Henry A. van Swieten

Pulmonary large-cell neuroendocrine carcinoma (LCNEC)

OBJECTIVE The experiences on the treatment of seven consecutive patients with large-cell neuroendocrine carcinoma (LCNEC) were studied, observed over 6 years from 1992. Since LCNEC was recognized as a separate histological entity, only very few series have been reported. Together with the carcinoids (atypical and typical) and the small-cell lung carcinoma (SCLC), it forms the spectrum of neuroendocrine tumors. METHODS Between 1992 and 1997, seven patients who underwent surgical resection were diagnosed as LCNEC postoperatively. Mean age was 65 years (range 54-77 years), five patients were male, all patients were heavy smokers. One patient was staged as IA, four as IB, one as IIIB and one as IV. RESULTS In five patients, preoperative diagnosis was unknown, in one squamous cell carcinoma and in one adenocarcinoma was suspected. There were four lobectomies, two bilobectomies and one resection of the lingular division with a wedge resection of the upper division of the left upper lobe. Three patients received adjuvant chemotherapy and one, adjuvant radiotherapy. Survival ranged from 7 to 39 months. There are no patients currently alive. CONCLUSIONS LCNEC is a high-grade neuroendocrine tumor with a poor prognosis. In our patients, after surgical resection or multimodality treatment, all have developed widespread metastatic disease with a rapidly fatal course. Due to the rarity of this tumor, the incidence, prognosis and optimal treatment remain to be determined.

Surgery as part of combined modality treatment in stage IIIB non-small cell lung cancer.

BACKGROUND The role of surgery after neoadjuvant chemotherapy in patients with stage IIIB non-small cell lung cancer (NSCLC) remains unclear. METHODS A prospective multicenter trial of neoadjuvant chemotherapy followed by surgery or radiotherapy or both was conducted with 41 patients with stage IIIB NSCLC. End points were toxicity, response, downstaging, complete resectability, and survival. The diagnostic value of repeat mediastinoscopy after neoadjuvant chemotherapy (three courses of gemcitabine/cisplatin) was also studied. RESULTS Response rate after neoadjuvant chemotherapy was 66% (27 of 41). Fifteen patients underwent repeat mediastinoscopy, which proved to be inadequate in 6 patients. Two repeat mediastinoscopies were false negative. Resection was performed in 18 patients, of which 10 proved to be radical. Hospital mortality was 2.4% (n = 1). Major complications occurred in 6 patients (fistula, empyema, hemorrhage). Histopathologically proven downstaging was seen in 16 patients (39%). Twenty-five patients underwent radiotherapy of whom 14 were diagnosed with stable/progressive disease and 9 with partial/complete response. Median survival for all patients was 15.1 months, for nonresponders 8.4 months and for responders 16.8 months (p = 0.11). Patients with partial/complete response had a mean survival of 21.5 months after resection and 13.0 months after radiotherapy (p = 0.0003). CONCLUSIONS Radical surgery can be performed in 37% (10 of 27) of the responders resulting in a prolonged survival. Surgery as part of combined modality treatment is feasible in stage IIIB NSCLC. Results of a repeat mediastinoscopy are disappointing and proved to be a not-so-effective restaging tool because of the high number of incomplete procedures and because it yields false negative results.

Results of surgical treatment of T4 non-small cell lung cancer

OBJECTIVE Because of location and invasion of surrounding structures, the role of surgical treatment for T4 tumors remains unclear. Extended resections carry a high mortality and should be restricted for selected patients. This study clarifies the selection process in non-small cell T4 tumors with invasion of the mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral body, and carina, or with malignant pleural effusion. METHODS From 1977 through 1993, 89 patients underwent resection for primary non-small cell T4 carcinomas. Resection was regarded as complete in 34 patients (38.2%) and incomplete in 55 patients (61.8%). Actuarial survival time was calculated and risk factors for late death were identified. RESULTS Overall hospital mortality was 19.1% (n=17). Mean 5-year survival was 23.6% for all hospital survivors, 46.2% for patients with complete resection and 10.9% for patients with incomplete resection (P=0.0009). In patients with complete resection, mean 5-year survival for patients with invasion of great vessels was 35.7%, whereas mean 5-year survival for invasion of other structures was 58.3% (P=0.05). Age, mediastinal lymph node involvement, type of operative procedure, and postoperative radiotherapy did not significantly influence survival. CONCLUSION In certain T4 tumors complete resection is possible, resulting in good mean 5-year survival especially for tumors with invasion of the trachea or carina. High hospital mortality makes careful patient selection imperative.

