Local tumor inflammation, lymph node metastasis, and survival of operated bronchus carcinoma patients.

Three hundred and fifty-three resection specimens with primary lung carcinomas were cut into serial sections, and the tumor volume was computed. Resected lymph nodes were cut into 0.3-mm serial sections and analyzed for metastasis. The inflammatory reaction of lung tissue was analyzed by grading the amount of inflammatory infiltrations of a complete tumor cross section. Survival of patients was evaluated by consulting the house physician every 3 months after surgical treatment. Percentage of specimens with severe inflammatory reaction of host tissue increased remarkably in tumors with a volume of 35-60 cm3. Percentage of patients with detectable lymph node metastasis increased with tumor volume but decreased at the tumor volume of 35-45 cm3. Mean tumor volume in patients with no detectable lymph node metastasis was increased if severe inflammatory response of host tissue existed. Survival of patients with severe inflammatory infiltrations was superior to survival of patients with no inflammatory infiltrations if grouped for tumor volume. Data indicated that inflammatory infiltrations in primary lung carcinoma may partly be related to the immunologic response of host tissue to tumor growth. Inflammatory infiltrations may delay tumor cell propagation into lymph nodes or may be even able to destroy small tumor cell agglutinations.

Five-year follow-up study of independent clinical and flow cytometric prognostic factors for the survival of patients with non-small cell lung carcinoma.

Fresh surgical specimens of tumors of 187 patients with previously untreated non-small cell lung carcinomas were investigated by means of flow cytometry. The aim of the study was to look for cellular prognostic indicators for survival times of these patients in addition to the well-known clinical prognostic factors. All patients had a minimum of 5 years follow-up. Patients with aneuploid tumors had significantly shorter survival times than did those with diploid tumors (P less than or equal to 0.001). Identical results are obtained when the analysis is restricted to just those patients with T3 tumors or to patients with metastatic tumors at time of surgery or who were classified as Stage III (P less than or equal to 0.01). These data indicate that DNA ploidy is a strong and independent prognostic factor in patients with non-small cell lung carcinoma. Patients having tumors with a high proliferative activity died significantly (P less than 0.05) earlier than patients having tumors with lower proliferative activity. As with tumor ploidy, survival time in patients with high or low proliferative tumor activities was independent of whether the patients had T3-tumors, metastases, or were in Stage III. Univariate and multivariate analyses of the data in this study demonstrate two groups of independent prognostic factors for the survival of patients with non-small cell lung carcinoma: a group of clinical factors and a group of flow cytometric factors.

Bronchioloalveolar carcinoma: a new cancer in Peutz-Jeghers syndrome.

Besides gastrointestinal hamartomatous polyposis and melanin spots in the skin and mucosa, patients with the Peutz-Jeghers syndrome (PJS) have repeatedly been observed with a variety of tumours, including lung cancer. Available data indicate an increased cancer risk among PJS patients, which suggests that the gene involved in PJS, STK11 on chromosome 19p13.3, may be a tumour suppressor gene. Herein, bronchioloalveolar carcinoma (BAC) of mucinous type is reported in a 22-year old male PJS patient with a novel germline frameshift insertion in exon 2 at codon 118 of the STK11 gene. Molecular studies of his BAC indicated loss of heterozygosity (LOH) in the region of STK11 on chromosome 19p13.3. This observation supports the hypothesis that STK11 is a tumour suppressor gene which is involved in the development of lung adenocarcinoma.

