Cancer cells suppress p53 in adjacent fibroblasts.

The p53 tumor suppressor serves as a crucial barrier against cancer development. In tumor cells and their progenitors, p53 suppresses cancer in a cell-autonomous manner. However, p53 also possesses non-cell-autonomous activities. For example, p53 of stromal fibroblasts can modulate the spectrum of proteins secreted by these cells, rendering their microenvironment less supportive of the survival and spread of adjacent tumor cells. We now report that epithelial tumor cells can suppress p53 induction in neighboring fibroblasts, an effect reproducible by tumor cell-conditioned medium. The ability to suppress fibroblast p53 activation is acquired by epithelial cells in the course of neoplastic transformation. Specifically, stable transduction of immortalized epithelial cells by mutant H-Ras and p53-specific short inhibitory RNA endows them with the ability to quench fibroblast p53 induction. Importantly, human cancer-associated fibroblasts are more susceptible to this suppression than normal fibroblasts. These findings underscore a mechanism whereby epithelial cancer cells may overcome the non-cell-autonomous tumor suppressor function of p53 in stromal fibroblasts.

Chromosomal aberrations and gene expression profiles in non-small cell lung cancer.

Alterations in genomic content and changes in gene expression levels are central characteristics of tumors and pivotal to the tumorigenic process. We analyzed 23 non-small cell lung cancer (NSCLC) tumors by array comparative genomic hybridization (array CGH). Aberrant regions identified included well-characterized chromosomal aberrations such as amplifications of 3q and 8q and deletions of 3p21.31. Less frequently identified aberrations such as amplifications of 7q22.3-31.31 and 12p11.23-13.2, and previously unidentified aberrations such as deletion of 11q12.3-13.3 were also detected. To enhance our ability to identify key acting genes residing in these regions, we combined array CGH results with gene expression profiling performed on the same tumor samples. We identified a set of genes with concordant changes in DNA copy number and expression levels, i.e. overexpressed genes located in amplified regions and underexpressed genes located in deleted regions. This set included members of the Wnt/beta-catenin pathway, genes involved in DNA replication, and matrix metalloproteases (MMPs). Functional enrichment analysis of the genes both overexpressed and amplified revealed a significant enrichment for DNA replication and repair, and extracellular matrix component gene ontology annotations. We verified the changes in expressions of MCM2, MCM6, RUVBL1, MMP1, MMP12 by real-time quantitative PCR. Our results provide a high resolution map of copy number changes in non-small cell lung cancer. The joint analysis of array CGH and gene expression analysis highlights genes with concordant changes in expression and copy number that may be critical to lung cancer development and progression.

Mediastinal dissection in head and neck cancer.

The superior mediastinum contains a considerable number of lymph nodes. Although occasionally involved in head and neck cancer, there are not many reports of mediastinal dissection in the practice of head and neck surgery. We present a group of seven patients with head and neck tumours that underwent mediastinal dissection in our department. Three patients are alive and free of disease six months to three years after the operation, two are alive with disease four and five years after the procedure, and two patients died peri-operatively. According to reviewed current literature, direct invasion of cancer of the head and neck to the mediastinum or mediastinal lymph node involvement is uncommon. Yet, mediastinal dissection provides the only chance for cure in selected cases.

Major bronchial trauma in the pediatric age group.

Tracheobronchial injuries are rare among all age groups and are extremely rare among the pediatric age group. Yet, the incidence has seemed to increase. Most of these patients die before reaching the hospital from severe associated injuries. Isolated bronchial injury is even more rare than tracheal injury, and it is the focus of the present study. A retrospective national survey was conducted among all tertiary referral and trauma centers in Israel regarding the period between the years 1983 and 1998. Only six cases (3 males and 3 females) of isolated bronchial rupture were found the throughout the country. Ages of the patients ranged from 2 to 14 years; all were involved in motor vehicle accidents, four of them as pedestrians. Ruptures occurred in the bronchus intermedicus (2 cases), left and right main bronchus (2 cases each). All but one patient went through primary repair. We give a full description of the procedure and discuss the literature regarding incidence, diagnosis, treatment, and outcome.

Diaphragm plication following phrenic nerve injury: a comparison of paediatric and adult patients.

