Joachim Hasse

Experimental use of an albumin-glutaraldehyde tissue adhesive for sealing pulmonary parenchyma and bronchial anastomoses.

OBJECTIVE Despite advanced surgical techniques, major complications of bronchial anastomoses and parenchymal repair, including early leak, fistula formation and granulations still occur. The purpose of this study was to test the performance of an albumin-glutaraldehyde tissue adhesive (BioGlue), CryoLife Inc., Kennesaw, GA) as a sealant for bronchial anastomoses and parenchyma lesions. METHODS Twenty-four sheep were split into two surgical groups. The first group consisted of six control sheep receiving standard sutured bronchial anastomosis with a 4-week end-point. The second group included 18 sheep receiving both a bronchial anastomosis and parenchymal defect repair using the adhesive with 2, 4, and 12 week end-point. Histopathologic evaluation was conducted at the study end-points. RESULTS Bronchial anastomosis and parenchymal tissue repair can be sealed successfully against air leakage with adhesive. Macroscopic evaluation revealed a tight closure of the anastomosis and parenchyma defect in all postoperative stages, initially by the adhesive layer, and later by connective tissue. On microscopic examination, an inflammatory tissue response consisting of polymorphonuclear neutrophils, macrophages, granulation tissue and foreign body giant cells were found surrounding the glued area after 2 weeks. After 4 weeks the tissue response presented a granulomatous character. No granulomatous or foreign body reaction was present in the hand sutured group. After 12 weeks few remnants of adhesive surrounded by fibrous scar tissue were detectable in bronchial anastomosis and parenchymal repair. Healing was not considerably complicated by foreign body reaction or tissue granulation. CONCLUSION This study supports BioGlue to be effective as an adjunct in sealing bronchial anastomosis and lung parenchyma defects in sheep, with minimal secondary healing disruptions such as granuloma formation. The results of this study indicate that the use of BioGlue in human pulmonary surgery should be effective.

Results in surgery for primary and metastatic chest wall tumors

OBJECTIVES Resection of chest wall tumors is often indicated for palliation from pain or chronic ulceration. However, under various conditions, it may lead to lasting tumor control and substantial freedom of disease might be achieved. Therefore, the long-term survival after chest wall resection for primary and metastatic tumors and its relation to the underlying histology was analyzed. METHODS The medical files of 82 consecutive patients with tumors of the chest wall operated between 1 January 1989 and 31 October 1998 were reviewed. Follow-up data were collected from the outpatients clinic and house physicians, respectively. Complete excision was accomplished in 71 patients. In 19 patients, partial or complete resection of the sternum was performed. Twenty-eight patients underwent chest wall resection extending to intrathoracic structures (lung, diaphragm, pericardium). The following subgroups were defined according to the histology: (A), sarcoma (n=32); (B), breast cancer (n=22); (C), renal cell cancer (n=9); (D), other metastases (n=7); (E), miscellaneous (n=12). The survival probability was calculated by the Kaplan-Meier method (SAS software system). RESULTS One of 41 female patients died from postoperative complications on day 30 after resection of ulcerating breast cancer recurrence (hospital mortality, 1.2%). The median survival times in groups A-E were 27, 32, 19, 16 and 22 months, respectively. CONCLUSIONS Chest wall resection offers immediate relief in the case of severe pain and unpleasant sequelae of ulceration. Moreover, it contributes to substantial long-term survival. This, in particular, applies to local recurrence after breast cancer.

Disease-free survival after resection of lung metastases in patients with breast cancer

AIMS Metastatic breast cancer is a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. METHODS Retrospective analysis of 25 patients with suspected pulmonary metastases operated between March 1989 and September 1998. Survival probabilities and disease-free survival was analysed using the Kaplan-Meier method and the log-rank test. RESULTS The median survival rate after resection of lung metastases for the 21 patients was 96.9 months. The disease-free survival (DFS) after resection of lung metastases was 27.6 months. Survival was not influenced by the receptor status, lymph node involvement, number of lung metastases (p=0.8) or the disease-free interval (DFI) (0.59). DFS was, however, influenced by the DFI. With a DFI of <2 years survival was 8.5 months, whereas with a DFI >2 years it was 36.1 months (p=0.012). The DFS was influenced, but not statistically significant, by the number of lung metastases (n=1/n>1). The median DFS was 28.8 months with one metastasis and 13.1 months with multiple metastases (p=0.29). CONCLUSIONS The indication to remove solitary lung metastases in patients with previous breast cancer is supported by these findings. Especially when the disease-free interval is greater than two years.

