Neopterin: a prognostic variable in operations for lung cancer.

BACKGROUND: We studied the prognostic value of preoperatively measured neopterin to predict survival of lung cancer patients. Neopterin is produced and secreted by interferon-gamma-stimulated monocytic cells. High urinary neopterin concentrations are found in patients with viral infections, allograft rejection episodes, and some malignant diseases. In various tumor types high urinary neopterin concentrations are associated with a worse prognosis. METHODS: Preoperative neopterin levels of 110 patients (29 women, 81 men) with lung cancer including 7 patients with small cell lung cancer were measured and related to the time of survival after operation. Patients with clinically suspected stage IIIB lung cancer were not operated and therefore not enrolled in this study. Infectious diseases were not apparent at the time of preoperative urine sampling. Median postoperative follow-up period was 17.4 months. RESULTS: In a univariate analysis, patients with a preoperative neopterin concentration of more than 212 micromol/mol creatinine (4th quartile) were determined to have a significantly lower survival probability. In a multivariate analysis, a neopterin concentration of more than 212 micromol/mol creatinine (p < 0.01) and T-stage status (p < 0.005) were determined to be significantly predictive variables for worse survival prognosis. CONCLUSIONS: Preoperative neopterin proved to be a reliable prognostic factor for survival. Immunology may provide an accurate assessment of tumor aggression and its clinical behavior. In this sense, neopterin can serve as an immunologically based estimation of malignant outgrowth. In patients who are operable by clinical tumor stage but have a high risk for operation, elevated preoperative neopterin may help in the decision for a nonoperative treatment.

Pulmonary Aspergillus colonization in humans and its impact on management of critically ill patients.

Samples of lung tissues were obtained and analysed for Aspergillus carriage in 56 patients undergoing thoracic surgical intervention and 18 people who had an unexpected death. Out of 74 samples, 46 (63%) had evidence of pulmonary fungal colonization. The surgery population had a rate of 62% of fungal growth. Aspergillus was present in 39%. The autopsy population had a rate of 61% of fungal colonization. Aspergillus was present in 41%. In these cases eradication of fungal spores residing in the lung prior to aggressive chemotherapy and prevention of further spore uptake during hospitalization is indispensable in preventing pulmonary aspergillosis.

Long-term results of surgery for adenoid cystic carcinoma of the trachea and bronchi.

AIMS: Over a period of 26 years, 16 patients (9 women, 7 men) underwent surgery for primary adenoid cystic carcinoma (ACC) of the trachea and bronchi. The median age at diagnosis was 41.4 years (range 25-67). Nine tumours were located in the bifurcational area, five in the trachea, one in the middle-lobe bronchus and one in the parenchyma of the left lower lobe. METHODS: Surgical procedures were as follows: three tracheal transversal resections; five resections of the distal trachea including the bifurcational region, followed by bifurcational reconstruction; two right-sleeve pneumonectomies; three left-sleeve pneumonectomies; two lobectomies; and one explorative sternotomy. RESULTS: Eleven patients were available for follow-up at least 5 years after surgery. Three of these patients (27%) had local recurrence 155+/-30 (range 120-175) months after surgery. Distant metastases occurred in six patients (55%) after a median time interval of 96+/-68 (range 24-180) months after surgery. CONCLUSIONS: Five-year and 10-year survivals were excellent, 79 and 57% respectively, but the long-term outcome was poor due to late local recurrences and late metastatic spread. It is not yet certain whether a cure can really be achieved in ACC.

Closure of complex defects in the chest wall with muscle flaps.

Aggressive treatment of thoracic malignancy may be complicated by complex defects in the chest wall. These may be associated with serious complications such as chronic infection, respiratory or cardiac failure, or major haemorrhage. Closure of the defect and restoration of the integrity of the chest wall is important for both functional and cosmetic reasons. Local flaps are often used, but may be inadequate or unavailable. Reconstruction with free flaps is better in these cases, as this provides as much abundant well-vascularised tissue as is required. We present 12 patients treated successfully for complex chest wall defects using various forms of local and free flap reconstruction. There were five complications, three healed spontaneously and two required secondary procedures before they healed.

Pain treatment after thoracotomy: is it a special problem?

BACKGROUND: Although it is frequently stated in the literature that thoracotomy is one of the most painful operative incisions, few data supporting this view are available. METHODS: Patients' postoperative pain experience can be assessed on the basis of their usage of patient-controlled analgesia. In a prospective trial the daily self-administered doses of analgesics in 55 patients within the first 4 days after posterolateral thoractomy were compared with those in 30 patients for the same number of days after median laparotomy. The visual analog scale was used as a second measure to evaluate postoperative pain. RESULTS: On the basis of patient-controlled analgesia usage on the first postoperative day and the visual analog scale score for the first 2 days, a small but significant difference between the two patient groups was found which showed that thoracotomy is less painful than median laparotomy. CONCLUSIONS: The common belief that posterolateral thoracotomy is a very painful operative access is not true. Therefore it is not necessary to use special techniques for postthoracotomy pain relief in these patients. Patient-controlled analgesia is sufficient for pain relief after major thoracic or abdominal incisions.