BACKGROUND: A study was undertaken to evaluate whether adults differ from children in the indications and outcome of diaphragmatic plication following phrenic nerve injury. METHODS: A retrospective study was performed of 21 patients, 10 below the age of 5 and 11 older than 37 years. The indication for surgery for all the children was failure to wean from ventilatory support. The indications for surgery in the adult group were ventilator dependency (n=4) and symptomatic dyspnoea (n=7). All patients had at least one imaging study confirming diaphragmatic paralysis. The American Thoracic Society (ATS) dyspnoea scale, pulmonary function tests, and quantitative pulmonary perfusion scans were used as evaluation parameters. At surgery the diaphragm was centrally plicated. RESULTS: One child died immediately after surgery due to irreversible heart failure and two children died within 2 months of surgery from ongoing complications of their original condition. These three patients were considered as selection failures. Seven children were weaned from ventilatory support within a median of 4 days (range 2-140). Only one of four ventilated adults was successfully weaned. Seven adults who underwent surgery for chronic symptoms had a marked subjective improvement of 2-3 levels in the ATS dyspnoea scale. Pulmonary function studies in the seven symptomatic adults showed a 40% improvement above baseline. Severely asymmetrical perfusion scans reverted to a normal pattern after plication. CONCLUSIONS: Diaphragmatic plication offers a significant benefit to children with diaphragmatic paralysis and should be performed early to facilitate weaning from mechanical ventilation. While plication is of limited benefit in weaning ventilated adults, it results in significant subjective and objective lifetime improvement in non-ventilated symptomatic adults.

Hyperthermic pleural perfusion with cisplatin: early clinical experience.

BACKGROUND: The preferred treatment for patients with pleural tumors or tumors with pleural extension has not been determined. Systemic and local modalities were studied, including intrapleural chemotherapy and hyperthermia, which mainly have been investigated separately. The objective of this study was to investigate the feasibility, toxicity and early results of a multimodality treatment consisting of surgery, chemotherapy, and hyperthermia in one session for the treatment of patients with pleural malignancies. METHODS: From November 1994 to September 1998, 26 patients (7 patients with mesothelioma, 11 patients with thymic neoplasms, and 8 patients with other tumors) underwent intraoperative hyperthermic pleural perfusion (HPP). Perfusion was performed with a roller pump and a heat exchanger. Cisplatin was added when the temperature stabilized to a mean of 40.8 degrees C (range, 40.2-41.5 degrees C). Dosages of cisplatin used were 60 mg in 2 patients, 100 mg in 2 patients, 120 mg in 1 patient, 150 mg in 18 patients, and 200 mg in 3 patients. The patients underwent the following associated surgeries: extended extrapleural pneumonectomy in 8 patients, resection of tumor without pleurectomy in 4 patients, resection of tumors with pleurectomy in 10 patients, and exploration and HPP only in 4 patients (thoracotomy in 2 patients and video-assisted thoracoscopy in 2 patients). RESULTS: There were no technical problems during the perfusion period. The systemic temperature rose to a maximum of 38 degrees C. There was no renal or hematologic toxicity, except in one patient who experienced thrombocytopenia. One patient died from complications related to a technical error. Eight patients had complications; the most bothersome were in four patients with empyema (early in two patients and late in two patients). The median postoperative hospital stay was 7 days (range, 2-50 days). Ten patients were alive 28-69 months after surgery. The overall 1-year, 2-year, and 3-year survival rates were 72%, 65%, and 44%, respectively. Complete ipsilateral pleuropulmonary control was achieved in 17 patients (9 patients who are alive and 8 patients who have died). CONCLUSIONS: Intraoperative HPP with cisplatin is feasible, easy to perform, and relatively safe. This method may offer excellent local control for patients with pleural tumors.

Prevalence of the juxtaphrenic peak after upper lobectomy.

OBJECTIVE: The purpose of this study was to determine the prevalence of the juxtaphrenic peak after upper lobectomy in a large number of consecutive patients. MATERIALS AND METHODS: Available chest radiographs of 172 of 199 sequential patients who had undergone upper lobectomy in a university hospital were evaluated for the presence of a juxtaphrenic peak. The study included 98 cases with right upper lobectomy and 74 with left upper lobectomy. Radiographs were grouped in three postoperative periods: period I, within 7 days after lobectomy (n = 142); period II, between 8 and 30 days (n = 113); and period III, 31 days or more after lobectomy (n = 101). Four experienced radiologists in consensus determined the prevalence of the "juxtaphrenic peak sign," in relation to age, sex, side of lobectomy, positioning (erect or supine), presence of juxtadiaphragmatic abnormalities, and time interval since surgery. RESULTS: The prevalence of the juxtaphrenic peak sign gradually increased from 40.6% in period I to 71.9% in period III after right upper lobectomy (p < 0.01), and from 19% to 47.7%, respectively, after left upper lobectomy (p < 0.01). Its overall prevalence was significantly higher after right upper lobectomy (58.2%) than after left upper lobectomy (40.5%) (p = 0.02), and on erect chest films (51.4%) than on supine ones (28.9%). CONCLUSION: The prevalence of the juxtaphrenic peak sign increases gradually during the weeks following lobectomy. It is more frequent on erect films and after right upper lobectomy. The juxtaphrenic peak may serve as an additional useful radiologic sign suggesting upper lobectomy.