Completion pneumonectomy: analysis of operative mortality and survival.

BACKGROUND A single-institution experience with completion pneumonectomy was analyzed to assess operative mortality and late outcome. METHODS A consecutive series of 138 completion pneumonectomies from 1975 to 1995 was reviewed, and compared with single-stage pneumonectomies performed during the same period. RESULTS Hospital mortality was 13.8%, including 4 intraoperative and 15 postoperative deaths. Hospital mortality was the same for lung cancer (13.2%) as for benign disease (15.5%). It was 37.5% if an early complication of the primary operation was the indication (p = 0.01). If infection of the pleural space was the indication for completion pneumonectomy, hospital mortality was 23.3% (p > 0.05). In 760 single-stage pneumonectomies hospital mortality was 8.7% (p > 0.05). Five-year actuarial survival after completion pneumonectomy was 42.5% for all patients, 32.3% for those with lung cancer, and 58.8% for those with benign disease. CONCLUSIONS Hospital mortality for completion pneumonectomy was the same for malignant as for benign indications. It was significantly higher if completion pneumonectomy was done for an early complication of the primary operation. Results at long term of lung cancer patients were the same for single-stage pneumonectomy and completion pneumonectomy.

Survival after resection of metachronous non-small cell lung cancer in 127 patients.

BACKGROUND In a number of patients with treated primary non-small cell lung cancer (NSCLC) a second primary tumor will be diagnosed. Our experience with surgery in these patients was analyzed and possible prognostic parameters were defined. METHODS Patients with metachronous NSCLC (n = 127) who underwent resection from 1970 through 1997 were analyzed. All tumors were classified postsurgically. Median interval between the tumors was 3.7 years. Actuarial survival time was estimated and risk factors influencing survival were evaluated. RESULTS Overall 5-year survival after the first resection was 70% and after the second resection was 26%. Patients with stage IA of the second primary tumor did have a significantly better survival (p < 0.005) as compared with patients with higher staged second primaries. Stage of second primary tumor and age were significant predictors of survival, whereas stage of first tumor, interval between resections, histology, and type of resection were not. CONCLUSIONS Survival of patients with metachronous NSCLC and resection of both tumors is high, but poorer than after resection of the first tumor. Irrespective of the interval, patients with stage IA second primary tumor may benefit more from pulmonary resection.

Combined off-pump coronary surgery and right lung resections through midline sternotomy

Concomitant severe coronary artery disease and lung malignancies are uncommon. Combining conventional coronary surgery with cardiopulmonary bypass with lung resection is still a controversial issue. Conversely, combining off-pump coronary surgery with right lung resections through a midline sternotomy can be an attractive approach. Off-pump coronary surgery avoids the risks of cardiopulmonary bypass, reduces systemic inflammatory response and does not affect the immune system. We report a series of three patients successfully operated using this approach.

Effect of metformin pretreatment on myocardial injury during coronary artery bypass surgery in patients without diabetes (MetCAB): a double-blind, randomised controlled trial

BACKGROUND During coronary artery bypass graft (CABG) surgery, ischaemia and reperfusion damage myocardial tissue, and increased postoperative plasma troponin concentration is associated with a worse outcome. We investigated whether metformin pretreatment limits cardiac injury, assessed by troponin concentrations, during CABG surgery in patients without diabetes. METHODS We did a placebo-controlled, double-blind, single-centre study in an academic hospital in Nijmegen (Netherlands) in adult patients without diabetes undergoing an elective on-pump CABG procedure. We randomly assigned patients (1:1) in blocks of ten via a computer-generated randomisation sequence to either metformin hydrochloride (500 mg three times per day) or placebo (three times per day) for 3 days before surgery. The last dose was given roughly 3 h before surgery. Patients, investigators, trial staff, and the statistician were all masked to treatment allocation. The primary endpoint was the plasma concentration of high-sensitive troponin I at 6, 12, and 24 h postreperfusion after surgery, analysed in the per-protocol population with a mixed-model analysis using all these timepoints. Secondary endpoints included the occurrence of clinically relevant arrhythmias within 24 hours after reperfusion, the need for inotropic support, time to detubation, duration of stay in the intensive-care unit, and postoperative use of insulin. This study is registered with ClinicalTrials.gov, number NCT01438723. FINDINGS Between Nov 8, 2011, and Nov 22, 2013, we randomly assigned 111 patients to treatment (57 to metformin and 54 to placebo). Five patients dropped out from the metformin group, and six from the placebo group. 52 patients in the metformin group and 48 patients in the placebo group were included in the per-protocol analysis. Geometric mean high-sensitivity troponin I increased from 0 μg/L to 3·67 μg/L (95% CI 3·06-4·41) with metformin and to 3·32 μg/L (2·75-4·01) with placebo at 6 h after reperfusion; 2·84 μg/L (2·37-3·41) and 2·45 μg/L (2·02-2·96), respectively, at 12 h; and to 1·77 μg/L (1·47-2·12) and 1·60 μg/L (1·32-1·94) at 24 h. The concentrations did not differ significantly between the groups (difference 12·3% for all timepoints [95% CI -12·4 to 44·1] p=0·35). Occurrence of arrhythmias did not differ between groups (three [5·8%] of 52 patients who received metformin vs three [6·3%] of 48 patients who received placebo; p=1·00). There was no difference between groups in the need for inotropic support, time to detubation, duration of stay in the intensive-care unit, or postoperative use of insulin. No patients died within 30 days after surgery. Occurrence of gastrointestinal discomfort (mostly diarrhoea) was significantly higher with metformin than with placebo (11 [21·2%] of 52 vs two [4·2%] of 48 patients; p=0·01). INTERPRETATION Short-term metformin pretreatment, although safe, does not seem to be an effective strategy to reduce periprocedural myocardial injury in patients without diabetes undergoing CABG surgery. FUNDING Netherlands Organisation for Health Research and Development and Netherlands Heart Foundation.