Induction chemotherapy with and without recombinant human granulocyte colony-stimulating factor support in locally advanced stage IIIA/B non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) in stage IIIA with more than minimal N2 involvement or in stage IIIB are considered unresectable. Response rates to chemotherapy for these patients are in the range of 40%. Reduction of tumor mass by induction chemotherapy may lead to resectability and to improved survival. We evaluated response rates and determined influence of induction chemotherapy on survival when followed by surgery and radiotherapy in 60 patients with primarily inoperable stage IIIA/IIIB NSCLC. The following cytotoxic regimens were used: cisplatin (100 mg/m2) and vindesine (3 mg/m2); ifosfamide (10 g/m2) and etoposide (360 mg/m2); or a combination of cisplatin (75 mg/m2), ifosfamide (6 g/m2), and etoposide (360 mg/m2). Sixty patients were treated with two to four cycles of these regimens between June 1988 and October 1992. In 40 patients chemotherapy was repeated every 4 weeks. In 20 patients chemotherapy was intensified by interval reduction to 3 weeks with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) support. The median patient age was 54 years, and Eastern Cooperative Oncology Group performance status was 0 to 2. Distribution of stages IIIA and IIIB was 21 and 39 in all patients and 5 and 15 in the group treated with r-metHuG-CSF support, respectively. The overall response rate (complete plus partial responses) was 35%. In patients treated with intensified chemotherapy and r-metHuG-CSF support, the response rate was 60%. In 37 patients (61.6%) tumor was resected 4 to 6 weeks after the last cycle of chemotherapy; R0 resection was achieved in 22 patients, R1 in eight patients, and R2 in seven patients. With a follow-up of 4 to 60 months, 1-year survival in patients with tumor regression after chemotherapy and tumor resection was 82.2% versus 35.7% in nonresponders; 2-year survival of responders and nonresponders was 50.9% and 12.8%, respectively; and median survival was 23 months and 9 months, respectively (P < .001). Median survival rates for responders with stage IIIA and IIIB disease were 39 and 17 months, respectively. Median survival after response to chemotherapy and incomplete resection (11 patients) was 17 months, whereas median survival after response to chemotherapy and complete resection (18 patients) has not yet been reached. Only four patients in this group have died with a follow-up of 4 to 60 months. Of 20 patients receiving accelerated chemotherapy with r-metHuG-CSF support, World Health Organization grades 3 and 4 neutropenia occurred in five and eight patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

The importance of surgical and multimodality treatment for small cell bronchial carcinoma.

In a cooperative international lung cancer multimodality treatment trial, 112 patients with small cell lung cancer underwent initial surgical resection and were then randomized to receive one of two intensive postoperative chemotherapeutic regimens, followed by prophylactic cranial irradiation in the disease-free patients. Regimen A consisted of eight courses of cyclophosphamide, doxorubicin, and vincristine and regimen B of two courses of three sequential drug combinations: (1) cyclophosphamide, lomustine, and methotrexate; (2) cyclophosphamide, doxorubicin, and vincristine; and (3) ifosfamid and etoposide. In 47 patients the diagnosis was known preoperatively and in 65 it was not confirmed until the resected specimen was examined (all diagnoses were reviewed by a referee pathologist). Each patient was classified by the pathologic TNM characteristics. There were 38 patients with stage I disease, 39 patients with stage II, and 35 patients with stage IIIa disease. In stage IIIa there were nine patients with T3 N0-1 disease and 26 with T1-3 N2 disease (most N2 disease was clinically undetected until thoracotomy or was discovered only by routine histologic examination of the resected mediastinal nodes). Early survival rates at 24 months calculated by the life table method are as follows: stage I, 76%; stage II, 56%; and stage IIIa, 49% (T3 N0-1, 89%; T1-3 N2, 35%). Survival rates at 36 months are 62%, 50%, and 41% (74% and 29%), respectively. The projected 36-month survival rate for 43 patients with N0 disease is 65%; for 43 with N1 disease, 52%; and for 26 with N2 disease, 29%. No difference in survival has been noted in either chemotherapy treatment group. It is concluded that initial surgical resection for limited small cell cancer (stage I, II, and T3 N0-1) followed by intensive chemotherapy is an appropriate therapeutic approach. For T1-3 N2 disease the results are inconclusive.

Pulmonary metastasectomy as secondary treatment for testicular tumors.

Patients presenting with synchronous and metachronous metastases of nonseminomatous testicular tumors are candidates for pulmonary metastasectomy after receiving definitive primary treatment, which includes semicastration, eventually retroperitoneal lymphadenectomy, and definitely chemotherapy. One hundred four such patients (age, 14 to 79 years; median age, 27 years) underwent pulmonary metastasectomy from 1972 to 1990, representing 15.8% of the pulmonary metastasectomies performed during the same period. Of the 117 operations performed, eight were repeat operations. Median sternotomy, posterolateral and, later, transverse thoracotomies were the standard surgical approaches used to remove the single and multiple metastases randomly distributed in both lungs. Wedge resections and atypical segmentectomies (66%), lobectomies (15%), anatomic segmentectomies (9%), pneumonectomies (3%), bilobectomies (3%), and mediastinal lymphadenectomies (65.4%) were the various procedures performed. Of the 104 patients, metastasectomy was complete in 80 and incomplete in 24. The 30-day mortality was 2.0%. Life table analysis revealed a survival rate of 77%, 70%, 66%, and 59% at 1, 2, 3, and 5 years, respectively. Of all prognostic factors examined, complete resection of the metastases seems to be the most significant factor influencing the prognosis.

Relevance of DNA-fluorimetry and short-term resistance testing for adjuvant treatment of non-small cell lung carcinomas.