Resection and perfusion thermochemotherapy: a new approach for the treatment of thymic malignancies with pleural spread.

BACKGROUND: Thymoma and thymic carcinoma with pleural spread have a high rate of locoregional recurrence and poor prognosis. Maximal debulking coupled with aggressive local treatment could offer a chance for cure. This study evaluates the early and midterm results of operation and hyperthermic pleural perfusion with cisplatinum for thymic malignancies. METHODS: Fifteen patients (11 men), 20 to 67 years old (10 thymoma, 4 thymic carcinoma, 1 carcinoma in thymic cyst) underwent resection and hyperthermic pleural perfusion between 1995 to 2000. All had pleural spread proven before or intraoperatively. Six of the thymoma cases were recurrent. Current operation included resection without pleurectomy (9 patients), resection with pleurectomy (5), and extrapleural pneumonectomy (1 patient) with intraoperative hyperthermic pleural perfusion in all. Intrapleural temperature reached 40.3 degrees C to 43 degrees C. The total dose of cisplatinum was 150 mg or more in 14 patients. RESULTS: Complete resection (R0) was achieved in 10 patients, subtotal (R1) in 3, and partial (R2) in 2. There was no operative mortality, no hemodynamic or respiratory disturbances during perfusion, and no hematologic, neurologic, or renal complications. Complications consisted of significant bleeding (2 patients), fever (2), and air leak (1 patient). Two patients with thymic carcinoma died after 27 and 34 months, and 1 is alive with no evidence of disease at 54 months. Two patients with thymoma died after 7 and 36 months. Eight are alive after 9 to 70 months. Four patients (all R0) are alive without local recurrence more than 60 months after operation and hyperthermic pleural perfusion. CONCLUSIONS: Operation and thermochemotherpy is feasible and safe in patients with thymic tumors. This method seems to offer excellent local control for patients with stage IV-a thymic malignancies. Midterm results suggest that operation plus hyperthermic pleural perfusion may lengthen survival in stage IV-a thymoma.

CT diagnosis of malpositioned chest tubes.

Insertion of a chest tube into the pleural space is standard management for various pleural disorders. Malpositioning of chest tubes in extrathoracic, intraparenchymal and mediastinal locations and in the fissures is common. Malpositioning results not only in inadequate drainage of air and fluid but may also result in increased morbidity and mortality. Diagnosis of a malpositioned tube is sometimes difficult to establish on a chest radiograph. CT, however, has proven to be extremely accurate in evaluating the position of a chest tube and has often provided additional valuable information with significant therapeutic impact.

Psammomatous melanotic schwannoma: presentation of a rare primary lung tumor.

A 30-year-old nonsmoking man underwent a left lower lobectomy with bronchoplasty for an obstructing lesion of the left lower lobe. Pathology results demonstrated a psammomatous melanotic schwannoma, a rare pigmented neural tumor of which only 25 cases have been reported as originating in the respiratory tract.

Postsurgical prevertebral abscess of the cervical spine.

OBJECTIVES: Prevertebral abscess formation is an uncommon occurrence following cervical spine fusion surgery. Abscesses may present early or in a delayed fashion and require surgical drainage and long-term antibiotic treatment. The issues of osteomyelitis and the need for plate removal remain unresolved. STUDY DESIGN: A case series of six tetraplegic patients admitted for rehabilitation to the Chaim Sheba Medical Center (Tel Hashomer, Israel) is presented. METHODS: Five patients were trauma patients; one patient underwent repeated procedures and irradiation for tumor of the cervical spine. All patients developed prevertebral abscesses after a mean period of 30 days from their fusion surgery. Computed tomography scan was used in all patients to establish the diagnosis and define the extent of the infective process. All patients underwent one or more drainage procedures. The plate was removed in two patients at 1 and 4 months. RESULTS: Infection completely resolved in four patient and was refractory in one patient with malignant tumor, and a chronic small fistula remained in one case. Staphylococcus aureus was the main infective organism, but mixed infections were the rule. Even for a protracted course of infection, no significant osteomyelitis was encountered. CONCLUSIONS: Abscess formation after instrumentation of the neck may be more common than formerly recognized. Despite the prolonged course of disease and treatment, osteomyelitis is not a major concern. There is no automatic indication for plate removal to control infection, although plating may be safely removed after 10 to 12 weeks if the neck is explored and the cervical spine is stable. A high index of suspicion is warranted, and early recognition and diagnosis, prompt surgical drainage under general anesthesia, and long-term antibiotic treatment are key for eradication of the infective process. Prophylactic antibiotics may be of value. Meticulous antisepsis and surgical technique should be maintained to reduce the incidence of these severe complications.

