The natural history of gastric cancer and prognostic factors influencing survival.

This study of 783 patients with histologically confirmed gastric carcinoma has confirmed the importance of several previously recognized patient- and tumor-related characteristics related to prognosis and identified some new ones. Of the tumor-related factors, the ones that showed the strongest relationship to survival following curative gastric resection were tumor stage, histologic type, breach of lymph-node capsule, sinus histiocytosis, and gross appearance. Of the tumor- and patient-related factors, the ones that showed the strongest relationship to survival from time of diagnosis of surgically noncurable disease were status of primary, liver metastasis, serum bilirubin level, ascites, extent of tumor burden, and weight loss. The effect of treatment with 5-fluorouracil (5-FU) on survival duration was at best only minimal. Only those patients who received two or more cycles of 5-FU therapy had survival advantage over the remaining patients. The use of regression analysis has made it possible to make predictions of the prognosis of the patients. These predictions could be used in future studies to determine comparability of prognosis of various groups included in different studies and different arms of a randomized study.

Comparison between clinical response and in vitro drug sensitivity of primary human tumors in the adhesive tumor cell culture system.

The newly described adhesive tumor cell culture system (ATCCS) offers a distinct advantage over other assays in that it has a high plating efficiency requiring low cell inoculum, it affords workable assays in approximately 70% of specimens from the heterogenous tumor types, and it has the ability to assay up to nine drugs at four different concentrations. Clinical correlations based on the ATCCS were obtained in 65 patients undergoing 71 clinical trials. Patients with melanoma, lung cancer, and sarcoma dominated the group. The most active in vitro drug was correlated per clinical trial. Thirteen of 17 (76%) sensitive in vitro predictions and 51 of 54 (94%) resistant in vitro predictions were accurate. The assay in this study had a sensitivity of 81% and specificity of 93%. These preliminary results are encouraging and warrant prospective trials to establish the true value of this assay to patients.

Evaluation of pre- and postoperative chemotherapy for resectable adenocarcinoma of the esophagus or gastroesophageal junction.

Thirty-five consecutive patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative and three or four postoperative chemotherapy courses consisting of etoposide, fluorouracil, and cisplatin (EFP) to evaluate the rate of curative resection, clinical and pathologic response, toxic effects, and survival. One hundred thirty-seven courses with a median number of five courses (range, one to six) were administered. Preoperative EFP resulted in 17 (49%) major responses, including six patients who did not have carcinoma cells in the repeat endoscopic biopsy specimens and cytologic brushings. Among 32 patients who had surgery, 25 (78%) had curative resection, one patient had a complete pathologic response, and one had microscopic carcinoma in the resected specimen. Six patients had microscopic carcinoma at the resection margins and received postoperative radiotherapy. At a median follow-up of 20 months, the projected survival of 35 patients is 23 months (range, 6 to 33+). Fifteen patients died of their carcinomas, and 15 patients were alive (median follow-up, 20+ months; range, 15+ to 33+ months) with no evidence of relapse. There were no deaths related to chemotherapy, surgery, or radiotherapy. EFP-induced toxic reactions were moderate. Our data suggest that multiple courses of EFP are feasible. Future strategies for this disease should consider prolonged chemotherapy with regimens that result frequently in pathologic complete responses.

Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction.

PURPOSE: The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression. PATIENTS AND METHODS: Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy. RESULTS: A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated. CONCLUSION: High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.

The role of adjuvant surgery in the combined modality therapy of small-cell bronchogenic carcinoma after a chemotherapy-induced partial remission.

Twenty-six patients with a limited-disease presentation of small-cell bronchogenic carcinoma (SCBC) had surgery after achieving a partial remission with three cycles of chemotherapy. Persistent SCBC was found in 15 patients (58%), non-small-cell bronchogenic carcinoma (NSCBC) in six patients (23%), and no malignancy in five patients (19%). Twelve patients have died since surgery. Tumor-node-metastasis (TNM) staging prior to or after chemotherapy was not predictive of outcome, but an N0 status found at pathological examination of the surgical specimen was predictive of long-term survival. Median survival for this group of patients was 25 months. Adjuvant surgery is feasible and may be beneficial.

Prolonged chemotherapy for localised squamous carcinoma of the oesophagus.