Comparison of the Sensitivity of Sputum and Brush Cytology in the Diagnosis of Lung Carcinomas

OBJECTIVE To describe the role of sputum and brush cytology in the diagnosis of lung carcinoma and to elucidate the influence of tumor location, histologic tumor type and stage on the sensitivity of both methods. STUDY DESIGN Retrospective and performed on 415 lung cancer patients. Two hundred of them were investigated only by sputum collection, 119 only by brushing and 96 by both methods. RESULTS The overall sensitivity of the sputum technique was 0.403 and that of the brush method 0.500, while a combination of both showed a sensitivity of 0.640. The diagnostic yield depended on tumor location, histologic tumor type and stage. Sputum specimens were most valuable in the detection of early and peripheral carcinomas, whereas brushing was superior in finding more advanced and centrally located malignancies. Regarding tumor type, squamous cell carcinomas were diagnosed to the greatest extent by both methods. CONCLUSION A complementary role of both cytologic techniques can be postulated by our data as well as by a literature review.

Role of thoracic surgery and interventional bronchoscopy in Wegener's granulomatosis.

BACKGROUND Wegeners granulomatosis (WG) is defined as granulomatous vasculitis affecting small and medium-sized arteries and veins. Histologically, inflammatory changes with infiltration of the endothelium, fibrinoid necrosis, and formation of necrotizing granulomas are found. Pulmonary involvement is one of the cardinal features of WG and occurs in 85% of patients during the course of disease. Surgery is often required for both diagnosis and therapy. METHODS Fifteen consecutive patients are presented to illustrate the spectrum of surgical interventions in WG. RESULTS In 8 patients open lung biopsy, wedge resection, or segmental resection for hitherto undiagnosed infiltrate revealed WG. Eight patients presented with tracheal stenosis and all 8 underwent repetitive tracheoscopic dilation. Five patients presented with subglottic stenosis without any signs of pulmonary manifestation. All patients underwent tracheoscopic dilation, 3 in conjunction with glucocorticoid injection therapy. After multiple dilations, 1 patient still had destructing ulcerative tracheitis in which total stenting maintained airway patency. One patient received subglottic tracheal resection prior to multiple dilations; another patient, because of expiratory tracheal collapse, underwent stabilization of the membranous part of the trachea and the large bronchi with a polytetrafluoroethylene implant. CONCLUSIONS Surgical lung biopsy in numerous patients established the final diagnosis. Thoracic surgery including bronchologic measures such as bouginage and stenting, however, also has a place in the long-term management of WG.

Results after surgery in undifferentiated large cell carcinoma of the lung: the role of neuroendocrine expression

OBJECTIVE The objective of this study was to define the incidence of light microscopically undifferentiated large cell carcinomas, to analyze tumor stages, types of resections necessary and postsurgical survival. Additionally we tried to evaluate whether or not neuroendocrine expression influences the biological behavior of these tumors. METHODS Light microscopic specimens of 105 patients having undergone surgery for undifferentiated large cell carcinoma were reviewed following the 1981 WHO criteria. Fifty eight cases were excluded because elements of adeno- or squamous cell carcinoma, neuroendocrine or combined patterns of histological differentiation were observed. The remaining 47 cases of pure undifferentiated large cell carcinoma were evaluated immunohistochemically for neuroendocrine differentiation using a combination of the markers neuron specific enolase, synaptophysin and chromogranin A. The hospital charts of the patients were analyzed retrospectively recording tumor stage, operative procedure, postoperative complications, postoperative adjuvant treatment procedures, actual tumor state and survival time. RESULTS Thirteen patients (27.7%) had postsurgical tumor stage I, 5 (10.6%) stage II, 15 (31.9%) stage IIIA, 9 (19.1%) stage IIIB, and 5 (10.6%) stage IV. In 46 of 47 patients resections of lung parenchyma were performed (wedge resection n = 5, segmental resection n = 1, lobectomy n = 27, bilobectomy n = 3, pneumonectomy n = 10), in 6 patients combined with broncho- and/or angioplastic procedures. At the time of chart review 20 (42.5%) patients were still alive. The cause of death in the remaining patients was recurrent lung cancer in the majority of cases (24 or 92.30%). The overall mean survival of the 46 patients undergoing parenchymal resections was 19 months, the 3-year survival rate 31.7%. The immunohistochemical examination demonstrated expression of neuron specific enolase in 15 cases. Synaptophysin and chromogranin A were not detected in any case. For these 15 patients the mean survival was 25.6 months (+/- 4.3) and the 1-year survival rate 67% (confidence interval 43-91%) compared to 13.8 (+/- 2.1) months and 33.5% (confidence interval 15.3-51.7%) in the remainder. The difference was not significant (P = 0.06). CONCLUSIONS The light microscopic diagnosis of undifferentiated large cell carcinoma revealed to be subject to considerable interobserver variability. Undifferentiated large cell carcinoma takes a more unfavorable clinical course than other non-small cell carcinomas. Despite lack of statistical significance, expression of neuron specific enolase appeared to be associated with less aggressive biological behavior of the respective neoplasms. Immunohistochemical evaluation of undifferentiated large cell carcinomas using a combination of neuron specific enolase, chromogranin A, and synaptophysin did not provide more therapeutically relevant information than that obtained by light microscopic assessment.