[Plication of diaphragm for postoperative phrenic nerve injury in infants and young children].

Paralysis of the diaphragm may cause life-threatening respiratory distress in infants and young children because of paradoxical motion of the affected diaphragm and contralateral shift of the mediastinum during expiration. Phrenic nerve injury (PNI) may follow chest operations. 10 children with diaphragmatic paralysis and severe respiratory distress underwent plication of the diaphragm. Ages ranged from 14 days to 5 years. 9 had PNI after operations for congenital heart disease and 1 after resection of an intraspinal cervical lipoma. The right side was affected in 7, the left in 3. Indication for surgery was inability to wean from mechanical ventilation, which had ranged from 11 to 152 days (median 35). 8 underwent plication via a thoracic approach and 2 via an abdominal approach. There were no complications directly related to the operation. The interval from plication to weaning from mechanical ventilation ranged from 2 to 140 days (median 4). 1 patient died 2 hours after plication due to severe heart failure and 2 after prolonged hospitalization due to sepsis and multi-organ failure. 6 were extubated 2-8 days (median 4) after plication and 1 only after 40 days. Early diaphragmatic plication is simple and avoids more serious surgery. While effective in ventilator-dependent infants and young children, it should not be used in those with multi-organ failure. Early plication may prevent the complications of prolonged mechanical ventilation.

Exostosis of a rib causing laceration of the diaphragm: diagnosis and management.

A 17-year-old boy presented with spontaneous hemothorax due to a puncture wound of the diaphragm by an inward facing exostosis of the rib. Diagnosis was made by computed tomographic scan, and the patient underwent a video-assisted thoracoscopic procedure to remove the exostosis. This is only the eighth reported case of an exostosis causing hemothorax.

Re-expansion pulmonary oedema following spontaneous pneumothorax.

Re-expansion pulmonary oedema may occur after chest tube drainage of pneumothorax and can give rise to cardiopulmonary manifestations which range from the mild to the severe. In order to evaluate the prevalence and the clinical manifestations of this complication, all patients with spontaneous pneumothorax managed with chest tube drainage were evaluated over an 8-yr period (1986-1994). A chest radiograph was performed routinely in all patients within 4 h of tube insertion. Lung expansion and the appearance of infiltrates within the lungs were investigated specifically. Re-expansion oedema was noted in three of 320 episodes (0.9%). Two of the three patients needed rapid and extensive clinical treatment.

Pleural abrasion via axillary thoracotomy in the era of video assisted thoracic surgery.

BACKGROUND: Recurrent episodes of spontaneous pneumothorax can be managed medically or surgically by various methods, video assisted thoracoscopy being the latest and most attractive. METHODS: A retrospective analysis was made of 43 pleural abrasions performed in 39 patients through a 4-6 cm axillary thoracotomy incision. RESULTS: There were no deaths and complications were few. At a mean follow up of 33 months there were two recurrences, neither of which required drainage. CONCLUSIONS: Compared with results achieved with video assisted thoracoscopic surgery, open pleural abrasion via a small thoracotomy may be the treatment of choice in most hospitals.

Main bronchial rupture from blunt trauma in a 2-year-old child.

The authors report on a 2 year old who sustained a bronchial rupture after a motor vehicle accident and was operated on soon after admission. This injury is very unusual in young children.

Fibrothorax associated with a ventriculopleural shunt in a hydrocephalic child.

Ventriculopleural (VPL) shunts are considered a safe alternative to peritoneal shunts in the management of hydrocephalus. Occasionally, however, they are associated with persistent pleural effusion. We report a child, aged 3 1/2 years, who developed severe fibrothorax following the use of a VPL shunt. The shunt was removed and decortication had to be performed to alleviate his respiratory symptoms. This serious complication, never reported previously, should be borne in mind when the pleural cavity is chosen for deviation of the cerebrospinal fluid in hydrocephalic children.