Sudden cardiac herniation 6 months after right pneumonectomy

Cardiac herniation is a rare complication of intrapericardial pneumonectomy and has a high mortality. The condition has been reported only within 24 hours after surgery. In this report, a case is described in which a total cardiac herniation took place 6 months after right intrapericardial pneumonectomy. The patient presented with an acute vena cava superior syndrome and underwent thoracotomy to reposition the heart into the pericardial sac and to close the pericardium with a patch.

Primary repair of rupture of a main and lobar bronchus

A 16-year-oJ[d boy was transferred from another hospital to our department because of clinical suspicion of a bronchial rupture after blunt chest trauma. He had been in a traffic accident as the driver of a small motorcycle. On admission he was intubated, nonsedated, and anxious. He had hypotension, tachycardia, and massive subcutaneous emphysema over the chest, the Upper part of the abdomen, and in the neck. A small thoracic catheter was in place. A roentgenogram of the chest made in the referring hospital showed a complete pneumothorax on the right side with extensive subcutaneous and mediastinal emphysema. He had a stable pelvic fracture, confirmed by radiography. The patient was sedated. An arterial pressure line, a jugular catheter, and a larger thoracic drain were placed. A major air leak was detected. A flexible bronchoscope, inserted in the emergency department, revealed a large defect of the right main bronchus just distal to the carina. The patient was then taken to the operating room for urgent thoracotomy. After placement of a single-lumen endotracheal tube into the left main bronchus, the patient was positioned on his left side and a right posterolateral thoracotomy above the fifth rib was performed. The right lung had collapsed and the right upper lobe contained a large intrapulmonary hematoma. A complex, double bronchial rupture was present--a complete transection of the right main bronchus and an incomplete rupture of the right lower lobe bronchus. The cartilaginous portion of the main bronchus was transected transversely about i cm distal to the carina. The membranous portion had ruptured transversely more proximally at the level of the carina. The two transection planes were connected by a double longitudinal tear at the junction between the cartilaginous and membranous parts of the right main bronchus (Fig. 1). The right lower lobar bronchus had an incomplete transverse rupture about half the circumference of the bronchus and 0.5 cm distal to the ostium of the bronchus for the right middle lobe. Both ruptures were

The importance of an organized follow-up for the evaluation of mortality after hospital discharge in cardiac surgery.

OBJECTIVES Does a structured follow-up, after cardiac surgery in an adult, provide additional information on the operation related mortality especially if mortality is used as an outcome parameter within the quality control? METHOD Mortality data of 1132 patients undergoing cardiac surgery in 2003 and 2004 in the Academic Hospital Nijmegen, The Netherlands were registered by a structured follow-up one year after surgery. RESULTS One year after surgery this follow-up is missing information for eight patients (0.7%). Six patients (0.5%) refused further follow-up. Of the 31 patients who died during the first postoperative year, 21 (68%) were registered thanks to this structured follow-up. In 29 patients it was possible to retrieve the cause of death. CONCLUSION A structured follow-up one year after cardiac surgery has a high response and not only provides a better total picture of mortality, but also information on the cause of death. Both aspects are important if mortality is used as a parameter for quality control in cardiac surgery.