In a clinical study 127 patients with previously untreated stage III non-small cell lung carcinomas (NSCLC) were investigated using flow cytometry and an in vitro short-term test for predicting resistance to cytostatic agents. Patients with aneuploid tumors and tumors with high proliferative activity had significantly shorter survival times than those with diploid or low proliferating tumors. The aim of this study was to find out whether groups of patients classified according to the additionally observed prognostic factors, experience an advantage or disadvantage from particular modalities of treatment. Seventy-nine patients had surgery alone, 18 patients were treated additionally with chemotherapy, and 30 patients with radiation. Patients with aneuploid, low proliferating and in vitro resistant tumors showed no different survival rates after treatment with chemo- and radiotherapy adjuvant to surgery. In contrast, patients with high proliferating tumors died earlier under adjuvant chemotherapy and radiation. Patients with in vitro chemosensitive tumors had shorter survival times after irradiation than patients who had surgery alone or who were treated with adjuvant chemotherapy.

Results of surgical treatment of pulmonary metastases.

Surgical removal of one or several metastases with a potentially curative aim is possible in the case of isolated pulmonary metastases. Surgery is part of a combined oncological concept. Between 1972 and 1986, surgical resection was indicated in 368 patients and 419 thoracotomies were carried out. Of the patients, 38% had more uni- or bilateral metastases than expected even after the most careful preoperative diagnostic examinations. The 5-year survival probability of all patients operated on was 33%. Corresponding to a differentiation between potentially curative and non-curative resections, the operation was classified as potentially curative in 73%. In this group, the 5-year survival was 39%. Differentiation into tumour groups (carcinomas of caval type, carcinomas of portal type and sarcomas) revealed no statistically significant differences in prognosis. Due to the excellent chemotherapeutical regimens, testicular teratomas achieved the best results in the early postoperative years. Long-term survival is decisively influenced by the removal of all visible and palpable metastases. If complete removal of all tumour tissue is possible, the number of metastases does not influence survival significantly. Besides radicality, the duration of the disease-free interval showed prognostic differences which were statistically significant (P less than 0.001). Considering the metastatic route and the type of primary tumour, there were slight prognostic differences which were not statistically significant. Recently, the median sternotomy has become the preferred method of access. Predominating resection procedures are wedge and segmental resections which yield the best survival rates.

Primary tracheal tumors: experience with 14 resected patients.

OBJECTIVE: Primary tracheal tumors are rare. Management includes interventional endoscopy, surgery and radiotherapy. METHODS: Between 1987 and 1996, 14 patients treated by resection and reconstruction of the trachea and bifurcation for primary tracheal tumors were retrospectively analyzed. RESULTS: The most common histological finding was adenoid cystic carcinoma (n=7), followed by a squamous cell carcinoma (n=2), a mucoepidermoid carcinoma (n=2), a carcinoid tumor (n=1) and two benign tumors (xanthogranuloma, pleomorphic adenoma). Various reconstruction techniques were used and one prosthesis was implanted. Eight of the patients required preoperative Nd-YAG laser recanalisation. Six were treated by postoperative external beam radiotherapy, in three cases combined with endoluminal brachytherapy. Two major postoperative wound-healing impairment at the anastomosis occurred. Four minor wound-healing disorders were successfully treated by interventional endoscopy. Two patients died postoperatively with mediastinitis respectively with bilateral pneumonia. A local recurrence was observed in only two cases. At the last follow-up in January 1998, nine patients were still alive. We observed five long-term survivors (>6 years) with an adenoid cystic carcinoma or mucoepidermoid carcinoma. CONCLUSIONS: Extensive segmental resection of the trachea is the treatment of choice for primary malignant and occasionally for benign tracheal tumors. Interventional endoscopy is a part of modern tracheal surgery.

Validation of the TNM classification (4th edn) for lung cancer: first results of a prospective study of 1086 patients with surgical treatment.

For the purpose of testing the validity of the new TNM classification (fourth edition) for lung cancer, data from 1086 patients with surgical treatment were analysed prospectively. Several items were examined: (1) the agreement between clinical (TNM) and pathologically confirmed classification (pTNM); (2) the value of the various diagnostic tests in estimating the pathologically confirmed classification; (3) the influence of the TNM definitions on separating distinct prognostic groups. With regard to the primary tumour (T), clinical and pathological classification were identical in 64% of the cases. With regard to lymph node involvement (N), the agreement was 48%, for distant metastasis 90% and for the staging 55%. As for the primary tumour (T), the accuracy of radiography (59%) was nearly identical with that of computed tomography (58%). Both these diagnostic techniques were less precise in determining the extent of lymph node involvement (computed tomography 50% correct assessments, radiography 43%). The statistically significant differences in the prognoses for the various pT, pN and pM categories as well as for the pathological stages and the categories of the new R classification could be confirmed. The new 1987 TNM definitions for lung cancer make possible international conformity; the classification is also practically useful and the prognostic relevance improved. The new classifications thus provide a more reliable basis for establishing guidelines for individual oncological therapy strategies and for the exchange of information between different centres on the progress made in diagnosis and therapy of lung cancer.