Predictive value of urinary neopterin in patients with lung cancer.

Concentrations of neopterin, which is produced by human monocytes/macrophages when stimulated by gamma-interferon, were measured in urine specimens from 72 patients with lung cancer at diagnosis. Other routine clinical and laboratory variables were concomitantly determined. Neither neopterin nor any other laboratory variable studied showed a significant correlation with clinical indicators of the disease (morphologic type, tumour stage, grading, lymph node status, presence of distant metastases). The cancer patients were followed up for up to 10 years, and the abilities of all variable to predict fatal outcome were assessed. In univariate survival analyses, all clinical indicators except morphologic type (P = 0.86) were significant predictors of survival (P < 0.002), but of all the laboratory variables studies, only neopterin was significantly predictive (P = 0.0013). By multivariate survival analysis, a combination of four variables was found to jointly predict survival: lymph node status (P = 0.003), multivariate model), tumour stage (P = 0.0006), grading (P = 0.0047) and neopterin (P = 0.0047). The data suggest that certain aspects of immune activation may have adverse consequences for the prognosis of patients with lung cancer.

Use of the greater omentum for treatment and prophylaxis of anastomotic and stump dehiscence in major airway surgery.

In 6 patients suffering from anastomotic dehiscence following bronchoplastic procedures of the central airways or from acute bronchial stump fistula following pneumonectomy, the therapeutic efficiency of omentopexy in the management of the fistula was investigated. In 5 other patients with an increased risk of anastomotic leakage after sleeve pneumonectomy or pneumonectomy with carinal resection the omentum was effectfully used to prevent such complication. 4 out of 5 evaluable patients had successful treatment of the anastomosis and stump fistula. Complications arising from the additional laparotomy were not observed.

Multimodal therapy of small cell lung cancer in TNM stages I through IIIa.

Since 1977, Innsbruck University Hospital has been employing a multimodal therapy concept for small cell bronchial carcinomas in stages I to IIIa. This concept includes all three treatment forms effective in this tumor, namely, chemotherapy, surgery, and radiotherapy. The therapy scheme is stage-dependent and begins in stages T1-3 N0-1 with lung resection and in stage N2 with chemotherapy. To date, 45 patients have been included in a prospective, nonrandomized (phase II) trial: 7 in TNM stage I, 11 in stage II, and 27 in stage IIIa (6 T3 and 21 N2). The actuarial 5-year survival rate of the entire group (including therapy-related lethality, early recurrences, and protocol violations) is 36%; it is 57% for those in stage I, 28% for those in stage II, and 34% for those in stage IIIa. Median survival time is 18 months. Patients with completed multimodal treatment have a 5-year survival rate of 56% regardless of disease stage. Three patients died of tumor-unrelated causes after 47, 52, and 54 months.

Critical checking of the radiological diagnosis of "complete remission" and "partial remission" following induction chemotherapy of small-cell lung cancer in the light of postoperative histological examination.

A multimodal therapy concept for small-cell lung cancer, which for patients with established pretherapeutic homolateral lymph-node metastases (N2) prescribes induction chemotherapy with subsequent resection as well as supplemental chemo- and radiotherapy, provided the opportunity to evaluate histologically the radiological diagnoses "complete remission" and "partial remission" using resection specimens. In 17 patients a 75% to 100% reduction in tumor size was achieved according to radiological diagnosis. Predictions of "no evidence of disease" or "evidence of disease" were only correct in ten cases. In the remaining seven cases, histology showed the radiological findings to be incorrect. This gives a 77% sensitivity for radiological diagnosis with no specificity. Moreover, differentiation between therapy effect on the primary tumor and on the N2 metastases gives similar results: sensitivity 64% and 67% respectively, specificity 33% and 25% respectively. It is concluded that, particularly after the tumor responds well to therapy, radiological techniques are unsuitable for establishing a diagnosis of "no evidence of disease" or "evidence of disease" in small-cell lung cancer. This is because on the one hand the radiological methods available do not permit clear differentiation between vital tumor tissue and necrosis or fibrosis, while on the other hand groups of vital tumor cells beyond the resolution power of X-ray technology will escape detection.

[Long-term results of multimodality therapy of small cell bronchial cancer including surgery]. / Langzeitergebnisse nach multimodaler Therapie des kleinzelligen Bronchialkarzinoms mit Einschluss der Chirurgie.