Infiltration of lung carcinomas with macrophages of the 27E10-positive phenotype

In order to gain insight into the role of macrophages in human lung carcinomas, we investigated material from 35 lung carcinomas and 5 healthy lungs with 4 different antibodies (CD68, MRP8, MRP14, 27E10) recognizing different macrophage subtypes. Infiltration with CD68-positive macrophages was highest and comparable in healthy lungs and lung carcinomas. Compared to healthy lungs, the infiltration of MRP8- and MRP14-positive macrophages was reduced in lung carcinomas while the number of 27E10-positive cells was enhanced. No difference in the infiltration of macrophages was observed between the different histological subtypes of carcinomas such as squamous carcinoma, small lung carcinoma, adenocarcinoma and bronchio-alveolar carcinoma. Furthermore, we present a highly suitable technique for the isolation and enrichment of macrophages from human lung carcinomas resulting in a 5-10 fold enrichment and a yield of e.g. 2-3 x 10(6) 27E10-positive macrophages/g tumor biopsy. Together with the recent findings that 27E10-positive macrophages are prevalent in early acute inflammation and release cytotoxic mediators and to inhibit tumor cell proliferation our findings suggest that 27E10-positive macrophages may play a role in antitumor cytotoxicity in human lung carcinomas.

Pulmonary arteriovenous malformations : case reports and literature review

Pulmonary arteriovenous malformations (PAVM) represent an uncommon disease with only 500 reported cases. To emphasize the resectional surgical standard, 2 patients with PAVM and pulmonary right-to-left shunt are presented and the optional treatments discussed. One patient had suffered from a cerebrovascular accident. The other patients diagnosis resulted from a coincidental finding in connection with an unrelated illness. Because of the risk of acutely developing complications, especially disabling or fatal cerebral ischemia, therapy is generally recommended even in asymptomatic patients. The 2 patients presented here were treated by resection. Surgical treatment with a very low risk and parenchyma-sparing technique remains the golden standard for large isolated malformations. In addition to the established and reliable operative therapy since 1978 catheter embolization is becoming the method of choice with an increasing range of indications in those centers experienced with this technique.

Experimental gluing of the bronchial stump after pneumonectomy in rats.

OBJECTIVE The objective of this experimental study was to evaluate the usefulness of gelatin-resorcinol-dialdehyde adhesive in sutureless closure of bronchial stumps. METHODS In 40 male Wistar rats bronchial stumps after left-sided pneumonectomy were closed by gluing with gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination four animals were sacrificed on postoperative days 2, 7 and 14 each, 14 animals on postoperative days 28 and 120 each. RESULTS On macroscopic examination the gelatin-resorcinol-dialdehyde adhesive proved in all cases effective in tight bronchial stump closure. The adhesive did not cause local infection or necrosis of the bronchial stump nor other intrathoracic inflammatory complications. All animals survived and made an uncomplicated postoperative recovery. Microscopic examination revealed that the gelatin-resorcinol-dialdehyde adhesive initially evoked an acute inflammatory response with polymorphonuclear neutrophils predominating. After an intermediate stage characterized by a granulomatous reaction and resorption of the adhesive by multinucleated giant cells, 120 days postoperatively the bronchial stumps at the sites of previous gluing showed a regular fibrous scar tissue without inflammatory cells. CONCLUSION The gelatin-resorcinol-dialdehyde adhesive showed effective in closing bronchial stumps after pneumonectomy in rats. The clinical extrapolation of this effect to thoracic surgical patients is uncertain at this time.

Thoracic cancer surgery in the elderly.

The risk of thoracic cancer surgery in patients of advanced age, i.e. 75 years or older, was analysed by reviewing 119 consecutive patients from August 1986 to May 1998 with bronchial carcinoma (n = 87), pulmonary metastases (n = 22), mesothelioma and pleural carcinosis (n = 7) and mediastinal or chest wall tumours (n = 3). Repeated surgery in one case of bronchial carcinoma and in another of metastases gave a total of 124 operations. Of the patients, 22 were 80 years or older (21%) and 32% were female. The median age was 77 years (range 75-87 years). Six fatalities occurred within 30 days or during hospitalization. This corresponds to a 4.8% mortality for the whole series and 6.8% for the subgroup of bronchial carcinoma. The causes of death were surgical complications in two patients, one died from heart failure after simultaneous combined coronary artery bypass grafting and left lower lobectomy 2 hours after the operation from heart failure refractory to resuscitation. With this exception all these patients had stage II (n = 2) or stage III A (n = 3) bronchial carcinoma. It is concluded that cancer surgery in the elderly is safe provided appropriate selection is observed. Indications should be very restrictive for advanced cancer and for pneumonectomy.