William H. Warren

Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma: Five-year survival and patterns of intrathoracic recurrence

One hundred seventy-three patients with stage I (T1 N0, T2 N0) non-small-cell lung cancer underwent either a segmental pulmonary resection (n = 68) or lobectomy (n = 105) from 1980 to 1988. Four patients were lost to follow-up, but the remaining 169 patients were followed up for 5 years. Survival and the prevalence of local/regional recurrence were assessed. Although no survival advantage of lobectomy over segmental resection was noted for patients with tumors 3.0 cm in diameter or smaller, a survival advantage was apparent for patients undergoing lobectomy for tumors larger than 3.0 cm. The rate of local/regional recurrence was 22.7% (15/66) after segmental resection versus 4.9% (5/103) after lobectomy. A review of histologic tumor type, original tumor diameter, and segment resected revealed no risk factors that were predictive of recurrence. An additional resection for recurrence was performed in four patients. Lobectomy is the preferred operative procedure for patients with stage I tumors larger than 3.0 cm. Because the rate of local/regional recurrence was high after segmental resections, diligent follow-up of these patients is mandatory.

Preoperative chemotherapy and irradiation for stage III non-small cell lung cancer

Surgical therapy for stage III non-small cell lung cancer (NSCLC) has not resulted in substantial long-term survival. Neoadjuvant treatment programs that could down-stage the tumor and achieve increased long-term survival would be of obvious benefit. We have used preoperative simultaneous chemotherapy and irradiation in 85 patients with clinical stage III non-small cell lung cancer considered candidates for surgical resection. One group of 56 patients was treated with cisplatin, 5-fluorouracil, and simultaneous irradiation for five days every other week for a total of four cycles. After treatment, 39 patients underwent resection, and the operative mortality was 2 (5%) of 39. A second trial was undertaken in which etoposide (VP-16) was added because of its synergism with cisplatin. In this group, 29 patients were considered to have potentially resectable disease, and 23 underwent thoracotomy with 1 operative death (4%). Of the total of 62 patients having thoracotomy, 60 underwent resection (97%). Complications were major, and there were four bronchopleural fistulas. For the 85 patients eligible for surgical intervention in these two groups of patients, the Kaplan-Meier median survival estimate is 40% at 3 years. The median survival of the 62 patients having thoracotomy is 36.6 months. Combination preoperative chemotherapy and irradiation is feasible with acceptable toxicity and operative mortality in patients with clinical stage III non-small cell lung cancer. Prospective randomized studies are suggested for further evaluation of this treatment program.

Pericardial effusion: subxiphoid pericardiostomy versus percutaneous catheter drainage

BACKGROUNDnOptimal management of cardiac tamponade resulting from pericardial effusion remains controversial.nnnMETHODSnCardiac tamponade in 117 patients was treated with either subxiphoid pericardiostomy (n = 94) or percutaneous catheter drainage (n = 23). Percutaneous catheter drainage was used for patients with hemodynamic instability that precluded subxiphoid pericardiostomy. Effusions were malignant in 75 (64%) of 117 patients and benign in 42 (36%) of 117.nnnRESULTSnSubxiphoid pericardiostomy had no operative deaths and a complication rate of 1.1% (1 of 94). In contrast, percutaneous drainage had significantly (p < 0.05) higher mortality and complication rates of 4% (1 of 23) and 17% (4 of 23), respectively. Patients with an underlying malignancy had a median survival of 2.2 months, with a 1-year actuarial survival rate of 13.8%. In comparison, patients with benign disease had a median survival of 42.8 months and a 1-, 2-, and 4-year actuarial survival rate of 79%, 73%, and 49%, respectively (p < 0.05). Effusions recurred in 1 (1.1%) of 94 patients after subxiphoid pericardiostomy compared with 7 (30.4%) of 23 patients with percutaneous drainage (p < 0.0001).nnnCONCLUSIONSnBenign and malignant pericardial tamponade can be safely and effectively managed with subxiphoid pericardiostomy. Percutaneous catheter drainage should be reserved for patients with hemodynamic instability.

Subxiphoid pericardial drainage for pericardial tamponade

As a result of recent reports and enthusiasm for video-assisted thorascopic pericardiectomy, we reviewed our experience with subxiphoid pericardial drainage. From August 15, 1988, to June 7, 1993, 155 patients underwent subxiphoid pericardial drainage for pericardial effusion associated with pericardial tamponade. The group comprised 85 female (55%) and 70 male patients whose ages ranged from 5 weeks to 88 years. The procedure was carried out with general anesthesia in 113 patients (72%) and with local anesthesia and sedation in 42 patients. Underlying cancer was present in 82 patients; 73 patients had benign disease. Follow-up is complete in all patients. The overall 30-day mortality was 20%; in patients with cancer it was 32.9% (27/82) versus 5.4% (4/73) for patients with benign disease. No postoperative death was attributed to the surgical procedure. Recurrent pericardial tamponade necessitating further surgical intervention occurred in four patients (2.5%), two with cancer (2.4%) and two with benign disease (2.7%). Median survival after subxiphoid pericardial drainage in patients with benign disease was more than 800 days versus 83 days in patients with cancer (p < 0.01). Median survival after pericardial drainage in patients with cancer who had malignant pericardial effusion was 56 days compared with 105 days for patients with cancer who did not have tumor in the pericardium (p < 0.05). We believe that subxiphoid drainage is the procedure of choice for patients with pericardial tamponade. It is accomplished quickly, is associated with minimal morbidity, and prevents recurrent tamponade in 97.4% (151/155) of patients.