Does ND-YAG laser extend the indications for resection of pulmonary metastases?

Surgery forms part of a combined oncological concept in the management of pulmonary metastases. The following questions are relevant for its role: Does survival depend on the type of primary tumor? Are there any prognostic factors? What are the limits on radical resection? We analyzed retrospectively 657 patients who had undergone 759 resections of pulmonary metastases between 1973 and 1990. After conducting in vitro and in vivo experiments with the non-contact neodymium aluminum garnet (Nd-YAG) laser with a generating and delivery power of 10-120 W at the site of operation for 0.1-9.9 s, we have treated 65 patients by laser resection and/or vaporization since January 1990. Our preferred surgical approach was median or transverse thoracotomy. The 5-year survival of all resected patients was 30%, ranging from 21% (soft tissue sarcoma) to 60% (testicular carcinoma). Statistically significant differences in prognosis were seen related to the type of primary tumor, the disease-free interval, the caval or portal type of metastatic spread, the number of metastases and the potential degree of radical resection. The potential degree of conventional radical resections (wedge, anatomical sub-/segmental) was negatively influenced by the number of metastases (n > 9: 79% "radical" surgery = 38% 5-year survival). Laser treatment allowed parenchyma-preserving resection in cases of metastases of more than 0.5 cm in diameter, and vaporization in smaller ones. Resection with the intention of achieving complete remission was possible in up to 72 unilateral metastases. The complication rate was comparable to conventional resections.

Computed tomography for staging bronchogenic carcinoma.

One hundred and fourty patients with a primary lung neoplasm underwent transmission computed tomography (TCT) for staging prior to therapy. TCT results were compared with the post-operative T- and N-stage. The preoperative TCT examination correctly classified 70% of all tumors. 73% of T1, 63% of T2 and 74% of T3 tumors did not require restaging after surgery. TCT correctly staged 80% of the patients with respect to the N-stage. Ninety-seven percent of the patients with N0, 42% with N1 and 79% with N2 tumors were correctly classified. Serious over- and understaging was observed in patients with centrally located bronchogenic carcinoma. This was due to the difficulty of distinguishing tumor tissue from enlarged lymph nodes and atelectasis.

[Stereoangiography of the bronchial arteries: technic and indications]. / Stereoangiographie der Bronchialarterien: Technik und Indikation.

Stereo-angiography of the bronchial arteries has been performed in 11 patients with bronchial carcinomas. An attempt has been made to establish the spatial relationship between their main stems and the proximal bronchial system. Important details were transferred from each half of the stereo pairs into transparent sheets; this improved stereoscopy and made it easier to appreciate the relationship to the tracheal bifurcation. Characteristic relationships between various types of bronchial arteries and the tracheo-bronchial system could be recognised. Improvements can be expected from the use of a stereo-DSA technique. Stereo-bronchial arteriography is useful for demonstrating pre-operatively their exact position in order to prevent unnecessary ligation and for improving localisation of bleeding points which can only be reached surgically.

[Computer tomographic evaluation of mediastinal lymph nodes in bronchial cancer]. / Computertomographische Beurteilung mediastinaler Lymphknoten beim Bronchialkarzinom.

Of all the mediastinal lymph nodes, the retrocaval and pre-tracheal groups can be most frequently demonstrated by computer tomography. With the aim of providing better quantitative assessment, the maximal diameter of these lymph nodes was measured in five patient groups: I Control group (132 cases), II patients with inflammatory lung disease (17 patients), III patients operated for bronchial carcinoma, but without lymph node involvement (62 patients), IV patients operated for bronchial carcinoma with lymph node involvement (eight patients), V patients who have not had surgery, but who had enlarged lymph nodes (16 patients).

[Pre-operative staging of bronchial carcinomas: a comparison of computed tomography and conventional radiography (author's transl)]. / Präoperatives Staging des Bronchialkarzinoms: Wertigkeit der Computertomographie im Vergleich zur konventionellen Radiologie.

Pre-operative staging was carried out in 52 out of 112 patients suspected of having bronchial carcinomas, using computed tomography and conventional radiology. CT was superior in demonstrating tumour infiltration of the mediastinum, of the thoracic wall and of metastases in mediastinal lymph nodes. Conventional radiology was better for demonstrating intrabronchial tumour and metastases of bronchopulmonary lymph nodes. By extending CT to the upper abdomen, it was possible to show metastases in 18% of patients.