The results of a prospective Phase II study of a multimodal treatment regimen including surgery of operable stages of small cell lung cancer are reported. Of 45 patients 24 received all parts of the projected treatment. The 5-year survival probability is 56% and 8 patients are still living after more than 60 months. Eleven patients with N2 lymph node metastases receiving the complete therapy have a projected 5-year survival of 60%.

Operation for N2 small cell lung carcinoma.

Of 48 patients with limited small cell lung carcinoma treated by different modes, but always including radical operation, a series of 25 patients with N2 lymph node metastases is reported. In a first period (1970 to 1977) treatment consisted solely of radical resection in 3 patients; chemotherapy was added to operation in 6, and local radiotherapy was added in 2. Since 1977, 14 patients were treated according to a comprehensive therapy protocol including radical resection (six pneumonectomies, one bilobectomy, seven lobectomies), chemotherapy, local radiotherapy, and prophylactic cranial irradiation. Eleven patients, in whom N2 disease was confirmed preoperatively, received chemotherapy as the first step, followed by "adjuvant" resection. Projected 5-year survival rate is 25% for the entire N2 group and 47% for the comprehensively treated group. Seven patients of this latter group are alive 12, 19, 30, 48, 66, 73, and 74 months after comprehensive therapy, equivalent to an observed 2-year survival rate of 38%. This is the largest reported series of patients with resected small cell lung carcinoma in the N2 stage treated at a single institution; the results are so encouraging that we can no longer advocate general refusal of radical lung resection for small cell lung carcinoma in the N2 stage if it is part of a multimodal therapeutic protocol.

The importance of surgery as the first step in multimodality treatment of small cell bronchial carcinoma. The ISC Lung Cancer Study Group.

For patients with small cell lung cancer (SCLC) in their early stages (TNM I, II), surgery for cure was used to eliminate the primary tumour and its regional lymph-nodes followed by intermittent chemotherapy and radiotherapy within the first six postoperative months. After the pathohistological examination of the operation-specimen a two-arm-randomization was performed: standard chemotherapy (1000 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine) compared with sequential chemotherapy using three different drug-combinations (A: 1500 mg/m2 cyclophosphamide, 100 mg/m2 lomustine, 15 mg/m2 methotrexate; B: 1000 mg/m2 cyclophosphamide, 40 mg/m2 doxorubicin, 1 mg/m2 vincristine; C: 5 x 1.6 g/m2 ifosfamide plus mesna, 5 x 120 mg/m2 etopside). Thereafter disease-free patients only received prophylactic cranial irradiation (PCI: administering 3600 TD Gy/18 fractions) according to the protocols of the International Society of Chemotherapy Studies I and II. Preliminary evaluations in March 1990 of 170 patients from 24 cooperating departments for thoracic surgery showed that the projected life-table four-year-survival rate of 63 patients with SCLC at pTNM-stage I was 61%, of 54 patients at pTNM-stage II was 35%, of 13 patients at stage pT3, 4 NO, 1 MO was 59% and of 40 patients at stage pT N2 MO was 35%. The indication for surgery is emphasized for pTNM-stages I + II. For N2-lesions surgery would not be recommended in general, but the survival rate seems to indicate that this treatment was not detrimental, being rather more favourable compared with chemotherapy or radiotherapy alone. The continuation and enlargement of these studies seem not only justified, but emphatically indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesophageal sonography in central bronchial carcinoma.

A new application of transesophageal sonography was tested in eight patients suffering from central bronchial carcinoma. Due to ultrasound technology, a real time investigation is feasible which enhances the diagnostic method of computed tomography (CT) by discriminating between tumour and mediastinal organs which cannot be delineated by CT only. Different sonographic densities and the movement between organ and tumour contribute to the diagnostic accuracy of sonography if operability is questionable due to possible organ infiltration by tumour. The method is limited by the air filled organs (trachea, bronchi), as ultrasound does not penetrate adequately.

Intraoperative cryoanalgesia for postthoracotomy pain relief.

In a randomized study, 63 patients were investigated for the benefits of cryoanalgesia after thoracotomy. Analgesia and its dependent effects such as enhancement of mobility, respiratory function, and reduced need of narcotics were evaluated. No significant differences in these variables were observed between the cryoanalgesia group and the control group. However, moderate to severe neuralgia was found in a number of patients in the cryoanalgesia group in the late postoperative period. Cryoanalgesia for pain relief after thoracotomy is not recommended.

Endoscopic removal of a pedunculated bronchial lipoma by means of the hot snare.

The complete endoscopic removal by means of the hot snare of a pedunculated bronchial lipoma with a carcinoma in situ in its covering bronchial epithelium is reported. To our knowledge, the endoscopic removal of peripheral polypoid bronchial lesions has not been reported to date. The advantage of this technique lies in its ability to permit an exact histologic examination of the lesion, in contrast to laser vaporisation.