We evaluated the feasibility of six courses of chemotherapy in 34 consecutive patients with localised squamous cell carcinoma of the oesophagus. All 32 evaluable patients first received at least two courses of chemotherapy. There were 18 patients with resectable carcinomas who underwent surgery and 14 patients with unresectable carcinomas who received definitive chemoradiotherapy. After two courses of 5-fluorouracil and cisplatin 21 (66%) of 32 patients had either a complete or major response. A median of five courses (range, 1-6 courses) was administered. 17 out of 18 (94%) patients with resectable carcinoma had a 'curative' resection (negative proximal, distal, and radial margins by histopathology in an en-block resection specimen) and 2 patients had a complete pathological response. The median survival duration of all patients was 28 months (range, 2-46+ months). The median survival duration of 14 patients with unresectable carcinoma was 23 months (range, 8-36+ months), and the median survival duration of 18 patients with resectable carcinoma has not been reached at a median follow-up of 24+ months (range, 10+ to 46+ months). No deaths occurred because of chemotherapy or chemoradiation therapy. Our data suggest that prolonged chemotherapy is feasible in patients with locoregional squamous carcinoma of the oesophagus. An ongoing controlled trial will determine the contribution of chemotherapy to patients' survival.

Primary mucinous adenocarcinoma of the lung with signet-ring cells: a histochemical comparison with signet-ring cell carcinomas of other sites.

Five cases of primary mucinous adenocarcinomas of the lung with signet-ring cells were studied with regard to clinical, pathologic, and prognostic implications and compared with the signet-ring cell adenocarcinomas of extrapulmonary sites. The patients ranged in age from 55 to 74 years, with a mean age of 67.8 years. There were three men and two women. Histologically, three cases were usual adenocarcinomas and two were bronchioloalveolar carcinomas. The percentage of signet-ring cells ranged from 10% to 50%, with a mean of 22% and a median of 20%. Therapy included lobectomy, radiation, and chemotherapy. Three of five patients died of their disease within 9 months and two patients showed no evidence of disease 5 months after presentation. Routine histology showed no significant differences between the signet-ring cells of any of the tumors; however, by special histochemistry, tumors originating from lung, stomach, and colon showed a more intense reaction with alcian blue stain than tumors from nose, breast, or bladder. Contrary to a previous report, we found no increase in sulfated acid mucins in these five cases of lung tumor. We also were unable to demonstrate a qualitative or quantitative difference between mucopolysaccharides produced by lung, stomach, or colon tumors. Although rare, mucinous adenocarcinoma of the lung with signet-ring cells can exist as a primary tumor.

Open lung biopsy in immunocompromised patients.

Increased use of open lung biopsy in the search for a treatable etiology of acute interstitial pneumonitis (AIP) in immunocompromised patients is based on the assumption that examination and cultures from biopsy specimens will yield significant information leading to beneficial treatment of the condition. To assess the true impact of the results of open lung biopsy on the subsequent treatment and outcome in such patients, a retrospective study was done of 64 consecutive patients undergoing the procedure in a recent five-year period. When open lung biopsy was performed for the diagnosis of AIP in immunocompromised patients after empiric broad spectrum treatment failed, it rarely missed a specific, treatable etiology, if present. However, the results from open lung biopsy infrequently lead to a change in the treatment that improves the patient's clinical course.

Roentgenographic evaluation of mediastinal nodes for preoperative assessment in lung cancer.

Evaluation of mediastinal nodal metastases is a critical step in the assessment of potential surgical candidates with lung cancer. Mediastinal tomography (TOMO) and chest computerized tomography (CT) visualize the mediastinal nodes more clearly than a chest roentgenogram (CXR). A prospective study was undertaken to determine the clinical value of these three tests for mediastinal staging in 102 surgical patients with lung cancer. All patients underwent thoracotomy and mediastinal nodal dissection. The roentgenographic findings were compared with the histologic evaluation of paratracheal, tracheobronchial angle, aortic window, subcarinal, and inferior pulmonary ligament nodes. TOMO, and especially CT, correctly predicted the size and location of mediastinal nodes; however, the overall accuracies were CXR (74 percent), TOMO (74 percent), CT (61 percent). These results demonstrated that the improvement in mediastinal imaging is counteracted by the fact that enlarged nodes need not contain metastases and normal-appearing small nodes may harbor microscopic disease. Computed tomography and TOMO had little clinical impact on the assessment of mediastinal nodes in potential surgical candidates with lung cancer.

Critical evaluation of the gallium-67 scan for surgical patients with lung cancer.