Bronchopleural fistula after stapled closure of bronchus

The incidence of bronchopleural fistula after stapling among 2,243 pulmonary resections at the Rush-Presbyterian-St. Lukes Medical Center has been reviewed. There were 35 fistulas in 1,773 stapled and in 470 sutured bronchi (segmentectomy, 2; lobectomy, 1; bilobectomy, 9; and pneumonectomy, 23). We have found that the stapler is expedient and simple to use, and that it produces a hermetic and uniform closure. The stapler is contraindicated when the bronchus is thickened, inflamed, or of insufficient length. The overall incidence of bronchopleural fistula was 1.6%. Approximately two thirds of the patients with bronchopleural fistula had preoperative radiation therapy or chemotherapy or both.

Immunohistochemical and ultrastructural analysis of bronchopulmonary neuroendocrine neoplasms. I. Carcinoids

Twenty-five strictly defined bronchopulmonary carcinoids were studied by light microscopic immunohistochemistry by the peroxidase technique for NSE (neuron-specific enolase), serotonin, and a broad spectrum of neuropeptides. Eighteen cases were also studied by electron microscopy. Twenty-three of the twenty-five cases showed immunostaining for NSE; 24 cases displayed immunostaining for at least two of the hormones tested for; the single case that failed to show hormonal immuno-reactivity was however positive for NSE and had granules by electron microscopy. Serotonin was the most frequently demonstrated hormone followed by bombesin, vasoactive intestinal peptide, gastrin, leu-enkephalin , alpha-melanocyte stimulating hormone, somatostatin, substance P, and calcitonin. In several cases, adjacent-step sections stained for different hormones strongly indicated immunoreactivity for more than one hormone in single neoplastic cells. By electron microscopy, all 18 cases studied showed generally abundant neurosecretory granules, which, however, displayed considerable heterogeneity in their size, shape, and density. Twelve of these eighteen cases displayed evidence of squamous differentiation and 10 showed characteristic exocrine lumina. The capability of single neuroendocrine tumors and single neuroendocrine tumor cells to produce more than one immunoreactive hormone is hereby amply confirmed; these broad capabilities are certainly reflected in the heterogeneous granule populations seen by electron microscopy. The synchronous presence of squamous and exocrine features in broncho-pulmonary carcinoids indicates that they too are capable of multidirectional differentiation, which should not detract from their being regarded basically as well-differentiated neuroendocrine neoplasms. The clinical significance of strictly defining bronchial carcinoids is underscored by the fact that of 25 cases followed for 2-13 years, only one developed metastases 9 years postoperatively.

Management of Malignant Pleural Effusions Using the Pleurx Catheter

BACKGROUNDnA malignant pleural effusion can cause significant morbidity to terminal patients. Drainage and control of the fluid can provide great palliation. Improving the quality of life for these patients on an outpatient basis is a worthy goal.nnnMETHODSnWe have inserted 231 Pleur(x) (Cardinal Health Systems, McGaw Park, IL) catheters into 202 patients with symptomatic malignant pleural effusions with the goal of treating the fluid on an outpatient basis. The catheters were drained at home, using vacuum bottles, every other day after an initial week of draining daily. No sclerosing agents were instilled. The catheters were removed when drainage was less than 50 mL/day. Primary tumor sites, irradiation to the hemithorax, and incomplete re-expansion of the lung were studied for their ability to predict prolonged drainage (over 100 days).nnnRESULTSnIn all cases, evacuation of the fluid with a Pleur(x) catheter palliated the patients symptoms. Overall, 134 of 231 (58.0%) catheters were removed after the drainage tapered off. Reaccumulation of the pleural effusion occurred in 5 of 132 (3.8%) patients. The incidence of infection was 5 of 231 (2.2%) and was usually limited to cellulitis at the insertion site. The incidence of blockage was 11 of 231 (4.8%) and was most common in patients with an underlying cancer at sites other than breast and gynecologic primaries. Drainage for more than 100 days was seen most often in patients who had incomplete reexpansion of the underlying lung (p < 0.001). Primary tumor site and irradiation did not have significant predictive value.nnnCONCLUSIONSnInsertion of Pleur(x) catheters is an effective way to treat patients with a malignant pleural effusion on an outpatient basis with a high degree of patient compliance and few complications. Overall, almost 60% of the catheters can be removed with a very low chance of reaccumulation, and without the need to instill a sclerosing agent. Even patients with a trapped lung can be palliated and released from hospital, although the likelihood of removing the catheter is small.