[CT morphology and clinical diagnosis of thoracic space-occupying lesions in patients under 40 years of age]. / CT-Morphologie und klinische Diagnose thorakaler Raumforderungen bei unter 40jährigen Patienten.

83 patients with thoracic masses and aged under 40 years, who had been seen in a chest clinic, were examined by CT. They were classified according to their diagnosis and typical CT findings were analysed. Bronchial carcinomas showed predominantly radial extensions and air trapping. Malignant lymphomas and benign tumours usually showed smooth outlines and evidence of some fat content. Malignant mediastinal or neurogenic tumours frequently contained liquid portions and calcification. The CT diagnosis of lymphomas (seven cases), metastases (28 cases) and benign tumours (13 cases) presented no problems in view of the typical appearance and position of the tumours; classification of malignant mediastinal or neurogenic tumours (seven cases) was difficult. Inflammatory masses (14 cases) and bronchial carcinomas (14 cases) showed similar CT appearances.

[Magnetic resonance tomography (MRT) and computed tomography (CT) of bronchial carcinoma. Comparison of the value of both study methods for preoperative staging]. / Magnetresonanztomographie (MRT) und Computertomographie (CT) bei Bronchialkarzinomen. Vergleich der Aussagekraft beider Untersuchungsmethoden im Rahmen des präoperativen Stagings.

Fifty patients with histologically proven bronchial carcinomas were examined by CT and MRT for preoperative T-staging and N-staging. CT and MRT provided the same classification in 87% of the T2 tumours, 78% of T3, 71% of N0, 74% of N1 and 100% of N2 tumours. MRT had advantages for demonstrating tumours at the apices, for central tumours and for demonstrating hilar and some mediastinal lymph node enlargement. CT was better at demonstrating small pulmonary metastases, small basal pleural effusions and also in showing pulmonary structure and bone lesions.

Evaluation of recurrent bronchogenic carcinoma by computed tomography.

Thirty-five patients with strongly suspected recurrent tumor of the lung and definitely positive computed tomography (CT) scan were reviewed. The patients had undergone surgery (group A, n = 17) or radiation therapy (group B, n = 18). TNM-staging of lung cancer in both groups revealed similar results. Small cell carcinoma (P less than 0.05), central tumors (P less than 0.003), and elderly patients (P less than 0.05) were more often found in group B. Disease-free interval was longer in patients with tumor resection (45.5 v 11.7 months, P less than 0.007) and depended on T-stage in irradiated cases (P less than 0.05). Local recurrence with or without mediastinal lymph node involvement occurred in all irradiated patients; 3 of 16 surgical patients showed isolated mediastinal lymph node enlargement without tumor relapse (not seen by plain chest roentgenographs). Plain films failed to detect nearly 20% of the space-occupying lesions, which could easily be identified by CT. In one patient the suspected tumor recurrence turned out to be a tuberculous infiltration. A second lung cancer (no tumor recurrence) was pathohistologically assumed in three of the resected cases with an interval from 10-181 mo after surgery. On the basis of these findings, CT-monitoring can be recommended when the patient is resected for cure. Some patients will benefit by an early diagnosis of a local-regional tumor recurrence when the time until the necessary secondary treatment may be shortened. Long-term survival may be achieved in a small group of these patients.

Bronchoplastic and angioplastic operation in bronchial carcinoma: long-term results of a retrospective analysis from 1973 to 1983.

From 1973 to 1983, 248 bronchoplastic and angioplastic operations were carried out in patients with bronchial cancer. The five-year survival rate of all radically operated patients (stages I and II, n = 108) was 35%. The three-year survival rate in bronchial sleeve resection in stages I and II (n = 46) was 46%. The thirty-day lethality in stages I and II was 9% in bronchial sleeve resection and 5% in combined bronchial and vascular sleeve resections. Indications, surgical technique and complications are discussed.

[Diagnostic thoracotomy--a contribution to its value, indications and results]. / Die diagnostische Thoracotomie--ein Beitrag zur Aussagekraft, Indikation und Durchführung.

Open lung biopsy by a limited thoracotomy has an important place in the diagnosis of localized or diffuse pulmonary disease. Its application provides adequate pulmonary or mediastinal tissue biopsy, and permits a reliable histologic evaluation. The postoperative risks are small if certain pre-requisites are observed. We recommend atraumatic removing of the tissue, excluding the middle lobe and lingula. To prevent complications careful suturing of the biopsy site with absorbable suture material seems essential.