Seventy-five patients with lung cancer underwent a gallium scan and thoracotomy with total mediastinal nodal dissection. Evaluation of mediastinal lymph nodes by means of the gallium scan showed a sensitivity of 23 percent (3/13), a specificity of 82 percent (31/38), an accuracy of 67 percent (34/51), a positive predictive valve of 30 percent (3/10), and a negative predictive value of 76 percent (31/41) in those patients whose primary tumors demonstrated uptake of radioactive gallium. The low sensitivity was due to an inability to detect microscopic disease in mediastinal lymph nodes. The specificity was decreased by gallium-67 uptake in enlarged inflamed nodes that contained no metastases. These results do not support the use of the gallium scan in the selection of patients with lung cancer for thoracotomy.

Primary osteosarcoma of the lung. Report of two cases and review of the literature.

Two cases of primary osteosarcoma of the lung are presented. In one case, the radiologic, clinical, and cytologic findings led to a preoperative diagnosis of undifferentiated carcinoma of the lung. In the second case, a lung nodule was discovered during postchemotherapy follow-up in a patient with lymphoma. Fine needle aspiration in the second case showed lymphoma, and further chemotherapy was instituted; however, persistent growth of the nodule prompted a resection. Microscopic examination of the resected tumors in both cases revealed histologic features of high-grade osteosarcoma. Flow cytometric analyses of the primary tumors showed abnormal hyperdiploid deoxyribonucleic acid populations in accordance with those seen in high-grade malignant neoplasms. Immunohistochemical studies supported a mesenchymal origin for these tumors. These tumors shared clinical features with other reported cases of primary osteosarcoma of the lung such as large size at diagnosis, occurrence in older individuals, and aggressive behavior.

Surgery for pulmonary metastasis: a 20-year experience.

During a recent 20-year period, 556 patients underwent operation for pulmonary metastasis at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston. The surgical mortality was 1.5% for 772 resections. A selection of 443 patients was made to evaluate the contribution of operative intervention as a primary treatment, with selective adjunctive therapy when applicable. The success of a surgical approach is dependent primarily on adherence to selection criteria; it is important that only patients in whom all known disease can be completely removed with the planned resection and who have full control of the primary site are treated. The overall survival for the group was 35%. For patients with carcinoma, survival ranged from 24% for those with primary uterine cervix tumors to approximately 54% for urinary tract, male genital tract, and corpus of uterus primary tumors. In the group with sarcoma, patients with skeletal tumors had a 46.4% survival rate (50.7% for those with osteogenic sarcoma), and 33% of the patients with soft tissue tumors had long-term survival. The outcome for patients with melanoma was poor; only 12.1% survived 5 years. If the original criteria apply, multiple and bilateral lesions can be successfully managed. Patients undergoing planned adjuvant treatment had a superior outcome compared with those not so treated. However, a significant survival advantage was shown only for patients with sarcoma. The failure to control all disease in patients in whom pulmonary metastasis is controlled surgically can only be improved on through the use of systemically active adjuvant treatment.

Diagnosis for interstitial lung disease in patients with acquired immunodeficiency syndrome (AIDS): a prospective comparison of bronchial washing, alveolar lavage, transbronchial lung biopsy, and open-lung biopsy.

This study was undertaken to compare prospectively the diagnostic yield of the various bronchoscopic techniques with that of open-lung biopsy for interstitial lung disease in patients with acquired immunodeficiency syndrome (AIDS). Under general anesthesia, 15 patients sequentially underwent bronchial washing, transbronchial lung biopsy, alveolar lavage, and open-lung biopsy in the same segment of lung. Of nine patients with Pneumocystis carinii, seven were diagnosed by means of the transbronchial lung biopsy, eight by the open-lung biopsy, and all nine by alveolar lavage. Of the six patients with cytomegalovirus, five were diagnosed by the open-lung biopsy, five by the transbronchial lung biopsy, and three by alveolar lavage. The sensitivities of the procedures for identifying infection were washings (15%), transbronchial lung biopsy (50%), alveolar lavage (73%), and open-lung biopsy (88%). Combined, transbronchial lung biopsy and alveolar lavage showed a diagnostic yield (85%) for infections comparable to that of open-lung biopsy (88%), thereby obviating the need for open-lung biopsy for such diagnoses. However, open-lung biopsy was the only procedure that diagnosed Kaposi's sarcoma in lung.

Current techniques for chest wall reconstruction: expanded possibilities for treatment.