Immunohistochemical evaluation of neuroendocrine cells and neoplasms of the lung.

The dispersed neuroendocrine (NE) system is represented in the bronchopulmonary tract by submucosal nerves and ganglion cells and, in the mucosal lining by solitary NE cells and neuroepithalial bodies (NEBs). The latter two components variably express pan-NE markers including NSE, chromogranin (s) and, notably, synaptophysin. The expression of serotonin, bombesin, calcitonin and leu-enkephalin has been well established; additional eutopic materials include somatostatin and calcitonin gene-related peptide. Solitary NE cells and NEBs are epithelial structures as defined by their consistent cytokeratin expression. Hyperplasia and dysplasia of NE cells may be found in association with various forms of chronic injury; they have been noted in chronic bronchiectasis and in the vicinity of neoplasms of various types. Hyperplastic and dysplastic pulmonary NE cells frequently express ectopic materials particularly ACTH. NE neoplasms of the bronchopulmonary tract comprice a spectrum that includes a) carcinoids, b) well differentiated NE carcinomas, c) intermediate cell NE carcinomas and d) small cell NE carcinomas. The precise pathologic criteria defining these entities are discussed in detail as are their clinical implications. The entire spectrum of lung NE neoplasms express NE markers demonstrable by immunocytochemistry; these include pan-NE markers, serotonin and numerous neuropeptides. The expression of multiple hormonal materials is frequent. Within any given tumor, some variation in expression may be noted in different sites and in different periods of the normal or therapeutically modified lifespan of the tumor. The entire spectrum of lung NE neoplasms is epithelial for they express cytokeratin polypeptides and desmoplakin; subsets of the tumors coexpress cytokeratins and neurofilament proteins. Also, subsets of these NE neoplasms may be immunostained with monoclonal antibodies to antigens related to exocrine phenotype suggesting focal amphicrine features.

Immunohistochemical and Ultrastructural Analysis of Bronchopulmonary Neuroendocrine Neoplasms. II. Well-Differentiated Neuroendocrine Carcinomas

We have attempted to characterize a group of bronchopulmonary neoplasms that share certain structural features with true carcinoids but appear distinctly more pleomorphic and behave far more aggressively. In reviewing our files from 1973 to 1982, 11 such neoplasms were identified; the original diagnoses were atypical bronchial carcinoid (3 cases), malignant carcinoid (1 case), bronchial carcinoid (3 cases), peripheral carcinoid (2 cases), and peripheral oat cell carcinoma (2 cases). Of the 11 neoplasms, 5 were central and 6 were peripherally located. At presentation, 7 patients had lymph node metastases and 1 had a distant metastasis. No patient had a conventionally defined hormonal syndrome; however, 2 patients had a history of episodic flushing, one of which was associated with diarrhea. All cases were studied by light microscopy and light microscopic immunohistochemistry for NSE (neuron-specific enolase), serotonin, and broad-spectrum neuropeptides. Five cases were studied by electron microscopy. By light microscopy, the tumors were composed of solid clusters of polygonal to fusiform cells in an evident organoid arrangement. Foci of glandular and/or squamous differentiation were seen in 7 cases. Pleomorphism was moderate and mitoses were readily found. Focal necrosis was seen. By immunohistochemistry, 10 cases expressed NSE immunoreactivity. All cases demonstrated hormonal immunoreactivity; in 9 cases, immunoreactivity for more than one hormone was observed. The hormones most frequently expressed were serotonin, bombesin, gastrin, leu-enkephalin, and ACTH. By electron microscopy, all cases studied contained heterogeneous populations of neurosecretory granules; the latter, however, were not abundant and tended to aggregate either in the basal pole of the cells or, more frequently, interlacing dendritelike cytoplasmic processes. Aggregates of intermediate filaments were frequently seen. Basal lamina deposition was seen but gaps and larger areas of discontinuity were frequent. We believe that these neoplasms constitute a distinct pathologic entity for which the term well-differentiated neuroendocrine carcinoma has been proposed. Clinically, these tumors merit special attention since they are demonstrably more aggressive than true carcinoids but are distinctly less malignant than the intermediate or small cell variants of neuroendocrine carcinoma.

Pulmonary Resection in Patients after Pneumonectomy

In 15 patients with a previous pneumonectomy (eight on the right and seven on the left), a new lesion developed in the remaining lung. Fourteen had the pneumonectomy for carcinoma (13 men and 1 woman), and 1 woman had a pneumonectomy for blastomycosis. At the second operation (4 months to 16 years after the pneumonectomy), limited resection of a primary or metastatic malignancy was done. The excision ranged from lobectomy to multiple wedges. One patient died on the sixth postoperative day, presumably a cardiac death. Eight patients died 2 to 33 months postoperatively. Six patients are now living: 3 have no evidence of disease (18, 35, and 70 months), and 3 have recurrent disease (26, 41, and 73 months). There is evidence that pulmonary resection after pneumonectomy is feasible with a low operative mortality and that resection of these secondary tumors can result in prolonged, worthwhile survival.