 mg/m2/d, each for 4 days). The cycles were repeated every 28 days. RESULTS: The patients received a mean of 2.8 cycles of PFE. Ten patients had a partial response to chemotherapy for an overall response rate of 28.6%. The median survival was 7.0 months. Toxicities included myocardial infarction (2 of 35), congestive heart failure (2 of 35), fatal pulmonary embolus (1 of 35), and a cerebrovascular accident (1 of 35). The incidence of Grade 4 neutropenia (5.7%) and thrombocytopenia (8.5%) was acceptable. CONCLUSIONS: The response rate, duration of response, and survival in this group of 35 patients treated with PFE was similar to that reported for cisplatin and etoposide. The increased cardiovascular toxicity may be the result of the infused 5-FU.

Adult↗

PubMed1993

Selected benefits of thoracotomy and chemotherapy for sarcoma metastatic to the lung.

To determine the benefit of aggressive surgical therapy, we studied 77 consecutive patients presenting to our sarcoma registry with pulmonary metastases. Detailed follow-up was available on all patients; the median follow-up of the 13 long-term survivors was 72 months from the date of diagnosis of the primary tumor. Survival of these 77 patients with metastatic disease was independent of the size, location, and histology of the primary tumor. Once metastases developed, survival of patients with pulmonary metastases was not influenced by the extent of surgical resection of the primary tumor or by the use of radiation therapy. Pulmonary metastases were initially treated with thoracotomy and metastasectomy in 34 patients. The median survival after thoracotomy was 26 months. Seven patients were alive more than 4 years after their diagnosis. Pulmonary metastases were treated with chemotherapy alone in 43 patients. Although the survival was shorter (median survival 14 months) in patients treated with chemotherapy, an objective response to chemotherapy was obtained in 13 (30%) patients. Four of these patients were alive 4 years after their diagnosis. These data demonstrate that both thoracotomy and chemotherapy are associated with long-term survival of patients with sarcoma metastatic to the lung.

Antineoplastic Combined Chemotherapy Protocols↗