Myocutaneous flaps and prosthetic materials have greatly facilitated reconstruction after massive chest wall resection. This series includes 112 such procedures. Latissimus dorsi, rectus abdominis, omental, pectoralis major, and contralateral breast flaps were used in 80 patients. Early in the series, 3 flaps were lost because of technical problems. Minor areas of incomplete healing that resolved completely with local wound care occurred in 16 of 80 flaps. Skeletal reconstruction was performed in 82 patients without complication. Marlex mesh was used for flat surfaces, and Marlex mesh with methyl methacrylate was used for the sternum and the curved surface of the lateral chest wall. These results have allowed an expansion of the indications for chest wall resection to include the curative treatment of primary chest wall tumors and palliative treatment for breast cancer patients with osteoradionecrosis, local recurrence (in select patients), chest wall infection, and tumors metastatic to the chest wall.

A perspective on chest wall resection in patients with breast cancer.

The morbidity from locally recurrent breast cancer or osteoradionecrosis and accompanying infection is substantial. The selective use of surgical resection offers good palliation. Extended full-thickness chest wall resection is facilitated by a variety of techniques available for closure and coverage including use of latissimus dorsi myocutaneous flap, rectus abdominus myocutaneous flap, pectoralis myocutaneous flap, breast flap, and omentum with skin graft. The experience with 43 consecutive chest wall resections in patients with breast cancer affords the opportunity to define indications and contraindications for such palliative procedures. Indications include local symptoms of pain and infection, tumor recurrence refractory to radiation therapy, and infection that precludes chemotherapy. Relative contraindications are pulmonary metastases, bone metastases, hepatic metastases, and malignant pleural effusions. Absolute contraindications are brain metastases, bone marrow involvement, bulky disease in two organs, and breakthrough on multiple chemotherapy regimens. Operative revision was only required in 4 of 43 patients. Minor wound complications occurred in 12 (28%). Three patients who underwent resection for local recurrence have survived 40 months or more free from disease. This procedure provides substantial palliation by relieving pain, controlling infection, removing a weeping wound, and allowing chemotherapy for metastatic disease. In the proper setting, chest wall resection is an important part of the armamentarium for palliation of the patient with breast cancer. It can markedly improve quality of life and occasionally may result in long-term survival.

Comparison of three techniques of esophagectomy within a residency training program.

Residency training programs commonly emphasize a single technique of esophagectomy, as the safety and the efficacy of teaching or performing more than one type of esophagectomy are unclear. Between 1986 and 1992, 248 patients were explored for possible esophageal resection. Thoracic surgical residents or fellows performed major components of all resections. Two hundred twenty-one patients (adenocarcinoma, 146; squamous cell carcinoma, 72; and other, 3) underwent transthoracic esophagectomy (n = 134), transhiatal esophagectomy (n = 42), or total thoracic esophagectomy (n = 45), a resectability rate of 89.1% (221/248). Complications occurred in 75% of patients with transthoracic esophagectomy, in 69% with transhiatal esophagectomy, and in 80% with total thoracic esophagectomy. The overall operative mortality rate was 6.8% (15/221). Patients with a cervical anastomosis had a higher leak rate (13%) than those with an intrathoracic anastomosis (6%). Median survival was 22 months (19% 5-year survival) and did not differ by operation type or stage. No patient with unresectable disease (n = 27) survived longer than 10 months. Survival for patients with adenocarcinoma stages 3 and 2a suggested a trend toward improved survival after transthoracic esophagectomy despite similar rates of local and distant recurrence. Transthoracic esophagectomy, transhiatal esophagectomy, and total thoracic esophagectomy performed within a residency training program have similar morbidity, mortality, and recurrence rates as those in other modern series. A specific technique of esophagectomy can be selected for individual patients. Survival and sites of recurrence primarily reflect disease stage, not the technique of esophagectomy used.

Predicted pulmonary function and survival after pneumonectomy for primary lung carcinoma.

Between 1982 and 1987, 139 patients with primary carcinoma of the lung were treated with pneumonectomy. Thirty-nine patients (28%) were in clinical stage I, 10 (7%) were in clinical stage II, and 90 (65%) were in clinical stage III. Overall actuarial 3-year survival was 33%. Actuarial 3-year survival for patients in clinical stage I was 44%; for those in clinical stage II, 48%; and for those in clinical stage III, 28%. Risk factors for operative mortality examined included preoperative forced vital capacity (FVC) of 2.13 L or less and forced expiratory volume in 1 second (FEV1) of 1.65 L or less, percent predicted FVC of 64% or less and FEV1 of 65% or less, predicted postoperative FVC of 1.31 L or less and FEV1 of 0.89 L or less, and predicted postoperative percent predicted FVC of 41% or less and FEV1 of 34% or less. Operative deaths occurred only in clinical stage III patients (7/90 or 8%). Patients with compromised pulmonary function based on one or more of the examined risk factors were at increased risk for death (2/10) compared with patients with better pulmonary function (5/80 or 6.25%). Actuarial 3-year survival for high-risk clinical stage III patients ranged from 0% to 16% compared with 28% for other clinical stage III patients. Thirty-day mortality for pathological stage III patients was 6.3% (5/79), and 3-year actuarial survival was 24%. No patient in pathological stage III who was at high risk survived beyond 3.1 years. Select individuals with adequate pulmonary function and stage III disease can achieve substantial long-term survival after pneumonectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of perioperative morbidity and mortality after pneumonectomy.

A total of 197 consecutive patients undergoing pneumonectomy at the M.D. Anderson Cancer Center from 1982 to 1987 were reviewed. Sixty-five variables were analyzed for the predictive value for perioperative risk. The operative mortality rate was 7% (14/197). Patients having a right pneumonectomy (n = 95) had a higher operative mortality rate (12%) than patients having a left pneumonectomy (1%, p less than 0.05). The extent of resection correlated with the operative mortality rate (chest wall resection or extrapleural pneumonectomy, n = 39, 15%; versus simple or intrapericardial pneumonectomy, n = 158, 5%; p less than 0.05). Patients whose predicted postoperative pulmonary function, by spirometry and xenon 133 regional pulmonary function studies, was a forced expiratory volume in 1 second greater than 1.65 L, forced expiratory volume in 1 second greater than 58% of the preoperative value, forced vital capacity greater than 2.5 L, or forced vital capacity greater than 60% of the preoperative value had a lower operative mortality rate (p less than 0.05). Atrial arrhythmia was the most common postoperative complication (23%). Xenon 133 regional pulmonary function studies are useful in predicting the risks of pneumonectomy.

Resection of sternal tumors: extent, reconstruction, and survival.

BACKGROUND: Resection of sternal tumors may be tailored to the patient and the location of the malignancy. METHODS: We reviewed our results of sternectomy (typically 5-cm margins) performed in 30 patients over a 10-year period. RESULTS: Thirteen patients had primary sternal sarcoma (six chondrosarcoma, five osteosarcoma, two other); 10 patients had local recurrence from breast cancer; 4 patients had metastases; 3 patients had other (two osteoradionecrosis, one malignant fibrous histiocytoma). Morbidity occurred in 8 patients (26.7%): wound dehiscence, 2; wound infection, 1; hemorrhage, 1; pneumonia, 1; prolonged air leak, 1; empyema, 1; and bronchopleural fistula, 1. One patient, with multiple metastases, died from adult respiratory distress syndrome on day 25 (overall mortality, 3.3%; 1 of 30). The area of reconstruction ranged from 35 to 264 cm2. The technique of reconstruction included muscle flap alone in 13 patients; muscle flap and mesh, 9; muscle flap and rigid prosthesis (Marlex methylmethacrylate), 7; or other, 1 patient. Nineteen patients (63%) were extubated within 24 hours after operation. Median intensive care unit stay was 2 days; median hospitalization, 6 days. Late local recurrence after resection occurred in 6 patients; 4 from breast cancer (3 patients had concurrent distant metastases). Five-year actuarial survival after primary tumor resection was 73% and 33% after resection of recurrent breast cancer (median, 21 months). CONCLUSIONS: Partial sternectomy may be performed for primary sternal tumors with short hospitalization and good local control. Wider local excision or total sternectomy may minimize local re-recurrence of breast carcinoma to the sternum.

Prognostic significance of computed tomography in resected N2 lung cancer.

We reviewed 124 patients from 1982 to 1988 who had a resected primary non-small cell lung cancer metastatic to mediastinal (N2) lymph nodes and a preoperative assessment of the mediastinum with computed tomography of the chest. Sixty-three patients studied had computed tomographic evidence of mediastinal lymph node enlargement. In these patients the survival at 5 years was only 6.6%, compared with the 5-year survival of 13.5% in 61 patients in whom the mediastinum was normal. Plain chest roentgenography with evidence of mediastinal adenopathy did not predict a poorer outcome. In addition, patients with tumors located in the left upper lobe were found to have an improved survival. These patients had a 5-year survival of 20.8%. Tumor histology, central location of the tumor, extranodal extension, and type of resection did not result in a significant survival difference.